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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 991 records · Page 55Linked to original sources
PubMed1967

Genetic control of lactate dehydrogenase formation in the hagfish Eptatretus stoutii.

The isozyme patterns of lactate dehydrogenases of various tissues were studied on 51 hagfish by starch-gel electrophoresis. Nine lactate dehydrogenase phenotypes were encountered, suggesting the coexistence of two alleles at each of the two separate gene loci. There apparently was no interaction between the products of these two separate loci. Even the products of two alleles at the same locus were apparently incapable of forming hybrid molecules, an indication of the possible monomeric nature of each lactate dehydrogenase molecule.

Animals↗
PubMedDate not supplied

A mouse geneticist's impatient waiting for the arrival of embryo-freezing techniques.

Four cases from the author's own experience are discussed where the freezing and freeze-storage of mouse embryos would have saved much research time, preserved valuable genetic material, and enabled important genetic studies to have been made. These cases illustrate the problems encountered when transporting a large collection of inbred mouse strains; the necessity to discontinue--because of lack of space--strains that nobody wants at the moment but that might become invaluable in the future; the unavoidable loss of parental stocks used for the development of a new congenic line; and the difficulties one faces when studying a genetic system that is extremely polymorphic. The need for a centralized and possibly international embryo freezing and storing facility is advocated.

Animals↗
PubMedDate not supplied

Maternal and neonatal characteristics following exposure to cocaine in Toronto.

We prospectively ascertained gestational cocaine use by neonatal urine and hair tests in 600 mother infant pairs in 3 nurseries in Toronto. The 37 (6.25%) babies who tested positive for cocaine and their mothers were compared to the 563 nonexposed with regard to pregnancy outcome and neonatal complications. Mothers using cocaine were not different in their ages, racial distribution, and obstetric history from those nonexposed. Cocaine-using women had significantly higher risk for vaginal bleeding (16% vs 6%, P < 0.05), hepatitis B carrier state (8% vs 0.8%, P < 0.005), and perhaps more urinary tract infections (8% vs 2.5%, P = 0.08). Cocaine-using mothers were significantly more likely to smoke cigarettes (29% vs 10%, P < 0.001). Infants exposed to cocaine in utero were of lower birth weight (3162 +/- 645 [SD] g vs 3391 +/- 573, P < 0.05) and birth length (49.9 +/- 2.9 cm vs 51.1 +/- 3.1 cm, P < 0.05). Further stratification of babies exposed to cocaine by maternal cigarette smoking suggests that cigarette smoking accounted for most of this variability [birth weight of babies exposed to cocaine and cigarettes 2899 +/- 7.50 g (and 50% of them weighed less than 2500 g), vs 3423 +/- 612 (and only 8% less than 2500 g) in those exposed to cocaine only (P < 0.05)]. Babies exposed to cocaine in utero were significantly more likely to need initial medical support or resuscitation (52% vs 30%, P < 0.05). We conclude that gestational exposure to cocaine, ascertained by a sensitive biologic marker, is associated with substantial perinatal risks.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Regulation of free choline in rat brain: dietary and pharmacological manipulations.

The present study analyses, comparatively, the kinetics of free choline in the brain of rats during dietary and pharmacological manipulations. Low-choline diet halved the choline plasma level but did not cause significant changes of CSF choline. High-choline diet, hypoxia and treatment with nicotinamide increased brain choline availability through a central site of action and increased the CSF choline concentration. CSF choline concentrations were more effectively elevated by nicotinamide treatment (20-25 microM) than by acute choline administration (13-15 microM). Increases of CSF choline, due to brain choline mobilization, were consistently associated with a net release of choline from the brain as reflected by strongly negative arterio-venous differences (AVD) of brain choline. The balance between release and uptake of brain choline was controlled by the arterial plasma choline level in all treatment groups; however, the normal 'reversal point' of 15 microM--representing the plasma choline level where uptake and release of brain choline are balanced--was shifted to more than 40 microM by high-choline diet and nicotinamide. In conclusion, our data characterize the release of choline into the venous blood as an important component of brain choline homeostasis. Furthermore, we demonstrate that the concentration of brain choline (e.g. as a precursor of acetylcholine) can be enhanced more efficiently by manipulating choline homeostatic mechanisms than by acute choline administration.

Animals↗
PubMedDate not supplied

[Significance of intravenous immunoglobulins to the neonate born of a mother with idiopathic thrombopenic purpura].

High dose gammaglobulin therapy for pregnant women with idiopathic thrombocytopenic purpura may be suitable for both mother and foetus during pregnancy. A newborn with severe thrombocytopenia secondary to maternal illness, was treated successfully by intravenous gammaglobulin, without toxicity. In such a case, we believe the platelet count is not the only criterion for starting immunoglobulin therapy.

Adult↗
PubMedDate not supplied

Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys.

There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.

Animals↗
PubMedDate not supplied

The effect of chronic cocaine exposure throughout pregnancy on maternal and infant outcomes in the rhesus monkey.

To explore the effects of gestational cocaine exposure in a nonhuman primate model, pregnant rhesus monkeys were either treated (N = 10) with escalating doses of cocaine up to 7.5 mg/kg (IM), three times per day, 5 consecutive days per week, prior to conception and throughout gestation, or were not treated (N = 10) with cocaine at all. Substantial levels of both cocaine and its major metabolite, benzoylecgonine, were observed in samples of hair taken at birth from mothers and infants of the cocaine-treated group. Despite these differences in cocaine exposure, the experimental groups did not differ significantly with respect to maternal outcome, as measured by body weight again during pregnancy and length of pregnancy. On the other hand, the experimental groups did differ significantly with respect to infant outcome, as measured at birth by body weight, overall length, and crown circumference, all of which were decreased in the cocaine-treated group. A variety of reflexes tested at birth were normal in the cocaine-treated group. It was concluded that, in a rhesus monkey model, chronic cocaine exposure throughout pregnancy had no significant effect on maternal outcome, but did significantly affect infant outcome as assessed in this investigation.

Animals↗
PubMedDate not supplied

Induction of regulatory T-lymphocyte responses by liposomes carrying major histocompatibility complex molecules and foreign antigen.

Regulatory (helper and suppressor) T lymphocytes become activated only when foreign antigen is presented to them on the surface of antigen-presenting cells (APC), together with class II major histocompatibility complex (MHC) molecules (heterodimers of polypeptides of 28,000 and 35,000 relative molecular mass). Once activated by a certain foreign antigen--MHC combination, T cells react to the same antigen only in combination with the same MHC molecule, a phenomenon termed MHC restriction of T-cell recognition (reviewed in refs 1,5). Studies of the mechanisms involved in antigen presentation and MHC restriction have been hampered mainly by the virtual impossibility of inducing T-cell responses in the absence of APC. We describe here the production of synthetic lipid vesicles with inserted class II MHC molecules and a protein antigen coupled covalently to the lipid. These liposomes are shown to stimulate cloned helper T cells and T-cell hybridomas in an antigen-specific, MHC-restricted manner in the absence of APC. Thus, the recognition of foreign antigen together with class II MHC molecules seems to be the only signal required for the activation of antigen-primed regulatory T cells. Furthermore, 'processing' of antigen by APC is not essential for its recognition by T cells.

Animals↗
PubMedDate not supplied

Direct peripheral effects of ghrelin include suppression of adiponectin expression.

The stomach-derived peptide, ghrelin, has recently been discovered as an important regulator of energy homeostasis. Central nervous system pathways involving stimulation of hypothalamic neuropeptides play a prominent role in mediating ghrelin's orexigenic effects. However, potential direct peripheral effects remain poorly understood. Using a brown adipocyte model, we tested ghrelin-mediated influences on adipose tissue. Chronic ghrelin stimulation of differentiating adipocytes did not affect the pattern or extent of fat accumulation. Furthermore, insulin-induced glucose uptake as a hallmark of adipocyte function was not altered by ghrelin pre-treatment. However, acute ghrelin treatment resulted in a significant time-dependent increase in p44/42 mitogen-activated protein kinase phosphorylation. There was no stimulation of phosphatidylinositol 3-kinase, JAK/STAT, or stress kinase signaling pathways. Furthermore, ghrelin did not significantly alter gene expression of the thermogenic uncoupling protein-1. By contrast, expression of the novel adipokine adiponectin, which has been implicated in the pathogenesis of insulin resistance and obesity, was strongly impaired. This inhibition occurred acutely, and was sustained for several hours. In summary, our data provide evidence for selective effects of ghrelin on adipocyte signaling and function and thus propose a role for adipose tissue as a novel mediator of ghrelin's effects on energy balance and glucose homeostasis.

Adipocytes↗
PubMedDate not supplied

Robertsonian variation in Mus musculus from Central Europe Spain, and Scotland.

Robertsonian translocations were found among mice captured on one of the Orkney islands in North Scotland, around Barcelona in Spain, and in Southern Germany around the cities of Tübingen and Ravensburg. Mice from Denmark, Poland, Astrachan in the Soviet Union Israel, and Egypt were found to be free of Robertsonian translocations. The Robertsonian variations in mice from Scotland and Spain are probably of independent origin and mostly likely also unrelated to the Alpine-Apennine system. On the other hand, the variation in mice from Southern Germany may be a part of the Alpine system. Hybrid zones were found near Barcelona and near Ravensburg. In the latter almost all the mice were heterozygous for at least one Robertsonian translocation, and often for several translocations. Three out of 14 typed mice were heterozygous for four metacentric chromosomes. The analysis revealed the existence of nine Robertsonian translocations not previously described: Rb(3.14)7Tu, Rb(4.10)8Tu, Rb(6.13)9Tu, and Rb(9.12)10Tu in Scotland; Rb(4.14)11Tu, Rb(6.10)13Tu, Rb(9.11)14Tu, and Rb(12.13)15Tu in Spain, and Rb(2.5)2Tu in Southern Germany.

Animals↗