Ethanol-reinforced behavior of rats with concurrent access to food and water.

Dippers filled with water or an ethanol solution were presented to male Wistar rats contingent on lever-pressing under a concurrent fixed-ratio 1 (water) fixed-ratio 1 (ethanol) schedule. During Phase I, when maintenance feedings were given during instead of following the daily 3-h sessions, the feedings increased drinking of both 8% (w/v) ethanol and water, with 8% ethanol being consumed in greater volumes than water. In Phase II, a 28-day transitional period from the food-deprived to the food-satiated state, continuous access to food during 3-h sessions moderately decreased 8% ethanol intake, and increased water intake and total liquid intake (water plus 8% ethanol). In Phase III, concurrent water and ethanol intake of food-satiated rats was compared over two identical series of ethanol concentrations (8, 11.3, 16, 22.6, 32, and 8% retest). Food was freely available in both the operant conditioning chambers and home cages. The number of dipper presentations of ethanol exceeded presentations of water for each rat at each concentration studied. Presentations of water were low in number and did not vary with the ethanol concentration. As the ethanol concentration was increased, the number of ethanol presentations decreased, while the quantity consumed (mg/100 g body weight/h) generally increased.


A near-lethal dose of ethanol, given intraperitoneally, does not affect memory consolidation of two different avoidance tasks.

Ethanol (3 g/kg, given i.p. as a 33% w/v solution), was given to adult Wistar rats 1 min after training in (1) a 50-trial session of shuttle avoidance, using buzzers and shocks, and (2) an inhibitory avoidance experience in a step-through apparatus. The animals were retested 7 days after training in condition (1), and 3 days after training in condition (2). There was no difference in retention scores between the ethanol-treated, saline-treated, or untreated animals. In addition, there was no evidence of an aversive effect of ethanol per se under any of the two training conditions, in spite of the fact that the dose of ethanol used caused a very profound ataxia, and was lethal for 14.3% of the animals (a slightly higher dose, 4 g/kg, is lethal for about 80% of our rats). These data do not favor the hypothesis that an acute administration of ethanol may influence memory consolidation.


Comparison of oral and intravenous methylphenidate.

Oral methylphenidate (1.0 mg/kg) and intravenous methylphenidate (0.5 mg/kg) were compared as to their ability to increase behavioral activation, pulse, blood pressure, and serum growth hormone. Intravenous methylphenidate was considerably more effective than oral methylphenidate in activating behavior and in increasing pulse and blood pressure. Although oral methylphenidate appeared to increase behavioral activation, this effect was not statistically significant.


The central antiserotonergic action of mianserin.

The central antiserotonergic action of mianserin (MS) was tested in mice, rats, and rabbits. MS, like cyproheptadine, to which it was compared, inhibits the head-twitch response to 5-hydroxytryptophan in mice and rats without affecting the pinna reflex. MS does not change the flexor reflex of the hind limb of the spinal rat; it antagonizes its stimulation induced by fenfluramine, LSD, and quipazine, but not that induced by clonidine. The hyperthermia in rabbits caused by the serotonergic stimulants cited above is also antagonized by pretreatment with MS. Unlike cyproheptadine, MS is not active in the oxotremorine test. The results indicate that at low doses MS is a central serotonergic-receptor blocker.


Evidence for cell loss in corpus striatum after long-term treatment with a neuroleptic drug (flupenithixol) in rats.

The number of nerve cells in two different areas of the corpus striatum (i.e., ventrolateral and dorsomedial) was estimated in rat brain after long-term (36 weeks) treatment with the neuroleptic flupenthixol. Nine rats were given weekly injections of 4 mg/kg flupenthixol dissolved in Viscoleo i.m., and seven rats received Viscoleo alone. Fourteen to 18 weeks after the last drug injection, the animals were decapitated and half of each brain was fixated with formalin for cell-count analysis and the remaining half used for a biochemical analysis (Nielsen, 1977). Separate cell counts in the ventrolateral and dorsomedial corpus striatum yielded a significant cell loss of approximately 10%, but only in the ventrolateral striatum of treated animals. These results suggest at least one concrete anatomical basis for the behavioral and biochemical deficits found in the same animals, as reported earlier. The results further suggest that persistent irreversible anatomical changes can follow long-term neuroleptic treatment. The inconsistencies of results regarding cell loss in the corpus striatum may be due to neglect of dorsal-ventral structural differences in corpus striatum.


Effect of intraperitoneally administered GABA on the locomotor activity of mice.

Gammaaminobutyric acid (GABA) was injected intraperitoneally (i.p.) into mice at doses from 25--2000 mg/kg, and spontaneous locomotor activity was recorded for the following 20 min. A slight but significant decrease in the spontaneous locomotor activity was noted only with the highest dose. The stimulation of motor activity induced by ethanol (2.4 g/kg i.p.) was significantly counteracted by GABA (100 mg/kg i.p. and upwards). A further suppression of ethanol-induced hyperactivity was reached by pretreatment with aminooxyacetic acid (AOAA, 15 mg/kg i.p.). The stimulation of motor activity induced by morphine (10 mg/kg i.p.) remained unaffected by even high doses of i.p. GABA. Motility produced by activation of postsynaptic catecholamine receptors, i.e., by apomorphine (3 mg/kg i.p.) and clonidine (3 mg/kg i.p.) following reserpine (10 mg/kg i.p.) and alpha-methyltyrosine (250 mg/kg i.p.) pretreatment, was not affected by i.p. GABA injections, whereas hypomotility caused by a low dose of haloperidol (150 microgram/kg i.p.) was enhanced. In conjunction with earlier biochemical data, these results suggest a certain access of blood-borne GABA to the CNS, leading to inhibition of dopaminergic neurons involved in motility regulation.


Preventive cranial irradiation in the treatment of acute lymphocytic leukemia in children.

From April 1971 to September 1977, 94 children with acute lymphocytic leukemia, in whom a complete clinical and hematologic remission had been obtained received preventive cranial irradiation at the University Clinic for Radiotherapy of Vienna. So far, only in 2 of the 94 patients an initial meningeal relapse occurred. After a minimum follow-up time of 3 years, the rate of primary CNS relapse is 8%. The combination of cranial irradiation and methotrexate intrathecally, beginning currently in the first month of the complete remission, seems to be the most effective and least hazardous regimen to prevent meningeal and CNS leukemia.


[Present state of the wide-field megavoltage radiotherapy of Hodgkin's disease. Fundamentals, performance, side effects (author's transl)].

Therapeutic results of Hodgkin's disease could be significantly improved by the introduction of megavoltage radiotherapy equipment and more profound knowledge about this disease. By this way, five year survival rates of 70% can be achieved for all stages and up to 100% for the early stages. The wide field technique enables the coverage of all lymph nodes with protection of non involved organs. Simultaneously, these improved technical conditions make optimal radiation planning necessary which demands numerous technical auxiliaries. Radiation type and radiation energy are important preconditions for the therapy; production and usage of shilding blocks are necessary for individual performance. The principle for optimal radiation dose distribution are measurements and calculations on the phantom which are now included in computer programs. Nevertheless, radiation of large volumes represent a high stress for the patient. Despite the improvement of the therapeutic results there are except the acute radiation side effects, also irreversible alterations. These can be analysed only after long time observations and has to be balanced with the therapeutic results. The knowledge of these side effects is very important for the radiologist. Beside that, the risk of induction of a second tumor has to be considered. The present possibilities of absolute control of this disease enables the overtreatment of lesions in the early stages. Therefore it has to be postulated to regard the present therapy concepts with attention and to consider the possible side effects.


Experience with a pair of matched diodes for constancy checks.

A unit is discussed which employs a pair of matched silicon diode detectors to check the constancy of the output, beam quality, field flatness, and symmetry of teletherapy equipment. The unit has proven useful, but the long-term stability of the diode-amplifier system must be considered, because two years of experience has demonstrated significant sensitivity changes in the diodes.


Prostaglandin biosynthesis in rabbit kidney medulla: inhibition in-vitro vs. in-vivo by aspirin, indomethacin and meclofenamic acid.

The non-steroidal anti-inflammatory drugs aspirin, indomethacin and meclofenamic acid were compared for their potency and duration of inhibition of prostaglandin biosynthesis in rabbit kidney medulla. Indomethacin and meclofenamic acid showed equal potency of inhibition in-vitro (IC50 0.88 micron and 0.85 micron respectively) while aspiring was a much weaker inhibitor (IC50 120 micron). In-vivo, indomethacin was the most powerful inhibitor (ID50 0.034 mg/kg) followed by meclofenamic acid (0.45 mg/kg) and aspirin (2.35 mg/kg). Studies on the duration of in-vivo inhibition by these compounds showed the effect of indomethacin and meclofenamic acid to be completely reversed within 4-6 hours. In contrast, return of kidney prostaglandin biosynthetic activity following aspirin inhibition is very slow and significant inhibition is still present 48 hours after a single aspiring injection. The inhibitory effect of aspirin in-vivo could be blocked by pretreatment with indomethacin, indicating that both drugs interact with related sites on the cyclo-oxygenase enzyme. The irreversible inhibition of the cyclo-oxygenase by aspirin as demonstrated in studies of other investigators suggests that the return of kidney prostaglandin synthetase activity after aspirin inhibition represents synthesis of new cyclo-oxygenase protein.


Metabolism of delta4-cis-PGF1alpha in the monkey.

This isomer of PGF2alpha is relatively resistant to metabolic degradation in the Cynomolgus monkey. Thus, 16-20 per cent of the amount injected was excreted unchanged in the urine. Five metabolites with 20, 18, 16 and 14 carbon atoms in the skeleton were identified. The data are similar to those earlier seen in the rat and further support the idea that this analogue of PGF2alpha could have a long half-life time in the mammalian body and thus a long duration of its pharmacological actions.


Effect of prostaglandin F2alpha on ovarian and pituitary function in the mid-luteal phase.

The effects of PGF2alpha infusion in a dose of 25 micrograms/min for 5 hours on serum levels of estradiol-17beta, progesterone, LH, FSH, TSH and prolactin, and on the pituitary hormone responsiveness to LRH and TRH were studied in 10 apparently healthy cycling women in the mid-luteal phase. No systematic alteration was seen in the pituitary and ovarian hormone levels during PGF2alpha infusion, and the pituitary hormone responses to releasing hormones were unaffected. Ovarian steroid production increased in response to increased gonadotropin levels after LRH injection during PGF2alpha administration. These results confirm that PGF2alpha is not luteolytic in humans and no apparent relationship between PGF2alpha and pituitary hormone secretion exists.


[Relative sensitivity of various cell cultures to the thermostable exotoxin of B. thuringiensis].

The "thermostable" B. thuringiensis exotoxin is active on cell cultures of Mammals "in vitro", except on the KB strain from a human tumor. The primary cultures are the most sensitive: first, with monkey kidney cells, the growth is inhibited by 0.1 mg of toxin per ml; next, the young rabbit kidney cells react to 0.25 mg of toxin per ml. The established lines of cells come last: human diploid cells (Lyon 4) and heteroploid cells (BHK21C13), with the same active dose of 1 mg of toxin per ml. No protection is obtained by adding ATP to monkey kidney cells at the same time as the exotoxin.


Laser differential light scattering bioassays for selected antitumor agents.

Bioassay methods for actinomycin D, 6-thioguanine, and adriamycin which utilize laser light scattering from suspensions of drug-sensitive bacteria have been developed. In 3 hours, serum and urine levels of the 3 drugs can be reproducibily measured. A sample volume of 0.1 ml may be assayed with a precision of +/- 10%. The linear response range for actinomycin D was 0.03 to 3.0 microgram/ml. For 6-thioguanine and adriamycin the linear responses range was 0.03 to 10.0 and 0.25 to 10.0 microgram/ml, respectively. Thetively. The present studies further confirm the general utility of differential light scattering as a rapid and inexpensive assay procedure of broad application.


Diagnosis of enzootic bovine leukosis: a comparison of haematological and immunodiffusion tests.

A total of 657 cattle from three different herds were tested for the presence of specific antibodies against EBL antigens by means of the immunodiffusion test and the results compared with the classification according to the lymphocyte counts. All animals with pathologically raised lymphocyte counts showed a positive immunodiffusion test reaction. In the majority of these both antigens, 'p24' and 'gp', gave positive results; in a smaller number antibodies against the gp antigen only were detected, but never against the p24 antigen only. It is concluded that for field testing programmes the use of the gp antigen is sufficient. In future experiments, however, both antigens should be employed, because the lack of one of them might perhaps prove to be correlated with the future course of the disease. The absence of specific antibodies, together with a normal number of lymphocytes, in young animals should, however, not lead to the conclusion that they are free of the disease.


The effects of passive antibodies to egg albumin on active immunity in lambs to Brucella abortus and egg albumin.

The long-term effects of colostrum on active immunity to two unrelated antigens are described. Lambs were fed with pooled colostrum--to equalise passive immunity--with or without added antibodies to egg albumin (Ea). There were significant breed differences in the response both to Brucella abortus measured at one month of age, and to Ea, measured at three months of age, although there was no significant correlation between the responses to the two antigens, either within or between breeds. Surprisingly, whereas antibodies to Ea caused a four-fold reduction in antibody production to B abortus, they did not affect the overall mean response to Ea. But the timing of the response to Ea was significantly affected, suggesting that the low persisting concentrations of antibody had caused qualitative changes in the response.


The scaling of maximal oxygen consumption and pulmonary dimensions in small mammals.

This report has reexamined the relationship between standard and maximal rates of oxygen consumption (VO2std and VO2max) and pulmonary surface area in mammals whose weights extend over the lower half of the total log weight range in mammals. For combined groups of wild and laboratory animals with body weights of 2--3700 g, the following equations pertain: VO2std (ml . min-1) = 0.0602 . W0.727; VO2std, or the factorial aerobic scope, is nearly constant over this weight range at approximately 6.6 (range 5.8--7.1). In view of this finding, earlier studies relating SA or pulmonary diffusion capacity to VO2std are still appropriate models for pulmonary constraints on metabolic rate. The data summarized here suggest that, at least for wild species of mammals, pulmonary diffusion capacity may limit VO2max.


[Familial Creutzfeldt-Jakob disease. A clinical and pathological study of three cases in a family with eight affected members in three generations (author's transl)].

We report here a family with three pathologically confirmed cases of Creutzfeldt-Jakob disease in three siblings and with transmission of one case to the squirrel monkey. This family, originating from the South-East of England, settled in France in 1870. Eight members of the family, distributed in three generations, were affected by the disease at the same age (about 50), with similar symptoms and length of evolution. Two cases were confirmed at post-mortem and one case by cerebral biopsy. The genealogic inquiry dealth with 46 members of 5 generations. All the affected members, six men and two women, belonged to the three older generations which were comprised of 15 individuals. All had lived in close relationship in a limited area of the north of Ardennas. The possible mechanisms of dominant inheritance or cross infection are discussed.


A comparison between diamine oxidases from human post-heparin blood serum, pregnancy blood serum and amniotic fluid.

Diamine oxidase (DAO) was purified from blood serum after intravenous heparin injection, from pregnancy blood serum and amniotic fluid. On DEAE-Sephadex, DAO from amniotic fluid as well as from pregnancy blood serum was separated in two active fractions with molecular weights of 245,000 and 485,000, respectively. Post-heparin blood serum contained only one active DAO fraction with a molecular weight of 185,000. The purified enzymes showed similar enzymatic properties.


Actions of thyrotropin-releasing-hormone on gastrointestinal function in man. I. Inhibition of glucose and xylose absorption from the gut.

We studied serum glucose levels following a peroral glucose test in 6 healthy subjects on 2 alternate days in random order; with or without an i.v. TRH infusion for 3 hours (0.66 mg/hour). TRH infusion reduced serum glucose levels following oral glucose in all 6 subjects investigated. Serum insulin levels were reduced accordingly. Furthermore, serum xylose levels following peroral xylose were studied in the same 6 subjects. TRH infusion i.v. reduced serum xylose levels in all 6 subjects studied. I.v. glucose tolerance tests with or without an i.v. TRH infusion (0.66 mg/h) for 3 hours were studied in 4 healthy subjects. No change in serum glucose or insulin levels following TRH infusion was observed. We conclude that an i.v. infusion of TRH reduces serum levels of glucose following a peroral xylose load. TRH thus has marked actions on gastro-intestinal function in man inhibiting and/or retarding the absorption of glucose and xylose from the gut.


Protein A reactivity of various mammalian immunoglobulins.

Serum samples and immunoglobulin fractions of eight mammalian species were applied to a Sepharose--protein A column. As with the human immunoglobulin subclasses IgG1, IgG2 and IgG4, all examined IgG classes and subclasses were bound to a greater or lesser extent to protein A. However, the binding of IgG1 of ruminants was very poor. Polyclonal IgM and IgA of the pig, the dog and the cat may be separated in protein A reactive and protein A non-reactive fractions. In addition, monoclonal canine IgM and IgA partially reacted with protein A. In combination with methods such as ammonium sulphate precipitation, ion exchange chromatography and gel-filtration, affinity chromatography with protein A is recommended for the rapid purification of certain Ig (sub)classes of a number of mammalian species.


Variable-region subgroup and specificity of cold agglutinins.

The variable-region subgroup determined by amino acid sequence analysis of heavy and light chains of two monoclonal cold agglutinins with the new anti-Gd specificity is reported. Both proteins belong to the VHIII subgroup of heavy chains; one light chain falls into the V kappaI subgroup, the other has a blocked N-terminus which so far has not been observed in human kappa chains. The comparison of anti-Gd with anti-I/-i or anti-Pr cold agglutinins indicates that anti-Gd differs from other cold agglutinins with respect to variable-region subgroup. The data extend previous findings on the restriction of certain antibodies to distinct variable-region subgroups.


Inhibition of human anti-Gd cold agglutinins by sialyllactose.

Two examples of IgM kappa-monotopic cold agglutinins occurring in patients with non-Hodgkin lymphomas, reacted with erythrocyte autoantigens, which were protease-resistant but were inactivated by neuraminidase. The cold agglutinins were inhibited by the trisaccharide sialyllactose [NeuNAc(alpha,2 leads to 3) Gal (beta, 1 leads to 4)Glc], which is not related to oligosaccharides known to inhibit anti-I/-i cold agglutinins, Anti-Pr cold agglutinins are not inhibited by sialyllactose, although N-acetylneuraminic acid (NeuNAc) is an essential component not only of Gd but also of Pr determinants. Gd determinants are not bound to erythrocyte membrane glycoproteins, but are apparently bound to membrane glycolipids (gangliosides).


The placental Fcgamma receptors studied using immune complexes of peroxidase.

Immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP were used to study the Fcgamma receptors in normal human placenta. Cryostat sections of placental tissue were incubated with the complexes, and the peroxidase activity was revealed histochemically. The bound complexes were localized to the apical surface of the trophoblasts and endothelial cells of the fetal stem vessels. Binding also occurred within the wall of some fetal vessels, to stromal cells and occasionally to areas corresponding to the trophoblastic membrane. The strongest binding was obtained with immune complexes prepared at slight antigen excess. Eight- to sixteen-fold increased concentration of human and rabbit IgG was needed to block the binding of immune complexes. Bovine and porcine IgG did not block the binding. Treatment of tissue sections with neuraminidase enhanced the binding activity of the receptors. The technique is very convenient for studies of Fcgamma receptors in tissue. However, unfixed frozen placental tissue was not suitable for ultrastructural studies.


Late appearance of an IgA (kappa) monoclonal protein in a patient with IgG (kappa) multiple myeloma: sharing of idiotypic specificities between the two serum proteins.

A patient with an IgG(chi) monoclonal serum protein developed in the course of the disease a second monoclonal spike of the same light chain type and of the IgA class. The latter monoclonal protein progressively increased and eventually exceeded the first IgG(chi) protein. Antigenic analysis of the two myeloma proteins demonstrated that they shared idiotypic determinants. Immunofluorescence studies, carried out with anti gamma and anti alpha reagents tagged with different fluorochromes revealed that the two isotypes were produced by different plasma cells. The data are discussed in the prospect of a possible transitional mechanism from IgG to IgA synthesis within a single B cell clone.


The mini-pig as a model for penetration of penicillins.

To be active, antimicrobials must reach the bacteria in the infectious foci in adequate concentrations. Direct measurements of levels in the various foci are difficult to perform, but a number of animal models with artificial extravascular foci have been developed. In many ways, the physiology of pigs resemble that of humans. Consequently, it was thought that pigs might also parallel humans in the handling of penicillins. General pharmacokinetics of ampicillin and flucloxacillin and the penetration of the substances to subcutaneously implanted teflon tistisue chambers were investigated. Ampicillin was given intramuscularly, orally, and as the pro-drug bacampicillin.


Factors affecting the intraocular penetration of antibiotics. The influence of route, inflammation, animal species and tissue pigmentation.

Antibiotics which are sparingly lipid-soluble, such as the penicillins, cephalosporins and aminoglycosides, penetrate the eye with great difficulty, achieving intravitreal concentrations which are only a small percentage of the peak serum level. As a result, it is common practice to administer these agents by periocular injection. We have compared the penetration of gentamicin in albino rabbits with that in squirrel monkeys, in normal and infected eyes, after retrobulbar and subconjunctival administration. Generally speaking, the subconjunctival route produced levels equal to or higher than those resulting from retrobulbar injection in both species; it was distinctly superior with regard to cornea and aqueous humor. Inflammation had a neutral or enhancing influence upon intraocular penetration in the monkey, but had a more variable effect in the rabbit; this may be related to the balance between diminution of the blood-ocular barrier and increased dissipation of antibiotic into the systemic circulation. Interspecies differences were much more striking in normal than in infected eyes. This underlines the necessity for the investigator to study inflamed eyes if the results are to be relevant to the clinical situation. Iris and choroid-retina from pigmented rabbits contained significantly more clindamycin and less gentamycin and less gentamicin, in terms of diffusible drug, than tissues from albino animals. These discrepancies reflect opposite interactions between melanin and the two antibiotics in vivo.


Penetration of antibiotics into the normal and diseased maxillary sinus mucosa.

A micro-method was developed for determination of the concentrations of antibiotics in the mucous membranes of the maxillary sinus in man. At different times after the administration of antibiotics (potassium phenoxymethylpenicillin, lymecycline and bacampicillin) the concentration was determined in serum and in pieces of maxillary sinus mucosa obtained at operation. It was found that the concentrations in the mucosa varied within wide ranges during the first 60 minutes after the operation but in samples taken at 90 minutes the fluctuations between the individuals were within the standard error of the method. Concentrations well above the MIC values for the majority of bacterias found in sinusitis were registered in the peaks. Six hours after the administration considerable amounts of active antibiotics were still detected in the maxillary sinus mucosa.


Induction of DNA synthesis in lymphocytes in vitro by various bacteria, with special reference to Neisseria gonorrhoeae, in patients with uro-arthritis (Reiter's disease).

Antigen-induced lymphocyte proliferation was studied by quantitation of 14C-thymidine uptake in cell cultures. The induction of DNA synthesis in vitro in lymphocytes from patients with uro-arthritis after stimulation by whole cells of virulent and avirulent N. gonorrhoeae, meningococci group B, and apathogenic Neisseria (N. pharyngis) was compared with the DNA synthesis in lymphocytes from healthy controls after stimulation with the same Neisseria antigens. The difference between patients and the controls was found to be highly significant after stimulation with virulent or avirulent N. gonorrhoeae organisms but not after stimulation with apathogenic Neisseria. An analysis of the correlation of the lymphocyte reactivity to all the Neisseria antigens showed a highly significant correlation between the response of uro-arthritis patients to the two types of gonococcal antigen (0.932*** and 0.859***), a lower correlation coefficient for group B meningococci and virulent or avirulent gonococci (0.724*** and 0.714***) and no correlation at all between apathogenic Neisseria and gonococci. The DNA synthesis in lymphocytes stimulated by N. gonorrhoeae and other Gram-positive and Gram-negative bacteria was also studied in cell cultures obtained from other healthy controls as well as uro-arthritis patients. There was no significant difference between the patients and the controls with regard to the response to apathogenic Neisseria and other non-Neisseria antigens.


[Uremic pericarditis: clinical aspects, echocardiography, therapy].

Over a 2-year period uremic pericarditis was observed in 11 of 62 patients treated by chronic dialysis. The uremic state appeared to be the most important contributing factor in these patients. Chest pain, fever and a pericardial friction rub were observed in the majority of patients; the illness may however be silent. Echocardiography proved to be the single most helpful diagnostic procedure. Intensive hemodialysis, indomethacin or steroid therapy given systemically or intrapericardially are generally accepted in the management of pericarditis. Although indomethacin produced regression of the clinical symptoms in these patients, the volume of fluid within the pericardial sac diminished in 3 of 9 patients only. 6 patients were given systemic steroid treatment and this was followed by prompt resolution of the effusion. Surgery was not necessary. All patients had an uneventful recovery.


[Are measles and mumps vaccinations worth while in Switzerland?].

Cost-benefit analyses have been performed in investigating the usefulness of general vaccination against measles and mumps in all children. Even by a conservative reckoning the cost of general measles immunization for all children in the second year of life is much lower than the financial effects of the disease. In the case of general mumps vaccination, cost-benefit analyses fo not give so significant an outweight of financial benefit as for measles vaccination. If only for economic reasons, however, general immunization against mumps is recommended for all children in the second year of life. From the economic viewpoint, general immunization programs for teenagers do not pay either with regard to mumps or measles. Such vaccinations may of course be recommended on an individual basis, especially for teenagers with a negative measles history.


[Metabolites of hypoglycemic sulfonylureas in kidney failure. Experience with glibenclamide].

Renal insufficiency is a factor which predisposes to hypoglycemic accidents in subjects treated with hypoglycemic sulfonylureas. Glibenclamide (glyburide) is eliminated from the body mainly by metabolism, with the result that renal insufficiency has little effect on its biotransformation. In order to determine to what extent the retention of the metabolities intervenes in such hypoglycemic accidents, rats with ligatured ureters received intraperitoneal injections of 1 mg/kg glibenclamide or hydroxy-glibenclamide (the main metabolite), or of saline. For each animal there was a control animal which had undergone a simulated operation. For six rats with renal insufficiency, glibenclamide caused hypoglycemia of the same intensity as in the control group but more prolonged. With hydroxy-glibenclamide the glycemia was signficantly lower than in the control group. Hydroxy-glibenclamide has an obvious hypoglycemic activity which represents 1/6 of that of the parent drug, but 50--100 times that of tolbutamide. Its retention contributed to the intensification and prolongation of the hypoglycemic effect of glibenclamide in rats with renal insufficiency.


Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone.

In rhesus monkeys with hypothalamic lesions that abolish gonadotropic hormone release by the pituitary gland, the constant infusion of exogenous gonadotropin-releasing hormone (GnRH) fails to restore sustained gonadotropin secretion. In marked contrast, intermittent administration of the synthetic decapeptide once per hour, the physiological frequency of gonadotropin release in the monkeys, reestablishes pituitary gonadotropin secretion. This phenomenon is attributable to the pattern of GnRH delivery rather than to the amounts of this hormone to which the cells of the pituitary are exposed. Moreover, the initiation of continuous GnRH administration in animals with lesions and in which gonadotropin secretion is reestablished by intermittent GnRH replacement can result in a "desensitization" or "down regulation" of the processes responsible for gonadotropin release.


Drosophila egg chambers develop to mature eggs when cultured in vivo.

Egg chambers were injected into the abdomen of adult Drosophila. When cultured in this manner, even the earliest detectable developmental stage developed into fully mature eggs. Both isolated egg chambers and those still associated with ovarian structures developed equally well. Maturation occurred within host flies of both sexes in the absence of any hormone treatment.


Early detection of Rickettsia tsutsugamushi in peripheral monocyte cultures derived from experimentally infected monkeys and dogs.

Rickettsia tsutsugamushi organisms were identified in Giemsa and fluorescent antibody stained monocyte cell cultures derived from experimentally infected monkeys and dogs. The identification of organisms in monocyte cell cultures compared favorably with the standard technique of mouse inoculation.


Escherichia coli shock in the baboon and the response to adrenocorticosteroid treatment.

Results of recent studies from this laboratory have demonstrated that methylprednisolone sodium succinate increases the survival rate of dogs given LD100 Escherichia coli endotoxin. This study was undertaken to determine the effects of methylprednisolone on the baboon infused with live Escherichia coli organisms. Awake baboons were paired by infusing intravenously comparable doses of Escherichia coli during a five hour period. Baboons given methylprednisolone received bolus injections of 30 milligrams per kilogram at 15 minutes after beginning the infusion of Escherichia coli and two hour infusions of 15 milligrams per kilogram at two hour intervals until death or for a 24 hour period. The mortality was unaltered by methylprednisolone. Six of seven baboons that were dying became progressively hypoglycemic, while hypoinsulinemia occurred in all baboons within six hours and was sustained until death. Systemic hypotension was observed. although pressures were variable. Potassium and lactate concentrations increased, while pH remained relatively constant in most baboons. Serum glutamic-pyruvic transaminase and arginase concentrations rose in most baboons dying with 18 hours. Results of morphologic studies revealed the presence of fibrin thrombi in the liver, kidney and adrenal tissue in most baboons. No significant differences in physiologic, metabolic, hematologic or morphologic parameters were observed between treated and untreated baboons.


Repair of pharyngoesophageal diverticulum by resection with myotomy and muscle closure.

This technique has been used on four of our patients undergoing resection of pharyngoesophageal diverticula during the past year. Short term results have been satisfactory. Long term follow-up study and numbers of patients are, as yet, insufficient to draw conclusions as to the late recurrence rate.


Preparation and evaluation of an antiserum to the carboxymethylated Aalpha chain of human fibrinogen.

Antiserum to the carboxymethylated Aalpha chain of human fibrinogen has been produced in rabbits and its reactions investigated in a double diffusion system. The antiserum reacts with the carboxymethylated Aalpha chains, but not with carboxymethylated gamma chains, nor with carboxymethylated Bbeta chains, provided that the antiserum had been absorbed with carboxymethylated Bbeta chains. The antiserum also reacts with Aalpha chains in the whole fibrinogen molecule, either in plasma or in the purified form, and spur formation was observed when intact fibrinogen was compared with high solubility fibrinogen, which contained little or no intact Aalpha chain.


Sugar metabolism in the crystalline lens.

Research on the sugar metabolism of the crystalline lens, past and preent, is reviewed. The chief energy source in the lens is the Embden-Meyerhof pathway; respiration and oxidative phosphorylation become more important as the lens ages. The function of the alpha-glycerophosphate cycle is not fully understood. The mechanisms involved in cataract formation, including those of hypoglycemic cataract and osmotic cataracts, are discussed. Sugar cataracts can be delayed or prevented with such aldose reductase inhibitors as flavonoids. By inhibiting aldose reductase, the formation and accumulation of sugar alcohols is stopped. This approach may be useful as a medical therapy for human diabetic senile cataracts.


Cell surface antigens detected on mature and leukemic granulocytic populations by cytotoxicity testing.

Using a microcytotoxicity assay, the serological reactivity of human granulocytes, namely neutrophils and eosinophils, and chronic myeloid leukemia (CML) cells and cultured CML cell lines (K562, NALM-1) were examined. Mature granulocyte forms and cord granulocytes are readily lysed by specific granulocyte cytotoxins that do not react with random T and B lymphocytes, monocytes, red blood cells, or platelets. Furthermore, certain antisera were preferentially cytotoxic for eosinophil-enriched populations. Granulocytotoxin detected antigens on one of three CML blast cell populations tested and K562, but failed to react with NALM-1. By cytotoxicity, mature granulocytes were poor targets for B2-microglobulin and the appropriate HLA antisera although both sera types are absorbed with granulocytes. Furthermore, granulocytes did not possess B-lymphocytes (Ia-like) or blood group A, B, and Rh (D) antigens. Except for K562, both HLA and heterologous B-lymphocyte antisera were cytotoxic for the CML blast cell populations tested.


Isolation and characterization of a Golgi-rich fraction from the Harding-Passey mouse melanoma.

Golgi-rich fraction was isolated from Harding-Passey mouse melanoma by centrifugation through the discontinuous sucrose density gradient and its properties were compared with those of the same fraction isolated from rat liver. The specific activity of UDP-galactose: N-acetylglucosamine galactosyltransferase was 35 times higher in the melanoma Golgi fraction than in the melanoma homogenate and was a half that in the rat liver Golgi fraction. The specific activities of marker enzymes for other subcellular components such as 5'-nucleotidase, acid phosphatase and glucose-6-phosphatase in the melanoma Golgi fraction were all one-third those in the melanoma homogenate. Electron micrographs of the negatively-stained Golgi fractions of melanoma and liver revealed the presence of a system of tubules, vesicles and plate-like center regions which are known as components of Golgi apparatus. Tyrosinase activity was found to be present in this fraction of mouse melanoma, but its specific activity was lower than that in the rough or smooth surface membrane fraction or in the melanosome fraction.


Persistent hyperplastic primary vitreous. A clinicopathologic study of 62 cases and review of the literature.

This is a clinicopathologic study of 62 cases of persistent hyperplastic primary vitreous (PHPV). The cases were divided into two main groups. Group 1 consisted of 55 unilateral cases not associated with any systemic abnormalities, including 36 eyes (58%) which were considered "pure cases" (Group 1A) and 19 (31%) which disclosed other ocular abnormalities in addition to PHPV (Group 1B). Group 2 consisted of 7 (11%) bilateral cases of PHPV accompanied by other ocular and systemic malformations. The most common presenting clinical signs are leukocoria, microphthalmia and cataract. The main histopathologic features of this condition are outlined, including those responsible for the disastrous results to the eye (retinal detachment, glaucoma, phthisis bulbi). Several clinical entities, usually mistaken for or associated with PHPV, such as retinoblastoma, congenital cataract, retinal dysplasia, trisomy 13 syndrome, and falciform retinal folds are discussed briefly.


Purification of rat prolactin releasing factor by gel filtration.

Pregnant rat hypothalamic fragments were extracted with 30 mM Tris-HCl buffer at pH 7.8, subjected to enzymatic digestion, and applied to gel filtration on Sephadex G-25 for purification of the prolactin releasing factor. Effect of the eluted fractions on the release of prolactin were tested by the determination of serum and pituitary prolactin after the injection in lactating rats. Prolactin was estimated by radioimmunoassay. One fraction (tube number 61--73) eluted later than synthetic ACTH enhanced release of prolactin 30 min after injection, but other fractions had no effect on the release of prolactin. Prolactin releasing factor would be quantitatively predominant over prolactin inhibiting factor in pregnant rat.


Effects of chronic beta-glycerophosphate administration on growth rate and on serum, liver and bile lipid composition in the squirrel monkey--a toxicity study.

Oral administration of beta-glycerophosphate lowers the lithogenic index in patients with cholesterol gallstones and is considered to have potential for dissolving them. A high dose of beta-glycerphosphate was fed to primates (Squirrel monkeys) for a period of 15 months. There were no adverse effects on body weight, hematological or liver function tests. Serum, liver and bile lipids concentrations were not significantly changed, although serum and hepatic bile phospholipids were increased. Organ weights expressed as percent of body weight were not changed except for a slight increase in kidney weight. Histological examination of liver and kidneys did not reveal any pathological findings. Slight renal hypertrophy was attributed to the sodium content of beta-glycerophosphate.


Toxicology studies of linear alkylbenzene sulphonate (LAS) in rhesus monkeys. II. The disposition of [14C] LAS after oral or subcutaneous administration.

The disposition of radioactivity has been studied after administration of single and repeated oral or subcutaneous doses of [14C] LAS to rhesus monkeys. After single 30 mg/kg oral doses the radioactivity was rapidly excreted, mostly during the first 24 h. Means of 71.2% and 23.1% of the dose were excreted in the urine and faeces respectively during 5 days. Similarly, after single 1 mg/kg subcutaneous doses, means of 64.1% and 10.9% were excreted in urine and faeces respectively during 5 days, mostly during the first 24 h. After single oral doses of 30, 150 and 300 mg/kh peak plasma concentrations, at 4 h in all cases, were very similar representing 34, 41 and 36 micrograms/ml respectively. After single subcutaneous doses of 0.1, 0.5 and 1 mg/kg, peak plasma concentrations increased almost proportionately and represented 0.16, 0.72 and 1.13 micrograms/ml respectively. During 7 consecutive daily oral (30 mg/kh/day) or subcutaneous (1 mg/kg/day) doses, there was no accumulation of radioactivity in plasma. Mean peak concentrations and biological half-lives were similar after the first and seventh doses. After 7 doses of [14C]LAS, there was no localisation of radioactivity in any tissue. No unchanged LAS was detected in urine samples after oral or subcutaneous doses. About 5 major radioactive components were detected in urine extracts; all were apparently more polar than LAS, but were not sulphate or glucoronide conjugates.


[Testing the disinfectant effect of calcium peroxide as a root canal filling material].

The authors have been using with success calcium peroxide as a root-canal filling material for many years. Its bactericidal and bacteriostatic effects are tested. Germ carrier tests illustrate the suitability of its pasty preparation for root-canal disinfection.


The metabolic fate of triamcinolone acetonide in laboratory animals.

The metabolic fate of 9-fluoro-11beta,16alpha,17,21-tetrahydroxy-1,4-pregnadiene-3,20-dione cyclic 16,17-acetal with 2(-14)C-acetone, triamcinolone acetonide (TA) was studied in rabbits, dogs, monkeys and rats and found to be qualitatively similar in all species. In the dog, rat and monkey the major excretory route was the feces irrespective of the mode of administration. In the rabbit the excreted radioactivity was equally distributed between urine and feces. The metabolites were isolated by preparative thin layer chromatography, located by autoradiography, eluted and analyzed by MS, IR, UV and NMR. The major metabolites of triamcinolone acetonide (TA) were identified as the C-21 carboxylic acids of TA and of the 6beta hydroxy-TA, (6BETA-OH-TA) and the previously identified (1,2) 6beta-OH-TA. In addition MS and UV data indicate the presence of 9-fluoro-11beta,16alpha, 17-trihydroxy-3,20-dioxo-1,4,6-pregnatrien-21-oic acid cyclic 16,17 acetal with 2(-14)C-acetone.


The comprehensive child health care centres in the Sudan.

In 1963, Morley initiated the concept of clinics for children under five years old. This paper describes our experience in applying that concept in Omdurman town (Sudan) where existing maternity and child health centres and hospitals in the area were involved in the scheme. It was found necessary to establish a main centre to develop methodology and to provide a specialized training of staff. The medical problems were similar to those described by Morley. The approach to their solution was essentially the same except that we used more professional staff and placed more emphasis on nutrition education than hitherto advocated. It is concluded that, in theory, Morley's concept provides a system of comprehensive child health care which suits the needs of developing countries. But our adaptation of Morley's ideas to existing health structures, even on the small scale we achieved in Omdurman, was difficult because of the high initial and running costs and in view of the long established dichotomy between curative and preventive medicine.


Prevention of persistent cerebral smooth muscle contraction in response to whole blood.

Using an in vitro system designed to measure arterial constriction, we have demonstrated the importance of platelet function in maintaining cerebral smooth muscle contraction after whole blood injection. We tested two agents, acetyl salicylic acid (ASA) and phthalazinol, both known to interfere with platelet function. In control tests normal rabbit and monkey blood produced a reliable and persistent arterial constriction. In experimental tests blood drawn from animals premedicated with ASA and phthalazinol failed to produce a persistent contraction. These results support the hypothesis that chemicals released during platelet aggregation may be important in persistent vasospasm.


Cerebral arterial lesions resulting from inflammatory emboli.

In order to study the effects of septic embolism on the brain, silicone rubber emboli of various types were injected into the carotid arteries of 35 dogs. Pathologic and angiographic studies were performed to assess the resultant arterial and parenchymal lesions. Pure silicone rubber emboli (14 dogs) produced occasional intra-arterial thrombosis but no arteritis. Sterile and bacterially contaminated emboli containing a lead-chromate pigment (similar to those used in previous studies of septic embolism) (11 dogs) and pure silicone rubber emboli with transversely oriented canals (10 dogs), after brief placement in a bacterial suspension, were associated with intense inflammatory arteritis. This was accompanied by focal meningitis, subarachnoid hemorrhage, thrombosis, and cerebritis of the underlying cortex. The findings resembled those found in mycotic aneurysm. Aneurysmal dilatation was observed in one postmortem angiogram. In previous models of mycotic aneurysm, the inflammation attributed to bacterial contamination was probably due to the lead-chromate pigment used.


Cerebral blood flow in the monkey after focal cryogenic injury.

A focal cryogenic lesion was made in the left superior frontal gyrus of the anesthetized macaque brain. Cerebral blood flow (CBF) was determined by the hydrogen clearance technique before and during the 4 hours following trauma. Local CBF in tissue adjacent to the lesion increased in the first half hour after the lesion was made and then decreased during the ensuing 3 1/2 hours. Local CBF in the contralateral superior frontal gyrus, as well as total CBF and oxygen consumption, were unchanged by cryogenic trauma. The spread of vasogenic edema into uninjured tissue probably accounts for the observed decrease in local CBF. This experimental model may assist in discovering therapy to alter favorably the spatial and temporal profile of pathologic CBF changes in tissue surrounding an acute lesion of the brain.


Influence of a single blood transfusion on kidney allograft survival in unrelated rhesus monkeys.

A prospective study was performed in moderately immunosuppressed unrelated rhesus monkeys to investigate the influence of a single transfusion on kidney allograft survival. The recipients received either whole citrated blood or plasma-free transfusates consisting of pure red blood cell or lymphocyte suspensions. Except for one group, in which blood and kidney donors were optimally matched, transfusions and kidney allografts were disparate for two to four A/B locus antigens with the recipients. Transfusions were given 2 to 4 weeks before kidney grafting, except in one experimental group where the recipients were transfused 0 to 12 hr before transplantation. The general trend was that graft prolongation could be obtained with all experimental protocols. However, it was also shown that a single transfusion entails the risk of accelerated rejection. This adverse effect was not observed in the animals receiving blood and kidneys from donors optimally matched for A/B locus antigens and in recipients transfused shortly before or during transplantation. These results may contribute to a further improvement of the current clinical transfusion policy.


Nonhemolytic IgG anti-IT.

Nonhemolytic, IgG, anti-IT autoantibodies were found in the sera of three Caucasian patients, none of whom had Hodgkin's disease. Each antibody reacted by indirect antiglobulin test. Two of the three also reacted in albumin at 37 C, and one of these was moderately enhanced by papain. As judged by transfusion responses, reticulocyte counts, hematocrit stability, and one hour 51Cr red blood cell survivals, none of the antibodies were considered to be hemolytic. When tested with anti-IgG serum, cells from all three had a positive direct antiglobulin test. Anti-IT antibody was eluted from their cells. Ii status of the patients' cells differed from normal in each case. These data suggest greater variation in the disease association, serologic reactivity, and clinical significance, of anti-IT than has been evident from previous studies.


Tuberculosis in Kenya: a second national sampling survey of drug resistance and other factors, and a comparison with the prevalence data from the first national sampling survey. An East African and British Medical Research Council Co-operative Investigation.

A survey was carried out in 1974 in the same random sample of 11 of 30 districts in Kenya that were surveyed in 1964, to obtain information on (a) the proportion of patients with pulmonary and with extra-pulmonary tuberculosis, (b) the prevalence of bacteriologically-positive pulmonary tuberculosis, (c) the prevalence of initial and acquired drug resistance, (d) the radiographic extent and type of pulmonary disease, and (e) the changes that had occurred in the 10-year period. Of 1490 patients, 88.5% had pulmonary tuberculosis only, 3.0% had both extra-pulmonary and pulmonary tuberculosis and 8.6% had extra-pulmonary tuberculosis only. Of the 172 patients with extra-pulmonary tuberculosis, 51% had lymph node involvement, 24% bone and joint disease and 9% a pleural effusion. Of the 1362 patients with pulmonary tuberculosis (with or without extra-pulmonary tuberculosis) 94% had no history of previous chemotherapy, fewer than 1% a history of possible and 6% a history of definite previous chemotherapy. (The proportions for the patients with extra-pulmonary tuberculosis only were 94%, 1% and 5% respectively.) A sputum specimen was produced by 1096 (80%) of the patients with pulmonary tuberculosis; 69% of smear results were positive, as were 74% of the culture results. In 2 (0.25%) of the 807 patients with a positive culture the strain was identified as being neither M. tuberculosis nor M. bovis. Of 702 patients with no history of previous chemotherapy and a sensitivity test result available, 10.1% had a strain resistant to isoniazid and/or streptomycin, 7.3% to isoniazid alone, 1.4% to streptomycin alone and 1.4% to both drugs. Of 1133 patients with chest radiographs available and a diagnosis in Kenya of pulmonary tuberculosis, a lung lesion or a pleural effusion was reported at independent assessment in London for 91%. Gross, extensive or moderate disease was present in 73% of the patients and cavitation was present in 72%. The radiographic disease was classified as acute in 31%, mixed-acute in 52%, mixed in 12% and chronic in 5%. The disease in children was usually less extensive, less often cavitated, and more acute than in adults. A comparison of the prevalence data in 1974 with that in 1964 suggested that there was a modest decline in the incidence of tuberculosis but that the characteristics of the registered patients and their disease were very similar in all respects; the disease was just as extensive radiographically and cavitation was, if anything, more common and more extensive in 1974 than in 1964.


Comparison of various measures of sensitivity of M. tuberculosis to ethambutol.

A sensitivity test for ethambutol was standardised, and performed on cultures isolated from patients before and after the start of chemotherapy with ethambutol and isoniazid. A discrimination type of approach was employed and three criteria of resistance were evolved: (a) growth of 20 colonies or more on ethambutol 4 microgram/ml, using a standard inoculum; (b) a proportion of 25% or more on ethambutol 1.4 microgram/ml; (c) a proportion of 5% or more on ethambutol 2 microgram/ml. The MIC definition appears to be the best in view of its simplicity and insensitivity of the classification (as sensitive or resistant) to variations in inoculum size.


Host-phage relationships in the genus Mycobacterium and their clinical significance.

Progress made during the last 15 years in the studies on the relationships between mycobacteria and their bacteriophages is reviewed. The basic biology of the phages and the applications of studies on adaptation and host range are discussed in relation to the development of phage typing systems for epidemiological purposes. The nature of lysogeny, its natural occurrence, its experimental establishment, the effect of the lysogenic state on the host bacterium and the evidence that lysogenic mycobacteria are involved in human disease, especially sarcoidosis, is reviewed.


Cutaneous reactions to local traumatization with heat in alloxan diabetic rabbits with and without ketosis.

Short-term alloxan diabetic rabbits with and without ketosis were traumatized with local cutaneous application of heat. The degree of traumatization varied with regard to the temperature and duration used. The lowest degree of traumatization which caused intravenously injected Evans blue to be observed within the area of traumatization was determined. There was no difference between diabetic animals without ketosis and controls. A more pronounced traumatization of animals with ketosis was necessary if Evans blue was to be observed, but there was then a significant difference between these and controls. The traumatized skin areas were also studied histologically. The inflammatory reaction induced was judged as being weaker in animals with ketosis.


[The effect of transurethral electrical stimulation on the paralyzed and incontinent bladder: objective results (author's transl)].

Using objective parameters, improvement of the detrusor function and bladder sensitivity can be obtained in most children. A significant improvement in incontinence appears possible in 30--40% of the patients. The method according to Katona is the only one which creates bladder sensitivity. This method is not a cure all but has improved our therapeutic possibilities, especially when it is combined with pharmacotherapy, long term low dose antibiotic therapy and sphincterotomy.


Enterococcal endocarditis: duration and mode of treatment.

This report summarizes data on sixteen patients with enterococcal endocarditis treated with penicillin and streptomycin. The experience reported suggests that a four week period is adequate for routine therapy in these patients, as in other forms of streptococcal endocarditis. It provides an additional group of patients successfully treated with penicillin and streptomycin. Two relapses were encountered. One of these received inadequate daily doses of penicillin. The other patient was clearly a failure of penicillin and streptomycin, but the failure in this instance could not be attributed to foreshortened treatment (6 weeks) or to high level streptomycin resistance of the infecting strain of Enterococcus.


[Identification of various porcine mycoplasmas using epi-immunofluorescence].

The responses of the field strains and type strains of Mycoplasma hyorhinis are compared in epi-immunofluorescence, in growth-inhibition tests, and growth-precipitation tests. The type strains, together with the field strains, could be definitely identified by direct and indirect epi-immunofluorescence. In indirect epi-immunofluorescence, all rabbit antiserums against the strains of Mycoplasma hyorhinis tested by us always gave positive cross reactions with all the tested strains of Mycoplasma hyorhinis. On the other hand, in the growth-inhibition cross test and growth precipitation cross test, the type strains of Mycoplasma hyorhinis always reacted positively only with the homologous antiserums, whereas the heterologous reactions were mostly negative or dubious. The clearly positive epi-immunofluorescent reactions with serums against any strain of Mycoplasma hyorhinis suggest that this method is more suitable for the identification of Myocplasma species than the other two tests studied.


[Study on the possible presence of aflatoxin B 1 in liver and muscle tissue of slaughter animals].

Seventy-seven samples of liver (from pigs, bulls, cows, broiler chickens, layers), twenty-eight samples of white muscle (from pigs, broilers, layers), and twenty-four samples of red muscle (from pigs, broilers, layers) were examined by the modified Jacobson method (Jacobson et al. 1971) for the contingent presence of aflatoxin B1. The samples came from healthy animals, part of them from animals fed non-traditional feed containing pig excrements. Positive findings were only obtained in two samples of pork liver, out of the total number of 30 samples. One sample came from pigs fed a ration containing 5% of pig excrements, the other from a traditionally fed pig. The amounts of aflatoxin B1 found in these two samples can be treated as trace quantities, since the concentration did not exceed 0.1 microgram per kg. In the samples of muscle and liver of the other farm animals, the chromatogram did not show the presence of spots which might resemble, in colour and position, the spots of aflatoxin B1.


[Examination of market carps for residues of antimicrobial agents].

The residues of inhibitory substances in the muscle, hepatopancreas, bile, and pyloric caeca of 30 carps from ponds south of Brno were examined by the microbiological diffusion method. The following testing micro-organisms were used: B. cereus var. mycoides (ATCC 11778), B. subtilis (ATCC 6633), Sarcina lutea (ATCC 9341), and Micrococcus flavus (ATCC 10240). Residues of inhibitory substances were not found in any of the muscle samples tested. The rest of the tested tissues showed, in some cases, small inhibition zones which seem to be due to the presence of natural antimicrobially active substances in the bile and gastro-intestinal tract of the fish rather than to the persistence of the residues of drugs given to the fish during their life.


[Distribution of orally administered aflatoxin B 1 in the tissues and organs of the goat (Capra)].

In the experiment the goat was administered an amount of 450 mg aflatoxin B1. The milk taken during the experiment was lyophilized and aflatoxins B1 and M1 were isolated. After the death of the goat some tissues, blood and bile of the experimental animal were analyzed to find out the aflatoxin content.


[Selection of methods for the determination of aflatoxin presence in liquid milk].

Seven methods, recommended for determining aflatoxins in liquid milk, were tested. Most of them were variously modified, mainly for the unavailability of some chemicals needed. Samples of liquid milk, normally prepared for direct consumption, were taken from the retail market (bottled and plastic-sacheted milk, durable milk in speical boxes). The authors describe in detail the two methods now appearing to be the best for current screening tests of market samples of liquid milk. Seventy samples of market liquid milk were tested by these methods, and 25 of them were found to be positive. However, there was no sample to contain as much aflatoxin as determined in the proposed admissible concentration for food.


[Detection of inhibitory substances in milk using the modified reduction micromethod].

In order to rationalize work and to reduce the consumption of laboratory glassware a reduction micromethod with the bacterial stain Streptococcus thermophilus has been modified; the method is used to detect inhibitory substances in genuine, pausteurized and dried milk, and it is performed on a serological plate made from organic glass. The method is sensitive to most antibiotics used in the veterinary clinical practice. The detection sensitivity to penicillin residua ranges from 0.0015 to 0.0015 i.u. in 1 ml of milk. The method may be assessed as semi-quantitative.


[Dynamics of uric acid concentration in the liver of cockerels subjected to model stress situations induced by fasting].

A model stress situation was created by nutrition deprivation. The experiment was performed with 130 cockerels of the initial breed White Leghorn. The experimental cockerels of the age of 18 to 24 days fasted for 24, 48 and 72 hours. Uric acid was determined in the supernatant of liver homogenate by means of a colorimetrically reductometric method with phospho-wolframic agent. A significant increase in the uric acid concentration in the liver of cockerels was found out during the model stress: the concentration of uric acid increased progressively from the initial 70.25 +/- 8.94 mg per 100 g to 93.15 +/- 9.66 mg per 100 g after 24-hour fasting, to 90.23 +/- 7.84 mg per 100 g after 48-hour fasting and even to 137.04 +/- 15.59 mg per 100 g after three-day fasting of 72 hours. After re-alimentation, the concentrations of uric acid were reduced to physiological values already within 24 hours.


[Diagnostic value of agglutination reaction with buffered Brucella antigen stained with rose bengal].

A specific buffered antigen has been obtained, employing a method developed by the authors, stained with Bengal rose and intended for performing a fast agglutination reaction to confirm brucellosis. The antigen produces a clear and demonstrative agglutination reaction with positive sera. Practically, the test is readily carried out, and can be made a routine both in every serologic laboratory and for investigations under field conditions. The reaction produced with this antigen can determine dependably the epizootic status on a farm or in the herd. The diagnostic value of the antigen is essential, especially with swine. Besides, it shows a wide a diagnostic scope for brucellosis with all species of animals (97--98 per cent).


Electron microscopy of cellular immunity reactions in B-cell deprived rabbits. Thymus derived antigen reactive cells, their micro-environment and progeny in the lymph node.

Three times sublethal total body X-irradiation with thymus shielding--at 14 days' intervals--established an 'isolated T-cell system'. Cellular immunity reactions in draining lymph nodes of rabbits have been analyzed at the ultrastructural level after challenge with horse spleen ferritin, the chemical sensitizer, 2-phenyl-4-ethoxymethylene-5-oxazolone and after skin allografting. A basic pattern of interdigitating cells (IDC) is described as a specific constituent of the thymus-dependent areas of peripheral lymphoid tissue. Their ultrastructural features and presumable functional relationship to the afferent loop of cellular immunity reactions are presented. The differentiation pathway of two T-cell lines is shown and discussed in relation to cellular and thymus-dependent humoral immunity reactions.


Intermediate (10 nm) filaments in human malignant mesothelioma.

Human malignant mesotheliomas were studied by electron microscopy. Three main types of cells were seen--submesothelial epithelioid cells, epithelial lining cells and fibroblast-like cells. In submesothelial epithelioid cells prominent arrays of intermediate (10 nm) filaments were often seen attached to plasma membrane, mitochondria, nuclei and concentric whorls of rough endoplasmic reticulum. The other types of cell found in the tumors, epithelial lining cells and fibroblast-like cells, lacked such distinct filaments. The intermediate filaments were especially abundant in cells with extensive whorling of endoplasmic reticulum. The association of intermediate filaments with such deranged cytoplasmic organization suggests that they play a role in the altered behavior of malignant cells.


Autoradiographic demonstration of DNA repair synthesis in ganglion cells of aquarium fish at various age in vivo.

Unscheduled DNA synthesis in highly differentiated ganglion cells of adult medaka (Oryzias latipes) was demonstrated by autoradiography. For this, part of bony skull of the fish was surgically removed and the brain of the living fish was directly exposed to a solution of 2 carcinogen and 3H-TdR. This technique is suitable for precise measurement of DNA repair synthesis in non-dividing cells of the central nervous system in vivo. Using this system, the effect of aging on the levels of DNA repair was investigated. There was no age-associated change in the ability of repair in ganglion cells of the medaka of various ages.


The formation of contacts between HeLa cells. Directed mutual outgrowth of cell surface protrusions.

The contacting behavior of HeLa cells in subconfluent monolayer cultures has been studied by phase contrast and scanning electron microscopy. We present further evidence that cells separated from each other by a cell-free space up to 20 micron width can simultaneously form directed and mutual protrusions against each other. A statistical analysis demonstrated that in more than half of the possible contact events a reciprocal outgrowth of cell surface protrusions had occurred. This suggests that contact formation is not just a random process, but may be influenced by so far unrecognized factors.


Morphometric and fine structural study of experimental autoallergic sialadenitis of rat submandibular glands.

To further our understanding of the immunopathologic mechanisms involved in experimental autoallergic sialadenitis of rat submandibular gland (EAS), histometric and fine structural studies were undertaken. Rats were immunized with allogeneic submandibular glands (SMG) emulsified in complete Freund's adjuvant. Control rats were not treated (C) or adjuvant treated (At). The rats were sacrificed 7, 14, 21 and 28 days after immunization and their SMG were processed for light and electron microscopy. Groups "C" and "at" showed normal acini and ducts. The SMG at 14 days showed significant loss of acini and granular ducts, severe lymphocytic infiltration and the appearance of undifferentiated ducts. The cells of the latter showed abundant free ribosomes, few profiles of rer, no secretory granules and in some cells autophagic vacuoles. Pseudopods of many lymphocytes were found in juxtaposition to degenerating parenchymal cells, mast cells and eosinophils. The extralobular ducts were significantly increased at 7, 14, and 21 days. The immunized glands showed evidence of regeneration at 21 and 28 days. Terminal tubule cells, proacinar cells and acinar cells, at various stages of maturation, were found in the regenerating glands.


Some cellular changes associated with triton WR-1339 accumulation in rat hepatocytes.

Electron microscopic morphological and cytochemical techniques were used to follow the sub-cellular events that accompanied Triton WR-1339 accumulation in hepatocytes. Localization of two lysosomal enzymes, acid phosphatase and aryl sulfatase, clearly established the lysosomal nature of the Triton WR-1339 containing electron-lucid structures that appear in hepatocytes following treatment with this compound.


The pattern of lymphocytes in the thymus and spleen after labeling with 3H-thymidine and 3H-deoxycytidine.

Adult male untreated mice (NMRI) were investigated after radioactive labeling with 3H-thymidine and 3H-deoxycytidine to find out whether the lymphocytes in the cortex and medulla of the thymus as well as in the perifollicular and periarteriolar regions of the spleen show a labeling pattern which allows a classification into T- and B-lymphocytes. The percentages of radioactively labeled small lymphocytes and their mean grain counts were determined. The percentages of radioactively labeled small lymphocytes after 3H-TdR and 3H-CdR showed no significant differences in both splenic zones. The grain counts over the lymphocyte nuclei in the periarteriolar zone showed lower values after 3H-TdR than after 3H-CdR. The lymphocytes in the perifollicular zone were strongly labeled with 3H-TdR and weakly labeled with 3H-CdR. In the thymus medulla, lymphocytes were weakly labeled with 3H-thymidine and strongly labeled with 3H-CdR. In the cortex no significant differences were observed. 75 to 80% of the small lymphocytes in the peripheral blood were weakly and 20-25% strongly labeled after 3H-TdR. Therefore there are similarities in the radioactive labeling pattern of thymic medulla lymphocytes and that of small lymphocytes of the periarteriolar zone of the spleen by both DNA precursors. The small lymphocytes in the peripheral T-dependent tissue zones, for example in the spleen, as well as in the mixed lymphocyte population of the peripheral blood can be differentiated from the B-lymphocytes through the difference in the amount of incorporation of 3H-thymidine and 3H-deoxycytidine.


[Development of experimental brain tumors in modulated amine metabolism].

There was found a correlation between dynamic changes in the serotonin level and mortality in rats with 9,10-dimethyl-1,2-benzanthracene induced blastomogenesis. An estimation was made of the influence of monoamine oxidase inhibitors, transamine and D, L-malic acid benzyldihydrazide on the type of a tumor produced. Chemical blastomogenesis in the case of cerebellar tumors is shown to be associated with the decreased serotonin content at the site of a tumor. But fluctuations of the serotonin level in the hypothalamus have not been detected. This evidenced that the decreased mortality rate caused by the administration of monoamine oxidase inhibitor is due to a lower production of astrocytomas and genetically related glioblastomas. The role of serotonin in increasing the astrocyte resistance to malignant degeneration has been discussed.


[Relationship between aminoglucuronide synthesis in the bodies of white rats and the physico-chemical properties of the substrate].

In rats 5-substituted 2-aminobenzophenones (R-NH2; CH3; Cl) formed N-glucuronides. Amounts of free substances and of the glucuronyl-conjugates, excreted with the urine, depended on the nature of the radical; the derivatives differed in the values of Hammet's constants, in the lipophility and alkalinity. Estimation of Hammet's constants enabled to find a satisfactory correlation between the physico-chemical properties of the derivatives studied and the amounts of glucuronides excreted with urine.


[Long-term therapy with calcitonin in Paget's diseases (author's transl)].

16 patients with a Paget's disease at the age of 51--80 years were treated by synthetic salmon calcitonine in a dosis of 20 mcg (80 MRCU/die). 14 patients could be observed for a longer time. In all cases there was a statically significant decrease of the increased alkaline serum phosphatase. The excretion of hydroxyproline in the collected urine had a decreasing tendency. Other laboratory parameters as calcium, phosphatase and acid phosphatase in the serum and the excretion of calcium and phosphate in the urine were not significant influenced by therapy. The patients felt subjective a clear improvement of the bone pains. After a six month-treatment the dosis was reduced (each 2--7 days 20 mcg salmon calcitonin sc). There was observed a rebehaviour of the subjective symptoms and an increase of the alkaline serum phosphatase, which did not reach the unitial values before the beginning of treatment. Calcitonine is an effective substance for the treatment of an active Paget's disease.


[Demonstration of bacteriostatic substances in boric acid preserved urine specimens].

The results of bacterilogical investigations of urine specimens which contain chemotherapeutics or other germ-inhibiting substances are to be used only with limitation. In order to avoid malinterpretations of microbiological findings by unknown natibacterial autoactivity of the investigation material the routine proof of germ-inhibiting substances in the urine by means of a simple agar diffusion test has proved. By preservation of boric acid which is to be recommended for a longer transport of urine specimens which are to be investigated bacteriologically the results of the inhibitor tests is not falsified.


[Permeability of the arterial vessel wall for labeled plasma proteins].

The permeability of the large arteries may be analysed by different methods. It is of different size in the individual arteries and is increased by hypoxia, by hypertension and by mediators. Thus increasedly atherogenic substances may enter the wall of the vessel.


[Development of volatile compounds from radicals arising during intermediate steps of the lipoxygenase-reaction (author's transl)].

The development of volatile compounds arising from radicals during intermediate reaction steps of the lipoxygenase-linoleic-acid-reaction (from soy) was investigated in model experiments with defined conditions. The results indicate as follows: Among the volatile compounds formed, hexanal has a special position. Its development is closely connected to the enzymatic formation of the 13-linoleic-acid-hydroperoxide because it is formed from the 13-linoleic-acid-peroxy-radical, which is a direct precursor of the 13-linoleic-acid-hydroperoxide. The other volatile products are apparently formed in the same way as by autoxidation. Their development is favoured by lack of oxygen, when the primarily formed linoleic-acid-radicals cannot react rapidly with the oxygen-radicals to form hydroperoxides. A small part of the volatile compounds is formed by autoxidation which always accompanies the enzymatic reaction.


[Therapeutic problems in the "short-bowel-syndrome" (author's transl)].

The authors report on 6 children with short-bowel-syndrome. The expectancy of life of the patients depends on the mucosal surface of the residual intestine and on the degree of adaption. After removal of larger proportions of the intestine, nutrition should be started parenterally and followed by an early but cautious oral feeding. The administration must be distributed continuously over the day. At first carbohydrates are given as monosaccharides, fats as M. C. T. and proteins as amino acid mixtures. Carrot soup has proved useful as a water-binding substance for the improvement of stool consistency. An anabolic condition of the metabolism should be maintained. Therapy with cholestyramin is indicated in chologenic diarrhoea. Substitution of vitamins, especially vitamin B12 is very important after resection of the ileum.


[Changes in the histamine concentration, histaminase activity and histaminopexic index of the blood in acute cerebral circulatory disorders].

In 67 patients with ischemic and hemorrhagic strokes the authors studied the histamine metabolism in its development correlating the observed changes (in the acute stage of the disease and following medicative therapy). The results demonstrated that in the acute period of the disease the histamine content in the blood increases, while the histaminase activity and the histaminpexic index decreases. It was shown that these changes are more distinct in hemorrhagic strokes. In extensive processes involving the subcortical nodes, the internal capsule and hypothalamus, these parameters show deeper changes and in the future do not normalize. Such studies may be of topico-diagnostic importance as well as of prognostic and therapeutical significance.


[State of peripheral circulation in the late stages of vibration disease].

The paper is concerned with a description of the results of polyrheovasographical studies in 102 patients with late stages of vibrational disease. The authors distinguished 3 variants of vascular disturbances: hypertonic, hypotonic, dystonic. The cold test detected in most of the patients changes of the vascular reactivity in the form of increased, decreased and--less frequently--inverse reactions to this stimula. The conclusion is made that polyrheovazographical studies permit to clarify the character and degree of the expressiveness of vascular disorders in most of the patients with vibrational disease which is very important for defining the stage of the disease and the assessment of the working capacity in this contingent.


[Bilirubin UDP-glucuronyltransferase activity in human fetal liver homogenates].

The bilirubin UDP GT-activity of the liver was studied from week 15 of pregnancy in 23 human fetuses and mature and immature dead newborns, respectively. No measurable bilirubin UDP GT-activity was found up to week 26 of pregnancy. The development of enzymatic activity presumably starts only postnatally, irrespective of gestational age of birth weight. Up to the fifth day the bilirubin UDP GT-activity is less than 0.2 mg of conjugated bilirubin/g liver/h, reaching in the second week values that correspond to approximately 20--30% of adult values. This activity is sufficient to prevent a clinically important hyperbilirubinemia because the concentration of unconjugated serum bilirubin was in all children below 12mg/100 ml.


Effects of H1 and H2 receptor antagonists on Tetrahymena.

In Tetrahymena pyriformis the phagocytotic rate increases in response to histamine, but neither the H1 antagonist phenindamine nor the H2 antagonist metiamide stimulate phagocytosis. The H1 antagonist counteracts the effect of histamine, whereas the H2 antagonist does not. The histamine receptor of Tetrahymena is of H1-type, since it cannot distinguish between histamine and antagonists which are closely related to it chemically. It does, however, distinguish between histamine and the chemically unrelated H1 antagonist, phenindamine. The H2 antagonist does not interact with the receptor.


[Control of mitochondrial Mg++-efflux].

Inorganic phosphate stimulates the release of Mg++ from liver mitochondria, depending on concentration; a concentration as low as 0.1 mM phosphate is already effective. The process is dependent on the electron transfer of the respiratory chain, and its rate is highest under conditions of endogenous respiration and with ascorbate and TMPD as substrates, respectively. The phosphate stimulated release of Mg++ is followed, with a pronounced delay, by a Ca++ efflux and a swelling of mitochondria. Addition of EGTA strongly reduced the rate of Mg++ liberation in the presence and absence of inorganic phosphate. Exogenous Ca++ is able to abolish the EGTA effect. ADP and ATP inhibit the phosphate stimulated release of Mg++. Phosphoenol pyruvate and free fatty acids enhance the rate of Mg++ and Ca++ efflux from the mitochondria. The results permit the conclusion that inorganic phosphate, Ca++ and various metabolites of the cell metabolism influence the Mg++ distribution between the extra- and intramitochondrial space, thus controlling the permeability of the mitochondrial inner membrane for monovalent cations.


[Parenteral feeding of surgical patients].

1. Under stress an increased amount of labelled amino acids is incorporated. 2. Under the conditions of stress amino acids too participate in the process of synthesis. 15N-glycine was used as tracer in a quantity of 0.64 g of amino acid and 24 kcal per kg per day, that is at a 0.027 g per kcal. hour infusion rate, so that the infused 15N corresponded to 75% of the total residual nitrogen in healthy subjects and 57% in operated patients. 3. Sixteen percent of the infused 15N is secreted with the urine of healthy subjects as urine nitrogen, and 57% as urine nitrogen and 4--5% as ammonia nitrogen with the urine of the operated cases. 4. In contrast to normal conditions, under stress a higher percentage of the infused amino acids participates in energy production. 5. Stress enhances uropoiesis as in regards both quantity and speed. 6. No difference in acid-base balance was found in the case of postoperative infusion; urinary and plasma concentrations remained within normal limits.


Differentiation between benign and malignant monoclonal gammopathies by discriminant analysis on serum and bone marrow parameters.

Bone marrow samples of 28 individuals with clinically benign and of 41 patients with malignant monoclonal gammopathy were analyzed for the total number of lymphoplasmocellular elements containing cytoplasmic immunoglobulins and for the monoclonal fraction of these cells. Monoclonal immunoglobulin components were determined in sera. A discriminant analysis was performed on the data: the variables were transformed and in a stepwise procedure used for the construction of a discriminant function which by adividing point allowed a good distinction between the two groups of patients. By use of this discriminant function, 91% of the patients in the sample were correctly classified.


Cytoplasmic immunoglobulins in bone marrow cells of polyclonal and of monoclonal origin.

Cytoplasmic immunoglobulins in human bone marrow plasma cells and lymphoid cells were characterized by direct immunofluorescence with fluorochrome-labelled reagents specific for immunoglobulin heavy and light chains. The percentage distribution of cells containing IgA, IgG or IgM and kappa- or lambda-immunoglobulins was determined in bone marrow samples from 168 immunologically normal individuals, in 11 patients with polyclonal increase of bone marrow plasma cells and in 80 patients with benign or malignant monoclonal gammopathies. A clear differentiation between monoclonal and polyclonal cell populations could be obtained in all cases.


Multiple lymphocyte transformation tests by phytohemagglutinin in healthy individuals: transient episodes of decreased lymphocyte blastogenesis.

146 serial determinations of spontaneous and phytohemagglutinin-induced lymphocyte transformation as measured by tritiated thymidine incorporation, were performed in 24 healthy individuals. 9 persons were studied intensively during a mean period of 40 days and the other 15 underwent random investigations during a period up to 10 months. Transient episodes of significant decreased lymphocyte transformation were revealed in 14 persons (58.4%) with regard to the spontaneous blastogenesis and in 11 subjects (45.8%) with regard to PHA-induced reactivity. The occurrence of the decreased values in PHA responsiveness was significantly higher in the intensively studied group compared to the randomly investigated one (p = 0.001). The probability of detecting one low PHA-related response in a normal subject was 11%. In only half of the cultures with low spontaneous blastogenic response did a simultaneous decrease in PHA-induced lymphocyte transformation occur. In addition to the currently used stimulation index, a new index termed the Blastogenic Cumulative Index is proposed. It is defined as the sum of the logarithms of the dpm values of the spontaneous and the PHA induced lymphocyte transformation. The CI is suggested to describe lymphocyte blastogenic function more accurately, and due to its simplicity warrents further study. Other indices for lymphocyte blastogenesis determination are discussed.


Ethnical and clinical aspects of chronic lymphocytic leukemia in Israel: a survey on 288 patients.

The ethnic distribution of 288 patients with chronic lymphocytic leukemia (CLL) from five medical centers in Israel during the decade 1960--1970 was investigated as well as other features of the disease. 80.5% of the patients were of East European descent, 14.5% originated from Asia and Africa and 5% were born in Israel. Based on the ethnic distribution of the elderly population of Israel during the above period, it is suggested that CLL occurs more frequently in European-born Jews than in Asian and African Jews. A low occurrence of Coombs positive hemolytic anemia was revealed, amounting to 7.2% of the patients. Of 68 patients who underwent serum immunoglobulin studies, up to 74% exhibited deficiency of at least one type of immunoglobulin. Low levels of IgA were encountered in 61.2%, IgM in 51.5% and IgG in 29.5% of the patients. 26 of 206 patients with CLL (12.5%), all of East European origin, had an additional primary malignant tumor, cancer of the skin and breast being the most frequent associated malignancies. In 6 patients of the 26, two additional neoplasms were diagnosed. Hypogammaglobulinemia was more frequent in patients with additional primary malignant tumors and in patients with advanced disease. The possible causes for the ethnic distribution of CLL in Israil as well as of other tumors are discussed.


Collection of in vitro colony-forming units from dogs by repeated continuous flow leukaphereses.

The presence of in vitro colony-forming units (CFUc) was demonstrated in leukocyte suspensions collected by continuous flow leukaphereses performed serially in dogs. The CFUc yield of one leukapheresis was usually between 10(4) and 10(6). Higher yields were obtained in the 2nd to 5th leukaphereses than in the first one in the same dog. The number of CFUc collected during one leukapheresis was about four times the number of CFUc present in the circulating blood at the beginning of the leukapheresis. After a diminution during leukapheresis the circulating CFUc pool was restored in 2 or 3 days with an increase in the ratio of CFUc to mononuclear cells. These results indicate that CFUc entered the circulating pool during and after leukapheresis and that the population size regulation of canine-circulating CFUc is different from that of the bulk of the mononuclear leukoytes.


Inorganic iron absorption in subjects with iron deficiency anemia, achylia gastrica and alcoholic cirhosis using a whole-body counter.

A precise although technically complicated method is described for the estimation of iron absorption. A steel chamber is used to measure the total radioactivity of the patients. A dose of 59Fe is administered orally and the retention of radioactivity is measured on the 14th day, this amount being equivalent to the amount absorbed. In our male group, the mean absorption of inorganic iron was 22.5 +/- 8%, and in females it was 43.3 +/- 11%. In 10 patients with iron deficiency anemia, the mean was 92.2 +/- 6% , in 10 with gastric achylia it was 4.6 +/- 4%, and in 12 chronic alcoholics a value of 13.9 +/- 7% was found.


beta-Thalassemia in Sicily: hematological and biosynthetic studies.

The degree of imbalance in beta(0)-Th and beta(+)-Th as well as the frequency of the two forms in Sicilian beta-thalassemic subjects have been studied. The hemoglobin synthesis in Rietti-Greppi-Micheli disease (RGMD) and in the beta-thalassemia trait has also been studied. In an unselected thalassemic population, about 30% have been found to be beta(0)-Th. Both groups of beta(0)-Th and beta(+)-Th showed severe imbalance with alpha/non-alpha ratio of 4.22 +/- 1.88 (SD) and 3.46 +/- 1.36, respectively. This difference was not statistically significant. In RGMD the alpha/non-alpha ratio was 2.12 +/- 0.36 while in the beta thalassemia trait it was 1.76 +/- 0.35.


Relationship of density distribution and pyruvate kinase electrophoretic pattern of erythrocytes in sickle cell diseases and other disorders.

The density distributions of red cells from sickle cell disorders and other hematological diseases were determined. In sickle cell anemia there was an increase in the proportion of cells in both the heaviest and lightest fractions. In hemoglobin SC disease, a small fraction was shifted to heavier cells. Sickle cell trait blood had a normal density pattern. In hereditary spherocytosis an increase in the number of heavy cells was observed. Thin-layer polyacrylamide gel electrophoresis of red cell pyruvate kinase demonstrated that the pyruvate electrophoretic pattern was related to density distribution.


Functional heterogeneity of transferrin-bound iron: iron uptake by cell suspensions from bone marrow and liver and by cell cultures of fibroblasts and lymphoblasts.

According to the hypothesis of Fletcher and Huehns, functional differences exist between both iron-binding sites of transferrin. The site designated A should mainly be involved in the delivery of iron to erythroid cells, whereas site B should donate its iron preferentially to cells involved in the absorption and storage of iron. In the present study this hypothesis could be confirmed by in vitro experiments with various cell types. Iron transferrin preincubated with rat bone marrow cells donates less iron to rat bone marrow cells, Chinese hamster fibroblasts, human fibroblasts and human lymphoblasts than freshly prepared iron transferrin equal in iron and transferrin concentraion. Rat liver parenchymal cells, however, take up more iron from preincubated than from freshly prepared iron transferrin. Obviously, site A not only donates iron preferentially to erythroid cells but also to (rapidly) dividing nonerythroid cells in culture. From experiments with iron transferrin mixtures in which radioiron was present at low or high iron saturation, it could be concluded that rat bone marrow cells take up iron equally well from monoferric as from diferric transferrin. The observed functional heterogeneity could, therefore, not be ascribed to differences between monoferric and diferric transferrin.


Paraproteinemic variety of pure red cell aplasia: immunological studies in 1 patient.

A case of adult pure red cell aplasia (PRCA) with a serum IgG inhibitor to erythropoiesis and an IgG lambda M component is presented. The study of lymphocyte populations revealed a slight but definite decrease of E and EA rosettes, with dissociation between E rosettes and PHA blastic transformation of blood lymphocytes and increase of membrane IgM-bearing lymphocytes. The relationship between PRCA and paraproteinemia is discussed: it is suggested that the serum M component may derive from an immunological unbalance between T and B lymphocytes. Since a survey of the literature reveals 5 similar cases, it is suggested that paraproteinemia may be the hallmark of a particular variety of chronic PRCA 'type 1'.


A new method for the detection of the plasminogen activator content of vein walls.

The plasminogen activator content of a vein wall has been measured by estimating the radio-activity released from a 125I-tagged fibrin clot by incubating that clot with a known weight of the vein wall. This method could be used in the investigation of the fibrinolytic system of the body in its normal distribution and in the diseases of the vascular system.


Non-Hodgkin's lymphoma terminating in acute myelogenous leukemia.

The number of patients with non-Hodgkin's lymphoma who develop acute myelogenous leukemia is relatively small. The case of a patient with histologically proven diffuse histiocytic lymphoma who died with unequivocal acute myelogenous leukemia 5 years after the lymphoma diagnosis is presented. The difficulties in differential diagnosis are cited with a review of the literature.


Prognostic factors in multiple myeloma: a retrospective study using conventional statistical methods and a computer program.

The prognostic significance of age, sex, ethnic origin and various laboratory data was studied retrospectively in 69 patients with multiple myeloma using conventional statistical tests and the multiple regression computerized analysis. The conventional statistical analysis confirmed that age, anemia, uremia, hypoalbuminemia, hyperglobulinemia, hyperuricemia and IgA lambda type myeloma were associated with a poor prognosis. The multiple regression analysis indicated that age and blood urea nitrogen levels were the only variables which significantly affect the survival of patients with multiple myeloma. A correlation was found between blood urea nitrogen levels and other laboratory data of apparent prognostic value. The differences between our results and those of other authors are discussed and it is suggested that they may, in part, be due to the fact that the interplay between the various prognostic variables was not exposed in other studies.


"Idiopathic" Bence-Jones proteinuria.

During a prospective screening for proteinuria in diabetic patients, isolated Bence-Jones proteinuria was detected in 2 cases. The first patient, a 52-year-old black female, was seen for evaluation of a slow but progressive weight loss which was attributed to poor adjustment of insulin therapy. The patient gained weight after an increase of the daily insulin administration. She had plasmocytosis in a bone marrow aspirate, but no other evidence of myelomatosis. The second patient, a 59-year-old black male who was seen for routine evaluation of his diabetes, had no clinical or laboratory evidence of myelomatosis. Although precise definition of these cases as "benign" or "idiopathic" Bence-Jones proteinuria is impossible without prolonged follow-up, at the time of presentation they appeared to fit this classification. This observation is one further example that isolated Bence-Jones proteinuria may be seen without any evidence of malignant B-cell dyscrasia.


Lymphoid antigens on blast cells in the agranular metamorphosis of chronic myelogenous leukaemia.

Undifferentiated blasts from a Ph'-positive chronic myelogenous leukaemia (CML) in terminal metamorphosis were reacted in an indirect immunofluorescence test with antilymphocytic globulins (AHLGs), raised against cultured lymphoblasts, thoracic duct and peripheral blood lymphocytes from healthy donors. After proper myeloid and/or monocytic absorptions the AHLGs interacted strongly with the undifferentiated blasts of CML, while this was not true for parallel controls with non-lymphoid leukaemias, both acute and chronic. The intensity of fluorescence, as determined by the use of a microfluorimeter, on these agranular blasts was comparable to the positivity of lymphoid cells from acute and chonic lymphatic leukaemias. These findings lend further support to the conception of a lymphoblast-like variety of terminal blastic crisis in chronic myelogenous leukaemia.


Defect of bone marrow granulocyte reserve in liver cirrhosis evaluated with etiocholanolone.

In patients with cirrhosis, the etiocholanolone test showed a decrease in the bone marrow granulocyte reserve; in all the cases studied, the baseline counts of peripheral granulocytes were normla. The mechanisms leading to such a defect are explained.


Study of amino groups of the human platelet membrane.

The authors attempted to evaluate different reagents in order to quantify the amino groups of the platelet membrane. The study was carried out by the action of different aldehydes and acid anhydrides. The use of 2,4,6-trinitrobenzenesulfonic acid made possible an approach by electrophoresis and chemical assay. The results showed an increase in the surface charge corresponding to a mean number of amino groups varying from 1.86.10(5) groups with citraconic acid to 3.94.10(5) groups with acetaldehyde.


Chronic granulocytic leukemia, neutrophilic type, with paraproteinemia (IgA type K).

A patient with chronic granulocytic leukemia, neutrophilic type, was followed for 28 months. A paraproteinemia, IgA type K, and Bence Jones proteinuria (K) appeared without prior chemotherapy with alkylating agents.


The effects of ethylene-1-hydroxy-1, 1-diphosphonate on cellular transformation and organic matrix of the epiphyseal growth plate of the rat--a light microscopic and ultrastructural study.

Ethylene-1-hydroxy-1, 1-diphosphonate (EHDP) was administered intraperitoneally to one-day-old rats. In the first experiment, each animal was given 4 injections of EHDP distributed over two consecutive days and corresponding to a total amount of EHDP of 100 mg/kg bwt/day. The animals were sacrificed 12 hours after the last injection. In the second experiment, each animal was given 3 injections, each containing 50 mg of EHDP/kg bwt, with an interval of 6 hours and were thereafter left to survive for 4 days. Animals in the first experiment showed in comparison to normal controls an increased width of the hypertrophic zone; lack of calcified septa within the zone of provisional calcification; persistent atypical chondrocytes in the calcification zone and a large number of matrix vesicles lacking in crystals. The ground substance showed an accumulation of fine precipitates apparently representing undegraded aggregates of proteoglycan macromolecules. Animals in the second experiment formed a new apparently normal epiphyseal growth plate, while the "old" epiphyseal cartilage formed under the influence of EHDP remained largely unresorbed within the metaphysis. Besides the previously described inhibitory effects of diphosphonates on the crystallization of matrix vesicles and the growth of hydroxyapatite crystals, EHDP, at the doses used, was found to have a profound inhibitory effect on the differentiation and migration of the epiphyseal chondrocytes as well as on the degradation of proteoglycan macromolecules. The observed inhibition of vascular invasion appears to be related to inhibition of enzyme degradation of the ground substance, as evidenced by the observation of extracellular lysosomelike bodies in the erosion zone.