Biomedical subjects
Publications and source records attributed to V Garcia.
We have obtained bulk samples of the graphite intercalation compound, CaC6, by a novel method of synthesis from highly oriented pyrolytic graphite. The crystal structure has been completely determined showing that it is the only member of the MC6, metal-graphite compounds that has rhombohedral symmetry. We have clearly shown the occurrence of superconductivity in the bulk sample at 11.5 K, using magnetization measurements.
INTRODUCTION: Paraneoplastic nephrotic syndrome associated with malignant broncho-pulmonary tumors. Three cases and literature review. Malignant broncho-pulmonary tumours are the principal cause of a paraneoplastic nephrotic syndrome. These tumours are most often small cell or squamous bronchial carcinomas. In 75% of cases the nephrotic syndrome is due to a membranous glomerulonephritis and it usually precedes the discovery of the causative tumour. CASES REPORT: Three cases of paraneoploastic nephrotic syndrome associated with bronchial carcinoma are described. The first is of a bronchial carcinoid tumour associated with a membrano-proliferative glomerulonephritis. In the second a bronchial adenocarcinoma was revealed by a membranous glomerulonephritis. The last case concerns a squamous carcinoma associated with a nephrotic syndrome in which the histological lesions were not documented on account of progression to rapidly fatal acute renal failure. CONCLUSION: A revue of the literature describes the associations between paraneoplastic nephrotic syndrome and bronchial carcinoma.
Epidemiological studies have suggested that a high consumption of apples may protect against asthma and chronic obstructive pulmonary disease. This effect has been attributed to their high flavonoid content, but few studies have investigated the relationship between flavonoid intake and obstructive lung disease directly. In a population-based, case-control study of 1,471 adults aged 16-50 yrs in London (UK), the present study examined whether dietary intake of catechins, flavonols and flavones was negatively associated with asthma, asthma severity and chronic sputum production. Asthma was defined by positive responses to a standard screening questionnaire in 1996 and information about usual diet was obtained by a food frequency questionnaire in 1997. After controlling for potential confounders, dietary intake of these three flavonoid subclasses was not significantly associated with asthma, (odds ratio per quintile (95% confidence interval) = 0.94 (0.86-1.02); 1.00 (0.92-1.09); 0.98 (0.88 -1.08) for flavones, flavonols and total catechins, respectively) nor was it associated with asthma severity, or chronic sputum production. In conclusion, no evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease.
Two unigene datasets of Pinus taeda and Pinus pinaster were screened to detect di-, tri- and tetranucleotide repeated motifs using the SSRIT script. A total of 419 simple sequence repeats (SSRs) were identified, from which only 12.8% overlapped between the two sets. The position of the SSRs within their coding sequences were predicted using FrameD. Trinucleotides appeared to be the most abundant repeated motif (63 and 51% in P. taeda and P. pinaster, respectively) and tended to be found within translated regions (76% in both species), whereas dinucleotide repeats were preferentially found within the 5'- and 3'-untranslated regions (75 and 65%, respectively). Fifty-three primer pairs amplifying a single PCR fragment in the source species (mainly P. taeda), were tested for amplification in six other pine species. The amplification rate with other pine species was high and corresponded with the phylogenetic distance between species, varying from 64.6% in P. canariensis to 94.2% in P. radiata. Genomic SSRs were found to be less transferable; 58 of the 107 primer pairs (i.e. 54%) derived from P. radiata amplified a single fragment in P. pinaster. Nine cDNA-SSRs were located to their chromosomes in two P. pinaster linkage maps. The level of polymorphism of these cDNA-SSRs was compared to that of previously and newly developed genomic-SSRs. Overall, genomic SSRs tend to perform better in terms of heterozygosity and number of alleles. This study suggests that useful SSR markers can be developed from pine ESTs.
Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The purpose of this study was to analyze the diagnostic efficacy of PCR-RFLP compared to antigenemia for CMV disease (CMVD) in kidney transplant recipients. From November 2001 to February 2002, 19 renal adult transplant recipients were followed with weekly measurements of CMV pp65 antigen to monitor the activity of CMV from the week 4 to 12 posttransplantation. Only 4 (21.1%) patients did not develop viremia during the first 12 posttransplantation weeks. Active infection was observed in 15 patients (78.9%): asymptomatic viremia in 6 (31.6%) and CMVD in 9 (47%). All patients who developed CMVD showed positivity in both methods during the observation period. The number of positive cells ranged from 11 to 292 cells in patients with CMVD and one to eight cells among those with asymptomatic viremia. Both methods revealed 100% sensitivity for CMVD diagnosis. The specificity was 60% for antigenemia and 70% for PCR, with positive predictive values of 60% and 75%, respectively.
Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The aim of this study was to determine the incidence of latent and active infections with CMV during the first 3 months after kidney transplantation. From January 2000 to December 2001, 203 consecutive adult renal transplant recipients underwent weekly measurements of pp65 CMV antigen from the 4th to the 12th posttransplantation week. Latent infection (seropositivity) was found in 92% of the population. Primary infection occurred in 4.9% (10 of 203), among whom 66% were previously seronegative patients. Among the primary infection patients, 70% (7 of 10) developed severe disease. The overall incidence of viremia was 69.5%, being more frequent among cadaver recipients (79% vs 59%; P =.02). The overall incidence of CMV disease was 38.4% (78 of 203) with 24.6% classified as severe disease requiring antiviral therapy. In conclusion, our population showed a high prevalence of latent infection with viremia. Not all patients developed clinical disease. Most subjects experienced a mild spectrum of symptoms, probably due to the prospective search for active infection during the major risk period after kidney transplantation.
OBJECTIVE: To determine the level of agreement between the American (Chilean) and British food composition tables in estimating intakes of macronutrients and antioxidants. DESIGN, SETTING AND SUBJECTS: Information based on a food-frequency questionnaire with emphasis on antioxidants was collected from 95 Chileans aged 24-28 years. Nutritional composition was analysed using the British table of food composition and the American table of food composition modified by Chilean food items. Mean differences and limits of agreement (LOAs) of estimated intake were assessed. RESULTS: Mean differences between the two tables of food composition ranged from 5.3% to 8.9% higher estimates when using the American (Chilean) table for macronutrients. For micronutrients, a bias towards a higher mean was observed for vitamin E, iron and magnesium when the American (Chilean) table was used, but the opposite was observed for vitamin A and selenium. The intra-class correlation coefficient (ICC) ranged from 0.86 (95% confidence interval (CI) 0.81-0.91) to 0.998 (95% CI 0.995-1.00), indicating high to excellent agreement. LOAs for macronutrients and vitamins A and C were satisfactory, as they were sufficiently narrow. There was more uncertainty for other micronutrients. CONCLUSION: The American table gives relative overestimates of macronutrients in comparison to the British table, but the relative biases for micronutrients are inconsistent. Estimates of agreement between the two food composition tables provide reassurance that results are interchangeable for the majority of nutrients.
Activation of T cells requires both TCR-specific ligation and costimulation through accessory molecules during T cell priming. IFNgamma is a key cytokine responsible for macrophage activation during Mycobacterium tuberculosis (Mtb) infection while IL-10 is associated with suppression of cell mediated immunity in intracellular infection. In this paper we evaluated the role of IFNgamma and IL-10 on the function of cytotoxic T cells (CTL) and on the modulation of costimulatory molecules in healthy controls and patients with active tuberculosis (TB). gamma-irradiated-Mtb (i-Mtb) induced IL-10 production from CD14(+) cells from TB patients. Moreover, CD3(+) T cells of patients with advanced disease also produced IL-10 after i-Mtb stimulation. In healthy donors, IL-10 decreased the lytic activity of CD4(+) and CD8(+) T cells whereas it increased gammadelta-mediated cytotoxicity. Furthermore, we found that the presence of IL-10 induced a loss of the alternative processing pathways of antigen presentation along with a down-regulation of the expression of costimulatory molecule expression on monocytes and macrophages from healthy individuals. Conversely, neutralization of endogenous IL-10 or addition of IFNgamma to either effector or target cells from TB patients induced a strong lytic activity mediated by CD8(+) CTL together with an up-regulation of CD54 and CD86 expression on target cells. Moreover, we observed that macrophages from TB patients could use alternative pathways for i-Mtb presentation. Taken together, our results demonstrate that the presence of IL-10 during Mtb infection might contribute to mycobacteria persistence inside host macrophages through a mechanism that involved inhibition of MHC-restricted cytotoxicity against infected macrophages.
UNLABELLED: Outbreaks of meningitis are a public health problem in sub-Saharan Africa where more than thousand cases are declared every year In Chad, the last outbreak happened between 1998 and 2001. The objective of this study is to describe epidemiologic profile of meningitis in the province of Logone Occidental from 1998 to 2001. METHODS: Study used epidemiologic data of surveillance's tools from years 1998 to 2001 in Chad. RESULTS: Data of the study indicated a two-yearly cycle with outbreaks in 1998 and 2000 occurring in endemic background during 1999 and 2001. The first cases began in January with an incidence rate close to 30 for 100.000/week. The epidemic peak occurred on the 11th week (1999-2001), on the 12th week (1998-2000) during dry season. Outbreak continued 9 weeks and stopped on the 16th week (April-May). The lethality average was 12% and reached 30% at the beginning of the outbreak. DISCUSSION: Despite vaccination campaigns during outbreaks, epidemiology did not change in Chad. Quality of epidemiological surveillance is not sufficient and political reaction is too slow. Moreover, human, material and financial deficiency add to these difficulties. Integrated vaccination against meningitis into the immunization preventive program was evocated but would not permit enough collective immunity. Biotope changes generated by human activity could contribute to perpetuating outbreaks. New outbreak of W135 meningitis in Burkina Faso (2002) may change the epidemiological profile of the meningitis in sub-Saharan Africa. CONCLUSION: Meningitis outbreaks control using vaccination after the first cases appears to be limited, however this strategy must be evaluated in Chad to know vaccination covering, target population and protection after vaccination.
We have determined the number of circulating T, B and natural killer cells in renal transplant recipients in order to detect changes during cytomegalovirus (CMV) infections. Serial blood samples were taken from 61 patients on standard triple immunosuppression therapy (cyclosporin A, azathioprine and prednisone). Using two-color flow cytometry analysis, the absolute number of CD3+, CD4+, CD8+, CD19+, CD3+HLA-DR+ and CD16+56+ cells was determined. Forty-eight patients (78.7%) developed active CMV infection, and all of them subsequently recovered. Twenty of the infected patients (32.8%) presented symptoms compatible with CMV disease during the infectious process. The number of lymphocytes and their main subpopulations were normal before the onset of CMV disease. During the disease there was a decrease followed by a significant increase (P<0.005) in the number of CD3+, CD4+, CD8+ and CD3+HLA-DR+ cells. No significant changes were observed in natural killer cells or B lymphocytes during the disease. We conclude, as observed in all viremic patients recovering from infection, that recovery is associated with an increase in the number of T cell subsets. The monitoring of different lymphocyte subsets along with antigenemia can be extremely useful in the detection of patients at high risk of developing CMV symptoms, allowing the early introduction of antiviral therapy or the reduction of immunosuppression therapy.
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TNF-alpha is a pleiotropic cytokine activating several signaling pathways initiated at distinct intracellular domains of the TNF receptors. Although the C-terminal region is believed to be responsible for apoptosis induction, the functions of more membrane-proximal domains, including the domain that couples to neutral sphingomyelinase activation, are not yet fully elucidated. The roles of this region and of the associated adapter protein FAN (factor associated with neutral SMase activation) in the cytotoxic response to TNF have been investigated. We have now shown that stable expression in human fibroblasts of a dominant negative form of FAN abrogates TNF-induced ceramide generation from sphingomyelin hydrolysis and reduces caspase processing, thus markedly inhibiting TNF-triggered apoptosis. However, the cytotoxic responses to daunorubicin and exogenous ceramide remain unaltered, as do the TNF-induced p42/p44 MAPK activation and CD54 expression. Fibroblasts from FAN-knockout mice also proved to be resistant to TNF toxicity. These findings highlight the previously unrecognized role of the adapter protein FAN in signaling cell death induction by TNF.
Lawn mower-related injuries to children are relatively common and can result in severe injury or death. Many amputations during childhood are caused by power mowers. Pediatricians have an important role as advocates and educators to promote the prevention of these injuries.
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During development, control of proliferation of neuronal precursor cells plays a crucial role in determining the number of neurons. Proliferation is driven by mitogens, but how it is terminated remains a mystery. In this study, we examined the role of cyclin-dependent kinase inhibitors in the control of proliferation of cerebellar granule cell precursors (GCPs). Among the inhibitors we examined, only p27/Kip1 (p27) was expressed at significant levels in cells of the granule cell lineage in the developing and adult cerebellum. In developing cerebella, p27 was expressed in the external germinal layer (the deeper regions), the molecular layer, and the granule layer. In adult cerebella, p27 was expressed in the cells of the granule layer. We isolated and purified GCPs from cerebella of developing mice and examined their bromodeoxyuridine (BrdU) uptake and p27 expression at various times. We found that there was an inverse correlation between BrdU uptake and p27 expression. Even in the presence of saturating amounts of Sonic hedgehog, a potent mitogen, the cells eventually stopped dividing and differentiated, expressing p27 strongly. We also examined mice in which one or both copies of the p27 gene have been inactivated by targeted gene disruption and found that their cerebella were larger than those of wild-type mice. In cell cultures, GCPs prepared from p27-deficient mice showed enhanced proliferation compared with GCPs from wild-type mice. Taken together, these results suggest that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism.
ATM is a gene mutated in the human disease ataxia telangiectasia with reported homologues in yeast, Drosophila, Xenopus and mouse. Whenever mutants are available they all indicate a role of this gene family in the cellular response to DNA damage. Here, we present the identification and molecular characterisation of the first plant homologue of ATM. The genomic locus of AtATM ( Arabidopsis thaliana homologue of ATM ) spans over 30 kb and is transcribed into a 12 kb mRNA resulting from the splicing of 79 exons. It is a single copy gene and maps to the long arm of chromosome 3. Transcription of AtATM is ubiquitous and not induced by ionising radiation. The putative protein encoded by AtATM is 3856 amino acids long and contains a phosphatidyl inositol-3 kinase-like (Pi3k-l) domain and a rad3 domain, features shared by other members of the ATM family. The AtAtm protein is highly similar to Atm, with 67 and 45% similarity in the Pi3k-l and rad3 domains respectively. Interestingly, the N-terminal portion of the protein harbours a PWWP domain, which is also present in other proteins involved in DNA metabolism such as human mismatch repair enzyme Msh6 and the mammalian de novo methyl transferases, Dnmt3a/b.
BACKGROUND/PURPOSE: We sought to determine if properly restrained children, less than 13 years of age, placed in the front passenger seat are at greater risk for trauma from airbag deployment than unrestrained children. METHODS: The charts of children treated at any of 3 regional pediatric trauma centers in Ohio were reviewed for airbag injuries sustained in motor vehicle crashes between January 1995 and September 1998. Injury Severity Scores (ISS) were compared with Mann-Whitney Rank Sum Test and outcome data with Fisher's Exact Tests. Statistical significance was set at P< or =.05. RESULTS: Twenty-seven children aged 1 month to 12 years sustained airbag-related injuries. Sixty-one percent were girls. ISS ranged from 1 to 75 with a mean score (+/- SD) of 10 (14.5). All crashes were at reported speeds of less than 45 mph, and 64% were head-on collisions. No significant differences in the mean ISS (P = .074) occurred between groups. Both groups had similar closed head, ocular and facial injuries, extremity fractures, and number of deaths (P = 1.0). Abdominal organ injury was exclusive to the restrained group. Decapitation only occurred among unrestrained children. CONCLUSION: Our data showed that airbags, with or without proper safety restraints, can lead to mortality or serious morbidity in children.