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Biomedical subjects

M Gomez

Publications and source records attributed to M Gomez.

At least 37 records · Page 2Linked to original sources
PubMed2000

Coat proteins regulating membrane traffic.

This review focuses on the roles of coat proteins in regulating the membrane traffic of eukaryotic cells. Coat proteins are recruited to the donor organelle membrane from a cytosolic pool by specific small GTP-binding proteins and are required for the budding of coated vesicles. This review first describes the four types of coat complexes that have been characterized so far: clathrin and its adaptors, the adaptor-related AP-3 complex, COPI, and COPII. It then discusses the ascribed functions of coat proteins in vesicular transport, including the physical deformation of the membrane into a bud, the selection of cargo, and the targeting of the budded vesicle. It also mentions how the coat proteins may function in an alternative model for transport, namely via tubular connections, and how traffic is regulated. Finally, this review outlines the evidence that related coat proteins may regulate other steps of membrane traffic.

Adaptor Protein Complex alpha Subunits↗
PubMed2000

Control of pre-T cell proliferation and differentiation by the GTPase Rac-I.

The GTPase Rac-I has the potential for pleiotropic functions due to its ability to interact with multiple effectors. Here, activation of Rac-I is shown to potently regulate pre-T cell differentiation and proliferation at the point of T cell antigen receptor (TCR) beta selection. An activated Rac-I effector domain mutant that restricts signaling to particular actions on actin dynamics can drive pre-T cell differentiation. Rac-I activation cannot fully substitute for the pre-TCR complex but can fully correct defects in pre-T cell development in mice lacking the adapter molecule Vav-1. The present study identifies the subset of Rac-I responses that mediate Vav-1 action as critical regulators of TCR beta selection.

Animals↗
PubMed2000

Minimizing blood loss in burn surgery.

BACKGROUND: Significant blood loss continues to plague early tangential excision of the burn wound. Although various techniques to reduce intraoperative blood loss have been described, there is an absence of uniformity and consistency in their application. Furthermore, it is unclear whether these techniques compromise intraoperative tissue assessment and wound outcome. The purpose of this study was to evaluate the effects of a comprehensive intraoperative blood conservation strategy on blood loss, transfusion requirements, and wound outcome in burn surgery. METHODS: An intraoperative blood conservation strategy (CONSV) that included donor site and burn wound adrenaline tumescence, donor site and excised wound topical adrenaline, and limb tourniquets was prospectively evaluated and compared with a historical control group (HIST) where only topical adrenaline and thrombin were applied to donor sites and excised wounds. RESULTS: Estimated blood loss was reduced from 211 +/- 166 mL per percentage body surface area excised and grafted in the HIST group to 123 +/- 106 mL in the CONSV group (p = 0.02). Similarly, the intraoperative transfusion requirement in the HIST group was reduced from 3.3 +/- 3.1 units per case to 0.1 +/- 0.3 units per case in the CONSV group (p < 0.001). There was no compromise in wound outcome in the CONSV group, which had a mean skin graft take rate of 96 +/- 4.2%. CONCLUSION: The application of a strict and comprehensive intraoperative blood conservation strategy during burn excision and grafting resulted in a profound reduction in blood loss and transfusion requirements, without compromising wound outcome.

Adolescent↗
PubMed2000

Hearing conservation for farmers: source apportionment of occupational and environmental factors contributing to hearing loss.

Those who work on farms continue to have a strikingly high prevalence of hearing loss, despite efforts to promote hearing conservation in agriculture. To develop improved hearing conservation programs, we performed a source apportionment analysis for hearing loss in a large, multiphasic health survey, the New York Farm Family Health and Hazard Survey. We used information from audiometric, otoscopic, and tympanometric examinations; detailed general health and farm exposure interviews; and a second interview that focused on additional potential determinants of hearing loss. Hearing loss on audiometry was significantly associated with increased age, male gender, education through high school or less, lifetime years of hunting with guns, lifetime years of use of a grain dryer, and a history of spraying crops during the previous year. Hearing conservation programs for farmers should thus be directed toward reduction in noise exposure, both from occupational and non-occupational sources. Additional study is needed to evaluate the association seen between crop spraying and hearing loss.

Adult↗
PubMed2000

Identification of secreted proteins of Mycobacterium tuberculosis by a bioinformatic approach.

Proteins secreted by Mycobacterium tuberculosis are usually targets of immune responses in the infected host. Here we describe a search for secreted proteins that combined the use of bioinformatics and phoA' fusion technology. The 3,924 proteins deduced from the M. tuberculosis genome were analyzed with several computer programs. We identified 52 proteins carrying an NH(2)-terminal secretory signal peptide but lacking additional membrane-anchoring moieties. Of these 52 proteins-the TM1 subgroup-only 7 had been previously reported to be secreted proteins. Our predictions were confirmed in 9 of 10 TM1 genes that were fused to Escherichia coli phoA', a marker of subcellular localization. These findings demonstrate that the systematic computer search described in this work identified secreted proteins of M. tuberculosis with high efficiency and 90% accuracy.

Algorithms↗
PubMed2000

Use of coagulase gene (coa) repeat region nucleotide sequences for typing of methicillin-resistant Staphylococcus aureus strains.

Coagulase gene (coa) short sequence repeat region sequencing was used to measure relatedness among a collection of temporally and geographically diverse methicillin-resistant Staphylococcus aureus isolates. The results show that coa polymorphism is free of strong selective pressure and has a low index of variation that may be useful for long-term epidemiological investigations. coa typing is a useful addition to spa typing for analysis of S. aureus, including methicillin-resistant strains.

Amino Acid Sequence↗
PubMed2000

COPI vesicles accumulating in the presence of a GTP restricted arf1 mutant are depleted of anterograde and retrograde cargo.

Microinjection of the slowly hydrolyzable GTP analogue GTP(gamma)S or the ectopic expression of a GTP restricted mutant of the small GTPase arf1 (arf1[Q71L]) leads to the rapid accumulation of COPI coated vesicles and buds in living cells. This effect is blocked at 15 degrees C and by microinjection of antibodies against (beta)-COP. Anterograde and retrograde membrane protein transport markers, which have been previously shown to be incorporated into COPI vesicles between the endoplasmic reticulum and Golgi complex, are depleted from the GTP(gamma)S or arf1[Q71L] induced COPI coated vesicles and buds. In contrast, in control cells 30 to 60% of the COPI carriers co-localize with these markers. These in vivo data corroborate recent in vitro work, suggesting that GTP(gamma)S and arf1[Q71L] interfere with the sorting of membrane proteins into Golgi derived COPI vesicles, and provide the first in vivo evidence for a role of GTP hydrolysis by arf1 in the sorting of cargo into COPI coated vesicles and buds.

ADP-Ribosylation Factor 1↗
PubMed2000

Risk factors for Giardia intestinalis infection in agricultural villages practicing wastewater irrigation in Mexico.

This study assessed the risk factors for Giardia intestinalis infection in an agricultural population in Mexico. Exposure groups included 2,257 individuals from households exposed to untreated wastewater, 2,147 from a group using the effluent from a series of reservoirs, and 2,344 from rain-fed agricultural villages. Stool samples were collected from 6,748 individuals. Wastewater samples were tested for fecal coliforms/100 ml and Giardia sp. cysts/L. Untreated wastewater samples contained 10(8) fecal coliforms/100 ml and up to 300 Giardia sp. cysts/L. Hydraulic retention (3-7 months) in the reservoirs, however, provided an improved effluent quality (10(1)-10(4) fecal coloforms/100 ml and < or = 5 Giardia sp. cysts/L). Children 1-14 years of age had the highest prevalence of infection (20%). Data showed marginal associations between storing drinking water in unprotected containers and lack of facilities for feces disposal and the risk of infection (odds ratios [ORs] = 1.76 and 1.19, 95% confidence intervals [CIs] = 0.95-3.23, and 0.97-1.45, respectively). Individuals purchasing vegetables at the city market had higher rates of infection than those buying at the village shop (OR = 2.49, 95% CI = 1.00-6.17). No excess risk was found in individuals exposed to untreated wastewater compared with controls (OR = 1.07, 95% CI = 0.84-1.36); the group using reservoir water was not different from the controls (OR = 1.22, 95% CI = 0.94-1.58). No risk from agricultural activities was detected (OR = 0.83). This pattern of infection may be addressed by primary health care and wastewater treatment.

Adolescent↗
PubMed1999

ARDS in patients with thermal injury.

OBJECTIVE: To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population. DESIGN: Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions. SETTING: Regional, tertiary referral, adult burn unit in a university teaching hospital. PATIENTS AND PARTICIPANTS: Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of 469 consecutive admissions, 126 (26.9%) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 +/- 5.2 and 8.2 +/- 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2% developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2%) in those with ARDS compared to those without (p = 0.27). CONCLUSIONS: According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.

APACHE↗
PubMed1999

Identification of a novel inflammation-protective locus in the Fischer rat.

Inbred LEW/N rats are relatively susceptible, while histocompatible inbred F344/N rats are relatively resistant to development of a wide variety of inflammatory diseases in response to a range of pro-inflammatory stimuli. In a LEW/N vs. F344/N F2 intercross, we identified a quantitative trait locus (QTL) on Chr 10 that protects in a dominant fashion against the exudate volume component of innate inflammation in the F344/N rat, as well as a suggestive QTL on Chr 2 near the Fibrinogen cluster region. The exudate volume linkage region on Chr 10 may be similar to one of the multiple regions found to link to inflammatory arthritis phenotypes in other crosses. The suggestive linkage on Chr 2 has not been previously reported and does not seem to contribute to this phenotype in the same manner as the QTL on Chr 10. These findings are consistent with the hypothesis that the innate exudate volume trait is a sub-phenotype of more complex inflammatory phenotypes, such as arthritis, and genes within the Chr 10 linkage region could account for differences in this non-specific acute phase component of the inflammatory response. Since the rat Chr 10 exudate volume linkage region we have identified is syntenic with a region of human Chr 17 that has been shown to link to a variety of autoimmune/inflammatory diseases, including insulin-dependent diabetes mellitus, multiple sclerosis, and psoriasis, identification of genes within this linkage region will shed light on genes relevant to the earliest inflammatory component and to susceptibility and resistance to such human autoimmune/inflammatory diseases.

Animals↗
PubMed1999

Endogenous polyamines modulate Ca2+ channel activity in guinea-pig intestinal smooth muscle.

The polyamines spermine and spermidine inhibit L-type Ca2+ channels in whole-cell recordings from guinea-pig ileum cells (Gomez and Hellstrand, Pflügers Arch, 430:501-507, 1995 [4]). To study whether they modulate channel activity under physiological conditions, we further investigated their actions on Ca2+ channels and the effects of altered cellular polyamine contents. In inside-out patches, spermine (0.1-1 mM) inhibited channel activity without affecting the amplitude of unitary currents. In cell-attached recordings, addition of spermine to the bath did not influence channel activity in the patch, indicating that its extracellular action is direct and not mediated via passage of the polyamine through the cell membrane. Cellular contents of spermidine and spermine were decreased by about 50% by organ culture of ileum strips for 5 days with the adenosylmethionine decarboxylase inhibitor CGP 48664 (10 microM). This caused enhanced channel activity in cell-attached recordings, suggesting a reduced level of channel block by endogenous polyamines compared with control cells. Whole-cell recordings in the perforated patch mode showed increased current in polyamine-depleted cells, while this was not seen when cells were dialysed with the pipette solution. We conclude that polyamines block Ca2+ channels from the inside as well as the outside of the cell membrane, and that endogenous polyamines in smooth muscle modulate Ca2+ channel activity.

Amidines↗
PubMed1999

Pentacyclic triterpenes from Chuquiraga ulicina.

Four taraxastane triterpenes, 3 beta-acetoxy-6 beta-hydroxytaraxasta-20-ene, 6 beta-hydroxytaraxasta-20-en-3-one, 6 beta-hydroxytaraxasta-20-ene 3 beta-palmitate and 3 beta,6 beta-dihydroxytaraxasta-20-ene were isolated from the dichloromethane-methanol extract of Chuquiraga ulicina ssp. ulicina together with the known triterpenes lupeol, lupenyl acetate, lupenone, friedelinol, 3 beta-acetoxy-30-nor-lupan-20-one, and 30-nor-lupan-3 beta-ol-20-one.

Chile↗
PubMed1999

Identification and characterization of two divergently transcribed iron regulated genes in Mycobacterium tuberculosis.

SETTING: Low iron availability in the host induces the expression of iron acquisition systems and virulence genes in many pathogens. IdeR is a mycobacterial iron dependent regulator that controls the iron starvation and oxidative stress responses in Mycobacterium smegmatis. It is important to determine the role of IdeR and its regulon in M. tuberculosis, as identification of iron regulated genes can aid in the design of new drugs and generation of attenuated strains. OBJECTIVE: A potential IdeR binding site was found in the M. tuberculosis genome flanked by two divergently oriented open reading frames, irg1 and irg2. The aim of this study was to determine whether irg1 and irg2 were iron and IdeR regulated genes. DESIGN: Interaction of IdeR with the putative binding sequence was examined by gel shift and footprinting assays. Transcriptional fusions of irg1 and irg2 to IacZ were used to study the effect of iron levels on the expression of these genes. RESULTS: IdeR binds to the predicted binding site, which overlaps with the irg1 promoter. irg1 and irg2 expression was decreased by iron in M. tuberculosis and in wild type M. smegmatis, but not in a M. smegmatis ideR mutant. CONCLUSION: Two M. tuberculosis iron/IdeR regulated genes were identified. irg1 is predicted to be the M. tuberculosis hisE gene, which is involved in histidine biosynthesis. It is directly upstream of the M. tuberculosis hisG. irg2 encodes a putative membrane protein that is a member of the PPE family.

Bacterial Proteins↗
PubMed1999

Feasibility of vermicomposting dairy biosolids using a modified system to avoid earthworm mortality.

A laboratory study was conducted to examine the feasibility of vermicomposting dairy biosolids (dairy sludge), either alone or with either of the bulking agents-cereal straw or wood shavings, using the epigeic earthworm-Eisinea andrei. Earthworms added directly to these three substrates died within 48 hours. A system was developed to overcome the toxic effect of unprocessed dairy biosolids. The substrates were placed over a layer of vermicomposted sheep manure into which the earthworms were inoculated. Within two weeks, all earthworms were within the upper layer of substrate. Compared to sheep manure which is a favourable substrate for vermicomposting, the three substrates containing dairy biosolids were more effective in supporting earthworm growth and reproduction. The final products obtained after 63 days of vermicomposting had 39-53% less organic carbon than the initial substrates. Organic fractionation indicated that vermicomposting increased the stability of the materials to biological decomposition. The vermicomposts obtained from the three substrates with dairy biosolids had low heavy metal contents and electrical conductivities, and did not inhibit plant growth when compared with a commercial vermicompost in a bioassay.

Animals↗
PubMed1999

Utilization of intensive care unit days in a Canadian medical-surgical intensive care unit.

OBJECTIVES: To analyze the utilization of intensive care unit (ICU) days in a Canadian medical-surgical ICU and to identify ICU patients with prolonged ICU length of stay (LOS). DESIGN: Prospective descriptive study. SETTING: A Canadian tertiary care medical-surgical ICU. PATIENTS: Consecutive patients admitted to an adult medical-surgical ICU. Neurosurgical, cardiac surgical, and coronary care unit patients were excluded. MEASUREMENTS: For each ICU admission, patient demographics, diagnosis, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ICU LOS, and hospital mortality were collected. The patients' risk of death was calculated using the APACHE II equation. Admissions were stratified by ICU LOS into four groups: 1 to 2, 3 to 6, 7 to 13, and > or = 14 days. Among the four LOS groups, the number of ICU days and observed and predicted death rates were compared. Admissions were also stratified by risk of death into five probability range quintiles. Among the five risk groups, ICU LOS was compared between survivors and nonsurvivors. RESULTS: A total of 1,960 admissions utilized 9,298 ICU days. ICU LOS (mean +/- SEM) was 4.74 +/- 0.2 (median, 2; range, 1 to 178) days. Short-stay patients (ICU LOS < or = 2 days) accounted for 60.3% of total admissions but consumed only 16.4% of total ICU days. Long-stay patients (ICU LOS > or = 14 days) accounted for 7.3% of total admissions but consumed 43.5% of total ICU days. Among the long-stay patients, the most common reasons for admission were pneumonia, multiple trauma, neuromuscular weakness, and septic shock. The mortality for long-stay patients approached 50%. When analyzed by patients' mortality risks, those with a risk of death >0.8 (predicted to die) or <0.2 (predicted to live) whose outcomes were opposite to that predicted had twice the ICU LOS compared with patients whose outcomes were consistent with prediction. CONCLUSION: In a Canadian medical-surgical ICU, patients with ICU LOS > or = 14 days accounted for 7.3% of total admissions but consumed 43.5% of total ICU days. Identification of patients with prolonged ICU LOS who would ultimately die in the ICU may lead to earlier withdrawal of therapy in these patients, resulting in a substantial reduction in suffering and cost savings. In our study population, outcome prediction using the APACHE II equation did not provide sufficient power to accurately discriminate between nonsurvivors and survivors.

APACHE↗
PubMed1999

Transcriptional control of the iron-responsive fxbA gene by the mycobacterial regulator IdeR.

Exochelin is the primary extracellular siderophore of Mycobacterium smegmatis, and the iron-regulated fxbA gene encodes a putative formyltransferase, an essential enzyme in the exochelin biosynthetic pathway (E. H. Fiss, Y. Yu, and W. R. Jacobs, Jr., Mol. Microbiol. 14:557-569, 1994). We investigated the regulation of fxbA by the mycobacterial IdeR, a homolog of the Corynebacterium diphtheriae iron regulator DtxR (M. P. Schmitt, M. Predich, L. Doukhan, I. Smith, and R. K. Holmes, Infect. Immun. 63:4284-4289, 1995). Gel mobility shift experiments showed that IdeR binds to the fxbA regulatory region in the presence of divalent metals. DNase I footprinting assays indicated that IdeR binding protects a 28-bp region containing a palindromic sequence of the fxbA promoter that was identified in primer extension assays. fxbA regulation was measured in M. smegmatis wild-type and ideR mutant strains containing fxbA promoter-lacZ fusions. These experiments confirmed that fxbA expression is negatively regulated by iron and showed that inactivation of ideR results in iron-independent expression of fxbA. However, the levels of its expression in the ideR mutant were approximately 50% lower than those in the wild-type strain under iron limitation, indicating an undefined positive role of IdeR in the regulation of fxbA.

Bacterial Proteins↗