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Biomedical subjects

L M Brown

Publications and source records attributed to L M Brown.

158 records · Page 9Linked to original sources
PubMed1978

A simple radioimmunoassay for plasma cortisol.

A simple radioimmunoassay (RIA) for plasma cortisol is described which combines the advantages of (i) direct analysis of untreated plasma samples, (ii) use of solid-coupled anti-cortisol antibodies and (iii) use of a gamma-labelled radioligand. The reagents are relatively easily prepared and stable, and the analysis can be completed in 4 h. Inter-assay precision (C.V.) is 8-11%. Critical examination of specificity using high pressure liquid chromatography showed that 23-35% of the immunoassayable material in plasma was not cortisol. RIA results on samples collected under basal conditions were on average 40 nmol/l lower than fluorimetric results, while in insulin hypoglycaemia and synacthen (ACTH) stimulation tests, this difference increased to over 100 nmol/l. The RIA is technically more simple than fluorimetric, competitive-protein-binding, and many RIA methods, and can be used with advantage in the routine investigation of adrenocortical function. However, using the present antiserum, the RIA is not applicable to investigations on patients receiving metyrapone, nor in suspected cases of congenital adrenal hyperplasia.

Animals↗
PubMedDate not supplied

N-methyl-D-aspartate mediated responses decrease with age in Fischer 344 rat brain.

N-Methyl-D-aspartate (NMDA) receptor-mediated responses were studied in hippocampus, cortex, and striatum of Fischer 344 rats of various ages (3-5, 12-14, or 24-28 months old; young, middle-aged, and senescent or old, respectively) to determine whether aging alters the function of NMDA receptors. NMDA-induced inhibition of muscarinic-stimulated phosphoinositide hydrolysis in hippocampus, and NMDA-stimulated release of [3H]norepinephrine (NE) or [3H]dopamine (DA) were used as indices of NMDA receptor function. The muscarinic agonist carbachol (1 mM) stimulated PI hydrolysis in hippocampi from all three age groups with no significant differences between the groups. NMDA inhibited the carbachol-evoked PI response in a concentration-dependent manner (10-100 microM) in all age groups. However, the NMDA-induced (100 microM) inhibition of the carbachol-stimulated response was markedly reduced in an age-dependent manner with losses of 25% and 53% in middle-aged and senescent rats compared to young. Concentration-effect curves for NMDA-stimulated [3H]NE release were determined using hippocampal and cortical slices from rats of the three age groups. In the hippocampus the maximal response for NMDA was significantly decreased from 6.55 fractional [3H]NE release in young to 4.51 and 4.18 in middle-aged and old rats, respectively, with no age-related changes in the potency of NMDA or slope of the curves. In cortical slices the maximal response was significantly reduced in an age-dependent manner by 23% in the senescent rats compared to the young rats. NMDA-stimulated [3H]DA release from striatal slices was significantly lower in the senescent rats at concentrations of NMDA from 500-2000 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Ethanol and neuronal calcium channels.

Ethanol alters voltage-dependent calcium channels and receptor-operated channels which transport calcium [e.g., the ion channels associated with N-methyl-D-aspartate (NMDA) receptors]. However, the question which still remain unanswered is whether these modifications have any physiological significance. This review will focus on the effects of ethanol on various calcium-related parameters with an emphasis on the possible relevance to the behavioral effects elicited by ethanol.

Animals↗
PubMedDate not supplied

Alcohol inhibition of NMDA-stimulated catecholamine efflux in aging brain.

The influence of aging on the ability of ethanol to inhibit N-methyl-D-aspartate-stimulated catecholamine overflow in rat brain was examined. Alcohol effects on N-methyl-D-aspartate stimulated [3H]norepinephrine or [3H]dopamine overflow from the cortex, hippocampus, and striatum of aged (24-28 months) middle aged (12-14 months), and young (3-5 months) rats were examined. N-methyl-D-aspartate (500 microM) stimulated catecholamine overflow in all brain regions, with aged rats showing declines in overflow of 33% in the hippocampus and 41% in the striatum. Alcohol (30-200 mM) produced a concentration-dependent inhibition of overflow at all ages and brain regions tested. The IC50 for alcohol inhibition of NMDA-stimulated catecholamine release was not significantly different in aged brain or across brain regions. These results indicate that alcohol's ability to inhibit NMDA-stimulated catecholamine release is not significantly altered with aging.

Aging↗
PubMedDate not supplied

Omega-conotoxin increases sleep time following ethanol injection.

omega-Conotoxin and ethanol produce similar actions on in vitro calcium channel functions. The present study was designed to determine their possible behavioral interaction. omega-Conotoxin injected ICV at either 0.1 microgram or 0.3 microgram, produced an increase in spontaneous and evoked tremor activity in male Sprague-Dawley rats. The tremor was present at 30 min and continued at least 4 h after injection. At 4 h post ICV injection, animals were given an IP injection of ethanol (3 g/kg body weight). Although no blood alcohol differences were observed between groups, rats injected with omega-conotoxin showed a concentration-dependent increase in sleep times: Saline controls slept for an average of 84.7 +/- 16.7 min, 0.1 and 0.3 microgram conotoxin treated animals slept for 121.3 +/- 16.2 and 211.1 +/- 30.7 min, respectively. These results extend the class of calcium channel blockers capable of producing a behavioral interaction with ethanol.

Animals↗
PubMedDate not supplied

Granulocytic sarcoma in childhood acute myelogenous leukemia.

A 12-year-old boy with acute myelogenous leukemia developed acute weakness and paresthesias of the lower extremities after lumbar puncture. Computed tomography and magnetic resonance imaging revealed 2 large paraspinal masses (granulocytic sarcoma) causing spinal cord compression. Treatment with corticosteroids, radiation therapy, and chemotherapy caused complete resolution of symptoms; there was no evidence of tumor on subsequent magnetic resonance imaging or at autopsy. Granulocytic sarcomas (chloromas) rarely involve the nervous system in patients with acute myelogenous leukemia, although with increased survival it is apparent that the incidence may be greater than previously believed. Central nervous system prophylaxis was not administered to our patient but may be recommended for future patients if systemic disease can be controlled. General features of central nervous system complications of acute myelogenous leukemia, characteristics of granulocytic sarcoma, and review of current radiographic techniques used in the evaluation of these tumors are discussed.

Child↗
PubMedDate not supplied

Prophylactic granulocyte transfusions: results of a randomized controlled trial in patients with acute myelogenous leukemia.

A prospective randomized and controlled clinical trial of prophylactic granulocyte transfusions was conducted in an attempt to reduce the mortality from infection in newly diagnosed adults with acute myelogenous leukemia. Granulocytes were harvested from normal donors by cytapheresis, and transfused patients received a median of 1.45 x 10(10) granulocytes (range 0.28--3.45 x 10(10)) on alternate days during marrow aplasia caused by initial induction chemotherapy. Transfusion were started if the absolute peripheral granulocyte count was less than 500 microliters. Thirteen patients received from one to 12 granulocyte transfusions, and 11 control patients received no granulocytes. No significant advantage was demonstrated in the transfused patients compared with controls with regard to the following: 1) deaths due to infection, 2) reduction in the frequency of febrile episodes, 3) delay in the onset of fever, 4) reduction in the length of febrile episodes, or 5) reduction in the frequency of proven infection.

Adolescent↗
PubMedDate not supplied

Combined granulocyte and platelet transfusions. Development of alloimmunization as reflected by decreasing cell recovery values.

Twenty-three patients undergoing induction therapy for acute myelogenous leukemia (AML) received a total of 191 combined prophylactic granulocyte (PMN) and platelet (PLT) concentrates on alternate days (median 8, range 3-12 per patient). Each transfusion was assessed by monitoring the patient for reactions and by estimating the recovery of PMN in the circulation at 1 hour and of PLT at 1 and 20 hours. Seventeen patients developed alloimmunization to PLT from at least one donor, defined as either a PLT recovery of less than 15 percent at 1 hour and/or less than 10 percent at 20 hours. In this group there was a progressive reduction in PMN and PLT recovery with increasing transfusion number, strongly suggesting alloimmunization to both cells. Thirty-four transfusions were accompanied by transfusion reactions, thirty-two of which occurred in ten patients who had PMN recoveries of less than 5 percent after at least one transfusion (median 2.5, range 1-6 transfusions per patient). Actuarial calculations predicted that 70 percent of patients would become alloimmunized to PLT from at least two individuals after receiving 11 transfusions. These results suggest that combined PMN and PLT transfusion are associated with the rapid development of alloimmunization.

Cell Survival↗