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Biomedical subjects

G Mack

Publications and source records attributed to G Mack.

At least 19 recordsLinked to original sources

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

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

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

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

Modifications in the sarcoplasmic reticulum and subcellular calcium distribution in skeletal muscle in a case of Westphal's disease (hypokalemic periodic paralysis).

In a case of hypokalemic periodic paralysis with characteristic alterations of the sarcoplasmic reticulum (SR) in the skeletal muscle, subcellular calcium re-partition, as revealed with the pyroantimonate technique, appears disturbed during paralysis. Pyroantimonate precipitates, normally concentrated in the terminal cisternae of the SR, were localized in the T tubules, whereas the terminal cisternae appeared empty. The increase (about 14%) in muscular calcium during paralysis may result from the accumulation of calcium in the extracellular compartment (T tubules). Defects in calcium uptake and storage by the SR may be involved in the pathogenesis of the periodic paralysis syndrome.

Adolescent

Cholinergic involvement in ethanol intoxication and withdrawal-induced seizure susceptibility.

The enzymes of the cholinergic system have been investigated in discrete brain areas in alcohol-dependent rats, which were still intoxicated or were undergoing withdrawal. The ethanol intoxication resulted in a slight, but significant increase in choline acetyltransferase (CAT) activity in the caudate nucleus both 1 and 7 h after the last dose of ethanol. We also found a significant decrease in CAT activity in the temporal limbic cortex while rats were highly intoxicated. All other brain regions investigated, e.g., cerebellum, pons-medulla, frontoparietal cortex, hypothalamus and septum showed unchanged CAT activity. Rats were also analysed immediately following the onset of a withdrawal-induced audiogenic convulsive seizure where, in addition to the striatum, depressed CAT activity was observed in the hippocampus. In all the analysed situations acetylcholinesterase activity remained unchanged. These results show that ethanol intoxication leads to a perturbation in the synthetic capacity of acetylcholine in certain defined brain structures and that this may have some correlation to the observed behavioural impairments.

Acetylcholinesterase

Effects of apomorphine and sodium Di-n-propylacetate on the aggressive behaviour of three strains of mice.

1. The effects of apomorphine and sodium Di-n-propylacetate (DPA, sodium valproate) on pain-induced aggressive behavior were investigated in three inbred strains of mice: BALB/c, C57B1/6 and DBA/2, which exhibited spontaneously low levels of aggression. 2. Apomorphine elicited aggressive behavior in the three strains, the range of effective doses being different for each strain of mice. 3. Di-n-propylacetate was effective in inhibiting apomorphine elicited aggression but the three strains exhibited a different sensitivity to this drug. 4. The effects of Di-n-propylacetate were not related to pain sensitivity, posture and locomotion. Only C57 strain exhibited a slight postural and locomotor impairment when injected with a higher dose of Di-n-propylacetate. 5. The results are discussed in terms of a genetic inference and of biological differences existing between these three strains.

Aggression

[Renewal of noradrenaline in different zones of the central nervous system of inbred mice strains and their recombinants].

A good correlation exists between the learning capacity and norepinephrine metabolism in the neocortex of C57 and Balb inbred Mice strains, as well as their F1 hybrids and seven recombinant inbred strains derived from their cross. The animals with a better learning performance are characterised by low levels of norepinephrine, as well as a slow metabolic rate of this neurotransmitter in the cortex. Such a correlation has not been found to exist in the other cerebral regions studied.

Animals

Comparative study of miscellaneous properties of cysteine sulfinate transaminase and glutamate oxaloacetate transaminase in chick retina homogenate.

The activity, properties, and developmental pattern of cysteine sulfinate transaminase (CSA-T) were studied in chick retina and compared with the activity, properties, and developmental pattern of glutamate oxaloacetate transaminase (GOT). Their optimum pH is identical whereas the effect of pyridoxal phosphate seems to be different. Developmental patterns are also different. The Km and Vm of CSA-T and GOT were determined in chick retina homogenate. These results suggest that two different enzymes are responsible for the transamination of cysteine sulfinate (CSA) and aspartate.

Aging

[The effects of phenylbutazone on the decrease of lithium clearance].

During the treatment of a manic depressive patient, the authors reported some lithium toxicity signs, as lithium carbonate (3 X 300 mg p.d.) and phenylbutazone suppository (3 X 250 mg/p.d.) were associated, this last medication being prescribed for a phlebitis. Lithiemia increased from .70 to 1,44 mEq/l., the lithiemia clearance falling from 10 ml to 5 ml/mn/1.73 m2) and the lithium tubular reabsorption percentage increasing from 85 to 94% (standard rates: 77.4 +/- 1.3%). In a second time, a rat experimentation corroborated these findings: phenylbutazone treatment (100 mg/kg/p.o. for five days) resulted in a lithium tubular reabsorption increase. It seems that the association of lithium carbonate with phenylbutazone should be avoided. The authors point out the risk of prescribing lithium and pyrazolic by-products as phenylbutazone, which are potentially nephrotoxic.

Animals

[Inhibition of mouse-killing behavior by rats with taurine, GABA, and its analogues].

The injection of Gaba, of taurine or of a structural analog of GABA (n-dipropylacetate) in the olfactive bulb of "killer" Rats was found to inhibit the mouse-killing behaviour of the rat. The same effect was obtained when taurine or n-dipropylacetate (which increases GABA in the central nervous system), was injected intraperitoneally. The experiments reported here are interpreted to explain certain molecular mechanisms of muricidal behaviour.

Aggression