Insulin regulation of hepatic glycogen synthase and phosphorylase. The relative roles of insulin and glucose in the regulation of hepatic glycogen synthase and phosphorylase were studied in hepatocytes from fed rats. Elevation of extra-cellular glucose led to a rapid decrease in phosphorylase a activity followed by a slower increase in glycogen synthase I activity. A reciprocal and coordinate relationship between phosphorylase inactivation and synthase activation in response to glucose was observed; following initial glucose-induced inactivation of phosphorylase, there was a highly significant linear inverse relationship between residual phosphorylase activity and glycogen synthase activation. Insulin led to a further decrease in phosphorylase activity and a 30-50% additional increase in glycogen synthase activity over that caused by glucose. The effects of insulin required the presence of glucose and served to augment acute glucose stimulation of glycogen synthase and inhibition of phosphorylase. Insulin did not perturb the reciprocal and coordinate relationship between phosphorylase inactivation and synthase activation in response to glucose. The results suggest that the ability of insulin to activate hepatic glycogen synthase can be entirely accounted for by its ability to inactivate phosphorylase.


Neisseria pili proteins: amino-terminal amino acid sequences and identification of an unusual amino acid. The amino-terminal amino acid sequences of the pili proteins from four antigenically dissimilar strains of Neisseria gonorrhoeae, from Neisseria meningiditis, and from Escherichia coli were determined. Although antibodies raised to the pili protein from a given strain of gonococcus cross-reacted poorly or not at all with each of the other strains tested, the amino-terminal sequences were all identical. The meningococcal protein sequence was also identical with the gonococcal sequence through 29 residues, and this sequence was highly homologous to the sequence of the pili protein of Moraxella nonliquifaciens determined by other workers. However, the sequence of the pili protein from E. coli showed no similarity to the other sequences. The gonococcal and meningococcal proteins have an unusual amino acid at the amino termini, N-methylphenylalanine. In addition, the first 24 residues of these proteins have only two hydrophilic residues (at positions 2 and 5) with the rest being predominantly aliphatic hydrophobic amino acids. The preservation of this highly unusual sequence among five antigenically dissimilar Neisseria pili proteins implies a role for the amino-terminal structure in pilus function. The amino terminus may be directly or indirectly (through preservation of tertiary structure) important for the pilus function of facilitating attachment of bacteria to human cells.


Characterization of the collagen chains synthesized by cultured smooth muscle cells derived from rhesus monkey thoracic aorta. Five different collagen chains and one smaller collagenous fragment have been isolated from the collagens found in the combined cell layer and medium of rhesus monkey aortic smooth muscle cell cultures. The collagen chains which can be identified are alpha1 (III), alpha1(I), alpha2, A and B. The smaller collagenous peptide exhibits an apparent molecular weight of 45 000 and has been designated CP45 (Mayne, R., et al. (1977), Arch. Biochem. Biophys. 181, 462). Smooth muscle cells continue to synthesize the collagens from which these components are derived for at least eight passages in culture. At each passage the alpha1 (III) chain consistently represents about one-half of the total collagen which is recovered after initial fractionation by agarose gel chromatography. The results show that smooth muscle cells derived from rhesus monkey thoracic aorta are phenotypically stable for many generations in vitro.


Purification and characterization of GM1 ganglioside beta-galactosidase from normal feline liver and brain. GM1 ganglioside beta-galactosidase (GM1-beta-galactosidase) was purified from normal cat brain and liver by a combination of classical and affinity procedures. The final preparation of brain GM1-beta-galactosidase was enriched over 2000-fold with a 36% yield. However, the product was shown to contain several components by disc gel electrophoresis. GM1-beta-galactosidase was also purified from liver with greater than a 30 000-fold enrichment and 40% yield. The liver enzyme was judged homogeneous by disc gel electrophoresis at pH 4.3, 8.1, and 8.9 and by gel chromatography. Both liver and brain GM1-beta-galactosidase(s) eluted as sharp symmetrical peaks from Sephadex G-200 with molecular weights of 250 000 +/- 50 000. The apparent Km determined for 4-methylumbelliferyl beta-D-galactopyranoside (4-MU-Gal) using partially purified brain GM1-beta-galactosidase was 1.73 X 10(-4) M. Liver GM1-beta-galactosidase gave a Km with 4-MU-Gal of 3.25 X 10(-4) M and for [3H]GM1 ganglioside a Km of 4.51 X 10(-4) M was calculated. The pH optima of brain and liver GM1-beta-galactosidase using 4-MU-Gal was 3.8-4.5. By contrast, liver GM1-beta-galactosidase gave a sharp activity peak at pH 4.2 with [3H]GM1 ganglioside. Inhibition by mercuric chloride and sensitivity to hydrogen peroxide and persulfate suggest the involvement of a sulfhydryl in catalysis.


Dual action of ionophore A23187 on intact chloroplasts. 1. Ionophore A23187 induces uncoupling of potassium ferricyanide-dependent O2 evolution by envelope-free chloroplasts and oxaloacetate-dependent O2 evolution by intact chloroplasts. The half maximal concentration (C1/2) for stimulation of oxygen evolution in both cases is approximately 4 micrometer . 100 microgram chlorophyll . ml-1. 2. Ionophore A23187 also induces inhibition of CO2 and 3-phosphoglycerate-dependent O2 evolution by intact chloroplasts in the presence of 3 mM MgCl2. The half maximal concentrations (C1/2) for inhibition of O2 evolution are 3 micrometer and 5 micrometer respectively . 100 microgram-1 chlorophyll . ml-1. 3. A very high concentration of ionophore A23187 (10 microgram . 20 microgram-1 chlorophyll . ml-1) plus 0.1 mM EDTA lowers the fluorescence yield of intact chloroplasts suspended in a cation-free medium in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, indicating loss of divalent cation from the diffuse double layers of the thylakoid membranes. 4. These results are discussed in relation to ionophore A23187-induced divalent cation/proton exchange at both the thylakoid and the envelope membranes of intact chloroplasts.


Changes in photosynthetic activity in the cyanobacterium Chlorogloea fritschii following transition from dark to light growth. The cyanobacterium Chlorogloea fritschii loses Photosystem II activity, measured by delayed fluorescence and oxygen evolution, during dark heterotrophic growth, but retains Photosystem I, measured as light induced EPR signals. Following transition to the light, Photosystem II recovers in two stages, the first of which does not require protein synthesis. New Photosystem I reaction centres are not synthesised until after net chlorophyll synthesis has commenced. Carbon dioxide fixation recovery commences immediately, the initial rate being unaffected by chloramphenicol. The recovery of carbon dioxide fixation is not directly related to oxygen evolution rate and is only inhibited slightly by 3-(3,4-dichlorophenyl)-1,1-dimethylurea and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone.


Inhibition of conjugation in Tetrahymena pyriformis by cerulenin. Possible requirement for de novo lipid synthesis. Conjugation in Tetrahymena pyriformis is induced by the mixing of two starved complementary mating types. Addition of the antibiotic cerulenin, a specific inhibitor of de novo lipid synthesis, upon mixing of the mating types inhibited the conjugation process. The inhibition of conjugation was found to be reversible upon washing the cells. Cerulenin inhibited [14C]acetate incorporation into the lipid fraction of the cells, while it did not affect the incorporation of [3H]leucine into proteins. Analysis of the fatty acid composition of the whole cells revealed that during conjugation the ratio of saturated to unsaturated fatty acids is markedly changed. While the ratio of saturated:unsaturated fatty acids is 0.30 in unconjugated cells, it reached a value of 0.45 in conjugated cells.


The effect of toluene on the structure and permeability of the outer and cytoplasmic membranes of Escherichia coli. The effect of toluene on Escherichia coli has been examined. In the presence of Mg2+, toluene removes very little protein, phospholipid, or lipopolysacharide from E. coli. In the absence of Mg2+, or in the presence of EDTA, toluene removes considerably more cell material, including several specific cytoplasmic proteins such as malate dehydrogenase (EC 1.1.1.37). In contrast, glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and glutamate dehydrogenase (EC 1.4.1.4) are not released at all under the same conditions. Cells treated with toluene in the presence of Mg2+ remain relatively impermeable to pyridne nucleotides, while cells treated with toluene in the presence of EDTA become permeable to these compounds. Freeze-fracture electron microscopy shows that toluene causes considerable damage to the cytoplasmic membrane, while the outer membrane remains relatively intact. These results indicate that the permeability characteristics of toluene-treated cells depend at least partly on the state of the outer membrane after the toluene treatment.


Properties of alkaline phosphatase of the halotolerant yeast Debaryomyces hansenii. The molecular weight of a partially purified alkaline phosphatase (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.1) from the halotolerant yeast Debaryomyces hansenii was estimated to 110,000 by gel filtration. The isoelectric point determined by electrofocusing was at approximately pH 4.4. The enzyme had a broad specificity against phosphomonoesters and also attacked some acid anhydrides. Arsenate, molybdate, and orthophosphate acted as competitive inhibitors. Various metal-binding agents inhibited enzyme activity. A zinc addition almost completely reversed the EDTA inhibition. Magnesium stimulated enzyme activity and was required for maintenance of activity at high concentrations of Na+. Increasing glycerol concentration increased the value of the Michaelis constant (Km) and decreased the maximum velocity (V). Solutions equimolar in KCl and NaCl stimulated enzyme activity by increasing V, whereas the Km was almost unaffected by salt concentration. Enzyme extracted from cells cultured at low salinity was indistinguishable from that of cells grown in the presence of 2.7 M NaCl with respect to several criteria.


I-Cell disease: isoelectric focusing, concanavalin A-Sepharose 4B binding and kinetic properties of human liver acid beta-D-galactosidases. Isoelectric focusing of the acid beta-D-galactosidases (beta-D-galactoside galactohydrolase, EC 3.2.1.23) in normal crude liver supernatant fluids demonstrated multiple isoelectric forms in the pH range 4.58-5.15, while corresponding I-cell disease samples showed an absence of isoelectric forms in the pH range 4.99-5.15. Concanavalin A-Sepharose 4B chromatography of the I-cell disease mutant C.A. demonstrated a 31% and 37% decrease in the binding of 4-methyl-umbelliferyl-beta-D-galactosidase and GM1 beta-D-galactosidase activities, respectively, when compared to normal samples. Isoelectric focusing profiles of the concanavalin A-Sepharose 4B alpha-methyl-D-mannoside effluents containing normal and I-cell disease acid beta-D-galactosidase were generally similar, but the unadsorbed I-cell disease enzyme from concanavalin A-Sepharose 4B demonstrated more activity in the pH range 4.21-4.49 than normals. Normal and I-cell disease acid beta-D-galactosidase "A" and "B", separated by gel column chromatography were found to have similar properties with respect to apparent molecular weights pH vs. activity profiles and apparent Km values for the 4 methylumbelliferyl-beta-D-galactopyranoside, GM1-ganglioside and asialofetuin (ASF) substrates. However, the apparent V values for the ICD samples were consistently reduced when compared to the results obtained with the corresponding normal fractions. The greatest decreases in apparent V were obtained for acid beta-D-galactosidase activities in I-cell disease crude supernatant fluids, and for the separated I-cell disease "B" enzyme. The differences in the isoelectric focusing profiles, the altered binding to concanavalin A-Sepharose 4B, and the reduced V values with natural and synthetic substrates may be related to changes in carbohydrate composition of I-cell disease acid beta-D-galactosidase.


Interaction of trypsin-like protease from Streptomyces griseus with an immobilized inhibitor from kidney bean. An immobilized double-headed inhibitor from Phaseolus vulgaris L. selectively binds the trypsin-like enzyme produced by Streptomyces griseus. Binding takes place at pH 8.0, and at pH 2.0 the protease can be quantitatively released from the complex. Purified by affinity chromatography, the trypsin-like enzyme is homogeneous according to polyacrylamide gel electrophoresis and ultracentrifugation data. Physico-chemical and enzymic properties of the enzyme are identical to those exhibited by the enzyme purified by ion-exchange chromatography. Chymoelastases from Str. griseus as well as the subtilisin-like enzyme do not interact with an immobilized inhibitor. In solution, the inhibitor from P. vulgaris gives a stable ternary complex with bovine trypsin and chymotrypsin, whereas with an immobilized inhibitor the trypsin, if present, tends to displace chymotrypsin in an chymotrypsin inhibitor complex. This evidence suggests that immobilization results in considerable changes in inhibitor properties.


Purification and characterization of rat heart and brain catechol methyltransferase. In an effort to detect the similarities and differences in the properties of rat heart, brain and liver catechol methyltransferase (S-adenosyl-L-methionine:catechol O-methyltransferase, EC 2.1.1.6), we have determined the cellular distribution of this enzyme activity and extensively purified the soluble and microsomal enzymes present in these tissues. Purification of soluble heart (688-fold) and brain enzymes (240-fold) were achieved using an affinity chromatographic system. The properties of these enzymes were compared with respect to their molecular weights, substrate specificities, inhibitor specificities and immunological properties. The characteristics of the enzyme active sites were investigated using various methyl acceptor substrates and various analogs of S-adenosylmethionine as methyl donors. A series of analogs of S-adenosylhomocysteine was also evaluated as inhibitors of these enzymes. The immunological properties of the purified soluble and microsomal enzymes from heart and brain were investigated using an antibody isolated from rabbits which had been immunized with the soluble rat liver enzyme. In general the properties of catechol methyltransferases isolated from heart and brain were similar to the properties of the enzyme isolated from liver. Some minor differences in substrate and inhibitor specificities were observed which might suggest slight differences in the active sites of these enzymes.


Physicochemical and biological characterizations of pregnant mare serum gonadotropin and its subunits. Pregnant mare serum gonadotropin and its subunits have been further characterized. Ultracentrifugation of the gonadotropin at pH 1.3 and 11.5 showed little evidence of dissociation compared to pH 8.2. Highly purified subunits are obtained by urea dissociation and ion-exchange chromatography followed by gel-filtration. Circular dichroism spectra of the gonadotropin and its subunits are much like those of ovine lutropin and its subunits in that there is little evidence for secondary structure and one or more tyrosine residues are inaccessible in the intact gonadotropin compared to the subunits. The alpha-subunit possesses almost 3 times as much total carbohydrate as the beta-subunit; the individual sugar composition of each was determined as well as the amino acid composition. The alpha-subunit begins with the sequence NH2-Phe-Pro (Gly or Pro) ... and terminates with isoleucine. The beta-subunit has the sequence NH2-Ser-Pro-Gly ...; no C-terminal residue is detectable by either carboxypeptidase or hydrazinolysis. Biological studies show the gonadotropin to be active in assays specific for both lutropin and follitropin. Precipitin test in agar with rabbit antiserum against the gonadotropin show that the beta subunit cross-reacts whereas the alpha subunit does not.


Effect of calcium on extraction of Z-band proteins from I-Z-I brushes of rabbit striated muscle. 1. When rabbit striated muscle I-Z-I brushes were subjected to eleven extractions with three different extracting solutions, relatively more amount of proteins was extracted in the presence of 1 nM CaCl2 than in the presence of 5 mM EDTA or 5 mM ethyleneglycol-bisp(beta-aminoethylether)-N,N,N1,N1-tetra-acetic acid (EGTA). Among proteins extracted in the presence of 1 mM CaCl2, the protein components with molecular weights of 85,000, 95,000 and 220,000 were included, whereas these were not extracted in the other two. 2. Co-electrophoreses of 220,000 dalton protein and myosin heavy chain showed that these two protein components were distinct from each other. 3. Roles of Ca2+ are discussed on disintegration processes of I-Z-I brushes in special reference to its co-operative action with calcium-activated factor enzyme.


Biochemical studies on glucose initiated germination in Bacillus megaterium. Bacillus megaterium QM B1551 spores contained the enzymes for the Embden-Meyerhof pathway and the initial reactions in the hexose monophosphate pathway but not the Entner-Doudoroff pathway. With [U-14C]glucose no metabolism was detected until after about 30% of the spores had lost heat resistance. Mutants that lacked either phosphofructokinase or 6-phosphogluconate dehydrogenase were able to initiate germination on glucose like wild type. Purified methyl alpha-D-glucopyranoside, 6-deoxyglucose and 6-deoxy-methyl alpha-D-glucopyranoside were not substrates for spore enzymes yet these compounds still initiated germination. Therefore, metabolism of exogenously added glucose is probably not the primary stimulatory effect in germination.


[Characteristics of glycogen synthetase I from rabbit skeletal muscles]. Electrophoretic heterogeneity of glycosynthetase I from rabbit skeletal muscles is observed. Multiple glycosynthetase forms are separated in sucrose density gradient, their molecular weights are estimated. The existence of the enzyme as an equilibrium system of oligomeric forms, capable of reversible association-dissociation, is demonstrated. Dissociating effect of ATP, high pH values (11--12) and high ionic strength (2 M KCl) on oligomers of glycogen synthetase I is found to take place. Different activity of oligomers of different association degree is observed.


Renin production in Chagas' disease.

Renin production in Chagas' disease. In six controls and ten patients with Chagas' disease (Trypanosomiasis cruzi), plasma renin activity was measured in peripheral venous blood, after 12 hours lying supine, and subsequently in an upright position at 5, 15, 30, 60 and 240 minutes. Evidence of a postganglionic autonomic defect at the sympathetic efferent kidney innervation was observed, probably in two stages corresponding to the clinical form of the disease: The first (asymptomatic or intermediate clinical form) with high renin production and the second with low renin production associated with digestive form of Chagas' disease.


Deformation of human erythrocytes in a centrifugal field. A new method for altering red cell morphology by high-speed centrifugation of cells through a physiological medium is described. Cell shape is preserved for microscopic analysis by allowing the sedimenting cells to pass from the physiological medium into a glutaraldehyde fixative solution. Examination of the deformed, fixed cells indicates that the vast majority resemble spheres with a flat, triangular tail. Measurements of the overall length of deformed cells show a nearly linear relationship between cell length and centrifugal force; average cell length increased from 8 to 11 micrometer as the centrifugal field was increased from 2,000 to 15,000 g. These data suggest that this centrifugal technique may be useful for evaluating cellular deformability and, potentially, the material properties of red cells.


A kinetic model for microtubule polymerization during oral regeneration in Stentor coeruleus. The regeneration of oral cilia in the protozoan cell, Stentor coeruleus, has been investigated in the presence of agents which do not favor the polymerization of microtubules. These agents, low temperature and the tubulin binding drugs, podophyllotoxin and beta-peltatin, slow the rate of regeneration. A kinetic model is proposed to test the hypothesis that microtubule polymerization is the rate limiting step in oral regeneration. The results suggest that the tubulin concentration of normal regenerating cells is slightly in excess of an amount which would kinetically limit the regeneration rate.


["Transplanted cell antigen" and its detection in different human organs]. A cell membrane antigen was found in the continuous cell lines of epithelial origin, identical to the antigen revealed in the homogenates of human gastric mucosa. The antigen was detected with the aid of an antiserum against the solubilized membrane antigen from Hep-2 cells sorbed with a mixture of homogenates of human tissues--the lung, the liver, papillomatosis of the larynx and of the mammary gland. The described antigen was revealed in some (not all) adenocarcinomas of the stomach; it differs from carcinoembryonic Gold's antigen and from the secretory IgA component, it is not a structural component of D-type oncornoviruses (of primates) produced by Hep-2 cells, and does not seem to be coded by the genom of this virus.


[Use of the enzyme neuraminidase for immunotherapeutic treatment of chemically induced carcinogenesis]. The effect of vibrio cholerae neuraminidase (VCN) on the growth of dimethylbenzanthracene-induced sarcoma cells in the inbred CBA mice was investigated. The use of this preparation was started after the appearance of the tumour. Injection of 50 units of VCN twice a week for three months was effective at the early stages of carcinogenesis. An increase of the life-span of mice of comparison with control animals was also observed in the animals inoculated intraperitoneally with induced syngeneic sarcoma cells pretreated with VCN and simultaneously injected (into the developing tumour) with sensitized lymphocytes received from the syngeneic tumour-bearing mice. Lymphocytes were inoculated into the growing tumour. No positive effect ensued when the lymphocytes inoculated into the tumour region were pretreated with VCN. A simultaneous inoculation of neuraminidase into the growing tumour and of syngenous induced-sarcoma cells pretreated with this enzyme intraperitoneally was the most effective. Possibilities of application of neuraminidase under clinical conditions are discussed.


The role of extracellular calcium in the contractions produced by acetylcholine in chronically denervated muscle. 1 Acetylcholine-induced contractions of the isolated chronically denervated soleus muscle of the mouse consist of two phases, but both phases are equivalent to the contracture phase seen in vivo.2 Low [Ca(2+)](0) (0.5-1.5 mM) augmented peak tension, as well as the rate of relaxation, of the first phase, but inhibited the second phase. Ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) or La(3+) (2 mM) also inhibited the second phase, but not the first.3 It was concluded that the first phase requires Ca(2+) release from the sarcoplasmic reticulum, and is terminated by inactivation of the contractile process. The second phase is caused by the entry of activator Ca(2+) from the extracellular space.4 Increasing [Ca(2+)](o) to 5 or 10 mM after the addition of acetylcholine caused a contraction, starting after a delay of about 50 seconds. EGTA or La(3+) added during the second phase of the acetylcholine contraction caused relaxation after a much shorter lag time.5 It is concluded that most of the Ca(2+) entering from the extracellular fluid is taken up by the sarcoplasmic reticulum.6 The acetylcholine second phase was augmented in low (25 mM) [Na(+)](0). It is concluded that Na(+) and Ca(2+) compete for the acetylcholine controlled ionic channels.7 Isolated chronically denervated diaphragm muscles were less sensitive to acetylcholine and the contraction usually consisted of a first phase only.8 It is concluded that sequestration of Ca(2+) entering from the extracellular fluid is more complete in the diaphragm.


A technique for measuring the accumulation of 99 Tcm stannous-ethane-1-hydroxy-1, 1-diphosphonate in the canine tibia. An experimental technique is described to measure the accumulation of 99Tcm-stannous-ethane-1-hydroxy-1, 1-diphosphonate (99Tcm-EHDP) in the canine tibia. The method involves infusion at a constant rate of known amounts of 99Tcm-EHDP into the nutrient artery supplying the tibial bone. The accumulation of the diphosphonate in bone is measured by an external sodium iodide, Nal (T1), scintillation detector. Results are presented showing that for small amounts of 99Tcm-EHDP (0.004-0.300 mg per hour) the accumulation is a nearly linear function with time for 60 minutes, after which the uptake may become variable with either a plateau formation or considerable fluctuation of activity.


Differential androgen uptake by the lobes of the rhesus monkey prostate. The prostate of the rhesus monkey (Mucacca mulatta) consists of a cranial and a caudal lobe. The uptake of [3H] testosterone by these 2 lobes has been measured and compared with control tissues. A significantly higher uptake of radioactivity was found in the caudal lobe when compared to cranial as well as other control tissues. The uptake of radioactivity by the caudal and cranial lobes was suppressed when unlabelled testosterone was introduced into the incubation media. The relationship between these 2 lobes of the monkey prostate and the central and peripheral zones of the human prostate is described.


The circadian variation of catecholamine metabolism in the subhuman primate. Cerebrospinal fluid (CSF) was removed continuously in 2- or 3-h aliquots from the lateral and fourth cerebral ventricles of chronic chair restrained rhesus monkeys. Under conditions of 12 h light (06.00-18.00 h) and 12 h darkness (18.00-06.00 h) the concentrations of norepinephrine (NE) were found to describe a circadian pattern, with maximal concentrations occurring during the light hours and minimal concentrations occurring during the dark hours. The patterns were generally coincident with the circadian patterns of brain temperature and body activity. When assayed for 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA), samples of CSF collected over 3-4 days demonstrated no reproducible pattern of change. Fluctuation in the concentration of MHPG did not correspond in direction or magnitude to changes in the concentration of VMA. These random fluctuations may in part be accounted for by the influx of the metabolites from peripheral sources to the brain and CSF, and by the relatively slow movement of these metabolites as they diffuse from brain parenchyma to the CSF.


Cortico-striate projections in the rhesus monkey: the organization of certain cortico-caudate connections. The organization of cortical projections to the caudate nucleus was investigated in the rhesus monkey, using the autoradiographic tracing method. Following injections of tritiated leucine and proline into selected pre- and post-Rolandic association areas in the frontal, parietal, occipital and temporal lobes, widespread projections were observed to one, or more typically, more than one of the major subdivisions of the caudate nucleus. When cortical areas having strong reciprocal cortico-cortical connections were compared, a considerable communality of their cortico-caudate projections was noted; depending on the location of the cortical areas, the region of common distribution lay within the head, the body, or the tail of the caudate nucleus. This correlation between cortico-cortical and cortico-striate projections characterized all pairs of cases studied. It suggests a previously undescribed principle of organization within the telencephalon, namely, that areas of cerebral cortex having reciprocal cortico-cortical connections, while having unique overall patterns of projection to the caudate nucleus, project, in part, to one and the same region of the nucleus. This might imply that a given region of the caudate nucleus receives input not only from a particular area of cortex, but also from all other cortical areas reciprocally interconnected with that area.


A selective medium for the rapid isolation of pseudomonads associated with poultry meat spoilage. 1. A new selective medium (CFC) has been developed for the rapid isolation of pigmented and non-pigmented pseudomonads associated with the spoilage of poultry meat held under chill conditions. It comprises Difco Heart Infusion Agar supplemented with 50 microgram cephaloridine, 10 microgram fucidin and 10 microgram cetrimide/ml. 2. CFC medium was found to be more selective than three other media which have been used for isolating pseudomonads from foods, when tested with pure cultures of 28 reference organisms. 3. CFC supported the growth of a higher proportion of pseudomonads from freshly-eviscerated carcasses and processing equipment when the organisms were present only in low numbers relative to other genera.


The nacreous layer in Mytilus, Nucula, and Unio (Bivalvia). Crystalline composition and nucleation of nacreous tablets. Etching with the glutaraldehyde-acetic acid solution reveals that the nacreous tablets in Mytilus, Nucula, and Unio are composed of four crystal individuals which occur in two structurally different pairs and which are probably cyclically twinned. In Mytilus, one pair consists of horizontal lamellae, whereas the other pair lacks the lamellae. The lamellar pair of crystals is considerably less soluble in the etching solution than the non-lamellar pair. In the less-soluble crystal pair of Nucula and Unio, the lamellar structure is absent. In all three genera, the nucleation of new nacreous tablets invariably takes place on the top surface of the less-soluble crystal individuals. The stack-like growth of the nacreous tablets in the marginal region of the shell in Nucula is probably related to the exceptionally large-sized, less-soluble crystal individuals in the nacreous tablets of this region.


Changes in red cell, plasma, inulin, and total water compartments in rat femurs. Comparison of vitamin D deficiency and diphosphonate induced rickets. The vascular space, as measured with the use of 99m-technetium-labelled red cells and 131I-serum albumin, as well as the 14C-inulin and 3H2O fluid compartments were measured in rats which had been made rachitic by the use of a low phosphate vitamin D-deficient diet. A similar group of rachitic animals fed vitamin D2 50 IU, 5 and 3 days prior to sacrifice and a weight-matched control group were also studied. The same spaces were measured in rats made rachitic by daily s.c. injections of ethane-1-hydroxy-1,1-diphosphonate (EHDP) for 4 weeks and a weight-matched saline injected control group. Findings indicated that the red cell and RISA spaces were unchanged in the untreated D-deficient group as compared to controls but increased after being repleted with vitamin D. By contrast, the vascular space was depressed in the EHDP-treated group. The water content was elevated in D-deficient rickets returning towards normal on healing, whilst both inulin and water spaces were increased in the EHDP-treated animals. Thus, while the extravascular space reflected the presence of osteoid, the vascular space depended on cellular turnover and the process of mineralization.


Some biophysical and biochemical properties of poly(phthaloyl L-lysine) microcapsules containing hemolysate. Measurements of oxygen equilibrium, zeta-potential, resistance to flow, carbonic anhydrase activity, and catalase activity were made on sheep erythrocyte hemolysate-loaded poly(phthaloyl L-lysine) microcapsules (artificial red blood cells) prepared by an interfacial polycondensation technique. The measurements revealed that oxygen dissociation equilibrium, zeta-potential, and carbonic anhydrase activity of the microcapsules are almost the same as those of sheep erythrocytes, while the microcapsules have a higher resistance to flow and a lower catalase activity than the erythrocytes. Possible ways of improving the properties of the microcapsules were suggested.


The history, biology, and taxonomy of the Cytophaga group. The first section of this review covers the important characteristics of the genera Cytophaga and Sporocytophaga. The topics discussed include vegetative cell structure, the spreading habit, and degradation of macromolecules. A historical account of these two genera follows, together with a discussion on the definition of, and species differentiation with the genus Cytophaga, and on the taxonomy of Sporocytophaga. The third section deals with the relationships of the cytophagas with the flavobacteria and includes a brief history of Flavobacterium, reassignation of some species to Cytophaga, differentiation from Cytophaga, and a discussion on the definition of the genus Flavobacterium. This is followed by a section dealing with the relationship of Cytophaga with the flexibacteria, starting with an introduction to the diversity of flexing organisms and taxonomic developments, and proceeding with the differentiation within the family Cytophagaceae, and species differentiation in Flexibacter. The concluding section includes a proposed redefinition of Cytophaga, a proposal regarding species conservation in this genus, and discussions on the relationship between the cytophagas and the myxobacteria and on the significance of cytophagas in the environment. The characteristics of all described species of Cytophaga, Flexibacter, and relevant flavobacteria are tabulated and a bibliography is presented.


Pigmentation phenotype instability in Myxococcus xanthus. Cells of Myxococcus xanthus FB2 produce tan or yellow colonies. Subcultures of tan colonies yielded tan and yellow colonies and subcultures of most yellow colonies yielded only yellow colonies. Strain FB2 variants in which the color type is more stable were obtained. Yellow cells were distinguishable from tan by the presence of pigment(s) with an absorption maximum at 379 nm. Fluctuation Test experiments and the presence of this pigment(s) in liquid cultures of FB2 indicated that tan phenotype cells spontaneously became or segregated yellow cells in liquid culture. The frequency of appearance of yellow cells was increased in low density cultures (less than 10(6)/ml). The increase cannot be explained by differences in growth rates of the two phenotypes. No evidence that cell-cell contact or culture medium constituents affect the appearance of the yellow phenotype was found. Ultraviolet irradiation of FB2 resulted in an increased proportion of cells producing yellow colonies among the survivors. Greater UV resistance of yellow cells and UV-induced conversion of tan to yellow accounts for this increase. Low level photoreactivation of viability and of the tan phenotype occurred. Incubation of FB2 in medium containing mitomycin C, nalidixic acid, phenethyl alcohol, or at 36.5 degrees C also resulted in conversion of tan to yellow cells.


The electrochemical proton gradient and phenylalanine transport in Escherichia coli irradiated with near-ultraviolet light. Irradiation of Escherichia coli with near-ultraviolet (near-UV) light diminished the electrochemical proton gradient and the accumulation of L-phenylalanine. Inhibitors known to collapse the proton gradient and the comparison of two techniques measuring the electrical potential substantiated the estimates made. At several fluences (doses), a linear relationship was observed between the phenylalanine gradient and the combined electrical and chemical potentials (the electrochemical proton gradient), suggesting a close coupling between them. However, additional effects of near-UV light on the phenylalanine permease were not discounted. The combined potentials provided sufficient energy for the observed accumulation of phenylalanine, assuming a proton to amino acid cotransport ratio of 1. An increase in membrane permeability did not contribute to the loss of phenylalanine transport, as shown by an increase in the rate and extent of alpha-methylglucoside uptake.


A microbiologic disc assay for 5-methyltetrahydrofolate in the presence of methotrexate. High-dose methotrexate-citrovorum factor rescue regimens are used extensively for the treatment of human malignancies. Since the rescue agent citrovorum factor is rapidly converted to 5-methyltetrahydrofolate, it is desirable to follow the distribution kinetics of both of these coenzymes to assess the selective therapeutic effectiveness of the regimen. The assay methods using methotrexate-resistant strains of Lactobacillus casei ATCC 7469 (LC/A), Streptococcus faecium var. durans ATCC 8043 (SF/A), and Pediococcus cerevisiae ATCC 8081 (PC/A) have been developed to determine the concentrations of 5-methyltetrahydrofolate and other folates in the presence of methotrexate. Since LC/A determines the total folates, SF/A deterimines the total folates except 5-methyltetrahydrofolate, and PC/A by our procedure determines only the most stable form of reduced folates, citrovorum factor, the quantitation of both 5-methyltetrahydrofolate and citrovorum factor can very easily be achieved by differential assays. This report describes the determination of as low as 10 ng/ml of 5-methyltetrahydrofolate in the presence of as high as 500 microgram/ml of methotrexate. The assay method described here is currently used in studying the pharmacokinetics of 5-methyltetrahydrofolate in patients with meningeal neoplasms.


Evaluation of a hexamethylmelamine and 5-fluorouracil combination in the treatment of advanced ovarian carcinoma. The combination of two nonalkylating agents, hexamethylmelamine (HMM) and 5-fluorouracil (5-FU), was evaluated in 14 patients with advanced ovarian carcinoma. Nine patients had been treated previously with alkylating agents. The overall response rate was 36% which is not greater than could be expected with either HMM or 5-FU alone. However, the median survival of the five responders was greater than 24 months. Treatment had to be discontinued in five of 14 patients due to excessive toxicity. Although the toxic effects were predominately gastrointestinal, unpredictable hematopoietic and neurotoxic effects were observed.


The 5S genes of Drosophila melanogaster. We have cloned embryonic Drosophila DNA using the poly (dA-DT) connector method (Lobban and Kaiser, 1973) and the ampicillin-resistant plasmid pSF2124 (So, Gill and Falkow, 1975) as a cloning vehicle. Two clones, containing hybrid plasmids with sequences complementary to a 5S RNA probe isolated from Drosophila tissue culture cells, were identified by the Grunstein and Hogness (1975) colony hybridization procedure. One hybrid plasmid has a Drosophila insert which is comprised solely of tandem repeats of the 5S gene plus spacer sequences. The other plasmid contains an insert which has about 20 tandem 5S repeat units plus an additional 4 kilobases of adjacent sequences. The size of the 5S repeat unit was determined by gel electrophoresis and was found to be approximately 375 base pairs. We present a restriction map of both plasmids, and a detailed map of of the5S repeat unit. The 5S repat unit shows slight length and sequence heterogeneity. We present evidence suggesting that the 5S genes in Drosophila melanogaster may be arranged in a single continuous cluster.


Patterns of protein synthesis in imaginal discs of Drosophila melanogaster. Patterns of polypeptide synthesis in wing, leg and eye-antenna imaginal discs and in whole larvae of wild-type and and mutant Drosophila melanogaster have been examined using two-dimensional polyacrylamide gel electrophoresis and autoradiography. After 2 hr of labeling with 35S during the third larval instar, the synthesis of more than 318 polypeptides has been detected in imaginal discs. Of these, 268 are present in similar amounts in all three disc types. The remaining polypeptides detected in the three imaginal disc types fall into two categories: those unique to a particular disc type, and those specific for a particular pair of disc types. These results are discussed in relation to the spectrum of gene expression in imaginal discs.


Increased carbonic anhydrase activity in Friend erythroleukemia cells during DMSO-stimulated erythroid differentiation and its inhibition by BrdU. Carbonic anhydrase activity is increased in Friend erythroleukemia (FL) cells during the enhancement of erythroid differentiation in the presence of dimethylsulfoxide (DMSO) or butyric acid. Untreated FL cells show an increase in enzyme activity associated with logarithmic growth. The increase in the specific activity of carbonic anhydrase in the differentiating treated cells, however, appears to be due to at least two additional general mechanisms: (1) an induction of carbonic anhydrase paralleling the stimulation of hemoglobin synthesis and (2) the stability and/or retention of active carbonic anhydrase as compared to most of the other cell proteins. The stimulation of carbonic anhydrase activity in the treated cells is inhibited by 5-bromo-2'-deoxyuridine (BrdU). This is the first demonstration of BrdU inhibition of a DMSO induced product not directly related to hemoglobin.


Neutral and acid lipase of mouse 3T3 fibroblasts with increased adipose conversion. In the resting state, 3T3-L1 fibroblasts become adipose converted and increase their fatty acid and triglyceride synthetase. We have found that they contain four times the neutral lipase activity and 1.5 times the acid lipase activity of logarithmically dividing cells. The activities of lysosomal acid beta-galactosidase and N-acetyl-beta-D-glucosaminidase were the same in the adipose converted and logarithmically dividing cells. The data suggest a possible relation between the increased neutral lipase activity in 3T3-L1 cells and their adipose conversion and demonstrates that the adipose converted 3T3-L1 fibroblasts, unlike true adipose cells, contain high levels of lysosomal acid hydrolases.


Experimental activation of ascidian eggs. The effects of the ionophore A23187 on the activation of the eggs of Ascidia malaca have been studied. No common external ion in the sea water is found to be essential for the activation but lanthanum and manganese inhibit the response. These observations support the interpretation that activation of these eggs results from changes in free intracellular calcium levels. This has led to the prediction of two other activating treatments, namely high external calcium and addition of theophylline.


[Ossifying adrenocortical carcinoma with myelolipoma]. In a 25-year-old female in adrenocortical carcinoma with a myelolipoma and areas of ossification was removed by operation. The carcinoma did not penetrate the myeloadipose structure. The finding of an actively growing bone within the stroma of the adenocarcinoma can be explained by the local action of androgens produced by the tumour tissue.


Pesticide induced ouabain resistant mutants in Chinese hamster V79 cells. The effect of 3 insecticides (chlordane, dieldrin and carbaryl) and one herbicide (2,4-D-fluid) was studied on the induction of ouabain-resistant mutants in Chinese hamster V79 cells at concentrations approaching the Environmental Protection Agency (EPA) tolerance limits. The kinetics and dose range for cytotoxicity were determined by colony formation assay. Results showed that these compounds enhanced the number of ouabain-resistant mutants and acted as weak mutagens.


Non-Mendelian development defects: animal models and implications for research into human disease. The major groups of malformations in man are polygenic in origin but this review deals only with defects due to non-Mendelian factors. Animal models that help in identifying the causes and in understanding the numerous and often subtle mechanisms of human malformations are of particular value. Many chemicals, physical agents, and nutritional deficiencies affect experimental species but few are teratogenic for domestic animals and even fewer for man. The known fetopathic viruses of animals and man cross the placenta to cause chronic, nonlethal fetal damage without harm to the mother. Ionizing radiations are teratogenic for all species and hyperthermia for many, but the role of the latter in human development is uncertain. The identification of more animal species with spontaneous or induced defects comparable to those found in man and of additional causative teratogens will increase the resources available for research into the causes and mechanisms of abnormal development in man. No animal species is ideal in teratological research but each has its virtues. This report comments on the present status of research in teratology and the trends that might profitably be followed in the future.


A second controlled field trial of a serogroup A meningococcal polysaccharide vaccine in Alexandria. The encouraging results of an earlier controlled field trial of the serogroup A meningococcal polysaccharide vaccine in the prevention of clinical disease prompted this study, the aim of which was to evaluate further the effectiveness of another lot of this type of vaccine, the duration of immunity, and the effectiveness against meningococcal carriage. A controlled field trial was carried out in early 1973 on 176 646 schoolchildren 6-15 years of age, of whom half received the serogroup A polysaccharide vaccine and the other half tetanus toxoid as a control. The incidence of cerebrospinal meningitis caused by serogroup A meningococci was 89% lower in the immunized group than in the controls for one year only. With regard to its effect on carriage, the vaccine was found to reduce to less than half the rate of new acquisition of serogroup A meningococci during the period immediately following immunization. The duration of the carrier state was also shortened in the immunized group.


Naturally occurring antibodies to Neisseria meningitidis. Immunity in meningococcal diseases has been inadequately studied and, until now, most attempts at serotherapy and immunization against meningococcal meningitis have been unsuccessful. To ascertain the status of immunity among children at greatest risk of contracting the disease, 267 serum specimens from healthy children aged from 1 month to 5 years were examined with Farr's radioimmunological technique, as simplified by Gotschlich. The results showed that the children must have received maternal antibodies through the transplacental route. Antibodies persisted up to the third month of life, after which they were virtually undetectable until, at about 8 months of age, antibodies reappeared. Subsequently there was a gradual rise, especially from 2 to 5 years, 97% of children in the highest age group having serum antibody levels of 0.479 mug/ml or more. These children may have had meningococcal infections that were wrongly diagnosed as respiratory disease of unknown etiology.


A comparison of the serum agar grouping and slide agglutination methods for the identification of Neisseria meningitidis strains. The serum agar grouping (SAG) and slide agglutination (SA) tests were compared for their ability to identify strains of N. meningitidis. There was no significant difference between the two methods in respect of their relative sensitivity and detection ability. The most suitable concentration of antimeningococcal serum for SAG was found to be 1:10; however, the most suitable concentration will need to be established for each serum used. The ability of SAG to identify large numbers of N. meningitidis strains was confirmed.


[Effect of adrenaline on the influx of Na+ and Cl- in trout (Salmo gairdneri) adapted to seawater]. The effects of adrenaline on the Na+ and Cl- influxes in the seawater adapted trout were studied with the perfused isolated head technique. With 10(-5) M adrenaline in the perfusion fluid, the lamellar influx of Na+ is increased by 60%, while the Cl- influx is inhibited by 90%. This catecholamine does not modify the extra-lamellar entry of NaCl which passes into the filamental sinus.


[The effects of intraventricular injection of 6-hydroxydopamine on the sleep of kittens during development]. Intraventricular injection of 6-hydroxydopamine does not modify the states of alertness in the Kitten, if it is performed in the first week of postnatal life. At three weeks of age, it induces the same sleep impairments as those observed in the adult Cat. Therefore, in the immediate postnatal period, sleep control is not achieved through the monoaminergic systems.


[Immunocytological localization of peptide analogs of alpha-endorphin in several neurons of the lateral nucleus tuberis of Carassius auratus L. and Cyprinus carpio L]. Neurons of the pars lateralis of the N.L.T. of Carassius auratus and Cyprinus carpio display a positive immunocytological reaction with an anti alpha-endorphin serum. It is assumed that the peptides produced by these neurons are similar, if not identical, with alpha-endorphin, but their morphinomimetic properties have still to be established. Peptides of this kind may participate in the regulation of pituitary functions.


[Coagulation of the hemolymph in Macropipus puber (L)., Crustacea, Decapoda. Electrophoretic demonstration of a plasma component intervening in hemostasis]. Electrophoretical and immuno-electrophoretical analysis of plasma, serum and some plasmatic extracts of Macropipus puber (L). have evidenced the presence in the plasma of a component absent in the serum. This component which disappears from the plasmatic extracts after their coagulation must therefore plays a role in the clotting processes.


[Role of the Lewis (Le-le) and secretor (Se-se) systems in the rejection of kidney grafts]. ABH and Lewis antigens are secreted in distal convoluted and collector tubes of the kidney. The renal ABH secretion is genetically controlled by the Se-se system, while the Lewis specificities are controlled by the Le-le system. The secretory status of the recipient does not modify the probability of graft survival, while the Lewis phenotype seems to play a major role in rejection. The probability of graft survival at 2 years in le-le homozygous recipients (29%) is much lower than that of Le recipients (58%) p less than 0.01.


[Modes of influence of vision on postural reactions associated with voluntary arm movements]. Postural changes associated with voluntary movements of the arm as observed during a positioning task, were studied on subjects standing upright on a force platform. Subjects performed the movements with either a normal visual field or without peripheral vision (tubular vision). Data analysis comprised the EMG activity of soleus and tibialis anterior and the displacement of the vertical component of the force applied to the platform. Average data of EMG indicate that the masking of the extrofoveal receptors increases the desactivation of soleus before the onset of the movement and provokes a burst of activity in the soleus 80 to 100 ms after the onset of the movement.


[Combined effects of testosterone and estradiol on the ventral lobe of the rat postate in organ culture]. After organ culture without hormone, the epithelial gland cells of Rat veantral prostate undergo atrophic changes, whereas the interstitial stroma components tend to increase. Estradiol (1-1,000 nM),added to the culture medium, is ineffective. On the contrary, testosterone (1-100 nM) maintains epithelial cells and prevents the increase of interstitial stroma. When estradiol (1-1,000 nM) is combined with a physiological concentration of testosterone (1-4 nM), the epithelial cells are well maintained, but the inhibitory action of  testosterone on the stroma is counteracted so that the glandular epithelium and the interstitial stroma are both stimulated. However, when testosterone is used at supraphysiological (10-100 nM) concentrations, estradiol is completely ineffective and the structure of the prostate is identical to the one given by the androgen alone.


[Viral infection associated with mortality in the oyster Crassostrea gigas Thunberg]. Virus particles and their morphogenesis have been observed in the cytoplasm of connective cells in the Japanese Oyster Crassostrea gigas. This virus seems to be similar to those described in the Portuguese Oyster Crassostrea angulata when high rates of mortality were recorded in 1970-1973 and those found in gill disease of this species.


[The effect of alkaloids from Tabernanthe iboga H. Bn. on the response of isolated organs to catecholamines and the possible role of calcium exchange. Case of Ibogaine]. On isolated Rat duodenum, ibogaine (70 mumoles/l) increases the hypertonic effect following the addition of Calcium ions to the organ previously decalcified. Moreover, this alkaloid increases the hypotomic effect resulting from decalcification of the normal organs. These actions are taken into account with the potentiating effects of ibogaine on noradrenaline and dopamine responses observed on rat vas deferens.


[Radioimmunoassay of serum thyroxin-binding-globulin in euthryoid subjects]. The authors have set up a thyroxine-binding-globulin radio-immunoassay in blood serum. The standard used has been determined by gravimetry, its maximal thyroxine-binding capacity is 0,96 mole of thyroxine per mole of TBG. Serum concentration of TBG has been measured in 159 euthyroid normals. The mean value of the concentration is 20 mg/l.


[Anomalous incidence of chromosome 1 gh+ in chronic myeloid leukemia]. Chromosome C variants have been analyzed in individuals with hematological disorders. The incidence of chromosome 1 gh+ was significantly enhanced in CML patients (20/24) compared with controls (8/17). The distribution of C-variants of chromosomes 9 and 16 was not different in these individuals.


[Evaluation of cellular immunity after rabies vaccination in man]. The peripheral lymphocytes of vaccinated men were stimulated by homologous antigen or its subunits (nucleocapsid and glycoprotein) or by some parent viruses (Mokola and Lagos). All subjects produced a high level of antibody. A difference was noted between the two types of immunity. A lack of cell-mediated immunity could explain the very few failures in Pasteur antirabies treatment.


[Oncostatic activity of extracts from Alangium vitiense on murine lymphoid neoplasms]. A total alkaloid and two purified alkaloid extracts of Alangium Vitiense were revealed by our experimental screening to be oncostatic on L1210 leukemia and two other lymphoid neoplasias in Mice. They are not active on myelomonocytoid leukemia WEHI3 nor on B16 melanoma.


[Immunocytochemical labeling of human chromosomes by antibodies from human autoimmune serum]. Mitotic human chromosomes are successively irradiated by ultraviolet, incubated with serum from a patient showing systemic lupus erythematosus (S.L.E.), and antihuman Sheep serum conjugated with peroxidase. After revelation by diaminobenzidine (DAB) banding patterns are pointed out. The chromosome labelling is discussed in comparison with results obtained in other immunocytochemical experiments.


[Description of some simple tests allowing the distinction between bacteriocins sensu stricto and other antibacterial agents produced by bacteria]. In contrast with other antibacterial agents produced by bacteria, the bacteriocins of Gram -- bacteria (briefly: cins G--) are characterized by their primary lethal action, their inactivation by trypsin, their resistance to pH 2 (in the crude state) and insensitivity to DNase I after treatment with 7 M urea. Only 4 among 26 studied cins G + have the 4 above-cited properties and share most properties of cines G--.


[Phyletic affinities among Polystomatidae (Monogenea)]. The chaetotaxy and ciliated cells in two Monogenean larvae of marine fishes are described for the first time: a Monopisthocotylea Diplectanum aequans (Wagener, 1857) Diesing, 1858 parasite of Dicentrarchus Labrax (L) and a Polyopisthocotylea, Microcotyle mormyri Lorenz, 1878 parasite of Pagellus mormyrus (L). A comparative study with the known larvae shows evidence of two larval types in the Monogenea of fishes, related to the two great phyla of the class: the Monopisthocoytylea and Polyopisthocotylea. The Polystomatidae, Monogenea from Amphibia and Chelonia, belong to the Polyopisthocotylea on account of their larval chaetotaxy. But the proximity of the Polystomatidae with the Tetraonchidae, within the Polyonchoinea Bychowsky, 1975 is not confirmed.


[Increase in serum testosterone in newborn rats]. The changes in serum testosterone and dihydrotestosterone concentrations have been measured in the newborn Rat, before, during and up to 6 hrs after birth. A sudden and transient increase of serum testosterone has been found between 0 and 2 hrs. At 4 hrs, the value returns to that found in the foetus at the end of gestation.


[Nucleolar structure during the prophase of Physarum polycephalum]. With Sugihara's fixation technique, electron microscopic study of early-prophase nucleolus in the Physarm polycephalum showed the existence of particular fibrillar structures. The characteristic feature of these spherical structures is an electron-lucid center surrounded by a dense fibrillar component. Their relationships between the "fibrillar centers" and between the rate of ribosomal RNA synthesis are studied.


[Purification of a protein binding quinacrine and histrionicotoxin from membrane fragments rich in cholinergic receptors in Torpedo marmorata]. A protein is purified by differential centrifugation from membrane fragments rich in acetylcholine receptor prepared from Torpedo marmorata electric organ after dissolution by a mixture of non denaturing detergents. After polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate and Coomassie blue staining the purified protein yields a single band of apparent molecular weight 43,000. Spectroscopic experiments carried out in the absence of Ca++ and detergents reveal that the 43 K protein interacts with the fluorescent local anesthetic quinacrine and with the frog toxin histrionicotoxin (apparent KD : 7 X 10(-7) M) but not with carbamylcholine and the alpha toxin from N. nigricollis.


[Physicochemical properties of an extracellular polysaccharide isolated from culture media of Bacillus amyloliquefaciens]. A new extracellular polysaccharide has been isolated by chromatography on anion exchanger of a fraction obtained from highly viscous culture media of Bacillus amyloliquefaciens. This polysaccharide is characterised by high molecular weight (1,000,000 dalton) and intrinsic viscosity (323 ml/g). It contains 24% neutral sugar (galactose and mannose 5:1), 35% glucuronic acid and 51.5% N-acetylhexosamines (N-actylglucosamine, N-acetylgalactosamine and N-acetylbacillosamine 6:9:1).


[Mixed "n" type inhibition of alpha-glucosidase activity by glucose in hemolymph of honeybee prenymphs]. Under in vitro inhibition of alpha-glucosidasic activity by glucose in hemolymph of Bee prenymphas, the reaction order (n) (predetermined according to the initial natural glycemia) decreases with increasing inhibitor concentration and the affinity constant between enzyme and substrate undergoes lower variations than in other cases where (n) does not change. The study of inhibited molecular forms suggests the possibility of a gradual negative-cooperativity mechanism concerning a dimeric form of the enzyme.


Effects of glucocorticoids on ventricular performance and capillary permeability during hemorrhagic shock. The effects of glucocorticoids on fluid uptake and myocardial performance was investigated in 14 dogs and two baboons. The animals were placed into stimulated hemorrhagic shock using a servocontrolled pump to maintain arterial pressure at desired levels. Ventricular function curves were generated by stepwise changes in afterload or by venous infusion and the resultant data were grouped by digital computer into similar preload, heart rate, and afterload groupings. Fluid uptake was monitored from the pump reservoir. Methylprednisolone was given intravenously, 30 mg/kg, approximately 3 hr after the postinfusion period. Fluid loss decreased and ventricular performance improved, as measured by maximal dp/dt, (maximal dp/dt)/developed pressure, and time to peak ventricular pressure. The improvements with steroid infusion were relatively small, however, and were not maintained for more than about 3 hr. Heart rate decreased markedly in response to the steroid, despite a general vasodilator response. The glucocorticoids appear to have mild beneficial effects on the myocardium and on capillary permeability in the presence of high circulating levels of catecholamines in the postinfusion phase of hemorrhagic shock.


Contribution of vagal pathways to the renal responses to head-out immersion in the nonhuman primate. Studies were carried out to determine the contribution of cardiopulmonary receptors to the renal responses to head-out water immersion in the nonhuman primate. Immersion to the suprasternal notch was associated with significant increases in central venous pressure, urine flow, and sodium excretion. The increased sodium excretion was due primarily to a significant increase in the percent of the filtered sodium excreted. Deoxycorticosterone acetate (DOCA) and antiduretic hormone (ADH) had no substantial effects on these responses. The finding of a vasopressin-resistant hyposthenuria is consistent with the natriuresis of immersion being due, at least in part, to a decrease in sodium reabsorption proximal to the diluting segment, possibly the proximal tubule. Bilateral cervical vagotomy had no substantial influence on the renal responses to immersion, demonstrating that cardiopulmonary receptors whose axons traverse the vagus nerves are not necessary for the homeostatic adjustments to central hypervolemia in the primate. Since the renal and cardiovascular responses of the primate to immersion are essentially the same as those seen in man, it is probable that vagal pathways also are not necessary in man. However, it is possible that sympathetic afferents are involved in the natriuresis observed in the primate during immersion.


Failure of left atrial distension to alter renal function in the nonhuman primate. Experiments were undertaken to determine the influence of increasing left atrial pressure on renal function in the nonhuman primate. Significant elevations of left atrial pressure, produced by using an intra-atrial balloon, had no effect on salt or water excretion, renal plasma flow, or glomerular filtration rate. There were no significant changes in heart rate or blood pressure. We conclude that, unlike those in the dog, atrial receptors in the nonhuman primate play little or no role in modulating salt and water excretion.


[Radiocompetitive assay of sulfamido-3-chloro-4-benzoic acid with carbonic anhydrase as binding reagent (author's transl)]. The control of patients treated by diuretic sulfonamides can be carried out by a radiocompetitive assay using their binding properties to carbonic anhydrase (CA). In this paper we have studied the assay of sulfamido-3-chloro-4-benzoic acid (SD3) using dialysis equilibrium as separation procedure. With (CA) 2 X 10(-6) M and 14C-SD3 0.5 X 10(-6) M (specific activity: 2 muCi/mg), can be detected 0.5 X 10(-6) M of (SD3) in the assay medium. 6.5 mg protein present in serum lower the assay sensitivity twenty times, owing to an elevated value of the affinity constant, Ka, of albumin-(SD3) complex (10(3) mol-1). On the other hand, the molecules with sulfamidobenzoic group cannot be differentiated in this procedure.


Urinary excretion of amino acids in patients receiving intravenous hyperalimentation. Urinary outputs of amino acids in nine patients receiving intravenous hyperalimentation were estimated for evaluating adequacy of dosage and composition of the infusage for the maintenance of normal metabolism of tissue proteins in the subjects. The daily outputs of the methylated amino acids (3-methylhistidine, epsilon-N-methylated lysines and guanidino-N-methylated arginines), which are thought to be derived from tissue proteins, remained in the normal ranges, suggesting that the normal metabolism of tissue proteins was sustained during intravenous hyperalimentation. Relatively large urinary excretion of threonine, serine and glycine might reflect the large dosage of glucose in the infusate and disuse of these amino acids during the treatment, especially in the patients with hepatic dysfunction. Diurnal rhythms in urinary outputs of amino acids in patients receiving intravenous hyperalimentation were not observed, except for the outputs of threonine, serine and glycine, which were large during the 3.00-9.00 h and 15.00-21.00 h periods. The absence of daily fluctuations of the methylated amino acids in urine suggested that there were no diurnal rhythms in the metabolism of tissue proteins in the subjects.


Otolaryngological disturbances in Waldenstrom's macroglobulinaemia. Four cases of Waldenstrom's macroglobulinaemia (WM) are described in which otoloaryngeal symptoms were present. Symptoms in WM are related to (a) bleeding diathesis and (b) hyperviscosity of the blood. The bleeding diathesis was manifested as epistaxis in 2 cases. In one case which came to postmortem, histological examination of the temporal bone showed complete disruption of the labyrinth by haemorrhage. Hyperviscosity probably was the source of hearing loss which took place in all 4 patients and had the following characteristics: (a) sudden onset (b) cochlear type (c) bilateral (d) sequential involvement of the two sides (e) improvement on treatment of the disease with alkylating agents or plasmapheresis. Early diagnosis of WM is thus important.


Functional anatomy of the deep motor branch of the ulnar nerve. Our presently inadequate knowledge of the functional anatomy of the deep branch of the ulnar nerve handicaps our management of ulnar nerve lesions. The extensive anatomical variations in the distribution of this nerve preclude adherence to a textbook pattern of innervation. Electrophysiological recordings of single sensory fibers in monkeys along with fascicular stimulation studies provided novel information about the functional organization of the deep branch of the ulnar nerve: (1) there is a wide range of sensory fibers not currently recognized by textbook descriptions; (2) the innervation pattern is far more diffuse and covers greater areas than previously suspected; (3) at the distal forearm level the motor component of the deep ulnar branch is distributed throughout the entire ulnar nerve and is not restricted to specific fascicles; (4) contrary to previous assumptions, the deep branch of the ulnar nerve is mixed, and not purely motor. In fact, it may be mostly sensory. Afferent fibers arise from muscle, joints, deep subcutaneous tissues and even skin. These findings suggest that it is unwise to look at any nerve as purely motor or having a set innervation pattern, and emphasize the pressing need for objective preoperative and/or intraoperative functional assessment in peripheral nerve surgery.


Congenital pseudarthrosis of long bones: a clinical, radiographic, histologic and ultrastructural study. Sixteen patients with pseudarthrosis of the tibia and one of the radius were evaluated clinically, radiograpically, and microscopically and separated into 3 groups; 8 had neurofibromatosis clinically, 3 had fibrous dysplasia histologically, and 6 had no evidence of either neurofibromatosis or fibrous dysplasia. Prognosis and therapy were determined by correlated clinical, radiographic, and histological observations. Fracture before age 2 years carried a poor prognosis. Electron microscopy allowed neither differentiation among these fibrous lesions, nor any clue to their origin, nor did it support the concept of a neural or vascular derivation.


Bone mineral and surface charge.

Bone mineral and surface charge. A triple association has been observed between a high negative surface charge, bone morphogenetic activity, and in vitro recalcificaiton in implants of demineralized bone matrix. Proplast fills with bony tissue when implanted in the body and shows the same triple association. The higher the negative surface charge, the greater is the mass of new bone induced and the higher degree of mineralization when placed in a calcifying solution in vitro. Further investigations are necessary to determine whether in implants of demineralized bone, a high negative surface charge may cause the formation of discrete calcium deposits or whether it triggers the invading primitive cells to differnetiate and produce bone, or both.


Effect of inhibition of prostaglandin synthesis on the natriuresis induced by saline infusion in man. 1. The effect of oral administration of an inhibitor of prostaglandin synthetase, indomethacin, on the natriuresis induced by the infusion of sodium chloride (saline) was studied in 11 healthy volunteers. 2. The administration of indomethacin did not alter sodium excretion before saline infusion, but it resulted in a significant increase of the natriuresis after saline infusion. This increase was not accompanied by any change in post-infusion urine flow rate or free water reabsorption. 3. It is suggested that intrarenal prostaglandins might suppress the natriuretic effect of saline infusion, probably by increasing sodium reabsorption in the distal nephron.


Influence of indomethacin on the systemic and pulmonary vascular resistance in man. 1. Indomethacin, an inhibitor of the cyclo-oxygenase system that converts arachidonic acid into prostaglandins and related substances, was infused intravenously in 12 healthy volunteer subjects. 2. Systemic systolic and diastolic blood pressures and heart rate were recorded in all subjects, and in most of them also the systemic arteriovenous oxygen difference, the total oxygen uptake and the pulmonary arterial and wedge pressures. 3. The infusion of indomethacin was followed by a decreased cardiac output (from 7.3 +/- 0.3 to 6.3 +/- 0.3 litres/min) and an increased mean systemic blood pressure (from 92 +/- 1 to 102 +/- 1 mmHg), indicating an elevation of the total systemic vascular resistance (from 98 +/- 4 to 124 +/- 5 kPa 1(-1) s) by indomethacin. The ventilation and the pulmonary vascular resistance did not change after the infusion of indomethacin. 4. The results suggest that products formed by the cyclo-oxygenase system at rest exert a relaxing effect in certain parts of the systemic vascular bed, thereby lowering the systemic vascular resistance.


Concurrent estimation of total body and exchangeable body sodium in hypertension. 1. Total-body neutron-activation analysis in vivo was carried out in 11 hypertensive subjects to measure simultaneously the total body content of sodium, chlorine, calcium, phosphorus and nitrogen. 2. There was a highly significant correlation between total body sodium measured by activation analysis and total exchangeable sodium measured by a standard isotope-dilution technique (r = 0.92, P less than 0.001). Exchangeable sodium averaged 80.3% of total body sodium. 3. The measured values of chlorine, calcium, phosphorus and nitrogen were similar to those for healthy subjects reported by others. 4. Activation analysis in vivo appears promising as an additional tool for investigating sodium metabolism in hypertension, as it is the only method available for determining the total body content of this element. The radiation dose (1 rem) is sufficiently low to permit repeated measurements in the same subject.


Banded chromosomes of the owl monkey, Aotus trivirgatus. Chromosomes of the owl monkey, Aotus trivirgatus, with 2n=54, 53, or 52, have been stained to show quinacrine (Q-) and Giemsa (G-) bands, and a karyotypic arrangement has been proposed based on lengths, centrometric index, and banding pattern. C-bands were present at the centromeric region of every chromosome and over the entire short arm of certain acrocentric chromosomes; 5-methylcytosine was concentrated in the same regions. Bright Q-bands at the telomeric ends of the short arms of some chromosomes probably represent a second type of repetitive DNA. Ag-staining showed that only the chromosomes bearing a secondary constriction are nucleolus organizer chromosomes.


Rifampicin against experimental listeriosis in the mouse. The activity of rifampicin was compared with that of tetracycline, ampicillin, penicillin G, chloramphenicol, gentamicin and sulphadiazine in vitro and in experiments on mice infected with various strains of Listeria monocytogenes. Although the minimum inhibitory concentration of rifampicin was not appreciably lower than that of ampicillin, penicillin G and gentamicin, rifampacin was very much more active in vivo than any of these antibiotics. One of the reasons for its greater efficacy may be that it inhibits or destroys intracellular Listeria. In addition, a synergistic effect was observed in vivo when rifampicin was administered in combination with ampicillin or tetracyline. The combined administration of rifampicin with either of these antibiotics should prevent the emergence of rifampicin-resistant Listeria.


[Soft-tissue ossification following stable osteosyntheses using bone meal]. Ectopic ossifications occassionally occur after stable osteosyntheses. The literature and our own observations indicate that osseous bore-chips probably favour these ossifications, especially after intermedullary nailing. Experiments determined the weight of osseous bore-chips which occur in intermedullary nailing of femur and in plate osteosynthesis of radius and ulna. Conclusions drawn from these findings should be considered when performing osteosynthesis.


The replication of ribosomal DNA in the macronucleus of Tetrahymena. The replication of extrachromosomal rDNA molecules from the macronucleus of Tetrahymena was studied by electron microscopy. Replication begins in the center of the palindromic molecule and proceeds by means of bidirectional fork movement toward the free ends of the molecule.


Characterisation of male meiotic-sterile mutations in drosophila melanogaster. The genetic control of meiotic divisions and gametogenesis. Male meiotic sterile mutations were selected among X-linked male-steriles by detection of micronuclei in early spermatids. Despite severe defects in the 1st or 2nd meiotic spindles in all mutants, no effect on mitosis was observed. Various features of spindle structure, chromosome segregation, and centriole movements were compared in seven meitoic steriles and in XO males. Chromosome behaviour and centriole movement were always affected concomitantly, and were both shown to be genetically independent of "centre" formation in the meiotic spindles. Precocious and delayed centromere separation was observed in the various mutants in both divisions, and similarly attributed to basic spindle lesions rather than chromosome defects. Attachment of the centriole body to the membrane of the spermatid nucleus was normal only in mutants where second division nuclei were formed. The role of the centriole body was shown to be independent of membrane attachment.--The phenomena observed in this study were discussed mainly with regard to genetic interdependence of morphogenetic processes during male meiosis. A common base for the pleiotropic defects of meiotic steriles and XO males is suggested, and the genetic control of meiosis is re-evaluated in the light of comparison with fertile meiotic mutants.


Intestinal dipeptidases and the dipeptide transport in the monkey and in man. Among the powerful dipeptidases of the cytosol fraction the well-characterized 'master' dipeptidase of broad substrate specificity is an example of a 'true' dipeptidase. There are only a limited number of peptidases which together can hydrolyse the total range of the theoretically possible dipeptides. In the lumen, the dipeptides of dietary origin apparently enter the cell through a single transport system of broad specificity in the monkey and possibly also in man. Perfusion studies indicated impared absorption of glycine and Gly-Gly in Indian compared to English subjects, but the kinetic advantage of dipeptide uptake over that of the free amino acid was maintained. In patients with tropical sprue, apart from decreased peptide absorption, there was an increased 'backflow' of the constituent amino acids. The back-flow assumes nutritional significance since dipeptide uptake is competitively inhibited by amino acids of a certain specificity. Inhibition of brush border glycylglycine hydrolase (glycylglycine dipeptidase, EC 3.4.13.1) by L- leucine is non-competitive while that of cytosol enzyme is competitive. Certain other amino acids have no effect on glycylleucine hydrolase (glycylleucine dipeptidase, EC 3.4.13.2) from  either fraction but inhibit Gly-Leu uptake. Thus, the inhibition of dipeptide uptake appears to be a consequence of interaction of amino acids directly with the dipeptide transport system and not with dipeptidases.


Urgent opportunistic observations: the study of changing, transient and disappearing phenomena of medical interest in disrupted primitive human communities. Two newly identified foci of usually rare disease occurring in high incidence in isolated primitive populations of West New Guinea are discussed as examples of medical problems that demand immediate intensive investigation because the unique naturally occurring experiments they represent are soon likely to be altered. These are: (1) amyotrophic lateral sclerosis, Parkinsonism, and dementia syndromes in a small population of Auyu and Jakai peoples in the Lowlands, and (2) an epidemic of burns from cysticercosis epilepsy from newly introduced Taenia solium in pigs in the Ekari people of the Wissel Lakes in the Highlands. A third new example is a focus of male pseudohermaphroditism among the Simbari Anga in the Highlands of Papua New Guinea. These are presented along with a series of eleven further examples of the kind of problems that require urgent opportunistic observation because of the extreme changes that investigation and therapeutic and preventive efforts themselves, as well as the inevitable effects of acculturation, will evoke from the moment an investigator or other outsider from a technologically advanced culture enters the previously isolated community.


Retinal damage secondary to chronic light exposure, thresholds and mechanisms. The effect upon the retina of exposure to large fields of bright visible light has been evaluated. The thresholds for permanent retinal damage for four hour exposures in rhesus monkeys have been established for white light, and laser lines of 514.5 nm, 488 nm, 457.9 nm, and 590 nm. The damage has been evaluated by ophthalmoscopy, electroretinography and light and electron microscopy. The shortest wavelength light (457.9 nm) is more effective in causing damage, particularly histological damage, which is spread throughout the fundus and throughout the retinal layers. Functional damage shown by the electroretinogram follows a different action spectrum without the increased effect in the blue. There appears to be more than one mechanism for retinal damage in chronic light exposure, and at least one mechanism is not dependent solely upon the visual pigment and the pigment epithelium. Thresholds of permanent damage appear to be within one or two log units of light levels encountered in the normal visual environment. Newer data suggest that this damage is additive. Daily one hour exposures for four days produce damage equivalent to a single four hour exposure at the same retinal irradiance.


Pharmacokinetic models for lipophilic compounds. In many instances pharmacokinetic modeling offers the best method of interpreting the significance to man of results obtained with laboratory animals but first we must have accurate models for our laboratory animals. A physiological pharmacokinetic model has been used to simulate the disposition of polychlorinated biphenyls (PCBs) in the rat and to extrapolate results obtained with the rat to predict the disposition of PCBs in the mouse. The modeling methods have also been extended to predict the disposition of a polybrominated biphenyl (PBB) in the rat following IV, oral, and multiple oral doses. It is anticipated that with additional experience and work a physiological pharmacokinetic model can be used to predict the disposition of these and other xenobiotics in man.


Environment and the skin.

Environment and the skin. The skin is an important interface between man and his environment; it is an important portal of entry for hazardous agents and a vulnerable target tissue as well. It is a uniquely accessible model system for detecting hazards and for studying mechanisms of a wide variety of biologic funcitons. Environmental causes of skin reactions comprise a vast array of physical, chemical and biological agents. To appreciate the role of the skin as an interface with man's environment, it is necessary to understand the multiple adaptive mechanisms, and the defenses of the skin against the environmental stresses. The skin is endowed with a versatile group of defenses against penetration, fluid loss from the body, thermal stress, solar radiation, physical trauma and microbial agents. Patterns of adverse response range in quality and intensity from uncomplicated itching to metastatic neoplasia. Environmental problems comprise a large segment of disabling skin disease. Although critical epidemiologic data is limited, cutaneous illnesses comprise a significant segment of occupational disease. This represents a significant loss in productivity and a major cause of disability. The most serious research needs include the development of surveillance systems for identifying skin hazards and determining frequency of environmental skin disease; the development of new models for studying cutaneous penetration; the elucidation of the mechanisms of nonallergic inflammatory reactions (primary irritation) and of the accommodation phenomenon; the development of more sensitive models for predicting adverse responses to marginal irritants; the utilization of modern skills of immunobiology and immunochemistry to elucidate mechanisms of allergic responses; the launching of epidemiologic studies to determine the long term effects of PCBs and associated compounds such as dioxins; and the expansion of research in the mechanisms of skin cancer in relation to susceptibility, genetic and metabolic considerations, ultraviolet light, and phototoxic agents.


Identification of the mammalian DNA-binding protein P8 as glyceraldehyde-3-phosphate dehydrogenase. The DNA-binding protein P8 from transformed hamster fibroblasts (line NIL-1-hamster sarcoma virus) has been purified to homogeneity by DNA-cellulose and phosphocellulose chromatography. The molecular weight of dissociated P8 is 36000, the same as that reported for the subunits of glyceraldehyde-3-phosphate dehydrogenase, and the mobility of these proteins in polyacrylamide gels is identical. The amino acid composition of P8 is very similar to that of glyceraldehyde-3-phosphate dehydrogenase. When assayed for glyceraldehyde-3-phosphate dehydrogenase activity the P8 preparation had a specific activity of 54.6 units/mg, a value comparable to that of the crystalline enzyme from several sources. Furthermore, serum prepared against P8 crossreacts with glyceraldehyde-3-phosphate dehydrogenase from hamster muscle. These results show that P8 is glyceraldehyde-3-phosphate dehydrogenase. The interaction of P8 from transformed fibroblasts and glyceraldehyde-3-phosphate dehydrogenase from hamster and rabbit muscle with DNA has been studied using a Millipore filtration technique. These proteins have affinity for single-stranded DNA but not for double-stranded DNA.


Transport of D-glucose and 3-O-methyl-D-glucose in the cyanobacteria Aphanocapsa 6714 and Nostoc strain Mac. 1. The cyanobacterium Aphanocapsa 6714 which grow in the dark on D-glucose, will take up D-glucose and the analogue 3-O-methyl-D-glucose; uptake of each of these compounds was inhibited competitively by the other and by 6-deoxy-D-glucose. 2. This cyanobacterium accumulated 3-O-methyl-D-glucose up to 100-fold relative to the medium but did not modify or metabolize it to a significant degree. 3. Intracellular 3-O-methyl-D-glucose was rapidly displaced from Aphanocapsa 6714 by exogenous D-glucose and 3-O-methyl-D-glucose. 4. Although not characterized to the same extent, D-glucose and 3-O-methyl-D-glucose uptake by Nostoc strain Mac, another cyanobacterium capable of growth in the dark on D-glucose, was similar. 5. Other cyanobacteria that do not grow on D-glucose take up this compound at much lower rates which were unaffected by analogues of D-glucose that greatly reduced carbohydrate uptake by Aphanocapsa 6714 and Nostoc strain Mac. 6. It is therefore proposed that Aphanocapsa 6714 and Nostoc strain Mac possess a mechanism for the active transport of D-glucose. The absence of this transport mechanism is suggested as the reason why other strains fail to grow in the dark on this substrate. These latter organisms are therefore naturally cryptic with respect to D-glucose as a growth substrate.


Vestibular responses in the rhesus monkey ventroposterior thalamus. II. Vestibulo-proprioceptive convergence at thalamic neurons. The vestibular thalamic relay in the Rhesus ventrobasal complex, identified in a previous field potential study (part I, Deecke et al., 1974), has now been investigated with neuronal recordings in the thalamus in order to clarify its functional role. In part I, short latency responses (2.5 msec) were found in the corner between VPL, VPM and VPI nuclei, largely including dorsal portions of the VPI nucleus. Field potentials of somewhat longer latency (4-5 msec) were recorded in VPL and in other thalamic nuclei, including the posterior nuclear group. Neuronal responses were recorded in thalamic nuclei of awake flaxedilized Rhesus monkeys. Cells not responding to vestibular stimulation (round window polarisation of either labyrinth) were ignored. The great majority (80%) of those neurons responding to labyrinth polarisation showed convergence with deep somatic (proprioceptive) input from joints and muscles of vertebral column and limbs. 60% of these bimodal neurons responded to movement of cervical joints. Very few vestibularly responsive cells received cutaneous (6.6%), non-optokinetic visual or auditory (2.6% each) input. Proprioceptive fields tended to be large, frequently involving more than one joint, and could be even bilateral. For a few cells the pattern of vestibulo-proprioceptive convergence could be fitted to a coordinated body position that might occur during normal locomotion. 78% of the cells responded to polarisation of both labyrinths, indicating strong bilateral projection.


Stimulus dependent colour specificity of monkey lateral geniculate neurones. From six flaxedilized rhesus monkeys neuronal activity of 75 cells in the dorsal, and 45 cells in the ventral layers of the lateral geniculate body was recorded. Responses to large fields switched on and off, to moving slits, and to moving spots were obtained for several wavelengths. In the dorsal layers, colour selectivity was strong for large field stimuli but weak for moving spots. Residual colour selectivity for spots was more evident for smaller eccentricities. In comparison, ventral layer cells were less colour selective for all stimuli used. Large field responses were weak, they often consisted of a sequence of excitation and inhibition. The subdivision of the dorsal cells into different colour opponency types based on large field responses is compared to the subdivision based on centre and surround functions. Results are compared to colour responses in retina and visual cortex, and the tonic and phasic cell type subdivision is discussed.


Vestibular nuclei activity during optokinetic after-nystagmus (OKAN) in the alert monkey. Neurons which receive an input from the horizontal semicircular canals were recorded from the vestibular nuclei in chronically prepared monkeys (Macaca mulatta) during optokinetic after-nystagmus (OKAN). In complete darkness the vestibular neurons showed activity changes which closely paralleled the strength of nystagmus. The activity of vestibular units returned to baseline levels of spontaneous discharge only when all after-nystagmus had ceased, or when it was inhibited by stationary visual stimuli. The possible role of vestibular neurons in the generation of OKAN and its significance in vestibulo-visual interaction is discussed.


The intracerebellar nucleocortical projection in a primate. Experiments were performed to determine if a nucleocortical system, a projection from the cerebellar nuclei to the cerebellar cortex, was present in primates. Both electrophysiological and neuroanatomical techniques were employed to investigate this question. It was shown that neurons within the dentate and interposed nuclei were antidromically activated by stimuli applied to the cerebellar cortex. In addition, cells in these nuclei were retrogradely labelled following injections of small amounts of horseradish peroxidase in the cerebellar cortex. The injection of tritiated leucine in the deep nuclei resulted in the labelling of fibers projecting from these structures to the cerebellar cortex which appeared to terminate within the granular layer. Additional electrophysiological studies showed that neurons projecting to the cerebellar cortex could also be antidromically activated from the ventrolateral thalamic nucleus, indicating that the nucleocortical projection in the primate arises at least in part as collaterals from neurons in the deep cerebellar nuclei which also project to extracerebellar structures, as was shown in the cat.


Vestibular-related neuronal activity in the thalamus of the alert monkey during sinusoidal rotation in the dark. 1. In the alert monkey neuronal activity was recorded in the ventro-posterior nucleus (VP) of the thalamus in the dark during sinusoidal rotation over a frequency range from 0.01-1 Hz. 2. From 57 neurons 38 (67%) were activated with rotation to the ipsilateral side (type I) and 19 (33%) to the contralateral side (type II). The spontaneous activity was low (average 10.1 imp/sec) and irregular. No activity changes were found with eye movements. 3. At 0.2-0.1 Hz neuronal activity showed a phase lead of 10-20 degrees relative to chair velocity. At the lowest frequency (0.01 Hz) the phase lead was only slightly higher (about 30 degrees). Accordingly the decrease in gain was only moderate. 4. At lower frequencies the simultaneously recorded eye movements (nystagmus) showed an increase in phase lead comparable to the values for the neuronal activity in the thalamus. For both neuronal activity in the thalamus and nystagmus a time constant between 25-35 sec was calculated. 5. The data are compared with vestibular nerve and nuclei recordings. It is argued that the time constants of vestibular neurons in the thalamus are very similar to the time constants of neurons in the vestibular nuclei in alert animals.


Linear addition of optokinetic and vestibular signals in the vestibular nucleus. A simple model of the vestibuloocular reflex and the optokinetic system was used to simulate recent data on visual and vestibular responses of neurons in the vestibular nucleus. Contrary to a previous interpretation, the results support the hypothesis that the optokinetic and semicircular canal signals are combined simply by linear addition on the cells of the vestibular nucleus.


Projections from the primary somatosensory cortex to basal ganglia and thalamus in the monkey. Radioactive amino acids were injected into the postcentral cortex (areas 3, 1 and 2) in 6 monkeys (Macaca fascicularis). Fibers were traced to the ipsilateral putamen, to Olszewski's n. ventralis posterior lateralis pars caudalis, n. ventralis posterior medialis and inferior, to n. pulvinaris oralis, n. suprageniculatus and corpus geniculatum mediale pars magnocellularis. Furthermore, there were faint postcentral projections to claustrum, n. caudatus, n. centralis lateralis, n. centrum medianum, zona incerta and with respect to the postcentral face region to n. medialis dorsalis pars multiformis. Discrepancies with earlier findings were discussed and comparison was made between pre- and postcentral target regions.


Serum thyrosinase in human lung carcinoma. Compared to normal humans, lung carcinoma patients show increased tyrosinase activity. 7 serum enzymic fractions or carriers were present in the diseased state. Further, serum tyrosinase inhibitory factors generally were decreased in lung carcinoma patients compared to normal individuals.


In vitro effects of melanocytolytic agents and other compounds upon dominant human melanoma tyrosinase activity. The activity of dominant human melanoma tyrosinase isozyme was greatly decreased by certain reducing agents. The number and geometry of phenolic groups as well as free--SH group appear important for enzymic inhibition.


The use of fungal protoplasts in the study of aflatoxin biosynthesis. Protoplasts derived from Aspergillus flavus are shown to be capable of synthesizing aflatoxins when incubated in a chemically defined medium. 14C-Acetate and 14C-Versicolorin A, added to protoplasts from 3-day-old mycelium, are incorporated into aflatoxin B1.


[Phagocytic activity of the reticuloendothelial system in the rat after administration of an anticholinesterasic pesticide, carbaryl (author's transl)]. The effects of 4 carbaryl doses (0.375, 0.75, 1.50 and 3 mg/100 g) on the reticuloendothelial system (RES) phagocytic activity were studied 1 h after their administration to male rats. Carbaryl reduced RES phagocytic activity. Results showed a dose-dependent drop in RES phagocytic activity. Carbaryl might act as an inhibitor of phagocytes by saturing them to greater or lesser degree, depending on the dose administered.


[The study of poly(A)-containing RNA of lymphomatous baboons]. The presence of additional messenger RNA in lymphomatous baboon spleen cells as compared with healthy ones has been shown by hybridization-competition assay. The origin of this additional information is discussed.


[Cardiac contraction frequency in Macaca rhesus monkeys occupying different position in a group hierarchy]. Four variants of heart rate ratio were revealed in 8 groups of the monkeys of different hierarchic positions. Dependence of the heart rate in low-ranking monkeys on the character of their interrelationships with the dominant individual, was shown. The lowest heart rate was revealed in the monkeys protected by the drominand individual. The heart rate at rest and its shifts during feeding reflect the degree of emotional tension in monkeys of different ranks.


HLA antigens and insulin dependent diabetes mellitus. A family study. Sixteen insulin dependent diabetic patients (age at onset less than 35 years) and their families were tissue typed for HLA antigens. Glucose tolerance of relatives was also tested. Among diabetic patients two HLA antigens were found with increased frequency: B8 (31 percent, control 15 percent) and Bw35 (38 percent, control 23 percent). Among normal relatives B8 and Bw35 had the same frequency as the control group. Bw15 frequency was not increased in either group. In relatives, no correlation between HLA antigens (B8 or Bw35) and abnormal glucose tolerance, obesity and over-weight at birth was found. Present data confirm previous reports of high B8 frequency in early onset diabetic patients, but fail to demonstrate a raised frequency of abnormal glucose tolerance among relatives bearing B8 (or, in our cases, Bw35). B8 may be considered a genetic indicator for susceptibility to juvenile diabetes. On the basis of present results in families, however non genetic factors clearly also play a determinant role. Furthermore, that diabetogenesis arises from a link between Ir-genes and HLA-B8 antigen should only be considered a suggestive hypothesis.


Recent results of behavioural treatments of phobias and obsessions. The basic principle of treatment of phobias and obsessions is exposure of the patient to the evoking stimulus. Utilizing this principle, exposure in vivo seems an effective treatment for many, but not all, obsessional patients. The role of tricyclic drugs is at present being investigated. Nurse therapists have been found to be very competent in delivering treatment. Similar results, using an exposure in vivo model, have been obtained in the managment of phobias. Some reasons why patients do not comply with, or adhere to, treatment recommendations are put foward. Finally, the vexed question of the cost-effectiveness of treatment is considered.


Relative maturity of cebus and squirrel monkeys at birth and during infancy. Cebus monkey were less mature at birth than squirrel monkeys in terms of body weight and brain weight in proportion to adult weight. Postnatally, cebus were slower to develop locomotion, perceptual-motor capacities, and object permanence. The differences in rate of development between the species increased with age. The findings indicate that the cebus have a longer period of infancy before becoming skilled at locomotion and manipulation. In view of the cebus monkey's recognized skill as a manipulator and problem solver, the long period of infancy suggests that cebus have evolved further in the direction of higher primates.


Nocturnal sleep in isolation-reared monkeys: evidence for enviromental independence. Thirteen all-night recordings were obtained from 3 infant pigtailed (Macaca nemestrina) monkeys raised on a cloth surrogate mother and under conditions of social isolation. Totally implantable biotelemetry systems were used to record the sleep physiology from the unrestrained animals. Sleep stages and night-to-night variability were virtually identical to values previously found in 8 mother-reared group-living infants. Sustained alterations in the early rearing enviroment, even though considerably modifying the organism's development, did not appear to result in differences in sleep organization.