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Biomedical subjects

D Wilson

Publications and source records attributed to D Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Vitamin D status modulates rat colonic M3 muscarinic receptor characteristics and coupling to guanylate cyclase.

The present studies were conducted to determine whether [3H]quinuclidinyl benzilate binding in rat colonic membranes and/or carbachol-mediated stimulation of particulate guanylate cyclase were altered by changes in vitamin D status. EC50 values for the stimulation of colonic guanylate cyclase by carbachol were found to be significantly greater in vitamin D-deficient rats compared to their D-sufficient counterparts. Concomitantly, the density of receptors (Bmax) were significantly lower, and dissociation constants (Kd) were significantly higher in D-deficient colonic membranes. In vitamin D-repleted animals, moreover, all of these aforementioned alterations were at least partially corrected.

Animals↗
PubMed1994

Post-activation potentiation in the neocortex: I. Acute preparations.

Long-term potentiation is widely studied as a memory model, and has been demonstrated in a number of subcortical sites in both acute and chronic preparations. In the neocortex, however, most of the demonstrations of LTP have been in neocortical slice or acute preparations, and even these have often required a drug-induced attenuation of inhibition before the LTP could be reliably expressed. In this paper we show that LTP can be reliably expressed in adult rats in a number of neocortical sites, both ipsilateral and contralateral to the site of callosal stimulation. We also show that, when recording field potentials, LTP is expressed roughly equally at all cortical depths. In a third experiment, we monitored input/output (I/O), paired-pulse inhibition and short-term potentiation effects over the course of LTP induction. The ipsilateral responses were, as expected, of shorter latency and larger amplitude than contralateral responses. They also showed small spike-like components that correlated with cell discharge. Nevertheless, the contralateral responses tended to show the largest LTP effects. The paired pulse effect was mainly depression, lasting for up to 3000 ms, at both ipsilateral and control sites. The short-term potentiation components were best fit by two summed exponentials with time constants of about 70 s and 12 min. The LTP effect lasted at least two h which was the longest period monitored in these experiments.

Animals↗
PubMed1994

Post-activation potentiation and depression in the neocortex of the rat: II. Chronic preparations.

Although long-term potentiation (LTP) has been demonstrated in a number of subcortical sites in chronic preparations, there have been no demonstrations of LTP in the neocortex of chronic preparations. Even neocortical slice and acute preparations often require a drug-induced suppression of inhibition before LTP effects can be reliably induced. We have attempted to induce LTP in neocortical sites in 7 different experiments using chronically prepared adult rats. We were unable to obtain any evidence, even a trend, for the induction of LTP. The following manipulations were tested: (1) standard stimulation train parameters that have been shown to be highly effective in subcortical and hippocampal sites; (2) a 10-fold increase in the intra-train pulse durations; (3) variations in train pulse frequency (1 Hz to 300 Hz) and train duration (100 ms to 15 min); (4) co-activation of multiple inputs by stimulation of combinations of cortical sites or cortical and thalamic sites; (5) reduction of inhibition by administration of picrotoxin; 5) Housing of animals in an enriched environment; (6) utilization of the neocortical stimulation trains as a cue in a learning task; (7) application of pilocarpine to co-activate cholinergic systems. Although none of these manipulations produced LTP, the application of pilocarpine did facilitate the induction of a long-lasting depression effect. These findings contrast with the results obtained from anesthetized rats and from studies using brain slices, where LTP can be reliably induced. These results are discussed in light of other recent findings with respect to LTP and LTD effects.

Animals↗
PubMed1994

Depression, suicidal ideation, and substance use among adolescents. Are athletes at less risk?

OBJECTIVES: To determine the relationship between participation in high school athletic programs and depression, suicidal ideation, and substance use, and to study the high-risk behaviors of suicidal ideation and substance use. DESIGN: Survey. SETTING: A suburban public high school in Kentucky. PARTICIPANTS: We received 823 (80%) responses from 1030 potential respondents. Athletes (ie, participation on a high school athletic team) were compared with non-athletes. MEASURES: Depression was measured by the Children's Depression Inventory by an index of suicidal ideation by an indicator of a past suicide attempt, and by current use of tobacco, alcohol, marijuana, and cocaine. RESULTS: Thirty percent of the sample participate in school athletic teams. Athletes are less depressed, have less suicidal ideation and attempts, and are less likely to currently smoke cigarettes or marijuana. The use of smokeless tobacco and cocaine was not related to athletic participation. After controlling for demographic characteristics, no difference in alcohol use was found between athletes and nonathletes. CONCLUSIONS: Athletic participation is a marker for a decreased likelihood of depression and some high-risk behaviors in adolescents. Future research could help in creating alternative interventions beyond participation in varsity and junior varsity athletic teams.

Adolescent↗
PubMed1994

Receptor-mediated regulation of neuropeptide gene expression in astrocytes.

One of the functions of glial receptors is to regulate synthesis and release of a variety of neuropeptides and growth factor peptides, which in turn act on neurons or other glia. Because of the potential importance of these interactions in injured brain, we have examined the role of two different receptors in the regulation of astrocyte neuropeptide synthesis. Stimulation of beta-adrenergic receptors on type 1 astrocytes resulted in increased mRNA and protein for the proenkephalin (PE) and somatostatin genes. This receptor also increased expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). The potential role of opiate receptors was examined in several ways. Treatment of newborn rats for 7 days with the opiate antagonist naltrexone, prior to preparation of astrocytes, had no effect on PE mRNA or met-enkephalin content but resulted in a significant increase in NGF content. However, treatment of astrocytes in culture with met-enkephalin, morphine, or naltrexone had no effect on any of these parameters. No opiate binding could be detected, using either etorphine or bremazocine, to membranes of astrocytes prepared from cortex, cerebellum, striatum, or hippocampus of 1-day, 7-day, or 14-day postnatal rats. Thus we conclude that type 1 astrocytes do not express opiate receptors and that the in vivo effects of naltrexone are mediated indirectly via some other cell type/receptor.

Adrenergic beta-Agonists↗
PubMed1994

Renal function in children and adolescents following 72 g/m2 of ifosfamide.

A detailed analysis of the renal function of 18 children and adolescents aged 7-20 years (median, 16 years) was performed at least 3 months following the completion of a non-platinum-containing chemotherapy regimen with a total dose of 72 g/m2 of ifosfamide. Ifosfamide had been given as a 1-h infusion of 1.8 g/m2 daily for 5 days at 5- to 6-week intervals along with mesna uroprotection. The mean glomerular filtration rate (GFR) as determined by inulin clearance was 100 ml/min/1.73 m2. Although 6 of 18 patients had GFRs below normal, the lowest was only 18% less than the lower limit of normal and would not account for any clinical compromise. The renal plasma flow and filtration fraction were normal. Proximal tubular function evaluation revealed normal fractional excretion (FE) of glucose; normal mean tubular maximum phosphate reabsorption per GFR (TMP)/GFR values; high FE of urate (17%); and mild, generalized aminoaciduria in 6 of the 18 patients. Distal tubular function evaluation showed normal 24-h urinary calcium levels and FE of magnesium as well as normal urinary osmolality after water deprivation. Two patients had mild proteinuria. The findings in this study are encouraging in terms of the lack of clinically significant renal abnormalities observed in patients who had received a cumulative dose of 72 g/m2 of ifosfamide.

Adolescent↗
PubMed1994

Visualization of myocardial infarction six hours after injection of 111 In-antimyosin antibodies using an image subtraction technique.

111 In-antimyosin antibodies are capable of visualizing acute myocardial infarction (MI). Because of slow blood clearance, images are usually recorded 24 or 48 h postinjection. This pilot study was aimed at validating a blood pool subtraction technique, which makes it possible to visualize MI 6 h postinjection. Twenty-five patients with proven MI (16 anterior, 9 inferior) were imaged 10 minutes, 6 and 24 h after an injection of 110 MBq 111 In-labelled antimyosin antibodies, with a mean delay of two weeks after infarction. Three planar views were obtained each time. Using software which performs geometric registration, grey level normalization and subtraction of images, the blood pool image (obtained 10 minutes postinjection) was subtracted from the 6 hour image. The resulting image was the blood pool corrected 6 h image. The 24 h images and the blood pool corrected 6 h images were interpreted blindly and the number of correct, incorrect and indeterminate MI localizations were tabulated. The number of correct localizations was 19/25 for the standard 24 h images and 22/25 for the blood pool corrected 6 h images. With this blood pool subtraction method it was possible to visualize MI 6 h postinjection. Theoretically, this method could be applied six hours after myocardial infarction.

Antibodies, Monoclonal↗
PubMed1994

Hemorrhage complicating YAG laser feeder vessel coagulation of cornea vascularization.

A neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used in the thermal mode to coagulate blood vessels in a patient with a vascularized corneal leukoma in an attempt to reduce neovascularization before penetrating keratoplasty. Occlusion of the feeder artery at the periphery was followed by a large stromal hemorrhage. A successful keratoplasty was performed 2 days later.

Adult↗
PubMed1994

Absence of residual effects after physiological stimulation of the visual and motor cortex: an [15O]-H2O PET study in humans.

Cognitive experiments using positron emission tomography (PET) with [15O]-H2O require multiple scans done at 10 to 12 min intervals. Momose and colleagues reported that regional cerebral blood flow changes in response to visual stimulation do not return to baseline even 15 min after the stimulation. If confirmed, this fact would have important implications for the design and interpretation of PET cognitive studies. The purpose of this study was to determine the temporal course of residual effects following visual and motor stimulation. Six healthy volunteers undertook six scans each. Two scans were done to establish a baseline, one to observe the task induced activation, and three scans to investigate the residual effects at varying intervals after the task. The data were analysed using both statistical parametric mapping and a region of interest analysis. The visual and motor task produced robust activations bilaterally in the occipital cortex and in the contralateral primary motor cortex. There was no evidence for a statistically significant residue effect at any of the three intervals studied (30 s, 3 and 6 min). Our results refute the findings of Momose and colleagues and suggest that the 10-min interscan interval is more than adequate to re-establish a resting baseline.

Adult↗
PubMed1994

Skin fibroblast activity in pretibial myxoedema and the effect of octreotide (Sandostatin) in vitro.

The accumulation of glycosaminoglycans in the skin in pretibial myxoedema appears to be a response by local fibroblasts to a stimulating factor in the patient's serum, but the identity of the factor, its ability to stimulate skin fibroblasts as opposed to cultured thyroid cells, and the specificity of its effect to pretibial skin fibroblasts, are all controversial. We have studied fibroblasts cultured from the lesional skin of two women with pretibial myxoedema, and compared their proliferation and secretion of glycosaminoglycans with those of fibroblasts from the patients' forearms and from the forearm skin of two normal subjects. We found that in the presence of the patients' sera all six lines of fibroblasts secreted more glycosaminoglycans [205 +/- 21% (SD)] than with normal human sera (147 +/- 19%), or fetal calf serum (100%). Fibroblast proliferation showed the same pattern of differences: patients' sera 142 +/- 22%; normal human sera 116 +/- 9%, and fetal calf serum 100%. These experiments confirm the presence of a serum factor in pretibial myxoedema which is capable of stimulating the activity of skin fibroblasts in vitro, and show that its effects are not restricted to fibroblasts from pretibial skin or to those grown from the skin of the patients. Proliferation of normal fibroblasts cultured in medium supplemented with fetal calf serum was reduced by Sandostatin (octreotide), but it failed to inhibit their secretion of glycosaminoglycans. In contrast, secretion of glycosaminoglycans by a patient's pretibial skin fibroblasts was almost completely inhibited by 1 mM minoxidil. In the presence of patients' sera Sandostatin (0.1-10 micrograms/ml) reduced secretion of glycosaminoglycans by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Cardiovascular risk factors in South Australians with diabetes.

This study ascertained the prevalence of diabetes and compared the prevalence of cardiovascular risk factors among people with and without diabetes. Data were collected as part of the South Australian Health Omnibus Survey which involved a representative population sample of 6398 adults in metropolitan and country South Australia who were interviewed in their own homes. The self-reported prevalence of diabetes was found to be 3 per cent overall. This varied from approximately 1 per cent in the 15- to 39-year age group to 10.5 per cent in people aged over 80 years. Those with diabetes had a higher prevalence of cardiovascular risk factors than those without diabetes. There is a need for improved vigilance with people who have diabetes and interventions to modify the risk factors associated with cardiovascular disease.

Adolescent↗
PubMed1994

Characterization of a rabbit cationic protein (CAP18) with lipopolysaccharide-inhibitory activity.

Cationic antibacterial proteins (CAP) were purified from rabbit granulocytes, and the effects of CAP on lipopolysaccharide (LPS)-induced tissue factor generation by murine peritoneal macrophages and human blood monocytes were studied. CAP were purified from rabbit peritoneal leukocytes by using as an assay the agglutination of erythrocytes coated with Re-LPS. Two proteins with CAP activity, CAP18 (18 kDa) and CAP7 (7 kDa), were isolated by acid extraction, ethanol precipitation, affinity chromatography, gel filtration, and reverse-phase high-pressure liquid chromatography. On the basis of protein sequencing, CAP7 was identified as the C-terminal fragment of CAP18, designated CAP18(106-142). Various forms of LPS (S-LPS, Re-LPS, and lipid A) activate murine macrophages and human blood monocytes to generate tissue factor (tissue thromboplastin). Incubation of LPS for 18 h with partially purified CAP (heparin-Sepharose fraction) inhibited the capacity of LPS to induce tissue factor; however, purified CAP18 inhibited about 75% of the activity of S-LPS after 1 h of incubation. CAP more effectively inhibited S-LPS than Re-LPS or lipid A. Synthetic CAP18(106-142) inhibited LPS-induced tissue factor generation by murine macrophages. CAP18(106-142) has greater LPS-binding and LPS-neutralizing activities than CAP18. We hypothesize that CAP18 and the derivative peptide, CAP18(106-142), bind to LPS and alter the capacity of LPS to initiate disseminated intravascular coagulation. In this regard, CAP may have therapeutic potential for sepsis and endotoxin shock.

Amino Acid Sequence↗
PubMed1994

Nitric oxide synthase inhibition attenuates hypoglycemic cerebral hyperemia in piglets.

We tested the hypothesis that nitric oxide (NO) mediates hypoglycemia-induced cerebral vasodilation in piglets. Piglets (1-2 wk old) were made hypoglycemic with insulin (200 U/kg i.v.) with and without an NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg i.v.). Electroencephalogram (EEG), cerebral O2 consumption (CMRO2), and cerebral blood flow (CBF) were measured before L-NAME and insulin and for 180 min after insulin. Hypoglycemia led to isoelectric EEG earlier after L-NAME (87 +/- 8 min) than without L-NAME pretreatment (132 +/- 13 min). CBF increased in all brain regions during hypoglycemia at the onset of isoelectric EEG and was associated with increased CMRO2.L-NAME prevented the increase in CMRO2 and attenuated vasodilation in forebrain (154 +/- 37 vs. 400 +/- 60%), cerebellum (251 +/- 52 vs. 386 +/- 52%), and cortical gray matter (183 +/- 47 vs. 524 +/- 93%) but had no effect on CBF responses in brain stem, thalamus, caudate, or hippocampus. We conclude that NO or a NO-containing compound mediates cerebral vasodilation induced by profound insulin-hypoglycemia in piglets and that this vasodilation plays an important role in the adaptation of immature brain to hypoglycemia.

Amino Acid Oxidoreductases↗
PubMed1994

Utilization of dipeptides by the caprine mammary gland for milk protein synthesis.

Specific use by the mammary gland in vivo of amino acids (AA) of peptide origin has been demonstrated in lactating dairy goats using a dual-labeled tracer technique involving close-arterial (external pudic artery, EPA) infusion of 13C-labeled dipeptides. The extent of utilization does not appear to differ for glycyl-L-[1-13C]phenylalanine and glycyl-L-[1-13C]leucine, perhaps indicative of a common mechanism by which AA are incorporated from peptide into milk protein. [1-13C]phenyl-alanine of peptide origin appears to be concentrated within the red blood cell, suggesting a role for the erythrocyte in peptide metabolism in vivo. In conclusion, it appears that the lactating mammary gland of goats has the ability to utilize AA of peptide origin for milk protein synthesis, and while the mechanism by which [1-13C]AA are incorporated into milk protein is not clear, it may involve peptide hydrolysis by either mammary cell surface or red blood cell hydrolases followed by uptake of liberated AA by the mammary gland.

Amino Acids↗
PubMed1994

The role of protein kinase-C alpha in the activation of particulate guanylate cyclase by 1 alpha,25-dihydroxyvitamin D3 in CaCo-2 cells.

Recent studies have implicated protein kinase-C (PKC) in the regulation of guanylate cyclase in several cell types. In view of prior experiments by our laboratory which have demonstrated that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] can activate PKC in CaCo-2 cells, it was of interest to determine whether this secosteroid influenced particulate guanylate cyclase and, if so, to determine which isoforms of PKC were involved. To address these issues, CaCo-2 cells were treated with 1 alpha,25-(OH)2D3 or other agents (see below), and crude membranes prepared from these cells were assayed for guanylate cyclase activity. In several experiments, agents were added directly to isolated membranes, and guanylate cyclase activity was then assayed. These studies demonstrated that 1) the addition of 1 alpha,25-(OH)2D3 or 12-O-tetradecanoyl phorbol 13-acetate (TPA), a known activator of PKC, to intact CaCo-2 cells stimulated particulate guanylate cyclase activity in a time- and concentration-dependent manner; 2) these agents induced the translocation of PKC alpha, but not PKC zeta, from the cytosolic to the membrane fraction of these cells; 3) preincubation of cells with staurosporine (50 nM), a PKC inhibitor, or U73122 (10 microM), an inhibitor of phospholipase-C-dependent processes, significantly reduced (P < 0.05) the stimulatory effect of 1 alpha,25-(OH)2D3 (3 nM) on guanylate cyclase; 4) preincubation of isolated membranes with TPA, calcium, and Mg(2+)-ATP increased guanylate cyclase activity, an affect that was augmented by purified rat brain PKC and inhibited by the PKC inhibitor peptide, PKC-(19-36); and 5) selective down-regulation of PKC alpha by treatment of cells with TPA (200 nM) for 24 h concomitantly abolished the activation of guanylate cyclase by 1 alpha,25-(OH)2D3. Taken together, these studies demonstrate that 1 alpha,25-(OH)2D3 activates particulate guanylate cyclase at least in part via a PKC alpha-dependent mechanism.

Bacterial Toxins↗