Virodene--support misguided.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
M Lucas
Publications and source records attributed to M Lucas.
Cetirizine and pseudoephedrine retard, given alone or in combination, in patients with seasonal allergic rhinitis.
We compared the efficacy and safety of cetirizine (5 mg), pseudoephedrine retard (120 mg), and the combination of cetirizine (5 mg) with pseudoephedrine retard (120 mg), each given twice daily for two weeks to subjects with pollen-associated allergic rhinitis. The study was multicentre and of randomized, double-blind, parallel-group design. Five rhinitis symptoms were rated according to severity on a scale of 0 - 3, daily by patients and at each clinic visit by investigators. A total of 687 patients, aged 9 - 66 years (mean: 32 years) was randomised to treatment (cetirizine: 231; pseudoephedrine: 226; combination: 230). On entry, the three groups were comparable in relevant respects. The primary outcome measure was based on the five symptoms assessed by the patients over the 2-week treatment period. The combination was more effective, providing at least 20% more "comfortable days" (symptoms absent or at most mild) than cetirizine or pseudoephedrine given alone (median values: 53.3%, 30.8%, and 33.3%, respectively; p < 0.001). For nasal obstruction, the combination (mean score: 1.19) was more effective than cetirizine (mean score: 1.43; p = 0.0005), but there was little difference between the combination and pseudoephedrine (mean score: 1.22; not significant). Sneezing, rhinorrhoea, nasal and ocular pruritus were better controlled by combination (mean 4-symptom score: 0.77) than by pseudoephedrine alone (mean 4-symptom score: 1.12; p < 0.001) and also better than by cetirizine alone (mean 4-symptom score: 0.93; p < 0.001). No unexpected adverse reactions were observed. A combination of cetirizine and pseudoephedrine retard is well tolerated and superior to each given alone for moderate to severe allergic seasonal rhinitis, especially when nasal obstruction is a predominant symptom.
Adolescent↗
Cell surface proteoglycans modulate net synthesis and secretion of macrophage apolipoprotein E.
Using a macrophage cell line that constitutively expresses a human apolipoprotein E (apoE) cDNA, we have investigated the post-translational metabolism of endogenously produced apoE. Inhibition of lysosomal or cysteine proteases led to significant inhibition of apoE degradation but did not increase apoE secretion, indicating that cellular degradation is not limiting for apoE secretion in macrophages. Treatment of macrophages with inhibitors of proteoglycan synthesis (4-methylumbelliferyl-beta-D-xyloside) or sulfation (sodium chlorate) enhanced the release of apoE from cells and significantly attenuated the increase in secretion produced by incubation with phosphatidylcholine vesicles (PV). These observations suggested that a significant fraction of the apoE retained by cells (and released by incubation with PV) was associated with proteoglycans. Treatment of cells with exogenous heparinase led to a greater than 4-fold increase in apoE secretion and similarly attenuated the response to PV, suggesting that apoE was trapped in an extracellular proteoglycan matrix. This conclusion was confirmed in studies showing that PV could enhance the release of apoE from cells during an incubation at 4 degrees C, but this enhanced release was abolished in proteoglycan-depleted cells. Incubation with lactoferrin at 4 or 37 degrees C produced a similar decrement in cellular apoE, again indicating the existence of a cell surface pool of apoE. Pulse-chase studies showed that the apoE trapped in the proteoglycan matrix was susceptible to rapid cellular degradation such that net synthesis of apoE (secreted plus cell-associated) was increased significantly in proteoglycan-depleted cells compared with control cells as early as 45 min during a chase period.
Apolipoproteins E↗
N-monomethyl-arginine and nicotinamide prevent streptozotocin-induced double strand DNA break formation in pancreatic rat islets.
The impact of short term in vitro exposure to the diabetogenic drug streptozotocin on pancreatic islet glucose metabolism, insulin secretion, DNA fragmentation and cell viability, was studied. Streptozotocin impaired cell viability as well as insulin secretion and the oxidation of glucose. These effects were partially counteracted by inhibition of the inducible form of nitric oxide synthase with N-monomethyl-arginine and by scavenging oxygen free radicals with nicotinamide. Isolated islets underwent double strand DNA fragmentation after 24 h in culture. The degree of DNA breakdown was strongly enhanced by exposure of the islets to 0.55 mM streptozotocin for 30 min before culture. Prevention of streptozotocin-induced cleavage of islet DNA was obtained with N-monomethyl-arginine and nicotinamide. These data suggest that the generation of reactive oxygen and nitrogen species is involved in the deleterious action of streptozotocin on pancreatic islet tissue. A role for oxygen radicals generated during streptozotocin-induced islet cell damage as possible mediators of the expression of the inducible form of nitric oxide synthase and the scavenging action of nicotinamide on these radicals, is then proposed.
Animals↗
Pancreastatin action in the liver: dual coupling to different G proteins.
Pancreastatin is a 49 amino acid peptide first isolated, purified and characterized from porcine pancreas. Its biological activity in different tissues can be assigned to the C-terminal part of the molecule. Pancreastatin has a prohormonal precursor, chromogranin A, which is a glycoprotein present in neuroendocrine cells, including the endocrine pancreas. We have been interested in pancreastatin action in the liver. We found that pancreastatin has a glycogenolytic effect in the hepatocyte both in vivo and in vitro. We then studied and characterized the specific pancreastatin receptor in the rat liver plasma membrane, as well as the specific signal transduction. This receptor appears to be coupled to two different G proteins. A pertussis toxin-insensitive G proteins leads to the activation of phospholipase C, and therefore mediates the glycogenolytic effect in the liver by increasing cytoplasmic free calcium and stimulating protein kinase C. The role of cyclic GMP in the action of pancreastatin is not known yet, although it seems to regulate negatively the activation of phospholipase C. The precise mechanism by which pancreastatin stimulates guanylate cyclase activity remains to be studied.
Animals↗
Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation.
We have examined the regulation of neuron-specific gamma-enolase gene (NSE) expression in oligodendrocytes at various steps of their differentiation/maturation. We have demonstrated for the first time that NSE is expressed in oligodendroglial cells in vitro and in vivo, and only at a certain stage of differentiation. A heterogeneity of the gamma subunit was observed in cultured oligodendrocytes and the same one was found in adult rat brain. The level of gamma mRNA increased when precursor cells differentiated into oligodendrocytes. By contrast, no significant change in alpha-enolase gene expression was observed. High NSE (gamma gamma and alpha gamma) enolase activity was detected in cultured oligodendrocytes. Treatment with basic fibroblast growth factor, which stimulates the proliferation of oligodendrocyte precursor cells and reversibly blocks their differentiation, resulted in lower alpha gamma- and gamma gamma-enolase activities in these cells, but it enhanced alpha alpha-enolase activity slightly. These data indicate that gamma-enolase gene expression is associated with the differentiation of the oligodendrocytes and that it is repressed in adult fully mature cells.
Aging↗
Megasession hair transplantation with a CO2 laser Flashscanner technology.
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Hair↗
Pancreastatin: further evidence for its consideration as a regulatory peptide.
Pancreastatin is a 49 amino acid peptide first isolated, purified and characterized from the porcine pancreas, and whose biological activity in different tissues can be assigned to the C-terminal part of the molecule. Pancreastatin has a prohormonal precursor, chromogranin A (CGA), which is a glycoprotein present in neuroendocrine cells, including the endocrine pancreas. Both intracellular and extracellular processing of CGA can yield pancreastatin. This processing is tissue-specific, with the pancreatic islet and antral gastric endocrine cells being the major source of fully processed pancreastatin. Most of the circulating CGA is secreted by chromaffin tissue. Therefore, peripheral processing of CGA is probably the major indirect source of pancreastatin. Pancreastatin seems to have a general modulatory control on endocrine (insulin, glucagon, parathormone) and exocrine (pancreatic, gastric) secretion from tissues close to the source of production. This has led to the assumption that pancreastatin may be a peptide with an autocrine and paracrine function. It has recently been revealed to be a peptide with a metabolic function counter-regulatory to insulin action. This effect, in conjunction with the inhibitory effect on insulin and pancreatic exocrine secretion, points to a role in the physiology of stress. The molecular mechanism of the glycogenolytic effect of pancreastatin is better known, although further work is still needed. In general, more studies should be carried out at the molecular level to investigate the mechanism of action of pancreastatin and thus to clarify its physiological role in the neuroendocrine system.
Animals↗
A chemiluminescence method to analyze phosphatidylcholine-phospholipase activity in plasma membrane preparations and in intact cells.
We present a new method to analyze the hydrolysis of phosphatidylcholine by either phospholipase C (PLC) or phospholipase D. The method is nonradioactive, rapid, and very sensitive and is based on chemiluminescence. It relies on the peroxidase-catalyzed chemiluminescent oxidation of luminol by the H2O2 derived from choline oxidation. The enzyme activity can be quantified by calculation of produced choline in a standard curve. Data are accurate and reproducible in a large range of choline concentration. In fact, the response of PLC to GTP in plasma membranes was similar to the activity measured with radioactive methods of diacylglycerol or phosphatidylinositol triphosphate determination. The method can be applied to study the hydrolysis of phosphatidylcholine in plasma membrane preparations and in intact cells.
Animals↗
Transcriptional up-regulation of the mouse gene for the muscle-specific subunit of enolase during terminal differentiation of myogenic cells.
The glycolytic enzyme enolase (EC 4.2.1.11) exists as dimers formed from three structurally related subunits alpha, beta, and gamma, encoded by separate genes. The gene encoding the beta-subunit is expressed only in striated muscles. We have previously shown that the beta-enolase gene belongs to a small subset of muscle-specific genes showing transcriptional activity in cultured myoblasts, prior to withdrawal from the cell cycle. An increase in the level of beta-enolase mRNA occurs during terminal differentiation of myoblasts. To investigate the mechanisms underlying this increase, we have simultaneously estimated, under steady state conditions, the rate of synthesis and the stability of beta-enolase mRNA in proliferating C2.7 myoblasts as well as in differentiating myotubes. The method used is based on the isolation of newly synthesized RNA from the total RNA pool, following pulse-labeling of intact cells in the presence of 4-thiouridine. The results described here demonstrate a coordinate increase in newly synthesized and total beta-enolase mRNA, while the mRNA half-life, about 4 hr, remains unchanged in the course of terminal differentiation. The expression of the gene for insulin-like growth factor-II (IGF-II), a major positive regulator of myogenesis, was analyzed using the same approach. It is concluded that the up-regulation of beta-enolase as well as IGF-II gene expression in differentiating muscle cells reflects an increased rate of entry of newly synthesized mRNAs into the general pool of transcripts without changes in their respective half-lives.
Animals↗
Protein kinase C involvement in apoptosis.
1. Conflicting observations on the involvement of PKC in apoptosis point to a great variability depending on cell type, agent or condition causing apoptosis, phase of cell cycle and intracellular signaling pathway. 2. Inhibition by PKC of store-operated calcium entry mechanisms, which are sensitive to the oncoprotein bcl-2, should block the activation of calcium-dependent enzymes triggering the apoptotic cell death. 3. Activation of phosphatases by ceramide and inhibition of PKC by sphingosine seem to mediate the sphingomyelin pathway to apoptosis. 4. A putative target protein appears to be p34cdc2 which is regulated by a network of kinases and phosphatases. The uncoupling of timing for p34cdc2 activation and the completion of DNA replication results in the so-called "mitotic catastrophe" that shares some features with apoptosis.
Animals↗
Instability of the CGG repeat at the FRAXA locus and variable phenotypic expression in a large fragile X pedigree.
Fragile X syndrome is the major cause of inherited mental retardation. The molecular basis for the expression of the fragile X phenotype is the expansion of an unstable CGG repeat element which inhibits transcription of the FMR1 gene. The fragile X syndrome shows great diversity in its phenotype as well as in its cytogenetic and molecular status. We have studied, in a large fragile X family, the correlation between the molecular data and the phenotypic expression of the syndrome. We report two brothers who carry identical unmethylated premutated alleles but present different clinical phenotypes. We also suggest that reductions in allele size from one generation to another may be, as in other diseases, because of triplet amplifications, more common at the FRAXA locus than previously thought.
Alleles↗
Differential expression of alpha- and beta-enolase genes during rat heart development and hypertrophy.
We have analyzed the transition between isoforms of the glycolytic enzyme enolase (2-phospho-D-glycerate hydrolyase; EC 4.2.1.11) in rat heart during normal and pathological growth. A striking fall in embryonic alpha-enolase gene expression occurs during cardiac development, mostly controlled at pretranslational steps. In fetal and neonatal hearts, muscle-specific beta-enolase gene expression is a minor contributor to total enolase. Control mechanisms of beta-enolase gene expression must include posttranscriptional steps. Aortic stenosis induces a rapid and drastic decrease in beta-enolase transcript level in cardiomyocytes, followed by the fall in beta-subunit level. In contrast, alpha-enolase transcript level is not significantly altered, although the corresponding subunit level increases in nonmuscle cells. We conclude that, like fetal heart, hypertrophic heart is characterized by a high ratio of alpha- to beta-enolase subunit concentrations. This study indicates that the decrease in beta-enolase gene expression may be linked to beneficial energetic changes in contractile properties occurring during cardiac hypertrophy.
Aging↗
Customizable human resource software replaces incompatible systems at West Virginia University Hospitals.
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Hospitals, University↗
[Cytomegalovirus-induced colitis in HIV infection. Considerations on its diagnosis, treatment and complications].
The diagnosis of cytomegalovirus intestinal disease in patients with HIV (human immunodeficiency virus) infection frequently raises diagnostic problems in view of the absence of definite pathological, serological or virological markers of active CMV infection. We describe the case of a 47-year-old man with a CMV colitis which illustrates several diagnostic and therapeutic problems and that was complicated by an intestinal perforation. We emphasize that in HIV+ patients with chronic diarrhea, the presence of abdominal pain should suggest the possibility of a CMV colitis and that in such cases a colonoscopy with biopsies of the right colon should be performed, in view of the higher frequency of the typical histopathological changes at this level. On the other hand, this case presented a marked thickening of the colon wall, simulating pseudotumoral images on CAT scans, as recently described in literature. The therapeutic possibilities as well as the complications of CMV colitis are discussed in the context of the occurrence of an ileal perforation, which represents the first report of this complication in Portuguese literature and which had the particularity of having a long survival after surgery in comparison with the previous cases described in international literature.
AIDS-Related Opportunistic Infections↗
[Autoimmune hemolytic anemia and ulcerative colitis].
Although several associations of autoimmune disorders with ulcerative colitis have been reported, autoimmune hemolytic anemia is extremely rare. We report a case of a 35 year-old white woman with a twelve-year history of mild ulcerative colitis treated in the last 5 years with 5-amino-salycilic acid who developed a severe autoimmune hemolytic anemia. We discuss some particular aspects of the association of these two immunologically mediated disorders as well as the controversial aspects of autoimmune hemolytic anemia therapy in this context.
Adult↗
Receptor-independent mechanisms are involved in the priming of neutrophil's oxidase by vasoactive intestinal peptide.
Vasoactive intestinal peptide (VIP) primed the respiratory burst of human neutrophils induced by phorbol myristate acetate (PMA) and by the chemotactic peptide N-formyl-Met-Leu-Phe (fMLP). The sigmoidal-shaped curve of the priming effect of VIP differs for both agonist since the Hill coefficient was close to three in the case of neutrophil activation by fMLP whereas the corresponding value for PMA was close to one. The priming effect of VIP was enhanced when neutrophils were stimulated by FMLP in the presence of sphinganine, a protein kinase C inhibitor, at concentrations which almost abolished the response to PMA. VIP failed to increase resting cytosolic free calcium and to modify the transient increase in [Ca2+]i induced by fMLP. The described results point out that the mechanism of the priming of neutrophils by VIP is also independent of calcium and protein kinase C. The absence of VIP receptors in plasma membrane of neutrophils suggests that a receptor-independent mechanism modulates the agonist-triggered signaling pathway. The priming of neutrophils by VIP can not be considered as a pharmacological effect, as may be deduced from the required VIP concentration; it should be rather considered that the enhancement of the formation of reactive oxygen metabolites by VIP may be interesting in the understanding of the neuroimmune axis.
Calcimycin↗
Pancreastatin activates protein kinase C by stimulating the formation of 1,2-diacylglycerol in rat hepatocytes.
We describe here the stimulation by pancreastatin of 1,2-diacylglycerol production and protein kinase C activity in liver plasma membrane and isolated hepatocytes. The dose-dependency for the stimulation of both processes was similar to the recently described pattern of glucose output and cytosolic Ca2+ transients produced by pancreastatin. The time course of diacylglycerol production at 30 degrees C showed a rapid increase within 5 min, reaching a maximum at 10 min. Protein kinase C from hepatocytes was dependent on Ca2+ and phosphatidylserine. Neither the pancreastatin-stimulated diacylglycerol production nor the activation of protein kinase C was affected by pretreatment with pertussis toxin. However, the presence of GTP partially inhibited this pancreastatin stimulation of 1,2-diacylglycerol in a dose-dependent manner, although GTP alone stimulates diacylglycerol accumulation. This inhibitory effect of GTP on pancreastatin stimulation of diacylglycerol synthesis was completely abolished by the pretreatment with pertussis toxin. In conclusion, this study provides evidence that pancreastatin stimulates the formation of 1,2-diacylglycerol by a pertussis-toxin-independent mechanism, which may be responsible for the pancreastatin activation of protein kinase C.
Adenosine Diphosphate Ribose↗