The relative importance of central nervous catecholaminergic and cholinergic mechanisms in drinking in response to antiotensin and other thirst stimuli.

1. Intracranial or subcutaneous doses of atropine or atropine methyl nitrate that were fully effective at preventing drinking in response to intracranial carbachol did not block angiotensin-induced drinking. 2. The nicotinic antagonist dihydro-beta-erythroidine given intracranially affected neither angiotensin- nor carbachol-induced drinking. 3. The dopaminergic antagonists haloperidol and spiroperidol injected intracranially blocked angiotensin-induced drinking but did not affect carbachol-induced drinking. 4. Angiotensin- and carbachol-induced drinking were unaffected by alpha- or beta-adrenergic antagonists except at toxic doses. 5. Destruction of catecholaminergic neurones with 6-hydroxydopamine markedly reduced angiotensin-induced drinking, but had relatively little effect on carbachol-induced drinking. 6. Intracranial haloperidol reduced the amount of water drunk in response to overnight deprivation of water, but did not affect feeding in response to overnight starvation or to intracranial noradrenaline. 7. Drinking following overnight water deprivation was unaffected by intracranial alpha- or beta-adrenergic antagonists. 8. Preventing dopaminergic transmission with intracranial haloperidol decreased the water to food ratio of the rat's intake after overnight starvation, whereas increasing the dopamine levels with the combination of FLA-63 and L-DOPA increased the ratio. 9. Intraventricular dopamine in large amounts caused the water-replete rat to drink. 10. It is concluded that among the many functions of dopaminergic systems in the brain is a role in the control of water intake, and that these systems participate in an important way in drinking in response to angiotensin.


Ionic dependence of luteinizing-hormone-induced steroidogenesis in the rabbit ovary.

1. Investigations were made into the influence of the ionic environment on the steroidogenic response of the rabbit ovary to luteinizing hormone (LH). 2. Removal of Ca2+ from the medium was without effect on the response to LH. A similar result was obtained in Ca2+-free medium containing EGTA. 3. A tenfold increase in [Ca2+]o to 25.6 mM, or the addition of La3+ or Eu3+ (0.25 mM) to medium containing the normal concentration of Ca2+, caused a marked inhibition of the response to LH. 4. Removal of Na+ from the medium, and replacement by choline, had no effect on the response to LH. Replacement of Na+ by Li+ inhibited the response to the hormone strongly, but the addition of 4 mM-Li+ to normal medium was without effect. 5. Removal of K+ from the medium inhibited LH-induced steroidogenesis, whereas a twentyfold increase in [K+]o to 100 mM had no effect. The response to LH was also unaffected by the absence of Cl-. 6. Ouabain (10(-4) M) inhbited the response to LH, but nupercaine (10(-4) M) was without effect. 7. The inhibitory effect of ouabain was reversed by the addition of 2 mM-NADP+ to the medium. In contrast, the inhibitory effect of Eu3+ persisted in the NADP+-rich medium. 8. It is suggested that the intracellular ratio of Na+ or Li+) to K+ is important for the expression of the steroidogenic response of the ovary to LH. Altered concentrations of these ions might affect the formation or availability of NADP+. The inhibitory effects of high [Ca2+]o and lanthanide ions, however, are probably due to inhibition of hormone-stimulated adenyl cyclase.


The team; new roles for nurses in general practice--a lesson from America.

IN NORTH AMERICA ATTEMPTS HAVE BEEN MADE TO COUNTERACT THE SHORTAGE OF DOCTORS BY TRAINING ANCILLARIES: the physician's assistant (P.A.) and the family nurse practitioner (FNP). Though physician assistants may give rise to interpersonal difficulties within practices the concept of the family nurse practitioner has much application in Britain. The possibility of employing family nurse practitioners in British general practice is discussed particularly with regard to the help they might give in diagnosis, in psycho-social counselling and follow-up.


Alkylating analogs of bradykinin.

Three analogs of bradykinin have been synthesized which bear a bromoacetyl function on the alpha-amino group or on an anilinic amino group at position 5 or 8. It was hoped that one or more of these analogs might act as an irreversible bradykinin antagonist or as a long-acting converting enzyme inhibitor. Although none of the analogs exhibited the desired pharmacological properties, the methods described for the synthesis and characterization of peptides bearing anilinic bromoacetyl groups are of potential utility in the development of antagonists of other tyrosine--or phenylalanine--containing peptides.


Nonclassical nicotine antagonists.

A series of "nonclassical" nicotine antagonists was synthesized and compared to the "classical" nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure-activity relationship of this class of compounds are discussed.


Synthesis and antibacterial properties of methylsulfinyl and methylsulfonyl analongs of some nitrofurans.

The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested for antibacterial activity against a number of gram-negative and gram-positive organisms. The compounds are much less active than the corresponding 5-nitrofuran derivatives, possibly because their reduction potentials are too negative for them to interfere with reductive enzyme systems within the bacteria.


Complement-dependent and complement-independent interactions between Mycoplasma hominis and antibodies in vitro.

Several in vitro reactions between a strain of M. hominis (no. 4195) and homologous antiserum have been delineated and compared. One complement-dependent and four complement-independent activities of antibody have been studied. The complement-dependent activity was mycoplasmacidal and was inhibited by the presence of arginine in the test medium. The complement-independent antibody-mediated reactions were not mycoplasmacidal and were four in number: (a) agglutination, which was manifested in buffered saline after incubation for 24-48 h at 36 degrees C, and in which the end-points were dependent upon the concentration of antigen; (b) metabolic inhibition, in which antiserum added to liquid growth medium produced slowing of the rate at which the pH rises during growth; (c) agglutination during growth, which occurred in liquid growth medium after the addition of antiserum and coincided with, but generally preceded, metabolic inhibition; and (d) inhibition of multiplication in which high concentrations of antiserum led to inhibition of multiplication or metabolic activity, with persistence of viable mycoplasmas, under otherwise favourable conditions of growth. The end-points for each of the above methods of detecting antibody are not identical.


Cephalexin monohydrate suspension. Treatment of otitis media.

Cephalexin monohydrate suspension was used in the treatment of 97 children with otitis media. Pretreatment middle-ear exudate specimens in pure or mixed culture yielded Diplococcus pneumoniae in 47 cases, Haemophilus influenzae in 26, Neisseria catarrhalis in 20, group A beta-hemolytic streptococci in 13, and Staphylococcus aureus in one. The usual dosage was 100 mg/kg/day given orally in divided doses for 10 to 12 days. After 48 hours of treatment, follow-up cultures showed that therapy had been successful in 90 children; 81 remained clinically and bacteriologically free of disease for at least three weeks following therapy. Of the seven children for whom therapy failed, H influenzae persisted in five and D pneumoniae in two. Acceptance of the drug was entirely satisfactory with no important side effects encountered.


Employment of MEDEX graduates and trainees. Five-year progress report for the United States.

The MEDEX approach to the training and deployment of physician extenders is described and contrasted with other physician-extender training models, and results of a survey of 277 MEDEX graduates and 207 trainees are presented. Practically all MEDEX graduates and trainees are employed in full-time practice and are working with fee-for-service family physicians in the rural areas of the United States, which suggests that the strategy used to place Medex practitioners into communities requiring additional health services has been successful.


Juvenile temporal arteritis. Biopsy study of four cases.

Two young adults (aged 21 and 22 years) and two children (aged 7 and 8 years) complained of an unsightly, soft, painless unilateral nodule in the temporal region, ranging from 0.5 to 1.5 cm in diameter, clinically diagnosed as lipoma, sebaceous cyst, or dermoid cyst. In each instance, the patient had no evidence of systemic disease or history of trauma, and the nodule was excised for cosmetic reasons. Histologic examination of the lesions showed non-giant-cell granulomatous inflammation of the temporal arteries with intimal proliferation and microaneurysmal disruption of the media. Whether the lesions represent a juvenile form of temporal arteritis, an unusual form of localized polyarteritis nodosa, or Kimura disease (subcutaneous angiolymphoid hyperplasia with eosinophilia) remains conjectural.


[Agar tube method for the bioassay of antibiotics (author's transl)].

A simplified bioassay system for antibiotics has been presented. Glass tubes with open ends and pits are filled with agar medium containing test microbes by immersing vertically into the agar medium while it is warm. These agar tubes are inserted in test solutions and incubated. The growth-inhibitory zones appear in respective tubes due to upward diffusion of the antibiotic. The heights of such zones from the bottom of agar tubes are measured.


An alpha adrenergic mechanism in the ascending reticular activating system.

The effect of electrical stimulation of the mesencephalic reticular formation (MRF) on the pyramidal tract (PT) response to cortical stimulation in adult rats was examined with and without alpha adrenergic blocking agents and other chemicals, applied intravenously, intraperitoneally or topically to the exposed cerebral cortex. 1. By MRF stimulation, the initial component of the PT response (D wave) was not significantly altered but the later component (I waves) was initially facilitated and subsequently inhibited. 2. Intravenously applied alpha adrenergic blocking agents, phentolamine and phenoxybenzamine consistently blocked reticulo-cortical inhibition. The reticulo-cortical facilitation was significantly reduced by phentolamine but the effect of phenoxybenazmine was not consistent on this mechanism. Neither the PT response nor the effect of MRF stimulation on it was affected by propranolol or atropine. 3. Phentolamine or phenoxybenazmine, topically applied to the cortical surface, blocked the reticulo-cortical inhibition but did not alter the reticulo-cortical facilitation. 4. A monoamine oxidase inhibitor, iproniazid (i.p.), significantly potentiated the reticulo-cortical inhibition but the effect on the reticulocortical facilitation was not statistically significant. 5. These results suggest that the reticular inhibitory effect on the motor cortical activity is mediated through an alpha adrenergic mechanism and the receptor site is distributed in the cerebral cortex.


[Fat-emulsions and acid-base balance in neonates of low weight at birth (author's transl)].

The influence of a single intravenous infusion of triglycerides (1 g triglyceride per kg body weight) on the acid base equilibrium was investigated in 16 newborn infants with low birth weight during the first days of age. No changes of pH, PCO2 and standard bicarbonate, base excess, buffer base and actuelle bicarbonate, respectively, were observed. Fat emulsions can be used, therefore, without hazards in the parenteral feeding of newborn infants.


[A method for quantitative dertermination of 20-keto steroids in urine during the use of a 3 alpha-, 20 beta-hydroxysteroid: NAD oxidoreductase (author's transl)].

A method is described for the quantitative determination of 20-ketosteroids in urine during the application of a 3alpha, 20beta-hydroxysteroid: NAD oxidoreductase. In the presence of NADH H+ the enzyme catalyses in an "equimolar" developing reaction the reduction of 20-keto groups of C-21 steroids giving 20 beta-alcohols. The measurable NADH H+ consumption is a measure for the quantity of those 20-ketosteroids present in the reaction mixture. The 3alpha-hydroxysteroid: NAD oxidoreductase activity of the enzyme does not influence the specificity of the method to determine the 20-ketosteroids because,-under the present extraction and purification conditions-those 3alpha-hydroxy-5alpha-androstan derivatives are not reaching the reaction mixture of determination. The demands towards the criterions of reliability (correctness and exactitude) come to be fulfilled by this method.


[The role of cyclic adenosine 3':5'-monophosphate as "second messenger" in gastric acids secretion (author's transl)].

The criteria to determine whether cyclic adenosine 3':5'-monophosphate (cyclic AMP) is or is not involved in a particular hormone response require to look for positive qualitive, quantitative and temporal correlations between the effects of the hormone on cyclic AMP levels and the physiological response. These requirements have been shown to be fulfilled in histamine and pentagastrin-stimulated gastric acid secretion of the frog (Necturus maculosus) and the rat. In dog and man, however, the available evidence does not support a role for cyclic AMP in the gastric secretory process; it remains a challenge for future research whether in those species cyclic guanosine 3':5'-monophosphate acts as an intracellular substitute for cyclic AMP.


Changes in ethanol consumption by C3H and CF1 mice with age.

Water or a 3% alcohol solution was offered for 4 weeks to groups of male C3H mice initially aged 3, 13, 20 and 60 weeks, and to male CF1 mice from age 10 weeks until they died. Differences in the consumption depended on age and the rate at which response patterns to the solution develop.


Voluntary consumption of alcohol by baboons. Effects of flavor, concentration and temperature of solution.

Nonrestrained, group-housed baboons drank the greatest amounts of alcohol when it was presented as a 10% to 20% solution in cold fruit juice.


Effects of long-term administration of alcoholic beverages on the kidney, heart, skeletal muscle and pancreas of rats. A histological study.

No pathological changes in the pancreas, kidneys or skeletal muscle were found in rats maintained for 8 to 9 months with a diet in which alcohol made up 50% of the total calories. An increase of the dietary fat content to 38% did not cause any fatty infiltration of the myocardium.


Social control of drinking among the Aztec Indians of Mesoamerica.

In the Aztec culture of pre-Columbian Mexico the rules for the use of alcoholic beverages were clearly defined and strictly enforced. Drinking was permitted only on religious occasions and the amount drunk was restricted.


Measurement and interpretation of drinking behavior. I. On measuring patterns of alcohol consumption. II. Relationships between drinking behavior and social adjustment in a sample of problem drinkers.

Different systems for measuring drinking behavior were reviewed and compared. A revised system based on volume and pattern was devised, and its utility in predicting social adjustment was tested.


Situations related to drinking alcohol. A factor analysis of questionnaire responses.

Problem and nonproblem drinkers indicated on a questionnaire the degree to which they used alcohol in certain situations. The responses were factor analyzed and seven factor scales were developed. It is suggested that the questionnaire could be used as an initial diagnostic step leading to specific treatment alternatives.


The predisposition toward alcohol-related interpersonal aggression in men.

Men social drinkers participated in experimental "parties' which were videotaped and coded for instances of interpersonal aggression. Participants with a history of arguments and other aggressive acts and low scores on measures of socialization, self-control and responsibility demonstrated interpersonal aggression after heavy drinking.


Collision behavior of young drivers. Impact of the change in the age of majority.

A comparison of the number of collisions experienced by young male drivers in London, Ontario, before and after the reduction in the legal age for drinking and purchasing alcoholic beverages from 21 to 18, indicated that the change in the law led to an increase in the collision involvement of young drivers.


Death in young alcoholics.

Homicide, accidents and heart disease were the leading causes of death among young alcoholics treated at an outpatient alcoholism clinic over a 3-year period. Ways of preventing early death in alcoholics are suggested.


Use of the MMPI in predicting completion and evaluating changes in a long-term alcoholism treatment program.

Veterans admitted to a 90-day alcoholism treatment program were administered the MMPI, and those who completed the program were retested before discharge. Completers differed significantly from noncompleters on the Pd scale. Although responses on most MMPI scales indicated improvement after treatment, those on the MacAndrew Alcoholism Scale were not affected. Neither the MacAndrew nor the Unitary Alcoholism Factor differentiated between completers and noncompleters.


Changes in construing and outcome of group therapy for alcoholism.

Consistent changes in the way they construed their drinking problem were found in alcoholics who completed an inpatient group therapy program. Patients who showed most change in construal were the ones most likely to relapse.


Self-reported coping behavior of wives of alcoholics and its association with drinking outcome.

The frequency of the use of coping behavior by wives of alcoholics was found to be related to their husband's drinking outcome. In general, a high frequency of coping behavior was associated with a poor outcome, but some components of coping behavior were more likely than others to be linked with a poor prognosis.


Effects of discontinuity of medication on the results of a double-blind drug study in outpatient alcoholics.

When the analysis of results of a double-blind drug study included outpatient alcoholics who missed clinic visits no differences were found between drug and placebo groups. When only patients who took adequate levels of medication were considered, the drug group fared significantly better than the placebo group.


Effects of crowding on alcohol consumption by rats.

Rats housed eight to a cage consumed significantly more 10% ethanol mixed with milk than did rats housed individually.


Comparison of outcome in a 9-day and 30-day alcoholism treatment program.

At 3 and 6 months after discharge no differences in abstinence rates were found between patients who completed a 9-day inpatient alcoholism treatment program and those who participated in a 21-day treatment program.


Evidence that revascularization by ventricular-internal mammary artery implants increases longevity. Twenty-four year, nine month follow-up.

Revascularization of the heart is a means of relieving symptoms of coronary artery disease--such as angina, fatigue, and dyspnea. The question of whether revascularization prolongs the life of the patient has been debated. My colleagues and I have reviewed our years of experience with patients treated by implantation of internal mammary arteries into the ventricles. We have compared our series with other groups of patients treated medically. Our conclusion is that revascularization via internal mammary artery implants does increase longevity.


Myocardial scintigraphy. Post-Vineberg study.

In order to assess myocardial perfusion of Vineberg implants, tracer particles (99mCc and 131I-MAA) were injected into the internal mammary implants of 7 patients (6 years after the operation) after selective contrast visualization. The myocardial perfusion images were correlated with the internal mammary arteriographic findings. Of those patients with patent implants with communication, the myocardial scintigrams demonstrated even distribution of radioactive particles reflecting myocardial perfusion at the capillary or precapillary bed.


Selection of coronary bypass. Anatomic, physiological, and angiographic considerations of vein and mammary artery grafts.

Results of direct coronary revascularization with 511 grafts in 213 patients from 1971 to 1974 are reviewed. To improve an early saphenous vein graft (SVG) patency of 84 per cent in the first 85 patients, we have used internal mammary artery grafts (IMAG), when possible, since January, 1973. In 1973 to 1974, 15 patients had SVG's only (36 grafts) and 113 received one or two IMAG's with or without additional SVG's (total 282 grafts); in 26 we used a crossed double IMAG. Forty-seven of 48 patients with unstable angina survived and did well. Flows in SVG's and IMAG's were comparable. Flows in right IMAG's to diagonal or marginal vessels were higher than in right IMAG's to right or left anterior descending (LAD) vessels. In 12 patients with both SVG and IMAG, there was no difference in flow response of either graft to vasoactive drugs. Survival, functional, and patency results with IMAG's were as good as or better than results with SVG's. We conclude that IMAG's yield higher patency and comparable flow rates to SVG's and should be used when the IMA approximates the recipient artery in size and when a high pulsatile free flow is measured from the end of the graft. IMAG's are also safe and feasible for unstable angina.


Myocardial injury and bypass grafting. Value of serum enzymes in diagnosis.

To clarify the value of serum enzymes in the detection of intraoperative and postoperative myocardial injury associated with coronary artery bypass grafting, we evaluated 70 consecutive patients (151 grafts). We used electrocardiograms and serial determinations of serum levels: serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), and LDH isoenzymes on Days zero, 1, 3, 5, 7, and 10. Patency of all grafts 1 week postoperatively was 92 per cent. Fourteen patients (20 per cent) had ECG evidence of acute myocardial infarction (AMI) or ischemia lasting longer than 48 hours. This incidence of AMI was attendant with no deaths or discernible changes in postoperative ventriculography. LDH-1 (cardiac fraction) was elevated in all patients with myocardial injury. Late elevation of LDH-1 occurred in 2 patients at the time of postoperative catheterization, 1 of whom had negative findings on ECG. Diagnostic correlation was not observed with total LDH, CPK, or SGOT. Predisposing factors to AMI included preinfarction angina (4 of 14 patients), occluded grafts (4 of 14), and a bypass time greater than 120 minutes.


Manual coronary endarterectomy. Clinical experience in 315 patients.

From July, 1970, to December, 1973, manual endarterectomies were performed on 330 coronary arteries in 315 patients. The procedures were performed on either an elective or nonelective basis. The over-all hospital mortality rate was 1.27 per cent. Postoperative myocardial infarction occurred in 4.8 per cent of these patients. Postoperative catheterization was performed on 186 endarterectomized arteries; the average time of postoperative catheterization was 13.1 months after surgery. The over-all patency rate was 76.3 per cent. This experience suggests that endarterectomy is a safe and useful adjunct to saphenous vein bypass grafting procedures when used in a restricted fashion as detailed in this presentation.


Helix-coil stability constants for the naturally occurring amino acids in water. IX. Glutamic acid parameters from random poly(hydroxybutylglutamine-co-L-glutamic acid).

The synthesis and characterization of water-soluble random copolymers containing L-glutamic acid with N5-(4-hydroxybutyl)-L-glutamine and the thermally induced helix-coil transitions of these copolymers in water and in 0.1 N KCl are described. The incorporation of L-glutamic acid was found to increase the helix content of the polymer at low pH and to decrease it at high pH even though the presence of 0.1 N KCl effectively eliminated the difference between the electrostatic free energies of the helix and the coil. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-glutamic acid) in water and in 0.1 N KCl were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The synthesis of N-acetyl-N'-methylglutamic acid amide and its titration, as well as that of the copolymers and poly(L-glutamic acid), in 0.1 N KCl are described.


[Role of ferredoxin in the metabolism of hydrogen by Rhodospirillum rubrum].

Ferredoxin was purified after isolation from the cells of Rhodospirillum rubrum grown under photoheterotrophic conditions; A385/A280 in the absorption spectrum was not less than 0.53; the molecular weight was ca. 7700; E0' (pH 7.0)--430 mv. Ferredoxin was easily reduced in the presence of dithionite and provided a high rate of NADP reduction by pea chloroplasts. The extracts of R. rubrum containing ferredoxin or the extracts, to which it was added, reduced NAD in the presence of hydrogen and evolved H2 in the presence of NAD(P)H. ATP or light were required for the evolution of H2 from NAD(P)H.


[Oral administration of an acidiferous drug and its effect on carbohydrate metabolism of maturity-onset-diabetics treated by oral hypoglycaemic agents].

Subacidity or anacidity may lower glucose-tolerance in elder diabetics. 65 Patients, who showed not sufficient effect of oral hypoglycaemic agents, got an acidiferous drug. Diabetes could be ameliorated significantly. Some results are contrary to itself. In 8 patients our hypothesis came true in all points. Further investigations are necessary.


[Distribution of pyrimidine blocks in the DNA of Brevibacterium linens, Arthrobacter globiformis, Nocardia corallina and Nocardia rubra].

The nucleotide composition and the frequency of pyrimidine blocks were studied in DNA of the following bacteria: Brevibacterium linens (Weignamm, 1910) Breed, 1953; Arthrobacter globiformis (Conn, 1928) Conn et Dimmick, 1947; Nocardia corallina (Bergey et al., 1923) Waksman et Henrici, 1948; Nocardia rubra (Krassilnikov, 1949) Waksman et Henrici, 1948. These organisms are classed by some microbiologists as mycobacteria (the Mycobacteriaceae family) while other authors regard them as representatives of three families belonging to two orders. About 60 percent of all pyrimidines in DNA of these bacteria are found in the sequences pur-pyr-pur and pur-pyr-pyr-pur, the number of dipyrimidines being higher than the amount of monopyrimidine nucleotides. The content of dipyrimidine nucleotides in DNA of Nocardia corallina and Nocardia rubra is higher (16.8 mole %) than the content of dipyrimidine blocks in DNA of Brevibacterium linens and Arthrobacter globiformis, in which the quantity of dipyrimidines is almost the same (13.9 and 14.4 mole %). A new characteristic, the selected mean value, is suggested to evaluate differences in the distribution of pyrimidines in DNA.


[Ribonucleotide reductase in Propionibacterium shermani].

The cell-free extract of Propionibacterium shermanii was found to contain B12-dependent ribonucleotide reductase. The extract of the cells grown under the conditions of the inhibited synthesis of vitamin B12 reduces ribonucleotides with the participation of B12-independent enzyme. The synthesis of B12-dependent apoenzyme of ribonucleotide reductase is partially maintained under these conditions. Both enzymes reduce preferably ribonucleoside diphosphates. The reducing agent of nucleotides in vitro is lipoic acid or dithiothreitol, in the B12-dependent pathway, and NADPH and thioredoxin, in the B12-independent pathway. Only B12-independent ribonucleotide reductase requires Mg2+ ions. Vitamin B12 in the coenzyme form inhibits the activity of B12-independent enzyme.


[Effect of hydrogen ions on the morphology and ultrastructure of Bacillus megaterium].

The morphology and ultrastructure of the cells of Bacillus megaterium depend on the concentration of hydrogen ions in the medium which affect, first of all, the function of division. The changes induced by hydrogen ions are temporary and disappear when the cells are put under normal conditions of growth. The "acid-resistant" strain of Bac. megaterium remains viable at a very high concentration of hydrogen ions (pH=4.2) and, though its morphology changes drastically, no essential damages are found, i.e. the cells become adapted to new conditions. The changes are reversible.


Energy metabolism of isolated rat thymus cells.

The energy metabolism of rat thymus cells has been investigated using preparations of isolated cells obtained by mechanical treatment of whole organs. The addition of glycolytic substrates such as glucose, pyruvate and lactate stimulates the endogenous respiration of these cells by 50%. On the other hand, succinate, glutamate and malate do not produce any effect. Oligomycin (10 mug/ml) inhibits both endogenous and glucose stimulated respiration by about 40%; 2, 4-DNP (50 muM) increases by 100% glucose induced respiration. The results obtained by using mitochondrial and glycolytic inhibitors as well as aminoxyacetic acid (AOA) and following pyridine nucleotides redox changes, support the idea that in thymus cells glucose is able to induce a great enhancement of O2 consumption both by raising the level of endogenous pyruvate and feeding the mitochondrial respiratory chain with cytosolic reducing equivalents, through an active malate-aspartate shuttle. Thymus cells exhibit a high Pasteur effect (74%). Both AOA and 2,4 DNP are able to stimulate aerobic lactate accumulation by 200% and 100% respectively, indicating that either the redox or phosphate potential do influence the rate of aerobic glycolysis in isolated thymus cells. Similar experiments are also reported on other cells with well known biochemical characteristics.


Fatty acid hydroxylation in rat kidney cortex microsomes.

Rat kidney microsomes have been found to catalyze the hydroxylation of medium-chained fatty acids to the omega- and (omego-1)-hydroxy derivatives. This reaction, which requires NADPH and molecular oxygen, is a function of monooxygenase system present in the kidney microsomes, containing NADPH-cytochrome c reductase and cytochrome P-450K. NADH is about half as effective as an electron donor as NADPH and there is an additive effect in the presence of both nucleotides. Cytochrome P-450K absorbs light maximally at 452-3 nm, when it is reduced and bound to carbon monoxide. The extinction coefficient of this complex is 91 mM(-1) cm(-1). Electrons from NADPH are transferred to cytochrome P-450K via the NADPH-cytochrome c reductase. The reduction rate of cytochrome P-450K is stimulated by added fatty acids and the reduction kinetics reveal the presence of endogenous substrates bound to cytochrome P-450K. Both cytochrome P-450K concentration and fatty acid hydroxylation activity in kidney microsomes are increased by starvation. On the other hand, phenobarbital treatment of the rats has no effect on either the hemoprotein or the overall hydroxylation reaction and 3,4-benzpyrene administration induces a new species of cytochrome P-450K not involved in fatty acid hydroxylation. Cytochrome P-450K shows, in contrast to liver P-450, high substrate specificity. The only substances forming enzyme-substrate complexes with cytochrome P-450K are the medium-chained fatty acids and certain derivatives of these acids. The chemical requirements for substrate binding include a carbon chain of medium length and at the end of the chain a carbonyl group and a free electron pair on a neighbouring atom. The distance between the binding site for the carbonyl group and the active oxygen is suggested to be in the order of 16 A. This distance fixes the ratio of omega- and (omega-1)-hydroxylated products formed from a certain fatty acid by the single species of cytochrome P-450K involved. The membrane microenvironment seems also to be of importance for the substrate specificity of cytochrome P-450K, since removal of the cytochrome from the membrane lowers its binding specificity to some extent. A comparison between the liver and kidney cytochrome P-450 systems suggests that the kidney cytochrome P-450K system is specialized for fatty acid hydroxylation.


Studies of 3-aminopyridine adenine dinucleotide phosphate.

3-Aminopyridine adenine dinucleotide phosphate (AADP) was prepared from NADP and 3-amino-pyridine through the pig brain NADase-catalyzed pyridine base exchange reaction. The purified dinucleotide was chemically characterized and spectral properties of the compound were determined. The importance of the application of AADP in studies of NADP-requiring biochemical processes was indicated by the demonstration of AADP as an effective inhibitor of five NADP-requiring enzymes, by the demonstration of the fluorescence enhancement on the binding of AADP to yeast glucose-6-phosphate dehydrogenase when glucose-6-phosphate is present, and by the functioning of AADP as a fluorimetric substrate for snake venom nucleotide pyrophosphatase.


[Tuberous sclerosis as cause of neuropathological symptoms allegedly due to smallpox vaccination (author's transl)].

Following smallpox vaccination a patient presented with neuropathological symptoms, the real cause of which was tuberous sclerosis, a congenital disease.


[The medicinal treatment of anxiety in alcoholism in the withdrawal stage (author's transl)].

The benzodiazepine preparation Camazepam was tested for its anxiolytic activity and found to be effective. It differs from preparations which have already been in use for a long time, especially by the lack of any hypnotic and muscle relaxant effects. In the clinical trial it was also free from side effects so far as they could be detected by the usual routine investigations of the technical laboratory.


Cerebrospinal-fluid acid base and electrolyte changes resulting from cerebral anoxia in man.

To study metabolic changes in the central nervous system after profound anoxia, we measured changes in cisternal and lumbar cerebrospinal fluid. Acid-base values and electrolyte concentrations were determined in cisternal and lumbar fluid from 12 severely anoxic patients (cardiac arrest), and from 15 within 24 hours after cardiac resuscitation. In the severely anoxia patients the normal cisternal-lumbar pH gradient was reversed, cisternal fluid was more acid (pH 6.815 vs. 6.953), and cisternal potassium concentration was twice that of lumbar (6.7 vs 3.5 mEq per liter). These findings indicate that during anoxia potassium and hydrogen ion flow from brain cells into the brain extracellular fluid, and that acute changes are reflected more accurately by cisternal than by lumbar fluid. In resuscitated patients cisternal fluid was normal, and normal cisternal-lumbar differences were found; thus, the normal milieu of brain cells is rapidly reestablished after resuscitation.


Effect of hypophysectomy on cAMP changes in rat adrenal medulla evoked by catecholamines and carbamylcholine.

It was the aim of this study to investigate the mechanisms responsible for changes in 3',5'-cyclic adenosine monophosphate (cAMP) in the rat adrenal medulla occuring after administration of carbamylcholine, histamine, ACTH and various phenylethylamines. Carbamylcholine, ACTH, histamine, noradrenaline and dopamine produced marked (500-900%) increases in adrenal cAMP which were very similar in both adrenal cortex and medulla both with respect to time-course and relative extent. Interestingly isoprenaline and adrenaline did not influence cAMP levels even at excessively high doses. In all cases studied transsection of the splanchnic fibers supplying the adrenals reduced the increase in medullary cAMP by not more than 25--30%, suggesting that cAMP levels in the adrenal medulla are predominantly regulated by non-neuronal mechanisms. This assumption was strongly supported by the observation that hypophysectomy completely abolished the 500--600% increase in cAMP produced by 50 mumol/kg of dopamine and reduced the 700% increase resulting from 4.4 mumol/kg of carbamylcholine to 70%. In spite of the marked increase in cAMP produced by single and repeated doses of dopamine in the adrenal medulla there was no subsequent induction of tyrosine hydroxylase (TH). Moreover carbamylcholine (8.2 mumol/kg) evoked TH induction only in innervated adrenals whereas after denervation, in spite of the large (+ 500%) and prolonged (more than 90 min) increase in cAMP, no TH induction could be observed. It is concluded that adrenal medullary cAMP is predominantly regulated by the pituitary gland via the adrenal cortex and only to a much smaller extent--if at all--by direct cholinergic mechanisms, which are responsible for the initiation of TH induction.


Effect of bulbocapnine as a peripheral dopamine receptor antagonists in the anesthetized cat.

We have found bulbocapnine to be an effective, apparently competitive inhibitor of dopamine depressor responses in the anesthetized, phenoxybenzamine-treated cat. The duration of action of the compound as a dopaminergic antagonist exceeded 3 hrs after an intravenous dose of 8 mg/kg. In the same preparation, however bulbocapnine did not at all inhibit the depressor responses to acetylcholine, histamine and isoproterenol, indicating a selectivity of action. Although administration of a high dose of propranolol (2 mg/kg, i.v.) did not alter the response of the alpha-receptor blocked cat to dopamine, the subsequent infusion of bulbocapnine remained effective. These results suggest that dopamine is acting as a blood pressure depressor agent via a unique receptor mechanism.


The effect of pre- and postnatal undernutrition on the development of the cerebellar cortex in the rat. II. Histochemical observations.

The effect of pre- and postnatal undernutrition on the neuronal enzymatic maturation of the neocerebellar hemispheral lobules VI b, VI c and VII (according to Larsell 1952) was studied. Postnatally oxidative enzyme histochemistry (LDH, SDH, NADH, NADPH, G6PDH) revealed a delayed enzymatic development in the cerebellum between days 8 and 22, as an effect of pre- and postnatal undernutrition. In the Purkinje cell apical cone a delayed increase in enzyme activities could be seen at days 8 to 11 as well as a delayed decrease in Purkinje cell perikaryal enzyme activities at days 11 to 14 post-partum. The retarded enzymatic development seemed to parallel the retarded morphological development (cf. Sima & Persson 1975).


Effects of stress on catecholamines and tyrosine hydroxylase activity of individual hypothalamic nuclei.

The effects of acute stress on norepinephrine (NE) and dopamine (DA) concentrations and of repeated stress on tyrosine hydroxylase (TH) activity were measured in individual hypothalamic nuclei and other rat brain regions. A microdissection technique and radioisotopic enzymatic assays enables these studies to be performed. NE and DA concentrations were reduced and TH activity increased selectively in the arcuate nucleus. These results suggest that the arcuate nucleus may be selectively involved in the stress response and support the hypothesis that catecholamines in the medial basal hypothalamus mediate certain of the neuroendocrine changes observed in stress.


[Gamma glutamly transpeptidase in chronic anicteric hepatopathies].

Serum levels of gammaGT were determined in 51 patients suffering from bioptically verified chronic anictereric liber disease. GammaGT proved to be much more sensitive than the other enzymes studied and presented a significant increase particularly in cases of steatosis and chronic "alcoholic" liver disease with a markedly steatosic character.


Utilization of dietary calcium by iron-deficient rats.

Iron deficiency causes cytological and enzymic changes in the gastrointestinal mucosa of animals and man that can be expected to impair the digestion and absorption of other nutrients. In experiment 1, healthy, weanling, female rats were grouped into pair-mates and pair-fed either an iron-deficient or an iron-supplemented diet for 19 weeks. In experiment 2, iron-deficient offspring reared by iron-deficient females were grouped into pair-mates and pair-fed either an iron-deficient or an iron-supplemented diet for 15 weeks. In experiment 1, apparent absorption of calcium was significantly depressed in week 9 (p less than 0.001) and slightly depressed in weeks 10 and 11. In experiment 2, the apparent absorption of calcium was significantly (p less than 0.001) depressed in weeks 6, 13, and 14. Absorption was not measured in other weeks in these experiments. The concentrations of calcium and magnesium were consistently higher in the fecal dry matter of the iron deficient rats in both experiments. It was concluded that any defects in digestion and absorption by the iron-deficient rats was confined primarily to the mineral nutrients because in both experiments apparent absorption of dry matter was consistently higher in these animals compared to their iron-supplemented pair-mates.


Correlation of fetal heart rate-uterine contraction patterns with fetal scalp blood pH.

The significance of fetal heart rate-uterine contraction (FHR-UC) monitoring as a means of predicting the condition of the fetus during labor was studied by correlating 460 fetal pH determinations obtained from 216 patients with the analysis of the 20-minute FHR-UC record preceding the fetal scalp blood sample. Both qualitative and quantitative analyses of the FHR-UC record were performed. The results indicate a less than 10% chance of fetal pH less than or equal to 7.250 with an normal baseline FHR and no periodic changes or with periodic accelerations, early decelerations, and uncomplicated baseline bradycardia or tachycardia. Variable or delayed decelerations with a total surface area (TSA) of 1-100 for the 20-min period were associated with a fetal pH less than or equal to 7.250 in 23 and 34% of cases, respectively. Variable or delayed decelerations with a TSA greater than 100 had a 35 or 47% chance of fetal pH less than or equall to 7.250. It is concluded that FHR-UC monitoring can be used to screen the innocuous from the ominous periodic change but that fetal scalp blood pH must be obtained to identify accurately the true from the false-positive ominous pattern.


Puncture wounds of the foot.

Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr. Charles A. Janeway Child Health Centre. Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated. Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management. The combined surgical and medical management of this complication is outlined. Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound. Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection. A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available.


Factors affecting surface changes in intact cercariae and cercarial bodies of Schistosoma mansoni.

The effect of different incubation media and of temperature on the induction of water sensitivity has been investigated in intact and tailless Schistosoma mansoni cercariae. Removal of the cercarial tail by vortex stirring and elevation of the temperature of the medium from 27 to 37 degrees C resulted in the rapid onset of permeability changes in the larvae. The rate of change was greater in water than in TC-199 or Hanks' BSS media. Lowering the pH of the medium or increasing the concentration of Ca2+ ions decreased the rate of permeability change: raising the pH of the medium or the addition of 10(-5) M EDTA enhanced the rate. Raising the temperature of the medium also increased the rate of permeability change in intact cercariae although the rates obtained varied with the different media tested, being greatest in TC-199. It is concluded that both temperature elevation and loss of the cercarial tail influence the onset and rate of permeability changes in cercarial bodies during the transformation to schistosomula.


[Sézary's syndrome].

In Sézary's syndrome (SS), cutaneous manifestations are associated with an abnormal mononuclear cell in the blood. Clinically, the differential diagnosis with Mycosis fungoides is impossible. However, some of the symptoms are more in favor of SS, such as leonin face, palm and sole hyperkeratosis and changes in pigmentation. The diagnosis of SS rests upon the identification on ordinary blood smears of a lymphocytic cell, the size of which is variable and which exhibits a grooved, folded and lobulated nucleus. This cell is negative for both esterases and peroxydases. It is not a monocyte. Large cells have big nuclei with tetraploid DNA values, whereas small variants have near diploid values. Chromosome analysis may reveal near hypertetraploid, hyper or hypodiploid counts. Marker chromosomes have been seen which could be common to all types. However, many cases are known in which the karyotype was normal. In addition, there are cases in which chromosome analysis was impossible due to poor responses of the Sézary cells to PHA. As regards surface markers, there is general agreement that Sézary's cells are non-B lymphocytes. In some cases, the cells had both T markers (antigen and E-rosettes), whereas in others, only one (antigen) was expressed. In still other cases, the abnormal blood cell had neither B nor T markers. In at least one case, the cells had both B and T surface receptors. The diversity of the Sézary's cell would be explained by the immunologic pressure exerted upon skin lymphocytes by the epidermis due to a change in the antigenicity of this tissue in relation to ageing or to the presence of exogenous chemicals, or to physically induced mutations. Recent studies from this laboratory, using autoradiography after incorporation of tritiated thymidine, have shown labelled lymphocytes in the skin of three out of four cases of SS. These results suggest that cutaneous manifestations in SS, as well as in Mycosis fungoides, are comparable to a chronic Graft-Versus-Host reaction (GVH).


Study of renal functions by repeated constant infusion of radiotracers before and after initiation of therapy in hypertension or in diabetes mellitus.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were simultaneously measured by obtaining an isotopic steady state during a continuous infusion of 125I orthoiodohippurate (OIHA). A good correlation was found between the clearances of Ioth (y) and of inulin or polyfructosan (x) : y = 1.18 X (x) + 8.43 (r = 0.96; P less than 0.001) and between the clearances of OIHA (y') and of PAH (x') : y' = 0.62 X (x') + 21.2 (r = 0.93; P less than 0.001). When renal functions were impaired the use of Ioth was not convenient since the infusion time necessary to reach a radioactive plateau was longer than 3 hours. On the contrary, excellent results were obtained by using OIHA. In this case, the main advantages were the absence of urine collection and the rapid obtention of an isotopic equilibrium. The repeated determination of renal clearances in hypertensive or diabetic patients appears to be useful in the study of changes induced by antihypertensive drugs or insulin. Clearances were slightly improved by clonidine, claimed to be useful in hypertension associated with chronic renal failure. GFR and ERPF were rapidly increased by insure on the metabolic and hemodynamic changes induced by insulin than on the return to normal of glomerular basement membrane permeability.


[Study of the criteria of evaluation of the exercise capacity of the chronic hemodialyzed subject].

Direct measurement methods (or the forecast related to indirect measurements) of the maximal oxygen uptake are reviewed. 15 patients suffering from renal failure, performed a total of 28 exercises. One can draw the conclusion that the maximum VO2 is inferior in these subjects to the values usually determined in normal healthy subjects of the same age. This decrease can be significantly correlated with the haematocrit. Comparison between direct measurement methods of the maximal oxygen uptake and indirect methods allowing its forecast from the heart rate, shows that only direct methods are to be used in these patients.


[Quantitative study of multimolecular forms of serum gamma glutamyl transferase by polyacrylamide gel electrophoresis].

The quantitative distribution of the multimolecular forms of serum gamma-glutamyl-transferase is studied in 286 sera by acrylamide gel electrophoresis, incubation, coloration in situ, photography, slide reading and integration. In 43 normal sera, the fast fraction represents 66% of the total activity; the ratio of the mean fast fraction to the medium and slow fraction was 2. During pregnancy (53 cases), in cord blood (54 cases), in hepatic cytolysis or cholestasis (55 cases), and in secondary liver carcinoma (21 cases), this ratio is considerably lower, demonstrating the predominance of medium and slow fractions. A similar decrease in the ratio, with predominance of the medium and slow fractions was seen in 22 cases of advanced cancer without metastases in the liver.


Hemophilus and pneumococcal peritonitis in children with the nephrotic syndrome.

Two children are reported whose nephrotic syndrome was complicated by peritonitis due to H. influenzae type b. In Pittsburgh, the leading organism for peritonitis in nephrosis remains D. pneumoniae with a disproportionately high incidence in black children. Although H. influenzae is a rare cause of this complication, it should be considered along with the other previously recognized etiological bacterial agents.


Susceptibility to interference effects in short-term memory of normal and retarded readers.

The short-term memory for serial order of third and fourth grade normal and retarded readres (Ns = 13) was studied. Six pictures of common objects were spatially presented and subjects were required to reconstruct the sequence. On the first six trials, the same pictures were repeatedly presented in different sequences. On the seventh trial, a new set of stimuli was introduced. Analysis of short-term memory over trials showed that normal and retarded readers were similar on Trial 1 but the performance of retarded readers deteriorated more over trials than the performance of normal readers. Short-term memory of both groups improved on Trial 7. The results indicate a greater susceptibility to interference in the short-term memory of retarded readers.


Effects of pH and ionic strength on the potassium system in the internally perfused giant barnacle muscle fibre.

Membrane potentials in single barnacle muscle fibres of Megabalanus psittacus, internally perfused with 200 mM K-acetate (KAc) solution of pH 7.5 were in the range --53 to --60 mV. These were followed as a function of pH of the external chloride saline. Decrease of pH of the Cl-saline from 8.5 to 3.5 hyperpolarized the membrane reversibly by about 8 mV. On further decrease of pH to 3.0, a transient hyperpolarization (from --60 to --65 mV) followed by a sudden and irreversible drop of potential to --40 mV was observed. Replacement of the external Cl-saline by acetate saline in the pH range 8.5 to 6.5 had no effect on the membrane potential. Further decrease of pH to 5.0 brought about an irreversible reduction of membrane potential. For fibres bathing in Cl- or Ac-saline at pH 7.5 when the internal pH was changed to 5.5, a transient hyperpolarization in Cl-saline and a sustained hyperpolarization in Ac-saline were observed. Further studies of membrane potential changing the concentration of external K, keeping the concentration of Cl or Ac constant, and changing the concentration of Cl or Ac, keeping the concentration of K constant, at different internal and external pHs showed that as the pH was reduced the membrane became more permeable to anions, Cl being more permeable than Ac. Experiments in which the membrane potential was controlled showed that when the internal pH of 200 mM KAc solution was reduced from 7.5 to 6.5 or raised to 8.5, the changes in outward K currents at various depolarizations were negligible. However, when the pH was reduced to 5.5 or 5.0, there was a progressive decrease in the outward K currents. The leakage currents in all these cases were relatively small. Use of high ionic strength solution of 580 mM KAc internally protected the K system in that when the pH was lowered the depression of the outward K current was smaller than that observed at a corresponding pH when the internal solution was 200 mM KAc. Use of low ionic strength solution of 50 mM KAc had the opposite effect. The results have been explained in terms of the ion exchange theory by postulating that the membrane has fixed amphoteric groups.


Calculation of O2 saturation and of the oxyhemoglobin dissociation curve for different species, using a new programmable pocket calculator.

The degree of O2 saturation and different data of acid-base status are determined from pO2, pH, and pCO2 values bya programmable pocket calculator. Since the operating program should be usable for different species and also in the range of very low O2 saturations, obviously the usual Hill equation for calculating the oxygen dissociation curve of hemoglobin is not applicable; the same is true is some cases for the Adair equation. Thus a 3-fold subdivision of the dissociation curve was undertaken and programmed. Suitable programs for several species could be established despite the limited number of program steps in the new calculator, giving systematic deviations in calculated O2 saturations of less than or equal to +/- 0.9 saturation precent over the full range of dissociation curves. A reverse procedure for calculation of pO2 from saturation is added. In situations where pCO2 or base excess are not known or only estimated, limits of the arising error are stated. In the acid-base program 7 parameters are evaluated partially using empirical formulae derived from nomograms. The programmable pocket calculator offers advantages of small size, economy, and independence of line voltage compared to much more spacious units and a precision equal or superior to nomograms.


The rates of saxitoxin action and of saxitoxin-tetrodotoxin interaction at the node of Ranvier.

Voltage clamp experiments were done on single nodes of Ranvier of Rana esculenta. Equilibrium effects were obtained from INa-V curves, the rates of action from changes in INa on changing solutions during repetitive depolarizing pulses. 2. Saxitoxin (STX) exclusively and reversibly blocked Na channels, the effect being fully described by a one-to-one reaction between STX and a receptor at the channel with an equilibrium dissociation constant, Ks, of 1.4 nM; the mean offset rate constant k2s, was 1.76 X 10(-2) sec-1 (16 +/- 1 degree C;pH 7.2), 1.7 times the value for tetrodotoxin (TTX). 3. At pH 5.6, K2S WAs increased by a factor of 1.33 while the equilibrium STX effects was decreased in a way suggesting competition between STX and protons. 4. After pretreatment of nodes with 3.1 nM TTX the extra block on adding 9.0 nM STX as well as its relief on taking out STX of the TTX-STX mixture revealed transients in the time course of receptor occupation. 5. These non-monotonic time courses are incompatible with the idea of two independent blocking sites (for STX and TTX) per channel but could be quantitatively fitted by analog-computed curves assuming competition between STX and TTX for the same site.


[Biological diagnosis of Zollinger-Ellison syndrome in the context of a polyendocrine adenomatosis].

The diagnostic features of Zollinger-Ellison syndrome (ZES) in patients with type I poly-endocrine adenomatosis with a gastrinoma are analysed on the basis of 11 cases. Both from a clinical (frequency of ulcer disease and of diarrhoea) and biological standpoint (hypersecretion of gastric acid, hypergastrinaemia, or results of secretin stimulation test), the characteristics of ZES are not different whether a gastrinoma is present alone or in association with involvement of other endocrine glands. However the signs may be either masked by changes related to another endocrine disorder or appear late. They should therefore be sought routinely in all patients with an endocrine disorder which might fall into the context of a type I poly-endocrine adenomatosis. The sole difficulty is the interpretation of gastric acid hypersecretion and/or hypergastrinaemia in a patient with hyperparathyroidism. In this latter case, such abnormalities are not necessarily due to ZES and may disappear after removal of the parathyroid adenoma.


The photochemistry of purine components of nucleic acids. I. The efficiency of photolysis of adenine and guanine derivatives in aqueous solution.

It has been shown that the quantum yield of the photochemical conversion of adenine and the corresponding nucleosides and nucleoside 5'-phosphates in liquid (pH 5.6 and 2.0) and frozen aqueous solutions do not exceed 10(-4). The quantum yield of the photoconversion of guanine-containing nucleosides and nucleoside 5'-phosphates in liquid aqueous solution (pH 5.6) after removal of oxygen by passing through nitrogen and in the frozen state do not exceed 0.3 x 10(-4). The quantum yield in oxygen-containing liquid aqueous solutions increase to 0.3 x 10(-3), i.e. to values commensurate with the quantum yield of pyrimidine photolysis.


Complex formation between nuclear RNA and mitochondrial proteins.

Specific proteins are present in mitochondria that are capable of forming complexes with nuclear RNA. Complex formation is time and temperature dependent and requires optimal conditions of Mg2+, K+ and H+ concentrations. The complexes are stable towards most denaturing agents and their component nucleic acids and proteins are resistant to nucleolysis and proteolysis respectively.


[Adsorption properties of Beidellite (author's transl)].

The beidellite is both an activator and an adsorbing agent for certain clotting factors: at low concentration (1 p. 1 000), factors XII and VII of human plasma are activated. At a concentration of 10 p. 1 000, the fibrinogen is totally adsorbed, leaving in the supernatant most of the VIII. At alpha 20 p. 1 000 concentrations, most of factor II remains unabsorbed, the remaining plasma being devoided of other clotting factors except minute amounts of factors XI and XII. Contrarely to bentonite, which has similar properties, beidellite does not absorb water and does not modify the pH. Beidellite is therefore a very useful agent for selective adsorption of clotting factors.


Blood parameters in Leucocytozoon smithi infected poults fed clopidol.

Poults naturally infected with L. smithi demonstrated a significant (P less than 0.01) decrease in arterial PO2 (mm. Hg) during the second and third weeks after exposure to black fly bites. Poults fed Clopidol (0.0125%) during the exposure period and subsequent experimental periods showed very little parasitemia and no significant reduction in arterial PO2.


The pharmacology of new ethylenediamine derivatives (ROM-126, ROM-131, MK-142) with antiarrhythmic action. Part I. General pharmacological properties.

Mentioned compounds, studied on several species of animals, decrease blood pressure and the heart rate, modify catecholamine-induced effects, show properties characteristic for the beta-receptor blocking agents. The stated differences being due mainly to the power of their action. These compounds possess also spasmolytic and locally anaesthetic action of various degrees. Only ROM-131 has antihistamine action.


Extraction of Renilla-type luciferin from the calcium-activated photoproteins aequorin, mnemiopsin, and berovin.

Photoproteins, which emit light in an oxygen-independent intramolecular reaction initiated by calcium ions, have been isolated from several bioluminescent organisms, including the hydrozoan jellyfish Aequorea and the ctenophore Mnemiopsis. The system of a related anthozoan coelenterate, the sea pansy Renilla reniformis, however, is oxygen dependent, requiring two organic components, luciferin and luciferase. Previously published indirect evidence indicates that photoproteins may contain a Renilla-type luciferin. We have now extracted in high yield a Renilla-type luciferin from three photoproteins, aequorin (45% yield), mnemiopsin (98% yield), and berovin (85% yield). Photoprotein luciferin, released from the holoprotein by mercaptoethanol treatment and separated from apo-photoprotein by gel filtration, no longer responds to calcium but now requires luciferase and O2 for light production. Photoprotein luciferin is identical to Renilla luciferin with respect to reaction kinetics and bioluminescence spectral distribution. In view of these results, the generally accepted hypothesis that the photoprotein chromophore is a protein-stabilized hydroperoxide of luciferin must be modified. We believe, instead, that the chromophore is free luciferin and that oxygen is bound as an oxygenated derivative of an amino-acid side chain of the protein. We propose the general term "coelenterate luciferin" to describe the light-producing chromophore from all bioluminescent coelenterates and ctenophores.


Crosslinking and labeling of membrane proteins by transglutaminase-catalyzed reactions.

Transglutaminase enzymes catalyze for the formation of epsilon(gamma-glutamyl)lysyl crosslinks, or the substitution of a variety of primary amines for the amide function of protein-bound glutaminyl residues. These enzymes should therefore be useful in crosslinking the proteins of membranes and in attaching a variety of chemical probes and labels to these proteins. This usefulness is demonstrated in experiments with the enzyme liver transglutaminase and the membranes with the enzyme liver transglutaminase and the membranes of mouse erythrocytes and of rabbit skeletal muscle sarcoplasmic reticulum.


Functional arginyl residues as ATP binding sites of glutamine synthetase and carbamyl phosphate synthetase.

The reaction of phenylglyoxal with two enzymes in which ATP plays a complex role has been studied. Both ovine brain glutamine synthetase and Escherichia coli carbamyl phosphate synthetase [carbamoyl-phosphate synthase (glutamine); ATP:carbamate phosphotransferase (dephosphorylating, amido-transferring); EC 2.7.2.9]were inactivated by phenylglyoxal. The specificity of this reagent for arginyl residues of the two proteins was confirmed by amino acid analysis. ATP, but not the other substrates, protected these enzymes against inactivation by phenylglyoxal. Carbamyl phosphate synthetase was also protected by IMP and ornithine, positive allosteric effectors that alter the enzymatic activity be increasing the affinity for ATP. UMP, a negative allosteric effector that decreases the affinity for ATP, did not protect against inactivation. Differential labeling experiments with [14C]phenylglyoxal showed that the number of arginyl residues protected by ATP corresponded quite well to the known number of ATP catalytic sites for each protein. These data indicate that arginyl residues at the active sites of glutamine synthetase and carbamyl phosphate synthetase are involved in the binding of ATP. This phenylglyoxal inactivation study also provided information about the mechanistic role of ATP in the two synthetases. The data obtained on glutamine synthetase support the theory that ATP is attached to the enzyme as a portion of the catalytic site, and that its presence is essential for the binding of glutamate and glutamine. The data obtained on carbamyl phosphate synthetase are consistent with the previous proposal that carbonyl phosphate is an intermediate in the ATP-dependent activation of bicarbonate by this enzyme. It is also of interest that, with both glutamine synthetase and carbamyl phosphate synthetase, only a small portion of the total arginyl population of these enzymes reacted with phenylglyoxal. A summary of previous studies on the modification of enzyme arginyl residues is presented.


An octamer of histones in chromatin and free in solution.

Crosslinking with dimethyl suberimidate reveals a chain of histone octamers in chromatin. The octamer can be isolated free in solution at high ionic strength and pH. The identification of dimers formed by crosslinking reveals two or more contacts of each histone with others within the octamer. The molecular weight (110,000) and pattern of dissociation of the octamer are compatible with the composition (F2A1)2(F3)2(F2A2)2(F2B)2.


Influence of alterations in meal frequency on lipogenesis and body fat content in the rat.

Rats were allowed to eat only 2 hr per day (meal-fed) or were fed ad libitum (nibbler) for 12 wk; another group of animals was meal-fed for 3 wk and then fed ad libitum (converted I) while the fourth group of rats (converted II) was meal-fed for 3 wk, allowed to nibble for the next 3 wk, meal-fed from the 6th to 9th wk and then returned to ad libitum feeding for the last 3 wk. Body fat gain and food efficiency was increased in converted I rats. The lipogenic capacity of adipose tissue from meal-fed rats was greater than observen meal-fed rats were reverted to ad libitum feeding whereas lipogenic activity increased rapidly when ad libitum fed rats were switched to meal-feeding.


Methodological studies on the uptake of zinc by 3T3 cells.

In the present work, experiments were conducted on the uptake of zinc by 3T3 cells. (1) The percent Zn uptake gradually decreased with addition of increasing amount of zinc (0.05-8.4 mug). (2) With the increase of the incubation period from 2 to 16 hr, Zn uptake by nearly confluent cells increases gradually; however, confluent cells which are newly replated show a distinct cyclic increase in the Zn uptake after 2, 6, and 10 hr. (3) The amino acids of DMM and serum decrease Zn uptake. (4) Histidine at a molar excess of 1:50, 1:500, and 1:5000 reduces Zn uptake in comparison to a treatment with 65Zn-Zn-L-hist2 at a molar ratio of 1:5. (5) When zinc is added in the form of different Zn compounds, at a molar ratio of 1:2 or 1:1 (Zn:ligand), EDTA decreases the Zn uptake markedly. A small influence was shown also by albumin and histidine; however, other amino and organic acids at a molar ratio of 1:2 did not alter Zn uptake significantly.


Sodium urate accelerates precipitation of calcium oxalate in vitro.

Precipitation of calcium oxalate crystals from a metastable solution can be detected within 10 min if crystalline sodium urate is added at a solid to liquid ratio of 0.1 mM or more. Without urate, precipitation begins after 50 min. Uric acid is not effective. Pyrophosphate inhibits the effects of sodium urate.


Heterogeneous nucleation of calcium oxalate by seeds of monosodium urate.

Seeds of monosodium urate caused heterogeneous nucleation of calcium oxalate at pH 5.7 and 6.7, and of calcium phosphate at pH 5.3, 5.7, and 6.7 from metastably supersaturated solutions in vitro. Seeds of uric acid had a small or no effect. The results could account for the formation of calcium stones among patients with hyperuricosuria and normocalciuria.


Effects of ganglionic and beta-adrenergic blockade on cardiovascular responses to the bisenoic prostaglandins and their precursor arachidonic acid.

Arachidonic acid (AA) 300 mug/kg, and PGE2, 5 mug/kg consistently produced a decrease in systemic arterial pressure in anesthetized dogs. PGF2alpha, 5 mug/kg, produced a pressor response. All three compounds increased myocardial contractile force, but the magnitude of the change following AA was less prominent. After ganglionic blockade, the depressor response to AA and PGE2 persisted and the pressor response to PGF2alpha was augmented. Myocardial contractile force did not increase following AA in ganglion-blocked animals indicating that the cardiac responses observed before hexamethonium were mediated by the baroreceptor reflexes. A much larger dose of AA (900 mug/kg) resulted in a small positive inotropic effect on the heart. This possibly represents a direct cardiac effect of AA, or may be indicative of increased biosynthesis of an intermediate endoperoxide, or PGE2 and PGF2alpha. Both PGE2 and PGF2alpha have a direct positive inotropic effect on the heart. The persist cardiac effects of PGE2 and PGF2 after beta-adrenergic blockade suggests that these compounds may not interact with the beta-receptors of the myocardium.


Hemodynamic effects of procainamide and quinidine and the influence of beta-blockade before and after experimental myocardial infarction.

The use of antiarrhythmie drugs in combination has been limited because of possible side effects secondary to myocardial depression in the acute myocardial infarction patient. Therefore, we investigated in intact dogs (group I) the hemodynamic interaction of propranolol plus procainamide (subgroup A) or quinidine (subgroup B) and in dogs after experimental myocardial infarction produced by coronary artery ligation (group II). Infusion of procainamide (30 mg/kg over 5 min) in animals of group IA produced a significant (P less than 0.05) decrease of 30% in mean aortic pressure, a decrease of 40% in left ventricular dp/dt and 29% in cardiac output. When procainamide was reinfuse after propranolol (1 mg/kg), its hemodynamic effects were not significantly different from those observed before propranolol in both groups IA and IIA. Infusion of quinidine (10 mg/kg over 5 min) in animals of group IB (intact dogs) also produced significant decreases of 24% in mean aortic pressure and 38% in dp/dt while cardiac output was unchanged. However, these hemodynamic changes were seen only after beta-blockade and were significantly different from those obtained before propranolol, where heart rate increased by 14%, dp/dt by 30%, and cardiac output by 35%. These changes occurred despite a similar reduction in mean aortic pressure. This drug combination produced similar response in animals after coronary artery ligation (group IIB). In conclusion, we feel that the administration of propranolol does not prevent the depressive circulatory effects of procainamide. The combined use of quinidine and propranolol also has a negative circulatory effect although not as marked as the effects observed after procainamide with propranolol.


Organ-specific DNA damage induced in mice by the organotropic carcinogens 4-nitroquinoline 1-oxide and dimethylnitrosamine.

The extent of DNA fragmentation induced in lung, kidney, and liver of mice injected with the chemical carcinogens 4-nitroquinoline 1-oxide (4NQO), dimethylnitrosamine (DMN) and the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO) was estimated by the alkaline sucrose gradient technique. A floating of minced lung tissue pieces in the alkaline lysing solution on top of the gradients afforded a gentle method of lung DNA extraction. This technique minimized mechanical shearing of lung DNA and permitted comparisons to be made with liver and kidney DNA sedimentation patterns. The extent of DNA damage induced by 4NQO followed the order: lung, kidney, liver, while that induced by DMN followed the order: liver, kidney, lung. The sites of greatest DNA damage appeared to correlate with sites of high levels of DNA repair synthesis and the sites of tumor induction. No DNA damage was induced by the noncarcinogenic 4-aminoquinoline 1-oxide (4AQO).


Oxidation-reduction potentials in the cecal contents of rats and mice.

The oxidation-reduction potential (ORP) in the cecal contents of conventional rats, germ-free mice, and mice with a Colonization Resistance Factor flora (CRF-mice) was investigated. By using animals that were anaesthetized for a longer period of time, we attempted to eliminate the disturbing influence of oxygen. In addition, measurements were made under anaerobic conditions. For the rats, the ORP values reached a more or less constant level after about 30 min following the insertion of the electrodes. The mean ORP at that time was -458 mV (SD = 45 mV). The mean ORP values for the mice showed a more gradual reduction than was found in the rats. The curves leveled off at about 100 min following the insertion of the electrodes. The mean ORP values 100 min after electrode insertion were: germ-free mice, + 3 mV (SD = 39 mV); CRF-mice, -554 mV (SD = 29 mV). In rats, the ORP value decreased after death; no decrease was observed in mice. No difference was found in the values obtained when measuring under anaerobic or aerobic conditions after death.


Application of Gran's potentiometric method in pharmaceutical analysis.

Because of weak acid-base properties, many pharmaceuticals cannot be determined by the convenient neutralization titrimetric method. It is shown that such substances can be precisely analyzed by applying the graphic pH-potentiometric method of Gran. Some water-soluble and insoluble pharmaceuticals, which usually are analyzed in nonaqueous solvents, have been determined precisely in water solution by this method. The latter is also applied successfully to the analysis of mixtures and impurities in pharmaceuticals.


Factors related to the cariogenic potential of breakfast cereals.

Reported is a series of studies in which several breakfast cereals were tested for the following properties: sugar retained by, and plaque formed on, extracted teeth that chewed the cereals: ability of the cereals to induce acid formation when incubated with saliva and to neutralize acids when mixed with water: and, as a summary, ability to induce caries formation under mouth-simulation conditions. It was found that the cariogenic potential of the cereals tested is not dependent upon their sugar content, their retentiveness on the teeth, the amount of sugar retained by the teeth, or the amount of plaque formation they induced on the teeth. The only parameter that related well with the carcinogenic potential of the cereals was their buffering (or acid-neutralizing) ability: the greater the buffering, the lesser the carcinogenic potential. These results, which were confirmed in independent animal studies, case some doubts upon the role traditionally attributed to sugars in caries formation. At least they caution against generalizations and point out other factors that should be studied before a thorough understanding of the factors determining the cariogenicity of foods can be gained.


Prostaglandin-E2-9-ketoreductase in rabbit kidney.

The 100,000 xg supernatant of rabbit kidney contains a prostaglandin-E2-9-ketoreductase which has an obligatory requirement for NADPH. This enzyme is localised in the renal cortex and is able to quantitatively convert PGE2 to PGF2alpha. A broad pH profile was evident with an optimum at pH 7 with 5. Kinetic studies indicated a Km of 3 with 2 x 10-4M PGE2. The isoelectric point was at pH 5 with 65 and the molecular weight, as estimated by gel filtration, was 21,800. These values differ from those obtained with enzyme from monkey brain tissue and suggest a tissue specificity of PGE2-9-ketoreductase. By combining isoelectric focussing techniques with sephadex filtration considerable purification of the renal enzyme was achieved.


Interactions of adrenergic stimulants and blockers on self-stimulation behavior in rats.

Self-stimulation behavior in rats was facilitated by two adrenergic stimulants, amphetamine (0.5 or 1 mg/kg, intraperitoneal, i.p., or 100 mug, intracerebroventricular, i.c.v.) and cocaine (5 mg/kg, i.p.). Three alpha-adrenergic blockers (phenoxybenzamine, dibenamine, phentolamine) and a beta-adrenergic blocker (propranolol) decreased self-stimulation responding at 100 mug i.c.v. doses, but showed very little effect at small i.p. doses. Pretreatment with alpha- and beta-adrenergic blockers (i.c.v.) also decreased amphetamine-facilitated responding. The effects of amphetamine or cocaine (i.p.) were not significantly altered by these blockers at the doses used. The depressant effects of the alpha- and beta-adrenergic blockers on self-stimulation behavior appear to be nonspecific with respect to the type of adrenergic receptors.


The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed rats.

Minor tranquilizers have been shown to be specific inhibitors of the elevation of plasma corticosteroid levels in rats subjected to mild stress. The inability of several anxiolytic compounds to show activity at high doses prompted an investigation of the effect on corticosteroid levels of these drugs over a wider dosage range. It was found that at high doses, the drugs themselves cause an elevation of corticosteroid levels masking the blocking of the stress-induced elevations. It was discovered that upon sub-chronic administration, the drug-induced elevation diminishes while the ability to inhibit stress-induced elevation persists. Finally, an extensive dose response curve for phenobarbital demonstrated a variety of responses, depending upon the dose; an antistress effect at low dose, a relatively ineffective dose range from 50-100 mg/kg, and a corticosteroid lowering effect at anesthetic doses. The lack of effect of moderately high doses has been explained through their depressant side effects, which in themselves are stressful to the animal.


Interaction of psychoactive drugs with the Mg+2 requiring ATPase associated with isolated synaptic vesicles.

A large series of CNS active drugs have been tested for their possible effect on the Mg+2 dependent ATPase associated with isolated synaptic vesicles. Antipsychotic agents and cocaine showed inhibition, of a non-competitive type. The implications of this finding for a synaptic theory of psychosis are discussed.


Inhibitory effect of anti-obesity drugs on NADH dehydrogenase of mouse heart homogenates.

Propylhexedrine and chlorphentermine inhibit the activity of NADH cytochrome c reductase but to a lesser extent than fenfluramine. Diethylpropion and phendimetrazine have little effect.


Antagonism of fenoterol against beta-blocking drugs bunitrolol and practolol in asthmatics.

In 4 X 10 young white male histamine-sensitive asthmatics without bronchitis or emphysema, the antagonism of fenoterol (40 mug) to bunitrolol (2.5 and 5 mg) or practolol (20 and 30 mg) was tested in an open comparative trial. Pulse frequency and several physiological parameters were determined before and after histamine challenge test, after injection of beta-blocking drug and after injection of fenotrolol. All groups were found to be equally sensitive to histamine. Bunitrolol and practolol were found to have no influence on histamine effect. It was also found that bunitrolol in the dosages tested is a much more potent beta-blocking drug in the bronchi compared to practolol in the dosages tested were equivalent. beta-Blockade of practolol (20 or 30 mg) could completely be antagonized by 40 mug fenoterol; this dosage was not sufficient to antagonize 2.5 or 5 mg bunitrolol.


A fish in extreme alkalinity.

Tilapia grahami (Boulenger), a small cichlid fish, inhabits extremely alkaline water where the total CO2 concentration exceeds 200 meq.L(-1), osmolality is about 600 mosm.L(-1), pH ranges between 9.6 and 10.5 and temperature may be 43 degrees C. Venous blood drawn anaerobically by heart puncture had pH values as high as 8.4 at 35 degrees C. A 10-15-fold bicarbonate concentration gradient exists across the gills of Tilapia. It is suggested that the uniquely high and variable blood pH results when blood in the gills are exposed to water in which free CO2 can hardly exist. Blood CO2 must be correspondingly low resulting in pH values hitherto unknown to occur in vertebrates.


Factors controlling the in vitro and in vivo oxygen affinity of the hemocyanin in the crab Carcinus maenas (L.).

The oxygen affinity of the hemocyanin of the crab Carcinus maenas was studied in vitro by measuring the O2 partial pressure at 50% saturation, P50, at various conditions of pH, temperature and salt concentration. At alkaline pH, the hemocyanin exhibits a normal Bohr effect, inverted below pH=pH0=6.9 at 15 degrees C. A rise of temperature provokes an increase of both P50 and pH0. Within the physiological range, only Ca++ and Mg++ ions influence the oxygen affinity. Both ions decrease P50, and Mg++ increases the Bohr factor, deltalogP50/deltapH. The variations of P50 due to changes of pH, temperature (degrees C) and Ca++ and Mg++ concentrations (mEq-L-1) are satisfactorily described by the empirical quantitative expressions: see article. Long-term temperature adaptation of the animals results in changes of the parameter k' which appears to be dependent on the concentration of an unidentified dialysable substance in blood. As temperature rises, this phenomenon limits the in vivo increase of P50 induced by both the intrinsic temperature effect and the decrease of in vivo blood pH. When external salinity decreases, lower blood Ca++ and Mg++ concentrations entail an increase of P50, but without changes of k', an effect compensated for in vivo by an increase of the blood pH. The observations suggest that the functional oxygen affinity of the pigment is physiologically regulated to ensure an adequate oxygen transport by the blood in quite varied conditions of temperature and salinity.


Blood and CSF acid-base changes, and rate of ventilatory acclimatization of awake dogs to 3,550 m.

Awake, intact dogs trained to wear a respiratory mask were studied in a hypobaric chamber at 140 m and at various stages of a 4-week exposure to 3,550 m. Resting ventilation, pulmonary gas exchanges, arterial blood gases and pH, acid-base status of the cisternal fluid (CSF) and ventilatory responses to transient O2 inhalation were measured. Attention is focussed on the time course of ventilatory acclimatization to altitude, characterized by hyperventilation with hypocapnia and a consequent increase of arterial Po2. (1) 75 percent of the increment in pulmonary ventilation due to hypoxia was achieved in 30 minutes; (2) the further increase, 25 percent of the total hyperventilation, was complete after 3 hr, with a corresponding Pco2 drop and pH increase in blood and CSF, and an increase in Pao2; (3) the secondary increase in ventilation, beyond the acute exposure period, was not related to return of [H+] in CSF towards control value; (4) the large transient decrease of ventilation following brief oxygen inhalation demonstrated a strong arterial chemoreflex drive in acclimatized animals. The extremely rapid ventilatory acclimatization to moderately high altitude in normal dogs appears to be mediated not by CSF hydrogen ion concentration but by a strong chemoreflex drive of ventilation.


Electrochemical improvement of the performance of PO2 electrodes.

Rotating ring-disc electrode studies have indicated that relatively large quantities of hydrogen peroxide ion, HO2-, are produced when oxygen is reduced at a platinum or gold polarographic electrode surface. The electrochemical reduction processes are improved and the quantity of HO2- is reduced by using alkaline buffer electrolytes (pH 10 to 11) and by polarising the electrode at voltages more negative than -0.9 V. The presence of HO2- in the electrolyte has been shown to be the cause of excessively long time response in both blood-gas and respiratory polarographic PO2 electrodes; electrode alinearity on micro-blood-gas PO2 electrodes has also been shown to be due to the absence of a plateau on the polarogram of electrodes when used with conventional electrolytes. The use of a high pH buffer and high negative voltage results in a long, flat plateau and a marked improvement in both electrode linearity and response time. This two-fold improvement in electrode performance holds true for both platinum and gold polarographic respiratory gas and blood-gas PO2 electrodes.


Cerebrospinal fluid alkalosis during high-altitude sojourn in unanesthetized ponies.

Unanesthetized adult female ponies were studied near sea level (250 m) and during sojourns to 3400 m (N=6) and 4300 m (N=7) altitude. The pH, PCO2, and PO2 of arterial blood and pH and PCO2 of cerebrospinal fluid (CSF) were measured under conditions of acute (1 hr) and chronic (1-45 days) hypoxia. Cerebrospinal fluid was sampled from the cisterna magna of the awake pony and arterial blood withdrawn from an indwelling arterial catheter. In both groups of animals, PaCO2 decreased slightly after 1 hr of hypoxia (delta PaCO2= - 0.6 mm Hg at 3400 m; - 3.9 mm Hg at 4300 m), decreased further after 1-5 days at high altitude (delta PaCO2= - 7.2 mm Hg at 3400 m; - 12.3 mm Hg at 4300 m) and then increased significantly after 6 days of chronic hypoxia (delta PaCO2= + 4.1 mm Hg at 3400 m; + 4.7 mm Hg at 4300 m). Although PaO2 decreased markedly during acute hypoxia, subsequent changes in PaCO2 at high altitude did not alter PaO2 from that observed during acute hypoxia (PaO2=52 mm Hg at 3400 m; 41 mm Hg at 4300 m). The pH of CSF increased during acute hypoxia (delta pH= + 0.013 unit at 3400 m; + 0.033 unit at 4300 m) and became more alkaline after 1-2 days at high altitude (delta pH= + 0.031 unit at 3400 m; + 0.064 unit at 4300 m). At 4300 m, CSF pH remained alkaline to control values throughout sojourn. Under these conditions of chronic hypocapnic hypoxia, CSF pH was imperfectly regulated and regulated in a magnitude equal to (3400 m) or less than (4300 m) arterial blood. Furthermore, the similarity of relative changes in CSF [HCO3-] and arterial [HCO3-] during chronic hypoxia may indicate a passive regulation of CSF [HCO3-] rather than local 'CSF-specific' mechanisms as previously proposed.


pH changes in dental plaque caused by sweetened, iron-containing liquid medicine.

Five commercially available liquid iron medicines and a 5% aqueous sucrose solution were tested in a randomized cross-over study with six subjects at intervals of 3-4 d. The pH in plaque was measured in minute samples taken 5 min before and 5, 10, 20, and 40 min after oral intake of 10-ml volumes of the test solutions. The iron-containing medicines differed with respecto to pH (2.8-7.0), buffer capacity, viscosity, and iron content; two contained sorbitol (28 and 42%) and three sucrose (9, 17, and 47%). As expected, all sucrose-containing preparations produced a significant decrease in pH while no appreciable pH changes followed those with sorbitol. The pH readings after 5 min were affected by the sucrose content rather than the initial pH of the solutions. The decrease in pH was of shorter duration after exposure to the sucrose-containing iron medicines than after the 50% aqueous sucrose solution.


Reduced capacity to produce specific 'effector' cells after injection of CBA mice with C3H cells.

Lymphocytes from mice of strain CBA are strongly MLC-responsive to lymphocytes from the H-2-compatible but M-antigen-incompatible strain C3H. This strong reactivity disappears after infusion of CBA mice with C3H lymphocytes. This study shows that the host-versus-graft reactivity (swelling of local lymph node after antigen injection) is specifically reduced after injection of CBA mice with C3H times CBA spleen cells. However, lymphocytes from such mice showed a specifically increased GVH reactivity (inhibition of erythroid cell growth) compared with lymphocytes from unimmunized mice. Lymphocytes from normal CBA mice showed a high proliferative rate in the spleens of irradiated C3H times CBA mice. Such 'educated' cells showed strongly increased specific GVH reactivity. Lymphocytes from CBA mice previously injected with C3H times CBA cells showed reduced capacity to proliferate when injected into irradiated C3H times CBA hybrids and a poor capacity to develop new 'effector' cells reactive against C3H times CBA bone marrow target cells. The results indicate that the presence of specifically 'MLC-responsive' lymphocytes in a lymphoid cell population is a prerequisite  of its production of 'effector' cells able to respond in this GVH assay.


Immunoelectroosmophoresis (IEOP) for detection of bacterial antigens in cerebrospinal fluid.

365 cerebrospinal fluid specimens from 259 patients were tested by the immunoelectroosmophoretic (IEOP) method to detect bacterial antigens. 25 patients had bacterial meningitis. The bacterial agent was identified by IEOP in 16 of 21 cases with aetiological agents detectable with the antisera employed. No false positive reactions occurred. The test gave true negative results in 340 instances. The rapidity, simplicity, sensitivity, reliability and low cost are emphasized.


Meningitis developing during cephalothin therapy of septicaemia.

A 63-year-old woman developed pneumococcal meningitis during cephalothin treatment for pneumococcal septicaemia. The poor penetration of this antibiotic over the blood-brain barrier makes it unsuitable for the therapy of meningitis. If cephalothin is used in other serious infections, the patient should be closely observed for the development of meningitis.


Erythromycin stearate in acute maxillary sinusitis.

76 patients with acute maxillary sinusitis were treated with oral erythromycin stearate (500 mg twice or 3 times a day for 10 days). The mean concentration of erythromycin in the sinus secretion after 3-5 days' treatment was 0.6 mug/ml with the lower dosage and 1.3 mug/ml with the higher. The concentration of erythromycin in the sinus secretion was, on the average, 10-20 times higher than the minimum inhibitory concentration (MIC) for group A streptococci and pneumococci, and reached MIC values for 15-30% of 100 examined strains of Haemophilus influenzae. 81% of the patients given the smaller and 94% of those given the larger dose improved or recovered. Radiological improvement was demonstrated in both groups. The infections with H. influenzae tended to respond somewhat less to the treatment than those with pneumococci. Comparisons of the roentgen findings and the findings at aspiration showed good agreement. An extra projection taken with the patient recumbent and the affected side downwards gave no information above that obtained from the routine projections. The large dose caused side effects more often (in 17/41 patients) than the smaller one (4/35 patients). In 10 patients treatment was discontinued because of side effects; 8 of them had received the larger dose.


Neurotransmitters increase cyclic nucleotides in postganglionic neurons: immunocytochemical demonstration.

Dopamine increases adenosine 3',5'-monophosphate (cyclic AMP) but not guanosine 3',5'-monophosphate (cyclic GMP) in slices of bovine sympathetic ganglion; this increase is localized to the postganglionic neurons. Conversely, acetylcholine increases cyclic GMP but not cycle AMP in the ganglion; this increase also occurs within postganglionic neurons. Thus, different neurotransmitters can selectively alter cyclic nucleotide levels within the same neuronal population.


Effect of anesthetics on the heart.

In man, high doses of the "group 1" inhalation anesthetics (diethylether, cyclopropane, and fluroxene) produce relatively minor depression of ventricular function, although it is possible to depress the heart if the dose is great enough. The "group 2" drugs (halothane, methoxyflurane, etc.) produce dose-related depression in cardiac function, but reasonable caridac outputs and blood pressure can be maintained at light anethetic levels. Much the same can also be said for the intravenous barbiturates and other hypnotics. If ventilation is supported and hypovolemia avoided, large doses of the narcotic analgesics appear to produce minimal cardiac effects. The only intravenous drug which stimulates the heart is the dissociative anesthetic ketamine, and this is probably an autonomic, reflex phenomenon (as with group 1 inhalation anesthetics). Regional anesthesia and the neuromuscular blocking drugs appear to have relatively little effect on ventricular function. Most of the work in man on the effect of anesthetics has been in healthy patients or volunteers. The effects on patients with severe heart or other systemic disease may well be different. In fact, low concentrations of fluroxene have been shown to produce significant depression of stroke volume in patients with aortic vavular disease in contrast to the effects on healthy volunteers. All potent central nervous system depressant drugs possess the potential for significant cardiac depression. If such depression is undersirable in a particular patient, the only safe way to administer anesthesia is by careful titration of the dose against the best measurement of cardiac function which is available. At the present time, this would mean measuring at least direct arterial pressure, central venous pressure, and a continuous electrocardiogram. The optimal management would prpbably include recording systolic time intervals, pulmonary capillary wedge pressure, and some measure of cardiac output as well. All the skill and pharmacologic knowledge available connot substitute for vigilant monitoring and carful tiration of drug dose in the clinical situation.


[Occurrence, diagnosis and course of chronic hepatitis in weaned lambs of a flock of Texel sheep (author's transl)].

A disease of weaned lambs is described, which is attributable to chronic hepatitis marked by impaired secretion of cholephils in the acute or early stage and by inadequate growth due to persistent dysfunction of the liver during the subsequent or chronic stage. Regardless of its duration, the disease may be diagnosed in the living animal by determining the SDH and gammaGT activity levels, the total serum protein, the serum iron concentration and the serum iron-binding capacity.


[The use of analgesic and antiphlogistic agents in small animals (author's transl)].

The metabolism of many analgesic and antiphlogistic agents in dogs and cats differs markedly from that in man or other animals. When the known data on the subject are borne in mind, potentially toxic agents such as acetosal, phenylbutazone, ibuprofen and indomethacin may be used without much risk in various indications. It is pointed out that double-blind studies on the clincal effectiveness in patients unfortunately have not yet become available.


Hydro-proteolytic activity in rat's pancreas after irradiation.

Investigations were carried out on the problem of hydrolytic ability of rat's pancreas 24 h after whole body irradiation with the single dose of 800 R and after fractionated irradiation (5 x 150 R). Besides kallikrein, enzymes of intracellular digestion (B-glucuronidase, acid phosphatase, cathepsin) and enzymes of intraluminal digestion (amylase, lipase) were chosed for examination. It was stated, that single irradiation evokes rather moderate changes in the activity of examined enzymes causing increase of catheptic and lipolytic activity and decrease in amylase activity accompanied by sharp increase of kallikrein activity in the tissue. Mechanical obstruction of biliopancreatic duct renders trend to decrease of enzymatic activity in almost all enzymes of irradiated group. After fractionated irradiation the general increase of hydroproteolytic activity (with one exception of pancreatic amylase) was stated.


Radiation effects on rat testes. IX. Studies on oxidative enzymes after partial body gamma irradiation.

Oxidative enzymes in the rat testes have been studied after gamma irradiation. The role of these enzymes in relation to spermatogenesis and steroidogenesis after radiation injury to testis has been discussed. Loss of succinic dehydrogenase and sorbitol dehydrogenase reflects the losts of germ cell population. Malic enzyme and malic dehydrogenase seem to the related to the deficiency of steroid hormones, whereas increase in glucose-6-phosphate dehydrogenase and NADP isocitric dehydrogenase is due to secondary stimulation of pituitary.


24xi-Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate, a novel polyoxygenated marine sterol.

24xi--Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate has been isolated from an Alyconarian and its structure was established in part through extensive high resolution mass spectral and nmr studies and partly through the nonidentity of one of its degradation products with 24xi-methylcholestane-3beta, 5alpha, 6beta, 12alpha-tetrol synthesized from deoxycholic acid.


Bone marrow transplantation in the busulfan-treated rat. I. Effect of cyclophosphamide and rabbit antirat thymocyte serum as immunosuppression.

It was previously shown that lethal doses of busulfan (BU) were not immunosuppressive in the rat. In the present studies the effect of rabbit antirat thymocyte serum (RARTS) and cyclophosphamide (CY) as immunosuppressive preparation for marrow allografts in the rat given supralethal doses of BU was investigated. Lewis or LBNF rats were given RARTS for 4-12 consecutive daily doses. They were given a supralethal dose of BU in addition on the last day of RARTS administration. Ag-B-incompatible (ACI). Ag-B-compatible (F344), or syngeneic marrow was infused 24 hr later. In general, RARTS was not toxic to the marrow graft and permitted engraftment of Ag-B-incompatible and compatible marrow. All animals given Ag-B-incompatible marrow and Ag-B-compatible marrow that survived to day 21 were shown to be chimeric, but all those with incompatible marrow subsequently died from severe graft-versus-host disease (GVHD). In other experiments Lewis or LBNF1 rats were given Ag-B-incompatible (ACI) and compatible (F344) marrow after a supralethal dose of BU and single graded doses of CY. Doses of CY as low as 25-50 mg/kg provided sufficient immunosuppression to allow allogeneic engraftment. Transient chimerism was seen up to doses of 100 mg/kg of CY. Permanent chimerism was seen with doses of CY from 150 to 250 mg/kg. The incidence of lethal GVHD increased in parallel with the percentage of animals that were demonstrated to be chimeric. Mild but transient GVHD was seen with Ag-B-compatible marrow given to Lewis rats.