[Changes in leucocyte metabolism during growth in children born with malnutrition]. Changes of energy metabolism in leucocytes have been studied longitudinally as well as cross-sectionally in three groups of children born: 1.- at term, with normal weight; 2.- with intra-uterine malnutrition; 3.- prematurely. The longitudinal study showed that, at birth, the activity of adenylate kinase as well as concentrations of ATP, ADP AND AMP were significantly lower in the malnourished than in the normal child. At one year of age, the values of enzyme activity are approximately equal in both groups, while the concentrations, of ATP and ADP are higher in malnourished children. Finally, at two years of age all values found, with the exception of AMP concentration, were higher in malnourished than in normal children born at term. In the data of the cross-sectional study this accelerated biochemical maturation is also shown.


[Food additives and their possible genetic toxicity; microbiological determination]. In the present work we intend to find an accurat methodology to establish in an easy way the mutagenic potential of drugs employed as food additives. For that purpose we first selected a microbiological system for performing this assay. The method assayed consisted of investigating the effect exerted on genetic recombination by the following chemical agents: Chloroacetic Acid, Iodoacetic Acid, Sorbic Acid, Potassium Metabisulfite, Sodium Nitrite, Auramine and Erythrossine. The activity of these agents was detected though their effect on the transformation of an auxotrophic strain of Bacillus subtilis. Comparative assays of reversion of characters have been made with strains of Salmonella typimurium already used by other authors. These assays have also been repeated with several auxotrophic strains of Bacillus subtilis and different genetic characters have been studied. Most results suggest that changes in the recombination process should have occured at different levels according with the drugs assayed. On the other hand, the results of reversion have not been significant enough. We think that more accuracy is afforded by both the recombination and the reversion assay developed to other for this kind of detection.


[Peptidoglycan type and cell wall polysaccharide composition of Cellulomonas cartalyticum and some coryneform organisms (author's transl)]. Cellulomonas cartalyticum was found to contain a peptidoglycan type different from that of the other species of Cellulomonas. The diamino acid is lysin instead of ornithine and the interpeptide bridge consists of D-Asp-D-Ser. The same peptidoglycan type occurs in Corynebacterium manihot, Brevibacterium liticum and Arthrobacter luteus. These non cellulolytic organisms are most likely not closely related with Cellulomonas cartalyticum, as indicated by the very different G +C content of their DNA, although they formed a narrow cluster including C. cartalyticum when numeric taxonomical methods were applied.


Transient change in the ATP pool of Anabaena cylindrica associated with ammonia assimilation. When N2-grown cells of Anabaena cylindrica were exposed to ammonia (50 micron to 5 mM) in the dark, the size of the ATP pool was reduced by 40% within 1 min, but restored after 5 or 6 min. The decrease in ATP was accompanied by increases in ADP and AMP, while the total adenylate content remained unaltered. The ammonia-induced change in the ATP pool was completely eliminated when algal cells were treated with L-methionine-DL-sulfoximine, an inhibitor of glutamine synthesis. These results suggest that ammonia is rapidly assimilated through the pathway mediated by glutamine synthetase accompanied by reduction of the ATP pool.


The occurrence and identification of intracellular polyglucose storage granules in Methylococcus NCIB 11083 grown in chemostat culture on methane. The accumulation of intracellular storage granules (0.03--0.5 micrometer) by Methylococcus NCIB 11083 when grown under conditions of ammonia limitation with methane as the sole source of carbon and energy was inversely proportional to the dilution rate. The isolated material was composed entirely of glucose residues and the infra-red spectrum exhibited characteristic absorption bands at 925 cm(-1), 845 cm(-1) and 745 +/- 4cm(-1), indicating the presence of alpha (1 leads to 4) glycosidic linkages. The polymer dissolved in hot water to give an opalescent solution that formed a violet iodine complex with an absorption maximum at 550nm, identical to that observed with reference amylopectin. The percentage of the polysaccharide released as maltose by the action of beta- and alpha-amylases was 55--64% and 80--90% respectively, values very similar to those obtained by the action of these enzymes on reference amylopectin and glycogen. Methylation analysis indicated that the average interior and exterior chain lengths of the polymer were 2.7 and 10.0 glucose units respectively and confirmed that the Methylococcus polyglucose is a branched polymer composed of units joined by 1 leads to 4 and 1 leads to 6 linkages. The number average molecular weight of the polymer is 2--4.5 x 10(5). The stored polymer was metabolised by the organism and its metabolism resulted in the synthesis of protein.


[Enterocutaneous fistulas of the small intestine in children: therapeutic approach. Study of 22 cases]. 25 cases of post-operative small intestinal fistulae in children are described. 24 benefited by intensive feeding either exclusively parenterally (20 cases) or orally by constant infusion of an elemental diet (4 cases). In 13 cases the fistulae closed spontaneously but the other 11 needed further operations after an average of 41 days feeding. 2 children died; 1 was operated on early and the other had chronic granulomatous disease. Thus it is important to avoid early surgical intervention and to ensure adequate drainage of fistulae. Intensive feeding either parenterally or orally has an important role in this condition.


Long-acting oral vs injectable antipsychotic drugs in schizophrenics: a one-year double-blind comparison in multiple episode schizophrenics. Sixty patients meeting the criteria established for schizophrenia who attained a clinical plateau following hospital discharge were randomized to receive for one year either penfluridol, 20 to 160 mg orally once each week, or fluphenazine decanoate, 0.5 to 4 ml every two weeks. The relapse rate for both treatments was low and equal. The rate of recurrence of psychosis for patients receiving penfluridol was 7% and for those receiving fluphenazine decanoate 10%. A retrospective comparison of the penfluridol group was made to a similar group of patients assigned to placebo in an earlier study. Placebo-treated patients had a relapse rate of 68%. Penfluridol patients had statistically fewer psychotic relapses. Questions about the possible carcinogenicity of penfluridol in animals will have to be resolved before it can be widely used. This study demonstrates the feasibility of using an oral, long-acting antipsychotic agent. It would be a useful psychopharmacologic addition in the treatment of outpatient schizophrenics.


Behavioral effects of protirelin in schizophrenia. The effects of protirelin were compared with those of placebo in a multi-institutional, double-blind, controlled study of 143 chronic schizophrenic patients. Treatment with neuroleptics was continued during the study and 4 mg protirelin per day was orally administered for 14 days. Protirelin appeared to be significantly superior to placebo on the physicians' global ratings of efficacy. Increased motivation for work was isolated as a target effect but such symptoms as facial expression, emotional rapport, and psychomotor activity also appeared to be improved by addition of protirelin to the neuroleptics. Onset of the therapeutic effect of protirelin occurred within a week of medication in most of the patients who showed improvement. No adverse reactions were encountered.


Thyrotrophin-releasing hormone (TRH) stimulation test in manic-depressive illness. The thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH 200 microgram intravenously was studied in 19 patients with unipolar depression, 12 with bipolar depression, 14 with mania, and 5 with mixed manic-depressive illness. The TSH responses were decreased in all of these affective disorders compared to those found in 10 patients with reactive depression, 5 with reactive paranoid psychosis, 14 with neurotic depression, and 60 controls. The decrease of the TSH response in manics could not be accounted for by the effects of neuroleptic drugs. The TSH response in the groups with reactive depression, reactive paranoid psychosis, and neurotic depression, respectively, did not differ significantly from that found in controls. With the exception of a decrease in serum T3 level and free T3 index in the manics, no significant differences in serum T3 level or in free T3 and T4 indexes were found between the groups. Changes found in serum T4 level were due to changes in the thyroxine-binding proteins.


[Preparoxysmal fits of laughter from misformation of the hypothalamus (author's transl)]. Fits of laughter have been described in a number of instances with a differentiation made between primary and secondary fits. Fits of laughter in the case of pubertas praecox resulting from a hyperplastic deformation at the base of the IIIrd ventricle have not been observed as yet. The case here described shows that fits of laughter of this type can be observed prior to commencement of the actual epileptic fit itself. A short description if given of how normal laughing and crying comes into being, referring to the relevant literature.


Induction of arylhydrocarbon hydroxylase and UDP glucuronosyl transferase by PCB in hepatic cell cultures. The purpose of the investigation was to derive a hepatic cell line to be used in induction studies of drug metabolizing enzymes. Two pure cell lines were isolated from primary liver cell cultures, one with an epithelial-like appearance, the other with a fibroblast-like appearance. The specific activities of arylhydrocarbon hydroxylase (AHH) and UDP glucuronosyl transferase (UDPGT) were greater in hepatocyte cultures than in primary cultures or in fibroblast cultures. PCB enhanced the activity of AHH and UDPGT in hepatocyte cultures. These results indicate that cultured hepatocytes can be used to study the effect of PCB on drug metabolizing enzymes.


[Alteration of the construction and cellular composition of ileo-colonic lymph nodes of rhesus macaques after administration of salmonella vaccine]. In stained histological sections, percentage ratio of areas to different cellular elements in structural components of the ileocolonic lymph nodes was studied in mature Macaca rhesus, normal and after injection of salmonella vaccine. A rather considerable reaction in all structural components and cell composition of the lymph nodes was demonstrated as a response to immunization of the animals. These changes were demonstrated in decreased area occupied by the cortical substance and in increased area occupied by the medullar substance of the lymph node. In the cortical substance, together with decrease in the cortical plateau, total number of folliculi rises with formation of light centers in them. Calculation of cellular elements revealed that in the cortical substance cytopoietic function was inhibited; that was expressed in decreasing mitoses and blast forms in the cells. Most drastic alterations occur in myelin cords of the lymph nodes. Together with increasing area, a considerable reaction of acidophilic leucocytes, premature plasma cells and macrophages is observed. Their number increases notably.


[Cytoarchitectonics of ileocecal lymph nodes in newborn and sexually mature simians (pavian hamadrils)]. Cell composition of various components (cortical plateau, folliculi and cords) of ileocecal lymph nodes was studied in newborn, 1.5 and 2.5 months of age (2 animals) and in mature (3 animals) monkeys, Papio hamadryas. In histological sections obtained at the level of hilus of the lymph node cellular elements were counted by means of morphometric grid of Glagolev modifoed by S. B. Stefanov. The data obtained were statistically treated. Newborn and mature monkeys have their peculiar cytological profile in every structural component of the lymph node. The lymph nodes in the newborns contain much more reticular cells and young cellular forms (blast forms and large lymphocytes) than mature animals. In the newborns, the number of mitotically deviding cells in the cortical plateau and in folliculi is 6 times and in myelin cords 10 times as great as in mature monkeys. A much greater per cent of plasmatic cells in mature animals suggests their greater immunological activity. Age differences in cell composition of lymph nodes in young and mature monkeys seem to be connected with accumulation of cellular mass and growth of the node in young animals, as well as with general rearrangement of the organism as a whole (in particular with changes in nutrition, intensity of movement, hormonal background).


Ocular flora in the severely burned patient. One hundred six eyes of 53 patients with severe thermal burns were studied with serial conjunctival cultures during a four-month period. A dramatic shift of the normal conjunctival flora from the preponderance of Staphylococcus epidermidis and Corynebacterium to S aureus and Gram-negative bacilli was observed. This commonly occurred on the fifth to sixth postburn day and represented colonization of the conjunctiva by bacteria recovered from other sites in the body. Despite the high incidence of Pseudomonas aeruginosa isolates (34%) of these eyes, deleterious effects were noted in only three eyes in two patients in whom infectious corneal ulcers developed before these patients died.


A spectrophotometric assay of ATP synthesized by sarcoplasmic reticulum. The problems encountered with a coupled enzyme assay for ATP using glucose, hexokinase and glucose-6-phosphate dehydrogenase are discussed and a modification where fructose and glucosephosphate isomerase were substituted for glucose is described. This modified assay was used successfully to measure the ATP synthesized by reversal of the sarcoplasmic reticulum ATPase. ATP synthesized by adenylate kinase contaminating the sarcoplasmic reticulum was easily corrected for by a subtraction procedure.


Cytotoxic T cell responses to a syngeneic tumour: conditions for primary activation in vitro. Primary cytotoxic responses of DBA/2 lymph node cells to a syngeneic tumour (the mastocytoma P815) have been generated in vitro. The development of these responses is dependent on the addition of a soluble factor (CSCS) which is produced by concanavalin A-activated spleen cells. The response is mediated by T lymphocytes, can be detected at low effector to target cell ratios and is directed against P815 tumour-associated antigens.


Effect of surgical stress on serum thyroid hormones in hyperthyroidism. The effect of elective non-thyroidal surgery on serum total and free triiodothyronine (T3), reverse T3 and thyroxine (T4) has been studied in one patient with mild, untreated typical hyperthyroidism, one with mild T3 toxicosis and in four euthyroid patients. The high T3 level of typical hyperthyroidism became normal post-operatively, decreasing to 47% of the mean pre-operative level 24 hours after surgery, while total reverse T3 doubled. In euthyroid subjects T3 decreased to 57 +/- 6 (SEM)% of the pre-operative level 24 hours after surgery, associated with a doubling of reverse T3. The patient with T3 toxicosis, whose surgical  stress was less severe, showed a 17% decrease in T3 without change in reverse T3. Because the inverse post-operative changes in T3 and reverse T3 described in euthyroid subjects also occur in typical hyperthyroidism, measurement of serum T3 may be diagnostically unreliable after surgical stress.


Experience with large volume plasmapheresis in malignant paraproteinaemia and immune disorders. Clinical experience with large volume plasmapheresis in a wide range of malignant and immune disorders is described. An average of 4 litres of plasma was exchanged for various colloid and electrolyte solutions. Patient tolerance was good but close medical and nursing supervision in monitoring fluid balance and adverse reactions to replacement fluids is necessary. Plasmapheresis has been established to be of benefit in immunoproliferative diseases when complicated by hyperviscosity, and may also have a place in other cases with haemostatic or renal impairment. Autoantibodies, alloantibodies and immune complexes can be removed by plasmapheresis, but the effect is usually transient and the procedure should be combined with immunosuppressive therapy in most cases. The removal of blocking factors in disseminated malignant melanoma is an experimental procedure at present, but initial results have been encouraging.


The neural basis of aggression and its treatment by psychosurgery. The limbic system and its connections provide the neural basis for aggressive behaviour. Violent individuals may differ quantitively or qualitively from normal. Many of the latter suffer from epilepsy. In some the epileptiform discharges from the amygdala can only be recorded using depth electrodes. It can be taken that the control of abnormal degrees of violent behaviour is now possible. Should such operations be used? If so who should have them? What preacutions need to be taken that such operations are not abused? How can informed consent be obtained? The development of new surgical techniques make these questions pertinent if not urgent.


Cold-induced vasodilatation response at different water bath temperatures in monkeys. The response of cold-induced vasodilatation (CIVD) at different water bath temperatures was studied in 20 monkeys (3.5 kg) in a conscious state in a thermoneutral room. The animals were controlled by seating in a monkey chair, and the right hind limb up to 7.5 cm from the heel was immersed in a water bath for 60 min. Four series of experiments were conducted at water bath temperatures of 0 degrees, 4 degrees, 8 degrees, and 12 degrees C, respectively, at weekly intervals and the skin temperatures were measured from three sites in the foot. Marked CIVD response was noted from the dorsum and, to a lesser extent, from the sole of the foot, but no response was seen from the tip of the middle toe at 0 degrees, 4 degrees, and 8 degrees C water bath temperatures. The pattern of CIVD response at 4 degrees C was identical to that of 0 degrees C, but the response at 8 degrees C was poor and was absent at 12 degrees C. Three patterns of CIVD--such as hunting, proportional control, and slow, steady, and continuous rewarming--was observed. However, 15% of the animals did not exhibit any CIVD. The observations show that the CIVD response of monkeys is remarkably similar to that of man.


Effects of increased ambient CO2 on brain tissue oxygenation and performance in the hypoxic rhesus. Alterations of cerebral gas tensions and performance in response to hypoxia, with or without 5% CO2 in the ambient inspirate, were studied in eight conscious rhesus monkeys. The animals were trained to perform a lever press (Sidman) avoidance task. Physiological and performance data were obtained during exposures to normal (21% O2) and hypoxic (12, 10, and 8% O2--all with N2 balance) breathing atmospheres, with or without the addition of 5% CO2. With hypoxia, cerebral PO2 and PCO2 declined steadily, but a significant performance decrement was noted only at the 8% O2 level. With the addition of 5% CO2 to the inspired atmospheres, cerebral PO2 was elevated relatively but still declined as hypoxia intensified. Cerebral PCO2 and the avoidance task performance were sustained at near baseline values with the 5% CO2 inspirate.


Effect of dehydration on erythropoiesis in mice: relevance to the "anemia" of space flight. Mice deprived of water for 24 h showed an increase in hematocrit and loss of body weight comparable to that seen in men during space flight. The increase in hematocrit was entirely due to a decrease in plasma volume and was associated with suppression of erythropoiesis, but with no significant change in the serum titer of a presumptive humoral regulator of erythropoiesis, Erythroid Stimulating Activity (ESA). Mice deprived of water for 24 h may be a useful model for the study of the early hematological effects of space flight. The suppression of erythropoiesis due to a relative erythrocytosis appears to be independent of ESA.


Studies on the pathogenesis of hemorrhagic enteritis of turkeys. The infectivity of turkey hemorrhagic enteritis (HE) virus was studied in poults with no detectable maternal antibody and in turkeys bursectomized or injected with killed-virus preparations. Poults less than three weeks old were not infected by hemorrhagic enteritis virus, and survivors were susceptible to challenge at the age of eight weeks. Three- and four-week-old poults were susceptible to HE, and survivors resisted challenge. Bursectomy partially interfered with the immune response but did not alter the course of the disease, and survivors were resistant to challenge. Injections of spleen suspension containing 1% formalin produced antibody in only two of six turkeys. Three of the four poults without detectable antibody resisted challenge.


Variation in amount of enzyme protein in natural populations. Among strains of Drosophila melanogaster each derived from a single fertilized female taken from natural populations, there is variation in both alcohol dehydrogenase (ADH) activity and the amount of ADH protein. The correlation between ADH activity and number of molecules over all strains examined is 0.87 or 0.96 in late third instar larvae depending on whether the substrate is 2-propanol or ethanol. With respect to the two common electrophoretic allozymic forms, F and S, segregating in these populations, the FF strains on the whole have higher ADH activities and numbers of ADH molecules than the SS strains. Over all strains examined, enzyme extracts from FF strains have a mean catalytic efficiency per enzyme molecule higher than that of enzyme extracts from SS strains when ethanol is the substrate, and much higher when 2-propanol is the substrate. One FF strain had an ADH activity/ADH protein ratio characteristic of SS strains.


Alcohol metabolism in Drosophila melanogaster: uselessness of the most active aldehyde oxidase produced by the aldox locus. Alcohol dehydrogenase is necessary for ethanol detoxification and metabolic utilization. It has been generally assumed that aldehyde oxidase (AO) produced by the Aldox locus (3-56.7) is necessary for a further transformation of acetaldehyde into acetate. We find that various mutant strains (ma-l or Aldoxn) which do not produce an active enzyme show about the same tolerance to alcohol as do wild strains. This physiological paradox is probably to be explained by the discovery of another locus (not localized) which produced a small amount of AO in all tested strains. The adaptive significance of the genetically polymorphic Aldox locus is probably to be looked for in physiological pathways other than ethanol metabolism.


A simple approach for discovering common nonelectrophoretic enzyme variability: a heat denaturation study in Drosophila melanogaster. A simple procedure is described to detect genetic heterogeneity within electrophoretic classes at a locus in Drosophila, based on electrophoresis and heat denaturation studies. Temperature-resistant (tr) and temperature-sensitive (ts) isoelectrophoretic alleles at the phosphoglucomutase locus (Pgm) are present at polymorphic frequencies in natural and in laboratory populations of Drosophila melanogaster.


Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys. A semipurified diet containing 1.2 mg of cholesterol/Cal was fed to cynomolgus monkeys (Macaca fascicularis). At the end of 6 months, a group of 18 animals was killed for evaluation of atherosclerosis in the aorta and the coronary arteries. The remaining monkeys were assigned to three groups of 18 animals each and fed, during the following 18 months, semipurified diets containing 0.34 mg of cholesterol/Cal with or without alfalfa meal, or a diet consisting entirely of Monkey Chow. a decrease in cholesterolemia and plasma phospholipid levels, normalization in the distribution of plasma lipoproteins, and reduction in the extent of aortic and coronary atherosclerosis were observed in monkeys fed the semipurified diet containing alfalfa, although the intake of cholesterol remained as high as in the usual American diet. These changes, also observed in monkeys fed a chow diet almost devoid of cholesterol, suggest that alfalfa counteracts the atherogenic effect of dietary cholesterol.


Effects of some hypoxic cell radiosensitizers on the decay of potentially lethal oxygen-dependent damage in fully hydrated spores. Using a stopped-flow mixing and pulsed irradiation apparatus, a study has been made of the decay, to a harmless form, of radiation-induced species that would otherwise be lethal to spores on contact with oxygen. Aqueous suspensions of Bacillus megaterium spores were irradiated with electrons for approximately 1 s; at various times after irradiation oxygen in solution was added. As the interval between anoxic irradiation and introduction of oxygen increased, the fraction of spores surviving increased. This change in survival reflects the decay of potentially lethal species. The presence of electron-affinic radiosensitizers during irradiation enhanced the decay rate of this damage, the greatest enhancement being seen with sensitizers of the highest electron affinity. In contrast, the nitroxyl-free radical sensitizer TAN fixed the radiation-induced damage so that no increase in survival, and hence no decay, was seen.


[Fungal activity of various alkaloids isolated from Catharanthus roseus G. Don]. Evaluation is made of the fungal activity of ajmalicine, aparacine, catarantine, reserpine, tetrahydroalstonine, vincubine, vindoline and vindolinina--alkaloids isolated from C. roseus growing in Cuba--on new fungi strains and yeasts which include some of human clinical interest. The method employed was the diffusion in an agar mean with sections or cylinders containing solutions of the alkaloids at 2% and 3% concentrations. The best results are obtained with an aparicine base, while tetrahydroalstonine, vincubine and vindolinine solutions did not inhibit the growth in any of the germs tested.


Hypoxic radiosensitizers: prospects for effective compounds with fewer toxic side-effects. Several radiosensitizing chemicals, including a family of simple nitroimidazoles, were examined in E. coli and compared with misonidazole for toxic side-effects on endpoints such as mutagenesis, cell killing and inhibition of the synthesis of the inducible enzyme beta-galactosidase. While all the compounds were similar to misonidazole or better in radiosensitization, marked differences in the various side effects were found. There results show that for E. coli it is possible to find compounds that sensitize as well as misonidazole but which have decreased mutagenicity and fewer other side-effects. Of the compounds examined, KA121 (2,5-dinitroimidazole) is the most promising for future study because it combines good radiosensitization with low mutagenicity and toxicity.


Quantitative histological changes during early experimental carcinogenesis in the hamster cheek pouch. Sequential changes in the hamster cheek pouch epithelium following application of the carcinogen dimethyl benzanthracene have been assessed using stereological techniques. The most important progressive change found following cessation of carginogen painting appears to be an increase in the number and size of progenitor cells. Much of the marked increase in stratum corneum thickness seen in the early stages appeared to be related to a hyperplasiogenic rather than a neoplasiogenic action of the carcinogen.


In vitro effects of pemphigus antibodies on skin. Acantholysis occurring in rhesus monkey skin explants cultured on sera of 9 pemphigus patients was found to be largely dependent on the titre of intercellular antibody, and not on the participation of complement. Skin explants cultured on normal human sera and pemphigoid sera failed to give rise to intercullular staining or to develop lesions. Six of eight 'negative' pemphigus sera with intercellular antibody titres of less than 20 on skin (and titres ranging from 20 to 160 on monkey esophagus) reacted with the skin explants as revealed by direct immunofluorescence with an anti-IgG conjugate. The binding of antibodies from 3 of these 6 reactive sera resulted in some pathological changes in the explants. At least two of these 3 'negative' sera came from pemphigus patients with skin lesions.


Preparation of coenzyme M analogues and their activity in the methyl coenzyme M reductase system of Methanobacterium thermoautotrophicum. A number of 2-(methylthio)ethanesulfonate (methyl-coenzyme M) analogues were synthesized and investigated as substrates for methyl-coenzyme M reductase, an enzyme system found in extracts of Methanobacterterium thermoautotrophicum. Replacement of the methyl moiety by an ethyl group yielded an analogue which served as a precursor for ethane formation. Propyl-coenzyme M, however, was not converted to propane. Analogues which contained additional methylene carbons such as 3-(methylthio)propanesulfonate or 4-(methylthio)butanesulfonate or analogues modified at the sulfide or sulfonate position, N-methyltaurine and 2-(methylthio)ethanol, were inactive. These analogues, in addition to a number of commercially available compounds, also were tested for their ability to inhibit the reduction of methyl-coenzyme M to methane. Bromoethanesulfonate and chloroethanesulfonate proved to be potent inhibitors of the reductase, resulting in 50% inhibition at 7.9 X 10(6) M and 7.5 X 10(5) M. Analogues to coenzyme M which contained modifications to other regions were evaluated also and found to be weak inhibitors of methane biosynthesis.


Physicochemical and immunological homogeneity of spinin, the subunit-protein of bacterial spinae. Bacterial spinae from marine bacterium D71 are multi-subunit structures of a single protein. This protein, called spinin, is homogeneous by immunodiffusion and immunoelectrophoresis, amino acid composition, polyacrylamide gel electrophoresis with a number of buffer systems, sedimentation velocity and diffusion boundary analysis. Sedimentation equilibrium gives Mr = 19,000, while phosphate polyacryl-amide gel electrophoresis in presence of dodecyl sulfate gives Mr = 32,000. The lower Mr estimate for spinin is supported by sedimentation equilibrium in 6 M guanidine . HCl, and covalent cross-linking with dimethyl suberimidate or glutaraldehyde. The higher Mr value probably arises from an anomalous spinin-dodecyl sulfate interaction. Isoelectric focusing in polyacrylamide gel gives pI = 3.45; however, the focusing pattern also contains three distinct bands that may arise from hydrolysis of the spinin protomer during anodic migration. This study presents the first extensive physicochemical characterization of spinin and provides the basis for investigating the subunit assembly of spinae.


Hyperbilirubinemia connected with parenteral administration of higher amounts of fluids in premature infants. During a study on the influence of different amounts of fluid intake on water and electrolyte metabolism in the first 3 days of life, a high incidence of hyperbilirubinemia was observed in infants receiving a large water load (150 ml/kg/24 h) intravenously. The amount of meconium excreted during the 3-day period in newborns with total parenteral alimentation was significantly lower than in controls. Hyperbilirubinemia is considered to be due to the enterohepatic circulation of bilirubin present in the retained meconium. The role of slight hemolysis and insufficient stimulation of choleresis is discussed.


Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta). Experiments were conducted measuring the gastrointestinal absorption and elimination of a single dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead was followed for 23 days. Infant monkeys eliminated less and absorbed more orally administered lead. Adult animals excreted more absorbed lead in feces, while urinary excretion between adults and infants was similar. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in significantly greater body burden of lead-210 in infant animals. Blood lead values were increased in the infant animals, and were inversely correlated with body burden and percent absorption of ingested lead.


Token economy, pimozide and chronic schizophrenia. Response to a token economy was assessed in male chronic schizophrenic in-patients who were given, in a double-blind cross-over trial, pimozide (up to 20 mg daily) or chlorpromazine )up to 1,000 mg daily), each for three months. After six months there was little change in the patients' mental state, but general ward behaviour and token-rewarded "target"  behaviours improved significantly. There were no statistically significant between-drug differences, but the trend was that general ward behaviour, but not token-rewarded behaviour, improved more on pimozide. The patients who showed initiative and cooperated best with staff were those whose token-rewarded behaviour was most satisfactory.


Long-term parenteral nutrition.

Long-term parenteral nutrition. Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities.Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life.


Genital inoculation of male Macaca fascicularis with Neisseria gonorrhoeae and Ureaplasma urealyticum. Inoculation of the urethra, conjunctiva, pharynx, and anal canal of six male crab-eating macaques (Macaca fascicularis) with urethral exudate from male patients with urethral gonorrhoea or with laboratory gonococcal strains was unsuccessful in establishing infection or producing increased polymorphonuclear leucocytes on Gram stain. Intraurethral inoculation with laboratory strains of Ureaplasma urealyticum resulted in transiently positive urethral cultures for U. urealyticum and was associated in some cases with increased numbers of polymorphonuclear leucocytes on Gram stain of urethral material. The findings suggest that the crab-eating macaque may be useful for studying the pathogenesis of urethral infection with U. urealyticum.


Effects of various divalent cations on the survival of Neisseria gonorrhoeae in liquid media. The effect of various concentrations of divalent cations on survival of gonococci in liquid medium was studied. The growth of Neisseria gonorrhoeae was inhibited by manganous chloride in concentrations above 1 X 10(-5)mol/l while the growth of control organisms such as Neisseria meningitidis and Escherichia coli was not inhibited by the same salt even at 1 X 10(-2)mol/l. Copper sulphate, cobaltous nitrate, nickel chloride, and zinc sulphate also had deleterious effects on gonococci. Magnesium chloride at 1.5 X 10(-1)mol/l permitted the growth of gonococci. The toxicity of manganous chloride and copper sulphate in the liquid media was in some measure reduced by adding charcoal but not by adding starch. The significance of these findings is discussed in relation to the efficiency of primary isolation and transport media for gonococci.


A cell group associated with vertical eye movements in the rostral mesencephalic reticular formation of the monkey. A cytologically distinct group of cells in the rostral mesencephalic reticular formation was strongly labelled by injections of anterograde tracer substances into the caudal paramedian pontine reticular formation (PPRF) of the monkey. The cell group lies ventral to nucleus of Darkschewitsch (nD), rostral to the interstitial nucleus of Cajal (iC) and the tractus retroflexus (TR). It receives inputs from areas which control eye movements, PPRF and the vestibular nuclei, and sends efferents to the oculomotor nucleus. Physiological, anatomical and clinical evidence support the conclusion that this cell group is involved in the generation of vertical eye movements. In an attempt to be anatomically specific the name rostral interstitial nucleus of the medial longitudinal fasciculus (rostral iMLF) has been used.


TRH-like immunoreactivity in urine, serum and extrahypothalamic brain: non-identity with synthetic pyroglu-hist-pro-NH2 (TRH). TRH-like immunoreactive substances obtained from several areas of rat brain and from human serum and urine were chromatographically separated by TLC and the resulting immunoreactive 'elution profiles' compared with that obtained for pyroglu-hist-pro-NH2 (TRH). For hypothalamus and septal-preoptic samples TRH was present, but represented less than 100% of the immunoreactive substances. For cortex, amygdala, brain stem, serum and urine, no TRH was detectable in the immunoreactive substances from those samples. The implications of these findings in relation to 'TRH' distribution studies and validation of small peptide RIAs are discussed.


Epileptic and normal neurons in monkey neocortex: a quantitative study of degree of operant control. The object of this study was to quantify and compare the degree of control monkeys may assert over firing patterns of normal and epileptic neurons. Thirty-seven epileptic and 70 normal neurons were studied in detail. The operant task was for the monkey to generate specified consecutive interspike intervals (ISI). The monkeys demonstrated far greater accuracy in controlling consecutive ISIs of normal neurons and were only able to control the intervals between bursts from epileptic neurons. The data implies that high frequency bursts of action potentials from epileptic neurons are all-or-nothing events initiated by synaptic mechanisms. In addition, some data are from a monkey with epilepsia partialis continua; in comparison to less active foci, this focus was comprised of a higher percentage of 'pacemaker' epileptic neurons.


Visuotopic organization of the cebus pulvinar: a double representation the contralateral hemifield. The projection of the visual field in the pulvinar nucleus was studied in 17 Cebus monkeys using electrophysiological techniques. Visual space is represented in two regions of the pulvinar; (1) the ventrolateral group, Pvlg, comprising nuclei P delta, P delta, P gamma, P eta and P mu 1; and (2) P mu. In the first group, which corresponds to the pulvinar inferior and ventral part of the pulvinar lateralis, we observed a greater respresentation of the central part of the visual field. Approximately 58% of the volume of the ventrolateral group is concerned with the visual space within 10 degrees of the fovea. This portion of the visual field is represented at its lateral aspects, mainly close to the level of the caudal pole of the lateral geniculate nucleus (LGN). Projection of the vertical meridian runs along its lateral border while that of the horizontal one is found running from the dorsal third of the LGN's hilus to the medial border of the ventro-lateral group. The lower quadrant is represented at its dorsal portion while the upper quadrant is represented at the ventral one. In Pmu the representation is rotated 90 degrees clockwise around the rostrocaudal axis: the vertical meridian is found at the ventromedial border of this nucleus. Thus, the lower quadrant is represented at the later portion of Pmu and the upper at its medial portion. Both projections are restricted to the contralateral hemifield.


Multiple sclerosis: oligoclonal IgG, kappa-lambda light chain distribution and measles antibodies in brain extracts. The presence of measles antibodies in white and grey brain material and in 8 demyelination plaques from 6 patients affected with multiple sclerosis was investigated with the hemagglutination inhibition (HI) and complement fixation (CF) techniques. White and grey matter of 5 controls were run in parallel. No measles antibodies could be detected, except for one plaque, where the answer could be considered as doubtful. The immunoglobulin G (IgG) content and the kappa/lambda light chain ratios of all the samples were evaluated. No unique monoclonal immunoglobulin population could be detected, but kappa or lambda predominant oligoclonal populations appeared in controls as well as in MS IgG.


Information about movements in monkeys (Macaca mulatta) with lesions of dorsal prefrontal cortex. It is not known on what information prefrontal cortex acts. Since it has been suggested that it might operate on information about movements, rhesus monkeys were trained on a counting task testing memory for movements. They had to tap a key until a light went out and then repeat, either immediately or after a delay, the number of presses they had made. Monkeys with lesions of dorsal prefrontal cortex were impaired on this task, unlike monkeys with lesions of sulcus principalis alone. Cortex on the dorsal prefrontal convexity appears to act on information about movements.


The coordination of eye and head movement during smooth pursuit. Eye and head movements during tracking of a smoothly moving visual target were recorded in trained monkeys. The head movement clearly followed the target, although with considerable variability from cycle to cycle. The eye stayed relatively near the primary position and moved in an apparently irregular fashion; however, the sum of eye and head, or gaze, remained accurately on target despite the irregularity of the individual eye and head movements. When compared with tracking with head fixed, head free tracking was not measurably different in accuracy. Further experiments were performed which demonstrated a role for the vestibular system in coordinating eye and head during smooth pursuit. The results of these experiments can be best explained by postulating an internal smooth pursuit command driving both eye and head movements. In the case of the eye movement, this smooth pursuit command is combined with vestibular feedback from head movement before being forwarded to eye movement centers.


Microbial degradation of [C14C]polystyrene and 1,3-diphenylbutane. Microbial degradation of [beta-14C]polystyrene and 1,3-diphenylbutane, a compound structurally representing the smallest repeating unit of styrene (dimer), was investigated in soil and liquid enrichment cultures. Degradation rates in soil, as determined by 14CO2 evolution from applied [14C]polystyrene, varied from 1.5 to 3.0% for a 4-month period. Although relatively low, these percentages were 15 to 30 times greater than values previously reported. Enrichment cultures, containing 1,3-diphenylbutane as the only carbon souce, were used to determine the mechanisms of microbial oxidation of the polymer chain ends. Metabolism of 1,3-diphenylbutane appeared to involve the attack by a monooxygenease to form 2-phenyl-4-hydroxyphenylbutane followed by a further oxidation and subsequent fission of the benzene ring to yield 4-phenylvaleric acid and an unidentified 5-carbon fragment via the classic meta-fission pathway. Phenylacetic acid was probably formed from 4-phenylvaleric acid by subsequent beta-oxidation of the side chain, methyl-oxidation and decarboxylation. An initial examination of the population of microorganisms in the diphenylbutane enrichment cultures indicated that these oxidative reactions are carried out by  common soil microorganism of the genera Bacillus, Pseudomonas, Micrococcus, and Nocardia.


[Study of lysogeny in Bacillus thuringiensis and B. cereus]. Forty-eight strains of Bacillus thuringiensis and 12 strains of B. cereus were treated with ultraviolet light and mitomycin C. The former agent was the more effective inducer. Bacillus thuringiensis produces at least seven different phage particles with long, non-contractile tails. The frequencies of lysogeny and polylysogeny are 83 and 25% respectively. Morphologically defective phages occur in 25% of strains, whereas five of them produce low molecular-weight bacteriocins. One strain of B. cereus harbors "killer-particles." There is no apparent correlation between the presence of phage-like particles, phage senstivity, and serotypes, biotypes, or the origin of B. thuringiensis strains.


Comparative virulence and immunodiffusion analysis of Petriellidium boydii (Shear) Malloch strains isolated from feedlot manure and a human mycetoma. The virulence to mice of a Petriellidium boydii strain isolated from feedlot manure was compared with that of a strain from a human mycetoma. Washed spores suspended in 5% hog gastric mucin were injected intraperitoneally into non-inbred female albino Swiss mice. In 21 days, the mycetoma strain killed 95% of the test animals whereas injection of eight times as many feedlot strain spores resulted in only 28% mortality. A progressive, exclusively sinistral (leftsided) torticollis was the most obvious symptom of experimental petriellidiosis. Mycelia bearing annellospores were observed in PAS-stained sections of most internal organs, including the brains, of the test animals. Immunodiffusion analyses were  conducted on soluble antigen preparations with concentrated antisera produced in rabbits using live spore suspensions. The two strains contained common antigen but the proportions of two were significantly different.


Characteristics of PR5, a lipid-containing plasmid-dependent phage. An extensive characterization of plasmid-dependent phage PR5 isolated from sewage has been carried out. The phage has a head diameter of 65--68 nm, is isometric with a double-layered capsid, and a minority possess tails. It adsorbs to many but not all types of bacteria possessing P, N, or W plasmids. The phage contains 20% lipid, 15.1% DNA, and 64.9% protein by weight and has a buoyant density of 1.265 g/ml in CsCl. The DNA is double-stranded with a G + C content of 49% and a molecular weight of 7.4 +/- 0.6 x 10 (6) as shown by electron microscopy. Phospholipid content is 66% of lipid and consists of cardiolipin (13%), phosphatidylethanolamine (43%), and phosphatidylglycerol (44%) and differ quantitatively from that of host bacteria. Anti-PR5 serum inactivates other similar phages, PR3 and PR4. Phage adsorption is impaired in deep rough mutants of Salmonella minnesota.


Esophagitis due to adriamycin and radiation therapy for childhood malignancy. Esophagitis occurred in seven patients receiving mediastinal radiation and chemotherapy including adriamycin for non-Hodgkin's lymphoma, osteogenic sarcoma, and acute lymphocytic leukemia. Radiation doses were 500-2500 rad, below the reported esophageal tolerance dose. With subsequent adriamycin, recall esophagitis occurred in three of five patients at risk, two of whom developed strictures. Comparison to patients similarly treated without developing esophagitis revealed no specific risk factors, but suggested that the complication was less likely to occur if adriamycin therapy were completed more than two months before starting radiation. Adriamycin and radiation potentiate and recall each other's toxic effects on the esophagus. The interaction both increases the severity and lowers the radiation dose threshold for inflammation and stricture.


Histochemical and ultrastructural study of lactic dehydrogenase in chemically induced lung cancer. Light and electron microscopy studies of lactic dehydrogenase activity were carried out in embryonic, neonatal, and adult mouse lungs and in lungs undergoing chemically induced carcinogenesis. Embryonic mouse lungs were collected on the 6th, 12th, and 18th days of gestation; 1-day-old lungs were used for the neonatal model. These were compared with adult normal mouse lung and lungs of the animals treated with 4-nitroquinoline 1-oxide at a monthly interval until cancer developed. Enzymatic activity was seen in the embryonic, precancerous, and malignant lung tissues and was found diffusely in the cytoplasm of the epithelial cells.


A substrate for direct measurement of L-iduronic acid 2-sulfate sulfatase. Commercially available sodium heparinate has been sequentially treated with methanolic 0.06M hydrogen chloride and nitrous acid. The nondegraded material was separated by gel filtration from the nonsulfated and monosulfated disaccharides produced. The latter ones, obtained in 10% yield, have been used as a substrate for the direct measurement of the enzyme L-iduronic acid 2-sulfate sulfatase present in human plasma and fibroblast homogenates. Studies of the kinetics and pH optimum of the enzyme, by use of plasma of a patient with mucolipidosis II, indicated an apparent Km of 2.5mM and a pH optimum of 4.6--4.8. The levels of activity in normal plasma and plasma of a patient with Hunter's disease were found to be 20.4 +/- 1.22 units (mumol sulfate/24 h/g protein) and 3.25 +/- 0.35 units, respectively. In homogenates of cultured skin fibroblasts, the levels were 137.6 +/- 10.7 units for normal controls and 6.4 +/- 5.1 for patients with Hunter's disease. The plasma two obligated heterozygotes gave intermediate levels of activity, whereas the plasma of two possible heterozygotes gave either intermediate levels or entirely normal levels of activity.


Tumor localizing agents: the transport of meso-tetra(p-sulfophenyl) porphine by Vero and HEp-2 cells in vitro. The mechanism of transport of the tumor localizing agent, meso-tetra(p-sulfophenyl)porphine (TPPS4), was investigated in Vero and HEp-2 cells in vitro. Vero cells proved to be basically impermeable to the porphyrin, but a slow transport was observed. The uptake was linear with time and appeared to be carrier mediated, as it was strongly inhibited by cyanide or low temperature and demonstrated saturation kinetics. Transport in HEp-2 cells was more rapid and non-linear, reaching a plateau after about 2 h. Analysis of this uptake over a 20-fold range of porphyrin concentration revealed it to be biphasic. A low affinity, high capacity component appeared to be unsaturable and was unaffected by low temperature or metabolic inhibitors. This system is probably one of a passive diffusion. The high affinity, low capacity phase is probably carrier mediated. The tumor cells appear to be "leaky" to the porphyrin, with respect to the Vero cells. This may explain part of the localizing ability of TPPS4.


Species variability in plasma S-sulfonate levels during and following sulfite administration. It has been shown that S-sulfonate compounds (R-S-SO-3) are produced by the action of sulfite on reactive disulfide bonds [4,5]. Plasma S-sulfonate production was determined as a function of sulfite ingestion and intraperitoneal injection in rats, mice and rhesus monkeys. The tendency of these species and of the rabbit [8] to produce S-sulfonates in plasma was related to the availability of sulfite and of reactive disulfide bonds and to the stability of plasma protein S-sulfonates. The rhesus monkey and the rabbit accumulated plasma S-sulfonates much more readily than did the rat, while the mouse produced little, if any, under the same test conditions. Plasma protein S-sulfonate fractions in the rat and rhesus monkey were characterized by half-lives of approximately 4 and 8 days respectively. The sensitivity and precision of the analytical method for plasma protein S-sulfonate were improved by incorporation of 35S into the outer sulfur atom of the S-sulfonate moiety (R-S-35SO-3).


Alterations in calcium levels of coronary sinus blood during coronary arteriography in the dog. Intracoronary administration of contrast materials causes myocardial depression which is related to serveral physiochemical properties of the contrast solution. The role of variations in ambient calcium ions (Ca++) in mediating this effect was evaluated in 19 anesthetized dogs. Sodium meglumine diatrizoate caused decreases in left ventricular peak systolic pressure (LVPSP),-12.6 +/- 3.2%, and dp/dt at a left ventricular pressure (LVP) of 40 mm Hg, -14.3 +/- 4.1%. The total calcium (Cat) decreased from 10.2 +/- 0.2 to 6.5 +/- 0.2 mg%, while Ca++ decreased from 4.6 +/- 0.1 mg% to 2.3 +/- 0.7 mg%. In the presence of systemic hypocalcemia the myocardial depressant actions of this contrast materials were accentuated. Intracoronary administration of contrast material with added Ca++, calcium sodium meglumine metrizoate, caused no myocardial depression. Total calcium decreased only slightly (10.2 +/- 0.2 to 9.1 +/- 0.2 mg%), while Ca++ increased (4.8 +/- 0.1 to 5.1 +/- 0.2 mg%. During systemic hypocalcemia, the calcium metrizoate compound induced increases in LVPSP and dp/dt/LBP40. Thus, contrast materials caused myocardial depression which, at least in part, was related to reduction of ambient calcium through a dilutional and binding action. The addition of Ca++ to monomeric contrast materials reversed the myocardial depressant action and produced a transient rise in ambient Ca++.


Automated tests for the assessment of thyroid function. Fully automated methods have been developed for the determination of thyroxine and triiodothyronine levels, antibodies to thyroglobulin and the assessment of thyroid hormone binding proteins in serum, using a continuous flow radioimmunoassay system. In addition the feasibility of a partially automated assay for thyrotrophin levels has been demonstrated. These employ Auto Analyzer modules and antibodies covalently linked to a magnetisable solid phase support. Separation of bound and free antigen is achieved by applying an external magnetic field. The system currently operates at a rate of 30 samples/h and requires only 10 minutes incubation since it is not necessary to reach equilibrium. The results are similar to those obtained by conventional manual techniques, however the precision is improved and operator error eliminated.


Correlation of free thyroxine index and thyroxine: thyroxine-binding globulin ratio with the free thyroxine concentration as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays. The concentration of thyroxine-binding globulin in the serum can now be measured by a simple and specific radioimmunoassay. Triiodothyronine uptake and measurement of total thyroxine have been combined to yield a free thyroxine index which has been found to correlate with the clinical state of the patients. An estimate of the free thyroxine concentration, as measured by the thyroxine and thyroxine-binding globulin radioimmunoassays, provided a good correlation with the free thyroxine index and the thyroxine: thyroxine-binding globulin ratio. However, the thyroxine: thyroxine-binding globulin ratio is inaccurate when thyroxine-binding globulin concentrations are high or low.


A sensitive procedure for the diagnosis of N-acetyl-galactosamine-6-sulfate sulfatase deficiency in classical Morquio's disease. The trisaccharide 6-sulfo-N-acetylgalactosamine-glucuronic acid-6-sulfo-N-acetyl-[1-3H]galactosaminitol was used as a substrate for the determination of N-acetylgalactosamine-6-sulfate sulfatase activity. The amount of liberated sulfate was measured indirectly by separating monosulfated reaction products from the substrate on Dowex 1 X 2 microcolumns in a simple two step procedure. Fibroblast homogenates from patients with various genotypes, except classical Morquio's disease, released 410 +/- 90 pmol sulfate/h/mg cell protein. The enzyme exhibited a pH optimum of pH 4.8 and a KM of about 1 X 10(-4) mol/1. It was strongly inhibited by phosphate, sulfate and chloride ions. In three cell lines from patients with classical Morquio's disease a residual activity between 1 and 2% of the mean normal activity was found. All cell lines tested released sulfate from 6-sulfo-N-acetylglucosamine-glucuronic acid-[1-3H]-anhydromannitol. Cell extracts from cultured amniotic fluid cells exhibited a N-acetylgalactosamine-6-sulfate sulfatase activity between 120 and 320 pmol/h/mg protein. An enzyme activity of 370 +/- 100 pmol sulfate/h/mg protein was found in peripheral leucocytes from healthy donors. The determination of N-acetyl-galactosamine-6-sulfate sulfatase activity in one family with an affected patient indicated that the enzyme deficiency is also expressed in leucocytes.


Effect of a lipid load on blood and urinary carnitine in man. Blood and urine carnitine contents have been determined in patients before and after a lipid load and in patients on haemodialysis. Oral and intravenous lipid administration significantly depressed blood carnitine content and after 500 ml intravenous Intralipid urinary carnitine excretion fell by 43%. Blood carnitine was reduced by 50% by haemodialysis and returned to the pre-dialysis value within 20 h in 5 out of 8 patients. It is concluded that the blood carnitine level is normally controlled over a narrow range. The fall in blood carnitine concentration and urine excretion which follows a lipid load indicate a limiting role for carnitine in lipid utilization in man, and suggest that carnitine supplements could be of value during parenteral nutrition with fats.


Radioimmunoassay for 3,3'-diiodothyronine in human serum. A specific radioimmunoassay for measurement of 3,3'-diiodothyronine (T2') is presented. With the method described (ethanol extraction of native serum and lyophilisation of the extract) the application of 400 microliter serum equivalent in the assay is possible. Standards and sera are treated similarly. The detection limit is 0.625 ng/dl, comparison between direct assay and dried extract assay shows good correlation. Mean normal T2' serum concentration in man is 7.2 ng/dl (range 3 to 11 ng/dl), hypothyroid: below 3.0 ng/dl, hyperthyroid: 11-64 ng/dl (range). T2' level in cord-blood of newborns: 16.5 ng/dl. The urinary excretion of free T2' of normal man is 0.49 microgram/24 h (mean), a relatively high excretion rate in comparison to the low serum level.


Thyrotrophin, prolactin and growth hormone responses to TRH in barbiturate coma and in depression. The effects of 200 microgram thyrotrophin-releasing hormone (TRH) i.v. on thyrotrophin (TSH), prolactin (PRL), growth hormone (GH) and triiodothyronine (T3) were studied in eight patients with barbiturate coma due to attempted suicide, in the same patients after recovery, in eight depressive patients and in eight normal controls. The patients with barbiturate coma presented normal basal TSH and PRL, elevated basal GH and normal PRL but blunted TSH responses to TRH; their GH concentrations varied widely without consistent relation to TRH administration. The same patients after recovery from coma presented normal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a clear-cut rise in GH (i.e. more than 10 ng/ml) occurred after TRH administration. The depressive patients presented normal basal TSH and PRL, slightly elevated basal GH, and normal PRL but blunted TSH responses to TRH; in four of these patients, a moderated rise in GH (less than 10 ng/ml) occurred after TRH administration. The increment in T3 concentrations 120 min after TRH was found reduced in the comatose patients only. Basal cortisol was measured in all the subjects and found elevated in the comatose patients only. It is concluded that the abnormal TSH and GH responses to TRH observed in patients with barbiturate coma are more likely related to depressive illness than to an effect of barbiturates at the pituitary level. Barbiturates might affect thyroid secretion.


Atypical expression of beta-galactosidase deficiency in a child with Hurler-like features but without neurological abnormalities. A 28-month-old child was found to have several clinical features of lysosomal storage diseases, including: coarse facies, hepatosplenomegaly, lumbar kyphosis due to hypoplastic beaked L1 and L2 vertebral bodies, vacuolated lymphocytes in blood smears and rare foamy hystiocytes in bone marrow. However, no signs of neurological or ocular abnormalities were detected. A beta-galactosidase deficiency was demonstrated in leukocytes and cultured skin fibroblasts, with a residual activity toward 4-methylumbelliferyl-beta-galactopyranoside ranging between 5 and 15% of the normal mean. Normal activities were found for several other lysosomal acid hydrolases. beta-Galactosidase activities in leukocytes and cultured skin fibroblasts from both parents were within the normal ranges. The patient seems to represent an atypical expression of acid beta-galactosidase deficiency, since his clinical picture does not exaclty correspond to that of either the two classical types of GM1-gangliosidosis or other atypical patients reported in the literature havining beta-galactosidase deficiency.


Design and evaluation of leukaemia trials. A satisfactory clinical trial in acute leukaemia has always required a substantial investment in terms of both time and resources. Today, the therapeutic success in the disease is increasing further the difficulty in carrying such trials through to completion. Unless careful thought is given to all aspects of these trials prior to their initiation, there is a very real risk that discoveries of further improvements in treatment through clinical trials may be greatly delayed.


The effect of ethane-1-hydroxy-1, 1-diphosphonic acid (EHDP) on matrix induced ectopic bone formation. The effect of diphosphonates (EHDP) was studied on induced ectopic osteoneogenesis. Decalcified allogeneic bone matrix was implanted into the lumbar muscles in rabbits for an ectopic osteoinductor. The ectopic new bone formation was studied under continuous EHDP administration and after discontinuation of EHDP. Although there was no inhibitory effect of EHDP on the osteoinduction, the calcification of the new bone and the resorption of the implanted matrix was retarded. The induced "osteoid-like" tissue had an atypical structure with a small number of cells and a deficiency in collagen fiber bundles. There were also large fields of new cartilage formation. Thus remodelling and mineralization were inhibited under the influence of continuous administration of EHDP. After discontinuation of EHDP administration a recovery phase was observed which seemed to lead to the formation of a normal ossicle.


67Ga-citrate scanning in gastrointestinal malignancies. The value of 67 Ga-citrate scanning in cases of gastrointestinal malignancies is discussed. Seven cases are presented, including lymphomas of the stomach, small bowel, and rectum, and adenocarcinomas of the stomach and colon. In a review of the literature, there is general pessimism regarding the use of 67Ga scans in GI malignancies. Based on previous reports and our own experience, specific clinical situations are cited in which the scan is of considerable value for diagnosis and followup of GI malignancy.


Organization of immunoglobulin genes.

Organization of immunoglobulin genes. The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.


The handedness of rhesus monkeys: II. Concurrent reaching. Of 171 monkeys tested for handedness, 60 were found to make occasional bilateral concurrent reaches. These reaches accounted for only 1.3% of the total of 600 reaches observed for each animal. Younger animals were observed to make such reaches more frequently than older animals. Concurrent reaching was characterized by a lower degree of preference for the overall preferred hand than unilateral reaches made by the same animals at comparable periods of testing.


Bacterial endocarditis on a prosthetic valve. Oral treatment with amoxicillin. A patient with endocarditis due to Streptococcus faecalis on an aortic valvular prosthesis was successfully treated using large oral doses of amoxicillin concurrently with intramuscular administration of streptomycin. Oral therapy was employed because of a persistent reaction to intravenously administered antibiotics. Oral therapy for bacterial endocarditis occurring on an artificial valve may be attempted as a last resort when all other accepted therapeutic measures have failed.


Econazole: a review of its antifungal activity and therapeutic efficacy. Econazole1 is a recently introduced imidazole antifungal agent which is very closely related structurally to another imidazole derivative, miconazole. For local application the nitrate salt of econazole is used, while in preliminary investigations of systemic use in a few patients econazole base has been administered orally or intravenously. In uncontrolled studies in large numbers of patients, econazole nitrate has been administered topically in the treatment of dermatomycoses due to a wide variety of fungi, and vaginally in the treatment of vaginal candidosis; but it has not been compared with any other antifungal drug in controlled therapeutic trials in mycoses of the skin and has only been compared with nystatin in a few patients with vaginal candidosis. Until adequate comparative studies are done the relative place of econazole in the treatment of dermatomycoses and vaginal condidosis, compared with traditional antifungal agents and with other imidazole derivatives such as miconazole or clotrimazole, cannot be clearly stated. Nevertheless, econazole nitrate is an effective antifungal drug. In dermatological studies about 90% of a large number of patients were cured, often after a relatively short treatment period (2 to 6 weeks, as occurs with other imidazole antifungal agents). The cure rate was only slightly lower (about 85%) in patients with severe mycoses of many years' duration than in those whose infections were of more recent onset. In vaginal candidosis a 3-day treatment regimen using a 150mg suppository once daily was only slightly less effective (85% mycological cure rate) than a 15-day regimen using a 50mg dose (suppository or cream) once daily (90% cure rate). A 3 to 5 day 'higher' dose regimen was slightly more effective than a standard 15-day regimen of nystatin vaginal inserts in a small group of patients with vaginal candidosis. The convenience of the higher-dose shorter term regimen would likely be an important advantage to most patients. Whether other agents useful in vaginal candidosis would be as effective as econazole were they to be used in this way, has not been determined. Topical or intravaginal econazole nitrate has usually been well tolerated, side effects being limited to local irritation in about 1 to 4% of patients in most studies.


Appearance of EEG changes reminiscent of a secondary generalized epilepsy in a rhesus monkey inoculated with a strain of kuru. In a group of rhesus monkeys (Macaca mulatta) inoculated intracerebrally and intravenously with a strain (Enage strain rhesus L6 56) of kuru already passaged in rhesus monkeys, 1 monkey presented the typical EEG pattern of epileptogenic encephalopathy reminiscent of the Lennox-Gastaut syndrome. This observation provides no direct evidence for the viral origin of epilepsies of this type. It does, however, show that it is possible to induce an epileptogenic encephalopathy by an unconventional infectious agent.


Anticonvulsant action of a 1,5-benzodiazepine, clobazam, in reflex epilepsy. Clobazam, an anxiolytic 1,5-benzodiazepine, has been evaluated as an anticonvulsant in 2 animal models. In mice showing sound induced seizures, clobazam, 1--4 mg/kg, i.p., blocked seizure responses for 1--2 hr. In Senegalese baboons Papio papio showing photically induced myoclonus or seizures, clobazam, 2--12 mg/kg, i.v., totally prevented such responses for up to 6 hr. In baboons pretreated with allylglycine, 170--185 mg/kg, a similar but briefer protection was induced by clobazam. Neurological toxicity was not prominent (transient, slight nystagmus after clobazam, 2--6 mg/kg; muscular hypotonia after clobazam, 12 mg/kg). The possibility that 1,5-benzodiazepines are superior to 1,4-benzodiazepines in the therapy of epilepsy requires clinical investigation.


Alterations in learning performance in the seizure-prone baboon: effects of elicited seizures and chronic treatment with diazepam and phenobarbital. A comparison was made of the effects of chronically administered diazepam and phenobarbital with those of elicited seizures on repeated acquisition learning in 3 prepubertal Papio papio. The learning task required the baboons each day to perform different sequences of lever presses on a three-lever behavior panel. Middle dose levels of both diazepam and phenobarbital were found to improve learning performance relative to base-line control levels, as measured by total errors, efficiency, and time required to complete chains of various lengths to a fixed criterion. The doses were well within therapeutically relevant seizure control and clinical blood level ranges. Higher doses of both drugs generally abolished the performance gains achieved with the lower doses. Seizures elicited twice weekly for 2--3 weeks, or daily for 7 days, induced no overall decrement in performance. Cyclicity in subsequent performance was, however, induced by each individual seizure during the twice weekly seizure period, and learning performance was found to be significantly worse at 42 hr than at 18 hr after each seizure. Implications of these data for acquisition of learning in the epileptic are discussed.


Purification and partial characterization of three extracellular cellulases from Cellulomonas sp. Three extracellular cellulases have been purified from cultures of Cellulomonas. One was found in solution in the cell-free supernatant and two others were found to be bound to the cellulose added as a carbon source. The free enzyme and one of the cellulose-bound enzymes bind to Sephadex. The two cellulose-bound enzymes are glycosylated. The three enzymes behave as endocellulases towards soluble carboxymethyl-cellulose and have little activity on cellulose powder.


Introduction of hidden breaks during rRNA maturation and ageing in Tetrahymena pyriformis. The stability of Tetrahymena pyriformis cytoplasmic rRNAs and nuclear rRNA precursors has been studied by polyacrylamide gel electrophoresis under partly and completely denaturing conditions. Cytoplasmic 17-S rRNA (Mr = 0.66 X 10(6) consists of a continuous polynucleotide chain throughout its lifetime, whereas the bulk of 26-S rRNA (Mr = 1.2m X 10(6) dissociates upon denaturation. Two large fragments (F1, F2) of somewhat different molecular weights (Mr 0.63 X 10(6) and 0.58 X 10(6) and the small 5.8-S rRNA fragment (Mr about 50 000) are regularly observed. Some additional distinct minor fragments (F3-F6) are noted under certain preparative conditions, suggestive of artifactual origin. The following conclusions were made from the data obtained . (a) Newly synthesized 26-S rRNA molecules do not contain the 'central' hidden break (separating F1 and F2) until about 15 min after their appearance in the cytoplasm; however, they release during denaturation the 5.8-S and/or a short-lived 7-S fragment (Mr about 75 000) which might represent a direct precursor to the 5.8-S rRNA. (b) The immediate nuclear precursor to the 26-S rRNA (Mr 1.39 X 10(6) releases a small fragment of similar size (7 S). (c) The largest stable transcription product of the rDNA (pre-rRNA) does not contain any hidden break.


Morphologic aspects of the neurofibrosarcoma (neurogenic sarcoma). Two cases of malignant tumours of the nerve sheaths are reported. In the first patient, who had von Recklinghausen's disease, light- and electron-microscopic investigations showed an undifferentiated mesenchymal tumour of the radial nerve with the property of producing collagen fibres, an aspect characteristic of sarcoma of the fibroblastic type. In the second case a pleomorphic cell sarcoma of the cranial nerves of the left cerebellopontine angle was present. The morphologic aspects of these tumours show them to be primary mesenchymal tumours of the nerve (neurofibrosarcoma, neurogenic sarcoma) originating in the fibroblastic-like elements of the nerve sheaths. The clinical and nosologic framework of this type of malignant tumour of the nerve sheaths is discussed.


Moderate nonketotic hyperglycemia--a cause of focal epilepsy. Report of two cases and review of literature. Nonketotic hyperglycemia has a definite convulsive effect, which may manifest itself in generalized or focal seizures. This report deals specifically with focal convulsive phenomena. Two patients with nonketotic hyperglycemia focal seizures are described. Focal seizures are of motor Jackson, aphasic, adversive or of the 'epilepsia partialis continua' type. Different types of focal seizures may appear in one and the same patient. Focal epilepsy can be the first manifestation of a diabetic disorder. Focal epileptic seizures are linked with moderate nonketotic hyperglycemia with values of 360 mg% sugar and 310 osm. Higher values lead to generalized seizures and coma. The mechanisms are discussed and pertinent literature is reviewed.


Response variability of auditory cortex cells in the squirrel monkey to constant acoustic stimuli. Sixty-three cells in the superior temporal gyrus of awake squirrel monkeys were tested with 8 species-specific vocalizations plus noise, clicks and tones. Identical series of stimuli were repeatedly presented over 1-5 hour intervals. The responses elicited by both vocalizations and artificial stimuli in primary and secondary cortical neurons often varied over time. In several cases the selectivity of a cell to specific vocalizations appeared to change, i.e., a vocalization which was effective in eliciting a response at one point in the experiment, later became ineffective. In the primary cortex 50% of the cells gave variable responses to one or more of the vocalizations. Twenty percent of the primary cortical cells appeared to change the selectivity of their responses to specific vocalizations. In the secondary cortex 62% of the cells varied in their responses to vocalizations; 42% showing apparent changes in selectivity.


Subcortical projections of the dorsomedial visual area (DM) of visual association cortex in the owl monkey, Aotus trivirgatus. The efferent subcortical connections of the dorsomedial cortical visual area (DM) in the owl monkey were determined by tracing degenerating axons following lesions or by tracing axonal pathways following injection of radioactively labeled proline. Areas of termination included structures which are known to receive input from many other regions of cortex such as the claustrum, putamen, caudate nucleus, reticular nucleus of the thalamus and pontine nuclei. Other terminations were in subcortical structures which primarily receive input from visual area: these included the pregeniculate nucleus, the medial and central divisions of the inferior pulvinar nucleus, two loci in the superior pulvinar complex, the pretectum and the superior colliculus. Terminations were also seen in the lateral posterior nucleus, a part of the thalamus associated with the somatosensory system. These results further identify Area DM as an integral part of the visual system, suggest functional subdivisions of the pulvinar complex, and implicate the lateral posterior nucleus in the mediation of visual, as well as somatosensory, behavior.


Single unit responses in the inferior colliculus of the awake and performing rhesus monkey. 1. The activity of single units in the inferior colliculus of unanesthetized monkeys was recorded during performance in an auditory reaction time task. Stimulus intensity and frequency were varied. 2. Spontaneous rate of unit discharge varied from 0 to 78.2 discharges per second, with a mean of 14.7 discharges/sec. 3. Both broadly and narrowly tuned units were encountered in the central nucleus of the inferior colliculus. The temporal discharge pattern of most units varied with changes in stimulus frequency; onset bursts and/or sustained discharge suppression dominated the unit discharge at the edges of receptive fields. 4. Half of the units examined at several intensity levels displayed nonmonotonic relationships between evoked discharge rate and stimulus intensity, with most nonmonotonic units showing a distinct "best intensity". The temporal response pattern of almost all units varied with changes in stimulus intensity, with onset bursts and discharge suppression increasing in occurrence with increasing intensity. 5. Units recorded in the external nucleus of the inferior colliculus displayed spontaneous rates which were similar to those of central nucleus units, and were affected by variation in stimulus intensity in the same fashion. However, the average initial latency of such units to intense stimuli was no longer than the latency of central nucleus units. 6. Variations in unit discharge with changes in stimulus frequency and intensity are consistent with an interaction of excitatory and inhibitory inputs with different initial latencies, dynamic ranges and receptive fields. In particular, our data suggest that inhibitory inputs have longer initial latencies and higher thresholds. Inhibition is stronger at the edges of a unit's receptive field, and dominates at high frequencies in units with low characteristic frequency. 7. Our data are not consistent with previous reports that single units in the unanesthetized animal display uniformly monotonic intensity functions and uniformly broad frequency responses.


Behavioral and physiological studies of hearing in birds. Studies of hearing thresholds and frequency- and intensity-difference limens for birds are reviewed. Where possible these are related to limitations placed on auditory function by stimulus processing at peripheral levels of the avian auditory system. The high frequency limit of bird hearing is about 10 kHz; this limit is shown to be imposed in part by middle ear function and in part by cochlear mechanisms. For frequencies greater than 1.0 kHz, frequency-difference limens (DLs) show a similar dependence on frequency in birds as in mammals. Correspondingly, cochlear filtering is shown to be as good in birds as in mammals. At frequency below 1.0 kHz, frequency DLs in birds are poorer than in mammals. These low frequency differences may not be attributable to peripheral processing. Intensity-difference limens are worse in birds than mammals; there seem to be no differences in peripheral processing between birds and mammals which can account for this behavioral difference. Finally, complexities in processing at higher levels of the avian auditory system which have been related to detection of species-specific vocalizations are shown to appear in the first brainstem auditory nuclei.


Response variability in the mammalian auditory cortex: an objection to feature detection? Research strategy in the auditory system has tended to parallel that in the visual system, where neurons have been shown to respond selectively to specific stimulus parameters. Auditory neurons have been shown to be sensitive to changes in acoustic parameters, but only rarely have neurons been reported that respond exclusively to only one biologically significant sound. Even at higher levels of the auditory system very few cells have been found that could be described as "vocalization detectors." In addition, variability in responses to artificial sounds have been reported for auditory cortical neurons similar to the response variability that has been reported in the visual system. Recent evidence indicates that the responses of auditory cortical neurons to species-specific vocalizations can also be labile, varying in both strength and selectivity. This is especially true of the secondary auditory cortex. This variability, coupled with the lack of extreme specificity in the secondary auditory cortex, suggests that secondary cortical neurons are not well suited for the role of "vocalization detectors."


Comparison of the effects of contraceptive steroid formulations containing two doses of estrogen on pituitary function. A pituitary stimulation test with gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) was undertaken to determine (1) whether pituitary responses to GnRH vary in individual women taking oral contraceptive steroids over time, (2) whether a less suppressive pituitary gonadotropin effect is produced by formulations containing less than 50 microgram of estrogen, and (3) to obtain more information concerning prolactin secretion in users of oral contraceptive steroids. The same subjects who had had a suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response 6 to 9 months previously also had a suppressed response, indicating that this effect persists over time. Contraceptive formulations containing less than 50 microgram of estrogen have a lesser suppressive effect on LH release than do formulations containing 50 microgram of estrogen or more. The basal prolactin (PRL) response as well as the maximal PRL response to TRH were found to be significantly greater in subjects using oral contraceptives than in the control subjects. However, no difference in PRL response was found between the subjects using low or high doses of estrogen fomulations.


Comparative studies of the ethynyl estrogens used in oral contraceptives. VI. Effects with and without progestational agents on carbohydrate metabolism in humans, baboons, and beagles. Human subjects, baboons, and beagles were given cyclic regimens of ethynylestradiol or mestranol; after a number of such cycles, concurrent administration of norethindrone acetate, dl-norgestrel, or megestrol acetate was introduced for a similar number of cycles. Carbohydrate tolerance was evaluated by oral glucose tolerance testing in the human subjects and by intravenous glucose tolerance testing in the baboons and beagles. In the human subjects, neither mestranol nor ethynylestradiol at daily doses of 50 to 100 microgram/day produced any effect on fasting glucose levels or on glucose tolerance even after six cycles of treatment. The addition of the progestational compounds also had no effect on these two variables. In baboons, ethynylestradiol and mestranol were bioequivalent and produced a dose-related decrease in the glucose disposal rate. All three progestational agents counteracted this effect in a comparable manner. In beagles, on the other hand, estrogens produced an increase in the glucose disposal rate, and the addition of progestational agents produced an initial fall and a subsequent return to pretreatment levels.


Passive immunization with an antibody to the beta-subunit of ovine luteinizing hormone as a method of early abortion--a feasibility study in monkeys (Macaca radiata). Antiserum to the beta-subunit of ovine luteinizing hormone (oLH-beta) raised in monkeys (Macaca radiata) has been tested by a variety of criteria both in vivo and in vitro to establish its ability to neutralize oLH, hLH, and human chorionic gonadotropin (hCG). Passive administration of this antiserum caused inhibition of ovulation and termination of pregnancy in recipient monkeys as indicated by premature vaginal bleeding and a significant reduction in serum progesterone and estrogen levels. The results suggest that antiserum raised in monkeys against oLH-beta can neutralize monkey LH as well as monkey CG.


Sensitivity of gonococcus strains isolated in Rotterdam to epicillin, ampicillin, penicillin and tetracycline. Quantitative determinations of the sensitivity to epicillin, ampicillin, penicillin and tetracycline were carried out for 67 gonococcus strains isolated from 67 males with urogenital gonorrhoea, and 38 strains isolated from 38 females with urogenital/rectal gonorrhoea. The results of the sensitivity determinations for ampicillin, penicillin and tetracycline were compared with the findings of a previous investigation. It was found that the gonococcus strains isolated from males had become slightly less sensitive to penicillin between 1971-1972 and 1976. The penicillin and tetracycline had not changed during this period. It was also striking that the in vitro activity of epicillin for strains isolated both from males and females was significantly greater than that of ampicillin.


Increased binding of concanavalin A at the cell surface following exposure to thyroliberin. Thyroliberin (THR) binds specifically to SD1 rat prolactin cells and increases prolactin release. THR-induced modifications of surface membrane of intact SD1 cells were looked for, using concanavalin A (Con A) as a probe. At the electron microscope level the binding was restricted to the cell surface. Preexposure of the cells to TRH (27 nM) for 30 min at 37 degrees C increased the binding of Con A by 28--120%. Such an increase was not observed with low doses of TRH (13.5 and 2.7 nm) nor after only a 10-min exposure to 27 nM TRH. This effect is specific for TRH; it was not observed with other peptiDES. Simultaneous exposure to Con A and [3H] TRH did not alter [3H]TRH binding, but preexposure to Con A reduced the [3H]TRH binding by 10%, which may be due to steric hindrance. It is concluded that TRH induces an increased exposure of surface membrane glycoproteins in intact SD1 cells.


Pre-immunization and post-exposure treatment with inactivated rabies vaccine of chick embryo cell culture origin (CEC). Routine laboratory assay revealed that the potency of concentrated rabies vaccine of chick embryo cell culture (CEC) origin was in the same level compared with suckling mouse brain (SMB) vaccine. Over one hundred persons received two doses of CEC vaccine at an interval of one week and produced high level of neutralizing antibody against rabies virus. The monkeys experimentally infected with street rabies virus were satisfactorily protected by subcutaneous inoculation with CEC vaccine one hour after exposure. Eight persons bitten by dogs known to have rabies or suspected of it, survived after post-exposure treatment with CEC vaccine.


[Titration of serum and antirabies immunoglobulins by the radial immunodiffusion method]. Titration on mice of sera and immunoglobulin rabies anibodies is expensive, tedious and long. We are proposing a cheap, easy and rapid method which could be useful during the preparation of immunoglobulin or for the final titration. The antigen is a purified inactivated vaccine cultured on human diploid cells and purified by dextran sulfate and ultracentrifugation; it is included in agar on a glass slide. The reference serum was given us by Dr Atanasiu from Pasteur Institute; its titre was compared with international reference on mice test and was given a titre of 65 IU per ml. Five specific rabies immunoglobulin and 3 sera were received from two producers for titration. For IDR test, immunoglobulin and reference serum dilutions are diposed in wells of the same agar slide and then incubated at ambiant room temperature during 48 hours. Migration of each Ig and serum dilution is measured after coloration reported on a graph and compared. Each of the samples was checked 4 times by radial immunodiffusion test and twice by seroneutralization test on mice. Statistical analysis of the results by Student's test demonstrates that both methods are comparable.


Production of an inactivated rabies vaccine in primary dog kidney cells. In this paper the large-scale production of a purified inactivated rabies vaccine in primary dog kidney cells cultivated in microcarrier culture is described. The potency in the NIH-test and the antigenicity of this vaccine in other animal experiments were comparable with the antigenicity of vaccine prepared in human diploid cells. The antibody response was greatly enhanced by the addition of AIPO4 as adjuvant. The results of an initial clinical trial are presented.


A pharmacologic profile of McN-3495 [N-(1-methyl-2-pyrrolidinylidene)-N'-phenyl-1-pyrrolidinecarboximidamide], a new, orally effective hypoglycemic agent. McN-3495, a new compound unrelated strucuturally to the sulfonylureas or phenformin, has been found to produce a hypoglycemic effect in nondiabetic rats, dogs, mice, and monkeys. The minimum effective dose of McN-3495 that lowers fasting blood glucose and improves glucose tolerance was found to be about 2.5 to 5 mg-per kilogram, per os, except in fasted monkeys, in which a tenfold greater potency was observed. When McN-3495 was given repeatedly for three to five days, no tolerance to the hypoglycemic activity occurred and no changes in other biochemical parameters were observed. In addition to being three to four times more potent than tolbutamide, McN-3495 also differs from the sulfonylureas in lowering blood glucose concentrations of streptozotocin-diabetic rats and db/db mice, and, moreover, oral administration to normal fasted dogs did not produce the characteristic rise in insulin concentrations observed with tolbutamide. Furthermore, unlike the biguanides, McN-3495 can lower dog and rat fasting blood glucose concentrations and can improve glucose tolerance whether the glucose is administered orally or parenterally. However, McN-3495, as phenformin, fails to work in totally depancreatized dogs.


Distribution of 4-nitroquinoline 1-oxide reductase in the mucosa of canine digestive tract. The distribution of 4-nitroquinoline 1-oxide (4-NQO) reductase, assumed to be closely related to the carcinogenesis of 4-NQO, was investigated in the mucosa of canine digestive tract, and its results indicated following points. 1) The activity of 4-NQO reductase was highest in the esophagus, next in the stomach, and remarkably low in the small and large intestines. 2) There is no significant difference in the 4-NQO reductase activity between the upper, middle, and lower portion of the esophagus, but its activity was higher in the female than in the male in its upper and middle portions. 3) Among the esophageal tissue, its activity was high only in the mucous epithelium and very low in all other layers. 4) Most of the enzymic activity in the esophageal mucosa existed in the cytosol fraction and activity of the microsome fraction was remarkably low. Even if NADPH or NADH was used as the hydrogen donor, its activity was not different in the cytosol fraction, but the former was a better hydrogen donor in the microsome fraction. 5) In the gastric mucosa, the enzymic activity was equally high in various portions of the corpus ventriculi; the greater and lesser curvatures, anterior and posterior parietes, and fundus. It was remarkably low only in the pyloric antrum.


Histopathological and ultrastructural study on extramedullary hematopoietic foci in early stage of 3'-methyl-4-(dimethylamino)azobenzene hepatocarcinogenesis. A quantitative analysis was performed on the extramedullary hematopoietic foci which appeared in the liver during the early stages of hepatocarcinogenesis with 3'-methyl-4-(dimethylamino)azobenzene in rats. The frequency in the appearance of the foci reached a maximum at around 3 weeks of azo-dye feeding. Since the liver in this period has been known to show deviation of various characteristics toward fetal liver, an intimate correlation of the appearance of the foci and fetal character of the liver was suggested. Histologically the hematopoietic foci were always observed in the sinusoidal space of original hepatocytes adjacent to the oval cell proliferating area. Ultrastructurally the cells of the foci were identified as erythroblasts and were found in the space of Disse as seen in the hematopoiesis in fetal liver.


Ulcer occurring in Zenker's diverticulum. The radiographic and pathologic findings of a Zenker's-type diverticulum containing multiple ulcers are described. This rare complication probably represented peptic ulceration of the diverticular mucosa resulting from reflux of the gastric content.


Esophagobronchial fistula secondary to ruptured traction diverticulum. An unusual complication of benign esophagobronchial fistula, secondary to a ruptured esophageal traction diverticulum, is reported and illustrated. The patient presented with a history of chronic, recurrent bronchitis and intermittent episodes of paroxysmal attacks of coughing and strangling on the ingestion of fluids (Ono's sign). A review of the literature with emphasis on the occurrence, pathogenesis, radiographic features, and clinical implications of esophageal traction diverticula is presented.


Gastric diverticula following subtotal gastrectomy. Four cases of gastric diverticula following subtotal gastrectomy are described. This type of diverticula associated with partial gastrectomy are probably true, acquired, pulsion diverticula. In two of our patients the diverticula were associated with significant prolapse of gastric mucosa causing obstruction at the anastomosis.


Immunoreactive secretin in gastrointestinal mucosa of several mammalian species. Immunoreactive secretin in hydrochloric acid extracts is relatively constant in the duodenum and proximal jejunum of pig and dog (3 microgram per g), but peaks in the distal duodenum of guinea pig (1 microgram per g), no secretin being detectable in the ileum of these species. Secretin is relatively constant throughout the small intestine of the rat and rabbit (0.4 to 0.1 microgram per g). Sephadex gel filtration patterns of all species and throughout the gastrointestinal mucosa revealed primarily a single peak with elution characteristics identical with that of purified or synthetic porcine secretin. The "big" secretin prominent in Boots secretin may be an alteration product perhaps attributable to chemicals used to stabilize the preparation. The "intermediate secretin" described by others has not been detected. It is concluded that in a variety of mammalian species most of the immunoreactive secretin extractable from the intestinal tract lies distal to the proximal duodenum and is not distinguishable from duodenal secretin in terms of molecular size.


Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery. Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.


[Triphenylstilbene as a polymodifying agent]. The metalorganic product, triphenylstibine, added to the nutrition medium for Drosophila melanogaster larvae induces multiple modification effects, such as rough eye, wing incision, small bristles and others. Cytological analysis has shown that triphenylstibine induces new puffs and also causes the activation and depression of control puffs in giant chromosomes. A new effect of triphenylstibine is observed: it inhibits the evolution of puffs in giant chromosomes during metamorphosis. The average frequency of "inhibited" puffs is about 15%.


Isolation of antitumor polysaccharide fractions from Yucca glauca Nutt. (Lilliaceae). An aqueous alcoholic extract of fresh flowers of Yucca glauca Nutt. showed striking antitumor activity against B16 melanoma in mice. Systematic fractionation of the extract by means of solvent extraction and gel permeation chromatography led to separation of two galactose containing polysaccharide fractions with marked inhibitory activity against B16 melanoma in mice. The extraction, fractionation, purification and preliminary characterization of the active polysaccharide fractions are described. The materials showed no activity against L1210 or P388 leukemias in mice. The implications of the findings for searches for both natural and synthetic anticancer agents are discussed.