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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 19 recordsLinked to original sources
PubMed2006

Hyperhomocysteinemia is a risk factor of recurrent coronary event in young patients irrespective to the MTHFR C677T polymorphism.

Despite the well-known pro-coagulant effect of hyperhomocysteinemia, data is limited regarding the result on recurrent coronary event (RCE) in young people. One hundred and forty patients <55 years old with a first acute coronary syndrome (ACS) were prospectively followed for a mean (+/-S.D.) follow-up of 49+/-14 months in order to investigate the relationship between homocysteine levels (tHcy) at admission and the incidence of RCE. The tHcy values were divided into quartiles to examine their relationship with end points. Furthermore, we determined the effect of C677T methylene tetrahydrofolate reductase (MTHFR) polymorphism, as well as other risk factors for developing a RCE. The median plasma homocysteine concentration was 9.6 mumol/L (interquartile range, 3.7). In the screening of MTHFR C677T polymorphism in patients with ACS, the T allele frequency was 0.4 and the genotype frequency distributions were in Hardy-Weinberg equilibrium. At time of final evaluation, 49 (35%) of the 140 valuable patients had developed a RCE. Increasing numbers of RCE were observed for increasing quartiles of tHcy according to Kaplan-Meier survival (Log-rank test=0.0092). The MTHFR C677T polymorphism was not associated with an increased incidence of RCE. In multivariate analysis, the variables independently associated with a higher risk of RCE were age older than 45 years [HR=2.7; (95% CI, 1.3-6.1); p=0.030], body mass index more than 25 [HR=2.6; (95% CI, 1.1-5.9); p=0.034] and tHcy levels into quartile 4 (tHcy>12.37 mumol/L) [HR=2.5; (95% CI, 1.1-4.7); p=0.04]. Elevated plasma homocysteine level at admission is an independent risk factor for RCE after the first episode of ACS in young patients irrespective of the status of MTHFR C677T.

Acute Disease↗
PubMed2006

Molecular characterization of two isoforms of defensin from hemocytes of the oyster Crassostrea gigas.

Antimicrobial peptides (AMPs) are important components of the host innate immune response against microbial invasion. We previously characterized the first AMP from an oyster, a defensin, that was shown to be continuously expressed in the mantle of Crassostrea gigas. In this study, we report the cDNA cloning of two new isoforms of the defensin AMP family (Cg-defh1 and Cg-defh2) from the hemocytes of the oyster. The deduced amino acid sequences reveal two peptides of 73 amino acid residues with a mature portion consisting of 43 amino acid residues. Cg-Defh1 and Cg-Defh2 share 86% amino acid identity and belong to the "arthropod-molluscs defensin family". qRT-PCR analyses indicate that Cg-defh2 is continuously expressed in the hemocytes of C. gigas. In addition, after a bacterial challenge, the level of Cg-defh2 transcripts decreases dramatically in the circulating hemocyte population and this decrease can be correlated with an increase of Cg-defh2 transcripts in the gill and the mantle tissue, suggesting a possible migration of the hemocytes expressing Cg-defh2 towards the tissues implicated in the first defense barrier of the oyster. These results would suggest an important role of Cg-Defh2 in the oyster response to a microbial challenge.

Amino Acid Sequence↗
PubMed2006

[Surgical treatment of duodenal stenosis in Crohn's disease].

Crohn's disease may involve any part of the alimentary tract, including the stomach and duodenum. We report herein the case of a 22 year-old male in whom Crohn disease was diagnosed due to weight loss in relation with a stenosis of the first and second parts of the duodenum. A gastrojejunostomy was performed with a good subsequent result. The initial management of a Crohn's disease with involvement of the duodenum is medical. When there is an indication for surgery, a gastroenterostomy is preferred, albeit with a high incidence of outlet obstruction and marginal ulceration.

Adult↗
PubMed2006

[When should cholecystectomy be practiced? Not always an easy decision].

Gallstone disease is a frequent medical problem. Cholelithiasis affects 10% of the population and 30% of patients with gallstones will undergo surgery. The treatment of choice for symptomatic gallstones remains cholecystectomy. A prophylactic cholecystectomy is indicated for asymptomatic patients in the presence of polyps, porcelain gallbladder or during bariatric surgery. The management of the complications of gallstone disease is discussed. At present, common bile duct stones, even if discovered preoperatively, should be managed by a multidisciplinary team including surgeons trained in laparoscopic techniques and gastroenterologists. This review is complemented by the information from a prospective database generated by a program called "DODIG" on 1099 cholecystectomies performed in our institution.

Cholecystectomy↗
PubMed2006

Intestinal transplantation for short bowel syndrome secondary to gastroschisis.

BACKGROUND/PURPOSE: Gastroschisis is the most frequent cause of pediatric intestinal transplantation. This study reviews our experience of intestinal transplantation secondary to gastroschisis to elucidate those factors affecting the outcome of children with short bowel syndrome. METHODS: A retrospective review was performed for children who underwent intestinal transplantation for gastroschisis at the University of Miami between June 2003 and August 1994. RESULTS: Thirty-two transplants were performed in 28 children with gastroschisis during the study period. Associated intestinal anomalies were present in 22 infants (atresia [n = 14], volvulus [n = 3], and/or ischemia [n = 16]). Spontaneous prenatal closure of gastroschisis, a rare anomaly associated with bowel atresia and ischemia because of a very small abdominal defect, was seen in 9 patients. Most of the patients had a complicated course and required multiple abdominal surgeries before transplant. Fifteen (53.6%) patients are currently alive at a median follow-up of 23.5 months. Short-term survival rate has significantly improved in recent years. CONCLUSIONS: Patients with complex gastroschisis and intestinal anomalies have a significant risk for progression to short bowel syndrome. Intestinal transplantation can be a lifesaving option and provides a satisfactory outcome for children with short bowel syndrome secondary to gastroschisis.

Child↗
PubMed2006

TCRgammadelta+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRgammadelta+ T-cells.

T-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRalphabeta. Much less is known about the characteristics and pathogenesis of TCRgammadelta+ cases. We evaluated 44 patients with clonal TCRgammadelta+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRgammadelta+ T-LGL leukemia patients had similar clinical presentations as TCRalphabeta+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias - neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) - and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vgamma9/Vdelta2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vdelta1, reflecting the TCR-spectrum of normal TCRgammadelta+ T-cells in adult PB. Identification of the well-defined post-thymic Vdelta2-Jdelta1 selection determinant in all evaluable Vgamma9+/Vdelta2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRgammadelta+ T-LGL leukemia patients.

Adult↗
PubMed2006

Molecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumors.

A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II non-endometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.

Carcinoma, Endometrioid↗
PubMed2005

Toxoplasma gondii: partial cross-protection among several strains of the parasite against congenital transmission in a rat model.

Rats were immunized with cysts of two Toxoplasma strains or with RH strain tachyzoites prior to pregnancy. The litters of the 13 rats that received homologous challenges with cysts during pregnancy, were all protected, whereas of 173 rats that received heterologous challenges with cysts or oocysts, only 21 protected their litters. 38.3 and 17% of rats immunized with the RH and with complete strains respectively, and 57% of control rats challenged with cysts, transmitted the infection congenitally. The percentages when similar groups were challenged with oocysts, were 33.3, 48.2, and 56.2%, respectively. Immunization with cysts did not completely protect against challenge with oocysts, even if the same strain was used. The divergence of these results from the complete protection against congenital toxoplasmosis observed in immune women and ewes, might be due to the use of excessive challenge doses in the model.

Animals↗
PubMed2005

A functional CD40 receptor is expressed in pancreatic beta cells.

AIMS/HYPOTHESIS: Despite differences in function and embryonic origin, pancreatic islet cells and neurons express proteins belonging to the tumour necrosis factor receptor superfamily. While neurons express the CD40 receptor, it is unknown whether islet cells also express it. We investigated CD40 expression in human and mouse pancreatic islets as well as in NIT-1 insulinoma cells. METHODS: CD40 expression was studied by reverse transcriptase polymerase chain reaction, flow cytometry, immunohistochemistry and western blot. Responses mediated by CD40 were assessed by a luciferase gene reporter assay following stimulation with a CD40 agonist antibody. RESULTS: We found that CD40 is expressed in mouse and human pancreatic islet cells. CD40 is expressed by beta cells, and its expression is upregulated by proinflammatory cytokines (IL-1beta, IFN-gamma and TNF-alpha). CD40 signalling in NIT-1 insulinoma cells activates nuclear factor kappa-B, demonstrating that CD40 is functional. CONCLUSIONS/INTERPRETATION: We present evidence that, in addition to immune cell types, mouse and human pancreatic beta cells express CD40. Its expression is upregulated by proinflammatory stimuli, and signalling through this receptor activates NF-kappaB. We suggest that the effects of inflammatory stimuli that affect beta cell function and survival may be also mediated by signalling through the CD40 receptor. Thus, CD40 may have a role in processes associated with islet autoimmunity and transplantation.

Animals↗
PubMed2005

Staphylococcus aureus re-colonization in atopic dermatitis: beyond the skin.

Patients with atopic dermatitis (AD) are often heavily colonized by Staphylococcus aureus, which adversely affects eczema severity. Strategies to control S. aureus in AD include antibiotic and or antiseptics. However long-term efficacy is unclear. In this study we consider extra-cutaneous factors that may cause S. aureus re-colonization in adult AD. Twenty-one patients with AD were recruited and were assessed for: duration of AD, use of topical or oral antibiotic within the preceding 3 months, the number of hospital admissions during the preceding year and current treatment. The types of topical treatments used, vehicle, container and the expiry dates were also recorded. The severity of AD was assessed by SCORAD index. Microbiological assessment for S. aureus carriage from affected skin, anterior nares, emollient and topical steroid was undertaken using culture, Staphaurex test and antibiotic resistance. Of the patients 86% had S. aureus colonization. The median SCORAD score were greater in those colonized with S. aureus (P = 0.02) and those with contaminated treatments (P = 0.05). Prior antibiotic treatment, prior hospital admission and nasal carriage did not influence the median SCORAD. Three extra-cutaneous mechanisms by which S. aureus can re-colonize the skin were identified: antibiotic resistance, nasal carriage and treatment contamination.

Adolescent↗
PubMed2005

Rapid diagnosis of human brucellosis by SYBR Green I-based real-time PCR assay and melting curve analysis in serum samples.

The aim of this study was to develop a LightCycler-based real-time PCR (LC-PCR) assay and to evaluate its diagnostic use for the detection of Brucella DNA in serum samples. Following amplification of a 223-bp gene sequence encoding an immunogenetic membrane protein (BCSP31) specific for the Brucella genus, melting curve and DNA sequencing analysis was performed to verify the specificity of the PCR products. The intra- and inter-assay variation coefficients were 1.3% and 6.4%, respectively, and the detection limit was 5 fg of Brucella DNA (one genome equivalent). After optimisation of the PCR assay conditions, a standard curve was obtained with a linear range (correlation coefficient=0.99) over seven orders of magnitude from 10(7) to 10 fg of Brucella DNA. The LC-PCR assay was found to be 91.9% sensitive and 95.4% specific when tested with 65 negative control samples and 62 serum samples from 60 consecutive patients with active brucellosis. The assay is reproducible, easily standardised, minimises the risk of infection in laboratory workers, and has a total processing time of <2 h. It could therefore form a promising and practical approach for the rapid diagnosis of human brucellosis.

Benzothiazoles↗
PubMed2004

Glycosylation of immunodominant linear epitopes in the carboxy-terminal region of the caprine arthritis-encephalitis virus surface envelope enhances vaccine-induced type-specific and cross-reactive neutralizing antibody responses.

This study evaluated type-specific and cross-reactive neutralizing antibodies induced by immunization with modified surface glycoproteins (SU) of the 63 isolate of caprine arthritis-encephalitis lentivirus (CAEV-63). Epitope mapping of sera from CAEV-infected goats localized immunodominant linear epitopes in the carboxy terminus of SU. Two modified SU (SU-M and SU-T) and wild-type CAEV-63 SU (SU-W) were produced in vaccinia virus and utilized to evaluate the effects of glycosylation or the deletion of immunodominant linear epitopes on neutralizing antibody responses induced by immunization. SU-M contained two N-linked glycosylation sites inserted into the target epitopes by R539S and E542N mutations. SU-T was truncated at 518A, upstream from the target epitopes, by introduction of termination codons at 519Y and 521Y. Six yearling Saanen goats were immunized subcutaneously with 30 microg of SU-W, SU-M, or SU-T in Quil A adjuvant and boosted at 3, 7, and 16 weeks. SU antibody titers determined by indirect enzyme-linked immunosorbent assay demonstrated anamnestic responses after each boost. Wild-type and modified SU-induced type-specific CAEV-63 neutralizing antibodies and cross-reactive neutralizing antibodies against CAEV-Co, a virus isolate closely related to CAEV-63, and CAEV-1g5, an isolate geographically distinct from CAEV-63, were determined. Immunization with SU-T resulted in altered recognition of SU linear epitopes and a 2.8- to 4.6-fold decrease in neutralizing antibody titers against CAEV-63, CAEV-Co, and CAEV-1g5 compared to titers of SU-W-immunized goats. In contrast, immunization with SU-M resulted in reduced recognition of glycosylated epitopes and a 2.4- to 2.7-fold increase in neutralizing antibody titers compared to titers of SU-W-immunized goats. Thus, the glycosylation of linear immunodominant nonneutralization epitopes, but not epitope deletion, is an effective strategy to enhance neutralizing antibody responses by immunization.

Amino Acid Sequence↗
PubMed2003

De novo hemolytic-uremic syndrome/thrombotic microangiopathy in renal transplant patients receiving calcineurin inhibitors: role of sirolimus.

The aim of this study was to evaluate the outcome of ten renal transplant recipients who developed de novo hemolytic uremic syndrome/thrombotic microangiopathy (DnHUS) after treatment with calcineurin inhibitors among 3,862 patients transplanted during the period 2000-2001 in Spain, and the results of switching to sirolimus for resolution of this pathologic condition. No patient had end-stage disease due to primary HUS. The criteria of diagnosis were decreased renal function, biopsy-proven thrombotic microangiopathy, and no signs of acute rejection. Calcineurin inhibitors were completely removed and immediate treatment with sirolimus started after diagnosis. The follow-up period was 19.0+/-4.3 months, at least 12 months after diagnosis. One patient died of sepsis shortly after starting sirolimus therapy. The serum creatinine level in the series decreased from 5.2+/-2.6 mg/dL at the time of biopsy to 2.15+/-1.9 mg/dL 1 month later (P=.011). All but one of the nine recipients, who lost his graft 3 months later (80% success) maintained function, with a serum creatinine of 2.1+/-1.4 mg/dL and Cockroft index of 61.3+/-34 mL/min at the end of follow up. During this time, none of the patients experienced an acute rejection episode and sirolimus was maintained without any remarkable secondary effect. Sirolimus seems to be a promising alternative for the treatment of renal transplant patients who develop calcineurin inhibitor-induced DnHUS.

Adult↗
PubMed2003

Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning.

We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.

Adult↗
PubMed2003

Technical skills for weight loss: 2-y follow-up results of a randomized trial.

OBJECTIVE: To investigate the sustained effectiveness of a novel skill-based intervention for weight loss. DESIGN: Randomized, controlled trial. SUBJECTS: A total of 80 overweight/obese women living in Connecticut. MEASUREMENTS: Absolute weight difference measured in pounds and absolute change in body mass index (BMI). Secondary outcomes included changes in food frequency questionnaire (FFQ) data and waist-to-hip ratio. RESULTS: In all 61, 35, and 34% of study participants completed the 6-, 12-, and 24-month assessments, respectively. At 6 months postintervention, both counseling-based (CBI) and skill-based (SBI) intervention groups had statistically significant decreases in absolute weight (4.0+/-3.6 and 1.7+/-3.0 kg, respectively). Compared to their baseline values, both CBI and SBI groups still maintained weight losses at 24 months (1.1+/-5.8 and 0.59+/-3.3 kg, respectively); however, the differences were not statistically significant. FFQ results showed that, within the SBI group, there was a significant decrease (P<0.05) in percent fat from baseline to 12 months and a nearly significant decrease in saturated fat from baseline to 24 months (P=0.07). CONCLUSIONS: Both the novel SBI and conventional dietary counseling demonstrated some residual weight loss benefit at 2 y. Effects of the SBI on dietary intake patterns are encouraging, and warrant further study.

Adult↗