High momentum components in nuclei.
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Journal Article↗
Biomedical subjects
J Picard
Publications and source records attributed to J Picard.
Arm fat and muscle areas in infancy.
Growth of arm muscle, fat and water areas were evaluated longitudinally in a prospective study in 81 infants from birth to the age of 12 months. The percentage of arm fat area v the cross sectional upper arm area increased at the age of 15 days with a peak peak at the age of 6 months while arm muscle area increased progressively throughout the year. As arm water area represented only 1% of cross sectional upper arm area, calculations of arm fat and muscle areas can be carried out from measurements of mid arm circumference and tricipital skinfold at 15 seconds. Percentiles are presented for the upper arm fat and muscle areas, which can be used as index for the infants' nutritional state.
Adipose Tissue↗
In vitro studies of insulin resistance in patients with lipoatrophic diabetes. Evidence for heterogeneous postbinding defects.
We studied the binding and action of insulin in cultured fibroblasts from six patients with lipoatrophic diabetes and marked in vivo insulin resistance and from seven control subjects. The binding of insulin was not altered, which corresponds well with studies with circulating erythrocytes. Similarly, the action of the hormone on amino acid uptake (estimated by active transport of aminoisobutyric acid) was comparable in patient and control cells. Conversely, studies concerning the effect of insulin on glucose transport (estimated by facilitated diffusion of 2-deoxyglucose) or glycogen synthesis (estimated by incorporation of glucose into cellular glycogen) revealed the presence of heterogeneous alterations among the different patient cell lines. However, although the nature of the defect(s) varied among the patients, alterations in glucose metabolism were present in all cases. These data suggest the presence of primary postbinding defects in glucose cellular pathways that give rise to insulin resistance in cells from lipoatrophic diabetic patients.
Adolescent↗
[Regulation of glucose metabolism by insulin: dual role of protein kinase C].
The role that protein kinase C (PKC) may play on insulin regulation of glucose metabolism was investigated in rat adipocytes and Zajdela hepatoma cultured (ZHC) cells which are two cell types highly responsive to insulin. In rat adipocytes, 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (PMA, 0.1-1,000 ng/ml), a potent tumor promoter acting as a substitute for diacylglycerol which directly activates PKC, stimulated basal 2-deoxyglucose (2-DG) transport in a time- and dose-dependent manner, but decreased the activation of this process elicited by submaximal concentrations of insulin. PMA (0.1-1,000 ng/ml) also stimulated basal lipogenesis from [3-3H] glucose in a dose-dependent manner. Maximal PMA and insulin effects on both processes were not additive. The specificity of the insulin-like effects of PMA was assessed by the finding that 4 beta-phorbol 12, 13 dibutyrate (PDBu), mezerein, 1-oleyl-2-acetyl glycerol (OAG) and 1, 2 diolein, know as PKC activators, also markedly stimulated glucose metabolism whereas 4 alpha-phorbol 12, 13 didecanoate (4 alpha-PDD) and 4 beta-phorbol 13-monoacetate, shown not to activate PKC, were ineffective. PMA and insulin biological effects exhibited several similarities: both agents stimulated glucose transport and lipogenesis in a calcium-dependent manner, both activated glucose transport through an energy-requiring process, and the effects of both were markedly decreased by mellitin, a PKC inhibitor. Finally, fat cells made PKC-deficient by a chronic treatment with PMA exhibited a marked decrease in insulin responsiveness for stimulation of glucose transport and lipogenesis, with no change in either the hormone sensitivity or the insulin receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue↗
Role of proteoglycan in the binding of low-density lipoprotein to cultured arterial smooth muscle cells.
The role of proteoglycans in the binding of 125I-labeled low-density lipoproteins (LDL) to cultured arterial smooth muscle cells was examined. About 60% of cell bound 125I-labeled LDL could be released by unlabeled LDL, heparin, dextran sulfate or proteoglycan. Binding of 125I-labeled LDL decreased by about 50% when incubated in the presence of exogenous arterial proteoglycans. Exposure of cell cultures to rho-nitrophenyl-beta-D xyloside resulted in a 40% decrease in both the amount of 35S-labeled proteoglycan in the cell layer and the 125I-labeled LDL binding, without modifying significantly the cell number and amount of cell layer protein. These data suggest that cell surface and/or cell matrix proteoglycans may influence binding of LDL to either specific receptor or non-receptor sites and thereby play a role in the intracellular deposition of lipid in the arterial wall.
Aorta↗
Biosynthesis of glycosaminoglycans in the human colonic tumor cell line Caco-2: structural changes occurring with the morphological differentiation of the cells.
The human colon cancer cell line Caco-2 cultured in vitro displayed morphological differentiation which was shown to be a growth-related event. We have investigated this phenomenon further in relation to the cell surface glycosaminoglycans produced by growing (5-day, i.e., prior to differentiation) and confluent (9-day, i.e., after morphological and functional differentiation) cultures. Neosynthesized [35S]glycosaminoglycans were purified on DEAE-cellulose; at confluency, they were bound more strongly to the column than the corresponding fractions from the growing cells. Analysis of Kav values of heparan sulfate and chondroitin sulfates from growing and confluent cells indicated an increase in chain length of both glycosaminoglycans in morphologically differentiated cells. Heparan sulfate was the main 35S-labeled glycosaminoglycan of the cell surface of both 5-day and 9-day cultures. Paper chromatography of the unsaturated disaccharides obtained by chondroitinase digestion showed that chondroitin sulfate chains were primarily 6-sulfated in the 2 studied extracts. Heparan sulfate chains were isolated as chondroitinase-resistant material and treated with nitrous acid. Analysis of N- and O-sulfate group-related radioactivity showed an increase in the amount of 35S-label in the form of N-sulfate groups and an increase in the O-35S-sulfation pattern in heparan sulfate from morphologically differentiated cells. Thus, the structural features of both chondroitin sulfates and heparan sulfate were significantly different when the growing cells became morphologically differentiated.
Cell Differentiation↗
Effect of dibutyryl cyclic AMP and theophylline on lipoprotein lipase secretion by human monocyte-derived macrophages.
The effect of dibutyryl cyclic AMP and theophylline on lipoprotein lipase secretion was investigated after a 24 h pretreatment of human monocyte-derived macrophages. Both the effectors decreased in a dose-dependent manner the enzyme activity recovered in the culture medium. The decrease in lipoprotein lipase activity appeared to be related to reduced enzyme synthesis without apparent modification of its stability and half-life and was conversely associated with an increase of lysosomal acid hydrolase activities. This effect was reversible on removal of the nucleotide. The present findings suggest that cyclic AMP may play a role in lipoprotein lipase expression in human macrophages and therefore may participate in the regulation of lipoprotein uptake by these cells, which are strongly implicated in the atherogenic process.
Bucladesine↗
Calmodulin in Zajdela hepatoma cell growth.
Calmodulin levels were measured in Zajdela hepatoma cells growing both in vivo and in culture, with respect to the distribution of the cells into G1 and S+G2 phases of the cell cycle and growth conditions. These levels, expressed on a per-microgram of protein basis, were significantly elevated at the G1-S boundary and maintained throughout the remainder of the cell cycle. This elevation of calmodulin took place independently of the culture conditions. Taken together with previous observations, these data suggest that a threshold concentration for calmodulin is required for progression through the cell cycle, DNA synthesis and cell division.
Animals↗
Assessment of proportional growth of very low birth weight infants fed banked human milk.
Twenty appropriate (mean +/- S.D., gestational age (AGA): 29.9 +/- 1.5 weeks) and 15 small (GA: 34.6 +/- 2.4 weeks) for gestational age (SGA) very low birth weight infants fed banked mature human milk were studied until term for anthropometric parameters: midarm (MAC), chest (CC), head (HC) circumferences, triceps (TSKF) and subscapular (SSKF) skinfold thickness recorded at 15 and 60 s, dynamic skinfold (delta % SKF), muscle (AMA) and fat (AFA) areas, weight and length. In AGA infants, all the parameters at term were significantly lower in extrauterine (EUL) that in intrauterine life (IUL). At term the relative proportion of AFA to total arm area was increased in EUL compared to IUL both in AGA (25.87 +/- 3.8 vs. 23.26 +/- 1.27% respectively, P less than 0.01) and in SGA infants (21.89 +/- 4.63 vs. 18.81 +/- 3.9 respectively, P less than 0.05). SGA infants showed a similar growth in EUL compared to IUL, and a significantly lower AMA and AFA than in AGA infants in EUL. Although HC was in both infants below the 10th centile at term, the ratio weight/HC2 suggests a relative preservation of head growth in EUL compared to IUL (AGA: 20.72 less than 0.87 vs. 22.65 +/- 1.46 respectively, P less than 0.001; SGA; 20.82 +/- 1.16 vs. 21.62 +/- 1.86 respectively, NS). Delta %SKF were negatively correlated with post-conceptional age suggesting a loss of extracellular water in AGA (delta %TSKF: r = -0.287, P less than 0.02) and in SGA infants (delta %TSKF: r = -0.301, P less than 0.02; delta %SSKF: r = -0.316, P less than 0.02). An intrauterine model of discrimination between AGA and SGA infants does not apply to EUL. An equation was established in SGA infants with the best discriminant parameters giving a predictive post-conceptional age: post-conceptual age (PCA) (weeks) = 0.276 HC (cm) + 0.723 CC (cm) - 0.122 MAC (cm) + 0.5 TSKF (mm) + 10.173, (r = 0.867, P less than 0.001) allowing a clear discrimination between AGA and SGA infants. These results suggest that infants show quite different growth patterns between IUL and EUL both for AGA and SGA infants.
Anthropometry↗
Decreased insulin responsiveness in fat cells rendered protein kinase C-deficient by a treatment with a phorbol ester.
Insulin stimulation of 2-deoxyglucose transport and lipogenesis from glucose was examined in fat cells in which protein kinase C had been down-modulated by a 3 h pretreatment with 5 X 10(-7) M 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (PMA). As compared to control fat cells, the down-modulated cells exhibited a 55-65% decrease in insulin responsiveness with no change in either the hormone sensitivity or the insulin receptor affinity. The present study shows that fat cells made protein kinase C-deficient by chronic treatment with PMA exhibit an insulin-resistant state, distal to the initial step of hormone binding.
Adipose Tissue↗
Change in activities of lysosomal glycosidases in skin fibroblasts from controls and patients with cystic fibrosis.
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Chloroquine↗
[Detection by ultrastructure and STEM microanalysis of hepato-spleno-lymph node thorotrastosis].
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Aged↗
Synthesis of sulfated proteoglycans throughout the cell cycle in smooth muscle cells from pig aorta.
Cultured smooth muscle cells from pig aorta arrested in G0 phase by serum deprivation were stimulated to proliferate by replacing the medium with one containing 10% serum. Studies in DNA replication and proliferation of cells showed a relatively good synchrony: 90% of the cells were in G1 phase for 16 h after addition of serum; they entered S phase between 18 and 24 h, completed S phase and traversed G2 phase between 24 and 30-32 h; 75% of these cells multiplied after 30-32 h and the remainder were blocked at the end of G2 phase. The synthesis and secretion of sulfated proteoglycans were examined throughout a full cell cycle using metabolic labelling with [35S]sulfate. Smooth muscle cells in G1 or G2 phase synthesized and secreted sulfated proteoglycans with a possible pause at the end of the G2 phase but at the beginning of the S phase and during mitosis the incorporation of [35S]sulfate into these macromolecules stopped entirely. Structural characteristics of sulfated proteoglycans secreted into the medium during G1 phase and an entire cell cycle were investigated. The proportion of proteoglycan complexes and the relative hydrodynamic size of monomers and of constituent subunits of complexes were determined after chromatography on Sepharose CL-2B and CL-6B columns run under both associative and dissociative conditions. No significant differences were observed for the periods of the cell cycle that were studied: [35S]Proteoglycan complexes represented at the end of G1 phase and of the cell cycle respectively 19 and 16% of the total [35S]proteoglycans secreted into the medium. More than 90% of the subunits, obtained after dissociation of complexes, were characterized by a similar kav after chromatography on Sepharose CL-2B columns eluted under dissociative conditions (kav 0.68 at the end of G1 phase and 0.65 at the end of full cell cycle). About 95% of monomers synthesized at the two stages of the cell cycle were eluted at kav 0.25 after chromatography on Sepharose CL-6B column run under associative conditions and were characterized by a similar glycosaminoglycan distribution. These results suggest that smooth muscle cells in culture liberate similar populations of proteoglycans into the medium during the G1 and G2 phases.
Animals↗
Alteration by concanavalin A of the slow dissociable component in the human growth hormone-receptor interaction.
In mice liver plasma membranes (PM), the binding affinity of receptors for [125I] human growth hormone (hGH) was dependent on the association time: after 18 hours, a high affinity receptor form with KA = 6.8 X 10(9) M-1 accumulated and, as compared to after 1 hour, an increase up to 88%, in a slow dissociating component was observed. Preincubation of PM with concanavalin A (Con A) or other lectins from Lens culinaris (LCA), Ricinus communis (RCA I), Wheat germ agglutinin (WGA) specifically inhibited the binding of hGH to receptors by 54, 28, 50 and 25%, respectively. Furthermore, PM pretreatment with Con A concomitantly increased the rate of dissociation of the hormone-receptor (H-R) complex to 92 or 65% after association for 1 or 18 hours. These Con A-induced alterations resulted from a reduced fraction of the slow dissociable component together with an increased rate constant. The treatment of PM with Con A subsequent to incubation with the hormone did not decrease hormone binding but caused the conversion of the class of hGH receptors exhibiting fast dissociation kinetics towards a form exhibiting slow ones. These data strongly suggest a role for glycoproteins of the N-acetyllactosaminic type in the affinity state of liver membrane hGH receptors.
Animals↗
Insulin stimulation of glucose metabolism in rat adipocytes: possible implication of protein kinase C.
The hypothesis that insulin stimulation of glucose and lipid metabolism in rat adipocytes may involve the activation of protein kinase C was evaluated. 4 beta-Phorbol 12 beta-myristate, 13 alpha-acetate (PMA, 0.1-1000 ng/ml), a potent tumor promoter acting as a substitute for diacylglycerol to activate protein kinase C, stimulated 2-deoxyglucose transport in a time- and dose-dependent manner, without affecting passive glucose diffusion. PMA (0.1-1000 ng/ml) also elicited a dose-dependent activation of lipogenesis from [3-3H] glucose. Maximal PMA effects (100 ng/ml) on both processes were 60% of insulin maximal effects. In contrast, PMA (1-1000 ng/ml) failed to mimic the ability of insulin to stimulate lipogenesis from [3H]acetate. 4 beta-Phorbol 12,13 dibutyrate, mezerein, 1-oleyl-2-acetyl-glycerol, 1,2 diolein, known as protein kinase C activators, also markedly stimulated glucose metabolism whereas 4 alpha-phorbol 12,13 didecanoate and 4 beta-phorbol 13-monoacetate, shown not to activate protein kinase C, were ineffective. Mellitin, a cytotoxin-inhibiting protein kinase C, markedly decreased both PMA and insulin stimulation of glucose metabolism. PMA decreased insulin submaximal effects on 2-deoxyglucose transport without inhibiting insulin binding. Maximal PMA and insulin effects on 2-deoxyglucose transport and lipogenesis from [3-3H]glucose were not additive. Both PMA and insulin activated each metabolic process in a calcium-dependent manner. PMA, like insulin, no longer stimulated 2-deoxyglucose transport in fat cells treated with 2,4-dinitrophenol. These data show that PMA exhibited specific insulin-like properties on glucose metabolism in fat cells, without any effect on lipid synthesis from acetate. They indicate that PMA and insulin bioeffects may share a common step implicating a calcium- and energy-dependent process, distal to the initial insulin binding event. Our results suggest that protein kinase C may play a role in insulin regulation of glucose metabolism.
2,4-Dinitrophenol↗
[Role of acute alcoholism in violent death. Statistics of the Lyon Medico-Legal Institute (1981-2)].
Over a 2-year period (1981-1982), blood alcohol levels were measured in 1371 post-mortem examinations performed at the medico-legal Institute of Lyon. These levels were higher in men, in subjects who died between 9 p.m. and 3 a.m., in corpses found in water and in subjects killed by a fall or in a fire. Among the 4 main types of death (homicide, suicide, accident and natural death), those by homicide had the highest, and those by suicide the lowest blood alcohol concentrations.
Accidents↗
Further evidence for the involvement of a membrane proteolytic step in insulin action.
The hypothesis that insulin action involves a membrane proteolytic step was further explored, by using isolated rat adipocytes and liver plasma membranes. (1) The maximal insulin stimulation of 2-deoxyglucose transport and lipogenesis in fat-cells was selectively inhibited (73-88%) by N alpha-p-tosyl-L-lysine chloromethyl ketone (Tos-Lys-CH2Cl; active-site inhibitor of trypsin; 30-125 microM), p-nitrophenyl p'-guanidinobenzoate (active-site inhibitor of serine proteinases; 30-125 microM) and p-tosyl-L-arginine methyl ester (arginine ester substrate analogue of proteinases; 1-2 mM), under conditions where neither the basal rate of each metabolic process nor insulin binding nor cellular ATP content were affected. In contrast, N-acetyl-L-alanyl-L-alanyl-L-alanine methyl ester (alanine ester substrate analogue of proteinases; 1-2 mM) was ineffective. (2) Endoproteinase Arg-C (0.25-40 micrograms/ml) exerted dose-dependent insulin-like effects on both 2-deoxyglucose transport and lipogenesis in fat-cells, whereas endoproteinase Lys-C (5-100 micrograms/ml) was ineffective. The maximal activation by endoproteinase Arg-C of both processes (200 and 177% of control values respectively) was shown to occur under conditions where membrane integrity (assessed by measurement of lactate dehydrogenase leakage and passive glucose diffusion) was preserved. This effect was inhibited by Tos-Lys-CH2Cl (125 microM) and was not additive with the maximal insulin effect. (3) Insulin (1-100 ng/ml) produced a dose-dependent increase in the trichloroacetic acid-soluble 125I radioactivity released after a 30 min incubation at 37 degrees C of 125I-labelled liver plasma membranes, but was ineffective on 125I-labelled bovine serum albumin. Insulin effects on both radio-labelled proteins were reproduced by wheat-germ agglutinin (20 micrograms/ml), an insulin mimicker shown to act through the insulin receptor. These data provide further evidence for the hypothesis that insulin bioeffects involve the activation of a membrane serine proteinase with arginine specificity.
Adenosine Triphosphate↗
Anthropometric assessment of nutritional status in newborn infants. Discriminative value of mid arm circumference and of skinfold thickness.
74 appropriate-for-gestational age (AGA) and 22 small-for-gestational age (SGA) caucasian infants were studied for anthropometric parameters: mid arm circumference (MAC), triceps and subscapular skinfold thickness (TSKF and SSKF) recorded at 15 and 60 s, chest circumference (cc), head circumference, birth weight and length. MAC is highly correlated with birth weight either in AGA (r = 0.936; P less than 0.001) or in SGA infants (r = 0.860; P less than 0.001). MAC is also correlated with gestational age in AGA (r = 0.850; P less than 0.001) and SGA infants (r = 0.76; P less than 0.001). Similar correlations were found between TSKF, SSKF and birth weight or gestational age. Arm muscle and fat areas are also positively correlated with birth weight and gestational age, in AGA and SGA infants. A multiple regression analysis of our data allowed a classification of the best discriminant anthropometric parameters between AGA and SGA infants. MAC, SSKF15, SSKF60 and chest circumference were selected. An equation was established in AGA infants with these four parameters giving a predictive gestational age: gestational age (weeks) = 1.216 MAC (cm)-3.588 SSKF15 (mm) + 0.263 CC (cm) + 17.9. The ratio of predicted gestational age to the real gestational age was 1.0 +/- 0.044 in AGA versus 0.896 +/- 0.034 in SGA infants. Our data suggest that MAC and SSKF provide a simple measure of body composition of neonates and a useful tool for determining the degree of maturity of a newborn independent of birth weight.
Anthropometry↗