Biomedical subjects
Publications and source records attributed to J Simon.
In skin-blistering diseases, alteration of cellular adhesion results in a loss of cohesion of the epithelium of the skin and the mucous membranes. These disorders are often genetically determined and involve highly specific autoantibodies. A recent workshop discussed the immunology of these diseases.
Ducks (Anatidae Family, Anseriform order) are divided in two genera: Pekin duck (Anasplatyrhynchos genus) and Muscovy duck (Cairina moschata genus) and differ for their number of liver insulin receptors (despite rather similar plasma insulin levels). The possibility that the presence of different endogenous insulins account for the difference in insulin receptor number between the two duck species led us to purify, sequence and characterize the binding properties of Muscovy duck insulin. The sequence of Muscovy duck insulin (measured mass: 5729.11) was identical to that described in two other species from the Anseriforme order: Pekin duck or goose. The binding affinity of Muscovy duck insulin for rat liver insulin receptors (either membrane bound or solubilized receptors) was lower than that of porcine insulin (0.3), which most likely accounts for the low biological potency of Pekin duck insulin previously described. In contrast, liver receptors from chicken and both duck species exhibited the same affinity for duck and porcine insulin suggesting the presence of specific changes in the structure of binding sites of bird liver insulin receptors. The decrease in the number of insulin receptors in Muscovy duck liver is not therefore the consequence of a change at the level of the insulin molecule itself. As discussed, among bird insulins, the hypoactive "duck type" insulin would have appeared after the hyperactive "chicken type" insulin during the evolution of Aves.
It has been hypothesized that the role of obesity in the pathogenesis of coronary heart disease (CHD) may be mediated in part through its inverse relationship with high-density lipoprotein cholesterol (HDL-C). Obesity is inversely correlated with HDL-C, and HDL-C has been shown to be protective against CHD. Defining obesity as excess weight due to excess fat, the purpose of this analysis was to determine whether the effects of obesity are due to increased weight or to increased adiposity. Using baseline lipid and anthropometric data from the National Heart, Lung, and Blood Institute Growth and Health Study, cross-sectional associations among body mass, adiposity, HDL-C, and related lipid parameters (apolipoprotein [apo] AI and triglycerides [TGs]) were assessed in 821 white and 763 black 9- and 10-year-old girls, using multivariate linear regression models. Equations predicting HDL-C, apo AI, and TGs from age, race, race, sexual maturation stage, adiposity (sum of truncal--subscapular and suprailiac--skinfolds), and ponderosity (a ratio of weight to height) revealed that adiposity, not ponderosity, was the significant body composition variable to explain the variability of each of the lipids assessed. The amount of variance explained in each of the models was small (R2 <or= .10). When apo AI and TGs were added to the HDL-C model, R2 increased to 0.44 and race differences were no longer significant. These finding suggest that adiposity, not ponderosity, explains the effects of obesity on HDL-C, the effects are mediated through apo AI and TGs, and that black-white differences in HDL-C are a result of apo AI and TG-metabolic differences between the races.
BACKGROUND: Leukocyte binding to endothelial cells (ECs) is thought to contribute to the pathogenesis of leg ulcers caused by chronic venous insufficiency. In other systems, such binding is mediated by the interaction of adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule- (VCAM-1) and E-selectin (on ECs), and leukocyte function-associated antigen-1(LFA-1) and very late activated antigen-4 (VLA-4) (on Leukocytes). OBJECTIVE: Our purpose was to determine whether an increased expression of these adhesion molecules contributes to the pathogenesis of chronic venous insufficiency. METHODS: Twenty-seven biopsy specimens of inflamed dermatoliposclerotic skin adjacent to venous leg ulcers were stained immunohistochemically with monoclonal antibodies against ICAM-1, VCAM-1, LFA-1, VLA-4, and E-selectin. Staining intensity was compared with that of normal skin. RESULTS: Specimens of leg ulcers caused by chronic venous insufficiency showed increased expression of ICAM-1 and VCAM-1 but not of E-selectin on The expression of LFA-1 and VLA-4 on perivascular leukocytes was increased dramatically in comparison to healthy skin. CONCLUSION: Upregulation of ICAM-1 and VCAM-1 on ECs may contribute to the increased adherence and extravasation of LFA-1 and VLA-4-positive leukocytes in chronic venous insufficiency.
Numerous ubiquitous ribonucleic acid and deoxyribonucleic acid viruses, inducing acute, monophasic infections (mostly childhood diseases) have been considered as potential causes of multiple sclerosis. The present hypothesis reconsiders the role of the viral agent: not the virus, but the reaction of the defense system to the viral persistence, appearing after the acute phase, is postulated as a key factor. A prerequisite of multiple sclerosis is polygenetically determined or acquired immunodeficiency; the defense system is not able to stop repeated viral reactivations induced by a set of exogenous and/or endogenous factors. Thus, an aberrant virus production can appear repeatedly. If the virus spreads from primary target--the lymphoreticular system--into the central nervous system, the multiple sclerosis process can be initiated. Activated T cells and endothelial cells serve as first-host cells. Their infection triggers a set of reactive events: multiple microthrombosis and inflammation play a key role, both of which can result in nonspecific degradation of the myelin. An increased release of myelin antigens induces a homeostatic autoimmunity. Long-term repetition of the shifts and the infection of inflammatory cells can lead to disturbances in self-tolerance. A dysregulated pathological autoimmunity can develop, which acts as a main effector of the specific demyelination.
1. The immediate heart rate and blood pressure changes upon standing have been well documented. It has been recognized, that blood pressure transients elicit baroreflex responses contributing to the complex mechanism of post standing heart rate fluctuations. On the other hand the influence of heart rate changes on orthostatic blood pressure control is not well understood. Therefore we have studied the blood pressure regulation of 28 pacemaker dependent subjects with fixed ventricular pacemaker rhythm during active orthostasis, and their responses were compared to that of 10 elderly (66 +/- 11 year), and 12 young (35 +/- 5 year) volunteers. 2. The young volunteers exhibited the characteristic biphasic heart rate response on standing, with a maximum acceleration of 29 +/- 12 beats. The heart rate response of the elderly volunteers was very limited, and no response was seen among pacemaker subjects. A significantly greater (-37 +/- 15 mmHg) systolic blood pressure drop was seen in the pacemaker group than in the group of young volunteers (-22 +/- 13 mmHg). The systolic blood pressure overshoot of the young volunteers (36 +/- 17 mmHg) was significantly greater than that of the pacemaker patients' (11 +/- 22 mmHg). The blood pressure transients of the elderly volunteers and pacemaker subjects were very similar. Significant correlation was detected between the extent of maximum heart rate acceleration and the magnitude of the subsequent blood pressure overshoot (R = 0.68, p < 0.0005) among healthy volunteers. 3. Our results indicate that certain post standing blood pressure transients are heart rate dependent. The chronotrop incompetency of healthy elderly volunteers and pacemaker subjects result in similar alteration of the orthostatic blood pressure regulation, however this modified response does not interfere with a satisfactory hemodynamic stabilization.
Conjugative F-plasmid transfer is mediated by the transfer (tra) region which encodes nearly 40 genes, 25 of which are essential for this process in Escherichia coli. TraM is required for conjugation and is encoded on a separate operon between the origin of transfer and the traJ gene. The traJ gene product is the positive regulator of transcription of the 30 kb tra operon, the first gene of which is traY. Using primer-extension assays and immunoblots on the F plasmid itself and its derivatives, we demonstrate that F TraM regulates its own expression from two promoters and that it requires TraY as well as expression of the tra operon for maximal traM transcription. traY is the first gene in the tra operon under the control of the TraJ regulator, which is in turn negatively regulated by the antisense RNA, FinP, and the FinO protein. Thus, a control circuit has been established whereby traM is negatively regulated by the FinOP fertility inhibition system through its repression of TraJ expression, which adversely affects transcription of the traY gene.
Explore the source record for details and available documents.
In Manarintsoa, near Antananarivo, Madagascar, two groups of patients were defined in terms of malaria clinical immune status: Group MA+ consisted of 36 patients who suffered from between one to four malaria attacks (MA) during the 20-week study, and Group MA- who comprised of 48 persons who did not have any malaria attacks during this time. In group MA+, IgM and IgG antibody levels to Plasmodium falciparum exoantigens (E-Ag) were inversely related to the number of malaria attacks. The level of IgM antibodies were significantly higher in group MA+. In contrast, IgG, IgG1, IgG2, IgG3 and IgG4 antibodies to E-Ag were significantly higher in group MA-. The level of IgG1 antibodies was inversely correlated, and IgG2 antibodies were positively correlated to the number of malaria attacks.
Explore the source record for details and available documents.
BACKGROUND: Pulmonary vascular tone may be modulated by endothelium-derived vasoactive mediators. Endothelial dysfunction is thought to occur in primary pulmonary hypertension. The aim of this study was to evaluate the vascular responses of patients with severe primary pulmonary hypertension to endothelium-dependent vasodilators (for example, substance P) and non-endothelium-dependent vaasodilators (for example, adenosine). METHODS: Six patients with primary pulmonary hypertension (mean (SE) systolic, diastolic, and pulmonary artery pressures 91.1 (7), 45.2 (3), and 62 (4.2) mm Hg, respectively, and baseline total pulmonary vascular resistance (TPVR) 1949 (164) dynes.s.cm-5) underwent sequential infusions of substance P (5-100 pmol/min) and adenosine (5-50 micrograms/kg/min) in random order. Pulmonary and systemic haemodynamics were monitored by indwelling radial and pulmonary arterial catheters. RESULTS: Substance P caused a marked fall in systemic vascular resistance (SVR) but minimal pulmonary vasodilation (mean maximal percentage change from baseline in TPVR:SVR ratio 27.85 (6.5)%, p < 0.01). Adenosine caused TPVR to fall, but resulted in no change in SVR (mean maximum percentage change from baseline in TPVR:SVR ratio -9.85 (3.5)%, p < 0.05). CONCLUSION: Endothelium-dependent vasodilation is deficient in the pulmonary circulation of patients with primary pulmonary hypertension and may contribute to the abnormalities of pulmonary vascular tone and reactivity seen in that condition.
Control over the adsorption of proteins and over the adsorption and spatial orientation of mammalian cells onto surfaces has been achieved by modification of glass and other silicon oxide substrates with poly(N-isopropylacrylamide) (PNIPAM). The functionalization of the substrates was achieved either by a polymer-analogous reaction of aminosilanes with reactive N-(isopropylacrylamide) (NIPAM)-copolymers and by copolymerization of NIPAM with surface-bound methacrylsilane. The obtained coatings were characterized by FT-1R, ellipsometry, and surface plasmon resonance measurements. The adsorption of two proteins-fibrinogen and ribonuclease A-on these surfaces was studied in situ by real time surface plasmon resonance measurements. The PNIPAM-grafted surfaces prepared by either chemical procedure inhibited the adsorption of both proteins. More importantly they prevented the adhesion of neuroblastomaXglioma hybrid cells cultured either in serum-free medium or in a medium containing serum proteins. Deep-UV irradiation was used to perform ablation processes and to create patterns permitting the examination of spatially controlled adhesion and growth of cells. This study showed that patterned ultrathin polymer films on glass are suitable substrates for controlling the interactions of cells with surfaces and are capable of directing the attachment and spreading of cells.
We have previously shown that surface levels of the adhesive glycoprotein, L-selectin, are diminished on cord blood neutrophils (polymorphonuclear leukocytes, PMN) and associated with impaired adherence to endothelium under flow conditions. To test the hypothesis that diminished surface levels reflect a total cellular deficiency, we measured L-selectin in PMN lysates and plasma from cord and adult blood. L-selectin content was decreased in cord blood PMN lysates compared with those of adults by both Western blot analyses and ELISA (cord blood, 1195 +/- 160 pg/mL; adult, 1870 +/- 260 pg/mL; X +/- SEM; p < 0.05). Soluble L-selectin levels were also decreased in cord blood plasma (324 +/- 24 ng/mL versus 537 +/- 28 ng/mLiter in adult plasma, p < 0.01). To evaluate L-selectin function, we next compared the dose dependent effect of several chemoattractants on shedding of L-selectin from cord blood and adult PMN. Adult PMN showed greater overall shedding of L-selectin as compared with cord blood PMN after stimulation with fMet-Leu-Phe (p < 0.03) and granulocyte-macrophage colony-stimulating factor (p < 0.02). In contrast, shedding of L-selectin was similar between groups after IL-8 tested stimulation. We conclude that cord blood PMN have a decreased cellular content of L-selectin in addition to an impaired ability to shed surface L-selectin in response to specific inflammatory mediators.
The Sex comb on midleg (Scm) gene is a member of the Polycomb group (PcG) of genes in Drosophila melanogaster. The PcG genes encode transcriptional repressors required for proper spatial expression of homeotic genes. We report the isolation of new Scm mutations and the molecular characterization of the Scm gene. Scm mRNA is expressed maternally, at peak levels in early embryos and then at lower levels throughout the remainder of development. Scm encodes a putative zinc finger protein of 877 amino acids. Scm protein is similar to polyhomeotic, another member of the PcG, both in the zinc finger region and in a separate C-terminal domain of 60 amino acids, which we term the SPM domain. Sequence analysis of an Scm mutant allele suggests a functional requirement for the SPM domain. Scm protein also bears homology in multiple domains to a mouse protein, Rae-28 (Nomura, M., Takihara, Y. and Shimada, K. (1994) Differentiation 57,39-50) and to a fly tumor suppressor protein, the product of the lethal(3)malignant brain tumor gene (Wismar, J. et al., (1995) Mech. Dev. 53, 141-154). Possible functional relationships among these proteins and potential biochemical roles for Scm protein in PcG repression are discussed.
Partial nephrectomy and tumour enucleation are increasingly accepted as an organ sparing approach for small renal cell carcinomas. Repeated computed tomography or sonography for the early detection of tumour recurrence are mandatory during the follow-up. We report two cases of renal pseudotumour mimicking a tumour recurrence: one case is related to the pseudotumoral appearance on sonography of a tumour defect filled by a fatty flap, and the other to the relative migration of an accessory spleen into the site of the cuneiform nephrectomy. The recognition of renal pseudotumours following partial nephrectomy prevents confusion with tumour recurrence on follow-up examinations.
Explore the source record for details and available documents.
A partial cDNA was isolated by hybridization screening of an embryonic chick brain library for P2Y purinoceptors. After extension to full length, it revealed an open reading frame that encoded a protein, P2Y3, of 328 amino acids that is nearest in sequence identity to the G protein-coupled P2 purinoceptors obtained by DNA cloning. Expression of P2Y3 in cRNA-injected Xenopus oocytes confirmed that this cDNA encodes a member of the metabotropic purinoceptor family, with a novel order for the relative activities of nucleotides. At 100 microM concentrations, ADP gave the highest activity, and UTP and UDP were also strongly active. When expressed in the human T cell line Jurkat, P2Y3 mediated transient increases in intracellular Ca2+ in response to various nucleotides. Again, an unusual agonist rank order was revealed, with uridine nucleotides being more potent than adenosine nucleotides and UDP being the most potent agonist tested (half-maximal concentration, 0.13 microM) and 10-fold more potent than UTP. 2-Methylthlo-ATP was of relatively low activity in both systems. The receptor transcript is expressed in brain, spinal cord, kidney, and lung and is highly abundant in the spleen but not in other peripheral tissues that we tested. The results indicated that P2Y3 is a previously unknown P2 purinoceptor subtype with a preference for nucleoside diphosphates.
Explore the source record for details and available documents.