Galvanized caging as a potential factor in the development of the "fading infant" or "white monkey" syndrome.

Four rhesus females and their infants were kept in galvanized enclosures, and three were kept in stainless steel caging. All four offspring in the galvanized enclosures developed achromotrichia, alopecia, and weakness that varied from modererate to severe while the three infants in stainless steel cages were clinically normal. Plasma copper, zinc, and iron values as well as liver copper and zinc values of the infants were compared for the two types of caging. Plasma copper values were significantly lower (p less than 0.001) in the animals housed in galvanized cages. Plasma zinc and liver zinc levels were significantly elevated in these same animals (p less than 0.01 and p less than 0.05, respectively). Significant differences were not detected in liver copper values in the two groups of infants. Copper and zinc levels in the dams' plasma and milk were not statistically different between the two groups.


The isolation of herpesvirus from trigeminal ganglia of normal baboons (Papio cynocephalus).

A herpesvirus was isolated from the trigeminal ganglia of three of six normal baboons (Papio cynocephalus). This virus possessed the virologic characteristics of SA8, A herpesvirus known to be indigenous to the baboon.


Multiple urogenital and ocular anomalies occurring in a litter of guinea pigs.

Following an outbreak of proliferative pneumonia in a guinea pig breeding colony and subsequet treatment with Tylan, a litter of guinea pigs was found to have multiple urogenital and ocular anomalies. Subsequent mating of the parents produced no abnormal offspring. Chromosome typing on the litter showed no abnormalities. A review of normal developmental anatomy and reports of similar anomalies was made in order to elucidate the pathogenesis of the multiple anomalies seen. It was concluded that the teratogenic effect occurred after the formation of the masonephros. The teratogen may have been an infectious agent or the drug Tylan.


Medical and surgical approach to laryngeal air sacculitis in a baboon caused by Pasteurella multocida.

Air sacculitis was diagnosed in a chronically chaired baboon, Papio anubis. Pasteurella multocida was repeatedly isolated from the air sac for a period of 1 year. The condition was characterized by the continuous accumulation of either mucoserous or purulent fluid. Biopsies of the air sac taken during the course of the disease initially revealed goblet cell hyperplasia. Later a subepithalial mononuclear or polymorphonuclear infiltrate and necrosis was the predominate finding. Medical therapy was only intermittently successful and consisted of frequent drainage and antibiotics administered locally and intravenously. The condition was resolved after surgical resection of the air sac lining membrane.


Comparison of ketmine with the combination of ketamine and xylazine for effective anesthesia in the rhesus monkey (Macaca mulatta).

The addition of xylazine to ketamine hydrochloride was found to enhance analgesia, anesthesia, and muscle relaxation in rhesus monkeys. At 0.10 ml/kg body weight, this combination provided adequate anesthesia for such procedures as cisternal puncture, lumbar spinal puncture, insertion of urinary catheters, finger amputations, and tattooing. The combination of ketamine and xylazine did depress the heart rate, respiration rate, and body temperature more than the administration of ketamine alone. The period of anesthesia also was prolonged, but the monkeys regained consciousness more rapidly at the end of the anesthetic period.


Spontaneous preeclamptic toxemia of pregnancy in the patas monkey (Erythrocebus patas).

A disease characterized by edema, proteinuria, hypoproteinemia and hypertension was seen in late gestation in patas monkeys. The initial sign was edema of the perineum, ankles and lower trunk. The onset was abrupt, occurring 7 days or less prepartum. The affected animals were not depressed, and convulsions were not seen. In 6 of the 98 pregnancies during a 1-year period, symptoms of the disease were present. The highest incidence was manifested by primiparous animals with 3 of 36 pregnancies affected. Two of 38 second pregnancies and 1 of 24 third pregnancies were also affected. Five of the animals recovered spontaneously and were normal 14 days postpartum. Edema persisted for 30 days in one female. This animal continued to be hypertensive and had persistent mild proteinuria and hypoproteinemia. She was killed approximately 1 year postpartum due to severe renal disease. The spontaneous disease seen in patas monkeys resembled toxemia of pregnancy in humans more closely than the experimentally induced disease in other animals.


Therapy of filariasis in Tamarins.

A regimen of thiacetarsamide sodium (0.22 ml/kg twice daily for 2 days) plus levamisole phosphate (11 mg/kg/day for 10 days) was effective in eliminating unidentified microfilariae from the blood in seven of eight tamarins. No serious side effects resulted from the treatment. All of the animals were initially freed of circulating microfilariae after treatment, and five have remained microfilaria-negative for 1 year. Two of the tamarins died of causes unrelated to filariasis and were microfilaria-negative before death. One tamarin remained microfilaria-positive after two courses of this treatment.


A versatile primate cage for a multiple use facility.

A mobile-transport-squeeze cage for primates was constructed. The cage contained a clear plastic guillotine door, squeeze apparatus, ventilation holes and locking casters. The squeeze apparatus could be operated by one person.


Secondary thrombocytopenia following phenobarbital treatments in a rhesus monkey (Macaca mulatta).

A rare adverse reaction due to phenobarbital (10 mg/kg/day for 11 days) developed in a rhesus monkey (Macaca mulatta). Clinical signs and measured hematological parameters correlated closely with descriptions of thrombocytopenia. Following cessation of phenobarbital, the monkey recovered within 11 days. Five months after initial thrombocytopenia, the monkey was challenged again with phenobarbital (10 mg/kg/day for 11 days). Appearance and progression of clinical signs were identical to the initial crisis.


Mycobacterium scrofulaceum infection in Erythrocebus patas monkeys.

Mycobacterium scrofulaceum was cultured from two of seven tuberculin reactors in a group of 12 Erythrocebus patas monkeys. One monkey reacted atypically to 0.1 ml of 2.5 mg veterinary tuberculin after having shown no reaction to four previous tests administered at 2-week intervals. The reaction consisted of edema with no induration or erythema at 24 hours and was completely dissipated at 36 hours. Responses to additional tests using veterinary tuberculin (2.5 mg) and Mycobacterium bovis purified protein derivative (1.1 mg) ranged from negative to slightly edematous. Radiographs were suggestive of pulmonary tuberculosis. Extensive granulomas were observed in the lungs, liver and spleen at necropsy. Mycobacterium scrofulaceum was isolated from lung and liver granulomas in this animal and from lung granulomas in another. The atypical skin hypersensitivity and organism isolation from multiple organs suggested Mycobacterium scrofulaceum as the etiologic agent in these animals. Reactions of six other Erythrocebus patas to veterinary tuberculin (2.5 mg) ranged from edematous to indurated.


Fat droplet formation in rat lactating mammary gland and mammary carcinomas viewed by freeze-fracture.

The freeze-fracture morphology of the endoplasmic reticulum and Golgi apparatus membranes was analyzed in lactating rat mammary glands and in mammary carcinomas induced by 7,12-dimethylbenzanthracene or N-nitrosomethylurea. Membranes in close proximity with fat droplets present a spectrum of transformations, from the normal, wavy, particle-rich appearance of cytoplasmic membranes to rigid, particle-free bilayers. The following sequence of events is proposed for the biogenesis of fat droplets: (1) formation of particle-free areas in the endoplasmic reticulum and Golgi membranes; (2) apposition of the bilayered lipid membranes to the growing fat droplet; and (3) progressive conversion of the membrane lipids (or amphypathic lipid precursors) into triglycerides at the periphery of the fat droplet. Our results suggest that membranes are not only involved in the synthesis and secretion processes, but that some of their components are incorporated in the fat droplets and contribute to the secretory product itself.


Effects of divalent-cation chelators and chloramphenicol on the spatial relationship of the nuclear envelope to chromatin in micronuclei of Chinese hamster cells.

In the presence of the spindle poison Colcemid in the culture medium to prevent anaphase, approximately 20% of Chinese hamster metaphase cell were converted to micronucleated cells during 7 h. In the micronuclei the chromosome had become enclosed by a nuclear envelope (NE). In the light-microscope the micronuclei were of two kinds: with either visible chromatids or with decondensed chromosomes. In the electron microscope (EM) the spatial relationship of the NE to the chromatin was of two kinds only in the presence of Colcemid. In about 90% of the micronucleated cells the spatial relationship was normal, ie, the NE was immediately adjacent to the chromatin. In the remaining cells, the NE was distended so that the outer NE was separated from the inner one. In the presence of the divalent cation chelator, (ethylenedinitrilo) tetraacetic acid (EDTA) or the Ca2+-chelator [ethylenebis (oxyethylenenitrilo)] tetraacetic acid (EGTA) in addition to Colcemid, the amount of cells with micronuclei increased to 40%. The light-microscope appearance was the same as that found in the absence of the chelating agents. However, after Colcemid plus EGTA, EM revealed that only about 50% of the micronucleated cells had NE that was immediately adjacent to the chromatin and about 10% of them had distended outer NE. In the remaining 40% a third kind of spatial relationship was seen: the NE was intact but most of it was not adjacent to the chromatin. Furthermore, this type of micronucleus often contained mitochondria within the confines of NE. Thus, Ca2+ and possibly Mg2+ may regulate the rate of formation of the NE and also its ultrastructural relation to the chromatin. Mitochondrial function also appears to be involved in this relationship. In the presence of chloramphenicol (CAP), an inhibitor of mitochondrial protein synthesis, in addition to Colcemid, only about 50% of the micronucleated cells exhibited the normal relationship. The outer NE was separated from the inner NE in about 46% of the micronucleated cells and the third kind of NE-chromatin relationship was observed only in 2%. In the case of the third kind of relationship produced by CAP, inclusion of mitochondria within the micronuclei was not observed, in contrast to the finding with EGTA.


Role of physiologic autoantibody in the removal of senescent human red cells.

The mechanism by which mononuclear phagocytes distinguish mature "self" from senescent "self" was investigated. Evidence is presented indicating that human mononuclear phagocytes distinguish senescent RBC from mature RBC on the basis of selective Ig attachment to the membranes of senescent cells. This Ig, eluted from senescent human RBC, was shown to be IgG and free of other Igs by immunodiffusion, immunoelectrophoresis, and polyacrylamide gel electrophoresis. The IgG was polyclonal with respect to light chains. The eluted IgG reattaches to homologous stored RBC, but not to mature autologous or allogeneic RBC, via the Fab region. It then initiates phagocytosis of these stored RBC by mononuclear phagocytes. Evidence suggests that the IgG is directed against altered membrane receptors. Thus, this IgG may be a "physiologic" autoantibody and contribute to the maintenance of homeostasis by performing regulatory function.


[Determination of the blood group, Rh-D factor, and indirect Coombs' test using the amniotic fluid].

The number of Rh-D sensibilizations provided by pregnancy and delivery has decreased as the result of the preventive measures introduced to the combat this condition. The problem, however, still exists, and to cope with it, the determination of the blood group, Rh-D factor, and the Coombs' test using the amnionic fluid allows a timely preparation for the therapy of the newborn's hemolytic disease. The method of the neutralization technique employed by the authors has proved reliable.


Neurofibrillary pathology: current status and research perspectives.

The neurofibrils seen in the light microscope are shown, by electron microscopy, to be heterogeneous structures, formed of neurotubules and neurofilaments. A variety of pathological conditions (especially, presenile and senile dementia (are characterized by the presence of neurofibrillary tangles, formed either of paired helical filaments or of single filaments. The morphology, distribution and biochemistry of these various fibrillary structures is reviewed. Particular attention is devoted to the assembly of neurotubules, to the mechanism of action of drugs which prevent assembly, and to possible implications for the experimental induction of neurofibrillary pathology. Of central importance in the arguments is the emphasis on the normal neurofibrillary structures being single forms of pleomorphic proteins. The healthy neuron assembles these proteins into the required form as is necessary for the needs of that neuron. Interference with this process in neuronal cell biology may lead to the deposition of neurofibrillary tangles. On the basis of the morphological and biochemical evidence, several approaches to the experimental study of neurofibrillary pathology are proposed.


Influence of dietary fiber on bile acid metabolism.

Fiber, when fed to animals or man, will generally cause increased excretion of bile acids. The level of bile acid excretion appears to be a function of the structure of the fiber. Fiber binds bile acids and bile salts in vitro. The extent of binding is characteristic for each type of fiber and each substrate. Bile acid binding may be one mechanism of the physiological action of fiber.


Identification of 15-keto-9, 11-peroxidoprosta-5, 13- dienoic acid as a hematin-catalyzed decomposition product of 15-hydroperoxy-9, 11-peroxidoprosta-5, 13-dienoic acid.

A labile prostaglandin was isolated as one of the products generated from [1-14C] eicosatetraenoic acid incubated with sheep vesicular gland microsomes. The eicosatetraenoic acid metabolite amounted to ca. 16% of the total radiolabeled products. Formation of this new prostaglandin was prevented when heat-denatured microsomes were employed or when incubation mixtures were supplemented with indomethacin or phenol. However, incubation of prostaglandin G2 (PGG2) with hematin in the presence or absence of catalytically active or heat-inactivated microsomes led to production of approximately the same quantity of the new prostaglandin. These results indicated that the new prostaglandin can be formed nonenzymically. The new prostaglandin was conclusively identified by gas liquid chromatography-mass spectrometry analysis as 15-keto-9,11-peroxidoprosta-5,13-dienoic acid (15-keto-PGG2) after chemical conversion to known prostaglandins. The effects of 15-keto-PGG2 and PGG2 were similar on canine lateral saphenous vein; both promoted contraction followed by prolonged relaxation, but 15-keto-PGG2 appeared to be 1/50 as potent as PGG2.


Histidine sensitive variant of the blue-green alga Nostoc muscorum: response to corepressors of histidine biosynthesis.

A model has been proposed to account for growth inhibition by L-histidine in a variant strain of Nostoc muscorum. This strain has been characterized for its response to 3-amino-1,2,4-triazole and 1,2,4-triazole-3-alanine known to act as false core-pressors of the histidine biosynthesis genes. The histidine sensitive strain retained its sensitivity to triazole alanine while the inhibitory effects of aminotriazole were much reduced indicating a change in regulation of his genes. The probable interactions between nif and his genes in cyanobacteria (blue-green algae) have been discussed.


Transformation of Pseudomonas aeruginosa and Escherichia coli with resistance plasmid DNA: formation of smaller conjugative plasmids from RPI.

Sheared DNA from RPI, and R plasmid from a strain of Pseudomonas aeruginosa, was used to transform other strains of P. aeruginosa and Escherichia coli. From transformed cells other plasmids like RPI were isolated. These deletion plasmids were conjugally transferrable and confer resistance mainly against carbenicillin and tetracycline.


A missense mutation in the gene coding for ribosomal protein S17 (rpsQ) leading to ribosomal assembly defectivity in Escherichia coli.

The conditionally lethal mutation, 2861 mis, has been mapped inside the ribosomal protein gene cluster at 72 minutes on the Escherichia coli chromosome and was found to cotransduce at 97% with rpsE (S5). The 2861 mis mutation leads to thermosensitivity and impaired assembly in vivo of 30S ribosomal particles at 42 degrees C. The strain carrying the mutation has an altered S 17 ribosomal protein; the mutational alteration involves a replacement of serine by phenylalanine in protein S 17. Spontaneous reversion to temperature independence can restore the normal assembly in vivo of 30 S ribosomal subunits at 42 degrees C and the normal chromatographical behaviour of the S 17 ribosomal protein in vitro. We conclude therefore that the 2861 mis mutation affects the structural gene for protein S 17 (rpsQ).


Bacterial ribosomes with two ambiguity mutations: effects of translational fidelity, on the response to aminoglycosides and on the rate of protein synthesis.

A set of mutants affected in translational fidelity was constructed by transduction within an otherwise isogenic Escherichia coli B argF40 argR11 background. Alterations in ribosomal proteins S4, S5, S12 and L6 either as single mutations or in various combinations were compared for their effects on aminoglycoside phenotypes, on in vivo and in vitro misreading and on the rate of peptide bond formation. Results may be summarized as follows: (i) Strains carrying two ambiguity mutations on the ribosome without any restrictive mutation are viable. When together, they only weakly increase the level of mistranslation as judged by several in vivo and in vitro test systems. (ii) The combination of two ram mutations causes a very strong cooperative increase of streptomycin sensitivity, irrespective of whether the strains have a wild-type S12 or mutationally altered S12 proteins (of the drug-resistant or -dependent types) on their ribosomes; (iii) The S4 and S5 ram mutations do not alter the response of the ribosome to aminoglycosides of the 2-desoxystreptamine group which are structurally unrelated to streptomycin. This is interpreted in terms of an effect of these ram mutations on the streptomycin binding site but not on the site(s) of binding of the other aminoglycosides. (iv) The rate of polypeptide bond formation which was determined from the kinetics of beta-galactosidase induction is not significantly changed in strains bearing the ram and the strA (streptomycin-resistant) alleles. In contrast, the L6 and the strA (streptomycin-dependent) alleles strongly reduce the rate of polypeptide elongation which mechanistically might be connected with restriction of ambiguity (Nino, 1974) in these cases.


Genetic identification of dominant overproducing mutations: the Beadex gene.

A model system for the identification of presumptive overproducing mutations from among visible dominant mutations in D. melanogaster is described. An overproducing mutation is expected if a dominant mutation is readily reverted by gene deletion and if gene deletions suppress the expression of the original dominant mutation in flies heterozygous for the deletion. The Beadex (1:59.4) mutations are shown to satisfy these requirements, since a Bx dominant mutations is reverted by induced deletion [Df(Bx)/+) is wild type], and is also suppressed in trans by such a deletion [(Bx/Df)Bx) is wild type]. In addition, all 13 mutations recovered as Bx reversions or suppressors were associated with recessive held up (hdp) mutations allelic inter se, but not allelic to any known hdp gene. One such hdp mutations does not function as an independent dominant suppressor of Bx, is not always associated with Bx deletion, and in the latter situation is readily separable from Bx. We suggest that it functions as a Bx deletion, and may therefore represent the structural gene which is cis-regulated by the overproducing Bx mutations.


[Enzymes of intermediary metabolism in coryneform bacteria].

Enzymes of the intermediate metabolism were studied in ten strains of Corynebacterium-like organisms belonging to the genera Arthrobacter, Brevibacterium, Corynebacterium and Nocardia. All of these were found to contain enzymes of the glycolytic pathway, and nine strains among ten had dehydrogenases of the pentose phosphate shunt. The activity of enzymes of the citric acid cycle was low: alpha-ketoglutarate dehydrogenase was not found in Arthrobacter, Corynebacterium, Brevibacterium linens and Nocardia minima. Eight strains possessed the activity of the key enzyme of the gamma-aminobutyrate shunt, i.e. gamma-aminobutyrate aminotransferase. The activity of enzymes of the glyoxylate shunt was found in nine strains, and their level was rather high even during growth on glucose. Therefore, it is possible to study the taxonomic structure of this group of microorganisms by analyzing the composition and the level of enzymes involved in the intermediate metabolism. The competence of the Brevibacterium genus is corroborated by the typical species Brevibact. linens, as well as the reality of saprophytic representatives of the Corynebacterium genus, and a special taxonomic position of the group Brevibact. ammoniagenes--Brevibact. stationis.


[Conditions for the manifestation of cyanide-resistant respiration in Pseudomonas aeruginosa].

Conditions for manifestation of cyanide-resistant respiration were studied in Pseudomonas aeruginosa. Transition of the culture from the logarithmic to the stationary phase of growth, once the source of carbon (hexadecane, glucose, citrate, succinate) or nitrogen was exhausted, was accompanied with a decrease in the sensitivity of bacterial respiration to cyanide. As soon as the limiting factor was added, the culture started to grow again and its respiration became more sensitive to the inhibitor. Changes in the sensitivity of respiration to cyanide were observed when the bacterial growth was not limited with oxygen, and cyanide was not accumulated in the cultural broth. The manifestation of cyanide-resistant respiration was caused by changes in the physiological state of the bacterium induced by the cessation of growth. The culture formed phenazine pigments while growing on all of the studied substrates. However, no correlation was established between the resistance of respiration to cyanide and the concentration of the pigments in the medium. Therefore, the resistance of respiration of Ps. aeruginosa to cyanide should be attributed to changes in the electron transport chain.


[Pyruvate and phosphoenolpyruvate carboxylase in methylotrophs].

The activity of pyruvate and phosphoenolpyruvate carboxylases was determined in cell extracts of obligate and facultative methylotrophs which metabolized monocarbon reduced compounds via different pathways. Phosphoenolpyruvate carboxylase was found to be the only enzyme responsible for the high level of CO2 fixation by methylotrophs with the serine pathway (Methylosinus trichosporium, Hyphomicrobium vulgare, Pseudomonas methylica). Methylotrophs with the hexulose phosphate pathway Mehylobacter chroococcum, Methylomonas methanica, Pseudomonas oleovorans, Arthrobacter globiformis) and yeast (Candida methylica) assimilated less CO2 but contained more enzymes involved in arboxylation of phosphoenolpyruvate (phosphoenolpyruvate carboxylase, EG 4.1.1.31; phosphoenolpyruvate carboxykinase, EC 4.1.1.32) or pyruvate (pyruvate carboxylase, EC 6.4.1.1; malic-enzyme, EC 4.1.1.40). Phosphoenolpyruvate carboxytransphosphorylase (EC 4.1.1.38) was not found in any of the studied strains. The properties and the role of carboxylases in the metabolism of methylotrophs are discussed.


[Change in the constructive metabolism and ultrastructural organization of Bacillus cereus cells under the influence of a specific autoregulatory factor].

It has been found for the first time that an increase in the concentration of a specific autoregulatory factor in the medium is responsible for the hypometabolic state of vegetative cells; no principal cellular biopolymers are synthesized at this state (DNA, RNA, proteins and phospholipids), and no cellular structures are degraded. When the culture reverses to vegetative growth observed in the same medium, synthesis of the biopolymers is intensified and changes are detected in the ultrastructural organization of the cellular membranous apparatus, the cytoplasm, the nucleoide and the cell wall.


Evaluation of several enrichment procedures for the isolation of recombinant plasmid DNA.

A number of methods for the selective enrichment of recombinant plasmids were examined; these include alkaline phosphatase treatment of the restricted pBR322 vector, as well as a combination of this and S1 nuclease treatment of the ligated mixture of pBR322 and pCR1 plasmids or S. griseus DNA followed by D-cycloserine treatment to enrich for cells carrying recombinant molecules. The relative efficiencies of these methods were compared.


[Determination of the limits of the physiological action of mineral elements in hydrogen bacteria].

The growth of the hydrogen bacterium Hydrogenomonas eutropha Z-1 was studied in the conditions of continuous cultivation at different content of mineral elements in the medium. The physiological action of phosphorus, sulfur, potassium and magnesium in the bacterium was found to be displayed within a wide range of concentrations (mg/ml): P, 18-1400; S, 5.5-350; K, 4-550; Mg, 4.8-430. If the control of mineral elements was above or below these values, the specific growth rate of the cells decreased and their intracellular chemical composition changed.


[Effect of exogenous nucleodepolymerases on Bacillus subtilis multiplication].

The effect of exogenous nucleodepolymerases on cell growth was studied with Bacillus subtilis. Nucleodepolymerases of microbial and animal origin stimulated growth of the culture. The stimulating action of DNAases depended on the dose of the enzyme added to the growth medium and on the phase of the cultural growth. Acceleration of the cultural growth correlated with intensification of DNA synthesis in the bacterial cells.


[Indications and limitations of surgery of the sympathetic nervous system (author's transl)].

Two types of sympathectomy are common today, the lumbar and the cervicothoracic. It is a simple operation with extremely low mortality and morbidity although the patients are frequently of an advanced age. 8--10 days after the operation pains may occur, especially at night. The authors observed them in 3--15% of cases after lumbar sympathectomy, more rarely after cervicothoracic sympathectomy. The pains usually disappear after a few weeks or months. Sexual disturbances may occur in about 10--15% of young men. Therefore in these patients the first two lumbar ganglia should be spared. Arterial obstructions above all arteriosclerotic occlusions are the most important and most frequent indications for surgery of the sympathetic nervous system. Statistics from the Strasburg Hospital yielded a total of 56% good and very good results in 666 lumbar sympathectomies, and 31.2% successes even in Fontaine's stage IVa.


[Indications for surgical and conservative treatment of arteriosclerosis (author's transl)].

Operation is contraindicated in acute cerebral insults and neurological lesions which are already irreversible. A complete obstruction in the region where the great vessels branch off from the aorta are always surgically treated if the vessels distal to the lesion are still patent. Aneurysms in the aortoiliac region require resection and reconstruction of the vessels, stenoses and obliterating changes need reconstructive interventions. Angina mesenterica must be surgically treated if at least two intestinal arteries are damaged. Operative intervention in renal arteriosclerosis is only justified if hypertension is also present. Conservative therapy consists of prophylaxis or elimination of the risk factors, of the medical treatment of hyperlipemia and of inhibition of thrombocyte function.


[Chronic arterial occlusive disease of the lower body. Diagnostic-therapeutic, especially surgical-therapeutic aspects and postoperative care].

The treatment of chronic arterial circulatory disorders of the lower extremities depends on the one hand on the presence of a type of occlusive process which can be confirmed angiologically and on the other hand by the degree of severity and thirdly on the availability of operative and conservative methods of treatment. According to the stage of ischemia (Stage III and IV) possibly only surgical measures offer the possibility of preventing amputation. The nearer the stenotic process to the aorta, the greater the possibility of success of a surgical intervention if the general condition does not represent a contraindication to surgery. The questions of indications for operation and the problems of the most suitable procedure (endarterectomy, bypass, prostheses, Dotter's transluminal dilatation) are discussed on the basis of many years' experience.


[The weather and skiing accidents (author's transl)].

During the winter of 1974/75, 528 skiing accidents in the Davos area were investigated in connection the weather influences.  It was found that during high pressure conditions the accident rate increased and was very low under low pressure conditions. This result is explained by high pressure conditions often inducing the skier to more daring modes of skiing. Consequently the fine weather influences the accident risk to skiers through mental stimulation. The low accident rate in low pressure conditions can be explained insofar as in bad weather only advanced skier dare to go on the ski-run and the danger-prone beginners stay at home. In addition most skiers are conscious of the risk in unpleasant weather and ski correspondingly carefully. The accident rate decreased from the beginning to the end of the 1974/75 season.


[Human experimentation and criteria for obligatory medical care].

Human experiment and therapeutic trials are regulated by the drug law and the jurisdiction of the supreme court. The qualification of the trial leader and the personification of his responsibility with reference to indication, performance and evaluation of the trial are just as much criteria of his obligations as the protection--derived from medical ethical motives--of the patient or subject. It would certainly be welcomed if the legal regulations affecting the testing of drugs could simply be transferred to clinical research in humans and dispense with the all too closely meshed regimentation.


[Acute and subacute acral ischemia syndromes (author's transl)].

Acute and subacute acral ischemia syndromes must be carefully distinguished from chronic intermittent acral disturbances of circulation because of the differences in the genesis, in the clinical picture and in the treatment. Vasoconstriction caused by cold or emotion and which disappears on warming is the principal feature of the chronic intermittent syndromes. Prestasis and stasis are the basis of the ischemia of acute and subacute syndromes, which cannot be relieved by warmth. Vasodilation measures have no effect, whereas the circulation can be restored by the improvement of the fluidity and the flow conditions of the blood.


[Clofibrate banned - what now? (author's transl)].

Of the drugs which reduce triglycerides and cholesterol we recommend Cedur, Lipanthyl and Ronicol. Of the drugs which predominantly lower cholesterol levels, Skleronorm has proved useful for a long time in the treatment of HLP Types IIa and IIb. Quantalan or Colestid should be used for the severe forms of hypercholesterolemia in children and adults. beta-sitosterin is reserved for the milder types of hypercholesterolemia. The clofibric acid preparations commercially available should not be prescribed for the time being until the patients are reassured on the clofibrate problem. We do not advise essential phospholipids.


[Reintervention after choledocho-duodenostomy].

Shrinkage of the anastomosis and blind loop syndrome with impacted stones or sludge in the retroduodenal common bile duct caused by papillary stenosis are the main reasons for an ineffective choledochoduodenostomy. The clinical picture is that of an ascending cholangitis. 30 choledochoduodenostomy repairs were performed in our hospital. The operative treatment is described in detail. In a follow-up of 30 patients there was only one case with a persisting chronic cholangitis.


[Endoscopic papillotomy (author's transl)].

Endoscopic papillotomy is a method of incising the papillary spincters without opening the abdominal wall or the duodenum. It is successful in over 95% of cases. In over 80% of cases passage of choledochus concrement occurs, about half of these stones being excreted spontaneously and the rest having to be extracted actively with a small Domia basket. For large concrements which cannot be removed endoscopically even after wide papillotomy incision, there is the electrohydraulic lithotrite which crushes them so that they can be passed spontaneously or be actively extracted. Dissolution by a substance instilled through a catheter passed through the papilla into the common bile duct is still in the experimental stage. Altogether for this reason endoscopic papillotomy and removal of stones is an advance for the patient at risk, as it involves a lower lethality than the corresponding surgical method.


[Vascular replacement with plastics (author's transl)].

The plastic substitution of the aorta and its large branches may be considered largely solved today. For this purpose preference is given to highly porous, thin-walled double velour prostheses. The search for a biocompatible plastic substitute for small caliber arteries and the large veins of the body (portal vein, vena cava, iliac veins) is proceeding in two directions at the present time: on the one hand towards optimized bioprostheses and on the other hand towards plastics which apply the principle of microporosity or impermeability with the creation of antithrombogenic inner surfaces. In this respect expanded polytetrafluoroethylene and coating with carbon are very promising.


[Carcinoid of the digestive tract. Diagnostic possibilities (author's transl)].

Special features which enable preoperative differential diagnosis are dealt with in detail with reference to 44 patient with carcinoid of the digestive tract. Carcinoid of the appendix becomes noticable early with signs of acute or chronic appendicitis and in 94% of cases is operated on in good time. Angiography of the superior mesenteric artery shows a characteristic stellate figure in the mesenterium in carcinoid of the small intestine. In contrast to the primary tumor, liver metastases show intense vascularization in the angiogram. A rise in urinary excretion of 5-hydroxyindole acetic acid is pathognomonic for carcinoid, its determination permits the checking of operative radicality and shows the appearance of metastases early.


[Qualitative CSF cell diagnosis. Methods and conclusiveness (author's transl)].

In a review, the methods and value of CSF cytology as routine diagnostic investigation should be described summarily. Among the various methods of cell concentration, the sedimentation method permits the best cytological differentiation of the cells of the cerebrospinal fluid. Both neuro-immunological processes and unspecific irritation processes (e. g. subarachnoid hemorrhage, traumata), brain tumors and metastases can be differentiated. For prognostic and therapeutic questions, cytology of the CSF is sometimes the method of choice, as for instance in questions of CNS involvement in hemoblastoses. The spectrum of diagnostic possibilities recommends the cytology of CSF as a routine method in all neurological, internal medical and pediatric clinics.


[Benefits of spa treatment for gynecological tumor patients: (author's transl)].

Problems of psychosocial rehabilitation were studied in 308 women following treatment for genital and mammary carcinomata. One third felt more susceptible to disease. A quarter with earlier spa treatment showed greater susceptibility to disease twice as often as those without spa treatment. Women with higher education admitted to spa treatment twice as often as those with less education. Women who had had spa treatment admitted to a feeling of impaired self-evaluation twice as often as those without spa treatment. The patients assessed the benefits of spa treatment without reference to age, level of education and personality test. Women with sexual medical problems expected particularly great benefits from spa treatments.


Mutagenesis of free and intracellular cyanophage AS-1 by ultraviolet, N-methanyl-N'-nitro-N-nitrosoguanidine and acriflavine.

Mutagenic actions of ultraviolet irradiation (UV), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and acriflavine (photodynamic) were tested in free and intracellular phage AS-1 infecting Anacystis nidulans IU625. Spontaneous and induced mutations with particular reference to host range (h) and minute plaque formation (m) were investigated. The spontaneous mutation frequencies varied from 10(-9) to 10(-8) and from 2 X 10(-5) to 2 X 10(-4) for h and m mutants respectively. UV was efficient in inducing h and m markers in free phage particles as well as intracellular phage; MNNG induced both markers in intracellular phage only, and acriflavine induced m mutants only in free as well as in infecting phages. UV-induced mutations in free phage were photo-reactivable by visible light. With all the mutagens used, maximal induction of both markers was observed with treatment of 2-h complexes.


X-ray quality and the induction of meiotic recombination in Drosophila melanogaster males.

This paper reports a set of experiments designed to determine whether the radiation-quality effect, reported for the induction of somatic recombination, could be also demonstrated for meiotic recombination. Males heterozygous for markers on the 2nd chromosome were given an exposure of 600 R with either 55 kV or 100 kV X-irradiation. Treated spermatocytes were sampled by irradiating young pupae and then taking the first day sperm from the emergent adult males. When 2-h old pupae were irradiated there were significantly fewer centric and more non-centric recombinants, than when 4--6 h old pupae were irradiated. No radiation-quality effect was found.


Effects of caffeine on sister-chromatid exchanges (SCE) in vivo.

Chinese hamsters were twice treated with caffeine via stomach tube. The single doses were either 20, 100, 200 or 400 mg per kg body weight. A dose-dependent increase was observed in the frequencies of SCE induced in vivo in bone-marrow cells. Two intraperitoneal injections of the chemical mutagens, cyclophosphamide or benzo[a]pyrene, led to a pronounced increase of the frequency of SCE. Simultaneous applications of the chemical mutagens and caffeine decreased the rate of SCE. The effect of caffeine per se to induce SCE, and the mechanisms by which caffeine reduces the level of SCE induced by chemical mutagens are discussed.


Rhesus monkey (Macaca mulatta) model in genetic toxicology mitomycin C clastogenicity in germ cells.

The value of rhesus monkeys (Macaca mulatta) as a genetic toxicology model is limited by their scarcity, expense, and impracticality of progeny testing. However, in some special circumstances, e.g., accidental exposure of humans to potential mutagens, rhesus monkeys or other primates may provide a superior animal model to help to cope with a difficult public health situation. Using the testis as a target organ we found that when primary spermatocytes were treated in pre-leptotene stage with 1 mg mitomycin C/kg body weight, the frequency of exchanges, fragments, sex-chromosome and autosomal univalents increased significantly at diakinesis-metaphase I. This response was absent in cells treated during diplotene, late pachytene or during spermatogonial stages. We suggested that animals should be evaluated not only for genetic toxicology parameters, but also toxicologically, histologically, behaviorally, for carcinogenesis and seminal cytology. Whenever possible, the animals should be recycled.


A preliminary assessment of possible mutagenicity of betel nut and ingredients of the betel quid when administered alone or in combinations to larvae of Drosophila melanogaster.

The "carcinogenic" betel nut and constituents of betel quid were tested for possible mutagenicity in Drosophila. The test compounds were administered either alone or in combinations by larval feeding. The data on sex-chromosome loss, sex-linked recessive lethals and autosomal translocations suggest lack of mutagenicity.


Cyclopiazonic acid production by aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus.

Twenty-eight of 54 isolates of Aspergillus flavus grown on autoclaved agricultural commodities such as wheat, rice and corn were found to produce the mycotoxin cyclopiazonic acid. Eighteen of the A. flavus isolates produced aflatoxin, and fourteen isolates produced both cyclopiazonic acid and aflatoxin. A preliminary screening of some aflatoxin-contaminated corn samples revealed for the first time the natural occurrence of cyclopiazonic acid in agricultural commodities.


Gentic engineering for practical application.

Genetic engineering has ushered in a new era in biology. Although many problems are still to be solved, there are examples that point to a possible later application for the benefit of mankind: Bacteria can be manipulated to degrade crude-oil spillages, to produce human insulin and to bind nitrogen from the air. If all the bacteria that are indigenous to agricultural soils could be made to bind nitrogen, an increase in soil fertility might well result.


Vasopressin: deficiency, excess and the syndrome of inappropriate antiduretic hormone secretion.

The hypothalamic-neurohypophyseal system functions to maintain plasma osmolality within narrow limits. It also is an important mechanism in maintaining normal body fluid volume. The system exerts its influence via release or inhibition of vasopressin (antidiuretic hormone, ADH) which acts on the kidney to decrease water excretion. Deficiency of ADH is usually due to hypothalamic-neurohypophyseal lesions (central diabetes insipidus) or insensitivity of the kidney to ADH (nephrogenic diabetes insipidus). These patients, if untreated, have the predictable result of dehydration, hyperosmolality, hypovolemia, and eventual death in severe cases. On the other hand, ADH excess of the syndrome of inappropriate ADH secretion due to a variety of causes promotes water retention, hypoosmolality and hyponatremia which, if untreated, may progress to convulsions, coma, and death. It is obviously important to diagnose accurately these pathologic states of hydration. Not only is initiation of treatment in general dependent upon recognition of the disease, but each type of pathologic hydration state has specific treatment which rewards both patient and physician with effective correction of the problem.


Ossification of the posterior longitudinal spinal ligament in association with anterior longitudinal ligament ankylosing hyperostosis: case report.

A case of ossification of the posterior spinal longitudinal ligament in association with anterior ankylosing hyperostosis is presented, with a review of the relevant literature. Improvement followed laminectomy. Evaluation of this entity by computerized tomography is demonstrated.


Operant control of single neurons in monkey motor cortex.

This article reviews three points. Monkeys may be trained by operant conditioning to control the firing rate and pattern of single neurons in the precentral cortex. Recent data provide an explanation of how this control is mediated and an accounting of various factors that influence it. Using this technique to study cortical physiology, researchers have generated new insights into the pathophysiology and clinical effects of epilepsy.


Videotaping epileptic attacks during stereoelectroencephalography.

Relating the onset of clinical attacks as recorded on a videotape to surface and depth electrographic events improves our ability to define the local or diffuse origin of seizures. In two patients with complex partial seizures, all 14 attacks appeared 3 to 6 seconds after focal discharges began in the amygdala or hippocampus. This meant that the spread of focal electroencephalographic (EEG) paroxysms caused the eventual clinical seizure. In two other patients with 392 generalized seizures and secondary bilateral synchronous paroxysms, a significant number of clinical attacks preceded the first depth or surface electrographic event. This suggested that the attacks originated from brain regions remote from the recording electrodes.


Paroxysmal genital pain: an unusual manifestation of epilepsy.

A male patient who is now 15 years old has experienced a seizure disorder since age 9 years. The seizures were expressed as episodes of excruciating pain localized to the genital region. Appropriate anticonvulsant medication has controlled both pain and seizures.


Aphasia: the sole manifestation of focal status epilepticus.

Aphasia was the sole manifestation of focal status epilepticus in a man with an old left frontal contusion. The diagnosis was made by electroencephalogram (EEG), and the attack was terminated by anticonvulsant medication.


[Further observations on the HBeAg-HBeAb system in the course of hepatitis and in HBsAg carriers].

The HBeAg-HBeAb system has been studied by means of the microimmunodiffusion technique on agar in patients suffering from acute hepatitis at various stages of the disease, in patients with chronic liver diseases and in asymptomatic carriers of HBsAg. The results correlate the presence of HBeAg with the state of the disease (initial phase of acute or chronic hepatitis) and the presence of HBeAb with clinical cure of an acute hepatitis or with the condition of healthy carrier. It is a personal impression also that an HBsAg + hepatitis can be cured more rapidly the better the immune response expressed by the appearance of HBeAb, and that a lacking or deficient immune response to HBeAg may underlie the chronic course of the disease. Emphasis is also laid on the early disappearance of HBeAb in patients with acute hepatitis, this being matched by its persistence in asymptomatic carriers of HBsAg. In this regard, the first results reported here on the identification of the immune globulin class to which the HBeAb belongs would appear to confirm the hypothesis that the anti-e response is of IgM type in acute hepatitis and of IgG type in HBsAg carriers.


Effects of danazol on gonadotropin levels in castrated rhesus monkeys.

Danazol is widely used in the management of endometriosis and mammary dysplasia. However, its mechanism of action is still obscure because of the few studies done and the controversial results obtained. Antigonadotropic activity has been postulated by some investigators, whereas others have observed no effect on the gonads. In the present study, three castrated female rhesus monkeys received 400 mg of danazol daily, by gavage for 19 days, while 2 controls received 400 mg of lactose daily. Blood samples were drawn every other day from 2 weeks prior to 3 weeks after the administration of the drug. Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased rapidly and then were maintained until danazol was discontinued. Prompt return to pretreatment levels occurred 1-2 days after the discontinuation of therapy. Prolactin levels were normal during therapy. Luteinizing hormone releasing factor (LH-RF), 100 microgram, administered intravenously during danazol therapy, caused a normal, prompt release of gonadotropins, demonstrating an intact pituitary response. The authors conclude that 1) danazol is a potent antigonadotropic agent, 2) its effect is abolished promptly after discontinuation, and 3) its probable biological action is at the hypothalamic level.


Chronic occlusion of the monkey fallopian tube with silicone polymer.

Investigators have previously reported good retention, antifertility efficacy, and oviduct polymer compatibility in rabbit oviducts in studies of both short-term and chronic occlusion with high viscosity silicone polymer. The present study attempts to determine the chronic effects of the silicone polymer installed into the oviducts of 10 rhesus monkeys. Unlike former studies with rabbits, the polymer was installed into the fimbrial end of the monkey's oviducts because of the complexity of the uterotubal junction's musculature. Studies with light and scanning electron microscopy were conducted to examine tissue reaction to plug retention. Despite our major modification of the installation technique, we obtained a retention rate of 50%. In addition, there was no evidence of inflammation or tissue distortion, and the polymer plugs were not affected by menstrual bleeding.


Organ culture model for the study of HVH-II infections in carcinoma of the cervix.

An experimental model is described whereby human and monkey cervical tissues may be maintained as organ cultures for 21 and 40 days, respectively. Inclusion of sodium carboxymethyl cellulose in the culture medium prolongs the survival time of tissues considerably. The sequential cytologic changes associated with herpesvirus hominis type II (HVH-II) infection are reported. These changes are considered in relation to the possible causal role of HVH-II infection in cervical carcinogenesis.


[Visual future of prematures].

The retinal periphery of 60 premature children now between 5 and 8 years of age and with a weight at birth equal or less than 1,500 g has been investigated. In 20% of these children, pigmentary modifications were noted which were often associated with chorioretinal atrophy. Polymorphic vascular abnormalities were seen in 14% of the cases, i.e. sinuous vessels of irregular caliber or neovascularization. Abnormalities of the vitreous body were also noted in 12% of the patients with glial bags on the periphery and sometimes potentially dangerous tractions folds (4%). All these abnormalities could cause complications such as retinal tear, retinoschisis or retinal detachment. Even if these signs are discrete, they can later on be the source of complications. Refraction studies revealed 30% of myopic children. The most important group had myopias equal or higher than 8 d. The characteristics of the myopia of premature children are its constancy (all premature children are myopic at birth); its importance (it depends on birth weight and on the severity of the retinopathy), and its evolution (the myopia of premature children does not evolve or evolves very slightly).


Albinism.

There are seven forms of oculo-cutaneous albinism, which are all autosomal recessive: three are tyrosinase-negative (complete oculo-cutaneous albinism, Amish albinism, Hermansky-Pudlak syndrome) and four are tyrosinase-positive (incomplete oculo-cutaneous albinism, Chediak-Higashi syndrome, Cross syndrome, Bergsma's albinism). There are three forms of sex-linked albinism: ocular albinism, which is intermediary sex-linked, François-De Rouck syndrome and Ziprkowski syndrome, which show a generalized albinism and are recessive sex-linked. There are two principal forms of cutaneous albinism, one without deafness and the other with deafness (Waardenburg-Klein syndrome).


Lead poisoning. A comprehensive review and report of a case.

Lead, a ubiquitous heavy metal which has realized increased use, can cause poisoning by environmental contamination in either its organic or its inorganic form. Lead poisoning can be either acute or chronic, with the latter being the more common. The clinical signs and symptoms of lead poisoning are nonspecific, resulting in a difficult diagnostic problem, especially when it is not industrially related. On occasions, the dentist or oral surgeon may be the first to see an afflicted patient because of oral manifestations.


Transplantation of hamster buccal pouch carcinoma to neonatal hamsters.

Epidermoid carcinomas of oral mucosa were induced with DMBA in the buccal pouches of hamsters. The well-differentiated primary tumors were allografted into the peritoneal cavities of neonatal hamsters that had been treated with antilymphocyte serum. Solid tumors grew rapidly in the peritoneum and were harvested 6 to 31 days postimplantation. Gross and histopathologic specimens revealed infiltrative masses of tumor that had become more anaplastic than the original tumor. This in vivo model has considerable potential as a means of studying the immunology of oral cancers during tumor progression.


Response of periapical pathosis to endodontic treatment in monkeys.

Response of induced periapical lesions in monkeys to a conventional endodontic technique was investigated at varying periods ranging from 15 to 365 days after treatment. The findings indicate that response to treatment is influenced by the extent of the root canal filling, the time lapse between treatment and death, and the presence or absence of bacteria in the apical portion of the canal.


[New species of microsporidians (Microsporidia, Nosematidae) from horsefly larvae in the Ukraine].

A new species of microsporidians, Stempellia lairdi sp. n., was found in larvae of Tabanus autumnalis L. from Ukraine. It affects the muscular tissue and haemolymph of horse fly larvae. Spores of the species are oval, egg-shaped, 1.8--7.6 x 1.2--3.8 mu in size. The species is pathogenic and causes the mortality of infected larvae.


Liver disease in infants receiving total parenteral nutrition.

Progressive cholestasis and abnormal elevations of liver enzymes occurred in one third of 92, mostly preterm, newborn infants who received total parenteral nutrition (TPN) with protein hydrolysates, synthetic L-amino acids, and intravenous fat emulsion. The synthetic amino acid plus intravenous fat emulsion was not superior to the protein hydrolysate in preventing liver disease. The liver function returned to normal after discontinuation of TPN, which suggests a causal relationship. Hepatic microscopy was abnormal in 12 of 14 infants examined. The main features were progressive cholestasis and portal tract fibrosis and infiltration, which led to liver failure and death in two infants. In our experience, liver disease is the major metabolic complication of TPN in infants.


[Infection of blackflies (Simuliidae) with microsporidians in the Ob and Irtysh reservoirs].

Of 6 species of black flies from 6 water bodies microsporidians P. simulii, P. debaisieuxi and Th. varians are reported only in four species, B. maculata, Sch. pusilla, S. morsitans and S. argyreatum. Peculiarities in the infection of black flies larvae with microsporidians in various types of water bodies within a season were established. Under experimental conditions P. simulii and P. debaisieuxi cause mortality of larvae (68 to 87%) and decrease in the emergence of imago (5 to 19.6%).


[Effect of microsporidiosis on the fertility of Aedes caspius caspius (Culicidae) mosquitoes].

Effect of microsporidiosis on the fecundity of hosts A. c. caspius was studied. The calculation of eggs in hatches has shown that females developing from infected eggs lay 2--3 times lesser eggs than non-infected ones. Besides, the number of females laying eggs decreases considerably. Despite the females of mosquitoes suck blood before each egglaying the disease, which proceeds at their larval stage, affects greatly their fecundity. Additional feeding of females cannot compensate completely the disturbances caused by microsporidiosis.


[New species of parasitic infusoria of the family Urceolariidae].

Three new species of Ciliata of the family Urceolariidae were found as follows: Paratrichodina voikarensis sp. n. on the gills of Coregonus nasus and C. peled; P. uralensis sp. n. on the gills of the sterlet and Trichodina percae sp. n. in the nasal cavities of the perch. Figures and descriptions of the new species are given.


Neonatal hypothyroidism detected by the Northwest Regional Screening Program.

The Northwest Regional Screening Program to detect congenital hypothyroidism in infants born in Oregon, Montana, Alaska, and Idaho (combined birthrate of 69,000/ yr) was added to our ongoing screening program in 1975. The program utilizes dried blood filter paper specimens collected routinely in the first few days of life in all four states and again at about 6 weeks of age in Oregon only. The screening test consist of an initial thyroxine (T4) measurement; a thyroid-stimulating hormore (TSH) determination is performed on those specimens with T4 concentrations in the lowest 3% group. Serum samples obtained by venipuncture are requested for confirmation of the diagnosis. In the first two years of the program, 25 infants with primary hypothyroidism were detected amont 110,667 infants screened, a frequency of 1:4,430. Fourteen cases of thyroxine-binding globulin deficiency were also detected, a frequency of 1:7,900. Using the T4 followed by TSH testing approach, the frequency of request for repeat specimens was 0.4% in Oregon and 0.05% in the other states. The cost per specimen was $1.96. The majority of infants lacked clinical signs or symptoms of hypothyroidism; only one infant was clinically suspected of having hypothyroidism prior to detection. The most common neonatal symptoms were constipation, lethargy, and prolonged jaundice, while the most common physical signs were hypotonia, umbilical hernia, and large fontanels. Thyroid scans showed the most common etiology to be thyroid aplasia, followed by an ectopic gland, hypoplasia, and goiter. Serum T4 concentrations were lowest in those infants with aplasia, intermediate in infants with an ectopic gland or hypoplasia, and normal in the infant with the goiter. Neonatal hypothyroidism varies in degree and has several different causes; the capacity to secrete thyroid hormone, the duration before hypothyroidism becomes clinically manifest, and possibly the eventual prognosis for intellectual function depend on the nature of the underlying cause. While the mean age at treatment was 59 days, the goal of diagnosing congenital hypothyroidism and treating affected infants by 1 month of age seems realistic.


Acquisition and discrimination of appetitively and aversively conditioned heart rate responses in rhesus monkeys.

This report describes the acquisition of a conditional heart rate response to both classical aversive and appetitive conditioning in eight rhesus monkeys (Macaca mulatta). The behavioral paradigm consisted of two discrete one minute tones followed by the corresponding unconditional stimuli, i.e., electric shock or Purina monkey chow. A third tone followed by neither food nor shock served as a discriminative stimulus (DS). The conditional heart rate responses developed in two phases. The first phase was characterized by similar responses to both conditional stimuli and the DS. Control heart rate rose during this period. During the second phase, control heart rate decreased (five animals), the DS response disappeared, and different conditional heart rate patterns to food and shock emerged. The existence of distinct conditional response patterns indicates probable differences in the autonomic nervous regulation of the heart during aversive and appetitive conditioning.


Neonatal diagnosis of familial dysautonomia.

The serious prognostic implications of familial dysautonomia (FD) for the affected individual and his family make early definitive diagnosis mandatory. Familial dysautonomia has rarely been diagnosed in the neonatal period in hitherto unaffected families. We describe here three such newborn patients to reinforce the limited data available on this subject. In spite of the variability of expression and the incompleteness of the manifestations of FD in the neonatal period, as well as the presence of a number of "dysautonomic" features in normal newborns, we believe that it is possible to establish a diagnosis of FD neonatally. We pay particular note to the altered state of consciousness and behavior in neonatal FD, the unusual posture and limb movements, and the swallowing disorder with tendency to neonatal aspiration. In addition, the incidental finding of bile pigment in the amniotic fluid of an affected fetus without hemolytic disease may hint at a possible approach to fetal diagnosis of this condition.


Intravenous alimentation and insensible water loss in low-birth-weight infants.

Insensible water loss (IWL) was measured in six premature infants, between 4 and 21 days of age, by continuous weight monitoring on an electronic balance inside an incubator. Multiple measurements of IWL were made during the sequential infusion of 10% dextrose in 0.225% NaCl, 10% dextrose-amino acid solution, or 10% dextrose-amino acid and a commercial intravenous fat emulsion. Each solution was administered for three hours by constant infusion through a scalp vein needle. The order of the infusion was random and a 30- to 60-minute infusion with 5% dextrose water was given between each solution. During the infusion of 10% dextrose in 0.225% NaCl and 10% dextrose + amino acid solution, IWL was 1.0 +/- 0.8 gm/kg/hr and 1.1 +/- 0.8 gm/kg/hr, respectively. In contrast, IWL increased significantly to 1.6 +/- 0.7 gm/kg/hr when additional calories were given using the 10% dextrose-amino acid with the intravenous fat emulsion (P less than .005). There was a positive correlation between calorie intake and IWL. These data suggest that parenteral nutrition solutions with intravenous fat emulsion are rapidly metabolized and the increase in IWL is probably secondary to an increase in thermogenesis.


Anemia as a criterion for evaluation of a Special Supplemental Food Program for Women, Infants, and Children.

The background and rationale of the Special Supplemental Food Program for Women, Infants, and Children (WIC) are reviewed. Problems concerning the implementation of the program and the need for evaluation are discussed. The authors selected anemia as a WIC program criterion to evaluate the effectiveness of the program. The reasons for this selection are discussed. The study involves the evaluation of 37 of 311 infants who were enrolled in the WIC program of a local health department. Hemoglobin values were observed at certification and recertification and the expected change vs the observed change in hemoglobin during the six-month period was calculated. In addition to observing change in hemoglobin values, a cost analysis was done. Results showed 27 out of 37 infants had a positive increase in hemoglobin levels. Eight of the 37 infants had a negative hemoglobin level, whereas two of the 37 had a zero change. It is concluded that anemia as a criterion for the WIC program is cost effective if certain considerations and modifications in the anemia criteria are made. It is also pointed out that paired hemoglobin determinations at two separate points and time is the best assessment for changes in hemoglobin levels.


Antibody to B. subtilis DNA polymerase III: use in enzyme purification and examination of homology among replication-specific DNA polymerases.

Bacillus subtilis DNA polymerase III (pol III), an arylhydrazinopyrimidine-sensitive, replication-specific enzyme, was used to generate a non-precipitating rabbit antibody which specifically inhibited pol III activity in vitro. The antibody was used to examine structural relationships among several DNA polymerases, and it was linked covalently to agarose; the antibody:agarose was employed to develop a rapid, selective method of purification of catalytically active B. subtilis pol III.


Partial mapping of methylated sequences in Xenopus laevis ribosomal RNA by preparative hybridization to cloned fragments of ribosomal DNA.

Xenopus laevis rRNA was hybridised to either of two cloned fragments of ribosomal DNA. One fragment, designated X1r11, contains a short region of the 18 S rRNA gene and most of the 28 S rRNA gene. The other fragment, X1r14, contains a short region of the 28 S gene and most of the 18 S gene. After hybridization the non-complementary rRNA was removed by digestion with T1 RNase and the hybridized RNA was then eluted and examined by fingerprinting analysis. The 3' terminal sequence and the dimethyl-A-containing sequence of 18 S rRNA both hybridized to X1r11 rDNA, in agreement with the known direction of transcription of rDNA. The distribution of other methylated oligonucleotides between the various fingerprints permitted assigment of nearly all of the methylated sequences in 18 S and 28 s rRNA to either the short 3' region or the long 5' region of the respective molecules.


Effect of chlorinated hydrocarbons on reproductive performance of adult White Leghorn male chickens.

Two experiments of 20 and 40 weeks duration were conducted to determine the effects of feeding dieldrin or PCB (Aroclor 1254) on the reproductive performance of adult White Leghorn males. Dieldrin at the levels used (0, 25, and 50 ppm) produced no significant changes in semen volume, semen concentration, fertility, and hatchability of fertile eggs. Mortality increased with increased levels of dieldrin and appeared related to duration of exposure to the pesticide. A significant reduction (P less than .05) in feed consumption was observed at the 25 ppm level. No significant differences in body weights were observed except shortly before death when marked reductions in both feed consumption and body weight were noted. PCB at the levels used (0, 10, 20, and 40 ppm) produced no differences in fertiluty, hatchability of fertile eggs, body weights, feed consumption, or mortality. However, over a period of 40 weeks, PCB significantly (P less than .05) reduced semen volume, semen concentrations, and testes weights,


Preparative cell electrophoresis with D2O as a stabilizing agent.

The method of ascending preparative cell electrophoresis in a nonstabilized vertical column can be greatly improved by layering the cells on a starting cushion of buffer prepared in D2O and by stabilizing the liquid column above it with a D2O gradient. D2O/H2O mixtures have no apparent biochemical effects on the cells, and their physiochemical effects are short-lived and reversible. It was possible, by this method, to separate a mixture of glutaraldehyde-fixed erythrocytes of three species (rabbit, horse and chicken) into three distinct zones after 15 minutes of electrophoresis. It was also possible to obtain an enriched human lymphocyte fraction containing 96% T-cells, after 1 hour of electrophoresis.


Isolation and characterization of purine-nucleoside phosphorylase-deficient T-lymphoma cells and secondary mutants with altered ribonucleotide reductase: genetic model for immunodeficiency disease.

The inherited deficiency of purine-nucleoside phosphorylase (PNPase; purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) in humans is associated with a severe deficiency of the T lymphocytes of the immune system. Because of the unsatisfactory nature of previously described model systems, we have selected, cloned, and characterized a mutant mouse T cell lymphoma (S49) completely deficient in PNPase. Of the four substrates of PNPase, only deoxyguanosine at low concentrations is toxic to the PNPase-deficient (NSU-1) cells. In order to delineate the biochemical processes necessary for the sensitivity of the NSU-1 cells to deoxyguanosine, we have isolated a series of secondary mutants resistant to deoxyguanosine from the PNPase-deficient line. One of these mutants is defective in its ability to transport deoxyguanosine into the cell. A second type of mutant cannot phosphorylate the deoxyguanosine and is totally deficient in deoxycytidine kinase activity. A third type of mutant (NSU-1-dGuo-L) can both transport and phosphorylate deoxyguanosine and accumulates dGTP. However, unlike its parent, NSU-1-dGuo-L does not become depleted of dCTP and TTP when exposed to exogenous deoxyguanosine. This observation is accounted for by the fact that the reduction of CDP to dCDP by the ribonucleotide reductase (ribonucleoside-diphosphate reductase, 2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1) of NSU-1-dGuo-L cells is not normally sensitive to feedback inhibition by dGTP.Thus, in order to exert its toxicity deoxyguanosine must be transported into the cell, be phosphorylated by deoxycytidine kinase, and be accumulated as dGTP. By inhibiting ribonucleotide reductase, dGTP depletes the cell of dCTP and to some extent TTP, thus preventing the synthesis of DNA, a process necessary for any proliferation-dependent function of T cells.


Escherichia coli adenylate cyclase complex: regulation by the proton electrochemical gradient.

Sugars such as glucose are transported into Escherichia coli by a coupled phosphorylation mechanism (the phosphoenolpyruvate:sugar phosphotransferase system, PTS). Transport of sugars through the PTS results in inhibition of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity by a mechanism involving a change in the state of phosphorylation of PTS proteins. Other sugars (e.g., lactose) are transported without modification by a mechanism involving proton cotransport, which requires a proton motive force across the cell membrane. We show here that uptake of sugars through the lactose transport system results in inhibition of adenylate cyclase activity if the proton symport mechanism is also active. The protonophore carbonyl cyanide m-chlorophenylhydrazone also inhibits adenylate cyclase activity. These data suggest that the steady-state electrochemical proton gradient regulates the activity of adenylate cyclase. We propose that sugar-dependent inhibition of adenylate cyclase activity may occur by either of two mechanisms. Sugars transported by the PTS inhibited adenylate cyclase activity by dephosphorylation of a regulatory protein, while sugars transported by the proton motive force system inhibit adenylate cyclase activity as a result of collapse of the proton electrochemical gradient.


3'-Terminal nucleotide sequence of alfalfa mosaic virus RNA 4.

The sequence of the 3'-terminal 91 nucleotides of alfalfa mosaic virus RNA 4, the messenger for the viral coat protein, has been elucidated. A fragment containing the 3' terminus of the RNA was obtained by mild digestion with RNase T1. The primary structure of the fragment was deduced by labeling it in vitro at its 5' terminus and application of RNA sequencing techniques. The sequence is completely extracistronic and is believed to contain the binding sites for the viral coat protein and replicase.


Genetic control of chromosome breakage and rejoining in Drosophila melanogaster: spontaneous chromosome aberrations in X-linked mutants defective in DNA metabolism.

Eight X-linked recombination-defective meiotic mutants (representing five loci) and 12 X-linked mutagen-sensitive mutants (representing seven loci) of Drosophila melanogaster have been examined cytologically in neuroblast metaphases for their effects on the frequencies and types of spontaneous chromosome aberrations. Twelve mutants, representing five loci, significantly increase the frequency of chromosomal aberrations. The mutants at these five loci, however, differ markedly both in the types of aberrations produced and the localization of their effects along the chromosome. According to these criteria, the mutants can be assigned to four groups: (i) mutants producing almost exclusively chromatid breaks in both euchromatin and heterochromatin; (ii) mutants producing chromatid and isochromatid breaks in both euchromatin and heterochromatin; (iii) mutants producing chromatid mutants producing chromatid and isochromatid breaks clustered in the heterochromatin.


Myeloma proteins from NZB and BALB/c mice: structural and functional differences.

Structural and functional analyses of myeloma immunoglobulins from inbred BALB/c mice and humans have provided important insights into the structure of the antibody molecule and the expression and evolution of antibody genes. One important question concerning these analyses is whether the myeloma process selects, in a nonrandom manner, the lymphocytes to be transformed. The availability of myeloma tumors in a second inbred strain of mouse, NZB, permits us to approach this question. In this respect. the NH2-terminal amino acid sequences of 27 kappa light chains as well as data relating to the antigen-binding properties and immunoglobulin class distribution of NZB myeloma proteins are presented and compared with similar data from the BALB/c mouse. These studies suggest that the myeloma proteins from the BALB/c and NZB mice constitute two populations of immunoglobulins with distinct functional and structural properties. The implication of this observation are discussed.


Target-effector interaction in the natural killer cell system: isolation of target structures.

A sensitive target binding assay has recently been shown to detect natural killer (NK) cells in the mouse. Preincubation of NK cells with detergent-solubilized cell-surface proteins of YAC lymphoma cells prevented subsequent binding to intact YAC targets. The NK target structures (NK-TS) consisted of three molecular species tentatively assigned molecular weights of 130,000, 160,000, and 240,000 based on electrophoretic mobility in sodium dodecyl sulfate/polyacrylamide gels. Moloney cell surface antigen (MCSA), gp71, p30, H-2, and NK-TS were localized in distinct fractions of gels. The NK-TS bound to concanavalin A-Sepharose columns and could be eluted with the specific sugar, suggesting that the target structures may be glycosylated. NK-TS molecules could not be detected in gels of NK-insensitive target cells such as P815, A9HT, YWA, or EL-4. The quantity obtained from the gels varied directly with the NK sensitivity of YAC which is more sensitive when grown in vitro than when grown in vivo. The NK-TS molecules specifically inhibited the binding of NK cells but not alloimmune T cells to their appropriate targets. Additional NK-sensitive tumor cells also expressed some or all of the target molecules exhibited by YAC. Some of these structures shared specificities in the case of MPC-11 or were unique in the case of Molt-4 and K562, as shown by cross-inhibition studies. These results suggest that NK-sensitive cell lines express distinct target structures with possible relevance to natural tumor resistance.


Biochemical determinants of tumor sensitivity to 5-fluorouracil: ultrasensitive methods for the determination of 5-fluoro-2'-deoxyuridylate, 2'-deoxyuridylate, and thymidylate synthetase.

Techniques have been developed to measure FdUMP, the active metabolite of 5-FUra; thymidylate synthetase (TMP synthase; 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45), the target enzyme for this antimetabolite; and dUMP, the substrate that competes with FdUMP for binding to TMP synthetase. As little as 0.02 pmol of FdUMP can be quantitated with a competitive ligand binding assay by using homogeneous Lactobacillus casei/MTX TMP synthetase as a binding protein. A new binding assay for TMP synthetase allows detection of 0.005 pmol of enzyme. The quantitative enzymatic conversion of dUMP to [methyl-(14)C]-TMP using 5,10-methylene[(14)C]tetrahydrofolate by pure L. casei TMP synthetase is used as an assay for dUMP with a sensitivity of 10 pmol. Cultured CCRF-CEM human lymphoblastic leukemia cells formed high levels of FdUMP (2.6 nmol per 10(9) cells) within 11 hr after exposure to 30 muM 5-FUra. Tumor cell TMP synthetase levels dropped, and then free FdUMP appeared. The intracellular dUMP pool was low (2-5 nmol per 10(9) cells) in logarithmically growing cultures of several tumor cell lines but expanded rapidly in CCRF-CEM cells on exposure to 5-FUra after enzyme levels decreased. The levels of dUMP found after exposure to 5-FUra are sufficient to severely retard inhibition of TMP synthetase by FdUMP.The methods described are sufficiently sensitive to allow these biochemical parameters of 5-FUra action to be measured in cell culture or in needle biopsy samples of human tumors.


Rapid substitution procedure for intravenous drug self-administration studies in rhesus monkeys.

Rhesus monkeys were trained to press a lever one hundred times (FR 100) to obtain either a food pellet or an intravenous drug injection. Two daily experimental sessions, one in the morning and one in the afternoon, were divided into three 15 minute periods each. In Periods 1 and 3 lever pressing behavior was maintained by the delivery of food. Period 2 lever pressing was maintained by the intravenous injection of a drug solution. The drug available each day followed a four day sequence of cocaine (30 microgram/kg/injection), saline (1.0 ml/injection), cocaine, and test compound. This four day sequence was repeated to test a series of 16 psychoactive compounds at two doses each. These drugs were compared to saline for their ability to maintain Period 2 responding during the afternoon session. Morphine, oxymorphone, codeine, pentazocine, d-amphetamine and methylphenidate all maintained responding at rates significantly greater than for saline. Cyclazocine, naloxone, levallorphan, scopolamine, chlorpromazine, fenfluramine, and (+/-)-9-nor-9-alpha-hydroxy-hexahydrocannabinol (alpha-HHC) did not maintain responding during Period 2. The results with procaine, beta-HHC and nalorphine were considered equivocal. The authors suggest the use of a rapid substitution procedure as a method of initial screening of drugs with potential reinforcement efficacy.


[On the antimicrobial activity of propolis and propolis constituents (author's transl)].

After a survey of the literature on the antimicrobial activity of the bee product propolis, the authors discuss their own findings as compared to the chemotherapeutical agents streptomycin, oxytetracycline, chloramphenicol, nystatin, griseofulvin and sulphamerazine. According to the results obtained by testing 25 isolated constituents on Bacillus subtilis, Staphylococcus aureus, Candida albicans and Trichophyton mentagrophytes, the antimicrobial properties of this mixture of natural substances are mainly attributable to the flavonoids pinocembrin, galangin, pinobanksin, pinobanksin-3-acetate as well as to the p-coumaric acid benzyl ester and a caffeic acid ester mixture. None of the isolated substances was as potent as the antibiotics tested for the purpose of comparison. The relatively good antimycetic activity of the 5,7-dihydroxyflavanone pinocembrin seems noteworthy. Finally, possible mechanisms of the antimicrobial action of the flavonoids are discussed.


[Unusual course of a status epilepticus. (Case contribution to the problem of "interparoxysmal petit-mal-status")].

This is a record of a strange course of the petit mal status which persisted for almost four days following a series of grands maux. During the status, it was possible to observe in electroencephalogram a 2-2.5/sec and, finally, 2.5-3.5/sec spike and wave pattern which could be interrupted after the administration of 100 mg of diazepam. In contrast with the normally observed twilight state, this particular course of the petit mal status ("interparoxysmal petit mal status") is characterized by a marked disturbance of consciousness. There was no response to an intravenous administration of 750 mg of diphenylhydantoin.


Acquisition deficits induced by sodium nitrite in rats and mice.

Graded doses of sodium nitrite were administered shortly before or immediately after a single training trial in an inhibitory avoidance task. A retention test was given at 24 h (rats) or 72 h (mice) after training. The results indicate that sodium nitrite impairs acquisition of an inhibitory avoidance response in rats and mice. Retention was impaired with doses lower than those required for producing hypoxic effects, as measured by the EEG, methemoglobin levels in the blood, blood pressure, and heart rate. Since hypoxia was not involved, it is likely that the effects were mediated by some direct action of sodium nitrite on the CNS.


Probenecid-induced increase of 5-hydroxytryptamine synthesis in rat brain, as measured by formation of 5-hydroxytryptophan.

Probenecid blocks the efflux of 5-hydroxyindole acetic acid (5-HIAA) from the central nervous system, and has therefore been used for turnover measurements of central 5-hydroxytryptamine (5-HT). This substance also elevates tryptophan (TP) levels in rat brain. In this investigation, the time courses of probenecid and TP levels in rat serum and brain after administration of probenecid were studied. Maximal levels of probenecid were reached within 15 min, followed by 50% decrease of serum TP and a 40% increase of brain TP. Brain levels of probenecid were about ten times lower than those in serum. Because TP level in brain is an important factor in the control of cerebral 5-HT synthesis, the effects of probenecid on 5-HT formation in rat brain were investigated. By means of the aromatic L-amino acid decarboxylase inhibitors Ro 4-4602 and NSD 1015, an enhancement of TP hydroxylation of about 35% was demonstrated. It was concluded that penetration of probenecid into the brain is very limited and that probenecid, in addition to blocking egress of 5-HIAA from the CNS, stimulates 5-HT synthesis.


Delta 9-tetrahydrocannabinol sensitization of the rat brain to direct cholinergic stimulation.

In an attempt to define the nature of the involvement of delta 9-tetrahydrocannabinol (THC) with central cholinergic neurotransmission, the effects of THC on direct cholinergic stimulation of the rat brain were investigated. THC, in doses of 3 mg/kg and 6 mg/kg, administered intraperitoneally (i.p.), potentiated the effects of carbachol injection into the lateral septal nucleus, as manifested by enhancement of the drinking response elicited by the septal carbachol injection and by potentiation of the tendency of this carbachol injection to induce abnormal motor responses. Although atropine (10 mg/kg, i.p.) completely blocked the carbachol induced drinking, the atropine did not completely block the drinking response when THC was given with carbachol. The results indicate an apparent sensitization, by THC, of a limbic cholinergic system.


Behavioral evidence for supersensitivity after chronic bromocriptine administration.

Behavioral evidence for tolerance and supersensitivity during and after chronic (30 day) administration of bromocriptine (BRC) or bromocriptine + L-dopa in mice was assessed by measuring wheel running (WR) behavior during and after chronic drug administration, and apomorphine- and methylphenidate-(MP-)induced stereotyped gnawing after termination of chronic injections. In both BRC and BRC + L-dopa groups, tolerance developed fairly quickly to the depressing effect of BRC on WR seen on day 1 of drug administration. Mice receiving BRC showed significant increases in WR by week 2 of chronic drug administration, which persisted for at least two days after the termination of chronic injections. During the first week after termination of chronic injections, low doses of both apomorphine and MP induced significantly more stereotyped gnawing in BRC and BRC + L-dopa mice than in the control mice or the mice treated with L-dopa alone. This behavioral evidence for dopaminergic supersensitivity after chronic BRC administration may have relevance for the clinical use of BRC in combination with L-dopa or other dopamine agonists.


Acetylation of phenelzine.

Microsome-free preparations of rodent and human liver were shown to contain N-acetyl transferase from experiments using procainamide as substrate. These preparations then acetylated phenelzine from the quantitative transfer of radiolabeled acetate. This in vitro demonstration of phenelzine acetylation in rodent and human liver was corroborated by the finding of a negative correlation between excretion of phenelzine in urine and sulphadimidine acetylation in 27 patients.


Anticonvulsant activity in photosensitive baboons, Papio papio, of two new 1,5 benzodiazepines.

Two new 1,5 benzodiazepines have been evaluated acutely as anticonvulsants in baboons, Papio papio, with photosensitive epilepsy. BAU 426 (8-Chlor-6-[2-chlorphenyl]-4H-s-triazolo-[4,3-a] [1,5-benzodiazepin-5-[6-H]on) and BAU 500 (analogue of BAU 426 with [2-trifluor methylphenyl] substituted for [2-chlorphenyl]), 0.1--5.0 mg/kg, were administered i.v. to baboons with and without priming with D,L allylglycine. BAU 426 or BAU 500, 0.1--0.2 mg/kg, produced partial or transient protection against photically induced myoclonus or epileptic responses. Complete protection, in the absence of signs of sedation or acute neurological toxicity, was seen 1--4 h after 0.5--2 mg/kg. EEG changes typical of benzodiazepines were seen for 1--3 h and clinical signs of sedation with some muscular hypotonia were evident for 1 h after either drug, 5 mg/kg. Clinical trials are required to determine if these compounds are superior to 1,4 benzodiazepines as anticonvulsants.


The effects of alcohol on agonistic behavior in the Telomian dog.

The study analyzed the effects of alcohol on agonistic behavior in three independent social systems, each compromised of two male and one female Telomian dog. Three dose levels were used: 0, 0.8, and 1.6 g/kg body weight of absolute alcohol diluted to 20%. Observations were made when none, one (top, middle or low ranking), or all dogs in a system received a given treatment. At the 0.8 g/kg level, low ranking dogs showed an increased frequency of attacks and bone possession time, while top and middle ranking dogs showed a decrease. At the 1.6 g/kg level, all subjects decreased their attacks and bone possession time. Alcohol decreased frequency of agonistic vocalizations under all conditions. There were differential social rank effects on frequency of retreats. Overall, the results were similar whether one or all dogs received the particular treatment.


MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats.

Pretreatment with the MAO-inhibitors iproniazid, clorgyline, or deprenyl abolishes the effects of LSD on the conditioned avoidance response (CAR) in rats. The effects of serotonin (5-HT) and 5-methoxytryptamine (5-MT) are greatly potentiated by these substances. Brain levels of LSD are not affected by MAO inhibition whereas levels of 5-HT and 5-MT are significantly elevated. It is postulated that the decreased behavioral response to LSD is the result of 'MAO inhibitor-induced' changes whereas the increased response of 5-HT and 5-MT results from increased brain levels of these compounds.


Hypnotic susceptibility to various depressants in rats selected for differential ethanol sensitivity.

MA rats, bred for greater motor impairment following subhypnotic doses of ethanol, were found to be more sensitive to the hypnotic effects of phenobarbital and chloral hydrate than were LA rats. In addition, the previously reported finding of a difference between the two lines of rats in duration of loss of righting reflex following a hypnotic dose of ethanol was replicated. The results are discussed in terms of a phenotypic difference in central nervous systems sensitivity to a range of sedative-hypnotics.


Effects of ethanol on turnover and function of striatal dopamine.

Acute oral administration of ethanol increased the rate of depletion of dopamine in the striata of rats injected with alpha-methyl-p-tyrosine. This effect was eliminated by pretreatment with atropine or by lesioning of the striato-nigral tract. Ethanol also attenuated the inhibitory effect of apomorphine on turnover of striatal dopamine. Unilateral injection of ethanol into the neostriatum of rats followed by intraperitoneal injection of either apomorphine or amphetamine elicited marked ipsilateral head-to-tail body turning. This turning was blocked by pretreatment with haloperidol. Chronic intubation of ethanol to rats enhanced contralateral body turning elicited by unilateral intrastriatal injection of dopamine. Injection of 6-hydroxydopamine into the substantia nigra led to denervation supersensitivity of dopaminergic functions in the neostriatum. This effect was not seen in rats that were given ethanol postinjection of 6-hydroxydopamine. These results suggested that ethanol has an inhibitory effect on the nigrostriatal dopaminergic system.


Mutual antagonism of behavioral effects of TRH and thiobarbiturate on an operant task in rhesus monkeys.

Similar excitatory or depressant response rate dependent effects on monkeys responding on a variable interval reinforcement schedule were observed following intravenous administration of either thyrotropin releasing hormone (TRH) or thiobarbiturate. However, these agents were mutally antagonistic when given together even though the response rate altering effects of each agent were in the same direction. These findings establish an additional behavioral effect of exogenously administered TRH in primates and suggest that barbiturates might alter behavior in part through an interaction with brain TRH receptive mechanisms.


Interaction between discrimination of drug states and external stimuli.

Rats learned a two-choice operant response by discriminating differences between external stimuli, internal (drug-produced) stimuli, or a combination of these two types of stimuli. Separate groups of rats were used for each stimulus condition. A tactile and visual external cue was superior to the ethanol-saline cue in producing stimulus control, but the group receiving both drug and external stimulus cues performed in a manner very similar to the external cue-only group. The two stimulus sources thus did not "add" to promote more rapid or complete discrimination. After acquisition of discrimination, previously coincident drug and external stimulus states were reversed to determine which stimulus source had more behavioral control. This test for stimulus selectivity indicated that the external stimulus had essentially complete control of response choice.


The effect of clonidine withdrawal on total 3-methoxy-4-hydroxyphenylglycol in the rat brain.

The effect of clonidine withdrawal on the brain norepinephrine system was studied in the rat. Clonidine suppresses brain total 3-methoxy-4-hydroxyphenylglycol (MHPG) significantly and no tolerance to this effect was observed up to 21 days. Cessation of clonidine treatment resulted in an elevation in the level of brain total MHPG. The suitability of the clonidine withdrawal syndrome as a model of bipolar depression is discussed.


Variability of prolactin response to intravenous and intramuscular haloperidol in normal adult men.

Serum prolactin (PRL) concentrations were monitored in seven normal adult men for 1 h before and 7 h after i.v. and i.m. injection of 0.25 mg and 0.50 mg haloperidol. The magnitude of the PRL response was dose-related but quite variable across subjects. The patterns of PRL secretion over the 7 h post-injection period also varied greatly among the subjects. Differences in serum heloperidol concentrations accounted for 88% of the variability in the magnitude of the PRL response to the 0.5 mg IM haloperidol dose, but only accounted for 60% of the PRL variability following the 0.5 mg IV dose. The pattern of haloperidol disappearance from serum was similar across the seven subjects and thus unrelated to the variable patterns of PRL response.


Effect of caffeine on the memory of the mouse.

Albino mice were injected i.p. with caffeine (27.9 mg/kg) 10 min pre-trial. The mice had no trial retention (300-s period) after 24 h. This result suggests that caffeine, at this dose, would upset some mechanism involved in memory processes. No correlation is observed between serotonin (5-HT) increase and caffeine's effect on retention.


Inhibition-mediating dopamine receptors and the control of intracranial reward.

A receptor selective agonist and antagonist of inhibition-mediating dopamine receptors (type II receptors) produced significant and dose-related alterations in bar-pressing for intracranial reward. Receptor inhibition by piribedil increased responding for reward while receptor activation by 3,4-dihydroxyphenylamino-2-imidazoline reduced responding. Inhibition-mediating receptors may therefore play a role opposite to classic excitation-mediating receptors in controlling reward.


Effects of physostigmine, scopolamine, and mecamylamine on the sleeping time induced by ketamine in the rat.

Male Sprague-Dawley rats weighing 116--241 g were injected i.p. with ketamine hydrochloride, 80 mg per kilo of body weight. Immediately after loss of righting reflex, scopolamine, physostigmine, and mecamylamine were administered i.p. to different groups of rats. Control animals received sterile saline by the same route. The ketamine-induced sleeping time was significantly prolonged by physostigmine and scopolamine, but not by mecamylamine. After the delayed injection of physostigmine, the ketamine sleeping time was longer. These results, although too preliminary for a mechanistic interpretation, suggest that multiple neurotransmitter systems, probably including the cholinergic system, are involved in the mechanism of action of ketamine-induced narcosis.


Piracetam facilitates retrieval but does not impair extinction of bar-pressing in rats.

Rats were trained on a continuously reinforced bar-press response for water reward. Seven days later they were retested for retention, with or without pretest injection of the nootropic drug, piracetam. Drug-treated animals had significantly shorter response latencies than saline-treated animals. The results are interpreted as a facilitation of retrieval processes after forgetting. The experiment was extended under extinction conditions and it was found that after three sessions there was a tendency to facilitate extinction when response latency is used as the extinction index. The clinical interest of a drug which facilitates the retrieval aspect of the memory process without impairing extinction is discussed.


Sex differences in behavioral and thermal responses to pargyline and tryptophan.

The effects of parenterally injected pargyline and tryptophan on rectal temperature and behavior have been studied in male and female rats. Pargyline alone (50 mg/kg) produced hypothermia in both sexes. Pargyline (50 mg/kg) followed by low doses (20--50 mg/kg) of tryptophan caused a behavioral syndrome consisting of tremor, hindlimb abduction, forepaw treading, and straub tail. In females, but not in males, hypothermia was potentiated. The same dose of pargyline followed by higher doses (60--150 mg/kg) of tryptophan produced a short hypothermia followed by a dose-dependent behavioral syndrome, hyperthermia, and mortality. On all of these measures, females responded following shorter latencies and lower doses of tryptophan. Both hypothermia and hyperthermia were observed in treated animals following pretreatment with a peripheral decarboxylase inhibitor. The results suggest a complex role for serotonin in thermoregulation. The sex differences observed suggest higher activity of serotonin in female rat brains following the drug treatment, which may be accounted for by a higher utilization rate of tryptophan.


Dietary modification of amphetamine stereotyped behaviour: the action of tryptophan, methionine, and lysine.

Rats fed diets high in tryptophan, methionine, and tryptophan plus methionine or lysine were subsequently injected with 10 mg/kg d-amphetamine. The amount of amphetamine-induced stereotyped behaviour observed varied as a function of the dietary addition, with methionine showing the greatest difference to controls, and lysine the least. Whole brain catecholamine levels and 5-hydroxytryptamine levels also showed amino acid-specific changes.


[Effects of muscimol and diazepam: a comparative study on behavioral inhibiton induced by novelty, punishment, and nonreward (author's transl)].

Diazepam and muscimol, a direct GABA agonist, were compared on behavioral inhibition induced in rats by (1) novelty, (2) punishment, and (3) nonreward. (1) Muscimol (0.03--0.25 mg . kg-1 i.p. 30 min before testing, or i.v. immediately before testing) failed to enhance food intake consistently in a nonfamiliar situation and (0.125--0.5 mg . kg-1 i.p. or i.v.) to increase the ingestion of an unknown food (chocolate); (2) muscimol (0.125--0.5 mg . kg-1 i.p. or 0.25 i.v. 10 min before testing) was ineffective in reducing the inhibition of lever presses for food elicited by the delivery of an electric shock at every eighth press; (3) muscimol (0.125--0.5 mg . kg-1 i.p.) failed to attenuate the inhibitory effects on responding induced by the suppression of the reinforcement during extinction. Contrastingly, diazepam (2 mg . kg-1 i.p. 30 min before testing) was found to reduce each type of behavioral inhibition. These data lend no support to the hypotheses of GABA control of behavioral inhibition and of GABA involvement in the action of benzodiazepines on inhibition induced by novelty, punishment, or nonreward.


Effect of amphetamine on nondiscriminated key-pecking avoidance in pigeons.

Dose-effect curves for amphetamine on key-pecking behavior of pigeons maintained by two-component multiple schedules of shock postponement were determined. During the first experimental phase the response-shock interval (RS) was held constant and the shock-shock interval (SS) varied. Under these conditions, shock rate was greater during the component with the shorter SS. However, response rates were comparable in both components. Also, the magnitude of the response rate increments caused by appropriate doses of amphetamine during both schedule components were similar. During the second experimental phase, the SS was held constant and the RS varied. As a consequence, baseline response rate was considerably lower in the component with the longer RS than in the short RS component. Shock presentations were also less frequent during the former than during the latter component, but the differences in shock rate between the components were comparable or smaller than those observed during the first experimental phase. Under these conditions, the effects of amphetamine in the two schedules components were markedly different, lower response rates being considerably more increased than higher rates.