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Biomedical subjects

R Martinez

Publications and source records attributed to R Martinez.

At least 109 records · Page 6Linked to original sources

Ruptured abdominal aortic aneurysm. A ten year experience.

METHODS: During the last ten years, 84 patients treated for ruptured infrarenal aortic aneurysm have been reviewed to evaluate complications and mortality rates, to determine which factors influenced these rates and to identify the means to improve these results. RESULTS: The intraoperative mortality and the overall mortality rates were respectively 21.4% and 57%. The factors which influenced hospital mortality were analyzed. The most important factors were the age, the depth of the initial shock, the volume of blood transfused and the location of rupture. CONCLUSIONS: These factors cannot be controlled by the surgeon and it should be noted that a significant reduction of the mortality rate may be very difficult or even impossible to achieve. These findings support the concept of aggressive elective resection of abdominal aortic aneurysms.

Aged↗

Evaluation of Caribbean strains of Macrocyclops and Mesocyclops (Cyclopoida:Cyclopidae) as biological control tools for the dengue vector Aedes aegypti.

Fifteen Caribbean strains of copepods were assessed for their predation ability against mosquito larvae. Macrocyclops albidus from Nariva. Mesocyclops aspericornis from Oropouche, and Mesocyclops longisetus from E1 Socorro, Trinidad, were most effective against Aedes aegypti but not against Culex quinquefasciatus. Mesocyclops longisetus and Me. aspericornis prevented any mosquito survival over 25 wk of observation despite weekly challenges with Ae. aegypti. The copepods were tolerant to dosages of the insecticide temephos that are usually toxic to mosquito larvae. This indicated that copepods could be incorporated into an integrated control system. To determine whether pathogenic microbes might be introduced with copepods into drinking water, microbial studies were done on the copepods. These showed the presence of only Aeromonas sobria, Pseudomonas sp., Alcalignes sp., and gram-positive bacilli. Although none of these are highly pathogenic to humans, the application of these copepods has not yet been recommended for use in drinking water.

Aedes↗

GH and TSH deficiency.

Hypothyroidism is a recognised complication of GH therapy in GH deficient children. The mechanisms involved include direct effects on thyroid function but also result from the close interrelationship of pituitary cell-lines that differentiate during embryonic development of the anterior pituitary gland. Among numerous pituitary transcriptionfactors that orchestrate pituitary organogenesis Pit-1 was the first to be recognised and is the most extensively studied. Mutations in the Pit-1 gene account for a form of combined pituitary hormone deficiency for GH, Prolactin (Prl) and TSH (CPHD). Despite the variability of the clinical presentation of this syndrome at the time of initial diagnosis, all forms finally result in severe retardation of growth and development due to GH-deficiency and hypothyroidism. More than half of the families with a combined pituitary hormone deficiency have not disclosed any Pit-1 abnormalities. Evidence is accumulating that Prop-1, a transcriptionfactor expressed temporarily in the fetal anterior pituitary, could be a candidate for patients with a Pit-1 phenotype without any Pit-1 gene abnormalities.

DNA-Binding Proteins↗

Blastic transformation of p53-deficient bone marrow cells by p210bcr/abl tyrosine kinase.

Blastic transformation of chronic myelogenous leukemia (CML) is characterized by the presence of nonrandom, secondary genetic abnormalities in the majority of Philadelphia1 clones, and loss of p53 tumor suppressor gene function is a consistent finding in 25-30% of CML blast crisis patients. To test whether the functional loss of p53 plays a direct role in the transition of chronic phase to blast crisis, bone marrow cells from p53+/+ or p53-/- mice were infected with a retrovirus carrying either the wild-type BCR/ABL or the inactive kinase-deficient mutant, and were assessed for colony-forming ability. Infection of p53-/- marrow cells with wild-type BCR/ABL, but not with the kinase-deficient mutant, enhanced formation of hematopoietic colonies and induced growth factor independence at high frequency, as compared with p53+/+ marrow cells. These effects were suppressed when p53-/- marrow cells were coinfected with BCR/ ABL and wild-type p53. p53-deficient BCR/ABL-infected marrow cells had a proliferative advantage, as reflected by an increase in the fraction of S+G2 phase cells and a decrease in the number of apoptotic cells. Immunophenotyping and morphological analysis revealed that BCR/ABL-positive p53-/- cells were much less differentiated than their BCR/ABL-positive p53+/+ counterparts. Injection of immunodeficient mice with BCR/ABL-positive p53-/- cells produced a transplantable, highly aggressive, poorly differentiated acute myelogenous leukemia. In marked contrast, the disease process in mice injected with BCR/ABL-positive p53+/+ marrow cells was characterized by cell infiltrates with a more differentiated phenotype and was significantly retarded, as indicated by a much longer survival of leukemic mice. Together, these findings directly demonstrate that loss of p53 function plays an important role in blast transformation in CML.

Animals↗

A cell proliferation-dependent multiprotein complex NC-3A positively regulates the CD34 promoter via a TCATTT-containing element.

The CD34 cell surface antigen is a glycoprotein expressed by hematopoietic stem and progenitor cells and also by certain nonhematopoietic cell-types. Because CD34 expression is regulated both at the transcriptional and the posttranscriptional level, we attempted to identify factors that, by interacting with the 5' flanking region of the human CD34 gene, may regulate its promoter activity in proliferating hematopoietic cells. By electrophoretic mobility shift assay, UV cross-linking and DNase I footprinting analyses, we identified a multiprotein complex, designated NC-3A, that specifically interacts with the CD34 promoter region from nucleotides -375 to -351. Sequence analysis of this region revealed the presence of a distinct motif, TCATTT. Chloramphenicol acetyl-transferase assays used to assess promoter activity in transiently transfected cells showed that this TCATTT-containing element, which is conserved in both the human and the murine CD34 genes, mediates positive regulatory activity in hematopoietic and nonhematopoietic cells, and acts as an enhancer when placed upstream of a heterologous promoter. Moreover, loss of CD34 promoter activity was caused by mutation of the TCATTT motif. In addition, the interaction of the nuclear multiprotein complex NC-3A with this enhancer element is proliferation-dependent. These data indicate that, although not cell-type specific, the formation of a multiprotein complex NC-3A interacting with the region from nucleotides -375 to 351 plays an important role in controlling CD34 promoter activity in proliferating hematopoietic cells.

Animals↗

The product of a 1.9-kb mRNA which overlaps the HSV-1 alkaline nuclease gene (UL12) cannot relieve the growth defects of a null mutant.

Alkaline nuclease, a relatively abundant viral phosphoprotein in herpes simplex virus type 1 (HSV-1)- or HSV-2-infected cells, is encoded by a 2.3-kb mRNA (R. H. Costa, K. G. Draper, L. Banks, K. L. Powell, G. Cohen, R. Eisenberg, and E. K. Wagner, 1983. J. Virol. 48, 591-603). This mRNA is a member of a family of five unspliced 3'-coterminal messages. Costa et al. proposed that another member of this family of mRNAs (1.9-kb) may encode an N-terminally truncated protein which shares its carboxy-terminus with the alkaline nuclease protein. We previously described the isolation of AN-1, a deletion/insertion mutant of the alkaline nuclease gene (S. K. Weller, R. M. Seghatoleslami, L. Shao, D. Rowse, and E. P. Carmichael, 1990. J. Gen. Virol. 71, 2941-2952). The deletion in AN-1 would be predicted to abolish gene products of both the 2.3- and the 1.9-kb mRNAs. To investigate whether the putative truncated version of alkaline nuclease encoded by the 1.9-kb mRNA has enzymatic activity and plays a role in the viral life cycle, a viral mutant (AN-F1) was constructed which is predicted to abolish the gene product of the 2.3-kb mRNA (full-length alkaline nuclease) but leave intact the putative product of the 1.9-kb mRNA. Using a highly sensitive polyclonal antiserum raised against a bacterially expressed full-length alkaline nuclease, we observed a 60-kDa protein in KOS- and AN-F1-infected cells but not in AN-1-infected cells. This suggests that the 60-kDa protein is likely to be expressed from the 1.9-kb mRNA; the open reading frame is now designated UL12.5. Despite the presence of the 60-kDa band, AN-F1 failed to exhibit any alkaline exonuclease activity. This result suggests that the truncated polypeptide (UL12.5) is not enzymatically active, has low levels of activity, or possesses enzymatic activity which is not detected because of the low abundance of the polypeptide. AN-1 and AN-F1 are both severely restricted with respect to growth in Vero cells, as viral yields are 100- to 1000-fold lower than those of wild-type virus. We previously reported that the major defect in AN-1 is in the ability of DNA-containing capsids which form in the nucleus to mature into the cytoplasm (L. Shao, L. M. Rapp, and S. K. Weller, 1993. Virology 196, 146-162); AN-F1 exhibits the same defect. These results indicate that although the 1.9-kb mRNA encodes a 60-kDa protein presumably from the UL12.5 open reading frame, this polypeptide cannot substitute for the full-length UL12 product.

Animals↗

Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis.

Due to the resurgence of tuberculosis and the emergence of multidrug-resistant strains, fluoroquinolones (FQ) are being used in selected tuberculosis patients, but FQ-resistant strains of Mycobacterium tuberculosis have rapidly begun to appear. The mechanisms involved in FQ resistance need to be elucidated if the effectiveness of this class of antibiotics is to be improved and prolonged. By using the rapid-growing Mycobacterium smegmatis as a model genetic system, a gene was selected that confers low-level FQ resistance when present on a multicopy plasmid. This gene, lfrA, encodes a putative membrane efflux pump of the major facilitator family, which appears to recognize the hydrophilic FQ, ethidium bromide, acridine, and some quaternary ammonium compounds. It is homologous to qacA from Staphylococcus aureus, tcmA, of Streptomyces glaucescens, and actII and mmr, both from Streptomyces coelicoler. Increased expression of lfrA augments the appearance of subsequent mutations to higher-level FQ resistance.

Amino Acid Sequence↗

Effect of integration of injury control information into a high school physics course.

STUDY OBJECTIVE: To investigate the effects on knowledge, attitudes, and self-reported behaviors of a 1-week course of injury control and crash safety information integrated within a high school physics curriculum. METHODS: Students in an intervention high school (n=129) were compared with students in a control high school (n=74) enrolled in a comparable physics curriculum. A standardized survey was administered before instruction (time T1), and at 2 weeks (T2) and 6 months (T3) after instruction was completed. The behaviors measured were self-reported use of seat belts, speeding, drinking and driving, and intention to use seat belts in the future. RESULTS: At T2, students in the intervention group reported attitudes that were less favorable toward risk-taking in regard to speeding and seat belt use than those of the control group. At T3, there was still a difference in attitudes toward speeding but not toward seat belt use. The intervention significantly altered the knowledge level of the course participants, and these changes persisted to T3. The strongest and most persistent change was that students in the intervention group reported increasing their use of seat belts when riding as a passenger. (Seat belt use as a driver was high for both groups.) The intervention group showed a significant increase in their 1-year intentions to use seat belts both as a driver and as a passenger. CONCLUSION: This study demonstrated that driver safety education can be successfully integrated into a mainstream high school science curriculum. Future studies measuring the effects of this curriculum on observed behaviors are needed.

Accidents, Traffic↗

Literature and ethical medicine: five cases from common practice.

This essay is composed of five stories written by practicing physicians about their patients. Each clinical story describes a challenging ethical condition-potential abuse of medical power, gravely ill and probably over-treated newborns, iatrogenic narcotic addiction, deceived dying people. Rather than singling out one ethical conflict to resolve or adjudicate, the authors attempt, through literary methods, to grasp the singular experiences of their patients and to act according to the deep structures of their patients' lives. Examining these five stories with simple literary tools-attention to narrative frames, time, plot, and desire-reveals the mechanisms through which acts of writing and reading contribute to clinical clarity and ethical actions.

Adult↗

Herpes simplex virus type 1 alkaline nuclease is required for efficient processing of viral DNA replication intermediates.

Mutations in the alkaline nuclease gene of herpes simplex type 1 (HSV-1) (nuc mutations) induce almost wild-type levels of viral DNA; however, mutant viral yields are 0.1 to 1% of wild-type yields (L. Shao, L. Rapp, and S. Weller, Virology 195:146-162, 1993; R. Martinez, L. Shao, J.C. Bronstein, P.C. Weber, and S. Weller, Virology 215:152-164, 1996). nuc mutants are defective in one or more stages of genome maturation and appear to package DNA into aberrant or defective capsids which fail to egress from the nucleus of infected cells. In this study, we used pulsed-field gel electrophoresis to test the hypothesis that the defects in nuc mutants are due to the failure of the newly replicated viral DNA to be processed properly during DNA replication and/or recombination. Replicative intermediates of HSV-1 DNA from both wild-type- and mutant-infected cells remain in the wells of pulsed-field gels, while free linear monomers are readily resolved. Digestion of this well DNA with restriction enzymes that cleave once in the viral genome releases discrete monomer DNA from wild-type virus-infected cells but not from nuc mutant-infected cells. We conclude that both wild-type and mutant DNAs exist in a complex, nonlinear form (possibly branched) during replication. The fact that discrete monomer-length DNA cannot be released from nuc DNA by a single-cutting enzyme suggests that this DNA is more branched than DNA which accumulates in cells infected with wild-type virus. The well DNA from cells infected with wild-type and nuc mutants contains XbaI fragments which result from genomic inversions, indicating that alkaline nuclease is not required for mediating recombination events within HSV DNA. Furthermore, nuc mutants are able to carry out DNA replication-mediated homologous recombination events between inverted repeats on plasmids as evaluated by using a quantitative transient recombination assay. Well DNA from both wild-type- and mutant-infected cells contains free U(L) termini but not free U(S) termini. Various models to explain the structure of replicating DNA are considered.

Animals↗

Bronchiolar basement membrane changes associated with bronchiolitis obliterans in lung allografts: a retrospective study of serial transbronchial biopsies with immunohistochemistry [corrected].

Lung transplantation is an accepted mode of therapy for selected patients with end-stage lung disease. Their long-term survival is mainly limited by chronic rejection, i.e., bronchiolitis obliterans (BO), which represents a fibrosing inflammatory process of the terminal and respiratory bronchioles, leading to progressive small airway obstruction. To evaluate its development, and associated irreversible allograft dysfunction, we retrospectively studied the histological and clinical data from nine patients who developed BO, and nine matched control patients. A total of 152 serial transbronchial biopsies (87 from patients with BO; 65 from the control group) were studied using immunohistochemical stains, with antibodies to laminin, desmin, fibronectin, collagen IV, collagen III, and vimentin. The staining with anti-collagen IV antibody was the most productive and in eight of the nine patients with BO demonstrated early focal bronchiolar basement membrane damage, manifested by thickening and subsequent splitting and duplication. This was seen in association with the second episode and onward of clinically significant episodes of acute cellular rejection which occurred 7 to 12 months posttransplant. The larger airways were unaffected. The histological onset of BO exhibited varying degrees of obstruction of the bronchioles with no detectable basement membrane staining. The control patients failed to demonstrate these findings. The other immunohistochemical stains used were found to be noncontributory. We conclude that the usage of anti-collagen IV on lung allograft biopsies demonstrates the sequential changes of bronchiolar basement membrane disruption in lung allograft recipients who have multiple episodes of clinically significant acute cellular rejection and later develop BO.

Adolescent↗

[Frequency of pregnant HBsAg carriers in a Brazilian community].

In view of the benefits of immunoprophylaxis among newborns of mothers who are seropositive for hepatitis B virus (HBV) surface antigen (HBsAG), these women must be correctly identified so that this measure can be instituted in Brazil. The research reported here studied 7992 women who gave birth in the Hospital das Clínicas of the Ribeirão Preto School of Medicine, University of São Paulo (HCFMRP-USP), Brazil, in order to determine the rate of serum reactivity of HBsAg and other markers of HBV infection among these women, and also to evaluate the risk factors for this infection. Serum reactivity for HBsAg was determined by means of an immunoenzymatic test (ELISA) carried out in two stages: the first with an incubation period of 2 hours (screening), and the second with an incubation period of 18 hours (confirmation) for those samples that were positive in the screening test. The markers anti-HBsAg, HBeAg, anti-HBcAg, and anti-HBeAG were tested in the samples that were confirmed positive. The screening test found 1.05% (95% CI: 0.84 - 1.30) of the samples to be positive for HBsAg. However, only 0.95% (95% CI: 0.75 - 1.19) were confirmed positive, the percentage being significantly higher among patients whose pregnancies had ended in abortion (1.84%) than among those who had given birth (0.84%) (X2, Yates correction = 7.76; P < 0.005). Risk factors for HBV infection could be identified for only 27.6% of the study subjects, based on their recall and reporting. Of the women with confirmed positive samples, 21.3% also were positive for HBeAG, indicating that these patients ran a greater risk of transmitting the virus vertically. These results underline the need for specific serologic studies in the final stage of pregnancy in order to offer the maximum benefit of neonatal immunoprophylaxis.

Brazil↗

Neuropeptide Y and the nonpeptide antagonist BIBP 3226 share an overlapping binding site at the human Y1 receptor.

Neuropeptide Y (NPY) is a 36-amino acid peptide that exhibits actions on the cardiovascular system and the central nervous system. NPY can regulate blood pressure, psychomotor function, anxiety, food intake, and endocrine secretions. BIBP 3226, the first potent and selective nonpeptide antagonist at the NPY Y1 receptor, was designed by mimicking the carboxyl-terminal structure of NPY. We investigated the interaction of NPY and BIBP 3226 with the human Y1 receptor at the molecular level. Alanine mutants at positions Y100, D104, W288, and H298 of the human Y1 receptor showed no or significantly reduced binding for NPY but were not affected in their ability to bind BIBP 3226. Receptors with alanine mutations at positions W163, F173, Q219, N283, F286, and D287 showed reduced binding for both NPY and BIBP 3226. Mutations at other positions were tested (H105, S170, L174, V178, D200, D205, S206, H207, S210, T212, T280, T284, N289, H290, and Q291) and did not affect the binding of NPY or BIBP 3226. The human Y1 receptor mutant Y211A showed no affinity for BIBP 3226 but retained wild-type affinity for NPY. Based on these experimental results, a detailed model for the interaction of BIBP 3226 with the human Y1 receptor was developed using a Y1 receptor model and a three-dimensional model of BIBP 3226. The experimental results, supported by modeling studies, clearly suggest that the native ligand (NPY) and the antagonist (BIBP 3226) share an overlapping binding site.

Amino Acid Sequence↗

Improving air bags.

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Accidents, Traffic↗