Biomedical subjects
B Jacobson
Publications and source records attributed to B Jacobson.
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.
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.
Adaptation of glutathione peroxidase assay to the Technicon RA-1000.
Explore the source record for details and available documents.
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.
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.
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.
Effect of calcium channel blocking drugs on tumor cell oxygen utilization.
Explore the source record for details and available documents.
Cellular oxygen utilization and hypoxia: interaction of dithiols with cellular electron transfer systems.
Explore the source record for details and available documents.
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.
Pharmacokinetics and distribution of flucloxacillin in pacemaker patients.
The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t 1/2 alpha = 0.13 h). The plasma half-life of elimination (t 1/2 beta) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the beta-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 1/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the beta-phase (Vd beta free) was 2.18 1/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 micrograms/ml and 9.5 micrograms/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of vascular endothelial cell growth and trypsin activity by vitreous.
Vitreous from bovine, human and chick embryo has been found to contain a trypsin inhibitory activity. Chymotrypsin-inhibitory activity was also identified in bovine and chick embryo vitreous. Following either ultrafiltration or Bio Gel P-10 chromatography, these activities appear in fractions having a molecular weight greater than 10000 MW (ultrafiltration) or greater than 13000 MW (P-10 void volume), and are separable from low molecular weight aortic endothelial cell growth inhibitory activity present either in the ultrafiltrate or P-10 retarded volume. Treatment of the trypsin inhibitory fraction with hyaluronidase had no effect on trypsin inhibition, nor did addition of hyaluronic acid inhibit trypsin. Chick embryo vitreous and hyalocyte-conditioned medium were found to contain aortic endothelial cell growth inhibitory activity in both the void volume and retarded volume fractions following Bio Gel P-10 chromatography. Both the 6200 MW bovine vitreous endothelial cell growth inhibitor and the high molecular weight chick embryo vitreous endothelial cell growth inhibitor (greater than 13000 MW) were similar, in that most of the activity did not bind to heparin linked to Sepharose CL-6B.
Antibiotic prophylaxis in pacemaker surgery: a prospective trial with local or systemic administration of antibiotics at generator replacements.
Explore the source record for details and available documents.
Vascular endothelial cell growth inhibitor of normal and pathologic human vitreous.
Normal and pathologic human vitreous have been analyzed for the presence of a low-molecular weight inhibitor of aortic endothelial cell proliferation. Vitreous was subjected to gel chromatography and the material appearing in the retarded volume (less than 13,000 daltons) was tested for its ability to inhibit tritiated thymidine incorporation into DNA by calf aortic endothelial cells. Depending on the sample of vitreous analyzed, one or more fractions showing inhibitory activity were identified in each case.
Control of oxygen utilization in vitro and in vivo: implications for radiotherapy of tumors.
Explore the source record for details and available documents.
Degradation of glycosaminoglycans by extracts of calf vitreous hyalocytes.
The ability of extracts of calf vitreous hyalocytes to catalyze the degradation of glycosaminoglycans was studied by incubation with radioactively labeled substrates. The degradation of the polymeric substrates to lower molecular weight products was assayed by three methods: (1) paper chromatographic separation of low molecular weight, mobile digestion products from undigested, high molecular weight material which remains at or near the origin; (2) loss of the ability of the glycosaminoglycan to be precipitated by cetylpyridinium chloride; (3) gel chromatography to separate low molecular weight digestion products, which appear in the retarded volume, from undegraded, high molecular weight material, which is eluted in the void volume. The acidic pH optimum of the reaction suggests a lysosomal origin of the enzyme activity.
Biostator education for staff development.
Explore the source record for details and available documents.
Identification of sialyl and galactosyl transferase activities in calf vitreous hyalocytes.
Sialyl and galactosyl transferase activities are demonstrated in calf vitreous hyalocytes. For study of sialyl transferase activity, a partially purified vitreous preparation (collagen and hyaluronic acid removed), and bovine submaxillary mucin were treated with an insolubilized neuraminidase before use acceptor of radioactivity from CMP-[3H]-N-acetylneuraminic acid (CMP-[3H]-NAN). For study of galactosyl transferase activity the vitreous preparation was treated first with insolubilized neuraminidase and then with an insolubilized beta-galactosidase before use as acceptor of radioactivity from UDP-[3H]-galactose (UDP-[3H]-gal). Galactosyl transferase requires a divalent metal ion for optimal activity, and the reactions catalyzed by each enzyme are dependent upon pH, time of incubation and concentration of enzyme and/or acceptor.