Search PubMed⌕ Search

Biomedical subjects

E Garcia

Publications and source records attributed to E Garcia.

At least 91 records · Page 5Linked to original sources

Stress proteins in fungal diseases.

Heat shock proteins (hsps) are ubiquitous families of proteins, found in all organisms studied so far. They are highly conserved across the species barrier and serve fundamental functions in cell physiology. The term 'heat shock' was adopted because of the early observation of the heat-inducible nature of these proteins, although, as it is now realized that they can be induced by a variety of stressful stimuli, it is probably more appropriate to call them 'stress proteins'. The nomenclature of many hsps, for example hsp90, hsp70 and hsp60, reflects the approximate molecular mass of hsps within each of these families. For many bacterial and parasitic infections, hsps were first recognized as immunodominant antigens on immunoblots of extracts from the organism probed with immune sera, or in T-cell proliferation assays. They have now been identified in a range of fungal pathogens, again often linked to an immune response. In this symposium, we review the association of hsps with humoral immunity to candidosis and aspergillosis, cellular immunity to histoplasmosis, and the identification of hsp70 in another dimorphic fungus, Paracoccidioides brasiliensis. Finally, the crucial role of the membrane in setting the temperature of the heat shock response in yeasts is discussed.

Animals↗

Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review.

OBJECTIVE: To provide a quantitative review of the treatment effects of primary coronary angioplasty vs intravenous thrombolysis for acute myocardial infarction. DATA SOURCES: Ten randomized trials were identified through computerized bibliographic search of MEDLINE from January 1985 through March 1996 and by queries of principal investigators. STUDY SELECTION: Single-center and multicenter randomized trials comparing primary angioplasty with intravenous thrombolytic therapy among 2606 patients were included. Four trials compared angioplasty with streptokinase, 3 compared angioplasty with a 3- to 4-hour infusion of tissue-type plasminogen activator, and 3 compared angioplasty with "accelerated" administration of tissue-type plasminogen activator over 90 minutes. DATA EXTRACTION: Each investigator provided definitions and exact data for outcome events. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were calculated using exact tests for categorical data. DATA SYNTHESIS: Mortality at 30 days or less was 4.4% for the 1290 patients treated with primary angioplasty compared with 6.5% for the 1316 patients treated with thrombolysis (34% reduction; OR, 0.66; 95% CI, 0.46-0.94; P=.02). The effect was similar among thrombolytic regimens, and no subgroup demonstrated a significant reduction in death. The rates of death or nonfatal reinfarction were 7.2% for angioplasty and 11.9% for thrombolytic therapy (OR, 0.58; 95% CI, 0.44-0.76; P<.001). Angioplasty was associated with a significant reduction in total stroke (0.7% vs 2.0%; P=.007) and hemorrhagic stroke (0.1% vs 1.1%; P<.001). CONCLUSIONS: Based on outcomes at hospital discharge or 30 days, primary angioplasty appears to be superior to thrombolytic therapy for treatment of patients with acute myocardial infarction, with the proviso that success rates for angioplasty are as good as those achieved in these trials. Data evaluating longer-term outcomes, operator experience, and time delay before treatment are needed before primary angioplasty can be universally recommended as the preferred treatment.

Angioplasty, Balloon, Coronary↗

Expression, genomic structure and high resolution mapping to 19p13.2 of the human smooth muscle cell calponin gene.

Smooth muscle cells (SMC) express a battery of cell-restricted differentiation genes, many of which are down-regulated during the course of vascular disease. Here, we present the mRNA expression, genomic structure and chromosomal mapping of the gene encoding human smooth muscle cell calponin (SMCC). Human SMCC transcripts are restricted to tissues and cells of SMC origin and, in the latter case, appear to be uniquely controlled in two distinct human SMC lines of uterine and aortic origin. Restriction mapping. Southern blot and PCR analysis of a 70-kb human bacterial artificial chromosome (BAC) revealed a genomic structure (seven exons spanning > 11 kb) very similar to that reported for the mouse SMCC gene. Using a variety of human-rodent somatic cell hybrid and radiation hybrid mapping panels, the human SMCC gene was mapped to a genomic interval of less than 1.32 Mb in 19p13.2. These results provide new information concerning the regulation of SMCC gene expression and demonstrate the utility of two human SMC lines for the further characterization of this gene's expression control. The identification of a BAC harboring the entire human SMCC locus represents an important reagent for future analysis of SMCC regulatory sequences. Finally, the localization of SMCC to a defined genomic interval will facilitate an analysis of its potential as a candidate gene for disease phenotypes mapping to 19p13.2.

Amino Acid Sequence↗

Molecular cloning of human RP105.

RP105 is a 105-kDa type I membrane protein of the leucine-rich repeat (LRR) family. Anti-RP105 sensitizes B cells to antigen-receptor-mediated apoptosis, but protects B cells from radiation-induced apoptosis and stimulates B cell proliferation. The sequence of the mouse RP105 has been reported. Here, we report the characterization of the human RP105. The 2.6-kb cDNA encodes a protein of 661 amino acids which displays 78% homology with mouse RP105. The 22 LRR and the 9 potential N-linked glycosylation sites within the extracellular region are conserved. While previous studies have shown that RP105 is expressed on surface IgM+IgD+2 B cells in mice, human RP105 was shown to be expressed on all subsets of mature B cells and dendritic cells. Human RP105 gene was mapped to the long arm of chromosome 5, where numerous cytokines and receptors have been localized.

Animals↗

Surgical management of Candida suppurative thrombophlebitis of superior vena cava after central venous catheterization.

Septic deep venous thrombosis is a major complication associated with central venous catheterization in intensive care units. The most common causative organisms are Staphylococcus aureus, gram-negative bacilli and Candida species. The incidence of Candida infections is increasing, especially in intensive care patients receiving total parenteral nutrition and long-term broad-spectrum antibiotics. Although intravascular catheter-induced septic thrombophlebitis is quite common, superior vena cava obstruction is a rare complication. However, few data exist concerning the best strategy for managing septic thrombophlebitis, especially when medical therapy fails. We report successful surgical management of Candida albicans suppurative thrombosis of the superior vena cava in a young patient.

Adolescent↗

[Low molecular weight heparin, reviparin, after PTCA: results of a randomized double-blind, standard heparin and placebo controlled multicenter study (REDUCE Study].

BACKGROUND: Unfractionated heparin and its low molecular fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of a low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single lesion coronary artery obstructions suitable for PTCA. Three hundred and six patients received reviparin as a 7000 U bolus before PTCA followed by 10,500 U as an infusion over 24 hours and then twice a day 3500 U s.c. application for 28 days. The 306 patients in the control group received a bolus of 10,000 U unfractionated heparin followed by an infusion of 24,000 U over 24 hours. These patients then received 28 days of s.c. placebo injections. The primary endpoints were efficacy (defined as a reduction in the incidence of major adverse events, i.e., death, myocardial infarction, need for reintervention or bypass surgery), absolute loss of minimal luminal diameter, and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention-to-treat analysis for all patients, 102 patients (33.3%) of the reviparin group and 98 patients (32%) of the control group have reached a primary clinical endpoint (relative risk = 0.98; 95% confidence limit, 0.88-1.09; p = 0.707). Likewise, no difference in late loss of minimal luminal diameter was evident for either group. Acute events within 24 hrs occurred in 3.9% of the reviparin group and in 8.2% of the control group (relative risk = 0.49; 95% confidence limit, 0.26-0.92; p = 0.027) during or immediately after the initial procedure. In the control group, 8 major bleedings occurred, and in the reviparin group, 7 major bleeding complications were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.

Adult↗

Rotational coronary atherectomy with adjunctive balloon angioplasty: evaluation of lumen enlargement by quantitative angiographic analysis.

To evaluate the mechanisms of lumen enlargement and the respective contributions of rotational coronary atherectomy (RA) and adjunctive percutaneous transluminal coronary balloon angioplasty (PTCA), serial measurements were recorded in 70 consecutive patients by quantitative coronary angiography before RA, after RA, after adjunctive PTCA, and 24 hours later. Minimal luminal diameter (MLD) increased from 0.85 +/- 0.31 mm to 1.42 +/- 0.27 mm (p < 0.001) after RA and to 2.20 +/- 0.46 mm (p < 0.001) after PTCA. Minimal luminal area (MLA) increased from 0.64 +/- 0.50 mm2 to 1.63 +/- 0.60 mm2 (p < 0.001) after RA and to 3.97 +/- 1.68 mm2 (p < 0.001) after PTCA. Both 24-hour MLD and MLA showed a trend toward reduced values (2.07 +/- 0.45 mm and 3.52 +/- 1.70 mm2, respectively) when compared with immediate results after PTCA. The absolute gains in MLD after RA and after PTCA were 0.56 +/- 0.24 mm and 0.79 +/- 0.38 mm, respectively (p < 0.01). The absolute gains in MLA after RA and after PTCA were 0.99 +/- 0.49 mm2 and 2.34 +/- 1.41 mm2, respectively (p < 0.001). The respective contributions of RA and PTCA are highly variable, but in general, balloon dilatation accounts for most of the gain in lumen area and therefore is not an adjunctive but a primary technique.

Aged↗

Bronchiolitis obliterans organizing pneumonia associated with acute Mycoplasma pneumoniae infection.

A patient with bronchiolitis obliterans organizing pneumonia (BOOP) associated with acute Mycoplasma pneumoniae infection is described. Although mycoplasmas have occasionally been associated with bronchiolitis obliterans, to the best of our knowledge, this is the first well-documented case of BOOP associated with M. pneumoniae infection. The diagnosis of BOOP was made by open-lung biopsy after fiberoptic transbronchial biopsy proved nondiagnostic. Corticosteroid therapy was administered and a dramatic improvement was observed; the patient remained without complaints during a 3-year follow-up period.

Acute Disease↗

Isolation and Characterization of Strain MMB-1 (CECT 4803), a Novel Melanogenic Marine Bacterium.

A novel marine melanogenic bacterium, strain MMB-1, was isolated from the Mediterranean Sea. The taxonomic characterization of this strain indicated that it belongs to the genus Alteromonas. Under in vivo conditions, L-tyrosine was the specific monophenolic precursor for melanin synthesis. This bacterium contained all types of activities associated with polyphenol oxidases (PPOs), cresolase (EC 1.18.14.1), catecholase (EC 1.10.3.1), and laccase (EC 1.10.3.2). These activities were due to the presence of two different PPOs. The first one showed all the enzymatic activities, but it was not involved in melanogenesis in vivo, since amelanogenic mutant strains obtained by nitrosoguanidine treatment contained levels of this PPO similar to that of the wild-type MMB-1 strain. The second PPO showed cresolase and catecholase activities but no laccase, and it was involved in melanogenesis, since this enzyme was lost in amelanogenic mutant strains. This PPO was strongly activated by sodium dodecyl sulfate below the critical micelle concentration, and it is a tyrosinase-like enzyme showing a lag period in its tyrosine hydroxylase activity that could be avoided by small amounts of L-dopa. This is the first report of a bacterium that contains two PPOs and also the first report of a pluripotent PPO showing all types of oxidase activities. The bacterium and the pluripotent PPO may be useful models for exploring the roles of PPOs in cellular physiology, aside from melanin formation. On the other hand, the high oxidizing capacity of the PPO for a wide range of substrates could make possible its application in phenolic biotransformations, food processing, or the cosmetic industry, where fungal and plant PPOs are being used.

Journal Article↗

Control of rat preadipocyte adipose conversion by ovarian status: regional specificity and possible involvement of the mitogen-activated protein kinase-dependent and c-fos signaling pathways.

As ovariectomy induces obesity in rats, we have investigated the influence of ovariectomy and hormone replacement on the proliferation and differentiation capacities of rat cultured preadipocytes removed from different fat depots (femoral sc, parametrial, and perirenal). Ovariectomy induced increased proliferation and differentiation as well as high mitogen-activated protein (MAP) kinase activity and c-fos protein induction in both confluent and differentiated preadipocytes from perirenal fat depots. In parametrial preadipocytes, ovariectomy also increased proliferation and c-fos protein induction, but failed to alter the capacities of these cells to differentiate. Treatment of ovariectomized rats with estradiol and progesterone reversed the promoting effect of ovariectomy on proliferation, differentiation, and c-fos induction in perirenal preadipocytes, but not the MAP kinase activation observed during the proliferative phase. This treatment also reversed the promoting effect of ovariectomy on proliferation and c-fos induction seen in confluent parametrial preadipocytes. In contrast, sc preadipocytes were totally insensitive to ovarian status in terms of proliferation and differentiation capacities, MAP kinase activity, and c-fos induction. This study demonstrates that adipogenesis is site-specifically controlled by the ovarian status in the rat. It also suggests that ovariectomy-induced obesity (mainly abdominal) could be related to changes in some of the signaling pathways controlling adipogenesis in intraabdominal preadipocytes.

Adipose Tissue↗

Site-related specificities of the control by androgenic status of adipogenesis and mitogen-activated protein kinase cascade/c-fos signaling pathways in rat preadipocytes.

In rats, castration induces a complete defective adipose conversion of preadipocytes from the epididymal fat depots (Lacasa, D., B. Agli, D. Noynarol, and Y. Giudicelli, 1995, Endocrine 3: 789-793). The aim of this study was to establish the eventual site-specificity of this effect as well as the mechanisms involved. Therefore, the influence of androgenic status on the Fos protein induction and the Raf/mitogen-activated protein (MAP) kinase kinase (MEK)MAP cascade, which are all required for adipose conversion of preadipocytes, was compared in proliferating and differentiated preadipocytes from femoral sc and deep intraabdominal (epididymal and perirenal) fat depots. In epididymal and perirenal proliferating preadipocytes, increased proliferation due to castration is associated with increased MAP kinase activity. However, higher immunoreactive levels of the upstream activators of MAP kinase, Raf-1 and MEK, were observed only in epididymal cells. Moreover, in vivo testosterone treatment corrected the effects of castration on Raf-1 but not on MEK and MAP kinase. MAP kinase activity was decreased during the course of adipogenesis. In differentiated cells, MAP kinase activity showed variations according to the anatomical origin of preadipocytes but not to the androgenic status. In contrast, MEK and Raf-1 immunoreactive levels were both sensitive to androgenic status but were differently affected depending on cell origin. Finally, the defective adipogenesis seen in epididymal preadipocytes from castrated rats was associated with reduced Fos protein induction in these cells, an alteration which was partly corrected by testosterone-treatment. Taken together, these results suggest that androgenic status affects adipogenesis from deep intraabdominal preadipocytes through alterations of some components of the MAP kinase cascade/Fos signaling pathways.

Adipocytes↗

Enhancing member retention, satisfaction, and compliance.

The authors discuss a health care communications skills training workshop to teach providers how to enhance patient satisfaction, compliance, and loyalty. Participants are taught the characteristics and communication needs of the four basic behavioral styles. This knowledge can make for more beneficial provider-patient encounter and better outcomes.

Communication↗

Fluorine-18-FPCT: a PET radiotracer for imaging dopamine transporters.

UNLABELLED: Fluorine-18-labeled 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane (FPCT) has been synthesized as a new dopamine transporter imaging agent. METHODS: Fluorine-18 was introduced into 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-[-3-fluoropropyl) nortropane by preparation of 1-[18F]fluoro-3-iodopropane followed by alkylation of 2 beta-carbomethoxy-3 beta-(4-chlorophenyl)nortropane. RESULTS: Tissue distribution studies in rats with [18F]FPCT showed high striatal uptake (0.70% dose/g at 60 min; 0.38% dose/g at 120 min) and good striatal-to-cerebellum ratios (5.5 at 60 min; 6.2 at 120 min). Imaging studies in rhesus monkeys (n = 2) with [18F]FPCT showed high uptake and retention in the putamen (P) (P = 0.03%-0.12% dose/g; at 115 min) and good putamen-to-cerebellum ratios of 3.40-3.43 at 115 min. Plasma metabolites were analyzed in rhesus monkeys (n = 2) by ether extraction and HPLC. The radioactivity in the ether-extractable fraction displayed a single peak that corresponded on HPLC to unmetabolized authentic FPCT. CONCLUSION: These results suggest that [18F]FPCT is an excellent candidate for PET imaging of dopamine transporters.

Animals↗

Breakpoints of 19q13 translocations of benign thyroid tumors map within a 400 kilobase region.

Structural rearrangements involving the long arm of chromosome 19 characterize a cytogenetic subgroup of benign thyroid tumors. To localize the breakpoint of the 19q13 aberrations, we have established three cell lines derived from benign thyroid tumors showing translocations in this region. We have used these cell lines and four additional primary tumors with 19q13 abnormalities for fluorescence in situ hybridization (FISH) mapping studies with ten cosmid clones located between the molecular markers POLD1 and TNNT1. The breakpoints of all chromosome 19 abnormalities mapped within a 400 kb region.

Adenoma↗

UFT in combination as adjuvant therapy for breast cancer. Grupo Oncologico de Sevilla Seville, Spain.

Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a mean follow-up of 5.09 +/- 1.1 years (range, 2.9 to 7.1 years). The aim of the first trial was to demonstrate the activity of UFT 400 mg/day for 6 months plus prednimustine 60 mg/m2 for 7 consecutive days, every 28 days in 6 cycles given orally (arm B). This scheme was compared with 6 cycles of cyclophosphamide 600 mg/m2, plus methotrexate 40 mg/m2, plus fluorouracil 600 mg/m2, every 4 weeks (arm A). In this study, 187 premenopausal women were evaluable, 96 in arm A and 91 in arm B, all of whom had positive axillary nodes. Although there were more younger patients in arm A than in arm B, prognostic factors were similar in both groups. Disease-free survival and overall survival were similar in both arms. However, some concern is raised by the low disease-free survival rate. The toxicity was mild (mainly nausea and vomiting and alopecia) and slightly worse in arm A. We believe that oral administration could be a useful alternative to the parenteral route. In the second trial, 222 evaluable patients received 20 mg/day of tamoxifen (Nolvadex) for 1 year (arm A), or the same dose of tamoxifen plus UFT 400 mg/day for 6 months. All patients were postmenopausal, and the characteristics of the tumors were the same as those in patients in the first trial. In arm A there were 109 patients and in arm B, 113. The groups were well balanced. The overall survival and the disease-free survival rates were equal in both arms, but were longer in arm B in the subset of patients with five or more axillary-involved nodes. The toxicity was negligible in both arms. We conclude that UFT/tamoxifen might be useful in postmenopausal patients with five or more involved nodes who are unable to follow a more aggressive schedule because of their age or low performance status.

Administration, Oral↗

The stimulatory effect of rabphilin 3a on regulated exocytosis from insulin-secreting cells does not require an association-dissociation cycle with membranes mediated by Rab 3.

Rabphilin 3a is a Rab 3-GTP binding protein concentrated on secretory vesicles of neurons and endocrine cells. There is evidence that rabphilin 3a undergoes cycles of association-dissociation with membranes and that recruitment of rabphilin 3a to secretory vesicles is mediated by Rab 3a, suggesting that rabphilin 3a is a downstream effector of this Rab. In this study we have investigated whether a membrane-anchored form of rabphilin 3a mimics the action of rabphilin 3a on secretion and bypasses the need for Rab 3 function. Overexpression of both wild-type rabphilin 3a and of a transmembrane anchored form of rabphilin 3a stimulated (about 2-fold) evoked secretion of coexpressed human proinsulin from clonal HIT-T15 cells. A similar transmembrane-anchored protein which lacked the Rab 3 binding region stimulated secretion even more effectively. Unexpectedly, a rabphilin 3a deletion mutant missing the Rab 3 binding domain was also stimulatory on secretion, although a further deletion of rabphilin to exclude the first of the two proline-rich regions abolished its stimulatory effect. The first of these two mutants was primarily particulate, while the second mutant was primarily soluble, suggesting that the first proline-rich region of rabphilin 3a plays a role in targeting rabphilin to its site of action. We conclude that the action of rabphilin 3a can be independent of Rab 3 if other mechanisms produce a sufficient concentration of the protein in proximity of exocytotic sites. These results provide new evidence for a fundamental similarity in the mechanisms by which Ras and Rab GTPase produce their distinct physiological effects.

Adaptor Proteins, Signal Transducing↗