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Biomedical subjects

M Gonzalez

Publications and source records attributed to M Gonzalez.

At least 127 records · Page 7Linked to original sources
PubMed1997

Operational aspects of bednet impregnation for community-based malaria control in Nicaragua, Ecuador, Peru and Colombia.

Community intervention projects with pyrethroid (permethrin and lambdacyhalothrin) impregnated bednets and an accompanying community education programme were carried out in 6 malaria endemic areas on the Pacific coast of Nicaragua, Ecuador, Peru and Colombia as well as in the Peruvian Amazon basin. In this paper the operational aspects are analysed: bednet coverage, results of promotional activities for increased bednet use, the sale of low-cost bednets, techniques and difficulties with impregnation, acceptance of the programme (including washing of impregnated nets), side-effects, residual concentrations of the chemical in the nets, costs of the impregnation programme and insecticide resistance of the malaria vectors. We found that the local manufacture of bednets and their sale through village health workers, even in communities with low cash income, is a viable way of increasing bednet coverage; the impregnation of bednets is well accepted if villagers perceive a direct benefit; pretesting of the soaking capacity of different net materials should be done at central level; the instructions for the impregnation procedures of different net materials (cotton and synthetic) should be simple and unambiguous; very cheap thin net materials should be avoided, particularly in the case of lambdacyhalothrin impregnation; educational methods and/or promotion of dark-colour nets should be further tested in order to decrease the washing frequency of bednets at household level; in areas with early-biting mosquitoes further studies on the protective efficacy of bednets are necessary; careful monitoring of side-effects, particularly those of last-generation pyrethroids, is necessary; and the community-based impregnation programme is a powerful tool for strengthening community involvement in health actions.

Bedding and Linens↗
PubMed1997

Treatment of cutaneous leishmaniasis with allopurinol and stibogluconate.

We conducted a randomized, controlled study in southern Colombia to determine if the addition of allopurinol to stibogluconate was superior to stibogluconate alone in the treatment of cutaneous leishmaniasis. Lesions that healed after a 3-month course of therapy and remained so during a 1-year period of follow-up were considered cured. The cure rate for patients treated with stibogluconate was 39%; the addition of allopurinol increased this rate to 71% (P = .005). For the treatment of cutaneous leishmaniasis, the combination of allopurinol and stibogluconate is significantly more effective than is stibogluconate alone. These results support those of other clinical studies in which allopurinol and stibogluconate were shown to be superior to stibogluconate alone. The aggregate data support the use of allopurinol as an inexpensive, orally administered agent that can be used as an adjunct to stibogluconate or, perhaps, other oral agents in the treatment of cutaneous leishmaniasis.

Adolescent↗
PubMed1997

Modulation of motoneuron excitability by brain-derived neurotrophic factor.

The influence of neurotrophins on motoneuron survival and development has been well documented in cell cultures and neonates. In the present study, the role of brain-derived neurotrophic factor (BDNF) in the maintenance of motoneuron electrical properties was investigated. In adult male rats, BDNF- or saline-saturated gelfoam was inserted between the medial and lateral heads of the gastrocnemius muscles. After 5 days survival, in vivo intracellular recordings were obtained, and motoneuron biophysical properties were measured. In BDNF-treated rats, significant decreases in mean rheobase and in total cell capacitance of medial gastrocnemius motoneurons were observed. In addition, a concommitant increase in input resistance and decrease in membrane time constant were noted in BDNF-treated rats but were not statistically significant. No significant treatment effect was observed in motoneuron conduction velocity, action potential amplitude, equalizing time constant, electrotonic length, afterhyperpolarization amplitude and duration, and membrane potential sag during current injection. The observed changes in motoneuron rheobase and total cell capacitance suggest that application of BDNF produces an increase in motoneuron excitability coincident with a reduction in size. These data are discussed with respect to the possible role of BDNF as a muscle-derived trophic factor for the regulation of motoneuron excitability.

Animals↗
PubMed1997

The Latino Health Advocacy Program: a collaborative lay health advisor approach.

There have been numerous calls in the literature for health educators to develop programs to improve access to and utilization of health and human services by traditionally underserved communities, including Latinos. While the literature suggests several principles that can guide the development of these programs, it is important to address the needs, and build on the strengths, of the specific community of interest. It is, therefore, important to use collaborative approaches in which community members take an active role in the initiation, design, implementation, and evaluation of program activities. Lay health advisor programs are particularly well suited to this approach as they are designed to build on the strength of already existing community relationships to improve community health. This article describes a collaborative, culturally appropriate, holistic, and ecological lay health advisor program--the Latino Health Advocacy Program. Lessons learned and implications for future program development are discussed.

Community Health Services↗
PubMed1996

Turbulence effects upon the NO2/NO conversion in the vicinity of an urban area.

The dispersion and chemical transformation of nitrogen oxides have been studied in an urban atmosphere. In this work, nitric oxide is considered as being emitted from the ground. It is mixed with ambient ozone with which it reacts to produce nitrogen dioxide. Numerical integration of the transport equation of each species is carried out in the boundary layer, allowing for the effects of dipersion, macro- and micromixing and chemistry. The results show that the influence of turbulence on chemical reactions is important close to the emission zone. It is also found that the NO/NO2 conversion is low in this region and that it grows with increasing distances.

Air Pollutants↗
PubMed1996

Regulation of SOS mutagenesis by proteolysis.

DNA damage-inducible mutagenesis in Escherichia coli is largely dependent upon the activity of the UmuD (UmuD') and UmuC proteins. The intracellular level of these proteins is tightly regulated at both the transcriptional and the posttranslational levels. Such regulation presumably allows cells to deal with DNA damage via error-free repair pathways before being committed to error-prone pathways. We have recently discovered that as part of this elaborate regulation, both the UmuD and the UmuC proteins are rapidly degraded in vivo. We report here that the enzyme responsible for their degradation is the ATP-dependent serine protease, Lon. In contrast, UmuD' (the posttranslational product and mutagenically active form of UmuD) is degraded at a much reduced rate by Lon, but is instead rapidly degraded by another ATP-dependent protease, ClpXP. Interestingly, UmuD' is rapidly degraded by ClpXP only when it is in a heterodimeric complex with UmuD. Formation of UmuD/UmuD' heterodimers in preference to UmuD' homodimers therefore targets UmuD' protein for proteolysis. Such a mechanism allows cells to reduce the intracellular levels of the mutagenically active Umu proteins and thereby return to a resting state once error-prone DNA repair has occurred. The apparent half-life of the heterodimeric UmuD/D' complex is greatly increased in the clpX::Kan and clpP::Kan strains and these strains are correspondingly rendered virtually UV non-mutable. We believe that these phenotypes are consistent with the suggestion that while the UmuD/D' heterodimer is mutagenically inactive, it still retains the ability to interact with UmuC, and thereby precludes the formation of the mutagenically active UmuD'2C complex.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1996

Expression and folding of an interleukin-2-proinsulin fusion protein and its conversion into insulin by a single step enzymatic removal of the C-peptide and the N-terminal fused sequence.

We report the expression in E. coli of a proinsulin fusion protein carrying a modified interleukin-2 N-terminal peptide linked to the N-terminus of proinsulin by a lysine residue. The key aspects investigated were: (a) the expression of the fused IL2-PI gene, (b) the folding efficiency of the insulin precursor when still carrying the N-fused peptide and (c) the selectivity of the enzymatic cleavage reaction with trypsin in order to remove simultaneously the C-peptide and the N-terminal extension. It was found that this construction expresses the chimeric proinsulin at high level (20%) as inclusion bodies; the fused protein was refolded at 100-200 micrograms/ml to yield about 80% of correctly folded proinsulin and then it was converted into insulin by prolonged reaction (5 h) with trypsin and carboxypeptidase B at a low enzyme/substrate rate (1:600). This approach is based on a single enzymatic reaction for the removal of both the N-terminal fused peptide and the C-peptide and avoids the use of toxic cyanogen bromide.

Amino Acid Sequence↗
PubMed1996

Myocardial revascularization for severe left ventricular dysfunction. Factors influencing early and late survival.

The results of coronary bypass surgery have been assessed in 102 patients with severe left ventricular dysfunction who had a preoperative left ventricular ejection fraction of < or = 0.35 (mean (s.e.m.) 0.29 (0.01)). Independent risk factors influencing operative mortality were obesity (P = 0.0290) and the need for preoperative intra-aortic balloon counterpulsation (P = 0.0010). Cox regression analysis using as its end-point 'cardiac-related death' demonstrated three variables; the need for preoperative intra-aortic balloon counterpulsation (P < 0.001), advanced age (P = 0.011), and obesity (P = 0.36). In a subset of 43 patients who did not have these risk factors, the 4-year cardiac-related death rate was 95.1 (3.4)%. The operative mortality and long-term survival can be expected to be satisfactory in patients with severe left ventricular dysfunction, provided they have a viable myocardium rather than myocardial fibrosis.

Aged↗
PubMed1996

Yellow jacket venom allergens, hyaluronidase and phospholipase: sequence similarity and antigenic cross-reactivity with their hornet and wasp homologs and possible implications for clinical allergy.

Three known allergens of yellow jacket (Vespula vulgaris) venom are antigen 5, hyaluronidase, and phospholipase. Yellow jacket antigen 5 has been previously cloned and expressed in bacteria; it contains 204 amino acid residues, and it has 69% and 60% sequence identities with the homologous proteins of white-faced hornet (Dolichovespula maculata) and wasp (Polistes annularis), respectively. These studies are now extended to yellow jacket hyaluronidase and phospholipase; they contain 331 and 300 amino acid residues, respectively, and they show 92% and 67% sequence identity with their homologs of white-faced hornet. Tests with the natural and the recombinant vespid allergens in mice indicate partial antigenic cross-reactivity of their homologous proteins at both B- and T-cell levels. There is greater cross-reactivity among hornet and yellow jacket allergens than that among hornet or yellow jacket and wasp allergens. The order of cross-reaction of the three vespid allergens is hyaluronidase > antigen 5 > phospholipase. The continuous (linear) B-cell epitopes of vespid allergens show greater cross-reactivity than their discontinuous epitopes do. The discontinuous B-cell epitopes are immunodominant for all vespid allergens. The low degree of cross-reactivity of the immunodominant discontinuous B-cell epitopes of vespid allergens should be taken into consideration in selection of venoms for immunotherapy of patients with sensitivity to multiple vespids.

Allergens↗
PubMed1996

Propofol-alfentanil versus fentanyl-midazolam in coronary artery surgery.

OBJECTIVE: To compare intraoperative hemodynamics profiles and recovery characteristics of propofol-alfentanil with fentanyl-midazolam anesthesia in elective coronary artery surgery. DESIGN: Prospective, randomized study. SETTING: University hospital. PARTICIPANTS: Fifty patients with impaired or good left ventricular function. INTERVENTIONS: In group 1, (n = 25) anesthesia was induced with an infusion of propofol, 3 to 4 mg/kg/h, alfentanil, 500 micrograms, and pancuronium 0.1 mg/kg, and maintained with propofol, 3 to 6 mg/kg/h (variable rate), and alfentanil infusions, 30 micrograms/kg/h (fixed rate). Additional boluses of alfentanil, 1 mg, were administered before noxious stimuli; group 2 (n = 25) received a loading dose of fentanyl, 25 micrograms/kg, midazolam, 1.5 to 3 mg, and pancuronium, 0.1 mg/kg for induction, followed by an infusion of fentanyl, 7 micrograms/kg/h, for maintenance. Additional boluses of midazolam (1.5 to 3 mg) and fentanyl (250 micrograms) were administered before noxious stimuli. MEASUREMENTS AND MAIN RESULTS. Cardiovascular parameters at eight intraoperative time points as well as time to extubation, morphine consumption, and pain scores were recorded. Induction of anesthesia was associated in both groups with a small but significant decrease in mean arterial pressure (1: 15 mmHg (15%); 2: 8 mmHg (8%) with significant decreases in cardiac index (1: 8%; 2: 8%) and left ventricular stroke work index (1: 24%; 2: 21%). Throughout surgery, hemodynamic profiles were comparable between groups except after intubation when the MAP was significantly lower in group 1 (75 +/- 12 mmHg) than in group 2 (89 +/- 17 mmHg). Group 1 required less inotropic support. Extubation was performed faster in group 1 (7.6 h) than in group 2 (18.0 h). Morphine requirements and pain scores were comparable between groups. CONCLUSIONS: Propofol-alfentanil anesthesia provides good intraoperative hemodynamics and allows early extubation after coronary artery surgery.

Aged↗
PubMed1996

A randomized study comparing the effect of GM-CSF and G-CSF on immune reconstitution after autologous bone marrow transplantation.

Haemopoietic growth factors (HGFs) have been shown to accelerate recovery from severe neutropenia after autologous bone marrow transplantation (ABMT) but their effect on immune reconstitution is not well defined. The present study compares, through randomized trial, the in vivo effect of GM-CSF and G-CSF administration on the immune recovery of patients who underwent ABMT. For that purpose, we have sequentially analysed 14 different T, B and NK lymphoid cell subsets using appropriate dual staining during the first year following transplant (days +6, +17, +31, +66, +90, +120, +180, +360). 24 patients with lymphoproliferative disorders (20 lymphomas and four multiple myelomas) and who had undergone ABMT were included in the study. The median age was 43 years (range 22-62 years). All lymphoma patients were homogenously conditioned with BEAM. Our results show that both GM-CSF and G-CSF aid T-cell (CD3+/alpha beta) recovery though their contribution varies depending on the T-cell subset analysed. G-CSF contributed to a significantly faster recovery of CD8+ cells (P = 0.03). The CD8+ cell regeneration was produced mainly by activated cells (CD38+/HLA-DR+) which lacked the CD11b antigen. In contrast, GM-CSF favoured the regeneration of CD4+ cells (through both the CD45RO+ and CD45RA+ subset), leading to a higher CD4+:CD8+ ratio (P = 0.007). No statistically significant differences were detected in the three groups of patients as regards both the recovery of NK cells and NK activity. Furthermore, the use of HGF did not seem to exert a significant influence on the recovery of B lymphocytes. This recovery was based on the CD5+ subpopulation that showed a rapid rise after the first month. We suggest that G-CSF and GM-CSF not only influence myeloid recovery, but also regeneration of the immune system after ABMT.

Adult↗
PubMed1996

Peripheral-nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506.

The purpose of this study was to assess regeneration across peripheral-nerve allografts by electro-physiologic methods, in rats receiving transient or long-term immunosuppression with FK-506. Lewis rats (LEW, RT1(1)) were recipients of sciatic nerve isografts or allografts from donor LEW or ACI (RT1a) rats, respectively. This latter donor-recipient inbred combination represents a major histoincompatible mismatch. The sciatic nerve was exposed through a gluteal muscle-splitting incision. A 2.0-cm segment of nerve was excised and a 2.5-cm graft sutured into the gap in epineural fashion. Seven groups (n = 8 each) included: Group 1--isograft control (LEW/LEW): Group 2--allograft control (LEW/ACI); Group 3--allografts receiving cyclosporin A (CsA) (10 mg/kg BW/day) subcutaneously for 2 weeks; Group 4--CsA for 2 weeks then biweekly subcutaneously; Group 5--FK-506 (10 mg/kg BW) intramuscularly by single injection; Group 6--FK-506 (1.0 mg/kg BW/day) for 2 weeks then biweekly intramuscularly; and Group 7--FK-506 for 2 weeks then biweekly intramuscularly. At 7 months, conduction velocities were determined and statistical analysis was performed. Excellent neural regeneration was observed in the isograft group (61.6 m/s), the allograft groups receiving long-term immunosuppression with either CsA (62.3 m/s) or FK-506 (61.7 m/s), and the transient FK-506 group (60.2 m/s). The transient CsA group (41.9 m/s), the allograft control group (53.4 m/s), and the single-dose FK-506 group (40.8 m/s) demonstrated significantly poorer results. Transient immunosuppression with FK-506 allowed for the restoration of anatomic and physiologic function of a peripheral-nerve allograft in inbred rats.

Animals↗
PubMed1996

Expression of the CD117 antigen (c-Kit) on normal and myelomatous plasma cells.

The surface expression of CD117 on plasma cells (PCs) from normal individuals and patients with multiple myeloma (MM) has been analysed using triple-stained cells for flow cytometry. In addition, the clinical significance of CD117 expression in MM patients and its possible value for the evaluation of minimal residual disease was explored. A total of 11 healthy volunteers and 56 untreated MM patients were included in the study. The expression of CD117 was analysed by flow cytometry, using simultaneous staining with the MAbs BB4, CD117 and CD38. Cell acquisition was performed in two consecutive steps using a live gate drawn on SSC/CD38 cells and a total of 300,000 events were acquired. For data analysis, the Paint-a-Gate Plus software (Becton Dickinson) was used. PCs were identified according to their strong reactivity for CD38 and their positivity for BB4, as well as by their light scatter distribution. Dilution experiments of CD117+ myelomatous PCs with normal bone marrow (BM) cells were performed in order to assess the sensitivity level of the technique for detection of CD117+ residual PCs. None of the PCs from normal BM samples showed reactivity for the CD117 antigen. In contrast, CD117 antigen was present in 18/56 MM patients (32%), the proportion of positive cells in these cases being as high as 92.1 +/- 9%. Therefore, within PC lineage the c-Kit antigen would be restricted to the myelomatous population and thus could be considered as a 'tumour-associated marker' for monitoring minimal residual disease in about one third of MM patients. Dilution experiments indicate that the detection limit with this marker would be 10(-4) (one myelomatous PC/10(4) normal BM cells). Upon comparing the clinical and haematological disease characteristics of CD117-positive and CD117-negative cases, no significant differences were found.

Adult↗
PubMed1996

In vivo stability of the Umu mutagenesis proteins: a major role for RecA.

The Escherichia coli Umu proteins play critical roles in damage-inducible SOS mutagenesis. To avoid any gratuitous mutagenesis, the activity of the Umu proteins is normally kept to a minimum by tight transcriptional and posttranslational regulation. We have, however, previously observed that compared with an isogenic recA+ strain, the steady-state levels of the Umu proteins are elevated in a recA730 background (R. Woodgate and D. G. Ennis, Mol. Gen. Genet. 229:10-16, 1991). We have investigated this phenomenon further and find that another coprotease-constitutive (recA*) mutant, a recA432 strain, exhibits a similar phenotype. Analysis revealed that the increased steady-state levels of the Umu proteins in the recA* strains do indeed reflect an in vivo stabilization of the proteins. We have investigated the basis for the phenomenon and find that the mutant RecA* protein stabilizes the Umu proteins by not only converting the labile UmuD protein to the much more stable (and mutagenically active) UmuD' protein but by directly stabilizing UmuD' itself. In contrast, UmuC does not appear to be directly stabilized by RecA* but is instead dramatically stabilized in the presence of UmuD'. On the basis of these observations, we suggest that formation of a UmuD'C-RecA*-DNA quaternary complex protects the UmuD'C proteins from proteolytic degradation and as a consequence helps to promote the switch from error-free to error-prone mechanisms of DNA repair.

Bacterial Proteins↗
PubMed1996

Phenotypic changes in acute myeloid leukaemia: implications in the detection of minimal residual disease.

AIM: To explore the role of phenotypic changes as possible limiting factors in the immunological detection of minimal residual disease in patients with acute myeloid leukaemia (AML). METHODS: 20 relapses were evaluated, with special attention to changes in the criteria used for the definition of a phenotype as "aberrant". In all cases the same monoclonal antibody and fluorochrome were used at diagnosis and in relapse. RESULTS: Six out of the 16 patients showed aberrant phenotypes at diagnosis. At relapse, no changes in the aberrant phenotypes were detected in most of the patients; nevertheless, in two of the four patients with asynchronous antigen expression this aberration disappeared at relapse. At diagnosis in both cases there were already small blast cell subpopulations showing the phenotype of leukaemic cells at relapse. Ten out of the 16 cases analysed showed significant changes in the expression of at least one of the markers analysed. CONCLUSIONS: At relapse in AML the "leukaemic phenotypes" usually remained unaltered, while other phenotypic features--not relevant for distinguishing leukaemic blast cells among normal progenitors--changed frequently; however, they were not a major limitation in the immunological detection of minimal residual disease.

Acute Disease↗
PubMed1996

Incidence of chromosome numerical changes in multiple myeloma: fluorescence in situ hybridization analysis using 15 chromosome-specific probes.

The presence of complex karotypes with frequent numerical and structural abnormalities has been reported in 20 to 50% of multiple myeloma (MM) patients. This variability is mainly due to the difficulty of conventional cytogenetics to obtain tumor metaphases representative of all possible neoplastic clones in MM. To gain insight into the real incidence of numerical chromosome changes in MM we have studied by fluorescence in situ hybridization technique 15 different human chromosomes, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15, 17, 18, X, and Y, in a series of 52 MM patients. In all cases, the DNA index assessed by a propidium iodide/CD38 double-staining technique with flow cytometry was simultaneously investigated for correlation, with fluorescence in situ hybridization results. Additional aims of this study were 1) to analyze whether the abnormalities detected were common to all plasma cells or were present in only a subpopulation of tumor cells, 2) to explore changes caused by disease progression, and 3) to establish possible associations among the altered chromosomes. Although the overall incidence of numerical abnormalities was 67%, this frequency increased to 80% in the 41 cases in which 7 or more chromosomes were analyzed. Trisomies were significantly more common than monosomies (84% versus 16%). Chromosomes 9 and 15 were the most frequently altered (52% and 48% of cases, respectively), with all of their abnormalities corresponding to trisomies. The most frequent losses involved chromosomes 13 (26%) and X in females (32%). Other common numerical changes corresponded to chromosomes 1 (39%), 11 (37%), 6 (32%), 3 (31%), 18 (29%), 7 (28%), and 17 (22%). By contrast, chromosomes 8(13%), 10(8%), and 12(3%) were rarely altered. DNA aneuploidy by flow cytometry was detected in 67% of patients, and a high degree of correlation was observed between the DNA index obtained by flow cytometry and the chromosome index derived from fluorescence in situ hybridization studies, calculated according to two mathematical formulas (coefficient of correlation of 0.82 and 0.91 when at least 7 or 12 chromosomes were considered, respectively). The frequency of numeric chromosome aberrations was higher in those patients with progressive disease and, interestingly, trisomy of chromosome 8 was exclusively detected in this latter group of patients. Our study shows that, with the exception of chromosome 8, a possible marker of clonal evolution, the numeric chromosome changes are present in nearly all malignant plasma cells (r > 0.84). Finally, frequent associations between chromosomal aberrations were observed (ie, chromosomes 6, 7, 9, and 17; 7 and 15; and 11 and 17). By excluding them, it was found that two triple combinations of chromosome-specific probes, chromosomes 1 and 9 together with either chromosome 13 or 15, could be a useful marker for detection of residual disease, as it permits the identification of most MM patients displaying numerical changes.

Aged↗
PubMed1995

Clinical, biological, and immunophenotypical characteristics of B-cell chronic lymphocytic leukemia with trisomy 12 by fluorescence in situ hybridization.

The clinical, biological, and immunophenotypical characteristics of B-cell chronic lymphocytic leukemia (B-CLL) patients with trisomy 12 detected by fluorescence in situ hybridization (FISH) using a chromosome 12 alpha-centromeric probe (D12Z3) were analyzed in the present study. From a total of 104 consecutive B-CLL patients, 21 (20%) displayed trisomy 12, the percentage of trisomic cells ranging from 13% to 76%. From the clinico-biological point of view, patients with trisomy 12 were associated with atypical CLL morphology (43% vs 10%, P = 0.04) and BM diffuse pattern (75% vs. 25%, P = 0.02) together with increased WBC counts (141 +/- 220 vs. 58 +/- 67 x 10(9)/L, P = 0.04). In contrast, no association was detected between the presence of trisomy 12 and other disease characteristics such as age, sex, clinical stage, hepatomegaly, lymphadenopathies, haemoglobin levels and platelet counts, and the cell cycle distribution of PB leukocytes in both groups of patients. Trisomy 12 patients had a significantly higher expression of the FMC7 antigen both in percentage (34 +/- 34% vs. 13 +/- 20%, P = 0.02) and absolute numbers (29 +/- 62 vs. 7 +/- 17 x 10(9)/L, P = 0.007). No major differences were found regarding the expression of mouse rosettes, CD19+, and CD19+/CD5+ lymphocytes. Upon analyzing the correlations between the disease characteristics of trisomy 12 cases, significant associations were found between the percentage of trisomic cells and both the WBC count (r = 0.52, P = 0.02) and the PB lymphocyte count (r = 0.60, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗