Dose-dependence of the augmentation of hemopoiesis by thymocytes.

We have used the spleen colony assay and the 24-h uptake of 59Fe by hemopoietic tissues to study certain quantitative aspects of the interaction of parent-strain thymocytes and marrow cells transplanted into lethally irradiated F1 hybrid mice. The data show that thymocytes augment bone marrow growth at least partly by increasing the proportion of stem cells from parental marrow that from colonies in the hybrid animal. This increase in spleen colony number is a linear function of the number of thymocytes injected within certain dose ranges. At higher thymocytes doses, a plateau is reached where further increase in the number of thymocytes injected does not result in an increase in the number of spleen colonies; this plateau occurs at just that level of response given by the same marrow dose when transplanted into isogeneic (parent-strain) recipients. Experiments in which 59Fe uptake up red blood cells and spleen was used to measure marrow growth yielded similar results, except that the plateau in uptake occurred at a much lower level than that measured for the same marrow dose in isogeneic recipients. This apparent discrepancy in results obtained from the two different assays may best be explained by the recent observation that thymocytes shift the differentiation pattern of marrow stem cells away from erythropoiesis and toward granulopoiesis. The absolute thymocyte dose seems to be more important than the thymocyte: marrow-cell ratio in determining the degree of augmentation observed.


The nature of toxicity of human serum in the bioassay for erythropoietin using mouse foetal liver cells.

Using several immunological techniques, it was possible to demonstrate that toxicity of human serum in the foetal mouse liver cell bioassay for erythropoietin was due to complement-dependent IgM hetero antibodies to mouse foetal liver cells. The titre of the antibodies in 50 normal human sera ranged between 2 and 64 as measured in an agglutination test with mouse erythrocytes. Specificity of the antibodies for the ABO-or Ii-blood group system could not be established. Inactivation of complement by heating a serum for 30 minutes at 56 degrees C abolished toxicity.


Circles in spermatocyte chromatin loops. Electron microscopy and AgAs-NORs studies.

We describe the production of circles in chromomeric loops during the pachytene stage of the spermatocytes. These circles are found attached to chromatin or already free in the nucleoplasm. Each circle measures an average of 3700 A in circunference. We suggest that such circles might indicate the presence of tandem repetitions.


[Comparison of the effect of sidnocarb and other psychostimulants on discrimination and prediction processes in performing conditioned food-procuring reflexes].

In an Y-shaped maze a differentiation of the positive and negative reflex signals given at random in a ratio of 50 to 50 per cent and an active selection of one of two feeding troughs, reinforced at varying frequency (0.1--0.9), were determined. Sydnocarb (10--20 mg/kg) had no influence on the realization of the food-procurement response, but improved the discrimination of the signals. Only small doses of amphetamine (0.5 mg/kg), caffein (20 mg/kg) and acephen (10 mg/kg) also improved the response to conditioned signals. Sydnocarb reduced the number of runs to a rarely reinforced feeding trough and, at the same time, stimulated an active choice of the latter. Amphetamine largely facilitated an active choice of the runs direction. Caffein displayed a tendency to reduce the number of wrong approaches. Acephen hampered an active choice of compartments in the Y-maze without impairing the ability to distinguish the frequency of the feeding troughs reinforcement.


Hormonal and clinical responses in amenorrhetic patients treated with gonadotropins and a nasal form of synthetic gonadotropin-releasing hormone.

Synthetic gonadotropin-releasing hormone (GnRH) in the form of nasal drops was self-administered by five amenorrheic patients in an attempt to assess its therapeutic value in anovulatory infertility. After follicular maturation had been induced with human menopausal gonadotropins (HMG), a total daily dose of 7.5 mg of GnRH in the form of nasal drops was self-administered at 2-hour intervals for 6 hours on 3 consecutive days. In four patients, plasma luteinizing hormone (LH) levels were significantly elevated over a period of at least 8 hours. In three of these patients, in addition, there was a definite upward shift in the basal body temperature (BBT) curve, and uterine bleeding occurred 6 to 9 days after the first dose of GnRH. In the fourth patient, ovulation was induced as indicated by a biphasic BBT curve, a plasma progesterone level of 13 ng/ml, and a luteal phase of 15 days. In the remaining patient, there was a borderline LH response and no clinical response. It is concluded that GnRH, in the form of nasal drops, is effective in eliciting and maintaining elevated plasma LH levels in patients in whom follicular maturation has been induced with HMG. By obtaining ovulatory LH levels, such a regimen can lead to ovulation. In addition, intranasal self-administration of GnRH is convenient and may provide an alternative route of administration for long-term therapy with this hormone.


Remissions of mycosis fungoides induced by nitrogen mustard (HN2). Topical treatment and hydration of tumours and plaques with HN2. Topical desensitization to HN2. A clinical and histopathological controlled study.

In this study 12 patients with mycosis fungoides were treated with whole body topical application of HN2. In addition 4 of these patients had gauzes moistened with the same HN2 solution placed upon plaques and tumours. 4 patients developed in allergic contact dermatitis, and this complication was overcome by percutaneous desensitizing in 3 of them. After starting hydration of plaques and tumours with HN2, the average time to obtain complete clinical remission was shorted from 4.4 to 2.5 months. A little later at the optimal histologic response, there was no or almost no cellular infiltration in 5 cases, while in 6 cases there was only a slight, unspecific, lymphocytic infiltrate in the dermis.


Induction of delayed reaction to dinitrophenylated lymphocytes in guinea pigs with contact sensitivity to DNCB.

The incidence of dinitrophenylated cells in guinea pig lymphocytes incubated with 0-30 mM concentrations of DNBSO3Na in phosphate-buffered saline was examined by an immunofluorescence method using fluorescence-labelled anti-DNP antibody. Under our experimental conditions, the incidence was roughly proportional to the concentration used. Using DNP-lymphocytes as an antigen for skin testing, a marked delayed reaction was induced in guinea pigs sensitized by painting with DNCB and intradermal injection of Freund's complete adjuvant. The significance of these findings is discussed.


Comparative blanching activities of proprietary diflucortolone valerate topical preparations.

The blanching activities and hence bioavailabilities of the cream, ointment and fatty ointment preparations of Nerisone and Temetex (diflucortolone valerate 0.1%) were evaluated using an occluded and unoccluded blanching assay. These products were compared to Synalar ointment and cream (fluocinolone acetonide 0.025%), established topical corticosteroid preparations. Statistical analysis showed no significant differences between similar formulations of diflucortolone valerate. Significant differences were noted between diflucortolone valerate and fluocinolone acetonide preparations.


The relationship between congenital defects and the use of exogenous progestional "contraceptive" hormones during pregnancy: a 20-year review.

This review of 20 years of medical literature on the occurrence of congenital defects among offspring of women who ingested "progestational" or contraceptive hormones during pregnancy emphasizes the need for additional studies with carefully selected control groups. Other problems encountered in interpreting the existing literature, including the use of imprecise definitions, confusing nomenclature and inadequate clinical information, are also discussed.


Double-blind oral analgesic study of butorphanol in musculoskeletal pain: a comparison with codeine and placebo.

Butorphanol tartrate (4 mg and 8 mg) was compared to codeine phosphate (60 mg) and placebo for oral analgesic activity and side-effects employing a double-blind design in ninety-three out-patients suffering from moderate to very severe musculoskeletal pain. The study duration was 72 hours with medication administered every 4 to 6 hours (four times daily) for a total of twelve doses per patient. The results demonstrate that both the 4 mg and 8 mg doses of butorphanol were significantly better (p less than 0.u5) than placebo. While codeine 60 mg also proved active, it appears to be less efficacious than the high dose of butorphanol. The peak effect appeared to be evident in 1 to 2 hours. Butorphanol may be at least seven times more potent than codeine on a milligram basis. Although no serious side-effects were observed, butorphanol appeared to present a greater incidence of side-effects than codeine and placebo in this study.


Clinical trial with Lunerin mixture and Lunerin mite in children with secretory otitis media.

A double-blind comparison between a combined antihistaminc and vasoconstricting preparation (Lunerin Mixture, Lunerin Mite) and placebo was performed in children with secretory otitis media. It was shown that the children given the active drug reacted more favourably on every investigated parameter (hearing threshold, appearance and mobility of the ear drum, number of myringotomies and observation time) than the patients who were given placebo. The incidence of side-effects was low.


Clinical trial of acebutolol (Sectral) in hypertension.

Acebutolol (Sectral) was used successfully in a clinical trial involving thirty-two hypertensive patients. Twenty-three patients received acebutolol at a dosage of 400--800 mg daily as sole treatment and nine patients received concurrent treatment with thiazide diuretics. In both groups of patients there was a substantial fall in diastolic and systolic pressure to levels within the normotensive range. The combination of acebutolol with thiazide diuretics was a particularly effective form of anti-hypertensive treatment where a greater anti-hypertensive effect was required. Acebutolol did not significantly slow the heart rate. The only side-effect was slight pitting oedema of both legs in one patient. Acebutolol appears to be a useful anti-hypertensive in the management of hypertension.


An attenuated influenza virus vaccine: protection against homologous and heterologous strains of virus.

An effective influenza vaccine should be capable of providing protection against both the homologous virus strain and heterologous strains representing antigenic "drift". Two attenuated vaccines were evaluated, an A/Hong Kong/8/68 (H3N2) and an A/England/42/72 (H3N2) strain. Volunteers were immunized intranasally with either placebo or vaccine in a "double-blind" fashion in two doses, 2 weeks apart. Eighty-four subjects were challenged 30-100 days after the second dose with either the homologous or a heterologous strain. The heterologous strain for the A/Hong Kong/8/68 (H3N2) vaccinees was the A/England/42/72 (H3N2) virulent strain. The heterologous strain for the A/England/42/72 (H3N2) vaccinees was a virulent A/Dunedin/73 (H3N2) strain. Both vaccines led to good protection against both homologous and heterologous challenges. The protection rate against illness for the A/Hong Kong/8/68 (H3N2) vaccinees was 73% and 100% following homologous and heterologous challenges, respectively. The protection rate for the A/England/42/72 H3N2) vaccinees was 100% following both homologous and heterologous challenges. The protection rates against infection (as judged by antibody responses, irrespective of signs and symptoms) were also good. For the A/Hong Kong/8/68 (H3N2) vaccinees the rates were 73% (homologous) and 86% (heterologous). For the A/England/42/72 vaccinees, the rates were 72% and 60% respectively. Thus, immunity induced by these attenuated influenza vaccines extends to provide protection against related but non-identical influenza viruses.


Challenge versus natural infection as an index or protection after influenza immunization.

The most important consideration in evaluating an immunization procedure is protection from infection. Protection provided by influenza vaccines can best be determined by large scale field trials and natural infection. However, these are difficult to control and epidemics cannot always be accurately predicted. On the other hand, representative artificial challenge studies can be controlled and are easier to perform. In the studies, reported protection achieved against artificial challenge is compared with protection effected in vaccinees during natural influenza epidemic. Protection rate against artificial challenge with influenza A was 96% when vaccine and challenge viruses were homotypic. When the vaccine strain and challenges virus were heterotypic, protection ranged from 70-100%. Protection rate from infection during a homotypic epidemic was, retrospectively, 95%; while 50-87% protection from influenza illness was achieved during a heterotypic epidemic. In all instances, vaccinees experienced mild, mostly afebrile upper respiratory symptoms, unlike controls who had moderate to severe symptoms, often with fever. Infecting virus was shed more often by unvaccinated controls. Although artificial challenge was performed in healthy young adults, epidemiological results indicate that similar protection can be achieved for children, the elderly or high risk. Thus statistically representative sampling of immunized and non-immunized controls and challenge can be used as a direct indication of vaccine efficacy against natural infection in all populations.


Laboratory and clinical evaluation of new live influenza virus vaccines. Need for minimum requirements.

Recently, new methods for the selection of candidate live influenza vaccine viruses have become available. They are based on the characterization of the genetic material of these viruses and have been shown to correlate with attenuation for man. Adequately attenuated viruses have been obtained from various H3N2 strains using standard methods of attenuation for each strain. These  vaccine strains met the criteria for live attenuated influenza virus vaccines: they were attenuated, non-transmissible and immunogenic. The use of modern methods of attenuation also allows rapid updating of live influenza virus vaccines. Laboratory methods used, the safety testing of candidate vaccines in animals and man will be discussed. There is an urgent need for standardization and for the establishment of minimum requirements and specifications.


Small-scale field trial with neuraminidase vaccine.

An inactivated whole-virus vaccine was prepared from the influenza virus recombinant H0N2 and administered to two groups of subjects. A total of 1,200 subjects were vaccinated; comparable groups of subjects served as controls. From a portion of the vaccinees sera were obtained prior to vaccination and three to four weeks afterwards. Serological tests revealed development of or increase in the antibody against H0 in a great majority of the vaccinated subjects and against N2 in slightly more than half of them. Antibody response to H3 antigen was only rarely encountered. Approximately three months after vaccination an influenza epidemic caused by Victoria-like (H3N2) viruses broke out in Czechoslovakia. Numerous influenza cases occurred in the two populations followed. Morbidity was significantly lower among the vaccinated than among the control subjects, indicating a protective effect of the neuraminidase vaccine under field conditions.


Clinical reactions to an adsorbed killed trivalent influenza vaccine (including A/New Jersey 8/76 antigen) with different immunization methods.

The local and general reactions of 489 individuals vaccinated with an adsorbed killed influenza vaccine (containing A/New Jersey 8/76, A/Victoria 3/75, B/Hong kong 8/73 antigens) were studied on the fourth day after vaccination. 179 participants were vaccinated by syringe, the rest by jet injector. Local indurations were observed in 7.3% of participants injected by needle versus 14.1% to 19.5%, respectively in individuals immunized with two different jet guns (Lodi, Scherer). 2 ulcerations on the injection site were found in the jet group. Complaints about local sensations were much fewer in the group injected by needle (2.8%) than in the groups injected by jet injectors (11.8-14.1%). Postvaccinal systemic reactions were similar (between 8.5-11.2%) in both groups. Febrile reactions were altogether low (2.8%).


Experience with monovalent and bivalent influenza vaccines in Canada 1976. Clinical evaluation of vaccines from four sources.

Clinical trials in adults of monovalent (200 CCA Units per dose) and bivalent (400 CCA Units per dose) inactivated influenza whole virus A/Swine and A/Victoria vaccines from different sources resulted in variations in clinical reactivity which may not be significant because of lack of controls and observer bias. In adults with no pre-vaccine antibody (HI less than 1/10) the A/Swine Monovalent vaccine from one source evoked significantly lower response than did the A/Swine component of the Bivalent vaccine from another source. Serologic response to A/Victoria antigen was comparable for vaccines prepared with material from two sources. In medically high risk children two doses of Bivalent A/Swine A/Victoria influenza vaccine, with the dosage adjusted according to age, stimulated acceptable serologic response without an unacceptable frequency of local and general reactions. The response was higher in the youngest and older age groups included in the clinical trial than in the seven to twelve year old group implying a dose to age relationship.


Influenza surveillance of Wisconsin (USA) population-detection of A/New Jersey by isolation and serologic monitoring and vaccine evaluation.

The 1976-77 influenza surveillance in Wisconsin consisted of three major areas of study. Serum and virus isolation specimens were obtained from the practicing medical community and from epidemiologic studies. From all sources 1,132 throat specimens were tested by egg and tissue culture inoculations. Three isolations similar to A/New Jersey/8/76 were recovered from pig farm associated patients. One contact with one of the isolate patients seroconverted to A/New Jersey suggesting patient to patient spread. Serological monitoring of 1,361 patients showed no other A/New Jersey activity in the state. In addition 31 influenza B/Hong Kong and 8 A/Victoria isolates have been recovered as well as 34 B and 11 A seroconversions. A surveillance using primarily syphilis serology premarital serums has been conducted from August 29, 1976 through April 23, 1977. No significant influenza A activity in the state was recognized by this study. However, increased herd immunity from vaccination was detected. The last phase of this surveillance was an evaluation of the mass immunization program and the efficacy of the vaccines. Two-hundred-ninety individuals contributed pre- and post-vaccine serums to this study. Eighty-three percent of those persons with a pre-vaccine titer of 1:80 or less to A/New Jersey/8/76 developed a post-vaccine titer four-fold or greater to that virus type. Those who received vaccine containing A/Victoria/3/75 were less responsive. Refractiveness to vaccine antibody stimulation was greater than or equal to 1:160 for A/New Jersey and less than or equal to 1:40 with A/Victoria.


Mechanism of barbituric-acid protection against inhibition by alloxan of glucose-induced insulin release.

Isolated rat islets were maintained in a simple static incubation system and were exposed to alloxan for a period of five minutes. Alloxan inhibited subsequent glucose-induced insulin release in a dose-dependent manner at 37 degrees C., with 650 muM alloxan producing 94 per cent inhibition of insulin release. Barbituric acid, a compound structurally related to alloxan, provided complete protection (at 37 degrees C.) against this inhibition of insulin release when present during the alloxan exposure. At 23 degrees C., barbituric acid was shown to be absent from the intracellular space of the islet yet still protected completely against alloxan inhibition of insulin release. Thus, barbituric acid apparently provided protection against alloxan in the extracellular medium. By fluorometric and chromatographic analyses, it was determined that barbituric acid reacted rapidly with alloxan to produce a new compound. These findings indicate that barbituric acid protected against alloxan by a chemical reaction in the medium.


Clinical trials with a new influenza subunit vaccine in adults and children.

The reactogenicity and immunogenicity of a new influenza subunit vaccine containing essentially only hemagglutinin and neuraminidase has been studied in man. Studies in primed individuals demonstrated that the subunit vaccine induced antibody levels as high as those induced by a comparable whole virus vaccine, or a commercially available whole virus vaccine or by a split vaccine. The commercial whole virus vaccine caused systemic reactions, including fever and headache in 15% of volunteers. In contrast local and systemic reactions were significantly fewer after application of subunit vaccine. When unprimed individuals were vaccinated serological responses were, however, superior with whole virus vaccines. The subunit vaccine demonstrated good immunogenicity and a very low reactogenicity in children. Three months after vaccination, a number of the children were challenged intranasally with live attenuated influenza virus. All proved, as judged by virus isolation and antibody response to be resistant.


Serum SRH antibody level as a measure of the immunity against natural and artificial A/Victoria/3/75 infections.

A natural influenza A/Victoria/3/75 outbreak occurred in two communities where part of the residents had been vaccinated with a live recombinant vaccine strain, the RIT 4025 strain (A/Scotland/840/74 serotype). Using the single radial hemolysis technique to measure the antibody level, a relationship was established between the rate of infection and the pre-epidemic serum antibody titer. The higher the pre-epidemic antibody titer, the lower the rate of infection and illness. The protective titer 50% (PT 50) against infection was equal to 26.7 mm2. The same calculation was applied to a population of placebo recipients and RIT 4025 vaccinees challenged with a virulent A/Victoria/3/75 strain. Although the number of volunteers was much smaller, the same correlation was found for the infection detected by a significant antibody rise and for confirmed illness.


Incidence and significance of different types of connective tissue antibodies in adult and pediatric gastroenterological disorders.

The incidence of connective tissue antibodies was assessed in 3,000 adults and in 388 pediatric patients with gastroenterological disorders. Following a previous classification, connective tissue antibodies were distinguished in 5 different types, R1 and R2 reacting with reticulin components, KC with Kupffer cells, AC and Rs with intra- and extracellular mesenchymal antigens. R1 predominated in children and was observed only in patients with malabsorption; the great majority of them had celiac disease and an abnormal small bowel mucosa. Ac was rarely seen in children and occurred in several unrelated gastrointestinal diseases of the adult; its incidence, however, was significantly higher in disorders with idiopathic and secondary malabsorption. R2, KC and Rs were seen only occasionally in unrelated gastroenterological disorders without malabsorption. R1, therefore, seems to be strongly suggestive of a malabsorption syndrome with abnormal small bowel mucosa and AC is a nonspecific reaction occuring predominantly in primary and secondary malabsorption; the other connective tissue antibodies have no clinical significance in gastroenterological disorders.


Extrapancreatic glucagons.

From the mucosa of the gastrointestinal tract a number of peptides can be extracted, which are glucagon-like in their behavior towards antisera raised against the pancreatic hormone. The biochemistry and physiology of these peptides are critically reviewed. Although important advances have been made, facilitated by improved praparative and analytical techniques, many problems remain unresolved. It is, however, now well established that a peptide, which is indistinguishable from true, pancreatic glucagon (NW 3,485) is found in extrapancreatic gastrointestinal tissue from all species investigated. While abundant in dogs, especially in the gastric mucosa, much less is found in extra-pancreatic tissues of man and pig. Results from studies in dogs are therefore not necessarily relevant to other species. Human and porcine gut, however, contain other glucagon-like peptides (gut-type glucagon, enteroglucagon, gut GLI), one of which resembles true glucagon (MW 3,485) in its biological activity, but a definite physiological role for these peptides has not yet been established. The recent isolation and purification of one of the latter peptides undoubtedly will facilitate greatly future research in this field.


Possible toxic effects of normal and diabetic patient serum on pancreatic B-cells.

Serum from normal blood-donors and juvenile diabetic patients inhibited Rb+ accumulation and stimulated release of 51Cr and insulin in suspensions of dispersed pancreatic islet cells prepared from ob/ob mouse islets, which are rich in B-cells. The effects indicate the presence of a B-cytotoxic factor in human serum. Serum from mouse and fetal calf also inhibited the islet cell accumulation of Rb+. Toxicity was not suppressed by treating serum with protein A-Sepharose and did not correlate with islet cell binding of fluorescent antibodies to human immunoglobulin. Whereas all sera inhibited Rb+ accumulation, 3 of 6 diabetic patient sera, but no blood-donor serum, made the cells fluoresce on exposure to the fluorescent antibodies. Supporting a dependence on complement, toxicity remained after dialysis, but was destroyed by treating serum with zymosan-A or heating at 56 degrees for 30 min.


HI antibody response in volunteers vaccinated with live influenza A/New Jersey/76 vaccine.

Live freeze-dried influenza A/New Jersey/76 vaccine prepared from the "cold-adapted variant" of NIB-3 strain. Three groups of about 50 persons were included in a double-blind placebo-controlled field trial. One group received the vaccine with 7 log EID50/dose, the other 6 log EID50/dose and the third received placebo. One half of persons from each group were given a second dose of the corresponding preparation after two weeks. The immunogenicity of the vaccine was evaluated by the determination of HI antibody conversion rate in seronegative persons. The proportion of vacinated persons with seroconversion, regardless of the number of doses, increased with time, and 16 weeks after vaccination reached the maximum value of 0.87 in persons given vaccine with 7 log EID50 per dose and 0.55 in those given 6 log EID50/dose. In twice-vaccinated persons the proportion of seroconversion was higher regardless of the virus titre of the vaccine. The highest proportion of seroconversion (0.93) was recorded in persons vaccinated twice with 7 log EID50/dose 16 weeks after vaccination.


Attenuation of influenza A/New Jersey/76 virus strain, preparation of live vaccine and vaccine reactogenicity in volunteers.

The NIB-3 strain (a recombinant of influenza A/New Jersey/76 and X-31 strains) was further attenuated by nine egg passages at 28 degrees C for the purpose of obtaining a "cold-adapted variant" suitable for preparation of live freeze-dried vaccine with 5% peptone. The vaccine with two infectivity titres, of 7 and 6 log EID50/dose respectively, administered intranasally, was studied in a double-blind placebo-controlled field trial. The reactogenicity of the vaccine was evaluated on the basis of fever reactions during the first three days after vaccination and by the detection of local virus recovery from throat swabs taken on the first four days after vaccination. The majority of vaccines had no fever. On the first day following vaccination the proportions of persons with low-grade fever (up to 37.4 degrees C) were the same in the groups given placebo and vaccine with 6 log EID50/dose respectively. In the group vaccinated with 7 log EID50/dose there were 8% more persons with low-grade fever than in the group given placebo, but this difference was not significant (P greater than 0.05). On the second and the third day after vaccination there was no difference between the proportions of persons with low-grade fever in all the three groups. The highest number of virus isolations, i.e. 26%, was found in persons vaccinated with 7 log EID50/dose, 72 h after vaccination. In the placebo group the virus was not isolated from any person during the entire course of the study.


[A comparison between chromic catgut and polyglycolic acid sutures in episiotomy repair (author's transl)].

Polyglycolic acid sutures (Dexon) were compared to chromic catgut sutures in episiotomy repair. When polyglycolic acid sutures were used, the degree of postpartum perineal pain was approximately half as great, and the incidence of dehiscence of episiotomy was 3--5 times greater in the chromic catgut group. The cosmetic results 3 months postpartum were clearly better by using Dexon sutures, especially when the perineal skin was closed by a continuous intracutaneous suture.


[Mediolateral versus median episiotomy (author's transl)].

From 1969 to 1976, 15,715 episiotomies were done in 24,598 deliveries. The median episiotomy was progressively preferred and the technique of suture improved. The incidence of secondary sutures for dehiscence was reduced from 74 (3.4%) in 1971 to 6 (0.3%) in 1976. Extension into the rectum expectedly rose in incidence. The figures presented, show that the complication rate following mediolateral episiotomy is higher than following median episiotomy including the complication rate with extensions into the rectum.


[Diagnosis of candida albicans mycosis in gynaecology by the germ tube test (author's transl)].

Experience with the germ tube test for the diagnosis of candida mycosis in gynaecology and dermatology is reported. Candida albicans forms germ tubes in human serum and other culture media at 37 degrees C within 2 to 3 hours. If the initial culture grows yeast, the germ tube test permits the exact identification of the yeast as candida albicans within three to five hours. The specificity of the test is approximately 99%. Of 3270 samples 934 grew yeast and 742 were candida albicans by the germ tube test. 6 samples with a negative germ tube test were identified as candida albicans by the Chlamydospore test. 125 samples showed a candida species, 45 samples showed a torulopsis species and 16 tests identified a trichosporon species. This test is valuable in the routine office practice of gynaecology because of its simplicity and speed.


[Allele specificity of genetic recombination in T4 phage using the indicator crossing study method].

The diagrams of relative correction ability of eighteen rII mutants of T4 phage were constructed on the basis of two-factor crosses, which were grouped into indicator series. In each series a pair of closely linked compared markers was crossed against indicator ones, the latter being distant enough so as to avoid simultaneous correction with the compared marker. The differences between the frequencies of wild type recombinants in crosses of two compared markers with indicator ones remained constant within the series and can be used as a measure of the differences between the compared markers in their correction ability. Mutants of base substitution type have small but statistically significant differences in correction ability. Simultaneous substitution of two bases in one codon yields a mutant which shows higher correction ability when compared to the mutant obtained as a result of substitution of only one base in the same codon. Frame shift mutants show much wider range of correctibility: some of them are corrected more rarely and others more frequently than base substitution mutants are.


[Radiobiological method of studying the structure of the partially diploid area in T4 bacteriophage].

The mechanism of cross-reactivation after UV-irradiation was examined using different deletion mutants as recipients. A model of the rescue mechanism of partly diploid area was suggested. The method of cross-reactivation in demonstrated to permit an easy determination of the orientation of duplicated genes.


[Genetic study of plasmid-associated high-frequency mutations to streptomycin resistance in Escherichia coli].

Escherichia coli CTR1(RT1)RHfm1) carrying two H-factors and having unusually high frequency of mutation to high level streptomycin resistance is studied. The high frequency of mutation (about 10(-6) to streptomycin resistance is connected with the presence of R factor RHfm1, controlling the resistance to chloramphenicol and low level streptomacin resistance, but not with RT1, controlling the resistance to tetracycline. Spontaneous or ethidium bromide-induced loss of RHfm1 is accompanied by a decrease of the mutation frequency to 10(-9). RHfm1 is efficiently transmissible to other strains at 28 degrees C. The acquisition of RHfm1 by strains of E. coli K-12 ans S. typhimurium LT2 was followed by a 1000--10000-fold increase of the frequejcy of mutation to streptomycin resistance. Some streptomycin resistant mutants were isolated, and chromosome location of the mutations was demonstrated. The streptomycin resistant mutants were unable to transmit high level of resistance to streptomycin with R factor, but only low level one. The loss of RHfm1 by streptomycin resistant mutants was accompanied by the return to the streptomycin sensitivity of the initial R- strans (E. coli K-12 mutants) or by a decrease of the streptomycin resistance to the level, only 2-fold higher than that of R- wild type (E. coli CTR1 mutant). Thus, the mutantions had practically no effect on streptomycin resistance of R- strains, but could lead to high resistance phenotypes in the presence of RHfm1. The mutant loci in all three studied strains were found to be closely linked to the locus "fus" on the genetic map of E. coli.


[Competence in Escherichia coli cells. V. Interaction of the competence factor with the cells].

Some trends of the interaction of the competence factor with the cells are described on the model of phage lambda transfection. It is shown that this process depends on the composition of the recipients growth media, the temperature regime in the interaction processand on the concentration of the competence factor and the recipient cells. The preliminary treatment of the recipient by EDTA (0.0001 M), CaCl2 (less than 0.02 M), MgCl2 (less than 0.01 M), and NaCl (less than 0.01 M) resulted in the increaze of their sensitivity to subsequent treatment by the factor. Data are obtained demonstrating that after the treatment of cells by the competence factor their sensitivity to decreased CaCl2 concentration is increasing.


Assessment of drug therapy in chronic brain failure.

An 'arteriosclerosis score' has been devised in an attempt to differentiate between vascular and ideopathic chronic brain failure. The score was found to correlate closely with the ADL score, but not with MSQ score, nor with a battery of seven psychological tests. There are, however, close intercorrelations between certain psychological tests and the MSQ. This paper describes a series of tests, their correlations with each other in a group of elderly people, difficulties in their administration and the practical problems inherent in assessing drugs intended to be used in the prevention or treatment of brain failure.


Chronic laxative abuse associated with pancreatic islet cell hyperplasia.

Marked pancreatic islet cell hyperplasia was found in a patient with laxative-induced diarrhoea. It is suggested that laxative abuse might be an important aetiological factor in patients with pancreatic islet cell hyperplasia and the watery diarrhoea syndrome but in whom no hormonal excess can be demonstrated.


IgA and IgG reticulin antibodies in coeliac and non-coeliac patients.

Using indirect immunofluorescence, comparisons were made of patterns of staining of five tissue substrates with 28 RI reticulin antibody-positive coeliac sera, and 23 RI reticulin antibody-positive non-coeliac sera. IgA and IgG fluorescein conjugates were used separately. IgA antibodies were seen in 22 coeliac patients (78%) compared with three non-coeliacs (13%). Concomitant sinusoidal fluorescence (RS pattern) was seen more frequently with the non-coeliac (60.9%) than with the coeliac sera (10.7%). Such differences may help to distinguish those patients who should have a jejunal biopsy when using the reticulin antibody as a screening test for coeliac disease.


Localisation of e-antigen in nuclei of hepatocytes in HBsAg-positive liver diseases.

By the direct immunofluorescence technique 19 liver biopsies were examined for the presence of the e-antigen associated with the hepatitis B virus infection. With the use of double incubation and blocking experiments with FITC and Rhodamine labelled antisera against hepatitis B core antigen and e-antigen, evidence is presented that the e-antigen is localised in the nuclei of the hepatocytes. We conclude that the e-antigen and the core antigen are not identical, although they are often present simultaneously in the nucleus of the hepatocyte.


Can hepatic coma be caused by a reduction of brain noradrenaline or dopamine?

Intraventricular infusions of octopamine which raised brain octopamine concentrations more than 20 000-fold resulted in reductions in brain noradrenaline and dopamine by as much as 90% without affecting the alertness or activity of normal rats. As this reduction of brain catecholamines is much greater than any reported in hepatic coma, we do not believe that values observed in experimental hepatic failure have aetiological significance for the encephalopathy that ensues.


Carbenoxolone sodium capsules in the treatment of duodenal ulcer. An endoscopic controlled trial.

Eighty-six patients with duodenal ulcer were treated in a multicentre controlled trial with carbenoxolone capsules (Duogastrone, 50 mg four times a day for six weeks) or a placebo. Sixty-nine patients accepted endoscopy at the beginning and end of the treatment. Symptomatic responses and endoscopic improvement were significantly greater in those receiving the active preparation than in those receiving the control capsules, complete, endoscopically assessed, healing being achieved in 65% and 20%, respectively, of individuals having accepted endoscopy, after six weeks' treatment. Side-effects of salt and water retention or hypokalaemia were noted in over a quarter of those receiving the carbenoxolone capsules, but none of the adverse effects was severe enough to necessitate withdrawal of treatment.


Double-blind controlled trial of amylopectin sulphate (Depepsen) in the symptomatic treatment of duodenal ulcer.

In a double-blind controlled trial amylopectin sulphate (Depepsen) had no significant advantage over placebo in the symptomatic treatment of duodenal ulcer.


Portal circulation and portal hypertension.

During the last 25 years, there have been important developments in visualising the portal vein, in examining its contents, and in measuring the pressure of blood flowing within it. Radiologists have set the scene and now is the time of the scanner. These technical advances have been applied to the diagnosis and treatment of patients with portal hypertension, and many ingenious surgical techniques have been proposed. The problem of successful treatment of the patient with bleeding oesophageal varices and cirrhosis of the liver, however, has not yet been solved. This report discusses the portal vein in terms of pressure, flow, and regeneration factors. Portal hypertension is classified and methods of relief are discussed.


Results of the investigation of soil for contamination with pathogenic leptospires.

In the natural focus of leptospirosis at the lake Nero (Yaroslav region, USSR) 630 samples of soil were investigated for the presence of leptospires. Seven cultures of leptospires were isolated from the soil; five of them were pathogenic (four belonged to the serogroup Grippotyphosa and one to the serogroup Hebdomadis) and two were saprophytic. Among the cultures of pathogenic leptospires isolated from the soil there was observed the same quantitative ratio of serogroups as among cultures obtained from rodents, which suggests that the leptospires circulate from mammals to soil and vice versa.


Mesostigmatid mites of small mammals from the Hindu Kush (Afghanistan).

During the First Czechoslovak mountaineering expedition to the Hindu Kush (1965) a material of mesostigmatid mites was collected from small mammals, yielding 16 species. Due to the fact that it is the first collection of these parasites studied in Afghanistan, a zoogeographic analysis, altitudinal stratification and epidemiological estimation are appended.


Ticks of small mammals from the Hindu Kush (Afghanistan).

During the First Czechoslovak expedition to the East Hindu Kush in June-September 1965 a total of 193 hosts belonging to 12 species was examined on the presence of ticks. Specimens of the genera Ixodes, Haemaphysalis, Dermacentor and Rhipicephalus were found. Data and comments are given for the species collected.


An all-metal block for replica plating of microbial colonies.

The surface of a metal block made of an aluminium alloy is covered with narrow perpendicular grooves, which thus form an array of quadrangular pyramids touching base to base. The surface is further provided with a marker which assures the positioning of the master plate and the replica plate. Replicas prepared using this block are of higher quality than those using the velveteen-covered cylinder. A single master plate will provide ten or more replicas of good quality, the master plate being preserved for further work. Last but not least, the all-metal block can be easily cleaned and heat-sterilized.


Antimutagenic effects of caffeine during nitrosoguanidine-induced mutagenesis of Salmonella typhimurium cells and phages.

The effect of caffeine on nitrosoguanidine-induced mutagenesis of Salmonella typhimurium and its P22 and L phages was studied. The detected mutations included phage "clear" mutations, reversions of phage "amber" mutation, and prototrophic reversions of the his- auxotroph of Salmonella typhimurium. Neither the recA mutation of the host nor the erf mutation of the phage genome were found to affect the nitrosoguanidine-induced mutagenesis of the phage during vegetative growth. Beginning with a concentration of 0.2 mg/ml, caffeine decreased the frequency of mutants by 30--60%, attaining a maximum effect at 1.5 mg/ml and retaining this effect even at higher concentrations. A similar antimutagenic effect was observed with the mutagenesis of the host cells. The nitrosoguanidine-induced mutagenesis does not seem to be related to the function of the recA cell gene or the erf phage gene. The mechanism of mutagenesis by nitrosoguanidine probably has two components, one of them caffeine sensitive, the other caffeine-resistant.


Serum levels of prolactin, LH and LH-RH after ablation of the medial basal hypothalamus.

4 weeks after surgical ablation (MHA) of the medial basal hypothalamus (MBH) in adult male rats, serum levels of prolactin, LH, and LH-RH were determined by radioimmunoassay. Blood samples were obtained by jugular venipuncture under ether anesthesia (designated 'stress' samples) and 30 min after the ether stress by rapid decapitation (designated 'resting samples). 30 min after ether, serum levels of prolactin, LH, and LH-RH in MHA rats were comparable to those of intact and sham-operated controls. Among intact and sham-operated rats, ether elicited an initial increased in prolactin but not in LH or LH-RH. In the MHA group, prolactin levels were also acutely increased, although the increment was not as great as in control groups. The data indicate that considerable basal prolactin and LH secretion persists after MHA, and that this continued secretion may be regulated by neurohoromones such as LH-RH which arise from areas outside the MBH.


Endocrine studies in primary hypogonadism.

Two 15-year-old boys with primary hypogonadism had evaluation of their hypothalamic-pituitary-gonadal axis. Testicular biopsies and chromsomal studies were also performed. Both patients presented with delayed puberty and short stature and had prepubertal LH, FSH and testosterone concentrations. Serial 24-hour frequent-interval blood studies over a 2-year period in one patient (R.F.) showed a gradual progression from a normal early pubertal LH secretory pattern to one characteristic of 'primary' testicular failure. The testicular biopsies showed prepubertal tests with no significant germinal cell maturation. Although both patients had some somatic stigmata of Noonan's syndrome, they had different karyotypes (XY and xyq-). These studies show that elevated levels of LH and FSH in primary hypogonadism syndrome may not become apparent until after the onset of CNS puberty.


Yeast dipeptidase: active site mapping by kinetic studies with substrates and substrate analogs.

In order to characterize the active site of yeast dipeptidase in more detail, kinetic studies with a variety of dipeptide substrates and substrate analogs were performed. To analyze kinetic data, computer programs were developed which first calculate initial velocities from progress curves and then evaluate the kinetic parameters by nonlinear regression analysis. A free carboxyl group is a prerequisite for binding of dipeptidase substrates; its position relative to the peptide bond must not deviate from the normal L-dipeptide conformation. The spatial arrangement of the terminal ammonium ion seems to be less crucial. The enzyme's substrate specificity clearly reflects the interactions of the substrate amino acid side chains with complementary dipeptidase subsites. The domain of the enzyme in contact with the C-terminal substrate side chain seems to be an open structure of moderately hydrophobic character. In contrast, the binding site for the amino-terminal side chain is a more strongly hydrophobic "pocket" of limited dimensions. The kinetics of inhibition by free amino acids points to an ordered release of products from the enzyme.


tRNA isopentenyltransferase from Zea mays L. Characterization of the isopentenylation reaction of tRNA, oligo (A) and other nucleic acids.

The extraction and purification of the tRNA isopentenyltransferase from maize root tips and kernels are reported. The relative amounts of this enzyme in different organs of maize have been determined. Root tips have the highest enzyme activities, followed by kernels and young leaves. Old leaves exhibit very low activity. The molecular mass of the monomeric enzyme was determined to be 57000 - 63000 dalton. pH and Mg2 optima are in full agreement with the data reported for the enzymes from yeast and Escherichia coli. Spermine enhances the isopentenylation of tRNA from kernels. The "Km" values of KMnO4-treated or untreated bulk tRNA from yeast and maize root tips and kernels were in the range of 10 to 34 micrometer while the Km values of of single species like tRNASer4 from rat liver and tRNATyrKMnO4 from E. coli were 1.1 and 6.6 micrometer, respectively. The tRNA isopentenyltransferase from maize root tips and kernels catalyzes the incorporation of 2-isopentenyl groups into (Ap)3-7A, endogenous bulk oligonucleotos from maize root tips and kernels, and into poly(A), RNA from MS-2 phages and, to a very low extent, into adenosine. The Km values of (Ap)3-7 A varied in the range of 250 to 750micrometer. Although oligonucleotides have less affinity to the enzyme, the formation of i6A within oligonucleotides may occur in vivo, due to their higher concentrations in cells.


Differentiation of murine erythroleukemic (Friend) cells: an in vitro model of erythropoiesis.

Normal erythropoiesis involves differentiation of uncommitted stem cells through committed erythroid precursors into cells specialized for hemoglobin synthesis. Several aspects of this developmental sequence may be studied in murine erythroleukemic cells infected with Friend virus complex. These cells are arrested at the proerythroblast stage, yet capable of continuous growth in vitro. Maturation along an erythroid pathway is induced after treatment with a variety of agents (e.g. dimethylsulfoxide, butyric acid, hemin, ouabain). Following induction, the cells morphologically resemble normoblasts, accumulate globin mRNAs and strain-specific globins, increase heme synthesis and acquire erythrocyte membrane antigens. Cloned populations of erythroleukemic cells mature in a nonhomogeneous fashion upon induction, indicative of a stochastic response in the inductive process. This "probability of differentiation" phenotype is formally analogous to stem cell development in which hematopoietic precursor cells form a constant, dividing population from which cells are continuously maturing. Although the sequence of events involved in triggering differentiation is uncertain, cloning and cell hybridization experiments demonstrate that this phenotype is under rather stable genetic (or epigenetic) control. Recent molecular analysis shows that induced differentiation is accompanied by transcriptional activation of the globin genes rather than posttranscriptional stabilization of the globin RNAs. Further application of cellular, molecular and genetic approaches in this system may help to define specific control mechanisms in erythroid development.


Regulation of differentiation in normal and transformed erythroid cells.

Studies are described employing two erythropoietic systems to elucidate regulatory mechanisms that control both normal erythropoiesis and erythroid differentiation of transformed hemopoietic precursors. Evidence is provided suggesting that normal erythroid cell precursors require erythropoietin as a growth factor that regulates the number of precursors capable of differentiating. Murine erythroleukemia cells proliferate without need of erythropoietin; they show a variable, generally low, rate of spontaneous differentiation and a brisk rate of erythropoiesis in response to a variety of chemical agents. Present studies suggest that these chemical inducers initiate a series of events including cell surface related changes, alterations in cell cycle kinetics, and modifications of chromatin and DNA structure which result in the irreversible commitment of these leukemia cells to erythroid differentiation and the synthesis of red-cell-specific products.


Protection against syngeneic tumor grafts induced by inoculation with normal allogeneic tissues.

Subcutaneous injection of normal allogeneic kidney and liver tissues extended survival of DBA/2Cr mice challenged with a lethal dose of syngeneic L5178Y lymphoma cells. Immunization with a combination of tissues from five strains provided far more protection than immunization with tissue from any single strain. It is suggested that the basis of this protective effect is a cross-reactivity or identity between tumor-associated transplantation antigens (TATA) on the L5178Y tumor and non-H-2 alloantigens normally expressed by some allogeneic tissues.


Tumor inhibition by effector cells cultured from progressing sarcomas.

The effect of cytotoxic lymphoid cells emerging in primary cultures of an antigenic sarcoma of strain 13 guinea pigs was investigated on tumor growth in vivo. The growth of lethal tumor inocula was inhibited or the tumor cells were completely rejected in normal syngeneic recipients treated s.c. with low doses (5 X 10(5)) of effector cells which were mixed with the tumor cells. A higher dose (2.5 X 10(6)) of killer cells did not affect significantly tumor growth in normal recipients. Significant tumor inhibition was observed in X-irradiated recipients given high doses (2.2 X 10(6)) of effector cells locally although rejection did not occur with high frequency. Local treatment of X-irradiated recipients with low doses (5 X 10(5)) of effector cells did not influence tumor growth. Systemic treatment of normal or X-irradiated recipients with effector cells had little effect at any dose, although tumor inocula were occasionally rejected. Sonication of the cytotoxic effector cells prior to administration inhibited their tumor suppressing effect. Animals that rejected the first tumor inoculum were immune to a second lethal dose of sarcoma cells. It is indicated by the results that tumor rejection in vivo is not simply a matter of killer-target cell interaction, but rather a complex and poorly understood phenomenon.


Isolation and partial characterization of an antibody enhancing factor from leukaemic owl monkey cell cultures.

Herpesvirus saimiri inoculated into owl monkeys (Aotus trivirgatus) causes leukaemia and lymphoma. Peripheral lymphocytes from leukaemic monkeys grown in culture are predominantly T lymphocytes. The supernatants from these cultures  contain a factor which enhances the antibody response of murine B cells to sheep red blood cells (SRBC). The factor has been partially characterized by ammonium sulphate precipitation, DEAE-chromatography, gel filtration over Sephadex G-150 and disc-gel electrophoresis. The enhancing factor is a protein with a molecular weight of approximately 40,000.


The immunological response of CBA mice to P. yoelii. II. The passive transfer of immunity with serum and cells.

CBA mice infected with the malaria parasite Plasmodium berghei yoelii (P. yoelii) develop a self-resolving infection lasting 15-18 days; on recovery from a primary infection they are immune to further infection. Cell and serum transfers from immune to non-immune mice were used to analyse the mechanism of resistance. Whereas serum from mice which had recovered from a single infection was ineffective in transferring immunity, hyperimmune serum (from mice repeatedly challenged with P. yoelii) protected against challenge inocula of 10(4) and 5 X 10(4) but was ineffective against higher inocula (10(5)). Doses of serum which completely protected intact mice were ineffective when administered to T-cell deprived recipients. The injection of spleen cells from recovered mice conferred immunity on both normal and T cell deprived mice. Pretreatment of immune cell donors with cyclophosphamide reduce the ability of spleen cells to transfer immunity. Treatment of the immune cells with an anti-Thy 1 antiserum and complement in vitro did not abrogate their protective effect. The significance of these results is discussed in relation to the effector mechanisms which might operate in murine malaria.


Further studies of the adjuvant properties of homologous IgG split products: mode of action of F(ab')2 and related fragments.

Peptic bivalent and monovalent Fab' fragments as well as F(ab')2 fragment from a purified rabbit anti-DNP antibody were equally effective in enhancement of the immune response to SRBC. In contrast, the papain Fab fragment of normal IgG possessed a considerably lower enhancing activity. These data indicate that the effector site(s) controlling the adjuvant activity of F(ab')2 and related fragments is structurally distinct from the antibody active site(s) within the fragment molecule, and is located in C-terminal region of the heavy chain Fd fragment. When F(ab')2 fragment was injected into rabbits together with the proteinase inhibitor Trasylol it failed to enhance the immune response to SRBC. Furthermore, Trasylol interferes with the ability of F(ab')2 or Fab' fragment to activate the complement system both in vivo and in vitro. This, together with the observation that F(ab')2 fragments enhance the response to T-dependent antigens (SRBC and bovine gamma globulin) but fail to augment the response to LPS, suggests that these fragments may operate via activation of complement and thereby influence indirectly the reactivity of complement receptor B cells.


Suppression of primary immune response by heterologous anti-lymphocyte sera.

The effect of anti-lymphocyte serum (ALS) on the primary immune response to sheep erythrocytes (SRBC) in rats was studied by the Jerne Plaque technique. ALS against normal rat lymph node cells, ALS(N) suppressed the immune response to SRBC when administered before the antigen and had no effect on the immune response when administered either with or after the antigen. ALS(I), which was produced against lymph node cells from SRBC immunized rats, produced significant immunosuppression when administered either before or after the antigen.


Differential tolerance of thymus-independent and thymus-dependent antibody responses.

The effect of pre-immunization with soluble haptenated serum proteins or haptenated carbohydrates on the subsequent responses to the hapten in thymus-dependent or thymus-independent form was investigated. In certain cases both thymus-dependent and -independent responses were suppressed whilst in others a differential suppression of thymus-independent responsiveness was observed. These results are discussed in terms of B-cell subpopulations and mechanisms of tolerance induction.


Relationship between bactericidal action of complement and fluidity of cellular membranes.

The mode of complement-mediated killing of Escherichia coli B cells grown at 25 and 42 degrees C and of E. coli K-12 UFAts cells grown in the presence of oleic and elaidic aicds was examined in relation to their membrane lipid compositions and the thermodynamic properties of membrane phospholipids. Phospholipids isolated from 25 degrees C-grown cells of strain B and from oleic acid-incorporated cells of strain K-12 UFAts had lower phase transition temperatures than did phospholipids from E. coli strain B grown at 42 degrees C or those from strain K-12 UFAts grown on elaidic acid. The rate of cellular susceptibility to complement action closely correlated with the liquid crystalline phase of phospholipids of cell membranes. These findings suggest that membrane fluidity is obligatory for the final expression of complement action.


Demonstration of the role of cytophilic antibody in resistance to malaria parasites (Plasmodium berghei) in rats.

This paper reports the results of a study of the nature of the immune response against Plasmodium berghei parasites by inbred rats. A macrophage-cytophilic antibody specific for malarial antigens was identified and characterized. Detection of the antibody on the macrophage surface was accomplished by the parasite adherence tests and by the indirect fluorescent antibody technique. Isolation and purification of the macrophage-cytophilic and opsonic antibodies from hyperimmune rat serum was accomplished by QAE-Sephadez A-50 elution chromatography, and of the macrophage-cytophilic antibody by adsorption with and elution from syngeneic macrophages as well. Characterization of the cytophilic antibody as immunoglobulin G1 was done by immunoelectrophoresis and by Ouchterlony-type double diffusion in gel. Passive protection tests in weanling inbred rats have demonstrated that the opsonizing antibody conferred some protection against P. berghei. The macrophage-cytophilic antibody, on the other hand, was not protective alone but acted synergistically with the opsonizing antibody.


Effect of L1210 leukemia on the susceptibility of mice to Candida albicans infections.

This study was carried out to determine whether animals bearing L1210 leukemia were more susceptible to candida infection in the absence of immunosuppression and to determine also if the L1210 cells suppressed the inflammatory response of the animal host. Systemic infection was studied by intravenous injection of Candida albicans and checking for the number of candida organisms cultured from the blood and the kidneys. Localized infection was studied by intramuscular injection of C. albicans into the thighs and measuring the changes in the thigh size. Compared with tumor-free controls, the intravenous injection resulted in higher counts of C. albicans from the blood and the kidneys of tumor-bearing animals. No significant difference in the localized swelling was noted between tumor- and nontumor-bearing mice with respect to intramuscular injection of C. albicans. The results thus indicate that L1210 leukemia increases susceptibility of tumor-bearing animals to systemic candida infection. L1210 cells were shown to reduce the accumulation of neutrophils and to suppress the inflammatory reaction elicited by C. albicans.


Secretion of antimycobacterial fatty acids by normal and activated macrophages.

Cellular resistance to facultative intracellular parasites has been studied by determining the antimycobacterial activity and the amount of fatty acids in sera and in heptane extracts of freshly collected and 24-h-cultured normal and activated guinea pig alveolar macrophages and liver cells. The quantity and the antimycobacterial activity of extractable fatty acids were determined by gas chromatography and the agar plate diffusion test, respectively. These determinations showed that heptane extracts of activated cells inhibited the growth of BCG much more effectively than fractions prepared from normal cells; chromatographic analyses showed that extracts of activated cells contained six times more C(16) and C(18) long-chain fatty acids than did fractions of normal cells. Heptane extracts of 24-h-cultured cells and of their media showed that during incubation normal and activated cells release fatty acids into the culture media without apparent cell injury; in all experiments liver cells produced larger amounts of fatty acids than alveolar macrophages. Sera collected from activated guinea pigs inhibited the growth of BCG and contained two to five times more total fatty acids than did the growth-supporting normal serum. That bactericidal fatty acids are excreted into the tissue culture medium of incubated cells or into the blood of immunologically stimulated animals suggests that macrophages can exert antibacterial effects without phagocytosis.


Effect on particle size of solubilization of wild-type and Re chemotype lipopolysaccharides solubilized with bovine serum albumin and triethylamine.

Disaggregation of wild-type and Re chemotype lipopolysaccharides (LPS) has been accomplished by solubilization with triethylamine followed by stabilization with bovine serum albumin in order to determine the degree of aggregation. Solubilization with 1.5% triethylamine was found to be more effective than with lower concentrations, as judged by permeation chromatography. Chromatographic analysis of triethylamine-bovine serum albumin-disaggregated LPS showed a range of particle sizes. Wild-type LPS yielded size classes of 1 X 10(6) to 4 X 10(6) daltons, 250,000 daltons, and 20,000 daltons. Re LPS yielded size classes of 1 X 10(6) to 4 X 10(6) daltons and 20,000 daltons. Untreated LPS was always greater than 4 X 10(6) daltons. Chemical characterization of the size classes revealed 3-keto-2-deoxyoctonate in all size classes and suggests that the O-antigenic side chain length may determine the aggregate size in solubilized LPS.


Role of bacterial products in periodontitis: immune response in gnotobiotic rats monoinfected with Eikenella corrodens.

The development of humoral and cell-mediated immune responses to Eikenella corrodens (a bacterium that causes periodontal lesions in gnotobiotic rats) was measured and compared with the rate of appearance of macroscopic lesions. A possible inverse relationship was found. A strong cell-mediated immune response, as measured by skin reactivity and lymphocyte mitogenesis, occurred between 4 and 6 weeks after infection and subsided soon thereafter to a low response level. Humoral antibodies to endotoxin from E. corrodens could not be detected at any time. The disease developed only after the cell-mediated immune response diminished, thus suggesting that lack of an efficient immune response may permit the development of the disease. This is seemingly in contradiction to the assumption that tissue destruction in such cases is caused by the immune response and its products. We are inclined to believe, based on our findings reported here, that the lack of immune responsiveness to the bacterium and/or its products is the major causative factor in the development of periodontitis. At the same time, we wish to emphasize that occurrence of both phenomena during the long development of periodontal disease is possible.


O antigen as virulence factor in mouse typhoid: effect of B-cell suppression.

Immunosuppression by cyclophosphamide was used to make mice incapable of B-lymphocyte responses; they could not make an antibody response to NIP-Ficoll. These mice, as well as untreated mice, were challenged intraperitoneally with graded doses of isogenic O-4,12 or O-6,7 Salmonella typhimurium derivatives. The 50% lethal dose of the O-6,7 strains was 35- to 70-fold higher than that of the O-4,12 strains, both in the normal and the immunosuppressed animals, although the latter were approximately 1,000-fold more susceptible to the infection by either challenge organism. We conclude that the O-antigen-dependent difference in the mouse virulence of these sister strains is not mediated through differences in their capacity to evoke B-lymphocyte-mediated immune responses.


Detection of heat-labile enterotoxin-like activity in stools of patients with cholera and Escherichia coli diarrhea.

The Y1 adrenal cell tissue culture assay was used to detect heat-labile enterotoxin-like activity in the stools of 14 of 74 patients with diarrhea. A positive effect of the stool on the adrenal cells was heat-labile and neutralized by cholera antitoxin. Enterotoxin-like activity was detected in the stools of 10 of 30 patients with cholera and in those of 2 of 4 from whom heat-labile Escherichia coli were isolated. None of the stools from nine individuals with Vibrio parahaemolyticus, Salmonella, or Shigella infections were positive. Two of 31 individuals from whom no pathogens were isolated had detectable toxin-like activity in their stools. The Y1 adrenal cell assay provides a rapid method of diagnosing heat-labile enterotoxigenic diarrhea and could be an adjunct in epidemiological studies of gastroenteritis.


Alteration of clearance function by group A streptococcal pyrogenic exotoxin and its relation to suppression of the antibody response.

The effect of purified group A streptococcal pyrogenic exotoxin (SPE) type A on the processing of and antibody response to sheep erythrocytes (SRBC) was studied in BALB/cWat mice. The rate of clearance of 51Cr-labeled SRBC from the bloodstream was decreased 3 or 24 h following a single intravenous injection of 1 or 10 microgram of SPE. Delayed uptake of label was observed in both the livers and spleens of SPE-treated mice, suggesting an inhibitory effect of the toxin on phagocytic cells of the reticuloendothelial system. Three daily intravenous injections of 0.1 or 1 microgram of purified SPE type A suppressed the early immunoglobulin response to SRBC. The role of altered macrophage function in producing the immunosuppression was tested in macrophage transfer experiments. SPE treatment suppressed the antibody response to SRBC transferred by normal macrophages, indicating that the immunosuppressive effect of the toxin was not due solely to altered antigen processing by macrophages.


Mitogenic activity of bacterial lipopolysaccharides in vivo: morphological and functinal characterization of responding cells.

The in vivo effect of bacterial lipopolysaccharides (LPS) on mouse spleen cell subpopulations was investigated. Intravenous administration of LPS resulted in marked enlargement of the spleen, accompanied by increased cellular proliferation and enhanced nucleated cell recoveries. At least two morphologically distinct cell types appeared to be targets for LPS. Polymorphonuclear leukocytes accumulated rapidly with a relatively minor degree of cell division. In contrast, a substantial proportion of splenic lymphocytes transformed into large lymphocytes and blast cells which actively incorporated [3H]thymidine. Proliferating cells were identified as bone marrow-derived (B) lymphocytes by their ability to form C3-dependent rosettes and to synthesize immunoglobulin. These cellular responses were not antigenically induced, since LPS derived from mutants lacking the polysaccharide moiety gave similar results. Thus, splenic B lymphocytes appear to interact and respond to LPS in vivo in the same manner as observed in vitro. These data suggest that the capacity of LPS to directly activate B lymphocytes, initiate cellular proliferation, and induce immunoglobulin production by bone marrow-derived cells in vivo may contribute to its adjuvant activity.


Elicitation of endotoxemic  effects in C3H/HeJ mice with glucocorticoid antagonizing factor and partial characterization of the factor.

C3H/HeJ mice were used to study the origin  and nature of endotoxin-induced glucocorticoid antagonizing factor (GAF). In conventional mice GAF is believed to be responsible for a variety of effects that occur as a result of an injection of endotoxin, including the inhibition of hormonal induction of hepatic phosphoenolpyruvate carboxykinase and of glyconeogenesis. Responses in such animals are seen whether the endotoxin is extracted with phenol-water or with trichloroacetic acid. C3H/HeJ mice do not respond (or produce GAF?) after an intravenous injection of phenol-water lipopolysaccharide, but they react normally (produce GAF?) when given a trichloroacetic acid preparation. They also behave the same as conventional animals when injected with serum from poisoned normal mice, especially when the reticuloendothelial system of the donors has been activated by prior injections of Zymosan or heat-killed tubercle bacilli. The C3H/HeJ mice have been used, therefore, as assay animals to establish that peak levels of GAF appear in donor serum about 2 h after an injection of lipopolysaccharide, and it is produced intraperitoneally in C3H/HeJ mice given a mixture of endotoxin and peritoneal exudate cells derived from responder mice. GAF elutes from Sephadex G-200 along with markers of known molecular weight in the region of 100,000 to 200,000. It is inactivated by trypsin and by heating at 75 degrees C for 1 h.


Microfluorometric analysis of anti-complement and indirect immunofluorescence tests for human papovavirus (JCV and BKV) T antigens.

The anti-complement immunofluorescence (ACIF) test was compared with the conventionally used indirect IF (IIF) in regard to its usefulness for the detection of low amounts of human papovavirus tumor (T) antigen. Fluorescence microscopic analysis revealed that it is significantly more sensitive. Microfluorometric measurements on the intensity of staining of T-antigen-positive nuclei demonstrated that JCV T in HJC-15 cells was 35-fold and BKV T in BK-L3 cells 94-fold more intensively stained in the ACIF then in the IIF. It appears that the lower the actual amount of a given antigen the more valuable is the ACIF test.


Human natural cytotoxicity in the blood and lymphoid organs of healthy donors and patients with malignant disease.

Natural cytotoxicity against CLA-4 and D6 target cells was determined in the peripheral blood of healthy donors and women with mammary carcinoma (localized to the breast and axilla), and in human normal and regional tumour lymph nodes. The NK cell activity in the blood of women with clinically localized mammary carcinoma showed a wide range of reactivities but was similar to the pattern detected in healthy controls. The NK cell activity in human normal lymph nodes also showed a wide range and was the same irrespective of the anatomical site of origin of the lymph node. Lymph nodes draining a variety of solid tumours had a similar spectrum of NK cell activity, there being no obvious correlation between the level of NK cell activity and such parameters as size and histological type of tumour, hyperplasia or metastatic spread in the regional node. Trypsin treatment of lymphocyte suspensions from the various lymphoid compartments suggested that the cell responsible for natural cytotoxicity in blood was probably different from the NK cell in tonsil and lymph nodes.


Isolation of a sulfated glycopeptidic antigen from human gastric tumors: its localization in normal and cancerous gastrointestinal tissues.

A sulfated glycopeptidic antigen (SGA) was purified from papain-digested cancerous human gastric mucosa. The amino acid composition of this antigen was characterized by a high percentage of threonine and proline. Serine was present in small quantities and aromatic amino acids were absent. The amount of sulfate present was evaluated at 7.5%. Fucose, galactose, N-acetyl glucosamine, N-acetyl galactosamine and sialic acid were found to be present in the molar ratio 1:4.6:3.0:6.2:5.0. With immunofluorescence techniques, a rabbit antiserum against the sulfated glycopeptide stained adult gastric mucosa when this tissue had intestinal metaplasia and stained the goblet cells of the intestinal tract (small and large intestines). About 50% of colonic carcinomas and some gastric carcinomas contained SGA. This sulfated antigen was present in well-differentiated tumors and there was a good correlation between tumoral acid mucous secretory activity and the SGA positivity.


The effect of the electron affinic sensitizers Ro 07-0582 and Ro 03-6156 on the survival of several E. coli mutants.

Concentration versus radiosensitizing effect curves have been determined for four E. coli strains with two nitroaromatic sensitizers. The data are consistent with a simple competition kinetic model of sensitization, and K values for Ro 07-0582 are reported. An empirical relationship, DMF=alpha o.e.r., relating the dose-modifying factor produced by a given concentration of sensitizer to the oxygen-enhancement ratio of a bacterium was found to hold for all the mutants tested for values of alpha greater than 1/o.e.r. The limiting value of alpha at high concentrations of sensitizer was 0.75. Some implications of this relationship and the limiting value of alpha are discussed.


[Penfluridol. Results of a year-long clinical trial].

During an open clinical trial, 51 schizophrenic patients were treated with Penfluirdol, 34 for 1 year and 17 for a shorter time. The mean dosage of Penfluirdol was 22 up to 28 mg per week. Assessments were made on days 0, 14, 28, 56, 90, 180, 270, and 365 using the AMP system and the EPRS scale of Simpson and Angus. The symptomatology was mainly reduced during the first 3 months of treatment and remained afterwards relative unchanged. Penfluridol showed a good antipsychotic effect on productive schizophrenic symptoms (thought disorders and paranoid symptoms, autism and schizophrenic affective disorders). The dosage used showed only a slight sedative effect and was well tolerated concerning autonomic and extrapyramidal side-effects.


A review of nicotinic acid, N-methylated indoleamines and schizophrenia.

The hypothesis that endogenously formed, N-methylated metabolites of indoleamines may play a role in the pathogenesis of schizophrenia was reviewed. Although N-methylated indoleamines can be produced in vivo and have significant psychotomimetic effects, there is little evidence for a specific increase in the methylation of indoleamines in schizophrenic patients. It was noted that even if the relationship between schizophrenia and N-methylated indoleamines had existed, nicotinic acid would not be an appropriate therapeutic agent.


Double-blind trial of thiothixene and chlorpromazine in acute schizophrenia.

In a double-blind trial of chlorpromazine and thiothixene conducted with 79 acutely ill, newly hospitalized schizophrenic patients, chlorpromazine and thiothixene were shown to be equally effective in producing meaningful symptomatic improvment over an average period of approximately 3 weeks, as measured by Global Assessments (CGI), BPRS, and NOSIE.


Differences in effect between nomifensine and nortriptyline.

A double-blind study comparing the effects of nomifensine and nortriptyline, which was carried out exclusively on outpatients with retarded depressions, showed nomifensine to have a distinctive antidepressive and activating effect. 40 patients (17 male and 23 female) with either endogenous, endogenous/psychogenic or psychogenic depression were divided into two treatment groups (20 patients to each group). During the 21-day study, all patients were given three 50 mg capsules of nomifensine or nortriptyline per day. With the aid of a depression scale, a significant improvement in the psychic symptoms was noted both in the nomifensine and the nortriptyline group. There was no evidence of a significant difference in the two drugs. The data obtained from the dropouts suggest that nomifensine had a better effect. From the results of the study, it can be concluded that nomifensine is suitable for the treatment of patients with retarded depressions.


Host response to allogeneic implants in the anterior chamber of the rat eye.

The anterior chamber of the eye has long been considered an immunologically privileged site, but the nature of this privilege has been re-examined recently. In our study, we used rats with defined genetic differences as the donors and the recipients. Implants were from split-ear sections, and the host response was measured both in vivo, by implant survival time, and in vitro, by the mixed-leukocyte reaction and the 51Cr-release cytotoxicity assay. Controls consisted of syngeneic implants and allogeneic orthotopic skin grafts. This study has shown that (1) host sensitization occurs approximately 7 days after implantation, (2) cytotoxic effector cells are produced by day 14, with a peak on day 21, (3) implant survival time is long in spite of the presence of competent effector cells, and (4) the survival time of implants is directly related to the degree of genetic histoincompatibility. The reasons for the long implant survival in hosts with a demonstrable immune reactivity has not been established, but the survival time appears to be related to the route of sensitization (vascular rather than lymphatic), which lends itself to the production of serum blocking factors and the procurement of supressor T cells.


M-K medium and postmortem cytologic damage.

Freshly enucleated rabbit eyes were refrigerated at +4 degrees C under standard eye bank conditions for 2, 6, 9, and 21 days. One group of corneas with a scleral rim were excised and placed in M-K medium, stored for 18, 24, or 48 hr at +4 degrees C; they were then removed, and endothelial cell viability was evaluated with nitroblue tetrazolium. The cells were examined by light microscopy and scanning and transmission electron microscopy. A second group of corneas were similarly obtained and then used as donor corneas from 6 mm transplants. Each recipient rabbit was evaluated daily by slit-lamp biomicroscopy and corneal pachometry. Fourteen days postoperatively, the rabbits were sacrificed, the eyes enucleated, and the excised corneas were evaluated in a fashion similar to those of group 1. M-K medium storage protected the morphology and functional integrity of the rabbit corneal endothelium up to 48 hr beyond moist chamber storage for 2, 6, and 9 days. However, M-K medium appeared to have no such effect on corneas that had been moist chamber--stored for 21 days. These results suggest that some human corneas with a prolonged time from death to moist chamber storage may be utilized for corneal transplantation after further storage in M-K medium.


Collagen polymorphism in mature rabbit cornea.

Sequential extraction of mature rabbit corneal stroma with NaCl-Tris buffer and acetic acid solubilized only 12% of the total corneal collagen. Pepsin (E:S 1:10,4 degrees C, 48 hr) in 0.4 M acetic acid solubilized 91% to 95% of the total collagen in the residue. Approximately 68% of the solubilized material could be precipitated at 2.5M NaCl and a further 3% to 9% at 3.5M NaCl. The collagenous material precipitating at 2.5M NaCl contained alpha, beta, gamma, and some higher molecular weight components and had a CNBr profile similar to bovine type I skin collagen. It had an hydroxylysine/lysine (OHLys/Lys) ratio of 0.43, similar to that of skin collagen, but unlike skin collagen was 52% glycosyled. Although the 3.5M NaCl precipitate had a CNBr peptide profile similar to that of type I collagen, it contained two additional collagen chains of molecular weight approximately 140,000 and 100,000 daltons, had an OHLys/Lys ratio of 0.62, and was 66% glycosylated. Individual chains were separated from the collagen precipitates by gel electrophoresis,and the additional collagen chains were shown to be carbohydrate rich. These additional collagen chains may be derived from one or more molecular species which are physiologically important in the maintenance of the unique organization of corneal collagen.


A reconsideration of visual evoked potentials for fast automated ophthalmic refractions.

Visual evoked potentials (VEP's) recorded from the scalp are sensitive to retinal image sharpness and thus to changes in the refractive state of the eye. Initially the responses to checkerboard flash or reversal stimuli were computer-averaged in order to raise the signal above the noise, primarily the electroencephalogram (EEG). Recently analogue Fourier signal analysis has been proposed for using the VEP for rapid clinical refraction. We have confirmed that this method can measure the spherical refractive state to within +/- 0.50D. However, because of large slow-wave fluctuations, measurements of changes within +/- 1.00D are not always clear. Despite its promise the method does not appear to be clinically useful at present.


The influence of N-[4-(5-nitro-2-Furyl)-2-thiazolyl]formamide and phenacetin on the immune status in male Fischer rats.

The effect of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANTF) and phenacetin on the immune status of Fischer rats was determined utilizing the spleen plaque and phytohemagglutinin blastogenesis assays 6, 10, and 15 weeks after administration at doses of 0.2 per cent and 0.535 per cent, respectively. Azathioprine (0.02 per cent of the diet) was tested as a known immunosuppressive chemical for comparison, and a negative control group, fed a control diet without added chemicals, was also tested. Immunosuppression was shown in the rats receiving azathioprine at all times by both assays, whereas in FANFT-fed rats immunosuppression was greater than in the control group (not statistically significant). Results from rats fed phenacetin were not significantly different than those of the control group. These results show that immunosuppression does not occur in rats administered phenacetin for up to 15 weeks, nor in FANFT-induced bladder carcinogenesis at the time of reversible bladder mucosal hyperplasia (6 weeks), or when the mucosal lesions have become irreversible, non-invasive carcinomas (10 and 15 weeks).


[Antibody monstration in blastomyces infections].

The evidence of humoral antibodies against yeasts can be a valuable help in the diagnosis of such infections. It is however necessary to use several sensitive methods, which complete one another in the detection of the different immunoglobulins. In the interpretation of the results the titer dynamic is decisive, especially in those patients whose antibody answer is suppressed by their disease and/or their therapeutic treatment. In most of the yeast infections Candida albicans can be used as antigen for the detection of antibodies because there is a strong relationship between the antigens of most of the yeasts important in human infections. C. krusei, C. pseudotropicalis and C. guilliermondii do not display enough common antigens to make a diagnosis against these yeasts possible with C. albicans. In that case homologous antigens have to be used. Cross reactions with other microorganisms are less frequent than usually supposed. Therefore so called false positive Candida titers have to be examined very carefully by clinical signs and culture methods.


[Reconstruction of injured veins under the ligament].

The difficulties met, when reconstructing an injured v. femoralis communis, are greater than those of other veinous segments of the leg. This is due to the fact that the vein, being disconnected from its natural braces, is compressed by the inguinal ligament. In order to overcome this elective difficulty, a modification of the ring of Kunlin, especially thought out for this part of the body and clinically tested, is presented.


[Quality of life and the subjective well-being after successful kidney transplantations].

The quality of life following kidney transplantation is examined. For this reason a total of 38 patients were questioned. There were three subgroups: 18 adults and 10 children with excellent kidney function and 10 patients in whom nephrectomy had to be performed after rejection of the transplanted organ. The extent and importance of the changes of various criteria considered essential for judgement of the quality of life are illustrated. Adults and children alike consider the improvement of drinking and eating habits, improvement of physical fitness and of the capability to deal with psychological problems as the essence of their greater joy in life. For children there are added advantages at school and in the choice of their occupational activity. In conclusion there is a definite improvement of the quality of life following renal transplantation.


[Experiences of tangential excision of burned hands].

Tangential excision and immediate grafting of deep burns of the hands enable wound closure within 14 days. Mobility of the hand is rapidly restored, pain is practically omitted, scar formation is minimized, and sensitivity is restored to normal in the majority of cases. Considering only surviving patients accounting for a total of 247 hand (hospitalisation from January 1974 to June 1977), we tangentially excised 118 hands. Two thirds of the tangential excisions needed no more corrections. One third had corrections of interdigital webs, dermabrasion of graft margins, excision of scars, or correction of contractions mainly of the fifth finger. On questioning, half of the patients admitted increased vulnerability of the transplanted skin but were not impeded by this. Work incapacity in those cases in which the hands determined the uptake of manual labour was only 5 weeks.


[Groin flap plastic surgery using McGregor's method].

The specific advantages of the groin flap to the other axial pattern flaps from the trunk are outlined, followed by a detailed description of the operative procedure and the postoperative management. Based on our experience, the groin flap is an uncritical flap and can be recommended in numerous instances either of primary repair or secondary reconstruction of the injured hand.


Haemoglobin--a frustrated oxidase? Implications for red cell metabolism.

The haem proteins can be considered, in one aspect of their function, as machines for activating oxygen. In the case of oxygen-carriers such as haemoglobin, the globin has evolved so that its conformation limits access to the haem group, with resultant reversible release of oxygen. However, distortion of the globin may allow either the discharge of oxygen as the activated product superoxide or, more threateningly, allow direct function of the haemoglobin as an oxidative enzyme. Support for this is shown by the reaction with acetylphenylhydrazine where haemoglobin functions as both an oxidase and oxygenase. An implication of oxidase activity is the potential to initiate free radical formation particularly with unsaturated lipids. Observations of the acetylphenylhydrazine reaction emphasize the role of glutathione as a free radical scavenger.


Adrenergic innervation of the human gall bladder.

Adrenergic innervation of the human gall bladder was studied using two specific fluorescence histochemical methods. Blue-green fluorescing varicose nerves were scarce and mostly followed the course of blood vessels as typical perivascular plexuses. However, some adrenergic nerves not associated with the vessels were occasionally seen, as well as structures suggestive of a pericellular arrangement of varicose adrenergic nerve terminals on non-fluorescing ganglion cells. A few enterochromaffin cells were seen in the epithelial lining, also in the deep invaginations obviously representing the Aschoff-Rokitansky sinuses. Occasionally, small rounded cells with a rounded, relatively large nucleus, and exhibiting a weak yellow-green to blue-green granular cytoplasmic fluorescence, were observed in the wall of the gall bladder. The possible functional and evolutionary significance of these neural and endocrine elements was discussed against the data on physiological and pharmacological studies obtained from the literature. It was concluded that their significance is, in all probability, secondary to the influence of the intestinal polypeptide hormones, vagal innervation and circulating catecholamines upon the normal function of the gall bladder. The glyoxylic acid-induced fluorescence histochemical method was found to be superior to the conventional formaldehyde technique in studies on human tissue.


Change with age of Feulgen-DNA values in the blood-sucking insect, Triatoma infestans Klug.

Feulgen-DNA values were evaluated cytophotometrically in the Malpighian tubes of T. infestans at the nymphal, adult and ageing life periods. In all cases the total nuclear Feulgen-DNA contents were found to be distributed within the 32C and 64C classes. However, part of the Feulgen-DNA values is shifted to lower intervals in ageing insects, as compared with nymphal and adult individuals, promoted by decrease in Feulgen-DNA values of the euchromatins. Changed response to Feulgen reaction due to some aging-induced alteration in DNP complexes, and/or breaks and loss of DNA in the euchromatins, as part of the senescence process, are ascribed to be responsible for such phenomenon.


[The development of the vertebrate skull (author's transl)].

The greater metabolic demands for oxygen in warm-blooded animals led to the separation of the upper respiratory tract from the digestive during development and the evolution of a "respiratory skull." The sphenoid sinus originated from the posterior divisions of the nasal cavity, and adapted itself functionally to the other pneumatic cavities. The latter represent inversions of the main nasal cavity and are found only in mammals. The "respiratory skull" is considered to be not only a clinical nosologic entity but also a development step of vertebrate skull formation.


Effect of positive end-expiratory pressure on intracranial pressure in dogs.

Application of positive end-expiratory pressure to dogs with noncardiogenic pulmonary edema increased intracranial pressure (measured as cerebrospinal fluid pressure) and decreased cerebral perfusion pressure. The magnitude of these changes depended on the amount of end-expiratory pressure applied and the lung compliance.


Mastitis and other diseases of the goat's udder.

Udder problems of modern dairy goats are similar to those seen in dairy cows. Anomalies of the goat's udder and teats are common, and many may be hereditary. Skin diseases of the udder include viral infections, mange, sunburn, wounds, and staphylococcal dermatitis. There are numerous known causes of caprine mastitis. These include streptococci, hemolytic and nonhemolytic staphylococci, corynebacteria, and mycoplasmas. Diagnosis of mastitis in goats is often difficult, as the udder secretion may remain grossly normal and somatic cell counts in nonmastitic goats are higher than the recognized normal range for cows. The importance of nonhemolytic staphylococcal cultures remains uncertain. Nonhemolytic staphylococci were isolated at the New York State Mastitis Laboratory from 30% of normal halves and from 22% of halves of udders from goats with assorted clinical problems. Treatment and prophylaxis of caprine mastitis closely parallel the standard technique recommended for bovine mastitis.


The response of gut-associated lymphoid tissue in gnotobiotic piglets to the presence of bacterial antigen in the alimentary tract.

The cellular changes in the ileum and duodenum and in the mesenteric and prefemoral lymph nodes of gnotobiotic piglets were observed following feeding with a live culture of a non-pathogenic E. coli. There was a rapid and intense reaction in the lower ileum, and follicles were formed; germinal centres were formed in the mesenteric lymph node after a short delay. Germinal centres were not seen in the prefemoral lymph node, though there were pyroninophilic cells in the cortex of this node. Plasma cells were not detected in the medulla of either the mesenteric or the prefemoral lymph nodes, but pyroninophilic cells and plasma cells were found in the lamina propria of the duodenum from 7 days after infection oneards. These observations demonstrate the requirement of an intestinal flora for the development of normal Peyer's patch architecture and indicate that the Peyer's patch response secondarily affects the mesenteric lymph node. The observations also suggest that there is a haematogenous dissemination of pyroninophilic cells from gut-associated lymphoid tissue to, amongst other sites, the duodenum; this may be of importance in both natural and artificial immunization by the oral route.


Complexity of branching dendritic trees: dependence on number of trees per cell and effects of branch loss during sectioning.

We have investigated whether the complexity of dendritic trees is correlated with the number of primary dendrites per neuron (trees per cell). In estimating the average number of branches of centrifugal orders 1-5 per tree we used statistical methods to compensate for loss of parts of trees during sectioning. Limitations of these methods are discussed. Neurons from four populations, stained by the Golgi-Cox method, were examined: stellate cells from layer IV, area 17 of visual cortex, in normal and dark-reared cats; the pyramidal cells from layer V, somatosensory cortex, in two strains of rats. In all four groups of neurons the average number of branches of higher orders (3, 4, 5) per tree tended to be smaller in neurons bearing more trees. Thus all trees from a population of neurons should not be assumed to be equivalent. The decreasin high-order branches per tree tended to offset the increase in number of trees per cell. In three of the four groups these opposed tendencies maintained the average number of high-order branches per neuron nearly independent of the number of trees per cell. Natural selection may have favoured near-constancy in the number of high-order branches to reduce dispersion among neurons of one type in functional input-output rleations.


Vascular permeability and axonal regeneration in skin autotransplanted into the brain.

Pieces of skin were autotransplanted from the pinna of an ear into a cerebral hemisphere in 36 albino rats. The grafts were examined 2, 4 and 6 weeks later for signs of vascular permeability and for the presence of nerve fibres. An intravenously injected fluorescent protein exuded into the connective tissue of the dermis and into the spaces between epidermal cells. Extravascular leukocytes were also seen in the dermis. Nerve fibres, derived from the caudate nucleus, corpus callosum and neocortex, were seen in nearly all the grafts, entering both the dermis and epidermis. They were more numerous after the fourth and sixth than after the second post-operative week. A few of these axons were myelinated and a few contained acetylcholinesterase. It has thus been shown that central axons can regenerate into a region in which they are surrounded by proteins and cells derived from the blood, for at least 6 weeks. This observation does not support a recently advanced hypothesis invoking autoimmunity as the cause of the failure of most axons to regenerate following severance within the central nervous system. It is tentatively suggested that the presence of plasma proteins in the extracellular fluid around the tips of axons may be necessary for the occurrence of regeneration.


A32390A, a new biologically active metabolite. III. In vitro and in vivo antifungal activity.

A32390A, an isonitrile-containing derivative of mannitol, represents a new class of antifungal antibiotics. In vitro antifungal activity of A32390A was found against Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum. In vivo antifungal activity of A32390A was demonstrated in mice infected with C. albicans. Accumulative doses of 37.5 approximately 600 mg/kg, administered subcutaneously over a 24-hour period, showed significant activity without demonstrating toxicity. A32390A was effective, but not as effective as amphotericin B, in reducing the number of Candida cells isolated from the kidney of infected mice. Urinary excretion of A32390A accounted for only 10% of the administered dose. Improved bioavailability of A32390A was accomplished when the antibiotic was combined with polyvinyl pyrrolidone (PVP) in a solid dispersion. Administration of A32390A as a 10% dispersion in PVP resulted in increased urinary excretion of the drug and reduced the amount of drug required for in vivo activity.


Carriomycin, a new polyether antibiotic produced by Streptomyces hygroscopicus.

Carriomycin, a new polyether antibiotic, was isolated from culture broth of Streptomyces hygroscopicus strain T-42082. It is active against Gram-positive bacteria, several fungi, yeasts and mycoplasma. It is also coccidiostatic. The free acid of carriomycin occurs as colorless prisms having the molecular formula C47H80O15 (M.W. 885.15), m.p. 120 approximately 122 degrees C and [alpha]25D -0.5 in methanol. It has no characteristic absorption maxima in the ultraviolet spectrum. The presence of one carboxyl and three methoxy groups was observed from its infrared, PMR and CMR spectra.


The effects of trimethoprim and erythromycin on polysome metabolism in Escherichia coli.

Trimethoprim and erythromycin were shown to have different overall effects on in vivo polysome metabolism in Escherichia coli. In a rel A+-rel A pair of strains, trimethoprim treatment induces a reduction of polysome level to a variable extent, similarly to aminoacyl tRNA deprivation of cells, but persisting polysomes remain dynamic structures in a state of continual turnover. In contrast, erythromycin stabilizes polysome level to a high value in either kind of strain, but maintained polysomes appear as "frozen" structures unable to undergo ribosome translocation.