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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 487 records · Page 27Linked to original sources
PubMed1994

In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery.

On the basis of the knowledge that the pulmonary and bronchial circulations have extensive anastomoses, we hypothesized that gene transfer to the endothelium of both pulmonary and bronchial circulations might be achieved with replication-deficient recombinant adenovirus (Ad) vectors administered to the pulmonary circulation. To evaluate this concept, the right upper lobe branches of the sheep pulmonary artery and vein were temporarily occluded and a replication-deficient recombinant Ad vector containing the Escherichia coli lacZ reporter gene coding for beta-galactosidase (beta-Gal) was infused into the lumen of the occluded pulmonary artery. After 15 min, the pulmonary circulation was restored, and 1 or 4 days later the lungs were evaluated by histochemical analysis for beta-Gal activity. Gene transfer and expression were positive in 13 of 17 evaluated sheep. No beta-Gal activity was detected in any category of cells of uninfected lobes. As hypothesized, beta-Gal activity was detected in endothelial cells of the right upper lobe pulmonary and bronchial circulations. Unexpectedly, gene transfer was also observed in epithelial cells of the alveoli and the airways (bronchi and bronchioles) as well as in the epithelium of submucosal glands. These studies demonstrate that it is possible to use Ad vectors for transfer and expression of genes to lung parenchymal cells served by both the pulmonary and bronchial circulations. Furthermore, whereas administration of such vectors via the airways results in gene transfer only to the epithelium, pulmonary artery administration permits gene transfer to both endothelium and epithelium, thus expanding the target range of Ad gene transfer to the lungs.

Adenoviridae↗
PubMed1994

Epicutaneous test in carbamazepine cutaneous reactions.

Carbamazepine is a widely used drug associated with numerous side effects including skin eruptions that appear in about 4% of patients. Epicutaneous tests have been used with variable success in skin drug reactions. The purpose of this study was to work out the efficacy of this type of test in carbamazepine reactions. Five patients with carbamazepine cutaneous reaction were studied. Clinical, laboratory and histopathological data were recorded. The 5 patients and 20 controls were tested with carbamazepine 1% in petrolatum. In 4 patients the carbamazepine epicutaneous test was positive. The 20 healthy controls were negative. Epicutaneous testing is a simple and helpful method in detecting carbamazepine hypersensitivity.

Adult↗
PubMed1994

Evaluation of mitral regurgitation using a digitally determined color Doppler flow convergence 'centerline' acceleration method. Studies in an animal model with quantified mitral regurgitation.

BACKGROUND: The imaging and measurement of the proximal flow convergence region in the left ventricle have been reported to be useful for identifying the site of mitral regurgitation (MR) and for evaluating its severity. However, the application of this method has not gained general acceptance. There have been few in vivo studies with quantified reference standards for determining regurgitant volume, and those that have been reported used spectral Doppler standards and/or nonsimultaneously performed contrast ventriculography. The purpose of the present study was to evaluate the proximal flow convergence centerline velocity-distance profile method applied to chronic MR resulting from flail mitral leaflets in an animal model in which regurgitant flow rates and regurgitant volumes were determined simultaneously with electromagnetic flow probes and flowmeters. METHODS AND RESULTS: In six sheep, a total of 18 hemodynamically different states were obtained when the animals were restudied 6 months after surgical induction of MR produced by severing chordae tendineae to the anterior (three sheep) or posterior (three sheep) mitral leaflet. Echocardiographic studies with a Vingmed 750 were performed to obtain complete proximal axial flow acceleration velocity-distance profiles for each hemodynamic state. The color Doppler velocity data were directly transferred in digital format from the ultrasound instrumentation to a microcomputer. The severity of MR was assessed by the magnitude of the mitral regurgitant fraction determined using both mitral and aortic electromagnetic flow probes balanced against each other to yield regurgitant volume. MR was classified as grade I when the regurgitant fraction was < 20%, as grade II when it was 20% to 35%, and as grade III to IV when it was > 35%. Thus, of the 18 hemodynamic states, 4 (from two sheep) were grade I, 7 (from five sheep) were grade II, and 7 (from three sheep) were grade III to IV. All of the velocity-distance acceleration curves showed organized acceleration fields with highly significant correlations using multiplicative regression fits (y = a.x-b, r = .90 to .99, all P < .01). Grade III to IV MR resulted in rightward and upward shifts of the velocity-distance profile curves compared with those produced by grade II and grade I MR. All of the centerline velocity-distance profiles for grade III or IV regurgitation resided in a domain encompassed by velocities > 0.5 m/s at distances from the orifice > 0.6 cm; the profiles for grade I regurgitation resided in a domain encompassed by velocities < 0.3 m/s at distances from the orifice of < 0.45 cm. The profiles for grade II regurgitations resided in a domain between them. Regression analysis for the distance at which a velocity of 0.5 m/s was first reached bore a close relation to regurgitant fraction (r = .92, P < .0001) and peak regurgitant flow rate (r = .89, P < .0001). In addition, an equation for quantitatively correlating both a and b (coefficients from the multiplicative regression fits) with the peak regurgitant flow rate (Qpeak in L/min) was derived from stepwise regression analysis: Qpeak = 12a + 2.7b-2.4 (r = .96, P < .0001, SEE = .45 L/min). CONCLUSIONS: In this study, using quantified MR volume, we demonstrate that the proximal flow convergence axial centerline velocity-distance profile method can be used for evaluating the severity of MR without any assumption about isovelocity surface shape geometry.

Animals↗
PubMed1994

An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration.

The sequestration of parasitized erythrocytes in the microvasculature of vital organs is central to the pathogenesis of severe Plasmodium falciparum malaria. This process is mediated by specific interactions between parasite adherence ligands and host receptors on vascular endothelium such as intercellular adhesion molecule-1 (ICAM-1) and CD36. Using immunohistochemistry we have examined the distribution of putative sequestration receptors in different organs from fatal cases of P. falciparum malaria and noninfected controls. Receptor expression and parasite sequestration in the brain were quantified and correlated. Fatal malaria was associated with widespread induction of endothelial activation markers, with significantly higher levels of ICAM-1 and E-selectin expression on vessels in the brain. In contrast, cerebral endothelial CD36 and thrombospondin staining were sparse, with no evidence for increased expression in malaria. There was highly significant co-localization of sequestration with the expression of ICAM-1, CD36, and E-selectin in cerebral vessels but no cellular inflammatory response. These results suggest that these receptors have a role in sequestration in vivo and indicate that systemic endothelial activation is a feature of fatal malaria.

Adult↗
PubMed1994

Class pi glutathione S-transferase: Meisenheimer complex formation.

The enzyme-catalysed formation of the dead-end Meisenheimer complex, 1-(S-glutathionyl)-2,4,6-trinitrocyclohexadienate, between glutathione and 1,3,5-trinitrobenzene by two class pi glutathione S-transferases was studied under equilibrium conditions. The apparent formation constant of the complex at pH6.5, is 1.21 x 10(3) M-1 and 1.47 x 10(3) M-1 for isoenzyme pGSTP1-1 from porcine lung and hGSTP1-1 the human recombinant orthologue, respectively. These values are about 40- to 50-times larger than that determined for the nonenzymatic reaction in solution. Competitive inhibitors in the form of glutathione analogues that bind the G-site (glutathione sulphonate) or both the G-site and the H-site (S-hexylglutathione) regions of the active site markedly diminish complex formation. Comparison of kinetic data for glutathione S-transferase isoenzymes from the pi and mu gene classes suggests that the catalytic efficiencies for nucleophilic aromatic substitution reactions correspond with the ability of the enzyme's active site to stabilise the Meisenheimer complex. Formation of the red-coloured complex in orthorhombic crystals of pGSTP1-1 demonstrated that the crystallized protein retains its catalytically functional conformation in the crystal lattice.

Animals↗
PubMed1994

Lymphangiogenesis in vitro: formation of lymphatic capillary-like channels from confluent monolayers of lymphatic endothelial cells.

Lymphatic endothelial cells grown long term in culture form lymphatic capillary-like tubes. Examination by light and transmission electron microscopy showed that these structures were closed loops composed of one to several cells connected by intercellular junction to form a luminal space. This first demonstration of lymphangiogenesis in confluent monolayer cultures of lymphatic endothelial cells (a) showed that collagen type I accelerated lymphatic capillary tube formation, whereas fibronectin and matrigel had no effect; b) provided a model to study lymphatic endothelial cell function and differentiation; and c) offered a possibility to distinguish differences between the process of lymphangiogenesis and angiogenesis by testing various factors and conditions that effect endothelial cell behavior.

Animals↗
PubMed1994

The spectrum of "complicated spastic paraplegia, MASA syndrome and X-linked hydrocephalus". Contribution of DNA linkage analysis in genetic counseling of individual families.

X-linked hydrocephalus and the X-linked MASA syndrome (Mental retardation. Adducted thumbs, Shuffling gait and Aphasia) both have a variable clinical spectrum with great overlap. Data from DNA linkage analysis placed the locus for both conditions at Xq28. On clinical and molecular grounds it has been hypothesized that both MASA syndrome and X-linked hydrocephalus are caused by a mutation in the same gene at Xq28. There is no significant clinical marker in the obligate female carriers and prenatal diagnosis by ultrasound is not reliable; DNA analysis can offer an improved genetic counseling for the families and more reliable prenatal diagnosis. In the gene encoding for Ll, a neural cell adhesion molecule and located at Xq28, several different mutations have been reported in X-linked hydrocephalus families and in a MASA family. We report data on DNA linkage analysis in 6 families with X-linked hydrocephalus/MASA syndrome. These data illustrate the importance of DNA linkage analysis in the individual family; they also show, however, the problem of studying small families. Genetic heterogeneity cannot be excluded.

Abortion, Eugenic↗
PubMed1994

A novel internal antigen which distinguishes germinal centre cells from other B-cell types.

A new monoclonal antibody, 4KB51, is described which labels the majority of B cells in blood and in mantle and marginal zones but not germinal centre lymphocytes or plasma cells. Antibody 4KB51 also stains monocytes, neutrophils and the majority of T cells. It recognizes an intracellular antigen of 160,000 MW (unreduced) and 68,000 MW (reduced). Antibody 4KB51 labels the tumour cells in all cases of hairy cell leukaemia and in four of the 16 cases of centrocytic B-cell lymphoma studied. No labelling of the other lymphomas (114 cases) or lymphoid leukaemias (13 cases) tested was seen. Antibody 4KB51 may be of value in defining B-cell subsets and in the differential diagnosis of hairy cell leukaemia and centrocytic lymphomas. The pattern of reactivity of 4KB51 suggests that its target antigen may play a functional role, possibly involved in lymphocyte homing.

Antibodies, Monoclonal↗
PubMed1993

Detection of T and B cells in many animal species using cross-reactive anti-peptide antibodies.

A wide range of lineage-specific Ag are detectable in the human lymphoid system using mAb, but only a few such markers are detectable in animal species. In this paper, we have investigated the interspecies reactivity of antibodies raised against intracytoplasmic peptide sequences from two T cell Ag (CD3 and CD5) and two B cell markers (the Ig-associated polypeptides encoded by the mb-1 and B29 genes). Immunocytochemical labeling of tissue sections showed that these antibodies cross-react widely between different species (including ungulates, rodents, and marsupials), staining B or T cell areas selectively in lymphoid tissue. The specificity of these antibodies for the animal homologues of the human T and B cell markers was confirmed for the rat by Western blotting analysis. The broad cross-reactivity of these antibodies appears to be due to the fact that they were raised against intracytoplasmic peptide sequences that are highly conserved between humans and rodents, i.e., 80% for mb-1, 85% for CD5, and 100% for CD3 and B29. This strategy should, in the future, widen the range of lineage-associated markers detectable in experimental animals.

Amino Acid Sequence↗