Plasma glucagon after kidney exclusion: experiments in somatostatin-infused and in eviscerated dogs. Bilateral kidney exclusion in the anesthetized dog is followed by a rapid and sustained increase in arterial plasma glucagon. This occurs even if endogenous glucagon secretion is inhibited by somatostatin or completely suppressed by abdominal evisceration and, in both cases, replaced by a constand infusion of exogenous glucagon. It is concluded that the rise in plasma glucagon occurring after bilateral kidney exclusion is not due to an increase in endogenous glucagon production but results from an abrupt cessation of kidney glucagon uptake.


Carbohydrate and lipid metabolism during human labor: free fatty acids, glucose, insulin, and lactic acid metabolism during normal and oxytocin-induced labor for postmaturity. This investigation was performed to study the metabolism of the major body fuels (viz. glucose and free fatty acids), insulin, and lactic acid during the stress of human labor. In addition, the role of the normal placenta in the transport of these substances between mother and the fetus was evaluated by measuring them in the mother and cord blood at delivery. To study possible alterations of this role in the placenta which had exceeded the normal period of gestation, a second comparable group of women had labor induced with oxytocin 16-18 days beyond the expected date of delivery. A dramatic twofold increase in maternal plasma free fatty acids was observed during labor. There was a lesser but definite increase in blood glucose concentrations. No rise in serum insulin levels was noted which coincided with the changes in blood glucose. Lactic acid concentrations during the course of labor were variable from baseline but at delivery, the concentrations rose to very significant levels. Free fatty acids and blood glucose levels were significantly higher in the maternal than in the fetal side. A significantly positive correlation was noted between the maternal and cord blood values except for free fatty acids in the postmature group. No significant difference, nor a correlation was found between the two compartments in the insulin nor lactic acid levels. These results suggest that during human labor free fatty acids are the principal metabolic fuel. This increase in maternal free fatty acids may serve to spare glucose as a metabolic fuel in the fetus. The mechanism responsible for the increase maternal free fatty acid mobilization remains to be determined. It is not possible to discern any consistant alteration in placental function as a consequence of prolonged gestation.


Synthesis and degradation of methylated proteins of mouse organs: correlation with protein synthesis and degradation. L-(Methyl-14C)-methionine was administered i.p. to mice, and the incorporation of radioactive methionine into proteins and methyllysine and methylarginine residues formed by the transfer of the methyl-14C group of methionine were measured. Tissue protein was actively methylated in organs having a high activity of protein synthesis, and the in vivo methylating activity in organs was not correlated with theprotein methylating activity of the organs determined in vitro. Puromycin inhibited both protein synthesis and protein methylation in mouse organs to a similar degree. Neither the formation of S-adenosyl-(methyl-14C)-methionine nor protein methylase was inhibited by puromycin. The data suggests that proteins are methylated immediately after protein synthesis, that is, newly synthesized proteins are the substrates of protein methylation. Radioactive methionine and the [C14] methyl groups of methyllysine and methylarginine residues of tissue proteins are degraded in parallel over a period of 3 wk, suggesting that protein methylation is an irreversible type of protein modification.


Reversible and irreversible glucose disposal in dogs: influence of fasting and cold exposure. Rates of total glucose entry rate, irreversible loss, and recycling were measured in unanesthetized dogs with indwelling arterial and venous catheters. Four experimental conditions were selected: 16 or 26 hr of fasting and neutral (+25 degrees C) or cold (-21 degrees C) ambient temperatures. A mixture of U 14C-glucose and 2-3H-glucose was used as a tracer, according to the primed infusion technique. No matter what the ambient temperature was, increase of fasting time from 16 to 26 hr induced a slight, but nonsignificant, decrease in both the total glucose entry rate and the irreversible loss. At neutral ambient temperature, the amount of glucose promptly recycled was less after 16 hr than after 26 hr of fasting, while an opposite pattern was observed during cold exposure. Thus, that part of hepatic glucose entry promptly recycled was significantly increased from 22% (16 hr of fasting) to 31% (26 hr of fasting) at neutral ambient temperature. It remained almost unchanged (20% and 18%) in cold. It was, therefore, suggested that this increase might be considered as an compensatory mechanism, exerting a sparing effect on glucose utilization. This mechanism does not occur in cold ambient temperature, thus, worsening a possible shortage in glucose supply.


[The effect of metal ions on the lipolytic activity of Mycobacterium rubrum and Actinomyces streptomycini]. Hydrolysis of olive oil by intact cells of Mycobacterium rubrum 403 and "acetone" preparations of Actinomyces streptomycini 116 was found to be inhibited by the following ions: Ca2+, Mg2+, Mn2+, Ba2+, Co2+, Cd2+, Cu2+, Zn2+, Fe2+, Fe3+, Ni2+. Olive oil is hydrolyzed by the growing culture of Act. streptomycini 116 only in the presence of bivalent metal ions. The biosynthesis of lipase by Mycobatcerium rubrum 403 and Act. streptomycini 116 is increased twofold by magnesium ions. The biosynthesis of lipase by Act. stroptomycini 116 is stimulated also by calcium ions.


[An electron microscopic study of the vegetative mycelia of Actinomyces flavus during flavofungin biosynthesis]. The vegetative mycelium of a submerged culture of Actinomyces flavus 12 was studied by complex electron microscopy (negative and positive contrasting, cryofractography) in the course of biosynthesis of flavofungin. The antibiotic is accumulated first in the cytoplasm as singular small granules which later grow larger. Accumulation of flavofungin is accompanied with destruction of the cytoplasm, nucleoid and other structures. Secretion of the antibiotic is supposed to be accomplished according to holocrine type.


[Detection of cyanide resistant respiration among Candida lipolytics yeasts]. Conditions causing cyanide-resistant respiration were studied in the yeast Candida lipolytica. This type of respiration was found when the culture growing on glucose, glycerol, hexadecane, or acetate exhuasted the substrate and passed from the logarithmic to stationary growth phase; the same phenomenon can be induced by exhaustion of phosphorus or nitrogen in the glucose medium. The yeast culture growing on lactate, ethanol, pyruvate, alpha-ketoglutarate, malate, or succinate is characterized by cyanide-resistant respiration even at the beginning of the logarithmic growth phase. The values of pH in the incubation medium have no effect on the time of manifestation of cyanide-resistant respiration.


[Dark metabolism of Rhodospeudomonas sulfidophila]. A new strain of phototrophic purple bacterium Rhodopseudomonas sulfidophila RP-6 has been isolated from samples of the salty meromictic lake Repnoye. The bacterium utilizes thiosulphate yielding sulphates and assimilates molecular hydrogen in the darkness under aerobic conditions. Thiosulphate stimulates fixation of 14C-bicarbonate by the cells both in the light and darkness. Organic compounds are necessary for growth of the bacterium in the darkness. R. sulphidophila RP-6, R. palustus, and Rhodomicrobium vanniellii CO-1 do not grow in the presence of carbon monoxide neither in the light or in the darkness.


[Determination of the specificity of microbial esterases in vivo]. Gas chromatography is used to determine the specificity of microbial esterases in vivo. The technique is based on hydrolysis by the cells of esters of fatty acids containing different alcohol groups. The specificity was evaluated by means of the coefficient Kc which changed from 0 to 1 and did not depend on the time of hydrolysis. The esterases of M lysodeicticus were more specific than the esterases of S. marcescens by a factor of 30 during hydrolysis of the equimolar mixture of methyl ester of pelargonic acid and ethyl ester of caprylic acid. This criterium of specificity may be used for rapid identification of bacteria.


[Annual production of bacterioplankton in the deep sea area of Southern Baikal]. The time of generation of bacterioplankton in the pelagic zone of Baikal differs in various seasons of the year: the minimum time is in December (25 hours), the maximum time is in October of 1970 (580 hours) and in June of 1971 (560 hours). Monthly production of bacteria for a layer of 0 to 50 m varies from 0.07 g in January to 49 g of wet weight per 1 m2 in September. Annual production of bacterioplankton in a layer of 0 to 50 m is 118.5 g of wet weight per 1 m2 of the lake surface. The P/B coefficient of micro-organisms varies from 0.02 in January to 1.1 in December. The most favourable conditions for bacterial growth therefore are in April, July--September, and December. The annual P/B is 4.42.


[The mechanism of action of trisportic acids on the carotene-synthesizing enzymes of the (-) strain of Blakeslea trispora]. Trisporic acids were found to increase the content of carotene, protein, and RNA in the (-)strain of Blakeslea trispora. Trisporic acids are inductors of the synthesis of carotenogenous enzymes as was found in experiments with the inhibitor of transcription (cycloheximide) and translation (actinomycin D). Trisporic acids stimulate the formation of neutral fractions of the sex hormone, the process being regulated presumably at the level of posttranscription control.


[Hydrogenase activity of different strains of Clostridium butyricum]. Extracts of the cells of Clostridium butyricum, strains MO-1, USA, TM-7B, WS-6K, and C. pasteurianum 038 absorb hydrogen in the presence of its different acceptors; hydrogen is absorbed most actively by the cell extracts of C. pasteurianum 038. The cell extracts of all studied strains of Clostridium liberate hydrogen from reduced methylviologene, benzylviologene, and azocarmine. The rate of this process in the presence of reduced methyl-viologene was highest in the strains of C. butyricum, TM-7B, and MO-1. Hydrogenases of all studied Clostridium strains are susceptible to the action of heat and oxygen.


[The activity of citrate glyoxylate and pentosephosphate cycle enzymes during yeast growth on hexadecane and glucose]. The activity of key enzymes of the citrate (CC), glyoxylate (GC), and pentose phosphate cycles (PPC) was determined in the cells of Candida lipolytica and Candida tropicalis growing on hexadecane and glucose. The activity of isocitrate lyase and malate synthase (enzymes of GC) was very high in hexadecane grown cells but was almost absent in "glucose" grown. The activity of citrate synthase and aconitase was 2-4 times and 1.5-2 times, respectively, higher in the cells, grown on n-alkane. The activity of citrate synthase of "hexadecane" and "glucose" yeasts was higher than the activity of other enzymes of CC (aconitase and isocitrate dehydrogenase), especially in the "hexadecane" cells. The activity of the key enzymes of PPC was almost the same in the yeast cells, grown on "hexadecane" and "glucose". Possible factors causing differences in the activities of the enzymes of GC and CC are discussed. Yeast organisms incapable to grow on n-alkanes were found to be able to grow on acetate (43 strains belonging to 35 yeast species have been studied) and to have a high activity of isocitrate lyase. Therefore, the absence of growth of many yeast strains on n-alkanes is not caused by the absence of the activity of enzymes of GC in these strains.


[The influence of the composition of the culture medium on the isoenzyme spectrum of Penicillium claviforme ribonucleases]. The dynamics of the activity of extracellular and intracellular RNases was studied with Penicillium claviforme growing (1) on the modified Ogata medium and (2) on the medium whose composition was optimized for biosynthesis of intracellular RNases. RNA-depolymerazing enzymes were compared when produced on the media 1 and 2. The isoenzyme composition of RNases was the same on both media though the ratio between the components and the time of their appearance were different. Changes in the activities of RNase, PME, and protease were similar during cultivation of Pen. claviforme on the media 1 and 2.


[The effect of nitrate and nitrite on the respiration and cytochrome system of Rhizobium lupini]. Differential spectrophotometry and oxygen electrode were used to study the effect of nitrate and nitrite on the cytochrome system and respiration of Rhizobium lupini cultivated in the conditions of different aeration, and bacteroids of this strain isolated from lupine nodules. In the anaerobic conditions, nitrate (10(-3) M) accepts electrons from the cytochrome system in suspensions of bacteroids and bacterial cells grown in the microaerophilic conditions (12 muM O2), but does not oxidize cytochromes of the cells cultivated in the aerobic conditions (240 muM 32). Nitrate (10(-3) M) oxidizes actively only the cytochrome system of the cells grown in the microaerophilic conditions. Nitrite inhibits oxygen uptake by suspension of the bacteroids and pure culture of the cells; its necessary concentrations and the mode of action depend on the conditions of cultivation. Nitrite, like cyanide, blocks the terminal step in the cytochrome chain of Rh. lupini. Some properties of the cytochrome system are similar in the bacteroids and the bacterial culture grown in the conditions of oxygen deficiency.


[Primary metabolic pathways of methylated amines in Hyphomicrobium vulgare]. As was established by isotopic and ezymatic studies, there are some common features and certain differences in primary metabolic pathways of methanol, methylamine and trimethylamine in Hyphomicrobium vulgare ZV. Assimilation of the carbon of these compounds at the level of formaldehyde through the serine cycle is in common, formaldehyde being partly oxidized to CO2. The differences are manifested in the steps of conversion of C1-substrates prior to formaldehyde formation. The carbon of methanol enters the serine cycle immediately after the oxidation to formaldehyde. In the case of methyl-amine N-methylation of glutamate firstly occurs and gamma-glutamylmethylamide and N-methylglutamate are formed. Trimethylamine is oxidized by phenazine methosulphate-linked dehydrogenase to dimethylamine and then to methylamine by NADPH-dependent mono-oxygenase. Here two formaldehyde units are liberated which enter directly the serine cycle. The third formaldehyde unit is formed from methylamine via N-methyl-glutamate pathway.


[Respiration in Thiocapsa roseopersicina cells]. Oxygen is taken up by the cells of purple sulphur bacterium Thiocapsa roseopersicina BBS grown in the light under anaerobic conditions and in the darkness under aerobic conditions. Respiration is stimulated by sulphide and thiosulphate but not by organic substrates which increase the yield of the cultures. Azide and cyanide inhibit oxygen uptake by the cells in the presence of sulphide and thiosulphate, and also utilization of these compounds. Amytal, atebrin, and rotenone inhibit oxygen uptake by the cells in the presence of sulphide but have no effect on their respiration in the presence of thiosulphate. Light produces reversible inhibiting action on respiration of the cells. Therefore, Thiocapsa roseopersicina can grow in the darkness by oxidizing sulphur compounds with the participation of oxygen.


[The fatty acid composition of total lipids and triglycerides in several actinomycetes]. Saturated and unsaturated fatty acids (C13-C18) have been found in the composition of lipids and triglycerides of actinomycetes by GLC. Qualitative composition of fatty acids was identical on chemically defined and organic media. Synthesis of unsaturated fatty acids by the actinomycetes was intensive (total yield over 50% and even 84.2% in Act. canosus) on the organic medium I which may be recommended for production of lipid fractions with elevated content of unsaturated fatty acids.


Corollary to the embolic theory of cancer dissemination. The accepted embolic theory of cancer metastasis has hitherto been taught strictly in terms of discrete deposition of tumor tissue away from the primary site. However, since metastasis is a dynamic phenomenon, discrete deposits do not remain static after their formation but grow further and coalesce either with each other or even with the primary tumor. Thus, coalesced deposits are a natural sequel to discrete deposits. Accordingly, the phenomenon of coalescence deserves the status of a corollary to the main theory of embolism.


[Changes in the concentration of extracellular products and their composition in a synchronous culture of Chlorella pyrenoidosa in the presence of light and an elevated 02 concentration]. An increase of oxygen concentration in a gaseous mixture passed through cell suspensions of Chlorella pyrenoidosa (from 21 to 100%) stimulates the production of extra-cellular organic substances and changes their composition. The cells accumulate in the medium glycolic acid rather than a variety of other substances. The accumulation of glycolic acid depends on the growth stage of the cells. The relation of production of extracellular organic substances by the algal cells to the ratio between the carboxylase and oxgenase activities of ribulose diphosphate carboxylase is discussed.


Complex tubular flow in the acutely obstructed kidney. Application of Poiseuille's Law of Laminar Flow to the renal tubules using published figures for their dimensions permits estimates of the pressure differences required to produce flow through the different types of nephron and their different segments. In the obstructive situation the pressures, flows and osmolar relationships (particularly those associated with the concentration mechanism) are greatly altered. It may be predicted that this, together with a greater osmotic leak from the distal convoluted tubules of nephrons arising from peripheral glomeruli, will lead to complex (i.e. mixed forward and retrograde) flow in the respective distal convoluted and collecting tubules. Such an hypothesis would explain some hitherto ill-understood phenomena, including resorption from the obstructed renal pelvis, some aspects of ascending renal infections, reflux nephropathy and chronic obstructive disease, and certain radiological appearances in acute ureteric obstruction in man.


Pathogenesis of sarcoidosis: an hypothetical model. An hypothetical model for the pathogenesis of sarcoidosis is presented which is compatible with its generalized nature, lack of an apparent etiologic agent and biochemical difference from other granulomas, including marked elevation of angiotensin converting enzyme. Widespread genetic alteration of epithelioid cell precursors by a virus or early precursor mutation is hypothesized to trigger transformation to epithelioid cells and the synthesis of certain proteins which may differ qualitatively from those of non-sarcoid epithelioid cells. At some point in the transformation the epithelioid cells develop an affinity for each other by altered surface properties, resulting in the widespread formation of granulomas.


[Reaction of peripheral veins and arteries following administration of beta-active agents. Studies on isoproterenol, propranolol, and practolol]. The local effect on veins and arteries of isoprenaline, propranolol and practolol was investigated in the human after intra-arterial application at the forearm. The injection of isoprenaline was followed by a dilatation of the arteries and veins. This effect was inhibited by propranolol, but not by practolol. The results demonstrate, that the peripheral vasoactive beta-stimulatory effect is mediated by so-called beta2-receptors, which were not influenced by a selective beta1-blocking agent like practolol. The results were discussed in respect to their clinical relevance.


Psychosomatic disease and the problem of causation. Despite its impressive rate of growth in the past decades, an increasing amount if dissatisfaction with the area of psychosomatic medicine is reflected in recent literature. The discipline's failures relate to concepts of pathogenesis and therapeutic application of research findings. These failures are explained as a necessary consequence of the philosophical tenet of mind-body dualism which underlies medical theory. It is urged that advocates of psychosomatic medicine give the concept of "holism" meaning at the most fundamental level by establishing a rational basis for theory, or else forsake this line of research for others which yield causal relationships conductive to effective therapy.


Two roads to coma: the Scottish hypothesis. Clinical experience seems to indicate two separate types of entry to coma. Some patients follow a pathway characterized by confusion, hallucinations, mumbling delirium, myoclonic jerks, and seizures. The author has called this sequence of symptoms the high road to coma and hypothesized that its basic underlying pathophysiology involves increased neuronal firing rates. Other patients develop somnolence, lethargy, obtundation, and unresponsiveness without seizures or muscle twitches. This low road to coma involves either anatomical compression of the midbrain reticular formation or a metabolic or toxic disorder characterized by membrane stabilization and decreased neuronal excitability.


A new model for regulation of sodium transport in high resistance epithelia. A new three barrier, four compartment model for sodium transport in high resistance urinary epithelia is presented. This model provides a unified and simplified mechanistic explanation for sodium transport and its quantitative regulation. Sodium enters the epithelial cell by passive diffusion. Active extrusion occurs across the lateral cell membrane into the lateral intercellular space (LICS). Sodium movement from the LICS into the serosal compartment is not free and unobstructed as in the models for low resistance epithelia, but rather occurs through a regulatory channel of the LICS passing through desmosomes and the basilar slit. The exact configuration of this regulatory channel controls the rate of sodium movement from the LICS into the serosal compartment. Thus, the configuration of the regulatory channel controls the afterload on the sodium pump and thus ultimately controls the rate of transepithelial sodium transport. Antidiuretic hormone could act by increasing the effective width of this regulatory channel by contraction of intracellular microtubules or microfilaments. Present theories for regulation of transepithelial sodium transport in high resistance epithelia invoke a regulatory barrier at the apical cell membrane or at the active sodium pump located in the basolateral cell membrane. The hypothetical model presented here invokes a new alternative: regulation of the active pump rate by the sodium concentration in the LICS serving as an afterload on the pump; sodium escape from the LICS into the serosal compartment thus becomes the regulatory step for transepithelial transport.


A vibrational model of the excitable membrane. A hypothesis is proposed which attributes the dynamic behaviour of the excitable biological membrane to postulated thermal vibrations of polar molecules in the membrane. It is suggested that these vibrations constitute the physical pumping mechanism for active transport and are also the seat of excitability. To illustrate the latter property the construction of a working mechanical model of coupled oscillators is described producing impulses which resemble the behaviour of the nerve impulse in all major aspects. A reinterpretation of this and some other prominent properties of the membrane is attempted in the light of the hypothesis.


The genetic instabilities of the mating type locus in fission yeast. Certain genetic instabilities of the "mating type locus" in the yeast Schizosaccharomyces pombe are interpreted in terms of transposition: Homothallic strains are characterized by two adjacent mating type genes (mat1-mat2+) with sexually complementary functions. One of these genes (mat2+) is able to duplicate itself, and the duplicated copy maps at the position of mat1-. The former function of mat1-is lost (owing to insertion), and only becomes reactivated when the inserted sequence (mat1+) is again excised. Analyses of analogous instabilities expressed by the partially defective mutation mat2+ -B102 have substantiated this transposition scheme. Homothallism is acribed to alternate and mutually exclusive activation of mat1- or mat2+ genes.


Inactivation of catalase by near ultraviolet light and tryptophan photoproducts. Certain ocular proteins have been found to be chemically modified by exposure to near-UV light (320-390 nm) in the presence of tryptophan. Colored and fluorescent tryptophan photoproducts bind firmly to proteins, thereby altering their physico-chemical properties. The question of whether such a reaction would inhibit the catalytic action of catalase is herein raised. When solutions of bovine liver catalase were re-incubated up to 24 hr under near-UV with preirradiated tryptophan and dialyzed, most of the ability of the enzyme to decompose H2O2 was lost. Similar results occurred for catalase activities of bovine cornea and lens epithelia. The enzyme protein exhibited altered UV absorption and fluorescence spectra and increased electrophoretic mobility after binding photoproducts, Near-UV light photoproducts of tryptophan are thus capable of deactivating crystalline and tissue catalase.


Chemical modifications of histidine residues in cytoplasmic asparate aminotransferase from beef kidney. Holo and apoenzyme of aspartate aminotransferase from beef kidney are 80% inactivated by photoxidation in the presence of 2 X 10(-6) M tetraiodofluroescein with the modification of two histidine residues per enzyme protomer. At a higher concentration (1 X 10(-5) M) a tyrosine residue is also modified. The keto substrates, ketoglutarate and oxalacetate, protect the enzyme from photoxidation. Diethylpyrocarbonate modifies three histidine residues per enzyme protomer and reduces the activity only 10%. These results suggest that the two histidine residues photoxidized through the sensitizer, are located in the active site of the enzyme, at least one of these appears to be involved in ketosubstrate binding. The other three histidines modified by diethylpyrocarbonate are likely located on the enzyme surface and are not involved in the catalytic activity of the enzyme.


Properties of chloroplasts isolated by phase partition. Chloroplasts from spinach can be separated into at least three different populations by countercurrent distribution using polymer two-phase systems. The chloroplast particles of the three populations differ in protein/chlorophyll ratio, ultrastructure and metabolism. One population, peak I, consists of intact chloroplasts surrounded by the chloroplast envelope; the second population, peak II, consists of chloroplasts, which have lost their envelopes and much of their stromal material; the third population, peak III, consists of particles containing intact chloroplasts surrounded by a membrane-bound cytoplasmic layer including mitochondria and peroxisomes. Rapid batch procedures of peak I chloroplasts incorporated 14C almost entirely into glycolate and intermediates of the Calvin cycle and starch synthesis. Only small amounts were found in sucrose and amino acids. On the other hand preparations of peak III chloroplasts have a much broader spectrum of 14C-labelled products. Sucrose, malate and some amino acids contained about 40% of the 14C incorporated. It is concluded from these experiments that sucrose is formed not within the chloroplast but in the cytoplasm from intermediates exported by the chloroplast. The origin of peak III particles and their use for studying the cooperation between the chloroplast and the surrounding cytoplasm including mitochondria and peroxisomes is discussed.


Thymidine kinase, DNA synthesis and cancer. A resume has been presented of some recent investigations which show that DNA synthesis can be initiated in many types of quiescent animal cells by external stimuli, by introducing a quiescent nucleus into the cytoplasm of a proliferating cell, or by a virus infection. The components of the DNA replication apparatus are described. It is shown that deoxyribonucleoside triphosphate pools increase substantially in animal cells at the time DNA synthesis is initiated due to the enhanced activities of enzymes functioning in nucleotide synthesis. Especially striking is the increase of thymidine kinase activity, indicating that this enzyme may be a useful marker of the shift from the quiescent to the replicative state. The thymidine kinase isozymes of vertebrate cells have been characterized. Thymidine kinase F, which is found principally in the cytosol, is the isozyme that increases when G1 (Go) phase cells are stimulated or infected with oncogenic viruses. Chick cytosol thymidine kinase F can also be reactivated by introducing differentiated chick erythrocyte nuclei into the cytoplasm of enzyme-deficient LM (TK-) mouse cells. Furthermore, herpesviruses code for distinctive, virus-specific thymidine kinase isozymes, so that another way to transform thymidine kinase-deficient LM TK-) cells to kinase-positive cells is by infecting them with UV-irradiated herpes simplex viruses. The experiments on the activation of DNA synthesis and thymidine kinase F activity have been discussed in the context of the proliferative activity in vivo and the immortalization in culture of neoplastic cells. These experiments suggest that genes determining cell cycle proteins are readily accessible to transcription and translation in essentially all nucleated cells. The tendency of transformed cells to become multinucleated after cytochaliasin B treatment also suggests that one important difference between malignant cells and most normal cells may be the ability of malignant cells to 'stockpile' the proteins (and/or their messenger RNAs) of the DNA replicative apparatus and to maintain the 'stockpiles' in progeny cells.


[The effect of the concentration and nature of 1-1-valent electrolytes on acid-base equilibrium in solutions of DNA]. The effect of concentration of LiCl, NaCl, KCl and NH4Cl on the potentiometric titration curves of chicken erythrocyte DNA has been studied. Two inflections have been found in the titration curves at pH 5 and pH 8, respectively. The ionization constant corresponding to the second inflection is slightly increased when the concentrations of NaCl, KCl and NH4Cl are increased. Both constants are increased when the concentration of LiCl is increased. It has also been found that the addition of LiCl to the DNA solution lowers the pH of the solution but the addition of the other investigated salts causes an increase of the pH of DNA solutions. The results found are used for discussion of the nature of acid groups of DNA.


[Aggregation of 4-vinyl-protochlerophyll and protochlorophyll in solutions]. The addition of water to dioxane solution of protochlorophyll (PChl) and 4-vinyl-protochlorophyll (4VPChl) results in a number of transformations related with pigment molecule associations into polymer formations and with their conversion. By variation of pigment concentration and composition of binar mixture of solvents a set of aggregated forms with different electronic spectra can be obtained. At the first stage the monomeric pigment converts into polymer with long-wavelenght absorption maximum of 633 nm (P633). During 1-3 hours P633 converts into other aggregated forms: either P639 or P645 depending on the proportion of dioxane and water. The pigment aggregates are characterized by fluorescence (quantum yield less than or equal to 1%) with maxima close to the main maxima of absorption spectra. Alongside with the main aggregated forms of PChl and 4VPChl the presence of a small number of longer-wavelength aggregates in solutions is established by fluorescence spectra. The investigation of dependence of fluorescence spectra on excitation wavelength, as well as of fluorescence excitation spectra of pigments in binary mixture shows that the long-wavelength aggregates can form part of complex associate and be effective trapping centres of electronic excitation of shorter wavelength aggregated forms. The phenomenon of 4VPChl association in concentrated solutions of castor oil (c greater than-10(-2) m/l) is discovered, which is especially marked after a long storage of the solutions at lower temperature (t=-2 degrees C). Under these conditions the two aggregated forms P640 and P650 alongside with monomer are present. The aggregate P650 is characterized by fluorescence with maximum of 655 nm and spectrally similar to the natural form of photoactive protochlorophyll. The experimental data show that the protochlorophyll pigments form a set of aggregated forms and that the medium conditions favour the predominance of some of the forms and their interconversion. The results obtained evidence that the main reason of the long-wavelength shift of electronic spectra for PChl natural forms is the intermolecular interaction related with the association of pigment monomeric molecules.


[The compact form of DNA in solution. V. The heat effect preceding compactization of double-chained DNA in PEG containing water-salt solutions]. DNA-dependent heat effects accompanying mixing of water-salt (0.3 M NaCl) solutions of PEG and DNA within the range of PEG 10-50 mg/ml at 25 degrees C were determined by the method of difference microcalorimetry. It was found that, unlike optical and hydrodynamical methods, microcalorimetry makes it possible to detect some changes of the DNA-PEG system preceding formation of compact particles of DNA. In the studied range of DNA concentrations (up to 50 X 10(-3) MG/ML) the specific DNA-dependent heat effect is essentially independent of DNA concentration. It is negative and its absolute value increases from 0 to 5 cal/g of DNA in the PEG concentration range from 0 to 35-40 mg/ml after that the rate of its increase raises greatly and at PEG concentration of 50 mg/ml it is equal to 35 cal/g of DNA. It is suggested that the studied DNA dependent heat effects at low concentrations of PEG (less than 40 mg/ml) are caused by dehydration of DNA preceding its compactization.


[Primary photoprocesses in light chloroplast fragments]. An attempt has been made to study the mechanism of photoinduced separation of charges and their recombination in reaction centres of the photosystem 1 of the light fragments of chloroplasts. It has been shown, in agreement with recent papers, that the studied properties of electron donor of the photosystem 1 correspond to P700 pigment (with absorption maxima at 430 and 700 nm), the properties of electron acceptor correspond to that of ferredoxin type compound (P430) (with absorption maxima at 420, 444 and 717 nm) and heat stable compound (Px). Accumulation of the charges both for P700+-P430 and P700-P430- has been accompanied by increase of the fluorescence yield and shift of chlorophyll absorption band from 680 nm to approximately 690 nm. The recombination process of P700+ and P430- has been accompanied by the delayed luminescence. The study of kinetics of interaction between chlorophyll excited states and reaction centres and also kinetics of charge recombination and luminescence decay has shown that the primary photoprocesses in the photosystem 1 occur with interaction of several (greater than 3) centres of charge separation (P700-P430).


[Specific chemical modification of ribosomes in the vicinity of their mRNA-binding center]. 4-N-2-chloroethyl-N-methylamino-benzaldehyde acetal derivatives (RCL-derivatives) of octauridylic and nanauridylic acids were used to localize the structures organizing mRNA-binding site of ribosomes. These derivatives, like free oligonucleotides, stimulate binding of 14C-phenylalanyl-tRNA to ribosomes. They effectively alkylate ribosomes within the specific complex. The extent of 30S subunit alkylations is much greater than that of 50S subunit, alkylation being completely inhibited by preincubation with polyridylic acid, suggesting that the chemical alteration occurs near mRNA-binding site. Both rRNA and proteins undergo modification in 30S subunit (75% and 25% of the total 30S subunit modification, respectively).


[The secondary structure of amides of adenylic acid containing D- and L-aromatic amino acids]. Adenylyl-(5'leads to N)-amino acids containing as amino components, methyl esters of D-, L- and DL-phenylalanine, D-, L- and DL-tyrosine, and D-, L- and DL-tryptophan have been investigated by proton magnetic resonance (PMR) spectroscopy and circular dichroism (CD). The temperature and pD dependences of proton chemical shifts of these compounds have been studied. These data, together with the magnitudes of the upfield chemical shifts of the PMR signals of adenine and aromatic amino acids residues in adenylyl-(5'leads to N)-amino acids, have enabled us to construct conformational models of these compounds. The proposed conformation has been substantiated by the CD results. It is shown that in adenylyl-(5'leads to N)-amino acids the planes of adenine and amino acid aromatic moieties are roughly parallel. The aromatic rings of phenylalanine and tyrosine are localized approximately above the centre of adenine. In adenylyl-(5'leads to N)-D, -(L)-tryptophan, the six-membered rings of the indole overlaps the five-membraned ring of adenine indole partially overlaps the six-membered ring of adenine. A difference in the non-covalent interactions of D- and L-amino acids with nucleotides has been revealed. The mutual localization of the aromatic systems of AMP and the amino acids and also the positions of -OCH3 group with respect to the centre of the amino acid aromatic moiety differs in the series of the studied nucleotide derivatives of D- and L-amino acids.


[A theoretical analysis of the binding of methyl derivatives of uracil at the contact portion of the active center of ribonuclease S]. In terms of the mechanical model of molecules, a calculation has been carried out of possible positions and binding energies of 1-methyl uracyl in the contact region of the ribonuclease S active site. In the most preferential orientation, 1-methyl uracyl forms hydrogen bonds C(2)=O(uracyl)...H-N(Thr-45), N-H...Ogamma (Thr-45), C(4)=O... ...H-Ogamma (Ser-123). The base position found (atom coordinates are given) is in complete qualitative agreement with the position of the uracyl in UpcA bound to ribonuclease S as revealed by X-ray analysis. The influence studied of methyl substitution in positions 3 and 5 of the pyrimidine cycle on the base orientation within the protein field. It has been shown that the formation of hydrogen bonds with Thr-45 and Ser-123 is not prerequisite for productive fixation of the phosphoribosyl nucleotide moiety in the catalytic region of the enzyme active site.


[Detection and several characteristics of leach genome palindromes]. About 5% of the loach (Misgurnus fossillis L.) DNA reassociates at Cot values virtually equal to zero. 50% of the reassociate are resistant to nuclease S1 treatment and reveal the properties of double-stranded structure when chromatographed on hydroxyapatite. Some proofs of palindromic (hair-pin) nature of this fraction have been obtained. An introduction of nicked scissions into the palindromic DNA by pancreatic DNAse treatment under pessimal conditions made it possible to investigated reassociation kinetics of the nucleotide sequences forming palindromes. Two different types of nucleotide sequences appeared to exist in the palindromic fraction with repetition frequencies (ni) equal to 3 X 10(2) and about 1. Homologies were revealed between these sequences and the fraction of corresponding repetition frequency of the main part of the genome. Adjacent sequences contain repetitive regions with ni equal to 10(5) and 5 X 10(3). On the basis of the data obtained some conclusions were made about the distribution of usual and inverted repetitions in the loach genome.


[Hypoglycaemia in neonates following exchange transfusion (author's transl)]. In 30 newborns the blood sugar level was determined before and after exchange transfusion. At the end of exchange transfusion, the blood sugar reached in each case 200 mg-% or more, but with in one hour fell back to the starting level. If the patient did not get an adequate quantity of sugar during that time, hypoglycaemia developed. It is known, that patients with severe haemolytic disease have hyperinsulinism, but we investigated only such patients, who were born with Hgfv levels above 10 g-%. Therefore, it seems, that the hypoglycaemia in those cases is not due to the haemolytic disease, but a reaction to the sugar, given with the ACD blood.


[Possibilities for a reduction of long-term steroid treatment in asthmatic children during a stay in northsea climate (author's transl)]. 1. 40 children with Asthma bronchiale under long-term Cortisone therapy were admitted as in-patients of a clinic in the climate of the Northsea. 37 children needed Cortisone therapy because of serious attacks of Asthma bronchiale, and 3 children because of disturbing neurodermitis constitutionalis. -- 2. Corticoids were discontinued abruptly, immediately after admission. a) In 34 children the discontinuation had no adverse effect the following 6 to 8 weeks, or even longer, there was no need for Cortisone therapy. b) In 4 children during the first 2 weeks and in 2 further children during the 5th or 6th week, the asthmatic disorder deteriorated to such a degree that Cortisone therapy had to be re-introduced. -- 3. On the base of the reported observation, it is concluded that under the conditions of the Northsea climate it is of advantage for children with Asthma bronchiale and Neurodermitis to discontinue abruptly Cortisone therapy because a) this type of therapy which involves the potential risk of unwanted side effects can be shortened and b) the specific positive effect of climatic changes during the first couple of weeks is utilized to a greater extent. The gradual reduction of steroid therapy would diminish this particular stimulation. However, this kind of treatment requires close clinical observation to anticipate an acute "Addison-Crises". -- 4. All children with serious dispuce already during the first days of their stay in the clinic clearly need continuation of steroid therapy. -- Otherwise, even previous steroid therapy for more than one year is no contradiction for the recommended procedure as long as the clinical condition of the patient allows for it.


[Intracellular distribution of RNA in Acetabularia mediterranea]. RNA synthesis and distribution in cytoplasm of Acetabularia mediterranea cell were studied by radiochemical and ultramicrobiochemical methods. Existance of an apico-basal gradient of RNA concentration in the cytoplasm was shown. Variations in the rate of the RNA synthesis in different regions of the cytoplasm are of great importance for the formation of this gradient whereas a contribution of nuclear RNA transport is insignificant. Sedimentation coefficients of about 23S and 16S were detected for the most part of the synthesized cytoplasmic RNAs. Evidently these RNAs represent rRNA of chloroplast ribosomes. Basal region of cytoplasm contains a relatively large amount of low molecular weight RNA. The differences in stability of newly-synthesized RNA were found in cytoplasmic regions under examination.


[The principle of instantaneous action in photosynthesis]. The principle of instant action for photosynthesis is grounded. According to this principle, all primary photophysical events of energy delivery from light harvesting Chl molecules to reaction centres proceed at time intervals not exceeding critical value approximating 10(-10) seconds. This provides: a) high quantum yield (more then 90%) of primary photosynthesis: b) Chl protection from irreversible photodestruction. Original experimental data obtained by V.I. Godik and the author support the above principle at least for purple bacteria, green bacteria and photosystem I of plants.


[The mechanism of the reaction forming tryptophanyl-tRNA, catalyzed by tryptophan:tRNA-ligase]. The rates of tryptophanyl-tRNA formation catalyzed by beef pancreas tryptophanyl-tRNA synthetase were measured in a concentration range of each substrate (tryptophan, ATP and yeast tRNATrp) and also in the presence of various concentrations of substrate analogues (tryptamine and alpha,beta-methylene analogue of ATP) concentrations. The data obtained were compared with the kinetic equations which described various possible mechanisms of the reaction. The comparison of the mechanisms was based on the calculation of relative probabilities of each hypothesis the efficiency of which was demonstrated earlier. The calculations have shown that two mechanisms according to which the intermediate enzyme-aminoacyl-adenylate complex formation involves the enzyme-aminoacyl-tRNA complex are the most probable ones.


[The structure of microtubules].

[The structure of microtubules]. Cytoplasmic microtubules, plane monolayers of tubulin filaments and single filaments have been investigated by electron microscopy. The methods of optical diffraction, filtering and three-dimensional reconstruction have been used to analyse the micrographs and to construct a model of the dimeric molecule of tubulin. When viewed in the direction perpendicular to the longitudinal axes the molecule bear resemblance to the figure "8". When rotated by 90 degrees it looks as if composed of two globules. Two variants of the quoternary structure are considered: 1) each of two subunits is a deformed ring; 2) each rings of the "8"-like particles consists of two halves of different subunits. The second protein layer which is formed on microtubules in the presence of protamine consists of tubulin and is characterized by the crystal lattice similar to that of the microtubule itself, but rotated through the angle of about 95 degrees. In the presence of protamine we also detected flat spirals and stacks of such spirals forming short tubules.


[Light and electron-cytochemical analysis of acetylcholin-positive esterase-structures in the area postrema and subpostrema in rats]. Localization of acetylcholinesterase (AChE) in the area postrema and area subpostrema of the rat was investigated by light- and electronmicroscopic histochemical methods. AChE-positive small cells probably identical with parenchyma cells are spread evenly in the area postrema. Since axosomatic synapses and axons could not be identified, the neuronal character of these cells could not be unequivocally proved. AChE-positive suggests, however that the parenchyma cells of the area postrema of the rat are more closely related to neurons than to glial cells.  Capillaries possessing fenestrated endothelium of the area postrema and various types of glial cells do not exert any AChE-positivity. The area postrema is surrounded by a meshwork of AChE-positive capillaries, constituting the area subpostrema. Since we found no signs of AChE synthesis in the endothelial cells of these capillaries, the possibility of dendritic secretion as the source of AChE activity of the basement membrane and pinocytotic vesicles, cannot be excluded. On the basis of the results it seems possible that the AChE activity is related to the specific structure of the basement membrane; participation of enzyme activity in the presumed function of the area postrema and area subpostrema is suggested.


[Effect of dextran of 250.000 molecular weight on experimental cholesterin-sclerosis in rabbits]. Effect of dextran of 250000 molecular weight on experimental cholesterin-sclerosis of rabbits was studied. Doses of 120 (mg/week) kg and 1200 (mg/week) kg administered during 12 weeks have resulted a protective effect. When doses of 1200 (mg/week) kg have been administered--in the aortic adventitia intensive cellular reaction, no hitherto described was revealed, which was considered to be a sing of the exhaustion of RES. This publication authors regard as a preliminary one. To clear whether the cellular reaction observed is a dextran-specific or macro-moleculespecific one further investigations are needed.


[Foreign body causing coronary artery occlusion]. Authors in the descending branch of the left coronary at the autopsy of a 45 years old male--as an incidental finding--have found a foreign-body (sewing needle). Occlusion of the coronary was followed by necrosis and fibrosis of the myocard. During one year no clinical symptoms of myocard lesion were observed.


[Experimental study of the heaptotoxic effect of toluol III. Quantitative morphological study]. Hepatotoxic effect of the analitically pure toluene used in the Chemical Factory "Tiszai" was investigated by the aid of quantitative morphological method on male rats of line CFY. Toluene was administered intraperitoneally and subcutaneously. It was established, that there exists a nearly lineal correlation between the logarithms of intraperitoneally administered doses of toluene, the number and area of mitochondria localized in the unite area of the hepatocyte, and between the increase of number of matrix-granules in the mitochondria. The average-area of the mitochondria remained unchanged. As an effect of large intraperitoneal doses of toluene increase of the density of nuclei and the nucleus-plasma proportion could be revealed. There exists a nearly lineal correlation between the logarithms of intraperitoneal and subcutaneous doses of toluene and the decrease of volume of the cell nuclei. Statistical curves of the nuclei-variation-study as an effect of large doses show two peaks. Authors stress the importance of quantitative morphological studies in the toxicology. Results of such investigations should be evaluated in connection with each other.


[Misleading self-inflicted gunshot wound]. One deceiving case of suicide with firearm is reported. In the heart area three entrance-wound were seen. At first sight these were the injuries to account for the death. At the autopsy in the mouth another entrancewound was, found. The death occurred due to gunshot into the mouth.


[Non-specific dye absorption studies in quantitative cytochemical reactions with alkalic fast green and heparin-alcian blue (model experiment)]. Stöchiometria of the alkalic Fast green and Heparin-alcianblue was studied in model experiment by the aid of integrating microdensitometer. The changes of the optical density in cases of Heparin-alcian-blue occurred to be proportional to the histon quantity, in cases of staining with alkalic Fast green nonspecific dye-absorption was revealed. Results of the model experiment indicate that in quantitative cytochemical studies Heparin-alcian-blue should be preferred to alkalic Fast green.


[Unusual cases of adolescent suicide].

[Unusual cases of adolescent suicide]. Two cases of hanging--boys of 11 and 14 years of age--are described. Investigation of the cases have thrown light on the antecedents. The first case was really suicide, but the second one was an accident. The young boy intended to "stretch" himself out, since he was short. He had tied the rope around his neck and the other end of it around the door-handle. Accidentally he strangulated himself. In connection with these cases author stresses the role of physicians in prevention of suicide and attempted suicide in youth.


[A case of lupus pancreatitis (?) in systemic lupus erythematosus]. The cause of death of a 52 year old female suffering from disseminated lupus erythematosus was acute (steroide-induced?) pancreatitis. Histologically in the pancreas spontan nucleophagocytosis, leukophagocytosis, erythrophagocytosis, presence of haemtoxylin-body-like structures could be revealed by HE, methyl-green-pyronin staining and by Feulgen reaction.


Jamaican vomiting sickness. Biochemical investigation of two cases. We identified methylenecyclopropylacetic acid, a known metabolite of hypoglycin A, in the urine of two patients with Jamaican vomiting sickness. Excretion of unusual dicarboxylic acids such as 2-ethylmalonic, 2-methylsuccinic, glutaric, adipic and dicarboxylic acids with eight and 10 carbon chains were also detected in both patients. The amounts of these dicarboxylic acids were 70 to 1000 times higher than normal. These metabolites have also been identified in urine of hypoglycin-treated rats. This evidence links hypoglycin A to Jamaican vomiting sickness as its causative agent. Urinary excretion of short-chain fatty acids was also increased up to 300 times higher than normal. These results indicate that, despite their clinical and histologic similarities, the cause and biochemical mechanisms of Jamaican vomiting sickness differ distinctly from those of Reye's syndrome in which these abnormal urinary metabolites are not appreciably increased.


The histologic spectrum of Barrett's esophagus. To define the histology of the columnarlined esophagus, we obtained esophageal biopsies from various levels with manometric control from 11 patients. There were three types of columnar epithelia above the lower esophageal sphincter: atrophic gastric-fundic-type epithelium with parietal and chief cells; junctional-type epithelium with cardiac mucous glands; and distinctive specialized columnar epithelium with a villiform surface, mucous glands and intestinal-type goblet cells. When present, specialized columnar epithelium was always the most proximal, and gastric fundic epithelium the most distal epithelium. Junctional epithelium was interposed between gastric fundic and specialized columnar or squamous epithelium. Four patients had unequivocal esophagitis in squamous epithelium, but its presence and severity did not correlate with inflammation in or length or type of distal columnar epithelium. Histoligic study of the columnar-lined esophagus demonstrated a spectrum of epithelial patterns. This heterogeneity helps to explain prior discrepant reports.


Stimulation of sympathetic cardiovascular centres by RA 642, a new pyrimido-pyrimidine derivative. RA 642, 2,2'-[14,8-bis(diethylamino)-pyrimido[5,4-d] pyrimidine-2,6-diyl)di-(2-methoxyethyl)-imino]diethanol, has formerly been described to hypertensive when administered systemically. In the present experiments injection of 50 mug/kg RA 642 into the vertebral artery (i.a. vert.) of the cat exerted hypertension, while the same dose given intravenously (i.v.) elicited no effect. Since the drug was still effective in cats of which the brain was removed rostrad of the myelencephalon but not in spinal animals, its site of action was concluded to be in cardiovascular centres of the medulla oblongata. An i.a. vert. injection increased total peripheral resistance of the vasculature. The electrical discharge rate in preganglionic cervical sympathetic nerve fibres increased in parallel to the arterial blood pressure following the i.v. injection of 1 mg/kg of the substance. 1 mg/kg RA 642 i.v. decreased the reflex bradycardia elicited by the i.v. injection of angiotensin in dogs pretreated with a beta-adrenoceptor blocking drug to study the vagal effector reactions of the baroreceptor reflex, and treated with clonidine to facilitate the reflex. Thus, RA 642 increased sympathetic and, following clonidine treatment, decreased vagal reflex activity. RA 642 stimulated the respiration by a central action. The drug had no convulsant action.


Responsiveness of isolated canine cerebral and peripheral arteries to ergotamine. Changes in tension of spiral strips from dog saphenous, external carotid and basilar arteries were monitored isometrically. Serotonin (5-HT) contracted the 3 arterial preparations in about the same concentration range. Compared with noradrenaline (NA) (100%) the efficacy of 5-HT was about 60% on saphenous, 150% on external carotid and about 500% on basilar arteries. Ergotamine (E) stimulated the 3 vascular preparations in concentrations about 100 times lower than 5-HT. Compared with NA the efficacy of E was about 20% on saphenous, 50% on external carotid and 200% on basilar arteries. Compared with 5-HT (100%) however, E had similar constrictor activities in the 3 arteries. It seemed likely therefore that 5-HT receptors are involved in the vasoconstrictor activity of E. Evidence for this was obtained in experiments in which cyproheptadine (Cy), a 5-HT antagonist, was used. For antagonism of E concentrations of Cy about 6 times higher than those required to inhibit 5-HT were necessary, whereas for antagonism of NA about 500 times higher Cy concentrations were necessary. The results suggest that on canine arterial vascular smooth muscle the constrictor activity of E is mediated mainly through serotoninergic receptor sites.


Recovery of dopamine in peripheral adrenergic nerves after reserpine treatment. The endogenous levels of dopamine (DA) in the rat heart and submaxillary gland after a single, large dose of reserpine (10 mg/kg i.p.) were reduced to near zero within 1 h and were restored to normal within 48 h, while the noradrenaline (NA) levels reacted much more slowly. The data suggest that newly formed DA is rapidly taken up by the reserpinesensitive mechanism of the amine storage granules. The more rapid restoration of DA than of NA levels may be due to preferential release of newly formed NA by the nerve impulse. Electrical stimulation of the cervical sympathetic with 5 Hz for 30 min 4 h after the administration of reserpine increased the DA level of the submaxillary gland of the stimulated side, suggesting an increased tyrosine hydroxylase activity during stimulation, also in nerve terminals affected by reserpine. The use of an inhibitor of monoamine oxidase (pargyline) and/or an inhibitor of dopamine beta-hydroxylase (FLA-63) did not significantly alter the increase of DA following nerve stimulation, suggesting DA was protected by granular uptake. The stimulation-induced increase in DA was, however, much less in reserpine-treated than in normal animals, demonstrating the importance of the reserpine-sensitive uptake mechanisms for preserving newly formed DA.


Inhibition of receptor-mediated noradrenaline release from the sympathetic nerves of the isolated rabbit heart by anaesthetics and alcohols in proportion to their hydrophobic property. The actions of anaesthetics (diethyl ether, enflurane, chloroform, methoxyflurane) and alcohols (ethanol, 1-propanol, 1-butanol, 1-pentanol) on the noradrenaline release from (and uptake into) the sympathetic nerve terminals were studied in isolated rabbit hearts perfused with Tyrode solution at constant flow rate. The noradrenaline in the perfusate was assayed spectrofluorimetrically. 1. Ethaonol, 1-propanol, 1-butanol and all anaesthetics (at concentrations which decreased by more than 65% the noradrenaline output in response to activation of the nicotinic receptors) did not significantly affect the spontaneous noradrenaline output. Only 1-pentanol (3.75 X 10(-3) M) caused an increase in spontaneous noradrenaline output. 2. The uptake of exogenous noradrenaline from the perfusion fluid into the sympathetic nerve terminals was not influenced by the anaesthetics and alcohols (at concentrations which decreased by more than 65% the noradrenaline output evoked by stimulation of the nicotinic receptors). 3. All anaesthetics and alcohols caused a concentration-dependent inhibition of the noradrenaline release in response to activation of the nicotinic receptors on the nerve terminals by 1,1-dimethyl-4-phenylpiperazine or acetylcholine in the presence of atropine. The concentrations of the compounds which decreased the noradrenaline output by 50% were as follows: diethyl ether: 5.1 X 10(-3) M; enflurane: 2.9 X 10(-4) M; chloroform: 2.6 X 10(-4) M; methoxyflurane: 3.8 X 10(-5) M; ethanol: 1.5 X 10(-1) M; 1-propanol: 1.9 X 10(-2) M; 1-butanol: 6.0 X 10(-3) M; 1-pentanol: 1.2 X 10(-3) M.


Membrane SH-groups related to adrenaline action in rat adipocytes: a comparative study using sulfhydryl reagents of different molecular size. The orientation of SH-groups within the fat cell membrane involved in adrenaline (and NaF) action was studied by comparing the effects of uncoupled p-CMB with those of a large derivative of this reagent -- p-CMB-dextran --. Preincubation of intact adipocytes with uncoupled p-CMB caused a dose-dependent inhibition of adrenaline (and NaF) stimulated adenylate cyclase activity as determined in ghosts prepared subsequently. Preincubation with p-CMB-dextran, however, influenced neither the lipolytic response to adrenaline nor the catecholamine (and NaF) activated adenylate cyclase activity. When p-CMB-dextran was present during ghost preparation, a dose-dependent inhibition of adrenaline (and NaF) stimulated adenylate cyclase activity was observed. These results suggest that the binding sites of adrenaline as well as SH-groups essential for activity of adenylate cyclase are not localized near enough to the exterior surface to be accessible for p-CMB-dextran. The polarity in the sensitivity of fat cell adenylate cyclase could not be observed when p-CMB-dextran was added directly to intact or fragmented ghosts. The abbreviations used are: Cyclic AMP, cyclic adenosine 3',5'-monophosphate; p-CMB, p-chloromercuribenzoate.


RA 642, a pyrimido-pyrimidine-derivative with vasodilating and hypertensive potency. 2,2'-[(4,8-bis(diethylamino)-pyrimido[5,4-d]-pyrimidine-2,6-diyl)di-(2-methoxyethyl)imino]diethanol), RA 642, combines hypertensive and vasodilating effects. In anaesthetized animals arterial blood pressure was increased by i.v. doses of 0.25-4 mg/kg in cats and 0.025-0.25 mg/kg in dogs. In conscious dogs, 25 mm increase of mean blood pressure was achieved with 0.2 mg/kg i.v. and 18.8 mg/kg p.o. Cerebral blood flow was enhanced and calculated cerebral vascular resistance was reduced by RA 642. Total peripheral resistance was diminished by 0.25-1.0 mg/kg i.v. A vasodilatation of femoral and coronary vessels was shown after intraarterial injection. This effect as well as a BaCl2-antagonism in the isolation ileum is explained by a papaverine-like relaxant effect on smooth muscle. Activity on peripheral adrenergic receptors was excluded. Hypertension was abolished in spinalized cats, indicating a central mechanism of this effect.


The distribution of 3H-(+/-)noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes. Rabbit aortic strips (nerve-free, reserpine-pretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) were exposed to 1.18 muM 3H-(+/-)noradrenaline for 30 min (in most experiments). At the end of the incubation some strips were used for analysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 240 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. 1. Extracellular amine distributes into "compartment I + II" (characterized by a half time for efflux of less than 1 min); compartment size and half time for efflux were similar to those obtained for 14C-sorbitol. 2. The extraneuronal accumulation of noradrenaline is a quickly equilibrating process which involves compartments III and IV (with half times for efflux of 3 and 11 min, respectively). Compartment IV represents not only extraneuronally but also neuronally distributed noradrenaline (see below, 4). 3. The neuronal accumulation of noradrenaline is a slowly equilibrating process which can be subdivided into axoplasmic and vesicular accumulation. 4. The axoplasmic accumulation of noradrenaline is associated with compartments IV and V (the latter characterized by a half time for efflux of 95 min). The half time of the efflux from compartment V was independent of the original filling of this compartment (the degree of filling having been varied by changes in the duration and the amine concentration of the incubation). 5. The vesicular accumulation of noradrenaline resulted in the appearance of a "bound fraction" (i.e., of amine not participating in the efflux determined during 240 min of wash out) and in an increase in the half time of the efflux from compartment V. 6. The results support the view that the rate of relaxation (of strips initially exposed to noradrenaline and then washed out) is affected by the efflux of unchanged amine from extraneuronal and neuronal stores.


Stereoselectivity of the distribution of labelled noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes. Rabbit aortic strips (nerve-free, reserpine-pretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1mM U-0521) were exposed to 1.18 muM labelled (-)- or (+)noradrenaline for 30 min. At the end of the incubation period some strips were used for analysis of radioactive (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 250 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves. 1. The mechanisms responsible for the accumulation of radioactivity in extraneuronal and axoplasmic compartments lack stereoselectivity; the rate constants for the efflux of radioactivity from these compartments are the same for (-)- and (+)noradrenaline. 2. The accumulation of radioactivity in storage vesicles is stereospecific with preference for the (-)isomer. 3. Despite the use of enzyme inhibitors, the "late neuronal efflux" of radioactivity (i.e., the efflux collected between the 200th and 250th min of wash out) contained a considerable proportion of metabolites of noradrenaline. The metabolism of noradrenaline was stereoselective: while dihydroxyphenylglycol (DOPEG) was the predominant metabolite in the efflux from strips incubated with (-)noradrenaline, a considerable part of the efflux from strips incubated with the (+) isomer consisted of dihydroxymandelic acid and "O-methylated and deaminated" metabolites (in addition to DOPEG).


The effect of cocaine on the distribution of labelled noradrenaline in rabbit aortic strips and on efflux of radioactivity from the strips. Reserpine-pretreated or normal rabbit aortic strips (whose noradrenaline-metabolizing enzymes were inhibited by treatment with 0.5 mM pargyline and by the presence of 0.1 mM U-0521) were incubated with 1.18 muM labelled noradrenaline for 30 min. Subsequently, strips were either analysed or washed out with amine-free solution for 240 to 250 min. From the efflux curves the original distribution of radioactivity was estimated by compartmental analysis. 1. The accumulation of radioactivity in the strips was reduced by 30 muM cocaine to that observed for nerve-free strips. In reserpine-pretreated strips this was due to a partial reduction of the filling of comartment IV (characterized by a half time of efflux of 10 to 20 min; earlier evidence had already shown that part of this compartment is of neuronal origin; Hensling et al., 1976) and a pronounced decrease of the filling of compartment V (characterized by the longest half time). In normal strips the same changes were observed as well as pronounced reduction of the "bound fraction". Thus, cocaine reduced the filing of those compartments which had been identified as neuronal ones (Henseling et al., 1976). 2. When 30 muM cocaine was added to the wash out solution only, the neuronal efflux of radioactivity from reserpine-pretreated strips was accelerated, while the efflux from extraneuronal or extracellular compartments remained unaffected. This effect of cocaine was the same for (-)- and (+)noradrenaline, and its was not significaltly decreased when paired strips exposed to an inhibitor of extraneuronal uptake (86 muM corticosterone) throughout the experiment. In normal strips, cocaine had very little or no effect on the efflux of radioactivity. 3. The results are consistent with the view that cocaine impairs the influx of amine into the neurone, while block of re-uptake of unchanged amine is one of the determinants of its effect on the rate of efflux from the axoplasm. Comparison of efflux curves with corresponding relaxation curves (determined in the absence and presence of cocaine) indicates that, when both noradrenaline-metabolizing enzymes are inhibited, relaxation of the strips is accounted for by a) the efflux of unchanged amine from neuronal (and extraneuronal) stores and b) the sensitivity of the preparation to noradrenaline.


Action of prostaglandin, PGF2alpha, on the uterus of the pregnant rat. The effects of prostaglandin F2alpha (PG) have been studied on the transmembrane potentials and contractions in isolated myometrial strips from pregnant rats. The results showed that: 1. The sensitivity of the myometrium to exogenous PG increases from day 19 to day 22 of gestation. 2. The electrical response to PG, at maximally effective doses (10-6 to 10-5 M) consists of a slow depolarization which upon reaching threshold initiates spike discharge. 3. These actions are most pronounced at term (day 22) and are due to a direction of PG on the myometrial cells. 4. D-600 (a methoxy derivative of verapamil) abolishes spike discharge and the phasic contractions induced by PG but has no effect on the slow depolarization and the accompanying increase in tonic tension. 5. The slow depolarization is dependent upon the presence of sodium in the external environment and is unaffected by the removal of calcium. 6. The spikes (and phasic contractions) are dependent upon the presence of calcium in the external environment.


The uptake and subcellular distribution of radio-labeled metabolites of digoxin in the isolated perfused guinea-pig heart. Cardiac glycosides like digitoxin and digoxin with three digitoxoside sugar residues have been reported to undergo step-wise degradation to yield the corresponding genins, and the importance of the digitoxoside side-chain for the pharmaco-dynamics property of cardiac glycosides has also been suggested. A sytematic study was therefore undertaken on the cleavage products of digoxin. Digoxigenin-bis-digiitoxoside (with two sugar residues) digoxigenin-monodigitoxoside (with one sugar residue) and digoxigenin (with no sugar) were compared with the parent compound, digoxin. The radio-labeled compounds were perfused through isolated guinea pig hearts using 10-7 M concentration in the perfusion medium for a fixed period of 64 min followed by an 8 min period of wash-out with normal medium. The uptake and sub-cellular distribution of the drugs were thereafter measured scintillation counting. All the compounds produced postive inotropic responses, the mondigitoxoside producing the greatest effect, digoxigenin next in order of inotropic response magnitude, the bis-digitoxoside produced the least effect, and digoxin was intermediate between the genin and bis-digitoxoside. The uptake of the monodigitoxoside was the highest, and in general, the quantitative uptake was related to the inotropic response. The greatest binding of each digitoxoside was found in the microsomal fraction. Both mechanical activity and uptake of all four drugs were uniformly reduced by an increase in potassium concentration in the perfusion medium.


Ferrihemoglobin formation by monohydroxy aniline derivatives in erythrocytes of some avian species in comparison with mammals. Ferrihemoglobin formation nitrosobenzene and p-, m- and o-animophenol was studied in erythrocyte supspensions from a number of avian and mammalian species. Compared with the mammalian erythrocytes, bird red cells show little species differences in susceptibility. In birds, dose-effect relationship are different for nitrosobenzene and the aminophenols: using low concentration nitrosobenzene is more active than the aminophenols, while at higher concentrations o-aminophenol is at least equally effective. In birds, o-aminophenol is about eight times more potent than p-aminophenol. m-Anminophenol is not an inducer of ferrihemoglobin in erythrocytes of the cat, the goat and the Japanese quail.


The effect of some glucocorticoids on hepatic microsomal hydroxylation in the rat and hamster. The effect of some glucocorticoids on hepatic microsomal biphenyl and aniline hydroxylations were investigated in rat and hamster. Steroids were either added to the standard incubation mixture or given as a single dose intraperitoneally before preparation of the liver microsomes for enzyme determination. The addition of steroids in vitro enhanced biphenyl-2-hydroxylation activity in hepatic microsomes of rat but not of hamster and the most pronounced effect was obtained with betamethasone. A similar species difference in the effects of betamethasone on this enzyme was also observed after administration of a single dose of the steroid in vivo.


Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin. 1. The acidic peptide crotapotin potentiated the toxicity of the basic crotalus phospholipase A in all species tested. The order of sensitivity to the lethal action of the phospholipase was: chick greater than mouse larger than or equal to rabbit greater than rat. After a latency period of a least 20 min the animals died of respiratory paralysis. Rabbits survived for more than 10 h, if they were artificially respired. The animals recovered very slowly from respiratory depression. 2. In rabbits even high doses of the basic crotalus phospholipase A or its complex with crotapotin did not affect the respiratory center nor its reactivity to asphyxia. Conduction of action potentials in the phrenic nerve was not changed. 3. Phospholipase-crotapotin complexes decreased the contractile response of isolated phrenic-hemidiaphragms of rats to direct and indirect stimulation in an irreversible manner. A latency period 20-100 min preceded the paralysis. 4. A similar block of neuromuscular transmission developed in vivo. After i. v. injection of PC-complexes the contractile response of isolated rat phrenic diaphragms to nerve stimulation was considerably lower than to direct stimulation. 5. Crotalus phospholipase A alone as well as its complex with crotapotin reduced the contractions of the isolated chick biventer cervicis muscle but did not cause a contracture, thus indicating that the phospholiphase PC-complexes act not as depolarizing blockers. 6. Blood pressure, heart rate and electrocardiogram were not substantially altered, when phospholipase A or PC-complex were injected slowly i.v. into rabbits or rats. No cardiotoxic effect was observed in the Langendorff preparation of rat hearts perfused with phospholipase A alone (6 x 10(-6) M) or together with crotapotin (10(-5) M).  Rapid i.v. injection of the venom produced hypotension. The degree of haemolysis correlated with the enzymatic activity, and was low for the highly toxic PC-complexes.


[The interaction of impulses evoked by stimuli of different modality in neurons of the parietal association cortex]. Interaction of visual, auditory and electro-dermal signals in neurons of the parietal associative cortex was investigated in acute experiments on cats anesthetized by chloralose and nembutal. Two types of the interaction were found, one of which was characterized by inhibition or inhibition followed by facilitation of the response to testing stimuli, and the other by facilitation or facilitation followed by inhibition of background impulses. The interaction between signals of different modality is shown to depend on the properties of the neuron. Interaction ability in polysensory neurons was evidently higher than in bi- and monosensory ones.


[Reactions and properties of the receptive fields of neurons in the visual projection zone of the pigeon hyperstriatum]. Impulse responses of neurons of the pigeon forebrain hyperstriatal part to stationary and moving visual stimuli were investigated. Particular attention was given to revealing a retinotopic projection in the region of visual representation in Wulst. It is shown that as the electrode moved gradually in the caudal direction in the region of visual projection of the hyperstriatum, the receptive fields of the neurons under observation displaced in the visual field in the opposite direction. The receptive fields of the ventral and dorsal hyperstriatum cells remain higher in the visual field and have larger diameters than the receptive fields of neurons of the accessory hyperstriatum. Neurons responses of the visual projection of the Wulst region depend on luminosity, size, speed and direction of the movement of the test-objects through the receptive field. The functional role of the retino-thalamo-telencephalic system in the visual integration in birds is discussed and a supposition is advanced on possibility to compare the Wulst region with striatal and frontal visual areas of the mammalian cortex.


[Generation of action potentials by cortical neurons in turtles. Dendritic and somatic spikes]. Action potentials in single neurons were studied intracellularly in the general cortex of the turtle. It is shown that neurons generate full spikes and, besides them, partial spikes of different amplitude. The partial spikes can be combined into a full spike. The threshold of generation and the amplitude of each partial spike are not constant values, they fluctuate within certain limits spontaneously and gradually without any change in the resting potential of the neuron. Somatic spike and dendritic spikes can be distinguished. Zones of the dendritic spikes initiation are located at different distances from the soma. Under orthodromic activation of cortical neurons the dendritic spikes are generated in succession and conducted to the soma electrotonically with a decrement. The dendritic spikes can reach the threshold for initiation of a somatic spike.


[Centrifugal and centripetal connections of the cat visual cortex]. The responses of the dorsal LGB units to the striate cortex stimulation were examined in cats paralized with d-tubocurarine. Most cells studied were activated antidromically but only 8% demonstrated orthodromic responses. Some units studied intracellularly exhibited antidromic spikes followed by IPSPs, sometimes only IPSP was observed. The conduction velocities of the corticipetal fibres ranged between 28 and 4.3 m/s; three groups of fibres with conduction velocities 28-19, 14-12, 10-9.5 m/s could be separated in them in most cases. Some of the antidromically responding units had different response latencies to different striate areas stumulation, indicating that these units project to the striate cortex by means of a branching axon. Possible mechanisms of cortical influence on the LGB neurons are discussed.


[Functional characteristics of the basic internal system of hippocampal connections]. Functional characteristics of two main intrahippocampal connections (dentate fascia-field CA3 and field CA3-field CA1) were studied in unanesthetized rabbits. Electrical stimulation of FD or CA3 was used during extracellular recording of the CA3 or CA1 neuronal activity, respectively. The system CA3-CA1 is a highly effective, with a very narrow threshold zone and wide range of active frequencies. The process of recruitment during continuous rhythmic stimulation is weak, any signs of prolonged potentiation are absent. The system FD-CA3 is characterized by low effeciency, a wide threshold zone, narrow range of active frequencies. It is able of gradual building up and prolonged preservation of potentiated state. The morphological reasons of these differences and possible role of these systems in the hippocampal activity are discussed.


[The functional role of the septum].

[The functional role of the septum]. A study of the electrical activity (background and at sensory stimulation) of the motor and visual areas of the cortex, hippocampus, septum (in some cases the lateral geniculate body and the midbrain reticular formation) was carried out on rabbits by the method of spectral-correlation analysis. The method of driving reactions to electrical stimulation of the lateral and medial nuclei of the septum was used to investigate its functional role as a pace-maker. The spectograms of all the analyzed areas of the brain showed the presence of acquired rhythms during electrical stimulation at 4-30 Hz. The acquired rhythm was most prominent in cortical potentials. It is assumed that the generation of rhythmical cortical activity is due to physiological interaction of the cortex and septum.


[Reactions of the neurons of the anterior and posterior regions of the hypothalamus to light stimulation and stimulation of the splanchnic and sciatic nerves]. Responses of single hypothalamic neurons to splanchnic, sciatic nerves and photic stimulation were studied in anesthetized, curarized cats. It is found that units of the posterior and anterior hypothalamus are "convergence neurons" with multisensory inputs. Convergence of somatosensory and visceral (splanchnic) impulses to such neurons was complete. No neurons responding only to the splanchnic nerve stimulation were found. In the posterior hypothalamus some units responded only to stimulation of splanchnic and sciatic nerves and were unresponsive to a flash. On the contrary, in the anterior hypothalamus a part of units responded only to photic stimulation. The polysensory neurons of the posterior and anterior hypothalamus were of a nonspecific modality: they responded with a similar pattern of phasic or tonic discharge with a predominance of phasic responses. Units were more often excited than inhibited. A high responsibility (68%) of spontaneously active neurons to somato-visceral and photic stimulation was observed in the posterior, as well as in the anterior hypothalamus. The principles of functional organization of hypothalamic afferent system are discussed.


[Reproduction of delayed evoked potentials during amygdaloid complex stimulation]. Influence of amygdaloid stimulation on retrieval of the electric correlate of time connection, delayed evoked potentials recorded in the cortex, midbrain reticular formation, lateral geniculate body and hippocampus, was studied in experiments on currarized unaesthetized cats. Delayed evoked potentials were formed after 10-400 pairings of light flash and hypothalamic stimulation and were manifested as potentials appearing in response to a conditioned stimulus with a delay equal to the interval between conditioned and unconditional stimuli. Amygdaloid stimulation facilitated their retrieval if they were previously extinguished or did not appear during initial testing.


[The effect of several surface-active substances on neuromuscular transmission in frogs]. The action of bile salts, saponin and tween-80 on miniature end-plate potentials (MEPP) and electrotonic potentials (ETP) of the muscle fibre membrane was studied in frog Rana ridibunda. Bile salts in a concentration of 10(-4) g/ml increased the frequency and amplitude of MEPP. The input resistance of the muscle fibre membrane decreased under the action of these substances. At higher concentrations (to 10(-3) g/ml) the frequency of the MEPP initially increased, then these potentials were depressed and finally they completely disappeared. Tween-80 did not change noticeably spontaneous synaptic activity, and saponin inhibited it. In Ca-free solutions bile salt were less effective. It is suggested that bile salts change the structure of the presynaptic membrane and at the same time stimulate the release of acetylcholine form the nerve terminals.


[Antidromal and synaptic potentials of motoneurons of the cat accessory nerve nucleus]. Field potentials were recorded in segments C1-C4 after stimulation of n. accessorius. In this region antidromic and synaptic potentials 20 n. accessory motoneurons were recorded. They were produced by stimulation of the accessory nerve and other peripheral nerves. The latency of antidromic potentials was 0.6-1.1 ms. Only EPSPs and action potentials were produced by stimulation of different peripheral nerves. EPSP's latency were 2.2-4.4 ms for the third cervical nerve, 3.8-5.8 ms for n. splenius, 11-20 ms for n. radialis superficialis, 2.2-3.5 ms for n. infraorbitalis.


[The effect of sodium amytal on the electrophysiologic properties of snail giant neurons]. Sodium amytal increased resting potential decreased and finally abolished action potentials and temporarily decreased input resistance of the neuron membrane. Simultaneously, the intracellular potassium content decreased, but sodium content was almost unchanged. These effects are suggested to be connected with changes in the membrane potassium permeability and with disturbances in the mechanisms of action potential generation.


[The ultrastructure of portions of the cat spinal cord gray matter connected to fibers of different descending tracts]. Definite ultrastructural features were found in the regions of the cat spinal grey matter connected with different descending pathways, especially in the structure of dendritic membranes and relative quantities of axon terminals. Two types of destructive changes in myelinated axons and axon terminals in these regions were observed during experimental degeneration of descending fibres. Axon terminals of small size and F-type vesicles were subjected to degeneration after pyramidal tract lesion, while large terminals of both S-type and F-type were affected after sectioning of extrapyramidal tracts.


Haemoglobin and serum iron responses to periodic intravenous iron-dextran infusions during maintenance haemodialysis. Patients with chronic renal failure who were on maintenance haemodialysis, were given monthly 600 mg iron intravenously as iron-dextran complex to a body replacement total of 5-6 g iron. Those patients who had been on maintenance haemodialysis for a long period and had received numerous blood transfusions failed to show a rise in haemoglobin levels. Those patients who received iron from the commencement of maintenance dialysis, and who had not received blood transfusions, showed a significant increase in haemoglobin concentrations which has been maintained for more than 18 months after iron therapy ceased, despite a concurrent decrease in serum iron concentrations. Pre-treatment and post-treatment levels of serum iron are not of predictive value for the success of iron treatment, neither for the haemoglobin nor the serum iron response. A body replacement dose of iron given intravenously over a year benefits the majority of patients on maintenance haemodialysis and is recommended for the treatment of their anaemia.


Glycolipid modifications during peritoneal dialysis in patients with chronic renal failure. Ten patients with progressive CRF were studied for the major indices of glycolipid metabolism during the first application of peritoneal dialysis. From the 2nd hour the concentration of dialysis fluid is 4.5g%, while the electrolyte content is unchanged. During treatment a constant increase of glycemia and insulinemia with a fall of plasma-free fatty acids and serum triglycerides was observed. The authors attribute such modifications to hyperglycemia and consequently to the high glucose of the dialysis bath.


Parathyroid hormone plasma level in untreated chronic renal failure and in hemodialyzed patients. In 42 untreated patients at various stages of chronic renal failure, plasma level of parathyroid hormone was directly proportional to the degree of renal failure and inversely proportional to the serum calcium level. Plasma parathyroid hormone levels were frequently elevated in 21 patients undergoing regular dialysis treatment, in spite of normal levels of serum total calcium and magnesium. Serum-ionized calcium levels measured in dialyzed patients were usually reduced and inversely correlated with the creatinine levels. Parathyroid hormone levels were correlated with the creatinine levels, but the inverse relationship with ionized calcium was not significant.


The effect of acute uremia on liver mitochondrial activity. The effect of acute uremia on the liver mitochondrial activity was studied in Swiss albino mice subjected to complete urethral obstruction and sacrificed at different time intervals. The specific respiratory coefficient (measured as microliters of oxygen utilized per milligram of total proteins X 10(-1)) was similar in uremic and sham-operated control groups. The utilization of succinate as substrate was also similar in uremic and controls. There was a tendency for decreasing utilization of alpha-glutarate as substrate by the uremic group, particularly after 48 h of total urinary obstruction. There was no correlation between the retention of urea and the degree of mitochondrial respiratory inhibition.


Intrafamily identity and home dialysis success. The entire family participates in the success of the home dialysis patient. Isolation and study of discrete quantifiable aspects of behavior within the family may allow identification of patients with a greater risk of failure, thus making it possible to help such patients succeed. A single such factor, 'intrafamily identity', measured in each of 40 diverse families before one family member began a home dialysis program, was found to correlate with success in the program 1 year later. This finding also may contribute to an understanding of systematic patterns of behavior within all families, with special emphasis upon the ability of family members to cope with continuing stress.


Renal microangiopathy of the hemolytic-uremic syndrome in childhood. 18 children with clinical and laboratory findings characteristic of the hemolytic uremic syndrome were retrospectively studied. Thrombocytopenia due to platelet destruction was accompanied by only minimal changes in fibrinogen turnover and fibrinolytic degradation products. The most consistent pathologic feature was severe renal endothelial cell injury, which was postulated to produce both platelet and red cell destruction. Despite initially severe renal damage, 90% of the patients ultimately recovered normal renal function if adequately supported during the acute phase of the disease.


The role of tubular necrosis in the pathophysiology of acute renal failure. Renal tubular function was evaluated in vitro by kidney slice uptakes of p-aminohippurate (PAH) and tetraethylammonium (TEA) at 24 and 48 h in water-drinking rats and at 24 h in chronic saline-loaded rats after induction of acute tubular necrosis (ATN) by HgCl2 and glycerol injection. Significant correlations between decrease tubular uptake of PAH and TEA and elevated serum creatinine levels were noted in both models of ATN in water- and saline-drinking rats. However, with the same degree of impairment of PAH and TEA uptakes the creatinine was significantly lower in saline-loaded rats than in water-drinking rats in both forms of ATN. The correlation between impaired tubular function and elevated creatinine suggests that tubular damage and glomerular filtration reduction might be pathophysiologically related in ATN.


Hypertension and plasma renin activity in experimentally induced chronic pyelonephritis. The present authors conducted a series of experiments with mongrel dogs, in which unilateral chronic pyelonephritis was induced and postoperative changes in blood pressure and plasma renin activity were observed over a period of 3 months. The pyelonephritis infection was brought about by a method involving vesicoureteral reflux and ureteral dysfunction, as described in a previous paper. Pre- and postoperative levels of systolic pressure were compared, but no definite trends were found for the first 3 weeks after operation. At 30, 60 and 90 days the pressures were found to have risen by 21.2 +/- 14.6 and 17.1 +/- 16.7 mm Hg, respectively. No appreciable change in the plasma renin activity was found, however, at any stage. From these results it was concluded that experimentally induced chronic pyelonephritis in dogs caused a rise in blood pressure. No connection between the pyelonephritis and the renin angiotensin system was found.


Solute transport in comparable surface area dialyzers. The present study compared clearance (K) for urea (U), uric acid (Ua), and BSP in relatively equal surface area dialyzers, EX-29 to dual EX-21 in parallel (DEX-21) at QB and QD 300 ml/min, and hollow fiber kidney model 5 (HFK-5) to dual HFK model 4 in series (DHFK-4) at QB 200, QD 500 ml/min. KU was 158 +/- 20 ml/min, 129 +/- 22; KUa was 106 +/- 10, 96 +/- 5, and KBSP was 80 +/- 11 and 67 +/- 12 (p less than 0.01) for EX-29 and DEX-21, respectively. KU was 173 +/- 8 ml/min, 159 +/- 6; KUa was 131 +/- 6, 117 +/- 8, and KBSP was 65 +/- 9 and 56 +/- 7 (p less than 0.01) for HFK-5 and DHFK-4, respectively. Comparable changes in outlet pressure had a varied effect on ultrafiltration and solute transport. 3-hour hemodialysis in the same patients showed that EX-29 was better tolerated than DEX-21. The data suggest that dialyzer designs with the same membrane of equal surface area may significant affect K for both small and middle molecular weight solutes. Comparable changes in outlet pressure may have a varied effect on K in different designs. Due to these variations, comparison of dialysis schedules with different dialyzers on the basis of the square meter hour dialysis to prove validity of middle molecule hypothesis should be interpreted cautiously.


Hormonal function of a granulosa cell tumor. Granulosa and theca cell tumors are rather common gonadal stromal tumors. A postmenopausal patient with a granulosa cell tumor, who complained chiefly of breast tenderness and enlarging, abdomen, is presented. Preoperative and postoperative studies including serum estrone, estradiol, prolactin, FSH, and LH,as well as urinary estrogens, 17-ketosteroids, and 17-hydroxysteroids are reported. A plan of treatment and followup is suggested. It is recommended that survival data on patients with such slow-growing tumors be adjusted to reflect the true incidence of death from the specific tumor in question.


Partial exchange transfusion in a pregnant patient with sickle cell anemia. A pregnant patient with symptomatic sickle cell anemia is presented, and the rationale and technic of management by partial exchange transfusion near term is discussed. Observations concerning the comparative safety of the protocol are made, and suggestions offered for a more widespread adoption of this plan. The outcome for mother and baby was good.


Male hermaphroditism with bilateral testes, well-formed Müllerian structures, and 45,X chromosome complement. A patient is presented who was short in stature and had an enlarged phallus, normal vagina, uterus, fallopian tubes, and bilateral testes but with a 45,X karyotype from peripheral leukocytes. This is believed to be the first such patient ever reported. Such patients and other previously described male hermaphrodites with a 45,X karyotype indicate that, contrary to the general rule that patients with 45,X karyotype do not require a laparotomy, patients with such a karyotype should be explored if their genitalia are ambiguous.


Hyperamylasemia associated with gonococcal salpingitis and perihepatitis. A case of hyperamylasemia associated with gonococcal salpingitis and perihepatitis (Fitzhugh-Curtis syndrome) is reported. Other potential causes of hyperamylasemia such as pancreatic, parotic, biliary, or intestinal disease were carefully excluded. In addition, the amylase to creatinine clearance ratio was within normal limits, suggesting tubal rather than pancreatic source of hyperamylasemia. This finding is of clinical importance since acute salpingitis is a prevalent disease and its initial presentation may mimic acute pancreatitis or other causes of surgical abdomen. The amylase to creatinine clearance ratio is of value in differentiating such cases from those with hyperamylasemia due to pancreatitis.


Myasthenia gravis and preeclampsia.

Myasthenia gravis and preeclampsia. Myasthenia gravis in pregnancy is rare, and its occurence in conjunction with preeclampsia has not been previously described. A case report of preeclampsia in a myasthenic patient is described with recommendations for management. The authors conclude that magnesium is a contraindicated pharmacologic agent in a myasthenic patient.


Plasma oxytocin determinations in pregnancy with diabetes insipidus. Diabetes insipidus is an extremely rare condition complicating pregnancy. The deficiency in antidiuretic hormone production has led to the assumption that oxytocin synthesis may also be affected. For this reason spontaneous onset of labor in a number of previously reported cases has been considered as evidence against implicating oxytocin as a relevant factor in the evolution and maintenance of labor. For the first time, plasma oxytocin levels were determined in a patient with known idiopathic diabetes insipidus during pregnancy, labor, and postpartum, using radioimmunoassay. Oxytocin was not detectable in plasma before labor. There was however a surge of plasma oxytocin detected during labor and puerperium, a pattern somewhat similar to that seen in normal pregnancy. Our findings suggest that at least some patients with diabetes insipidus do secrete oxytocin and that the role of oxytocin, threfore, cannot be discounted in the labor process.


Laceration of umbilical artery and abruptio placentae secondary to amniocentesis. A case of a lacerated umbilical artery causing an abruptio placentae and subsequent emergency cesarean section is presented, with a review of the complications of amniocentesis. A search of the literature has failed to reveal that this particular complication has been previously reported.


Sonographic demonstration of fetal death in the absence of radiographic abnormality. A case of intrauterine fetal demise was monitored over a 5-week period with serial sonographs and simultaneous radiographs. The diagnosis could not be established from the radiographs even 7 weeks postmortem. However, the initial sonographs established the diagnosis and subsequently presented a picture of increasing degeneration. Possible explanations for this are suggested.