Sexual differences in hepatic metabolism and intracellular distribution of corticosterone studied by pulse labeling with (1,2,6,7-3H)corticosterone. The subcellular distribution of corticosterone and its metabolites in liver was studied 5, 30, and 90 min after injection of (1,2,6,7-3/)corticosterone in adult male and female rats that were adrenalectomized or hypophysectomized: 5 min after administration of isotope, the adrenalectomized male rats contained ten times as much labeled unconjugated corticosterone, 5alpha-dihydrocorticosterone, and 3alpha- and 3beta,11beta,21-trihydroxy-5alpha-pregnan-20-one on the nuclear fraction than the corresponding female rats. The metabolites of corticosterone in the soluble fraction of liver from adrenalectomized females occurred as about 90 per cent steroid monosulfates and disulfates already 5 min after administration of isotope. In contrast, the soluble fraction of liver from males contained only 38 per cent labeled monosulfate 5 min after injection of (1,2,6,7-3H)corticosterone. The individual labeled metabolites from the different subcellular fractions were identified by thin-layer and radio-gas chromatography. The major metabolites found in the female were mono- and disulfurylated 3alpha,11beta,15,21-tetrahydroxy-5alpha-pregnan-20-one, 3alpha,15,21-trihydroxy-5alpha-pregnane-11,20-dione, and 3alpha,11beta,21-trihydroxy-5alpha-pregnan-20-one. The predominant metabolites in the male were 5alpha-pregnane-3alpha(and 3beta),11beta,20beta,21-tetrol and 3beta,11beta,21-trihydroxy-5alpha-pregnan-20-one which mainly occurred as mono- and disulfates. Hypophysectomized female rats showed a corticosterone metabolite pattern with almost no 15-hydroxylated metabolites but with large amounts of isomers of pregnane-3,11beta,20beta,21-tetrol, i.e., a "masculinized" pattern. It is concluded that hepatic intracellular metabolism and transport of corticosterone in vivo in rats are characterized by large sexual difference which are at least partly under hypophyseal control.


Membrane conductance changes in single nodes of Ranvier, measured by laser-induced temperature-jump experiments. Temperature-jump experiments on isolated myelinated nerve fibers were done using a pulsed laser system in the Q switched mode. Voltage-clamp and temperature perturbations were used to measure the relaxing ionic conductances of both the Na+ and K+ systems. It is shown that the T jump can be used to probe the K+ and Na+ conductances during non-steady state conditions and thereby elicit relaxation times for a variety of initial states. Temperature-induced K+ conductance relaxation times were consistent with voltage-clamp measurements. The temperature-perturbation experiments were done as a combination of a temperature step and impulse change due to an adsorption of carbon black particles on the nerve. The experiments support the hypothesis that the relaxation times of the K+ system are independent of the previous history of the axon. It is concluded that the K+ conductance is at least a second-order system whose relaxation spectrum is composed of two exponential terms the magnitudes of which are markedly dependent on the initial conditions.


The release of dopamine from synaptosomes from rat striatum by the ionophores X 537A and A 23187. The antibiotics X 537A and A 23187 are negatively charged divalent cation ionophores. X 537A may, in addition, be an ionophore for amines including catecholamines. The effects of these ionophores were examined on the uptake and release of dopamine by synaptosomes prepared from rat corpus striatum. Both X 537A and A 23187, at concentrations less than 0.5 muM, release both endogenous and [3-H]-dopamine from synaptosomes. They had virtually no effect on the uptake of exogenous dopamine. These compounds act by different mechanisms. X 537A causes divalent ion-independent release in which a large fraction of the effluent consists of deaminated products. X 537A, in addition, releases [3-H]dopamine from rat adrenal medullary chromaffin granules. The results suggest that X 537A causes release of dopamine from intrasynaptosomal storage vesicles and perhaps is acting as a catecholamine carrier across the vesicular membrane. A 23187, on the other hand, causes a Ca-2+-dependent release in which only a small fraction of the catechol in the effluent is deaminated. A 23187 has little effect on the release of [3-H]dopamine from chromaffin granules. These results suggest that A 23187 carries Ca-2+ into the synaptosomes and thereby initiates exocytotoc release.


The interaction of atebrin with phospholipid vesicles. The interaction of atebrin with phosphatidylcholine and phosphatidylcholine-phosphatidic acid vesicles has been followed by equilibrium dialysis, and by photometric, fluorimetric and NMR techniques. The presence of negative charges in the phospholipids enhances the binding of atebrin. The absorbance and NMR spectral changes and fluorescence quenching occurring with phosphatidic acid are attributed to dimerization of the dye interacting electrostatically with negative groups. The dissociation constant of the binding of the dye to phosphatidylcholine vesicles was 1.4 mM; those of binding to the negative sites of phosphatidic acid were approx. 150 and 3 muM. The dye is probably located at the interphase with the acridine ring interacting with the anionic groups of phosphatidic acid and the tail freely floating in the aqueous phase. The results are discussed also in view of the use of atebrin as a probe of the energized state in natural membranes and of the suggestion that atebrin may be used as a transmembrane pH indicator in liposomes or natural membranes.


Non-parallel transport of membrane proteins and content proteins during assembly of the secretory granule in rat parotid gland. The insertion of newly synthesized protein molecules into the membrane of the secretory granule of the rat parotid gland was studied by in vivo labeling with [3-H]-proline and [3-H]leucine. 2 h after the injection of the amino acid into the rat, the membrane fraction isolated from the secretory granules was found to be highly labeled with proline but only slightly labeled with leucine. The ratio of proline label in the granule membrane to that in the granule's secretory content was roughly equivalent to the ratio of total proline in the proteins of these two fractions. In contrast the ratio of leucine label in the membrane to that in the secretory content was much less than would be expected from the relative amount of leucine in both fractions. Separation of the proteins of the granule membrane by gel electrophoresis in presence of sodium dodecylsulfate showed that a considerable amount of these proteins was unlabeled. The labeled proteins could be selectively extracted from the membrane by 0.15 M Nacl solution or by dilute buffer at pH 4.5. These extracted proteins were found to contain a high proportion of proline residues and a negligible amount of leucine residues. In the extract proline constituted 36 mole % of the total amino acids. Proline plus glycine plus glutamic acid constituted more than 80 mole % and leucine constituted about 1 mole% of the total amino acids. Further analyses by gel electrophoresis in presence of sodium dodecylsulfate showed that the fractions of secretory granule membrane and secretory granule content are relatively free of contamination by proteins from other subcellular structures. It is suggested that the proteins which will constitute the mature secretory granule are transported to the site of final assembly by two pathways. The proline-rich proteins are transported to the site of assembly in close coordination with all the exportable proteins. The other membrane proteins arrive by a different pathway. Two alternative mechanisms are suggested to explain the finding that a considerable part of the membrane proteins are not labeled. I. The pathway of the intracellular transport of the unlabeled membrane proteins is similar to that of the secretory proteins but the newly synthesized membrane protein molecules are diluted in a large intermediate pool--the GOLgi complex. II. The proteins that did not get labeled are derived by a process of reutilization, from membranes of granules which have previously discharged their content in the process of secretion.


Cysteine metabolism in vivo of vitamin B6-deficient rats. The expirations of 14CO2 from DL-[1-14C]-, DL-[3-14C]- and L-[U-14C] cysteine used as isotopic tracers were estimated in order to determine the in vivo metabolic distribution of L-cysteine in pyridoxine deficient rats. The expired 14CO2 from L-[U-14C] cysteine was increased by pyridoxine deficiency. The loading of non-physiological dose of L-cysteine resulted in remarkable increase in the expiration of 14CO2 from each tracer in deficient rats as well as in controls. The in vivo metabolic distributions of L-cysteine were calculated from the expired 14CO2 from these isotopic tracers. The in vivo metabolic distribution of L-cysteine calculated showed that the remarkable lesion in taurine pathway occurred in pyridoxine deficient rats, and when non-physiological dose of L-cysteine was loaded the catabolism of L-cysteine of controls was markedly increased in either pyruvate or taurine pathway, whereas the L-cysteine catabolism in deficient rats was increased only in pyruvate but not in taurine pathway. The urinary excretions of 35S-labeled metabolites such as sulfate or taurine were also examined in deficient and control rats.


Cellulose synthesis by Acetobacter xylinum. III. Matrix, primer and lipid requirements and heat stability of the cellulose-forming enzymes. The addition of soluble cellodextrins of increasing size to a cell envelope preparation of Acetobacter xylinum stimulated cellulose synthesis from UDPG. This stimulation was attributed to both acceptor and activator effects. Enzymes required for cellulose synthesis were found to be heat-unstable and those required for synthesis of glycosylated lipid components from UDPG, heat-stable. Both heat-inactivated envelope fragments and supernatant fluid from whole cells were necessary for cellulose synthesis from UDPG. Cellulose was not formed from UDPG in the presence of either supernatant fluid alone or heat-inactivated envelopes alone. The combined results of this and previous studies suggest that either the cell envelope is necessary for synthesis of a more immediate precursor to cellulose than UDPG, or that the synthesis from UDPG requires a matrix. The former suggestion and its possible link with lipid intermediate involvement was strengthened by the observation of inefficient glycosylated lipid formation by a celluloseless mutant strain of A. xylinum. The possible locations of various enzyme activities required for the synthesis of the cellulose precursor are indicated and a possible microfibril nucleation process is discussed.


The response of small intestinal villous and crypt epithelium to choleratoxin in rat and guinea pig. Evidence against a specific role of the crypt cells in choleragen-induced secretion. 1. Some kinetic properties of adenylate cyclase in separately isolated upper villous and crypt cells from rat and guinea pig small intestine were compared. An apparent Km of 0.4 mM was found for both enzymes in the rat. The slight difference between the V-values measured in the fluoride-stimulated state (132 and 165 pmoles cyclic AMP formed per min per mg protein respectively) indicated an approximately equal enzyme content of both cell populations and argues strongly against a preferential localization in the brushborder region of the epithelial cell. 2. Prolonged contact of the small intestine with luminally administered choleragen led to an irreversible activation of adenylate cyclase in both villous and crypt compartments. The maximal stimulation of the upper villous enzyme (4-7 times) exceeded the maximal effect on the crypt enzyme by two-fold. 3. A lag phase of at least 30 min was found between the first luminal contact with the purified choleragen and a significant activation of the adenylate cyclase associated with isolated intestinal brushborders from the upper villous region. 4. By using a short exposure time (2 min) of the luminal surface to high amounts of choleragen, adenylate cyclase activity in the upper villus could be optimally stimulated in the absence of any alteration of crypt cell activity. 5. By comparing, in vivo, the effects of short and prolonged contact with choleratoxin on the unidirectional and net flux of ions and water in ileal and jejunal segments, it was concluded that both villous and crypt regions contribute to the secretion of water and electrolytes (sodium, chloride and bicarbonate ions) during cholera. The serosal to mucosal flux of sodium and chloride ions increased without a significant alteration of the opposite flux. These results imply that absorptive and secretory processes occur within the same epithelial compartment. 6. The view that the crypt epithelium fulfills a specific role during the choleragen-induced secretion of ions and water is incompatible with the results of the present study.


Incorporation of hypoxanthine into adenine and guanine nucleotides by human platelets. 1. Incubation (1-4 h) of normal human washed platelets (5-11-10-8 per ml) with [8-14C] hypoxanthine at a concentration of 10-5 M resulted in a linear incorporation of radioactivity into adenine and guanine nucleotides. 2. Washed platelets from patients with Lesch-Nyhan syndrome, deficient in hypoxanthine: guanine phosphoribosyltransferase, failed to demonstrate any significant incorporation of [8-14C] hypoxanthine but did incorporate [8-14C] adenine like normal platelets under the same incubation condition. 3. These findings are taken to indicate that normal platelets have the enzymes necessary for salvage of hypoxanthine and that hypoxanthine: guanine phosphoribosyltransferase is the obligatory first step in this pathway.


32P distribution into 2,3-bisphosphoglyceric acid from human erythrocytes following molybdate-catalyzed hydrolysis. Normal human washed erythrocytes were incubated in autologous plasma with 32P for varying periods of time. 2,3-Bisphosphoglyceric acid the major organic phosphate ester of red cells, was first isolated and purified by anion-exchange chromatography; subsequently, the C-2Pi was selectively hydrolyzed by a molybdate-catalyzed reaction. The C-2-bound Pi of 2,3-P2-glyceric acid was found to have a significantly higher specific activity than C-3 Pi. Intramolecular equilibration was not reached until the 180-min incubation. No evidence of overhydrolysis or internal randomization by the molybdate reaction was noted which was confirmed following hydrolysis of double-label 2,3-P2-glyceric acid 32P C-2, 33P C-3.


Investigations on the venom of the South Indian scorpion Heterometrus scaber. The enzymes from the venom of Heterometrus scaber, the indole compounds present and the toxic protein of the venom have been studied. The venom contains acid phosphatase, ribonuclease, 5'-nucleotidase, hyaluronidase, acetylcholine esterase and phospholipase. A. The indole compounds present in the venom have been identified as 5-hydroxytryptophan, tryptophan, serotonin and tryptamine, along with two unidentified indole compounds. The venom produces hyperglycaemia in sublethal doses and this has been found to be due to increased adrenaline secretion. The toxic protein of the venom has been obtained in a pure form by (NH4)2SO4 fractionation, followed by fractional precipitation with acetone and chromatography over DEAE-Sephadex. The toxic fraction has been found to be homogeneous on acrylamide gel electrophoresis. It is a glycoprotein (molecular weight 15 000) containing 1.74% glucosamine, 0.87% galactosamine, 0.313% sialic acid, 3.25% fucose and 0.45% of an unidentified neutral sugar. It did not show any enzyme activities, haemolytic activity or inhibition of succinate dehydrogenase activity but it produced hyperglycaemia in sublethal doses. The toxic level (intravenous administration in rats) was found to be 0.72 mg/kg body weight.


The role of mannosylphosphorylpolyisoprenol in glycoprotein biosynthesis in Mycobacterium smegmatis. A particulate enzyme preparation of Mycobacterium smegmatis catalyzes the transfer of labeled mannose from GDP-[14C] mannose into several endogenous acceptors. In one of these transfer reactions, the radioactivity is incorporated into an insoluble polymeric product that is present at the interphase after extraction of reaction mixture with chloroform-methanol. Solubilization of this product was achieved by digestion with proteolytic enzymes or treatment with 0.1 M NaOH indicating that the material was glycoprotein in nature. The solubilized material obtained after proteolytic digestion followed by treatment with alkali (representing 80-93% of the total interphase product) was shown to consist of a series of small molecular weight [14C] mannose containing oligosaccharides and glycopeptides by Bio-Gel column chromatography. A kinetic study of the enzymatic transfer of [14C] mannose from GDP-[14C] mannose into the glycoprotein suggested that the mannosylphosphorylpolyisoprenols are the obligatory mannosyl donor.


Reduced response to phenobarbital by the liver of rats fed a choline-deficient diet. 1. The response of the liver to phenobarbital administration was compared in rats fed either laboratory chow, a semipurified choline-supplemented diet or a semipurified choline-deficient diet. 2. The liver contents of proteins, lipids and cytochrome P-450, as well as the activity of aminopyrine and ethylmorphine demethylases, were measured after 5 days of feeding and five daily injections of phenobarbital. Liver sections were examined electron microscopically. 3. In rats fed the choline-supplemented diet, phenobarbital administration caused increases in cellular constituents, enzyme activities and smooth endoplasmic reticulum membranes as great as those seen in rats fed laboratory chow. However, in rats fed the choline-deficient diet, the response of the liver to phenobarbital administration was severely reduced in comparison to that in rats fed the other diets. 4. It is concluded that dietary choline and an adequate synthesis of lecithins are necessary for the induction of microsomal mixed-function oxidases and the concomitant accumulation of smooth endoplasmic reticulum in hepatocytes.


Glycopeptides from the egg jelly coat of the toad Bufo vulgaris. 1. Glycopeptides isolated by exhaustive pronase digestion from the egg jelly coat of toad, Bufo vulgaris, were separated by DEAE-cellulose chromatography into two fractions. These fractions each gave a single band when they were subjected to electrophoresis on cellulose acetate strips. The glycopeptides behaved as a kind of "macroglycopeptide" on gel chromatography. 2. The glycopeptide fractions contained as sugar components galactosamine, glucosamine, galactose, fucose and N-acetylneuraminic acid. The amino acid composition was characterized by the presence of threonine and serine, which accounted for approximately 70% of the total amino acids. 3. Large amounts of galactosamine, threonine and serine were destroyed by treatment with alkali, indicating that the carbohydrate-peptide linkage in the glycopeptides is mostly an O-glycosidic bond between N-acetylgalactosamine and the hydroxy groups of threonine and serine.


Localization of nascent NADPH-cytochrome c reductase in rat liver microsomes. Rat liver microsomes incubated with [3H] puromycin in high salt buffer were digested with a mixture of protease, trypsin and chymotrypsin, in both the presence and absence of 1 % deoxycholate. Our observations revealed that the proteolysis of peptidyl puromycin labeled with [3H] puromycin was at least partially protected by the presence of microsomal membrane. Immuno-chemical analyses have further shown that most of the nascent NADPH-cytochrome c reductase in the microsomes was digested with the proteases while serum albumin was effectively protected from the digestion. It is thus proposed that NADPH-cytochrome c reductase synthesized on the membrane bound ribosomes is not transported to the vesicular cavity but directly to the outer surface of the microsomal membrane in a form which is accessible to the proteases.


On the association of glycolytic enzymes with structural proteins of skeletal muscle. 1. The effects of protein concentration and ionic strength on the adsorption of the individual glycolytic enzymes to F-actin and F-actin--trypomyosin--troponin have been studied. 2. Appreciable association was demonstrated under conditions of physiological ionic strength and high protein concentration, and tropomyosin--troponin established as an important and generalized component of these interactions. 3. Phosphofructokinase, aldolase, pyruvate kinase, lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate isomerase were strongly bound under these conditions, while triosephosphate isomerase, phosphoglycerate kinase, phosphoglycerate mutase, enolase and hexokinase displayed less adsorption to the structural proteins. 4. The influence of a number of parameters on the adsorption phenomena was examined. Ca2+ and fructose 1,6-diphosphate increased the adsorption of aldolase, lactate dehydrogenase and pyruvate kinase, while decreasing the adsorption of the enzymes of the constant-proportion group. 5. Of the other major enzymic components of skeletal muscle, creatine kinase, adenylate kinase and malate dehydrogenase showed no adsorption to F-actin--tropomyosin--troponin under the experimental conditions. Some adsorption was evident, however, in the case of aspartate aminotransferase, (NADP) isocitrate dehydrogenase and alpha-glycerolphosphate dehydrogenase. 6. These results have been discussed in relation to their functional significance and the roles of enzyme compartmentation in the cell.


Evidence for structural dissociation of two biologic actions of growth hormone. The effects of purified growth hormone and its CNBr fragments on somatomedin induction and on the stimulation of hepatic and renal ornithine decarboxylase (L-ornithine carboxylase, EC 4.1.1.17) activity in rats have been investigated. At the doses tested, none of the CNBr fragments induced somatomedin as evidenced by lack of an effect on sulfate, leucine, and thymidine incorporation into cartilage of hypophysectomized rats. However, the largest fragment, consisting of two peptides corresponding to Residues 6-124 and 150-179 linked by a disulfide bridge, stimulated both renal and hepatic ornithine decarboxylase activity in hypophysectomized rats and the activity of the hepatic enzyme in intact animals. A smaller CNBr fragment corresponding to Residues 125-149 slightly stimulated the activity of renal ornithine decarboxylase but failed to increase activity of the hepatic enzyme. A similar slight stimulation of the activity of the renal, but not the hepatic, enzyme was produced by a large carboxyl-terminal fragment (molecular weight 8000) prepared by proteolytic cleavage of partially purified ovine growth hormone. Circular dichroic spectra of the CNBr fragments demonstrated that the largest fragment retained much of the ordered secondary structure of intact growth hormone while two smaller CNBr fragments were devoid of ordered secondary structure. These observations indicate that different biological activities of growth hormone may be dissociated by fragmentation of the parent molecule.


Correlation between erythromycin and acid phosphatase in mouse liver. 1. Whole liver homogenates obtained from mice 1h after an intraperitoneal injection of erythromycin lactobionate (343 mg/kg, 1/3 LD 50) were fractionated into nuclear (7000 times g min), mitochondrial (33000 times g min) and lysosomr-rich (250 000 times g min) fractions. 2. The resulting fractions, as well as the final supernatant, were analyzed for erythromycin, acid phosphatase and protein. 3. The highest relative specific activities (per cent total protein) of erythromycin and of acid phosphatase were exhibited by the lysosome-rich fraction. 4. It was of interest, therefore, to examine the effects of erythromycin upon the free activity of acid phosphatase in soluble form and on its in vitro and in vivo release from liver lysosomes. 5. Concentrations of 1.7 - 10-4 M, 3.4 - 10-4 M, 6.8 - 10-4 M and 13. 6 - 10-4 M of erythromycin lactobionate had no significant effect upon the free activity of acid phosphatase in soluble form but retarded the release of this enzyme from the liver lysosome-rich preparation. This effect of erythromycin lactobionate was dose- and time-dependent. 6. Treatment of mice with erythromycin lactobionate (343 mg/kg, 1/3 LD 50) iwtraperitoneally for 7 days significantly decreased the unsedimentable acid phosphatase activity expressed as per cent of total activity in whole liver homogenates. This indicated an in vivo diminished release of acid phosphatase from liver lysosomes by erythromycin. 7. Since erythromycin lactobionate is ionisable it could be possible that erythromycin basis as many other cationic molecules accumulates in lysosomes. 8. The in vitro and in vivo diminished release of acid phosphatase may suggest that erythromycin decreases permeability of lysosomal membrane.


Citrate formation by rat lung mitochondrial preparations. Rat lung mitochondrial preparations were incubated in the preasence of pyruvate and malate. The principal metabolic products measured were citrate and CO2. Citrate formation from pyruvate was found to be dependent on the presence of malate. Significant citrate was formed in the presence of isocitrate and the rate of citrate formation was increased by the addition of pyruvate. Small amounts of citrate were formed by lung mitochondrial preparations in the presence of 2-oxoglutarate and succinate only after the addition of pyruvate. The level of acetyl-CoA was significantly greater in the presence of pyruvate than in the presence of pyruvate plus malate. The addition of malate to lung mitoochondrial preparations increased 14CO2 production from [2-14C] pyruvate into malate and citrate. A low level of pyruvate-dependent H14CO3-incorporation into acid-stable products was observed, principally citrate and malate, but this rate did not exceed 5% of the rate of net citrate formation in the presence of malate and pyruvate. The capacity of rate lung mitochondria to form oxaloacetate from pyruvate alone in vitro is very limited, and would appear to cast doubt on a major role of pyruvate carboxylase in citrate formation. It is concluded that the rate of citrate formation from pyruvate is limited by the availability of intramitochondrial oxaloacetate and the rate of citrate efflux across the mitochondrial membrane.


Phosphopeptide and phosphoprotein metabolism in brain. Phosphopeptide and phosphoprotein phosphorylation was studied in rat brain microsomes and rat brain slices which were incubated in the presence of [gamma-32 P] ATP under various experimental conditions. Radioactive phosphoserine was isolated from phosphopeptides and phosphoproteins. Naplus, K+, Mg2+ and cyclic AMP had a stimulating effect on the labelling of phosphopeptides. Ouabain and Ca2+ lowered the level of 32P incorporation into the phosphopeptides. The phosphoproteins behaved similarly to the phosphopeptides except for the potassium effect. Chase experiments showed a faster decrease in the labelling of phosphopeptides than in phosphoproteins. We suggest that both compounds may be involved in active transport phenomena.


The phosphorylation region of lysine-rich histone in dividing cells. N-Bromosuccinimide cleavage of in vivo 32P-labelled lysine-rich histone isolated from rapidly dividing cells has been studied. N-Bromosuccinimide cleaves F1-histone into two fragments, a small N-terminal piece and a larger C-terminal portion. The phosphate-induced microheterogeneity and associated radioactivity which has been linked to cell replication, is found in the carboxyterminal fragment, No phosphorous is found associated with the amino-terminal fragment when histone phosphorylation is associated with cell division. The specific tryptic phosphopeptides obtained from in vivo labelled F1 are clearly different from those obtained from in vitro incubations of free F1-histones and cytoplasmic protein kinase.


Incorporation and metabolic conversion of cyanocobalamin by Ehrlich ascites carcinoma cells in vitro and in vivo. 1. Cyano [57 Co] cobalamin bound to murine transcobalamin, associates with Ehrlich ascites carcinoma cells. Association was found to be dependent on temperature, and to require between 7.2 - 10-5 and 2 - 10-4 M ionized calcium. 2. Association was blocked by vinblastine and colchicine, but not cytochalasin, suggesting that microtubules may be involved in this phenomenon. 3. Although irreversible association of radioactivity with cells was observed within minutes, appearance of significant radioactivity associated with the intracellular B12 binder, and conversion of cyanocobalamin to methyl- and 5'deoxyadenosylcobalamin required more than 18 h of incubation. 4. A pool of free vitamin B12 was found in cell extracts. This was composed of metabolically-active cobalamins characteristic of the interior of the cell, and not of cyanocobalamin recently incorporated. 5. Incorporation of 57Co-labelled vitamin B12 by these cells involves two major processes: a rapid irreversible association of transcobalamin-B12 complex following reaction with a presumably calcium-dependent receptor, and a much later entry of vitamin into the cytoplasm to become exposed to enzymes and associated with an intracellular binder.


Proline recycling during collagen metabolism as determined by concurrent 18O2-and 3H-labeling. In a previous study where rat skin collagen was labeled with 180 in the hydroxyl group of the collagen hydroxyproline we noticed that the decat rate of this label was much faster than had been observed when the skin collagen hydroxyproline was labeled with oH in the prolyl ring. In this study a ratwas labeled concurrently with [1802] and [3H] proline and the rate of decline of both labels was determined in rat skin collagen hydroxyproline. After correction for growth dilution of the skin collagen the [180] hydroxyproline was found to have a half-life of 27 days while the [3H] hydroxyproline had a half-life of 53 days. The decay rate of the [180] hydroxyproline represents the true turnover rate of collagen since there is no possibility of recycling this label. Hence, the difference between this and the [3H] hydroxyproline decay rate is due to recycling of L-[3H] proline into new collagen. The efficiency of recycling of proline from catabolized collagen into new collagen was about 93%.


Multi-exponential analysis of plasma free amino acid kinetics in the rat. A multi-exponential analysis has been made of the curve of decreasing specific radioactivity with time after intravenous injection of a mixture of (U-14C)-labelled amino acids in rats. The data were shown to accord well with a linear model which was tested using an approximate linear regression method. This confirmed the satisfactory fit of the data to the model. Values for total entry into and of irreversible disposal from plasma were calculated and the extent of external recycling of amino acids obtained by difference.


Synthesis of a fluorogenic mucopolysaccharide by chondrocytes in cell culture with 4-methylumbelliferyl beta-D-xyloside. Culture of chondrocytes in the presence of 4-methylumbelliferyl beta-D-xyloside resulted in a synthesis of protein-free, fluorogenic chondroitin sulfate which was heterogeneous on DEAE-cellulose chromatography. Degradation of the major chromatographic fraction with chondroitinase-ABC yielded, in addition to a large quantity of delta4-glucuronic acid-containing disaccharides, two fluorogenic oligosaccharides of different size. Quantitative analysis showed that delta4-glucuronic acid, galactose, xylose, and 4-methylumbelliferone were present in the small oligosaccharide fragment in a molar ratio of 1:2:1:1. Since these analytical data are analogous to those reported for glycopeptides derivedfrom proteochondroitin sulfates, it may be suggested that 4-methyl-umbelliferyl beta-D-xyloside replaces the need for xylosyl protein core in the normal synthesis of proteochondroitin sulfate with a resultant production of the unusual polysaccharide bearing the added xyloside at the reducing end.


[Evoked automatism (repeated responses) of cat cardiac ventricular fibers]. Repeated responses (RR) of cat papillary muscle fibres have been studied. Threshold current of the occurrence of repeated responses (2t) and saturation current (Is) on the accomodation curve have been determined. Two zones of autooscillations were revealed according to the ratio brage from low levels of the membrane potential (-80 divided by -55 mv). The second RR zone (It is not equal to Is) was activated in more than 70 per cent of preparations in the average from higher levels of the membrane potential (-40 mv and higher). A comparison was carried out between muscle and specialized fibres RR. The experimental data were analysed by the method of phase plane.


[Uniform polarization of fibers and syncytial structures by extracellular electrodes]. The method is described which enables to measure the voltage-current relations of the membrane of fibres and of syncytial structures by means of the current passed through the extracellular electrodes. The method is based on such a distribution of extracellular resistances that the polarization of the membrane was uniform on a large area. For this purpose the extracellular longitudinal gradient of potential had to increase linearly as a function of distance from one of the edges of the preparation. Such a distribution of potentials was achieved by passing current along the conducting agar-layer, the thickness of which decreased with distance from the edge. The length of the agar-layer where the longitudinal potential gradient increased must be large in comparison with the space constant. It is shown that in the zone where polarization is uniform the density of the current crossing the membrane is proportional to the current passed through the preparation independently on the membrane resistance. The method was applied for measuring the voltage-current relations of the horizontal cell membrane in the fish retina.


[Electrical connections between myocardial fibers and genesis of the electrocardiogram]. The ECG genesis was analysed in the light of electric anisotropism of myocardium. The radial dipole P-r of interfiber currents for man's heart is estimated to be 50 mV with cm-2. These currents could be essential in ECG generation.


[Theory of syncytial tissues. II. open syncytiae]. An infinite opened syncytium besides a common description as an infinite tree may be presented as a periodical structure and as a net with infinite dimensions. The first presentation singificantly simplifies the solution of the problem concerning the inpuf resistence, the second one-that concerning potential distribution. The third one permits an evaluation of asymptotics of the electrical properties of the nets with finite dimensions with the growth of their dimensions. It has been shown that the electrical properties of the opened syncytiae as infinite nets do not differ much from the threedimensional ones, and therefore they can be used as convenient models of real threedimensional tissues for practical calculations.


[Study on the Noble model of the synchronization of spontaneously active myocardial cells connected by highly permeable contacts]. Synchronization of two cells differing in sodium permeability has been studied. More frequent contractions of myocardial cells under synchronization described in [3], when the frequency of simultaneous excitation of cells is higher than that of each of them before the contact, can be explained by the electrical properties of the membranes of myocardial cells.


[Role of functional reorganization of the receptive fields in forming a relationship between visual acuity and pupil diameter]. A visual acuity of the human eye with correction is independent of pupil diameter within the 8 mm to 2 mm. The effect of functional reorganization of receptive fields compensate the influence of the change of optical quality of the eye as it is shown with the help of a model.


[Calculation of elementary components of evoked potentials]. The mean electric field in nerve tissue generated by the activation of a single synapsem and all synapses of a single axon are calculated.


[Mathematical modeling of the dynamics of biokinematic chains]. The method of mathematical modelling of the dynamics of biokinematic chains based on the application of Lagrange equations is considered. An algorythm of determining articulate moments in the matrix form. As an example of the biokinematic chain a model of man's upper extremity is considered. Correctness of the model and of the system of differential equations describing its dynamics is proved experimentally.


[Reproduction by means of a methematical model of the dynamic characteristics of human vertical posture maintenance]. Some peculiarities of invisible oscillations of man's body during his standing are reproduced using a mathematical model. The stability of the corresponding dynamic system with two delayed feedbacks and its behaviour in response to irregular and regular effects has been investigated. The results are compared with the experimental data. It is suggested that the mathematical model satisfactorily reflects principal peculiarities of the process of equilibrium support of man's body.


[Letter: Temperature dependence of myosin fluorescence]. It was shown that an increase of temperature (from 0 to 37 degrees C) did not affect the maximum position of the myosin fluorescence spectrum and relative contribution of tyrosine to fluorescence intensity. The spectral band width increases to 2-3 nm. The I (t-o) relationship permits us to sugges that the temperature change causes structural changes of myosine molecules.


[Letter: Hemoglobin equilibrium with carbon monoxide in conditions of incomplete photodissociation]. Change of human hemoglobin equilibrium with CO was studied during short-term illumination. The change of the saturation curve of Hb is discussed taking into account an increase of free gase concentration in solution accompaniing the photodissociation.


[Letter: Change in the amplitude of miniature potentials due to analgesics]. A decrease of the amplitudes of miniature end-plate potentials is observed in the presence of analgesics (promedol, tecodine, estocine).


[Letter: Nature of concentration quenching of luminescence in chlorophyll solutions]. Luminescence yield, absorption spectra and molecular weight dependence of chlorophyll in methylethylketone and n-hexane on concentration was investigated. It was shown that the quenching of luminescence in solutions was determined by the association of pigment molecules.


[Letter: Study of the interaction of histones F1, F2b, F2a1, F3 with nucleotides by the method of high resolution nuclear magnetic resonance]. Interaction of nucleotides with histones F-1, F-2b, F-2a1, F-3 have been studied by NMP method. It has been found that the interaction of nucleotides with histones increase in the line F-1. F-2b, F-3, F-2a1. It is suggested that histone F-1 is bound with the nucleotides mainly by electrostatic forces. Bounding of histones F-2a1 and F-3 with nucleotides is due not only to electrostatic sinteractions but also to more specific bonds of the base ring with protein.


[Semiempirical calculation of the relation of the interaction energy between complementary pairs of nitrogenous bases to nucleic acid conformational parameters]. The calculations of interaction energy between complementary base pairs of nucleic acids in the function of 5 variables determining parameters of double helix (Arnott's parameters) have been carried out by the method of atom-atom potential functions. Four of these parameters are essential in the case of mutual positions of bases corresponding to conformational A-family, and only two parameters (the distance between pairs along helical axis and the angle of rotation around this axis)--in the case of B-family. Positions of the interaction energy minima over each of the essential variables are close to experimentally determined parameters. The interaction energy minima are more pronounced for A-family conformations. The positions of minima in this case are determined by dispersion and short range repulsion energy.


[Letter: Effect of a reversible increase in plasma membrane permeability of plant root cells during deplasmolysis]. The studied effect of a reversible increase of permeability of plasmic membranes of plant root cells does not depend on chemical nature of plasmolys-inducing agents. This effect is conditioned by the process of deplasmolysis itself. It is suggested that the process of reversible depolimerization of the protein component similar to F-action and located in the membrane polar regions.


[Letter: Effect of lipid peroxidation on the permeability of liposome membranes for Ca2+ ions]. Efflux of Ca2+ ions from liposomes after peroxidation of their lipids was studied using fluorescent assay with chlorotetracicline. It was shown that products of lipid peroxidation disturbed the stability of liposome membranes and increased their permeability for Ca2+ ions.


[Letter: Velocity of passive conductance in a branching fiber]. The explicit formula  for the conduction velocity of the electrotonic potential in the fiber with infinitely long branches is obtained.


[Letter: Work of the impulse section of the horseshoe bat echolocator]. Peculiarities of location impulse of Rhinolophidae bring about a distinctive combination of dopler and impulse parts working almost independently, in its locator. In particular the range of the effect of impulse locator connected with the presence of LFM splash in the end of location cry is determined by the value of the period of its repetition. The existence of a long monofrequent part of locaion impulse providing the work of acholocator dopler part due to its narrow bands presents only a comparatively small obstacle to the impulse locator.


[Letter: Analysis of the lateral stability of the protofibril lattice in the a-disk of striated muscle]. The stability of a long cylinder system in electrolytic solution is calculated numericaly, suggesting that the equibrium arises from the balance between electrostatic and disperion forces. The influence of such parameters as Hammakker's constant, ionic strength and surface potential are considered. Our results show a much better agreement with X-ray difrecation experimental data, than the results of approximate calculation do.


[Letter: Transfer of neutral excitation from photosystem 2 to photosystem 1 in higher plants]. Arguments pro et con the hypothesis about the transfer of neutral excitation between photosystems have been studied qualitatively; experiments which could help to solve this problem are proposed.


[Study of the hydration of nucleic acids (DAN and RNA) and their derivatives by an ultrasonic method]. Adiabatic compressibilty and the values of hydration of nucleic acids (DNA and RNA) and their derivatives: nucleosides, (cytidine, adenosine, uridine) and adenine nucleotides (AMP, ADP, ATP) in neutral aqueous solutions at T= 25 degrees C have been calculated from the data of measuring the rate of ultrasound propagation and other parameters. The data obtained well agree with the results of other methods.


[Sorption of water on biopolymers].

[Sorption of water on biopolymers]. NMR-spin echo and dielectric studies of water in biopolymers have been carried out. According to the data on the relationship between the time of spin-spin relaxation, the energy of movement activation and electroconductivity, and moisture-bearing it can be concluded that water sorption on biopolymers of the type of gelatin, starch, cellulose up to a certain humidity value takes place in a vacuum. With an increase of moisture-bearing the process of sorption may be presented as a solution of low-molecular substance in a high-molecular one.


[Photochemiluminescence of tryptophan-containing peptides and proteins during photooxidation. V. Effect of cysteine on the photochemiluminescence of glycyltryptophan solutions]. The action of temperature in the range of 10-40 degrees C on the main characteristics of photochemiluminescence in glycyltryptophane solutions at cystein addition is studied. The changes in photochemiluminescence upon cystein addition are connected with reaction of peptide peroxy free radicals with cystein. The rate constant of this reaction appeared to be 4 with 10-7 times exp (-9000 plus or minus 1000/kT) with M-1 sec-1.


[Possible structure of myosin filaments in vertebrate striated muscle]. A 3-D molecular packing of the thick filament is proposed, which is based on the results of a study of the geometrical possibilities of packing together molecules of definite size into a helical filament with definite coordinates of cross-bridges (heads of molecules). There are 18 molecules in the cross-section of the suggested model of the thick filament, 6 in the inner and 12 in the outer hexagonal layer. The helical line of molecules in the outer layer has a pitch of 12 times 14.3 equals 171.6 nm; the tails of the molecules in the inner layer are parallel to the axis of the filament. As the thin filament has a right screw sense (Depue, Rice. 1965), and our rotatory sliding mechanism of contraction requires certain rotatory contacts between the corss-bridges of both filaments, the molecules in the thick filament should have a left screw sense.


[Excitation energy transfer between chlorophyll a molecules in detergent solutions]. Chlorophyll-a absorption and luminescence as well as the transfer of electronic excitation energy between chlorophyll-a molecules were studied in micellar solutions of triton X-100 as a function of both chlorophyll-a and detergent concentrations. It is shown that the spectral properties of chlorophyll-a are closely related to the ratio between the concentrations of X-100 and chlorophyll-a. Concurrent evaluation of the curves for depolarization and relative quantum yield of fluorescence show that two different mechanisms of energy transfer are involved: energy transfer between monomers of chlorophyll-a, and energy transfer from excited monomers to aggregates of chlorophyll-a. Using the theoretical value for the critical distance of energy transfer (Ro=56-58 A) as well as experimental data from depolarization and fluorescence curves for solutions containing 3-10-3 M triton X-100 we determined the local concentration of chlorophyll-a in the detergent micelles.


[Interaction of pancreatic RNAase A with platinum ions]. Complex formation between RNAase and Pt(II) has been studied by gel filtration and conductometry, and spectrophotometry. Existence of three strong binding locations with the binding location of 2 times 10-4 M-1 has been stated. Effect of Pt(II) on hydrolase activity of RNAase Ahas been investigated. An inhibiting effect showed itself at high concentrations of platinum ions. A conclusion has been made concerning the nature of groups participating in complex formation with Pt(II). Modification of three methionin residues does not influence the enzyme activity at 24-48 hour preincubation.


[Mechanism of photooxidation of porphyrins with oxygen]. Dependence of quantum yield of porphyrines photooxidation with oxygen on their concentration has been shown. Sensitized by some porphyrines oxidation of other ones with oxygen has been studied in relation to concentration, intensity and wave length of absorbed light, quantum yield, interconversion and life time of the molecules in triplet state. Common mechanism for direct and sensitized photooxidation has been suggested.


[Receptor potential fluctuations in a pacinian corpuscle]. On the basis of the model proposed earlier fluctuations of the receptor potential and their dependence on the value of the latter are calculated. It is shown that the model of the corpuscle as a sum of independent mechanosensitive channels with fluctuating conductivity agrees satisfactorily with the experimental data.


[X-ray diffraction study of muscles in disease]. Structural parameters of muscles in some diseases have been studied using X-ray diffraction methods. Fixed parts of muscles dissected in the operation correcting the vertebrate shape were used as samples in the case of patients III-IV stage of scoliosis muscles. The sarcomere protofibrillar lattice in muscles was found to be retained until the destruction of the muscle tissue; no differences between the muscles from the convex and concave sides of the vertebrate were observed. This seems to be an evidence of functional inertia of the diseased muscles and of their atrophy. Fixed parts of myocardial muscles taken during surgical correction were used as samples in investigating the Tetralogy of Fallot heart disease in children. A disturbance of packing parameters of the protofibrillar apparatus was observed in a significant part of the apparatus volume. In the case of critical experimental heart deficiency in dogs the protofibrillar lattice structure was retained, probably due to its resistance nature.


Quantitative description of the sodium conductance of the giant axon of Myxicola in terms of a generalized second-order variable. A variety of experimental observations in Myxicola and other preparations indicate that the sodium conductance, gNa, has properties quite different from those described by the m and h variables of Hodgkin and Huxley. A new quantitative description of the gNa is presented in which the gNa is assumed to be proportional to the fifth power of a generalized second-order variable, i.e., gNa = g'Na times v to the fifth, v = -Kav + K2U = K3, U = K4U + K5v + K6. This model is shown to be able to quantitatively simulate all of the experimentally observed behavior of the gNa. A view of the sodium gate consistent with these kinetics is to imagine it to be composed of five independent subunits, each of the type A eq. B eq. C eq. A where A represents the resting state, B the conducting state, and C the inactivated state. A model in which the subunit is of the type A eq. B eq. C could not simulate the experimental observations. It was concluded that two processes are sufficient to account for all of the behavior of the gNa.


[Adaptation to darkness and far red light of leaves of higher plants in conditions of oxygen deficiency]. The adaptation process of the leaves of higher plants to dark and far red light under the conditions of oxygen deficiency was investigated. The reaction constant for the oxidation of the electron carrier molecules with oxygen in the dark was obtained and found to be 1.4 with 10-3 M-1 min-1.


[Free radical oxidation of biological membrane lipids. IV. iron salts in peroxidation catalysis of linoleic acid]. The validity of Nernst law for oxidative-reductive pair Fe3+:Fe2+ and absence of reproducible potential for pure solution of linoleic acid is shown. The value of Eo is calculated. It is found by comparing ORP values and spectrophotometrically measured concentrations of hydroperoxides that: 1) the rate of accumulation of hydroperoxides is determined by the initial concentration bivalent ferrum salt and seems not to depend on the kinetics of further change of ORP in the system; 2) during oxidation of linoleic acid the stationary concentration of Fe3+:Fe2+=40:1 is established which is independent of the initial concentration of ferrum ions; 3) ORP zone necessary for maximum rate of catalysis of free radical oxidation of linoleic acid in methanol lies in a more positive region than normal ORP of the pair Fe3+:Fe2+.


On the theory of ionic solutions.

On the theory of ionic solutions. One of the purposes of this paper is to assess the degree of applicability of the nonlinear Poisson-Boltzmann equation. In order to do this we compare the thermodynamic properties calculated through this equation with Monte Carlo data on 1-1 and 2-2 electrolytes described by the restricted primitive model, in which the ions are modeled by hard spheres with a coulombic potential and the solvent is modeled as a continuum dielectric medium of uniform dielectric constant epsilon. We choose Monte Carlo data rather than real experimental data since all parameters are completely specified and there is no liberty for "adjustment." Thus this serves as a definitive test. In addition, we present a simple but numerically accurate alternative approximation scheme which is not only numerically superior to the Poisson-Boltzmann equation but avoids the necessity of solving a nonlinear partial differential equation which is approximate in the first place. The new approximation scheme that is presented here is suggested by recent developments in the statistical mechanical theories of ionic solutions which are reviewed in the Introduction. Although these theories themselves yield exceedingly good comparison with experimental (Monte Carlo) data, they involve fairly advanced theoretical and mathematical techniques and do not appear to be readily solvable for other than very simple geometries. The two approximations suggested here require only the solution of the linear Debye-Hückel equation, which has been solved for a variety of systems. These two approximations are simple to apply and yield good thermodynamic properties up to concentrations of 2 M for the restricted primitive model. In addition, they have a sound theoretical foundation and are offered as a substitute for the difficult-to-solve nonlinear Poisson-Boltzmann equation.


[Temperature dependence of the intensity of long-wave fluorescence of leaves of higher plants]. Continuous change of fluorescnece intensity with the maximum of 735 mu (F735) has been investigated in higher plants leaves at emperature decrease up to that of liquid nitrogen. F 735 remains approximately constant at temperature decrease up to -60degrees C. In temperature range -60divided by -80 degrees C the intensity F 735 increases. This increase proceeds up to-160 degreesC. Such temperature relationship is not changed with the addition of Mg+ ions. Speculations are presented concerning the nature of such relationships.


Quenching of excited chlorophyll A in vivo by nitrobenzene. Nitrobenzene exerts a dual effect on the excitation of chlorophyll a(Chl a) in vivo. (a) A 3(3,4-dichlorophenyl)-1,1-dimethylurea-inhibited quenching that manifests as a partial inhibition of variable chloroplast fluorescence and of 2,6-dichlorophenol indophenol (DCPIP) photoreduction and saturates at ca. 5-10 muM. Since nitrobenzene is not a Hill oxidant, this effect is attributed to a catalyzed back flow of electrons from intersystem intermediates to pre-photosystem II oxidants. (b) A direct quenching of the excited Chl a in vivo. This effect has a threshold of ca. 100 muM nitrobenzene; at higher concentrations it leads to almost complete suppression of chloroplast fluorescence and DCPIP photoreduction. Tris-washed chloroplast enriched in the photosystem II reaction center species Z+Q- and ZQ- are nearly four times more sensitive to nitrobenzene quenching than those enriched in Z+Q. On the other hand, normal chloroplasts are about 10 to the fourth times more sensitive. Hence, it is argued that the extreme sensitivity of normal chloroplast fluorescence is not due to a preferential association of nitrobenzene with a particular redox species of the reaction center.


Phase transitions in planar bilayer membranes. Temperature-dependent structural changes in planar bilayer membranes formed from glycerol monooleate (GMO) dispersed in various n-alkane solvents (C12-C17) have been studied using precise measurements of specific geometric capacitance (Cg). Cg generally increases as temperature (T) decreases. A change in the slope of Cg(T) occurs between 15 and 18 degrees C for all solvent systems examined. Measurements of the interfacial tension (gamma) of the bulk GMO-alkane dispersions against 0.1 M NaCl show that gamma generally decreases with decreasing temperature. The data can be fitted with two straight lines of different slope which intersect on the average at 17 degrees C. Pagano et al. (1973, Science (Wash. D.C.). 181:557) have shown using calorimetry that GMO has a phase transition at about 15 degrees C. Thus, the changes in Cg and gamma with temperature are likely to result from a GMO phase transition. A second structural change is observed to occur between 5 and 10 degrees C which has not been detected calorimetrically. Calculations of Cg based on various estimates of the hydrocarbon dielectric coefficient (epsilon-b) and/or hydrocarbon thickness (delta-b) leads to models for the structure of the bilayer above and below the phase transition temperature.


[Responses of the mesenteric microcirculatory bed of rats with experimental renal hypertension to histamine and adrenaline]. Reactions of the blood flow and of the diameter of mesentery arterioles were studied in vivo after the application of histamine (100--500 gamma) and adrenaline (1--10 gamma) in normal rats and in the animals with renal hypertension. A decrease of sensitivity of the microvessels, 10--30 mu in diameter, to the action of these substances was shown in the animals with hypertension.


[Qualitative features of erythropoiesis in men and animals adapted to prolonged hypoxia]. A three-month adaptation to hypoxia was shown to cause not only a quantitative increase in the erythropoietic bone marrow function, but also its qualitative change. This was indicated by a gradual increase in the proliferative activity of all the cells of the erythroid series, including such young cells as basophilic normoblasts and erythroblasts; an increase in the intensity of DNA synthesis; a cut of the reticulocyte maturation period and of the mean duration of erythrocyte survival in the peripheral blood. It is supposed that the whole vital cycle of erythocytres from the time of their origination in the bone marrow--to their death in the peripheral blood was accelerated.


[The effect of loading liver lysosomes with triton WR 1339 on the development of chronic toxic hepatitis]. Preliminary administration of triton WR 1339 produced a favourable effect on the course of chronic toxic hepatitis. This was expressed in a reduction of necrotic zones, a delay in development of connective tissue and in improvement of the functional capacity of the liver. Lysosomes of the liver of animals subjected to the action of CCl-4 under conditions of preliminary administration of a detergent were more stable to the injurious actions in vitro.


[Suprasegmentary inhibition and facilitation following administration of tetanus toxin to nuclei of the medulla oblongata (concerning the "starting point" phenomenon)]. Changes in the descending inhibition and facilitation produced by stimulation of the fastigial nucleus of the cerebellum after injection of tetanus toxin into the relay-nuclei of the medulla oblongata were studied in experiments on cats under light nembutal-chloralose anesthesia. The toxin was used as an agent distributing the inhibitory processes. Injection of tetanus toxin into the indicated nuclei was followed by increase in the functional dispatch formed in these nuclei. This was manifested in a repeated increase in the descending inhibition (in case of injection of tetanus toxin into the giganto-cellular nucleus) and the descending facilitation (in case of injection of the toxin into the Deiter's nucleus and the ambigus nucleus), a sharp increase in their intensity to the maximum and their marked lengthening. The data obtained are explained on the basis of the concepts of formation of powerful generators of excitation in the complex relay switching connected with disturbance of the inhibitory mechanisms. The results of these investigations extend the "dispatch station" concept as applied to the supraspinal structures.


[Inhibition of tetanus poisoning by vitamin B-1]. It was shown in experiments on rabbits that preliminary injections of vitamin B-1 with their continuation after the administration of tetanus toxin increased the animal resistance to tetanus. A more distinct protective effect was noted after the administration of tetanus toxin in vitamin B-1 solution. A tendency to increase of resistance was observed after the use of the vitamin 2 hours after the toxin injection.


[Corticofugal influences of somatosensory areas of the cortex on signal transmission in the posterior ventral nucleus]. Acute experiments were conducted in cats under nembutal anesthesia. A study was made of responses in the thalamo-cortical fibers coursing to the first somato-sensory area of the cortex to the electric stimulation of the fibers of the medial lemniscus. Application of penicillin to the somato-sensory cortex and development of epileptoid activity considerably diminished the amplitude of the responses in the thalamo-cortical fibers. The first somato-sensory zone proved to be much more effective than the second one. The appearance of the epileptoid activity in the projection cortex considerably diminished the inhibitory process in the posterior ventral nucleus; this was revealed by giving paired stimuli to the medial lemniscus.


[The effect of alcohols on mitochondrial monoamine oxidase activity]. Effects of alcohols on the activity of mitochondrial monoamine oxidase (MAO) were studied using rat liver mitochondria and highly purified MAO preparations from rat and pig liver. It was shown that benzyl, beta-phenylethyl and octyl alcohols caused a competitive and reversible inhibition of deamination of tyramine, 4-amino- and 4-metoxy-derivatives of beta-phenylethyl amine and practically failed to affect deamination of beta-phenylethyl amine and its 4-chloro-derivative. The inhibitory properties of aliphatic alcohols were exerted only when the carbohydrate chain had the length of five methylene residues.


[The blocking action of snake venom polypeptides on the cholinergic mechanisms of leech dorsal muscle]. The blocking action of alpha-polypeptides from the venoms of elapid snakes (Bungarus multicinctus and Naja naja siamensis) was studied on leech dorsal muscle. It was shown that these neurotoxins failed to inhibit the responses to mononitrogen cholinomimetics (acetylcholine, nicotine, carbamylcholine, etc.). The capacity of neurotoxins to inhibit the responses to the bisquaternary cholinommimetics depended upon the length of the molecule. The neurotoxins were active against the "shorter" cholinomimetics, such as decamethonium, and bischolinic esters of malonic, succinic and glutaric acids. The "longer" cholinomimetics (bischolinic esters of adipinic, pimelic, suberic, azelaic, sebacic acids retained their full activity after the treatment of leech dorsal muscle by neurotoxins. Possible explanations of the selective action of neurotoxins are discussed.


[The protective effect of serotonin against the depolarizing influence of aminazine on the membrane potentials of mouse embryos, in vitro, at the 2-blastomere stage]. The action of chlorpromazine, serotonin and prostaglandin F2-alpha on the cellular membrane potential of 2-cell mouse embryos, as well as a protective effect of serotonin and prostaglandin F2-alpha against the inhibition of the membrane potential by chlorpromazine were studied. Chlorporomazine (1.10-5 g/ml) proved to induce a strong decrease of the membrane potential, but serotonin, prostaglandin F2-alpha were ineffective. Serotonin (1.10-4 g/ml) prevented the action of chlorpormazine (2.10-6 g/ml), whereas prostaglandin F2-alpha (4-8.10-6 g/ml) was ineffective in this respect.


[The ultrastructural immunomorphology of antibody synthesis]. Antibody genesis in the lymphoid cells of C3HA mice was studied using horse radish peroxidase as an antigen. The zones of synthesis and concentration of antibodies within the immune competent cells were primarily the perinuclear space and the tubules of the granular endoplasmic reticulum. Less activity of the reaction was exhibited by the lamellar component of the Golgi apparatus and on the polyribosomes.


[The effect of stimulators of immunoglobulin biosynthesis on the phenomenon of lymphocyte transformation by macrophages]. The effect of pyrogenal and of the adjuvant of Freund's type on transformation of blood lymphocytes into macrophagal cells was studied. Experiments were conducted on rabbits with the use of the method of lymphocyte culture in vitro. These stimulants of immunogenesis increased the intensity of the process of lymphocyte transformation in a culture. It was also noted that action of pyrogenal and of complete adjuvant of Freund's type was expressed as soon as the first day after the administration. As supposed, there existed an interrelationship between the capacity of lymphocytes to transform into cells of macrophagal type and formation of immunological response of the organism.


[Electrophysiologic characteristics of fibers of the eyebrow-ear muscle of rabbits]. By intracellular leading off of potentials a study was made of an electrophysiological characteristics of the fibers of the eyebrow-auricular muscle in rabbits anesthetized with urethane. The muscle fibers were stimulated by current impacts, 5 msec in duration with the frequency of 5 pulse/sec. Membrane rest potentials, amplitudes of action potentials, duration of action potentials and latent periods had mean values typical of the muscle fibers of phasic type. A conclusion was drawn that the fibers of the muscle under study were homogenous and belonged to the phasic type.


[Ultraviolet and visible chemoluminescence of mouse liver under different thermal regimens]. It was shown that following a 10-minute maintenance in the exposed liver of a temperature of 30 degrees C, subsequent chilling (by 5 degrees C) led to degradational radiation of both the visible and the UV part of the spectrum. The presence of UV item is explained by a greater energy level of unbalanced molecular constellations in the cell substrate at 30 degrees C in comparison with the action in the previous experiments, in which only a visible component was registered after cooling. A greater metabolic level at 30 degrees C was also indicated by the curves of changes in the rectal temperature at various thermal regimens.


[An electron-autoradiographic study of RNA transfer from nucleus to cytoplasm]. By electron-autoradiographic study of the RNA synthesis in the hepatocytes of mice there were revealed marked differences in the content of labeled RNA in the nucleoli of the same nucleus. The silver granule concentration was sometimes greater in the areas of the cytoplasm located near the nuclear membrane with the neighbouring nucleolus than in the rest of the cytoplasm. It is supposed that the nucleoli of the same nucleus synthesized the RNA at a different time, transfered it to the nuclear membrane and discharged the RNA into the cytoplasm also at a different time. Due to this the discharge of the RNA into the cytoplasm assumed a definite rhythm. The number of nucleoli and the frequency of discharge of the RNA portions into the cytoplasm can increase under pathological conditions.


[Cerebrovascular response in newborns].

[Cerebrovascular response in newborns]. It was shown by the plethysmographic method that, in contrast to adult animals, in the newborn rats the blood vessels of the cerebral hemispheres and of diencephalon while displaying a distinct response to oxygen, failed to react to carbon dioxide, the latter being attributed to the low carbonic anhydrase activity in the tissues of these portions of the brain.


[Obtaining distinct images of biological forms with the raster electron microscope]. Not only fixation of material, but also conditions of studying it in the raster electron microscope influence the quality of the image. In case the carbon or the heavy metal layer is thin there is danger during rapid scanning of charging the sample by the electron beam, the quality of the image thus becoming worse. It is best to study the biological samples at the two nominals of the accelerating voltage (for example, 10 and 4 kV); this permits to avoid mistakes in interpretation of the results. Neither the thickness of the carbon or the heavy metal layer not the different nominals of the accelerating voltage could influence the value of the information obtained if analysis with consideration to the physical basis of the image formation and experimental conditions were conducted in each individual case. The archives material fixated in common formalin can be used for the study in the raster electron microscope.


[Blood coagulation in man during a 3-week daily rg L(+)-ASCORBIC ACID ADMINISTRATION]. A daily dose of 4 g L (+) ascorbic acid administered for 3 weeks showed no significant influence on coagulation of venous blood, as determined by thromboelastography. The investigation was carried out on 11 healthy men aged from 25 to 45 with no history of abnormal blood clotting. The mean values of 7 different coagulation parameters are given, the differences in these parameters in individual subjects (before and after administration of ascorbic acid) being checked for significance by means of the Wilcoxon test for pair differences. The values found are comparable with those in the literature.


[Polymorphism of human erythrocyte-uridyltransferase (E.C.2.7.7.12). Studies on a sample of Berlin population]. In a random population sample in Berlin (West) the following Ut-frequencies were found: Ut1 0.938; Ut2 0.062. This is consistent with other results obtained in German populations.


Evidence of platelet complement-fixing and lymphocytotoxic anti-A-1 antibodies. 3 human antisera exhibiting non HL-A specific antibody were studied in micro-complement fixation with platelets and micro-lymphocytotoxicity. Screening studies as well as absorption and elution studies with platelets, lymphocytes and erythrocytes revealed an antibody activity associated with blood group A-1. Within blood group A-1, a subpopulation of A-1 donor cells- provisionally called "weak A-1" - was defined, which had a minor ability for complement-fixing and lymphocytotoxic A-1-antibody absorption. Contrary to HL-A specific antibodies, acid eluates from platelets of these 3 sera were always negative whereas heat and ether eluates gave positive results. From neutralization studies and studies on the hemolytic activity against A-1 erythrocytes it was concluded, that the A-1-specific antibodies probably are immune antibodies belonging to the IgG class of immunoglobulins.


[Possible errors in leukocyte count caused by carryover in the Coulter counter S]. In 163 samples of venous blood with significant leukocytosis (20 000 to 172000 cells pro mm-3) a carryover of 400 to 22000 leukocytes up to the third count of the following specimens (200 to 9300 cells/mm-3) could be observed. Even after 41 specimens of normal leukocyte range and low leukocytosis (6700 to 17700 cells/mm-3) in cases of extreme leukopenias (less than 2000 cells/mm-3) the correct result was exceeded by 500 to 1000 cells. In four additional machines of other laboratories a carryover of different extent could be reproduced. In comparison to samples of venous blood only a very small carryover into subsequent samples of isotonic solution was found. The considerable spreading of the coefficient of variation between 1.7 and 16.2% (arithmetic mean 7.1%) prohibited a mathematical correction of error. Erroneously too high numbers of leukocytes could be absolutely avoided by at least two repeated counts.


An alternative method of large scale plasma fractionation for the isolation of serum albumin. Human plasma may be separated into five fractions using the method described by Cohn in 1946. Although there are several drawbacks to alcohol precipitation, especially in albumin isolation, it is still used throughout the world. This paper describes an alternative procedure for albumin isolation from plasma or albumin-containing plasma fractions using a combined heat fraction/polyethylene glycol precipitation method. No polyethylene glycol is detected in the final product which is immunoelectrophoretically 100% pure, salt poor, heat resistant during pasteurization, and stable during long-term room temperature storage. The yield is at least 90% of the original plasma albumin. In comparison with the Cohn method, fractionation time and expense are significantly reduced.


Platelet adhesiveness and aggregation in congenital afibrinogenemia. An investigation of three patients with post-transfusion, cross-correction studies between two of them. Platelet adhesiveness and aggregation were studied in three patients with congenital afibrinogenemia. The results obtained may be summarized as follows: The retention of platelets to a glass-bead filter determined with the Salzman method was significantly decreased; it was normal after fibrinogen infusion. With a modification of the Hellem test the values obtained were slightly decreased. Adrenalin-induced aggregation was absent whereas ADP-and collagen-induced aggregation was near normal or slightly decreased. Thrombofax aggregation was absent in citrated plasma. The abnormalities of platelet aggregation were corrected after fibrinogen infusion or after addition in vitro of fibrinogen, hemofilia A plasma and PPP obtained from an afibrinogenemic patient after fibrinogen infusion. The abnormalities of platelet aggregation were corrected well by ADP, collagen and Thrombofax in heparinized blood, but only a slight correction of adrenalin-induced aggregation was noted. Thrombin aggregation proved to be normal with the higher concentrations, whereas it was defective with the lower ones. Ristocetin aggregation was normal in citrated plasma at the concentration of 1.5 mg per ml but it was absent at the lower concentration (1.0 mg per ml). Ristocetin aggregation was, on the other hand absent in heparinized blood regardless of the concentration. These findings are in agreement with the presence of a prolonged bleeding time in congenital afibrinogenemia and suggest that fibrinogen plays an important role in platelet aggregation and adhesiveness.


The response of the lower oesophageal sphincter to maximal doses of pentagastrin. Measurements of the lower oesophageal sphincter pressure and gastric secretion were made in patients with dyspepsia but no reflux and in patients with a hiatus hernia and reflux in response to a near maximal dose of pentagastrin. Patients with hiatus hernia had lower resting sphincter pressures than those with dyspepsia. The magnitude of the pressure rise following pentagastrin was related to the resting tone of the sphincter. However, in terms of percentage increase over resting sphincteric pressure, patients with dyspepsia and patients with a hiatus hernia had similar response.


Relationship between changes in plasma gastrin and lower oesophageal sphincter pressure after meals. Changes in plasma gastrin and lower oesophageal sphincter pressure were measured in 20 subjects after a standard protein meal. Significant increases in both gastrin and sphincter pressure were seen. Peak gastrin response occurred an average of 19-5 minutes and peak lower oesophageal sphincter response 40-0 minutes after the meal. Both gastrin and sphincter pressure showed a wide spectrum of response. In 5 subjects there was no appreciable rise (less than 5 pg/ml) in plasma gastrin after the meal, and 3 of these had symptoms of oesophageal reflux. In this group there was only a small but nervertheless significant rise in lower oesophageal sphincter pressure (mean pressure rise 18-0 per cent of fasting value, p less than 0.05). Greater increases in sphincter pressure (mean rise 54-2 per cent, p less than 0.005) were seen in subjects with a moderate (up to 50 pg/ml) rise in plasma gastrin, and those with the most marked gastrin response (less than 50 pg/ml) showed the greatest rise in pressure (mean rise 80-3 per cent, p less than 0.0025). These results suggest that endogenous plasma gastrin is the main stimulus to the rise in lower oesophageal sphincter pressure after food. Subjects with a poor gastrin response to the meal have only a small increase in sphincter pressure and as a result may be more liable to develop gastro-oesophageal reflux.


A survey of the results of the Boerema anterior gastropexy for hiatus hernia over a 4-year period. The results obtained by using the Boerema anterior gastropexy for symptomatic hiatus hernia over a 4-year period are reviewed. All 68 patients were operated upon by the same surgeon. The success rate as judged by relief of the patient's symptoms was 90 per cent. It is felt that the operation has advantages such as to justify its wider use.


Atrophic gastritis in gastrectomy specimens. Examination of gastrectomy specimens has shown that atrophic gastritis and intestinal metaplasia are widespread and have the same distribution in cancer of the stomach as in gastric ulcer affecting the body. Their distribution is restricted to the distal part of the stomach in pyloric ulcer. After gastrojejunostomy the distribution is also like that seen in cancer. There is a close association of widespread atrophic gastritis and intestinal metaplasia with the development of cancer and a high cancer rate after stomach operation for benign conditions. The similarity of distribution of atrophic gastritis and intestinal metaplasia in the stomach with body ulcer to that in cancer and after gastrojejunostomy points to a higher cancer risk in the stomach containing a body ulcer.


A clinicopathological review of 68 carcinomas of the gallbladder. A clinical and pathological review of 68 patients with a primary carcinoma of the gallbladder was undertaken. A prolonged preceding history of biliary disease was noted. Preoperative radiological and biochemical investigations were not helpful, but an isolated elevation in serum alkaline phosphatase level in the absence of any biliary obstruction or hepatic dysfunction was noticed in some patients. The significance of stones in relation to pathogenesis is discussed. A more radical surgical approach involving a partial hepatectomy appears to be the only possible treatement in veiw of the mode of spread of this tumour and the bad overall prognosis.


The natural and unnatural history of pancreatic pseudocysts. Experience with 131 pseudocysts of the pancreas in 112 patients has been analysed with a view to answering specific questions. Spontaneous regression was documented in 8 per cent. Complications occurred in 33-5 per cent of the pseudocysts, including obstruction of adjacent organs, rupture, haemorrhage and pancreatic ascites. In 14 pseudocysts, rupture into the gastrointestinal tract, the peritoneal cavity or the pleural cavity when unassociated with haemorrhage, had a mortality rate of 14 per cent. Sixteen patients with significant haemorrhage associated with a pseudocyst had a mortality rate of 61 per cent; early direct surgical control is advocated. Pancreatic ascites was associated with 14-5 per cent of the pseudocysts and had a 40 per cent recurrence rate, which can be greatly diminished when operative procedures are guided by pancreatography. The mortality rate for the surgical treatment of 97 uncomplicated pseudocysts was 6 per cent and the recurrence rate was 11 per cent. The prime cause of death was haemorrhage. Seven of the 131 pseudocysts were synchronous and 12 were metachronous. The actual figure is probably higher. Small cysts of the head of the pancreas, impalpable at operation but demonstrable by pancreatography, may be the cause of severe, continuing or recurrent symptoms.


The occult osteomatous changes in the mandible in patients with familial polyposis coli. Characteristic radio-opaque lesions were detected in the manibular bone, most clearly on the panoramic X-ray, in 27 or 93-2 per cent out of 29 cases in 15 families with familial polyposis coli, including 21 cases without Gardner's stigmata, 7 cases with the incomplete syndrome and 1 with the complete syndrome. Only 3 out of 19 members of these families who were free from polposis had radio-opaque jaw lesions. The cases with polyposis of other types also showed a negative result. The radiological diagnosis suggested that the lesions were of the character of endosteoma. Our observation is considered to be significant evidence in the understanding of the pathogenesis of Gardner's syndrome as well as a useful method of the early detection of carriers in the polyposis family.


Torsion of the testis: a review of 22 cases. Improved diagnosis and earlier correction. Greater awareness of the possibility of torsion of the testis and earlier exploration has led to the saving of 14 out of 19 acutely twisted testicles.


Fatal cardiac tamponade and other mechanical complications of central venous catheters. A fatal cardiac tamponade caused by an intact polyethylene central venous catheter perforating the wall of the right ventricle is reported. A retrospective review of 105 central venous catheters used in an intensive care unit revealed a high incidence of catheter malposition and a 20 per cent mechanical complication rate. The possible causes of these malpositions and complications are discussed. Guidelines for the safer use of central venous catheters are presented.


The relationship between ultrasound assessment and angiography in occlusive arterial disease of the lower limb. The Doppler ultrasound technique has been used to assess the haemodynamics of the peripheral circulation in patients with arterial disease. Using this method the resting pressure index and the response after exercise of the systolic pressure at the ankle was determined in 62 limbs. Following exercise, four patterns of abnormal response to exercise were found and graded in severity from 1 to 4. A single aorto-iliac lesion was associated with a normal or slightly reduced resting pressure index but with a severe reduction of pressure (grade 3-4) after exercise. A single femoropopliteal lesion was usually associated with a low resting pressure index but only a slight (grade 1-2) fall after exercise. A low resting pressure index and a severe postexercise grade were found in patients with multiple occlusions. Disease of the profunda femoris artery was associated usually with both a low resting pressure index and a grade 3-4 post-exercise curve.


Secondary involvement of the penis by rectal cancer. Two cases of metastasis to the penis from a primary rectal carcinoma are described. The clinical features, treatment and prognosis together with the probable modes of metastasis are discussed. All previously reported cases of penile metastasis from the rectum are reviewed. It is suggested that contrary to previous reports that prognosis is not uniformly poor and hence a more aggressive attitude to treatment should be adopted. Metastatic lesions in the penis should also be considered as a cause of urinary obstruction following abdominoperineal excision of the rectum.


Idiopathic paroxysmal ventricular tachycardia in infants and children. Seven children with idiopathic PVT ranging in age from one day to 18 yr, have been observed during the past three years. The presenting complaints and frequency of paroxysms varied greatly. Three patients presented with syncope; four were asymptomatic. Lidocaine was effective in terminating acute symptomatic attacks; procaine amide and propranolol were effective in long-term control of the arrhythmia. Monitoring of the dynamic ECG was invaluable in establishing the diagnosis, characterizing the arrhythmia, and evaluating the effects of activity and therapy.


Operative repair of atrial septal defect without cardiac catheterization. Thirty-three children with secundum or sinus venosus atrial septal defects underwent operative correction at the University of Minnesota Hospitals between January, 1972, and December, 1973. Nineteen of these patients (58%) did not have cardiac catheterization as part of their preoperative evaluation, since clinical assessment of the child, with or without corroborative evidence obtained by echocardiography and radionuclide angiocardiography, provided sufficient information to permit recommendation of operation. In the majority of patients with uncomplicated atrial septal defect, cardiac catheterization is not a necessary part of the preoperative evaluation and may be reserved for those patients with unusual clinical or laboratory features.


Iron-deficiency anemia: evaluation of compensatory changes. Compensatory mechanisms in children with iron-deficiency anemia were evaluated by measuring erythrocytic organic phosphates and, in some cases, shifts in the P50 of the oxygen dissociation curve. In 19 children with nutritional anemia (hemoglobin values of 3.2 to 8.2 gm/dl) there was a calculated improved oxygen delivery to tissues equivalent to a hemoglobin level of at least 7.5 gm/dl. Transient decompensation was observed during acidosis. In five children with iron-deficiency anemia due to blood loss and in one child with rheumatoid arthritis no such compensatory changes were observed.


Erythropoietin excretion in the premature infant. Urinary erythropoietin was determined sequentially in four premature infants throughout their period of physiologic anemia. After the first day of life, no erythropoietin was found, even though there was a marked fall in hematocrit. Among seven premature infants with severe respiratory disease, three excreted elevated amounts of erythropoietin. Premature infants appear able to respond to hypoxia by increasing erythropoietin production. In the absence of hypoxia, however, diminution of erythropoiesis in the early weeks of life is not accompanied by elevated excretion of erythropoietin.


The relationship of concentrations of serum hormones to pubertal gynecomastia. Pubertal gynecomastia occurred in 20 to 29 boys who were followed for 24 or more months during puberty. Mean concentrations of LH, FSH, prolactin, testosterone, and estrone and estradiol were compared. Although levels did not differ between boys who developed gynecomastia and those who did not, when compared with the stage of puberty, changes were noted between mean concentrations from samples before and when gynecomastia was first noted. A significant increase of estradiol occurred with the onset of gynecomastia, while testosterone levels did not change; thus the testosterone-estradiol ratio decreased. Prolactin concentrations fell significantly with the onset of gynecomastia. These data indicate a difference of hormonal dynamics between boys with and without gynecomastia.


Copper infusion therapy in trichopoliodystrophy. The effect of repeated intravenous infusions of cupric salts was studied in two patients (cousins) with trichopoliodystrophy identified at the ages of 3 days and 2 and-one-half mo, respectively. The intravenous doses of copper were gradually increased and normal or near-normal serum values were achieved after 150 mug/Cu2+/kg were administered daily for 5 days. At that time the hepatic concentration of copper in the two patients increased from 14 to 38 mug/gm of dry weight from 7 to 45 mug/gm of dry weight, respectively, and the muscle homogenate exhibited the capacity to oxidize pyruvate-3-14C. Continued infusions of cupric salts in doses of 190-220 mug/kg/day once or twice weekly were necessary to maintain elevated hepatic and serum concentrations of copper. At 6 mo of age the younger infant had reached a functioning level of 4 mo. The older infant demonstrated progressive loss of neurologic functions and died at 15 mo of age. These observations suggest that the neurologic and biochemical dysfunctions of trichopoliodystrophy may be altered by infusion of cupric salts early in the course of the disease.


The LaBrosse VMA spot test revisited.

The LaBrosse VMA spot test revisited. The LaBrosse spot test, in our experience, is not very useful as a screening procedure since the majority of specimens give an intermediate reaction, representing a heterogeneous group which may include many patients with abnormal 24-hour VMA excretion. The test is helpful only if either "positive" or "negative" in the individual patient who presents symptoms or signs compatible with abnormal catecholamine excretion. It is also of value in following patients with catecholamine-secreting tumors. The clinician should be aware of the limitations of VMA screening tests as they exist to date, and should assure himself, as well, that a specific quantitative assay is used to confirm doubtful or positive screening test results.


Leukocyte count differences in healthy white and black children 1 to 5 years of age. A group of 150 healthy American black children were found to have neutrophil counts significantly lower than those of a similar group of healthy American white children. Absolute lymphocyte counts were similar in the black and white children. The lower neutrophil counts in black children may represent a genetic or hitherto unidentified acquired differences.


DNA polymerase activity in normal and malnourished rat placentas. DNA polymerase activity has been measured in placentas of normal and protein-restricted rats and correlated with the mean percent daily increase in DNA. During normal placental growth, increases in DNA fell rapidly from 13 to 19 days and polymerase activity using denatured DNA template showed a similar pattern falling from values of 10,000 mumu mols dAMP incorporated per mg DNA at 12 days of gestation to 3,100 at 19 days. Protein restriction during gestation reduced placental DNA content after 14 days; by 19 days the DNA content was 81% of normal. The increase in DNA between 13 and 19 days in placentas of malnourished animals paralleled the normal but was significantly lower. Malnutrition markedly reduced enzyme activity at 12, 14, and 16 days; at 19 days, when DNA synthesis has normally ceased, values of DNA polymerase were not different in control and malnourished placentas. Thus DNA polymerase activity using denatured DNA as template, as measured in vitro, was an index of proliferative cell growth in both normal and malnourished placentas. Furthermore, the decrease in enzyme activity in malnourished samples preceded by at least two days any measurable decrease in total placenta DNA content. It is suggested that future clinical application of this technique may provide an index of nutritional status in "at risk" pregnancies.


Iron intake and transferrin saturation in adolescents. The relationship of maturity, age, race, sex and income level to dietary intake and body stores of iron, as indicated by percent of transferrin saturation, was studied in healthy adolescents. Maturity rating, sex, and race were significant. Level of family income was not a significant factor. Both boys and girls increase the intake of iron as they mature, boys more than girls, and white adolescents slightly more than their black counterparts. Range of intakes was large, and there was no significant correlation between quantity of dietary iron and the percent of transferrin saturation. Norms for dietary intake of iron and percent of transferrin saturation, based on sex, race, and maturity, are presented for use by physicians and nutritionists.


Absorption of digoxin in children with cystic fibrosis. The absorption of digoxin in cystic fibrosis was evaluated in 16 subjects by assessing the relationship between dosage expressed in mug/kg/day and serum digoxin concentration. The results indicate that the same relationship exists between maintenance dosage and serum levels in these patients and in patients without cystic fibrosis. Thus, no evidence of impaired absorption was found.


Role of lymphography in carcinoma of the prostate. The results of bilateral pedal lymphography in 83 patients with adenocarcinoma of the prostate gland are presented. The patients were divided into two groups: 45 new cases and 38 late or old cases presenting several years after the onset of the disease. Altogether 25 of the new patients and 29 of the late patients had lymphographic evidence of lymph node metastases. The lymphogram results in relation to local tumour size, histological grade, the presence of skeletal metastases, and acid phosphatase levels are discussed. Of the new patients with T1 and T2 tumors--that is, those still localized within the prostatic capsule--41% had positive lymphograms. The inaccuracy of acid phosphatase estimations in detecting early extraprostatic spread is shown and compared with the greater accuracy of lymphography. Lymphography should be used as an initial investigation in all cases where aggressive therapy is being considered, and the importance of regular follow-up radiographs is emphasized.


Effect of maximal respiratory manoeuvres on bronchial sensitivity of asthmatic patients as compared to normal people. Cumulative dose-response curves to carbachol given by aerosol were established using plethysmographic measurements of specific airways resistance (SRaw) in 10 patients with asthma and five healthy subjects. Two experiments were performed--a control test and one in which maximal respiratory manoeuvres (MRM) (two maximal inspirations and two maximal expirations) were made before each carbachol inhalation. MRM did not modify the dose-response curves in the normal subjects. In the patients these manoeuvres enhanced the bronchoconstrictor effect of carbachol: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.373 mg to 0.189 mg (P less than 0.001). Bronchial provocation tests using methods which require MRM--for example, forced expiratory volume at one second--could overestimate the bronchial sensitivity of patients with asthma.


Haemolysis complicating viral hepatitis in patients with glucose-6-phosphate dehydrogenase deficiency. Out of 20 patients with viral hepatitis whose glucose-6-phosphate dehydrogenase (G-6-PD) levels were normal, 14 had clinical evidence of a mild to moderate degree of haemolysis but in all the patients studied the half life of chromium-51-labelled red cells was shortened. Out of 18 viral hepatitis patients deficient in G-6-PD 17 had clinical evidence of haemolysis, and in eight this was more severe than in the group with normal G-6-PD values. Massive intravascular haemolysis occurred in four, three of whom died. The massive haemolysis was attributed to the presence of additional drug-induced oxidative stress to the G-6-PD-deficient red cells.


Use by general practitioners of obstetric beds in a consultant unit: a further report. Of 1,700 women booked for delivery by general practitioner obstetricians in a consultant unit, 1,399 had uncomplicated deliveries and the co-operation between practitioner and consultant was an obvious advantage for the 257 who were transferred completely to consultant care during pregnancy, labour, or puerperium. The scheme, which started in 1964, has enabled general practitioners to continue to give complete obstetric care to their patients. The number of participating practitioners has, however, declined from 80 to 16 indicating that many preferred to concentrate on antenatal work.


Examination of the Distinctive Awards System. When they stopped secrecy, the consultants of an internationally-famous postgraduate teaching centre in psychiatry--not a designated teaching hospital--discovered that they had one-tenth the national average of distinction awards.  Subsequent investigation of the whole system suggests that this is not an isolated case.  Moreover, official figures are scanty and misleading.  This paper explores the difficulties in understanding, investigating, and influencing the system.  The composition of the committees involved, the de facto quota system, the method of collecting information, and the convention of secrecy are examined and critized.


Role of taurocholic acid in production of gastric mucosal damage after ingestion of aspirin. The possibility that aspirin-induced gastric mucosal damage may occur more readily in the presence of bile has been studied in man using measurement of transmucosal electrical potential difference as a marker of disruption of the gastric mucosal barrier. After the introduction of acetylsalicylic acid (600 mg) in suspension to seven subjects the mean electrical potential difference (plus or minus S.E. of mean) fell significantly from -33-3 plus or minus 2-0 mV to - 17-1 plus or minus 2-1 mV, and after the introduction of taurocholic acid (5 mmol/1) to seven other subjects the electrical potential difference fell significantly from -38-1 plus or minus 3-0 mV to-19-1 plus or minus 3-4 mV, the mean duration of these changes being 14-4 and 17-5 minutes respectively. When a combination of acetylsalicylic acid and taurocholic acid was introduced to eight subjects the mean electrical potential difference also fell significantly from -38-6 plus or minus 1-8 mV to -17-9 plus or minus 1-8 mV, but mean duration of this change (27 minutes) was significantly longer than that found after acetylsalicylic acid or taurocholic acid alone. These results indicate that the ingestion of aspirin, together with coincidental reflux of bile from duodenum, may be a factor in the pathogenesis of aspirin-induced gastric mucosal damage.


The HL-A system in asbestos workers.

The HL-A system in asbestos workers. In a study of the HL-A system in 56 selected asbestos workers referred to the Pneumoconiosis Medical Panel with definite or suspected asbestosis, the W 27 antigen was found more often than among a control population.  Six of the 10 asbestos workers with the W 27 antigen had definite radiographic evidence of asbestosis compared to 13 out of 46 without the W 27 antigen.  These observations, if confirmed, suggest that the W 27 antigen may provide a useful marker of an enhanced susceptibility to the tissue-damaging effects of asbestos dust.


Wife battering: a preliminary survey of 100 cases. One hundred battered wives were interviewed.  All had bruising, often together with other injuries, such as lacerations and fractures,  There was a high incidence of violence in the family histories of both partners, and of drunkeness and previous imprisonment among the husbands.  Netherless, both husbands and wives had wide range of educational achievements.  Mmost wives were subjected to repeated violence because they had no alternative but to return to the marital home;  There was an association between wife battering and child abuse.  Places of sanctuary are needed where a woman can take her children when violence is out of control.