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Biomedical subjects

M Garcia

Publications and source records attributed to M Garcia.

At least 235 records · Page 13Linked to original sources

Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency.

Cathepsin D, an aspartic lysosomal proteinase, is overexpressed by breast cancer cells and highly correlated with the occurrence of metastasis in patients. We used an adenovirus transformed rat cell line that does not secrete cathepsin D, to study the consequences of transfecting human cathepsin D cDNA. Overexpression of human cathepsin D in stable transfectant clones, results in higher initial growth rates in low serum conditions, overgrowth at high cell densities resulting in stellate aggregates, and greater anchorage-independent growth in soft agar. The metastatic activity (mostly in liver) of cathepsin D clones injected into athymic mice was significantly higher than that of control clones. These results show that overexpression of cathepsin D increases the transformed phenotype of malignant cells in vitro and their metastatic potency in vivo.

Animals↗

Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary human breast cancer.

The Mr 52,000 cathepsin D is the precursor of a lysosomal protease secreted in excess by breast cancer cells. This protease can degrade extracellular matrices and proteoglycans and is induced by estrogens in estrogen receptor-positive breast cancer cell lines. In a 4- to 6-yr retrospective cohort study, the concentration of the total cathepsin D (precursor plus intermediate and mature chains) was assayed in cytosols of primary tumors from 242 pre/perimenopausal and 154 postmenopausal breast cancer patients in a solid-phase immunoassay using two specific monoclonal antibodies. Patients were initially divided into groups with low, intermediate, or high concentrations of cathepsin D corresponding to the quartiles of the overall distribution. Using these groupings, the level of Mr 52,000 cathepsin D was not significantly associated with the recognized prognostic factors of age, lymph node involvement, tumor size, and/or grade of anaplasia. A significant association was found between cathepsin D concentrations and estrogen receptor status only among pre/perimenopausal patients. Receptor-positive tumors (greater than or equal to 10 fmol of estrogen receptor/mg of cytosol protein) had a significantly greater proportion of patients with high Mr 52,000 cathepsin D concentrations. Patients with high Mr 52,000 cathepsin D concentrations (greater than 78 pmol/mg for pre/perimenopausal and greater than 24 for postmenopausal patients) have shorter recurrence-free survival (P = 0.06 for pre/peri- and P = 0.039 for postmenopausal patients) and have a trend toward shorter overall survival (P = 0.30 and P = 0.089 for pre/peri- and postmenopausal groups, respectively). In multivariate analysis, Mr 52,000 cathepsin D status was found to be an independent prognostic factor for recurrence-free survival of about the same import as lymph node status for both menopausal groups. This first retrospective study demonstrates that the level of Mr 52,000 cathepsin D in cytosol of primary breast cancer biopsies is an independent prognostic factor in predicting relapses in both pre/peri- and postmenopausal patients.

Adult↗

The male factor in the etiology of cervical cancer among sexually monogamous women.

To address the hypothesis that male sexual behavior may affect the etiology of invasive cervical cancer, a case-control study was undertaken in Panama, Costa Rica, Colombia and Mexico. The study enrolled husbands of those women with invasive cervical cancer and of those age-matched controls who reported only one lifetime sexual partner. A total of 204 case and 485 control husbands (78% and 72%, respectively, of identified husbands) were interviewed, clinically examined, and had penile swabs taken for papillomavirus assays. Risk increased significantly (p = 0.005) with the number of sexual partners reported by the husband (RR = 2.0 for 26+ vs. less than 6 partners). Low educational status of the husband was also an important predictor of risk, possibly indicating the role of unmeasured aspects of sexual behavior. Visits to prostitutes, circumcision status and sexually transmitted disease histories were not important predictors of risk, but evidence from clinical examination indicated that poor genital hygiene may be involved. Human papillomavirus (HPV) expression as defined by filter in situ hybridization was detected in 20-23% of subjects and, except in the small group with both HPV types 6/11 and 16/18, was not related to risk. This may reflect sampling problems in the male or the importance of host factors which enhance viral carcinogenicity in the female.

Circumcision, Male↗

Invasive cervical cancer and smoking in Latin America.

A case-control study of 667 patients with invasive squamous cell carcinoma of the cervix and 1,430 controls from four Latin American countries showed an age-adjusted relative risk (RR) of 1.2 [95% confidence interval (CI) = 1.0-1.4] for women who had ever smoked, with risk rising to 1.7 (95% CI, 0.8-3.6) for women who smoked greater than or equal to 30 cigarettes per day. The associations were practically eliminated after adjustment for the number of sexual partners and alcohol consumption, probably a surrogate for an unidentified life-style risk factor. Some excess risk persisted among women who smoked for extended periods (RR = 1.5 for greater than or equal to 40 yr), as well as those who began smoking at older ages (RR = 1.7 for greater than 30 yr), which suggests a late-stage effect. In addition, among women who tested positive for human papillomavirus (HPV) type 16 or 18 by filter in situ hybridization, there was an increased risk for women who had ever smoked and a dose-response relationship with the number of cigarettes smoked (adjusted RRs compared with HPV-negative nonsmokers = 5.0 for HPV-positive nonsmokers, 5.5 for less than 10 cigarettes/day, and 8.4 for greater than or equal to 10 cigarettes/day). In contrast, HPV-negative women had no increased risk associated with smoking. These results, from a high-incidence area where intensive smoking among women is still relatively rare, suggest that smoking has a limited effect on cervical cancer risk, possibly only among women with specific types of HPV.

Age Factors↗

Familial transmission of 16p trisomy in an infant.

Based on four reported cases including the present case, 16p trisomic infants have remarkably similar features. These are severe developmental delay, psychomotor retardation, typical facies, and anomalies of extremities.

Chromosome Banding↗

Barbara Snell Dohrenwend memorial lecture. The impact of AIDS on a gay community: changes in sexual behavior, substance use, and mental health.

This report describes progress made to date on a study of the impact of the AIDS epidemic on the gay community of New York City. Using a model of the life stress process described by Barbara Dohrenwend and her colleagues, the AIDS epidemic was conceptualized as a community stressor resulting in two key stress-inducing events: death of loved ones due to AIDS and potential illness and death of oneself due to infection with human immunodeficiency virus (HIV). It was hypothesized that these stressors would be significantly related to three domains of health outcomes: sexual behavior, drug and alcohol use, and psychological distress. Descriptive trends over time are provided for both the health outcome variables and the stressor variables. Cross-sectional analyses for 3 years of data provide evidence in support of the main hypothesis. The implications of these findings are discussed from the standpoints of methodology, public health, and the psychology of stress processes in community settings.

Acquired Immunodeficiency Syndrome↗

Renal vein leiomyosarcoma: a case report and literature review.

A case of leiomyosarcoma of the renal vein occurring in a 48-year-old woman is reported, and the literature is reviewed. Ultrasonography (US) revealed a rounded uniform echogenic mass in the renal hilus. Computed tomography (CT) showed a well-demarcated, uniform, soft tissue density mass. Both US and CT were useful to detect the renal mass in the present case, and may be useful for staging of renal vein leiomyosarcoma. However, these imaging procedures did not reveal diagnostic features of leiomyosarcoma.

Female↗

Overexpression and hormonal regulation of pro-cathepsin D in mammary and endometrial cancer.

Pro-cathepsin D is overexpressed in breast cancer cells compared to normal mammary epithelial cells. Moreover, its processing and maturation are altered resulting in increased secretion. In estrogen-responsive breast cancer cell lines such as MCF7 cells and ZR75-1 cells, the 2.2-kb cathepsin D mRNA is accumulated specifically by estrogens and growth factors. Estrogen regulation is mostly transcriptional, while growth factors stabilize the mRNA and act indirectly. In estrogen-receptor-negative cell lines, there is a constitutive high production of cathepsin D mRNA. Moreover in uterine cells, progesterone is the inducer rather than estrogen, indicating the complexity of regulation by steroids, depending on the tissue. The increased production of cathepsin D appears to be correlated with the aggressiveness of the tumour, as shown by retrospective clinical studies, suggesting a role in mammary carcinogenesis.

Breast↗

Depressive symptomatology among Mexican-American adults: an examination with the CES-D Scale.

The presence and persistence of specific depressive symptomatology among a large sample of Mexican-American adults (n = 3,084) were examined with the Center for Epidemiologic Studies Depression (CES-D) Scale. Compared to studies of Anglos, a substantially larger percentage reported persistent hopelessness about the future (29%), self-depreciation (21%), and lack of enjoyment out of life (14%). The prevalence of these symptoms was higher among those who had not adapted to mainstream American society and among older participants. Women were generally more distressed than men. Factor analyses of the items demonstrated a slightly different factor structure than previously obtained with Anglos. For both sexes and for those under age 30 and ages 30-59, the items "loneliness," "sadness," and "crying" loaded on a common factor. The tendency for these items to group together was stronger for those exhibiting a low or medium degree of cultural adaptation than for those exhibiting a high degree of adaptation. Discussion focuses on the cultural variation of response to items on the CES-D.

Acculturation↗

Differential regulation of cathepsin D by sex steroids in mammary cancer and uterine cells.

The precursor of cathepsin D, a lysosomal acidic protease, is secreted by human breast cancer cells, where its synthesis is specifically induced by estrogens and growth factors. In this study, we investigated the hormonal regulation of cathepsin D and its mRNA in uterine cells. In the Ishikawa endometrial cancer cell line, epidermal growth factor (EGF) increased the level of cathepsin D and its mRNA 2- to 3-fold. Although expression of the transiently transfected estrogen-responsive recombinant (Vit. tk. CAT) and the endogenous progesterone receptor was markedly increased by estradiol in Ishikawa cells, estradiol did not alter the level of cathepsin D or its mRNA. The progestin R5020 induced the expression of the LTR sp65 CAT, which contains the progesterone-responsive element of the MMTV but it too was without effect on cathepsin D. By contrast, the expression of cathepsin D gene, in normal rat uterus, was increased by R5020 but not by estradiol. We conclude that cathepsin D gene expression is regulated differently by sex steroid hormones in endometrial and breast cancer cell lines, whereas it is similarly induced by EGF in these cells.

Animals↗

Effects of a high molecular weight toxin from Physalia physalis on glutamate responses.

The effects of a high molecular weight toxin from Physalia physalis (P3) were investigated on glutamate evoked potentials in snail (Zachrysia guanesis) neurons and in crayfish (Cambarus clarkii) neuromuscular junction. The glutamate evoked potentials of snail neurons were reversibly blocked by P3 in a dose-dependent manner (2-200 microM). A reversible blocking action was also found for P3 on excitatory junctional potentials and on glutamate potentials of crayfish at a concentration range of 6 nM-60 microM. Experiments carried out with independent stimulation of the excitatory and inhibitory nerves showed that the effect of P3 (60 nM-10 microM) was exerted predominantly on excitatory junctional potentials. However, at higher doses (greater than 10 microM) a slight reduction of the inhibitory potentials was also observed. These results suggest that P3 reversibly blocks glutamate receptors. Thus, it could be a promising tool for further studies on glutamatergic transmission.

Action Potentials↗

Genital human papillomavirus infection in Panama City prostitutes.

Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present.

Adolescent↗

Reduced productivity in adult yellowfever mosquito (Diptera: Culicidae) populations.

Male and female Aedes aegypti (L.) mosquitoes of the laboratory strain ROCK were irradiated with 130 mw of argon 514.5 nm laser microbeams for 0.04, 0.25, 0.4, and 0.5 s, respectively. Egg production, percentage hatch, and productivity (average number of adults surviving after 3 wk) were used to assess mutagenic effects. Mortality was high for males in all laser radiation groups and increased with time of exposure. Except for the group treated for 0.25 s, significant reductions in total F1 progeny also were demonstrated for all other experimentals when male parents were exposed to laser radiation. Females showed a high mortality when subjected to 0.4- and 0.5-s laser radiation. No F1 progeny were produced when parental females were exposed for 0.25, 0.4, and 0.5 s. Numbers of F1 progeny from females exposed to 0.04 s of laser radiation were significantly reduced. A comparison of weekly mean number of progeny showed that the important differences in productivity occurred during the first and second week, respectively, when either male or female adult parents were subjected to laser radiation.

Aedes↗

Parity as a risk factor for cervical cancer.

In a case-control study of 759 invasive cervical cancer patients and 1,430 controls in Colombia, Costa Rica, Mexico, and Panama conducted during 1986-1987, an association with number of pregnancies persisted after adjustment for sexual and socioeconomic variables. Risks rose steadily to 5.1 (95% confidence interval 2.7-9.7) for those with 14 or more pregnancies and a relation of risk to multiparity was observed in all four study countries. Pregnancy associations appeared to relate to the number of live births rather than to miscarriages or abortions, with multiparity relations most pronounced among premenopausal women and oral contraceptive users. Human papillomaviruses types 16 and 18, as measured by filter in situ hybridization, were not significantly associated with number of births and did not explain the strong relation of parity to risk. Our results indicate the need for further consideration of reproductive factors on cervical cancer risk, with attention given to possible mechanisms of action, including hormonal factors and cervical trauma.

Adult↗

Studies on chorionic gonadotrophin hormone in rhesus monkeys--disappearance rates.

The disappearance rate of macaque chorionic gonadotrophin (MCG) was investigated in six pregnant monkeys. The animals were hysterectomized with a rapid initial ligature of the uterine and ovarian vessels with minimal uterine manipulation. The entire procedure lasted less than 2 min. Blood samples were drawn before and after the hysterectomy (5, 20, 30, 45, 60, 90, 120 min), and MCG was measured in serum by radioimmunoassay. For all animals, a progressive decrease (rate of disappearance) of MCG values in serum was found, which appeared to follow a double exponential curve. Averaged curves produced disappearance rates of T1/2(1) = 17.2 h for the first compartment (72 h), and T1/2(2) = 87.1 h for the second compartment (156 h). The results suggest that the disappearance of MCG after interruption of pregnancy in rhesus monkey is very similar to that occurring in humans. These data demonstrate that the rhesus monkey is an excellent animal model to study the dynamics of placental hormone secretion in humans.

Abortion, Induced↗

Eating attitudes, sociodemographic factors and body shape evaluation in adolescence.

The Eating Attitudes Test (EAT) and another questionnaire aimed at sociodemographic and body shape information were administered to an adolescent population of 1554 students from Barcelona in the 12-19 age group. The highest scores on EAT were obtained by girls, older adolescents, overweight adolescents, adolescents practising restrictive diets, adolescents considering themselves obese and those wishing to modify their body size. The same characteristics were associated with EAT scores higher than 30 (the cut-off score, established by the authors of the questionnaire, above which the anorexic population is placed). Results are analysed in terms of sociocultural pressures on adolescents, particularly females, who are subjected to the 'culture of slenderness'.

Adolescent↗