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Biomedical subjects

J F Martin

Publications and source records attributed to J F Martin.

At least 181 records · Page 10Linked to original sources
PubMed1990

The relationship between megakaryocyte nuclear DNA content and gene expression.

Megakaryocytes are a distinct population of bone marrow cells that have the unique feature of increasing their DNA content without undergoing division. The biological effect of ploidy distribution on gene expression, receptor expression and protein synthesis is still unknown. Using molecular hybridization techniques, we have started a systematic analysis of mRNA expression in megakaryocytes for a number of proteins involved in clot formation. These data will be related to ploidy. Platelets are the unnucleated product of megakaryocytes, having their protein content derived from the precursor cell. Therefore, the understanding of the molecular mechanisms regulating megakaryocyte biology and the consequent type and reactivity of platelets produced is of fundamental importance in both physiological and pathological conditions.

Blood Proteins↗
PubMed1990

The control of megakaryocyte ploidy and platelet production: biology and pathology.

Following experimental platelet destruction in animals, large platelets, which are more hemostatically active, are produced before any change in bone marrow megakaryocyte DNA content. When platelet production is stimulated by administration of i.v. vincristine in rats, megakaryocyte ploidy is increased, but mean platelet volume is unchanged. When platelet production and destruction are both stimulated by chronic hypoxia or administration of anti-platelet serum, mean platelet volume and megakaryocyte DNA content are both increased. Since platelet volume is determined primarily at thrombopoiesis, these results imply that mean platelet volume and megakaryocyte DNA content are under separate hormonal control. Therefore, it has been postulated that changes in mean platelet volume occur following changes in platelet production rate, whereas changes in megakaryocyte ploidy are associated with an increased rate of platelet production. In myocardial infarction, platelets have increased mean volume and reduced bleeding time more than in controls. In addition, men with myocardial infarction have increased megakaryocyte size and increased DNA content when compared to controls. These changes are similar to those observed in rabbits following cholesterol feeding. If megakaryocyte polyploidy and mean platelet volume are under separate hormonal control, this suggests that in myocardial infarction, both hormones are active--one stimulating an increased platelet size, the other stimulating the increased megakaryocyte DNA content. In contrast, patients with lymphoma exhibiting a secondary thrombocytosis have no change in mean platelet volume. However, these subjects also have larger bone marrow megakaryocytes when compared to controls. The relation between megakaryocyte size and ploidy implies that the DNA content of these cells is increased in lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Fast imaging.

Gradient-echo pulse sequences are a valuable adjunct to the standard spin-echo sequences used for MR imaging of the brain and spine. Gradient-echo techniques enhance the signal of flowing fluids and increase the conspicuity of vascular lesions. They also increase the sensitivity of MR for chronic hemorrhage and calcification. Finally, steady-state techniques produce a myelographic effect to help evaluate degenerative diseases of the spine.

Arterial Occlusive Diseases↗
PubMed1990

Cloning and characterization of a gene of Streptomyces griseus that increases production of extracellular enzymes in several species of Streptomyces.

A 7.2 kb Bg/II restriction fragment, which increases the production of several extracellular enzymes, including alkaline phosphatase, amylase, protease, lipase and beta-galactosidase, was cloned in Streptomyces lividans from the DNA of S. griseus ATCC 10137. This gene (named saf) showed a positive gene dosage effect on production of extracellular enzymes. When the saf gene was introduced into cells in high copy numbers it delayed the formation of pigments and spores in S. lividans and also retarded actinorhodin production in Streptomyces coelicolor. The saf gene hybridized with specific bands in the DNA of several Streptomyces strains tested. A 1 kb fragment containing the saf gene was sequenced and contains an open reading frame (ORF) of 306 nucleotides which encodes a polypeptide of Mr 10,500. This ORF is contained within a fragment of 432 bp which retained activity in Streptomyces. A fragment with promoter activity is present upstream of the saf reading frame. The predicted Saf polypeptide has a strong positive charge, and does not show a typical amino acid composition for a membrane protein, and contains a DNA-binding domain similar to those found in several regulatory proteins.

Alkaline Phosphatase↗
PubMed1990

Endothelin and PDGF do not stimulate peripheral blood monocyte chemotaxis, adhesion to endothelium, and superoxide production.

Endothelin is a potent vasoconstrictory endothelial-derived peptide which can induce smooth muscle proliferation and therefore may be proatherogenic. Platelet-derived growth factor is also a potent mitogenic vasoconstrictory protein which is proatherogenic. We report that neither endothelin nor PDGF stimulate superoxide production, or monocyte adhesion to porcine aortic endothelial cell monolayers; additionally endothelin is not a chemoattractant factor for monocytes. If endothelin and PDGF are important in atherogenesis it is unlikely that a monocyte response to these mediators is involved.

Adult↗
PubMed1990

Differences in bleeding time, aspirin sensitivity and adrenaline between acute myocardial infarction and unstable angina.

STUDY OBJECTIVE - The objective was to measure platelet function in vivo (as cutaneous bleeding time), the role of catecholamines, and the effect of inhibiting thromboxane synthesis on bleeding time, in patients with myocardial infarction, unstable angina, and non-cardiac chest pain. DESIGN - Haemotological variables and plasma catecholamines were compared between patient diagnostic groups using the Kruskal-Wallis test, Conover's multiple comparison test, and Wilcoxon paired rank sum test. PATIENTS - 49 patients entered the study and 45 were assigned to three groups: myocardial infarction (n = 26), unstable angina (n = 9), and non-coronary chest pain (control) (n = 10). There were no significant differences between groups for age or sex. Patients with myocardial infarction smoked more than others. MEASUREMENTS and RESULTS - Compared to the controls, bleeding time in patients with myocardial infarction was shortened, while in unstable angina it was normal. Plasma adrenaline and noradrenaline concentrations were higher in the myocardial infarction group than in the unstable angina and control groups, but were not correlated with bleeding time. Bleeding time was remeasured 2 h after ingestion of 300 mg aspirin and increased in all subjects, especially in those with myocardial infarction, but it remained significantly shorter in the infarct group than in the comparison groups. Plasma adrenaline was inversely correlated with the bleeding time after aspirin in the infarct group. CONCLUSIONS - The shortened bleeding time may be an indicator of an increased prethrombotic tendency present in patients with myocardial infarction but not in those with unstable angina. The effect appears to be mediated by both thromboxane A2 and adrenaline.

Aged↗
PubMed1990

Supersensitivity to vasoconstrictor action of serotonin precedes the development of atheroma-like lesions in the rabbit.

We have studied the relationship between the early morphological changes and arterial responsiveness to vasoactive agents in a new animal model that is proposed to mimic the events of early human atherosclerosis. Atheroma-like lesions were produced by positioning a hollow Silastic collar (referred to as a cuff) around the common carotid arteries of rabbits. Following a period of either 48 h or 1, 2, or 4 weeks after surgery, vessels from both cuffed and sham-operated animals were removed, and vascular reactivity to cumulative concentrations of agonists were studied in isolated rings in organ baths. The contralateral arteries were perfused and fixed, studied by light microscopy, and the degree of intimal thickening was quantified by computer-assisted morphometric analysis and expressed as changes in the ratios of the cross-sectional areas of the intima and media in each artery. At 48 h, rings prepared from cuffed arteries were sixfold more sensitive to the contractile effects of serotonin (5-HT) than the corresponding controls. Histologically, such vessels showed some perivascular inflammation but no other morphological abnormality. At 7 days, cuffed vessels were again sixfold more sensitive to 5-HT than controls, and showed a thickened intima with marked smooth muscle proliferation and some infiltration by monocytes. Intimal/medial cross-sectional area ratios remained elevated at 2 and 4 weeks, but the supersensitivity to 5-HT diminished by 2 weeks to threefold and was absent at 4 weeks. The augmented reactivity to 5-HT at 48 h was specific, in that it did not occur for the alpha-adrenoceptor agonist, phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Identification of mRNA for PDGF B-chain in human megakaryocytes isolated using a novel immunomagnetic separation method.

A rapid and simple method has been developed for the separation of pure populations of intact human megakaryocytes from whole bone marrow. Megakaryocytes were specifically recognized using monoclonal antibodies coupled to magnetizable articles. Cells labelled with the magnetizable probe were separated from unlabelled cells by introduction of a magnetic field. The technique yields megakaryocyte suspensions with a purity of greater than 98%. Electron microscope examination showed that the ultrastructure of the isolated megakaryocytes was well preserved. Using this method of cell purification, we have investigated expression of the gene for platelet-derived growth factor (PDGF). RNA was isolated from cells harvested from either ribs or posterior iliac crest. The RNA was spotted onto nitrocellulose, and then hybridized using a c-sis riboprobe specific for PDGF B chain mRNA. We demonstrate that mRNA for PDGF B-chain is identifiable in samples of 50,000 cells. We conclude that PDGF is synthesized by the megakaryocyte.

Antibodies, Monoclonal↗
PubMed1990

Accelerated atherogenesis occurs following platelet destruction and increases in megakaryocyte size and DNA content.

Platelets and megakaryocytes have a role in atherogenesis. In this study the effect of platelet destruction, caused by injection of serum containing anti-platelet antibodies, on the development of atheroma and on megakaryocyte size and DNA content was studied in rabbits on a high cholesterol diet. Seven days after destruction of the circulating platelets a significant (150% and 300% in two separate studies) increase in the area of atheroma in the aorta was demonstrated. Histological examination revealed that large quantities of extracellular lipid and connective tissue were present in these plaques. The acceleration of atherogenesis in this model was found to be preceded by a significant increase in megakaryocyte size and in the frequency of megakaryocytes with a high DNA content. Platelets derived from large, high ploidy megakaryocytes may be of importance for the development of the atherosclerotic lesion. Neither the endothelial permeability as assessed by injection of Evans blue nor the prostacyclin production by the aorta of animals injected with anti-platelet serum were significantly different from the aortas of control animals.

Animals↗
PubMed1990

Arterial wall hypoxia following hyperfusion through the vasa vasorum is an initial lesion in atherosclerosis.

Pressure on the outside of arteries can cause physical and biochemical changes in the vessel wall of rabbits which are characteristic of atherosclerosis. It is hypothesized that occlusion of the vasa vasorum causes ischaemia of the arterial media which results in smooth muscle cell proliferation and cellular accumulation of cholesteryl esters. Hypoxia increases mRNA for platelet-derived growth factor in arterial wall cells and increases the activity of acyl CoA: cholesterol acyltransferase (ACAT). Such a mechanism may explain many of the anatomical, actuarial and environmental risk factors for atherosclerosis. Hyperfusion of the vasa vasorum may follow thrombosis.

Animals↗
PubMed1990

[Primary non-Hodgkin's high grade malignant lymphoma of the digestive system. A prospective study of the combination of surgery-chemotherapy-radiotherapy].

We report a prospective study concerning the association of surgery-chemotherapy and radiotherapy in the treatment of primary high grade digestive non-Hodgkin's lymphomas in 19 patients. The analysis of 11 stages IE, 5 stages II1E and 3 stages II2E allowed us to evaluate the efficacy and the tolerance of this triple therapeutic association. Fifteen patients are alive and well with a median follow-up of 54 months. One of these patients relapsed, but after autologous bone marrow transplantation is in second unmaintained complete remission. Four patients died of intercurrent aetiology although one death was related to treatment morbidity. Our results and the analysis of literature data lead us to recommend the triple association in the treatment of stage II2E high grade primary digestive lymphomas (PDL) and for PDL without complete resection. However, surgery and chemotherapy appear to be sufficient in the treatment of stages IE and II1E with complete resection.

Adult↗
PubMed1989

Myocardial creatine kinase exchange rates and 31P NMR relaxation rates in intact pigs.

In this study, we used 31P NMR to investigate the relationship between cardiac workload and creatine kinase flux in intact pigs. NMR measurements were performed on anesthetized miniature swine in which a surface coil was surgically implanted on the surface of the left ventricle. Cardiac workload was varied by infusion of norepinephrine. Phosphate exchange between creatine phosphate and ATP was measured by a combined saturation transfer, saturation recovery pulse sequence. Exchange measurements showed that creatine kinase flux and concentrations of PCr and ATP were independent of workload for a 2.5-fold range of cardiac rate-pressure products. It appears that, if creatine kinase flux is coupled to work load, the pig heart operates in a regime where small changes in metabolite concentrations or creatine kinase flux are sufficient to maintain elevated workloads. Exchange and relaxation measurements, at 2.0 and 4.7 T, yielded T1 relaxation times for creatine phosphate and ATP which are longer than most reported values. Analysis of the T1 data indicates that chemical-shift anisotropy is a plausible mechanism for a portion of the spin-lattice relaxation rate at high field strengths.

Animals↗
PubMed1989

Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation.

A new rabbit model of atherosclerosis is described in which several of the features seen in early human atherosclerosis are generated within a period of 7 days. The positioning of a hollow silastic collar around the carotid artery of a cholesterol-fed rabbit results in macrophage and smooth muscle cell infiltration into the arterial subendothelium, foam cell formation and the deposition of extracellular lipid. A time-dependent accumulation of extracellular cholesteryl ester occurs within the arterial wall. Each of these changes occurs in the presence of a morphologically intact endothelium as assessed using light microscopy, scanning and transmission electron microscopy. A high cholesterol diet did not affect the extent of proliferation but exacerbated cholesteryl ester accumulation. It is proposed that the changes induced by the collar may be mediated by obstruction of the adventitial vasa vasorum with the creation of a localised ischaemic region.

Animals↗
PubMed1989

Flow cytometric analysis of the megakaryocyte DNA distribution in whole and partially purified human and rabbit bone marrow.

Megakaryocytes are polyploid cells that constitute less than 0.1% of the nucleated cells in the bone marrow of most mammals including man. The DNA content of megakaryocytes has previously been measured by microdensitometry. Flow cytometry has also been used in the analysis of bone marrow megakaryocytes, but the general prerequisite for prior enrichment has made this technology less attractive. We describe here a modification to the mode of analysis of megakaryocyte DNA content that can be applied to whole, partially purified and elutriated human and rabbit bone marrow. The electronic masking of low-ploidy cells makes it possible to visualize the DNA content of minority, high-ploidy populations of megakaryocytes within a few minutes. In addition, this rapid technique can be combined with monoclonal antibody analysis of bone marrow cells to aid megakaryocyte identification.

Animals↗
PubMed1989

Characterization of sugar uptake in wild-type Streptomyces clavuligerus, which is impaired in glucose uptake, and in a glucose-utilizing mutant.

Wild-type Streptomyces clavuligerus NRRL 3585 is unable to utilize glucose. A glucose-utilizing (gut-1) mutant of S. clavuligerus NRRL 3585 has been obtained by N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The gut-1 mutant is able to grow on glucose or galactose, while the wild type is unable to catabolize these hexoses. Similar binding affinities of glucose by cells of the wild type and the gut-1 mutant were found, but the wild type was unable to complete glucose transport. A soluble intracellular ATP-dependent (but not phosphoenolpyruvate-dependent) glucokinase activity was found both in the wild type and the gut-1 mutant. The gut-1 mutant has acquired a functional transport system that allows transport of glucose, 2-deoxyglucose, and galactose, as shown by hexose competition experiments. The gut-1 transport system concentrates glucose inside the cell at least 10- to 20-fold and is strongly inhibited by respiratory inhibitors, which prevent the establishment of a proton motive force, and by proton-conducting ionophores, suggesting that it is energized by a proton motive force. The new transport system is not completely sugar specific (transporting galactose and glucose through the same system), as opposed to the hexose-specific system reported in wild-type Streptomyces griseus.

Biological Transport, Active↗