Biochemical studies on the cell wall lipopolysaccharides (O-antigens) of Vibrio cholerae 569 B (Inaba) and El-tor (Inaba). Lipopolysaccharides were isolated from the cell walls of Vibrio cholerae 569 B (Inaba) and El-tor (Inaba). Chemical analysis revealed the presence of glucose, fructose, mannose, heptose, rhamnose, ethanolamine, fatty acids and glucosamine. The lipopolysaccharides do not contain 2-keto-3-deoxyoctonate, the typical linking sugar of polysaccharide and lipid moieties of enterobacterial lipopolysaccharides. Galactose, a typical core polysaccharide component of many gram-negative bacteria was also absent from lipopolysaccharides of these organisms. By hydrolysis in 1% acetic acid, the lipopolysaccharides have been separated into a polysaccharide part (degraded polysaccharide) and a lipid part (lipid A). Components of degraded polysaccharide and lipid A moiety were identified and determined. The lipid A fractions contained fatty acids, phosphorus and glucosamine. All the neutral sugars detected in lipopolysaccharides were shown to be the constituents of its polysaccharide moiety. The fatty acid analysis of lipopolysaccharide and lipid A showed the presence of both hydroxy and non hydroxy acids. They were different from those of lipids extracted from cell walls before the extraction of lipopolysaccharides. 3-Hydroxylauric and 3-hydroxymyristic acids predominated in lipopolysaccharide and lipid A of Vibrio cholerae and El-tor (Inaba).


Relationship between prostaglandin biosynthesis and the effect of insulin on hormone-stimulated lipolysis in rat adipose tissue. Lipolysis in rat fat pads was studied by determination of free fatty acid and glycerol production in various experimental conditions (in the absence or presence of glucose, adrenalin and insulin). These results were compared to the accumulation of endogenous prostaglandins E2 and F2alpha during lipolysis. In the absence of glucose the prostaglandin production followed the adrenalin-induced fluctuations in released free fatty acids both in the presence or absence of insulin. In the presence of glucose and insulin, a drop in prostaglandin accumulation was observed whereas free fatty acids production was strongly stimulated. These results suggest that either free fatty acid composition is modified, influencing the activity of prostaglandin synthetase, or that there exists a specific mechanism controlling prostaglandin synthesis.


125I derivatives of prostaglandins. A novel approach in prostaglandin analysis by radioimmunoassay. We report the production of radioactive iodinated (125 I) derivatives of prostaglandins E1, E2, F2alpha and their use in radioimmunological assays. Histamine or tyramine was coupled to the prostaglandins carboxyl group and the iodination was accomplished using the chloramine T method. The high specific radioactivity of these tracers and the resolution of the purification procedure allowed the detection of 0.5 pg of prostaglandins. A comparison with tritiated prostaglandin was made and showed a 10-fold gain in sensitivity. Furthermore in the case of the prostaglandin E1 system using 125I-labelled histamine or tyramine as tracer the cross reaction curves obtained were different from those obtained with [3H]prostaglandin E1; we suggest that the blocking of the carboxyl group alters the prostaglandin E1 structure, modifying its immunoreactivity.


Intra- and extracellular forms of lipoprotein lipase in adipose tissue. The location of lipoprotein lipase activity in rat adipose tissue was studied using intact epididymal fat pads, isolated adipocytes, and lipoprotein lipase activity secreted from adipocytes as enzyme sources. The enzyme activities of these preparations were characterized by gel filtration. The method used for isolation of adipocytes had been modified to minimize activation of lipoprotein lipase during the procedures. Extracts of intact adipose tissue separated into two major lipoprotein lipase activity peaks, designated "a" and "b", the "a" fraction representing about 30 (fasted rats) to 50% (fed rats) of the total enzyme activity. An intermediate fraction (designated "i") was frequently observed. Extracts of isolated adipocytes from fed rats contained about 35% and those from fasted rats about 65% of the lipoprotein lipase activity present in intact tissue. The "b" fraction constituted 80--97% of the adipocyte lipoprotein lipase activity. In contrast, the enzyme activity secreted from the adipocytes contained only the "a" and "i" fractions. These data implicate the existance of one intracellular form of lipoprotein lipase (corresponding to the "b" fraction), different from extracellular forms of the enzyme (corresponding to fractions "a" and "i"). A transformation of the intracellular to the extracellular forms appears to occur in conjunction with secretion of enzyme from the fat cell.


The age-related occurrence of wax esters in the mouse preputial gland tumour. The mouse preputial gland tumour (ESR-586) accumulates wax esters from between 20 and 25 days after transplantation until they become the most abundant lipid class. Prior to this time wax esters are not detectable. The process occurs in both male and female host mice and appears to be determined by a response of the host to the tumour, rather than by a property of the tumour itself. The most abundant fatty alcohol present in the wax esters is hexadecanol. This contrasts with the greater proportions of the C20 to C24 chains found for the alkyl portion of the alkyldiacylglycerols, for which the precursors are fatty alcohols.


Synthesis of anacardic acids in seeds of Ginkgo biloba. Anacardic (6-alkylsalicylic) acids and common lipids are efficiently synthesized by immature seeds of Ginkgo biloba. The seeds were incubated with 14C-labeled acetic, malonic and palmitoleic acids, glucose, and other potential precursors. Levels of 14C in common lipids and in anacardic acids, and the distribution of 14C in anacardic acids were determined. The results show that the salicylic moiety is synthesized by a polyketide pathway via malonic acid. The chain moiety for anacardic acid synthesis is in a different state of activation and/or site than chains that are used for synthesis of the common lipids. Labeled shikimic acid did not contribute 14C to anacardic acids, nor to other lipids, and palmitoleic acid was incorporated only into common lipids.


Isomerization of prostaglandin H2 into prostaglandin D2 in the presence of serum albumin. The prostaglandin endoperoxide, prostaglandin H2, decomposes in aqueous media mainly into prostaglandin E2. This paper shows that in the presence of serum albumin from a number of species prostaglandin H2 decomposes mainly into prostaglandin D2, an isomer of prostaglandin E2. The effect on endoperoxide decomposition exerted by serum albumin may well have physiological significance since intace endoperoxides can be released from tissues and since the biological properties of prostaglandins E2 and D2 are quite different.


Metabolism of erucic acid in the isolated perfused rat heart. In the present work the uptake and utilization of [14C]erucic acid by the perfused rat heart has been investigated and compared with those of [14C]-palmitic acid. Both fatty acids were found to be taken up by the heart at the same rate. On the other hand, the incorporation of erucic acid into tissue lipid during 30 min perfusion were significantly high and CO2 production low as compared with palmitic acid. Incorporation of erucic acid into diacylglycerol, triacylglycerol and cholesterol ester was considerably higher than that of palmitic acid. During a 30-min period, a large amount of [14C]erucic acid was accumulated in tissue fatty acid fraction. Similarly, relatively high labelling was found in the fatty acid and diacylglycerol fraction during the initial 300 s of perfusion with erucic acid. When [14C]erucic acid and unlabelled palmitic acid was used, the radioactivity was very high in the fatty acid fraction of the heart lipid in comparison with the experiment when [14C]palmitate and unlabelled erucic acid was used. Therefore, erucic acid is poorly oxidized by the heart and is preferentially incorporated into heart lipids. There was relatively high incorporation of [14C]erucic acid into diacylglycerol and addition of unlabelled palmitic acid tended to decrease it, probably converting more diacylglycerol to triacylglycerol. When [14C]palmitic acid and erucic acid were used together, incorporation to triacylglycerol was high and diacylglycerol low. These results, therefore suggest that palmitic acid is a more suitable acyl donor than erucic acid for the C-3 position of triacylglycerol, especially when the diacylglycerol contains erucoyl moieties.


Effects of detergents and choline-containing phospholipids on human spleen glucocerebrosidase. 1. Glucocerebrosidase, extracted from human spleen lysosomal membrane by sodium cholate and recovered in a high speed centrifugation supernatant, aggregated following removal of the detergent. 2. Re-solubilization of the enzymatic activity from the aggregate was achieved by treatment with the non-ionic detergents Triton X-100 and Tween 20. The anionic detergents sodium cholate and sodium taurocholate and the cationic detergents cetyltrimethylammonium bromide and cetylpyridinium chloride were also effective. The solubilizing capacity of the anionic detergents was smaller than that of the nonionic detergents. Quantitative evaluation of the solubilizing capacity of the cationic detergents was not feasible because of their being potent inhibitors of glucocerebrosidase activity. 3. Treatment of the enzyme aggregate with acetone rendered it buffer-soluble. 4. In addition to the above cationic detergents some choline-containing and highly hydrophobic phospholipids were found to inhibit the glucocerebrosidase activity.


Studies on lysophospholipases. VI. The action of two purified lysophospholipases from beef liver on membrane-bound lysophosphatidylcholine. The action of two lysophospholipases purified from beef liver on lysophosphatidylcholine in microsomal membranes has been studied. Enzyme I, which has been shown to be localized in the soluble fraction of the beef liver cell, has a higher specific activity on microsomal lysophosphatidylcholine than Enzyme II, which originates from the microsomal cell fraction. This trend is also observed with phosphatidylcholine liposomes and single bilayer vesicles in which lysophosphatidylcholine has been incorporated. At low mol fractions of lysophosphatidylcholine in liposomes, the maximum enzymatic rate is proportional to this mol fraction. Similar results are obtained with mixed micelles of lysophosphatidylcholine and Triton X-100. The results are explained in terms of a model in which the two-dimensional substrate density in the membrane surface controls the rate of enzyme action.


Is phospholipase D really an enzyme? A comparison of in situ and in vitro activities. Leaf phospholipase D activity was compared in vitro and in situ. In the in situ reaction stimulated by methanol only phosphatidylcholine and phosphatidylethanolamine were degraded until approx. 80% of these endogenous substrates had been consumed. Only then was a limited amount (approx. 20%) of endogenous phosphatidylglycerol degraded. Endogenous phosphatidylinositol was apparently not susceptible to phospholipase D in situ. In the vitro reaction the relative susceptibilities to degradation of added phospholipid substrates were (a) in the absence of "activators" phosphatidylethanolamine greater than phosphatidylglycerol greater than phosphatidylcholine, (b) in the presence of diethyl ether phosphatidylcholine greater than phosphatidylethanolamine greater than phosphatidylglycerol and (c) in the presence of sodium dodecyl sulphate phosphatidylcholine greater than phosphatidylethanolamine = phosphatidylglycerol. Minimum rates calculated for the in situ reaction in cauliflower leaf were 5-fold higher than maximum in vitro rates reported for the same material. Phospholipase D activity has been demonstrated by the in situ reaction in all leaf tissue so far examined. From these data we conclude that phospholipase D may be an integral part of membranes containing phosphatidylcholine and phosphatidylethanolamine, but not of membranes containing phosphatidylglycerol. We also suggest that phospholipase D may not be a physiological enzyme, but rather a structural protein of phosphatidylcholine- and phosphatidylethanolamine-containing membranes and which, under certain non-physiological conditions, possess enzymic properties.


In vivo metabolism of labeled oleic and linoleic acids by the laying hen. Radioactive oleic and linoleic acids, labeled with 3H in the chain and 14C in the carbonyl group, were administered to white leghorn laying hens. Mixtures fed in separate experiments included: (1) 3H- and 14C-labeled oleic acid, (2) 3H- and 14C-labeled linoleic acid and (3) [3H]oleic aicd and [14C] linoleic acid. The 3H/14C ratios of both the neutral lipid and phospholipid fractions from the egg yolk and of the isolated acids from these lipid fractions were compared to that in the administered mixture. Agreement in the 3H/14C ratios for the neutral lipid fraction from each of the feeding experiments indicated that neither the 3H- and 14C labeled acids nor the oleic or linoleic acids were distinguishable during synthesis of the neutral lipid. Analysis of the phospholipid fractions showed that when dual-labeled mixtures of oleic acid were administered, 3H/14C ratios were elevated and, therefore, there was selective elimination of the 14C label. When dual-labeled mixtures of linoleic acid were administered, the 3H/14C ratios were in agreement; and when the two acids were administered simultaneously as a dual-labeled mixture, there was selective incorporation of linoleic acid. These findings indicate separate metabolic pathways for synthesis of neutral lipid and phospholipid in egg yolk as expected, as well as preferential use of the essential fatty acid in the phospholipid by the hen.


Methylation analysis of the major gangliosides of the human alimentary mucosa. The five major gangliosides of the human alimentary mucosa were purified with silicic acid column chromatography and with thin-layer chromatography. The linkages in the carbohydrate portion were analysed by permethylation with gas chromatography-mass spectrometry. A succesful analysis of the linkages of two hematosides and three tetraglycosylceramides was performed. Two of the tetraglycosylamides had a galactosamine in their chain and one had a glucosamine.


DNA sequence repetition in the genome of the American oyster. The genome of Crassostrea virignica, the American oyster, has been studied by reassociation kinetics in order to construct a profile of DNA sequence frequency components. Oyster DNA has been shown to contain at least 51% single copy DNA sequences and two classes of middle repetitive DNA. The major repetitive class contains sequences which are repeated on the average 20 times and comprise 29% of oyster DNA. The other class represents 10% of oyster DNA and contains sequences repeated approx. 3000 times. In addition the DNA of oyster contains at least 1% foldback sequences. The spectrum of DNA repetition components in the American oyster is similar to that found in the genomes of other mollusks.


Interspersion and transcription of repeated sequences of rat DNA. Repetitive rat DNA reassociated to Cot=0.1 and deprived of "foldback" sequences showed close interspersion with unique sequences. As measured by electron microscopy, the average length of repetitive segments was about 600 +/- 400, and of unique segments 1800-3600 base pairs. Pyrimidine tracts over 80 nucleotides in length were found mainly in foldback and repetitive fractions. Oligo(dT) tracts, 20-30 bases in length prevailed in the DNA fraction reassociated to Cot=0.1. Repetitive and unique DNA fractions were annealed to Millipore filters and hybridized with hnRNA. Up to 1.6% of repetitive DNA reassociated to Cot=0.05 showed base complementarity with hnRNA, whereas the comparative figures for DNA reassociated to Cot=10 and for the unique fraction were 0.8% and 0.3% respectively. When hybridization of hnRNA was carried out in solution in vast DNA excess, no hybrid formation with repetitive sequences reassociated to Cot=0.1 was observed, although hybridization with DNA reassociated to Cot=10 was noticeable.


Specific ribonucleoprotein fragments from 40-S ribosomal subunits. Well-defined ribonucleoprotein fragments, resulting from the action of endogenous nuclease on 40-S subunits, were able to be separated when using high concentrations of LiCl. The ribonucleoproteins obtained sedimented at 12, 17 S, 23 S and 30 S and contained 8 S, 12 S and 17 S RNA, respectively, associated with a few proteins. The proteins extracted from the fragments were [3H] labeled by reductive methylation and their molar proportion was determined. The smallest fragment (12, 17 S) contained only three proteins, S8, S9 and S24. The 23-S and 30-S materials contained some proteins in common, S15, S19, S22, S25; S16 was found mainly in 30 S. Two proteins, S26 and "protein y" were found mainly in 23 S material. Thus, these results can give information on the relative location of certain proteins in the 40-S subunits.


Dual transcription of the tryptophan operon translocated into the early region of gamma. The mode of transcription of the trp operon translocated into the early region of bacteriophage lambda was studied. Synthesis of trp mRNA specific for the translocated trp operon in lambdatrp phage was assayed after infecting a bacteria carrying a deletion mutant (trpAE1), which lacks the whole trp operon but retains a trp regulator gene (trpR). To determine trp mRNA from lambdatrp, phage phi80trp was employed as a source of DNA in hybridization assays. trp mRNA synthesis by lambdatrpE-A, which possesses the intact trp operon, was found to be only partially repressed by fully activated trp repressor in strain trpAE1. On the other hand, trp mRNA synthesis by lambdatrpE-A in strain trpAE1 (lambda), lysogenic for lambda and therefore possessing lambda repressor, was completely repressed when the trp repressor was fully activated by the addition of excess tryptophan. trp mRNA synthesis from the trp operon segment in lambdatrpBA, which carries the trpA and trpB genes but does not possess the trp promoter and operator, was not affected at all by trp repressor but was regulated completely by lambda repressor. The possibility was excluded that the trp mRNA whose synthesis is insensitive to trp repressor is anti-messenger originating from the nonsense(r)-strand of the translocated trp operon of lambdatrp. These observations led to the conclusion that transcription of the translocated trp operon in lambdatrpE-A consists of two types; one is initiated at the trp promoter and is controlled by the trp repressor, another is initiated by a lambda promoter (PL of gene N) and is controlled by the lambda repressor.


Differential sensitivity to antibiotics of trp mRNA synthesis originating at the trp promoter and the lambda promoter. Transcription of the Escherichia coli trp operon translocated into the early region of bacteriophage lambda can occur under the control of either of two promoters, the trp promoter on the lambda promoter (OL of N gene). (Imamato, F. and Tani, S. (1972) Nat. New Biol. 240, 172-175 and Ihara S. and Imamoto, F. (1976) Biochim. Biophys. Acta 432, 199-211). Trp mRNA synthesis originating at the trp promoter stopped when translation was blocked by chloramphenicol tetracycline erythromycin or puromycin. In contrast, trp mRNA synthesis originating at the lambda promoter was not affected by antibiotic action. This probably is a reflection of the properties of the "immediate early" class of genes of lambda, whose transcription in initiated at the PL. promoter and is not inhibited by the antibiotic. The inference is strengthened by comparable results with phage lambdatrpE-A (carrying an intact tro operon) and lambdatrpBA (carrying the operator-distal two genes but missing the trp promoter and operator). Thus it seems that either the promoter or other gene(s) located at the beginning of the operon, either at polymerase addition or because of some feature of the transcript, can determine a requirement for "coupling" of RNA polymerase to the translational machinery in vivo.


Complex mitochondrial DNA in animal thyroids. A comparative study. 1. The frequency of circular dimers and catenanes was determined in thyroid mitochondrial DNA (mtDNA) from rabbits, mice, pigs, sheep and cattle. 2. The mtDNA from freshly removed thyroids was isolated by buoyant density centrifugation in ethidium bromide/CsCl gradients after DNAase treatment of the mitochondrial pellet. Typically, more than 90% of the recovered mtDNA was found in the lower band, indicating a low rate of nicking during isolation. A sample of the total mtDNA (upper and lower bands) was examined by electron microscopy after preparation by the aqueous protein film technique. 3. The frequency of circular dimers generally ranged from 0.1 to 0.3%. However, in an mtDNA sample from cow thyroid, the frequency of circular dimers was 0.6% (0.9% if circular dimers occuring in catenanes are included(, differing significantly from the frequency of these forms in bull thyroid, 0.1%. A small but significant variability also occurred in the frequency of catenanes ranging from 2 to 8% in the different groups; this variation is within the limits usually observed in normal tissues. 4. These observations indicate that thyroids, like other normal tissues examined so far, have a low content of circular dimers. A high frequency of these forms seems to be the trademark of some genetically and physiologically abnormal cells such as certain established cell lines, virus-transformed cells and malignant or otherwise pathological tissues.


The effect of 313 nanometer light on initiation of replicons in mammalian cell DNA containing bromodeoxyuridine. After unifilar substitution of thymine with bromouracil in either human HeLa or bovine cells, exposure to 313 nm light inhibits initiation of clusters of replicons. Since this treatment results in damage only to DNA and because the effect is the same as observed after 100-1000 rads of X-ray irradiation to the same cells, we infer that the effect of the later treatment is also mediated almost exclusively by DNA damage.


5-Methylcytosine in Chlorelle pyrenoidosa DNAs. The presence of 5-methylcytosine in Chlorella pyrenoidosa (strain 211/8b) DNA's has been investigated by means of paper chromatography and thermal chromatography on hydroxyapatite. It has been shown that nuclear DNA contains 3.5 mol% 5-methylcytosine whereas no significant amount of this base can be detected in chloroplast DNA. The thermal chromatography of nuclear DNA labelled from [6-3H]- or [Me-14C] methionine lead us to conclude that the 5-methylcytosine content is directly proportional to the G + C content of the various DNA fractions. The existence of methylated sequences in DNA is postulated and the biological function of the 5-methylcytosine is discussed.


Investigation of human lymphocyte plasma membrane associated nucleic acid. Plasma membranes were prepared from the human lymphocyte cell line WIL23A by hypotonic swelling, Dounce homogenization, differential and equilibrium centrifugation. The resulting vesiculated membrane fragments were found to have densities of 1.10 and 1.17 g/ml, and were defined by lactoperoxidase mediated whole cell iodination, L-[3H] fucose incorporation, 5'-nucleotidase activity (EC 3.1.3.5) and electron micrographic visualization. Recovery of plasma membrane from whole cell homogenates was estimated to be approximately 30-35% as judged by the recovery of 125I-labeled cell surface protein. When plasma membranes were prepared from cells which had been incubated for 18 h in the presence of 0.5 muCi/ml [3H] thymidine such that greater than 10(9) acid insoluble counts could be demonstrated in the whole cell homogenates, no [3H] thymidine label and presumably, therefore, no DNA, could be shown to be coincident with either the 1.10 or 1.17 density. Similar experiments with [3H] uridine suggested that 90% of the plasma membranes did not contain RNA, while 10% remained questionable.


Evidence for the presence of mRNA in the post-ribosomal cytoplasm of sheep lymphocytes. Several fractions of RNA prepared from the post-ribosomal cytosol of sheep lymphoid cells were found to include messenger-like RNA as defined by the following criteria: a, template activity, i.e. the ability to promote the incorporation of radioactive amino acids into protein in cell-free protein-synthesising systems derived from wheat embryos or ascites tumour cells; b, a low magnesium optimum (1-2.5 mM) for template activity which is characteristic of many natural mRNAs; c, sensitivity of the template response to aurintricarboxylic acid, a specific inhibitor of the initiation of protein synthesis. The lymphoid post-ribosomal RNA fractions, however, were translated less efficiently than were rabbit reticulocyte globin mRNA or tobacco mosaic viral (TMV) RNA; no explanation for this relatively poor template activity was found. The major fraction of messenger-like RNA had an average sedimentation coefficient of 12 S; this fraction directed the translation of several discrete polypeptides in the molecular weight range 10 000-25 000. On average the products of 12 S RNA-directed protein synthesis appeared lysine rich compared with TMV RNA-directed products. It is suggested that the apparent pool of uncommitted mRNA in resting lymphocytes may be utilised during the early stages of lymphocyte activation, and that the mRNAs could be stored in forms similar to those evident in other dormant tissues.


Inhibitory action of different RNA fractions on the translation of globin mRNA in vitro. Preparations of 28S rRNA and 12S RNA, obtained from sheep lymphocytes, were shown to inhibit the translation of globin mRNA. An inhibition by a given amount of 12S or 28S RNA was only obvious at saturating or near saturating levels of globin mRNA, suggesting that the inhibitory RNAs interacted with some factor essential for protein synthesis other than mRNA. The inhibitory RNAs had no effect on the translation of the synthetic template polyuridylic acid. It is suggested therefore that the target for inhibitory RNAs might be a natural mRNA specific initiation factor.


The electrophoretic mobility of double-stranded RNA in polyacrylamide gels as a function of molecular weight. A re-evaluation of the mobility of double-stranded RNA on polyacrylamide gels over a molecular weight range of 0.46-6.3 . 10(6) was carried out using double-stranded RNAs of: bacteriophage ø6; virus like particles or mycoviruses of Penicillium chyrsogenum, Penicillium stoloniferum and Helminthosporium maydis, and reovirus type III. When the relative mobility on polyacrylamide gels was plotted as a function of log molecular weight, a smooth curve could be drawn which passed through all points. The implications of these findings to the determination of molecular weight of double-stranded RNA by polyacrylamide gel electrophoresis are discussed.


Directed cleavage of ribopolynucleotides with nucleases restricted by multiple modification of substrate. Simultaneous exhaustive modification of cytidine and uridine residues of rRNA with methoxyamine and sodium metabisulfite renders adjacent phosphodiester bonds resistant to pancreatic and T2 ribonucleases. Another method of T2 RNAase restriction is modification of cytidine with methoxyaminebisulfite followed by modification of guanosine residues with beta-ethoxy-alpha-ketobutyraldehyde. Mild alkaline treatment leads to demodification of uridine and guanosine residues leaving intact modified cytidine residues, thus providing a means of stepwise, directed cleavage of the polynucleotide. The series of combined cleavage procedures and methods of isolation of oligo(C), oligo(G) and oligopyrimidine tracts, as well as the procedure of selective cleavage at uridine residues elaborated in the course of the present studies may serve as a basis for more rational procedures of RNA sequencing.


Comparisons of the low resolution structure of several small RNA-containing viruses. A comparison is made of the structure of five small RNA-containing viruses and their accompnaying particles. The data obtained by a small-angle X-ray scattering at low resolution indicate that the radial distributions of electron density are quite similar for particles with similar percentage of RNA. Evidence is also presented indicating that the RNA probably penetrates the wall of the protein shell of most if not all of the virus particles.


[Theoretical conformational analysis of doulble-stranded polynucleotides]. Calculations of intramolecular interaction energy of two-stranded helical homopolynucleotide in the function of nine conformational variables have been carried out by the method of atom-atom potential functions. Four of these variables determine mutual position of base pairs, other four--deoxiribose ring conformation and other one--orientation of this ring with respect to the base. For this purpose an algorythm connecting dependent variables with independent ones has been developed. The investigation of energy function has shown that in the space of conformational parameters there are two valleys, which correspond to A-and B-families of conformations. Experimentaly determined conformations of two-stranded helical polynucleotides are located along the bottoms of these valleys. Along the bottom of each valley the intramolecular interaction energy changes rather little when conformational parameters change within a wide range. The valleys are separated by an energetical barrier.


[Dynamic theory of enzymatic catalysis]. Formal kinetics of an enzymatic reaction is considered in terms of a dynamic scheme of catalysis. Conformation reconstructions of a liberated enzyme and e-s-complex are analysed upon the phase plane. An expression for the enzyme stationary activity depending on the rate of conformation reconstructions is obtained. The case of purely dynamic catalysis is analysed and possible initiation of enzymatic activity variation in time connected with initial synchronization of molecules is shown. This phenomenon is considered as a possible criterion of the dynamic character of enzymatic catalysis.


[Hysteresis, multiplicity of stationary states and auto-oscillations in the reversible flow-through reaction]. A mathematical model has been investigated of a reversible flow-through reaction S1 reversible S2 catalyzed by an olygomeric enzyme E(R,T) the protomers of which undergo concerted conformational transitions R reversible T. The isosteric activation of olygomer E by product S2 binding preferably to protomer active sites in conformation R is shown to be a possible cause of hysteresis in the quasi-stationary input characteristic of the reaction, v (s2). The latter determines the rate law of the reaction, provided the concentration of S2 is a quasi-stationary one. The hysteresis of the characteristic v (s1) gives rise to multiple steady states and self-oscillations in the reaction.


[Autocatalysis in a stoichiometric model of energy metabolism]. A simple kinetic model of the energy metabolism with autocatalytic stoichiometric structure is analysed. The model includes the participation of ATP (a product of energy metabolism) in the activation of oxidation substrate. It is shown that the energy metabolism displays multiple steady states and autooscillations in the absense of all kinds of non-stoichiometric (allosteric, isosteric and cooperative) interactions. The results of the analysis are represented in the form of a parametric portrait. The domains of the parameter values of the oxidation substrate source are separated, which correspond to qualitatively different patterns of the model dynamic behavior. Under specified conditions the model is reduced to various versions of the Lotka model.


[Kinetic regularities of RNA synthesis. VII. Accumulation of RNA precursors and the inverse problem]. Applicability limits are specified for earlier obtained solutions of particular inverse problems of accumulation kinetics of newly synthesized RNA using isotope label for immitating unstationary state in stationary cell cultures.


[Spectral studies of beta-melanocyte-stimulating hormone and beta-lipotropic hormone fragment]. Secondary structure of beta-melanocyte-stimulating hormone was studied by circular dichoism and infra-red spectroscopy. Left-helical conformation of poly-L-proline II type which was stabilized by temperature reduction was found in aqueous solution; in 60% ethanole the quota of this structure sharply decreased. The investigation of hormone films at different values of relative humidity (in the course of H--D metabolism) made it possible to discover a twisted beta-form and an elongated helix of poly-L-proline II type. Temperature induced changes of circular dichroism spectra specify the peculiarities of poly-L-proline II conformation in C-end fragment of beta-lipotropic hormone.


[Significance of chiral purity of biomolecules for self-reproduction of organisms]. Living systems mainly syntesise and utilise chiral pure polimers which have only one form of enantiomers (l, l,..., l-proteins, d, d, d,..., d-sugars). The biologycal meaning of chiral purity of molecules in organisms is discussed. It is shown that chiral purity of biomolecules is necessary to ensure ordering of organisms during selfreproduction. Even when formation of chiral pure form does not have any advantages over formation of a set of other stereoisomers, only chiral pure molecules may act as regulators of further syntheses. Molecules with distorded chiral purity are not able to maintain the initial order during selfreproduction.


[Physical model of electroexcitable membranes. II. Mechanism of excitation]. The proposed model of action potential generation in electroexcitable membranes is based on physical phenomenon of the reversible thermal dielectric breakdown induced by injection of the activating charge carriers in the membrane under irritation. The model has been shown to describe well the main features of nerve excitation.


[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. I. Statement of the problem. Stationary transfer]. The communication presented is the first in the cycle on comparative analysis of hopping (three barrier) and electrodiffusion description of particle movement in thin membranes. A case of stationary transfer is considered. It is shown that the three barrier hopping description is adequate to the electrodiffusion one when the membrane is non-uniform with a high narrow barrier in the middle. The uniform electrodiffusion description is adequate to the three barrier one only in the cases when the limiting stage is presented by the transfer through a membrane surface or the border of small outer electric fields.


[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. II. Potential clamping. Jumping and continuous uniform mechanism]. Electric relaxation of the membrane in three-barrier hopping and electrodiffusion uniform models has been considered. Both models are shown to have different relaxation characteristics which do not coiside with each other.


[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. III. Potential clamping in a uniform membrane]. Electric relaxation of a non-uniform membrane was considered during potential clamp. It is shown that in the case of non-uniformity as a high narrow potential barrier in the middle and deep holes along the membrane edges the electrodiffusion model is adequate to the three-barrier hopping one.


[Structure of the double electric layer at membrane/aqueous solution interfaces in the presence of tetrapentylammonium cations]. Data are presented on the conductivity of bilayer lipid membranes of phosphatidilethanole amine with different surface charges in the presence of tetrapentylammonium chloride. It follows from the analysis of experimental data that to describe the effect of surface charge on membrane conductivity it is necessary to use a complicated model of double electric layer. Only in some cases Gouy-Chapman theory well describes the experimental results.


[Free radical oxidation of biological membrane lipids. VII. Effect of ultraviolet radiation on free radical oxidation of lipids complexed with protein and in biomembranes]. Promoting effect of protein component on the development of free radical oxidation in the systems ethylarahidonate--bovine serum albumin and mitochondria suspension under UV irradiation has been shown. Connection between the processes of peroxide formation and the change of the functional activity of organells has been followed.


[Structural rearrangements in membranes induced by anesthetics]. Studies were carried out on the effects of anesthetics on the stability of membranes to sodium dodecylsulfate and trypsin. The initial rate of membrane desintegration by detergent evaluated by light scattering with stopped flow method was increased in the presence of ethanol, propanol, benzyl alcohol, procain-amide (erthrocyte membrane) and chlorpromazine (rat brain synaptosomes). Concentrations of anesthetics which correspond to half of the maximum effect were very close to that of blocking the action potential and inducing 50%--antihemolysis. Alcohols and procaine at anesthetic concentrations inhibited proteolysis of isolated erythrocyte membranes but were without effect on their ultrasonic fragments. Increase of membrane desintegtation rate is interpreted as structural rearrangements of membranes with the weakening of detergent sensitive intermolecular interactions. Proteolysis inhibition of ghosts but not the gragments indicates against the participation of the basic func of proteins in the structural membrane rearrangements.


[Energy migration in photoactive complexes of chlorophyll precursor in etiolated leaves and spectroscopic characteristics of pigment forms]. Migration energy between three forms of the precursor of chlorophyll and chlorophyllide are measured and calculated. Absorption coefficients, fluorescence yields of pigment forms and dimensions of native complexes (20-22 molecules) are calculated.


[Luminescence of bacteriorhodopsin in purple membranes from Halobacterium haolbium cells]. Red luminescence of purple membranes from Halobacterium halobium cells was found out, and its emission, excitation and polarization spectra were investigated. Simultaneous parallel measurements of absorption and luminescence changes in one sample brought about by the action of light were also carried out. The bands in the spectra can be attributed to a number of bacteriorhodpsin (BR) forms: BR(595,520), BR(650,575),BR(600-620), BR(700,625), BR(730,660) BR(780,695), where the number above is the position of the luminescence maxima, below--that of absorption. Proceding from the quantum yield of the luminescence (10(-3)) and of photoreaction (10(-1)) of BR, the photoisomerization rate constant of the latter was estimated (10(11) sec(-1). The temperature dependence of the luminescence quantum yield points to the existence of two or three quenching processes with different activation energies. BR phosphorescence was not observed in the region 500-1100 nm. High degree (36%) os luminescence polarization shows that there is no homogeneous energy transfer between BR molecules, or there is regularity in orientation of their dipoles. Energy migration from the bulk of carotenoids to BR was not found. However limited heterogeneous transfer between the different BR forms cannot be ruled out. The absence (or limitation) of migration indicated that there is a spatial separation of the chromophores. Data on possible participation of triplet states in the BR photoconversions are discussed.


[Structural rearrangements in synaptosomal membranes of the brain]. Studies were carried out on structural state of synaptosomes and synaptic plasma membranes from brain of rats and guinea pigs at 5--50C. In membranes from guinea pig brain there were two breaks at 8 and at 18--20C in the curves of temperature dependence of light scattering. At the same temperatures adhesive properties of membranes had changed in jump-like manner when evaluating the degree of aggregation at pH4. The degree of aggregation in membranes from rat brain as well as rate of solubilization by 0.2% SDS (stoped-flow measurements) are characterized by single break point at 27C in Arrhenius curves. The breaks were interpreted as phase transitions with membrane surface involvement. Chlorpromazine and tetraciane (10(4)--10(3) M) abolished or modified these transitions. Because the number of negative charges and tryptophanyl and ANS fluorescence parameters were unchanged it was suggested that redistribution of ionogenic and hydrophobic goups took place at membrane surface during phase transitions.


[Change in the activity of calcium ions during illumination of a suspension of visual cell outer segment fragments]. Changes in the activity of calcium ions in the medium containing outer fragments suspension of bovine eye retina rods have been studied by the method of calcium-selective electrodes. Illumination of the suspension increases calcium ion activity in the incubation medium. Photoinduced yield of calcium ions depends on Ca+2 concentration: it equals 0.11+/-0.015 M Ca2+/1m rodopsin in the medium containing 0.1 mM CaCl2 and 0.046+/-0.002Ca2+/1M rodopsin in the medium containing 0.05 mM CaCl2. In the medium containing more than 10(-4) M CaCl2 both an increase and a decrease of Ca2+ ions have been observed.


[Minimal mixture principle as a method of choosing the form of a dynamic model]. The extremality principle for molecular processes in biological systems is considered. The principle is based on an assumption that the main function of biological processes is the separation of the "product" from the "scheme". The form of the dynamical model of the process is determined from the requirement of the "minimum mixture". As an example Selkov's model of glycolysis is considered.


[Changes in the electrical properties of atrial trabecula induced by an electric stimulus]. Electrical activity, excitation threshold and "steady--state" current-voltage, relationship (estimated under voltage clamp conditions) in the membrane of chicken embryo atrial trabecula were investigated by means of double succrose-gap technique. Application of short (10 msec) electrical stimuli with magnitudes up to 6.10(-5) a (1-150 threshold) resulted in increased excitability and appearance of spontaneous activity. Release of neurotransmitters and polarity of the applied sitmulus are shown not to play a significant role in the changes in membrane excitability observed, the main cause of the latter being the increased sodium permeability of the membrane.


[Theory of EEG potentials in a model of thin brain integuments. II. Model of a multilayer flat cable]. A model of a polylayer spheric cable for estimating EEG potentials was discussed earlier [1]. As far as the holes in the natural scull were ignored in that model, the contrary assumption is useful: the scull is regarded as an infinite plain. Among the solution of the equations of both models there exist uncomplicated relations.


[Effect of delay on auto-oscillations in cell populations]. A model of homogenous cell population is analysed, the mitotic activity of which is controled by an inhibitor produced by the cells themselves. While deducing the model it is assumed that the inhibitor concentration is proportional to the population density at some preceding time moment. The density change in time is described by a delay differential equation: dx/dt=alpha x/(1+x(v)(t--0))--x. According to this equation oscillation of cell number may be observed in the population with an increase of the critical value of delay in the mechanism of mitotic activity inhibition. The oscillation period determined analytically in linear approximation equals the quadruplicated time of delay. Numerical integration of the model has shown that the period observed is close to the calculated one.


[Role of entering currents in the accommodation of myocardial fibers]. Varying ionic composition of outher medium and applying specific agents the role of fast and slow systems of entering currents in the accommodation of cats ventricular fibres has been studied. In potential region close to the level of resting potential (membrane depolarization no larger than 20-30mv), accomodation mainly depends on fast sodium currents. It is inhibited with a rise of this current (akonitin 0.1--1 mg) and, on the contrary, it increases when it gets weaker (novacain 2--5 mM). In the region of more positive potentials (membrane depolarization more than by 30 mv) the accommodation is mainly determined by the slow NA--Ca-systems of channels. The agents which strengthen NA--Ca--current (Si2+--5mM, Ca2+--10mM, Ba2+--0.1 mM) reduce the accommodation in the activation region of the Na--Ca--system. The agents which weaken the slow current (Mn2+--3 mM, isoptin--2+5 mg/l, inderal--2 mg/l) produce an opposite effect.


[Dynamics of O2 and CO2 tensions in the brain (mathematical modeling)]. The mathematical model for description of the circulation and gas exchange dynamics in the brain is suggested. The model is based on a cell of two compact parallel capillary network with a brain tissue within. The equation system describing the model was calculated on a computer. The simulation showed that steady state pO2 in the cell during blood flow changes from 0.5 mm/sec to 0.25 or 1 mm/sec is reached within 2--5 sec. The dynamics of pCO2 is more inert. It was shown that the main factor in the dynamics of pO2 in the brain is the velocity of blood flow in capillaries. The dynamic pattern of pCO2 depends on haemodynamical condition, the structure of capillary network and physical properties of CO2.


[Identification of neuronal system objects with standards]. At some fixed position of a three-dimensional object in relation to the retina plane let us name the set of coordinates of its characteristical points the standard. It is shown that the projections of the objects to the retinamay be identified with their standard (independent of the objects shift, their rotation, change of the scale and of partial shielding of some objects by the other). The structure of the net system is presented which consists of linear, threshold and integrating neurons where such identification may be performed. The system consists of a net with a feedback for calculating optimal transformations, a net for calculating the degree of proximity between the reflection and the standard and a net generator of hypotheses on the correspondence of characteristical points. All the objects whose standards are presented in the system may be identified simultaneously.


[Phenomenological model of the system for exact determination of target direction by the bat echolator]. A functional scheme of correlation treatment of an echosignal during the determination of a direction to the target by rats echolator is considered. The scheme proceeds from a suggestion that for an exact measurement of angle coordinates of the target the rat applies a location method of unisignal zones resulting from the pulsation of direction diagram when LFM impulse is emitted. Some considerations in favour of the suggested phenomenological model are presented. An experimental set-up which permits to test and specify the model is proposed.


[Further study of the model of a human skull as a cupola with a plane base]. An experimental study of the base deformation of isolated human scull under conditions of scull collision with an obstacle has been carried out. The findings are compared with human cerebrospinal traums phenomena. An earlier suggested continuous scull model is modified on the basis of the data obtained. It is shown that the modified model (a part of spherical shell with the flat base) resembles scull behaviour in statics and dynamics better than the scull model in the form of spherical shell.


Biochemical and ultrastructural study of human diabetic conjunctiva. Combined biochemical and ultrastructural study of conjunctival biopsies of 27 normal subjects and 45 diabetics (40 to 60 years old) was made. The "in vitro" incorporation of 14C-glucosamine and 3H-proline in freshly excised conjunctival biopsies was studied. The alterations of the capillary basement membrane of the conjunctiva were studied by electron microscopy. The following results were obtained: 1) A decrease of the specific activity of 14C-glucosmaine incorporation was found in fractions of diabetic conjunctiva. 2) In diabetic conjunctiva the percentages of 3H-proline incorporation in polymeric collagen containing fraction and structural glycoproteins containing fraction were significantly increased with a parallel decrease of 3H-proline incorporation in "crude soluble collagen" fraction expressed as a percentage of total incorporation. 3) Significant thickening of capillary basement membrane was observed with the appearance of collagen-like fibrils within the basement membrane in diabetic conjunctiva. Such fibrils were not seen in normal basement membranes. A relation between the extent of basement membrane thickening and the appearance of collagen-like fibrils is suggested. 4) The higher percentage of incorporation of 3H-proline in polymeric collagen may be related to the appearance of collagen fibrils in thickened basement membranes of the diabetic conjunctival capillaries. 5) These results suggest an abnormal regulation of the relative rate of biosynthesis and/or excretion of intercellular matrix macromolecules (collagen, structural glycoproteins) as part of the metabolic disorders characterising diabetes.


[Effects of arginine and growth hormone, administered in vivo and in vitro, on the oxygen consumption of rat liver hemogenates]. Effects of arginine aspartate, arginine chlorhydrate, potassium aspartate, with equal arginine base and aspartate ion available for all there compounds, growth hormone, and association of these different substances, are studied on rat hepatic homogenates oxygen consumption during 7 to 12 h, after injection to rats 1 h before sacrifice (A.A.: 0.50 g, C.A.: 0.34 g, A.K.: 0.22 g, STH: 2 U.I.), or "in vitro" adjunction to the preparation (A.A.: 0.125 g, C.A.: 0.085 g. A.K.: 0.055 g. STH: 0.5 U.I./0.25 g of liver). 1) "In vivo", arginine (endogenous STH secretion stimulation) is active: A.A. (+23% to +96% from 1 h to 8 h, p is less than 0.01), C.A. (+49% from 5 h to 8 h, p is less than 0.01), whereas potassium aspartate is inactive. "In vitro", aspartate is active: A.K. (+24% to +147% from 4 h to 12 h, (p is less than 0.01), A.A. (+56% to +53% from 7 h to 12 h, p is less than 0.01), whereas arginine without aspartate: C.A. is inactive. 2) Exogenous STH is active "in vivo" (+111% from 5 h to 8 h, p is less than 0.01) and "in vitro" (+31% from 4 h to 7 h, p is less than 0.01). 3) Association A.A. + STH (endogenous STH + exogenous STH) when given "in vivo", dose not produce any additive effect the tissue Vo2 release (+91% from 5 h to 8 h, p is less than 0.01) does not differ from STH and A.A. Aspartate added to STH "in vitro" enhances STH effects: (A.A. + STH: + 44% to +114% from 4 h to 12 h, p is less than 0.01, A.K. + STH: 73% to + 152% from 4 h to 12 h, p is less than 0.01).


[Effects of colchicine, vinblastine and mercury p-hydroxybenzoate on the multiplication of adenovirus 5 in HeLa cells]. After 30 min incubation at 37 with 10(-4) M PHMB (p-hydroxymercuribenzoate), monolayers of HeLa cells are not affected; after 3 h exposure to 10(-5) M colchicin or 2.5 X 10(-5) M vinblastine, HeLa cells are not altered morphologically but the number of cells is decreasing between 1 and 2 days post treatment. When cells are kept in suspension after trypsinization, their ability to adhere to the Petri dishes is not altered with 10(-4) M PHMB but only 50% of the cells are able to attach after treatment with colchicine or vinblastine. Adenovirus type 5 is unsensitive to the effect of colchicine and vinblastine at various concentrations, after 3 h incubation at 37. With 10(-3) M PHMB, the virus is inactivated, infectivity and hemagglutinating activity are almost abolished but the particles are unsensitive to pancreatic DNase, so that the structure of the viral particle is intact. This effect is reduced with 10(-4) M PHMB. The adenovirus 5 multiplication is not affected when HeLa cells are treated with 10(-5) M colchicine or 2.5 X 10(-5) M vinblastine, before and during adsorption of the virus. The viral production decreases after 24 h treatment with colchicine or vinblastine. Treatment with 10(-4) M PHMB does not influence intra- or extracellular viral yield.


Qualitative and quantitative mass spectrometry of some biologically important trace metals as their tetraphenylporphyrin chelates. The use of the mass spectrometric integrated ion current technique for the quantitative analysis of some trace metals at their tetraphenylporphyrin chelates is described. The linearity of the calibration curves and the sensitivity of the technique are improved by employing deuterated tetraphenylporphyrin chelates as loading agents. Femtomole quantities of the chelates may be detected. The use of deuterated tetraphynylporphyrin chelates as internal standards overcomes the problems of losses occurring during chromatographic separation and by thermal decomposition in the mass spectrometer.


Gas chromatographic mass spectrometric evaluation of free organic acids in human saliva. Excellent resolution and subsequent identification of free organic acids extracted from mixed, unstimulated human saliva was obtained by gas chromatography using high resolution open tubular glass capillary columns coupled with mass spectrometry computer instrumentation. In addition to the organic acids, identified as their trimethylsilyl derivaties, the presence of 2,6-di-t-butylcresol--a food preservative--and cholesterol was established by mass spectrometry. The effects of aspirin ingestion as well as diurnal variation were studied to demonstrate the possible clinical significance of this noninvasive approach to metabolic profiling.


Mass spectra of delta 4- and 5 alpha-3-ketosteroids formed during the oxidation of some 3 beta-hydroxysteroids by cholesterol oxidase. Thirty-six delta5- and 5'alpha-3beta-hydroxysteroids have been oxidized with cholesterol oxidase to give the corresponding delta4- and 5alpha-3-ketosteroids, respectively. The mass spectral characteristics of the products (or their trimethylsilyl ether derivatives, in the case of 3-keto-hydroxysteroids) varied considerably, depending especially on the nature of the C-17 sidechain. The ion of m/e 124 (or its equivalent) from cleavage of ring B was frequently a major fragment from delta4-3-ketosteroids, but in some instances was of insignificant abundance. Trimethylsilylation of the product of the oxidation of neoergosterol gave neoergosterone enol-trimethylsilyl ether. Fragmentations of the sidechain predominated in the mass spectra of the 5alpha-3-ketosteroids.


Adsorption of tryptophan metabolites from physiological fluids on XAD-2 and determination by single ion monitoring. Endogenous tryptamine, 5-hydroxytryptamine, indoleacetic acid, 5-hydroxyindoleacetic and tryptophan have been recovered from urine and cerebro-spinal fluid by adsorption on XAD-2 resin (0.3 g). After adsorption of the sample on the resin, desorption with methanol provides a single fraction that contains all of these metabolites. The mass spectra of their pentafluoropropionyl derivatives show prominent ions at m/e 276 and 438 which are characteristic of indoles and 5-hydroxyindoles, respectively, a feature that allows the concurrent determination of all the components of each group by functional group analysis. A method has been developed to carry out single ion monitoring with the peak matching system of an Hitachi RMU-6H mass spectrometer. Identifications are based on the respective Kovats Indices and single ion monitoring of two characteristic ions per compound: tryptophan (m/e 276 and 347); tryptamine (m/e 276 and 289); indoleacetic acid (m/e 276 and 335); 5-hydroxytryptamine (m/e 438 and 451); 5-hydroxyindoleacetic acid (m/e 438 and 497). The method described illustrates the feasibility of assaying biogenic indoleamines and acidic metabolites, as well as their precursor amino acid on a single fraction in contrast to other standard fractionation methods. This is possible even if the mass spectrometer is not equipped with an alternating voltage accelerator provided that it has a peak matcher, although the lack of an alternating voltage accelerator requires two separate injections of the same sample, for quantification and identification; one for the indole profile and another for the 5-hydroxyindole profile. Both profiles can be verified by individual monitoring of the other confirmatory ions. With this method the use of a multiple ion detector would allow a simultaneous determination of all of these metabolites in one gas chromatograph mass spectrometer run.


Autoclavable low cost serum-free cell culture media: the growth of established cell lines and production of viruses. Five cell lines (BSC-1, CHO, Balb/c 3T3, HeLa, and KB) have been grown in serum-free media for several months with regular schedules of media changing and subculturing. The medium found to be successful in all cases was MEM-alpha (without the ribosides and deoxyribosides) supplemented with 1% bacteropeptone, although simple MEM (minimum essental medium (Eagle) with bacteropeptone (BP) gave fairly good growth in the case of BSC-1 and 3T3 cells. The addition of insulin was necessary for CHO, 3T3, HeLa, and KB cells. Only the BSC-1 cells grew exclusively as a stationary suspensions and the 3T3 cells growing as a combination of monalayer and suspension depending on the age of the culture and the nature of the growth surface. SV40 was produced in BSC-1 cells grown and infected in the MEM-alpha, bactopeptone medium and adenovirus-2 was produced in spinners of HeLa and KB cells grown in MEM-alpha, bactopeptone, PVP-360, and insulin. The yield of virus and infectivity of the viruses produced were about the same as those produced in conventional serum-containing systems.


Kinetic analysis of penicillin production by semicontinuous fermenters. The relationships between the specific rate of nutrient consumption and biomass growth and between the specific rate of penicillin production and oxygen concentration in the broth are analyzed. The functional dependencies which have been obtained from the experimental data of industrial fermenters are used with the mass balances to develop a model of the behavior of semicontinous operations. The proposed model allows one to study the influence of some operational parameters. The obtained results agree with the data of industrial processes.


The influence of oxygen concentration and of specific rate of growth on the kinetics of penicillin production. The role of fundamental parameters in the conduction of penicillin semicontinuous fermentations is analyzed. Biomass concentration, penicillin production, and main nutrient consumption are particularly studied. Furthermore, the conduction of the operation is simulated with regard to conditions of constant specific rate of growth and of constant oxygen concentration in the broth. An intermediate condition is also considered.


Time delay in simple chemostat models.

Time delay in simple chemostat models. The models of Monod and Williams, for the growth of unicellular organisms in chemostats, give strongly damped transients in the biomass and cell number when the flow rate of the chemostat is changed. A simple trick is used to incorporate time delay in these models while still allowing a conventional stability analysis. For long enough time delays the equilibrium point is unstable and limit cycles can be compared. Results obtained using Williams' model, with weakly damped transients as a result of using moderately long time delay, are compared with his data in which cell numbers show weak damping but biomass shows strong damping.


Electromagnetic induced kinetic effects on charged substrates in localized enzyme systems. An analytical expression for the rate efficiency factor of planar localized enzyme systems is derived. The derivation takes into account the isothermal kinetic effect under the externally imposed perturbation of combined electrostatic and high frequency time-varying fields. The contribution of each individual field to the enzyme reaction is examined through the basic mechanism in which charged substrates interact with the specific perturbing field. The interaction mechanisms for the electrostatic and for the time-varying fields are found to be different. This difference regulates the different manners in which enzymatic reaction rates are altered. Enzymatic reactions under electrostatic perturbation can be retarded or enhanced depending on the field polarization. At sufficiently high field intensities the reaction rate may approach zero or approach a maximum value equal to the turnover number of the enzyme. Time-varying field perturbations, on the other hand, always enhance the enzymatic reactions if bunching effects are negligible. At sufficiently high field intensities, the reaction may approach a value equal to that of the free enzyme system. Several typical numerical examples on pure eletrostatic field perturbations, pure time-varying field perturbations, and combined field perturbations are also presented.


[3 cases of eosinophilic leukemia with atypical granulation in the eosinophils and neutrophils]. Three patients with eosinophilic leukemia and atypical granulation in the eosinophils are described. A remarkable light and electron microscopic finding was the appearance of enormous granules in the neurtophils and eosinophils. In addition the usual anomalies seen in acute leukemia, for example asynchronisation in cell maturation, fibrillar bundles, shrinkage of nucleolus and cell organelles, signs of degeneration and also the auer-rods characteristic of AML are observed.


[Electronic thrombocyte count from total blood]. Platelets were simultaneously counted in 52 persons by the conventional method of Cronkite and Brecher and with a new electronic cell volume analyser. The platelet counts estimated by the electronic analyser were 10% lower than that measured with the conventional method. This difference decreased to 1.5% when the same diluent was used for both methods. The described electronic counting method of platelets in whole blood is a simple procedure, which gives well reproducible and exact results.


Inhibitory activity of medium-dialyzed transfer factor on lymphocyte blastogenesis. Human transfer factor was prepared from normal donors with marked skin reactivity against common microbial antigens by dialysis of lymphocyte extracts versus tissue culture medium (TFmd). Several batches of TFmd were tested for their ability to specifically increase the DNA synthesis of unsensitized lymphocytes in vitro in the presence of the corresponding antigens (PPD, SKSD, Candida, Thistoplasmin). No transfer or immunologic reactivity by TFmd was observed. There was, however, a significant unspecific inhibition by TFmd of lymphocyte cultures stimulated by antigens, PHA or allogeneic cells.


An auto-anti-b in an a1b person. Serological studies. The serum of a patient (Mr. Lat) with the regular blood group A1 B contains an anti-B reacting with all cells having a B antigen except Bx and cis AB. The anti-B reacts at 4 degrees C and occasionally at room temperature as shown by agglutination, absorption-eluction and by thermo-dynamic assays. The antibody is regarded as an irregular autoantibody belonging to the group of the  so called "suppressed" or "latent" antibodies.


P,p-DDT and p,p'-DDE effects on egg production, eggshell thickness, and reproduction of Japanese quail. p,p' -DDT and p,p' -DDE were investigated for effects on egg production and eggshell thickness in Japanese quail.  p,p' -DDT was examined for effects on hatchability and fertility. DDE was tested at 0, 2, 10, 40, and 200 ppm in the diet. No evidence suggested that DDE affected number of eggs laid, egg weight, or eggshell thickness at any level of DDE tested. DDT was tested at 1,2.5, 10 and 40 ppm in the diet. In one experiment, quail fed DDT at 40 ppm and caged in male-female pairs broke more eggs than quail caged similarly but fed lower amounts of DDT or than quail fed an equal amount of DDT but caged alone. DDT did not detectably reduce eggshell thickness, number of eggs laid, fertility, or hatchability. However, paired quail laid fewer eggs than did single quail in two experiments and laid eggs with thinner shells in one experiment.


Antioxidant and antitranspirant protection of apple foliage against ozone injury. Visible injury to apple foliage from exposure to ozone includes brown stippling on lower leaf surfaces and a light yellow mosaic on upper surfaces. Histologically, chlorophyll is destroyed and palisade and spongy mesophyll cells collapse following disintegration of their protoplasm. Foliar spray applications of the antioxidant, diphenylamine (DPA) or the antitranspirant, Wilt Pruf offer protection against this visible and histological injury. Superior protection results from application of both agents in combination.


Worker environment research. IV. The effect of dust derived from several soil types on the dissipation of parathion and paraoxon dislodgable residues on citrus foliage. Parathion sorbed to dust can persist as dislodgable residues on citrus leaves. Semi-logarithmic plots of parathion dislodgable residue data were initially linear for the 6 soils studied and then a distinct change to lower rates occurred with 5 of the soils. As initial rates and the residue level at the rate change are dependent on the soil, foliar dust is implicated as a causative factor in the non-uniformity of residue dissipation rates. Soils can influence the conversion of parathion to paraoxon. Paraoxon levels differed greatly with the type of soil and were highest with Pike's Peak clay. Thus, its use in a parathion formulation could produce relatively high levels of paraoxon dislodgable residues. It is significant that, second to Pike's Peak clay, the highest total dislodgable residue level was found with Visalia silt loam which was collected from a grove where a worker poisoning episode had occurred in 1974.


Effects of chitosan--a coagulating agent for food processing wastes--in the diets of rats on growth and liver and blood composition. Effects of feeding free chitosan to rats at graded levels up to 15 percent of the diet for eight weeks was investigated. Animals receiving diets containing 5 percent or less of chitosan grew well at comparable rates. Progressive growth reduction occurred when chitosan was increased to 10 and 15 percent of the diet and enlargement of liver and kidneys was observed only in animals receiving the highest level of dietary chitosan. Liver moisture, protein, lipid, ash, and nucleic acids; blood hemoglobin and packed cell volume; and serum total protein, albumin, ceruloplasmin and transferrin were determined. Values for these components of liver and blood were altered significantly in the animals receiving the highest level of chitosan when compared to control animals. However, in animals receiving 5 percent or less of dietary chitosan none of these measures of tissue composition was different from controls, except for liver protein concentration of rats fed the 5 percent of chitosan diet. Animal feeds containing coagulated by-products are not expected to contain over 0.2% chitosan in the total diet. No adverse effects have been observed at this level in rat feeding studies. Therefore the tolerance level for dietary chitosan appears to be well above the levels expected to be in animal feeds containing by-products recovered from food processing wastes by coagulation with chitosan.


90 day dermal toxicity of DDVP in male rats. Exposure of male rats to DDVP (21.4 mg/kg/day) through dermal painting for a period of 90 days did not produce any changes in skin or testis. None of the animals showed any clinical symptoms of DDVP poisoning or mortality during experimentation. Rapid degradation of DDVP and further its detoification in in liver of rats and other species of mammals seems to be the prime reason for the non-toxic effect of the insecticide.


On effect of chlordane on the blood glucose and of glucose administration on the acute chlordane toxicity in Meriones hurrianae Jerdon, the indian desert gerbil. The effect of 25, 50 and 75 mg/kg body wt. chlordane on the blood glucose level and of glucose administration in chlordane intoxicated Indian desert gerbils are investigated. Chlordane produces hyperglycemia and lowers the glucose tolerance indicating an impairment in the uptake and utilization of glucose in intoxicated gerbils. The possible reasons for these effects are discussed.


Acute toxicity of ammonia-base neutral sulfite pulp mill waste liquor to rainbow trout. The acute toxicity to rainbow trout of untreated ammonia-base neutral sulfite pulp mill waste liquor was demonstrated in these experimants. A mean LC50 of 0.82% and 95% confidence interval of 0.08 - 1.56% was obtained in four static bioassays. Lignin, sulfur dioxide, and ammonia were implicated as toxic components. The latter two were probably the most toxic.


Breast augmentation with gluteal dermofat grafts: a 5-10 year follow-up. Of a series of 3 dermofat grafts, about a quarter had either to be removed or disappeared completely, while the remainder shrank unpredictably and were all calcified by the end of 4 years. The donor site on the buttock was often unsightly.


Selective neurectomies to achieve symmetry in partial and complete facial paralysis. Experience with selective facial neurectomies, in partial and total palsies, is reported. If under careful control by faradic stimulation the area to be weakened is conpletely, and the neighbouring musculature partly denervated, consistently satisfactory results can be predicted. Evidence suggests that rather than recovery of motion by axon regeneration, there is a marked tendency for collateral regeneration of peripheral facial nerve fibres from muscles left intact, into denervated muscles.


Assessment of the influence of the timing of repair on flexor tendon injuries in chickens. The flexor tendons of the middle toes of chickens were divided and the flexor profundus repaired after varying intervals up to 6 weeks. The best results were obtained with repairs within a few hours, the next best with repairs any time after the 10th day and the worst with repairs between the 4th and 7th days.


Quantity conceptions in university students: another look. One hundred and thirty-eight post-graduate students enrolled in a Diploma in Education course were tested for their ability to converse weight and volume. A methodological criticism of the earlier work or Elkind (1962) and Towler & Wheatley (1971) is offered which casts doubt on the extremely high proportion of non-conservers of volume reported in those studies. Nevertheless, using a modified version of Elkind's methodology, 18 per cent of our sample were non-conservers of volume, a result providing some support for the generaltiy of Elkind's findings. The results are discussed under the four headings of horizontal decalage, sex differences, possible effects of pre-graduate courses of study and educational implications. The importance of the individual as constructor and interpreter of his own experience is emphasized.


Inspection time and measured intelligence. Ten subjects with WAIS Full Scale IQ scores ranging from 119 to 47 were required to discriminate between two lines of markedly different length, exposed in random order for ten different durations, by pressing one of two keys. Estimates of inspection time gamma, the rate at which sensory input is accumulated and passed to subsequent decision processes, were calculated directly from the psychometric functions obtained gamma was found to correlate negatively with subtests contributing to Performance IQ. There was a substantial degree of consistency between estimates of gamma on two different occasions and training did not appear to affect the index, although differences between the two estimates increased as the value of the first estimate increased. Mean overall response latency did not correlate significantly with intelligence and measures obtained from retarded subjects were very like those reported in similar experimental situations utilizing normal subjects. This unexpected finding is interpreted as suggesting that, in this situation, retarded subjects have been prepared to respond on the basis of less evidence than is usually required by intellectually normal subjects.


Some evidence for 'speech' as an acoustic feature. Under conditions of serial recall of auditorily presented lists of digits, recall of the last item has been shown to be adversely affected by the presence of a redundant item following the list. This is known as 'the suffix effect' (Crowder & Morton, 1969). In a series of experiments it is shown that the size of this effect is not influenced by the phonological complexity of the suffix. Non-speech sounds, on the other hand, produce no suffix effect even when the subjects are forced to process them. Certain speech sounds were also found to produce no effect. It is concluded that these sounds lacked properties which are characteristic of speech sounds and so were classified as 'non-speech' and that as a result, these sounds are processed by a separate system from the speech sounds.


Extraversion and reinforcement in verbal operant conditioning. The present investigation was designed to study the relationship between extraversion and modes of reinforcement in verbal operant conditioning. A 4 X 3 randomized block design was replicated ten times. Eighty graduate and post-graduate male students were individually subjected to the standard Taffel conditioning procedure. When the numbers of conditioned responses produced by introverts and extraverts were compared, it was found that: (1) under negative reinforcement ('bad' and electric shock), with both the female and male experimenters, and under positive reinforcement ('good') with the male experimenter, the introverts' score was the higher of the two; (2) under positive reinforcement ('good') with the female experimenter, the extraverts' score was higher than that of the introverts.


Extraversion, activation and the recall of prose. Subjects were divided into four groups on the basis of their scores on the extraversion scale of the Eysenck Personality Inventory and the general activation scale of Thayer's Activation-Deactivation Adjective Check List. A prose passage was presented to subjects who then attempted to recall it under strict instructions to avoid errors. There were significant interactions between activation and extraversion for the error data, and the phrase-correct data, with moderate levels of arousal (high activation extraverts and low activation introverts) being associated with the fewest errors and the most phrases correctly recalled. It was concluded that the study showed the importance of arousal to recall performance, possibly due to the effects of arousal on retrieval processes.


Memory deficits in early infantile autism: some similarities to the amnesic syndrome. Autistic children were compared with control children on tasks in which retention was tested by different methods. In three tests of recall, using named pictures, written words and spoken words as test stimuli, autistic children were impaired in comparison with age-matched normal children and with controls matched for verbal ability. In one test of forced-choice recognition of pictures, autistic children were impaired in comparison with ability-matched controls. In three tests of cued recall, using named pictures, written words and spoken words as test stimuli, and acoustic, graphemic and semantic cues, autistic children were not impaired in comparison with normal age-matched controls. In one test of paired-associate learning using non-related word pairs as test stimuli autistic children were not impaired in comparison with normal age-matched controls. These experimental paradigms were similar to some that have been used to investigate the amnesic syndrome in man. Thus findings on paired-associate learning differ in autistic and amnesic subjects, but findings on recall, recognition and cued recall are comparable. A possible parallel between autism and amnesia is discussed.


Constraints on classificatory skills in young children. On three occasions over a one-year period 23 children aged 3-4 were asked to match target objects with other objects which were similar to the target in shape or in colour but not in both. A sequence of matches to each target was asked for. The structure of these sequences is examined for evidence of classifacatory abilities. Many subjects appear to be attempting (not always successfully) to follow a strategy of 'holding fast' to their original choice of matching criterion (colour or shape) on subsequent trials. The striking differences between performance after a first-trial colour-match and after a first-trial shape-match are described. It is argued that development during this period involves an increasing ability to ignore the more salient attribute (shape) when matching by colour. The general developmental significance is discussed.


Uric acid disorders in patients with calcium stones. Plasma and uric acid levels were measured in 132 men with calcium-containing renal stones and in 24 healthy men of similar ages. Fasting resulted in a significant fall in the mean plasma uric acid level of normal subjects. Intermittent hyperuricaemia was observed in 7% of fasting patients. Intermittent hyperuricosuria was found in 17% of non-fasting patients but in only 2 to 6% of fasting subjects. Most of the uric acid abnormalities in patients with calcium stones therefore appear to be due to diet and may be prevented by reducing the consumption of purine-rich foods. A direct relationship was observed between uric acid excretion and urine flow at normal flow rates. It is suggested that the apparent increase in stone incidence, which occurs with rising living standards, may be due partly to increased consumption of purine-rich foods.


The elastic component of normal and dilated ureters in children: chemical and histochemical characterisation. Using chemical and histochemical techniques, it has been possible to calculate the exact amount and distribution of the elastin in normal and abnormal ureters in children. From the quantitative analyses, it has been calculated that in the dilated ureters the elastin content represents the 3% to 5% of the organic material, while in the normal ureters it is less than 1%.


Experience with the ileal ureter.

Experience with the ileal ureter. The isolated ileal loop often provides a satisfactory solution to the problem of extensive ureteric defects. Our experience in 18 cases of diseased ureters partially or totally replaced by isolated ileal loops is presented. The indications for the operation and important operative and preoperative details are discussed. The operation presents a definite method for renal conservation in many cases in which nephrectomy would otherwise have been unavoidable.


Endometriosis mimicking ureterolithiasis. A case of endometriosis obstructing the right ureter is described, with a clinical picture mimicking ureterolithiasis. The usefulness of rapid sequence camera-scintigram in the early diagnosis of ureteral obstruction is discussed.


Re-implantation of the ureter.

Re-implantation of the ureter. For 10 years a modified Politano-Leadbetter technique with extravesical as well as intravesical exposure has been used for re-implantation of the ureter. The results suggest that the passive mechanism of prevention of reflux is more important than any active mechanism and that it is unnecessary to excise the lower end of the ureter.


Urinary citrate excretion in stone-formers and normal controls. A specific method was used for the estimation of citrate in 24-hour urine collections from 108 young adult controls, 158 patient controls and 164 stone-formers. Stone-formers excreted significantly less citrate in 24 hours than either patient controls or young adult controls. Stone-formers had a lower concentration of citrate in their urine than either of the control groups. The young adult females exhibited a much greater excretion of citrate relative to calcium than the young males. Because of the ability of citrate to complex with calcium ions and keep them in solution, the relatively low incidence of calcium-containing stones in females under 50 years of age could well be the result of their high excretion of citrate and their increased excretion of this substance relative to calcium.


A study of concentrations of trimethoprim-sulphamethoxazole in the human prostate gland. The ability of trimethoprim (TMP) and sulphamethoxazole (SMX) components of co-trimoxazole to penetrate the human prostate gland was investigated. After a single 4-tablet dose TMP was evenly distributed between prostate and plasma, whereas SMX was mainly associated with plasma. Following a week's therapy significant accumulation of TMP was seen in the prostate relative to plasma whereas SMX although still associated with plasma had increased drug levels in prostate compared with the single dose study. It is concluded that co-trimoxazole produces effective antibacterial levels in the human prostate and has indications in the treatment of prostatitis.


Badenoch's pull-through operation for urethral stricture. 14 patients with strictures in the region of the membranous urethra were treated by Badenoch's urethral pull-through operation or a slight modification of this. The results were good in 10 of the cases. This procedure has advantages over those using scrotal flaps in hot climates.


Thyroidectomy for non-familial medullary carcinoma. Two cases of non-familial medullary carcinoma of the thyroid which had thyroid tissue remaining after initial thyroidectomy were shown to contain residual, intra-glandular carcinoma at reoperation. This observation, the distribution of C cells in the normal thyroid gland and the lymph node spread of this carcinoma have led to the proposal of a bilateral 90 per cent upper pole thyroidectomy including the superior parathyroids for cases of non-familial medullary carcinoma. This operation removes all the C-cell-bearing area and leaves a small thyroid remnant at the lower pole for preservation of the inferior parathyroid glands. The operation is discussed with reference to these factors.


Biopsy of the impalpable breast lesion detected by mammography. Specimen radiology plays an essential part in the surgical management of the impalpable breast lesion detected by mammography. It also plays a necessary part in the complete pathological examination of the specimen. A method for preoperative localization of the mammographically detected impalpable breast lesion is described.


The association of duodenogastric reflux with dumping and gastric retention. Gastric emptying of solid and liquid meals together with duodenogastric reflux has been measured in a prospective trial of proximal gastric vagotomy and truncal vagotomy and antrectomy. Three abnormalities of motility associated with postoperative symptoms have been defined. If more than one abnormality was present in an individual there was an 80 per cent incidence of associated symptoms. Proximal gastric vagotomy produced significantly fewer abnormalities of gastro-duodenal motility than did truncal vagotomy and antrectomy.


Subphrenic abscess: a study of 241 patients at the Royal Prince Edward Hospital, 1950-73. A series of 241 patients with subphrenic abscess was analysed to seek reasons for the continuing mortality. Aspects of pathology, clinical presentation, special investigations and management were affected by therapy with broad spectrum antibiotics to make diagnosis more difficult, particularly in relation to left subphrenic abscesses. When transperitoneal exploration and drainage were employed, high morbidity and mortality resulted. Satisfactory results followed extraserous drainage. The introduction of parenteral hyperalimentation promised control fistulas associated with abscesses, a situation hitherto associated with a poor prognosis.


Salvage of the lower limb.

Salvage of the lower limb. This is a retrospective study of 80 patients with 94 severely ischaemic lower limbs treated over a period of 6 years. Arterial reconstruction was possible in 47 patients (54 limbs) and 76 per cent of these limbs were salvaged. There was no operative mortality. An attempt has been made to analyse the reasons for the failure. The fate of the patients who underwent major amputation is described. The selection of patients for direct arterial surgery is discussed, together with some of the technical problems involved.


The clinical significance of venous thrombosis of the calf. A total of 379 general surgical and hip replacement patients were studied with the radioactive fibrinogen uptake test and the Doppler ultrasound flow detector to determine the incidence and natural history of postoperative deep vein thrombosis (DVT) in their lower limbs. The overall incidence of DVT was 33 per cent, but clinical follow-up indicated that the great majority of these patients suffered no ill effects. It is concluded that thrombosis diagnosed by the radioactive fibrinogen uptake test is of very limited clinical significance and that the technique cannot be recommended as a screening test for DVT.


The prognosis after surgical treatment for carcinoma of the rectum. The results of surgical treatment of 550 cases of carcinoma of the rectum presenting to the Professorial Surgical Unit of the General Infirmary, Leeds, from 1955 to 1968 have been analysed.


Rectal sphincter reconstruction in perineal colostomies after abdominoperineal resection for cancer. A surgical technique is proposed for the reconstruction of the anal sphincter in perineal colostomies after abdominoperineal resection for cancer. The procedure, which employs the gracilis muscle for the sphincteric reconstruction is described and the operative results and complications are analysed in 24 patients submitted to this type of surgery. Of the 22 patients who were followed up, 17 had excellent or good results with retention of solid or soft stools. Three patients had poor results with no voluntary retention, while 2 others were partly incontinent of solid faeces. In this group of 5 patients, 3 had stenosis of the colostomy and 1 had no sensibility of impending defaecation.


Jaundice and wound healing: an experimental study. Obstructive jaundice was induced in rats by ligation and division of the common bile duct. The healing of a standard gastric incision and a parietal peritoneal defect in these animals showed histological evidence of delayed healing compared with controls. The bursting strength of the abdominal incision was also lowered, but not that of the stomach, probably because of the adhesions which reinforced the gastric incisions. Angiography did, however, reveal delay in angiogenesis in the gastric wounds of jaundiced animals. The possible causes of this delay in healing and its clinical implications require further investigations.


The results of colostomy closure.

The results of colostomy closure. Complications arouse in 93 (44 per cent) of 213 patients following the closure of a temporary colostomy. These complications include 1 death, 19 faecal fistulas, 3 large bowel obstructions and 24 incisional hernias. Complications were most commonly seen following closure of colostomies of the sigmoid colon, especially when such closure was undertaken between the fourth and twelfth weeks after definite surgery. It is concluded that still greater care is needed in both the operative technique and the preoperative care of these patients.


Manometric studies of anorectal disorders in infancy and childhood: an investigation of the physiopathology of continence and defaecation. Anorectal manometry was performed on 126 infants and children with anorectal dosorders. In addition, 14 normal children were studied. Pressure measurements were taken with two perfused open-tip catheters. The activity of the external and internal balloon was used to distend the rectal ampulla with air.


The hydraulic impedance of the lower limb: its relevance to the success of bypass operations for occlusion of the superficial femoral artery. Simultaneous measurements of pressure and flow waves were made in the course of 25 femoropopliteal bypass operations. From these measurements the the hydraulic impedance of the arterial system in the lower limb was calculated. The values obtained were correlated with the results of the operations. Although reconstruction reduced the impedance we were unable to predict accurately the probable result of the operation on the basis of these measurements. The results suggest that success is more closely related to a good collateral circulation than to "run off".


Impedance plethysmography: evaluation of a simplified system of electrodes for the measurement of blood flow in the lower limb. Venous occlusion plethysmography was used to measure the flow of blood into the lower limbs of 30 normal volunteers. An impedance plethysmograph, using disposable point electrodes, was compared with a mercury in Silastic strain gauge plethysmograph in 20 subjects. The effect of changes in the configuration of the point electrodes was studied in 10 subjects. Impedance plethysmography was shown to be reproducible, and one particular configuration of point electrodes was shown to be superior to the others.


Myocardial infarction: a comparison between home and hospital care for patients. To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infarction within 48 hours 1895 patients were considered for study in four centres in south-west England. Four-hundred-and-fifty patients were randomly allocated to receive care either at home by their family doctor or in hospital, initially in an intensive care unit. The randomised treatment groups were similar in age, history of cardiovascular disease, and incidence of hypotension when first examined. They were followed up for up to a year after onset. The mortality rate at 28 days was 12% for the random home group and 14% for the random hospital group; the corresponding figures at 330 days were 20% and 27%. On average, older patients and those without initial hypotension fared rather better under home care. The patients who underwent randomisation were similar to those whose place of care was not randomised, except that the non-randomised group contained a higher proportion of initially hypotensive patients, whose prognosis was poor wherever treated. These results confirm and extend our preliminary findings. Home care is a proper form of treatment for many patients with acute myocardial infarction, particularly those over 60 years and those with an uncomplicated attack seen by general practitioners.


Impaired Lignocaine metabolism in patients with myocardial infarction and cardiac failure. Plasma concentrations of lignocaine were measured during and after infusion of lignocaine at 1.4 mg/min for 36-46 hours in 12 patients with myocardial infarction and one patient with cardiac failure due to uncontrolled ventricular tachycardia. In six patients without cardiac failure the plasma concentrations of lignocaine rose progressively during the infusion and the mean lignocaine half life was 4.3 hours compared with 1.4 hours in healthy subjects. Mean plasma lignocaine concentrations were significantly higher in seven patients with cardiac failure, and concentrations also rose during the infusion and the half life was considerably prolonged to 10.2 hours. Lignocaine concentrations rose rapidly to toxic levels when cardiogenic shock developed in one patient and did not fall when the infusion was stopped. The mean plasma antipyrine half life was moderately prolonged (19.4 hours) in a larger group of patients with myocardial infarction and cardiac failure but returned to normal during convalescence (13.2 hours). The metabolism of lignocaine is grossly abnormal in patients with cardiac failure and cardiogenic shock after myocardial infarction.


Nurse specialist in family planning.

Nurse specialist in family planning. In an experimental clinic, run by nurse specialists in family planning, a total of 768 patients were seen in the first year. Oral contraception was dispensed for 377 patients and 187 intrauterine devices (IUCDs) were inserted; a further 204 IUCD patients attended only for follow-up visits. All side effects were adequately diagnosed by the nurse specialist.


Prognosis of new and worsening angina pectoris. The natural history of new and worsening angina pectoris was studied in 251 men aged under 70 years. Most were ambulant and all were referred by selected general practitioners to a special hospital clinic over two and a half years. Heart attacks developed in 39 patients, nine of whom died. Seventy-two per cent of the attacks occurred within six weeks of the onset or worsening of angina. Of the 212 patients who did not suffer myocardial infarction and who were clinically reviewed six months after their first attendance 66 had been pain free for the previous three months and 14 had experienced only infrequent attacks of angina. Of the 128 men aged under 65 years who were previously in employment 81% had returned to full-time work six months after their first attendance. A discriminant function analysis using many variables was made to develop a predictive index that would allow patients with new or worsening angina who were likely to develop serious cardiac complications to be identified. This did not prove possible, and the only predictive factor of significance was an increased cardiothoracic ratio. The syndrome of new and worsening angina has a low risk of early death, and many patients are symptom free six months later. In general, emergency coronary arteriography and surgery is not indicated.


Influence of maternal obesity on subcutaneous fat in the newborn. Skinfold thickness measurements were made at biceps, triceps, subscapular, and suprailiac sites on both sides on 265 full-term newborn infants. The mothers were classified as thin (25), normal (179), or obese (61) on the basis of their triceps skinfold thicknesses. At all skinfold sites the babies of the obese mothers were significantly fatter than the babies of normal mothers, and the babies of the normal mothers were significantly fatter than those of the thin mothers. There was a highly significant positive correlation between maternal triceps thickness and the baby's sum of skinfold thicknesses. Hypertension was common during the pregnancies of the obese mothers and was associated with a significant reduction in the babies' skinfold thicknesses. When each of the 61 obese mothers were matched for parity, blood pressure, and smoking habit with 61 non-obese mothers the babies of the obese mothers still had significantly greater skinfold thicknesses than the babies of non-obese mothers.


Comparison of intravenous oxytocin and prostaglandin E2 for accelerating labour. In a prospective study of 52 consecutive women who required acceleration of labour intravenous prostaglandin E2 (PGE2) was used as the oxytocic agent. These mothers were matched for age, parity, height, gestational age, initial cervical dilatation, and station and position of the fetal head with 52 women whose labours were accelerated with oxytocin; both drugs were equally effective. Acceleration to delivery intervals, second-stage durations, the number of assisted deliveries, and Apgar scores were similar regardless of the oxytocic used. Although PGE2 compares well with oxytocin, it offers no further advantages and is more expensive and less well tried than oxytocin.


Plasma nicotine levels after cigarette smoking and chewing nicotine gum. Plasma nicotine levels were measured over seven hours of smoking cigarettes (1-2 mg nicotine) in a single subject under standardised conditions, and were compared with the levels obtained from chewing-gum containing either 2 mg or 4 mg nicotine. Levels comparable to those resulting from smoking were not obtained with the 2-mg gum, but peak levels on the 4-mg gum averaged 40-1 ng/ml from the third gum onwards compared with 49-2ng/ml after cigarettes. Nicotine was absorbed much more slowly from the gum than from cigarettes. It took 15-30 minutes for the 4-mg gum to raise the plasma nicotine by an average of 11-9 ng/ml compared with an average increase of 27-8 ng/ml within two minutes of completing each cigarette. In a sample of 15 smokers attending a withdrawal clinic the average plasma nicotine concentration while taking 2-mg nicotine chewing-gum was only 10-8 ng/ml compared with 30-4 ng/ml two minutes after smoking a cigarette. Although plasma nicotine levels equivalent to those following cigarette smoking may be  obtained by chewing at least 10 pieces of 4-mg nicotine gum daily, the slower rate of absorption may limit its therapeutic value as a substitute for cigarette smoking.


Renal function studies after nephrectomy in renal donors. Two to six years after they had donated a kidney the 24-hour creatinine clearances of five women and four men had recovered to 85% and 87% respectively of prenephrectomy performance. The male donors had a lower 24-hour creatinine clearance than age-matched controls, but during dextrose and inulin infusion they had similar values for inulin clearance, creatinine clearance, and glucose reabsorption. By contrast, the female donors had significantly reduced clearances both over 24 hours and during infusion, as well as impaired ability to reabsorb glucose. This suggests that potential female donors should be more vigorously investigated before nephrectomy.


Volvulus of the small bowel.

Volvulus of the small bowel. Over two years in a major hospital in northern Uganda 12 cases of primary volvulus of the small bowel were seen out of a total of 65 cases of intestinal obstruction which did not include external hernias. This relatively high incidence was associated with drinking large amounts of local "kongo" beer. General systemic symptoms of circulatory collapse were conspicuous by their absence. The kongo beer was found to have a high concentration of serotonin, and this substance may have caused the volvulus of the small bowel in three quarters of the cases.