[Official recognition of a social problem: maternal mortality in Ecuador].
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Biomedical subjects
Publications and source records attributed to R Torres.
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The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.
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The genomic organization and nucleotide sequence of the human homeobox gene Prox 1 as well as its chromosomal localization have been determined. This gene spans more than 40 kb, consists of at least 5 exons, and encodes an 83-kDa protein. It shows 89% identity with the chicken sequence at the nucleotide level in the coding region, while the human and chicken proteins are 94% identical. Among the embryonic tissues analyzed (lens, brain, lung, liver, and kidney), the human Prox 1 gene is most actively expressed in the developing lens, similar to the expression pattern of the chicken Prox 1 gene. The Prox 1 gene was mapped to human chromosome 1q32.2-q32.3.
Autotaxin, a potent human tumor cell motility-stimulating exophosphodiesterase, was isolated and cloned from the human teratocarcinoma cell line NTera2D1. The deduced amino acid sequence for the teratocarcinoma autotaxin has 94% identity to the melanoma-derived protein, 90% identity to rat brain phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha), and 44% identity to the plasma cell membrane marker PC-I. Utilizing polymerase chain reaction screening of the CEPH YAC library, we localized the autotaxin gene to human chromosome 8q23-24. Northern blot analysis of relative mRNA from multiple human tissues revealed that autotaxin mRNA steady state expression is most abundant in brain, placenta, ovary, and small intestine.
The antiemetic effect of tropisetron was studied in 97 cancer patients (67 men, 30 women) receiving cisplatin in doses of 75 mg/m2 or higher. On 279 chemotherapy cycles studied (max 6 per patient) 5 mg of tropisetron was administered once a day i.v on day 1 and p.o. on days 2 to 6. Efficacy preventing vomiting and nausea was measured in 24 hour period as: complete control O episodes, major control 1 to 2 episodes, minor control 3 to 4 episodes and no control 5 or more episodes. Satisfactory vomiting control (complete and major) was 69%, 63%, 82%, 88%, 96% and 96% in days 1 to 6 of cycle 1. Satisfactory nausea control (complete and major) for the same days was 70%, 66%, 72%, 85%, 92% and 97%. Similar data was obtained for the subsequent cycles. Complete vomiting control was obtained in 47%, 35%, 56%, 72%, 81% and 84% and for nausea in 42%, 39%, 48%, 64%, 81% and 87%. 19 patients presented adverse effects (19.6%). Only 2 headache episodes had a definite relation with the antiemetic drug. 12 patients discontinued the medication; 6 due to drug inefficacy, 2 to illness unrelated to the drug, 1 to lack of collaboration, and 3 due to other reasons. We conclude that tropisetron allows satisfactory control of acute and delayed vomiting in a high percentage of patients treated with high doses of cisplatin. The drug does not have significant secondary effects. Tropisetron administration in only one daily dose implies an evident advantage and a treatment cost reduction.
Camptothecin (CPT) derivatives are presently in ongoing Phase I/II clinical trials. The interactions between 9-aminocamptothecin (9AC) and cisplatin (CDDP) have been studied in the IGROV-1 human ovarian cancer cell line used in the National Cancer Institute Drug Discovery Anticancer Screen. One-h simultaneous treatment with 9AC and CDDP produced synergistic cytotoxicity. Under these conditions, 9AC delayed the reversal of CDDP-induced DNA interstrand cross-links (ISCs) without modifying the maximum ISC frequency at 6 h after drug treatment. CDDP did not affect the amount and the kinetics of reversion of 9AC-induced DNA single-strand breaks. Simultaneous treatment with CDDP and 9AC prolonged the DNA synthesis inhibition produced by each drug alone. Consistently, flow cytometry analyses showed enhanced S-phase arrest in cells treated with the CDDP-9AC combination. The DNA polymerase inhibitor aphidicolin also increased the residual CDDP-induced ISCs. These results suggest that prolonged inhibition of DNA synthesis by CPTs potentiate the cytotoxicity of CDDP by inhibiting the reversal of CDDP-induced DNA damage. Therefore, the combination of CPTs and CDDP appears to be worthwhile in cancer chemotherapy.
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Documented interactions among members of the Myc superfamily support a yin-yang model for the regulation of Myc-responsive genes in which transactivation-competent Myc-Max heterodimers are opposed by repressive Mxi1-Max or Mad-Max complexes. Analysis of mouse mxi1 has led to the identification of two mxi1 transcript forms possessing open reading frames that differ in their capacity to encode a short amino-terminal alpha-helical domain. The presence of this segment dramatically augments the suppressive potential of Mxi1 and allows for association with a mammalian protein that is structurally homologous to the yeast transcriptional repressor SIN3. These findings provide a mechanistic basis for the antagonistic actions of Mxi1 on Myc activity that appears to be mediated in part through the recruitment of a putative transcriptional repressor.
The antimicrobiol properties and preliminary chemical information of the resinous exudates from twigs and leaves of nine Haplopappus species from Chile: H. diplopappus; H. anthylloides; H. schumannii; H. cuneifolius; H. velutinus; H. uncinatus; H. multifolius, H. illinitus and H. foliosus are presented. The results show that those species of genus Haplopappus share similar antimicrobial activities although they differ dramatically in the chemical composition.
PURPOSE: To study the relationship between personality attributes and health behaviors and practices during adolescence. DESIGN: We have studied a total of 100 subjects aged 12-13 and 16-17 years of both sexes. To examine self-esteem and the value of health in a series of habitual practices of health, a stepwise multiple regression analysis was undertaken. The instruments used were the Gordon Personal Profile (GPP) (1978) to evaluate self-esteem, the Costa et al.'s (1989) Value of Health Scale to estimate the value of health and, the Rivas Torres (1991) Health Behavior Questionnaire to measure health behavior. RESULTS: Self-esteem explains 39% of the mental health behavior and 5% of the social health behaviors. Meanwhile, the value of health, in the case of security behaviors, explains 13%, and in relation to personal health behaviors, 9%. CONCLUSIONS: The importance assigned to certain personality attributes in relation to adolescent health behavior shows the need for additional investigations that incorporate other variables and subject groups with different ages.
Pycnodysostosis (OMIM 265800) is an autosomal recessive skeletal disorder first described by Maroteaux and Lamy that is characterized by short stature, increased bone density, delayed closure of cranial sutures, loss of the mandibular angle, dysplastic clavicles, dissolution of the terminal phalanges of the hands and feet, dental abnormalities and increased bone fragility. Patients have a typical appearance secondary to prominence of the calvarium, smallness of the facial features, prominent nose and micrognathia. The French painter, Henri de Toulouse Lautrec (1864-1901), is believed to have had the disorder. Although more than 100 cases have been reported, we are aware of only two large consanguinous pedigrees in which the pycnodysostosis disorder segregates. We have studied the segregation of the pycnodysostosis phenotype in a large consanguinous Mexican pedigree, the clinical features of which are very similar to those described in the Arab pedigree studied by Edelson et al. Here, we report linkage for the pycnodysostosis phenotype in the 1cen-q21 region of human chromosome 1, and discuss candidate genes for this skeletal disorder.
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As part of a project aimed at developing an adolescent health education program, 100 subjects aged 12-13 and 16-17 years were studied to determine the possible relationship between self-esteem and value of health and positive health behavior. Self-esteem was measured with the Gordon Personal Profile (Gordon, 1978), and value of health with Costa et al.'s (Costa, Jessor, & Donovan, 1989) Value of Health Scale. Both factors were found to be significantly correlated with certain dimensions of health behavior in both groups of adolescents.
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Several bicyclic dihydropyrimidines were synthesized and evaluated for their calcium antagonistic activities by comparison with the usual 1,4-dihydropyridine calcium antagonist reference compound nifedipine. The solid-state structure of the isopropyl 2-methyl-4-(3'-nitrophenyl)-1,4-dihydrobenzo[4,5]imidazo[1,2- a]pyrimido-3-carboxylate shows that these compounds can adopt the most important structural features of the 1,4-dihydropyridine and 1,4-dihydropyrimidine calcium channel blockers. The high-potassium depolarized rat aorta assay was used for testing the compounds as calcium channel blockers. Some compounds showed interesting vasorelaxant activity.
In mammals, current evidence supports the view that Myc-responsive activities are regulated in part through an intracellular balance between levels of transcriptionally-active Myc/Max heterodimers and those of transcriptionally-inert Max/Max, Mad/Max and Mxi1/Max complexes. To gain insight into the roles of Mad and Mxi1 in cellular growth and differentiation and to fortify key structure-function relationships from an evolutionary standpoint, low stringency hybridization screens were used to identify potential homologs of these Max-associated proteins in the zebra fish genome. A single class of cDNA clones that cross-hybridized both to human mad and mxi1 probes was shown to encode a putative protein with significantly greater homology to mammalian Mxi1 than to Mad, particularly in the basic and helix-loop-helix (bHLH) regions. The high degree of structural relatedness between vertebrate Mxi1 proteins apparent in molecular modelling studies was consistent with the findings that the HLH/leucine zipper (LZ) region of zMxi1 exhibited the same profile of dimerization specificities as its mammalian counterpart in the two-hybrid system and that zmxi1 could, like human mxi1 (Lahoz et al., 1994), suppress the oncogenic potential of mouse c-myc in a mammalian cell. Finally, a comparison of steady-state zc-myc and zmxi1 mRNA levels during zebra fish embryogenesis demonstrated (i) high levels of zc-myc relative to zmxi1 mRNA during initiation of organogenesis, a period characterized by intense growth and active differentiation and (ii) rising levels of zmxi1 mRNA during progression towards the terminally differentiated state. These contrasting patterns of developmental expression together with the capacity of zmxi1 to repress myc-induced transformation support a model for the regulation, by Max-associated proteins, of Myc functions in the control of normal cell development and neoplastic growth.