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Biomedical subjects

B Jacobson

Publications and source records attributed to B Jacobson.

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

Defective control of cytoplasmic calcium concentration in T lymphocytes from old mice.

Cytoplasmic calcium concentration ([Ca]i) rises within minutes of exposure of T lymphocytes to a mitogen. T cells from old mice are defective in this reaction, a defect that could reflect either altered signal transduction or instead a more general age-associated change in intracellular calcium regulation. We therefore tested the ability of T cells from old mice to regulate their [Ca]i concentration after exposure to low concentrations of ionomycin, an agent that raises [Ca]i but bypasses receptor-mediated signal transduction mechanisms. Exposure of T cells to ionomycin leads to an abrupt increase in [Ca]i followed by stabilization at a dose-dependent plateau level that is affected by extracellular EGTA, by calmodulin inhibitors, and by modulators of protein kinase C. Plateau levels of [Ca]i after ionomycin challenge were consistently lower in T cells from old mice than in T cells from young mice. Flow cytometric experiments showed that while essentially all T cells from both old and young mice responded to ionomycin, they did so to an extent that depended on donor age. The age-dependent increase in resistance to ionomycin-induced changes in [Ca]i cannot be attributed to diminished membrane permeability to the ionomycin-calcium complex. The data suggest that aging may lead, in T lymphocytes, to a relative resistance to increases in [Ca]i, a resistance that in turn prevents cell activation.

Aging↗
PubMed1989

Selenium deficiency in low birth weight neonates: an unrecognized problem.

To determine whether selenium deficiency is common among low birth weight infants in our neonatal intensive care unit, we surveyed blood samples from healthy full-term and preterm infants born in our hospital over a 3-month period. Selenium was measured by electrothermal atomic absorption spectrometry. Glutathione peroxidase was measured in plasma by an automated method. Baseline (less than 72 hours postnatal) selenium concentration and glutathione peroxidase activity were significantly lower in low birth weight infants than in full-term babies. Sequential selenium analyses were obtained in 16 sick low birth weight neonates who remained in the intensive care nursery for up to 6 weeks because of lung disease. All were fed parenterally without supplemental selenium, with or without oral intake, for periods varying from 3 to 60 days. All had a marked decrease from baseline selenium levels, and values below the detection limit of our assay were found in seven infants. Selenium deficiency is much more common in small infants than is generally realized, but the clinical significance in neonates is poorly understood.

Bronchopulmonary Dysplasia↗
PubMed1988

Cyclic AMP concentrations modulate both calcium flux and hydrolysis of phosphatidylinositol phosphates in mouse T lymphocytes.

Activation of T cells by lectins or mAb directed at components of the Ag-specific TCR results in hydrolysis of phosphorylated derivatives of phosphatidylinositol and an increase in intracellular free calcium concentration (Cai). We report that cholera toxin, which activates adenylate cyclase by ADP ribosylation of a G protein, also reduces both inositol phosphate (IP) production and the rise in Cai in Con A-stimulated murine T cells. We find that similar dose-dependent inhibitory effects can be induced by each of four other agents that raise cAMP levels in such cells: forskolin, PGE2, 2-chloroadenosine, and isoproterenol. The effects of these agents on IP production are reversible and therefore do not simply reflect cytotoxicity. Activation by PHA and by antibody to the T3-epsilon-chain of the TCR complex are also inhibited by agents that increase intracellular cAMP. Thus, changes in cAMP concentration seem to regulate both IP production and the Ca2+ response, two early components of the mitogen-induced activation process.

2-Chloroadenosine↗
PubMed1988

Obstetric pain medication and eventual adult amphetamine addiction in offspring.

Our purpose was to investigate whether obstetric analgesia, particularly by nitrous oxide, constitutes a risk that the infant might develop amphetamine addiction in later life. Of 200 current amphetamine addicts born between 1945 and 1966 in Stockholm, proportionately more were born at hospitals where pain medication had been administered in large doses (p less than 0.05). A blind matched comparison was made between 73 addicts and 109 non-addicted siblings by logistic regression, in which nitrous oxide administration was tested in competition with 12 other natal variables as possible confounders. The risk for amphetamine drug addiction in offspring was found to increase with duration of intermittent administration of pure nitrous oxide, i.e. it was estimated to be 5.6 times greater (95% confidence intervals 1.6-16.9, p = 0.005) when nitrous oxide had been given for greater than or equal to 4.5 h vis-à-vis less than or equal to 0.25 h. Calculated risks are probably underestimates. Results can be explained as an effect of imprinting. It is concluded that local or regional anesthesia are preferable to general anesthesia which allows substantial amounts of drugs to cross the placenta.

Adult↗
PubMed1988

Age- and sex-specific pediatric reference intervals and correlations for zinc, copper, selenium, iron, vitamins A and E, and related proteins.

Age- and sex-specific reference intervals based on the 0.025 and 0.975 fractiles of data derived from a healthy pediatric population are presented for zinc, copper, selenium, iron, ferritin, retinol, alpha-tocopherol, and related analytes in serum. Age was an important covariate for copper, selenium, retinol, and tocopherol, and ferritin in boys. Strong correlations were found between retinol and retinol-binding protein, prealbumin (transthyretin), alpha-tocopherol, and selenium. Tocopherol was highly correlated with both cholesterol and triglycerides. We found no relationship between serum zinc and either retinol or retinol-binding protein. Despite exclusion of children in whom anemia, microcytosis, or variant hemoglobins were found, the 0.025 fractile for iron in several age groups was even less than the concentration considered to indicate poor iron nutritional status.

Adolescent↗
PubMed1987

Diminished calcium influx in lectin-stimulated T cells from old mice.

T lymphocytes from aged donors function poorly, but the biochemical basis for the defect remains uncertain. We tested the hypothesis that T cells from old mice had a diminished ability to transmit extracellular signals into the cytoplasm, by measuring intracellular free calcium concentrations (Cai) in T cells stimulated by the polyclonal activator concanavalin A (Con A). Using the second-generation fluorochrome indo-1 as a reporter of Cai, we found that the Con A-induced elevation of Cai levels is reduced both in rate and extent in old T cells, as compared to T cells from young mice. Flow cytometric analysis showed that this age-sensitive change represents a decline, with age, in the number of T cells that can respond to Con A by increasing their Cai above resting baseline levels (100-120 nM). These results thus show that defects in activation are manifested by T cells from old donors within the first 5 minutes of the activation process, and suggest that aging may lead to alterations either in the surface molecules that receive extracellular signals, or in the sequence of coupled events by which these extracellular signals bring about alterations in the intracellular ionic milieu.

Aging↗
PubMed1987

Perinatal origin of adult self-destructive behavior.

The study was undertaken to test whether obstetric procedures are of importance for eventual adult behavior of the newborn, as ecological data from the United States seem to indicate. Birth record data were gathered for 412 forensic victims comprising suicides, alcoholics and drug addicts born in Stockholm after 1940, and who died there in 1978-1984. The births of the victims were unevenly distributed among six hospitals. Comparison with 2,901 controls, and mutual comparison of categories, showed that suicides involving asphyxiation were closely associated with asphyxia at birth, suicides by violent mechanical means were associated with mechanical birth trauma and drug addiction was associated with opiate and/or barbiturate administration to mothers during labor. Irrespective of the mechanism transferring the birth trauma to adulthood--which might be analogous to imprinting--the results show that obstetric procedures should be carefully evaluated and possibly modified to prevent eventual self-destructive behavior.

Adult↗
PubMed1986

Blood serotonin concentrations and fenfluramine therapy in autistic children.

Whole-blood serotonin concentrations of 31 autistic children, aged 2 1/2 to 16 years, 10 non-autistic retarded children, and 18 children with Down syndrome were measured by a fluorometric method and compared with those of normal children of similar age range. No significant difference in the serotonin concentration per milliliter of whole blood or per 1000 platelets was found between groups for autistic, retarded, or normal children, but the values for those with Down syndrome were significantly lower. A double-blind cross-over study on the effect of fenfluramine versus placebo in seven autistic boys over a period of 8 months demonstrated a significant decrease in blood serotonin levels during the fenfluramine phase in all subjects. Slight improvements were found in short-term auditory memory and some measures of receptive language skills, particularly in children functioning at a high level. There was no significant change in global psychometric measurements of general intelligence during therapy. No adverse clinical effect was observed other than weight loss of 6% in one child. We conclude that fenfluramine may have some selective favorable effects on increasing attention in high-functioning autistic children. Blood serotonin concentration may be followed as an indication of drug compliance during fenfluramine therapy, but does not appear to reflect clinical efficacy.

Adolescent↗