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Biomedical subjects

M Torres

Publications and source records attributed to M Torres.

At least 55 records · Page 3Linked to original sources

Prolonged exposure to YC-1 induces apoptosis in adrenomedullary endothelial and chromaffin cells through a cGMP-independent mechanism.

YC-1, a benzyl indazole derivative, is an NO-independent direct activator of soluble guanylyl cyclase (sGC), which presents a synergistic action with NO in stimulating cGMP synthesis. These properties have served to suggest YC-1 as an attractive therapeutic agent by permitting the reduction of nitrovasodilator dosage and regulating endogenous cGMP metabolism. Here we studied the effect of prolonged exposure of adrenomedullary endothelial and chromaffin cells to YC-1. We found that YC-1 increased cGMP in the two types of cells and this action was blocked by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cells underwent apoptotic death in association with increased caspase-3-like activity, DNA fragmentation, cytoskeletal disorganization and changes in membrane permeability after prolonged incubation with YC-1. Caspase-3-like protease activity and DNA fragments in the cytoplasm were increased in a dose-dependent manner by 16 h YC-1 treatment. The specific and cell permeable caspase-3-like protease inhibitor DEVD-CHO effectively inhibited YC-1-mediated caspase-3-like activation and DNA fragmentation. Moreover, YC-1 also induced cell shape changes accompanied by actin filament disorganization and alterations in membrane permeability. Cells incubated for 24h with YC-1 showed damaged membranes by binding to nucleic acid of a dye excluded by the intact plasma membrane of live cells. YC-1 also induced a decrease in the intracellular non-specific esterase activity, another indication of cell toxicity. Apoptotic phenomena were not prevented by the presence of ODQ although it effectively inhibited the YC-1-elicited cGMP increases. These findings indicate that YC-1 induces apoptosis by activating caspase-3-like protease through a mechanism independent of sGC activation.

Adrenal Medulla↗

Electrophysiological and hemolytic activity elicited by the venom of the jellyfish Cassiopea xamachana.

In this study, we determined hemolysis activity in human and sheep erythrocytes, and characterized the electrical responses in Xenopus oocyte membrane elicited by the venom of the jellyfish Cassiopea xamachana (Cx). The Cx venom produced hemolysis in both species, being more potent on human red cells. The electrophysiological study showed that the Cx venom elicited three different responses in the oocytes. One current was generated in all the oocytes tested and corresponded with a slow inward current (I(Cx)) associated with an increase in membrane conductance. I(Cx) was concentration-dependent and had a reversal potential of -10.3+/-0.4 mV. Ionic substitution studies indicated that the conductive pathway was mainly permeable to cations and non-selective. The oocyte membrane resistance was completely recovered after washout of the venom, this suggested that the effect was due to generation of a specific membrane conductance as opposed to a possible non-specific membrane breakdown. A comparative study with three distinct native cationic channels present in the oocyte membrane [i.e. (1) hemi-gap-junction channels, (2) mechanosensitive channels, and (3) the ouabain-sensitive channel activated by palytoxin], showed that I(Cx) might correspond to opening of mechanosensitive channels or to activation of an unknown cationic channel located in the oocyte membrane. The bioactive fraction eliciting I(Cx) were peptides and was separated from two other peptidic hemolytic fractions by chromatography.

Animals↗

Similarity of the patterns of sensilla on the antennae of Triatoma melanosoma and Triatoma infestans.

The patterns of sensilla on the antennae of sylvatic Triatoma melanosoma Lent, Jurberg, Galvao and Carcavallo 1994 were compared with those of three samples of Triatoma infestans (Klug 1834) - one of domestic populations in Paraguay, Bolivia, Argentina and Chile, one of the sylvatic 'dark morph' from the Bolivian Chaco, and one from sylvatic sites in the Cochabamba region of Bolivia. The results of multivariate analysis indicated that, in terms of their antennal sensilla, the T. melanosoma and the 'dark morph' of T. infestans were more similar to the domestic T. infestans than to the sylvatic T. infestans from Cochabamba. As in previous molecular and genetic studies, there was no evidence to indicate that the bugs identified as T. melanosoma and those identified as T. infestans belonged to different species. The taxonomic position of T. melanosoma should therefore be reconsidered.

Analysis of Variance↗

Signaling by the respiratory burst in macrophages.

During phagocytosis or stimulation with a wide variety of agents, macrophages and other phagocytic cells produce reactive oxygen species (ROS) through activation of a multicomponent NADPH oxidase. ROS production through related NADPH oxidases has recently been demonstrated in several other cell types. Furthermore, the physiological generation of ROS production has now been clearly implicated in activating signaling pathways resulting in a broad array of physiological responses from cell proliferation to gene expression and apoptosis. This brief review suggests that: 1) hydrogen peroxide and superoxide, but not the hydroxyl radical, function as second messengers; 2) antioxidant enzymes function in the "turn-off" phase of signal transduction; 3) the chemistry of thiols is critical in redox signaling; and 4) the primary physiological role of the respiratory burst in macrophages may be in redox signaling rather than microbicidal activity.

Animals↗

CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses.

CCR6 expression in dendritic, T, and B cells suggests that this beta-chemokine receptor may regulate the migration and recruitment of antigen-presenting and immunocompetent cells during inflammatory and immunological responses. Here we demonstrate that CCR6-/- mice have underdeveloped Peyer's patches, in which the myeloid CD11b+ CD11c+ dendritic-cell subset is not present in the subepithelial dome. CCR6-/- mice also have increased numbers in T-cell subpopulations within the intestinal mucosa. In 2,4-dinitrofluorobenzene-induced contact hypersensitivity (CHS) studies, CCR6-/- mice developed more severe and more persistent inflammation than wild-type (WT) animals. Conversely, in a delayed-type hypersensitivity (DTH) model induced with allogeneic splenocytes, CCR6-/- mice developed no inflammatory response. The altered responses seen in the CHS and DTH assays suggest the existence of a defect in the activation and/or migration of the CD4(+) T-cell subsets that downregulate or elicit the inflammation response, respectively. These findings underscore the role of CCR6 in cutaneous and intestinal immunity and the utility of CCR6-/- mice as a model to study pathologies in these tissues. This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.

Animals↗

Vanadyl sulfate improves hepatic and muscle insulin sensitivity in type 2 diabetes.

Vanadyl sulfate (VOSO(4)) is an oxidative form of vanadium that in vitro and in animal models of diabetes has been shown to reduce hyperglycemia and insulin resistance. Small clinical studies of 2- to 4-week duration in type 2 diabetes (T2DM) have led to inconsistent results. To define its efficacy and mechanism of action, 11 type 2 diabetic patients were treated with VOSO(4) at a higher dose (150 mg/day) and for a longer period of time (6 weeks) than in previous studies. Before and after treatment we measured insulin secretion during an oral glucose tolerance test, and endogenous glucose production (EGP) and whole body insulin-mediated glucose disposal using the euglycemic insulin clamp technique combined [3-(3)H]glucose infusion. Treatment significantly improved glycemic control: fasting plasma glucose (FPG) decreased from 194 +/- 16 to 155 +/- 15 mg/dL, hemoglobin A(1c) decreased from 8.1 +/- 0.4 to 7.6 +/- 0.4%, and fructosamine decreased from 348 +/- 26 to 293 +/- 12 micromol/L (all P < 0.01) without any change in body weight. Diabetics had an increased rate of EGP compared with nondiabetic controls (4.1 +/- 0.2 vs. 2.7 +/- 0.2 mg/kg lean body mass.min; P< 0.001), which was closely correlated with FPG (r = 0.56; P< 0.006). Vanadyl sulfate reduced EGP by about 20% (P< 0.01), and the decline in EGP was correlated with the reduction in FPG (r = 0.60; P< 0.05). Vanadyl sulfate also caused a modest increase in insulin-mediated glucose disposal (from 4.3 +/- 0.4 to 5.1 +/- 0.6 mg/kg lean body mass x min; P< 0.03), although the improvement in insulin sensitivity did not correlate with the decline in FPG after treatment (r = -0.16; P = NS). Vanadyl sulfate treatment lowered the plasma total cholesterol (223 +/- 14 vs. 202 +/- 16 mg/dL; P < 0.01) and low density lipoprotein cholesterol (141 +/- 14 vs. 129 +/- 14 mg/dL; P < 0.05), whereas 24-h ambulatory blood pressure was unaltered. We conclude that VOSO(4) at maximal tolerated doses for 6 weeks improves hepatic and muscle insulin sensitivity in T2DM. The glucose-lowering effect of VOSO(4) correlated well with the reduction in EGP, but not with insulin-mediated glucose disposal, suggesting that liver, rather than muscle, is the primary target of VOSO(4) action at therapeutic doses in T2DM.

Blood Pressure↗

Control of retinal ganglion cell axon growth: a new role for Sonic hedgehog.

Retinal ganglion cell (RGC) axons grow towards the diencephalic ventral midline during embryogenesis guided by cues whose nature is largely unknown. We provide in vitro and in vivo evidence for a novel role of Sonic hedgehog (SHH) as a negative regulator of growth cone movement. SHH suppresses both the number and the length of neurites emerging from the chick retina but not from neural tube or dorsal root ganglia explants, without interfering with their rate of proliferation and differentiation. Similarly, retroviral-mediated ectopic expression of Shh along the chick visual pathway greatly interferes the growth of RGC axons. Upon SHH addition to grown neurites, the intracellular level of cAMP decreases, suggesting that the dampening of growth cone extension mediated by SHH may involve interaction with its receptor Patched which is expressed by RGC. Based on these findings, we propose that Shh expression at the chiasm border defines a constrained pathway within the ventral midline which serves to guide the progression of RGC axons.

Animals↗

Life cycle and reproductive parameters of Clerada apicicornis signoret (Hemiptera: Lygaeidae) under laboratory conditions.

The life cycle of Clerada apicicornis was determined under laboratory conditions. Mean development times in days were: egg 27.2, nymph I 12.5, nymph II 12, nymph III 13.4, nymph IV 16.4, nymph V 26. The life expectancy of adults ranged from 117 to 317 days (mean 196 days). Based on a cohort of 29 females of C. apicicornis, a horizontal life table was constructed. The following predictive parameters were obtained: net rate of reproduction (Ro = 48.31), intrinsic rate of population increase (r(m) = 0.153), generation time (Tc = 28.20 weeks), and finite rate of population increment (lambda = 1.16). The reproductive value (Vx) for each age class of the cohort females was calculated. The following observed parameters were calculated after mortality in each stage: net rate of reproduction (R'o=13.4), intrinsic rate of population increase (r c' =0.09 ), and finite rate of population increment (lambda' =1.1). The generation time (Tc' =27.4) was estimated using the methods of Laughlin and Bengstron. A vertical life table was elaborated and mortality was described for one generation of the cohort.

Animals↗

[Influence of breakfast on cognitive functions of children from an urban area in Valencia, Venezuela].

It's well known that physical growth and intellectual activity is influenced by nutritional status. With the purpose of evaluate the fasting effects on the cognitive functions, anthropometric state and cognitive functions (logic and school work performance), under fasting and post-breakfast condition were assessed in a group of 68 school children age 9 and 10 years, who studied in a private school (1998-1999). Logic reasoning was measured with Raven test and attention, precision, velocity and fatigue with the Lepez test. The main of the children (80%) were well-nourished and 20% had showed overweight. At breakfast condition all subjects were over 50 percentil for Raven test. Consumption of breakfast influence on logic reasoning (p < 0.001) and school work performance (p < 0.01). It is concluded that in these well nourished children, breakfast consumption improved cognitive performance.

Anthropometry↗

Parametric Bragg resonances in waves on a shallow fluid over a periodically drilled bottom.

Bragg resonances involving strong interactions among Fourier wave components of a periodically drilled bottom and parametrically driven surface waves on a shallow liquid are experimentally shown to break down the secular dispersion relation of surface waves. When the fluid is sufficiently shallow, wave components that match reciprocal wave vectors of the bottom topography are dominant. Experimental evidence of band-gap phenomena in these surface waves are also shown. Moreover, the prevalence of Bragg resonances is so strong that one of them is excited anomalously within the band gap.

Journal Article↗

Use of coping strategies and breast cancer survival: results from the Black/White Cancer Survival Study.

This analysis was designed to evaluate the association between coping strategies and breast cancer survival among Black and White women in a large population-based study. A total of 442 Black and 405 White US women diagnosed with invasive breast cancer during 1985-1986 and actively followed for survival through 1994 were administered a modified Folkman and Lazarus Ways of Coping questionnaire. Coping strategies were characterized via factor analyses of the responses. Hazard ratios associated with coping strategies were estimated using Cox proportional hazards models, with adjustment for age, race, tumor stage, study location, tumor hormone responsiveness, comorbidity, health insurance status, smoking, relative body weight, and alcohol consumption. Emotion-focused coping strategies were significantly associated with survival. Expression of emotion was associated with better survival (hazard ratio = 0.6; 95% confidence interval: 0.4, 0.9). When it was considered jointly with the presence or absence of perceived emotional support, women reporting low levels of both emotional expression and perceived emotional support experienced poorer survival than women reporting high levels of both (hazard ratio = 2.5; 95% confidence interval: 1.7, 3.7). Similar risk relations were evident for Blacks and Whites and for patients with early and late stage disease. These results suggest that the opportunity for emotional expression may help improve survival among patients with invasive breast cancer.

Adaptation, Psychological↗

Beryllium presentation to CD4+ T cells underlies disease-susceptibility HLA-DP alleles in chronic beryllium disease.

Chronic beryllium disease results from beryllium exposure in the workplace and is characterized by CD4(+) T cell-mediated inflammation in the lung. Susceptibility to this disease is associated with particular HLA-DP alleles. We isolated beryllium-specific T cell lines from the lungs of affected patients. These CD4(+) T cell lines specifically responded to beryllium in culture in the presence of antigen-presenting cells that expressed class II MHC molecules HLA-DR, -DQ, and -DP. The response to beryllium was nearly completely and selectively blocked by mAb to HLA-DP. Additional studies showed that only certain HLA-DP alleles allowed presentation of beryllium. Overall, the DP alleles that presented beryllium to disease-specific T cell lines match those implicated in disease susceptibility, providing a mechanism for this association. Based on amino acid residues shared by these restricting and susceptibility DP alleles, our results provide insight into the residues of the DP beta-chain required for beryllium presentation.

Alleles↗

Periconceptional vitamin use, dietary folate and occurrent neural tube defected pregnancies in a high risk population.

PURPOSE: This 5 year (1992-1997) population-based case control study was conducted to determine if supplemental or dietary folate taken during the periconceptional period reduces the risk of occurrent neural tube defect (NTD) affected pregnancies in a high risk population.METHODS: Cases were all NTD pregnancies including elective terminations, fetal deaths and live births in South Carolina. Only isolated, occurrent NTD affected pregnancies were included (N = 179). Controls (N = 288) were randomly selected from each hospital in proportion to the hospital's contribution to the total live births in the state for the previous year. All mothers were interviewed in person using a modified Centers for Disease Control and Prevention Birth Defect Risk Factor Surveillance Mother's Questionnaire and the Harvard Food Frequency Questionnaire.RESULTS: Women who used a vitamin with 0.4 mg or more of folate at least 3 times per week during the 3 months before and 3 months after conception had a lower risk of having an NTD affected pregnancy than women who took no folate supplementation at any time during pregnancy [adjusted odds ratio (AOR) = 0.42; 95% confidence interval (CI) = 0.19-0.94]; women who used a vitamin with 0.4 mg or more of folic acid for less than 3 times per week or in partial months during the 6 month periconceptional period also had a slightly lower risk of having an NTD affected pregnancy relative to women who used no folate supplementation at any time during pregnancy [AOR =.72; 95% CI = 0.41-1.30]. The risk of NTD affected pregnancy was also lower for women who daily consumed foods containing higher levels of folate: AORs were 0.36 (95% CI = 0.18-0.73), 0.72 (95% CI = 0.42-1.22), and 0.61 (95% CI 0.36-1.04) from the highest to lowest quartile of dietary folate which were 0.457-3.12 mg, 0.322-0.457 mg, and 0.236-0.322 mg respectively.CONCLUSIONS: A reduction in occurrent NTD risk associated with folate supplementation and dietary intake was observed.

Journal Article↗

Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in healthy household contacts of patients with active tuberculosis and healthy controls from the community.

Protective immunity against Mycobacterium tuberculosis requires CD4+ lymphocyte-mediated immune responses and IFN-gamma activity. As the primary portal of entry of M. tuberculosis is the lung, pulmonary immune responses against multiple M. tuberculosis Ags were compared between both M. tuberculosis-exposed tuberculin skin test-positive healthy household contacts (HHC) of patients with active sputum smear and culture-positive tuberculosis and tuberculin skin test-positive healthy control individuals from the community (CC). Frequencies of M. tuberculosis Ag-specific IFN-gamma-producing cells, IFN-gamma concentrations in culture supernatants, and DNA synthesis in bronchoalveolar cells (BAC) and PBMC were studied in HHC (n = 10) and CC (n = 15). Using enzyme-linked immunospot assay we found higher frequencies of IFN-gamma-producing cells with specificity to M. tuberculosis-secreted Ag 85 (Ag 85) in BAC from HHC than in BAC from CC (p < 0.022) and relative to autologous PBMC, indicating compartmentalization of Ag 85-specific cells to the lungs. Further, IFN-gamma-producing cells with specificity to components A and B of Ag 85 were specifically compartmentalized to the lungs in HHC (p < 0. 05). IFN-gamma concentrations in culture supernatants of BAC and Ag-specific DNA synthesis were low and comparable in the two subject groups. Increased immune responses to Ag 85 at the site of repeated exposure to M. tuberculosis (the lung) may represent an important component of protective immunity against M. tuberculosis. Correlates of protective immunity against M. tuberculosis are required for assessment of the efficiency of anti-tuberculous vaccines.

Acyltransferases↗