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Biomedical subjects

A M Gonzalez

Publications and source records attributed to A M Gonzalez.

At least 19 recordsLinked to original sources
PubMed2007

Liver transplantation from deceased donors serologically positive for Chagas disease.

The high mortality rates among patients waiting for liver transplantation has motivated the use of "marginal livers", among which are included livers from deceased donors serologically positive for Chagas disease (CD). The present work describes the outcome of orthotopic liver transplantation in six patients with severe liver disease (Child Pugh C), with livers from donors serologically positive for CD. Transplantations were performed from November 2000 to January 2005, and the patients received prophylactic treatment with benznidazole for 60 days, as a recommended by the Brazilian Consensus in Chagas Disease. The transplantation procedures presented no technical problems, and all the patients were discharged from hospital. Five of them did not present side effects demanding interruption of the prophylactic treatment. Four of the patients were clinically well over 1 year after transplantation (mean follow-up of 42.1 months), with negative serological results for CD. Two patients died, one of them 6 months post surgery of sepsis due to biliary complication and other one due to pulmonary (tuberculosis) complications. They were both serologically negative for CD. These results suggest that liver transplantation from CD donors, followed by benznidazole prophylactic treatment, is an important therapeutic alternative for severe liver disease.

Adult↗
PubMed2004

The alpha4 laminin subunit regulates endothelial cell survival.

The alpha4 laminin subunit is a major structural component of assembling basement membranes of endothelial cells. We have been investigating its functions with regard to endothelial cell survival. An anti-laminin alpha4 antibody (2A3), directed against the G domain of the alpha4 laminin subunit of laminins-8 and -9, inhibits proliferation and enhances apoptosis of endothelial cells when cells are maintained in vitro. Activation of caspases-9 and -3 plays a role in 2A3 antibody-induced apoptosis, since inhibitors specific for these caspases and overexpression of the anti-apoptotic protein Bcl-X(L), but not c-FLIP, inhibit 2A3 antibody-triggered endothelial cell death. Extracellular matrix is known to play a role in regulating programmed cell death in an integrin-dependent fashion. The alpha4 laminin subunit conforms to this idea since activation of beta1 integrin subunits on endothelial cells blocks the ability of 2A3 antibody to induce endothelial cell death. In summary, our data indicate that complexes composed of alpha4 laminin/beta1 subunit-containing integrins at the cell surface support endothelial cell survival. Furthermore, we propose that antagonists of alpha4 laminin function, including antibody 2A3, have value as angiogenesis inhibitors in a clinical setting where blocking aberrant growth of blood vessel by triggering apoptosis of endothelial cells may be therapeutic.

Antibodies↗
PubMed2004

Risk factors for the development of posttransplantation diabetes mellitus in simultaneous pancreas and kidney recipients.

We sought to determine the risk factors involved in the development of posttransplantation diabetes mellitus (PTDM) following simultaneous pancreas and kidney transplantation. Correlations were sought between tacrolimus (FK-506) levels/dose 2-hour capillary glucose (CG) and glycosylated hemoglobin (HbA(1c)), cyclosporine (CSA) levels/dose with HbA1c, 2-hour CG with prednisone dose and body mass index (BMI) and PTDM. Four patients (9.3%) developed PTDM. Three treated with FK-506 had altered 2-hour CG at 3 months after transplantation; 1 prescribed CSA displayed diabetes diagnosed after 1 year. There was no statistically significant difference among HbA(1c) values and FK-506 (P =.18) or CSA (P =.81) doses or FK-506 (P =.53) and CSA (P =.54) levels. In contrast, there was a statistically significant relationship between elevated 2-hour CG (> or =200 mg/dL) and daily prednisone dose (9.7 mg vs. 16.2 mg; P =.003). There was no correlation between 2-hour CG and FK-506 dose (P =.084) or FK-506 levels (P =.075). The greater BMI correlated with an increased risk of PTDM (21.25 +/- 3.13 kg/m(2) vs 24.67 +/- 2.38 kg/m(2); P =.034). Two-hour CG may be a useful tool to screen the diabetogenic effects of corticosteroids. A BMI increase should be discouraged due to the risk of PTDM.

Adolescent↗
PubMed2004

Simultaneous pancreas-kidney transplantation: infectious complications and microbiological aspects.

OBJECTIVE: The purpose of this study was to describe the clinical and microbiological characteristics of the infectious complications among simultaneous pancreas-kidney transplantations (SPKT). MATERIALS AND METHODS: Among the first 45 SPKT the mean age was 34 years (range, 21 to 49) and the mean duration of follow-up 13 months (range, 2 to 27 months). RESULTS: Twenty-three patients (51%) presented at least one to three episodes (1.7 mean) of infectious complications that needed hospitalization. The etiology of the infections included 71% bacterial (44% gram-negative rods and 27% gram-positive cocci), 16% viral (12% from CMV and 4% from Herpes sp) and 13% fungal (8% by Candida sp and 4% by others fungus). Wound and urinary infections were most frequent, occurring in 22% and 28% of the patients, respectively. All patients who were submitted to vesical drainage developed infections in contrast a rate of only 44% among patients undergoing enteric drainage. CONCLUSION: Infectious complications are the main cause of morbidity and mortality following simultaneous pancreas-kidney transplantation, especially with vesical drainage. The use of enteric drainage combined with administration of broad spectrum prophylactic antibiotics is recommended.

Adult↗
PubMed2004

Magnetic resonance cholangiography in the diagnosis of biliary complications after orthotopic liver transplantation.

OBJECTIVE: The aim of our study was to evaluate the role of magnetic resonance cholangiography (MRC) in the diagnosis of biliary tract complications (BC) after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Among 21 OLT patients who underwent routine follow-up MRC using a breath-hold T2-weighted turbo spin-echo sequence with half-Fourier acquisition (HASTE), 5 had an elevated serum alkaline phosphatase level. Diagnostic confirmation was obtained with endoscopic retrograde cholangiography (ERC) (n = 11), surgery (n = 3), or clinical and laboratory follow-up of at least 1 year (n = 8). RESULTS: In 13 patients, no abnormality of the biliary tract was detected using MRC. In 8 patients, anastomotic strictures were diagnosed, 7 of which were confirmed at surgery or using ERC. One patient with normal findings at MRC and abnormal liver function test results was found to have a stricture at ERC. All patients with normal MRC and liver function tests had 1 year of uneventful follow-up and were considered true-negative cases. We found that MRC had 87.5% sensitivity, 92.3% specificity, 87.5% positive predictive value, 92.3% negative predictive value, and 90.4% accuracy for the diagnosis of BC. CONCLUSION: MRC is a valuable examination to detect BC after OLT. It provides useful information for planning interventional procedures.

Cholangiography↗
PubMed2003

Flow cytometry assessment of bacterioplankton in tropical marine environments.

Flow cytometry was used to characterize bacterioplankton from two tropical environments in Brazil: the eutrophic Guanabara Bay and the oligotrophic southwest Atlantic Ocean. Bacterial abundance was evaluated by flow cytometry, and cells were stained with SYTO 13, allowing demonstration of differences in nucleic acid content. Bacterial production was also evaluated by means of 3H-leucine incorporation. Bacterial numbers were different for both sites. In Atlantic Ocean samples, we found a maximum of 5.50 x 10(5) cells ml(-1), and low nucleic acid content organisms predominated. In Guanabara Bay, bacterial numbers were one order of magnitude higher than in the ocean, and they varied from outer bay (1.01 x 10(6) cells ml(-1)) to inner bay (6.90 x 10(6) cells ml(-1)). Bacterial activity in ocean samples varied from 4.6 to 126 ng C l(-1) h(-1), while in the bay, mean values ranged from 1.95 microg C l(-1) h(-1) (outer bay) to 7.35 microg C l(-1) h(-1) (inner bay). Values found for both parameters are characteristic of different trophic situations. These results illustrate the utility of cytometric analyses of bacterioplankton populations in characterizing their large spatial and temporal scales of distribution in aquatic ecosystems.

Atlantic Ocean↗
PubMed2003

Influence of preservation solution on early lung function (Euro-Collins vs Perfadex).

BACKGROUND: This clinical study was performed to evaluate the efficiency of 2 different preservation solutions (Euro-Collins [EC] vs Perfadex [P]) on organ function in human lung transplantation. METHODS: The donor lungs for 46 patients were flushed either with EC solution (25 cases, EC group) or Perfadex (21 cases, P group). Transplant function was assayed using PaO2/FiO2 ratio after transplantation upon intensive care unit (ICU) arrival and at 12 and 24 hours later (T1, T2, and T3, respectively). We also compared the duration of mechanical ventilatory support and ICU stay. RESULTS: The PO2/FiO2 ratio was significantly better in the P than EC group at T1, T2, and T3. The duration of mechanical ventilatory support and ICU stay were lower also in P group, whereas age, sex, aetiology of lung disease, donor, PaO2/FiO2 ratio, and ischemia time did not show differences between the 2 groups. CONCLUSIONS: Our data on graft function tend to confirm better graft preservation using the P preservation solution.

Humans↗
PubMed2002

Evaluation of pain and disability in plug repair with the aid of a personal digital assistant.

The purpose of this paper is to illustrate the method of real-time data collection using a hand-held personal digital assistant (PDA) in the operating suite, hospital, and office. The technique for the placement of a round Atrium ProLite self-forming, layered polypropylene plug in 155 hernia repairs is described. The study measured postoperative pain by the number of pills used (6.6) and categorizes patient return to work according to sedentary, manual, and standing with an average return to work time of 15.6 days for unilateral repair and 20.4 days for bilateral repair. Return to normal daily activity was within 22.3 days for unilateral- and 28.5 days for bilateral repair.

Computers, Handheld↗
PubMed2001

Matrix immobilization enhances the tissue repair activity of growth factor gene therapy vectors.

Although growth factor proteins display potent tissue repair activities, difficulty in sustaining localized therapeutic concentrations limits their therapeutic activity. We reasoned that enhanced histogenesis might be achieved by combining growth factor genes with biocompatible matrices capable of immobilizing vectors at delivery sites. When delivered to subcutaneously implanted sponges, a platelet-derived growth factor B-encoding adenovirus (AdPDGF-B) formulated in a collagen matrix enhanced granulation tissue deposition 3- to 4-fold (p < or = 0.0002), whereas vectors encoding fibroblast growth factor 2 or vascular endothelial growth factor promoted primarily angiogenic responses. By day 8 posttreatment of ischemic excisional wounds, collagen-formulated AdPDGF-B enhanced granulation tissue and epithelial areas up to 13- and 6-fold (p < 0.009), respectively, and wound closure up to 2-fold (p < 0.05). At longer times, complete healing without excessive scar formation was achieved. Collagen matrices were shown to retain both vector and transgene products within delivery sites, enabling the transduction and stimulation of infiltrating repair cells. Quantitative PCR and RT-PCR demonstrated both vector DNA and transgene mRNA within wound beds as late as 28 days posttreatment. By contrast, aqueous formulations allowed vector seepage from application sites, leading to PDGF-induced hyperplasia in surrounding tissues but not wound beds. Finally, repeated applications of PDGF-BB protein were required for neotissue induction approaching equivalence to a single application of collagen-immobilized AdPDGF-B, confirming the utility of this gene transfer approach. Overall, these studies demonstrate that immobilizing matrices enable the controlled delivery and activity of tissue promoting genes for the effective regeneration of injured tissues.

Adenoviridae↗
PubMed2001

Sustained effects of gene-activated matrices after CNS injury.

We show that when gene-activated matrices (GAM) are placed between the proximal and distal stumps of severed rat optic nerves, DNA is retained within the GAM, promoting sustained transgene expression in the optic nerve, in the GAM itself, and, more importantly, in axotomized retinal ganglion cells (RGC). Plasmids that encode basic fibroblast growth factor (FGF2), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) promote sustained survival of RGC for over 3 months after the initial injury. These findings suggest that immobilized DNA implanted into a CNS lesion will be delivered by axon terminal uptake and retrograde transport to axotomized neurons. GAM may therefore be a useful agent for promoting sustained neuron survival and axon regeneration. Whether further optimization of the matrices, plasmids, promoters, and genes present in the GAM will promote even more survival or, alternatively, axon regeneration remains to be determined.

Animals↗
PubMed2001

Interactions of a hemidesmosome component and actinin family members.

Hemidesmosomes are multimeric protein complexes that attach epithelial cells to their underlying matrix and serve as cell surface anchorage sites for the keratin cytoskeleton. Two hemidesmosome components, the alpha6beta4 integrin heterodimer and a human autoantigen termed BP180, are transmembrane proteins that link the extracellular matrix to the keratin network in cells. Here, we report that actinin-4, an actin-bundling protein, is a potential binding partner for BP180. Using yeast two-hybrid, we have mapped the binding site for BP180 to the C-terminal region of actinin-4. This site contains two EF-hand, Ca2+ regulation domains and shares 87% sequence homology with the same region in actinin-1. Consistent with this, BP180 can bind actinin-1 in both the yeast two-hybrid assay and in immunoprecipitation assays. To determine whether the EF-hand domain is a consensus binding sequence for BP180, we tested whether other proteins with this domain bind BP180. None of the proteins tested including calmodulin, with 4 EF-hand domains, and myosin regulatory light chain, with 1 EF-hand domain, interacts with BP180 in yeast two-hybrid system and immunoprecipitation studies, suggesting that the interaction between BP180 and actinin family members is specific. We have compared the distribution of actinin-1 and actinin-4 with that of BP180 in MCF-10A and pp126 cells. Surprisingly, BP180 localizes not only to sites of cell-substratum interaction, but is also present at sites of cell-cell contacts where it co-distributes with both actinin-1 and actinin-4 as well as other adherens junction proteins. In oral tissues, BP180 is present along the basement membrane and at cell-cell contact sites in basal epithelial cells where it co-distributes with adherens junction proteins. Since BP180 antibodies inhibit association of junction proteins at sites of cell-cell contact in oral keratinocytes, these results suggest that BP180 may play a role in establishing cell-cell interactions. We discuss a role for BP180 in crosstalk between cell-matrix and cell-cell junctions.

Actinin↗
PubMed2001

Helicobacter pylori infection in patients undergoing gastric bypass surgery for morbid obesity.

BACKGROUND: Studies suggest that the incidence of Helicobacter pylori infection in obese patients, including those undergoing gastric reduction surgery, may be increased. METHODS: We examined the histologic findings at the time of surgery in a series of patients who were undergoing Roux-en-Y gastric bypass (RYGBP) for morbid obesity and compared these results with patients in our institution undergoing endoscopy. RESULTS: Of 60 patients undergoing RYGBP, material for histologic examination was available in 56 cases, and in 40 cases gastric fundic mucosa from the anastomotic site was sampled at the time of surgery. Active chronic gastritis was present in 6 (15%), and chronic gastritis was present in 27 (68%). H. pylori was present in all 6 cases of active chronic gastritis and in 9 cases of chronic gastritis (total 38%). This incidence of H. pylori infection was higher than that found in the series of gastric biopsies (107/500, 21%, p = 0.03) and fundic biopsies (10/80, 13%, p = 0.003), but was not different when compared with age-matched gastric biopsies (44/177, 25%, p = 0.12). CONCLUSIONS: The incidence of H. pylori in patients undergoing RYGBP was higher than that found in all patients undergoing endoscopy and biopsy and than those undergoing fundic biopsies, but not higher when age-matched controls were considered.

Adult↗
PubMed2000

Fibroblast growth factor 2-retargeted adenoviral vectors exhibit a modified biolocalization pattern and display reduced toxicity relative to native adenoviral vectors.

Targeted vectors provide a number of advantages for systemic and local gene delivery strategies. Several groups have investigated the utility of using various ligands to alter the tropism of adenovirus (Ad) vectors. We have previously demonstrated that fibroblast growth factor (FGF) ligands can specifically target DNA transfection and Ad transduction through high-affinity FGF receptors (FGFRs). FGFRs are overexpressed in abnormally proliferating tissues, such as malignancies. The present studies explore the effects of retargeting with FGF2 on the tissue localization pattern and the systemic toxicity of Ad in mice. Results of semiquantitative PCR analyses indicate that the distribution of FGF2-Ad vector genome sequences after intravenous administration in mice is altered. Markedly lower amounts (10- to 20-fold) of FGF2-Ad localize to the liver when compared with native Ad. This decrease in liver deposition translates into a significant reduction in subsequent toxicity as measured by serum transaminases and histopathology in mice injected with FGF2-AdHSV-thymidine kinase with and without ganciclovir administration. In an intraperitoneal model of ovarian cancer, FGF2-Ad generates increased transgene expression in tumor tissue when compared with Ad. Taken together, these results indicate that the retargeting of Ad with FGF2 results in a more efficient vector system for systemic and regional gene therapy applications, with concomitant lower levels of systemic toxicity.

Adenoviridae↗
PubMed2000

FGF2-Targeted adenovirus encoding platelet-derived growth factor-B enhances de novo tissue formation.

Gene therapy has yet to achieve reproducible clinical efficacy, due to inadequate gene delivery, inadequate gene expression, or dose-limiting toxicity. We have developed a gene therapy technology for tissue repair and regeneration that employs a structural matrix for DNA delivery. The matrix holds the DNA vector at the treatment site and provides a scaffolding for in-growth and accumulation of repair cells and efficient DNA transfection. We now report, for the first time, matrix-mediated delivery of targeted DNA vectors for soft tissue repair. A collagen matrix was used to deliver an adenoviral vector encoding platelet-derived growth factor-B (AdPDGF-B), resulting in efficient transgene expression in vitro and in vivo. Increases in the overall levels of expression and in the relative amounts of secreted PDGF-BB were achieved when AdPDGF-B was conjugated to fibroblast growth factor (FGF2) such that the virus was targeted for cellular uptake via FGF receptors. Matrix-mediated delivery of AdPDGF-B enhanced wound healing responses in vivo, and FGF2 targeting generated effects comparable to nontargeted vectors at significantly lower doses. Therefore, matrix-mediated delivery in combination with FGF2 targeting overcomes some of the safety and efficacy limitations of current gene therapy strategies and is an attractive therapeutic approach for tissue repair and regeneration.

Animals↗
PubMed2000

Identification of G protein-coupled signaling pathways in cardiac fibroblasts: cross talk between G(q) and G(s).

Cardiac fibroblasts (CFs) are an important cellular component of myocardial responses to injury and to hypertrophic stimuli. We studied G protein-coupled receptors to understand how CFs integrate signals that activate G(q), G(s), and G(i). We predicted that the second messenger pathways present in CFs were distinct from those in cardiac myocytes and that unique signaling interactions existed in the CFs. ANG II, bradykinin, ATP, and UTP stimulated inositol phosphate (IP) production 2.2- to 7-fold. Each of these agonists elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) via release from the intracellular Ca(2+) storage compartment. Endothelin-1 (ET-1), carbachol, and norepinephrine failed to increase either IP production or [Ca(2+)](i). Although agonists that activated IP and Ca(2+) transients had no effect on cAMP production when administered alone, these agents potentiated the beta(2)-adrenergic response two- to fourfold. Hormones known to inhibit adenylyl cyclase activity in cardiac myocytes, such as ET-1 and carbachol, failed to lower the beta-adrenergic response in fibroblasts. Order of potency and inhibitor data indicate that the functional receptor subtypes in these cells are beta(2), P2Y(2), and AT(1) for isoproterenol, ATP, and ANG II, respectively. We conclude that CFs express functional G protein-linked receptors that couple to G(q) and G(s), with little or no coupling to G(i). The expression of receptors and their coupling to G(q)- but not to G(i)-linked responses distinguishes the signaling in CFs from that in myocytes. Furthermore, agonists that activate G(q) in CFs potentiate stimulation of G(s), an example of signaling cross talk not observed in adult myocytes. These data suggest that G protein-mediated signaling in CFs is unique and may contribute to the specificity of hormone and drug action on individual cell types within the heart.

Adenosine Triphosphate↗
PubMed2000

Dietary intake and nutritional status in Italian elderly subjects.

Dietary intake and nutritional status was assessed in a random sample of 190 Italians (70-75 years of age) participating in the Survey in Europe on Nutrition and the Elderly (EURONUT-SENECA). The daily energy intake as assessed by a Modified Dietary History, was 2208+/-562 Kcalories in men and 1742+/-527 Kcalories in women. The alcohol intake was significantly higher in men than in women (35. 9+/-32.5 g/day vs 14.7+/-15.4 g/day; p<0.0001). As for calcium, there was a high percentage of men (77%) and women (86%) with a lower intake than the recommended values. The subjects underweight (BMI<20) were only 4.1% men and 9.7% women, while the great part was normal (BMI= 20-24.9) and overweight (BMI=25-29.9). The body composition parameters showed a significant difference between two genders. Men had a Total Body Water (56.5+/-4.5% vs 51.3+/-5.4%; p<0. 001) and Fat-Free Mass (80.4+/-5.2% vs 70.9+/-6.8%; p<0.001) higher than women. Few subjects were at high risk of deficiency with regard to plasma levels of vitamins, haemoglobin and albumin. If we analyse the composition of the diet consumed, we can remark the characteristics of a typical Mediterranean diet. We conclude that the general nutritional status of our sample was fairly good.

Aged↗