[Preservation of food wastes by a mixture of quinosol and salicyclic acid]. A 90-day experiment has shown that a number of toxic gaseous contaminants are released into the atmosphere as a result of storage of mixed food wastes. The microorganisms dwelling upon decaving food wastes include different microbial species from the environment and food products. A preserving agent consisting of a mixture of quinosole and salicylic acid (1:1) has been used. The agent inhibited microbial activity and terminated processes of decay. This was indicated by a decline in the concentration of ammonia and amine compounds. In the presence of the agent fermentation processes, on the contrary, continued and increased.


Treatment outcome in a drinking-decisions program. Of 98 alcoholics who were free to decide whether or not to drink during a 6-week inpatient treatment program, 55 chose to drink. The nondrinkers tended to show more improvement at a 6-month follow-up than did the drinkers.


Intellectual competence of alcoholics.

Intellectual competence of alcoholics. Alcoholic and psychiatric inpatients matched in age and education performed comparably on a battery of cognitive tests. The absence of impairment in the alcoholics is attributed to the relatively short duration of their alcoholism (mean, 7.2 years) and the nature of the tasks involved.


Field dependence and self-actualization in alcoholics. Field independence and self-actualization were significantly increased in alcoholic patients following a 6-week treatment program. There were no differences, however, between patients treated by drug-assisted individual therapy, individual therapy, or milieu therapy. Some causal factors are hypothesized, and implications for treatment are discussed.


Personality and temperament differences between alcoholics with high and low records of traffic accidents and violations. Significant differences on scales of the Guilford-Zimmerman Temperament Survey and the Minnesota Multiphasic Personality Inventory were found between alcoholics with high and low records of traffic accidents and violations.


Spouse response to a self-administered alcoholism screening test. A self-administered, expanded version of the Michigan Alcoholism Screening Test was completed by a group of hospitalized alcoholics and by their spouses and counselors, describing the patients. The data obtained from spouse responses was accurate in 90% of the cases; the spouse may be a more reliable source of information about drinking problems than the alcoholic.


The impact of specialized training in alcoholism on management-level professionals. Administrative and management-level social workers and nurses significantly increased their alcohol-related work activities during the year after they attended an 8-week alcoholism training program. Measures of attitude change, however, showed no appreciable differences.


A descriptive analysis of alcohol education materials. Analysis of 832 alcohol education materials (books, pamphlets and leaflets) indicates that the quantity and quality of the materials have increased in recent years. Alcoholism and the effects of alcohol are the major themes for all audience levels. There are few good quality resources for the junior-high and elementary school levels.


Defense mechanisms in men and women alcoholics. The responses of men and women alcoholics to the Defense Mechanism Inventory showed that the women scored significantly higher in "turning against self" and the men in "turning against others." Although such differences may underlie reported sex differences in the incidence of depression and sociopathic personality disorder, they have also been found in studies of nonalcoholics and psychiatric outpatients.


A report of a 1972 survey of physician's assistant training programs. This article presents select results of a 1972 survey of all physician's assistant training programs in the United States and its territories. The survey gathered a broad range of information useful to federal health manpower policymakers, physician assistant training program administrators, guidance counselors, and prospective students. Responses were received from 75 operational programs and 13 programs still in planning for an estimated response rate of 81 per cent from the estimated 108 programs in existence.


Peanut alkaline lipase.

Peanut alkaline lipase. Peanut alkaline lipase, (glycerol ester hydrolase EC 3.1.1.3), pH optimum 8.5, was isolated from acetone powders prepared from developing and germinated peanut seed (arachis hypogaea L. var. NC-2). Enzyme activity/seed increased in successive developmental stages. The course of the hydrolytic reaction was linear with regard to enzyme concentration and all times tested up to periods exceeding 60 min. Km for the reaction was determined to be 2.6 times 10-4M. Molecular weight of peanut lipase, as estimated by Sephadex gel filtration and sodium dodecyl sulfate gel electrophoresis, was ca. 55,000.


The clinical pharmacology of hypotensive vasodilator drugs. Drugs which lower arterial blood pressure by direct vasodilator action usually have to be combined with beta adrenergic blocking drugs and diuretics for maximum clinical effectiveness. Appreciation of the pharmacodynamic interactions is necessary to individualize drug programmes rationally. Vasodilator drug therapy is remarkable for the lack of side effects such as central nervous system effects, postural hypotension and sexual difficulties which usually characterize most "antiadrenergic" drug regiments.


Vasodilators in the treatment of hypertension. Vasodilator drugs play an important role in the treatment of hypertension in 1974. A powerful vasodilator such as diazoxide may be necessary in the control of the most severely affected patients. It should not be forgotten that drugs of the benzothiadiazine group probably act mainly as vasodilators and that their effect is not dependent upon natriuresis and diuresis. New vasodilators such as minoxidil may have an important role in the treatment of hypertension, but these have not yet been adequately assessed in Australia. Both hydrallazine and prazosin produce a significant fall in the blood pressure when added to a combination of a beta blocker and a diuretic, and double-blind studies have shown that the side effects are more predominant with hydrallazine than with prazosin.


The non-enzymic reduction of nitrite by benzyl viologen (free-radical) in the presence and absence of ammonium sulphate. Some similarity is inferred between the reaction or reduced benzyl viologen with undissociated nitrous acid, which is significant at pH values below 7 and that with the undissociated product of nitrite ion and ammonium sulphate; presumably ammonium nitrite. This would explain why the presence of ammonium sulphate appreciably offsets the effects of decreasing pH and also the exponential relationship between rate of nitrite loss and ammonium sulphate concentration. There are other features of the reaction which cannot be explained at present, especially with regard to the degree of reduction of benzyl viologen. It is nevertheless apparent that a complex non-enzymic reaction yielding several products occurs when ammonium sulphate is present and that the presence of likely residual quantities after its use in enzyme purification may cause serious errors in enzyme assay.


On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase. A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components.


["Drinking the waters" as a therapeutic exercise in the ionic range]. While "drinking the waters" (198 spa patients), longitudinal section inograms were made - Na, K, Ca, Mg, Cl, P and pH in serum, urine, saliva and perspiration were determined simultaneously and also the acid-base balance conditions in the blood by Astrup's method--and investigated from the point of view of the electrolyte metabolism. Carbonic acid absorbed from the intestine exerts a powerful action, triggering compensatory processes against acidification and leading to an increase in calcium and/or magnesium in the serum. Further, various changes in the ion concentrations, according to the mineral water, can sometimes be traced to an increase in the anion column and sometimes to hormonal effects (suprarenal cortex and medulla). They persist for several weeks after the course of treatment.


Diuretics, urate excretion and sodium reabsorption: effect of acetazolamide and urinary alkalinization. The uricosuric properties of acetazolamide were investigated in order to elucidate the relationship between changes in proximal tubular sodium reabsorption and urate excretion in man. Acetazolamide produced a modest uricosuric response which was not suppressible by pyrazinamide. Alkalinization of the urine with sodium bicarbonate elicited an even smaller increment in the urate clearance. If urinary alkalinization does play a role in the uricosuric response to acetazolamide, it probably decreases urate reabsorption within the distal nephron. The present studies, when taken together with previous work, suggest that alterations in proximal tubular sodium and water reabsorption probably do not play an important role in the normal control of urate excretion or in the pathogenesis of hyperuricemic states. Diuretic-induced hyperuricemia occurring during extracellular fluid volume depletion probably results from either diminished tubular secretion of urate, accelerated postsecretory urate reabsorption, or both.


Hyperuricemic nephropathy: pathologic features and factors influencing urate deposition. The three general types of renal pathology associated with hyperuricemia are reviewed. Factors influencing urate solubility are discussed, as well as the effect of uricosuric drugs on renal urate handling, with particular emphasis upon their efficacy in competing with urate for protein binding sites. In addition, a new experimental model of hyperuricemic nephropathy is described which could yield valuable data concerning the complex relationships between hyperuricemia, urate deposition and renal function.


Central nervous system findings in the newborn monkey following severe in utero partial asphyxia. Seizures, brain swelling, and cortical necrosis have been observed in the newborn rhesus monkey following a 2 to 4-hour period of intrauterine partial asphyxia produced by halothane-induced maternal hypotension. These clinical and neuropathologic findings are similar to those seen in human newborn infants who have experienced an episode of intrauterine asphyxia from such a cause as premature placental separation. The present study strongly indicates that fetal partial asphyxia, from any cause, in the absence of fetal circulatory collapse or fetal head compression, may be the primary event that sets in motion a vicious cycle of brain swelling and impaired cerebral blood flow, leading finally to cerebral necrosis.


[Crocodile tears syndrome].

[Crocodile tears syndrome]. Among 245 patients with peripheral facial nerve paralysis in 16 cases gustatory lacrimation was observed to remain as a sequel of paralysis. On the basis of clinical observation, testing of nerve excitability, Schirmer's test, examination of taste and laryngological examinations it was found that gustatory lacrimation occurs only in patients with complete and incomplete degeneration of the nerve situated most frequently at the ganglion geniculi or in the suprageniculate region. Already in the first stage of paralysis when degeneration of the nerve is found with lack or very marked reduction of lacrimation on the involved side it may be predicted with a high probability that crocodile tears will appear. In treatment of this phenomenon antihistamine and anticholinergic agents may be tried with good effects. In severe cases surgical intervention may be considered with elimination of the pathological reflex by sectioning the chorda tympani or Jaeobsen's nerve depending on the pathway of the reflex.


Metabolic studies of a family with massive formiminoglutamic aciduria. We have described two siblings who excrete massive amounts (up to 3.89 mmol/24 hr) of N-formiminoglutamic acid (FIGLU) in their urine. This unusual compound was isolated from urine, purified, and firmly identified as FIGLU by combined gas chromatography-mass spectrometry. The patients presumably have a deficiency in activity of the hepatic enzyme, glutamate formiminotransferase, which carries out the fourth sequential step in the main pathway of histidine degradation. Unlike children reported previously with this disorder, our patients had normal serum folate levels, had no hematologic abnormalities, and were not mentally retarded. Very small amounts of FIGLU were present in the plasma of one of the patients, but FIGLU was not detectable in the cerebrospinal fluid of either patient. Administration of pharmacologic doses of folic or folinic acid produced a decrease in excretion of FIGLU in urine. Histidine loading caused a small and comparable urinary excretion of FIGLU in the children's parents and in control adult subjects.


Symposium. ENT for nonspecialists. Serous otitis media. Serous otitis media is a capricious entity that can cause conductive deafness. The condition is most common in children, who often cannot describe the attending symptoms of deafness, fullness, and pressure. The basic contributing factor is inadequate function of the eustachian tube. Function improves as the child approaches 12 years of age. Underlying factors such as infections, adenoidal hypertrophy, and allergic states also must be managed. The otitis media may be treated medically or surgically.


Symposium. ENT for nonspecialists. External otitis. Simple treatment usually suffices for the control of acute external otitis, This consists of meticulous cleaning of the ear canal and application of antibiotic-corticosteroid drops. Good local care of the ear can prevent both the chronic and the acute forms of external otitis. Malignant external otitis is an uncommon but lethal type that most often accompanies diabetes. If this condition is diagnosed, hospitalization and aggressive treatment are then a necessity.


13-C nuclear magnetic resonance studies on the mechanism of action of carbonic anhydrase. Binding of the substrate, bicarbonate, to bovine cobalt carbonic anhydrase (carbonate hydrolyase, EC 4.2.1.1) has been studied with 13-C nuclear magnetic resonance. Two binding sites for bicarbonate have been identified. One loosely binds bicarbonate, inhibits p-nitrophenyl acetate activity, and must be the bicarbonate substrate binding site; the other tightly binds bicarbonate, is noninhibitory, and plays another role. Spinlattice relaxation times for the carbon atom of bicarbonate indicate that the substrate bicarbonate is bound directly to the metal center of the enzyme, while the other bicarbonate is bound in the outer coordination sphere of the metal. It is proposed that dehydration proceeds via HCO-3 minus coordinated directly to the metal center, while the outer sphere bicarbonate facilitates catalytically important proton transfers.


Nerve growth factor induces volume increase and enhances tyrosine hydroxylase synthesis in chemically axotomized sympathetic ganglia of newborn rats. Concomitant daily treatment of newborn rats for a 2-week to 1-month period with 10 mug/g of body weight of nerve growth factor and 100 mug/g of body weight of 6-hydroxydopamine produces in the cell bodies of adrenergic neurons the characteristic effects of the growth factor but in the nerve terminals the characteristic effects of 6-hydroxydopamine. The dual opposite effects result in a striking volume increase of sympathetic ganglia which far exceeds that produced by nerve growth factor alone. The selective induction of tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] in these chemically axotomized adrenergic neurons is even more pronounced than that produced by nerve growth factor alone in intact neurons.


Ultrastructural localization of tyrosine hydroxylase in noradrenergic neurons of brain. Tyrosine hydroxylase (EC 1.14.16.2), the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis, was localized by electron microscopy within noradrenergic neurons of the nucleus locus coeruleus of the rat brain with a specific antibody to tyrosine hydroxylase labeled by the peroxidase-antiperoxidase immunohistochemical method. Labeled cell bodies and their processes were easily distinguished from unstained neuronal elements in the neuropil. The hydroxylase was only seen in the neuronal cytoplasm. Its distribution in processes was different from that in cell soma. In longitudinal sections of axons and dendrites, the peroxides reaction product appeared as fiber-like strands aligned parallel with the plasma membrane. In cross section, the labeled structures had a diameter of 220 A and exhibited an orderly distribution within the processes. The size and distribution of the peroxidase-stained structures suggest that they are neurotubules. In the perikarya, the cytoplasm was diffusely stained; the reaction was most intense on membranes of endoplasmic reticulum and Golgi apparatus, whereas lysosomes and mitochondria did not stain. The ultrastructural localization of tyrosine hydroxylase is consistent with biochemical data suggesting that the enzyme exists in different states in cell body and processes. The ultrastructural identification of enzymes subserving synthesis of neurotransmitters in central neurons and their processes may provide a useful tool in mapping the distribution of chemically specific synapses on identifiable neurons in brain.


Life history of Coelomomyces psorophorae. The mosquito parasite, Coelomomyces psorophorae (Blastocladiales, Chytridiomycetes) alternates obligately between the larvae of Culiseta inornata and the copepod Cyclops vernalis. Isogametes, derived from heterothallic, wall-less gametangia which develop in the copepod, fuse to produce a diploid zygote that subsequently infects the mosquito host. Zoospores from the resistant sporangia which are produced in the haemocoel of the mosquito infect the copepod. A tentative life-history is proposed and implications of these discoveries for the biology, taxonomy, and possible role of Coelomomyces in biological control are discussed.


Role of amino groups in formation of human lymphocyte-xenogeneic erythrocyte rosettes; a proposed mechanism for antigen recognition. Formation of coulombic and possible hydrogen bonds between amino groups on human lymphocytes and negatively charged sites on sheep erythrocytes is involved in rosette formation. Supportive evidence includes rosette inhibition by chemical binding of lymphocyte membrane amino groups, and the results of changing the pH, ionic concentration, and temperature of the reaction. Although the possibility has not been excluded that the amino group dependence of this reaction is related to the property of certain proteins attached to the T-cell (thymus processed) surface, it is suggested that this dependence may be related to a charge pattern recognition in the form of "codes" present on the T-cell membrane. It is speculated that this type of recognition may be a contributory mechanism in the initiation of the T-cell-dependent immune response.


Lipoprotein lipase of ovarian follicles in the domestic chicken (Gallus domesticus) (38537). A lipase, bearing the characteristics of adipose tissue lipoprotein lipase (LPL) has been characterized in avian ovarian granulosa cells. The activity is low in cells from follicles weighing less than 0.5 g; in heavier follicles which have entered the rapid growth phase, significant activity (1 mumole fatty acid/mg protein/hr) could be identified. Granulosa LPL provides follicular tissues with the requisite enzyme system to hydrolyze very low density lipoprotein triglyceride en route to the oocyte.


Isolation and some characteristics of glutathione reductase from rabbit erythrocytes (38548). Glutathione reductase from rabbit erythrocytes was pruified to homogeneity and found to be a monomer with a mol wt of 60,000. Both NADPH and HADH were capable of acting as cofactors for the reduction of GSSG and the following kinetic values were obtained: Km, GSSG = 120 muM; Km, NADPH = 37 muM; Vmax = 23 mumoles NADPH/min/mg protein, Km, NADH = 420 muM; Vmax = 3 mumoles NADH/min/mg protein. Rabbit erythrocyte GR exhibited substrate inhibition, and was susceptible to inhibition by p-hydroxymercuribenzoate under certain conditions.


Mechanisms of oral staphylococcal enterotoxin B-induced emesis in the monkey (38553). Vomition is the most consistent response to oral SEB challenge in the monkey.  The technique of cross-circulation clearly differentiates local neural phenomenon from humoral mechanisms.  Our results support the theory that SED-induced vomition follows stimulation of local neural receptors in the gut.  The evidence indicates no significant amount of enterotoxin absorption or stimulation of vomition by any centrally acting humoral mechanism.


Effect of water and mouthwashes on pH of oral monkey mucosa. Among the many factors involved in homeostasis, maintenance of hydrogen-ion concentration is one of the most important functions of the body. Surface pH measurements of oral tissues after rinsing with water or mouthwashes are meager. This report presents results of the effect of tap water and 9 commercial mouthwashes on intraoral pH under controlled conditions. Nine rhesus monkeys, 5 females and 4 males between 3 and 8 years of age, were used in this study. During measurements they were sedated with phencyclidine hydrochloride and anesthetized with pentobarbital sodium. A Beckman pH meter with potassium chloride and silver chloride combination electrode was utilized. The pH was measured on the lingual gingva opposite the right lower first molar. Control readings were obtained, then a 30-sec pulsed-water-jet lavage with tap water with a force of 5 psi was given, and the pH was observed for 5 min. The 1 ml of mouthwash was administered on a thoroughly soaked gauze for 30 sec. This procedure was repeated 3 times on different days for each of the 9 mouthwashes used. All of the measurements showed a decrease in pH after tap-water lavage. In general, acid mouthwashes decreased the pH, while mouthwashes with alkaline pH's increased the pH of the oral tissues. The effects on pH was, however, transitory since the major change appeared within 8 min and approached equilibrium by 12 to 16 min.


Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. The effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat have been investigated. Haloperidol, perlapine and thioridazine induce catalepsy and enhance the turnover of DA in the striatum as indicated by the dose-dependent increase in the DA-metabolites, HVA and DOPAC. These effects are due to blockade of dopaminergic transmission, haloperidol being far more potent than perlapine or thiridazine. Clozapine differs from these agents in that it elevates the concentration of striatal DA. The increase of the concentrations of HVA and DOPAC by clozapine is not accompanied by development of catalepsy. Therefore, clozapine seems to influence striatal DA by a mechanism other than DA-receptor blockade. All four drugs enhance the turnover of NA in the brain stem. This effect is probably secondary to the blockade of NA-receptors. There was no correlation between the effects on NA-metabolism and the EEG-arousal inhibitory activities of these agents or their clinical antipsychotic effects. Clozapine increase the concentration of 5-HT and 5-HIAA in the brain. This effect was not seen with the other drugs. Perlapine seems to enhance the turnover of 5-HT, whereas haloperidol reduced the 5-HT concentration. Thioridazine appears to have no effect on the metabolism of 5-HT.


Effects of iproveratril on isolated heart mitochondria. The effects of iproveratril on oxygen uptake and oxidative phosphorylation of succinate, glutamate and alfa-ketoglutarate were studied. Oxidative phosphorylation and oxidation of NAD+-linked substrated by heart mitochondria were depressed by 1.15 times 10-3M iproveratril. The activity of NADH-oxidase, NADH-cytochrome c reductase and heart mitochondrial transporting particles were depressed by iproveratril. When succinate was the substrate oxidative phosphorylation was depressed but oxygen uptake was stimulated about 370%. Swelling induced by iproveratril was analysed by electron microscopy.


Coenzyme specificity in the glycolysis of intraocular fluids. Toward elucidation of the glycolysis in the vitreous and aqueous of several animal species, coenzymes of this scheme, NAD, NADH and ATP were assayed but found to be virtually absent. To further assess this pathway, ADP and NADPH in addition to the above were introduced singly and in combination with 0.20 ml-aliquots of the guinea pig aqueous and vitreous under anaerobic conditions and the absorbance followed spectrophotometrically at 340 nm. Only NADH produced an immediate observable response and the rate of change was greater for the virteous. The action of oxamate and iodacetate was also screened. The experiments point to the LDH-catalyzed step as responsible for the observed effect.


Evidence for a small functional pool of serotonin in neurohumoral transmission. "Scottie Cramp" is a genetic neurologic disease which occurs in the Scottish terrier  breed of dogs. Decreasing central nervous system (CNS) concentrations of serotonin (5-HT) via para-chlorophenylalanine (pCPA) will profoundly increase the severity of the disease although the basic defect does not involve serotonergic neurons. The purpose of this study was to attempt to correlate the effect of p-CPA on the clinical signs of the disease with the alteration in serotonin synthesis and concentration in the CNS. Synthesis was estimated by following the rise in cisternal cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations with time following probenecid injection. Concentration of serotonin in the CNS was estimated by measuring cisternal CSF 5-HIAA concentrations. The results suggest that serotonin may be synthesized in excess of neuronal transmitter needs and that the estimation of whole brain turnover rates and concentrations of 5-HT may not yield a true measure of serotonergic neuronal activity.


Myocardial function during hypoxia: protective effect of dimethyl sulfoxide (DMSO). Electrically driven rabbit left atria were exposed to 20 min periods of hypoxia in the presence and absence of dimethyl sulfoxide (DMSO) or sucrose. Contractile strength declined significantly less than control when tissues were exposed to DMSO during hypoxia. On reoxygenation tissues treated with DMSO recovered pre-hypoxia contractile strength more slowly. Sucrose did not protect tissues during hypoxia. Comparison of results with DMSO and sucrose indicated that tissue depression prior to hypoxia could not explain the action of DMSO. Kinetic analysis performed on tension decline which occurred during hypoxia showed that two components were involved; rate of tension loss in both components was decreased by DMSO and there was a shift in the percentage of decline to the slower component. These data indicate that DMSO may increase energy availability, increase efficiency of energy utilization, or possibly affect the shift from aerobic to anaerobic metabolism during hypoxia, but not during the post-hypoxic recovery period.


Effect of gastric surgery on the gastrointestinal drug absorption in man. The effect of gastric surgery on the absorption of quinidine, ethambutol, and sulphafurazole was studied in 14 male patients, all serving as their own controls. Antrectomy with gastroduodenostomy (ABI) and selective vagotomy lowered the serum levels of all drugs significantly during the 6-hour test period. Excretion of drugs in 6-hour urine also decreased. Three patients showed practically no absorption up to 2 hours, and even therafter the absorption was lowered. Over one year after operation the urinary excretion of ethambutol, but not of the other drugs, was improved. ABI alone did not modify absorption. Preoperative gastric retention seemed to delay absorption.


The effect of duodenal juice on the intrinsic factor (IF) activity in gastric juice. Duodenal juice, collected during basal conditions and during stimulation by pentagastrin, secretin, or cholecystokinin, was incubated with neutralized normal gastric juice. High concentrations of bile or proteolytic activity were accompanied by decrease of IF concentration. The inhibition was time- and temperature-dependent, increased significantly at low pH values, and seemed to be partly due to competitive inhibition by unspecific vitamin B12-binding activity. The results are of importance for measurements of IF concentration in gastric juice.


The effect of carbachol and pentagastrin on the gastric secretion of acid pepsin, and intrinsic factor (IF) in man. Intravenous infusions of carbachol and pentagastrin were given separately or simultaneously in 6 healthy students. The volume of gastric secretion and the concentration and output of acid, pepsin, and IF increased significantly during infusion of carbachol alone, whereas the plasma gastrin concentration remained unchanged. Carbachol had no effect on the acid, pepsin, and IF secretion by pentagastrin. The results indicate an effect of carbachol on acid, pepsin, and IF secretion, independent of changes in plasma gastrin concentration. No synergistic or potentiating effect was demonstrated between carbachol and pentagastrin.


The effect of atropine and vagotomy on the secretion of gastric intrinsic factor (IF) in man. The gastric secretion of IF, acid, and pepsin during basal conditions and stimulation by pentagastrin decreased significantly in 8 unoperated duodenal ulcer patients following administration of atropine. The basal concentrations of acid and pepsin decreased, whereas that of IF remained unchanged. An increase of plasma gastrin concentration from the basal value was observed after injection of atropine alone. The secretions of IF and acid decreased significantly from the pre-operative values after proximal gastric vagotomy in 7 duodenal ulcer patients. The basal IF output decreased by 19.8 per cent and the stimulated output by 41.4 per cent. The basal and stimulated secretions of acid decreased by 50.0 and 44.1 per cent, respectively. It is suggested that the smaller reduction of IF than of acid may be of importance for the vitamin B12 absorption after vagotomy. The decreased secretion of IF was secondary to the reduction of volume both after'medical' and surgical vagotomy.


Intragastric pressure/volume relationship before and after proximal gastric vagotomy. The examinations were performed before and after proximal gastric vagotomy (PGV) in 10 patients with duodenal ulcer. A flaccid plastic balloon located in the corpus-fundus region was stepwise filled with known volumes of water. Post-operative insulin tests were negative in 8 patients and late positive in two. Basal and pentagastrin-stimulated acid output were reduced by a mean of 88 and 62 percent, respectively. Intragastric pressure was significantly increased after PGV, whereas rhythmic contractions were reduced in all cases. It is concluded that PGV interferes with gastric motility and adaptation to volume variations.


Gastric acid response to antrum distension in man. Gastric acid secretion under basal conditions and in response to graded balloon distension (50 ml, 100 ml, 150 ml) of the antrum was determined in healthy subjects and in peptic ulcer patients. In patients with a quiescent duodenal ulcer or a gastric ulcer antrum distension produced slight acid responses. The acid response to antrum distension was of quantitative importance only in patients with an active duodenal ulcer, amounting to 35 percent of the maximal acid response to pentagastrin. The healthy subjects did not respond with acid secretion to antrum distension. The pH of the gastric contents in the present series was 1.8-3.0, being lowest in patients with an active duodenal ulcer. Thus, the acid secretory effect of mechanical stimulation of the antrum seems qualitatively different in healthy subjects and ulcer patients, with a marked acid response in patients with an active duodenal ulcer.


[Thyreotoxic crisis triggered by stimulation of the adrenal gland medulla]. Thyroid storm was observed in a patient with Grave's disease after stimulation of release of epinephrine and norepinephrine with 2-DG. Measurements of catecholamine secretion before and during onset of thyrotoxic crisis suggested the important bearing of increased activity of the sympathetic nervous system on pathogenesis of thyroid storm.


Influence of the ionic composition of the medium on the sensitivity of fertilized sea urchin ova to neuropharmacological preparations. The removal of Ca2+ from the incubation medium leads to an increase in the sensitivity of early sea urchin embryos to neuropharmacological blockers of development. The removal of SO4-2-, half of the K+, as well as an increase in the Ca2+ content, have no effect on the sensitivity of fertilized eggs to these preparations. The sensitivity to puromycin, colchicine, triton X-100, and 2, 4-dinitrophenol is unchanged by the removal of Ca2+ from the medium. The protective action of exogenous monoamines and acetylcholine is not manifested in a solution that does not contain Ca2+. Serotonin, catecholamines, and acetylcholine have no appreciable effect on cleavage either in sea water of normal composition or in water without Ca2+.


Chromatographic separation of pigments produced by Arthroderma benhamiae. Variations in pigment production under different cultural conditions have limited the usefulness of pigmentation for identifying strains of Arthroderma benhamiae. If culture conditions are constant, pigmentation by individual strains is reproducible, and may be extracted and separated by thin layer chromatography. This allows recognition of pigment similarities which may be masked in whole colonies, thereby greatly enhancing the value of pigmentation in strain identification.


Effect of ischemic anoxia on myoelectrical and mechanical activity of the totally isolated canine stomach. Electrical and mechanical activities were recorded from the totally isolated canine stomach perfused with homologous blood of a living oxygenator-supported dog. Stagnant ischemic anoxia was induced by closing inflow and outflow blood from the isolated organ for various periods of time up to four hours. Recording of electrical and mechanical activity was performed prior to, during, and after the anoxic periods. After a given period of ischemia, blood was recirculated for ten minutes, and the pentagastrin was injected into the gastric artery. After up to three hours of anoxia, stomachs were able to show recordable electrical activity when perfused for ten minutes with homologous blood. Up to this period of three hours, stomachs also responded to the injection of pentagastrin. Pentagastrin accelerated the normalization of electrical and mechanical activity of previously anoxic stomachs. After 3.5 to 4.0 hours of anoxia, recirculation of blood through the stomach and injection of pentagastrin had no effect on electrical and mechanical activity of the gastric musculature.


Heart transplantation in endotoxin shock. The condition of the heart from dogs in endotoxin shock was evaluated, and all dogs in the control group receiving 5 milligrams per kilogram to Eschericia coli endotoxin died within two to 14 hours. Hearts from four other dogs receiving the same dosage of endotoxin were allografted orthotopically into healthy recipient dogs. The donor heart was taken in the terminal phase of shock, after the blood pressure of the donor had declined to 50 millimeters of mercury or less. All four heart allografts functioned normally in the healthy hosts, demonstrating that lethal levels of gram-negative endotoxin do not produce direct irreversible damage to the myocardium or to the conduction mechanism of the heart. This also was shown in one pair of monkeys; the donor monkey had received ten times the dosage of endotoxin used in the dogs. This heart transplant model offers considerable advantage in functional studies of the heart after irreversible shock.


Spontaneous rupture of the liver and the spleen: report of a successfully treated case with immunopathologic reaction. A patient with a spontaneous rupture of the liver, followed by a spontaneous rupture of the spleen and gastrointestinal bleeding, is reported. The patient was operated for both ruptures and survived. We could not find any corresponding reports in the literature. Histological findings both in the liver and in the spleen were suggestive of an acute immunologic reaction and the symptoms of the patient resembled those of an autoimmune disease. Attention is drawn to the possibility that the ruptures of the liver and the spleen might have represented an allergic reaction reminiscent of the general type of Schwartzman reaction. This also could explain the other systemic manifestations of the disease. In the present patient steroid therapy eliminated all symptoms, and this possibility should be kept in mind when treating obscure ruptures of the liver and the spleen.


Analysis of results of catheter tip cultures in open-heart surgery patients. A statistical analysis of 628 consecutive catheter tip cultures is presented. All were from patients undergoing open-heart surgery. The previously noted effects of early removal are shown to be significant. The possible effects of stasis, flushing, handling, and place of insertion are discussed. The unresolved significance of isolations of aerobic sporing bacilli is noted, and a decreasing incidence of postoperative infective endocarditis in the same group of patients is an encouraging sign.


The lungs in renal failure.

The lungs in renal failure. Pulmonary function was studied in 55 patients with renal failure and no clinical or radiographic evidence of lung disease. A defect of gas transfer was found to be the rule due to a reduction in the diffusing capacity across the alveolar capillary membrane; this abnormality appeared to be related to the severity of the renal impairment. There was also a restrictive ventilatory defect which was more marked in male than in female patients. The significance of these findings is discussed, and attention is drawn to their relevance for patients receiving immuno-suppressive therapy or renal transplantation, in whom pulmonary complications are relatively common.


Comparative effects of beta adrenergic blocking drugs. Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action ("local anaesthetic effect" or "quinidine-like effect"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further.


Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat. Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants.


Toxicity of aerosol propellants in the respiratory and circulatory systems. VII. Influence of pulmonary emphysema and anesthesia in the rat. Experimental induction of pulmonary emphysema caused an increase in sensitivity of the rat to toxicity from inhalation of propellants. The emphysematous rat showed an exaggerated reduction in pulmonary compliance in response to inhalation of trichlorofluoromethane (FC 11). In emphysematous and non emphysematous rats without anesthesia the inhalation of FC 11 caused tachycardia, arrhythmias and other abnormalities in the electrocardiogram. The tachycardiac response was eliminated by induction of barbiturate anesthesia, which increased the sensitivity of the heart to occurrence of abnormalities in the electrocardiogram in response to inhalation of FC 11 as well as of dichlorodifluoromethane (FC 12) and difluoroethane (FC 152a). The acceleration in heart rate in response to inhalation of FC 11, hypoxia or hypercapnea was prevented by prior treatment with a beta-blocking drug.


Immunological aspects of the acquired B antigen. Nine cases of acquired B antigen were studied. By quantitative methods the variation of the A reactivity and of the number of A sites was found to be inversely related to the variation of the B reactivity. By agglutination kinetics using an immune anti-B, the acquired B reactive structure was found to differ from that of a normal B. Agglutination variation, with pH, points out to the part played by one electrically charged chemical group. No transferase galactosyl activity was found in the serum, and no B substance in the plasma. According to these results the B reactive structure must have been formed at the expense of the A reactive structure. This "acquired B" type may have arisen as a result of the action of a bacterial deacetylase, transforming the A reactive N-acetyl galactosamine into galactosamine.


True Arrhenius relationships of human lactate dehydrogenase. The pyruvate and NADH concentrations and the buffer pH which gave maximal activity with LDH isoenzymes derived from human heart and liver tissue were established for the temperatures 25 degrees C, 30 degrees C, 35 degrees C, 37 degrees C,, 40 degrees C, 45 degrees C, and 50 degrees C. The velocities of the LDH isoenzymes using these maximal assay conditions were used to obtain Arrhenius plots, i.e. log initial velocity against inverse absolute temperature. The Arrhenius plots were linear with both isoenzyme preparations up to 45 degrees C. Between 45 degrees C and 50 degrees C it appeared that this linear relationship no longer held, particularly with the liver tissue. When the activation energies were calculated both isoenzyme preparations exhibited several points of inflexion, in each case occuring at the same temperatures. These inflexions represent a change in the reaction kinetics, possibly a conformational change in the enzyme. The results also indicate that the LDH 1 and 2 isoenzymes are more efficient than LDH 4 and 5.


[Calculation of the parameters of the acid-base balance with the aid of a small computer]. The application and modification of a program published by Hardt (1972), Clin. Chem. 18,658--661) for the calculation of the true pCO2, the standard bicarbonate and the base excess are reported. 217 Determinations of a random patient sample were evaluated graphically, with the aid of a nomogram of Siggaard-Andersen, and mathematically with a computer program. There was good agreement between the two evaluation methods.


[Sialic acid in F. tularensis and F. novicida antigens]. Sialic acid was revealed in the antigens of virulent (503/830 and Schu) and vaccine (Schu-attenuated and 15-reduced) strains of F. tularensis and also in the antigens of F. novicida isolated by the treatment with trichloracetic acid, by the thiobarbiturate method of Warren. Its content depended on the culture virulence. Sialic acid was absent in the antigens of avirulent strains of the causative agent of tularemia (503-attenuated, 15-attenuated and 21/400), but, in difference from the virulent strains, there was revealed 2-desoxyribose on account of the presence of DNA. Serological activity of F. tularensis antigen decreased only 15 times in the antibody neutralization reaction after a complete release of sialic acid as a result of hydrolysis of the preparation in 0.1 N, H2SO4 at 80 degrees C for one hour, i.e. it persisted at a sufficiently high level. On the basis of investigations carried out it can be admitted that there existed a chemical association between the sialic acid and other composites in the polysaccharide of the virulent and the vaccine strains of F. tularensis, but that this acid played no significant role in the manifestation of specific properties by the antigen.


[Identification of mycoplasmas isolated from monkeys]. The authors identified 15 strains of mycoplasmae isolated from Papio hamadryas suffering from leukemia and from healthy Macacus rhesus, a green monkey and saimiri. A study was made of their biochemical properties, antigenic properties in the reaction of growth depression with immune sera to a number of standard strains, and also the protein composition by electrophoresis in polyacrylamide gel (EPAG). A number of mycoplasmae were identified as A. laidlawii, M. arthritidis--Campo and M. cynomolgus KI, affilated to M. orale II. Four strains were apparently a mixture of three mycoplasmae (M. cynomolgus KI, M. arthritidis--Campo, and M. hyorhinis). Six strains of mycoplasmae (three enzymatically active, belonging according to EPAG data to a single serological type, and three--enzymatically inert, differing by EPAG) could not be identified.


[The possibility of predicting the degree of plasmacyte reaction in response to administration of soluble antigen to mice]. The work is devoted to the mathematical description of the accumulation of plasma cells in the spleen of CBA mice immunized intraperitoneally. A dependence between the dynamics of the soluble antigen concentration in the blood and the plasmocytic reaction in the spleen was confirmed under experimental conditions. Index A was suggested for detection of a change from the antigenic function to the accumulation of plasma cells. The mean values of index A were used to compare the calculated values of the plasmocytic reaction and the experimental data; differences between these values were insignificant. Analogously index A was used for predicting the accumulation of plasma cells in the animals to which a mixture of the two soluble antigens (a capsular antigen of the causative agent of plague and a complete antigen of the causative agent of tularemia) was administered. The calculated values of the plasmocytic reaction in this experiment satisfactorily correlated with the data obtained experimentally.


Chemical dissection of mammalian spermatozoa. Mammalian spermatozoa have been dissected by a variety of chemical techniques to yield free heads, tails with attached midpieces, and tails without mitochondria. By brief exposure to trypsin, mouse and rat spermatozoa were cleaved at the junction of the head and the tail, while human, guinea pig and rabbit spermatozoa were cleaved by trypsin only after prior incubation with a sulphhydryl reducing agent. Treatment with acid or base cleaved spermatozoa of all species examined. In contrast, exposure of spermatozoa to 1% sarkosyl NL-97 resulted in the quantitative cleavage of mouse cells without noticeable effect on the spermatozoa of the other species. Mitochondria were removed from the midpiece of intact sperm and isolated tails by gentle shaking after treatment with reducing agents. Homogeneous populations of spermatozoan subcellular components were obtained by density gradient centrifugation. Ultrastructural analysis showed that cleavage of mouse spermatozoa by trypsin occurs at a specific location in the neck of the cell without trypsin occurs at a specific location in the neck of the cell without observable damage to other cell structures. The basal plate remained attached to the head structures. In contrast cleavage of spermatozoa by sarkosyl or acid left the basal plate attached to the spermatozoan midpiece. Sarkosyl also removed the plasma membrane and extracted mitochondrial components. Treatment with acid or base also resulted in vesiculation of the plasma membrane and dissolution of the acrosome. Molecular probes have also been used to facilitate mapping of the cell surface. Each mouse spermatozoon has about 10-7 receptors for the lectin concanavalin A. Binding of fluorescein-labelled concanavalin A indicated that the majority of the receptors is in the acrosomal region; this polar distribution was confirmed by measurement of the number of sites on purified heads and tails. In addition, the low molecular weight probe ANS bound to the plasma membrane of spermatozoa from all species examined, with immediate immobilization of the cells. Ethidium bromide bound to the spermatozoan head without affecting motility.


Fibrinoid necrosis of liver parenchymal cells. By means of different histological and histochemical investigations and fluorescence microscopy it has been possible to demonstrate fibrinoid necrosis of parenchymal liver cells in cases of delayed chloroform death and in septic, toxic and infectious hepatitis. This type of necrosis has previously been observed only in connective tissue and in vessel walls, in particular in collagenoses. It was also possible to provoke this type of liver cell necrosis in animal experiments. Reference has been made to differences in the chemical composition of the fibrinoid substance and to relations to other related substances (amyloid, keratin, fibrin). The importance of fluorescence microscopic invesitgations with fluorochromes, using Novelli's method, and with certain other procedures is emphasized.


Subcellular distribution of amino acid naphthylamidase isozymes in human leucocytes. Three isozymes (A, B and C) of amino acid naphthylamidase were found in human leucocytes. Isozyme B and C had close biochemical similarities and differed from isozyme A. Isozyme A was localized in the cytosol. Results obtained by combining electrophoresis with gradient centrifugation suggested that isozyme B originated in granules of polymorphonuclear leucocytes enriched in alkaline phosphatase. Isozyme C was found in granules of low density of polymorphonuclear as well as mononuclear leucocytes.


Natural antibodies in healthy adults.

Natural antibodies in healthy adults. The serum of 100 adults living in Budapest was examined for isohaemagglutinin titre with haemaglutination, for staphylococcal-antitoxin titre with haemolysis inhibition and for bacterial antibody titre against 17 different groups of bacteria with passive haemagglutination. Antibody levels in males, except for certain bacterial antibodies, were somewhat lower than in females. The antibody titres, especially in men, decreased gradually from 20 to 50 years of age and were usually lower in Rh negative than in Rh positive persons.


The thyroid in ulcerative colitis and Crohn's disease. I. Thyroid radioiodide uptake and urinary iodine excretion. In order to investigate the prevalence of iodine depletion in chronic inflammatory bowel disease two separate studies have been performed. One was devoted to the 24-hour urinary iodine excretion and 50 patients with ulcerative colitis or Crohn's disease were examined and compared with 102 controls. In the other study the thyroid 131I uptake was compared in 38 patients and 36 controls. Ten of the 50 patients with chronic inflammatory bowel disease had a 24-hour urinary iodine excretion less than 40 mug, compared with 5 of the 102 controls (p greater than 0.01). Sixteen of the 38 patients had a 24-hour thyroid 131I uptake of 50% or more of the administered test does, compared with 4 of the 36 controls (p smaller than 0.01). These results are compatible with an increased occurrence of iodine deficiency in patients with chronic inflammatory bowel disease. Treatment with corticosteroids or Salazopyrin or a milk-free diet did not influence these findings. No evidence was found of an impaired absorption of inorganic iodide from the gut.?31


Circulatory effects of tazolol in experimental myocardial infarction. The hemodynamic effects of tazolol, a new long-acting beta-stimulating drug, were studied in dogs with acute pump failure caused by experimental myocardial infarction and the results were compared with the actions of isoproterenol given in small and large doses. Tazolol produced a significant and sustained increase in cardiac output and stroke volume, while causing a decrease in peripheral resistance and mean aortic pressure. Heart rate was only modestly increased. Compared with isoproterenol at equivalent doses. tazolol appeared to cause less S-T segment elevation at the margin of infarction. The increase in double product (systolic pressure X heart rate) produced by tazolol was also considerably less than that of isoproterenol. Tazolol may prove to be a useful addition to the drugs available for the treatment of myocardial failure of various causes. It is now being studied in patients with heart failure due to coronary artery disease.


Double-blind comparison of the effectiveness of azathioprine and sulfasalazine in idiopathic proctocolitis. Preliminary report. A double-blind therapeutic trial of azathioprine in 20 patients with acute proctocolitis was performed over a 3-month period. Azathioprine was compared with sulfasalazine in patients paired and treated in a sequential order. Clinical, laboratory, endoscopic, biopsy, and radiologic data were assessed by semiquantitative criteria. No significant difference in the effect of the drugs was observed. Both azathioprine and sulfasalazine produce significant improvement in clinical symptoms, some laboratory findings (ESR, serum iron), and endoscopic and biopsy findings (P smaller than 0.05). Radiologic improvement was less evident (P smaller than 0.10). On the overall final evaluation of the trial, 14 patients were improved, and 6 remained stationary or worsened (P smaller than 0.10). This short-term trial confirms previous uncontrolled experiences of one of the authors on larger series of patients.


Influence of the proximal small intestine on the gastric hypersecretion in pylorus-ligated rats. The mechanism of the gastric secretory inhibition caused by the simultaneous ligation of the upper and lower duodenum or the jejunum in pylorus-ligated rats was studied. The data obtained from the experiments on surgical manipulation of the small intestine indicated that the absorption of certain substances appeared to be important in maintaining gastric secretion of pylorus-ligated rats. The participation of biliary secretion was negligible, while the ligation procedure per se, which results in the accumulation of duodenal contents, might be partly involved in the mechanism of acid secretion. Pharmacological techniques suggested that the inhibition appeared to be independent of cholinergic nervous reflex and hormonal influence, which is assumed to be released by intestinal acidification.


Inhibitory effect of bromazepam on insulin-stimulated gastric acid secretion in man. The action of bromazepam on insulin-stimulated gastric acid secretion was examined in 5 healthy volunteers in a randomized study. To measure acid output, the intragastric titration technique and a pH-sensitive telemetering capsule were used. Three series of experiments were performed: (1) insulin (0.2 U/kg body weight), stimulation alone; (2) simultaneous injection of insulin and bromazepam (0.1 mg/kg body weight), subjects kept awake; (3) synchronous injection of insulin and bromazepam but with subjects allowed to fall asleep after drug administration. In all three series after insulin administration a significant initial inhibition of gastric secretion occurred. There were no significant differences between the three series regarding the intensity of hypoglycemia. Blood glucose levels lower than 25 mg/100 ml were reached in all experiments. Bromazepam in subjects kept awake caused drowsiness and a lower gastric acid response to hypoglycemia as compared to insulin alone, but the difference was not significant. In subjects allowed to sleep, this reduction was marked and gastric acid output was significantly lower than in both other series. These findings suggest that sleep and drowsiness, rather than bromazepam itself, cause inhibition of insulin-induced gastric secretion.


Ecologic studies of Venezuelan encephalitis virus in Peru during 1970-1971. Venezuelan encephalitis (VE) virus has intermittently produced epidemics and equine epizootics on the dry Pacific coastal plain of Peru since at least the 1930's. However, evidence that the virus exists in the Amazon region of Peru to the east of the Andes mountains was not obtained until antibodies were found in human sera collected in 1965, and 10 strains of the virus were isolated in a forest near the city of Iquitos, Peru during February and March 1971. Eight strains came from mosquitoes and two from dead sentinel hamsters. Three hamsters exposed in forests near Iquitos developed VE virus antibodies suggesting that hamster-benign strains also exist there. Antibody tests of equine sera revealed no evidence that VE virus was actively cycling during the late 1950's or 1960's in southern coastal Peru, where equine epizootics had occurred in the 1930's and 1940's. In northern coastal Peru bordering Ecuador, antibodies were present in equine sera, presumably residual from the 1969 outbreak caused by subtype I virus, since neutralizing antibody titers were higher to subtype I virus than to subtypes III or IV. No VE virus was detected in this northern region during the dry season of 1970 by use of sentinel hamsters. The possibility is considered that VE epidemics and equine epizootics on the Pacific coast of Peru are caused by movements of virus in infected vertebrates traversing Andean passes or in infected vertebrates or mosquitoes carried in airplanes from the Amazon region.


Antigenic and biologic characteristics of Venezuelan encephalitis virus strains including a possible new subtype, isolated from the Amazon region of Peru in 1971. Nine strains of Venezuelan encephalitis (VE) virus isolated from the Amazon region of Peru in 1971 were identified as antigenic subtype I based on plaque-reduction neutralization tests with four and 20 units of antibody. A tenth strain, 71D1252, was possibly a new subtype, but was related to subtypes I and III. Hemagglutinins of each strain made from infected mouse brains had optimals pHs of 6.2 and 6.4. Nine strains were pathogenic for adult hamsters and adult mice, but strain 71D1252 inapparently infected some adult hamsters and mice inoculated peripherally. Plaques of nine strains in Vero African green monkey kidney cell cultures were intermediate in size between representative epizootic and enzootic strains, but plaques of strain 71D1252 were small like epizootic strains.


Effect of briefly heating cyclophosphamide solutions. Solutions containing cyclophosphamide monohydrate were heated to 50 C, 60 C, 70 C and 80 C for 15 minutes and then assayed for potency. Solutions heated to 50 Cor 60 C did not change appreciably; those heated to 70 C and 80 C assayed at 90.2% and 77.5%, respectively, of initial potency. The values compared well with those calculated using the Arrhenius equation. It is concluded that warming vials of cyclophosphamide monohydrate after adding an aqueous vehicle (in order to achieve rapid dissolution) could decrease the potency of the final injectable product.


Current therapy of hypertension. A pharmacologic approach. Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents. Although no drug is without adverse reactions, it should be possible to choose an agent or combination of agents which can effectively lower blood pressure and be tolerated by the patient. The indications, proposed mechanisms of actions and adverse effects of the following antihypertensive drugs are discussed: thiazide diuretics, spironolactone, triamterene, trimethaphan, Rauwolfia alkaloids. guanethidine, bethanidine, methyldopa, clonidine, pargyline, propranolol, hydrazaline, minoxidil, guancydine, diazoxide and sodium nitroprusside.


Adverse reactions and interactions limiting the use of antihypertensive drugs. One major problem in the management of hypertensive patients is their lack of compliance with therapeutic regimens. Some of the problem with compliance is due to side effects of the drugs being used. Additionally, drug resistance may be related to interactions of antihypertensive drugs with other prescription and nonprescription drugs. By classifying drugs into common modes of action, common side effects can be predicted. However, each drug has its own spectrum of other side effects which can be dose-limiting. Most of the side effects are extensions of the pharmacologic actions of these drugs, and only relatively rarely is an allergic reaction a problem. Drug interactions can be important in explaining some side effects or drug resistance. A knowledge of the pharmacology of the antihypertensive drugs allows the physician to predict, in many cases, the possibility of an interaction and, indeed, can allow the use of interactions to advantage as with combinations of vasodilators and beta adrenergic blocking drugs. Until such time as the perfect antihypertensive drug is discovered, most patients can be managed satisfactorily with minimal side effects by judicious combination of available drugs and avoiding drugs which interact to cause more side effects or decrease the antihypertensive effects.


Aqueous humor pH changes after experimental alkali burns. Following application of 2N sodium hydroxide, or 8.1N ammonium hydroxide to rabbit cornea, the aqueous humor pH reached a maximum of 10.2, 11.9, and 12 within six minutes following 20-, 50-, and 100-mu1 sodium hydroxide burns, respectively; after two hours the pH had fallen to 8.5, 10, and 10.5. The maximum rise following application of 100-mu1 of ammonium hydroxide was 10.8, declining to about 9 at two hours. The fall in pH following a 100-mu1 sodium hydroxide burn was not greatly influence by external lavage. However, the pH was significantly lowered (12 to 10) by paracentesis alone and further reduced by immediate or delayed intracameral administration of phosphate buffer. On the basis of these results moderately severe and severe alkali burns of the eye should be treated by paracentesis and if possible with anterior chamber reformation with a sterile solution.


Ophthalmic manifestations of Aarskog (facial-digital-genital) syndrome. Four boys with facial-digital-genital or Aarskog syndrome were whort with triangular faces, characteristic deformities of the hands and feet, and anomalies of the external genitalia. The syndrome appears to be inherited in an X-chromosomes-limked recessive manner. Previous reports emphasized the presence of hypertelorism but careful measurements of the interorbital dimensions revealed primary telecanthus in addition to hypertelorism. The palpebral fissures had a marked antimongoloid obliquity and in half the reported cases, there was unilateral or bilateral congenital blepharoptosis. Strabismus, hyperopic astigmatism, and large corneas may be additional features.


Steady-state glucose oxidation by dog kidney in vivo: relation to Na+ reabsorption. In eight experiments at normal or slightly elevated blood glucose concentration we quantified the steady-state renal glucose oxidation rate (see article) during control, at reduced Naomega absorptive rates (raised ureteral pressure), and during respiratory alkalosis. A tracer amount of either [1-14C]glucose or or [U-14C]D(omega)-glucose was infused at a constant rate into one renal artery. (see article) was calculated from the renal 14CO2 production rate (corrected for recirculation) and the specific activity of glucose in renal arterial blood. The control (see article) (n equals 8) equals 4.40 plus or minus 0.9 mumol/100 g-min (mean plus or minus SE). When net Naomega reabsorption was decreased by 45% (n equals 6), or when the pH of extracellular fluid was raised (n equals 2), no significant effect on (see article) (9.1 plus or minus 4.2 and 3.9 plus or minus 2.3 mumol/min-100 g, respectively) occurred. The mean glucose oxidation rate for all experiments was 5.65 plus or minus 1.73 mumol g-1-min-1 and required similar to 13% of the renal O2 utilization. Glucose oxidation provides energy either for basal renal work or for some portion of renal transport work not affected by increased ureteral pressure.


Neuroleptics, catecholamines, and psychoses: a study of their interrelations. The authors examined central catecholamine metabolism in various symptomatological psychotic disorders and the relationship between the biochemical and therapeutic action profiles of neuroleptics. Haloperidol and (to a lesser entent) chlorpromaziner icrease the dopamine (DA) turnover in the central nervous system, but the authors influenced; oxypertine has the reverse effect. The authors question whether disorders of DA-metabolism underlie or result from disorders of motor activity, postulating that the hyperdopaminergic activity observable in psychoses is dependent on motor hyperactivity rather than on "true" or psychotic symptoms such as delusions and hallucinations.


MMPI delineation of a subgroup of depressed patients refractory to lithium carbonate therapy. The authors found that in a sample of 26 severely depressed hospitalized patients, 5 patients with low depression and psychasthenia profiles on the Minnesota Multiphasic Personality Inventory did not show an antidepressant response to lithium carbonate. Seventeen of 21 depressed patients with high depression and psychasthenia profiles did  respond to the antidepressant effects of the drug. They tentatively conclue that by using the MMPI it is possible to delineate a subgroup of depressed patients who are refractory to lithium carbonate therapy.


[Blood gas studies on the efficiency of the ventilator "Pulmomat" (author's transl)]. Efficiency of ventilation of Pulmomat has been examined in 48 patients under general anaesthesia and relaxation during normoventilation and hyperventilation of 15 and 30% degree. For criteria the acid-base status of arterial blood has been used. In normoventilation acid-base status remained unchanged within the normal range providing a regular control respectively correction of ventilationvolumes. There was no significant difference between results of 15 and 30% hyperventilation. In both situations arterial pCO-2 was reduced 15-20%. There was a tendency to acidosis in all kinds of ventilation presumably as a consequence of surgical effects. For security using the Pulmomat as respirator, a hyperventilation of 15% degree is recommanded in clinical use.


[PO-2-PCO-2-pH-nomograms for rat blood at 37 degrees C (author's transl)]. In order to determine the interdependence of the parameters of the respiratory gas transport in rat blood (Sprague-Dawley) CO-2-equilibration curves in fully oxygenated and deoxygenated blood are measured. The results are presented in the form of pH-log P-CO-2-diagrams. O-2-dissociation curves of rat blood are registered at different CO-2 partial pressures. The P-02 at S-02 equals 50% ranged between 27.7 mm Hg for P-C0-2 equals 20 mm Hg. 35.1 mm Hg for P-C0-2 equals 40 mm Hg and 42.2 for P-C0-2 equals 60 mm Hg. Cartesian and alignment nomograms are constructed using CO-2 equilibration curves and O-2 dissociation curves. These nomograms give the interrelations between P-O-2, P-CO-2, pH and S-0-2 of rat blood. Separate nomograms are presented for Hb-concentrations of 10-13 g-% and 13.1-16 g-% because of great variations of Hb concentration in rat blood. If two of these values are known the nomograms permit the reading of the remaining paramters.


Neurohumoral mechanisms in hypertension. Neurohumoral mechanisms operating via the catecholamines are discussed in their relationship to such hypertensive diseases as pheochromocytoma and labile and established essential hypertension. 2. In pheochromocytoma, diagnosis depends almost entirely on identification of increased amounts of catecholamine metabolites in the urine. Because of the danger, manipulative or invasive procedures both for diagnosis and during surgery should be kept at a minimum. 3. In established essential hypertension, reactivity to norepinephrine and plasma norepinephrine are increased, whereas norepinephrine uptake and apparent secretion rate are decreased. 4. In labile essential hypertension, reactivity to epinephrine and probably plasma epinephrine are increased and uptake of epinephrine decreased. 5. Labile hypertension with all its characteristics may or may not coexist with established  essential hypertension with all its features. 6. The sympathetic nervous system is also involved in other types of hypertensive disease. Many patients with renovascular hypertension as well as with primary and secondary hyperaldosteronism also have essential hypertension. Angiotensin II affects the sympathetic nervous system and the juxtaglomerular apparatus appears to be beta adrenergic receptor activated, at least in part.


Arterial blood-gas analyses during electroconvulsive therapy in a parturient. Arterial blood gases and vital signs were monitored in a patient receiving electroconvulsive therapy (ECT) during the third trimester of pregnancy. Alterations in blood pressure and heart rate were similar to those noted in prior studies. Pretreating with 100 percent oxygen (02) and assisting ventilation until return of adequate spontaneous respirations, prevented hypoxemia, significant hypercarbia, and cardiovascular changes. The administration of succinylcholine prevented the systemic manifestations of the electrically-induced seizure. One fetal arrhythmia occurred, apparently unrelated to changes in maternal Pa02, and resolved spontaneously. This technic of anesthesia would appear to be acceptable for ECT in the parturient.


A neurochemical hypothesis for halothane anesthesia. We hypothesize that anesthetic agents exert their effects through an inhibition of oxidation of reduced nicotinamide adenine dinucleotide (NADH) in the synaptic regions of the brain. This inhibition could lead to gamma-amino-butyric acid (GABA) accumulation in the synaptic cleft and to hyperpolarization of the post-synaptic membrane. The resulting reduction in synaptic transmission then would manifest itself as the anesthetic state, reducing the work performed by the brain so that cerebral respiration is reduced and cerebral metabolite energy is conserved.


Reassessment of the assumed A-V oxygen content difference in the shunt calculation. A study was undertaken in 15 patients to compare measured and assumed arteriovenous oxygen (A-V O2) content differences and their effects on resultant shunt calculations. All patients were on volume ventilators and demonstrated a stable cardiovascular state. Simultaneous measurements of the O2 content of a pulmonary artery (PA) and of a superior vena cava (SVC) sample were compared. A mean A-V 02 content difference of 3.5 plus or minus 0.8 volumes percent was obtained from the PA and 2.6 plus or minus 1.1 volumes percent from the SVC. The resultant shunt calculations derived from measured A-V 02 content differences were compared with the calculation based on an assumed A-V O2 content difference of 5 volumes percent. A method for extrapolating a "true" A-V 02 content difference from an SVC blood sample was obtained. The extrapolated value resulted in a more representative "true shunt" calculation in 13 of the 15 patients.


Duck viral enteritis (duck plague) characteristics and immune response of the host. Duck viral enteritis (DVE) is caused by a herpesvirus whose biologic and physical characteristics are similar to those described for the group of herpesviruses. Only one immunologic and serologic type is known. A low level of neutralizing antibodies is developed in waterfowl vaccinated with the chicken embryo attenuated DVE virus. A marked anamnestic serologic response resulted from challenge with virulent virus. Waterfowl resisting exposure with virulent virus were solidly immune. However, waterfowl which possessed moderate level of neutralizing antibodies succumbed when their immunity was challenged with virulent virus when secondary or latent microbial invaders were present. This may partially explain the lack of correlation between the levels of neutralizing antibodies and mortality from infection with DVE virulent virus.


Pulmonary function in asymptomatic adolescents with idiopathic scoliosis. Pulmonary function studies were performed in 28 asymptomatic adolescents with idiopathic scoliosis. Tests included spirometry, flow volume curve, measurements of inspired gas distribution, diffusing capacity, closing volume, ventilatory response to carbon dioxide, and arterial blood gas analysis. In addition to the well-known decreases in lung volumes, a reduction in diffusing capacity, arterial oxygen tension, and ventilatory response to carbon dioxide were also documented. Significant correlations existed between the severity of the spinal curvature and the decrease in lung volumes. A significant correlation was also found between the degree of hypoxemia and the reduction in the diffusing capacity, suggesting that a low diffusing could be the cause of the observed arterial hypoxemia.


Stress ulceration and the gastric mucosal barrier. The role of the gastric mucosal barrier in the pathogenesis of post-traumatic stress ulcerations is far from clear. Clinical studies on critically ill patients have shown disrupted gastric mucosal barriers with hydrogen ion back diffusion, but no correlation has been made between these findings and gastric erosions. In addition, numerous assumptions concerning gastric secretions, pyloric loss and esophageal contributions to the assayed gastric juice have to be made in these patients. There is contradictory experimental evidence concerning the theory that gastric mucosal ischemia or hypotension disrupts the normal gastric mucosal barrier. In subhuman primate studies, there is no increased back diffusion acid during hypotension or during the reinfusion periods. Even though there may not be increased permeability to H+, the presence of acid is a requirement for the development of stress ulcerations. The role of agents such as bile salts and aspirin is clearer. If these agents are present, increased back diffusion of acid is likely, but its role in the pathophysiology of post-traumatic gastric erosion awaits further clarification.


Total coronary blood flow measurements and myocardial metabolism during cardiopulmonary bypass in a canine model. Myocardial respiratory function and total coronary blood flow were evaluated during cardiopulmonary bypass in 18 dogs. The fibrillating heart was found to be associated with an increase in myocardial oxygen utilization and metabolic rate which was compensated for by a corresponding increase in total coronary blood flow. Following anoxic arrest of the heart, there appears to be an initial impairment to oxygen utilization. Oxygen consumption does not return to normal after 15 minutes of restoring coronary blood flow. The stability of the experimental model as outlined in this study is thought to be related to the use of autologous blood in priming the extracorporeal circuit.


Ocular penetration of pilocarpine: the effect of pH on the ocular penetration of pilocarpine. Under the conditions of this study, tritiated pilocarpine was topically applied to rabbits, and the activity in the aqueous humor was measured at selected times. It was found that higher pH affords greater pilocarpine penetration. At pH 7.5, for example, penetration into the aqueous was twice as great as at pH 4.


Gas tension and pH in middle ear effusion. The composition of gases and the gas tension in middle ear effusion in patients with serous otitis media have been investigated. By using a specially designed micro-method, very small amounts of middle ear fluid could be analyzed. The effusion was obtained by puncturing the air cells of the mastoid process. The average value of P-O2 was 41 mm Hg; Pco2 was 58 mm Hg, pH 7.24. The possible mechanism for the impaired perfusion of the mucous membranes is discussed as well as some clinical consequences.


[Study of oxytetracycline solubility in an aqueous medium]. Solubility of oxytetracycline dihydrate in aqueous media was studied. It was shown that solubility of the drug in bidistillate at a temperature of 20 degrees was 195 gamma/ml, which was much lower than the requirements of some pharmacopoeia with respect to the drug solubility. Dependence of oxytetracycline dihydrate solubility in the aqueous medium on the values of pH and temperature was found. Indigency of the procedure described in the literature for determination of antibiotic solubility according to the dry weight of the filtrate on addition of large excesses of the solid phase to the system was shown.


Molecular construction of Clostridium botulinum type F progenitor toxin. Molecular dissociation of purified type F progenitor toxin with an S20,W of 10.3 and a molecular weight of 235,000 into two components, toxic and atoxic, was demonstrated by ultracentrifugation, gel filtration, and diethylaminoethyl-Sephadex chromatography at pH 7.5. The ultracentrifugal analysis indicated that type F progenitor toxin dissociates into components of the same molecular size of 5.9S. The toxic component contained a toxicity of 2.5 times 10-8 50% lethal doses per mg of N. Much higher stability of progenitor toxin than that of derivative toxin, particularly at pH below 5, suggests that only progenitor toxin can act as an oral toxin.


Rhythmic changes in dry heat resistance of Bacillus subtilis spores after rapid changes in pH. Heat resistance of freeze-dried Bacillus subtilis spores varied in a rhythmic manner as a function of time between acidification to about pH 1.5 and freezing. A comparable rapid shift to pH 11 produced little change in resistance to heat.


Lymphomatoid granulomatosis of the skin. A new clinocopathologic entity. Lymphomatoid granulomatosis is a necrotizing arteritis primarily affecting the lungs but also found in the skin, kidneys, central nervous system, and other extra-pulmonary sites. Cutaneous involvement occurred in 45% of the cases described by Liebow in his original series. Light microscopy studies were performed. The IgA and IgG levels were slightly decreased and the IgE level was elevated. Cell-mediated immunity was impaired. No viruses were isolated or identified by immunofluorescence. A man had cutaneous lesions as the first sign of lymphomatoid granulomatosis.


Arbovirus infections in Sarawak, October 1968--February 1970 Tembusu and Sindbis virus isolations from mosquitoes. Thirty isolations of Tembusu virus and four of Sindbis virus were obtained from approximately 280 000 mosquitoes collected between October 1968 and February 1970 in Sarawak, particularly from K. Tijirak, a Land Dyak village 19 miles South of Kuching. Twenty-two isolations of Tembusu virus and two of Sindbis virus were from Culex tritaeniorhynchus; two of Tembusu virus and two of Sindbis virus came from Culex gelidus. Tembusu virus was active throughout the year at K. Tijirak, the highest infection rates in C. tritaeniorhynchus being in January-March and May-August, when the C. tritaeniorhynchus population was declining and ageing. These results confirm that C. tritaeniorhynchus is the principal arthopod host of Tembusu virus in Sarawak. Antibody studies suggest that birds, particularly domestic fowl, are probably vertebrate maintenance hosts of Tembusu and Sindbis viruses in Sarawak.


Management of flail chest without mechanical ventilation. The pathophysiology of flail chest is usually described only on the basis of paradoxical respiration, ignoring underlying pulmonary contusion. Two groups of comparable patients were treated either with early tracheal intubation and mechanical ventilation (Group 1), or with fluid restriction, diuretics, methylpredinisolone, albumin, vigorous pulmonary toilet, and intercostal nerve blocks, ignoring the paradox and treating only the underlying lung (Group 2). When tracheostomy and mechanical ventilation were not used the mortality rate went from 21% to O(p = 0.01), the complication rate from 100% to 20% (p = 0.005), and the average hospitalization from 31.3 to 9.3 days (p = 0.005). We conclude that most patients with flail chest do not need internal pneumatic stabilization if the underlying lung is treated appropriately and that tracheostomy and prolonged mechanical ventilation with a volume respirator, as practiced in most respiratory care centers, is usually a triumph of technique over judgment.


Exercise tolerance after repair of tetralogy of Fallot. Twelve patients who had undergone complete repair of tetralogy of Fallot at ages ranging from 8 to 27 years were studied for exercise tolerance several years later. Work performance ranged from 58 to 130% of that predicted. Increased physiological dead space and alveolar-arterial Po2 difference at exercise suggested pulmonary vascular disease, which was confirmed in 1 patient by pulmonary angiography. Excercise tolerance decreased with increasing age at time of repair, underlining the desirability of early corrective operation.


Labeling effects in psychiatric hospitalization. A study of diverging patterns of inpatient self-labeling processes. This report explores two theoretical positions regarding psychiatric inpatient self-labeling processes over time. One position suggests that acceptance of the deviant label "mentally ill" is benign; the other suggests that such label acceptance may be harmful to patients. Employing empirical, longitudinal data from a sample of 43 inpatients, three complex, but discernible, patterns of "acceptance," "rejection," or "denial" of the "deviant" label of mental patient emerged over time within a short-term hospital setting. The three patient groups varied on Minnesota Multiphasic Personality Inventory scales, staff behavioral ratings over time, involvement in approved ward activities, and length of hospitalization. Results were discussed in terms of patient-staff interaction and its possible relation to patient self-labeling.


Cerebral vasculitis in rheumatoid arthritis. A 63-year-old man with severe, untreated rheumatoid arthritis and pleuritis developed an unusual neurological syndrome similar to Gerstman syndrome, followed by dementia and blindness, six weeks before his death. An autopsy showed extensive necrotizing vasculitis, resembling polyarteritis nodosa, involving the brain and resulting in numerous infarcts. The disease was most severe in the posterior portion of the cerebral hemispheres. Other organs were only slightly involved. Severe amyloidosis of cerebral arterioles and senile plaques were noted in the areas of brain with most severe vasculitis. Review of literature indicated only six cases of cerebral vasculitis in rheumatoid disease, five of which were treated with corticosteroids.


[Production of histological preparations from implanted vascular protheses (author's transl)]. The above mentioned method is suitable for the production of intact histological preparations of implanted vascular protheses. An even mounting of the sections is as possible as the application of the usual staining procedures except those containing methanol or any other agent dissolving collodion.


The aetiology, characteristics and diagnostic relevance of late deceleration patterns in routine obstetric practice. A retrospective study is described in which all the late deceleration patterns seen in one obstetric unit over the course of 34 months have been reviewed with regard to their apparent aetiology, their characteristics and associated abnormal fetal heart rate patterns and the incidence of fetal distress. The results show that, regardless of the aetiology and the characteristics, the incidence of fetal distress (defined as a pH of less than 7-25 or an Apgar score of less than 7 at one minute) lies between 40 and 50 per cent. The implications of this degree of diagnostic inaccuracy are discussed and the importance of fetal blood sampling as the final arbiter in the diagnosis is emphasized. During the course of the study a significant relationship was demonstrated between the use of epidural analgesia and the incidence of late deceleration patterns. This finding is discussed.


Beta-mimetic drugs and possible prevention of respiratory distress syndrome. The prophylactic value of beta-mimetic drugs in preventing respiratory distress syndrome (RDS) is investigated by comparing 29 preterm infants of ritodrine treated mothers with 34 preterm infants of a control group. Five cases of RDS (17 per cent) occurred among the infants of treated mothers as compared with 12 cases (35 per cent) in the control group (p = 0-09). The difference is, however, statistically significant for the group of infants weighing less than 2300 grams (p = 0-01) which includes all infants affected with RDS.


The effect of different feeds, including those containing soya-bean products, on the passage of digesta from the abomasum of the preruminant calf. 1. The effects of various factors on rates of flow and composition of digesta leaving the abomasum of preruminant calves were studied. The possible relation of some of these effects to the development of serum antibodies to certain dietary constituents has also been examined. Two situations were distinguished: (a) unsensitized responses, shown by calves receiving milk protein or soya-bean products for the first one or two occasions; (b) sensitized responses, shown by calves receiving certain soya-bean products, after a number of these feeds had been given. 2. For unsensitized calves, the rate of flow of total digesta from the abomasum was greater in the first few hours after a feed consisting of a mineral solution was given, than after cow's milk was given. This difference wasapparently due to differences in the composition of digesta entering the duodenum. Total digesta flows after giving synthetic milk feeds, prepared from different protein sources, were similar to those after cow's milk was given. 3. For sensitized calves, rates of flow of total digesta from the abomasum were greatly affected by the nature of the protein source used in the diet. Soya-bean flour (heated or unheated) generally caused inhibition of flow for some hours after feeding; a soya-bean protein isolate (isoelectric) had a similar but smaller effect, but a soya-bean concentrate (prepared by alcohol extraction of a soya-bean flour) and milk protein had little or no effect. The inhibition, believed to be a sign of more general disorders, appeared to be caused by a factor entering the duodenum which induced a change in the way in which the calf responded, probably as the result of a gastrointestinal allergy. 4. Calves given soya-bean flour or a soya-bean protein isolate (isoelectric) in their diets for several weeks, showed respectively high and low titres of serum antibodies to an antigen prepared from soya-bean flour. Calves given alcohol-extracted soya-bean concentrate had no similar antibodies. 5. In addition to variations in total digesta flow, dietary nitrogen compounds were held up in the abomasum to different extents after different feeds. After a whole-milk feed or a synthetic feed prepared from casein, a slow, steady release of N occurred over at least 9 h. N hold-up after giving soya-bean-containing feeds was slight for the soya-bean flour, but extremely marked for the soya-bean protein isolate (isoelectric). The latter hold-up was followed after several hours by a rapid outflow of N from the abomasum.


A relationship between the molar proportion of propionic acid and the clearance rate of the liquid phase in the rumen of the sheep. 1. Four rumen-cannulated sheep were given a forage mixture (F) of chopped hay-ground, pelleted, dried grass (92:8, w/w) and two concentrate mixtures (C and S) of ground barley-ground hay-flaked maize (46:24:30 and 56:24:20, by wt respectively) in twenty-four hourly meals each day. Each of the diets was offered in successive periods of 16 d to give a feeding sequence F-S-C-S for one pair of sheep and C-S-F-S for the other pair. 2. The average composition (mol/100 mol) of the mixture of short-chain fatty acids, acetic, propionic and butyric, in the rumen was respectively 70-1, 18-5 and 7-5 with diet F, and 55-8, 24-8 and 13-6 with diet C. With diet S, the pattern of fermentation varied both between animals and in the same animal for different periods having either 'high' (28-39 mol/100 mol) or 'low' (16-21 mol/100 mol) proportions of propionic acid. On average when diet S followed diet F there was less propionic acid in the fermentation mixture than when diet S followed diet C (59-3 acetic, 22-2 propionic and 14-1 butyric as compared with 52-7, 29-4 and 13-1 respectively) but this trend was not significant and there was evidence of interactions between the feeding sequences and the individual sheep. 3. The mean concentrations of ammonia, sodium, potassium and chloride were similar for all diets but the pH and concentrations of calcium, magnesium and phosphorus tended to be higher and the buffering capacity lower for diet F than for diets C or S. In animals receiving diet S there was no relationship between the concentrations of minerals, the pH or buffering capacity and the pattern of fermentation except for ammonia, the concentration of which was high when the molar proportion of propionic acid was low. 4. Rumen volume, outflow rate and clearance rate, determined using polyethylene glycol, were higher for diet F than for diets C and S but within each diet, particularly for diet S, values varied considerably between sheep and between periods. 5. There was evidence of an interrelationship between the molar proportion of propionic acid in the fermentation products and the clearance rate, which indicated that the clearance rate may be an important factor influencing the pattern of fermentation in the rumen.


On the DNA polymerase III of mouse myeloma: partial purification and characterization. A high molecular weight membrane-bound DNA polymerase from the mouse myeloma, MOPC-104E, has been purified extensively, and characterized with regard to physical and reaction properties. This enzyme, which is readily distinguishable from other myeloma enzymes that are analogous to the recognized forms of cellular DNA polymerase, is ddesignated DNA polymerase III. DNA polymerase III activity in whole homogenates from MOPC-104E was solubilized and then prurifed using a series of ion-exchange chromatographic procedures followed by DNA-cellulose chromatography and glycerol gradient centrifugation; the enzyme activity as measured with poly(rA)-(dT)12-18 as template-primer and Mn2+ as divalent cation, was purified as much as 18,000-fold. In the final stages of the pruification, DNA polymerase III possessed no detectable RNA polymerase activity, nucleoside diphosphokinase activity, or nucease activity toward DNA or single- and double-stranded RNA...


Mitochondrial poly(A) polymerase from a poorly differentiated hepatoma: purification and characteristics. Poly(A) polymerase (EC 2.7.7.19) solubilized from mitochondria of a poorly differentiated rat tumor, Morris hepatoma 3924A, was purified more than 1000-fold by successive column chromatography on phosphocellulose, DEAE-Sephadex, and hydroxylapatite. Purified enzyme catalyzed the incorporation of ATP into poly(A) only upon addition of an exogenous primer. Of several primers tested, synthetic poly(A) was the most effective. The enzyme utilized mitochondrial RNA as a primer at least five times as efficiently as nuclear RNA. The enzyme required Mn2+, and had a pH optimum of 7.8-8.2. The enzyme utilized ATP exclusively as a substrate; the calculated K-m for ATP was 28 muM. The polymerization reaction was not inhibited by RNase, ethidium bromide, distamycin, or alpha-amanitin. The reaction was sensitive to O-n-octyloxime of 3-formylrifamycin SV (AF/013). As estimated from glycerol gradient centrifugation and acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the molecular weight of the enzyme was 60,000. The product was covalently linked to the polynucleotide primer and the average length of the poly(A) formed was 600 nucleotides.


Thermal transitions of myosin and its helical fragments. I. Shifts in proton equilibria accompanying unfolding. The thermal transitions of myosin and its helical fragments have been studied with pH as the observable. Heating unbuffered solutions of these proteins near their pI values causes an abrupt rise in pH at a characteristic temperature (the "melting temperature," Tm) which is due to structural changes within the protein. Since the pH shift turns out to be insensitive to the degree of protein aggregation, we have obtained acceptable melting curves even under conditions where the protein coagulates during melting. The melting profiles and Tm vlaues of myosin, myosin rod, and light meromyosin have been found to be remarkably similar (Tm equal to 40 plus or minus 1 degree, 0.5 M KCl, pH 5.9). Proton binding which occurs during melting coincides with the unfolding of a section of myosin rod. Taken in the context of other studies, the proton binding is thought to occur near the "hinge region."


Thermal transitions of myosin and its helical fragments. II. Solvent-induced variations in conformational stability. The melting behavior of myosin and myosin rod has been studied over the pH range 5.4-7.0, in 0.5 M KCl. Both proteins exhibit almost identical T-m values, which increase from about  37 to 43 degrees as the pH is elevated through the range of study, T-m follows a sigmoidal dependence upon pH, and the inflection point occurs near pH 6.5. The influence of salt concentration on T-m was studied, by the variation of KCl from 0.15 to 2.92 M. With an increasing KCl concentration, both proteins exhibit similar, sigmoidal declines in T-m from about 44 to 34 degrees. Under all conditions of pH and ionic strength studied, melting is accompanied by an absorption of H+ by the protein. The concentration of the protein, the age of the preparation, and the presence of divalent metal ions fail to exert a significant effect on the T-m values obtained by our methods. The effects of salt concentration and pH on the thermal stability of myosin and myosin rod are discussed in terms of the location of the melting process within the myosin molecule. Myosin is shown to possess several of the requisite features for energy transduction via a proton-coupling mechanism. These features provide a framework for investigating some aspects of the molecular basis of muscle contraction within the context of the sliding filament model.


Analysis of cooperativity in hemoglobin. Valency hybrids, oxidation, and methemoglobin replacement reactions. An allosteric model proposed previously for structure-function relations in hemoglobin is applied to the analysis of low- and high-spin valency hybrids. By assuming that the low-spin oxidized chains have the tertiary structure of oxygenated chains while the high-spin oxidized chains have a tertiary structure intermediate between that of deoxygenated and oxygenated chains, the model parameters associated with the different valency hybrids can be obtained, and their equilibrium properties can be estimated. The hybrid results are used also to provide an interpretation of methemoglobin and its ligand replacement reactions and of the oxidation-reduction equilibrium of normal hemoglobin. For the various systems studied it is found that the effects of pH and 2,3-diphosphoglycerate are in agreement with the model.


Hydrolysis of ribonucleoside 3'-diphosphates by rye grass 3'-nucleotidase. Rye grass 3'-nucleotidase has been purified to apparent homogeneity on Sephadex A-25 and CM-cellulose columns and shown to hydrolyze 2'-O-methyladenosine 3'-monophohate and 2'-deoxyadenosine 3'-monophosphate 35.8 and 542 times more slowly than the normal substrate (3'-AMP), verifying the importance of the 2'-beta-OH group of the substrate in the overall hydrolysis process. Although neither was hydrolyzed as rapidly as 3'-AMP, both the 2'-O-methyl and 2'-deoxy analogs acted as competitive inhibitors of the hydrolysis of 3'-AMP (K-m equals 0.12 mM), with apparent K-i's of 0.39 and 0.51 nM, respectively. In order to determine the possible susceptibility of naturally occurring ribonucleoside 3'-diphosphates, such as guanosine tetraphosphate (ppGpp), to 3'-phosphohydrolase activities, the 3'-nucleotidase was also employed in the attempted pyrophosphorolysis of adenosine 3'-diphosphate and guanosine tetraphosphate. Neither adenosine 3'-diphosphate nor guanosine tetraphosphate was degraded at a significant rate by the nucleotidase, relative to the normal substrate.