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Biomedical subjects

V Garcia

Publications and source records attributed to V Garcia.

At least 19 recordsLinked to original sources
PubMed2004

Comparison between RFLP-PCR and antigenemia for pp65 antigen for diagnosis of cytomegalovirus disease after kidney transplantation.

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.

Acute Disease↗
PubMed2004

Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation.

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.

Adult↗
PubMed2004

Effect of the choice of food composition table on nutrient estimates: a comparison between the British and American (Chilean) tables.

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.

Adult↗
PubMed2003

Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients.

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.

Adolescent↗
PubMed2001

Involvement of FAN in TNF-induced apoptosis.

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.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Lawn mower-related injuries to children.

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.

Accident Prevention↗
PubMed2000

A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation.

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.

Age Factors↗
PubMed2000

An ATM homologue from Arabidopsis thaliana: complete genomic organisation and expression analysis.

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.

Amino Acid Sequence↗
PubMed2000

Pediatric airbag injuries: the Ohio experience.

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.

Accidents, Traffic↗
PubMed2000

Hyperopic laser in situ keratomileusis with the Nidek EC-5000 excimer laser.

OBJECTIVE: To evaluate the efficacy, safety, and predictability of hyperopic laser in situ keratomileusis (H-LASIK) using modified software. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The first 72 consecutive eyes of 44 patients with up to +5.00 diopters (D) hyperopia. INTERVENTION: Hyperopic LASIK using the Automatic Corneal Shaper (ACS; Chiron Vision, Claremont, CA) and the Nidek EC-5000 excimer laser (Nidek, Tokyo, Japan). MAIN OUTCOME MEASURES: Uncorrected visual acuity, manifest spherical equivalent (MSE), best-corrected visual acuity (BCVA), and complications were studied. RESULTS: At 6 months, in the low hyperopia group (<3.00 D), mean MSE was +0.30 +/- 0.71 D, with 88.9% eyes within 1 D of emmetropia compared with +1.09 +/- 0.92 D and 51.8% within 1 D of emmetropia in the moderate hyperopia group (> or =3.00 D; P = 0.003). Uncorrected visual acuity was 20/40 or better in 43 of 45 eyes (95.6%) and in 21 of 27 (77.8%) eyes in the low and moderate hyperopia groups, respectively. Only one eye (1.4%) from the moderate hyperopia group lost two lines of BCVA. Eighteen eyes (25%) required retreatment to correct residual hyperopia, 9 eyes (20.0%) in the low hyperopia group and 9 eyes (33.3%) in the moderate hyperopia group. Retreatments resulted in an MSE of +0.02 +/- 0.45 D and +0.04 +/- 0.73 D in the low and moderate hyperopia groups, respectively. No flap-related complications were seen. CONCLUSIONS: Hyperopic LASIK with the ACS and the Nidek EC-5000 excimer laser using our modified software is a safe, effective, and predictable procedure for low hyperopia. Results are satisfactory up to moderate hyperopia. Significant regression can occur for low and moderate hyperopia. Retreatment can be performed safely and effectively to improve the visual and refractive results.

Adult↗
PubMed1999

CD40 signals apoptosis through FAN-regulated activation of the sphingomyelin-ceramide pathway.

The possibility that the sphingomyelin (SM)-ceramide pathway is activated by CD40, a transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily and that plays a critical role in the regulation of immune responses has been investigated. We demonstrate that incubation of Epstein-Barr virus-transformed lymphoid cells with an anti-CD40 antibody acting as an agonist results in the stimulation of a neutral sphingomyelinase, hydrolysis of cellular SM, and concomitant ceramide generation. In addition, SM degradation was observed in acid sphingomyelinase-deficient cells, as well as after ligation by soluble CD40 ligand. The anti-CD40 antibody, as well as the soluble CD40 ligand induced a decrease in thymidine incorporation and morphological features of apoptosis, which were mimicked by cell-permeant or bacterial sphingomyelinase-produced ceramides. Stable expression of a dominant-negative form of the FAN protein (factor associated with neutral sphingomyelinase activation), which has been reported to mediate tumor necrosis factor-induced activation of neutral sphingomyelinase, significantly inhibited CD40 ligand-induced sphingomyelinase stimulation and apoptosis of transformed human fibroblasts. Transformed fibroblasts from FAN knockout mice were also protected from CD40-mediated cell death. Finally, anti-CD40 antibodies were able to co-immunoprecipitate FAN in control fibroblasts but not in cells expressing the dominant-negative form of FAN, indicating interaction between CD40 and FAN. Altogether, these results strongly suggest that CD40 ligation can activate via FAN a neutral sphingomyelinase-mediated ceramide pathway that is involved in the cell growth inhibitory effects of CD40.

Animals↗
PubMed1999

Retrovirus-mediated correction of the metabolic defect in cultured Farber disease cells.

Farber disease is a rare severe lysosomal storage disorder due to a deficient activity of the enzyme acid ceramidase (AC). Patients have granulomas along with lipid-laden macrophages that accumulate in a number of tissues, leading to multiple diverse clinical symptoms. There is no therapy for the disorder and most patients succumb to the disease in early childhood. The severity of the disease progression seems to correlate with the amount of the accumulated ceramide substrate. Since the cDNA for human AC has been elucidated we sought to establish if genetic transfer of this sequence would lead to enzymatic and, especially, functional correction of the catabolic defect in Farber patient cells. To do this, a novel amphotropic recombinant retrovirus was constructed that engineers transfer of the human AC cDNA. On infection of patient fibroblasts, AC enzyme activity in cell extracts was completely restored. Further, substrate-loading assays of intact living cells showed a fully normalized catabolism of lysosomal ceramide. Lastly, as reported for some other corrected enzymatic defects of lysosomes, metabolic cooperativity was seen, in that functionally corrected patient fibroblasts secreted AC that was taken up through the mannose 6-phosphate receptor and used by uncorrected fibroblasts as well as recipient Farber lymphoblastoid cells. This overall transduction and uptake scenario for Farber disease allows future treatment of this severe disorder to be envisioned using gene transfer approaches.

Acid Ceramidase↗