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Biomedical subjects

T May

Publications and source records attributed to T May.

At least 19 recordsLinked to original sources

Striatal dopamine D1-like receptors have higher affinity for dopamine in ethanol-treated rats.

Experiments were carried out with brain tissues of ethanol-experienced (long-term ethanol intake but withdrawn) vs. ethanol-naive animals. The in vitro 3H antagonist binding of [3H]SCH 23390 and of [3H]spiperone to striatal dopamine D1- and D2-like receptors revealed no significant changes in KD and Bmax values. Displacement of the 3H antagonist binding by dopamine indicated high- and low-affinity states, which also showed no significant alteration at the D2-like receptor but a 5-fold increase of dopamine affinity at the high-affinity state of the D1-like receptor of the ethanol-experienced rats.

Animals

Peripheral B cells with intracytoplasmic mu chains in HIV infection.

Besides the major alteration of T lymphocytes, B-cell anomalies have been reported in HIV infection, related to late stages of B-cell maturation, and considered to result from the dysregulation of T/B interactions. Because T cells are also involved in the control of lymphopoiesis and/or because of specific alterations of the B lineage, anomalies of B-cell maturation could occur in HIV-infected patients. We investigated the presence of immature pre-B lymphocytes, characterized by cytoplasmic mu chains, in 35 peripheral blood samples from healthy controls, 82 from HIV-positive/non-AIDS patients, and 45 from AIDS patients. Significant numbers of such cells were observed in 48% of HIV-seropositive patients and in 40% of the patients with AIDS disease. The presence of pre-B cells correlated with higher numbers of CD8+ and/or CD57+ cells and of peripheral lymphocytes. These data suggest that B-cell dysregulation in HIV infection may lead to the abnormal release of immature B cells in the peripheral blood. This observation may be interpreted as a sign of bone marrow activity.

Acquired Immunodeficiency Syndrome

Central actions of neuropeptide-Y may provide a neuromodulatory link between nutrition and reproduction.

Central injection of neuropeptide-Y (NPY) has been shown to attenuate secretion of LH in ovariectomized rats, rabbits, and monkeys. Several investigators have reported elevated concentrations of NPY in the central nervous system of undernourished animals. The relationship between nutrition and reproduction positions NPY as a potential neuromodulator involved in nutritionally induced changes in secretion of LH. Three experiments were conducted with the following objectives: 1) to examine the effects of NPY on secretion of LH in ovariectomized (OVX) ewes and the influence of estradiol-17 beta (E) on these effects; 2) to determine whether NPY may act through direct effects on the pituitary to influence secretion of LH; and 3) to determine changes in concentrations of NPY in laterocerebro-spinal fluid (CSF) of food-restricted ewes compared to well-fed ewes. In Experiment 1, OVX ewes with s.c. implants of E (OVX + E, n = 4) or no steroid treatment (OVX, n = 4) were fitted with intracerebroventricular (i.c.v.) and jugular cannulae. One of 4 doses of porcine NPY (pNPY; 0, 0.5, 5, or 50 micrograms) was injected i.c.v. and blood samples were collected every 10 min for 4 h prior to and following i.c.v. injection. Blood serum was assayed for LH. The experiment was replicated four times such that each ewe received each dose of pNPY. Mean concentrations of LH as well as frequency and amplitude of pulses of LH were attenuated in response to i.c.v. injection of pNPY in a dose-related manner in both OVX and OVX + E ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena

Postmortem concentrations of phenytoin in different regions of the brain and in the serum: analysis of autoptic specimens from 24 epileptic patients.

Postmortem concentrations of phenytoin (PHT) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex and white matter, as well as cerebellum) of 18 epileptic patients who died following chronic diseases (group A) and of six otherwise healthy epileptic patients who died suddenly and unexpectedly (group B). The free concentrations in the serum correlated considerably better (r = 0.987) than the total concentrations in the serum (r = 0.871) with the concentrations in the frontal cortex. The concentrations in the frontal cortex were about nine times that of the free serum concentrations. The data show that the PHT concentrations in the frontal, temporal and occipital cortex largely agree. The concentrations in the white matter were significantly higher (frontal region 54%, temporal region 30%, occipital region 36%) than in the cortex. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical with those in the frontal cortex. Regression analysis showed that on comparable total serum concentration the patients of group A had significantly higher free serum concentrations and significantly higher concentrations in the frontal cortex than the patients of group B. In respect of the concentration ratios cortex to serum free and in regard of the local distribution of PHT in the brain no difference, however, was found between those patients who died from chronic diseases and those who died suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Use of DNA probes to monitor nutritional effects on ruminal prokaryotes and Fibrobacter succinogenes S85.

We used DNA probes to study dietary effects on the prokaryotic population in the rumen. Procedures used to isolate and quantify prokaryotic 16S ribosomal RNA (rRNA) from the rumen using universal and species-specific DNA probes were evaluated. In this experiment, three ruminally fistulated steers were fed orchard-grass hay, and ruminal digesta were collected at 0, 3, and 9 h after offering hay (0800). Samples of ruminal digesta were taken from the interior portion of the digesta mat and from the fluid below the mat in the dorsal rumen. Freezing (-65 degrees C) and blending samples both increased (P less than .07) the yield of 16S rRNA from ruminal digesta. Extraction of prokaryotic rRNA was greater (P less than .04) when phenol buffered with sodium acetate was used than when it was buffered with hydroxymethyl-amino-methane. Prokaryotic 16S rRNA concentration of the fluid phase was similar (P greater than .10) at 0, 3, and 9 h after offering hay. Prokaryotic 16S rRNA concentration of the mat phase increased up to the 9 h after feeding. The proportion of Fibrobacter succinogenes remained constant in both digesta phases at all times measured. From these data we concluded that DNA probes can be used to monitor bacterial population shifts in the rumen.

Animals

Expression of the T-cell receptor in HIV infection.

Expression of the T-cell receptor (TCR) was investigated on peripheral lymphocytes in 270 samples from HIV+ patients at different stages of infection. TCR is composed either of an alpha and a beta chain, or, in a smaller subset of T-cells, of a gamma and a delta chain, closely associated with CD3. The numbers and percentages of positive cells were established using monoclonals to the alpha and delta chains of TCR. The values of alpha-TCR positive cells were constantly lower than those observed for CD3, with a mean of 53% (+/- 19%) versus 66% (+/- 17) respectively for asymptomatic patients or patients with persistent generalized lymphadenopathy, and of 36% (+/- 19) versus 46% (+/- 21) for patients with AIDS disease. There was no compensatory increase in the number of cells expressing delta-TCR. These data demonstrate a new alteration of the immune system in HIV infection, which appears to occur early in this disease.

Acquired Immunodeficiency Syndrome

Steady state concentrations and diurnal fluctuations of carbamazepine in patients after different slow release formulations.

The bioavailability and serum level fluctuations of three carbamazepine (CBZ, CAS 298-46-4) slow release preparations marketed in Germany were compared in patients with epilepsy. Ten patients who were on CBZ monotherapy and had reached a steady state with morning trough levels above 10 micrograms/ml received all 3 preparations in sequential 3-day periods. On the 3rd day of each period, a 24-h serum drug level profile was determined. Only minimal differences could be found. One preparation had a significantly higher AUC than one of the others (p less than 0.05), and this difference seemed to be correlated with higher fluctuations of serum levels and, especially, an increased Cmax. Although the group differences are minimal, more important differences could be observed individually. One patient had, with one of the three preparations, a reduction in seizure frequency but simultaneously developed important signs and symptoms of toxicity. It is concluded that all 3 preparations are equally suitable for chronic antiepileptic drug treatment. In a well-controlled patient, however, interchange between preparations is not advisable as their kinetics in individual patients can be sufficiently different to cause toxicity or seizure relapse.

Adolescent

[Anal and perianal lesions in symptomatic HIV infections. Prospective study of a series of 190 patients].

The aim of this study was to determine the prevalence and type of symptomatic anal and perianal diseases in patients belonging to group IV of the Centers for Disease Control classification of infections with human immuno-deficiency virus. Among the 190 prospectively included patients, 31 (16.3 percent) (30 men, 29 homosexuals or bisexuals; 1 woman) had anal symptoms and were referred for proctological examination. Thirty-five "specific" diagnoses were reached in 25 (13.2 percent) patients: 21 ulcerations, 7 condyloma acuminata, 6 perianal sepsis and 1 non-Hodgkin malignant lymphoma. The causes of ulcerations were 16 herpes, one syphilitic chancre and one fissure-in-ano. Three ulcerations remained unexplained despite bacteriological, viral, and histological investigations. Eight patients underwent 10 surgical procedures without significantly delayed wound healing.

Acquired Immunodeficiency Syndrome

[Hyponatremia in AIDS. Etiology and diagnosis].

Hyponatremia is a common electrolyte abnormality in AIDS patients. In this study, hyponatremia was defined as natremia less than 130 mmol/l at two different samplings. Medical records of 160 hospitalized AIDS patients were exhaustively reviewed in search for hyponatremia and, if present, of its etiology. 45 cases of hyponatremia were identified in 43 AIDS patients. Two causes were predominant: hypovolemic hyponatremia, due to water and salt losses (11 cases) and the syndrome of inappropriate antidiuretic hormone secretion (10 cases). These results are consistent with those of the literature and were used to develop a simple diagnosis schedule based on the analysis of limited clinical and biological data: hydration status, serum and urinary osmolality, natriuria and creatininemia.

Acquired Immunodeficiency Syndrome

A cis-acting element responsible for early gene induction by extracellular cAMP in Dictyostelium discoideum.

We have analysed the promoter of the Dictyostelium discoideum alpha-L-fucosidase (ALF) gene, and have identified a 58 bp fragment responsible for transcriptional activation mediated by extracellular cAMP. Replacement of regulatory sequences in the cAMP-independent actin 15 promoter by this fragment confers cAMP regulation to the hybrid promoter. A cAMP analog with high affinity to the cell surface cAMP receptor can induce transcription from the endogenous as well as from the hybrid promoter. Gel-shift experiments show that the 58 bp fragment is a target for nuclear DNA-binding proteins, and that a specific complex is formed in response to cAMP stimulation. The major cAMP-dependent DNA.protein complex is formed with a 22 bp subfragment which we have termed DCRE (Dictyostelium cAMP responsive element).

Base Composition

[3H]harman binding experiments. I: A reversible and selective radioligand for monoamine oxidase subtype A in the CNS of the rat.

Harman (1-methyl-beta-carboline) is an endogenous compound with neurotropic properties in rats and humans. In a novel in vitro binding assay, the binding site of [3H]harman has been characterized in the rat crude mitochondrial (P2) fraction. The binding was saturable and reversible. Only a single high-affinity binding site was detected by kinetic, saturation, and displacement analyses in the cerebral cortex of the rat. The linear Scatchard plots revealed equilibrium dissociation constant (KD) values of approximately 2.5 nM at 0 degrees C, approximately 9 nM at 23 degrees C, and approximately 30 nM at 37 degrees C. Among six CNS regions (hypothalamus, hippocampus, cerebral cortex, striatum, cerebellum, and spinal cord), the highest density of binding sites (Bmax) was determined in the hypothalamus (approximately 5.5 pmol/mg of protein) and the lowest in the spinal cord (approximately 2.0 pmol/mg of protein). Several drugs known to affect serotonergic, adrenergic, dopaminergic, cholinergic, or GABAergic neurotransmission inhibited specific binding at best in the micromolar range. In contrast, potent and selective inhibitors of monoamine oxidase subtype A were active in the lower and middle nanomolar range. The displacing potency (apparent Ki) of substrates and inhibitors of monoamine oxidase correlated positively and highly significantly with the corresponding values of the inhibition of monoamine oxidase activity of subtype A (r = 0.92, p less than 0.001, n = 17) but not of subtype B (r = -0.47, p greater than 0.05, n = 15). In conclusion, [3H]harman was identified as a specific ligand of the active site of the A subtype of monoamine oxidase in rat brain.

Animals

[3H]harman binding experiments. II: Regional and subcellular distribution of specific [3H]harman binding and monoamine oxidase subtypes A and B activity in marmoset and rat.

[3H]Harman (1-[3H]methyl-beta-carboline) was used in a novel radioligand binding assay to label selectively and with high affinity monoamine oxidase (MAO) type A. The concentration of the enzyme was determined in six CNS regions of the primate species marmoset (Callithrix jacchus) and of the rat: hypothalamus, hippocampus, cerebellum, cerebral cortex, striatum, and spinal cord. The specific [3H]harman binding in the CNS of the marmoset reveals the same pharmacological profile and other characteristics (affinity, saturability, and reversibility) as in the CNS of the rat. The regional distribution of the [3H]harman binding density (Bmax) in the CNS exhibits a distinct pattern in the marmoset and the rat and a 35 (hypothalamus) to 75% (hippocampus) lower Bmax in the marmoset than in the rat. The Bmax values of [3H]harman binding in the CNS of the marmoset and the rat combined as well as those from visceral organs of the rat (liver, heart, lung, thymus, spleen, and kidney) correlated positively and highly significantly with the respective Vmax values of specific MAO activity of the A type but not of the B type, determined with kynuramine as the substrate. In subcellular fractionation experiments with rat cerebral cortex, the highest [3H]harman binding density (Bmax) and MAO-A activity (Vmax) were detected in mitochondrial fractions and severalfold lower values in the synaptosomal membrane fraction. In conclusion, we suggest that [3H]harman binding is a biochemical tool as a selective marker to quantify MAO-A in the CNS of different mammalian species as well as in extraneuronal tissues.

Aging

Plasma norharman (beta-carboline) levels are elevated in chronic alcoholics.

Based on the hypothesis that condensation products of neurotransmitters with aldehydes are involved in the pathogenesis of alcoholism, aromatic beta-carbolines (norharman and harman) were measured in the blood plasma of alcoholics and nonalcoholics. The identity of the extracted compounds was confirmed by various elution conditions of the high performance liquid chromatography (HPLC), newly developed radioreceptor assays, and the mass spectrum of norharman. The levels of norharman and harman in nonalcoholics were unchanged after a load with ethanol (1 g/kg body weight). The norharman levels of the alcoholics were significantly higher than that of the nonalcoholic controls (99.5 +/- 26.6 pg/ml vs. 26.9 +/- 10.7 pg/ml; p less than 0.001) and did not change significantly during a 3-week detoxication period. In the subgroup of alcoholics with delirium or hallucinosis, a slight increase of norharman during detoxication could be detected while in alcoholics with vegetative withdrawal symptoms norharman levels dropped slightly over time (p = 0.07). No difference was found with respect to harman between nonalcoholics and alcoholics. These results suggest disturbed regulatory processes in the formation and/or metabolism of norharman in alcoholics. Further investigations are needed to reveal a possible marker function of norharman in alcoholic patients.

Adolescent

Evaluation of dairy food processing wash water solids as a protein source: I. Forage intake, animal performance, ruminal fermentation, and site of digestion in heifers fed medium-quality hay.

Twelve ruminally, duodenally, and ileally cannulated (average initial BW 313 +/- 20 kg) and 27 intact Hereford heifers (average initial BW 256 +/- 17 kg) were used in two experiments to evaluate dairy food wash water solids (WWS) as a protein source in medium-quality hay diets. Heifers received a basal diet of orchardgrass hay (7.4% CP) and were assigned to one of three supplement treatments: control (C; .9% CP), WWS (18.8% CP)-, and soybean meal (SBM; 19.1% CP)-based supplements (fed at 1.5 kg of DM/d). Supplements were formulated to have similar ME concentrations. Ruminal ammonia concentrations were greater (P less than .10) for WWS- and SBM-supplemented heifers than for C heifers at most sampling times. Moreover, WWS and SBM increased (P less than .10) total VFA (mM) and acetate (mol/100 mol) and lowered propionate (mol/100 mol) at several sampling times. Ruminal fluid volume (liters) was unchanged (P greater than .10) by treatment; however, fluid dilution and flow rate (liters/h) were less (P less than .10) in C heifers than in heifers fed SBM or WWS supplements. Wash water solids and SBM supplementation increased (P less than .10) OM, NDF, and ADF digestibilities compared with C heifers. Feeding WWS and SBM supplements increased BW at 84 d (P less than .10) compared with C-supplemented heifers. Forage intake at 54 and 84 d by heifers supplemented with SBM or WWS was greater (P less than .10) than by C heifers. Control-supplemented heifers had the least, WWS intermediate, and SBM the greatest ADG at 84 d (P less than .10; .14 vs .35 vs .48 kg/d, respectively). These data indicate that WWS may be used as a protein source without serious adverse effects in heifers consuming medium-quality hay for 84 d.

Ammonia

Evaluation of dairy food processing wash water solids as a protein source: II. Microbial protein synthesis, duodenal nitrogen flow, and small intestinal amino acid disappearance.

Twelve ruminally, duodenally, and ileally-cannulated Hereford heifers (average initial BW 313 +/- 20 kg) were used in a replicated experiment to evaluate dairy food processing wash water solids (WWS) as a protein source. Heifers were fed 2.8 kg of chopped (7.6 cm) hay and one of three supplements (1.5 kg/d, DM basis). Supplements were formulated to be similar in energy and contained 1.0 (control), 23.2 (WWS), and 21.6% (soybean meal; SBM) CP on an OM basis. Total N and nonammonia N entering the duodenum (g/d) were greater (P less than .10) for heifers fed WWS and SBM supplements than for controls. Bacterial N flow (g/d) at the duodenum was less (P less than .10) for controls (43.9) than for WWS- (63.9) and SBM- (69.9) supplemented heifers. Feed escape N (g/d) was greater (P less than .10) for WWS-fed heifers than for those fed SBM (32.1 vs 20.7 g/d, respectively). Total tract N digestion (g/d) was greatest (P less than .10) for SBM, intermediate for WWS, and least for control heifers. Microbial protein synthesis (g/kg of OM intake) was enhanced (P less than .10) by WWS and SBM supplementation, but efficiency of synthesis (g/kg of OM fermented) did not differ among treatments. Essential amino acid (AA) disappearance in the small intestine (g/d) was less (P less than .10) for control than for the other two treatments. Nonessential AA disappearance was greatest (P less than .10) for the WWS and least (P less than .10) for the control treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Evaluation of dairy food processing wash water solids as a protein source: III. Nitrogen utilization by heifers fed medium-concentrate diets.

Eight multicannulated heifers (average BW 415 +/- 34 kg) were used in a replicated 4 x 4 Latin square to evaluate fluid milk processing wash water solids (WWS) as a dietary N source. Heifers were fed corn/cottonseed hull-based diets containing soybean meal (control, 0% WWS N) or WWS replacing soybean meal at 33, 67, or 100% of supplemental dietary N. Total tract and ruminal DM and OM digestibilities decreased linearly or cubically (P less than .05) as dietary WWS N increased. Total ruminal VFA concentration (P less than .05) and propionic acid molar proportion (P less than .10) were greater in heifers fed 0 vs 100% WWS N. Heifers fed 0% WWS N had the greatest (P less than .05) ruminal ammonia concentration at all sampling times. Dietary WWS did not affect (P greater than .10) ruminal pH, fluid dilution rate, fluid flow, fluid volume, or turnover time. Total tract N digestibility decreased quadratically (P less than .10) with increasing WWS N in the diet. Supplemental WWS N did not affect (P greater than .10) flow of duodenal ammonia N or bacterial N, or efficiency of microbial N synthesis. Diets containing WWS N resulted in a cubic increase (P less than .10) in duodenal flow of essential amino acids compared with 0% WWS N; however, there were no differences in small intestinal amino acid disappearance. Data indicate that WWS can replace 33% of the soybean meal N in a corn/cottonseed hull-based diet without decreasing ruminal fermentation, fluid digesta kinetics, microbial efficiency, or small intestinal amino acid utilization.

Amino Acids