Characteristics of the enteral hyperalimentation literature.

There is a bias in secondary literature sources, such as MEDLINE, that results in an information gap on enteral hyperalimentation. This gap accentuates the problem of locating papers on enteral hyperalimentation with medical foods, a problem shared by physicians, dietitians, pharmacists, and information scientists. A complete information package on enteral hyperalimentation with chemically defined elemental diets was identified and collected for use in determining the characteristics of that literature. Less than 20 journal titles contain over half of the published papers which are predominantly published in English from research done in the United States. As the medical community's interest in the enteral route for hyperalimentation escalates, so does its need for information in this vital patient support area. Any possible hindrance to obtaining access to published information should be recognized and challenged.


Microcentrifuge technique and its application for visualizing the simultaneous replication and transcription of an adenovirus DNA.

Miller's technique (microcentrifuge method) of visualizing transcriptional events at the molecular level is introduced with a review on the work that applied this technique, and followed by presentation of an article describing one such application in which the modes of replication and transcription are electronmicroscopically demonstrated in an adenovirus-infected cell nucleus. Adenovirus is chosen owing to its character of multiplying in a mammalian cell nucleus. Recently, there have been many important discoveries on the modes of DNA replication and RNA transcription through biochemical probes. It is confirmed by Miller's technique that large primary precursor messenger RNA is first transcribed at a late stage in a cell nucleus productively infected with adenovirus. Evidence is shown that a replicating viral DNA molecule can be simultaneously transcribed.


Combined action of semisynthetic penicillin and macrolide antibiotic on Pseudomonas aeruginosa in vitro and in vivo.

For the purpose of studying therapy for pseudomonas infection, the synergistic effect of carbenicillin and midecamycin or 9,3''-di-O-acetyl midecamycin on Pseudomonas aeruginosa were studied in vitro and in vivo. Midecamycin and 9,3''-di-O-acetyl midecamycin were effective against spheroplasts of P. aeruginosa induced by carbenicillin treatment. As a result of investigating treatment using a combination of both carbenicillin and macrolide antibiotics on mouse infection model caused by subcutaneous injection of carrageenan solution containing viable cells of P. aeruginosa, the combined treatment was demonstrated to be significantly more effective than the control's single treatment by carbenicillin or the macrolide antibiotic alone.


Enzyme linked immunosorbent assay (ELISA) for detection of Clostridium botulinum type B toxin.

The enzyme-linked immunosorbent assay using different techniques has been applied to determine botulinum type B toxin. With the so-called "sandwich" technique, about 5,000 mouse ip LD50 of type B toxin can be detected. With the "double-sandwich" technique, about 400 mouse ip LD50 of toxin is detected and different commerical antisera are useful. For accurate quantification of botulinum toxins in culture filtrates, addition of EDTA to samples seems to be necessary. Cross-reactivity of the assay depends on the specificity of the antisera against botulinum type B toxin used and is almost eliminated with antiserum prepared against the toxic component of type B toxin.


Studies on adjuvants for human prophylactics. III. Comparison of adjuvanticity in different animal species.

Activities of common adjuvants were compared in mice, rabbits and monkeys with tetanus toxoid as an antigen. Aluminium gel showed consistently high adjuvanticity for antitoxin production in all animal species examined when administered subcutaneously. Water-in-oil in water (w/o/w) showed high activity comparable to that of aluminium in mice and rabbits but no activity in monkeys. Endotoxin was considerably effective in rabbits and monkeys but not so in mice. Production of both IgM and IgG antitoxin was promoted by the effective adjuvants in rabbits and monkeys. In mice, however, the effects of adjuvants on the production of IgM antitoxin was less significant and inconsistent. Contrary to the case of guinea pigs, tetanus antitoxin was produced in mice by ip injection to a level comparable to that induced by sc injection. The effects of adjuvants in mice administered by ip and sc injection were not significantly different from each other.


Mixed cell agglutination reaction of ABO substances in the saliva and determination of human-type ABO blood groups in the cynomolgus monkey.

For detection of ABO substances in the saliva of the cynomolgus monkey, the mixed cell agglutination reaction (MCAR) gave specific and clear results with a very small amount of saliva. Anti-A and anti-B antibodies in the sera of the same species showed the clearest hemagglutination by the saline agglutination method. The combined use of both methods was demonstrated to be easily and accurately applicable to the determination of human-type ABO blood groups of the cynomolgus monkey.


Experimental renal disease due to schistosomiasis.

Although there is a marked variability in the development of renal lesions among individual animal models of schistosomal infections, much has been learned about the mechanisms leading to renal injury. The lesions in S. mansoni and S. japonicum infections correspond quite closely to the immune complex type of lesions, with complement involvement. The main antigens involved seem to be polysacharides of worm-gut origin, but participation of other antigens (including soluble egg antigens) cannot be excluded. Many observations testify to the localization of immune complexes, preformed in circulation, but the possibility that antigens, filtered through glomeruli, deposit incapillary walls first and bind with corresponding antibodies later on should be considered also. Deoxyribonucleic acids also may play a role in the pathogenesis. The perpetuation of the lesions is probably due to constant supply of antigens. In some models, renal pathology was related to the dose of infection, but in others there was no relation to worm burden. Renal pathology in S. haematobium infections is different, being related to the lower urinary tract, with obstructive lesions causing pyelonephritis and hydronephrosis.


Primate disease and breeding rates.

33 species were compared for 12 disease categories over 3 years of laboratory housing. There were low correlations between popularity, birth, death, and illness rates. Highest rates were: birth, Macaca nemestrina; illness, Pongo pygmaeus; death, Cercopithecus aethiops. Lowest rates were: birth, Lemur catta; illness, Sanguinus mystax; death, Galago crassicaudatus. Galago crassicaudatus and Macaca fasicularus had low disease and high birth rates.


Anaesthetic effects of various ratios of ketamine and xylazine in rhesus monkeys (Macacca mulatta).

Intramuscular injection of selected ratios of ketamine and xylazine provided smooth anaesthetic induction, a wide safety margin, and no significant undersirable side effects. Induction and recovery times, duration of anaesthesia, and thermoregulatory ability can be affected by different combinations of ketamine and xylazine. The addition of xylazine to ketamine increases muscle relaxation, recovery time, and duration of anaesthesia, while generally decreasing induction time and thermoregulatory ability.


Aerometric study of viable fungus spores in an animal care facility.

Studies of airborn fungi were undertaken to evaluate exposure risks for laboratory animals and human handlers which might lead to allergic or invasive disease. Although sporadically high fungus levels were encountered, counts of viable fungus particles were in general low. Recoveries on malt extract agar significantly exceeded those on Sabouraud dextrose agar. The taxa most frequently and abundantly recovered were Penicillium species. Data analyses suggest that 'clean' bedding material may be the principal source of these spores, that cleaning temporarily increases spore levels, and that outdoor airborne fungi contributed little to the indoor air spora identified. Aspergillus fumigatus was infrequently encounted in our samples, and dermatophytes were not recovered.


Flexible fiberoptic bronchoscopy of the rhesus monkey (Macaca mulatta).

Using a flexible fiberoptic bronchoscope, 10 rhesus monkeys were bronchoscoped 30 times without complication. The bronchoscopic anatomy was found to be similar to that of the human except for the presence of a right cardiac lobe in the monkey.


A survey for Anatrichosoma (Nematoda: Trichinellida) in wild-caught Macaca mulatta.

One hundred rhesus monkeys which were captured from two geographical sites were tested for Anatrichosoma, a nematode that lives in the nasal passages. The monkeys were tested using both fecal examinations and nasal swabs. Three percent of the monkeys from one site were positive, and 68% from the other site were positive. Twenty-one percent of the animals tested by fecal examination were positive and 48% were positive using nasal swab examination.


Chylothorax in rhesus monkeys with intravenous catheters.

Chylothorax associated with the use of indwelling intravenous catheters was diagnosed in 13 Macaca mulatta. Clinical signs were marked respiratory embarrassment or sudden death. Lesions at necropsy included large quantities of sterile pleural fluid, pulmonary atelectasis and chronic fibrinous pleuritis. Lipid was present in the effusion and in tissue sections of visceral pleura.


Urinary cystic calculi in a cynomolgus monkey (Macaca fascicularis): a case report.

An adult female Macaca fascicularis monkey became acutely anorexic and depressed and was found dead approximately 24 hours later. Necropsy revealed three hard brownish-yellow stones within the urinary bladder and urethra, a moderately shrunken left kidney, hemorrhage of the medulla of the left adrenal gland and a yellow liver. The stones, one of which was lodged in the urethra, were 1-2.5 cm in diameter, and their surfaces were rough and covered with spines. Chemical analysis of the stones revealed oxalates, phosphates, carbonates, ammonium salts, magnesium and calcium. Microscopic examination revealed chronic interstitial and glomerular nephritis and papillary hyperplasia of the transitional epithelium of the bladder.


Prevalence of ocular disease in a colony of tamarins and marmosets.

In a large tamarin and marmoset experimental colony, 526 animals were examined by biomicroscopy and ophthalmoscopy for the presence of ocular disease. In 109 animals, there were 147 abnormalities involving the eyelids, cornea, iris, lens, retina or optic nerve. Most abnormalities were unimportant in terms of ocular function, but a few did cause loss of vision and included diffuse, progressive retinal atrophy and a severely traumatized globe. The survey indicated that while usually minor, ocular disease in the tamarin and marmoset was widespread.


Indoor-outdoor housing systems for a self-sustaining marmoset breeding colony.

Indoor-outdoor housing of three types was designed, constructed, used and evaluated for housing a breeding colony of common (Callithrix jacchus) and cottontop (Saguinus oedipus) marmosets. All types were relatively inexpensive to construct, required minimal care, simulated a natural environment and allowed for some isolation between units and between individual runs within units.


[Meningococcus profilaxis (author's transl)].

In a General Hospital in San Sebastian, 96 cases of Neisseria meningitidis infections were detected in a two years period. By the use of the disk diffusion method, we found that all causative meningococcal strains but 4 were resistant to sulfonamide (with a 300 microgram sulfadiazine disk, all isolates with a zone diameter of less than 20 mm were considered to be resistant of sulfadiazine, whereas those with zone diameters of greater than 30 mm were considered susceptible). No rifampin nor minocycline-resistant meningococci were isolated. All strains had a disk zone diameter (30 micrograms rifampin and 30 micrograms tetracycline) of greater than 20 mm. The serogroups of meningococcal strains were as follows: group A, 1; group B, 67; group C, 5 and 23 were no typed. Children less than four years of age were most frequently attacked (67,7%). The attack rate was only slightly higher in males than in females (52 and 44).


Effect of estrogen on fatty acid synthetase in the chicken oviduct and liver.

Estrogen administered to one-month-old female chickens resulted in a 180-fold increase in the amount of fatty acid synthetase, a seven-fold increase in the enzyme activity per gram of tissue and a 25-fold increase in the weight of the oviduct. In contrast, the fatty acid synthetase content in liver increased three-fold; activity per gram of tissue increased two-fold and the weight increased two-fold. The large increase in the fatty acid synthetase activity in the oviduct was due to a corresponding increase in the amount of the fatty acid synthetase protein since the specific activities of highly purified preparations of oviduct and liver fatty acid synthetases were the same and the two enzymes had the same end point as determined by immunoprecipitation. That the increase in activity of the oviduct enzyme is not due to a modification was further supported by physicochemical comparison of the oviduct enzyme with the chicken liver enzyme. Thus, the synthetase complexes have similar size, their subunit composition and size appear to be the same, and both are multifunctional enzymes. Finally, kinetic studies and product analyses indicated no catalytic difference between the enzyme induced by estrogen in the oviduct and the liver enzyme.


Construction of a colony bank of E. coli containing hybrid plasmids representative of the Bacillus subtilis 168 genome. Expression of functions harbored by the recombinant plasmids in B. subtilis.

A collection of about 2500 clones containing hybrid plasmids representative of nearly the entire genome of B. subtilis 168 was established in E. coli SK1592 by using the poly(dA).poly(dT) joining method with randomly sheared DNA fragments and plasmid pHV33, a bifunctional vector which can replicate in both E. coli and B. subtilis. Detection of cloned recombinant DNA molecules was based on the insertional inactivation of the Tc gene occurring at the unique BamHI cleavage site present in the vector plasmid. Thirty individual clones of the collection were shown to hybridize specifically with a B. subtilis rRNA probe. CCC-recombinant plasmids extracted from E. coli were pooled in lots of 100 and used to transform auxotrophic mutants of B. subtilis 168. Complementation of these auxotrophic mutations was observed for several markers such at thr, leuA, hisA, glyB and purB. In several cases, markers carried by the recombinant plasmids were lost from the plasmid and integrated into the chromosomal DNA. Loss of genetic markers from the hybrid plasmids did not occur when a rec- recipient strain of B. subtilis was used.


Ability of the male recombination factor 31.1 MRF to be transposed to another chromosome in Drosophila melanogaster.

By classical genetic experiments, evidence is provided that the male recombination factor, 31.1 MRF, has the ability to be transposed to another chromosome. The procedure by which the transposition occurs must be different from that of classical crossing over. It appears that transposition occurs only when the factor is active in male germ cells. Moreover, the factor appears to be able to undergo successive transpositions. Furthermore, the integration sites of the factor, when transposed into another chromosome, may not be completely random. Finally, the third chromosome of the 31.1/CyL4 strain can also induce male recombination.


The analysis of a temperature-sensitive (ts) mutation influencing the expression of heat shock-inducible genes in Drosophila melanogaster.

The effect of a ts-mutation belonging to the cell-lethal type on protein and RNA synthesis under heat shock conditions has been investigated. The mutation studied, l(l)ts-403, localized in the X-chromosome has significant effect on the kinetics of protein synthesis in salivary gland subjected to heat treatment under in vivo and in vitro conditions. The animals homozygous for l(l)ts-403 are characterized by a rapid drop of label incorporation into heat shock proteins. It is shown that the mutation affects not only the kinetics of heat-shock proteins synthesis but their electrophoretic pattern as well. The experiments performed enable us to conclude that the presumptive regulatory gene realized its action at the level of transcription of heat shock loci.


[Ebola virus three years later (author's transl)].

Sporadic cases and data from serologic surveys give evidence that Ebola virus is still active in Northern Zaïre after the first outbreak in 1976. It is also active in Southern Sudan where it is, from August 1979, responsible of a new epidemic focus. In addition, serological surveys demonstrate that its dispersion area comprises several other african countries. Physicians practising in central Africa must be aware of this fact. Serological test is necessary to confirm the diagnosis. This confirmation is necessary to obtain convalescent patient plasma, the only specific treatment. The clinical, epidemiological and virological aspects of Ebola virus disease are reviewed as well as precautionary measures to be taken by medical and nursing staff to avoid infection.


Some antigenic properties of cultured cell and bacteroid forms of fast- and slow-growing strains of Lotus rhizobia.

Immunodiffusion cross-reactions of 62 fast- and 76 slow-growing of Lotus rhizobia with antisera to four of the fast-growing and five of the slow-growing strains were studied. No sharing of antigens by both fast- and slow-growing strains was found. Somatic antigens were very strain specific with only eight of the fast-growing and five of the slow-growing strains tested having somatic antigens identical to those of one or more of the strains of the same group used for antisera production. In contrast, internal antigens were shared by all fast-growing strains and with seven exceptions by all slow-growing strains. Antigens of cultured rhizobia, and bacteroids from nodules formed on different legumes by the same strain of Rhizobium, were similar. However, incontrast to cultured cells, bacteroids generally required no pretreatment (heat or ultrasonic disruption) to give a strong somatic antigen reaction in immunodiffusions.


Comparison of three procedures for isolating DNA from bacteria.

Three methods employing chloroform-isoamyl alcohol (CI), phenol, or enzymes, were evaluated for isolating DNA from Escherichia coli, Bacillus subtilis, and Arthrobacter globiformis. For the amounts of reagents employed at optimum conditions in the CI and phenol procedures, 0.4-0.9 mg of DNA/g wet weight of cells was isolated. Using the enzymatic procedure, approximately twice as much DNA was isolated. DNA isolated by the CI procedure contained 0.03-0.09% protein and 0.08-0.12% RNA. DNA isolated by the phenol procedure contained 0.02-0.05% protein and 2.2-2.6% RNA. DNA isolated by an enzymatic procedure, which is described in detail, contained 32.2-45.7% protein and 0.3-0.6% RNA. DNA isolated by all three procedures are double-stranded and at least 10(6) in molecular weight, as suggested by data from thermal transition analyses and transformations. These data emphasize that the desired characteristics of DNA for experimental purposes must be considered in selecting an isolation procedure.


Cadmium and zinc sensitivity and tolerance in Bacillus subtilis subsp. niger and in a Pseudomonas sp.

The action of Cd2+ and Zn2+ on Bacillus subtilis subsp. niger ATCC 9372, and on a Pseudomonas sp. (possibly Pseudomonas fluorescens), isolated from cadmium-polluted soil has been determined and compared with results obtained previously with Klebsiella aerogenes. In liquid medium the lag and the mean generation time of Bacillus subtilis subsp, niger increased with increasing Cd2+ or Zn2+ concentrations whereas only the total biomass of the Pseudomonas sp. was affected. Nevertheless, the responses of both species indicated a specific action at low concentrations and a more general toxic action at high concentrations. The survival on Cd2+ - or Zn2+ - agar depended on the state of the metal ions with regard to chelating ligands and on the nutritional stage of the organisms. In admixture, the metal ions acted synergistically, particularly on the Pseudomonas sp. Resistance to both metal ions developed. It was graded to the training concentration and reciprocal cross-resistance occurred with Bacillus subtilis. subsp. niger but not with the Pseudomonas sp.


The formation of serine from glycine and formaldehyde by cell free extracts of Clostridium acidi-urici.

Cells of Clostridium acidi-urici which were grown in a medium containing uric acid were harvested, disrupted by sonication and centrifuged. After centrifugation the supernatant which served as the cell free extract was used to study the synthesis of serine from 2-14C glycine and formaldehyde. Serine was isolated from the reaction mixture by column chromatography. After identification by paper chromatography, serine was degraded carbon by carbon to locate the position of the labelled carbon. Radioactivity was confined almost exclusively to the alpha carbon of serine which was derived from the alpha carbon of glycine. Formaldehyde, therefore, binds at the alpha carbon of glycine to form serine. Conversion of serine to pyruvate was prevented by adding EDTA to the reaction mixture.


Scanning electron microscopy of the infective eggs of Hydatigera taeniaeformis.

Scanning electron microscopy of the outer surface coat of the infective eggs of Hydatigera taeniaeformis examined at high magnifications revealed the presence of scale-like features. At low magnifications the surface of eggs appeared smooth. Eggs that were fractured showed a thick inner surface layer of ridges and striations. A second layer characterized by a smooth membrane surface presumably the basement membrane was observed beneath the innermost surface layer. When the eggs were treated with 0.02 M of EDTA the outer surface coat became distorted and the emerging hooks of the embryo could be seen. Small, spherical bosses were observed on the surface of some eggs. Other eggs possibly at an earlier stage of development contained pit-like depressions.


Irgasan-induced pigmentation in Serratia marcescens and Pseudomonas aeruginosa.

Two irgasan-resistant micro-organisms (P. aeruginosa and S. marcescens) were used to study the effects of various antibiotic and chemotherapeutic agents on pigment production. These agents included streptomycin, thallium acetate, polymyxin B, hexachlorophene, irgasan, prodigiosin and DMSO (dimethyl sulphoxide). Only irgasan, compared to other drugs and membrane-active agents showed the unique property of inducing pigmentation in both P. aeruginosa and S. marcescens, i.e. prodigiosin in S. marcescens and pyocyanin in P. aeruginosa.


Two methods of large-scale extraction of an antibiotic produced by Myxococcus coralloides.

Two methods for the isolation of an antibiotic produced by Myxococcus coralloides have been developed: the chloroform extraction method and the charcoal adsorption method. The recovery of antibiotic in each case was 25% and 30%, respectively, by the two methods. Although the two methods yield a relative low recovery, the charcoal adsorption method seems more attractive and promising due to its simplicity and economic advantages.


Differential cell membrane labilizing effect of adenovirus type 5 and 12 observed during productive and abortive infection.

Culture fluid of human epitheloid (HEp-2) cells was examined for extracellular lactate dehydrogenase activity as an indicator of cell damage during a 48 h period in which virus replication and changes in cell morphology occurred. Uninfected and adenovirus type 5-infected cells had the same levels of extracellular enzyme activity both before and after the appearance of morphological changes in cells due to virus infection, whereas adenovirus type 12-infected cells showed increased extracellular enzyme activity. Cells infected with either adenovirus type 5 or type 12 had the same total cellular and extracellular lactate dehydrogenase activity. Hydrocortisone, a membrane stabilizing agent, prevented abnormal leakage of lactate dehydrogenase from adenovirus type 12-infected cells, but had no effect on virus replication or total enzyme activity of infected cells. After inoculation of monkey kidney (Vero) cells the yield of progeny adenovirus type 5 virions was greatly reduced and there was no production of adenovirus type 12 virions. The pattern of extracellular lactate dehydrogenase activity of uninfected and adenovirus type 5- and type 12-infected Vero cells was like that with HEp-2 cells. Therefore, production of adenovirus type 12 virions is not necessary for the virus-cell interaction causing cell membrane labilization.


[Change in ratio between citric and oxalic acid in Aspergillus niger upon exposure to mutagenic factors].

Stepwise selection of Aspergillus niger producing citric acid in highly buffered molassa media was carried on in order to decrease the biosynthesis of oxalic and gluconic acids using the following mutagenic factors: diethyl sulfate, thiophosphamide, cyclophosphan, N-methyl-N'-nitro-N-nitrosoguanidine (NG), 5-fluorouracil, 1,4-bis-diazoacetylbutane, and UV. The ratio between the acids changed in mutants obtained upon the combined treatment with UV and NG. Mutants producing twice as less oxalic acid were characterized by weak growth and formation of conidia.


[Adsorption of phenylurea derivative and chlorine-substituted aniline herbicides by microorganisms].

Adsorption of phenylurea derivatives and chlorosubstituted anilines by Pseudomonas and Aspergillus was studied. All these substances were adsorbed by the microorganisms in large quantities. The bacteria adsorbed more of these substances per biomass unit than the fungi. Adsorption of herbicides by the microorganisms is a physical process and is characterized by the same correlation as adsorption of herbicides by soil. Derivatives of phenylurea and chlorosubstituted anilines are easily washed from the cells with water. Conditions under which the substances were completely desorbed have been studied. Acetylation of 3,4-dichloroaniline by Pseudomonas aurantiaca results in desorption of 3,4-dichloroaniline from the cells of Pseudomonas boreopolis.


Bowel preparation with mannitol.

Orally administered mannitol has been used for colonic preparation before operations, for colonoscopy, and before barium enema X-ray examinations. It is quick, effective, comfortable, safe, and cheap. The metabolic effects have been evaluated and found to be minimal, and recommendations for the use of orally administered mannitol are given.


Macrodosage of phenytoin.

Large doses (up to 1200 mg) of phenytoin were required to achieve therapeutic plasma concentrations and to control post-traumatic seizures in a 62-year-old woman. The elimination half-life of phenytoin was calculated to be 3.5 hours. Frequent monitoring of the plasma concentration was essential to optimize the therapeutic control and to avoid systemic toxicity.


[Blooming and destruction of cyanobacteria in the drainage bassin of the hydrogen sulfide spring of Staraya Matsesty].

The growth of cyanobacteria belonging to the genera Oscillatoria and Anabaena (up to 2.1 x 10(7) filaments per 1 g of wet sample) was found in a water reservoir with a high content of sulfides (up to 9 mM) in Staraya Matsesta throughout the year. The spots of Oscillatoria are located in the spring in more illuminated areas as compared to Anabaena. In the spring, not only spots of actively growing cells were detected, but also accumulations of Oscillatoria cells being destroyed (blue spots). Water-bloom spots in which Oscillatoria prevailed can transform into the spots of Anabaena. The main accompanying forms in the spots of Anabaena are long thin filaments of the flexibacterial type while short rods are found in the spots where Oscillatoria predominates. Heterotrophic enteric bacteria (48 x 10(4) cells per 1 g), Bacillus, Pseudomonas, and coryneform bacteria were also detected. Green bacteria (Chlorobium) and nonsulfur purple bacteria (Rhodomicrobium) were present in small quantities (16 x 10(3) cells per 1 g) as well as sulfate-reducing bacteria (5--15 x 10(2) cells per 1 g) and thiobacilli (40--60 cells per 1 g). In the spring, stones were covered with pink spots of spherical motile purple bacteria and with yellow-green spots of filamentous green bacteria. The cyanobacteria from the spots are capable of oxygenated photosynthesis. Fixation of CO2 by them in situ is 0.08 mcg per 1 g of dry sample per hour or 0.06 mcg per 10(6) cells per hour, and is inhibited by 10(-5) M DCMU by 70%.


[Carboxylation enzymes of coryneform bacteria].

The enzymes of carbon dioxide heterotrophic fixation were studied in six strains of coryneform bacteria belonging to the genera Arthrobacter, Brevibacterium, Corynebacterium and Nocardia. All of the strains were found to contain PEP (phosphoenolpyruvate) carboxylase (EC 4.1.1.31), NADP or NAD dependent malic enzymes (EC 1.1.1.38--40). Pyruvate carboxylase (EC 6.4.1.1) was found only in three strains of coryneforms: Brevibacterium ammoniagenes, Corynebacterium aquaticum and Nocardia erythropolis. PEP carboxykinase (EC 4.1.1.32) was detected in Brevibacterium ammoniagenes and Nocardia erythropolis. PEP carboxytransphosphorylase (EC 4.1.1.38) was found only in Brevibacterium ammoniagenes. These data suggest that carboxylation of C3-acids is one of the essential pathways in some coryneforms supplying the citric acid cycle with the products of glycolysis. The composition and the level of carboxylation enzymes reflect the ecological characteristics of the organisms rather than their taxonomical relations.


[Secretion of substances by different actinomycetes which induce sporulation by an asporogenic mutant of Streptomyces griseus].

The asporogenic mutant of Streptomyces griseus 1439 sporulates under the action of factor A, a regulator of differentiation, liberated by the parent strain. It has been found that 11 out of 30 cultures belonging to various species of actinomycetes induce formation of spores in strain 1439. The response of this strain to each of the 11 strains of actinomycetes has shown that they liberate stimulating substances in different quantities and at different periods of time.


Effect of a single dose of inducers and inhibitors on the rate of synthesis of cytochromes and reductases in liver organelles.

Measurement of the effect of drugs on the in vivo rates of synthesis of rabbit liver organelle bound proteins were measured following individual treatments with the inducers phenobarbital, 3-methylcholanthrene and PCB (a mixture of polychlorinated biphenyls) and the inhibitors, cycloheximide, aflatoxin B1, chloramphenicol and actinomycin D. Following their isolation from a homogenate containing the combined livers of 14C-leucine injected experimental animals and 3H-leucine injected control animals, purified fractions of the following proteins were prepared: microsomal cytochrome b5, cytochrome P-450, NADH-cytochrome b5 reductase, NADPH-cytochrome P-450 reductase and proteolipids, outer mitochondrial membrane cytochrome b5, NADH-cytochrome b5 reductase and proteolipids, inner mitochondrial membrane cytochrome c, NADH dehydrogenase and proteolipids, intermitochondrial membrane cytochrome b5 and circulating serum albumin. The effect of a drug was examined by measuring the 14C/3H ratio of leucine incorporation of each fraction; ratios which differed markedly from a control value of 1 represented actual changes in the relative rates of protein synthesis. Increased rates of synthesis of cytochrome P-450 and its reductase, intermitochondrial membrane cytochrome b5 and all three proteolipid fractions resulted from each inducer treatment. Treatments with 3-methylcholanthrene and PCB also increased the rate of synthesis of cytochrome b5 and its reductase in both the microsome and outer mitochondrial membrane. In addition, the PCB treatment increased the rates of synthesis of cytochrome c and NADH-dehydrogenase. The rates of synthesis of cytochromes, reductases and of circulating serum albumin were inhibited following treatments with cycloheximide, aflatoxin B1 and actinomycin D. Actinomycin D appeared to inhibit the release of newly synthesized albumin into the bloodstream while chloramphenicol treatment appeared to inhibit the incorporation of cytochrome c into the mitochondria. After 20 hours of treatment with inhibitors, the inhibitory effect of actinomycin D and cycloheximide were still apparent while the rates of protein synt;esis in chloramphenicol and aflatoxin B1 treated animals increased to levels above the controls. The incorporation of radioactively labeled leucine into the proteolipids of the microsomal, and the outer and inner mitochondrial membranes were inhibited following the treatment with actinomycin D and stimulated following the treatment with cycloheximide.


[Effect of sterigmatocystin on the toxinogenesis of the Aspergillus flavus group].

The aflatoxinogenesis of Aspergillus parasiticus is significantly enhanced by the presence, in the medium, of sterigmatocystin at a high level (35--50 microgram/ml); low concentrations, in the order of 175 microgram/ml, have no effect on the production of aflatoxins. During the period where the aflatoxinogenesis of the culture is high, no variation of the sterigmatocystin level is noted, Experiments with 14C-sterigmatocystin indicate that the mold does not utilize the metabolite itself as a precursor of aflatoxins.


Effects of satiety on self-stimulation of the orbitofrontal cortex in the rhesus monkey.

Self-stimulation of the orbitofrontal cortex of the rhesus monkey was found to be attenuated after the monkeys were fed to satiety. Self-stimulation at some other sites (e.g. the nucleus accumbens septi, the region of the substantia nigra, and the caudate nucleus) was relatively unaffected in the same test sessions by the satiety. In recordings from single neurons in the monkey orbitofrontal cortex, neurons of the type found in the lateral hypothalamus with sustained responses associated with the sight of preferred foods were not found. However, some orbitofrontal neurons did respond to the removal of food or other desired objects. These experiments show that self-stimulation of the monkey orbitofrontal cortex in modulated by hunger, and show that some orbitofrontal neurons have complex responses which could be related to the control of feeding.


Hormonal requirements for neuronal survival in culture.

The inability to grow neurons in culture in the absence of complex and undefined biological fluids (e.g. serum) has proved a major obstacle to a rigorous formulation of the growth, nutritional and hormonal requirements of the developing nervous system. We have been successful in maintaining dissociated chick dorsal root ganglia neurons in a serum-free, defined medium composed of F12 synthetic medium and, substituting for serum, a combination of hormones (insulin, PTH, triiodothyronine, TRH, somatomedin, hydrocortisone, testosterone) and other factors (transferrin). Not only were these hormones found to be sufficient for the maintenance of neurons in vitro, but, by the selective elimination of one component from the mixture, the role of specific hormones in neutral development could be grossly assessed. The elimination of insulin proved to be most inimical to neuronal survival.


L-histidine: effects on sensitivity of cat spinal neurones to amino acids.

L-Histidine enhanced the inhibitory actions of GABA, muscimol and beta-alanine rather than that of glycine on spinal neurones in pentobarbitone-anaesthetised cats. L-Histidine also enhanced the excitatory action of L-glutamate, D- and L-aspartate, L-homocysteate and especially that of quisqualate, whereas the actions of acetylcholine, kainate, N-methyl-D-aspartate and D-homocysteate were more commonly reduced. These actions of L-histidine are best ascribed to an effect on amino acid transport systems, probably of the low affinity type, which therefore appear to be partially responsible for the inactivation of exogenously administered amino acids.


Neurons with presynaptic somatic protrusions in the visual cortex of monkeys.

In layer IV of the visual cortex of two primate species three small neurons were found that gave rise to short presynaptic somatic protrusions. The protrusions contained a cluster of predominantly round vesicles and established asymmetrical synaptic contacts with the characteristics of Gray's type 1 terminals.


The ventral dendritic arbor of marginal (lamina I) neurons in the adult primate spinal cord.

The ventral (gelatinosal) dendritic arbor of marginal neurons taken from lumbosacral cord was examined in Golgi preparations from adult Macaque monkey and adult Squirrel monkey where neurons were filled with horseradish peroxidase (HRP) via secondary diffusion. Based on morphological criteria two types of marginal neurons were found which give rise to a substantial ventral dendritic arbor. These dendrites penetrate the depth of lamina II and some extend well into lamina III. The cell bodies are medium to large in size and confined to the medial half of lamina I. Marginal neurons located in the lateral half of the marginal layer lack gelatinosal dendrites and are characterized instead by numerous interstitial dendrites.


Quantitative analysis of dendritic branching. II. Fundamental dendritic numbers as a tool for the study of neuronal groups.

The fundamental dendritic numbers [14] were studied in various neuronal groups from different species. Their mean values allow group characterization on a quantitative basis. This allows group comparisons and classification. Four sets of polydendritic neuronal groups are isolated: fewly branched Golgi I groups (A), mainly stemmed Golgi I groups (B), Golgi II groups (C) and highly branched Golgi I groups (D). Numerical interspecific comparisons allow quantitative phylogenetic studies. Only groups of the D set exhibit a significant evolution. Dendritic numbers are an efficient tool for neuronal group studies.


Influences of cerebellar hemispherectomy on slow potentials in the motor cortex preceding self-paced hand movements in the monkey.

With chronically implanted electrodes, surface negative and deep positive, slowly increasing potentials were recorded in the forelimb area of the motor cortex prior to self-paced movements of the contralateral hand in monkeys. The slow premovement potentials were markedly reduced in size after ablation of the cerebellar hemisphere on the contralateral side to the motor cortex under recording. It was suggested that the cerebellar hemisphere (neocerebellum) participates in preparing the activity of the motor cortex prior to voluntary movements.


The crossed cortico-caudate projection in the rhesus monkey.

In the normal young adult rhesus monkey, reduced silver staining of degenerating axons revealed that the lateral prefrontal cortex projects to the caudate nucleus of the contralateral hemisphere. This crossed prefronto-caudate projection provides a means whereby the prefrontal cortex can affect the neuronal activity of the extrapyramidal motor systems in both hemispheres. These findings also support the concept that apparent neuronal plasticity in this primate telencephalic system is a result of expanded projections of axons that normally issue a minor projection to the contralateral caudate nucleus.


Excitatoty effects of TRH on medullary reticular neurones.

Thyrotropin releasing hormone (TRH) was applied iontophoretically to single neruones in the rat bulbar reticular formation. TRH excited 41 to 56 cells tested; none were inhibited. Excitation developed slowly and was prolonged, and desensitization often occurred. TRH effects were not correlated with effects of acetylcholine, noradrenaline, dopamine or serotonin on the same cells. Atropine applied to cells affected by both acetylcholine and TRH did not affect TRH responses although the acetylcholine actions were blocked. The results support a transmitter role for TRH in this brain area and may explain certain arousal effects of TRH mediated via the reticular formation.


Cortical projections of the medial visual area in the owl monkey, Aotus trivirgatus.

The cortical projections of the Medial Area (M) of the owl monkey were studied using the autoradiographic method. Area M projects to several extrastriate areas, including Area 18, in a pattern of terminations unlike that which would be expected if M was part of a larger Area 19 or V III band. The pattern of terminal lamination was found to be somewhat unusual in that projections were to layers VI, I and the deep portion of layer V in the major target areas.


Identification of the pallidal and peripallidal cells projecting to the habenula in monkey.

Injections of horseradish peroxidase (HRP) into the habenula of squirrel monkeys labeled a multitude of neurons in the lateal hypothalamus and a lesser number of neurons in the internal pallidum (GPi). The distribution of labeled cells is heterogeneous and many HRP-marked pallidal neurons are intermingled with acetylcholinesterase (AChE)-rich cells in the internal medullary lamina. However, these AChE neurons do not appear to contribute significantly to the innervation of the habenula. These findings suggest species differences between rodents and primates in regard to the organization of the pallidohabenular system.


Slow potentials preceding self-paced hand movements in the parietal cortex of monkeys.

In our previous paper, surface negative-deep positive slow potentials were reported to appear prior to self-paced hand movements in the premotor and the forelimb motor cortices of unanesthetized, freely moving monkeys, as recorded with the elctrodes implanted chronically in the cortices. The present study revealed that similar slow potentials were recorded also in the somatosensory cortex in most cases, but infrequently and unmarkedly in area 7, never in area 19.


Considerations on the importance of genetics in ophthalmology.

On the basis of his studies on Fabry's disease, the dyscephalic syndrome of François, ligneous conjunctivitis and macular dystrophy of the cornea, the author stresses the importance of heredity in ophthalmology.


Antiviral update.

There are two antiviral agents that are commercially available for use in ocular herpes infections, idoxuridine, and vidarabine (Ara-A). In topical usage, these medications are similar in their effectiveness and toxicity; however, vidarabine is systemically active for treatment of deep ocular disease. Trifluorothymidine, which is still an experimental drug, has been shown in double-blind clinical trials to be the most potent antiviral drug for ocular use. These three antiviral drugs, however, are not truly selective in their action and interfere with normal cellular functions as well as virus synthesis. Several new drugs have been reported that are selective and are only effective in herpes virus infected cells; the most active of these compounds appears to be acycloguanosine.


Vitreous fluorophotometry in diabetes mellitus.

Vitreous fluorophotometry has proved to be a useful method to evaluate the integrity of the blood-ocular barrier to fluorescein in clinical and experimental diabetes mellitus. Diabetic patients with or without background retinopathy had increased vitreous accumulation of fluorescein after intravenous injection when compared with age-matched controls. Streptozotocin-induced diabetes in rats increase vitreous fluorescein levels. In the rat, this abnormality was reversed with insulin therapy and with pancreatic islet transplantation. The breakdown of the blood-ocular barrier to fluorescein appears to be the earliest detectable ocular abnormality of diabetes.


A pharmacologist looks at medical treatment in glaucoma--in retrospect and in prospect.

The histochemical distribution of carbonic anhydrase activity in the ciliary processes is shown. There is a multiplicity of possible points of attack of carbonic anhydrase inhibitors, We do not know which sites are critically inhibited at clinical dosage. One primary mechanism of the therapeutic action of miotics is ciliary muscle contraction, but on prolonged treatment, subsensitivity of the muscle may shift emphasis to miotic inhibition of aqueous secretion by unknown mechanisms. The trabecular meshwork is a slow tissue living off the aqueous. Aqueous composition in chronic simple glaucoma should therefore be studied with a view to possible treatment of the sick meshwork.


[Plasma cell granuloma of the lung (author's transl)].

Case-report of a plasma cell granuloma of the lung found in a girl aged 8 years 6 months. The lesion of the lung was first interpreted as a metastasis of a suspected primary tumor in the right calf. It was only later that plasmacell granuloma of the lung was diagnosed. Plasma cell granuloma of the lung often gives rise to confusion, a fact illustrated by the various names applied to it, e.g. pseudosarcoma, postinflammatory pseudotumor of the lung, histiocytoma, xanthoma, fibroxanthoma, xanthogranuloma. On histological examination, this tumor consists of proliferations mainly of plasmacells and reticulo-endothelial cells, with some polymorphism and some giant cells. The tumor appears as a single, sharply circumscribed mass, is usually asymptomatic and therefore found mostly on routine-chest-films. Rarely is it found as an obstructive mass in the bronchi or in the trachea. The histopathogenesis of the tumor is not known, the lesion benign. Treatment is resection.


[Therapy of bacterial infections in infancy and childhood (author's transl)].

83 in-patients, age 3 months to 12 years, with tonsillitis, otitis, bronchitis and pneumonia were treated with a new galenic preparation of phenoxymethylpenicillin V potassium (Star-Pen Trockensirus SANABO). The drug was very well tolerated, no skin-rash was observed, no problems occurred with the oral administration. Diarrhea, not infrequent in oral penicillin therapy, was -- with one exception -- not noticed in patients above one year of age.


The Wildervanck syndrome: cervico-oculo-acoustic dysplasia.

The Wildervanck syndrome consists of the Klippel-Feil deformity of the spine, eyeball retraction, lateral gaze weakness, and hearing loss. Conductive hearing loss, as well as a more frequently occurring sensorineural hearing loss, is caused by dysplasia of the inner ear. Typically, polytomograms demonstrate a bulbous vestibule and dilated lateral semicircular canals with basilar impression of the skull. The Duane's eyeball retraction phenomenon completes the syndrome; this may be explained either by misdirected innervation of the extraocular muscles or by atrophy or fibrosis of the lateral rectus muscles.


Deglutition after conservation surgery for cancer of the larynx and hypopharynx.

Conservation surgery for cancer of the larynx results in deglutition problems. Rehabilitation of swallowing function can successfully be managed by a team including a surgeon, a dietitian, and a nurse. This report details surgical reconstruction to prevent or treat aspiration, postsurgical dietetic management, and the nursing approach to deglutition training in a group of patients.


Long-term retention of a visually cued poison-based aversion in monkeys.

Retention of a poison-based aversion after a 3-yr. period by 8 vervet monkeys (Cercopithecus aethiops) was found. The color of the visual cue appeared to effect the retention of the aversion.


[Studies on the function of the autonomous adenoma of the thyroid gland (author's transl)].

Although the clinical picture of autonomous adenoma of the thyroid gland has been well known for a long time, a series of connections has in some cases been unclarified, and in other cases contradictory so far. This applies in particular to the relationships between the scintigraphic image and the metabolic balance of the autonomous adenoma. In 98 patiets aged from 21 to 70 years old (80 women, 18 men) with autonomous adenoma unequivocally verified by suppression or stimulation test, it was therefore investigated whether such connections can be demonstrated. The following could be established: 1. In patients with an autonomous adenoma, there is an established connection between the scintigraphy image, the thyroxine and triiodothyronine levels in the serum as well as the delta-TSH. In patients with scintigraphically compensated autonomous adenomas, the hormone levels are all in the euthyroid range. In patients with scintigraphically decompensated autonomous adenoma, the values of thyroid hormones are found in some cases in the euthyroid, and in other cases in the hyperthyroid range. 2. Scintigraphically decompensated autonomous adenomas always display a negative TRH test, whereas this may be negative and in other cases also postivie in scintigraphically compensated autonomous adenomas. The TRH test may be negative in compensated and in decompensated autonomous adenoma even in patients in whom the thyroid hormone values in the serum are in the euthyroid range. The TRH test thus does not permit evaluation of the current functional activity of the autonomous adenoma. It is furthermore unsuitable for delimitation of a compensated from a decompensated autonomous adenoma as well as for different diagnosis between a nodular goiter and a scintigraphically compensated autonomous adenoma. 3. There is a statistically established relation between the size of the autonomous adenoma, the age of the patient as well as the thyroid hormone values. Autonomous adenomas accordingly become larger with increasing age. The values of thyroid hormones increase and lead to corresponding alterations in the TRH test.


Biological effects of some N-substituted (meth)acrylamides.

This paper reports an investigation of the biological effects of monomers of N-substituted (meth)-acrylamides used in the preparation of polymers suitable for medical purposes. By combining tests carried out on cell cultures and on living animals, we found thpheral nervous system. Tests performed on cell cultures can be used as preliminary and supplementary ones in testing the toxicity of substances on living animals.


Biological tolerance of copolymers of N-substituted (meth)acrylamides in the test organism.

The mechanical properties of hydrolphilic crosslinked polymers of N-substituted (meth)acrylamides may be improved by copolymerization with N-tertbutylacrylamide [1] so that the mechanical properties of resulting copolymers satisfy requirements on polymers used in medicine. Tests of the biological tolerance of the above copolymers have shown that the latter are completely nontoxic with respect to cell cultures and do not cause any reaction or changes in the subcutaneous implantation into a living organism.


Uniform depth dose distribution for biological irradiation using negative pions.

A simple, flexible technique has been developed to generate uniform depth dose profiles for the biomedical pion beam at TRIUMF using dynamic momentum control and linear programming. Either the entrance dose or the irradiation time required for a certain dose over the uniform region can be minimised. The dynamic momentum control can operate automatically under computer control even with a highly unstable beam. Cell survival profiles have been obtained for this uniform dose distribution using the gelatin technique. The RBE increases with increasing depth through the uniform dose region.


The adaptability coefficient (AC)--an ergometric test in evaluation of the general functional capacity.

The AC test, based on the relation between the heart rate (fh) and triangular submaximal exercise intensity, was applied for 4 years on over 2000 healthy persons, and patients with cardiac and respiratory disorders. In this work there are presented the results of a reference group, made up of 20 male healthy students. The fh increased on an average with 5.32 beats/min for every 10 W step. The recovery of fh was obtained in 201 +/- 82 s, and the hemirecovery time in 38.5 +/- 15 s. We found the AC using the formula: (see text). The average value of the AC was 131 +/- 26. Together with the AC test, the Vo2 max, was also estimated during submaximum exercise--Astrand test; the average value was 35 +/- 6 ml/kg.min, with a semnificative linear correlation. This pleads, together with other data, for the value of AC test in clinical ergometric investigation.


The discrepancy between the inhibitory activity induced on passive hemagglutination by the free and conjugated hapten. The significance of the phenomenon for the explanation of the drug allergy.

The capacity of the free and conjugated haptens to inhibit passive hemagglutination has been comparatively studied in five immunological systems, using hapten specific antisera prepared in rabbits and conjugates of the respective haptens with rabbit serum proteins. The results demonstrate that the affinity of the free hapten for the specific antibodies is 100 to 10,000 times lower than the affinity of the conjugated hapten. This finding constitutes an explanation for the occurrence of the allergic drug reactions under the circumstances where the concentrations of the free hapten are much higher than the concentrations of the hapten bound in in vivo formed conjugates. Using the passive hemagglutination inhibition test, the affinity of the various forms of a given hapten for the specific antibodies can be comparatively evaluated.


Oxidative mechanisms in the granulocyte activity.

The bactericidal and bacteriolytic activity of the granulocyte occurs with the participation of some species of high oxidative potential such as singlet oxygen (1O2) and hydroxyl radical (.OH). These derive from the superoxide anion (O2-) produced by a pyridine nucleotide oxidising system, initiating phagocytosis.


Enkephalin-induced myoclonic twitches blocked by ergometrine and potentiated by haloperidol.

Myoclonic twitches (MT) in the submandibular muscles induced by intraventricular administration of D-ala2-met-enkephalinamide (DALA) were studied electromyographically in the rat. Measurement of MT activity was selected since it permits parallel study of the effect of enkephalin on both dopaminergic and serotonergic transmitter systems. The twitches induced by enkephalin were blocked by naloxone, gamma-hydroxybutyrate, and ergometrine, but potentiated by haloperidol. Methysergide did not alter the stimulatory effect of DALA. These results were interpreted as a possibility for a specific enkephalin-induced activation of the so-called inhibition-mediating dopaminergic system, which is sensitive to the blocking action of ergometrine, but resistant to the blocking action of haloperidol.


Memory facilitation by post-training injection of ethanol.

Immediate post-training IP injection of ethanol (0.75--4.5 g/kg) significantly enhanced retention of a one-trial passive avoidance task in mice compared to saline controls. Ethanol (4.5 g/kg) in the absence of footshock did not affect test performance. The memory facilitation may reflect ethanol's effects on neurotransmitter, macromolecular, or hormonal systems, or a reduction in interference.


Altered pilocarpine- or chlorpromazine-induced catalepsy after long-term treatment with cholinergic drugs.

Long-term administration of the cholinergic drug pilocarpine attenuates the catalepsy induced by an acute injection of pilocarpine or the deopamine antagonist chlorpromazine. Similar results (i.e., tolerance to pilocarpine and cross-tolerance to chlorpromazine) were noted in mice chronically treated with the cholinesterase inhibitor physostigmine but not in mice chronically treated with neostigmine, a cholinesterase inhibitor which does not penetrate the central nervous system. Mice maintained on the anticholinergic scopolamine showed the opposite effect; there was an increase in the sensitivity to the catalepsy induced by pilocarpine or chlorpromazine. The results suggest that long-term changes in cholinergic receptors may indirectly alter the behavioral effects of drugs which act via dopamine.


Effects of ethyl alcohol on behaviour in nursing female mice.

Effects of administering 10% ethyl alcohol as drinking fluid to mice during pregnancy and lactation have been examined by ethological analysis of behaviour of nursing females in their home cages at 1 day, 5--7 days, and 12--14 days postpartum. The treatment with alcohol did not affect gestation period or litter size, and fluid intake of treated mice remained similar to that of controls, the average intake of alcohol amounting to 29 mg/g body weight during lactation. Increase in frequency of exploration at 1 day postpartum was the only significant behavioural effect of alcohol on the nursing female mice. Duration of Non-Social Behaviour was unaltered, and no effects of the treatment on Maternal Behaviour or on Social and Sexual Investigation of male partners could be demonstrated. Behaviour of nursing females changed with increase in age of their pups. This occurred to a similar extent in treated and control animals. Maternal and Non-Social Behaviours declined in frequency as the pups became older although the time spent in these behaviours remained fairly constant. Social Investigation of the male partner declined both in frequency and duration while females were nursing their pups.


Development of behavioral tolerance: a search for subcellular mechanisms.

Development of behavioral tolerance is one of the processes by which living organisms adjust to changes in their internal and external environments. The search for neurochemical mechanisms underlying such processes requires the testing of many hypotheses. The present study was designed to examine the possible involvement of certain subcellular events. The concentrations of acetylcholine (ACh) and choline (Ch), the high-affinity transport of Ch, and the rate of synthesis of ACh were measured in synaptosomes prepared from the brains of rats. The assays were made at critical times during the acute changes in behavior induced by administration of the anticholinesterase, di-isopropylfluorophosphate, and during the development of behavioral tolerance to this compound as chronicity of administration continued. No statistically significant differences were found among treatment groups in the total concentration of ACh or Ch, the synthesis of ACh, or the high-affinity transport of Ch. These results, plus evidence from previous experiments, indicate that the development of behavioral tolerance does not relate to the factors studied. Consequently, alternative mechanisms should be considered. In addition to changes in cholinergic (muscarinic) receptors already shown to occur concomitantly with the development of behavioral tolerance, it is suggested that the possible involvement of mechanisms controlling release of ACh should be studied.


Effect of anorexic drugs on food intake and the micro-structure of eating in human subjects.

Human volunteer subjects of normal weight received oral doses of (+)amphetamine (10 mg) or (+/-)fenfluramine (30 mg and 60 mg) together with a placebo control according to a within-subjects design. The effects of these treatments were monitored by measuring food intake in a test meal, subjective ratings of hunger motivation and the micro-structure of eating behaviour abstracted from videotaped recordings of the test meal. Various measures of the rate of feeding were computed from these recordings. Amphetamine and fenfluramine (60 mg) showed generally similar effects on food intake and on the subjective experience of hunger, but displayed differing actions on the fine structure of eating. Amphetamine increased latency to initiation of eating and increased the rate of food ingestion, whilst fenfluramine slowed the local rate of eating and eliminated the characteristic decline in the rate of feeding across the course of a meal. These findings display certain resemblance to the results of animal experiments involving similar pharmacological manipulations and emphasise the importance of measuring rate of feeding in animal and human studies. The results of this study suggest that the micro-analysis of feeding behaviour not only provides a tool for understanding systems involved in the modulation of food consumption but also reveals information which may be helpful for the use of drugs in the treatment of obesity.


The dorsal noradrenergic bundle and varieties of passive avoidance.

Neither acquisition learning nor 24-h retention was significantly altered by 6-hydroxydopamine intracerebral injections which depleted forebrain noradrenaline (NA) to less than 5% of control values. The absence of passive avoidance impairment cannot be ascribed to functional recovery following the lesion (indicated by testing 24 h post-operation) and by using the F-344 strain of rat which does not show denervation supersensitivity as measured by NA-sensitive adenylate cyclase. Nonassociative freezing to electric footshock, changed by the injections, resulted in slower acquisition at a footshock level 4 mA, but not at 1 mA.


Strain differences in amphetamine sensitivity in mice. I. A diallel analysis of open field activity.

Experiments are reported which show that 1 mg/kg of d-methylamphetamine HCl induced hyperactivity in pigmented strains (C57BR, C57BL/6, and SEC) and hypoactivity or no change in albino strains (BALB/c, A, and AKR) of mice. In F1 hybrids, the B6 genotype was partially dominant over BR and C, and BR over C. In animals back-crossed to C parents widespread distributions with two peaks were obtained in control experiments, and amphetamine induced hyperactivity in 38% of the albino population, and hypoactivity or no significant change in 45% of the pigmented one. This genetic study indicates that genes influencing locomotor activity are independent from those influencing amphetamine sensitivity. From results obtained in back-crosses and C57BL/6-c2J mice, the albino gene does not seem to be involved in the hypoactive effect of amphetamine.


Disruption of taste aversion learning by pentylenetetrazol.

Rats were taught an aversion to a sucrose taste cue (CS) by pairing it with lithium chloride-induced toxicosis (UCS). The CS-UCS interval was 30 min. Animals were injected with pentylenetetrazol (PTZ) (50 mg/kg at 0, 15, 25, 28 or 30 min after the CS in an attempt to disrupt taste aversion learning. Only animals given PTZ 30 min after the CS (simultaneously with the UCS) showed a significant learning deficit. However, learning deficits were also observed in individual animals in groups given PTZ at 15, 25 and 28 min. As lithium salts may produce seizures and abnormal electroencephalographic activity, it is suggested that the neurophysiological consequences of PTZ administration may interact with those of LiCl, causing a greater amnesic effect than PTZ by itself. The resulting interference with the memory trace is probably affecting either the neural engram underlying the CS or the associative bond between the CS and UCS. Evidence was also found that PTZ could act as a UCS with which to establish a mild taste aversion.


The effect of naloxone on audiogenic seizures.

The severity of audiogenic seizures was increased in two strains of mice 5--10 min after naloxone (2 or 4 mg/kg IP). This may indicate involvement of an endorphin or enkephalin in the modulation of reactivity.


Desmethylimipramine (DMI) counteracts learned helplessness in rats.

In a study of the mechanisms controlling the learned helplessness phenomenon, rats were exposed to either inescapable preshocks or control procedures, treated with one of three dosages of desmethylimipramine, and tested for later adaptive responding. This catecholamine modulator attenuated the deficits in escape responding that ordinarily follow prior exposure to inescapable preshocks, and it did so in a dose-dependent fashion. These findings support the position that the learned helplessness phenomenon is mediated by catecholamine changes.


Effects of dopamine receptor blockade on alimentary behaviors: home cage food consumption, magazine training, operant acquisition, and performance.

Administration of the dopamine receptor blocker pimozide (1.0 mg/kg) disrupted the initiation, but not the maintenance, of home cage food consumption. Likewise, the number of pellets consumed during magazine training was decreased among pimozide-treated rats during the first, but not the second day of training. The acquisition of a bar-press response for food reinforcement (using a retractable bar) was severely retarded by pimozide. However, such an impairment was not evident if animals initially received 2 training days in the absence of the drug. Further, among rats trained to bar press to asymptote using a nonretractable bar, pimozide reduced the within and between days bar-press rate such that performance was indistinguishable from that of animals placed on extinction in the absence of the drug treatment. When transferred from the pimozide treatment to extinction in the absence of drug, the response rate increased to the level observed during the first session of either extinction or pimozide in the continuous reinforcement condition. The results are discussed in terms of sensory-motor and reinforcement consequences of dopamine receptor blockade.


Differential effects of chlordiazepoxide on comparable rates of responding maintained by food and shock avoidance.

Comparable rates and patterns of lever-pressing by rats were obtained under a multiple variable interval schedule of food reinforcement and continuous shock avoidance. Chlordiazepoxide (1.0--17.0 mg/kg) produced increases in food maintained responding at doses that decreased avoidance responding. Removing food, shock, or both in separate individual probe sessions did not produce differential effects. Under certain circumstances, the effects of chlordiazepoxide appear to be best predicted by knowledge of maintaining conditions.


Treatment of Schizophrenia with ergot derivatives.

Seven neuroleptic-free schizophrenic patients received bromocriptine and eight schizophrenic patients received CF 25-397, both ergot derivatives with dopamine agonist activity. Psychosis failed to improve in response to either drug at the relatively low doses administered. Unlike the antipsychotic property of apomorphine at low dose levels, neither of these ergot drugs improved schizophrenic symptomatology.


Metrazol-produced impairment of passive avoidance retention specifically antagonized by anti-petit mal drugs.

In a single session, naive female 250-g Wistar rats were trained to remain for 3 min on a platform located above an electrifiable grid. During training, animals were shocked (4 mA) after they stepped down. Retention of the step-down avoidance was tested 24 h later in rats treated SC 30 min before the session with saline or a subconvulsive dose of metrazol (40 mg/kg). During the retention test no shock was delivered. The latency to step down and the time on the grid were recorded. The metrazol rats significantly failed to retain the avoidance task. Groups of six rats per dose were trained and 24 h later pretreated, 5 min before metrazol, with an IP injection of the following antiepileptics (dose range in mg/kg): Ethosuximide (20--320); trimethadione (20--320); clonazepam (0.04--0.63); sodium valproate (20--320); carbamazepine (1.25--20); phenobarbital (5--80); or diphenylhydantoin (5--80); or high dose of haloperidol (0.16) and amphetamine (0.63). Only ethosuximide, trimethadione, and clonazepam significantly increased the latency to step down and significantly shortened the time on the grid. Sodium valproate only shortened the time spent on the grid. The results suggest that only anti-petit mal drugs antagonize the retention impairment of passive avoidance produced by metrazol.


Discriminative stimulus properties of intravenous morphine in the rat.

Using a single-lever operant task, rats were trained to discriminate between the effects of 1 mg/kg morphine and saline administered intravenously 15 min prior to sessions. Tests of stimulus control indicated that responding appropriate to the morphine training treatment was present at 5 min and persisted for at least 60 min following intravenous administration. Morphine administered intraperitoneally 15 min prior to sessions resulted in dose-related responding with 6 mg/kg producing stimulus control not significantly different from the intravenous training treatment. These results suggest that the discriminative stimulus properties of morphine in the rat are qualitatively similar following intraperitoneal and intravenous administration.


Severe aggression in rats induced by mescaline but not other hallucinogens.

Pairs of male Sprague-Dawley rats were administered mescaline, lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), 3,4-dimethoxyphenylethylamine (DMPEA), or 5-hydroxydopamine (5-OHDA) IP prior to being placed in a shock-elicited aggression situation. When foot shock was delivered, controls struck each other with their forepaws, but never engaged in either biting or injurious fighting. Mescaline-treated rats (50 or 250 mg) rarely struck each other, but engaged in nearly lethal biting. While LSD (25--400 micrograms/kg), psilocin (2.0 mg/kg), and DMT (5 mg/kg) produced some biting, this did not significantly differ from controls and never resulted in injuries. At higher doses, psilocin, DMT, and DMPEA decreased the amount and intensity of fighting. Rats treated with 5-OHDA (8--200 mg/kg) or LSD (25--400 micrograms/kg) did not differ from controls. These results suggest that mescaline's ability to induce pathological aggression in rats exposed to foot shock is not shared by other hallucinogens or nonhallucinogenic mescaline analogues.


An open field study of stereotyped locomotor activity in amphetamine-treated rats.

It is said that amphetamine induces stereotypy and locomotion in rats; however, the present paper shows amphetamine-induced stereotyped locomotion by analyzing the route of locomotion in an open field. Details of the analysis are given, normal as well as stereotypic features are discerned, and the results are discussed in relation to contemporary views on locomotion and exploration and on the mechanisms of amphetamine effect.


The effect of propranolol phentolamine and pimozide on drug-induced anorexia in the mouse.

Pimozide was a potent antagonist of (+)amphetamine, diethylpropion, mazindol and phentermine anorexia in the mouse. Phentolamine and propranolol produced no such antagonism, but either potentiated or had no effect on the drug-induced anorexia. Although the mechanism of action of the four anorectic agents appears to involve dopamine receptor agonist activity, an antagonist or partial agonist effect at noradrenergic receptors may also be involved.


Differential tolerance to dietary amino acid-induced changes in aggressive behavior and locomotor activity in mice.

Male albino mice were maintained on a semisynthetic 12% casein protein diet for 2 weeks, then switched to diets modified by the addition of a 4% L-amino acid supplement (L-tyrosine, L-phenylalanine, and L-tryptophan) or 4% casein (control). Territorial=induced aggressive behavior increased following 1 week on the amino acid supplements, especially after tyrosine, but an apparent tolerance developed to these effects after 5 weeks on the amino acid supplements. Locomotor activity also increased following 1 week on the supplements, most notably after phenylalanine alone or in combination with tyrosine, and these effects tended to persist after 5 weeks on the supplements. Endogenous whole brain levels of dopamine, norepinephrine, serotonin, 5-hydroxyindoleacetic acid, tyrosine, phenylalanine, and tryptophan showed no tolerance to increased concentrations of brain catecholamines and indoleamines over the 5-week period, and no clear relation between the concentrations of these monoamines and the behavioral changes.


Biosynthesis of prostaglandin (PGI2) and 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) by pericardium, pleura, peritoneum and aorta of the rabbit.

Prostacyclin generation by pericardium, pleura, peritoneum, aorta and dura mater of the rabbit was assessed as platelet aggregation inhibitory activity in platelet rich plasma. All tissues except the dura mater, were also incubated with labelled (1-14C) arachidonic acid and (1-14C) prostaglandin endoperoxide H2 and the various metabolites formed were identified radiochromatographically. Pericardium, pleura and peritoneum form substantially high amounts of prostacyclin and HETE indicating that these tissues contain both cyclo-oxygenase and prostacyclin-synthetase. They also show considerable lipoxygenase activity.


[8-Quinolinol-5-sulfonic acid-loaded resin as a preconcentrating agent in the neutron activation analysis of the chalcophile elements (author's transl)].

A chelating agent-loaded resin consisting of 8-quinolinol-5-sulfonic acid and an anion-exchange resin (HOx-resin) was prepared in order to concentrate trace chalcophile elements in natural water samples selectively before neutron activation analysis. The exchange capacity of the Diaion SA No. 100 for the reagent (1.8 meq . g-1 resin) corresponds approximately to that for chloride ion (1.83 meq . g-1 resin), indicating that 8-quinolinol-5-sulfonic acid is adsorbed quantitatively on the exchange site of the resin through the sulfonate anion in the reagent. The basic conditions for the adsorption of the metal ions on the resin were investigated by employing the column method. The nitrate concentration and the pH of the sample solution affect the adsorption behavior of metal ions. Several solutions containing metal ions with varying pH or varying nitrate concentration were applied to the resin column (35 mm x 7 mm phi) with a flow rate of 2.0 cm3 . min-1. As a result, the optimum conditions for the quantitative adsorption of copper(II), zinc(II), cadmium(II), cobalt(II), nickel(II) and manganese(II) were as follows: NO3- less than 0.01 mol . dm-3 pH greater than 4.6. Furthermore, the feasibility of the above conditions as well as quantitative adsorption of the chalcophile elements was confirmed through the neutron activation analysis of the synthesized metal solutions.


[Influence of EDTA on growth and reproduction of Biomphalaria glabrata (author's transl)].

The influence of EDTA on B. glabrata has been investigated. Newly hatched snails were exposed to concentrations of EDTA from 1 to 64 ppm, and young (diameter of 6 mm) snails to concentrations of 50, 80 and 100 ppm, for periods of 90 days. Fifty percent reduction of egg productivity has been caused by concentration of 16 ppm of EDTA while 50% of mortality has occurred at about 70 ppm. The calcium and iron content both in treated and non-treated young snails have been estimated by atomic absorption photometry. The uptake of calcium was 40, 83 and 90% less for calcium and 37, 77 and 81% less for iron as compared with the untreated group. The calcium content of the shell was 5--15 times greater than that of the soft body, while the iron content of those two parts was in the proportion of 1:1. These proportions were maintained constant in the treated and non-treated groups. The interference of increasing concentrations of EDTA has resulted in the proportional reduction of growth-rate, reproduction rate and of longevity of the exposed snails.


[Information on a wild rodent and marsupial collection from a "cerrado" region of Central Brazil (author's transl)].

A list of wild rodents and marsupials from "cerrado" region captured in six conties of Goiás, Mato Grosso State and Federal District of Brasil, is presented. This list includes twenty-four rodent species and four marsupials species.


[Influence of the sterilization technic and culture media components on the growth and dissociation of Brucella abortus strain 19 in submerged cultures].

Submerged cultures of Brucella abortus strain 19 were studied in shaking flasks. The influence of the sterilization methods and the medium composition on the bacterial yield and cellular dissociation were studied. The selected medium was as follows (amounts in g/l): casein pancreatic hydrolizated 30; yeast extract 10; glucose, 30; sodium phosphate dibasic anhydrous 3,3; sodium monobasic monohydrate 9. Cell concentration of 8 . 10(10) viable cell/ml was obtained after 48 hours when the medium components were separated and sterilized at 121 degrees C for 20 min in autoclave.


[Significance of epileptic seizures occurring during the first week of traumatic coma (author's transl)].

Clinically evident epileptic seizures were observed in 145 patients during the first week of traumatic coma. They frequently occurred during the first day in young subjects in reactive coma, and were often isolated attacks. When ssen at a later stage they are more common in adults with non-reactive coma. The partial or generalised nature of the seizures, the depth of the coma, and the chronological order in which the seizures appear have no bearing on the etiology; the only positive finding was that recurrent seizures were more frequent in patients with intracranial hematoma (18,6% of the patients). The early appearance of seizures does not worsen the prognosis of reactive coma or non-reactive coma in young people. Critical discharges without clinical manifestations were present in 37 patients with traumatic coma during the first week. The average age of these injured patients was higher, and the prognosis for non-reactive coma worse in this group. The comatous state does not modify the clinical aspects or the etiological significance of these early post-traumatic discharges.


The pharmacology of diclofenac sodium (Voltarol).

Diclofenac is a potent anti-inflammatory and analgesic compound with good antipyretic and uricosuric properties. It is one of the most potent inhibitors of prostaglandin synthetase known. It shows a favourable therapeutic ratio considering its efficacy, and proved superior to the reference drugs in terms of gastro-intestinal tolerability. All metabolites are clearly less potent than the parent compound.


[Radiographic identification of duodenal ulcer by ingestion of iodine tablets (radiological clinical case)].

Radiological diagnosis of peptic ulcer disease is currently made with a barium meal examination occassionaly is possible to demonstrate an ulcer by air contrast in a plain film of the abdomen or by the retention of a cholecistographic agent in the crater. In the present case, the ulcer was opacified by the ingestion of an antiamoebic yodinated drug. The value and possible mecanisms of its findings are discussed.


[Prostatic osteosis. Retrospective study of 110 cases treated with high-dose estrogens].

On the basis of 110 prostatic osteoses that were histologically proven, constantly painful and demonstrated by X-ray, treated by early estrogenotherapy using very high doses, backed up by a high-dose maintenance estrogenotherapy, the authors study the clinical, radiological, histological and biological profile of this metastatic cancer, as well as the response to treatment. The median actuarial survival time of the patients studied is 18.5 months. No statistically significant prognostic correlation was found. Only patients who are clinically estrogen-sensitive, are suffering from bone metastases without a combined visceral conditions, and have a normal initial rate of alcaline phosphates, tend to have a better prognosis (median actuarial survival 31 months versus 18.5 months for the overall population).


A radioimmunosorbent technique for the assay of B- and C-types of carbonic anhydrase in human tissues.

A radioimmunosorbent technique for the assay of the human carbonic anhydrase isoenzymes HCA B and HCA C in tissue fluids was developed. The sensitivity of the method was 0.2 ng/ml and the precision was 5% in duplicate determinations for both enzymes. The presence in a tissue of up to 20 times higher concentrations of one isoenzyme will not interfere with the assay of the other. Haemolysates contained (mean +/- SE, n = 11) 12.1 +/- 0.52 and 1.5 +/- 0.06 mg enzyme/g Hb, and serum 0.63 +/- 0.12 and 0.2 +/- 0.02 microgram/ml of HCA B and HCA C, respectively. Pilot experiments indicated that the isoenzymes can be determined also in tissues, i.e. urine, saliva and cerebrospinal fluid, where catalytic methods previously have indicated absence of or only weak carbonic anhydrase activity. N-terminals of both enzymes were not antigenic.


Effect of Sar1-ala8-angiotensin II on blood pressure and renin in Bartter's syndrome, before and after treatment with prostaglandin synthetase inhibitors.

Three patients suffering from Bartter's syndrome were studied before and after 5 days of treatment with the prostaglandin synthetase inhibitors, aspirin and indomethacin. Saralasin was given by intravenous infusion in increasing doses from 0.6 to 42 micrograms/min.kg/BW. During saralasin infusion a blood pressure reduction was observed in all patients. Aspirin treatment did not affect this response and nor did it affect other manifestations of the syndrome. Indomethacin treatment changed the blood pressure response to saralasin in such a way that the blood pressure was increased in one patient and was unchanged in the other. Indomethacin also tended to normalize other features of Bartter's syndrome, such as the hyperreninaemia and angiotensin unresponsiveness, but did not affect the hypokalaemia. The saralsin effect on blood pressure is thus evidently inversely related to the prevailing activity of the renin-angiotensin system in this condition also, and the patients obviously depended on the renin-angiotensin system to maintain their blood pressure. Our findings, together with data in the literature, indicate that angiotensin unresponsiveness of the vascular bed is not a primary feature in Bartter's syndrome. Chloride loss is currently thought to be the basic abnormality and this may link the Bartter's syndrome with other diseased states characterized by chloride loss, such as the syndrome of habitual vomiting and chronic treatment with loop diuretics.


Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system.

Gamma-Trace was purified in large amounts from urine and used for the production of a specific rabbit antiserum. An enzyme immunoassay for quantitation of gamma-trace was developed using the pure protein as a primary standard. Its sensitivity was approximately 30 microgram/l. An enzyme amplified single radial immunodiffusion was developed as well. Its sensitivity was approximately 0.3 mg/l. These assays allowed quantitation of gamma-trace in normal human biological fluids. The following results were obtained (mean +/- SD): cerebrospinal fluid: 5.8 +/- 2.2 mg/l, plasma: 1.1 +/- 0.42 mg/l, saliva: 1.8 +/- 0.88 mg/l and urine: 0.095 +/- 0.057 mg/l. Plasma samples from patients with advanced renal failure revealed gamma-trace values up to 13 times the normal mean plasma value. The results indicate a production of gamma-trace in the central nervous system and that the protein is primarily catabolized by the kidney.


EDTA effect on creatine kinase (CK) and on the SCE reagent.

The inclusion of EDTA in the creatine kinase reagent recommended by the Scandinavian Committee on Enzymes was shown to increase reagent stability from less than 24 h to 5 days. Part of this effect can be explained by the fact that EDTA delays the formation of inhibitory products formed when N-acetyl cysteine is oxidized. The addition of EDTA to the reagent also results in increased measured CK activity. This effect is more pronounced for CK-BB than for CK-MM. Calcium and ferric ions are shown to inhibit the enzyme and the chelation of these ions can partly explain the observed increase of CK acitivity.


Serum T3 and T4 determinations during the TRH test as a complement to improved discriminatory power in suspect hyperthyroidism.

The aim of the study was to determine whether the addition of T3 and T4 determination in connection with a routine TRH-test could increase the discriminatory power of the test. Thus, forty-one patients with suspect hyperthyroidism were examined and samples for T3 and T4 and TSH determinations were drawn prior to the administration of TRH and at 20 and 60 min thereafter. The results showed that the addition of these thyroid hormone estimations did not increase the clinical value of the TRH-test.


Intestinal lysosomal enzymes in the diagnosis of pancreatic disease.

Acid hydrolases (lysosomal enzymes) were analyzed and compared with trypsin in duodenal juice obtained after a test meal (Lundh test). The possible diagnostic role of acid hydrolases in pancreatic disease was investigated. In all patients with chronic pancreatitis normal values of acid hydrolases but subnormal trypsin activities were found. In pancreatic cancer normal values of acid hydrolases and normal trypsin values were seen in three patients with small tumors, whereas five patients with more advanced cancer of the pancreas had decreased trypsin activity and three of them high activities of acid hydrolases in duodenal juice. In five patients operated on with a gastroenteroanastomosis acid hydrolases were markedly increased. Five patients had no activity of acid hydrolases in the aspirate, probably reflecting technical failure with dislodgement of the catheter from the duodenum to the stomach. In conclusion the assay of acid hydrolases does not seem to increase the diagnostic value of the conventional Lundh test (trypsin).


Fluid and electrolyte absorption and renin-angiotensin-aldosterone axis in patients with severe short-bowel syndrome.

In eight patients who had received long-term parenteral nutrition because of short-bowel syndrome the need for parenteral supply of fluid, sodium, and potassium was estimated by balance studies. Six patients had jejunostomies. In two, most of the colon was preserved. Jejunostomy patients had a huge stool mass (1710--5270 g, median 2530 g/day) with fixed concentrations of sodium (92 +/- 10 mmol/l) and potassium (15 +/- 4 mmol/l). In contrast, two patients with massive small-bowel resection but with more than half of the colon intact showed almost normal sodium absorption and considerably smaller stool mass (170--510 g/day). Despite apparently good health and normal plasma electrolytes, urea, and haematocrit, four of six jejunostomy patients were sodium-depleted with low plasma volume, low sodium excretion in the urine, and increased plasma renin activity and, in the three most severe cases, increased aldosterone. Even in case of sodium depletion the sodium loss from jejunostomy effluents remained high and presumably unaffected by salt-retaining hormones. The study confirms the importance of preservation of part of the colon for maintenance of fluid and electrolyte balance in patients with extensive bowel resection. Jejunostomy patients who are eating normally may need large parenteral saline supply. Assessment of water and electrolyte homeostasis in these patients requires determination of the urinary sodium excretion and is supported by measurements of plasma renin activity and plasma aldosterone concentration.


Parietal and chief cell sensitivity to histamine and pentagastrin stimulation before and after cimetidine treatment in healthy subjects.

Gastric acid and pepsin output in response to 2.5 and 25.6 micrograms . kg-1h-1 of histamine dihydrochloride and 0.10 and 6.0 micrograms . kg-1h-1 of pentagastrin was studied before and after cessation of 4 weeks of cimetidine treatment, 1 g/day, in 10 healthy volunteers. Acid output in response to the low dose of histamine increased significantly from an average of 6.7 mmol +/- 1.3 mmol (S.E.M.) before to 10.1 mmol +/- 0.9 mmol after treatment (p = 0.02), whereas acid output in response to the maximal dose of histamine was not significantly different. Parietal cell sensitivity to histamine stimulation increased significantly after the treatment period from a mean of 28.2% +/- 3.2% before treatment to 49.3% +/- 2.8% afterwards (p less than 0.01). The results indicate augmented parietal cell sensitivity in response to histamine stimulation after withdrawal of cimetidine. Both acid output in response to the two doses of pentagastrin and parietal cell sensitivity to pentagastrin stimulation were not significantly different after cessation of cimetidine treatment. Pepsin output and chief cell sensitivity to histamine and pentagastrin stimulation were not significantly influenced by cimetidine treatment.


Bilateral adrenalectomy: effect of tryptophan on protein synthesis and pepsin activity in the stomach of rats.

The effect of bilateral adrenalectomy and subsequent force-feeding of L-tryptophan on the gastric mucosal pepsin activity and [3H]leucine incorporation into total protein of the stomach (fundus) in vivo were investigated. One month after bilateral adrenalectomy the gastric mucosal pepsin activity and overall protein synthesis in the stomach were decreased by 72% and 52%, respectively. Twenty-four hours after a single tube-feeding of tryptophan (30 mg/100 g body weight) both activities returned to sham-operated control levels. In adrenalectomized rats the tryptophan-mediated stimulation of gastric mucosal pepsin activity was found to be sensitive to the RNA synthesis inhibitor, actinomycin-D. The diminution in gastric mucosal pepsin activity after adrenalectomy and its enhancement by tryptophan could not be related to the presence of an inhibitor or activator in the tissue. One month after adrenalectomy serum gastrin concentration was found to be 36% above that of the sham-operated control. In adrenalectomized rats, 24 and 48 h after tryptophan force-feeding, serum gastrin concentrations were decreased by 50% and 20%, respectively, but none of the values differed significantly from those of water-fed adrenalectomized controls.


Senile cardiac amyloidosis: evidence of two different amyloid substances in the ageing heart.

In a material of seventy-two persons over 70 years of age, forty-seven cases of amyloidosis of the heart were found. In thirty-nine cases, deposits occurred only in the atria (isolated artrial amyloidosis, IAA), while in eight cases amyloid also was seen in the ventricles (senile cardiac amyloidosis, SCA). In some of the latter cases, small amyloid deposits occurred in other organs, especially the lungs. Some definite differences existed between the amyloid substance in SCA and IAA. Thus, tryptophan was demonstrated histochemically in SCA but not in IAA, and, furthermore, amyloid fibrils isolated from patients with IAA lacked protein Asca, the fibril subunit protein of senile cardiac amyloid. It is concluded that the ageing heart may be the target of two different forms of amyloid, one only affecting the atria, while the other is more widespread within the heart and sometimes also is found in other organs.


A high frequency of cytotoxic precursor cells for a syngeneic tumour.

The average frequency of cytotoxic precursor cells in DBA/2 lymph node cell preparations reactive to the syngeneic tumour P815 has been determined as 1 in 2000. This frequency is similar to the precursor frequency for an allogeneic tumour EL-4. The normal lack of response of DBA/2 lymph node cells to the syngeneic tumour P815 in vitro cannot be attributed to a lack of cytotoxic precursor cells. We conclude that in this tumour-host system non-immunogenicity reflects a defect at the inductive step.


Clinical, epidemiological and prognostic aspects of hepatitis "non-A, non-B"--a comparison with hepatitis A and B.

Sera of 480 hospitalized hepatitis patients were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and to hepatitis B core antigen (anti-HBc), antibody to hepatitis A virus (anti-HAV) and anti-HAV of IgM-class. Serological markers indicating hepatitis A infection were found in 107 (22.3%) and markers indicating hepatitis B in 297 patients (61.9%), while 63 patients (13.1%) were classified as hepatitis type "non-A, non-B". The latter group mainly comprised drug addicts (50.8%), cases of post-transfusion hepatitis (11.1%) and patients without obvious hepatitis exposure (28.6%). In spite of these epidemiological similarities to hepatitis B, the maximum levels of serum alanine aminotransferase and bilirubin were comparable to those in patients with hepatitis A and significantly lower than in hepatitis B infection. Chronic hepatitis developed in 7.1% of the "non-A, non-B" patients, a figure close to that reported for hepatitis B.


Fabry's disease. A brief review in connection with a Scandinavian survey.

Fabry's disease is an X-linked inborn error of glycosphingolipid catabolism, resulting from deficient activity of the enzyme alpha-galactosidase. The wide variety of symptoms may make it difficult to establish a diagnosis. This study was based on a Scandinavian survey of cases between 1967 and 1975. Altogether 13 cases were collected. Enzymatic studies and electromicroscopy confirmed the diagnosis in all cases. Renal transplantation has been performed in one Swedish patient and 8 years later his general health is good. Three of the patients died at about 50 years of age, which illustrates the grave prognosis of the disease. The report is concluded with a short review of the symptomatology, diagnosis and treatment of Fabry's disease. The possibility of enzyme replacement therapy and the potential value of renal transplantation are discussed. Prenatal diagnosis of Fabry's disease may also be possible.


Immunoprofile studies in patients with pulmonary tuberculosis. II. Correlation of levels of different classes of immunoglobulins and specific antibodies with the extent of tuberculosis.

Humoral immune response of patients with newly detected, bacteriologically confirmed pulmonary tuberculosis was determined prior to initiation of chemotherapy. Correlation with the extent of the disease was studied. A significant rise in the IgA and IgG levels in the serum was observed, the increase in the IgA levels correlated with the extent of the disease. In tuberculous patients elevated levels of anti-OT (ppd) antibodies were found by haemaggluination, but no marked correlation was observed with the extent of the disease. There was no interrelationship between the IgA or IgG increase and that of specific anti-OT (PPD) antibodies. The importance of the mentioned findings is discussed.


[Effect of aerobic and anaerobic germs on the healing of decubitus ulcers].

Bacteriological examinations of decubitus ulcers were performed in 34 geriatric patients. A total of 179 wound swabs were analyzed for aerobic and anaerobic bacteria. The decubitus ulcers were divided into three groups according to wound healing: group A with progressive worsening, group B, stationary, and group C with healing within 10 weeks. The aerobic bacteria isolated from the three groups were significantly different (p less than 0.0001). In group A Pseudomonas aeruginosa was isolated in 88%, enterococci in 73% and Providentia in 34%, whereas in group B staphylococci were found in 69%, enterococci in 62% and E. coli in 32%. In group C staphylococci dominated with 91%, followed by enterococci (51%) and E. coli (25%). Anaerobic microorganisms were significantly (p less than 0.01) more frequent in decubitus ulcers with poor healing tendency (group A and B) than in healing ulcers (group C). These results suggest that bacterial growth on decubital ulcers significantly influences decubital ulcer healing. Furthermore, bacteriological examinations are of prognostic value and the results should be considered in treatment.


[High-dose ifosfamide therapy: systemic use of a mucolytic agent for the reduction of urotoxicity].

Ifosfamid is an alkylating cytostatic agent which appears to differ in its clinical spectrum from the chemically similar cyclophosphamid. So far, however, its pronounced urotoxicity has limited dosage. In spite of prophylactic measures such as forced diuresis and alkalinization of the urine, the treatment has frequently has to be broken off because of macrohematuria and hemorrhagic cystitis. By repeated intravenous administration of sodium-mercapto-ethan-sulfonate (NNI: Mesnum) the urotoxic side effects of ifosfamid can largely be prevented. During 26 cycles of treatment in 18 patients, asymptomatic microhematuria was observed 6 times and macrohematuria only once in a patient with vesico-vaginal fistula. In another case where therapy had had to be discontinued because of hemorrhagic cystitis in spite of conventional prophylaxis, the treatment could be continued without change in the urine sediment under prophylaxis with Mesnum. Mesnum does not affect the antitumoral activity of ifosfamid.


[Value of the oral TRH test for the evaluation of thyroid function in impaired TSH reserve. Preliminary report].

Oral TRH (40 mg) exerts a marked and protracted stimulatory effect on TSH release. The potency of oral TRH in stimulating TSH and T3 was evaluated in 26 euthyroid patients with absent or impaired TSH response in the i.v. TRH test (200 micrograms). All were given i.v. and oral TRH at an interval of at least 3 days. Based on the response to i.v. TRH, they were divided into "non-responders" (TSH increment less than 1.0 microU/ml) and "low-responders" (TSH increment 1.0--3.7 microU/ml). The results were compared with those in 11 patients with overt hyperthyroidism. 10 "non-responders" were additionally tested with 400 micrograms TRH i.v. to study the effect of a supramaximal dose. Most patients unresponsive to i.v. TRH had a pronounced response to oral TRH (TSH increment 0.1 +/- 0.1 and 4.0 +/- 0.9 microU/ml (mean +/- SEM) respectively, p less than 0.005). The "low-responders" in the i.v. test had a significantly enhanced response to the oral dose (2.4 +/- 0.3 and 7.6 +/- 1.6 respectively, p less than 0.005). The euthyroid patients with treated Graves' disease with a weak response to i.v. TRH showed a distinct response to the oral dose. On the other hand, plasma TSH in patients with overt hyperthyroidism failed to increase either after intravenous or after oral TRH. In contrast to oral TRH, the supramaximal dose of 400 micrograms i.v. TRH did not enhance the TSH-response in the "non-responders". In most patients with absent or impaired response to i.v. TRH, a marked increase in T3 could be demonstrated (0.5 +/- 0.1 ng/ml and 0.6 +/- 0.1 ng/ml in "non-responders" and "low-responders" respectively, p less than 0.01); thus, oral administration allows simultaneous stimulation of TSH and triiodothyronine. Oral TRH can be considered the test of choice for the investigation of patients with diminished TSH reserve.