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M Rocha

Publications and source records attributed to M Rocha.

At least 37 records · Page 2Linked to original sources
PubMed1999

Genetic structure of natural populations of Escherichia coli in wild hosts on different continents.

Current knowledge of genotypic and phenotypic diversity in the species Escherichia coli is based almost entirely on strains recovered from humans or zoo animals. In this study, we analyzed a collection of 202 strains obtained from 81 mammalian species representing 39 families and 14 orders in Australia and the Americas, as well as several reference strains; we also included a strain from a reptile and 10 from different families of birds collected in Mexico. The strains were characterized genotypically by multilocus enzyme electrophoresis (MLEE) and phenotypically by patterns of sugar utilization, antibiotic resistance, and plasmid profile. MLEE analysis yielded an estimated genetic diversity (H) of 0.682 for 11 loci. The observed genetic diversity in this sample is the greatest yet reported for E. coli. However, this genetic diversity is not randomly distributed; geographic effects and host taxonomic group accounted for most of the genetic differentiation. The genetic relationship among the strains showed that they are more associated by origin and host order than is expected by chance. In a dendrogram, the ancestral cluster includes primarily strains from Australia and ECOR strains from groups B and C. The most differentiated E. coli in our analysis are strains from Mexican carnivores and strains from humans, including those in the ECOR group A. The kinds and numbers of sugars utilized by the strains varied by host taxonomic group and country of origin. Strains isolated from bats were found to exploit the greatest range of sugars, while those from primates utilized the fewest. Toxins are more frequent in strains from rodents from both continents than in any other taxonomic group. Strains from Mexican wild mammals were, on average, as resistant to antibiotics as strains from humans in cities. On average, the Australian strains presented a lower antibiotic resistance than the Mexican strains. However, strains recovered from hosts in cities carried significantly more plasmids than did strains isolated from wild mammals. Previous studies have shown that natural populations of E. coli harbor an extensive genetic diversity that is organized in a limited number of clones. However, knowledge of this worldwide bacterium has been limited. Here, we suggest that the strains from a wide range of wild hosts from different regions of the world are organized in an ecotypic structure where adaptation to the host plays an important role in the population structure.

Americas↗
PubMed1999

[Years of life lost by mortality: a component of the burden of disease].

INTRODUCTION: The register of death by cause, sex and age groups of residents in 1994 in Rio Grande do Sul (RS) and Santa Catarina (SC), two Brazilian southern states, were studied to calculate the years of life lost (YLL), one of the two components that summarize disability adjusted life years (DALY), in RS, SC and Brazil. METHODS: The methodology employed is the same used in the Global Burden of Disease study to quantify the mortality component (YLL) of DALY in the world. RESULTS: The results show that the greatest proportion and rates caused by Group II (Noncommunicable diseases), linked with more advanced stages of the epidemiological transition, in RS, SC and Brazil. But in both states and especially in Brazil, Group I (Communicable, maternal, perinatal and nutritional conditions) causes an important proportion of YLL. The Group III (Injuries) was the second more important group in RS and SC and the third in Brazil. Road traffic accidents are particularly important in SC, where the intentional injury rate is half than the one in RS. The leading causes of YLL were road traffic accidents, ischemic heart disease and cerebrovascular disease in SC, and ischemic heart disease, cerebrovascular disease and road traffic accidents in RS. CONCLUSIONS: Death certification in the southern region of Brazil has a complete coverage and miscoded death proportion is small, providing a reliable mortality information. DALY allow comparing fatal and nonfatal health outcomes to determine the importance of different diseases and to establish health priorities. DALY are also an useful tool to identify disadvantaged groups, target health interventions and provide information for social control of resource allocation.

Adolescent↗
PubMed1999

A unified framework for data modeling on medical information systems.

Medical Information Systems (MIS) are seen as a way of optimizing the use of existing health-care infrastructure, without resorting to new and costly hospital (re)construction. The qualitative (re)design of such an environment requires a basic understanding of patient and doctors related characteristics and capabilities. Patient care, patient education, medical education, and clinical research need to be considered to meet the basic requirements on the level of services desirable, determined on the basis of the patient's length of stay; i.e., used for modeling the significant entities of such a world. The aim is to extract conclusions for the level of services provided to the users. One's concept will capture, as well as will integrate, the basic design principles under which MIS may be set.

Artificial Intelligence↗
PubMed1998

Identification of four genes in endothelial cells whose expression is affected by tumor cells and host immune status--a study in ex vivo-isolated endothelial cells.

A spontaneously metastasizing, well-defined mouse lymphoma was chosen as an in vivo model to study the effect of tumor-host interaction on gene expression in liver sinusoidal endothelial cells. Forty-nine bovine aortic endothelial cell (BAEC) genes, recently isolated by a differential screening approach of a cDNA library enriched for tumor necrosis factor-alpha (TNF-alpha) suppressed genes, were investigated. Four of these genes were finally selected because they were affected differentially by host immuno-competence, TNF-alpha, and tumor cells. Sequence analysis showed them to encode the bovine polyubiquitin (A4), elongation factor 1alpha (B2), the acidic ribosomal phosphoprotein PO (C3), and the ribosomal protein S2 (E10). Gene expression was analyzed by dot-blot or Northern blot analysis. TNF-alpha and tumor cell conditioned supernatant suppressed the genes additive in BAEC but not in other endothelial cells except for bovine capillary endothelial cells. Ex vivo-isolated liver endothelial cells of tumor-bearing syngeneic DBA/2 mice showed strong downregulation of these four genes in comparison to normal control values. In contrast, endothelial cells of tumor-bearing immuno-incompetent Balb/c (nu/nu) mice showed no downregulation but upregulation of these genes. Consistently, all four genes were also downregulated when BAEC were incubated with supernatants derived from ex vivo-isolated liver metastases from immuno-competent but not from -incompetent mice. Thus, the expression of a group of genes involved in protein translation and processing was more profoundly altered in endothelial cells in vivo than in vitro, suggesting that microenviromental factors and cell-cell and cell-matrix interactions play an important role.

Amino Acid Sequence↗
PubMed1998

Loss of endogenous mouse mammary tumor virus superantigen increases tumor resistance.

From a cross between a tumor-susceptible mouse strain (DBA/2; D) and a tumor-resistant MHC-identical strain (B10.D2; D2) new recombinant inbred mouse strains were established over many generations of inbreeding and tumor resistance selection. Since resistance to the highly metastatic DBA/2 lymphoma variant ESb had an immunologic basis, and the two parental strains differed in endogenous viral superantigens (vSAGs), DNA of three D2 x D recombinant inbred mouse lines was typed for endogenous mouse mammary tumor viruses using mouse mammary tumor virus long terminal repeat- and env gene-specific probes. The resistant D2 x D mice were very similar to the susceptible parental strain D in their Mtv Southern blots, except for the lack of a single band corresponding to Mtv-7, the provirus coding for the strong DBA/2 superantigen Mls-1a. A backcross analysis revealed that Mtv-7-negative F2 mice were significantly more resistant than Mtv-7-positive F2 mice. When Mtv-7 was reintroduced into the resistant lines by crossing them with either CBA/J or BALB/D2.Mls-1a, the mice became again more tumor susceptible. Finally, we demonstrate the ability to transfer immunoresistance and graft-vs-leukemia reactivity from tumor-resistant to tumor-susceptible mice.

Animals↗
PubMed1998

Caspase activation is required for nitric oxide-mediated, CD95(APO-1/Fas)-dependent and independent apoptosis in human neoplastic lymphoid cells.

Nitric oxide (NO), an important effector molecule involved in immune regulation and host defense, was shown to induce apoptosis in lymphoma cells. In the present report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant Jurkat subclone showed substantial protection from apoptosis after exposure to NO. NO induced mRNA expression of CD95 (APO-1/Fas) and TRAIL/APO-2 ligands. Moreover, NO triggered apoptosis in freshly isolated human leukemic lymphocytes which were also sensitive to anti-CD95 treatment. The ability of NO to induce apoptosis was completely blocked by a broad-spectrum ICE (interleukin-1beta converting enzyme)-protease/caspase inhibitor and correlated with FLICE/caspase-8 activation. This activation was abrogated in some neoplastic lymphoid cells but not in others by the inhibitor of protein synthesis cycloheximide. Our results were confirmed using an in vitro experimental model of coculture of human lymphoid target cells with activated bovine endothelial cells generating NO as effectors. Furthermore, the inhibition of endogenous NO production with the inducible NO synthase inhibitor NG-monomethyl-L-arginine caused a complete abrogation of the apoptotic effect. Our data provide evidence that NO-induced apoptosis in human neoplastic lymphoid cells strictly requires activation of caspases, in particular FLICE, the most CD95 receptor-proximal caspase. Depending on the cell line tested this activation required or was independent of the CD95 receptor/ligand system.

Animals↗
PubMed1998

Changes in cytochrome oxidase activity in brown adipose tissue during oestrous cycle in the rat.

Cold-acclimated female Wistar rats were killed at a known phase of the oestrous cycle to investigate whether natural fluctuations of female sex steroids during the cycle are mirrored by changes in brown adipose tissue (BAT) activity. Four phases: proestrus, oestrus, dioestrus I and dioestrus II, were identified by the cells types appearing in vaginal smears. BAT was removed and analysed for composition and specific indicators of BAT activity. No changes in BAT mass, protein or mitochondrial content were detected during the cycle. Thermogenesis was also unchanged as judged by both lipid multilocularity and mitochondrial GDP-binding. However, cytochrome c oxidase (COX) activity did cycle with a minimum at proestrus and a maximum at dioestrus I. The involvement of oestradiol in such a cycle is suggested by the fact that oestradiol treatment decreased COX activity to values similar to those found in proestrus. The physiological function of a cyclic oxidative capacity remains to be elucidated.

Adipose Tissue, Brown↗
PubMed1998

Effect of fat distribution on the pharmacokinetics of cortisol in obesity.

OBJECTIVE: Patients with predominantly upper body obesity are at greater risk for developing diabetes mellitus, hyperlipidemia, hypertension, and cardiovascular disease. Little is known about the mechanisms involved in the regulation of regional body distribution. It has been accepted that the accumulation of fat into adipose tissue depends on regional metabolic regulation of adipocytes and that glucocorticoids play a role in this mechanism. The aim of the present study is to investigate how the pharmacokinetics of cortisol correlate to intraabdominal and subcutaneous fat distribution in obese patients. METHODS: A group of 24 obese patients (13 males and 11 females) were submitted to a CT scan for intraabdominal and subcutaneous fat area evaluation. A 30-min cortisol infusion (0.25 mg/kg) was administered and plasma cortisol was measured over 6 hours. RESULTS: Patients with larger intraabdominal fat areas were found to have a higher cortisol clearance than those with lower intraabdominal fat areas. Cortisol clearance (both, absolute and body-weight corrected) showed a statistically significant correlation with intraabdominal fat area, either expressed by waist-hip ratio or obtained by computerized tomography. CONCLUSIONS: These findings indicate a more effective clearance capability for cortisol in patients with central obesity resulting in lowered cortisol plasma levels despite an increased cortisol secretion observed in this patient group.

Abdomen↗
PubMed1998

Graft-versus-leukemia reactivity involves cluster formation between superantigen-reactive donor T lymphocytes and host macrophages.

T-cell-mediated antitumor effects play an important role clinically in allogeneic graft-versus-leukemia (GvL) reactivity, whereas T-cell-mediated antihost effects are associated with a risk of developing graft-versus-host (GvH) disease. GvL and GvH were compared in an animal tumor model system after the systemic transfer of allogeneic antitumor immune T lymphocytes from B10.D2 [H-2d; minor lymphocyte-stimulating antigen (Mls)b] mice into ESb-MP tumor-bearing or normal DBA/2 (H-2d; Mls(a)) mice. Here we demonstrate that this T-cell-mediated therapy involves the formation of clusters of donor CD4 and CD8 T cells with host macrophages, in particular, with a subpopulation expressing the lymphocyte adhesion molecule sialoadhesin. DBA/2 mice and the derived tumor ESb-MP express viral superantigen 7 (Mls(a)), an endogenous viral superantigen that is absent from B10.D2 mice. To test the contribution of viral superantigen 7-reactive Vbeta6 donor T cells in the GvL-mediated eradication of liver metastases, we performed immunohistological and transmission electron microscopy studies. Vbeta6+ CD4 and CD8 T cells from B10.D2 donors formed tight clusters with host sialoadhesin-positive macrophages, and transmission electron microscopy pictures revealed direct membrane-membrane interactions between T cells and macrophages. Clusters were more abundant and consisted of more cells in tumor-bearing hosts (GvL model) than in non-tumor-bearing hosts (GvH model). In addition, Vbeta6 T cells within the clusters showed a strong proliferation activity, indicating stimulation. Moreover, in an in vitro tumor cytostasis assay, primed as well as nonprimed purified Vbeta6 T cells from donor mice were able to inhibit the proliferation of superantigen-expressing ESb-MP lymphoma cells. This suggests that the transferred superantigen-reactive Vbeta6 T cells contribute to the eradication of metastases. The observed cell clusters might be sites for antigen presentation and the activation of tumor-reactive T cells.

Animals↗
PubMed1997

Differences between graft-versus-leukemia and graft-versus-host reactivity. I. Interaction of donor immune T cells with tumor and/or host cells.

Graft-versus-leukemia (GVL) and Graft-versus-host (GVH) reactions were compared after systemic transfer of allogeneic antitumor immune T lymphocytes from B10.D2 (H-2d; Mls(b)) into DBA/2 (H-2d; Mis(a)) mice. Before immune cell transfer, recipient DBA/2 mice were sublethally irradiated with 5 Gy to prevent host-versus-graft reactivity. Recipients were either bearing syngeneic metastatic ESb lymphomas (GVL system) or were normal, non-tumor-bearing mice (GVH system). We previously reported that this adoptive immunotherapy protocol (ADI) had pronounced GVL activity and led to immune rejection of even advanced metastasized cancer. In this study, monoclonal antibodies were used for immunohistochemical analysis of native frozen tissue sections from either spleen or liver to distinguish donor from host cells, to differentiate between CD4 and CD8 T lymphocytes, and to stain sialoadhesin-positive macrophages at different time points after cell transfer. The kinetics of donor cell infiltration in spleen and liver differed in that the lymphoid organ was infiltrated earlier (days 1 to 5 after transfer) than the nonlymphoid organ (days 5 to 20). After reaching a peak, donor cell infiltration decreased gradually and was not detectable in the spleen after day 20 and in the liver after day 30. The organ-infiltrating donor immune cells were mostly T lymphocytes and stained positive for CD4 or CD8 T-cell markers. A remarkable GVL-associated observation was made with regard to a subset of macrophages bearing the adhesion molecule sialoadhesin (SER+ macrophages). In the livers of tumor-bearing mice, their numbers increased between days 1 and 12 after ADI by a factor greater than 30. Double-staining for donor cell marker and SER showed that the sialoadhesin-expressing macrophages were of host origin. The SER+ host macrophages from GVL livers were isolated by enzyme perfusion and rosetting 12 days after ADI, when they reached peak values of about 60 cells per liver lobule, and were tested, without further antigen addition, for their capacity to stimulate an antitumor CD8 T-cell response. The results of this immunologic analysis suggest that these cells in the liver function as scavengers of the destroyed metastases and as antigen-processing and -presenting cells for antitumor immune T cells.

Animals↗
PubMed1997

Risk factors in obese women, with particular reference to visceral fat component.

Possible associations between increased visceral fat component and serum lipid concentrations, glucose tolerance and insulinaemia (specific radioimmunoassay) were studied as risk factors for cardiovascular disease in 50 adult obese women without known diabetes and 11 lean normal women. Visceral abdominal fat areas were evaluated by computed tomography and "true" insulin concentrations. Diabetes was observed in 6 obese women (12%) and impaired glucose tolerance in 13 (26%). In obese women, visceral fat area correlated significantly with VLDL-cholesterol, triglycerides, and systolic and diastolic blood pressure, whereas subcutaneous area correlated negatively with cholesterol and LDL-cholesterol. Insulinaemia was not increased in visceral obesity nor correlated with other risk factors. An association between increased visceral fat accumulation, dyslipidaemia and increased diastolic blood pressure was observed, but no significant correlations were noted between fasting "true" insulin or insulin response on an oral glucose tolerance test and intra-abdominal fat areas or dyslipidemia. The gender of the patients could have been an important factor in these last observations.

Adipose Tissue↗
PubMed1997

Does pulmonary tuberculosis change with ageing?

SETTING: In most low prevalence countries, tuberculosis has become a disease of the aged; it has recently been suggested that the elderly may present a specific pattern. OBJECTIVE: To compare clinical, bacteriological and radiological features of pulmonary tuberculosis between young and elderly populations in a high incidence country. PARTICIPANTS AND METHODS: We retrospectively studied 337 consecutive pulmonary tuberculosis patients without confirmed HIV infection, hospitalised from 1989 to 1993. The clinical, bacteriological and radiological features of the two age groups considered, young adults (< 60 years) and elderly (> or = 60 years), were compared. RESULTS: Thoracic pain (16.3% vs 32.7%) and fever (27.2% vs 50.6%) were significantly less frequent in the elderly, while the frequency and duration of other symptoms before hospitalisation were similar. After admission, fever remained longer in young patients (P < 0.05). No significant differences were found regarding the general health status at hospitalisation, or associated illnesses (83.7% vs 73.5%; P = 0.068). Radiological lesions not related to the present diagnosis (14.1% vs 2.0%; P < 0.05), and a presumed diagnosis of tuberculosis (11.7% vs 4.1%; P = 0.02) were more frequent in the elderly. CONCLUSION: This study showed no specific clinical, bacteriological or radiological features between age groups, and does not support the hypothesis of any age-related patterns in pulmonary tuberculosis.

Adolescent↗
PubMed1997

[Anal tuberculosis. Report of a case].

We report a 70 years old man presenting with malaise, anal pain and progressive defecation difficulty, with a decrease in stool caliber. The patient had no contact or past history of tuberculosis. On physical examination, there was an ulcerated anal lesion with purulent discharge, that produced an anal stenosis. The patient had an erythrocyte sedimentation rate of 108 mm/h, images of active tuberculosis in both apical pulmonary lobes and a chronic tuberculous inflammation with caseation and epithelioid tubercles was observed in a biopsy of the anal lesion. Treatment with antituberculous drugs produced a categorical remission of anal lesions and after five months of therapy the patient is well.

Aged↗
PubMed1996

New insights into tumor-host interactions in lymphoma metastasis.

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual "cross-talks") of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA-1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.

Cell Adhesion Molecules↗
PubMed1996

Liver endothelial cells: participation in host response to lymphoma metastasis.

Interactions between metastasizing tumor cells and host cells in target organs determine the outcome of metastasis. This review discusses the dual role of activated host endothelial cells in the metastatic process. On one hand, the upregulation of the expression of particular adhesion molecules leads to increased tumor cell binding, and the stimulation of angiogenesis provides the vascular support for the growth of already established metastases. On the other hand, endothelial cells can contribute to host anti-metastatic responses, e.g. by production of the cytotoxic molecule nitric oxide (NO) from arginine with the help of the inducible nitric oxide synthase (iNOS). Using a well-characterized ESbL-lacZ mouse T lymphoma model with a typical three phasic growth profile, we showed during the period of growth retardation a stimulation of NO production by ex vivo isolated liver sinusoidal endothelial cells. The induction of NO synthesis in liver endothelial cells did not require the presence of Kupffer cells and appeared to be stimulated by and dependent on mature T lymphocytes. A breakdown of this NO synthesis coincided with the second tumor expansion phase.

Animals↗
PubMed1996

The influence of organic acids on the proliferation of human peripheral lymphocytes activated by concanavalin A and pokeweed mitogen.

The present study was undertaken to assess the influence of 25 organic acids, which appear in high concentrations in tissues of patients with various organic acidaemias, on the proliferation of human peripheral lymphocytes stimulated with concanavalin A (Con A) (a T-cell activator) and pokeweed mitogen (PWM) (predominantly a B-cell activator). Mononuclear cells were cultivated in flat-bottomed 96-well microplates at 37 degrees C for 96 (Con A) or 144 h (PWM) in the presence of one mitogen at different concentrations and of one acid at doses ranging from 1 to 5 mM. Control cultures did not contain any acid. Cell reactivity was measured by the incorporation of tritiated thymidine into cellular DNA. We observed that, among the 25 acids tested, aminoadipic (AAD), 2-hydroxy-3-methylvaleric (HMV), 2-ketoisocaproic (KIC), 2-methylbutyric (MBA), propionic (PPA) and tiglic (TIG) acids strongly suppressed lymphocyte DNA synthesis in Con A-supplemented cultures, whereas in cultures stimulated with PWM, 2-ketoisovaleric (KIV) and PPA acids presented the same effect. In contrast, lactic (LAC) and pyruvic (PYR) acids activated lymphocyte DNA synthesis in cultures treated with Con A, the same effect occurring with LAC acid for PWM-stimulated lymphocytes. The most inhibitory or stimulatory acids were added to cultures at different times after the beginning of the incubation period when mitogens were added. Except for HMV, KIC, PPA and LAC acids, whose actions persisted even after 24 h from the beginning of culture, the others only exerted their effects when added at time zero. The present study therefore demonstrated that some organic acids modulate DNA synthesis in Con A- and PWM-stimulated human lymphocytes.

2-Aminoadipic Acid↗
PubMed1996

Dissection of tumour and host cells from target organs of metastasis for testing gene expression directly ex vivo.

We report on a new methodology which allows the direct analysis ex vivo of tumour cells and host cells (lymphocytes, macrophages, endothelial cells) from a metastasised organ (liver or spleen) at any time point during the metastatic process and without any further in vitro culture. First, we used a tumour cell line transduced with the bacterial gene lacZ, which permits the detection of the procaryotic enzyme beta-galactosidase in eukaryotic cells at the single cell level thus allowing flow adhesion cell sorting (FACS) analysis of tumour cells from metastasised target organs. Second, we established a method for the separation and enrichment of tumour and host cells from target organs of metastasis with a high viability and reproducibility. As exemplified with the murine lymphoma ESb, this new methodology permits the study of molecules of importance for metastasis or anti-tumour immunity (adhesion, costimulatory and cytotoxic molecules, cytokines, etc.) at the RNA or protein level in tumour and host cells during the whole process of metastasis. This novel approach may open new possibilities of developing strategies for intervention in tumour progression, since it allows the determination of the optimal window in time for successful treatments. The possibility of direct analysis of tumour and host cell properties also provides a new method for the evaluation of the effects of immunisation with tumour vaccines or of gene therapy.

Animals↗