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Biomedical subjects

N Martinez

Publications and source records attributed to N Martinez.

At least 19 recordsLinked to original sources

15-Deoxy-Delta12,14-prostaglandin J2 and peroxisome proliferator-activated receptor gamma (PPARgamma) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARgamma agonist on nitridergic and lipid placental metabolism.

15-Deoxy-Delta(12,14)-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor (3) (PPAR(3)) ligand that regulates lipid homeostasis and has anti-inflammatory properties in many cell types. We postulated that 15dPGJ2 may regulate lipid homeostasis and nitric oxide (NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes-induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin-induced diabetic rats, 15dPGJ2 concentrations were decreased (83%) and immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/nitrites (an index of NO production) were diminished (40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPAR(3) activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of (14)C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPAR(3) activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPAR(3). We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPAR(3) were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.

Acetates↗

Genetic basis of antimicrobial drug resistance in clinical isolates of Salmonella enterica serotype Hadar from a Spanish region.

The genetic bases of antimicrobial drug resistance (R) of 79 Salmonella enterica serotype Hadar clinical isolates (recovered during 1995-2001 in a Spanish region) was investigated. The isolates showed a limited genomic variation, as demonstrated by PFGE analysis using XbaI (three profiles, S>or=0.77) and BlnI (seven profiles, S>or=0.49; with 95% of the isolates falling into two clusters, S>or=0.75). Thirteen R-profiles, ranging from susceptible to multidrug resistant, were recognized. All susceptible isolates (14%) were recovered before or during 1998, when multidrug resistance (MDR) was still uncommon (20% from 1995-1998). In later years, the percentage of MDR increased considerably (92% in 2001). Resistance to nalidixic acid, tetracycline, streptomycin and ampicillin-cefalotin, encoded by gyrA-Asp87/Asn, tet(A), strA/B, and bla (TEM) genes, respectively, were the most common, appearing together in 38% of the isolates. In all tetracycline- and streptomycin-resistant isolates, strA/B and tet(A) were chromosomally located, whereas bla (TEM) was plasmid-born. Five different bla (TEM) plasmids (pUO-ShR1 to pUO-ShR5, of about 9.4, 23, 30, 45, and 95 kb, respectively) were identified. pUO-ShR3 and pUO-ShR5 harbored additional R-genes: [dfrA1] and [acc(3)IV-strA/B], respectively. pUO-Sh2, pUO-Sh3, pUO-ShR4, and pUO-Sh5 were self-transferable, and the latter could also mobilize pUOShR1. The reported data constitute a useful background for further epidemiological studies of MDR in S. Hadar.

Drug Resistance, Multiple, Bacterial↗

Genetic diversity among sapoviruses.

Norovirus and Sapovirus are two genera of the family Caliciviridae that contain viruses that can cause acute gastroenteritis in humans. Noroviruses (NOR) are genetically highly diverse but limited studies of the genetic diversity of sapoviruses (SAP) have been reported. In this study we characterized twenty-five SAP detected in our laboratory from outbreaks or sporadic cases of acute gastroenteritis in children from different geographical locations and in adults involved in a cruise ship outbreak investigation and a nursing home outbreak. Based on significant differences of partial RNA polymerase sequences (278-286 nt), the 25 strains were grouped into 12 genetic clusters, including 9 potential new clusters. Extended sequence analysis of the capsid gene of selected strains representing five potential new clusters supported this grouping. Four strains (Hou7-1181/90, Mex340/90, Cruise ship/00 and Argentina39) had <84% amino acid (aa) identity to each other and to the published sequences in the GenBank. Mex14917/00 was almost identical to Stockholm/97/SE whose RNA polymerase sequence was unknown. Phylogenetic and distance analyses of the capsid region of the four new strains showed that Hou7-1181/90 and Argentina39 represent two new genogroups and Mex340/90 and Cruise ship/00 belong to two new clusters within the London/92 genogroup. Thus, based on the capsid sequences we propose to classify the currently known SAP into nine genetic clusters within five genogroups, including one genogroup that is represented by an animal calicivirus, the porcine enteric calicivirus (PEC).

Adult↗

Molecular studies and NK cell function of a new case of TAP2 homozygous human deficiency.

In this paper we describe the clinical and molecular features of a new case (GOR) of homozygous human TAP2 deficiency, analysing the phenotype and function of NK cells. The patient presented from infancy with recurrent sinopulmonary infections; a selective IgG2 deficiency, negative antibody response to polysaccharide vaccination and low level of cell surface expression of HLA class I antigens were found. The sequence of TAP2 gene identified a single mutation, a C to T substitution changing the CGA arg codon at amino acid 220 into TGA stop codon in exon 3. By using MoAbs for KIRs, CD94, CD94/NKG2A and ILT2 we observed, in agreement with others, that the latter two receptors were overexpressed on TAP2-deficient NK cells. The inhibitory CD94/NKG2A and triggering CD94/NKG2C NK receptors, specific for HLA-E, appeared to be functional in a limited number of NK clones that could be expanded in vitro. Expression of HLA-E was virtually undetectable in GOR B-LCL and very faint in PBMC, further supporting that interactions of class I leader sequence nonamers with HLA-E in the ER depend on a functional TAP complex.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A novel, nuclear pore-associated, widely distributed molecule overexpressed in oncogenesis and development.

Nuclear pore complexes are large, elaborate macromolecular structures that mediate the bidirectional nucleocytoplasmic traffic. In vertebrates, nuclear pore complexes comprise 50 to 100 proteins termed nucleoporins (Nup). An 88-kd nucleoporin (Nup88) has been recently cloned and characterized, and found to be associated in a dynamic subcomplex with the oncogenic nucleoporin CAN/Nup 214. We have produced a polyclonal antiserum to Nup88, and found that it immunoreacts convincingly in conventional tissue sections of 214 samples of malignant tumors of many types. All carcinomas were stained irrespective of site or line of differentiation; the majority of cases reacted strongly and extensively. In situ carcinomas and highly dysplastic epithelia were similarly reactive. Samples of malignant mesotheliomas, gliomas, sarcomas, and lymphoreticular tumors were also stained. Substantial reactions were also found in certain fetal tissues. Focal reactions were noted in some reactive-proliferative processes. Most benign epithelial and mesenchymal tumors and hyperplasias, and normal adult tissues reacted weakly and sporadically or not at all. Immunoblot analysis of selected samples strongly corroborated those findings. If further substantiated, our findings indicate that Nup88 could be regarded as a selective yet broadly based proliferation marker of potential significance in the histological evaluation and diagnosis of malignant transformation. Its ready applicability on conventional paraffin sections and on cytological preparations may broaden its clinical and investigative significance.

Adult↗

Genomic and antigenic variation among rotavirus strains circulating in a large city of Argentina.

Knowledge of the antigenic diversity of rotaviruses circulating in a region should be acquired before introducing a rotavirus vaccine. In a collection of 151 rotavirus-positive samples from Mendoza, Argentina, strain diversity was evaluated utilizing G-typing monoclonal antibodies (MAbs), reverse-transcriptase-polymerase chain reaction (RT-PCR) G and P typing, and electropherotyping (PAGE). The G type of 137 (91%) specimens was determined. Typing MAb reactivity with the homologous type ranged from 25-94%. For the seven G1 MAbs utilized, 28 patterns of reactivity among 68 G1 strains occurred. For the 48 G2 strains, six patterns of reactivity occurred utilizing three G2-specific MAbs. Of the 92 samples G- and P-typed by reverse-transcriptase-polymerase chain reaction, 89% had single G/P combinations: eight G1[P4], one G1[P6], twelve G1[P8], 58 G2 [P4], and two G2 [P6]. Nine samples had more than one G type with a single P type, one sample had two P types associated with one G type, and one sample contained multiple G and P types. Twenty-nine PAGE patterns occurred for all G types, but differences of antigenic reaction did not predict differences in migration of gene segments 7, 8, and 9. For three specimens showing discordant results between G type by enzyme-linked immunosorbent assay (EIA) and RT-PCR, we observed unexpected electropherotypes. Complementary evaluation by RT-PCR and MAb-based EIA with multiple typing MAbs revealed genetic and antigenic diversity of circulating rotaviruses, including extensive intratypic variation of the G1 and G2 neutralization antigens, in Mendoza during a single season of rotavirus activity.

Antibodies, Monoclonal↗

Diarrhea and enteric emerging viruses in HIV-infected patients.

To evaluate the prevalence of enteric viruses and their possible association with diarrhea, 244 stool samples were collected from HIV-infected and uninfected patients with or without diarrhea (subgroups I-a, Ib, II-a, and II-b, respectively). Subjects were screened by polyacrylamide gel electrophoresis, latex agglutination, and enzyme immunoassays for rotaviruses, adenoviruses, picobirnaviruses, and astroviruses. Enteric viruses were found significantly more often in specimens from HIV patients (20%) than in specimens from uninfected HIV patients (0%) (p < 0.05). Picobirnavirus was detected in 14.63% of 82 HIV-infected patients with diarrhea, but it was detected neither in those without diarrhea (0%) (p < 0.05) nor in the groups of uninfected HIV subjects (0%) (p < 0.05). Nor could astrovirus (subgroups I-a [4.00%] versus subgroup I-b [5.26%],p > 0.05) or enteric adenovirus (subgroup I-a [1.22%] versus subgroup I-b [0%], p > 0.05) be linked to the diarrhea disorder in HIV-infected patients. Rotaviruses were not detected in any of the clinical subgroups studied. Enteric viruses were detected in 15 of 93 (16.13%) of the HIV-infected patients with CD4+ T cell count <200/microl and 3 of 19 (15.79%) of those HIV-infected individuals with a CD4+ T cell count 200-499/microl, showing no significant difference (p > 0.05). According to our data, unusual enteric viruses such as picobirnavirus, astrovirus, and enteric adenovirus occur in HIV-infected population in Córdoba, Argentina. However, only picobirnaviruses could be significantly associated with diarrhea in these patients.

Argentina↗

Blood metabolites and their relationship with production variables in dual-purpose cows in Venezuela.

A survey was carried out on 79 lactating Bos taurus/indicus cross-bred cows on three dual-purpose cattle farms to measure the blood concentration of metabolites and to evaluate possible relationships with nutritional status and productive variables. A rotational grazing system on Star grass and other tropical pastures (10-12% CP in leaves) was used and 2-3 kg/cow/day of concentrate were fed on two farms. Restricted calf suckling was used in two herds. Average milk yield sold per farm was 6 kg/day/cow and body condition scores (BCS) were between 3.0 and 3.8 on a scale of one-to-five. On two farms, the average interval from calving to conception (ICC) was more than 145 days. Mean blood concentrations of albumin, globulin, urea, beta-hydroxybutyrate and phosphorus were generally within reference values, but a significant group of cows had low levels of albumin and urea and high levels of globulin. Packed cell volume (PCV) was below normal values, with anemia in 63% of cows during the second trimester of lactation, which was negatively correlated to milk yield. The high incidence of anemia could be related to factors such as hematophagic parasites, not evaluated in this study. ICC values were negatively related to albumin level and could be associated with protein deficiency in the diet or with disease, as globulin values were high in many cows. Based on these diagnoses, an experiment was carried out on one of the farms to evaluate the influence of supplementation with 0.5 kg/cow/day of fish meal. Total milk yield was not influenced by the fish meal and reproductive efficiency was high in the two supplemental treatments. It was shown that supplementation with undergraded protein is not required in these cows.

3-Hydroxybutyric Acid↗

Prevention by a silymarin/phospholipid compound of ethanol-induced social learning deficits in rats.

We explored the possibility that silymarin (SY), a fraction from Silybum marianum, might protect against the effects of in utero exposure to ethanol upon subsequent social memory function. Three groups of 8 pregnant female Sprague-Dawley rats each were provided with a liquid diet containing 35% ethanol derived calories (EDC). One experimental group received a daily subcutaneous injection of 400 mg/kg SY, the second, a 400 mg/kg oral dose of SY, a third group was maintained on the 35% EDC diet. A fourth group served as the pair-fed control group. The liquid diet regimen was maintained throughout pregnancy. Rats pups were fostered by dams in a fifth group that had been maintained on rat chow. At 90 days the pups were tested for social memory. Social recognition scores recorded for the ethanol pups were significantly poorer than those observed in both SY/ethanol groups and the chow group.

Animals↗

Recurrent hepatitis C virus infection after liver transplantation: immunohistochemical assessment of the viral antigen.

BACKGROUND: The value of immunohistochemical methods to identify hepatitis C virus antigen (HCVAg) in liver tissue has not been established. We have evaluated the significance of HCVAg expression in livers of patients with transplants and recurrent hepatitis C virus (HCV) infection. METHODS: Forty-two liver biopsy specimens from 32 liver-transplant recipients with recurrent HCV infection were tested for HCVAg using fluorescein isothiocyanate-labeled polyclonal, polyreactive human immunoglobulin. Histologic assessment of liver and quantitation of HCV RNA in sera were carried out in specimens obtained simultaneously with biopsies. RESULTS: HCVAg was found in 33% of the liver specimens obtained during the first month after transplantation and in all liver specimens obtained between 1 and 18 months after transplantation. Amounts of the antigen were significantly greater in specimens obtained more than 1 month after transplantation. A statistically significant increase of the average HCV RNA level in serum was observed in samples tested after the first month after the transplantation, and some decrease in the HCV RNA level was found in those obtained between 6 and 18 months after transplantation. Larger amounts of HCVAg were observed in specimens corresponding to episodes of acute or chronic hepatitis than in those associated with minimal parenchymal evidence of rejection. CONCLUSIONS: OBSERVATIONS of HCVAg expression in liver biopsy specimens indicated that the presence of viral antigens in hepatocytes is a constant finding in specimens obtained 1 month or longer after transplantation. Although large amounts of HCVAg correlated with acute or chronic hepatitis, the nature of this association with the development of pathologic changes remains to be established.

Adult↗

IgA anticardiolipin antibodies--relation with other antiphospholipid antibodies and clinical significance.

OBJECTIVE: To evaluate the usefulness of IgA antiphospholipid antibodies as markers of thrombosis and/or antiphospholipid antibody syndrome. PATIENTS AND METHODS: A cross-sectional study design in a tertiary, university-based, autoimmune reference hospital. Seven-hundred ninety-five patients classified into five different groups--autoimmune diseases (255), deep vein thrombosis (153), transitory ischemic attacks (108), obstetric complications (196), infectious diseases (83) and controls (81)--were tested for IgA, IgG and IgM aPL, and lupus anticoagulant. Plasma and serum samples were drawn for detection of aPL using an internationally standardized ELISA method and LA was carried out using coagulometric assays. RESULTS: True IgA aPL were found only in two patients with systemic lupus erythematosus; these patients were also positive to IgG aPL. CONCLUSION: The incidence of true positivity to IgA anticardiolipin antibodies is extremely low. Their determination was not helpful in diagnosing the antiphospholipid syndrome or in explaining thrombotic events or aPL related manifestations--fetal loss--in the groups studied.

Antibodies, Anticardiolipin↗

Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents.

Platinum-type drugs have proven to be valuable in the treatment of a variety of solid tumors, beginning with the commercial approval of cisplatin 18 years ago. There are several clinically important toxicities commonly associated with the administration of these drugs. Despite the extensive use of cisplatin and carboplatin, the fundamental chemical transformations and mechanisms that underlie their antitumor and toxic effects have not been fully characterized. Several first-generation protective thiols have been clinically studied in an attempt to reduce the toxicity of platinum-type drugs; while some of these agents appear to protect against certain toxicities, nearly all platinum-protecting drugs have their own intrinsic toxicities, which can be additive to the toxicity of platinum-type drugs. Tumor protection by platinum-protecting drugs is an additional untoward effect that is associated with certain types of agents and must be addressed with care. Recent advances in theoretical and laboratory methods and the use of supercomputers have extended our understanding of the possible major mechanisms underlying platinum drug antitumor activity and toxicity; we present strong evidence that there are two classes of chemical species of platinum drug. One class appears to predominantly account for the antitumor activity, and the other class of chemical species produces many of the toxic effects of platinum drugs. We have discovered a new nontoxic, second-generation platinum-protecting agent, known as BNP7787, which appears to selectively inactivate and eliminate toxic platinum species. BNP7787 has recently entered phase I clinical testing in cancer patients.

Amifostine↗

Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes.

We have attempted to identify any characteristics which could be used to predict the development of cerebral edema in four children under 5 years of age with new onset insulin-dependent diabetes mellitus and diabetic ketoacidosis. We retrospectively analysed and compared the concentration of serum sodium (corrected for serum glucose value) and effective serum osmolality of these 4 children with values of 10 age-matched controls with new onset insulin-dependent diabetes mellitus who did not develop cerebral edema during treatment of diabetic ketoacidosis. The initial serum sodium values of the two groups were not statistically different. Patients who developed cerebral edema had lower initial serum glucose values and effective serum osmolality. During treatment, patients who developed cerebral edema had consistently lower mean serum sodium and osmolality than controls at each 4-h interval after the first 4 h of therapy. Serum sodium and osmolality declined progressively after the initiation of therapy in cerebral edema patients, while remaining stable in controls. These data suggest that children who develop cerebral edema during treatment for diabetic ketoacidosis initially may have a relatively normal serum osmolality and subsequently develop progressive hyponatremia and/or a trend of declining serum sodium before developing cerebral edema.

Brain Edema↗

Effects of aspirin or basic amino acids on collagen cross-links and complications in NIDDM.

OBJECTIVE: To determine if long-term therapy with aspirin or basic amino acids for subjects with NIDDM reduces the severity of clinical complications and/or reduces tissue levels of markers of glycooxidative damage. RESEARCH DESIGN AND METHODS: Subjects with NIDDM were administered either aspirin (100 mg/day) or a combination of basic amino acids consisting of L-arginine (2 g/day) plus L-lysine (0.5 g/day) for 1 year. The study was double-blind and placebo-controlled. The presence and severity of retinopathy, nephropathy, and neuropathy were assessed in all subjects at 4-month intervals, as were serum blood glucose, glycohemoglobin levels, and presence of albuminuria. Collagen cross-linking and collagen glycation were measured in skin collagen obtained by biopsy at the beginning and the end of the study. Skin biopsies were also obtained from age-matched control subjects. RESULTS: Skin samples obtained from NIDDM subjects at the beginning of the study had significantly increased levels of glucitolyllysine, pentosidine, and hydroxypyridinium, as compared with age-matched control subjects. Pentosidine levels were significantly correlated with severity of retinopathy and neuropathy, but not nephropathy. Subjects receiving aspirin, but not amino acids or placebo, had significantly decreased levels of skin pentosidine after 1 year of therapy. CONCLUSIONS: It is concluded that 1) low-dose aspirin may reduce glycooxidative damage in people with NIDDM, and 2) treatment may need to continue for more than 1 year before clinical status improves.

Analysis of Variance↗

Clinical predictors of acute radiological pneumonia and hypoxaemia at high altitude.

Fast breathing has been recommended as a predictor of childhood pneumonia. Children living at high altitude, however, may breathe faster in response to the lower oxygen partial pressure, which may change the accuracy of prediction of a high respiratory rate. To assess the usefulness of clinical manifestations in the diagnosis of radiological pneumonia or hypoxaemia, or both, at high altitude (2640 m above sea level), 200 children aged 7 days to 36 months presenting to an urban emergency room with cough lasting less than seven days were studied. Parents were interviewed and the children evaluated using standard forms. The results of chest radiographs and pulse oximetry obtained after clinical examination were interpreted blind. Radiological pneumonia and haemoglobin oxygen saturation < 88% were used as 'gold standards'. One hundred and thirty (65%) and 125 (63%) children had radiological pneumonia and hypoxaemia respectively. Crepitations and decreased breath sounds were statistically associated with pneumonia, and rapid breathing as perceived by the child's mother, chest retractions, nasal flaring, and crepitations with hypoxaemia. The best single predictor of the presence of pneumonia is a high respiratory rate, although the results are not as good as those reported by other studies. A respiratory rate > or = 50/minute had good sensitivity (76%) and specificity (71%) for hypoxaemia in infants. Hypoxaemia had a good sensitivity and specificity for pneumonia mainly in infants (83% and 73%, respectively). Logistic regression analysis showed that decreased or increased respiratory sounds and crepitations were associated with pneumonia, and that hypoxaemia is the best predictor when auscultatory findings are excluded. These results suggest that some clinical predictors appear to be less accurate in Bogota than in places at lower altitude, and that pulse oximetry can be used for predicting pneumonia.

Acute Disease↗