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Biomedical subjects

M W Martin

Publications and source records attributed to M W Martin.

At least 19 recordsLinked to original sources
PubMed2001

Typical antipsychotics exhibit inverse agonist activity at rat dopamine D1-like receptors expressed in Sf9 cells.

The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, alpha-flupenthixol, fluphenazine and thioridizine were found to inhibit dopamine-dependent stimulation of adenylyl cyclase. However, these compounds were also found to inhibit adenylyl cyclase activity in the absence of agonist in Sf9 cells expressing dopamine D1-like receptors. Therefore, these nonselective dopamine receptor compounds displayed negative intrinsic or inverse agonist activity. None of the compounds tested were neutral antagonists.

Adenylyl Cyclases↗
PubMed2001

Sick sinus syndrome in nine West Highland white terriers.

Sick sinus syndrome is a clinical term used to describe the clinical signs of sinus node dysfunction. This paper describes the clinical data from nine West Highland white terriers, eight females and one male, in which a diagnosis of sick sinus syndrome was made. The most common clinical signs were episodic weakness and presyncope. Electrocardiographic findings included sinus bradycardia, sinus arrest with or without escape complexes, disturbances of atrioventricular conduction, paroxysmal supraventricular tachycardia, or some combination of these dysrhythmias. The main radiographic changes were mild right-sided cardiomegaly in five cases, and a slight increase in bronchial and interstitial markings in four, but there was no evidence of congestive heart failure in any of the dogs. Echocardiography revealed mild to moderate mitral endocardiosis in three cases with no other significant abnormalities. The dogs' responses to parenteral atropine were variable and were not necessarily related to their response to oral anticholinergic agents. Five of the dogs were initially treated with propantheline bromide, but in only two of them were the clinical signs controlled in the long term. Six of the dogs were successfully treated by the implantation of a transvenous pacemaker.

Animals↗
PubMed2000

Characterization of (125)I-IABN, a novel azabicyclononane benzamide selective for D2-like dopamine receptors.

The properties of an (125)I-labeled structural analog of 2, 3-dimethoxy-N-[9-(4-fluorobenzyl)-9-azabicyclo[3.3. 1]nonan-3beta-yl]benzamide (MABN), (125)I-IABN, are described. (125)I-IABN was developed as a high-affinity radioligand selective for the D2-like (D2, D3, and D4) dopamine receptor subtypes. (125)I-IABN binds with picomolar affinity and nonselectively to rat D2 and D3 dopamine receptors expressed in Sf9 and HEK 293 cells. (125)I-IABN binds with 7- to 25-fold lower affinity to human D4.4 dopamine receptors expressed in HEK 293 cells. Dissociation constants (Kd) calculated from kinetic experiments were in agreement with equilibrium Kd values obtained from saturation binding studies. Saturation plots of the binding of (125)I-IABN with rat caudate membrane preparations were monophasic and exhibited low nonspecific binding. The pharmacologic profile of the binding of (125)I-IABN to rat caudate was consistent with a D2-like receptor, suggesting that the ligand binds primarily to D2 dopamine receptors. In addition, IABN was found to bind with low affinity to D1 dopamine receptors, as well as to the sigma1 and sigma2 receptor subtypes. Quantitative autoradiographic studies using rat brain slices indicate that (125)I-IABN selectively labels the striatum and the olfactory tubercle area, which is consistent with the labeling of D2-like receptors. IABN blocks dopamine-dependent inhibition of adenylyl cyclase activity at D2 or D4.4 receptors expressed in HEK cells. Therefore, (125)I-IABN appears to be a high-affinity, selective antagonist at D2-like dopamine receptors. Finally, a unique property of the azabicyclononane benzamide (125)I-IABN compared to previously studied substituted benzamides is that the binding of this radioligand is not effected by variations in Na(+) concentration.

Animals↗
PubMed2000

Age of Neoproterozoic bilatarian body and trace fossils, White Sea, Russia: implications for metazoan evolution.

A uranium-lead zircon age for a volcanic ash interstratified with fossil-bearing, shallow marine siliciclastic rocks in the Zimnie Gory section of the White Sea region indicates that a diverse assemblage of body and trace fossils occurred before 555.3 +/- 0.3 million years ago. This age is a minimum for the oldest well-documented triploblastic bilaterian Kimberella. It also makes co-occurring trace fossils the oldest that are reliably dated. This determination of age implies that there is no simple relation between Ediacaran diversity and the carbon isotopic composition of Neoproterozoic seawater.

Animals↗
PubMed2000

The association between severity of sanction imposed for violation of tobacco policy and high school dropout rates.

This investigation explored the association between severity of sanctions imposed on students resulting from tobacco policy violation and the event dropout rate in South Carolina public high schools. The study employed a cross-sectional design (n = 132). Surveys were mailed to school principals to assess tobacco policy and sanctions for violation. Severe sanctions were categorized as those resulting in the student being denied onsite instruction, such as out-of-school suspension or expulsion. General linear regression models adjusting for SES, ethnicity, and rural/urban status, tested for an association between event dropout rate and severity of sanction imposed. The mean dropout rate in 1998 for high schools in South Carolina was 2.58% (+1.74). Suspension at first violation and expulsion were associated with lower dropout rates. Suspension at second violation was not associated with dropout behavior while suspension at third violation was associated with higher dropout rates. Results from the study provide preliminary evidence that severe sanctions imposed for violation of tobacco policy may help reduce high school dropout rates.

Adolescent↗
PubMed1999

Chronic pulmonary disease in West Highland white terriers.

This paper describes the clinical features, and diagnostic findings of a chronic respiratory condition in 29 West Highland white terriers. Typically, the dogs were coughing chronically, had dyspnoea and tachypnoea of varying severity, and had deteriorated progressively over months to years. The mean (sem) survival time in months from the clinical signs being first noted by the owners was 17.9 (2.3). Most cases had a combination of respiratory signs, but coughing was the predominant sign in 18 cases. Inspiratory crackles were audible on chest auscultation in 28 cases, 10 of which were also wheezing. Rhonchi were the predominant sound in the remaining case. The main radiographic changes were mild to severe increased Interstitial markings in all cases, with additional bronchial markings in 14 of the dogs. Right-sided cardiomegaly (cor pulmonale) was recorded in 15. Bronchoscopic findings in 17 of the dogs were either normal or involved a mild airway mucoid reaction in eight. Chronic mucosal changes were observed in eight, but in two this finding was equivocal. Dynamic changes to the lumen of the airway were present in seven cases. No significant haematological or biochemical changes could be detected in 20 cases, but four cases were hypercholestrolaemic. A histopathological assessment of four cases revealed alveolar septal fibrosis to be the predominant change. Prednisolone, with or without bronchodilators, was the most commonly used therapy, and the response was variable. The condition appears to be associated with significant pulmonary interstitial fibrosis of unknown aetiology and has clinical similarities to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in human beings.

Animals↗
PubMed1999

Secondary school tobacco policy and prevention curricula in South Carolina.

The primary purpose of this study was to describe tobacco control policy in secondary schools in South Carolina, and sanctions imposed on students for violation of these policies; and to explore potential associations between policies and sanctions. A secondary purpose was to explore the use of tobacco education curricula in the state. This study employed a cross-sectional design in which two surveys were mailed to all secondary schools in South Carolina (n = 437): the School Principal Questionnaire (SPQ) and the Lead Health Education Teacher Questionnaire (LHETQ). The SPQ elicited information about tobacco control policies and the sanctions imposed on violators of such policies. The LHETQ was sent to lead health education teachers to elicit information about use of packaged curricula addressing tobacco use and prevention. Over 95% of respondents reported having school policies that prohibited use of tobacco inside buildings, and explicitly prohibited the use of cigarettes for students anywhere on school grounds. Sanctions imposed for violation of tobacco policy were severe. For a second offense, nearly 68% of students were suspended out-of-school or expelled, and for a third offense, almost 28% of students were expelled. There is some evidence to suggest that more stringent policies were associated with more severe sanctions. Cessation from tobacco programs were rarely used as a sanction, and in fact, tobacco education curricula were rarely used by health education teachers. In South Carolina secondary schools, tobacco policies are prevalent. Student violators of such policies are punished by means that potentially detract from their educational experience (e.g., out-of-school suspension, expulsion). It is recommended that school administrators and school health education teachers implement tobacco cessation programs as part of appropriate sanctions for violations of school tobacco use policy.

Adolescent↗
PubMed1995

Inhibition by cromoglycate and some flavonoids of nucleoside diphosphate kinase and of exocytosis from permeabilized mast cells.

1. The anti-allergic compound, cromoglycate, is reported to possess affinity for, and to suppress the autophosphorylation of a 72kDa protein having the sequence of nucleoside diphosphate kinase (NDPK). 2. We have tested the ability of cromoglycate, and a panel of ten structurally related flavonoids of plant origin, to inhibit the NDPK reaction and the exocytotic process of permeabilized mast cells. The conditions of permeabilization (use of an isotonic medium based on sodium glutamate) were selected to ensure that NDPK activity would be an essential component in the induction of Ca(2+)-induced exocytosis in which ATP is required for generation of GTP. For comparison, we also measured the inhibition of exocytosis induced by GTP-gamma-S; this proceeds in the absence of ATP and bypasses the need for NDPK activity. 3. We found that cromoglycate does not discriminate between Ca2+ and GTP-gamma-S-induced exocytosis and is a poor inhibitor of NDPK activity. Concentrations in the millimolar range are required for inhibition of all these functions. By comparison, many of the flavonoids are effective at concentrations in the micromolar range. 4. While we were unable to discern any systematic relationships between their ability to inhibit the three functions, two compounds, quercetin and genistein, inhibit Ca(2+)-induced, but not GTP-gamma-S-induced exocytosis. Inhibition of the late stages of the stimulus-response pathway in mast cells by these compounds is therefore likely to be due to inhibition of NDPK and the consequent failure to generate GTP.

Animals↗
PubMed1991

Modulation of benzodiazepine agonist and inverse-agonist receptor binding by GABA during ethanol withdrawal.

1. The present study examined the capacity of GABA to modulate flunitrazepam and Ro15-4513 binding to putative GABAA receptors. Binding was measured in distinct brain regions both before and during selected periods of withdrawal from ethanol. 2. Rats were fed a nutritionally complete liquid ethanol (4.5% w/v) diet for 4 days and at various times after the last dose of ethanol (0, 12, 24, & 72 hr), rats were sacrificed and extensively washed brain membrane fractions were prepared. 3. Competitive inhibition of 3H-flunitrazepam binding by either flunitrazepam or Ro15-4513 (10(-10)M to 10(-7)M) was performed in the absence and presence of GABA (10(-5)M). In the presence of GABA, the apparent affinity for flunitrazepam was increased approximately 1.7 fold and the apparent affinity for Ro15-4513 was decreased by 1.7 fold. 4. No alteration in the capacity of GABA to modulate flunitrazepam or Ro15-4513 affinity (e.g. GABA-shift) was observed in cortical membrane preparations either 12 or 72 hr following ethanol cessation. 5. Further, no changes in GABA-modulation of flunitrazepam binding was evident 0, 12, 24, or 72 hr after the last ethanol dose in membranes prepared from cortex, hippocampus or cerebellum. 6. Therefore, results from the present study indicate that the capacity of GABA to modulate receptor affinity for benzodiazepine agonists and inverse-agonists in rat cortex, hippocampus or cerebellum is not altered during withdrawal from chronic ethanol.

Animals↗
PubMed1991

A survey of cattle for antibodies against bluetongue and epizootic hemorrhagic disease of deer viruses in British Columbia and southwestern Alberta in 1987.

In 1987 a serological survey of cattle for antibodies (Ab) to bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) was undertaken in British Columbia and southwestern Alberta after infection with the viruses was diagnosed in wild and domestic ruminants in the Okanagan Valley. Of 4610 cattle tested, five had Ab only to BTV, 125 had antibodies only to EHDV and 16 had Ab to both viruses. The Ab were identified as specific for BTV type 11 (BT-11) or EHDV type 2 (EHDV-2). All but one of the seropositive cattle originated in the Okanagan Valley of British Columbia. The remaining one seropositive animal which had Ab to EHDV-2 was pastured with a bull purchased from the Okanagan Valley.

Alberta↗
PubMed1990

Biochemical properties of a P2Y-purinergic receptor.

The turkey erythrocyte has substantial value as a model for the study of a receptor that exhibits pharmacological properties very similar to those delineated in mammalian tissues for a P2Y-purinergic receptor. The G protein-dependent coupling of this receptor to phospholipase C can be studied in detail, and the availability of an abundant source of homogeneous cells from which highly purified plasma membranes can be prepared, has led to the development of a radiolabeled, reversibly binding radioligand for a P2Y-purinergic receptor and a photoaffinity covalent radiolabel for this receptor. This source of plasma membranes highly enriched in P2Y-purinergic receptors should also serve as a rich starting material for the eventual purification and structural characterization of this important signaling protein.

Adenosine Triphosphate↗
PubMed1989

Agonist-induced desensitization of a P2Y-purinergic receptor-regulated phospholipase C.

A guanine nucleotide-dependent P2Y-purinergic receptor-regulated phospholipase C activity of turkey erythrocyte membranes has been characterized in detail previously (Boyer, J. L., Downes, C. P., and Harden, T. K. (1989) J. Biol. Chem. 264, 884-890). The occurrence of agonist-induced desensitization of this receptor-regulated phospholipase C is now described. Preincubation of turkey erythrocytes with the P2Y-purinergic receptor agonist ADP beta S resulted in a marked loss of capacity of ADP beta S plus GTP to stimulate phospholipase C in membranes derived from these cells. The half-time of occurrence of desensitization was 0.5-2.0 min, and within 10 min responsiveness had reached a new quasi-steady state level representing 40-55% of control. Transfer of agonist-preincubated erythrocytes to agonist-free medium resulted in recovery of agonist plus GTP responsiveness of the membrane phospholipase C activity to control levels with a half-time of 10-20 min. The change in ADP beta S plus GTP responsiveness occurred as a loss of maximal effect with little or no change in the apparent affinity of agonist for stimulation of inositol phosphate production. Induction of desensitization occurred with an agonist-specificity that followed that expected of a P2Y-purinergic receptor. Neither the rate of activation nor the final phospholipase C activity attained in the presence of GTP gamma S alone was altered in membranes from cells preincubated with ADP beta S for 15 min. AlF-4-stimulated inositol phosphate production was also not modified in membranes from agonist-preincubated erythrocytes. In contrast, the capacity of ADP beta S to increase the rate of activation of phospholipase C by GTP gamma S was markedly reduced in membranes from agonist-preincubated cells. The amount of 3H-radioactivity in phosphoinositides, as well as the ratio of labeling among the phosphoinositides, was not altered by incubation of erythrocytes with a P2Y-purinergic receptor agonist. Taken together these data suggest that P2Y-purinergic receptor agonist-induced desensitization occurs as a consequence of a modification at the level of the receptor or at the level of receptor-guanine nucleotide regulatory protein (G-protein) coupling with no change occurring in the capacity of the G-protein to activate phospholipase C.

Adenosine Diphosphate↗
PubMed1988

Interaction of beta-adrenergic receptors with the inhibitory guanine nucleotide-binding protein of adenylate cyclase in membranes prepared from cyc- S49 lymphoma cells.

beta-Adrenergic receptors on membranes prepared from L6 myoblasts, wild-type S49 lymphoma cells, and an adenylate cyclase-deficient variant (cyc-) of S49 lymphoma cells bind the agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) with high affinity. In each case the agonist [3H]HBI is associated with a larger complex than is the antagonist [125I]iodopindolol, and the binding of [3H]HBI can be inhibited by GTP. These observations suggest that there is an agonist-dependent association of the receptor with a guanine nucleotide-binding protein. The goal of the present experiments was to investigate the possibility that an interaction of beta-adrenergic receptors with the inhibitory guanine nucleotide-binding protein of adenylate cyclase was responsible for these observations. Treatment of S49 cells with pertussis toxin decreased the extent of pertussis toxin-catalyzed [32P]ADP-ribosylation of a 41,000-dalton protein, measured in vitro, and decreased the inhibition of adenylate cyclase activity observed in the presence of somatostatin or analogues of GTP. Isoproterenol-stimulated adenylate cyclase activity was potentiated following treatment of wild-type S49 cells and L6 myoblasts with pertussis toxin. Although the ability of receptors on membranes prepared from L6 myoblasts to bind the agonist [3H]HBI was not affected by treatment of cells with pertussis toxin, treatment of cyc- S49 cells with pertussis toxin markedly decreased the ability of receptors to bind [3H]HBI. The observed inhibition of the binding of the agonist [3H]HBI to beta-adrenergic receptors on membranes prepared from cyc- S49 cells after treatment with pertussis toxin could be explained by an interaction between beta-adrenergic receptors and the inhibitory guanine nucleotide-binding protein. Such an interaction may represent a mechanism through which stimulation of the activity of adenylate cyclase by beta-adrenergic receptors can be regulated or through which beta-adrenergic receptors can affect the activity of cyclic AMP-independent cellular processes.

Adenosine Diphosphate Ribose↗
PubMed1988

Adenosine inhibition of the hormonal response in the Sertoli cell is reversed by pertussis toxin.

The rat Sertoli cell in culture expresses A1 inhibitory adenosine receptors. In this study, we have used pertussis toxin as a tool to characterize the mechanism of action of adenosine on these cells. Cells were preincubated for 18-24 h with pertussis toxin, and the responses to FSH and to the adenosine analog phenylisopropyladenosine (PIA) were measured by assaying cAMP accumulation. The effect of toxin on adenosine receptors was also evaluated by measuring binding of the adenosine agonist cyclohexyladenosine (CHA). The total number of specific CHA-binding sites was reduced 60-70% in membranes prepared from cells cultured for 24 h in the presence of pertussis toxin; the binding sites remaining after treatment displayed no apparent change in affinity for [3H]CHA. The effect of guanine nucleotides on CHA binding was also reduced after toxin pretreatment, but not abolished. PIA inhibited FSH-stimulated cAMP accumulation by 70-80%. Maximal inhibition was observed at a concentration of 10 nM PIA, and the ED50 of the dose-response curve was 1 nM. Pretreatment of the Sertoli cell with pertussis toxin completely blocked the PIA inhibition. The pertussis toxin effect was time and dose dependent. Reversal of the inhibition was observed after 6 h of treatment with a maximal dose of toxin (100 ng/ml). The dose of toxin producing a half-maximal effect was 10-30 ng/ml. In addition to this blockade of purine nucleotide inhibitory effects, exposure of the Sertoli cell to pertussis toxin concentrations ranging from 1-400 ng/ml consistently led to a potentiation of the FSH response measured as cAMP accumulation. In cell-free preparations (crude particulate fraction of the Sertoli cells, or sucrose gradient-purified plasma membranes), pertussis toxin catalyzed the incorporation of [32P]ADP ribose into a polypeptide with a molecular mass of 40-41 K. This peptide had electrophoretic mobility similar to that of a partially purified guanine nucleotide-binding protein (Gi). These data indicate that adenosine A1 inhibitory receptors are coupled to an inhibitory component (Gi) of adenylate cyclase. In the Sertoli cell, inhibitory and stimulatory signals interact in a bimodal regulation of adenylate cyclase and intracellular cAMP.

Adenosine↗
PubMed1987

Identification and purification from bovine brain of a guanine-nucleotide-binding protein distinct from Gs, Gi and Go.

A guanine-nucleotide-binding protein (G-protein) was purified from cholate extracts of bovine brain membranes by sequential DEAE-Sephacel, Ultrogel AcA-34, heptylamine-Sepharose and Sephadex G-150 chromatography. Guanosine 5'-[gamma-[35S]thio]triphosphate (GTP[35S])-binding activity copurified with a 25,000 Da peptide and a 35,000-36,000 Da protein doublet. Neither pertussis toxin nor cholera toxin catalysed the ADP-ribosylation of a protein associated with the GTP[35S]-binding activity. Photoaffinity labelling of the purified protein with 8-azido[gamma-32P]GTP indicated that the GTP-binding site resides on the 25,000 Da protein. The 35,000-36,000 Da protein doublet was electrophoretically indistinguishable from the beta-subunits of other GTP-binding proteins, and the 36,000 Da protein was recognized by antiserum to oligomeric Gt. The purified protein specifically bound 17.2 nmol of GTP[35S]/mg of protein. The Kd of the binding site for radioligand was approx. 15 nM. The brain GTP-binding protein co-migrated during SDS/polyacrylamide-gel electrophoresis with a GTP-binding protein, named Gp, purified from human placenta [Evans, Brown, Fraser & Northup (1986) J. Biol. Chem. 261, 7052-7059], and cross-reacted with antiserum raised against the placental protein, but not with antiserum raised to brain Go. SDS/polyacrylamide-gel electrophoresis of the brain and placental GTP-binding proteins in the presence of Staphylococcus aureus V8 protease yielded identical peptide maps.

Animals↗