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Biomedical subjects

C Díaz

Publications and source records attributed to C Díaz.

At least 73 records · Page 4Linked to original sources

Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2.

Arsenic (As) is a common metalloid which contaminates drinking water in several regions of the world and chronic exposure is associated with skin, lung, bladder, and kidney cancer. Previous studies suggest that arsenic exposure leads to a diminution of phytohemaglutinin (PHA) stimulated T cell proliferation in humans. In order to understand the mechanism of this suppression, the effect of As was evaluated on the expression of CD25, and IL-2 secretion in human peripheral blood mononuclear cells (PBMC). Inhibition of proliferation was observed in all donors studied. Most of the donors did not show any change in the expression of CD25, but IL-2 secretion was inhibited in 6 of the 7 donors tested. Proliferative inhibition was due to a suboptimal levels of IL-2 secreted by lymphocytes, since the addition of recombinant IL-2 to the cultures reversed in a dose-dependent fashion the inhibitory effect of As. The determination of the mRNA of IL-2 and the intracellular IL-2 levels demonstrated that the inhibition is not at the transcriptional level. Electron microscopy studies revealed that cellular ultrastructure in Golgi apparatus, mitochondria, cytoskeleton, and perinuclear membrane were altered. These alterations suggest that due to sodium arsenite effects on cytoskeleton, the intracellular secretion of proteins is affected, including the one of IL-2, leading to an impaired proliferation of the T cells when stimulated with PHA.

Adult↗

[Sweet's syndrome and motor neuron disease associated with esophageal carcinoma].

The paraneoplastic syndromes are an a group of clinical manifestations of uncommon frequency that they are associated with tumors and they often are precursors of these. The Sweet's syndrome is a dermatosis characterized by fever, erythematous plaques and infiltrate consisting of mature neutrophils. It occurs occasionally in association with hematologic malignancies and is very rare with solid tumors. The isolated motor neuron disease is rare like paraneoplastic syndrome. We report the case of a patient with epidermoid carcinoma of esophagus that it was diagnosed after beginning clinically with two paraneoplastic syndromes: Sweet's syndrome and motor neuron disease.

Biopsy↗

Plasma glutathione concentrations in non-infected infants born from HIV-infected mothers: developmental profile.

Glutathione (GSH) is the primary antioxidant in humans. Oxidative cellular injury is postulated to be centrally involved in diverse processes including aging, cancer, cardiovascular disease, and Human Immunodeficiency Virus (HIV) disease progression. Normal plasma GSH concentrations have been well characterized in healthy children and adults, but not during infant development. The objectives of this study were to: a) measure plasma GSH concentrations in non-infected infants born from HIV-infected mothers, to b) assess the developmental variations with age and gender, and c) evaluate for possible associations with growth, anemia, and other maternal and infant variables. One hundred and seventy (170) plasma samples from 44 HIV-uninfected infants (birth to 18 mos.) born to HIV-infected mothers from the Women and Infant Transmission Study (Puerto Rico site) were analyzed. The total plasma GSH geometric mean concentration for all samples analyzed was 1.94 (1.06) mumoles/L. A developmental effect of age was seen with lower concentrations in younger infants (0-2 months) than in older infants 4-18 months. There was no significant effect of gender, anemia, zidovudine exposure, maternal age, maternal CD4 cell percent, or infant growth, although a trend towards increasing GSH concentration was seen with increasing weight for height z-score. These findings have multiple clinical ramifications including prediction of capacity to detoxify oxidants at different ages, and partial explanation for the increased viral loads seen in HIV-infected infants.

Adult↗

Peritoneal kinetics of cancer antigen 125 in peritoneal dialysis patients: the relationship with peritoneal outcome.

Cancer antigen 125 (CA125) is a mesothelial product that has been directly related with mesothelial bulk in peritoneal dialysis (PD) patients. Here, we evaluate CA125 levels in peritoneal effluent over time on PD, and relate them to changes in peritoneal function. We analyzed 27 peritoneal kinetic studies in 20 stable PD patients. Three patients dropped out of PD for peritoneal membrane failure after the last kinetic study, and six patients required a peritoneal rest period as treatment for membrane failure type I. We recorded the standardized daily ultrafiltration capacity, net ultrafiltration during the kinetic study, peritoneal mass transfer coefficients, time from onset of PD, and incidence of peritonitis prior to the study. A linear increase in CA125 levels over time was observed, and a strong correlation appears among the levels at different dwell times (r: 0.85-0.98, p < 0.05). At 180 minutes, the mean CA125 concentration was 48.5 +/- 39.7 U/mL. We observed significant differences in CA125 levels in effluent between the group of patients who later required a peritoneal rest period and the group of stable patients (27.7 +/- 26.3 U/mL vs 55.7 +/- 41.5 U/mL respectively, p < 0.05). Patients who left PD showed lower CA125 levels in effluent (31.4 +/- 30.6 U/mL vs 52.3 +/- 41.1 U/mL, p < 0.1). No correlation was seen between CA125 levels in effluent and time on PD, episodes of peritonitis, accumulated days of peritoneal inflammation, ultrafiltration capacity, or urea and creatinine mass transfer coefficients (MTCs). In conclusion, we believe that serial determinations of peritoneal effluent CA125 levels may help in the early identification of patients who show abnormal responses to peritoneal dialysis or its complications.

CA-125 Antigen↗

The relationship between rhombomeres and vestibular neuron populations as assessed in quail-chicken chimeras.

The aim of this study was to evaluate the role segmentation plays in the determination of neuronal identity in the hindbrain. We focused on two specific sets of hindbrain neurons, namely, the vestibulospinal and vestibulo-ocular neurons, which comprise distinct groups that can be identified and distinguished by virtue of their axonal projection pathways. The relationship between rhombomeres and the vestibular neuron groups was assessed by a combination of quail-chicken chimeric grafting and selective retrograde axonal tracing. Individual quail hemirhombomeres were transplanted homotopically and isochronically into a chicken embryo host. Subsequently, vestibulospinal and vestibulo-ocular neurons with specific axon trajectories were labeled retrogradely with biotin-conjugated dextran-amines. The relationship between the spatial domains of the vestibular neuron groups and rhombomere-derived domains had the following features: (1) some groups were derived from single rhombomeres; (2) some groups were derived from multiple contiguous rhombomeres; (3) two groups occupied domains that could not be defined in terms of whole rhombomere lengths; (4) some groups spanning multiple rhombomeres exhibited an internal cytoarchitectonic organization that related to individual rhombomeres; and (5) some groups exhibited limited boundary violation. These results support the notion that positional information within defined domains of the neural tube provides a groundplan for the regional determination of neuronal identity and axon pathfinding, and that hindbrain segmentation contributes to this process. But they also indicate that segmentation is not the only mechanism that defines the rostrocaudal domains of neuron types. Moreover, they emphasize that the relationship between rhombomeres and neuronal determination cannot be couched simply in terms of segmental iteration or of bimeric (paired rule) specification.

Animals↗

3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.

Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to induce apoptosis in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis of VSMCs, cultured rat VSMCs were treated with increasing doses of atorvastatin in the presence of FBS as a survival factor. The presence of apoptosis was evaluated by morphological criteria, annexin V binding, and DNA fragmentation and quantified as the proportion of hypodiploid cells by flow cytometry. Atorvastatin induced apoptosis in a dose-dependent manner, an effect also seen with simvastatin and lovastatin, but not with the hydrophilic drug pravastatin. The proapoptotic effect of statins was seen only when the inhibition of acetate incorporation into sterols was >95% and was fully reversed by mevalonate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate but not by isopentenyl adenosine, ubiquinone, or squalene, suggesting a role for prenylated proteins in the regulation of VSMC apoptosis. To further assess the role of protein prenylation, VSMCs were exposed to the prenyl transferase inhibitors perillic acid and manumycin A. Both agents induced VSMC apoptosis as evaluated by the above-mentioned criteria. Finally, VSMC treatment with lipophilic statins was associated with decreased prenylation of p21-Rho B, further supporting the role of protein prenylation inhibition in statin-induced VSMC apoptosis. The present data suggest that interference with protein prenylation by HMG-CoA reductase inhibitors or other agents may provide new strategies for the prevention of neointimal thickening.

Animals↗

Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells.

Endothelial dysfunction associated with atherosclerosis has been attributed to alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or to an excess of endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to ameliorate endothelial function. However, the physiological basis of this observation is largely unknown. We investigated the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and protein levels in bovine aortic endothelial cells. These agents inhibited pre-proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70% maximum inhibition) and reduced immunoreactive ET-1 levels (25-50%). This inhibitory effect was maintained in the presence of oxidized LDL (1-50 microg/ml). No significant modification of pre-proET-1 mRNA half-life was observed. In addition, mevalonate, but not cholesterol, reversed the statin-mediated decrease of pre-proET-1 mRNA levels. eNOS mRNA expression was reduced by oxidized LDL in a dose-dependent fashion (up to 57% inhibition), whereas native LDL had no effect. Statins were able to prevent the inhibitory action exerted by oxidized LDL on eNOS mRNA and protein levels. Hence, these drugs might influence vascular tone by modulating the expression of endothelial vasoactive factors.

Animals↗

Amino acid sequence of a myotoxic Lys49-phospholipase A2 homologue from the venom of Cerrophidion (Bothrops) godmani.

The complete amino acid sequence of myotoxin II (godMT-II), a myotoxic phospholipase A2 (PLA2) homologue from the venom of the Central American crotaline snake Cerrophidion (Bothrops) godmani, was determined by direct protein sequencing methods. GodMT-II is a class II PLA2 showing a Lys instead of Asp at position 49. An additional substitution in the calcium binding loop region (Asn instead of Tyr at position 28) suggests the lack of enzymatic activity observed in this toxin is due to loss of its ability to bind the co-factor Ca2+, since the residues involved in forming the catalytic network of PLA2s (His-48, Tyr-52 and Asp-99) are conserved in godMT-II. This myotoxin shows highest sequence homology with other Lys-49 PLA2 s from Bothrops, Agkistrodon and Trimeresurus species, suggesting that they constitute a conserved family of proteins, yet in contrast presents lower homology with Bothrops asper myotoxin III, a catalytically-active PLA2. The C-terminal region of godMT-II, which is rich in cationic and hydrophobic residues, shares high sequence homology to the corresponding region in the myotoxin II from B. asper, which has been proposed to play an important role in the Ca(2+)-independent membrane damaging activity.

Amino Acid Sequence↗

Effect of hypolipidemic drugs on key enzyme activities related to lipid metabolism in normolipidemic rabbits.

The effect of atorvastatin (3 mg kg(-1) day(-1)), simvastatin (3 mg kg(-1) day(-1)) and bezafibrate (100 mg kg(-1) day(-1)) administered for 4 weeks to male New Zealand white rabbits on enzyme activities related to lipid metabolism has been studied. Only the statins reduced plasma cholesterol values, while none of the drugs modified plasma triglyceride or high density lipoprotein (HDL)-cholesterol concentrations, nor the activity of enzymes such as hepatic diacylglycerol acyltransferase, lipoprotein lipase or hepatic lipase, directly involved in triglyceride metabolism. Both statins elicited similar increases in the hepatic microsomal 3-hydroxy-3-methyl-glutaryl Coenzyme A (CoA) reductase activity (147 and 109% induction for simvastatin and atorvastatin, respectively), and none of the drugs assayed modified hepatic acyl-coenzyme A:cholesterol acyltransferase activity significantly. Only bezafibrate induced a significant 57% reduction in the activity of hepatic microsomal cholesterol 7alpha-hydroxylase. Regarding the rate limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyl transferase, atorvastatin and bezafibrate behaved similarly, decreasing the enzyme activity in the liver by 45% and 54%, respectively; simvastatin induced no modification of this activity. The reduction of CTP:phosphocholine cytidylyl transferase activity is not caused by a direct inhibition of the enzyme by bezafibrate and atorvastatin. Further, the inhibitory effect of atorvastatin appears to be unrelated to the inhibition of 3-hydroxy-3-methyl-glutaryl CoA reductase elicited in vivo.

Acyltransferases↗

Neuronal loss in human medial vestibular nucleus.

The data concerning the effects of age on the brainstem are inconsistent, and few works are devoted to the human vestibular nuclear complex. The medial vestibular nucleus (MVN) is the largest nucleus of the vestibular nuclear complex, and it seems to be related mainly to vestibular compensation and vestibulo-ocular reflexes. Eight human brainstems have been used in this work. The specimens were embedded in paraffin, sectioned, and stained by the formaldehyde-thionin technique. Neuron profiles were drawn with a camera lucida at x330. Abercrombie's method was used to estimate the total number of neurons. We used the test of Kolmogorov-Smirnov with the correction of Lilliefors to evaluate the fit of our data to a normal distribution, and a regression analysis was performed to determine if the variation of our data with age was statistically significant. The present study clearly shows that neuronal loss occurs with aging. The total number of neurons decreases with age, from 122,241 +/- 651 cells in a 35-year-old individual to 75,915 +/- 453 cells in an 89-year-old individual. Neuron loss was significant in the caudal and intermediate thirds of the nucleus, whereas the changes in the rostral third were not significant. The nuclear diameter of surviving neurons decreased significantly with age. There is a neuron loss in the MVN that seems to be age-related. It could help explain why elderly people find it hard to compensate for unilateral vestibular deficits. The preservation of neurons in the rostral third could be related to the fact that this area primarily innervates the oculolmotor nuclei; these latter neurons do not decrease in number in other species studied.

Adult↗

Leukotriene A4 hydrolase and leukotriene C4 synthase activities in human chondrocytes: transcellular biosynthesis of Leukotrienes during granulocyte-chondrocyte interaction.

OBJECTIVE: To investigate the cooperation of chondrocytes and polymorphonuclear cells (PMN) in the biosynthesis of leukotrienes (LT). METHODS: PMN, resting and interleukin-1beta-stimulated cultured human chondrocytes, and mixtures of both cell types were incubated with A23187 and/or 14C-arachidonic acid (14C-AA). To explore the presence of LTC4 synthase and LTA4 hydrolase, the chondrocytes were incubated with authentic LTA4. Eicosanoids were analyzed using high performance liquid chromatography techniques. RESULTS: Chondrocytes formed only prostaglandin E2 and minor amounts of 15-HETE and 11-HETE, the production of all of which was inhibited by 1 microM indomethacin. Incubation of PMN and chondrocytes produced more LTC4 from endogenous and exogenous AA, and more LTB4 from endogenous AA, than incubation of PMN alone, which was consistent with the presence of LTC4 synthase and LTA4 hydrolase activities in chondrocytes. Chondrocytes also slightly increased the level of PMN production of all 5-lipoxygenase (5-LO)-derived products from endogenous AA. CONCLUSION: Human chondrocytes form eicosanoids from AA only by the cyclooxygenase pathway. Chondrocytes cooperate in the transcellular biosynthesis of LT since they possess LTA4 hydrolase and LTC4 synthase activities and increase metabolism by the 5-LO pathway in PMN.

Arachidonic Acid↗

Chronic hepatitis C in children: a clinical and immunohistochemical comparative study with adult patients.

Limited information is available regarding the characteristics of the hepatitis C virus (HCV) infection in children. We compared the epidemiological background along with the virological and histological features as well as the intrahepatic immunologic phenotype of both children and adults with chronic hepatitis C (CHC). Serum samples of 24 pediatric and 32 adult patients were drawn for alanine transaminase (ALT) levels, HCV-typing, and viral load. The histological diagnosis and a semiquantitative immunohistochemical assessment were performed in all patients. The majority of children (62%) had been transfused and the mean duration of viral infection in these cases was 11 +/- 4 years, being similar in adults (11 +/- 9 years, not significant). Although genotype distribution was similar, viral load was lower in children than in adults. The mildest histological forms of chronic hepatitis along with a weak intrahepatic immunological phenotype were significantly more frequent among children than adult patients. In conclusion, in children with CHC, perinatal blood transfusion was the most frequent source of viral infection and the liver disease was characterized by both low ALT level and viral load, as well as the mildest histological and immunohistochemical forms of chronic hepatitis.

Adolescent↗

"Alone, I wouldn't have known what to do": a qualitative study on social support during labor and delivery in Mexico.

This article presents some of the most relevant qualitative results of a trial to evaluate the effects of the provision of psychosocial support to first-time mothers during labor, childbirth and in the immediate postpartum period in a social security hospital in Mexico City. The article focuses on the experiences of mothers who have received psychosocial support from a doula (the term doula is used to identify a woman who provides continuous support to a woman during labor. delivery and the immediate postpartum period) and compares them with the experiences of those women who gave birth following normal hospital routine. Sixteen in-depth interviews were held with women in the immediate post partum period (eight of whom had been accompanied by a doula and eight who had not) before they were discharged from hospital, and the results were analyzed using qualitative techniques. The interviews showed that the women accompanied by a doula had a more positive childbirth experience. The differences between both groups related to their perceptions of the childbirth experience; the treatment they received from hospital staff; the information they were given and how well they understood it; their perception of hospital routines; their feelings about cesarean sections and, spatial and temporal perceptions. The most important difference between the two groups was the way they expressed their feelings about their own labor, their sense of control and their self-perception.

Delivery, Obstetric↗

HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis.

OBJECTIVES: To study the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitor atorvastatin on the potential mechanisms involved in the recruitment of monocytic cells into the vessel wall. BACKGROUND: Inhibitors of HMG-CoA-reductase reduce cardiovascular mortality though the mechanisms yet elucidated. Most ischemic events are secondary to disruption of atherosclerotic plaques highly infiltrated by macrophages. METHODS: Atherosclerosis was induced in the femoral arteries of rabbits by endothelial damage and atherogenic diet for 4 weeks. Then, animals were switched to standard chow and randomized to receive either no treatment or atorvastatin (5 mg/kg/d) and killed after 4 weeks. RESULTS: Atorvastatin induced a significant reduction in serum lipids and in lesion size. Arterial macrophage infiltration was abolished by the treatment, and monocyte chemoattractant protein-1 (MCP-1) was significantly diminished in the neointima and in the media. Nuclear factor kappa-B (NF-kappaB) was activated in the 60% of the lesions, both in macrophages and vascular smooth muscle cells (VSMC), of the untreated group while only in 30% of the atorvastatin group. NF-kappaB activity was also lower in the uninjured aorta and liver of treated compared with untreated rabbits. In cultured VSMC, MCP-1 expression and NF-kappaB activity induced by tumor necrosis factor alpha were downregulated by atorvastatin. CONCLUSIONS: In a rabbit atherosclerosis model, atorvastatin diminishes the neointimal inflammation, and this could contribute to the stabilization of the atherosclerotic plaque. This may be an additional explanation for the reduction of acute ischemic events in patients treated with statins.

Animals↗

Troponin-T is a calcium-binding protein in insect muscle: in vivo phosphorylation, muscle-specific isoforms and developmental profile in Drosophila melanogaster.

Two sets of muscle polypeptides showing calcium-binding capacity and intense labelling in vivo with 32P were purified and characterized from Drosophila melanogaster adult extracts. The polypeptides exhibit crossed immunoreactivity and share similar biochemical properties such as those involved in purification. They have been identified as isoforms of troponin-T (TnT) by sequence analysis of a cDNA clone isolated from an embryonic library. The two sets of TnT polypeptides correspond to the fibrillar and non-fibrillar muscle isoforms, respectively. The non-fibrillar muscle isoforms separate into two bands which are differentially expressed during development. Analysis of TnT isoforms in bee thoraces indicates that the expression of the fibrillar muscle isoform correlates with the acquisition of functional flight capability. In vivo labelling experiments reveal that the two TnT sets are readily phosphorylated. The Drosophila TnTs show calcium-binding properties by three different types of assays. Our results suggest that this property could be specific to insect TnTs and may be related to the long, extremely acidic polyglutamic carboxy-terminus present in these polypeptides, which does not occur in non-arthropod TnTs.

Amino Acids↗

Antibodies against a novel nucleolar and cytoplasmic antigen (p105-p42) present in the sera of patients with a subset of rheumatoid arthritis (RA) with signs of scleroderma.

We identified three patients (two of them relatives) with RA and signs of scleroderma whose sera contained a high titre of IgG class antibodies against the nucleoli and the nucleoplasm of cells of different mammalian origins. Sera from these patients uniformly immunoprecipitated four polypeptides, from a 35S-methionine-labelled HeLa cell extract, whose mol. wts were 120, 105, 95 and 42 kD. Of these, the 95-kD protein was highly phosphorylated. By immunoblotting, these sera reacted with 105-, 95- and 42-kD proteins and affinity-purified antibodies from these, demonstrating that 105- and 95-kD proteins shared cross-reactive epitopes. Moreover, affinity-purified antibodies from each of these proteins immunoprecipitated the whole complex. Localization studies using immunoelectron microscopy and in vivo actinomycin-D-treated cells demonstrated that the 105-, 95- and 42-kD proteins were present in the granular component of the nucleolus and the nucleoplasm. In addition, the 105- and 95-kD were present in free polyribosomes as well as ribosomes attached to endoplasmic reticulum. Pulse/chase experiments strongly suggested that the complex was accomplished shortly after a 10-min pulse. It was preferentially present in the nucleus after a 2 h chase and in both nucleus and cytoplasm after a 5 h chase. We conclude that a protein complex with a main nucleolar distribution is a new autoantigen (p105-p42) recognized by autoantibodies present in the serum of a subgroup of patients with RA and scleroderma signs. These antibodies could be useful as diagnostic markers and as tools for further studies involving the biology of the nucleolus.

Antibodies, Antinuclear↗

Plasma glutathione concentrations in children infected with human immunodeficiency virus.

BACKGROUND: Glutathione (GSH) is the principal intracellular defense against oxidants, and HIV-infected individuals tend to have subnormal concentrations in plasma. This GSH deficiency may contribute to the pathogenesis of disease progression. In the pediatric population correlations between GSH concentrations with clinical, immunologic and virologic disease profiles are scarce. OBJECTIVES: The main objectives of this study were (1) to compare plasma GSH concentrations of HIV-infected children and healthy controls and (2) to correlate GSH values with clinical, immunologic and virologic disease indices. METHODS: Twenty-four HIV-infected and 24 healthy control children entered the study. Plasma concentrations of total glutathione and related thiols were determined. RESULTS: The difference in mean plasma GSH concentrations between HIV-infected (2.96 +/- 0.31 microM) and control (6.62 +/- 0.58 microM) groups was highly significant (P < 0.0001). Linear regression analyses in HIV-infected patients revealed significant correlations between GSH and both absolute CD4+ cell counts (r = 0.56, P = 0.004) and viral load measured as log HIV-RNA PCR (r = -0.49, P = 0.018). GSH concentrations did not significantly correlate with CDC clinical stage but were lower in HIV-infected patients with growth failure (1.60 +/- 0.54 microM) vs. non-growth failure (3.23 +/- 0.33 microM); P = 0.05. CONCLUSIONS: This study confirmed that HIV-infected children are deficient in plasma GSH concentrations compared with healthy controls. We documented that low GSH concentrations in HIV-infected children are directly correlated with CD4+ cell counts and inversely correlated with viral loads. These findings support a possible role of GSH in the pathogenesis of HIV disease progression.

CD4 Lymphocyte Count↗