[Characteristics of heterogeneity of serum albumin in heterosis-hybrid chickens]. A comparative study was performed for isoelectric and electrophoretic spectra blood serum albumin of parental breeds of chickens and their heterosis hybrids --broiler cocks. The method of isoelectric focusing within the surcrose density gradient and pH 4-6 created by the gradient of sucrose, mannitol and boron-borate buffer (pH 8.5) concentrations was applied. The electrophoretic spectrum of the serum albumin fraction homogeneous in the agar gel was obtained by electrophoresis in 7% polyacrylamide gel. The isoelectric spectrum of heterosis hybrid albumin is established to be more heterogeneous and during isoelectric focusing it is divided within a range of pH 4.6-5.2 into seven fractions against four-five components of the parent breed albumin. Among them it is possible to distinguish the fraction involving more than 50% of the total protein (the great component) and some small components with different protein content and belonging wither to a more acid or more basic region as compared to pI of the great component. The pI value of the great component for hybrid albumin is shifted towards the acid region (4.76 against 4.85 and 5.07 in albumin of the parent breeds). Small component of hybrid albumin are characterized by an increase in their amount, but pI of the fraction is within the range of values peculiar to albumin of the maternal and paternal lines. The albumin preparations of all the studied chicken breeds isolated from blood serum by electrophoresis in the agar gel manifest multiplicity of the protein bands in a 7% polyacrylamide gel. The electric spectra of hybrid albumin and parent breeds albumin differ in the distribution pattern of the components and their quantitative composition. A relative electrophoretic mobility of the intensively stained dense band which represents the main electrophoretic component is increased in hydrid albumin with the respect to albumin of the maternal line but is identical to the paternal line.


Metomidate as sole anaesthetic agent in tawny owls. Metomidate 1 per cent was administered intramuscularly as the sole anaesthetic agent on 22 occasions to seven tawny owls (Strix aluco). Four deaths occurred, none on the first administration. ECG findings and details of dosage are provided. The possible causes of death are discussed.


[Peculiarities of acid-base reserves in aging]. The age-dependent peculiarities of the acid-base balance at rest and with standard loads were studied in 466 rats. It was found that with age the pH value of blood decreases, the tension of the carbonic acid increases, but the values of BB, BE, SB, and AB do not undergo any significant changes. With loads, old animals showed more profound changes in the system and these changes were of decompensated character. The maximal changes in young animals were registered 1.5 hours after loading, in old rats--3 hours after. The normalization of the shifts in old rats occurred much more slowly than in young animals, and it does not reached the initial value by 24 hours after loading. The analysis of the data obtained shows that with aging the reserve potentialities of the organism's mechanisms of the acid-base balance regulation greatly decrease, which under certain conditions results in disturbance of the given system compensation, thus exerting a negative effect on the body vital processes.


[Dynamics of production and various properties of interferon-like inhibitors formed under the influence of AET and cystaphos in vivo and in cell cultures]. Interferon-like virus inhibitors appeared in the blood serum of animals and in the culture fluid 15 min.--1 hour and 4-6 hours after administration of AET (S, beta-amino-ethylisotiuronium) and cystaphos (monosodium salt of beta-aminoethylthiophosphorus acid). These inhibitors showed species-specificity, were inactivated by trypsin and by heating at 37 degrees C for 2 hours and at 56 degrees C for 1 hour, did not sediment at 100,000 g. It is assumed that these are two different inhibitors of which the one forming the early peak pre-exists in the cell. It is probably associated with cell membranes and is released as a result of chemical effect of aminothyols. The late peak of inhibitor is synthesized de novo as inducated by its sensitivity to the effect of puromycin and cycloheximide.


[Lipolysis in human adipose tissue (author's transl)]. Lipolytic activity was measured under different conditions in isolated fat cells and homogenates of human adipose tissue of the greater omentum. It was demonstrated that lipolysis took place in isolated fat cells at an optimum pH of 7.4 and was markedly stimulated by noradrenaline, but not by blood serum. By contrast lipolysis was significantly stimulated by blood serum, but not by noradrenaline, in homogenates of adipose tissue. Serum-stimulated lipolysis exhibited optimum activity at pH 8 and was inhibited by 1M sodium chloride. It is concluded that lipolytic activity in isolated fat cells can mainly be ascribed to the action of hormone-sensitive lipase, whereas lipolysis in homogenates of adipose tissue in the presence of serum is mostly regulated by lipoprotein lipase.


[Study of the influence of the beta-sympatholytic drug KO 1366 (Bunitrolol on lung function (author's transl)]. 20 untreated outpatients suffering from chronic obstructive airway disease were tested with a new beta-sympatholytic agent, Kö 1366 (bunitrolol) or placebo in a randomized symptoms of bronchitis, but hacetylcholine inhalation was followed by severe bronchospastic hyperreactivity. The intravenous administration of 2.5 mg Kö 1366 resulted in a rapid and statistically significant (p less than 0.001) marked decrease in heart rate due to the beta-sympatholytic effect. Airway resistance, however, measured by whole-body plethysmography, was not affected. Kö 1366 can be regarded as a cardio-selective beta-sympatholytic drug in so far as i.v. administration is possible in patients with airway disease during a non-obstructive period. Moreover, should a bronchospastic reaction occur immediate control by inhalation of adrenergic or vagolytic drugs is possible.


[Cerebral manifestations in the hepatic coma syndrome (author's transl)]. The pathogenesis of hepatic encephalopathy has been investigated in a two-stage devascularization model in the rat with portavacal shunt and hepatic artery ligation. There is a significant increase in brain octopamine and phenylethanolamine and a decrease in brain norepinephrine (NE) 6 to 9 hours after hepatic artery ligation. The depletion of NE seems the sequel of diminished synthesis in the presence of an unaltered turnover rate, due to a blockade of tyrosine hydroxylase either by accumulation of false neurochemical transmitters or by phenylalanine. It is most marked in the cortex and midbrain. The high-energy phosphate compounds, ATP, phosphocreatine and glucose-6-phosphate are not diminished in hepatic coma, nor is glucose, indicating that other mechanism are involved in the pathogenesis of metabolic state by the increased ammonia level. "intestinal sterilization" and total colectomy have no significant effect on the ammonia level, but cause a decrease in the level or aromatic precursor amino acids in the plasma and brain, with normalization of the level of cerebral transmitters. These results permit the formulation of a unified concept of the hepatic coma syndrome and its clinical manifestations such as flapping tremor, the hyperdynamic cardiovascular state and the hepatorenal syndrome. Moreover, they form the basis for the introduction of a new therapeutic principle in the management of hepatic encephalopathy by L-dopa or modified amino acid solutions, which act by altering the central and peripheral neurotransmitters.


[Urinary enzymes in the early detection of rejection reactions after renal transplantation (author's transl)]. Urinary enzymes were studied in 15 patients subjected to kidney transplantation. The investigation was initiated immediately after operation and was continued for a period of between 2 and 8 weeks. There was a significant increase in urinary MDH activity in 94.2% of cases, of LDH activity in 95,65% and of gamma-GT activity in 95,17% of the cases. This detected increase in urinary enzyme activities preceded the clinical diagnosis of rejection by activities preceded the clinical diagnosis of rejection by at least 24 hours. Determination of these enzymes provides a reliable tool for the early detection of rejection crises.


[Extracardiac factors in the development of arrhythmias (author's transl)]. A brief survey is given of some of the most frequent extracardiac causes which may provoke disturbances of rhythm. The importance of psychogenic and metabolic factors is emphasized. Additional organic lesions cannot be excluded in every case.


[Inducible accumulation of alpha-ketoglutaric acid in cultures of Streptomyces hygroscopicus JA 6599 producing a macrolide antibiotic]. The excessive production of pyruvic and 2-oxoglutaric acid by S. hygroscopicus JA 6599 grown on a medium rich in complex carbon and nitrogen sources was studied. Towards the end of the first day of batch cultivation a maximum level of both keto acids in the medium was observed. By diluting the complete culture with water at 22nd hour, however, a further increase in 2-oxoglutarate concentration was induced and the antibiotic production was slightly stimulated. In diluted cultures the oxygen saturation was found to be distinctly higher than in non-diluted ones and, on the other hand, the mycelial activities of both pyruvate and 2-oxoglutarate decarboxylases were decreased. Since the 2-oxoglutarate level was strongly influenced by inhibitors of glycolysis and of citric acid cycle, it is suggested that the metabolite accumulation in diluted cultures is mainly caused by modifications of the metabolic control of carbohydrate catabolism due to an improved aeration. Furthermore, the macrolide antibiotic A 6599 produced by S. hygroscopicus JA 6599 itself was shown to interfere with the accumulation of 2-oxoglutaric acid.


[Immunosuppressive treatment in autoimmune vasculities]. From own experiences the observations of 3 patients were reported who were immunosuppressively treated with purine antagonists (azathioprine and 6-mercaptopurine). Hereby in a severe allergic vasculitis in a 22-year-old patient and in a granulomatous arteritis during Wegener's granulomatosis in a 51-year-old patient remissions for more than 1 and 7 years, respectively, could be achieved under immunosuppressive long-term therapy. In the case of a periarteriitis nodosa death took place 2 months after administration of 6-mercaptopurine.


[Possibilities and limits of the intrauterine reanimation (author's transl)]. Intrauterine reanimation means the removal of acute maternal or fetal distress. Beside of maternal shock (traumatic, hoaemorrhagic, supine hypotension syndrome) all acute distress situation are seen during labour. The therapeutical possibilities and premises on the one side, the limits and dangers on the other are discussed. There are the change of position in bed, infusion of low molecular dextrane, O2- breathing, buffering of the mother, infusion of vasodilatators and beta-stimulators to the mother. The main therapeutical principle for intrauterine reanimation are change of side position and beta-stimulator therapy in case of disturbances in feto-maternal respiration because of an acute utero-placental insufficiency or a cord complication. As to an own patient group with intrauterine reanimation with the beta-stimulator "Partusisten" in 174 deliveries with cardiotocographic signs of fetal distress in the first stage of labour there is shown that threatened fetal distress because of uterine hyperactivity and cord complication is successfully treated by tocolysis. In case of chronic placental insufficiency there is no therapeutical success by intra partum tocolysis in 30%.


Graft-versus-host reaction: a pathogenetic principle for the development of drug allergy, autoimmunity, and malignant lymphoma in non-chimeric individuals. Hypothesis. It is proposed that the same diseases as those induced by the graft-versus-host reaction (GVHR) will arise in nonchimeric individuals, if structures of the major histocompatibility complex (MHC) on lymphocytes are altered, either by viral infection or by chemicals, in such a way that autologous T lymphocytes react against them as the react in the GVHR to semiallogeneic (F1) lymphocytes differing at the MHC. Diseases in which a GVHR-like pathogenesis is suspected will be discussed.


[Studies on the hatching of miracidia of Dicrocoelium dendriticum (author's transl)]. The eggs of Dicrocoelium dendriticum were induced to open by solutions of formic acid and caproic acid (Table 1). The miracidia hatched in O2-free water after the eggs had been dried with N2 or in vacuum. The miracidia were able to live for 3 hours if water contained 20 mM NaCl, 10 mM KCl, and 1 mM CaCl2. Ca++-ions are obviously necessary for the mobility of miracidia. The experimental use of intestinal juice of the Roman snail Helix pomatia gave hatching results which were dependent on the absence of O2 (exposure to N2) and the presence of bacteria with a still unknown function. The dependence on pH seems to be indirect (Abb. 2). Studies on the permeabilities of the egg shell and the embryonic membrane ("vitelline membrane"), the evidence of an oligosaccharide (Abb. 3) liberated from the "spaltraum" (Abb. 1) during egg-opening, and the determination of the osmotic pressure of the hatching process (50% hatching in 1.2--14. Osmols sucrose/1000 ml H2O; Abb. 4) led to the following hypothesis of hatching mechanism: After the activation of the granular gland of the miracidium an enzyme is released into the extra-embryonic "spaltraum". A polysaccharide is digested to an oligosaccharide which cannot permeate the egg shell and the embryonic membrane. The rising osmotic pressure bursts off the operculum.


[Long-term treatment of chronic polyarthritis using benorylate]. The antiphlogistic and analgesic effect and the compatibility of benorylate, a acetamidophenyl-acetoxy-benzoate, was tested in 33 patients with rheumatoid arthritis in an open study over a period of 6 months. Benorylate is particularly qualified for treatment of a beginning rheumatoid arthritis and for diseases with a low inflammatory activity. For patients with high inflammatory activity treatment with this substance alone is not sufficient. Side effects are mainly subjective troubles. Severe side effects were not observed. Besides the usual laboratory investigations a regular control of the blood count is advisable during long term treatment. Like with other antirheumatic drugs occasional investigations of the stool for occult blood are recommended.


[Studies of Nocardia pellegrino SN 5108 pigment mutants: reasons for differences in pigmentation (author's transl)]. Yellow and white mutants of the strains Nocardia pellegrino SN 5108 R have been isolated. Regarding their morphological and physiological properties, the mutants are identical with the wild type bacteria with the exception of their pigmentation and lipid composition. However, the pigment composition (number, Rf-values and spectra of the pigment components) of the yellow mutant is identical with that of the wild type; as a consequence, the modified pigmentation of the yellow mutant cannot be explained by an altered pigment synthesis. The wild type cells and the mutant SN 5108 G contain three main pigment components designated as I, II and III. Components II and III posses a marked indicator character and show a bathochromic shift in solutions of pH 12 or higher. Components II and III contain functional groups which are able to react with acetic acid yielding acetylated products; after acetylating, no bathochromic shift in alkali occurs. Intact cells of the wild type retain their orange-red pigmentation in buffer solution with a pH-value of 12 or higher. Cells of the yellow mutant, however, change the yellow color immediately after the alkali treatment to orange-red; this new color is identical with that of the wild type and can be changed to yellow by placing the cells into 1 N HCl. Regarding these facts it seems to be very probable that the functional groups of the pigment components II and III are differently bound in the wild type and mutant cells. In the mutant, they are accessible to OH- ions yielding a bathochromic shift while in the wild type cells, OH- ions are unable to provoke this shift. It seems to be also probable that different lipids in the two strains are responsible for the binding of the pigments. So far known, this is the first observation about the occurence of pigment mutants with an altered pigment binding site in the cells.


Formation and some factors influencing the activity of progesterone hydroxylases by Aspergillus niger. The formation of progesterone hydroxylases by Aspergillus niger 173 was investigated. The constitution of the fermentation medium influenced both the yield and the type of enzymes catalyzing the transformation of progesterone. The enzyme yield also varied with the pH value at which induction was performed as well as with the buffer used. The transformation activity of progesterone was more pronounced with mycelia induced in citrate-phosphate than in phosphate buffer. The results demonstrated that induction of 6beta-hydroxylase was favoured at pH values near neutrality while that of 11alpha-hydroxylase in the presence of citrate ions. The transformation activity of progesterone was optimal at pH 5.0. The action of 11alpha-hydroxylase was also optimal at pH 5.0, but other hydroxylase showed pH optima between 2.2 and 4.0. Progesterone concentrations higher than 6 mg in 50 ml reaction mixture was a limiting factor for the rate of transformation activity.


[Preparation of the lectin B component from the hemagglutinin of Lens culinaris]. Out of a mixture of both lectins of the lentil (Lens culinaris) the component B may be separated rapidly and easily because of the different temperature sensitivity of haptene protected isolectins A and B.


Alanine formation and alanine aminotransferase activity in the nerve tissue with proliferating macroglia. In the nerve tissue with proliferating macroglia cells were observed a lowered oxygen consumption, an increased aerobic glycolysis and alanine formation and a higher alanine aminotransferase and glutamate dehydrogenase activity than in the control tissue in the homogenates and in the cell sap fraction. The substrate saturation curves, apparent Km and pH optimum values in the tissue with proliferating macroglia and in the control did not differ from one another. The authors assume that a higher alanine aminotransferase activity in the tissue with macroglia proliferation can reflect either a higher synthesis of the enzyme in the altered tissue, or a predominance of glial elements in the altered tissue possessing a higher alanine aminotransferase activity than the nerve cells.


Influence of sugar content in soft bread on pH of human dental plaque. Quantitative determination of monosaccharides, disaccharides and sorbitol by use of gas-liquid chromatography (GLC) was performed on thirty-three samples of different commercial soft bread. Maltose was found in all the bread samples. Fructose and glucose were found only in samples of sweetened bread. Sucrose was detected in 5 samples, lactose in 2, and sorbitol in 2. Up to 20 per cent of the fresh bread weight was found to be low-molecular weight carbohydrates. Plaque pH-changes were studied in 18 persons following a 30-second month rinse with each of 3 solutions: (1) 50% sucrose, (2) water extract of sweetened bread, and (3) water extract of unsweetened bread. Mouth rinsing with the extract of sweetened wheat bread (sucrose 7.7 per cent of the dough weight) caused pH-decreases in plaque which were significantly more pronounced than those induced by the water extract of unsweetened wheat bread.


Preliminary study of parenteral lorazepam in status epilepticus. The authors report their experience with parenteral lorazepam in the acute treatment of 11 patients with EEG-confirmed status epilepticus. Ten adults and one 6-year-old child were injected respectively with 5 mg and 2.5 mg lorazepam. All of these patients exhibited prompt cessation of seizures both electrical and clinical. Some data indicate a longer lasting relief than that provided by an equal dose of diazepam.


Structure-basicity and structure-affinity relationships of beta-adrenergic blocking agents. pKa's of fourteen beta-receptor blockers, isoproterenol and norepinephrine, were determined potentiometrically. A Hammett analysis indicated that the influence of ring substituents on the basicity of the amines is attenuated by the ethanolic chain and abolished by the propranoloxy chain of beta-receptor blockers. The effect of ring substituents in phenoxypropranolamines upon affinity for the beta-adrengeric receptors is therefore unrelated to the strength of the bases. Two alterantive hypotheses are fowarded to explain why phenoxypropranolamines have greater affinities for the beta-receptors than phenethanolamines.


Inhibition by acidosis of adenosine 3',5'-cyclic monophosphate accumulation and lipolysis in isolated rat fat cells. Lipolysis and cyclic AMP accumulation were studied in isolated rat fat cells at normal (7.4) and decreased (7.0, 6.6) pH. Acidosis inhibited lipolysis and cyclic AMP accumulation due to NA non-competetively. Maximal lipolysis (3 muM NA) was inhibited by 25% at pH 7.0 and by 61% at pH 6.6 Cyclic AMP accumulation 5 min after 3 muM NA was inhibited by 57% at pH 7.0 and by 83% at pH 6.6. Between 10 and 60 minutes of incubation NA-stimulated lipolysis was linear at pH 7.4, whereas a progressively increasing inhibition was seen at lower pH. The FFA production was inhibited to the same degree as glycerol production by acidosis. The fraction of FFA associated with the cells was the same at all pHs. Thus, we have no evidence that acidosis inhibits lipolysis via accumulation of FFA intracellularly. NA-induced accumulation of 3H-cAMP from 3H-ATP, endogenously formed by prelabelling the cells with 3H-adenine, was inhibited by acidosis both in the presence and absence of theophylline in the incubation medium (by 48 and 44% respectively at pH 7.0 and by 74 and 68% at pH 6.6). Cyclic nucleotide phosphodiesterase in homogenates of fat cells was inhibited by decreasing the pH, whether measured at high or low substrate concentrations. Basal adenylyl cyclase activity in a cell membrane fraction from fat cells was affected to a minor degree, while NA-stimulated activity was inhibited by decreased pH. The response to 3 muM NA at pH 6.6 was inhibited by 43% relative to control. The results show that acidosis inhibits NA-induced cyclic AMP accumulation by interfering with the formation, rather than the inactivation of the nucleotide. Since NA-induced lipolysis is a cyclic AMP-mediated process it is suggested that at least part of the antilipolytic effect of acidosis is due to inhibition of cyclic AMP formation.


Cyclic AMP-dependent and independent inhibition of lipolysis by adenosine and decreased pH. NA-stimulated lipolysis and cAMP formation in isolated rat fat cells is inhibited by acidosis. In the present report we have examined the quantitative relationship between lipolysis and cAMP formation at normal and reduced pH and the possible involvement of adenosine, an endogenous inhibitor of cAMP formation. Adenosine antagonized cAMP accumulation and to a considerably lower degree lipolysis, effects potentiated by acidosis. Theophylline, an antagonist of adenosine effects, stimulated lipolysis and cAMP-accumulation, and potentiated responses to NA. Adenosine deaminase (ADA) had theophylline-like effects. Acidosis inhibited lipolysis and cAMP accumulation induced by ADA and theophylline to a larger extent than those induced by NA. It is suggested that adenosine modulates fat cell cAMP production and may contribute to the antilipolytic effect of acidosis. There was a curvilinear relationship between cAMP elevation and glycerol production in fat cell suspensions, which was different at pH 7.4 and at pH 6.6. The amount of cAMP needed for half-maximal activation of lipolysis increased from 1.3 (pH 7.4) to 3.1 pMol X 10(-5) cells (pH 6.6). The maximal glycerol production was reduced from 1 300 to 900 nMol X 10(-5) cells. The antilipolytic effect of acidosis is apparently due partly to an inhibition of cAMP formation and partly to inhibition of subsequent step(s) in the activation sequence.


Modification of the gastric secretory response to sham feeding by acidification of the antrum and the duodenum in dogs. The effect of closure of a gastric cannula on the acid response to sham feeding was studied in Pavlov-pouch dogs with intact antro-duodenal regions as well as in antrectomized dogs with gastroduodenostomies. In the latter dogs, the sham feeding response was augmented by infusions of low doses of exogenous gastrin. The acid output after sham feeding in intact dogs was reduced on average by 59% by closure of the gastric cannula. In antrectomized dogs receiving a back-ground stimulation with gastrin, the response to ham feeding was not inhibited by closure of the cannula. The results suggest that the observed hypersecretory response to sham feeding after diversion of gastric acid from antrum and duodenum is mainly due to inactivation of antral inhibitory mechanisms. The pepsin secretion following sham feeding was not consistently changed by closure of the gastric cannula.


Beta adrenergic dilator component of the sympathetic vascular response in skeletal muscle. Influence on the micro-circulation and on transcapillary exchange. A neurogenic beta-adrenergic vasodilatation in skeletal muscle has been indicated by some recent investigations. The present study describes the extent to which this neurogenic beta-dilator mechanism contributes to the integrated vascular response in consecutive sections of the muscle vascular bed during sympathetic nerve activation. This was done by studying the vascular reactions to graded sympathetic stimulation (1-16 Hz) before and after beta-adrenoceptor blockade. Beta-blockade did not influence significantly the sympathetically induced changes of total muscle vascular resistance or capacitance. Vascular tone in the "micro-vessels" during stimulation was, however, clearly more pronounced in the beta-blocked than in the non-blocked region, as revealed by segmental resistance analysis and by determination of precapillary sphincter tone (CFC). In addition, beta-blockade markedly reduced the net transcapillary absorption of extravascular fluid evoked by nerve activation. This effect could be ascribed to the mentioned influence on the precapillary sphincters, leading to a decrease of the number of capillaries available for transcapillary exchange, and to a limitation of the nerve induced fall of capillary hydrostatic pressure. The described effects of alpha-blockade were observed at all rates of sympathetic stimulation.--The conclusion was reached that the beta-adrenergic dilator component of the sympathetic vascular response in skeletal muscle significantly modifies the alpha-adrenergic constriction in the micro-vessels. It is suggested that, in the intact organism, this neurogenic beta-dilator mechanism is primarily aimed at improving the transcapillary exchange.


Haematologic adaptation in patients with chronic bronchitis and pulmonary insufficiency. The relationship between respiratory insufficiency, expressed by gas tensions in blood and bone marrow, and haematologic adaptation has been studied in 82 men with chronic bronchitis and persistent breathlessness for at least one year. For the group as a whole and for various subgroups, a linear correlation was demonstrated between arterial hypoxia and Hb concentration, haematocrit, blood volume, Hb mass and erythrocyte volume, respectively. The increase in Hb concentration compensated for the fall in arterial oxygen saturation. Only for one subgroup, with a pH difference between arterial and venous blood larger than or equal to 0.08, was no correlation found between the degree of hypoxia and Hb concentration. The haematologic parameters correlated significantly better with arterial oxygen tensions than with oxygen tensions in the bone marrow. There was no indication that decreased oxygen supply to the bone marrow led to the increased erythrocyte and Hb production in patients with arterial hypoxia caused by chronic bronchitis.


Pattern of enzyme activity following acute myocardial infarction with special reference to gamma-glutamyl transpeptidase. The present study on 55 consecutive patients with acute myocardial infarction (AMI) draws attention to the relationship between different enzyme maxima in AMI, with special reference to serum gamma-glutamyl transpeptidase (S-GT). In more than 60% of the patients the S-GT was increased during the hospital stay. The S-GT rise nearly always began during the first days,  reached a maximum within 5--8 days and normalized with 2--3 weeks. We failed to find the late increase in S-GT reported by others. The rise of S-GT is particularly common in patients with inferior infarction, with or without right ventricular involvement. We conclude that S-GT activity is not a useful early or late indicator of AMI but a very sensitive test for hepatic dysfunction in patients with AMI.


Diamine oxydase in rabbit small intestine: separations from a soluble monoamine oxidase, properties and pathophysiological significance in intestinal ischemia. From all mammals investigated so far only in rabbits diamine oxidase could not be detected in any tissue except the gut. Thus this species was chosen for studying the physiological and pathophysiological function of this enzyme in the gastrointestinal tract. By gel filtration on Sephadex G 50 and G 200 the enzyme was purified 100-fold, separated from a soluble monoamine oxidase, and the properties of the two enzymes were determined. Diamine oxidase from rabbit small intestine deaminated putrecine (Km = 1.3 times 10(-4) M, pH-optimum 6.4-6.9) and histamine (Km = 8 times 10(-5) M, pH-optimum 7.5), but not serotonin, and was inhibited by aminoguanidine, but not by pargyline. Soluble monoamine oxidase from rabbit small intestine catabolized serotonin (Km = 1.8 times 10(-4) M, pH-optimum 8.8) but not putrescine and histamine, and was inhibited by pargyline, but not by aminoguanidine. Based on its properties in vitro intestinal diamine oxidase could inactivate the vasoactive biogenic amine histamine in vivo. To confirm this hypothesis, in rabbits the small intestine was damaged severely by inducing total intestinal ischemia, which occurs as mesenteric infarction also in human subjects and is accompanied by histamine release. Treatment with aminoguanidine and ischemia killed the animals 3-times faster than ischemia alone, which supported our hypothesis on a protective role of intestinal diamine oxidase against histamine.


Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition. Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.


Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction. With use of a canine model of occlusion of the left anterior descending coronary artery and an intracellular lactic dehydrogenase stain to measure infarct size directly, the effects of allopurinol, methylprednisolone sodium succinate and propranolol were studied. Allopurinol did not influence the extent of myocardial necrosis, whereas both methylprednisolone and propranolol significantly reduced myocardial infarct size. Possible mechanisms of action and clinical applicability of these agents are discussed.


Effects of cedilanid-D in combination with metoprolol on exercise tolerance and systolic time intervals in angina pectoris. The interaction between cedilanid-D and metoprolol, a selective beta receptor blocking agent, on exercise tolerance and systolic intervals was studied in 15 patients with angina pectoris. The patients had been treated with metoprolol for several months in a dose of 50 mg, three times daily (one patient received 25 mg three times daily). Each patient participated in two studies separated by at least 1 week. After arriving at the laboratory each received 50 mg of metoprolol orally; thereafter, either cedilanid-D or placebo was infused intravenously in a double-blind study performed in randomized order. When the effect of the drugs was maximal, the systolic intervals and the heart volume were recorded at rest, and the exercise tolerance was tested with a bicycle ergometer. The mean maximal value of plasma concentrations of metoprolol assessed during the study was about 50 ng/ml but the variation among subjects was great (20 to 187 ng/ml). After administration of cedilanid-D there was a shortening of the pre-ejection period and left ventricular ejection time compared with results after placebo; the reduction was similar to that found after administration  of cedilanid-D without beta blocking drugs. The total heart volume decreased by an average of 55 ml, but the individual variation was great. The patients' average work capacity, expressed as total work, was not altered by cedilanid-D when compared with results after placebo. No relation was found between initial heart size and the effect of cedilanid-D on capacity for physical work. It therefore appears that there is no indication for the routine use of digitalis during beta blocking therapy in patients with angina pectoris who do not have cardiac failure.


Beta adrenergic blockade and diuretic therapy in benign essential hypertension: A dynamic assessment. Beta adrenergic receptor antagonists (beta blockers) differ greatly in their cardioselectivity and intrinsic sympathomimetic activity, and these differences may have important therapeutic consequences. We have therefore studied the effect on blood pressure, heart rate and plasma renin activity of the beta blocking drug oxprenolol (Trasicor) which has considerable intrinsic sympathomimetic activity, both alone and in combination with the benzothiadiazine cyclopenthiazide. Eleven patients with mild to moderate benign essential hypertension were randomly allocated to one of two treatment groups. Oxprenolol was given as the first drug to Group 1, and cyclopenthiazide as the first drug to Group 2. The patients were assessed before the start of treatment, after 2 to 3 weeks of treatment with one drug and after a further 2 to 3 weeks of treatment with both drugs. Heart rate, blood pressure and plasma renin activity were measured with the patients recumbent and after a standardized tilt to 85 degrees to provide a reflection of day to day cardiovascular stress. Oxprenolol reduced arterial blood pressure without inducing significant bradycardia. The addition of cyclopenthiazide had little further effect. Oxprenolol alone suppressed plasma renin activity both at rest and during tilt and also abolished the increase in plasma renin activity after administration of cyclopenthiazide. The combination of (1) moderate reduction of blood pressure. (2) inhibition of the otherwise inevitable increase in plasma renin activity with the use of a diuretic drug, and (3) only moderate inhibition of overall sympathetic activity indicates that it is possible to achieve physiologic balance with the appropriate beta blocking drug.


Control of renin release: a review of experimental evidence and clinical implications. Present knowledge of the mechanisms regulating release of renin is reviewed with particular emphasis on neural factors. Evidence is given for a direct effect of renal innervation on beta adrenergic receptors in juxtaglomerular cells, and for the involvement of reflex release of renin in conditions such as tilting and acute salt depletion. Participation of neural and nonneural mechanisms of control is also shown to occur in other conditions, such as aortic constriction and hemorrhage. The view is held that neural sympathetic factors might explain some of the renin disturbances found in essential hypertension. First, in patients with high renin hypertension part of the hypertension is renin-dependent, and these pressor levels of renin seem to be neurally induced since they can commonly be suppressed by beta adrenoreceptor blocking agents. Second, the hypothesis is presented that patients with low renin hypertension, at least those who have no volume disturbance, have a blunted sympathetic control of renin release. Therefore a sufficiently precise test of sympathetic activity, and possibly of body fluid volumes, should be associated with renin profiles for a better understanding of the pathophysiology of arterial hypertension and as a better guide to therapeutic management. Indeed, most of the available antihypertensive drugs act on sympathetic activity, body fluid volume or renin, and this multifaceted profile would provide more rational guidelines for treatment.


Syncope with prolonged QT interval.

Syncope with prolonged QT interval. Four children with syncope had a prolonged QT interval on the electrocardiogram. Neurologic studies were negative. One patient had associated deaf mutism, one had a family history of sudden death and prolonged QT interval, and two had ventricular arrhythmias while being monitored in the hospital. Treatment with propranolol hydrochloride eliminated the syncope in all patients, although the ECGs remained abnormal.


Quantitative determination of piperazine citrate in piperazine citrate syrup USP. An assay for piperazine citrate in Piperazine Citrate Syrup USP is described. The assay method is based on the formation of a complex of piperazine with an acid dye, bromothymol blue. The complex can be extracted with chloroform and measured spectrophotometrically. The method is accurate and requires only 15 minutes for analysis, compared to four to five hours by the USP method.


Personality and job satisfaction of medical technologists. The personality characteristics and job satisfaction patterns of a volunteer group of practicing medical technologists were measured by the Myers-Briggs Type Indicator and the Job Description Index. Data analysis was based on three groups of female subjects: clinical practitioners, educators, and administrators. There was little primary impact of personality upon job satisfaction, although definite patterns of personality are identifiable in the three groups. Implications for counseling students and placing practitioners in satisfying jobs were suggested, and additional studies to be conducted were identified.


Ventilatory and blood gas changes during laparoscopy with local anesthesia. A study was performed on a series of healthy patients undergoing laparoscopy for tubal ligation with local anesthesia in a non-operating room setting. Ventilatory parameters, blood gas, pH, blood pressure, and pulse were monitored. The results revealed that no adverse effect on hemoglobin saturation or carbon dioxide exchange were found when fentanyl alone was used as a supplementary analgesic. An occasional vagal reflex was observed, and it is recommended that an intravenous line be established in the event that pharmacologic intervention should become necessary. Nitrous oxide produced les with this minimal analgesia.


Bactericidal activity and pharmacology of flucloxacillin. Flucloxacillin, a recent addition to the group of isoxazolyl penicillins, was studied in vitro and in normal volunteers. The bactericidal activity of the drug against most strains of gram-positive bacteria including penicillin-resistant Staphylococcus aureus was similar to that of oxacillin and approximately fourfold greater than that of cloxacillin. Each of the three penicillins was administered orally to a group of ten volunteers for eight days in a dose of 500 mg four times a day. The mean concentrations of flucloxacillin in the serum were two- to sixfold higher than those of the other two agents on the first, fourth and eighth days of therapy. The percentage of flucloxacillin bound by serum protein was 94.6 per cent; for cloxacillin and oxacillin the values were 93.5 and 91.5 per cent, respectively. Using these data, the concentrations of free flucloxacillin in serum were found to be twice as high as those of cloxacillin and oxacillin. These findings suggest that, when administered orally, this new agent may offer some therapeutic advantage over oxacillin and cloxacillin.


Nephrology rounds, University of Iowa Hospitals: renal tubular acidosis. We have discussed two patients who had renal tubular acidosis complicated by hypokalemia. The first patient had a distal acidifying defect. Circumstantial evidence has been presented suggesting that exposure to toluene-diisocyanate or toluene-diamine played a role in the pathogenesis. The acidosis and the hypokalemia of this patient were easily corrected by the administration of small amounts of sodium bicarbonate without potassium supplementation. The second patient had an interstitial nephritis of unknown etiology and presented with moderate renal insufficiency, renal tubular acidosis, and proximal as well as distal acidifying defects. The proximal tubular dysfunction was associated with general aminoaciduria and glucosuria. This patient required large quantities of both alkali and potassium to correct the electrolyte abnormalities. The mechanisms of potassium wasting in proximal and distal renal tubular acidosis are reviewed. A classification is presented of cellular defects that may underlie the different renal acidifying defects. Attempts to distinguish between pump and permeability defects from urinary pCO2 levels must take into account the simultaneous HCO-3 concentration, since large pCO2 elevations require the presence of ample HCO-3 in the urine. Permeability defects may impair urinary acidification by either abnormal back flux of H+ out of the lumen or increased influx of HCO-3 into the lumen. In studies of acidification in vitro, amphotericin B causes increased H+ permeability and has little effect on HCO-3 permeability. Toluene-diamine causes a marked permeability defect which is reversible, but remains to be defined in terms of the ion species, HCO-3 or H+, affected. At times, hyperchloremic acidosis is caused by distal defects in net acid excretion that occur without impairment of the H+ gradient. In certain patients with hypoaldosteronism, for example, distal H+ secretion may be reduced without change in the force of the H+ pump.


Effects of salicylate and bile salt on ion transport by isolated gastric mucosa of the rabbit. The effects of luminal addition of salicylate and taurocholate on ion transport by fundic mucosa were examined in vitro using isotopic and pH stat techniques. Salicylate, 3 mM, did not alter, but 20 mM caused a 40% decrease in, the acid secretory rate. Taurocholate, 20 mM, caused a transient, apparent cessation of acid secretion followed by stimulation. Salicylate, 3 or 20 mM, increased Na+ but not Cl- permeability at luminal pH 7. At luminal pH 4, however, salicylate increased Cl- in addition to Na+ and H+ permeability. Taurocholate, 10 or 20 mM, increased both cation and anion permeability at pH 7 and 4. Addition of salicylate or taurocholate results in stimulation of net Na+ transport. While salicylate and taurocholate increase cation permeability at pH 7, they have differing effects on acid secretion and anion permeability. The data suggest that salicylate and taurocholate alter cation permeability by different mechanisms and are consistent with the concept that enhanced diffusion of H+ into the tissue causes a nonspecific alteration in the permeability pathway.


Characteristics of intestinal phase of gastric secretion. In four dogs provided with special gastroduodenal fistulas allowing for the complete separation of stomach and duodenum without interrupting the vagal connections between them, the magnitude of the gastric and intestinal phases was compared and their contribution to the total gastric response to a meal was established. A liver extract (LE) meal, confined to the stomach and maintained at pH 5.0 by an intragastric titration technique, produced acid output reaching 66% of the maximal response to histamine (MRH). Perfusion of the LE meal into the duodenum resulted in acid secretion amounting to 57% of MRH. The combination of the gastric and intestinal phases caused the highest acid output, amounting to about 90% of MRH. Gastric and intestinal phases induced separately were accompanied by a significant elevation in serum gastrin concentrations which reached the highest values when both phases were evoked simultaneously. Acidification of the intestinal meal resulted in pH-dependent inhibition of gastric secretion falling to the basal values at pH 1.0. These secretory changes were mimicked by exogenous secretin. Serum gastrin levels remained essentially unaffected by the acidification of the intestinal meal while exogenous secretin significantly lowered them. In conclusion, in the intact stomach with undisturbed nervous connections between the stomach and duodenum, a peptone meal in the intestine is capable of evoking a potent gastric acid and pepsin stimulation by a mechanism involving the release of antral hormone.


Inhibition of gastric secretion in the dog by 16,16-dimethyl prostaglandin E2. The synthetic prostaglandin 16,16-dimethyl E2 (PGE2) given by intravenous infusion at 0.4 mug/kg-h inhibited gastric secretion of H+, K+, Cl-, and pepsin in four fistula dogs stimulated by histamine (H), pentagastrin (P), urecholine (U), and 2-deoxy-D-glucose (2-DG). When given for 90 min during steady infusions of near-maximal doses of H, P, and U, PG-E2 caused 75% inhibition of H+ maximally at 90 min and over 85% inhibition of pepsin secretion maximally at 45 min. Recovery of secretion took 1-2 h after infusion of PGE2 was stopped. Injection of KCl, 1 meq/kg, during inhibition of histamine by PGE2 gave only a 15-min transient reversal in inhibition. When PGE2 was given as background to 45-min step-dose responses, 0.1 mug/kg competitively inhibited histamine stimulation and 0.4 mug/kg-h gave 100% inhibition. Against pentagastrin, 0.1 mug PGE2/kg-h had no effect and 0.4 mug caused uncompetitive inhibition; against urecholine, 0.4 mug PGE2/kg-h caused competitive inhibition of H+ secretion. Pepsin was more markedly inhibited in each case. There were no side effects at either dose of PGE2, which is a potent inhibitor of gastric secretion with all forms of stimuli.


Effect of carbon monoxide on equilibrium between oxygen and hemoglobin. Oxygen dissociation curves of partially CO-saturated human whole blood drawn freshly or preserved more than 3 wk were studied. With increasing CO-hemoglobin concentrations, oxygen affinity of the blood increased and the Hill coefficient, n, fell and gradually approached unity. The changes induced by CO-hemoglobin showed practically no difference in the presence or absence of 2,3-diphosphoglycerate. The Bohr coefficient, deltalog P50/deltapH, was determined as a function of oxygen saturation for various concentrations of CO-hemoglobin. The coefficient remained essentially unchanged in the presence of CO-hemoglobin. In the presence of less than 50% CO-hemoglobin, a good agreement was observed between the observed oxygen dissociation curves and the curves calculated according to Roughton and Darling (Am. J. Physiol. 141: 17-31, 1944). Based on these results, physiological implications of carboxyhemoglobinemia are discussed quantitatively in comparison with methemoglobinemia.


Erythropoietin production after renal denervation or beta-adrenergic blockade. The ability of either beta-adrenergic blockade or bilateral renal denervation to alter erythropoietin (ESF) production in rabbits exposed to hypobaric hypoxia was studied. ESF elaboration during 5 h of exposure to hypoxia was not affected by beta-blockade, but was markedly reduced by prior surgical denervation of both kidneys. After 18 h of hypoxia plasma ESF levels in renal denervated rabbits did not differ significantly from those of sham-operated controls. Previous studies have shown that ESF production during this more prolonged exposure to hypoxia was significantly inhibited by some beta-adrenergic blocking agents. Combined renal denervation and beta-blockade were more effective than renal denervation alone in attenuating ESF production during 5 h of exposure to hypoxia. However, ESF elaboration during 18 h of hypoxia was significantly greater in animals with combined denervation and beta-blockade than in control rabbits. These results suggest the existence of two distinct mechanisms for ESF production in rabbits exposed to hypobaric hypoxia.


The current status of behavioral psychotherapy: theory and practice. Behavioral psychotherapy has become one of the definitive treatments available for the relief of psychiatric suffering. Although hardly a panacea for all ills, the behavioral approach is the treatment of choice for certain selected problems. Behavioral methods make their contribution in the context of general psychiatric management and often must be used in conjunction with other treatment. The theoretical and practical aspects of behavioral psychotherapy have changed a great deal over the past few years and continue to evolve rapidly. Although useful molecular theories are emerging to guide the discipline, no global theory is likely to be satisfactory in the foreseeable future.


Effect of drug ritual changes on schizophrenic patients. The author evaluated the charts of 115 chronic schizophrenic patients who regularly attended a follow-up group to determine whether changes in long-standing medication regimens produced an increased dropout rate, decreased attendance, or psychotic decompensation. He found that although there were nonsignificant trends showing a relationship between medication change and group attendance for individual patients, there were no significant difference between group attendance and change or no change in medication routine for the group of patients as a whole. He concludes that necessary changes in medication routines for chronic schizophrenic patients are safe.


A simple technique for demonstrating transmission of dengue virus by mosquitoes without the use of vertebrate hosts. Aedes albopictus mosquitoes infected with dengue type 2 virus transmitted virus to measured small amounts of fluid which could be titrated readily for virus content. It was found that the percentage of mosquitoes transmitting was related to the extent of salivary gland infection. It was not uncommon for mosquitoes to transmit as much as 10(4) mosquito infectious doses50 of virus and transmission of significant amounts of virus was observed even though an insect only probed the test suspension without feeding to repletion. Transmission of virus was demonstrated as early as 10 days after oral infection when mosquitoes were held at 32 degrees C.


Ecologic studies of Venezuelan encephalitis virus and isolations of Nepuyo and Patois viruses during 1968-1973 at a marsh habitat near the epicenter of the 1969 outbreak in Guatemala. Ecologic studies of Venezuelan encephalitis (VE) virus at a marsh habitat near the epicenter of the 1969 outbreak in Guatemala revealed that the virus was enzootic there. VE virus was isolated yearly during 1968-1973 from sentinel hamsters exposed during the rainy seasons and from mosquitoes collected during July and August 1970. Hamsters yielded 41 strains of VE virus and virus was detected within 2 km of the edge of the marsh, in its interior, and at its western extreme 18 km from the central study site at La Avellana. One strain of virus came from a hamster that died in the dry season of January 1970. Culex mosquitoes yielded 20 strains of VE virus and Mansonia and Aedes one each. Culex (Melanoconion) and Aedes taeniorhynchus were most prevalent near the marsh. Hemagglutination-inhitibion (HI) and neutralization antibody tests of sera showed that wild terrestrial mammals (opossums and rodents), humans, and dogs, but not wild birds, were frequently infected. Seven of 16 susceptible residents of villages at the edge of the marsh developed antibodies without symptoms during an 18-month period between September 1971 and February 1973. Only 1 of 5 sentinel rabbits, and none of 30 sentinel chickens developed VE HI antibody during August-September 1971, a period when virus activity was readily detected by the use of sentinel hamsters. Five strains of group C arbovirus (one identified as Nepuyo) were recovered from sentinel hamsters during 1968 to 1970, and one strain of Nepuyo virus was isolated from the blood of a person with a febrile illness during 1972. Two strains of Patois group arboviruses were isolated from Culex mosquitoes during 1970.


Studies of possible movement of Venezuelan encephalitis virus from an enzootic focus in Guatemala during 1971-1974. During the wet seasons of 1972 and possibly 1971, sentinel horses became infected by Venezuelan encephalitis (VE) virus in a temporally and geographically progressive manner inland from an enzootic marsh focus of virus on the Pacific couast of southeastern Guatemala. During the wet seasons of 1972 and 1973, VE virus was detected by sentinel horses (and a sentinel hamster in 1972) in a small woods 10 km north of the marsh, but virus was undetectable there during the dry seasons of 1973 and 1974 and the wet season of 1974. Culex (Melanoconion) mosquitoes were found in this woods and at the marsh during August 1973. These observations are compatible with movement of VE virus from the marsh habitat during some wet seasons. However, virus activity in this region adjacent to the marsh was quantitatively unpredictable on a yearly basis and occurred in only very focal habitats during 1971 to 1974. Mechanisms of VE virus movement from the marsh are currently unknown, but bats are under study as a likely possibility.


Hepatitis B surface antigen (Australia antigen) in mosquitoes collected in Senegal, West Africa. During July and August of 1973, 9,198 mosquitoes were collected in the Republic of Senegal. Eight species of mosquitoes were found in the collections: Culex thalassius, Culex pipiens quinquefasciatus, Culex trigripes, Culex phillipi, Aedes irritans, Aedes aegypti, Anopheles gambiae, and Mansonia sp. Specimens were sorted by biological condition; those obviously engorged were designated as (E), females with swollen abdomens not conspicuously blooded were considered gravid (G), and those with normal or shrunken abdomens were considered neither blooded nor gravid (U). Representative samples of each species were tested by solid phase radioimmunoassay for hepatitis B surface antigen (HBSAg, Australia antigen). A total of 12 mosquitoes were found to be HBSAg positive out of 1,658 individuals tested. These were: 9 Culex thalassius, 1 (E), 5 (G), 3 (U); 2 Culex pipiens quinquefasciatus, 1 (E), 1 (U); and Aedes irritans, 1 (U).


Hemorrhagic shock in dogs. Comparison of treatment with shed blood alone versus shed blood plus Ringer's lactate: intravascular pressures, cardiac output, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2, electrolyte changes, and survival rates. The purpose of our study of hemorrhagic shock in dogs was to examine the efficacy of adding Ringer's lactate to shed blood replacement in increasing animal rates. The standard Wiggers' hemorrhagic shock technic was used in two groups of ten animals each. Intravascular pressures, cardiac outut, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2 and pH, electrolyte changes, and survival rates were determined. There was a positive correlation between changes in cardiac output, central venous oxygen content, and PO2 and extracellular fluid PO2 as measured using subcutaneously implanted Silastic tubing and perforated plastic balls. Four of the dogs that received shed blood alone survived, whereas five of the dogs that received shed blood plus Ringer's lactate survived. This difference was not statistically significant.


[Conformational changes of hyaluronic acid in acid medium (author's transl)]. Both vitreous body homogenate and a fibrous product containing hyaluronic acid and collagen isolated from vitreous humor by acetone precipitation were investigated to elucidate the liquefaction of vitreous body by acids. Graphic evaluation of the titration with hydrochlorid acid and viscosity measurements suggest a changed of the hyaluronic acid molecule in the pH-range between 5.2 and 4.1. Between these pH-values the ionization of carboxyl groups is decreased accompanied by conformational changes of the hyaluronic acid molecule. These results are in agreement with the conclusion of other authors that by lowering the pH of hyaluronic acid solutions a random coil to double helix transition of hyaluronic acid occurs.


Treatment of the diving casualty.

Treatment of the diving casualty. In a diving emergency a number of specific conditions are possible in addition to those which would ordinarily be considered in a life-threatening situation. There are many separate factors which, underwater, can lead by some unfortunate combination of circumstances towards death usually, but not always, by drowning. The other major category of accidents are those resulting from the ascent of the diver to the surface. These must be considered as medical emergencies and the majority respond to immediate recompression. In the absence of readily available recompression facilities,various measures may ameliorate the condition pending transfer to a suitable compression chamber.


Scanning electron microscopic study of chylomicrons incubated with lipoprotein lipase. The effects of lipolysis on the structure of chylomicrons were studied with the scanning electron microscope using rat chylomicrons incubated with purified bovine milk lipoprotein lipase for 20 minutes at pH 8.1. Since the amount of albumin added to the medium was limited, some of the free fatty acids and partial glycerides formed by lipolysis accumulated in the chylomicrons. Lipolyzed chylomicrons fixed with OSO4 at pH 7.4 appeared in scanning electron micrographs as spheres with multiply idented irregular surfaces, while those fixed at pH 5.5, AS WELL AS CONTROL CHYLOMICRONS FIXED AT BOTH PHs, appeared as spheres with smooth surfaces. Sections of OSO4-fixed specimens, viewed with the transmission electron microscope, showed that the core of lipolyzed chylomicrons fixed at pH 7.4 contained numerous circular electron-lucent areas at the periphery, thus accounting for the indented surfaces observed above, while the core surfaces of the other specimens were circular and smooth. These findings confirm an earlier report that aqueous spaces form in chylomicrons during lipolysis when albumin in the medium is limited, and that the aqueous spaces disappear when specimens are prepared at pH 5.5 for microscopy. Thin sections of specimens that had been prepared for scanning electron microscopy showed that the gold-palladium coating was desposited directly on the indented surface of the lipid core of lipolyzed chylomicrons fixed at pH 7.4. It is concluded that vacuum dehydration during specimen preparation ruptures the outer wall of the aqueous spaces in lipolyzed chylomicrons and thereby exposes the interior of the spaces to gold-palladium coating and viewing with the scanning electron microscope.


Effects of training on biochemical values in standardbred horses. Effects of training at a regular, fixed, standard exercise load on venous lactic acid, mixed venous and arterial blood gases and pH, and serum muscle enzymes were determined on previously unconditioned, healthy, adult, Standardbred horses. Arterial and mixed venous blood gases, pH, and serum muscle enzymes did not change in a consistent manner during training. Venous lactic acid concentrations did increase significantly with training and may be of value for the biochemical evaluation of fitness in horses.


Acid-base values of standardbred horses recovering from strenuous exercise. Blood gases, lactic acid concentrations, and pH were measured in arterial and mixed venous blood in moderately conditioned Standardbred horses after a standardized exercise load of 1.6 km in 2 minutes, 40 seconds. Samples were obtained at rest, immediately after exercise, and at 3, 6, 15, 30, and 60 minutes after exercise. Arterial oxygen tension and mixed venous oxygen tension increased after exercise, reaching peak values at 6 minutes. Arterial oxygen tension returned to the resting (preexercise) value by 15 minutes, and mixed venous oxygen tension by 30 minutes. Arterial carbon dioxide tension decreased immediately after exercise, reaching its lowest value at 6 minutes, and returned to resting value by 30 minutes. Mixed venous carbon dioxide tension reached its highest value immediately after exercise, then decreased to less than the resting value, reaching its lowest value by 15 minutes, and returned to normal by 60 minutes. Lactic acid concentration increased immediately after exercise, reaching its highest value at 6 minutes, and returned toward normal by 60 minutes. Arterial pH decreased immediately after exercise, reaching its lowest value at 6 minutes, and returned to normal by 60 minutes. Mixed venous pH reached its lowest value immediately after exercise, then began to increase, and returned to normal by 60 minutes. The decrease in mixed venous pH was more pronounced than that in arterial blood since, in addition to the increase in lartic acid, there was a considerable increase in mixed venous carbon dioxide tension.


[Metabolic acidosis and intravenous injections of fat emulsions (role of phospholipids. Experimental study)]. In explanation of metabolic acidosis during parenteral nutrition, the authors considered the supply of H+ ions by fat emulsion, containing phospholipids of egg or soy. During intravenous infusions of 24 grams of lecithins to two healthy subjects, they observed an increased output H+ ions in urine, about 74,05 and 75,88 mEq, and a metabolic acidosis of the plasma. The theorically forcasted supply of production was 74,6 mEq. Indeed the metabolism of phospholipids supplies phosphoric ions (PO4H3), giving H+ ions at pH 7,40. The most used fat emulsions are able to give between 37 (intralipid 10%) and 61 (lipihysan 15%) mEq of H+ ions/liter.


Identification of immunoglobulins associated with complement fixation, agglutination, and low pH buffered antigen tests for brucellosis. Serums from infected cattle, cattle with persistent postvaccinal antibody, and serologically "positive" noninfected cattle were fractionated into major immunoglobulin classes by diethylaminoethyl (DEAE)-cellulose chromatography and by sucrose density gradient centrifugation. Each fraction was assayed for anti-Brucella activity by standard tube-agglutination test (STT), buffered tube-agglutination test (BTT), and complement-fixation test (CF). In the serums from experimentally infected cattle, anti-Brucella antibody could be found by all tests in 6 DEAE fractions and in slow, fast, and sediment regions of the density gradient. Serums from cattle with persistent postvaccinal titers had STT activity in all 6 DEAE fractions, BTT activity in 5 fractions, and CF activity in only 1 fraction. The STT and BTT activities were found in the slow and the sediment regions of the gradient, whereas the CF activity was found only in the slow region. Serums from a chronically infected animal had STT and BTT activities in 2 DEAE fractions and CF activity in only 1. The STT, BTT, and CF activities were found in the slow and the sediment regions of the gradient. The principal antibody in serums from noninfected cattle was immunoglobulin M, which had all of the CF activity and most of the STT and BTT activities. Low levels of STT and BTT activities were found in 3 other DEAE fractions. Only STT and BTT activities were found in the fast and the sediment regions of the gradient.


Theoretic significance of pH dependence of narcotics and narcotic antagonists in clinical anesthesia. Determination of the effect of pH and temperature on pKa partition, and drug distribution coefficients in a series of common narcotics and their antagonists has shown that within the range of blood pH (7.1 to 7.7) encountered in the practice of anesthesiology, marked differences of distribution of the drugs between a model lipid (octanol) and water can occur. When these data are considered in the light of clinical experience with narcotics used in patients undergoing or recovering from surgical procedures, a correlation between the depth and duration of narcosis or the efficacy of narcotic antidotes and ventilatory status is seen. This correlation can be explained in part if the influence of blood pH on the probable CNS/blood distribution of a given drug is taken into consideration. Support is given to this proposal by representative studies in the literature. The very different drug distribution coefficients of two closely related narcotic antagonists, naloxone and naltrexone, correctly predicted the faster onset and shorter duration of the former, which was confirmed by reported clinical observations.


"Aspiration disease".

"Aspiration disease". Aspiration disease, a term used to define both an acute and chronic form of a disease entity, is described. Etiological factors, pathophysiology and therapy are discussed with emphasis on aspiration of gastric juice. A brief mention of a small clinical experience is included.


Plasmid-mediated penicillin beta-lactamases in Pseudomonas aeruginosa. A penicillin beta-lactamase (PCase) was extracted from Pseudomonas aeruginosa Rms139(+) and purified by means of column chromatography. The isoelectric point of Rms139 PCase was 5.7 and its molecular weight was 22,500 +/- 1,000. The optimal pH for the hydrolysis of benzylpenicillin was 7.0 to 7.5 and the optimal temperature was 45 C, with the PCase also showing high activity against carbenicillin. It is concluded that this enzyme is a new type of penicillin beta-lactamase different from the type I, II, or III R plasmid-mediated PCases reported previously.


Immunosuppressant activity of the ansamycins. The immunosuppressive effect of four analogues of rifampin and two streptovaracins on cell-mediated immunity has been determined. Tuberculin hypersensitivity in the footpads of immunized mice was inhibited by three of the rifampin analogues and by both streptovaracins. The observed in vivo immunosuppressive activity of the compounds tested was not correlated with their in vitro activity against mycobacterial growth but was associated with their toxicity in mice. These data indicate that some of the analogues of rifampin and the streptovaracins can significantly suppress cell-mediated immunity and suggest that other ansamycins may have significant immunosuppressant activity.


In vitro susceptibility studies with josamycin and erythromycin. The in vitro activity of josamycin and erythromycin against five bacterial species was compared. In general, erythromycin was slightly more active by weight than josamycin, although both agents had a similar range of activity.


Two XX males diagnosed in childhood. Endocrine, renal, and laboratory findings. Two prepubertal boys with bilateral cryptorchidism were identified as 46,XX after nuclear sexing studies in several tissues. Gonadal histology and chromosome studies suggested that true hermaphroditism or mosaicism were unlikely. Xg blood grouping was informative in one patient. Accepting paternity, this suggested either that both Xs were maternal, with loss, for example, of the male determining Y chromosome, or that the paternal X chromosome did not express, probably because of a deletion, the allele for the positive Xg blood group. The patients had normal thyroid stimulating hormone reserves but subnormal responses to human chorionic gonadotrophin stimulation, and may need hormonal replacement at puberty. Both had renal anomalies. We suggest that chromosome analysis is essential when cryptorchidism, hypospadias, or microgenitalia are found and that an intravenous pyelogram is desirable.


Establishment of a viable homograft cardiac valve bank: a rapid method of determining homograft viability. A method for determining the viability of homograft valves has been developed based on sequential measurements of glucose and pH levels of the culture medium in which cardiac valves have been maintained for short periods at 37 degrees C. Viable valves, as determined by tissue culture, showed a characteristic pattern of glucose utilization and pH reduction that was absent in nonviable valves. Upon explantation of valve leaflet fragments into tissue culture, only fragments from valves that metabolized glucose produced viable fibroblast cultures. The method reported here is rapid, requires no specialized equipment, is nondestructive, and can directly determine the viability of the valve homograft within 24 to 48 hours.


Resin hemoperfusion for acute drug intoxication. Eight patients with drug intoxication were hemoperfused on ten occasions at a blood-flow rate of 300 ml/min with a 650gm column of Amberlite XAD-4 resin, which is a macroreticular resin with a specific adsorptive attraction for lipid-soluble organic molecules. Column clearances of glutethimide and a variety of barbiturates ranged from 207 to 300 ml/min for treatment sessions extending from 2 1/2 to ten hours. After ingestion of 75 gm of glutethimide, one patient received hemoperfusion on three successive days for nine, ten, and eight hours, respectively. She recovered after the column removed over 30 gm of drug. The patients demonstrated dramatic clinical responses with no evidence of meaningful toxic reactions. Column hemoperfusion with Amberlite XAD-4 resin was simpler and more effective than any known method of removing barbiturates and glutethimide from the blood of patients with drug overdoses.


Increased mucociliary transport by adrenergic stimulation. Tracheobronchial clearance of inhaled 6mum Teflon particles (density 2 gm/cu cm) tagged with technetium 99m was studied in healthy subjects by external measurement of the radioactivity in the lungs for two hours. Clearance, salivary secretion, blood pressure, and heart rate were determined in eight subjects after double-blind, subcutaneous administration of 0.25 mg terbutaline sulfate, a beta-adrenoceptor stimulating compound and vehicle, respectively, in a crossover study. Terbutaline produced a marked increase in clearance and a slight increase in heart rate, but had no important effect on salivary secretion or blood pressure. The result indicates that the blood concentrations of catecholamines might be of importance for the regulation of the mucociliary transport rate.


Platelet aggregation in portal cirrhosis. Primary and secondary platelet aggregation in response to adenosine diphosphate was studied in 24 patients with portal (Laënnec) cirrhosis and compared with platelet aggregation in 14 normal subjects. In 12 patients with cirrhosis, platelet aggregation was diminished when compared to controls. Of the 12 patients with impaired aggregation, 6 had elevated levels of fibrinogen-fibrin degradation products (FDPs), 11 had thrombocytopenia, 10 had shortened euglobulin lysis times, 11 had prolonged bleeding times, 4 had hypofibrinogenemia, and all had prolonged thrombin clotting times. The data suggest that elevated levels of serum FDPs do not explain fully the impairment of platelet aggregation or the prolongation of the thrombin clotting time that was noted in patients with advanced liver disease. A possible explanation for the prolongation of the thrombin clotting time is the presence of "altered" plasma fibrinogen.


Study of guinea pigs fed Swiss chard grown on municipal sludge-amended soil. Multi-element content of tissues. Swiss chard, field-grown on soil amended with 100 dry tons per acre of municipal sewage sludge from Washington, DC, was fed to guinea pigs for 28 days. Control animals were fed Swiss chard grown on unfortified soi. Forty-one elements were determined in the sludge, the plant material, and liver, kidney, muscle, adrenal, and spleen tissues by neutron activation and other methods. Elevated concentrations of several elements found in the Swiss chard grown on the sludge-soil mixture also appeared at higher levels in certain of the animal tissues. These included antimony in adrenal, cadmium in kidney, manganese in liver tissues, and tin in several tissues. The animals showed no observable toxicological effects.


[Counter-immunoelectrophoresis in the diagnosis of meningoencephalitis by Diplococcus pneumoniae and Hemophilus influenzae]. The presence of antigen of D. pneumoniae and H. influenzae was detected by counter-immunoelectrophoresis (CIE) in 113 LCR of children with central nervous system (CNS) infection (17 viral, 70 bacterial and 6 tuberculous). From 41 normal children spinal fluid was obtained and used as control. Precipitation band was not observed in normal children cases of viral and tuberculosis meningitis. In 21 cases of bacterial meningitis, D. pneumoniae and H. influenzae was isolated in six cases each. In six cases of bacterial meningitis were positive both bacteriological study and CIE. In 49 cases in which culture was negative only 13 gave positive CIE. When other strains of bacteria were isolated, no positive band was detected with CIE. This technic was regarded as useful for detecting etiologic agent in purulent meningitis.


Alanine dehydrogenase of the N2-fixing blue-green alga, Anabaena cylindrica. The L-alanine dehydrogenase (ADH) of Anabaena cylindrica has been purified 700-fold. It has a molecular weight of approximately 270,000, has 6 sub-units, each of molecular weight approximately 43,000, and shows activity both in the aminating and deaminating directions. The enzyme is NADH/NAD+ specific and oxaloacetate can partially substitute for pyruvate. The Kampp for NAD+ is 14 muM and 60 muM at low and high NAD concentrations respectively.


Aromatic amino acid biosynthesis in Alcaligenes eutrophus H 16 III. Properites and regulation of anthranilate synthase. Properties and regulation of anthranilate synthase from Alcaligenes eutrophus H 16 were investigated. Anthranilate synthase was partially purified from crude extracts by affinity chromatography on tryptophan-substituted Sepharose, and was used for kinetic measurements. During the purification procedure the enzyme was stabilized by 50 mM L-glutamine or during chromatography on DEAE- cellulose and Sephadex G-200 with 30% glucerol, respectively.


Influence of industrial toxic compounds on pregnancy. VI. Some tissue enzymes in pregnant guinea pigs exposed to the action of triethylenetetramine. Gamma-glutamyl transpeptidase activity in kidney homogenates, aspartate and alanine aminotransferase activities in liver homogenates, and cholinesterase activity in brain homogenates were determined in nonpregnant and pregnant guinea pigs exposed to absorption through the skin of the epoxy resin triethylenetetramine. Elevated activity of gamma-glutamyl transpeptidase in the kidneys of pregnant animals, and aspartate aminotransferase in the liver of nonpregnant guinea pigs were observed.


[Histology and histochemistry of the seal ovaries and the age-related changes in the ovaries of the Greenland seal]. Histological and histochemical methods were used to study the ovaries of Greenland seal (Pagophoca groenlandica) from birth-time up to 30 years of age and mature females of Phoca vitulina and Erignathus barbatus. The ovary of the new-born Greenland seal has fetal medullary substance which is a provisory endocrinous gland producing not only sex hormones but also corticosteron. In other species of seals the intestinal cells of the medullary substance are the equivalent of this gland. Within 3-4 weeks after birth the reduction of the fetal medullary substance is completed, it is substituted by the connective tissue and the ovary acquires its typical structure. The rest of the fetal medullary substance is in the depth of the cortex and near the infundibulum of the ovary as lipofuscincontaining cells. When the maturation period approaches, the process of the follicle atresia regularly changes: the epithelium dies quicker, and the multiplication of intestinal cells increases. The ovaries of seals are rich in interstitial cells. Their amount cyclically changes. The cells producing steroid hormones always well hydrolize AS naphthyl-phosphates, the reaction with glycerophosphate is more variable. The connective tissue is poor in acid mucopolysaccharides, its amorphous substance in the ovary cortex is rich in protein. Senile changes of the ovary are noticed in the seal beginning from 20 years of age.


[Endocrine cells of the gastric mucous membrane]. In order to obtain an additional information concerning a possible functional role of the main types of the endocrine cells (EC and ECL) on investigation of aspiration biopsy specimens taken from the middle third of the stomach in patients with ulcerative disease of the duodenum and chronic gastritis was carried out. Changes in morphology, distribution and number of the endocrine cells in pathology of the mucosa and in various acidity of the gastric juice were followed up. On the basis of the data obtained the conclusion is made that serotonin-producing (EC) cells seem to have nothing to do with the regulation of the activity of the fundal glands, whereas the enterochromaffin-like cells (ECL) influence the production of hydrochloric acid by pavement cells.


Tranquilizers or anti-depressants for chronic schizophrenics: a long term study. The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years (mean). The role of adding an anti-depressant was also studied. Following a 4 week placebo period, high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks. Statistical analyses of the various change measures revealed that patients worsened significantly on placebo, all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration. No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage.


Physiological index as an aid in developing airline pilot scheduling patterns. A multiplicative and additive formula has been developed for assisting in the development of schedules for airline pilots and flight engineers. The formula is based on freshness/tiredness data derived from aircrews on world flights. It should materially assist those who develop the schedules to avoid, where possible, finalizing those crew patterns that would impose a severe physiologic load on cockpit personnel. The objective of the application of the formula is to assure that crew members retain adequate "physiologic reserve" in the course of flying various segments of a pattern. This enables them to absorb the stresses of schedule delays or disruptions, as well as unforeseen operational problems and flight emergencies.


A neutral collagenase from human gastric mucosa. Biopsy specimens of human gastric mucosa, maintained in culture for 7 days in the absence of serum, released a collagen-degrading enzyme into the medium. The yield of active enzyme reached a maximum after 2-3 days, and viable tissue, capable of protein synthesis, was essential for its production. 2. At 25 degrees C the enzyme attacked undenatured collagen in solution, resulting in a 55% loss of specific viscosity and producing the two products TCA and TCB characteristic of neutral-collagenase action. 3. Electron microscopy of segment-long-spacing crystallites of these reaction products showed the exact cleavage locus of the collagen molecules to be between bands 43 and 44 (I-43). The larger TCA and smaller TCB products were fragments representing 77 and 23% respectively of the length of the collagen molecule. 4. Optimal enzyme activity was observed over the pH range 7.5-8.5 and a mol.wt. of approx. 38000 was derived from gel-filtration studies. 5. The enzyme was shown to be inhibited by the human serum proteins alpha2-macroglobulin and a smaller component of mol.wt. approx. 40000; alpha1-anti-trypsin was not inhibitory. 6. EDTA, 1, 10-phenanthroline, cysteine and dithiothreitol all inhibited collagenase activity. 7. The gastric enzyme has properties similar to other well characterized collagenases, but differences exist with respect to its molecular size and the site of attack on the collagen molecule.


Adsorption of glyceraldehyde 3-phosphate dehydrogenase on condensed monolayers of phospholipid. The adsorption of [14C] alkylated glyceraldehyde 3-phosphate dehydrogenase from rabbit muscle to condensed monolayers of phosphatidic acid was investigated under a variety of conditions. 2. The rate constant for association at 20 degrees C depended on ionic strength. At I/2=60mM the rate constant was 0.39min-1. At I/2=260mM it decreased to 0.27min-1. 3. The apparent association constant (Kass.) for adsorption at I/2=60mM was 1.06 X 10(6)M-1 and was strongly influenced by subphase changes in pH and ionic strength. Measurements of Kass. at 20 degrees and 5 degrees C gave a value for the apparent enthalpy change on adsorption of -33kJ-mol-1. Calculations of the apparent change in free energy  and apparent entropy change for the adsorption process gave values of -34kJ-mol-1 and +2J-K-1-mol-1 respectively. 4. Decreasing the amount of phosphatidic acid in the monolayer by replacement with phosphatidylcholine caused the shape of the adsorption isotherm to change from apparent hyperbolic to sigmoid. Subphase changes in pH or ionic strength did not affect the shape of the adsorption isotherm. However, adsorption of enzyme on monolayers of 100% phosphatidic acid in the presence of 1mM-CaCl2 was sigmoid in nature. 5. It is concluded that glyceraldehyde 3-phosphate dehydrogenase binds to condensed charged monolayers by multiple electrostatic interactions. At low concentrations of phosphatidic acid in the monolayer or in the presence of Ca2+, this occurs in a two-step process and depends on lateral diffusion of phosphatidic acid for strong binding to take place.


Blood pH and PaCO2 as chemical factors in myocardial blood flow control. The effect of metabolic and hypercapnic acidosis on myocardial blood flow was studied during intravenous infusions of hydrochloric acid solutions (n = 12) and during passive ventilation with 5% CO2 (n = 5) in anaesthetized, closed chest dogs. Below a pH of 7.2 metabolic acidosis at normal arterial CO2-tensions caused an increase of coronary blood flow and a decrease of coronary vascular resistance associated with a narrowed myocardial arteriovenous O2-difference, indicating vasodilation at unchanged myocardial oxygen consumption. In propranolol-pretreated dogs myocardial blood flow and coronary oxygen AV difference remained unaffected, suggesting that the coronary dilatory effect of metabolic acidemia involves beta adrenergic stimulation. Coronary vasodilation induced by increasing arterial pCO2 was found to the significantly greater as compared with the dilatory effect of metabolic acidosis at the same blood pH level. Blocking of beta receptors did not reduce the coronary response to increased arterial CO2-tensions. It is concluded that the coronary vasodilation observed during hypercapnic acidosis is neither mediated by a beta adrenergic stimulation nor dependent of the concomitant change in blood pH. The possible sites of the coronary dilatory actions of increased arterial CO2-tensions are discussed.


Enzymic hydrolysis of acetylcarnitine in liver from rats, sheep and cows. 1. The enzymic utilization of O-acetyl-l-carnitine other than via carnitine acetyltransferase (EC 2.3.1.7) was investigated in liver homogenates from rats, sheep and dry cows. 2. An enzymic utilization of O-acetyl-l-carnitine via hydrolysis of the ester bond to yield stoicheiometric quantities of acetate and l-carnitine was demonstrated; 0.55, 0.53 and 0.30mumol of acetyl-l-carnitine were utilized/min per g fresh wt. of liver homogenates from rats, sheep and dry cows respectively. 3. The acetylcarnitine hydrolysis activity was not due to a non-specific esterase or non-specific cholinesterase. O-Acetyl-d-carnitine was not utilized. 4. The activity was associated with the enriched outer mitochondrial membrane fraction from rat liver. Isolation of this fraction resulted in an eightfold purification of acetylcarnitine hydrolase activity. 4. The K(m) for this acetylcarnitine utilization was 2mm and 1.5mm for rat and sheep liver homogenates respectively. 6. There was a significant increase in acetylcarnitine hydrolase in rats on starvation and cows on lactation and a significant decrease in sheep that were severely alloxan-diabetic. 7. The physiological role of an acetylcarnitine hydrolase is discussed in relation to coupling with carnitine acetyltransferase for the relief of ;acetyl pressure'.


Creatine kinase equilibrium and lactate content compared with muscle pH in tissue samples obtained after isometric exercise. Muscle biopsies taken from the musculus quadriceps femoris of man were analysed for pH, ATP, ADP, AMP, creatine phosphate, creatine, lactate and pyruvate. Biopsies were taken at rest, after circulatory occlusion and after isometric contraction. Muscle pH decreased from 7.09 at rest to 6.56 after isometric exercise to fatigue. Decrease in muscle pH was linearly related to accumulation of lactate plus pyruvate. An increase of 22mumol of lactate plus pyruvate per g of muscle resulted in a fall of 0.5pH unit. The apparent equilibrium constant of the creatine kinase reaction (apparent K(CK)) increased after isometric contraction and a linear relationship between log(apparent K(CK)) and muscle pH was obtained. The low content of creatine phosphate in muscle after contraction as analysed from needle-biopsy samples is believed to be a consequence of an altered equilibrium state of the creatine kinase reaction. This in turn is attributed mainly to a change in intracellular pH.


The microbial metabolism of acetophenone. Metabolism of acetophenone and some chloroacetophenones by an Arthrobacter species. 1. An organism that utilizes acetophenone as sole source of carbon and energy was isolated in pure culture and tentatively identified as an Arthrobacter sp. 2. Cell-free extracts of the acetophenone-grown organism contained an enzyme, acetophenone oxygenase, that catalysed an NADPH-dependent consumption of O(2) in the presence of the growth substrate; approx. 1mol of O(2) and 1mol of NADPH were consumed per mol of acetophenone oxidized. 3. Cell-free extracts also contained an enzyme capable of the hydrolysis of phenyl acetate to phenol and acetate. The amount of this esterase was increased markedly by growth on acetophenone. 4. The observed products of the acetophenone oxygenase reaction by crude cell-free extracts were phenol and acetate. However, inhibition of the phenyl acetate esterase by paraoxon resulted in the formation of phenyl acetate from acetophenone. 5. A degradative sequence is proposed in which acetophenone is metabolized by an oxygen-insertion reaction to form phenyl acetate. Further metabolism occurs by hydrolysis of this ester. 6. The organism and extracts were shown to metabolize chlorinated acetophenones. The environmental implications of this observation are discussed.


Permeability to calcium of pigeon erythrocyte 'ghosts' studied by using the calcium-activated luminescent protein, obelin. 1. Obelin, the Ca(2+)-activated luminescent protein from the hydroid Obelia geniculata, was sealed inside pigeon erythrocyte ;ghosts' in order to investigate effects on their permeability of different methods of preparation and of the bivalent cation ionophore A23187. 2. Changes in free Ca(2+) within the ;ghosts' were studied by following the rate of luminescence of obelin. The possibility that the obelin might have been released from the ;ghosts' during an experiment was investigated by studying the release of inulin and pyruvate kinase from the ;ghosts'. Less than 10% of the inulin or pyruvate kinase sealed within the ;ghosts' was released under any of the experimental conditions. 3. Triton X-100 (0.1-10%, v/v) made the ;ghosts' highly permeable to Ca(2+). In the presence of 1mm-Ca(2+) and Triton, 95-100% of the obelin was utilized within 10-20s. 4. A time-course of resealing ;ghosts' at 37 degrees C showed that over a period of 90min, the ;ghosts' became gradually less permeable to Ca(2+). ;Ghosts' which remained at 0 degrees C retained only a small concentration of obelin and ATP, and were highly permeable to Ca(2+). 5. Erythrocyte ;ghosts' resealed for 30min at 20 degrees C rather than 37 degrees C were more permeable to Ca(2+), as shown by the fact that 92% of the obelin in the ;ghosts' was utilized during the first 60s after the addition of 1mm-Ca(2+), as opposed to 44% for ;ghosts' resealed at 37 degrees C. 6. Haemolysis at pH6.0 rather than 7.0 resulted in ;ghosts' which were highly permeable to Ca(2+) after resealing for 60min at 37 degrees C. Of the obelin in the ;ghosts', produced by haemolysis at pH6.0, 90% was utilized in the first 60s after the addition of 1mm-Ca(2+) compared with 23% for ;ghosts' produced at pH7.0. 7. The bivalent cation ionophore A23187 increased the permeability of the ;ghosts' to Ca(2+). Maximum effects of the ionophore (16mug/ml) were obtained by preincubating the ;ghosts' with the ionophore A23187 (16mug/ml) in the presence of a low concentration of Mg(2+) and in the absence of Ca(2+).


The action of tributyltin on energy coupling in coupling-factor-deficient submitochondrial particles. 1. Tributyltin at concentrations of approx. 1nmol/mg of protein induces respiratory control and lessens the protein permeability of coupling-factor-deficient submitochondrial particles. 2. At these concentrations or lower, it increases the P/O ratio of the particles to a small extent and inhibits the adenosine triphosphatase activity without greatly increasing its sensitivity to uncoupling agents. 3. It fails to stimulate ATP-driven reversed electron transport or transhydrogenase, but stimulates the transhydrogenase driven by aerobic succinate oxidation. 4. The results indicate that, unlike oligomycin, tributyltin does not discriminate between damaged and intact ATP-synthesizing complexes. 5. The relationship between the oligomycin- and tributyltin-binding sites is discussed.


Effects of the cardioselective beta-adrenergic receptor blocking agent metoprolol in angina pectoris. Subacute study with exercise tests. The effect of a cardioselective beta-adrenergic blocking agent, metoprolol, on symptoms and exercise tolerance was studied in 16 patients with angina pectoris. Metroprolol was compared with placebo at two dose levels (20 mg t.d.s. and 50 mg t.d.s.) in a double-blind trial in 14 patients. Compared with placebo, metroprolol caused a significant reduction of heart rate and systolic blood pressure during exercise, and consequently a reduction of the rate-pressure product. The reduction was greater with 50 mg t.d.s. than with 20 mg t.d.s. The exercise tolerance measured as total work increased significantly by 21 per cent during treatment with metroprolol 20 mg t.d.s., and by 17 per cent during treatment with 50 mg t.d.s. There was a reduction in the number of anginal attacks and in nitroglycerin consumption, and subjective improvement of angina pectoris at both dose levels of metroprolol. No signs of cardiac failure appeared during any of the four treatment periods. Heart volume showed no significant change. Unwanted effects were of the same frequency and severity during treatment with metroprolol at both dose levels as with placebo.


The availability of folates in man: effect of orange juice supplement on intestinal conjugase. The mechanisms of the low availability of endogenous folates in orange juice and the inhibitory effects on the availability of pteroylheptaglutamate (PteGlu7) caused by orange juice supplements were investigated in man by the use of simulated orange juice (containing the principal components: citric acid, malic acid, etc.) with several different pHs. The endogenous folates in orange juice were identified as mainly 5-methyl reduced derivatives of pteroylpolyglutamates (40-45% pentaglutamate, 10-15% tetraglutamate, 30-40% monoglutamate, and the rest were tri-and diglutamates). The availability of PteGlu7 is decreased to 54% by supplementation with 600 g concentrated orange juice (pH 3.7) and to 39% and 66% by the supplement of 24 g and 12 g citric acid (pH 3.7), respectively. Neutralization of 12 g citric acid to pH 6.4 largely reverses the inhibitory effect. On the other hand, the availability of pteroylmonoglutamate (PteGlu) is not influenced by a supplement of orange juice or citric acid. The results suggest that the low availability of PteGlu7 is due to the inhibition of intestinal conjugase caused by the low pH. These observations suggest that pH of foodstuffs may be an important factor in the absorption of polyglutamate forms of folate.


The use of a single venous blood sample to assess oxygen binding in haemoglobin. The measurement of pH, PO2, PCO2 and SO2 in a single venous blood sample can be used to determine the P50 at standard or at in vivo conditions. This technique makes it feasible for a physician, firstly, to make an assessment of the net adaptation of the red cell to reductions in blood oxygen content or flow and, secondly, to make an initial assessment of whether a haemoglobin with altered affinity for oxygen is present in subjects with polycythaemia or anaemia.


The state of energization of the membrane of Escherichia coli as affected by physiological conditions and colicin K. The bacterial protein colicin K, when added to sensitive Escherichia coli in the presence of 3,3'-dihexyloxacarbocyanine, cuases a doubling in fluorescence of the probe. Glucose and oxygen cause a decreased fluorescence while anoxia and cyanide cause a rise in fluorescence. These results in conjunction with the work of other laboratories suggest that colicin K causes a depolarization of the transmembrane electrical potential. Fluorescence in the absence of colicin K was relatively independent of KCl, NaCl, and MgCl2 concentrations below 0.1 M. Although colicin K caused rapid efflux of the K+ analogue 86Rb+, the fluorescence rise was only partially blocked by 0.13 M KCl. The level of fluorescence caused by the action of colcin K was inversely proportional to the logarithm of the concentration of MgCl2 over the range of 2 muM to 4 mM. This suggests that a Nernst electrochemical potential for an anion can counteract a membrane depolarization caused by colcin. After colcin K action, the fluorescence of the carbocyanine could be further increased by anoxia or cyanide. The distribution of the weak base dimethyloxazolidinedione indicated that the pH in the interior of aerobic E. coli supplied with lactate was alkaline by 0.1 unit and unaffected by colicin. These results suggest that colicin K does not completely depolarize the membrane potential and does not interfere with the component of membrane energization generated by electron transport. Colicin K does not act as a cationophore. The partial depolarization of the membrane may account for the inhibition of active solute transport caused by colicin K.


The acid-catalyzed decompostion of phenacylcobalamin: evidence for the formation of an enol-Co(III) pi-complex intermediate. Phenacylcobalamin has been synthesized and characterized by thin-layer chromatography and uv-visible spectroscopy, as well as identification of the cobalt-containing and organic products of its cleavage in acid and base and by aerobic photolysis. The major organic product from all three cleavage reactions is acetophenone and the cobalt-containing product is aquacobalamin (or hydroxocobalamin, its conjugate base). In aqueous acidic solution (pH 0 to 7.3, ionic strength 1.0 M, and 25.0 degrees C), the kinetics of the formation of aquacobalamin are biphasic representing the linear sum of two exponential terms. The pH dependence of the first-order rate constant of both phases shows a first-order dependence on proton concentration but with an inflection point ot pH 3.55 for the faster phase and at pH 4.03 for the slower phase. This behavior is interpreted in terms of the specific acid catalyzed formation of an intermediate from both "base on" and "base off" phenacylcobalamin with different second-order rate constants for each form, followed by an intermediate decompotion step with a similar formal mechanism. The nature of the intermediate is discussed and it is concluded to be a pi-complex between cob(III)alamin and the enol of acetophenone.