Effects of various acids and salts on growth and aflatoxin production by Aspergillus flavus NRRL 3145. The effects of sodium chloride, sodium acetate, benzoic acid, sodium benzoate, malonic acid, and sodium malonate on growth and aflatoxin production by Aspergillus flavus were investigated in synthetic media. Sodium chloride at concentrations equivalent to or greater than 12 g/100 ml inhibited growth and aflatoxin production, while at 8 g or less/100 ml, growth and aflatoxin production were stimulated. At 2 g or less/100 ml, sodium acetate also stimulated growth and aflatoxin production, but reduction occurred with 4 g or more/100 ml. Malonic acid at 10, 20, 40, and 50 mM reduced growth and aflatoxin production (over 50%) while sodium malonate at similar concentrations but different pH values had the opposite effect. Benzoic acid (pH 3.9) and sodium benzoate (pH 5.0) at 0.4 g/100 ml completely inhibited growth and aflatoxin production. Examination of the effect of initial pH indicated that the extent of inhibitory action of malonic acid and sodium acetate was a function of initial pH. The inhibitory action of benzoic acid and sodium benzoate appeared to be a function of undissociated benzoic acid molecules. Aflatoxin reduction was usually accompanied by an unidentified orange pigment, while aflatoxin stimulation was accompanied by unidentified blue and green fluorescent spots but with lower Rf values that aflatoxins B1, G1, B2, and G2 standards.


[Constitutive synthesis of cellulase by Trichoderma lignorum]. The induction of cellulase synthesis by lactose was studied in the resting cells of Trichoderma lignorum OM 534. The effect depended on the concentration of lactose, pH, and the age of the mycelium. The induction of the enzyme synthesis by lactose is supressed by glucose and its metabolites. The repression by glucose is partly eliminated by Cyk 3'-5'-AMP, theophylline, and coffeine. The induction of cellulase by lactose is regarded as a derepression of the synthesis of this enzyme as a result of slow assimilation of the disaccharide. The synthesis of cellulase in T. lignorum is presumed to be constitutive.


[Characteristics of a new cyanophage lysing unicellular cyanobacteria of the genus Synechococcus]. A new cyanophage S-2L growing on three strains of the cyanobacterium belonging to the Synechococcus genus has been isolated. The cyanophage has an icosahedral head, 56 nm in diameter, and flexible tail with a non-contracting sheath, 120 nm long. Over 95 per cent of the cyanophage particles are adsorbed within 10 min, the rate constant of adsorption being 3.2-10(-9) ml/min. The latent period lasts 5 hours, the yield is 100 particles per cell. The intracellular growth is characterized by the accumulation of the cyanophage particles at the poles of the cell. The photosynthetic lamellae remain intact up to the beginning of lysis which consists in local disruptions of the cell envelope.


[Chemical composition of cells of a chemostatic culture of Bacillus megaterium during exposure to an alkaline pH value]. The culture of Bacillus megaterium was grown under chemostat conditions at a rate of 0.2, 0.4 and 0.7 hr-1, the growth being limited by a low content of citrate, and at alkaline pH values. Critical pH values were obtained for each growth rate: 9.6, 9.2 and 7.6, respectively. The content of protein decreased at alkaline pH, while the synthesis of total lipids, poly-beta-hydroxybutric acid and phospholipids was stimulated. Some changes were found in the ratio between polyphosphates of high molecular weight.


Syrup of ipecacuanha as an emetic in adults. The emetic actions of syrup of ipecacuanha have been evaluated in 105 adult patients presenting at the emergency department of the Royal Perth Hospital with a diagnosis of accidental or intentional poisoning. The australian Pharmaceutical Formulary (APF) and the United States Pharmacopeia (USP) formulations of the syrup were compared and gave similar overall emetic responses of 88% and 89% respectively at a dose level of 15 ml. A 30 ml dose regimen of the APF formulation gave a slightly but not significantly increased overall emetic response of 96%. There were no differences between the three groups of patients in the time taken to vomit, the duration of vomiting or the volume of stomach contents recovered.


Are the effects of psychomotor stimulant drugs on hyperactive children really paradoxical? The improved "attention" exhibited by hyperactive children treated with amphetamine-like compounds is postulated to be related to a normal action of these drugs in producing stereotyped behavior. Such activity can be conceptualised as an increased "focusing" of attention, which would be expected to aid performance in tasks involving sustained concentration of attention, but impair performance on tasks involving reversals in cognitive strategy. These behavioural actions of the drugs can be linked to the functioning of central dopaminergic mechanisms.


The firA gene, a locus involved in the expression of rifampicin resistance in Escherichia coli. II. Characterisation of bacterial proteins coded by lambdafirA transducing phages. The firA gene probably codes for an essential component of the transcription machinery in E. coli. Bacterial proteins coded by lambdafirA transducing phages have been examined after infection of a UV-irradiated lambda lysogen, and 2 major fir-specific proteins have been characterized. The larger protein has a molecular weight of 27,000 daltons. The smaller protein, of 17,000 daltons, is produced in a considerable molar excess over the larger protein, is basic and binds strongly to DNA-, to DEAE- and to phospho-cellulose. This protein is clearly visible upon 2-dimensional gel electrophoresis of unfractionated E. coli protein, showing that it is present in the cell in large quantities. Evidence is presented to suggest that this protein may be identical to the Kappa factor of Schäfer and Zillig (1973).


[Pyrivate kinase deficiency. II. Biochemical studies (author's transl)]. Pyruvate kinase deficiency was studied biochemically in ten homozygous and seven heterozygous individuals who previously had been examined clinically and hematologically (see part I). In crude hemolysates some properties of the deficient enzymes were found to be altered. The pH optimum was shifted towards the alkaline range, and the thermal optimum was found between 17 and 27 degrees Cinstead of between 37 und 47 degrees C. The abnormal enzymes were much less stable than normal pyruvate Kinase (PK), and more susceptible to inhibition by adenosinetriphosphate. The affinity to adenosinediphosphate was normal in all cases whereas the affinity to phosphoenolpyruvate was either normal (two cases/, increased (two cases) or slightly decreased (six cases). Fructosediphosphate activated the abnormal enzymes by a factor of 1.5--18 and simultaneously transformed the sigmoidal affinity curve with phosphoenolpyruvate into the hyperbolic curve known for the normal enzyme. The consumption of glucose and the formation of lactate were higher in PK deficient erythrocytes than in normal cells but lower than in erythrocyte populations with similar reticulocyte counts. The formation of 2,3-diphosphoglycerate was markedly increased, whereas its breakdown was low. A close relation between the degree of reticulocytosis and the impairment of glucose metabolism was found. In patients with high reticulocyte counts, i.e. in the splenectomized patients, the highest concentrations of glucose-6-phosphate, phosphoenolpyruvate, 3-phosphoglycerate and 2,3-diphosphoglycerate as well as a high formation and a low breakdown of 2,3-diphosphoglycerate and a deficit in lactate formation were found. In heterozygotes, small increases of the concentration of glucose-6-phosphate, phosphoenolpyruvate and 3-phosphoglycerate were demonstrated. Our results support the conclusion that PK deficiency is mainly a disorder of the reticulocytes. Their metabolism grossly deteriorates within the venous sinuses of the spleen. Splenectomy improves the clinical course because this critical area of microcirculation with a highly unfavourable metabolic milieu is eliminated.


[Preoperative treatment of hyperthyroidism (author's transl)]. The preoperative preparation of hyperthyroidism requires the selective use of various drugs. As in the past, Plummer's iodine therapy takes precedence. Thyrostatics or beta receptor blockers, on the other hand, are only used in selected cases. The aim of preoperative preparation is euthyroidism. It is most rapidly and safely attained with Endoiodin (prolonium iodide) or combination of Endoiodine plus beta receptor blokkers. Thyrostatics appear to be less suitable for preparation, because they have a slow onset of action. Moreover, thyrostatics lead to densifications and adhesions of the thyroid gland capsule to the surrounding tissue, so that the preparation becomes complicated. 254 patients with hyperthyroidism and decompensated toxic adenoma were surgically treated without complications as a result of preparation with Endoiodin.


[Hypertension and anesthesia (author's transl)]. Five to six millions of hypertensives live in the Federal Republic of Germany. Of these, about 70% are known to be hypertensives but only 30% are consistently treated. It is therefore not surprising that hypertension is one of the most common risk factors in patients who have to be operatively treated. The commonly approved principles of hypertensive therapy are compiled in the present study and classified with reference to the multivarious pathophysiological processes. In particular, special anesthesiologic problems are dealt with in detail. Furthermore, this paper provides the basic knowledge of the artificial fall in blood pressure under anesthetic conditions.


Natural history of lactic acidosis after grand-mal seizures. A model for the study of an anion-gap acidosis not associated with hyperkalemia. To define the time course of the metabolic acidosis that follows a single grand-mal seizure, we obtained serial blood samples from eight consecutive patients. Immediately after a seizure, the mean (+/- S.E.M.) venous lactate concentration was 12.7 +/- 1.0 meq per liter, the mean carbon dioxide content 17.1 +/- 1.1 mmol per liter, and the mean arterial pH 7.14 +/- 0.06. Sixty minutes later their values were 6.6 +/- 0.7 meq per liter (P less than 0.005), 23.6 +/- 1.1 mmol per liter (P less than 0.005) and 7.38 +/- 0.04 (P less than 0.005) respectively. The spontaneous resolution of the acidosis was due, in large part, to the metabolism of lactate and to the concomitant removal of hydrogen ion. There was no change in the serum potassium concentration, despite the development of a severe systemic acidemia and the subsequent return to normal of the pH. We suggest that the patient with seizures may serve as a unique model of lactic acidosis.


Drug impairment reviews: other drugs.

Drug impairment reviews: other drugs. This review will summarize a limited number of experimental studies concerning effects of tranquilizers, muscle relaxants, and antihistamine drugs, as well as combinations of these drugs with ethanol, on human performance related to driving. The first group of studies utilized batteries of psychological and/or psychomotor tests to assess drug effects, while the second group used driving simulators. Procedures and results of each study will be summarized, and this will be followed by a general critique of methodologies which have been used along with suggestions for improved methodologies.


Spontaneous hypoglycemia in end-stage renal failure. Five men with end-stage renal failure had spontaneous hypoglycemia during lengthy hospitalizations. Four were cachectic, and all five had weight loss and poor caloric intake. Malnutrition were seen also in some of the ten previous case reports of hypoglycemia in renal failure. Impaired renal gluconeogenesis may allow hypoglycemia in such patients.


Pituitary responsiveness to LH-RH in intact and ovariectomized androgen-sterilized rats. Serum LH changes in response to LH-RH injection were measured in intact and ovariectomized, steroid-treated female rats which were androgenized neonatally with 1,250 microgram testosterone propionate (TP) on day 5. At a dose of 20 ng LH-RH/100 g b.w., serum LH levels in intact rats increased over pre-injection levels, and at a dose of 100 ng LH-RH/100 g b.w., LH concentrations 15 min after injection were higher in nembutal-blocked proestrous rats than in androgen-sterilized rats. However, the ovulation response was not different between the groups. In ovariectomized estradiol benzoate (EB)-treated, androgen-sterilized rats, serum LH concentrations 15 and 60 min after LH-RH injection were lower than in similarly treated control rats. This effect was not secondary to the anovulatory state of the animal, since it also occurred in ovariectomized EB-treated prepuberal rats and in rats ovariectomized prepuberally and treated with EB in adulthood. Also, after treatment with 5alpha-dihydrotestosterone propionate (5alpha-DHTP), pituitary responsiveness to LH-RH in androgen-sterilized rats was lower than in control rats, which suggests that the subnormal response in the estrogen-treated rats was not due to a relative insensitivity to estrogen in the androgen-sterilized rats. The relatively high pituitary responsiveness to LH-RH in intact androgen-sterilized rats is probably due to the high circulating estrogen levels. The subnormal pituitary responsiveness to LH-RH after ovariectomy and estradiol treatment suggests, in addition to an effect on the hypothalamus, also a direct effect of neonatal androgen administration on the pituitary.


Melanocyte-stimulating hormone release-inhibiting factor (MIF): lack of dopaminergic and anticholinergic activity. In a sensitive animal model under the control of a dopaminergic-cholinergic balance, showing striking similarity to the extrapyramidal system, MIF did not possess dopaminergic or anticholinergic properties either with acute or chronic administration of the drug.


Adenylate cyclase and guanylate cyclase of normal and denervated skeletal muscle. Cyclic nucleotides mediate the intracellular effects of various extracellular influences. To explore the possibility that nerve-muscle influences are mediated by cyclic nucleotides, we studied the effect of denervation on the cyclase enzymes of rabbit gastrocnemius using the contralateral, unoperated limb as the control. Adenylate cyclase activity decreased dramatically after denervation, while guanylate cyclase activity increased several times in all tissue fractions studied. Neither enzyme demonstrated cholinergic responsiveness. The dramatic changes in cyclase activities following denervation could result from a role of these enzymes in the mediation of nerve-muscle influences.


Takayasu's syndrome in pregnancy.

Takayasu's syndrome in pregnancy. Two cases of Takayasu's syndrome in pregnancy are presented. The obstetric courses of these women are compared with those of 7 others described in the literature. Symptoms of this rare condition may respond variably during pregnancy. Of the 9 women, 5 had worsening of their symptoms during gestation while 4 had milder symptoms than they had had prior to pregnancy. The best therapy is rest. Vaginal delivery is recommended and cesarean section should be reserved for obstetric indications.


The role of mineral surfaces in the origin of life. Adsorption of nucleoside phosphates on the surfaces of volcanic rocks has been studied. Differences in the absorption of some nucleoside phosphates on the surface of basalt cinder have been found. Differences in the adsorption of similar molecules on different mineral surfaces have also been shown. Different adsorptive capacities may have served as a mechanism for the selection of organic molecules during prebiotic evolution.


Management of the child with recurrent asthma. A rational approach to the evaluation of the child with chronic asthma has been presented. The importance of careful historical, physical, and pulmonary assessment is stressed, especially since asthma may exist without overt wheezing. General allergic as well as sequential pharmacologic management of this disease is also discussed. A knowledge of the biochemical and pathophysiologic alterations in asthma should lead to rational and specific therapy that preserves normal function and decreases the long-term morbidity and mortality of the disease.


Early-onset pneumococcal sepsis in newborn infants. Five infants with pneumococcal sepsis presented with respiratory distress and clinical signs of infection in the first day of life. Although there was no apparent epidemiological relationship among the patients, four of the five were seen within a 12-month period. Pneumonia, prolonged rupture of fetal membranes, and prematurity were features in these patients. Three infants died, two within 12 hours of diagnosis. Streptococcus pneumoniae was isolated from the vagina of three of the mothers; in two, the serotype was identical to that recovered from their infants. Clinical features of neonatal pneumococcal sepsis are similar to those of early-onset group B streptococcal infection. Like the group B Streptococcus, S. pneumoniae acquired from the maternal vagina is a potential life-threatening pathogen in the newborn period.


[Effect of the landscape and climate on the distribution of blood-sucking mosquitoes in Murmansk Province]. According to its orographic characteristics and climate the Murmansk region represents a special landscape area of the Atlantic-Arctic zone with its peculiar zoogeographic characters. This specificity is clearly seen in the distribution of 19 species of bloodsucking mosquitoes over the above territory. Abundant and widely encountered are only two species, Aedes punctor and Ae. communis. 9 species, Culiseta alaskaensis, C. bergrothi, Aedes pullatus, Ae. excrucians, Ae. pionips, Ae. hexodontus, Ae. impiger, Ae. nigripes, Ae. diantaeus, are small in number and widely distributed. 8 species, Anopheles maculipennis, Aedes intrudens, Ae. cantans, Ae. cinereus, Ae. cataphylla, Ae. riparins, Ae. lencomelas, Culex pipiens pipiens, are rare and have a restricted distribution.


The effects of pH on the conductance change evoked by iontophoresis in the frog neuromuscular junction. The amplitude of the electrophoretically evoked end-plate potential increases with changing the pH of the bathing solution from 9.4 to 5.4 at room temperature. This change is not observed at lower temperature. The underlying current (e.p.c.I) is slightly decreasing at room temperature by lowering the pH. The relationship between the amplitude of the e.p.c.I and membrane potential is highly non-linear at pH 9.4, while it is quite linear at pH 5.4. The time course of the e.p.c.I is changed neither by different pH, nor by different membrane potential. The data suggest that during the e.p.c.I, the mediator (ACh), the receptor (R) and the mediator-receptor complex are in equilibrium: the amplitude of the e.p.c.I will thus depend on the affinity constant of the reversible reaction between ACh and R. It is concluded that by decreasing the pH, the affinity constant is decreased.


An automatically balancing isolation amplifier for the decoupling of measuring systems with high impedances. It is theoretically shown that different conditions of coupling and grounding cause error voltages with the simultaneous use of two high-impedance measuring systems (e.g. pH electrodes). By the use of special amplifiers using optical transmission systems these error voltages are prevented. The transmission characteristics of the couplers are sensitive to changes in temperature due to the incorporation of infrared emitters in the system. An amplifying equipment with high d. c. stability was developed. The temperature drift was suppressed by the use of a special chopper stabilisation.


Shear degradation of DNA.

Shear degradation of DNA. A concentric-cylinder flow-birefringence instrument is used to generate sufficient shear fields to break T2 DNA (M = 1.2 X 10(8)) and E. coli DNA (M = 2.5 X 10(9)) in dilute solution. Breakage is monitored in situ by measuring the change in birefringence relaxation after the flow has been stopped. The breakage of T2 DNA follows first-order kinetics. Rate constants are obtained as functions of shear rate and viscosity (varied by adding glycerol). The data are fitted by a modified Arrhenius equation, assuming that stess increases the rate by lowering the activation energy. The rate increases with temperature, pH, and water concentration, and appears to be a base-catalyzed hydrolysis of the phosphate-ester linkage. La3+ ions catalyze the reaction. E. coli DNA was reduced to half molecules at a shear stress of 0.4 dynes/cm2, which is about 2500 times less than that required for T2. The difference in rates is accounted for in part by the difference in size of the two, but may also reflect the presence of many single-strand nicks in the coli DNA.


Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide. The thermal stabilities of RNA:DNA hybrids are substantially greater than those of DNA:DNA duplexes in aqueous electrolyte solutions containing high concentrations of formamide. Association rates to form DNA:DNA duplexes and DNA:RNA hybrids have been measured in these solvents. There is a temperature range in which DNA:DNA rates are negligible and RNA:DNA rates close to optimal.


The properties of native and denatured DNA in buoyant rubidium trichloroacetate at neutral pH. Aqueous RbTCA is generally suitable as a buoyant solvent for both native and denatured DNA at neutral pH and room temperature. Native PM-2 DNA II, for example, is buoyant at 3.29 M salt, 25 degrees C; whereas the denatured strands band together at 4.52 M. Two properties of the solvent make this system uniquely useful for separations based upon the extent of secondary structure. First, the melting transition temperature for chemically unaltered DNA is depressed to room temperature or below. Second, the buoyant density increase accompanying denaturation is extraordinarily large, 174 mg/ml for PM-2 DNA II. This value is three times that found in aqueous NaI and ten times that for CsCl. The properties of the RbTCA buoyant solvent presented here include the compositional and buoyant density gradients and the buoyant density dependence upon base composition. The DNA remains chemically unaltered after exposure to RbTCA as shown by the absence of strand scissions for closed circular DNA and by the unimpaired biological activity in transformation assays. Intact virion DNA may be isolated by direct banding of whole virions in RbTCA gradients without prior phenol extraction. Strongly complexed or covalently bound proteins may be detected by their association with the buoyant polymer in the denaturing density gradient.


Model for "charge-relay": acceleration by carboxylate anion in intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group. The effect of benzoate anion on intramolecular general base-catalyzed ester hydrolysis by the imidazolyl group in endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate was examined in dioxane/H(2)O solutions. Benzoate anion exhibited a remarkable acceleration of the intramolecular general base-catalyzed hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate by the imidazolyl group. The rate of hydrolysis in the presence of the benzoate anion increased with the dioxane mole fraction and was proportional to the concentration of benzoate anion. On the other hand, the rate of hydrolysis of endo-5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate in the absence of benzoate anion decreased with the dioxane mole fraction. Thus, the ratio of the rate in the presence of benzoate anion to that in the absence of benzoate anion drastically increased with the dioxane mole fraction and attained a 2500-fold rate acceleration at a dioxane mole fraction of 0.42 (the highest experimentally attainable) when the concentration of benzoate anion was 0.5 M. The proposed mechanism involves proton abstraction by the benzoate anion from the imidazolyl group, followed by proton abstraction by the imidazolyl group from H(2)O, resulting in effective general base-catalysis of hydrolysis. The results of the present paper provide support for the "charge-relay" system in serine proteases.


Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems. Escherichia coli glutamine synthetase and glycogen phosphorylase are prototypes for models of "closed" and "opened" bicyclic cascade systems. Steady-state functions relating the fractional activation of interconvertible enzymes to the concentrations of allosteric effectors and to the catalytic constants of the several converter enzymes in such cascades were determined. The study shows that when the active form of an interconvertible enzyme in one cycle catalyzes the covalent modification of the interconvertible enzyme in a second cycle, the two cycles become coupled, such that the fractional activity of the second interconvertible enzyme is a multiplicative function of all parameters in both cycles, i.e., of 14 and 18 parameters for the closed and the opened bicyclic cascade, respectively. Therefore, from the standpoint of cellular regulation, bicyclic cascades are superior to the monocyclic cascades analyzed previously [E. R. Stadtman & P. B. Chock (1977) Proc. Natl. Acad. Sci. USA 74, 2761-2765], because: (i) they can respond to a greater number of allosteric effectors; (ii) they can achieve much greater amplification of responses to primary stimuli (e.g., with only 2-fold changes in each parameter the amplification factors of one-cycle and two-cycle cascades are 320 and 102,400, respectively); (iii) they can generate a sigmoidal response (Hill numbers of >2) of interconvertible enzyme activity to increasing concentrations of an allosteric effector. This is because there are more steps in a bicyclic cascade at which a given effector can interact. A similar analysis of multicyclic cascade systems shows that the capacity for amplification increases exponentially as the number of cycles in the cascade increases. In addition, regulation by cyclic cascades can achieve enormous variability of the fractional activity of the interconvertible enzyme by shifting the steady-state distribution between active and inactive forms. One equivalent of ATP is consumed in each interconversion cycle to provide the energy needed to maintain the steady-state activity of the modified enzyme at a metabolically required level. Therefore, the decomposition of ATP associated with the cyclic cascade is not a wasteful process.


[Enzyme immobilization on hydrated oxides of transition metals and aluminum]. The immobilization of alpha-chymotrypsin, trypsin and invertase on hydrated oxides of tin, titanium and aluminium was investigated. The degree at which the enzymes were bound upon immobilization was 83.2-2.6%. The amount of bound proteins was 64.2 mg/g carrier. The specific activity of enzymes reached the highest level in the case of hydrated tin oxide and amounted to 76.8%, 49.9% and 99.6%, of activity of native alpha-chymotrypsin, trypsin and invertase, respectively. The thermal stability of immobilized proteases was considerably higher and that of immobilized invertase was significantly lower than that of native enzymes. The pH optimum of immobilized enzymes shifted by 0.6-2.6 units towards the alkaline region.


Defective organization of actin in cultured skin fibroblasts from patients with inherited adenocarcinoma. In the cytoplasm of well-spread cultured normal fibroblasts, actin is organized into a network of cables that run the length of the cell just inside the adherent cell membrane. A diffuse matrix replaces the cables in fibroblasts that have become tumorigenic as a result of oncogenic transformation. We have found a similar disruption in actin organization in cultured skin fibroblasts (passage 6-10) obtained by biopsy from patients with the inherited colonic cancer, adenomatosis of the colon and rectum (ACR). Because ACR is inherited as an autosomal dominant trait, about half the children of ACR patients will develop colon cancer, but they typically remain asymptomatic until at least the second decade of life. Actin distribution within cultured cells from children of ACR patients was identical either to that seen in cultured cells from normal persons or to that seen in cultured cells from ACR patients. The two different patterns were independent of age, sex, drug treatment, or infections of the donors. Apparently, this class of colonic carcinoma is accompanied by a systemic aberration in the organization of fibroblast cytoplasm, and this aberration can be detected by immunofluorescent localization of actin within cultured skin fibroblasts, prior to manifestation of any colonic symptoms.


A protonmotive force drives bacterial flagella. Streptococcus strain V4051 is motile in the presence of glucose. The cells move steadily along smooth paths (run), jump about briefly with little net displacement (twiddle), and then run in new directions. They stop swimming when deprived of glucose. These cells become motile when an electrical potential or a pH gradient is imposed across the membrane. Starved cells suspended in a potassium-free medium respond to the addition of valinomycin by a brief period of vigorous twiddling. They also twiddle, although less vigorously, when the external pH is lowered. Valinomycin-induced twiddling occurs in the absence of external alkali or alkaline earth cations and without significant net synthesis of ATP. When a chemoattractant is added to cells swimming in the presence of glucose, twiddles are transiently suppressed, and the cells run for a time. Similarly, when starved cells are suspended in a potassium-free medium containing both valinomycin and an attractant, many cells initially run rather than twiddle. We conclude that the flagella are driven by a protonmotive force.


Electrical stimulation of preganglionic nerve increases tyrosine hydroxylase activity in sympathetic ganglia. The effect of synaptic stimulation on tyrosine hydroxylase [tyrosine 3-monooxygenase: L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] activity in the rat superior cervical ganglion was studied. The preganglionic cervical sympathetic trunk was stimulated unilaterally at 10 Hz for 30 min. Forty-eight hours later tyrosine hydroxylase activity was 33% higher on the stimulated than on the control side. The enzyme activity restimulated than on the control side. The enzyme activity remained elevated in the stimulated ganglia for 2 days. No change was observed in total ganglion protein. Comparable increases in tyrosine hydroxylase activity were observed in anesthetized and conscious animals.


Some characteristics of amnesia induced by FLA-63 an inhibitor of dopamine beta hydroxylase. The amnesic effects of FLA-63, a potent dopamine-beta-hydroxylase (DBH) inhibitor, were investigated in a food motivated spatial discrimination task. Groups of C57BL/6J mice were injected with either 5 mg/kg, 15 mg/kg, 25 mg/kg, 35 mg/kg or physiological saline 4 hr prior to training. Amnesia was observed 24 hr following training at all dose levels except 5 mg/kh. The performance deficit was specific to memory of the discrimination and not the result of state-dependency. Training conditions which produce an increase in habit strength prevented the amnestic effects of FLS-63. Spontaneous recovery of memory occurred 48 hr following drug administration. Recovery from amnesia was also induced by injections of a monoamine oxidase inhibitor, pargyline, administered 2 hr prior to the retention test. These data suggest that amnesia induced by norpinephrine (NE) depletion is the result of impairment of mechanisms necessary for memory retrieval.


Use of DRL in differentiating anxiolytic and neuroleptic properties of CNS drugs. Presented in this paper are the effects of chlorpromazine, clozapine, d-amphetamine and diazepam on DRL behavior in rats. D-Amphetamine and diazepam, which showed similar effects on response errors, could be identified on the basis of burst responding and drug interaction. Clozapine, a new antipsychotic agent which does not cause extrapyramidal side effect in man affected DRL behavior in the same way as did chlorpromazine. Thus, DRL schedules are probably not useful in differentiating various neuroleptic agents.


Plasticity in mammalian skeletal muscle. While it has been recognized for many years that different limb muscles belonging to the same mammal may have markedly differing contractile characteristics, it is only comparatively recently that it has been demonstrated that these differences depend upon the motor innervation. By appropriately changing the peripheral nerve innervating a mammalian skeletal muscle, it is possible to change dramatically the contractile behaviour of the reinnervated muscle. The manner by which the motor innervation determines the nature of a muscle fibre's contractile machinery is not completely understood, but it appears that the number and pattern of motor nerve impulses reaching the muscle play an important role. The biochemical changes occurring within muscle fibres whose contractile properties have been modified by altered motor innervation include the synthesis of different contractile proteins.


Early visual experience, learning, and neurochemical plasticity in the rat and the chick. Rats reared in the dark to 50 days show morphological and biochemical changes in the visual pathway. Light exposure results in elevated incorporation into protein in visual cortex, lateral geniculate and retina. Much of the visual cortex elevation is in a rapidly labelling, rapidly transported neuronal particulate protein. There are concomitant changes in lysosomal and transmitter enzyme activity. In chicks exposed to an imprinting stimulus (a flashing light) there are elevations in RNA polymerase and RNA and protein incorporation in the anterior forebrain roof (a.f.r.) compared with controls. There are changes in adenyl cyclase, cAMP and AChE. Behavioural controls show that although there are general biochemical sequelae of light exposure, the elevation in RNA synthesis in the a.f.r. is not a result of motor, stress or sensory activity, but is correlated with a measure of the learning of the stimulus characteristics. A model for neurochemical correlates of developmental plasticity, learning, and state-dependent transients is discussed.


Plasticity in the adult vestibulo-ocular reflex arc. Human subjects with maintained reversal of their horizontal field of vision exhibit very substantial adaptive changes in their 'horizontal' vestibulo-ocular reflex (v.o.r.). Short durations (8 min) of vision reversal during natural head movement led to 20% v.o.r. attenuation while long periods (4 weeks) eventually led to approximate reversal of the reflex. The reversed condition is approached by a complex, but highly systematic, series of changes in gain and phase of the reflex response relative to normal. Recovery after return to normal vision exhibits a similar duration, but different pattern, to that of the original adaptation. A chronic cat preparation with long-term optical reversal of vision has now been developed and shows similar adaptive and recovery changes at low test stimulus amplitudes, but different patterns of adaptive response at high amplitudes. An adaptive neural model employing known vestibulo-ocular pathways is proposed to account for these experimentally observed plastic changes. The model is used to predict the adapted response to patterns of stimulation extending beyond the range of experimental investigation.


Electrophysiological experiments on the mechanism and accuracy of neuromuscular specificity in the axolotl. The supracoracoideus muscle of the axolotl shoulder girdle is innervated by two nerves, the supracoracoideus nerve (SC) supplying most of the muscle and the posterior supracoracoideus (PSC) supplying the posterior corner. All the muscle fibres are multiply innervated and at the border between the two innervations many muscle fibres, when penetrated by a microelectrode, show junction potentials from both nerves. In such cases one junction potential is often very small, below the threshold for exciting muscle contraction, the other large and effective at exciting the muscle. If the SC nerve is cut, the territory of the PSC nerve expands over several weeks. Upon regrowth of the cut nerve it reinnervates its old muscle fibres and removes the previous foreign innervation, the borderline between the two nerve territories being established exactly as before. This depends upon two processes, sprouting of nerves and a competitive repression of transmission from nerves ending on foreign muscle fibres.


The presence of ineffective synapses and the circumstances which unmask them. In this paper, we shall show that there are substantial numbers of nerve terminals which are normally ineffective. In the intact animal, occasional signs of the postsynaptic effectiveness of these fibres can be seen under conditions of optimal spatial summation or increased excitability or decreased inhibition. If the normally functioning afferent nerve fibres are blocked or cut, some of the previously ineffective fibres immediately establish an effective drive of cells. If the normal afferents are cut and allowed to degenerate, large numbers of cells begin to respond to new inputs. The presence of ineffective synapses in the adult offers an alternative to sprouting or the opening up of polysynaptic pathways as a possible mechanism to explain plasticity of connections in adult brains.


Pharmacokinetics of N-desmethyldiazepam in healthy volunteers after single daily doses of dipotassium chlorazepate. Dipotassium chlorazepate was administered to 12 healthy volunteers (8 males and 4 females), aged 22-38 years, as a single daily dose of 20 mg for 14 days. Plasma concentrations of N-desmethyldiazepam were monitored with a gas-chromatographic method during the medication period and for 5 days after withdrawal of the drug. The plasma half-life (t1/2), the elimination coefficient (Kbeta), the concentration (Css), and the apparent volume of distribution (Vbeta) were calculated at steady state, and the mean values +/- SEM were 53 +/- 6 h, 0.0147 +/- 0.0013 h-1, 884 +/- 73 ng/ml, and 1.13 +/- 0.08 1/kg, respectively. A moderate interindividual variability was observed regarding these parameters. There was no tendency toward a biexponential elimination. A significant difference in the apparent volume of distribution was found when males and females were compared.


Morphine action in grouped and isolated rats and mice. The present study determines the analgesic effects of morphine in grouped and isolated rats and mice. Isolated animals developed altered behavioral patterns, including mouse-killing in rats and mutual aggressiveness in mice. The analgesic effect of morphine was tested by tail compression in rats and by the hot plate for mice. Isolated rats developing mouse-killing behavior had a raised pain threshold, while indifferent animals (nonkillers) responded less to morphine. Isolated mice, particularly low aggressors, gave enhanced responses to morphine.


Comparison of thyrotropin-releasing hormone with melanocyte-stimulating-hormone-release-inhibiting factor as pentobarbital antagonists in monkeys. Thyrotropin-releasing hormone (TRH), 0.1 mg/kg, i.m., significantly counteracted pentobarbital narcosis in six monkeys, but melanocyte-stimulating-hormone-release-inhibiting factor (MIF), 0.1 mg/kg i.m., did not. Earlier dose-response studies in unanesthetized monkeys had shown that this dose of MIF stimulated motor activity; this dose of TRH had shown no stimulant effect, but a higher dose depressed activity. Thus, an MIF dose that stimulates unanesthetized monkeys does not reverse pentobarbital narcosis;  a TRH dose that by itself is neither stimulant nor depressant does partially reverse pentobarbital narcosis.


Dose- and time-dependent effects of narcotic analgesics on intracranial self-stimulation in the rat. Rats were trained to bar-press in order to obtain electrical stimulation of the medial forebrain bundle through chronically implanted electrodes. Dose-response and time-effect curves were determined for morphine (1.0-30 mg/kg), levorphanol (0.1 to 3.0 mg/kg), methadone (0.1-3.0 mg/kg), meperidine (1.0-30 mg/kg), oxymorphone (0.03-1.0 mg/kg), and d-amphetamine (0.1-3.0 mg/kg). Dose-response and time-effect curves were also determined for morphine (1.0-30 mg/kg) in rats that had received multiple injections of morphine over a period of 3 days. All of the narcotic analgesics produced dose-related decreases in responding; the durations of these decreases were also dose-related. The relative potencies of the five narcotic analgesics with respect to the rate-decreasing effects for selt-stimulation responding were: oxymorphone greater than levorphanol greater than methadone greater than morphine greater than meperidine. In morphine-tolerant rats the rate-decreasing effects of morphine on responding for selt-stimulation were attenuated. These findings suggest that narcotic analgesics from diverse chemical families have a similar, predominantly depressant, effect on self-stimulation behavior and that the relative potencies of a series of narcotics for this effect are similar to those demonstrated for other properties of these drugs.


Influence of the suspension of continued treatment with flurazepam and amobarbital on two discrimination learning schedules. The authors have studied the effect of the suspension of chronic treatment with flurazepam and amobarbital on the operant behavior of rats that for the first time were in the presence of two fixed-interval discrimination schedules. With the sound discrimination schedule, the responses emitted by the treated animals had charactistics similar to those of control animals. With the temporal discrimination schedule, though it is not possible to distinguish between learning rates, modifications in the intensity of the effect (increases in lever pressing) indicate that, considering the doses, the action of flurazepam is slight and that of amobarbital clear and statistically significant.


Blockade of intracranial self-stimulation by antipsychotic drugs: failure to correlate with central alpha-noradrenergic blockade. The involvement of central alpha-noradrenergic receptors in intracranial self-stimulation (ICSS) was studied. Dose-response curves were established for the blockade of ICSS by the antipsychotic drugs chlorpromazine, thioridazine, clozapine, and pimozide and the alpha-antagonist phenoxybenzamine. Antagonism of the facilitation, produced by the central alpha-agonist clonidine, of flexor withdrawal reflexes in the reserpinized spinal rat was used to assess the central alpha-blocking potency of the same drugs, and dose-response curves were established. No correlation was found between central alpha-blockade, as reflected by the ED50 for blockade of clonidine-facilated spinal reflexes, and the ED50 for blockade of ICSS. Pimozide blocked ICSS at doses virtually devoid of central alpha-blocking activity, while phenoxybenzamine was a potent alpha-antagonist and a weak blocker of ICSS. The lack of correlation between central alpha-blockade and decreased ICSS suggests that alpha-receptors are not critically involved in self-stimulation behavior.


Negative naloxone effects in schizophrenic patients. On the basis of the hypothesis that the opiate-like neuropeptides, such as beta-endorphin, may be involved in the etiology of schizophrenic symptoms, naloxone 1,2 mg and placebo were administered intravenously to 8 schizophrenic patients, using a double-blind, crossover design. Naloxone was not found to be different from placebo in effecting schizophrenic symptoms, including hallucinations and delusions.


Effects of chronic hydrochloric and lactic acid administrations on food intake, blood acid-base balance and bone composition of the rat. In experiment 1, weanling rats were given, for 7 weeks, a commercial rat diet supplemented with hydrochloric acid at levels up to 560 mmol.kg-1 dry matter. The supplement increased water intake but did not significantly affect food intake, live-weight gain, blood haemoglobin and haematocrit values or acid-base balance. In experiment 2, adult rats were given, for 9 weeks, a commercial rat diet supplemented with hydrochloric acid at levels up to 1250 mmol.kg-1 dry matter. Food intake and liveweight gain were not affected by hydrochloric acid concentration up to 625 mmole but at 938 mmol.kg-1 they were considerably reduced and there was 100% mortality of the rats. In experiment 3, weanling rats were given, for 12 weeks, a commercial rat diet supplemented with hydrochloric or lactic acid each at 300, 600 and 900 mmol.kg-1 dry matter. Lactic acid at the three levels and hydrochloric acid at the two lower levels did not affect food intake or live weight gain and had only a slight effect on blood acid-base balance. At a dietary concentration of 900 mmol.kg-1 dry matter, hydrochloric acid decreased food intake, induced a mild degree of metabolic acidosis and resulted in 30% mortality of the rats. In the three experiments, the acid treatments dnot directly affect the length or composition of the femur of the rats.


The effect of fatigue on resident performance. Fourteen rested and fatigued residents read a set of 25 test radiographs on two separate occasions approximately one month apart. The radiographs were made with partial chest phantom using pulmonary nodules as test objects. Seven rested and 7 fatigued residents read the radiographs, and a month later the order of fatigue was reversed. Fatigued residents had worked a minimum of 15 consecutive hours before their interpretations. Performance did not deteriorate with fatigue, and the nodule detection rate was almost identical on both occasions.


Prostaglandin E1 modifies nerve conduction and interferes with local anaesthetic action. Prostaglandin E1 (PGE1) altered both the amplitude and conduction velocity of the compound action potential in frog sciatic nerve. Concentrations up to 1 ng/ml increased both amplitude and conduction velocity but at higher concentrations both effects were reversed. Procaine, chloroquine, indomethacin and SC19220 all reduced action potential amplitude and conduction velocity. These local anaesthetic type actions could be partially or completely prevented by PGE1.


On the structure of slow reacting substance of anaphylaxis: evidence of biosynthesis from arachidonic acid. The mononuclear cells in peritoneal washings from normal rats can be induced to produce large amounts of slow reacting substance of anaphylaxis by incubation with 10 mM cysteine in the presence of the calcium ionophore A-23187. This production of slow reacting substance could be inhibited by the addition of non-steroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and flurbiprofen, Furthermore, mediator production was inhibited by eicosatetraynoic acid, the substrate analog of arachidonic acid, and by 9,11-azoprosta-5, 13-dienoic acid (AZO analog 1), a structural analog of the prostaglandin endoperoxide, PGH2, which known to inhibit thromboxane synthesis. Relatively high concentrations of hydrocortisone acetate inhibited mediator production; this inhibition could be partly reversed by the addition of arachidonic acid or to a lesser extent by eicosatrienoic acid. Preliminary results suggest that a  small fraction of the 3H-labled arachidonic acid which was taken up by these cells in vitro was associated with slow reacting substance. We postulate that slow reacting substance of anaphylaxis may be derived from a prostaglandin endoperoxide which is formed during the oxidation of arachidonic acid by the prostaglandin fatty acid cyclooxygenase.


The TcO4-binding to human serum albumin --the stoichiometry and characteristics of the binding equilibrium. The stoichiometry and the characteristics of the TcO4-binding equilibrium to human serum albumin were investigated by the use of 99TcO4-. Based on the Scatchard plots, the number of binding sites and the association constants were obtained at pH 7.38,6.04, 5.10, 4.18, 2.80 and 0.65, respectively. From the parameters at pH 7.38, it was estimated that 64% of TcO4- added was bounded to human serum albumin under physiological condition. Variance in the values at pH 7.38, 6.04 and 5.10 shows that these bindings are stabilized by electrostatic forces. Below pH 4.18, the number of binding sites increased and the association constants constants diminished. These phenomena may be attributed to the conformation change of human serum albumin.


[Effect of methionine sulfone on the growth of Citrobacter intermedius C3 (author's transl)]. Specific activity of glutamate dehydrogenase (GD) and glutamate synthase (GtS) has been determined in the wild strain C3 and on a non excreting pro- mutant strain. Methionine sulfone shows inhibitory effects on their growth. The addition of alpha-ketoglutarate to the medium prevents the inhibitory effect and increases the GtS specific activity in both strains. The physiological effect of methionine sulfone and its suppression by alpha-ketoglutarate is discussed.


Comparative antisecretory activity of several drugs in the gastric fistula squirrel monkey and rat. A series of known antisecretory compounds, including glycopyrrolate, clonidine, propantheline bromide, CMN 131 (2-pyridylthiocetamide), and desmethylimipramine (DMI) were tested in the gastric fistula rat and monkey. The order of potency for inhibiting acid output was similar in both species. A general similarity exists in the responsiveness of the rat and monkey to gastric antisecretory agents. These data support the use of the squirrel monkey for assessment of gastric antisecretory activity.


The effect of pH on stereospecific opiate binding to mouse brain membranes. High-affinity, in vitro stereospecific binding of 3H-di-hydromorphine or 3H-naloxone to brain membranes shows a marked dependence on pH; maximal binding, observed at pH 7.5-8.0, is abruptly and reversibly reduced as the pH is lowered, with the binding half-maximal at about pH 6.8. A similar pH dependence of stereospecific binding is observed with the quaternary agonist N-methyl morphine, but non-specific 3H-di-hydromorphine of 3H-naloxone binding (that not displaced by a 100-fold excess of unlabelled levorphanol) shows only a slight decrease in this pH range. Binding of agonist and antagonist at pH 6.8 show the same differences with respect to trypsin sensitivity and to the effects of Na+ and Mn++ ions that are seen at pH 8.0. It is concluded that the ability of low pH to reduce stereospecific binding is due to protonation of a membrane-bound site, and that this site is probably the anionic site of the opiate receptor. Of the four anionic groups commonly found in biological membranes, only phosphate exhibits a pK close to that of this effect. Taken with other evidence, the results suggest that the opiate receptor may be a phosphoprotein.


[Use of chemical disinfectants in alcoholic fermentation of must of sugar cane molasses]. The use of hexaclorophene as desinfectant for alcoholic fermentation was studied. Its effect upon alcoholic yield and acidity levels of "beers" and "spirit" was observed. The optimal concentration of hexaclorophene in fermentation broth was found to be 4%.


Red cell lysis coupled to the peroxidation of liver microsomal lipids. Compartmentalization of the hemolytic system. As a contribution to the understanding of the mechanisms by which addition of erythrocytes to liver microsomes incubated in the NADPH dependent system results in hemolysis, experiments are presented here in which the system containing actively peroxidizing microsomes was separated from the system containing the red blood cells by a dialysis membrane. It is shown that when liver microsomes were incubated with NADPH, lipid peroxidation, as measured by the formation of malonic dialdehyde (MDA), rapidly took place. The MDA concentration tended to equilibrate across the dialysis membrane. After a lag phase of 60 min, lysis of erythrocytes contained in the dialysis tube, started. It reached its maximal level (more than 80%) at 110 min of incubation. These results strongly suggest the possibility that toxic products originating during the course of lipid peroxidation induce pathological effect at distant loci. Furthermore, the accomplishment of a compartmentalization of the two systems involved in the reaction, may offer an approach to the recognition of the toxic factors.


[Isolation of proteins in coconut water]. The isolation of protein fractions in cocont water was achieved by precipitation with controlled pH variation obtaining three isolates at pH 8,5, 10,5, and 11,5. By comparing each of these isolates with proteins of coconut milk, a similarity between properties of the first two isolates of the water - pH 8,5, 10,5--and those of coconut serum proteins -- glutelin and prolamin was observed. The third isolate is entirely absent from the milk, when coconut water is not used in the second pressing to obtain the milk.


Metal ion catalyzed oxidation of the antibiotic rifampicin. The metal ions Cu++, Mn++ and Co+++, but not Ca++, Fe+++, K+, La+++, Mg++, Na+, Sr++ or Zn++ catalyzed the oxidation of rifampicin from the naphthohydroquinone to the naphthoquinone form. This reaction was pH dependent, and occurred at neutral or basic pH more rapidly than at acidic pH. Mn++ catalyzed the most rapid oxidation, followed by Cu++ and then Co+++. Rifampicin oxidation was metal ion dependent and complete oxidation occurred at metal ion concentrations below stoichiometric values. Initial rate studies suggest that the oxidation mechanism is complex.


Regulation of intracellular cyclic GMP and cyclic AMP levels in mouse lung fragments by disodium cromoglycate, beta-adrenergic agonists, cholinergic activators, and histamine. The effects of adrenergic and cholinergic agents as well as the effects of disodium cromoglycate (DSCG) on the levels of cyclic AMP and cyclic GMP in mouse lung fragments were studied. Levels of cyclic AMP were enhanced by two of the known beta-adrenergic agonists, epinephrine and isoproterenol. This increase was abolished by propanolol, a recognized beta-adrenergic antagonist. Disodium cromoglycate, a proposed inhibitor of phosphodiesterases, alone caused a slight, significant increase in cyclic AMP. However, in the presence of epinephrine, levels of cyclic AMP were potentiated by DSCG. DSCG behaves, therefore, as a typical cyclic AMP phosphodiesterase inhibitor. Cyclic GMP levels were increased by carbachol, acetylcholine, and the phosphodiesterase inhibitor, aminophylline, but not by DSCG, or beta-adrenergic agonists.


Failure to observe pathology in the rat following chronic dosing with acetaminophen and acetylsalicylic acid. Male Wistar rats were dosed daily by gavage for 200 days with either (1) aspirin, 200 mg/kg; (2) acetaminophen, 200 mg/kg; (3) aspirin and acetaminophen, 200 mg/kg of each; (4) aspirin and acetaminophen, 100 mg/kg of each or (5) vehicle alone. None of the treatments produced any marked signs of toxicity and no drug related deaths were observed. The full dose combination (3) did significantly reduce the weight compared to the control group (5). When urinary lactic dehydrogenase and alkaline phosphatase were measured, all treatments caused some increase in activity but those containing aspirin had the greatest effect. Urinary pH and osmolarity were not effected by the treatments. Complete pathological examination of the animals failed to detect any significant changes when compared to the controls. It is concluded that there is no evidence of a toxic interaction between aspirin and acetaminophen in the rat.


Influence of catecholamine-derived alkaloids and beta-adrenergic blocking agents on stereospecific binding of 3H-naloxone. Alkaloids containing a catecholamine moiety, viz., tetrahydroisoquinolines and tetrahydroprotoberberines, and a group of beta-adrenergic blocking agents were examined for their effects on the binding of tritiated naloxone by rat brain homogenate. The stereospecific binding of the opiate antagonist was weakly inhibited by the catecholamine-derived alkaloids. The concentration of alkaloids producing 50% inhibition of binding ranged from 0.06 to 0.37 mM. The inhibitory effects of the beta-adrenergic blocking agents appear to parallel their reported relative local anesthetic actions.


Comparison of the effects of several selective B2-receptor agonists on bronchomotor function in vitro. Three selective B2-adrenergic stimulants were studied for their effect on the resting tone and on reversing acetylcholine (ACh)-induced bronchoconstriction in the intrapulmonary airways of rats in vitro. Neither 1-(3,5-dihydroxyphenyl)-2-[(1-[4-hydroxybenzyl]-ethyl)-amino]-ethanol-hydrobromide (Fenoterol) nor 2-tert-butylamino-1-(3,5-dihydroxyphenyl)-ethanol-sulphate (Terbutaline) had an effect on the resting tone. 4-Amino-3,5-dichlor-alpha-[(tert-butylamino)-methyl1-benzylalcohol-hydrochloride (NAB 365) caused a significant increase in the bronchial luminal diameter from control in the resting state at concentraions above 10(-5) g/ml. Only NAB 365 was effective in reversing ACh-induced bronchoconstriction in concentrations above 10(-6) g/ml. Terbutaline and Fenoterol reversed the ACh-induced bronchoconstriction only after the alpha-receptors had been blocked by phentolamine (10(-5)-10(-4)g/ml).


[Effect of beta-adrenergic stimulation on the closing volume in normal subjects (author's transl]. In 12 normal subjets we studies the effects of beta-adrenergic stimulation (Salbutamol, 500 microgram inhaled) on the closing volume (CV) and the closing capacity and on the ratios of these indexes to the vital capacity (VC) and the total lung capacity, respectively. CV and CV/VC % increased in ten subjects wereas it decreased in two subjects. On an average, the changes  were small but significant (p less than 0.01) and could be duplicated in four subjects. Similar studies have yielded variable results. The reasons for those variation could be attributed either to technical or/and individual differences in the resulting effect of beta stimulation on respiratory mechanics.


Blood respiratory properties of Bison bison. The respiratory properties and basic hematology of blood from seven adult bison and one calf were determined. Average oxygen-carrying capacity was 22.2 ml/100 ml blood from adults and 17.0 in calf blood; hemoglobin averaged 17.1 g/100 ml in adults and 13.6 in the calf. Half saturation of the blood occurred at 32mm Hg Po2 at pH 7.40 and 37 degrees C. The average Bohr effect was -0.40. Erythrocytes numbered 8.6 X 10(6)/mm3 and were 52 micron 3 in mean volume. Adult and calf cells differed in mean cell hemoglobin, adults 19.9 pg/cell vs 15.9 in the calf, and this difference evidently caused differences in Haldane effect, standard bicarbonate, and buffering capacity. Bison are capable of prolonged running. Two features of the blood that promote this capacity are its comparatively great oxygen-carrying capacity and low oxygen affinity.


Arterial hydrogen ion versus CO2 on depth and rate of breathing in decerebrate cats. Arterial blood hydrogen ion concentration (Ha+) was altered over the range of 25 to 110 nM (pH 7.60 to 6.96) by slow intravenous infusion of 1.0 N NaHCO3 or 0.5 N HC1 at controlled levels of Paco2in unanesthetized decerebrate cats. Respiratory f varied as a single function of Vt irrespective of a lterations in Paco2 and Ha+ even after interruption of the carotid sinus nerves. The dependence of f upon Vt was abolished by vagotomy. However, Vt continued to respond to changes in Ha+ over its entire range after combined section of the vagus and carotid sinus nerves. In all statxceeded by 5 to 10 times the delta Vt/delta Ha+ response to acid or bicarbonate infused under isocapnic control. Increases and decreases of ha+ caused downward and upward shifts, respectively, in the operating setpoint of the CO2 regulation system.


Thermorespiratory responses of shorn and unshorn sheep to mild heat stress. Three 3-year-old ewes with surgically exteriorized carotid loops were twice exposed to ambient temperatures (Ta) of 25, 30, 35 and 40 C (at constant 40% relative humidity) for 120 min in the presence (6.6 cm) and absence (less than 0.3 cm) of fleece. Thermoregulatory responses were evaluated during the last 30 min of each exposure by measurements of rectal (Tre), 6 skin surface temperatures (Ts), respiratory frequency (f), oxygen consumption (Vo2) and respiratory evaporative heat (Er); arterial blood samples were analyzed for pH, Pco2 and HCO-3 concentration. Both shorn and unshorn sheep exhibited a progressive increase in f, Er and Ts as Ta was elevated, with the unshorn group showing a higher Er than the shorn sheep at each Ta without a significant change in heat production. Er was found to be the principal avenue of heat loss, accounting for as much as 59% of the total in the shorn sheep compared to65% for the unshorn sheep. Increases in Er were accompanied by a decline in the arterial Pco2 which was linearly related to the Ta in both shorn and unshorn sheep. These data suggest that in defending against hyperthermia, sheep appear unable to increase Er without a concurrent elevation in Va at nearly allstages of acute heat stress.


Effect of simulated altitude on blood gas transport in the pigeon. Unacclimated pigeons were exposed to various simulated altitudes. Arterial and mixed venous blood gas levels were measured. At the highest altitude 9150m (Pb = 235 mm Hg) a remarkable degree of alkalosis was tolerated for several hours without ill effecrtant factor in the bird's ability to survive such altitudes.


Calcium fluoride formation on enamel and its influence on uptake of fluoride in the apatitic lattice. Human dental enamel was exposed to a pH 4 buffer containing 150 parts/10(6) fluoride. It was found that due to the arising degrees of saturation with respect to calcium fluoride and apatites, surface enamel dissolved coincident with a formation of calcium fluoride. The calcium fluoride redissolved while it kept the liquid saturated with respect to this salt. During this second period, fluorapatite was formed while hydroxyapatite dissolved. Finally, all calcium fluoride was dissolved and the unreacted fluoride was taken up in the apatitic lattice. The results are discussed with reference to the conditions of the oral cavity and enamel solubility experiments.


Standardization of the nitroblue tetrazolium test. Influence of pH, dye concentration and sample storage. The influence of pH, dye concentration and sample storage on the histochemical nitroblue tetrazolium (NBT) test in 45 patients with acute bacterial infections and 51 healthy individuals has been examined. Even minor deviations in pH and NBT dye concentration markedly influenced the reduction of NBT to formazan by patient and control neutrophils, and the differentiation between results in these groups was optimal at pH 7.2 and a concentration of 0.05% NBT in the final blood-NBT mixture. Storage of heparinized blood samples for more than 2 hours at 21 degrees C and for more than 6 hours at 4 degrees C is not recommended due to overlap between results in patients and controls. The error involved in counting of NBT-positive neutrophils accounted for the major discrepancies tests in patients and controls and in tests performed on different days. The reproducibility of the endotoxin stimulated test was inferior to that of the unstimulated test.


[Study of a new hypnotic drug: Ro 5-4200 (flunitrazepam)]. The Authors carried out a clinical study of a new benzodiazepinic derivative (Ro 5-4200) presenting hypnotic properties particularly "interesting". The results emerged from this study confirmed the hypnotic efficacy of the preparation also in case of insomnia of a certain seriousness, as well as its excellent tolerance.


Eschaemia during arterial reconstructive surgery. Biochemical changes as reflected in popliteal vein samples. Blood gases, electrolytes, metabolites and enzymes were studied in the venous effluate from the leg and in the systemic blood of 8 patients suffering from obliterating arteriosclerosis, during and after reconstructive arterial surgery. The common femoral artery was clamped for 50 to 180 min. Marked hypoxia and acidosis, together with a rise in lactate, phosphate and creatinine concentrations were found in the popliteal vein samples. Changes in the electrolyte concentrations were also observed. The rises in K+ and Mg++ were most pronounced. None of the changes wre correlated to the occlusion time and only small inter-individual variations were recorded. Only minor systemic change occurred after restoration of blood flow. The maximum postoperative CPK-activity, however, was closely correlated to the occlusion time, but judging by the level of this activity the actual muscular damage caused by the ischaemia was moderate, even after prolonged arterial clamping.


[Use of immunosuppressive agents in systemic diseases]. The use of immuno-suppressive agents in systemic diseases where the auto-immune origin is probable or certain is not yet based on definite physiopathological evidence. Therefore, it seems essential to use this treatment which has definite side effects only in cases where the progressive nature of the disease, renal complications or the incomplete or nil efficacy of less agressive treatments, leave no choice.


Demonstration of cryoprecipitable immune complexes in pneumococcal pneumonia. Cold-insoluble protein complexes (cryoprecipitates) can be found in the serum in a variety of infectious diseases. We studied serum cryoprecipitates isolated from three patients with pneumococcal pneumonia by counterimmunoelectrophoresis (CEP) and immunofluorescent technics for the presence of immune complexes. The cryoprecipitates and supernatant serum were tested for pneumococcal capsular polysaccharide (PCP) by CEP at 37 C and 56 C with the appropriate controls. Antibodies against PCP in the cryoprecipitates and the supernatant serum were detected as follows. Streptococcus pneumoniae from each case was fixed onto slides. The slides were incubated with each cryoprecipitate and supernatant serum at 37 C, and further incubated with fluorescein isothiocyanate-conjugated antisera to human IgG, IgM, and IgA. The slides were examined with an immunofluorescent microscope. PCP was demonstrated in all of the cryoprecipitates. IgG antibodies against PCP were detected in all of the cryoprecipitates, while IgM antibodies were detected in Cases 1 and 2, and IgA antibodies in Case 1 only. Complement components of C3 and C4 also were demonstrated in the cryoprecipitates by CEP. These findings suggest that some patients with pneumococcal pneumonia have cryoprecipitable-immune complexes consisting of PCP and its antibodies.


[Detection of excessive chronic alcoholic consumption and control of withdrawal. Comparative study of respective values of the mean red-cell volume and serum gamma-glutamyl-transferase activity]. The routine detection of chronic alcoholism is necessary during any medical examination whether private or in hospital, or in occupational medicine. The practitionner now has available a simple reliable and cheap test. It consists of the serum estimation of gamma-glutamyl-transferase (gammaGT) and interpretation of the average red cell volume supplied by automatic counting of the red cell. Out of 120 chronic alcoholic subjects ; 67% has a gammaGT increased and 44% had macrocytosis. Under the influence of weaning, there was a rapid fall in gammaGT and a slower reduction in average red cell volume. gammaGT estimation was thus a more sensitive test than M.C.V. for the detection of chronic alcoholics and the control of withdrawal. Its association with the rise in immunoglobulin A-transferrin ratio which we have suggested permits the detection of almost all chronic alcoholics in the population studied.


Gastric volume and acidity at caesarean section. The pulmonary acid aspiration (Mendelson's) syndrome may present after regurgitation and inhalation of acid gastric content during obstetric anesthesia. The stomach contents of 70 mothers were aspirated at caesarean section after pre-operative gastric 'emptying' and alkaline ingestion. The acidity of the gastric aspirate was analysed and volumes were measured. The patients were divided into 5 groups according to the time when gastric aspiration was carried out. A 'safe' gastric pH (pH greater than 3.5) was found in all patients up to 2 hours after antacid ingestion (groups 1-3). However, 2 1/2 hours after antacid ingestion (group 4y, 50% of patients had gastric volumes in excess of 25 ml and a pH of less than 3.5. We therefore recommend that, if general anaesthesia is to be induced or is in progress 2 hours after antacid therapy, the alkaline regimen should be resumed after repeated gastric aspiration.


[Comparative study of a factor-VIII inhibitor in a non-hemophylic patient and in a patient with hemophylia A gravis]. In this study, we tried to make a comparison between the findings concerning two human strong anti Factor VIII inhibitors. In one case, the strong inhibitor appeared in an old man without any particular antecedant. In the second case, it occurred in a young hemophiliac A. We found in both cases that the inhibitor was a immunoglobulin G with light chain lambda. Its activity site is on the fragment AB. These anticoagulants have a inhibitory action against only the Factor VIII procoagulant fraction and have exclusively neutralising properties. The inhibitor present in the non hemophiliac patient has particularly great resistance to temperature and pH variations.


The conjugation of testosterone with horseradish peroxidase and a sensitive enzyme assay for the conjugate. The formation of a horseradish peroxidase-testosterone conjugate for the enzyme-linked immunoassay of testosterone was investigated, using tritiated testosterone to follow the reaction. The formation of testosterone-3-(carboxymethyl) oxime-peroxidase by the mixed anhydride method was found to give a conjugate of high enzymatic activity and with three molecules of testosterone per molecule of peroxidase. The optimum conditions for the assay of peroxidase activity were studied and an assay capable of measuring 1 to 5 ng of the conjugate developed; the standard curve being virtually linear. The stability of the conjugate in solution and the effect of lyophilisation on enzymatic activity are also described. The peroxidase-testosterone conjugate was suitable for enzyme-linked immunoassay and the quantities measurable with the peroxidase assay covered the range necessary for a plasma testosterone assay. The stability of the conjugate was such that no particular precautions were necessary for its storage.


[Quantitative determination of protector activity of fibrinogen tryptic hydrolysates]. A method is developed for the quantitative determination of the protector activity. The method is based on registrating the coagulation time shortening for a mixture of fibrin monomer and fragment D. All determinations should be carried out at high concentrations of fragment D when its inhibitory effect on fibrin polymerization is very strong. It is necessary to control the exact conditions as to ionic strength and pH of the reaction mixture. Another approach to the protector activity estimation is demonstrated. It is based on determination of clot protein quantities after fibrin monomer clotting in mixtures with constant fragment D and different protector quantities.


[Effect of phosphoenolpyruvate on creatine kinase activity in rabbit muscles]. Phosphoenolpyruvate (PEP) is a potent inhibitor of muscle creatine kinase. The inhibition of ATP formation is more pronounced at pH 7.0. The substrates, creatine and creatine phosphate, partially prevent the inhibition of the enzyme activity by PEP, creatine being as an effector.


[Transfer electron and hydrogen atom in model and enzymatic reactions of NAD and NADP]. The paper deals with the mechanism of some model reactions of NAD and NADP which proceed with transfer of one electron and hydrogen atom. The joint oxidation of N-benzyl-1,4-dihydronicotinamide (I) and phenylglyoxal with hydrogen peroxide in the presence of cupric ions is found to result in transfer of one hydrogen atom from dihydropyridine molecule to hydroxy-radical and the electron to a molecule of oxygen or dinitrobenzene. The oxydation of I with benzoquinone is found to proceed with formation of free radicals as intermediate. The mechanism of NAD reduction with sodium hydrosulphite is proposed.


[Changes in lipid and carbohydrate metabolism in rat tissues under combined effect of hypercapnia, hypoxia and cooling]. The cooling of rats under conditions of hypercapnia and hypoxia during the first 15 minutes increases the contents of free fatty acids, acetoacetate and beta-oxybutyrate in the tissues of the brain, myocardium, liver, skeletal muscles and blood and decreases them by the end of the effect (120 min later) down to the initial values, in the liver and skeletal muscles tissues the content of the mentioned intermediates falls lower the initial values. In the carbohydrate metabolism the amount of phosphoenolpyruvate 15 and 120 min after the action beginning and the amount of malate in the myocardium and brain at the end of the experiment increase to a different extent; the content of lactate rises only in the brain 30 and 120 min after the beginning of cooling. In the rat venous blood the value of pCO2 increases up to 71.8+/-6.0 mm Hg, the total content of CO2 rises, the values of the standard bicarbonates decrease and the pH value drops sharply down to 6.98+/-0.03. It is suggested that one of the main reasons of such changes in metabolism is development of hypercapnia state and acidosis and the resulted increase in intensity of the carboxylation processes in the tissues.


[Peculiarities of aggregation in acid medium of immunoglobulin G peculiar to cancer]. Immunoglobulin G peculiar to cancer under the effect of acid medium changes to a slightly soluble form due to reversible formation of aggregates. The rest serum proteins transfer to the insoluble form in a more acid medium due to the irreversible denaturation changes in the protein molecules. When isolating aggregates of the mentioned protein from the blood serum of patients with cancer it is impossible to differ these sera from those of donors or patients with pathologies of nonmalignant character under the effect of acid medium. The amount of the aggregates isolated accounts for 1.1-1.2% of total amount of serum proteins and does not depend on affinity of the anion of acid in the presence of which the experiment was conducted for proteins.


[Structural changes in sarcolemma with E-avitaminosis dystrophy]. Sorption properties of sarcolemma preparations isolated from skeletal muscles of normal and E-avitaminous rabbits were studied relative to organic ions. Analysis of isotherms of sarcolemma equilibrium binding of neutral red cations and turquoise direct lightfast "K" anions made it possible to determine the number of positively and negetively charged sorption centres, which fix the mentioned dyes. With E-avitaminous muscular dystrophy the number of the centres increases considerably. A larger number of the positively charged centres fixing the surquoise dye are found both in the control and in case of dystrophy. The calcium ions prevent the neutral red sorption and intensify the turquoise direct sorption. In the sarcolemma preparations isolated from the muscles of the E-avitaminous rabbits the content of calcium ions is almost twice as high and the number of sulphydryl groups is 30-40% less as compare to the normal level. The data presented evidence for structural changes in sarcolemma with E-avitaminous muscular dystrophy.


[Pasteurella multocida bacteriophage adsorption]. Studied was the adsorption of 8 strains of Pasteurella multocida bacteriophages presenting three groups of phages isolated in Bulgaria. With the bacteriophages of groups I and II the adsorption in broth in the first 10 minutes amounted to 50-65%, and at the 80 the minute reached its maximum value--98-99%. With the bacteriophages of group III adsorption started with a lower percent and by the 140th minute reached 96-97%. It was by 60 min slower as compared with the adsorption with group I and II phages. In a veronal-medinal buffer the adsorption of all investigated phages of the three groups set in with a prolonged time of 60 min as compared with the time elapsed using broth. At the cross testing of adsorption the phages of group I were adsorbed by the hosts of the other two groups to a maximum level, however, the phages of groups II and III were adsorbed to a negligible extent on the other hosts (except for the adsorption on their homologous one). The difference established in the adsorption for a 60 minutes time so far as the phages of group III were concerned was sufficiently persuasive to consider this group as an individual one by this feature too. Adsorption appeared as a subsidiary taxonomic characteristic in the classification of Pasteurella multocida bacteriophages.


The effect of dehydroemetine on vascular tissue. The effect of dehydroemetine on vascular tissues was studied, using the aortic strip of the rabbit, the isolated perfused central ear artery of the rabbit and the perfused hind limb of the cat. Doses from 10(-6) to 10(-5) M inhibited the response of the aortic strip and the perfused ear artery to transmural electrical stimulation. 10(-5) M dehydroemetine completely blocked the response of the aortic strip to transmural stimulation. This dose however, had no significant effect on the response to exogenous noradrenaline and dexamphetamine. Doses ranging from 0.1-3 mg/kg caused transient falls in the perfusion pressure of the cat's hind limb. This fall was not blocked by propranolol, mepyramine nor atropine. It was concluded that the effect of dehydroemetine on vascular tissues was non-specific.


The metabolism of niclosamide and related compounds by Moniezia expansa, Ascaris lumbricoides var suum, and mouse- and sheep-liver enzymes. 1. Niclosamide and related nitro compounds were reduced to the corresponding amines by Moniezia expansa, Ascaris lumbricoides var suum and by enzymes prepared from these species and by mouse and sheep liver homogenates. The reduction of niclosamide by the helminths required as cofactors NADH2 and glutathione, but was inhibited 50% by 2 X 10(-7) M allopurinol. 2. Unlike benzanilide, niclosamide was not hydrolysed by either the helminths, or the mammalian liver preparations. Rates of hydrolysis of compounds related to niclosamide indicate that niclosamide was not hydrolysed because substituents in both benzene rings ortho to the amide bond sterically hinder the hydrolase. 3. Hydrolysis of benzanilide and related compounds was inhibited by anthelmintic organophosphates.


The metabolism of the neuroleptic agent 1 (4'-fluorophenyl)-4-(cyclohexyl-1'-piperzinyl-4'-carboxylated)-butan-1-one hydrochloride in rats and man. 1. An oral dose the neuroleptic agent 1-(4'-fluorophenyl)-4-(cyclohexyl-1'-(14C)piperazinyl-4'-carboxylate)butan-1-one was mainly eliminated in the urine within 12 h by rats and man. During 5 days, 63-6% and 83-3% was eliminated in the urine of rats and man respectively. 2. Plasma concentrations in man related a maximum during 30 min to 1 h, representing 1-43 microgram equiv./ml. The proportion of unchanged drug in plasma decreased from 48% at 15 min to less than 10% after 1 h. 3. Seven major radioactive components were detected in the chloroform extract of basified rat urine and five major components in similar extracts of human urine. The major rat metabolites were isolated and identified by mass spectrometry as components resulting from mono- and dihydroxylation in the cyclohexane ring, reduction of the keto group to a secondary alcohol and hydrolysis and decarboxylation of the cyclohexylcarbamoyl group. The major metabolite in the rat urine extract was the dihydroxylated secondary alcohol derivative while the major human metabolite was the monohydroxylated secondary alcohol derivative. The metabolites were also partly eliminated as conjugates.


[Thermal inactivation and storage behavior of technologically important enzymes. IV. Spinach lipid-acyl-hydrolase]. The thermal reaction of a lipid-acyl-hydrolase which seems to be important for the quality preservation of vegetable foods, was investigated in spinach. The authors applied a simple in-situ method using thin-layer chromatography which had been developed for the enzyme determination, to follow the thermal inactivation of the lipid-acyl-hydrolase by measuring the decomposition of lecithin, mono- und digalactosyl diglycerides. According to the inactivation curves, the enzyme is relatively little resistant to heat. Since the D- and z-values resulting from the inactivation curves for phospholipase, mono- and digalacto-lipase activities are almost the same, it can be assumed that the lipid-acyl-hydrolase is a multi-function enzyme in spinach.


[Thermal inactivation and storage behavior of technologically important enzymes. I. Horseradish and spinach peroxidase]. The thermal inactivation and storage behaviour for horseradish and spinach peroxidases were investigated in defined systems, in spinach also within its natural environment. The inactivation curves of either enzyme show a sharp bend which is clearly visible at low, but not at higher temperatures. The D-values were taken from the inactivation curves. z-values resulting from the D-values were 25.5 degrees C for horseradish peroxidase, 13 degrees C for isolated peroxidase and 18 degrees C for peroxidase in spinach extract. Horseradish peroxidase was relatively heat-resistent at pH 6.0, spinach peroxidase at pH 5.0-6.0; both enzymes were found to be highly susceptible to heat at pH 4.0. Peroxidase isolated from spinach responded differently to heating than the enzyme in spinach extract or suspension. This discrepancy indicates that certain model experiments cannot be transferred to foods. Heated peroxidase from horseradish and spinach were found to regenerate during storage; the extent of regeneration depended on the pH.


[Effects of a coffee-antacid-mixture and a commercial coffee with regard to gastrin, pH and gastric secretion (author's transl)]. The influence of a coffee-antazid-mixture was investigated at 30 patients with diseases of the stomach (17 with duodenal ulcer, 6 with gastric ulcer and 7 with chronic gastritis) in comparison to a commercial coffee. The parameters measured were the gastric basal acid output, the continuous registration of the pH by an intragastric electrode and the serum gastrin concentration before and after the application of the tests substances. 75% of the patients with duodenal ulcer showed a positive effect by means of a greater elevation of the intragastric pH after application of the mixture in comparison to coffee. The effect was strongly correlated to the basal acid ouptput. In the group with gastric ulcer and that with duodenal ulcer under the influence of the mixture the pH after the initial rise decreased to less deeper values. There was a close relationship to the patterns of gastric ulcer as well with chronic gastritis there was an additional facourable effect on the symptoms of abdominal pain which occured after coffee and not after the mixture. The group with chronic gastritis showed no difference between the pure coffee and the coffee-antacid-mixture. A possible relationship of the products of coffee roasting and the adsorptive properties of the antacid is discussed.


[Experiences on the effectivity of prostaglandin F2alpha during labor after insufficient effect of oxytocin]. A report is given about the efficacy of prostaglandin F2alpha for induction of labour after inefficient application of oxytocininfusion. In all cases induction of labour was indicated or labour should be supported. 80 of the 104 women with weak labour finally delivered on vaginal way. Only 9 of 24 caesarean sections were performed by reason of weak labour in spite of application of prostaglandin F2alpha. There was no influence on the state of the newborns, this was the result of postnatal judgment by Apgar-score.


[Morphofunctional changes in the thymus of semisyngenous chimeras during the "graft versus host" response]. Activation of the enzymatic processes in the thymus cells was noted in the thymus gland at the early stages of the "transplantat-versus-host" reaction; the later stages were attended by inhibition of metabolic processes and reduction in number of immature and mature thymocytes in the cortical substance of the thymus. Besides, the cortical substance displayed accumulation of mesenchymal macrophages rich in lysosomal enzymes, particularly in the subcapsular layer where small foci of destruction formed at the late stages of the reaction.


[Dynamic study of blood cholinesterase activity of paranoid schizophrenic patients]. A comparison of the cholinesterase blood activity with the clinical traits of the disease in 64 patients with paranoid schizophrenia treated by majeptile and haloperidol detected 2 variants in the reactivity of the enzyme link of the cholinergic system. A fluctuation of the cholinesterase activity of the sinusoid type (Ist variant) seen in patients with paranoial and hallucinatory-paranoid syndromes with a remission up to a year and more, speaks in favour of a relatively preserved compensatory-adaptive mechanisms in the neurohumoral regulation. The absence of fluctuation in the cholinesterase activity during the whole period of treatment (2nd variant) was characteristic of patients with negative results of treatment.


[Sex gland morphology of schizophrenic patients during treatment with psychotropic drugs]. A macro- and microscopic study of genital glands was conducted in 33 cases of schizophrenia (14 females and 19 males). A practically normal histological picture of the ovary and testis was found in 12 cases, different degrees of involutional (atrophic) changes in 19 and tumours in 2 cases. The degree of expressed histological changes correlated with age and duration of the disease. Correlation between the histology of genital glands on the one hand and the duration and intensity of psychopharmacological treatment on the other one (mainly by neuroleptics) were not found.


[Several indices of the methylation process in schizophrenic patients]. The paper deals with a study of 83 patients with different forms of schizophrenia and 15 normals where the methylating activity in converting nicotinamid into methylnicotinamid was determined and the activity of catechol-methyltransferase. In schizophrenic patients there is an increase of the methylating activity which significantly correlated with hallucinatory symptoms in the clinical picture. In patients with cataono-paranoid, paranoid syndromes and simple forms of schizophrenia the methylating activity is seen significantly less frequently. The disappearance of alleviation of hallucinations, due to neuroleptical drugs is accompanied by normalization of the methylating activity. Any significant differences in the excretion of isdarin as an index of cathechol-o-methyltransferase activity in normals and schizophrenic patients was not established.


The stenosis of the terminal esophagus after surgical repair of the hiatus hernia. Eighty-two operations of hiatus hernia repair were performed at the General Surgery Department of the University of Padua from 1966 to 1975. Two cases of iatrogenic stenosis of the the terminal esophagus, whose correction required postoperative dilatations, occurred in this series. This complication should be separated from the transient dysphagia frequent occurring, without radiologia or endoscopic evidence of esophageal lesions, after hiatus hernia repair. The stenosis followed two different repair techniques but, at present time, it is impossible to establish a relationship between occurrence of the iatrogenic lesion and repair techniques used. Eventhough iatrogenic stenosis of the terminal esophagus does not occur frequently, it is a possible complication to keep in mind while performing hiatus hernia repair, because it is exclusively related to defects of the surgical technique.


Saliva tests in the prognosis of caries in children. The purpose of the investigation was to find out whether the negative correlations between caries indices and the flow rate, pH and buffer effect of saliva that could be demonstrated in groups of 8- and 5-year-old children, were close enough to allow prediction of the development of caries in a given child. The results showed that the range of variation of the results of all analyses were very wide. This makes the use of saliva tests alone in the prognosis of caries development of less value in the individual child.


Ocular encephalitozoonosis (nosematosis) in blue foxes. Polyarteritis nodosa and cataract. In young blue foxes an association has previously been established between the protozoon Encephalitozoon (Nosema) cuniculi and generalized arterial lesions of the polyarteritis nodosa type. The same vascular changes are found in the posterior ciliary arteries and their intraocular branches of these foxes. Most of the eyes which are thus affected, have a severe cataract. The parasite can easily be demonstrated both in the arteries and the lenses. It is thought that the Encephalitozoon is the cause of the vascular lesions and the cataract, and that possibly an autoimmune reaction is involved.


Role of feeding on lipase activity in gastric contents. Lipase activity was recorded in gastric contents collected from healthy term and preterm neonates. In contrast to pancreatic lipase activity this lipase activity was higher at pH 5.5 than at pH 8.0 and it was more resistent to acid inactivation. Lipase activity was found in gastric contents from all infants who were regularly fed, but was not present in gastric contents from some infants when collected before regular feeding was established. During test meals lipase activity in gastric contents increased considerably in all infants studied. During such a test meal there was a progressive relative decrease in triglycerides whilst diglycerides showed a relative increase suggesting an active lipolytic process in the stomach. An assay procedure for determination of lipase activity in gastric contents is also described.


Prevention of kernicterus, based on recent progress in bilirubin chemistry. A review is presented of recent progress in bilirubin chemistry, its binding to albumin, displacement by drugs, and the mechanism of phototherapy. Quantitative formulations of the effect of albumin dosage, of varying pH, and of fatty acids result in a diagram which may be tried as an aid to indications for therapy.


Chemical composition, serological reactivity and endotoxicity of lipopolysaccharides extracted in different ways from Bacteroides fragilis, Bacteroides melaninogenicus and Bacteroides oralis. Lipopolysaccharides (LPS) extracted from strains of Bacteroides fragilis, Bacteroides melaninogenicus and Bacteroides oralis with phenol-water, trichloroacetic acid, EDTA or liquid phenol-chloroform-petroleum ether (PCP) and isolated by ultracentrifugation, varied considerably in their quantitative chemical composition. Negligible yields of LPS were obtained by PCP-extraction. All preparations were more or less serologically active. All methods (except PCP) extracted the same O-antigenic determinants from B. fragilis. Endotoxic activity, as measured by primary skin inflammations in rabbits, was low but was present in all preparations. Proteins (and/or lipoproteins) co-precipitated with LPS in the ultracentrifuge.


Purulent and non-purulent maxillary sinus secretions with respect to pO2, pCO2 and pH. Antral secretions from patients with maxillary sinusitis were aspirated for determination of pO2, pCO2 and pH. In 14 non-purulent secretions the mean pO2 was 12.7 kPa (96 mmHg) and the mean pCO2 5.2 kPa (39 mmHg). The mean pH was slightly alkaline. In 18 purulent secretions, usually with a heavy growth of pneumococci or H. influenzae, the pO2 was zero or close to zero and the mean pCO2 greater than or equal to 10.1 kPa (greater than or equal to 76 mmHg). The mean pH was slightly acid and significantly lower than in the nonpurulent secretions. The gas composition and the pH in purulent secretions do not only influence the metabolic activity and multiplication of bacteria, but may also interfere with the local protective functions of the sinus mucosa and with the bactericidal function of granulocytes.


Studies on fish liver protein synthesis. II. Factors influencing the aminoacylation of shark liver transfer ribonucleic acid. The influence of buffer, pH, Mg2+, ATP, Na+, K+ and temperature on the extent and rate of aminoacyl-tRNA synthesis was studied with the shark Mustelus mento liver tRNAs and aminoacyl-tRNA synthetases. The optimum pH for the aminoacylation of tRNAMet was 8.3 and for tRNAVal 7.0. For these two tRNAs the Mg2+ optimum was related to the levels of ATP required and to the pH of the reactions. It is suggested that the Mg2+ concentration required for each aminoacylation system reflects the true conditions under which the substrate for the enzyme, the MgATP2- complex, is formed. The effect of monovalent cations was also examined. Val-tRNA synthesis was slightly stimulated up to a concentration of 50 mM NaCl (KCl). Over 100 mM salt, a rapid inhibition was observed. Met-tRNA synthesis behaves differently by being stimulated over a wide range of salt concentrations.


Purchases of hypnotics, sedatives and minor tranquillizers among 2,566 individuals in the county of Jämtland, Sweden. A 6-year follow-up. Data from a continuous recording of drug prescriptions to 16,600 individuals in the county of Jämtland, Sweden, revealed that 2,566 patients (15.5%) obtained prescriptions for hypnotics, sedatives and minor tranquillizers in 1970. Occasional use (one purchase only, Group A) was seen in 7.4% of the population, intermediate use (two to six purchases, Group B) in 6.9% whereas 1.2% were regular users (seven purchases or more, Group C). For each group as a whole there was 5 years later a highly significant intraindividual reduction in the purchases of these drugs as well as of other psychotropic drugs. In all groups 10-23% had increased their purchases, most of them insignificantly. Fifteen of 30 patients with a marked increase in consumption developed a regular purchase pattern, but signs of overuse or abuse were seen in only four persons. During the studied period the benzodiazepines increased their share of the total from 45 to 60%. Antihistamines also increased in all groups while the proportion of barbiturates and combined preparations decreased markedly.


Peripheral haemodynamics in essential hypertension. Previous studies have indicated the existance of haemodynamically important structural vascular changes in patients and animals with hypertension. Possible pathophysiological implications of these changes are discussed. Two studies dealing with the question of reversibility of the structural changes on long-term blood pressure lowering therapy are described. The results indicate that the changes are partially but not completely reversible.


The oxygen sensing characteristics of microsomal enzymes. The microsomal electron transport complex, in particular the segment associated with cytochrome P-450 function, is both qualitatively and quantitatively an important contributor to the cellular respiration of tissues such as liver. Although our knowledge is still limited, it is apparent that oxygen plays a pivitol role in dictating the mode of substrate hydroxylation or the generation of hydrogen peroxide. As illustrated in Figure 7, current evidence suggests that hydrogen peroxide is formed by the dismutation of the superoxide anion resulting from the dissociation of oxycytochrome P-450. Of interest are recent studies demonstrating the ability of hydrogen peroxide to initiate a cytochrome P-450 dependent peroxidatic reaction competent for supporting substrate hydroxylation. The fact that the function of cytochrome P-450 is sensitive to changes in oxygen tension establishes its role as an "oxygen sensor" for cellular metabolism.


Evaluation of research on control of prolactin secretion. At least three substances have been reported to be present in the hypothalamus that can inhibit prolactin release, namely a PIF, catecholamines and acetylcholine. At least four substances have been reported to be present in the hypothalamus that can stimulate prolactin release, namely PRF, TRH, serotonin and prostaglandins. Neither the existence of a distinctive PIF or PRF in the hypothalamus can be considered as definitely established. The predominant action of the mammalian hypothalamus on prolactin release is inhibitory under most conditions, and is stimulatory in avian species. In addition to control by the hypothalamus, several hormones and drugs can act directly on the pituitary to alter prolactin release. The interrelationships of these agents within and without the hypothalamus on prolactin secretion are complex, and there are many questions about their mode of action. Studies on the regulation of prolactin secretion have resulted in development of many methods for either increasing or decreasing release of this important hormone, and thereby have provided opportunities for influencing lactation, growth of mammary and pituitary tumors and other tissues responsive to prolactin.


Effect of the diphosphonate EHDP on plasma inorganic phosphate and hemoglobin oxygen affinity of diabetic and healthy subjects. The effect of oral disodium ethane-1-hydroxy-1,1-diphosphonate, EHDP (20 mg kg-1 day-1) and placebo given for 28 days on plasma inorganic phosphate (Pi) red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin was evaluated in 14 insulin-treated diabetics and 5 healthy volunteers. EHDP significantly increased mean Pi (diabetics: 1.18 to 1.67 mmol/l, p less than 0.01, controls: 1.03 to 1.71 mmol/l, p less than 0.02) and P50 at in vivo pH of the oxyhemoglobin dissociation curve (diabetics: 25.4 to 26.6 mmHg, p less than 0.02; controls: 26.3 to 28.9 mmHg, p less than 0.02). Pi and P50 were correlated in both diabetics and in controls (p less than 0.05). 2,3-DPG increased when the diabetics were on EHDP (p less than 0.005). The study emphasizes the importance of Pi on red cell function and indicates that an elevation of Pi tends to counteract the defect in oxygen release capacity of the red cells in diabetic subjects.