Duodenitis.

Many questions regarding duodenitis remain unanswered. However, the evidence suggests that duodenitis is a clinical entity which can give rise to dyspepsia and, on rare occasions, gastrointestinal haemorrhage. Conventional and double contrast radiology has only a small part to play in the diagnosis of duodenitis but is important in helping to exclude other lesions such as duodenal ulcer. Provided care is taken during the fibre-optic visualization of the duodenal bulb, the endoscopic appearances of moderately severe duodenitis correlate well with the histological changes seen. A diagnosis of apparent duodenitis should be confirmed by the histological criteria described. Treatment at present is similar to that of peptic ulcer, with the withdrawal of any predisposing and precipitating factors such as aspirin, alcohol and smoking. Antacids may relieve the symptoms. It is not yet known what effect these measures may have on the duodenitis as opposed to the symptoms of dyspepsia. The H2-receptor antagonist, cimetidine, should be effective in treating duodenitis but double blind clinical and endoscopic studies are required to confirm this. The place of surgery is as yet undefined. With the data at present available, it appears that duodenitis is part of the pathophysiological spectrum of the duodenal ulcer diathesis rather than a separate disease. It may represent both the production and healing phases of duodenal ulceration. In some patients the duodenal mucosa may proceed from normal to duodenitis and then to normal again without the development of frank duodenal ulceration (Figure 4). Prospective studies are required which should include a long-term clinical follow-up of a large number of patients with duodenitis accurately and specifically diagnosed by endoscopy and histopathology.


Laser photocoagulation for gastrointestinal bleeding.

Endoscopic laser photocoagulation is one of the exciting developments in the field of gastrointestinal endoscopic therapy. However, much work needs to be done before these techniques should be allowed to proliferate into widespread use. There are few controlled randomized clinical studies evaluating any endoscopic treatment of bleeding, including argon laser and Nd:YAG laser photocoagulation. Despite this, uncontrolled clinical trials of both argon and Nd:YAG laser photocoagulation have begun. Laser photocoagulation of bleeding upper gastrointestinal lesions should be considered a procedure in an experimental stage of development, to be performed only under protocol studies at endoscopic research centres. Only after this or any other haemostatic technique has been proven effective and safe in thorough animal trials and then in controlled clinical trial should it be considered ready for general clinical use.


A double-blind trial of transfer factor vs placebo in multiple sclerosis patients.

A double-blind trial of the effect of transfer factor on multiple sclerosis patients was carried out. In a series of fifty-six multiple sclerosis patients treated with monthly injections of either transfer factor or placebo for 1 year, no beneficial effect of transfer factor was noted. In addition, none of the immunological and serological parameters studied (measles migration inhibition, measles HI titre or CSF immunoglobulin) changed as a result of transfer factor therapy. Histocompatibility typing and CSF IgG/TP ratios were correlated with the disease activity. Of interest was the finding that the presence of the DW2 antigen, when unassociated with HLA-B7 antigen, appeared to correlate with the mildest form of disease activity.


Complement-mediated immune mechanisms in renal infection. II. Effect of decomplementation.

Animals were depleted of complement using cobra venom factor and the influence of complement depletion on the course of renal infection was studied. Complement depletion markedly increased the susceptibility of renal tissue to a challenge with an E. coli strain sensitive to the bactericidal activity of normal serum, but did not influence the outcome of a challenge with a serum-resistant strain of E. coli. These observations are consistent with the hypothesis that complement-mediated host immune mechanisms do play a role in the biology of renal infection and are an important component of the host's immune response in pyelonephritis.


Induction of canine autoantibody to prostatic neoantigen.

Electrodesiccation surgery of the prostate glands was completed on a total of seventy-one dogs. Disc electrophoresis, thin layer gel electrofocus and agar double diffusion studies demonstrated unique changes in the extracts of convalescent prostatic tissue that had persisted for at least 6 months when compared with pre-treatment extracts from seventeen of these dogs. The length of the period following electrodesiccation did not appear to affect the quality of the changes observed. Rabbit antisera to extracts of desiccated prostatic tissue contained antibody specific only for the autologous extract; however, cross-reactivity with altered antigen in homologous extracts could not be verified. In all dogs, generalized adverse effects were not detectable up to 16 months post-surgery.


New concepts in the pathogenesis of primary and secondary amyloid disease.

Despite the marked progress obtained in the structural and amino acid sequencing data of amyloid proteins our understanding of the cellular mechanisms causing the deposition of amyloid fibrils is still poor. Some of the questions about the cellular events leading to the synthesis of amyloid fibrils can be approached by evaluating the immune reactivity of animals that develop amyloid after repeated daily casein injections. Recent studies carried out in a mouse model indicate that macrophage activation associated with T-cell suppression and followed by B-cell proliferation appear to be responsible for the immunopathological abnormalities in both primary and secondary amyloid disease.


Plasmodium berghei adoptive transfer and immunosuppression of immunity in allogenic neonates.

Outbred female rats were hyperimmunized with Plasmodium berghei and mated to produce progeny. Spleen cells from the immunized rats and from normal control mothers were adoptively transferred to their 48 hr old neonates. Some neonates from immune mothers were fostered to normal mothers and vice versa. Weanling rats were challenged 35 days after birth with Plasmodium berghei; immune and normal litters which had not received cells were also challenged at the same time. Rats which had received immune spleen cells from their mothers but were fostered on to non-immune mothers showed significantly lower parasitaemias and higher fluorescent antibody titres than any other combination of cell transfer and maternal milk. GVH reaction was minimal. These results suggest that the immune response to P. berghei was suppressed in the presence of passively transferred maternal antibody.


Sex steroid hormones and antibodies to Candida albicans.

The effect of changes in progesterone (P) and estradiol (E2) on titres of antibodies to Candida albicans was studied by measurement of these three parameters in the following endocrinologically diverse human groups: normal females, gonadal dysgenetics, users of a sequential oral contraceptive (Oracon) and normal males. In females, C. albicans titres (mean +/- s.e.m.) were significantly higher (P less than 0.05) in the luteal (74 +/- 14) than in the follicular phase (34 +/- 19) of the cycle, and there were similar significant increases in P and E2. In the gonadal dysgenetic group (n = 29), with E2 levels comparable with males, the antibody titres were also equivalent to those in normal males (40 +/- 0.5), but were significantly lower than those of normal females in the follicular phase (P less than 0.05). In contrast, Oracon users, with high blood progestin levels, had C. albicans titres (118 +/- 15) significantly higher (P less than 0.001) than those of control subjects during the follicular phase. A significant correlation (P less than 0.05) was observed between P and C. albicans titres (mainly IgA) in randomly selected samples (n = 112) from normal females during the follicular and luteal phases, and in two subjects from whom blood samples were drawn daily for the entire cycle. In the latter, an increase in E2 but not P in the late follicular phase was accompanied by a marked decrease in C. albicans titres. No changes were observed in total immunoglobulin levels or antibodies to SRBC or Herpes virus in response to the marked changes in hormones. These results indicate that the production of antibodies to C. albicans may be specifically influenced by sex steroid hormones, being enhanced by P and E2 at low levels but depressed by E2 at high levels.


Potential anticoagulant drug interactions in ambulatory patients.

Computer-generated prescription drug purchase records for ambulatory patients receiving oral anticoagulants (OAC) were studied for concomitant use of other drugs which have been reported to induce clinically significant interactions. One third of 479 patients taking OAC were exposed to a potentially interacting drug at some time during this 6-month period. The percentage of patients with drug interaction exposure correlated directly with total drug use (p less than 0.0005). There were no significant differences when interaction exposure rates were compared in the cases of single : multiple pharmacy and single : multiple physician-patient groups. Warfarin was the most common anticoagulant (greater than 95%) and barbiturates the most common interacting drug.


Effects of oxprenolol and propranolol on systolic time intervals.

Twenty patients with coronary heart disease participated in a double-blind, randomized, crossover study on three study mornings to evaluate the effect of oral oxprenolol 80 mg, oral propranolol 80 mg, and placebo on left ventricular contractility. Systolic time intervals were performed in the control period and at 60, 90, 120, 150, 180, 240, 300, and 360 min after medication. None of 20 patients developed adverse effects. The 80-mg doses of oxprenolol and propranolol had a negative chronotropic effect, with the resting heart rate slightly but consistently decreased more after propranolol, attaining statistical significance at 90, 150, and 300 min. That the 80-mg doses of oral oxprenolol and propranolol also induced a negative inotropic effect was indicated by a similar prolongation of the external isovolumic contraction time and pre-ejection period intervals. This equipotent dose of oxprenolol in producing a negative inotropic effect induces less resting bradycardia than propranolol.


Vitamin D and the syndromes of azotaemic osteodystrophy.

Intestinal malabsorption of calcium and the development of osteomalacia in conservatively treated renal failure is explained by a quantitative deficiency of 1,25-dihydroxycholecalciferol, which also contributes to the development of hypocalcaemia. Excess of 25-hydroxycholecalciferol can substitute for this deficiency. The presence and healing of azotaemic osteomalacia is unrelated to the prevailing plasma [Ca] x [P] product. The data suggest that "vitamin D" acts directly on bone mineralisation, but the claim that this apparent effect is normally due to 25-hydroxycholecalciferol is considered unproven. Most of the phenomena of azotaemic osteodystrophy are encountered in simple vitamin D deficiency; as in that condition, deficiency of 1,25-dihydroxycholecalciferol may be of primary significance in causing secondary hyperparathyroidism in renal failure.


The anatomy and physiology of the bovine respiratory system relating to pulmonary disease.

Bovine respiratory anatomy and physiology were reviewed and considered in relationship to the pathogenesis of pulmonary disease. Factors which may predispose cattle to respiratory disease included a small physiological gaseous exchange capacity, greater basal ventilatory activity, and greater anatomical compartmentalization of the lung as compared with other mammals, a low level and atypical bioactivity of bovine lysozyme, and low numbers of macrophages within the alveolar lumen.


Loxapine versus perphenazine in psychotic patients. A double-blind, randomized, multicentre trial.

A double-blind, randomized, multicentre trial was carried out in 47 psychotic patients to evaluate the efficacy of oral treatment with loxapine compared with perphenazine. In total, 22 patients were included in diagnostic Group I (cases of acute schizophrenia and psychogenic (reactive) psychoses). The average maximum daily dose was 60.0 mg in the loxapine group and 36.8 mg in the perphenazine group. After 3-weeks' treatment, no significant differences were found between the two treatment groups according to the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) Scale or side-effect records. Twenty-five patients were included in diagnostic Group II (cases of chronic schizophrenia). The average daily dosage was 81.1 mg in the loxapine group and 90.1 mg in the perphenazine group. After 10 to 12-weeks' treatment, no significant differences between the two treatment groups could be found according to BPRS, CGI scale, Nurses' Observation Scale for In-patient Evaluation (NOSIE) or side-effect records. The diastolic blood pressure (lying and standing) tended to increase slightly in both treatment groups. In conclusion, it was found that loxapine and perphenazine seemed to be equally effective and, based on experience with parenteral loxapine treatment, it is suggested that further investigation of oral loxapine should be carried out in psychotic patients in whom agitation is a feature.


A double-blind comparison of nefopam and placebo in post-operative pain.

Nefopam (90 mg), an analgesic, was compared with placebo in a double-blind trial in patients who had undergone total abdominal hysterectomy operations. Analgesic activity was assessed by patients rating their pain before and 1 hour after administration of each treatment, by sequential analysis of patient and observer preference for treatment, and by calculation of the time interval between doses of the two treatments. Nefopam was found by observer preference to be significantly better than placebo in relieving post-operative pain. In patients with severe initial pain, the time between doses after nefopam was significantly longer than after placebo.


Effect on platelet adhesiveness in diabetics after long-term treatment with a new oral hypoglycaemic agent, gliclazide.

Gliclazide is an oral hypoglycaemic agent which has been shown in animal models to reduce platelet adhesiveness. In this study, 50 patients with maturity onset diabetes treated with gliclazide (80 mg/day) were followed up for 6 months to 1 year to assess the effect on platelet adhesiveness and control of blood sugar. A significant fall in mean platelet adhesiveness from 29% before treatment to 19.5% after 1 year (p less than 0.001) was achieved without any deleterious effect on normal haemostasis. The drug was well tolerated and achieved a satisfactory control of blood sugar levels at the dosages used.


Controlled trial of a carbenoxolone/alginate antacid combination in reflux oesophagitis.

A double-blind controlled trial was carried out in 37 patients with oesophagitis, confirmed endoscopically and histologically, to compare the efficacy of treatment with a carbenoxolone/alginate antaacid combination with that of the alginate antacid compound used alone. The total daily dosage of carbenoxolone was 100 mg. During the 8-week-period of the trial patients were seen every 2 weeks and endoscoped at 4 and 8 weeks. Response to treatment was assessed symptomatically and endoscopically using 6-point grading scales, and multiple oesophageal biopsies were taken at each endoscopy. The addition of carbenoxolone to the alginate antacid compound was shown to enhance symptomatic relief and to increase healing of oesophagitis and oesophageal ulceration significantly. No serious side-effects were reported in either group. Although there were a number of biochemical or clinical abnormalities recorded, none required any alteration in treatment.


Endoscopic study of the gastro-intestinal tolerance of glucamethacin.

A gastroscopic study was carried out in patients with rheumatic disorders to investigate the gastric tolerance of glucamethacin, a new, non-steroidal anti-inflammatory agent. The first stage was a double-blind crossover comparison of the effects of glucamethacin (420 mg/day) and indomethacin (100 mg/day), each given for 15 days in random order to 30 patients. In the second, open stage, 70 such patients, most of whom also had gastrointestinal pathology, received glucamethacin (420 mg/day) for 25 days. The results of endoscopic findings showed that significantly fewer (p less than 0.05) gastric lesions were produced after treatment with glucamethacin than after indomethacin. In the patients with gastro-duodenal pathology treated only with glucamethacin there was no change in endoscopy findings in 74% of the patients and only slight changes in the others.


[Photochemotherapy of psoriasis: increasing its effectiveness with an oral aromatic retinoid (clinical results in 134 patients) (author's transl)].

The effectiveness of photochemotherapy can be substantially increased by the concomitant administration of an oral aromatic retinoid. 134 patients with severe plaque-type or palmoplantar psoriasis were given various combined treatment schedules. In the initial (clearing) phase a significant synergistic effect was achieved if retinoid administration was started before photochemotherapy, and if the dose was 1.0 mg/kg body-weight. This shortened by half the time required in a control group given photochemotherapy alone (7.7 +/- 4.5 irradiation sessions within 14.1 +/- 8.6 days), and reduction of the total UVA energy necessary for complete clearing to one third (32.4 +/- 40.0 J/cm2). After clearing the patients received standard photochemotherapy maintanance treatment. The incidence of relapses observed during a 10-month follow-up was the same as that in patients cleared and maintained with photochemotherapy alone. Short courses of retinoid treatment in addition to photochemotherapy were highly effective in clearing patients who had failed to do so or had not been maintained in a cleared state on standard photochemotherapy.


[Demonstration of antibodies against HBs antigen with the modified MICROELISA-hepanostika-test (author's transl)].

Among various modifications of the Hepanostika test a simple, sensitive and reproducible one is described as being the best. Of 689 sera from patients in a haemodialysis unit 110 had antibodies against HBs antigen in the Hepanostika test and 150 in the Ausab test. Those antibodies which were not demonstrated in the Hepanostika test had a relatively low concentration (mean impulses per minutes 4.3 X NCx). Those sera which were positive in both the Hepanostika and Ausab test contained antibodies in higher concentrations (mean impulse/min 29.5 X NCx). Only 11 of the 689 sera were positive in the migration-electrophoresis test. A particularly advantage of the modified Hepanostika test is that both HBs antigen and antibodies against HBs antigen can be demonstrated simultaneously on the same plate. Using this method 200 sera were examined. The same sera were tested in the Austria-II-125 test for HBs antigen and the Ausab test for antibodies against HBs antigen. The Hepanostika test was positive in five, the Austria test in four sera. According to the Hepanostika test 43 sera contained antibodies against HBs antigen, while 45 did according to the Ausab test. The two that were positive only in the Ausab test were only weakly positive.


Chlorinated benzenes in the environment.

Chlorinated benzenes are composed of twelve chemical species: one mono-, three di-, three tri-, three tetra-, one penta-, and one hexachlorobenzene. Most of these are not only important intermediates for various kinds of chemicals but are also extensively employed for various applications singly or in combination. For example, 1,4-dichlorobenzene is used chiefly against termites in soil; trichlorobenzenes are used as solvents for pesticides and also as heat transfer agents with PCBs; the mixture of trichlorobenzene and tetrachlorobenzene is applied in controlling shellfish predators; and hexachlorobenzene is applied to wheat as a fungicide in some countries and as an additive to rubber products. The annual production (1973) of monochlorobenzene, 1,2-dichlorobenzene, and 1,4-dichlorobenzene in Japan was about 23,000, 9000, and 20,000, tons, respectively. Production volumes of other chlorinated benzenes are not well known but are assumed to be smaller than those of the above three compounds. The total annual production of chlorinated benzenes far surpasses the peak production of PCBs (7000 tons/year) which are known as a ubiquitous pollutant in this country. Since chlorinated benzenes have a chemical structure and properties similar to those of PCBs and PCTs, it seemed necessary to direct our attention to environmental contamination by these materials. The present paper describes only the occurrence and the fate of these materials. Toxicity and biological impact are not referred to here.


Biological interactions of N-nitroso compounds: a review.

There have been efforts to acquire information on the carcinogenic hazards of environmental materials to which humans are exposed since the earliest indications that chemicals can induce cancer in man. N-Nitroso compounds represent a major class of important chemical carcinogens and mutagens that have been implicated as hazardous substances in the environment. This review discusses the relevant chemistry and biotransformation of N-nitroso compounds. It also considers the interaction of these compounds with biological material. Nitrosamines and nitrosamides have been shown to be versatile tools for the study of mutagenic and carcinogenic processes and also lend themselves to structure/activity studies. Attention is drawn to recent developments concerning the relationship between mammalian metabolism of N-nitroso compounds and the relative susceptibility to carcinogenesis and mutagenesis. The usefulness of nitrosamines and nitrosamides in mutagenicity and carcinogenicity studies has been amply demonstrated, and continued work with these substances can lead to a better understanding and evaluation of the potential risks of chemicals in the environment.


Human experience with dieldrin in perspective.

In this paper, the follow-up results of a long-term study of industrial workers are presented. In themselves, these results may be of interest. It is, however, in the context of all the known facts, in its synthesis with other studies that this human experience in pesticide manufacturing assumes its proper significance. Therefore, related animal and other studies are briefly mentioned before the results of our clinical--epidemiological human study. Thus, the latter can be placed in context, and conclusions can be based on all the established facts rather than on the opinions on isolated aspects.


Color chemistry and the environment.

Dyes, and by extension the various organic compounds used for coloration, including organic pigments and fluorescent whitening agents (FWAs), are among the organic chemicals which we encounter as technological and functional necessities in nearly every sphere of our daily lives. They also greatly influence our mood and thus contribute enormously to the very quality of the lives we lead. At the same time we have come to realize that our achievements and continuing technological progress are only worthwhile provided they pose no hazard to the environment. Tremendous efforts have been undertaken on a worldwide scale to identify, measure, evaluate, and eliminate the undesirable effects of chemicals and, hence, dyes on man and the environment. The present paper deals in particular with the environmental problems associated with the manufacture and use of dyes, problems so complex and so varied in impact that only a discerning appraisal can put them into proper perspective. An attempt is made to define and evaluate these problems and to show, with reference to selected examples, what measures have been and are being implemented to overcome them. Various aspects of the relevant legal regulations, the obligation on manufacturers to take due care in their operations, and product liability are touched upon. This much is certain: A good deal of creative, interdisciplinary effort and meticulous attention to minor detail will be necessary to master existing and future environmental problems in this area. That is the challenge facing all scientists engaged in color chemistry.


[Risk of psychotropic drug potentiation by dipropylacetamide (16 cases)].

We report 16 cases in which there is a dangerous potentialization of psychotropic drugs with dipropylacetamide, and compare them with 19 cases possible to control, that dipropylacetamide used alone, or in another association, was well tolerated. We pointed out the importance of a depressive evolution, and of dangerous associations, mainly with tricyclic compounds, lorazepam and 5-hydroxytryptamine. Clinical signs are described; they consist in a fast evolutive syndrome, which is the same that "syndrome malin of psychotrops" with neurovegetative signs and central fever, or ingravescent wakefulness disorders and spasmodic cerebellar signs. The importance for the diagnosis and the prognosis of E.E.G. data is pointed out; plasma levels determination does not seem to give important data. Drugs interactions studies are very important in the clinical evaluation of psychotrops. Several drugs may interact with dipropylacetamide. This fact sustains some hypothesises about the action site of the drug.


In vitro effect of LH-RH on RNA content and synthesis in isolated anterior pituitary cells from intact and castrated female rats.

The in vitro effect of LH-RH on isolated anterior pituitary cells from intact and castrated female rats has been examined. The cells isolated by trypsin maintained their viability and the ability to response to LH-RH by the release of LH. During the incubation period LH-RH significantly reduced the uridine incorporation into RNA in anterior pituitary cells from both intact and castrated females. There was a time- and dose-dependent response correlation. The RNA content was not affected by LH-RH after 2 h incubation. The administration of the LH-RH with estradiol showed a similar effect.


The effect of prednisolone and metyrapone on FSH release induced by the administration of LRH.

The response of follicle-stimulating hormone (FSH) to a single injection of synthetic LRH was established in 7 and 6 women following an intramuscular dose of 0.2 mg and 0.1 mg. The secretion of FSH was greater in the group injected with 0.2 mg LRH than in the group injected with 0.1 mg. On the other hand, the response of FSH to a single injection of LRH (0.1 mg/subject) was established in 7 men before and after the pretreatment with metyrapone for one dat (4.5 g/subject). Pretreatment with metyrapone provoked a hypersecretion of FSH following a single injection of synthetic LRH. Seven women, 21--48 years of age who were treated with prednisolone for at least 1.5 months were examined for the responsiveness of the anterior pituitary to a single injection of synthetic LRH (0.2 MG). The secretion of FSH was not suppressed and the maximal serum level of FSH was observed 60 min after LRH injection.


Effect of steroids in combination with LH-RH on the release of LH and FSH in LH-RH-primed immature male rat.

LH and FSH release of immature male rats was remarkedably enhanced by LH-RH if primed with LH-RH one hour before. The effect of exogenous steroids on the action of the second LH-RH was investigated. C-18, C-19 and C-21 steroids in different doses were tested. Blood samples were collected from the jugular vein immediately before and 30 min after the second LH-RH injection. Serum LH and FSH were determined by respective radioimmunoassays. The concomitant increase of LH and FSH was not induced by all the steroids administered iv. Estrone or 17alpha-hydroxyprogesterone suppressed LH and FSH release. Estradiol-17beta preferentially suppressed LH release. Cortisone, progesterone or dehydroepiandrosterone significantly facilitated FSH release, whiel 20alpha-dihydroprogesterone or 20beta-dihydroprogesterone selectively promoted LH release. The sc injection of most steroids dissolved in oil tended to augment the acute release of LH but not FSH. 20alpha-Dihydroprogesterone was particularly potent in this concern. Dehydroepiandrosterone or androstenedione was effective in maintaining FSH release for a longer period. These data revealed that potentiated LH and FSH release induced by the second LH-RH was readily modified by steroids administered simultaneously.


RNA-protein neighbourhoods of the ribosome obtained by crosslinking.

It is possible to crosslink protein to nucleic acid with diepoxybutane which reacts mainly with the N-7 of guanine as well as the thiol and aminogroups in protein; the resulting crosslinked complexes are cleavable. When this reagent is applied to ribosomes, even under conditions that minimize the extent of reaction, at least half of the ribosomal proteins can be recovered crosslinked to one or other of the major ribosomal RNA species. In addition, one fourth of the proteins can be recovered crosslinked to the RNA of the heterologous ribosomal subunit. Some of the remaining proteins may also be crosslinkable to the RNA, but additional experiments are required to confirm this.


A study of the thermal unfolding of Escherichia coli phenylalanine transfer RNA by chemical modification at elevated temperatures.

Escherichia coli tRNAPhe was modified by 3 M sodium bisulphite pH 6.0 for 24 h in the temperature range 25 degrees C (x 5 degrees C) to 55 degrees C and in the absence of added magnesium ions. The sites and extents of conversion of cytidines to uridine occurring at each temperature were determined by fingerprinting. The new sites of cytidine modification found at higher reaction temperatures were assumed to arise from breakage of secondary and tertiary structure hydrogen bonds involving cytidine residues. From these data, we conclude that hydrogen bonds within the 'complex core' of the tRNA (including the base pairs G-10 . C-25, C-11 . G-24 and C-13 . G-21 within the dihydrouridine stem and the tertiary structure base pair G-15 . C-48 melt at a lower temperature than the tertiary structure hydrogen bonds between G-19 in the dihydrouridine loop and C-56 in the TpsiC loop.


Dioxygen and temperature dependence of ubiquinone formation in Escherichia coli: studies of cells charged with 2-octaprenyl phenol.

The multiple aromatic auxotroph Escherichia coli K-12 strain AB 2847 (aroB-) was conditioned for efficient ubiquinone-8 formation. Resting cells readily convert 4-hydroxy[U-14C]benzoate into ubiquinone-8 (60 nmol per g wet weight). Under argon this processing stops at the stage of 2-octaprenyl phenol. Only upon admission of air is the pool of 2-octaprenyl phenol converted to ubiquinone-8. This reaction occurs in the cytoplasmic membrane and is significantly inhibited by cytochrome P-450 inhibitors. The rate for 2-octaprenyl phenol conversion is strongly dependent on temperature. The Arrhenius plot shows inflection points at 32 degrees C and 16 degrees C. Enzymes for ubiquinone-8 synthesis are absent from anaerobically grown E. coli. Processing of 4-hydroxy[U-14C]benzoate by these cells starts only when protein synthesis is permitted under aerobic conditions.


Polynucleotide-protein interactions in the translation system. Detection of contacts between some ribosomal split proteins and 16-S RNA in 30-S subunits of Escherichia coli ribosomes.

Direct contacts between 16-S RNA and split proteins S2, S3, S5, S14 and S21 inside the 30-S subunit of Escherichia coli ribosomes were evidenced by the formation of ultraviolet-induced (lambda = 254 nm) RNA-protein cross-links. 30-S subunits were reassembled from core particles and a mixture of split proteins containing in each case a single 125I-labelled protein. All the proteins tested are cross-linked as a result of a single-hit process; proteins S3 and S21 were cross-linked at the highest rate.


On the mechanism of assembly of the aspartate transcarbamoylase from Escherichia coli.

The mechanism of subunit assembly of aspartate transcarbamoylase from Escherichia coli was studied by following the kinetics of reassociation. The isolated trimetric catalytic subunit (c3) and dimeric regulatory subunit (r2) were mixed together and formation of the dodecameric native enzyme (c6r6) was monitored by measuring changes in activity. Under appropriate conditions the reassociation was second order with respect to the c3 concentration and the effects of varying r2 concentration on the second-order rate constant were examined. An optimum R2 concentration of about 0.07 micrometer was observed. A scheme of the assembly pathways is proposed and is based on the reversible formation of c3r2n (n = 0, 1, 2 or 3) as intermediates. Various combinations of two such c3r2n species are considered as possible rate-limiting steps. This model yields an expression which relates the experimentally determined (overall) second-order rate constant to the equilibrium constant (Kd) governing the formation of c3r2n, the r2 concentration, and four coefficients which reflect the contribution of different types of assembly processes. Using previously determined values of Kd, the above expression for each r2 concentration reduces to a linear equation with four unknowns. The experimental data were subjected to multiple linear-regression analysis and values for the four coefficients were found which gave an excellent fit. Our results show that reassociation of the subunits is a fast bimolecular reaction with rate constants in excess of 10(6) M-1 s-1. Our analysis also suggests that interactions involving a total of more than three r2 subunits (e.g. the combination of c3r2 with c3r6) might contribute significantly to the overall assembly. The influence of various ligands on the reassociation rate profile was also studied. All ligands examined were partially inhibitory to the formation of native enzyme. The effects of substrates were similar to those of CTP whereas the effects of ATP were substantially different. These observations can be readily interpreted by postulating different conformational changes induced by the ligands. These changes should alter the relative orientation of the subunit contacts which must be formed in the reassociation process. The interpretation is consistent with our previous model of the allosteric mechanism.


Enzymic and chemical synthesis of epilson-N-(L-propionyl-2)-L-lysine.

Pyruvate was shown to act as an oxo acid substrate in the reverse direction of saccharopine dehydrogenase [epsilon N-(L-glutaryl-2)-L-lysine: NAD oxidoreductase (L-lysine-forming)] reaction. The enzymic condensation product of lysine and pyruvate was isolated and identified as epsilon-N-(L-propionyl-2)-L-lysine by comparison with the synthetic compound. A method for the chemical preparation of diastereoisomers of epsilon-N-(propionyl-2)-L-lysine is also described.


The N-terminal sequence protein of L7/L 12 is responsible for its dimerization.

Ultracentrifuge studies of intact protein L7/L12, of its fragments  27--120, 1--74 and 74--120 and of protein L7/L12 with oxidized methionine residues, indicate that the N-terminal sequence of the protein L7/L12 is responsible for its dimerization. The symmetry model of the dimer is discussed.


Studies on the structure of protein L7/L12 from Escherichia coli ribosomes.

Circular dichroism, infrared and proton magnetic resonance spectroscopy as well as microcalorimetry methods were used to investigate the intact proteins L7/L12 in solution and their different derivatives (L7 with oxidized residues of methionine, fragments 27--120, 1--73 and 74--120)- On the basis of the data obtained the following conclusions have been drawn: (a) there is no beta structure in the protein L7, (B) the N-terminal region of L7 forms a long alpha helix (c) the Phe-30 residue within the N-terminal region of L7 takes part in the dimerization, (d) the C-terminal of L7 is globular and (e) the Phe-54 residue is included in the hydrophobic core of the globular C-terminal region.


Dimer state of protein L7/L12 and EF-G-dependent reactions of ribosomes.

A number of different monomer and dimer derivatives of protein L7/L12 has been studied in EF-G-dependent reactions on the ribosome. It has been shown that only dimer derivatives of protein L7/L12 are able to interact with the ribosome. This means that it is the dimer forms of protein L7/L12 that are present in the functionally active ribosome. It is likely that the N-terminal sequence of protein L7/L12 is responsible for dimerization of the protein in solution and at the same time contributes mainly to the interaction of the protein L7/L12 dimer with the ribosome. The results obtained suggest that there are four copies of protein L7/L12 in the translating ribosome.


Response of the pyrimidine pathway of Escherichia coli K 12 to exogenous adenine and uracil.

The effect of exogenous adenine or uracil upon the de novo pathway for synthesis of pyrimidine nucleotides in Escherichia coli K12 was investigated. Parameters studied were levels of the enzymes carbamoyl phosphate synthase (EC 2.7.2.9), aspartate carbamoyltransferase (EC 2.1.3.2) and orotate phosphoribosyltransferase (EC 2.4.2.10) and the intermediates carbamoyl phosphate, aspartate and orotate, together with the contributions of exogenous uracil and aspartate to intracellular pyrimidine nucleotide. Taken with earlier data [Bagnara, A.S. & Finch, L. R. (1974) Eur. J. Biochem- 41, 421--430] on contents of UTP, CTP and 5-phosphoribosyl 1-diphosphate in cultures of this strain after the addition of adenine or uracil, the results obtained provide new insights into the regulatory mechanisms operating on the pathway in vivo. These insights enable evaluation of the contributions of such factors as limitation for a substrate, feed-back allosteric control by end products and enzyme repression/depression mechanisms. The evidence presented indicates that depressed levels of orotate phosphoribosyltransferase in E. coli K12 result in the wasteful ultilization of asparatate for excess synthesis of pyrimidine nucleotide precursors during balanced growth of the strain in minimal medium. Exogenous adenine increases the excessive accumulation of these precursors by lowering the intracellular content of 5-phosphoribosyl 1-diphosphate (Bagnara and Finch, 1974). This causes a decrease in the conversion of orotate to orotidine 5'-monophosphate, thus lowering the utilization or orotate and its precursors for synthesis of pyrimidine nucleotides. Further, since the contents of these nucleotide end products are thereby decreased (Bagnara nad Finch, 1974), theri feed-back on the early steps in the pathway is diminished and the production of the precursors is increased. It is postulated that growth of E. coli K12 under these conditions is limited by a compound that is metabolically related to precursors to aspartate.


Evidences for the existence of two steps in DNA replication obtained in toluene-treated Escherichia coli.

Toluene-treated Escherichia coli can synthesize DNA in the presence of precursors and ATP [Moses, R.E. & Richardson, C.C. (1970) Proc. Natl Acad. Sci. U.S.A. 67, 674--681]. The replacement of ATP by another NTP or dNTP leads to the premature arrest of the reaction. Residual synthesis in the presence of an NTP or dNTP other than ATP differs from the complete reaction in the presence of ATP because it is less sensitive to nalidixic acid and novobiocin and because its maximal activity can be obtained with lower concentrations of dNTP or shorter times of toluene treatment. However, like the complete reaction, residual synthesis occurs at the replication fork pre-existing in vivo at the time of toluenization, produces short and long pieces of DNA, is inhibited by arabinosyl-adenine triphosphate, azide or mitomycin C, and is dependent on the dnaE, DNAB and dnaG gene products. We conclude from these data that ATP is specifically required for a step in DNA replication which involves the activity of DNA gyrase, the target of nalidixic acid and novobiocin [Higgins, N.P., Peebles, C.L., Sugino, A. & Cozzarelli, N.R. (1978) Proc. Natl Acad. Sci. U.S.A. 75, 1773-1777]. In the absence of DNA gyrase activity, short DNA pieces are formed and sealed but only a limited amount of the chromosome can be replicated (residual synthesis). In the presence of DNA gyrase activity, DNA synthesis can occur on a longer portion of the chromosome (complete synthesis).


Binding of Cibacron Blue F3GA to flavocytochrome b2 from baker's yeast.

1. Flavin-free cytochrome b2 has been prepared by rapid Sephadex filtration at acid pH. The method, which yields an apo-enzyme with high reconstitution potential and has several advantages over previously used procedures, is described in detail. 2. Flavin-free cytochrome b2 thus prepared is retained by blue-dextran-bound Sepharose. It can be eluted by an increase in ionic strength, by dilute ethylene glycol and specifically by low concentrations of FMN. The holoenzyme is not retarded at all. 3. Both flavin-free and holocytochrome b2 bind Cibacron blue F3GA with appearance of distinct difference spectra. Cibacron blue is an inhibitor for the holoenzyme, it shows mixed type inhibition with respect to lactate. 4. It is concluded that there are two types of binding sites for Cibacron blue F3GA on flavocytochrome b2. Both possess ionic and hydrophobic character; one of them, which is the flavin binding site, is only available in the absence of the cofactor. Taken together these results may mean that the enzyme possesses a local flavin-binding structure similar to the 'dinucleotide fold'.


Involvement of ribosomal protein S1 in the assembly of the initiation complex.

Antibodies against ribosomal protein S1 (anti-S1) have been used to determine the function of S1 in the partial reactions involved in the translation of MS2 RNA in vitro. Vacant ribosomes are fully sensitive to the antibodies, whereas elongating ribosomes are resistant. We have determined at which stage of translation the resistance to anti-S1 is acquired. We find that insensitivity to anti-S1 already arises upon mixing 30-S subunits with MS2 RNA. Apparently the two particles form a complex in which S1 is functionally protected against its antibody. Complex formation depends on elevated temperature, a suitable ionic environment and it is stimulated by the initiation factor IF-3. It does not depend on IF-1, IF-2 or fMet-tRNA. Thus ribosomes have the potential to recognize the messenger in the absence of fMet-tRNA. Protein S1 appears directly involved in this primary recognition reaction.


Treatment of disturbances of consciousness caused by measles encephalitis with levodopa.

Results are reported of a double-blind trial with L-dopa in 39 patients with measles encephalitis. In this treatment series, L-dopa improved the state of awareness and the diffuse disturbances in the EEG. There was a significant difference too, regarding the outcome between patients treated with L-dopa and placebo. The death rate in the L-dopa-treated group was lower and there were fewer mental sequelae. It is suggested, that L-dopa should be used in patients with measles encephalitis.


An improved method in rabbit intubation and thymectomy.

A procedure is developed for endotracheal intubation followed by positive pressure ventilation anaesthesia, allowing major thoracic surgery, including thymectomy, to be performed in the young and adult rabbit. A method is described to bring the animal in a position favourable for thymectomy. A detailed description is given of a thymus ablation technique in which the thoracic wall is left intact.


Further experiences with the specific red cell adherence test (SRCA) in bladder cancer. a histological and cytological study.

The red cell adherence test allows the disclosure of the blood group antigens incorporated on the surface of the urothelium. In the course of dedifferentiation the urothelium will lose its antigenicity. We applied this test on superfical bladder tumours (T1), carcinoma in situ and cytological specimens and observed a close correlation between the test results and the course of the disease, e.g. if the test was positive the recurrent tumour would be superficial and vice versa. As a rule the negative results revealed atypical hyperplasia and carcinoma in situ as areas of potentially malignant and invasive tumours. With the application of the red cell adherence test to cytological preparations we can probably improve the accuracy of the cytological examination in cases of transitional cancer of low malignancy.


Evidence for the presence of Thy-1 on cultured thymic epithelial cells of mice and rats.

Thymic tissue of C57BL/6 mice and DA rats was cultured. After 6--8 weeks, cultures were analyzed for their capacity to absorb anti-Thy-1 serum, and for the expression of Thy-1 on the surface of different cell types by means of the indirect peroxidase labeling method. Three main cell types were identified: epithelium-like cells, fibrocyte-like cells and macrophages, but no lymphocytes were found. The presence of Thy-1 on cultured nonlymphocytic thymus-derived cells was demonstrated by their ability to absorb the cytotoxic activity of the appropriate anti-Thy-1 sera. Electron microscopical analyses of labeling experiments revealed that Thy-1 was predominantly expressed on epithelium-like cells with preference for their cell protrusions. The possible role of Thy-1 expression, both on thymocytes and thymus epithelium for cellular interaction, is discussed.


Chemiluminescence and immune cell activation. I. Early activation of rat thymocytes can be monitored by chemiluminescence measurements.

Immediately after the addition of concanavalin A, rat thymocytes respond, in the presence of luminol, with a burst of chemiluminescence (CL) that can be conveniently monitored in an ordinary liquid scintillation spectrometer. Peak CL is reached after 50 sec. Addition of catalase suppresses 65% of the CL, suggesting that H2O2 generation may be its major source. CL with different kinetic characteristics can also be generated by the calcium ionophore A23187. Our rat thymocytes contain approximately 0.1% endogenous macrophages. Bone marrow-derived rat macrophages also respond to concanavalin A or A23187 stimulation with a burst of CL. However, the kinetic properties of CL as well as the inhibition of CL by catalase in these cells differ markedly from those of thymocyte preparations, suggesting that the major portion of the CL in rat thymocytes actually originates in T lymphocytes. Because CL measurements allow the monitoring of very early events in cell activation and because of the simplicity of the technique, CL measurements may become a useful method for the study of lymphocyte activation, of macrophage-lymphocyte interactions, as well as for the rapid screening for specificity and reactivity of T lymphocyte populations.


Incorporation of rat histocompatibility (AgB) antigens into liposomes, and their susceptibility to immune lysis.

The purification of detergent-solubilized rat histocompatibility antigens is described. The antigen may readily be incorporated into synthetic vesicles (liposomes) which appear to be unilamellar and between 0.1 microbeter and 0.2 micrometer in diameter. The addition of specific antibody leads to the agglutination and precipitation of the liposomes. An enzyme, horseradish peroxidase, may be incorporated into the trapped aqueous phase of the liposome, and its release by antibody and complement can be detected.


Vasodilation produced by prostacyclin (PGI2) and 9(O)-thiaprostacyclin (PGI2-S) in the canine femoral circulation.

The action of 9(0)-thiaprostacyclin (PGI2-S) was compared with that of prostacyclin (PGI2) and papaverine in the femoral circulation of dogs. PGI2-S, injected into the dog femoral artery in a dose of 0.1 microgram or higher, produced marked vasodilation in the femoral artery without any change in blood pressure. The potentcy of PGI2-S was one tenth that of PGI2, and was a hundred times that of papaverine. The stability of PGI2-S in neutral solution was forty times that of PGI2.


[Bibliography of technology for germfree animal research--1977 supplement (author's transl)].

Thirty-two references were added to the Bibliography of Technology for Germfree Animal Research which was published in this journal; Experimental Animals 24 (4), 229--253, 1975 and 25 (3), 223--225, 1976. The literature consists of useful technical reports concerning germfree mammalian and avian research classified as follows; 1: Isolator, 2: Diets, 3: Sterilization, 4: Obtaining germfree infants and hand rearing, 5: Animal care, management and transportation, 6: Experimental methods, 7: Sterility tests and contamination, and 8: Operating and patient isolators. Abstracts and brief description with no data have been excluded.


Studies by radioiodination of normal adult, fetal and leukemic cell membranes.

A comparison was made between cord blood lymphocytes, normal adult lymphocytes and leukemic cells after membrane iodination with lactoperoxidase. A double-labeling technique using lactoperoxidase iodination with 125I and 131I followed by analysis on polyacrylamide gel electrophoresis revealed a number of membrane differences between leukemic, normal and fetal cells. There was a reduction in the 70,000 molecular weight component in cord blood cells compared to adult lymphocytes, and an increase in membrane peptides with molecular weights of 35,000, 20,000, 9,000 and 4,000. Although smaller molecular weight peptides were also present in chronic lymphatic leukemia as well as acute myeloid leukemia, these were shown to be distinct from fetal type membrane components.


The marrow colony forming cell and serum colony stimulating factor of the chicken.

Marrow cells of the chicken produced colonies in semisolid media. Developing colonies consisted of granulocytes, macrophages or a mixture of these two cell types. The granulocyte-macrophage CFC was nonadherent. An adherent 'CFC' was also present and it differed in several ways from the nonadherent CFC: (a) clones contained only macrophages, (b) they contained a core of nonrefractile cells, (c) their appearance was delayed 1-2 weeks, (d) they were unaffected by the presence of erythrocytes and (e) the efficiency of cloning was increased but the percentage of clones able to produce 50 or more cells was markedly decreased, i.e., the cluster/colony ratio was increased. The growth of both colony types was strictly dependent on the presence of CSF. Data obtained from dose-response studies on unfractionated marrow indicated that clusters and colonies were derived from single cells. The CSF of chicken serum yielded sigmoid dose-response curves when tested on marrow cells. Calf serum could not support cluster or colony formation when tested alone but it did have an enhancing effect on the CSF of chicken serum. Levels of serum CSF were increased by injecting chickens with bacterial endotoxin. This phenomenon occurred with five chicken lines tested, but certain chickens of the Kimber line did not respond to endotoxin with elevated levels of CSF.


Treatment of severe aplastic anemia with antilymphocyte globulin and androgens.

The etiology of aplastic anemia is unknown. A stem cell lesion caused by a toxin, virus or microenvironment defect is the main hypothesis. An autoimmune origin has been recently suspected. In an attempt to demonstrate the autoimmune origin of the disease, 17 patients with severe aplastic anemia were treated with antilymphocyte globulin (ALG). Nine patients showed no improvement, developed infectious or hemorrhagic complications and died within 1 to 7 months. In contrast, eight patients had a prompt rise of granulocyte and reticulocyte counts. Although the hematological reconstitution is not complete, these eight patients are still alive between 11 months and 24 months after treatment. This study shows that ALG may have a beneficial effect in the treatment of patients with severe aplastic anemia.


Transfer of immunity by transfer of bone marrow cells: a requirement for T lymphocytes and sensitivity to cyclophosphamide.

Thymectomized, lethally irradiated mice reconstituted with bone marrow cells (TIR mice) from normal donors succumbed after i.p. challenge with xenogeneic (rat) Yoshida ascites sarcoma (YAS) given 1 month after irradiation and reconstitution. YAS rejection and production of YAS-antibodies was induced in TIR mice by a single i.v. injection of normal syngeneic spleen cells given 1 day after the tumor. Purified splenic T lymphocytes also induced YAS rejection in TIR mice, but splenic B lymphocytes did not affect progressive tumor growth. Tumor was also rejected in TIR mice that had been reconstituted with bone marrow cells from YAS-immune donors. The sera of these TIR mice did not contain tumor antibodies between reconstitution and YAS challenge, but a high YAS-antibody titer was present after YAS challenge and rejection. Immunofluorescence did not reveal any dramatic differences in the spleen and bone marrow content of T and B lymphocytes of TIR mice reconstituted with cells from normal donors and those reconstituted with cells from the YAS-immunized donors. Transfer of YAS-resistance was abolished when the bone marrow cells from immunized donors were treated with Thy 1.2 antiserum and complement, or when bone marrow donors were injected with cyclophosphamide 1 day after immunization. Cyclophosphamide was also shown to induce strong and specific suppression of YAS-antibody production in normal mice.


Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation.

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients received a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with successful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration.


Properties of cardioinhibitory factors produced in shock.

The widespread occurrence of circulating cardioinhibitory factors in many types of circulatory shock and in a variety of mammalian species is impressive. This review summarizes the properties of the nine best-known factors with regard to their occurrence, chemical properties, sites of origin, biological actions, and pharmacological modification. Cardioinhibitory factors appear to play a significant role in the pathogenesis of circulatory shock. There now are pharmacological means available with which to prevent the formation of such factors. With knowledge on the chemistry of cardioinhibitory factors rapidly accumulating, it is anticipated that specific antagonists to the action of these factors will become available in the near future.


The effect of luteinizing hormone-releasing factor on human chorionic gonadotropin secretion.

The effect of luteinizing hormone-releasing factor (LRF) on secretion of human chorionic gonadotropin (hCG) by the human placenta in culture was studied. A specific stimulation of hCG secretion was observed. The stimulation of hCG production correlated with the LRF dose in the culture medium. On the other hand, the secretion of human chorionic somatomammotropin was not affected. These data demonstrate a specific action of LRF on placental production of hCG in vitro.


Clinical studies with d-TRP6-luteinizing hormone-releasing hormone in men with hypogonadotropic hypogonadism.

Three male patients, diagnosed to have hypogonadotopic hypogonadism, were treated with intramuscular injections of 10 microgram of D-Trp6-luteinizing hormone-releasing hormone (D-Trp6-LH-RH) every 8 hours for more than 90 days (13 to 17 weeks). The gonadotropin and testosterone concentrations reached levels twice as great during the treatment as those measured previously and on one occasion increased 5-fold. Before treatment, the patients were clinically in grade 1 on Tanner's scale (Growth at Adolescence, Second Edition. Oxford, Blackwell Scientific Publications, 1962) but after treatment they advanced to grades 2 to 4. Testicular sizes before treatment were between 2 and 2 according to the scales of Waaler et al. (Acta Paediatr Scand [Suppl]249:1, 1974) and afterwards between 4 and 10. The penis of one of the patients grew 3 cm. The testicular biopsy after treatment showed significant increases in the number of Leydig and Sertoli cells. After treatment, spermatogonia were present in increased number, together with a much higher population of cells corresponding to additional stages of development (spermatids). We are of the opinion that therapy with D-Trp6-LH-RH may be beneficial for such patients.


[Interrelationships between the enzymatic functions of the pancreas and small intestine during adaptive processes].

In rats fed for 4, 15, and 30 days with increased amount of proteins, lipids, and carbohydrates, considerable shifts occurred in activity of enzymes of the pancreas (amylase, protease, and lipase) and small intestine (gamma--amylase, maltase group, invertase, peptidhydrolase, monoglyceriflipase). Mathematical analysis suggested a close connection between the adaptive shifts in the enzyme systems maintaining the lumen and the membrane types of digestion. The protein diet augments the proteolytic enzyme chain the lipid diet--the lipolytic chain, and the carbohydrate diet--the carbohydrate chain. The shifts should be regarded as an integrative adaptive response of the enzyme spectrum of the pancreas and small intestine to alterations in the food composition.


[Role of substrates in providing energy for the secretory function of the stomach].

Glycogen, general lipids and free fatty acids (FFA) contents in mucosa of the dog stomach were studied at rest, in latency period, and at peak secretion induced by histamine or carbocholine. Histamine increased the glycogen and FFA contents in mucosa and decreased that of general lipids. Carbocholine reduced the glycogen content at peak secretion as compared with the latency period. The decrease in general lipids content was less obvious than that induced by histamine. The data obtained suggest that energy supply for acid and pepsin formation in the gastric mucosa depends on the substances applied; lipids are mainly used for HCl formation, and glycogen - for pepsinogen formation.


[Histological study of pancreatic islets in hypothalamic obese rats (author's transl)].

It has been considered that hyperinsulinemia is one of the important factors in the development of obesity. With the purpose of investigating the mechanisms of hyperinsulinemia in obese rats induced by hypothalamic lesions (HTL), the time-caused changes in body weight, blood glucose and plasma immunoreactive insulin (IRI) levels in addition to histological changes in the pancreatic islet were studied. The following results were obtained. 1. The development of obesity, a rise of plasma IRI level and an enlargement of pancreatic islets were found in HTL rats. The enlargement of pancreatic islets was directly proportional to body weight, index of obesity and plasma IRI level. 2. The B cells of the pancreatic islets of HTL rats revealed well-developed Golgi apparatus and rough endoplasmic reticulum, and numerous degranulated and pale secretory granules. 3. A number of mixed cells were shown in the periphery of the pancreatic islets of HTL rats. 4. Emiocytotic phenomena of the granular discharge were encountered frequently in the B cells of the pancreatic islets of HTL rats. These histological findings of the B cells in HTL rats well reflected hypersecretion of insulin in this type of obesity.


Localization of a nuclear envelope-associated protein by indirect immunofluorescence microscopy using antibodies against a major polypeptide from rat liver fractions enriched in nuclear envelope-associated material.

The location of a specific major polypeptide present in nuclear pore complex-enriched fractions from rat liver was examined by indirect immunofluorescence microscopy using chicken antibodies against this polypeptide. In both whole cell preparations of cultured cells grown on cover slips (mouse 3 T 3, rat kangaroo PtK2) and in frozen sections through liver and mammary gland tissue a strongly preferential, if not exclusive, binding to the nuclear periphery of interphase cells was observed. The specificity of this localization was demonstrated in these cells by the decoration of chromatin with antibodies against histones and of elements of the endoplasmic reticulum--outer mitochondrial membrane--system with antibodies to cytochrome b5. In addition, the localization was examined by electron microscopy using frozen sections and "immunoperoxidase" techniques. The results suggest that this polypeptide is contained in a protein specific for the nuclear periphery, probably closely associated with the peripheral chromatin.


Double blind clinical trial of mazindol on weight loss blood glucose, plasma insulin and serum lipids in overweight diabetic patients.

Mazindol, a drug with tricyclic structure unrelated to amphetamine and other anorectic drugs, has been used as an anorectic agent in a double blind clinical trial at a dose of 2 mg/day for 12 week (mazindol v. s. placebo), associated with a 1000 calorie diet on 46 obese diabetic patients. Thirty seven patients completed the trial with no significant difference between the two groups in the drop-out population; mazindol was well tolerated. In the mazindol-treated group the mean weight loss was 13.5 kg (22.3%) which was significantly greater (p less than 0.001) than in the placebo treated group where the mean weight loss was 4.2 kg (9.8%). Comparing the two groups after the 12 week trial, decrease in fasting blood glucose, serum insulin and triglycerides was not significant. In the mazindol-treated group a significant decrease of serum cholesterol, triglycerides and of the mean area under the curve of insulinemia during the OGTT has been observed. In the placebo treated group only serum triglycerides decreased significantly. The variations of plasma insulin and serum cholesterol were found to be correlated to the magnitude of weight loss. In conclusion mazindol is an effective drug for weight loss on the whole well tolerated but without specific properties on metabolism.


[Diagnosis and management of the aminoacidopathies (author's transl)].

Since its description by Garrod, the concept of the "inborn errors of metabolism" has become a clinical reality that the physician cannot ignore. The aminoacidopathies represent a group historically notable in that they represent the first diseases recognized as metabolic in origin (alcaptonuria, albinism) and for which some measure of therapeutic success can be claimed. Dietary prophylaxis of the encephalopathy of phenylketonuria is a prominent example. Much progress has been made in the understanding of the aminoacidopathies that touch upon aspects as diverse as semiological study and prevention by pre- and neo-natal diagnosis. This brief overview presents the basic clinical, biochemical, genetic, physiopathological and therapeutic principles of these diseases. It provides representative examples of the diagnostic approach and draws particular attention to the need and the role of cross-disciplinary teamwork in the diagnosis and continuing care of the patient. While we wait for new methods of genetic correction, the main goal must be to prevent the clinical consequences of the metabolic defect.


Parietal cell vagotomy in dogs. A comparative study of the effects on gastric secretion and antral muscle contraction.

The aim of this work was to further investigate whether it is possible, through parietal cell vagotomy (PCV), to obtain both a complete suppression of the gastric secretory response to vagal impulses and to retain a normal contractile response of the antral muscle. Acid and peptic secretions, the electrical activity and the force of circular antral contractions were simultaneously studied in dogs, before and after PCV, under 2-deoxy-D-glucose (2DG) and pentagastrin (PG) stimulation. After PCV, the response to 200 mg/kg 2DG was reduced by about 70% for acid and 80% for pepsin; the slopes of the dose-response curves were significantly reduced after PCV. The slope of the regression line pepsin/acid after 2DG was decreased following PCV. The mean acid response to PG was reduced about 50% after PCV. Plasma immunoreactive gastrin increased following 2DG, and the variations were identical before and after PCV. The gastric control electrical activity in basal conditions (fasted dogs) and following 2DG was similar before and after PCV. The antral contractile response to 2DG was reduced by about 40% after PCV. In conclusion, when PCV induced an 80% reduction in the gastric secretory response to maximal vagal stimulation by 2DG, the contractile antral response was not entirely normal. This effect might be due either to a partial antral denervation or to some intrinsic influence of the denervated gastric body upon the strength of antral contractions.


Esophageal tamponade for bleeding varices. Controlled trial between the Sengstaken-Blakemore tube and the Linton-Nachlas tube.

To investigate the effectiveness and safety of the Sengstaken-Blakemore (SB) tube compared with the Linton-Nachlas (LN) tube, a randomized clinical trial was carried out between both types of balloon. Seventy-nine patients suffering from gastrointestinal bleeding attributed to esophagogastric varices were included in the study. Both types of esophageal tamponade showed great effectiveness in obtaining primary hemostasis (86%), but when the bleeding was from esophageal varices, the SB tube achieved permanent hemostasis more frequently (52%) than did the LN tube (30%). In bleeding gastric varices the SB tube failed in all of the cases, but primary hemostasis was obtained with the LN tube in 50% of them. Better tolerance and greater effectiveness were obtained when the SB tube was applied without external traction. The usefulness of esophageal tamponade for bleeding varices was higher when performed within 6 hr of the onset of hemorrhage.


Gastrin-producing cells in ectopic gastric mucosa of developmental and metaplastic origins.

Immunocytochemical techniques using antigastrin antibody were employed to localize G cells in ectopic gastric mucosa of metaplastic and congenital origins and to compare their distribution with that in normal gastric mucosa. Five examples of Barrett's esophagus, 8 Meckel's diverticula, and 2 small bowel duplications were studied. Although G cells were absent in the gastric mucosa from all cases of Barett's esophagus, four Meckel's diverticula and one small bowel duplication contained G cells. In all instances of congenitally derived ectopic gastric mucosa where G cells were demonstrable, the gastric mucosa showed areas of antropyloric differentiation, whereas in the remaining cases the ectopic gastric mucosa was exclusively of the body-fundic type. It is concluded that the presence of G cells within ectopic gastric mucosa of Meckel's diverticula and small bowel duplications in foci of antropyloric differentiation reflects their developmental origin, whereas the absence of G cells in Barrett's esophagus is in keeping with its metaplastic derivation.


Apoprotein synthesis by human duodenojejunal mucosa.

We tested whether human duodenojejunal mucosa is able to synthesize apoproteins from amino acid precursors because lipoprotein-like particles are visualized by electron microscopy in human absorptive cells and because apoproteins are synthesized by the perfused rat intestine. Duodenojejunal biopsies from 21 normal fasting volunteers were incubated with L-[U-14C]leucine; 15.6 +/- 3.3 nmoles of the [14C]leucine was incorporated into protein by 100 mg wet weight of biopsies during an incubation of 2 hr. No [14C]leucine was incorporated by boiled biopsies. Homogenates of incubated biopsies were fractionated by ultracentrifugation: 43 +/- 2% of the incorporated 14C as found in the d less than 1.006 fraction; 3.2 +/- 0.6%, 8.1 +/- 1.0% and 48 +/- 2% were found to be associated with the d = 1.006 to 1.063, d = 1.063 to 1.25, and d greater than 1.25 fractions, respectively. The specific activity in the d less than 1.006 fraction was 5.6 times greater than that in the other fractions. Of the 14C incorporated into the d less than 1.006 fraction, 10.8, 7.2, and 7.1% were specifically precipitated by rabbit antihuman apoproteins A-I, A-II, and B, respectively. Of the 14C incorporated into the d = 1.006 to 1.063 fraction, 11.3 4.1, and 8.5% were specifically precipitated by rabbit antihuman apoprotein A-I, A-II, and B,  respectively. Approximately 5% of the 14C incorporated by the d = 1.063 to 1.25 fractions were precipitated by rabbit antihuman apoprotein A-I or A-II. None of the d less than 1.25 fractions precipitated a significant amount of radioactivity with rabit antihuman apoprotein C-II, or antiarginine-rich apoprotein. None of the antibodies precipitated radioactivity from the d greater than 1.25 fraction. These experiments suggest that human duodenojejunal mucosa is able to synthesize in vitro apoproteins A-I, A-II, and B from amino acid precursors. The specificity of the immunoprecipitates was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis.


Prostaglandin and cimetidine inhibit the formation of ulcers produced by parenteral salicylates.

Antral ulcers were produced in unanesthetized rats in 3 hr by simultaneous intravenous administration of acetylsalicylic acid (ASA) and gastric perfusion with 0.15 M HCl. Intravenous infusion of ASA alone or gastric perfusion with HCl alone produced no antral ulcers. Plasma salicylate levels ranged from 250 to 350 microgram ml-1. 16-16 Dimethyl prostaglandin E2 (DMPGE2) (0.04, 0.40, 4.0 microgram kg-1 hr-1) and cimetidine (10, 50 mg kg-1 hr-1) significantly decreased the severity of antral ulcers in a dose-dependent fashion. In a separate group of unanesthetized rats prepared with gastric fistula and pylorus ligation, pepsin output during administration of parenteral ASA and gastric perfusion of HCl was reduced by the highest doses of 16-16 DMPGE2 and cimetidine. However, addition of exogenous pepsin to the HCl perfusate had no effect on the inhibition of ulceration afforded by 16-16 DMPGE2 and cimetidine. We conclude that both 16-16 DMPGE2 and cimetidine protect antral mucosa against injury by parenteral ASA plus topical HCl by some means other than their effect on acid and pepsin output.


K-cell-mediated antibody-dependent cellular cytotoxicity in chronic active liver disease.

These studies were designed to determine the ability of antihepatocyte antibodies from patients with chronic active liver disease to induce killing of rabbit hepatocytes by normal lymphocytes. Normal subjects and patients with chronic persistent hepatitis or chronic active liver disease served as sources of sera, and normal human peripheral lymphocytes and their subsets (T-enriched, K-enriched, and B) served as effectors. Only sera from patients with chronic active liver disease possessed membrane-reactive IgG directed against the surface of rabbit or human hepatocytes. After pretreatment of rabbit hepatocytes with sera from patients with chronic active liver disease, marked cytotoxicity mediated by normal lymphocytes was observed. K-enriched cells mediated the antibody-dependent cellular cytotoxicity, whereas T-enriched cells and B-cells did not. Heat-aggregated human IgG blocked the antibody-dependent cellular cytotoxicity. These data suggest that sera from patients with chronic active liver disease contain IgG antihepatocyte antibodies, which are capable of inducing normal K-cells to kill rabbit hepatocytes in vitro.


Topical aspirin plus HCl gastric lesions in the rat. Cytoprotective effect of prostaglandin, cimetidine, and probanthine.

The effect of representative agents of three classes of antisecretory compounds; prostaglandins, histamine H2-receptor antagonist, and anticholinergic agents, on acute gastric mucosal lesions produced by topical aspirin (200 mg/kg) plus HCl (150 mM) in the pylorus-ligated rat was studied. Acid was given exogenously so as to negate any antisecretory effect of the drugs studied. Both nonantisecretory and antisecretory doses of each agent as determined by preliminary secretory studies were employed. The postaglandin analogue 16,16-dimethyl prostaglandin E2, the H2-receptor antagonist cimetidine, and the anticholinergic agent probanthine, in both doses studied, all significantly reduced lesion formation. The H1-receptor antagonist mepyramine neither protected by itself nor enhanced the protective effect of cimetidine. Pepsin release into the gastric content increased with increasing mucosal damage. However, addition of pepsin to the gastric instillate had no effect on severity lesions in any group, which indicates that the increased pepsin was the result of, and not the cause of, the mucosal damage. The findings indicate that all three classes of antisecretory agents studied are also cytoprotective, i.e., they can protect against gastric mucosal injury by topical aspirin plus HCl by some mechanism other than inhibition of acid and pepsin secretion.


Comparison of intraduodenal and intravenous administration of amino acids on gastric secretion in healthy subjects and patients with duodenal ulcer.

The ability of an amino acid mixture given intraduodenally or intravenously to stimulate gastric secretion is compared in healthy subjects and in duodenal ulcer patients. Graded amounts of amino acids by both routes produced a similar increase in acid output in healthy subjects, reaching about 30% of the maximal response to pentagastrin. Serum gastrin concentrations remained virtually unchanged but serum alpha amino acid nitrogen levels were about twice as high with intravenous as with intraduodenal administration. Intravenously administered amino acids produced a significantly higher acid output in patients with duodenal ulcer than in healthy subjects, but did not produce a significant increase in gastric acid or pepsin secretion when combined with a pentagastrin infusion as compared with pentagastrin alone. Cimetidine (2 mg/kg/h) added to intravenous amino acid infusions caused almost complete suppression of acid secretion. This study indicates that amino acids are capable of stimulating gastric secretion after intraduodenal and after intravenous administration. The response to the latter is significantly higher in patients with duodenal ulcer than in healthy subjects, does not appear to involve gastrin release, is not affected by pentagastrin, and is strongly suppressed by histamine H2-blocker.


Preparation of lymphoid cells from small specimens of human gastrointestinal mucosa.

Several methods for the preparation of cell suspensions from human gastrointestinal mucosa were investigated. Satisfactory suspensions were obtained by incubating tissue fragments in a solution of collagenase and hyaluronidase overnight at 4 degrees C followed by 30 minutes at 37 degrees C. The resulting suspension contained large numbers of intact lymphoid cells; in addition, variable amounts of epithelial cells and cell debris were present. A high proportion of the lymphoid cells were shown by immunofluorescence to contain immunoglobulin (mainly IgA). Viability of these cells was demonstrated by dye exclusion, their ability to survive in short-term culture, and their ability to incorporate radio-labelled amino acid into immunoglobulin in vitro.


A gastrin releasing peptide from the porcine nonantral gastric tissue.

This paper presents evidence for the existence in extracts from porcine non-antral gastric tissue of a peptide capable of causing substantial rises of plasma immunoreactive gastrin levels in a dose dependent manner and of stimulation of gastric acid and pepsin secretion. Obtained data show that the peptide is basic and that its gastrin releasing properties are at least partially resistant to atropinisation and beta-receptor blockade. Antrectomy almost eliminates the rise in plasma IRGa when the peptide is administered. The possible relationship of this peptide to amphibian bombesin is discussed.


Clinical trial of deglycyrrhizinised liquorice in gastric ulcer.

Ninety-six patients with gastric ulcer were randomly allocated to treatment either with deglycyrrhizinised liquorice or placebo. After four weeks no differences were found between the treatment groups in the proportions with complete healing, whether assessed by gastroscopy or radiology, or in the percentage reduction in ulcer area, or in clinical improvement.


Experiments on prevention of the endotoxin-abortifacient effect by radiodetoxified endotoxin pretreatment in rats.

Endotoxemia has been induced in pregnant rats by intravenous injection of 1 mg Escherichia coli endotoxin which resulted in intrauterine death and abortion of fetuses in 24 h. The abortifacient effect of endotoxin was prevented in 90% by 200 microgram radiodetoxified endotoxin, injected intravenously 24 h earlier. The authors suppose that the radiodetoxified endotoxin can be a good tool also in the prevention of human septic (endotoxin) shock in pregnancy.


Management of lost finger tips in children.

A trial was run in the Hand Unit of the Royal Victoria Infirmary, Newcastle upon Tyne, involving sixty consecutive children who has sustained finger tip injuries with tissue loss over a period of three years. The three forms of treatment used in different groups of children were split skin grafting, local flap repair, and a conservative method, with twenty children in each group. The results are compared from both functional and cosmetic points of view and the results analysed.


Three-dimensional observations of microvasculature of human finger skin.

Resin casts of the fine vasculature of human digits in normal and some abnormal states were studied by scanning electron microscopy. The palmar skin contained terminal loops aligned with the finger-print, while the dorsal skin vasculature consisted of a coarse meshwork. Fine vessels in the nail bed had a parallel orientation as far as the lunula in adults, but were straight right up to the nail roots in young children. A deeper meshwork of capillaries (corresponding to the rete subpapillare and the rete cutaneum), vessels of the glomus bodies, and the dense meshwork of sweat glands were visible on the sagittal cut surface of the samples. A severely scarred index finger showed a coarse meshwork of surface capillaries. A skin-grafted index finger showed repaired terminal loops resembling normal skin in the area of grafted skin. The fine architecture of the digital vessels observed was discussed in terms of the physiology of blood circulation to the skin.


[Effect of alpha-mercaptopropionylglycine (alpha-MPG) and sodium dipropylacetate (DPA) on antibody formation (II). Immunosuppression induced by carcinostatic agents and glucocorticoid (author's transl)].

Previously, we reported that alpha-MPG and DPA stimulated humoral immuno-responses. In the present work, we investigated the effect of alpha-MPG and DPA on immunosuppression induced by carcinostatic agents including cyclophosphamide (CP), azathioprine (AP), methotrexate (MTX), actinomycin D (AcD) and mitomycin C(MMC) as well as prednisolone (Pred). The formation of hemolytic plaque forming cell (HPFC) in spleen of mice was clearly inhibited by treatment with immunosuppressive agents given s.c. for 5 days from the immunization. When alpha-MPG and DPA were given i.p. concomitantly with immunosuppressive agents, HPFC formation was not inhibited except when the combination of MTX and alpha-MPG was injected. With alpha-MPG, there was a tendency toward disappearance of the leucopenia induced by AP, MMC and Pred.


[Male sex hormones and their derivatives. Pathophysiology and therapy].

After a short review of the chemistry, biosynthesis and physiology (regulation of production and secretion, effects) of the male sex hormones, the possible disturbances of the male sex hormones, the possible disturbances of the male sex function are pathophysiologically listed and some instructive diseases, as castration, testicular feminization, Kallmann syndrome, prolactinoma and flour-bag-drawfs, are discussed. Regarding the main topic, influence of general diseases on sex hormones, the implications of the cirrhosis of the liver and the dialysis in kidney disease are listed as examples. Indications and particularly the contraindications and dangers of testosterone and anabolic steroid therapy are discussed.


[Practical significance of syphilis serodiagnosis].

Recent developments in syphilis serology are set down. The new specific tests for treponema pallidum are described. Reactivity in different stages of the disease including congenital and neurosyphilis is discussed. An outline is given of the possibilities of the IgM-FTA-ABS and 19 S IgM-FTA-ABS tests. Syphilis serology today requires only 3 tests: a screening procedure, where the specific AMHA-TP is the method of choice, FTA-ABS test should be used for confirmation, and the quantitative VDRL in order to follow up the effectiveness of treatment.


[Predisposing factors in candidiasis. Animal experimental studies and clinical findings with special regard to immunity].

In the presence of predisposing factors which are considered as a local or general impairment of the host's defence mechanisms, the opportunistically pathogenic character of Candida albicans transforms into a parasitic one thus favoring the development of candidosis. The clinically reporting part of the paper deals with the predisposing factors and clinical features of candidosis. In animal experiments, we attempted to find out to what extent and whether exclusively the cellular immune system protects the host from Candida albicans infection. Our findings suggest that the cell-mediated immunity and phagocytosis are of fundamental importance in overcoming a candidosis and in resistance to Candida albicans. The humoral immune system plays a minor role, which may be limited to the stimulation of macrophages.


[New aspects of anastomoses of severed peripheral nerves].

Nerve anastomoses glued with Fibrinkleber are stabilized against the plasminogen-activators of the tissue by natural and synthetical inhibitors of fibrinolysis administered locally and systemically. So the early lysis of the clots is inhibited. The glued nerve anastomoses do not reach the bond strength of sutured nerves, but foreign body reactions are avoided by this method. Glueing nerves with Fibrinkleber combined with inhibition of fibrinolysis seems to be a good method reuniting severed nerves, especially in nerve transplantation, provided too much tension is avoided.


Catecholamine-induced changes in plasma glucose, glucagon and insulin in rabbits: effects of somatostatin.

The present study was conducted to determine if glucagon release is involved in the hyperglycemic response to epinephrine and isoproterenol in the fasted and fed, unanesthetized rabbit. Epinephrine produced dose-related increases in plasma glucose and glucagon levels in fed and fasted rabbits whereas isoprotereol produced modest hyperglycemia without hyperglucagonemia. Infusion of somatostatin suppressed epinephrine-induced glucagon release and this was correlated with a 50% reduction in the hyperglycemic response. These data suggest that epinephrine-induced glucagon release is the primary reason for the difference in hyperglycemic activity between epinephrine and isoproterenol in the unanesthetized rabbit.


Secretion and immunochemical properties of the trypsin inhibitor from bovine colostrum.

A trypsin inhibitor was isolated from bovine colostrum by affinity chromatography. Immunoelectrophoresis detected two immunogenic components in the isolated inhibitor, but only one of these was specific for the inhibitor; the other one was identical with an antigen present in liver, kidney, spleen, adrenal, thyroid, thymus, brain, ovarian, testicular and udder tissue and in bull seminal plasma. Using immunoabsorption and immunofluorescence it was shown that the antigens specific for the trypsin inhibitor of colostrum could be demonstrated only in the tissue of an udder that is secreting colostrum. The inhibitor is secreted by the secretory epithelium of the milk alveoli of the udder, during the period when the latter secretes colostrum. This inhibitor was not detected in the milk. Cross-reaction between antisera to colostral inhibitor and basic pancreatic inhibitor or seminal plasma inhibitors yielded negative results. Antiserum to bovine colostral inhibitor showed a positive reaction with inhibitor isolated from porcine colostrum.


Molecular weight and hydrodynamic properties of a proteinase A inhibitor from baker's yeast.

The molecular weight of the proteinase A inhibitor IA3 from baker's yeast was determined by different methods. From gel-filtration experiments, a molecular weight of 19 000 was calculated for the native inhibitor, while under denaturing conditions a molecular weight of 7400 was found. From electrophoretic experiments with the native protein, a molecular weight of 9000 was calculated. A similar value was obtained from the analytical ultracentrifuge, even at a protein concentration of 12 mg/ml. The diffusion coefficient and the partial specific volume were measured and from these data the frictional ratio and the Stokes radius were calculated. These parameters indicate that the relatively high apparent molecular weight calculated from the gel-filtration experiments is caused by the assymetric shape of the inhibitor molecule rather than by an aggregation of subunits.


A new inhibitor protein from rat uterus against yeast proteinase B.

An inhibitor of yeast proteinase B has been enriched from uterine smooth muscle (myometrium) of the rat. This inhibitor behaves like a glycoprotein and has a molecular weight of 90 000. It activity can be clearly distinguished from the proteinase inhibitory activity of serum. Proteinase B inhibitory activity has also been demonstrated in liver, lung, heart, skeletal muscle, spleen and brain and these activities, too, are clearly distinguishable from the serum inhibitory activity. The activity in rat uterus decreases during the postpartal period.


Synopsis'78--NHI: a matter of degree.

Every year around this time, health care oracles ask the same questions about national health insurance: Will we get it? What kind? How much? When? We already have NHI, the author says. The question now is whether or not we should have more.


A simple technique for the utilization of postmortem tracheal and bronchial tissues for ultrastructural studies.

Human tracheal and bronchial tissues were taken from autopsy cases within five hours of death. The tissue was placed in a modified Krebs-Henseleit solution at either 37 degrees C. or 7 degrees C. A combination of 95 per cent oxygen and 5 per cent carbon dioxide was bubbled through the Krebs-Henseleit solution. Two hours after equilibration of the tissue in the bath at 37 degrees C. and electrical field stimulation was applied to the tissue and, if the tissue was physiologically active, it was utilized for further studies. At the termination of these studies the tissue was processed for electron microscopy. Control tissue was taken directly from the same area as the test tissue and was processed for electron microscopy without immersion in the Krebs-Henseleit solution. The tissue, after immersion in the Krebs-Henseleit solution for at least three hours, showed evidence of substantial recovery from the period of anoxia.


Thymic hyperplasia and neoplasia: a review of current concepts.

Although the term thymic hyperplasia is used most commonly to indicate the occurrence of germinal centers in the thymus, cognizance must be taken of the fact that such centers may occur in apparently normal thymuses in both children and adults. A concept of thymic compartmentalization is proposed with origin of germinal centers in the perivascular space (extraparenchymal compartment) of the thymus. These germinal centers contain a high percentage of B lymphocytes in contrast to the true thymic parenchyma. Although the significance of germinal centers in the thymus parenchyma. Although the significance of germinal centers in the thymus in myasthenia gravis remains controversial, removal of nonneoplastic thymus in this condition is of proven therapeutic value. A variety of neoplasms originating in the thymus have previously been lumped together under the single term "thymoma." It is apparent, however, that thymoma, thymic carcinoid, various lymphomas, and germ cell tumors that arise in the thymus differ not only pathologically but also in their clinical behavior. Thymoma is regarded as an epithelial neoplasm and ultrastucturally is characterized by many desmosomes and tonofilaments. The lymphocytes do not behave in a malignant manner, and lymphomas of the thymus should be sharply separated from true thymoma. Poorly differentiated thymic carcinoma and histiocytic lymphoma may be distinguishable only by the electron microscopic demonstration of desmosomes and filaments in the thymic carcinoma. The evidence that Hodgkin's disease of the thymus ("granulomatous thymoma") is not a variant of thymoma appears overwhelming. Lymphoblastic lymphoma of the thymus is a distinctive neoplasm that is especially prevalent in teenage males. High levels of terminal transferase characterize the lymphoblasts and there is a striking tendency for leukemia to occur. Thymic carcinoid is usually nonfunctional, although one-third of the reported cases are associated with Cushing's syndrome. On light microscopy a ribbon pattern and punctate necroses are characteristic of thymic carcinoids. Electron microscopic demonstration of many dense core granules is invaluable in establishing this diagnosis. An important clue to the diagnosis of thymic seminoma (a neoplasm that shows the same radiosensitivity as its testicular counterpart) is the frequent presence of epithelioid and giant cell granulomas and germinal centers. Separation of the various thymic neoplasms described not only is justifiable on pathologic grounds but is often essential for appropriate patient investigation and treatment.


Electron microscopic X-ray microanalysis of localized element concentrations in human cardiomyopathies: a pilot study.

The elemental content in localized cellular regions of human myocardial biopsy specimens was studied by electron microscopic x-ray microanalysis. The elements detected were phosphorus, sulfur, chlorine, calcium, and zinc and occasionally tracrs of iron and copper. Nucleoli and heterochromatin contained the highest concentrations of phosphorus and calcium, whereas sulfur was prominent in sarcomeres, dark mitochondria, and secondary lysosomes. Dark mitochondria often had more phosphorus, sulfur, and calcium than swollen, paler ones.


Age-dependent variations of antibody avidity.

Age-dependent variations of antibody avidity were studied in the C3HeB/FeJ mouse. Spleen cells from donors of different ages (10--720 days) were transferred and stimulated with TNP-HRBC in lethally irradiated syngenic recipients. The anti-TNP antibody response of the donor cells was estimated from the number of direct PFC per recipient spleen by the Jerne technique with TNP-SRBC. Avidity of the antibodies secreted by PFC was evaluated from the amount of added TNP-BSA that inhibited 50% of the anti-TNP PFC. Under these experimental conditions allowing the exclusion of any influence of the donor milieu during the immune response, age-dependent variations of the antibody response and avidity could be attributed to changes in the donor spleen cell population. Avidity was found to increase with the response and to vary parabolically with age. After appropriate correction of the number of PFC to make it independent from age, avidity values were fitted by a multiple curvilinear regression in which the independent variables playing a significant role were the corrected number of PFC in its linear term and the age in its linear and quadratic terms. From comparison of the standard coefficients of this regression, the observed variations of avidity could be attributed in part (82%) to the response and in part (18%) to the age. For any value of response, avidity increased 15-fold from day 10 to reach a maximum at day 110 and then declined 5-fold at the age of 720 days. Heterogeneity of avidity also changed parabolically with age as high avidity classes were present in adulthood and absent at 10 and 720 days.


Induction and modification of anti-TNP reaginic and IgG antibody responses by reactive trinitrophenyl derivatives.

The anti-TNP antibody response of mice exposed to picryl chloride is a response where IgE antibody can be preferentially produced. Skin-painting with picryl chloride induces IgM, IgG and IgE antibody. After repeated painting the titre and persistence of the IgE but not IgG antibody is increased. Feeding picryl chloride does not induce antibody but it does produce unresponsiveness for IgG without affecting responsiveness for IgE. Injection of picryl sulphonic acid produces unresponsiveness for both classes. The unresponsiveness (induced by feeding or injection) is found for responses to picryl chloride but responses to TNP-KLH are barely affected. Both the IgE and IgG responses to picryl chloride are initiated in the lymph nodes and then develop in the spleen. IgE and IgG antibody production are both T-cell dependent but not influenced by adult thymectomy.


Microassay for immunoglobulin G antibodies to Treponema pallidum with radioiodinated protein A from staphylococcus aureus: immunoglobulin G response in experimental syphilis in rabbits.

Radioiodinated staphylococcal protein A (SpA) was used to detect the immunoglobulin G (IgG) antibody response to Treponema pallidum in experimental syphilis. This solid-phase assay is based on the principle that SpA binds avidly to the Fc portion of mammalian IgG. The optimal number of organisms for detection of antibody was 10(5) per microwell. Of eight fixatives, 10% ethanol gave an optimum immune binding ratio of infected to normal rabbit serus at a 1:100 serum dilution. Kinetic studies demonstrated maximum binding and the highest immune binding ratio (15:1) with a 60-min incubation each for antibody and (125)I-SpA, respectively. The IgG response in rabbits intratesticularly infected with live T. pallidum and bled at -1, 9, 30, 90, 180, and 480 days was detected first at 9 days, reached a peak at 30 days, and remained elevated for 480 days. Absorption studies with an extract of T. phagedenis biotype reiterii demonstrated that 65 to 85% of the total antitreponemal IgG response was specific for T. pallidum throughout the course of infection. The microassay was quantitative and detected less than 2 ng of antibody.


Enterotoxigenicity of enteropathogenic serotypes of Escherichia coli isolated from infants with epidemic diarrhea.

Enteropathogenic serotypes of Escherichia coli which have been incriminated by epidemiological evidence as responsible for epidemics of acute diarrhea in infants are often found to be nontoxigenic when tested by conventional systems such as Y1-adrenal, Chinese hamster ovary, and suckling mouse assays. Twelve such strains, representing four different enteropathogenic serotypes, were examined for their capacity to elaborate toxic materials which alter water transport. Ultrafiltration fractions prepared to contain either a high-molecular-weight, heatlabile or a low-molecular-weight, heat-stable form of toxin from each strain were perfused through rat jejuna in graded concentrations ranging from 100 mug to 0.1 ng/ml. Ten of the twelve enteropathogenic strains produced one or both toxin forms that induced water secretion at concentrations of 1 to 10 ng/ml. Values in this range are considered indicative of clinically significant enterotoxigenicity in this assay system, and toxins from well-documented toxigenic strains examined in this study were active at these same concentrations. Similar preparations from ten control strains from healthy persons were either inactive or evoked water secretion only at concentrations of 10 to 100 mug/ml. These observations suggest that enteropathogenic serotypes of E. coli isolated from epidemics of infantile diarrhea produce diarrhea by elaborating potent heat-labile and heat-stable toxin forms which alter water transport but which are inactive in conventional assay systems. The manner in which these toxins differ either quantitatively or qualitatively from those which stimulate the conventional test systems is unknown.