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Biomedical subjects

G Mack

Publications and source records attributed to G Mack.

At least 37 records · Page 2Linked to original sources
PubMed1989

Toxic effects of 7 beta-hydroxycholesterol on rat liver primary cultures, epithelial lines and co-cultures.

The toxic effects of 7 beta-hydroxycholesterol (7 beta-OHC) on cultures and co-cultures of rat hepatocytes, rat liver epithelial cell lines, and rat liver fibroblast lines were investigated. Hepatocytes in primary culture or co-cultured with proliferative epithelial cells, were not affected by the presence of 7 beta-OHC at a concentration of 400 microM over a period of 72 hours. In contrast, proliferative cultures of liver epithelial cell lines and liver fibroblast lines were killed by 50 microM 7 beta-OHC within the first 24 hours. Established liver epithelial cells (hyperploid) were more sensitive to 7 beta-OHC than the same line at early passages (diploid). When hepatocytes and liver epithelial cells were co-cultured and treated with 100 microM 7 beta-OHC, only epithelial cells were lysed. A concentration of 50 microM 7 beta-OHC was toxic to co-cultures of liver epithelial cell and fibroblasts together. In a serum-free medium, the cytotoxic concentration of 7 beta-OHC was lower than that in the serum-supplemented medium. Thus, liver epithelial cells cultured alone or co-cultured with hepatocytes were killed at 12.5 microM and 50 microM 7 beta-OHC, respectively. Finally, cholesterol concentrations four-fold that of 7 beta-OHC antagonized the lethal effects of 7 beta-OHC in the serum-free medium.

Albumins↗
PubMed1989

Peripheral vascular reflexes elicited during lower body negative pressure.

To study the interaction between thermal reflexes and baroreflexes on human forearm vasomotor and venomotor control, and to test the hypothesis that peripheral veins are responsive to baroreceptor unloading during gravitational stress, we imposed lower body negative pressure (LBNP) between 10 and 50 mm Hg (Torr) at ambient temperatures (Ta) of 28 and 37 degrees C. We measured arterial and central venous pressures (CVP), heart rate, forearm venous volume, forearm venous pressure, and forearm blood flow in 12 volunteers. Decreases in CVP were relatively large at 10 mm Hg LBNP (p less than 0.01) at both Ta, and less thereafter. Arterial systolic and pulse pressures were not significantly reduced until LBNP exceeded 30 mm Hg (p less than 0.05). With LBNP up to 20 mm Hg, moderate decreases in forearm venous compliance and increases in forearm vascular resistance occurred. Between 30 and 50 mm Hg LBNP, the changes in both compliance and resistance per unit change in CVP were more than tripled. We concluded that unloading of cardiopulmonary mechanoreceptors stimulates increases in both forearm vasomotor and venomotor tone and that addition of arterial baroreceptor unloading adds to these reflex responses.

Adult↗
PubMed1988

Role of cardiopulmonary baroreflexes during dynamic exercise.

To examine the role of cardiopulmonary (CP) mechanoreceptors in the regulation of arterial blood pressure during dynamic exercise in humans, we measured mean arterial pressure (MAP), cardiac output (Q), and forearm blood flow (FBF) during mild cycle ergometer exercise (77 W) in 14 volunteers in the supine position with and without lower-body negative pressure (LBNP). During exercise, MAP averaged 103 +/- 2 mmHg and was not altered by LBNP (-10, -20, or -40 mmHg). Steady-state Q during exercise was reduced from 10.2 +/- 0.5 to 9.2 +/- 0.5 l/min (P less than 0.05) by application of -10 mmHg LBNP, whereas heart rate (97 +/- 3 beats/min) was unchanged. MAP was maintained during -10 mmHg LBNP by an increase in total systemic vascular resistance (TSVR) from 10.3 +/- 0.5 to 11.4 +/- 0.6 U and forearm vascular resistance (FVR) from 17.5 +/- 1.9 to 23.3 +/- 2.6 U. The absence of a reflex tachycardia or reduction in arterial pulse pressure during -10 mmHg LBNP supports the hypothesis that the increase in TSVR and FVR results primarily from the unloading of CP mechanoreceptors. Because CP mechanoreceptor unloading during exercise stimulates reflex circulatory adjustments that act to defend the elevated MAP, we conclude that the elevation in MAP during exercise is regulated and not merely the consequence of differential changes in Q and TSVR. In addition, a major portion of the reduction in FBF in our experimental conditions occurs in the cutaneous circulation. As such, these data support the hypothesis that CP baroreflex control of cutaneous vasomotor tone is preserved during mild dynamic exercise.

Adult↗
PubMed1987

Third component of rat complement. Purification from plasma and radioimmunoassay in culture media from cell lines.

A double antibody radioimmunoassay for rat C3 has been developed. The assay required the preparation of C3 from plasma. A new purification procedure using ion exchange high performance liquid chromatography is described. The final product was homogeneous on SDS-PAGE analysis. Rat C3 has an apparent molecular weight of 187,000 and is composed of two polypeptide chains with molecular weights of 125,000 and 73,000, respectively. The purified C3 antigen with high hemolytic reactivity, as assessed by its specific functional activity, was used in preparing anti-C3 sera to perform a specific radioimmunoassay for quantifying C3 in the presence of heterologous sera contained in the cell culture media. All the validating criteria, such as precision, recovery and dilution studies, were investigated. The high sensitivity of the method allowed replicate determination of C3 in small aliquots of the cell culture medium.

Animals↗
PubMed1987

Biosynthesis of the third component of complement in rat liver epithelial cell lines and its stimulation by effector molecules from cultured human mononuclear cells.

Rat liver epithelial cell lines, growing in a serum-supplemented medium, synthesize and secrete into the culture medium the third component of complement (C3). We studied the regulation of C3 production in this system. We found that human peripheral blood mononuclear leukocytes in culture released one or more soluble factors which stimulated rat liver epithelial cells to produce increased quantities of C3. This stimulating effect was strongly enhanced when the mononuclear cell cultures were treated with phytohemagglutinin, a T-lymphocyte mitogen. The factor(s) failed to enhance C3 biosynthesis by rat dermal fibroblasts, which are known to produce this protein. This reveals a tissue-specific differential response between the fibroblasts and the liver epithelial cells. The physical and chemical characteristics, such as heat sensitivity, 2.8 M ammonium sulphate precipitation, and lower activity after digestion by proteases unambiguously indicate that the effector molecules are proteins. When the crude supernatant of mononuclear leukocytes was fractionated by gel filtration, the stimulating factor(s) eluted as two peaks with apparent molecular weight of 25 to 60 and 15 to 20 kdalton, respectively. As to the cellular origin of the C3-stimulating factor(s), several observations were made: (a) in separate cultures containing either T-cells or monocyte-enriched populations from the same sample of blood mononuclear cells, no activity was detected in the presence or absence of phytohemagglutinin, (b) conditioned media from each of these cultures could not substitute for the corresponding intact cell populations, and (c) the addition of purified T-cells to the monocyte-enriched population in the presence of phytohemagglutinin restored the production of the stimulating activity by the mixed culture. Finally, experiments were carried out to verify whether monokine interleukin 1 affects the hepatic C3 biosynthesis. It was demonstrated that interleukin 1 enhanced this biosynthesis, but could not completely substitute for conditioned medium from stimulated mononuclear cells.

Animals↗
PubMed1987

[Neuroendocrine disorders observed in the post-critical phase in epileptic patients].

In 10 epileptic patients with generalized seizures, plasma levels of ACTH, prolactin, FSH, LH, TSH, were measured first within 60 minutes after the crisis, then 3 to 5 days later without changes in antiepileptic drugs. Within 1 hour after the seizure, a significant rise of ACTH and prolactin 3 - 4 folds the levels observed in the 2nd measure was present. This was compared to measures made within 1 hour after a syncope in which case it was not present. The post-critic rise of ACTH and prolactin would appear to be a characteristic of generalized epileptic seizures.

Adolescent↗
PubMed1986

[Post-crisis elevation of adrenocorticotropic hormone and prolactin in epileptic children].

In six children, aged from 8 to 12 years, presenting with primary generalized epilepsy a significant rise in plasma ACTH and prolactin levels (as compared with levels measured 5 days later) was observed either during a generalized seizure demonstrated by EEG (3 cases) or within 1 hour of a generalized seizure (3 cases). The neurophysiological basis for these post-epileptic endocrine disturbances is a sudden depression of dopaminergic and GABA-ergic pathways. As a result, these endocrine changes, already well documented in adults, may be regarded as a good biological marker of the epileptic origin of a paroxysmal attack.

Adrenocorticotropic Hormone↗
PubMed1983

Laser nephelometric measurement of seven serum proteins compared with radial immunodiffusion.

Quantification of immunoglobulins IgG, IgA, IgM, C3 complement, siderophilin, alpha 2-macroglobulin and haptoglobin in serum by a Behring laser nephelometer coupled with a date processing apparatus was compared with values obtained by the radial immunodiffusion method of Mancini. The precision was not improved by the use of the laser nephelometer as compared to Mancini radial immunodiffusion, but within run precision was better than that among runs for both methods. The analytical recovery studies for laser nephelometry showed a close concordance between the theoretical and measured values for all proteins. The two techniques were also compared by means of correlation studies.

Blood Proteins↗
PubMed1983

[Production of complement C 3 fraction by rat liver epithelial cells in culture. Stimulating effect of monocyte supernatants from human circulating blood].

A noticeable increase has been observed in the production of the C 3 component of the complement by Rat liver epithelial cells cultured in vitro in the presence of small quantities of supernatant of human blood mononuclear cells cultured for 72 hrs. with phytohemagglutinin. The physicochemical properties suggest that the stimulating factor(s) is(are) protein(s).

Animals↗
PubMed1982

Gangliosides in various brain areas of three inbred strains of mice.

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p less than 0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri- and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.

Animals↗
PubMed1982

Neurotransmitter modifications in human cerebrospinal fluid and serum during hepatic encephalopathy.

The concentrations of catecholamines, serotonin, histamine and GABA as well as some of their precursors and metabolites were measured in the CSF and the serum of human patients at different grades of hepatic encephalopathy. In all grades the CSF concentrations of the neurotransmitters were much increased over control levels, while the amount of metabolites varied with the grade of coma. The data suggest modifications of the cerebral turnover of dopamine, norepinephrine and serotonin. The "false transmitters" also occurred in high concentration in all grades of hepatic coma and could play a role in the alterations of synaptic transmission. The present results suggest that the biochemical changes between grade 2 and grade 4 hepatic coma could be due to an inhibition of dopamine beta-hydroxylase. Moreover, the levels of neurotransmitter precursors, tyrosine and 5-hydroxytryptophan, showed enhancement in grades 2 and 3 followed by an important reduction in grade 4. Finally, it seems that the biogenic amines measured in the CSF are of central origin and that their quantification in human lumbar fluid gives new information on the central mechanisms involved in hepatic encephalopathy.

5-Hydroxytryptophan↗
PubMed1982

Effect of valproic acid on brain serotonin metabolism in isolated and grouped rats.

The effect of the GABA transaminase inhibitor valproic acid (DPA) on serotonin (5HT) metabolism of different brain regions were studied in both grouped and isolated rats. One hour after DPA injection 5HT levels in the amygdala were increased in grouped and isolated rats. In the hypothalamus of grouped rats, changes in 5HT metabolism were also found. The alteration in 5HT metabolism in grouped rats was reversed 150 min after injection of DPA. At this same time, a large and significant increase in 5HT turnover was observed in all brain areas examined in isolated rats. It can be concluded that prolonged isolation induces a differential sensitivity to the effects of DPA leading to differences in 5HT metabolism: the drug effect being more intense in isolated rats.

Animals↗
PubMed1981

[Drug treatment of apnoea in premature infants (author's transl)].

Primary apnoea in premature infants can be treated by three categories of drugs. Drugs of the first category act on chemoreceptors and include doxapram and possibly almitrine if the latter proves non-toxic during the neonatal period. Phenobarbitone is so far the only representative of the second category of drugs which alter the pattern of sleep. As for the third category, it has the second messenger of respiratory centres for target and includes the phosphodiesterase's inhibitor (not yet tried in man) and the xanthines. At the moment, xanthines are the drugs of choice, since they are both effective and safe, provided dosage is adjusted to each patient.

Apnea↗
PubMed1981

[Influence of the GABAergic system on eating behavior induced by the tail pinching technic in rats].

The present experiment was undertaken to investigate the possible involvement of GABAergic neurons in the regulation of the feeding behavior induced by tail pinching. Injections before the tail pinching of gamma-aminobutyric acid (GABA) agonist (Muscimol: 570 micrograms.kg-1 i.p. 20 min before testing), GABA antagonist (Picrotoxine: 1,5 mg.kg-1 i.p. 30 min before testing) and a GABA transaminase inhibitor (Acetate dipropyle: 200 mg.kg-1 i.p. 40 min before testing) have no effects on the ingestion of sweet milk. These preliminary results provide support for the hypothesis that the feeding behavior induced by TP is not mediated through GABAergic system.

Animals↗