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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle.

Nitric oxide (NO) is a pluripotent molecule that can be secreted by skeletal muscle through the activity of the neuronal constitutive isoform of NO synthase. To determine whether skeletal muscle and diaphragm might also express the macrophage-inducible form of NO synthase (iNOS) during provocative states, we examined tissue from mice at serial times after intravenous administration of Escherichia coli endotoxin. In these studies, iNOS mRNA was strongly expressed in the diaphragm and skeletal muscle of mice 4 h after intravenous endotoxin and was significantly diminished by 8 h after challenge. Induction of iNOS mRNA was followed by expression of iNOS immunoreactive protein on Western immunoblots. Increased iNOS activity was demonstrated by conversion of arginine to citrulline. Immunochemical analysis of diaphragmatic explants exposed to endotoxin in vitro revealed specific iNOS staining in myocytes, in addition to macrophages and endothelium. These results may be important in understanding the pathogenesis of respiratory pump failure during septic shock, as well as skeletal muscle injury during inflammation or metabolic stress.

Animals↗
PubMed1996

Regulation of mitogen-activated protein kinase in the pars tuberalis of the ovine pituitary: interactions between melatonin, insulin-like growth factor-1, and forskolin.

The pars tuberalis (PT) of the anterior pituitary is notable for the expression of levels of melatonin receptors that consistently exceed those in all other tissues in mammals. For this reason and because of its anatomical position, it has been suggested that the PT may play a role in seasonal reproductive responsiveness. However, no data have been forthcoming on the nature of the melatonin-responsive cells in this tissue or on the interaction of melatonin with other hormonal signals in the control of PT cells. A number of recent studies have reported that the tubero-infundibular region of the pituitary in several species contains binding sites for insulin-like growth factor-1 (IGF-1). The present study, therefore, sought to address the question of whether functional receptors for IGF-1 exist in the ovine PT (oPT). Primary cultures of cells from the oPT contained a widespread distribution of cells staining positively with a monoclonal antibody to the human IGF-1 receptor, with the strongest staining occurring over the small phase-bright cells that predominate in this culture system and are thought to constitute the melatonin-responsive cell type. As a functional assay for responsiveness to IGF-1, primary cultures of oPT cells were assayed for activation of mitogen-activated protein kinase (MAPK) using a previously validated phosphotransferase assay. Cytosolic extracts from PT cells treated with IGF-1 (100 pM-10 nM) caused a dose-dependent increase in the rate of phosphorylation of myelin basic protein; in contrast, treatment with melatonin had no significant effect on myelin basic protein phosphorylation. Immunostaining of Western blots of PT cell extracts with a pan-extracellular regulated kinase antibody demonstrated that both p42 and p44 MAPK are strongly expressed in this tissue. To confirm that the effects observed in the cytosol assay were indeed attributable to increased activation of p42/p44, gel renaturation assays of protein kinase activity were performed. These experiments revealed that IGF-1 (10 nM) and forskolin (1 microM) were both potent activators of 42- and 44-kDa moeities; however, neither of these agents had any significant effect on the phosphotransferase activity associated with several other higher molecular weight kinases also detected by the gel-renaturation assay procedure. Melatonin (10 nm) was consistently found to be a highly potent inhibitor of the activation of MAPK induced by forskolin; in contrast, melatonin did not inhibit the activation of MAPK induced by IGF-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

Changes in scores on the profile of mood states following a single bout of physical activity: heart rate and changes in affect.

28 college age students participating in a weight lifting class exhibited significant decreases in negative affect and increases in positive affect. Changes in affect were correlated with average exercise heart rates. Higher heart rates were correlated with reductions in negative affect and increases in positive affect. Correlations of .37 and .40 suggest that, in accordance with earlier studies, exercise intensity may be indirectly related to exercise.

Adult↗
PubMed1995

5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity.

The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pKI 8.0) and 5-HT2B receptors (pA2 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pKI < 6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pKB 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

Administration, Oral↗
PubMed1995

Chicken beta B1 crystallin: gene sequence and evidence for functional conservation of promoter activity between chicken and mouse.

The complete sequence was determined for the chicken beta B1-crystallin gene and 2.2 kbp of its 5' flanking region; the chicken gene was then compared to its rat ortholog. Although both have a 5' non-coding exon followed by 5 protein coding exons, the chicken gene is only 2.2 kbp while the rat gene is 13.6 kpb due to longer introns. The coding exons of the chicken beta B1-crystallin gene, like those of the rat and other beta-crystallin genes, each correspond to one of the four 'Greek key' motifs of the encoded protein. The only obvious similarity between the 5' flanking sequences of the chicken and rat beta B1-crystallin gene is associated with the TATA box. A CR1 repetitive element is present at positions -559 to -730 of the chicken beta B1-crystallin gene. In vivo footprinting using dimethyl sulfate/ligation mediated PCR showed that the PL-1 (-116/-102), PL-2 (-90/-76), OL-2 (-75/-68) and OL-1 (-125/-118) control elements identified previously (Roth et al. (1991) Mol. Cell. Biol. 11, 1488-1499) bind proteins within the chromatin of cultured embryonic chicken lens cells. Both -2448/+30 and -434/+30 promoter fragments from the chicken beta B1-crystallin gene directed lens-specific CAT gene expression in a copy number and position independent manner in transgenic mice. These data indicate that the structure and lens-specific expression of this gene are highly conserved although, like other crystallin genes, the 5' flanking sequences have diverged appreciably during evolution.

Amino Acid Sequence↗
PubMed1995

Platinum anticancer drug binding to DNA detected by thickness-shear-mode acoustic wave sensor.

Nucleic acid has been attached to the electrodes of thickness-shear-mode acoustic wave devices to produce a biosensor for platinum-based drugs. The decreases in series resonant frequency for interactions of DNA with both cis- and transplatin are indicative of two distinct kinetic processes. The results of a kinetic analysis are interpreted in terms of nucleic acid binding of the hydrolysis products of the two drugs. Concentration-dependent decreases of series resonant frequency show that the limit of detection for the drugs is approximately 10(-7) M. Motional resistance changes for nucleic acid-drug interactions also convey information regarding the chemistry of the macromolecules at the interface.

Animals↗
PubMed1995

Progressive hippocampal loss of immunoreactive GLUT3, the neuron-specific glucose transporter, after global forebrain ischemia in the rat.

Brain damage after global forebrain ischemia is worsened by prior hyperglycemia and ameliorated by antecedent hypoglycemia. To assess whether GLUT3, the neuron specific glucose transporter and its mRNA, are affected by cerebral ischemia, we investigated the hippocampal pattern of GLUT3 immunoreactivity and GLUT3 gene expression 1, 4 and 7 days after global forebrain ischemia in a rat 2-vessel occlusion model. We used a newly generated, specific, C-terminally directed polyclonal antiserum against GLUT3 to stain coronal frozen sections. Thionin staining and the microglial marker, OX42, indicated the extent of ischemic damage in hippocampus and correlated with GLUT3 loss. One day after ischemia, no significant change in hippocampal GLUT3 immunoreactivity was observed; by 4 days however, there was consistent and pronounced loss; and at 7 days the loss of GLUT3 staining was maximal. The greatest loss of GLUT3 staining was in the CA1 region, especially the strata oriens and radiatum of Ammon's horn. By contrast, GLUT3 staining was undiminished in the stratum lacunosum moleculare, in the mossy fibers of the lateral aspect of CA3 and in all but the inner-most portion of the molecular layer of the dentate gyrus, immediately adjacent to the granule cells. GLUT3 mRNA levels were not significantly altered at 24 hours and significantly declined at 4 and 7 days after ischemia in the CA1 pyramidal layer. These data are consistent with the pattern of neuronal loss and microglial activation in hippocampus. Loss of GLUT3 may affect the availability of glucose, and possibly the viability of ischemically damaged neurons.

Animals↗
PubMed1995

Selective coagulation necrosis of canine adventitia and media induces extracellular matrix accumulation without neointima formation.

Endothelial cell injury, the disruption of the internal elastic membrane and medial damage represent important stimuli for the development of a neointima. It is unclear whether selective adventitial and medial injury also induce neointima formation. Incremental argon laser energies (11.4-180 J/cm2) were applied to the external surface of dog femoral arteries to evaluate the vascular repair of acute adventitial or medial necrosis without injury of the intima. The animals were sacrificed either one hour after the initial procedure or after an 8 week follow up period for histologic examination. Acute, and mild to moderate necrosis of the arterial wall was found above 50 J/cm2. Ablation of the internal elastic membrane or mural thrombi was not detected. Eight weeks after photocoagulation with laser energies above 50 J/cm2, a significant increase in mean wall thickness of the media was observed. The medial thickening was characterised by an accumulation of extracellular matrix and a loss of smooth muscle cells. Necrosis of adventitia and media resulted in arterial wall thickening without neointima formation. It is concluded that, in dogs, an acute, selective injury of adventitia and media stimulates the production of extracellular matrix and not the proliferation of cells. Smooth muscle cell migration and subsequently neointima formation are induced by viable smooth muscle cells when blood-borne stimuli are available.

Analysis of Variance↗
PubMed1995

Computerized three-dimensional activation mapping study of spontaneous ventricular arrhythmias during acute myocardial ischemia in dogs. Evidence against macroreentrant mechanism.

This study was undertaken to investigate the activation patterns of spontaneous ventricular arrhythmias during acute myocardial ischemia in dogs. In 14 open-chest dogs, the left anterior descending coronary artery was occluded for 2 hours. Three-dimensional activation maps were derived from 240 bipolar sites by insertion of 60 plunge needle electrodes into both ventricles and the septum. Global ventricular activation sequences were displayed in five planes in 10 dogs, whereas the high density regional activation maps of the anterior wall were displayed in four layers in 4 dogs. Three-dimensional activation maps of 95 sinus beats, 82 premature ventricular complexes (PVCs), and 210 beats of ventricular tachycardia (VT) were analyzed. Sinus beats had a uniform activation pattern with total ventricular activation times measuring 42 +/- 4 ms and 67 +/- 8 ms during baseline and ischemia, respectively (P < .05). The PVCs and VTs originated from the subendocardial and intramural layers, and activation patterns invariably suggested focal excitation. Macroeentry was not operative because (1) the breakthrough sites were always remote from the latest activation areas; (2) there was no electrical activity bridging the gap between the termination of a beat and initiation of the subsequent beat; and (3) impulse conduction was not sufficiently delayed to reexcite the area of impulse origin even though functional conduction block was frequently present. In high-density regional activation maps, fragmented activity spanning the diastolic interval was never found. In conclusion, spontaneously occurring PVCs and VTs during acute myocardial ischemia in dogs display focal excitation with no evidence of macroreentry.

Animals↗
PubMed1995

The changing workload of a surgical unit with a vascular interest.

OBJECTIVES: To examine the changing relationship between general and vascular surgical workload on a vascular "firm", over a 6-year period. DESIGN: Retrospective review. SETTING: Leicester Royal Infirmary and Professorial Surgical Unit, U.K. 1987-1992. METHOD: Analysis of audit of all surgical admissions. Relation of vascular surgery to general surgery. RESULTS: There has been a slight decrease (5%) in the number of general surgical elective admissions. Overall, the number of general surgical admissions, both elective and emergency, show a slight increase of about 3%. In contrast the number of vascular admissions increased by 42%. Of the general surgical procedures carried out 75.9% were either minor or intermediate, whereas 92.5% of vascular procedures were coded as major or higher. There has been a three times increase in the number of carotid endarterectomies, a similar increase in the number of the femorodistal bypass grafts and a halving of the number of major amputations. There has also been a five times increase in the number of angioplasties carried out. CONCLUSIONS: Our figures show the progressive, rapid increase in vascular surgical workload, compared to general surgery, and the need for the continued expansion of vascular surgery as a speciality.

Abdominal Pain↗