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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
PubMed1993

Centrosome repositioning immediately following karyokinesis and prior to cytokinesis.

The behaviour of the centrosome immediately following cell division in tissue culture cells has been investigated. We find that following karyokinesis, but preceding cytokinesis, sister centrosomes relocate from the spindle poles to a position adjacent to the intercellular bridge. This repositioning is accompanied by the appearance of a microtubule bundle that extends from the poleward region of the cell to the centrosome and increases in length as the centrosome approaches the intercellular bridge. Disruption of this bundle with colcemid interrupts centrosome repositioning. In contrast, centrosome repositioning persists in late mitotic cells grown in the presence of cytochalasin D. However, the position of the microtubule-centrosome complex within the cell is randomized suggesting that the path, but not the process, of centrosome repositioning is dependent on an intact actin filament network. This study points out, for the first time, that the complex migration of the centrosome preceding mitosis is paralleled by an equally complex set of events following cell division. We suggest that post-mitotic centrosome repositioning may play a role in ensuring that daughter cells have equal but opposite polarity and may reflect an interrelationship between the establishment of the interphase cytoskeleton and the completion of cytokinesis.

Anaphase↗
PubMed1992

Improved high-performance liquid chromatographic determination of ciprofloxacin and its metabolites in human specimens.

A simple approach to the quantitation of ciprofloxacin and its three metabolites, M1 (desethylene-ciprofloxacin), M2 (sulfo-ciprofloxacin) and M3 (oxo-ciprofloxacin), in human serum, urine, saliva and sputum is described. This assay allows the parent drug and its metabolites to elute and be resolved in a single chromatogram at 280 nm using a linear gradient. The procedure involved liquid-liquid extraction. Separation was achieved on a C18 reversed-phase column. The limit of detection of ciprofloxacin is 0.05 microgram/ml and that of its three metabolites is 0.25 microgram/ml. This method is sufficiently sensitive for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
PubMed1992

Radioimmunoassay for the measurement of serum IL-6 and its correlation with tumour cell mass parameters in multiple myeloma.

Interleukin-6 (IL-6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL-6 (S-IL-6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S-IL-6 levels in 102 patients with monoclonal gammopathy (MG). S-IL-6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti-IL-6 antibody and a human recombinant IL-6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within-run and between-run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL-6 standard and S-IL-6 was shown by dilution tests. IL-6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S-IL-6 values were 294 +/- 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S-IL-6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S-IL-6 levels correlated with bone-marrow plasmacytosis (P less than .0005), serum-lactate dehydrogenase (S-LDH; P less than .005), serum beta 2 microglobulin (S -beta 2m; P less than .01), and serum calcium (S-Ca; P less than .025) and inversely correlated with haemoglobin (P less than .025). Our results indicate that 1) radioimmunoassay is suitable for the measurement of human IL-6 in serum; 2) high S-IL-6 levels are observed in a small number of patients with MG; and 3) S-IL-6 level correlates with tumour cell mass in patients with overt MM.

Bone Marrow↗
PubMed1992

MSA-36: a chromosomal and mitotic spindle-associated protein.

We have identified a novel M(r) 36,000 protein (MSA-36) that has a complex cell cycle dependent distribution. This protein is first detected in interphase nuclei just prior to the onset of chromosome condensation. MSA-36 is found along condensing chromosomes and is a component of the centromere through metaphase. At anaphase, this protein is no longer detected in association with the chromosomes but appears at the forming stembodies and subsequently within the intercellular bridge at either side of the midbody. At the completion of cell division, the amount of MSA-36 in the bridge appears to decline concurrent with the appearance of this protein briefly within the reforming nucleus. To investigate whether MSA-36 is an active component of the chromosome or a passive passenger protein, we studied the behaviour of this protein in cells exhibiting premature chromosome condensation and in cells during and following recovery from mitotic arrest. These studies suggest that MSA-36 is not essential for a variety of major chromosome-associated events.

Autoantigens↗
PubMed1991

Methadone levels and neonatal withdrawal.

The purpose of this study was to observe the effects of methadone exposure in utero, with special reference to maternal and neonatal methadone concentrations and neonatal withdrawal. Two groups of mother-infant pairs were studied. In the first group, serum methadone concentrations were determined in infants at 1, 6 and 24 h after delivery. In the second group, blood was obtained at 24, 48, 72 and 96 h after birth. There was no correlation between neonatal serum levels and the intensity of withdrawal symptoms. There was no relationship between maternal methadone dose at delivery or maternal serum levels and neonatal methadone levels. The results of this study may be complicated by the prenatal exposure of the neonates to other drugs of abuse apart from methadone.

Adult↗
PubMed1991

Effects of enzyme supplementation on oral absorption of ciprofloxacin in patients with cystic fibrosis.

The effect of pancreatic enzyme supplementation on the absorption of an oral dose of 250 mg of ciprofloxacin was studied in six patients with cystic fibrosis in a crossover design. The time to achieve maximum serum concentration was slightly reduced upon coadministration of pancreatic enzymes. There were no significant differences in peak concentration, elimination half-life, and area under the concentration-time curve.

Administration, Oral↗
PubMed1991

Single-dose concentrations of tinidazole in gingival crevicular fluid, serum, and gingival tissue in adults with periodontitis.

Previous studies have shown that metronidazole is effective in the treatment of subgingival microflora associated with destructive periodontitis. The aim of this study was to determine whether tinidazole, a close analogue of metronidazole, would reach sufficient concentrations in serum, gingival crevicular fluid, and gingival tissue, to inhibit putative periodontopathic bacteria. Ten adult patients with moderate to advanced periodontitis took a single 2-g dose of tinidazole orally. Samples were assayed by high-performance liquid chromatography. The concentrations of tinidazole in serum and GCF were in a similar range (3.2-46.5 micrograms/mL). Tinidazole was not detected in the GCF in three of the patients. The drug was found in gingival tissue obtained at two h (0.17 +/- 0.14 micrograms/mg) and six h (0.15 +/- 0.18 micrograms/mg) after oral administration. The mean concentration of tinidazole in serum at 24 h (13 +/- 3.0 micrograms/mL) is greater than the minimum inhibitory concentration for anaerobic bacteria as reported by others. The present data suggest that a single 2-g oral dose of tinidazole may lead to the presence of potentially bactericidal levels of tinidazole for up to 24 h in the periodontal pockets of some patients with periodontitis.

Administration, Oral↗
PubMed1991

Exacerbation of Gilles de la Tourette's syndrome associated with thermal stress: a family study.

Gilles de la Tourette's syndrome (TS) is a familial disorder that is often exacerbated by stress or fatigue. Here we present a family of a TS proband that has several members with obsessive-compulsive symptoms, a bleeding disorder, and an unusual sensitivity to heat. The proband, who is affected by all of these traits, was challenged with heat or exercise in climate-controlled conditions and showed a marked increase in the frequency of tics.

Adolescent↗
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↗