Search PubMed⌕ Search

Biomedical subjects

C Rodriguez

Publications and source records attributed to C Rodriguez.

At least 73 records · Page 4Linked to original sources
PubMed2000

At least five regions of imbalance on 6q in breast tumors, combining losses and gains.

The long arm of chromosome 6 is frequently rearranged in human cancer. In breast cancer, allelotyping studies have indicated the existence of three to four distinct regions of allelic imbalance. Chromosome transfer studies have shown the presence of several growth inhibiting or senescence promoting genes in the segment between 6q13 and 6q27. Moreover, results from comparative genomic hybridization (CGH) analyses have indicated that 6q was indeed a site of chromosomal losses, but that it was also involved in a substantial number of gains. In the present work, we allelotyped 178 pairs of breast tumor and normal tissue DNAs using 30 CA repeat markers from the Genethon collection. Seventy-six percent of the tumors in our panel displayed allelic imbalance (AI) of at least one locus, but patterns of AI could be complex. Whereas 11 tumors showed AI at all markers tested, 57 presented zebra profiles, and 28 showed AI at one site only. We characterized five distinct domains of AI defined, from centromere to telomere, by D6S300 (domain 1), D6S434 (domain 2), D6S261 (domain 3), D6S314-D6S409 (domain 4), and D6S441-D6S415 (domain 5). Some of the domains could be narrowed down to intervals of 1cM or less. We performed CGH analysis on a subset of 34 tumors presenting AI of variable extent at 6q. In 10/34 tumors, CGH did not reveal any anomaly on 6q. Most of these presented AI on short intervals, thus being below the detection threshold by CGH. Of the remaining 24 tumors presenting anomalies by CGH, 11 presented gains involving all or portions of 6q and 15 losses (2 presented combined losses and gains). By CGH, the 6q21-22 region was most commonly involved in gains, whereas 6q13-14 and 6q25-27 were frequently lost. Thus, allelic imbalances on 6q can either represent a gain or a loss depending on the region involved. Genes Chromosomes Cancer 27:76-84, 2000.

Alleles↗
PubMed2000

Salivary gland ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom.

In this work we have studied the possible relationships between clinical manifestations such as sialorrhea, appearing in response to the toxic aggression by Tityus discrepans venom, and the alterations or changes at cellular or subcellular levels in sub-maxillary salivary glands in the murine model. To evaluate salivary gland subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: a group of mice were intraperitoneally injected with Tityus discrepans venom at a dose of 5 mg/Kg of weight and controls received saline solution. In the salivary glands from the envenomed animals sub-cellular changes such as hyperchromatic nucleus, swollen rough endoplasmic reticulum, granules of different electron density, some of them practically transparent, nucleolus of low density and big size and electron-transparent cisterns were observed. Capillary wall was augmented in certain areas and thin in others. Endothelial cell infolding to the lumen was seen. The distribution of the vesicles and its density varied. Macrophages and plasmocytes were observed next to the damaged capillaries. Different electron density of cytoplasm was noticed. In conclusion, we suggest that sialorrhea is determined by salivary gland damage produced by toxins present in this venom.

Animals↗
PubMed2000

[Evaluation of a new preservation solution for hypothermic heart transplant].

AIM: One of the major problems encountered in heart transplant is the limited cardiac preservation time. The time limit from the moment the donor heart is removed to the transplant itself is 4-6 hours at maximum. Extending the preservation time would therefore provide access to a larger pool of donors, and also permit long-distance (transfrontier) organ transfer. To attain this aim, a number of different cardiac preservation solutions have been proposed and evaluated either clinically or experimentally; however, no consensus has yet been reached by the various heart transplant teams involved. As finding an optimal solution is of major importance, the aim of the present study was therefore to assess the efficacy of several cardiac preservation solutions: the University of Wisconsin solutions (UW-1 and UW-1 + calcium = UW-2), the Saint-Thomas' Hospital solution (STH-1) and a new solution (NS) developed by our laboratory. METHOD: Male Wistar rats (n = 60) were anesthetized by i.m. injection of pentobarbitol, and randomized into six groups, i.e., NS (group I), STH-1 (group II), UW-1 (group III), UW-2 (group IV), saline solution, NaCl (group V), and controls (group VI). All the hearts except those in the control group were preserved by immersion (8 hours, 4 degrees C) in the different solutions (n = 10/group). The hearts were either a) reperfused in Langendorff mode (functional assessment, n = 5/group); or b) frozen (energetic assessment, n = 5/group). RESULTS: The hearts treated with NaCl displayed arrhythmia and a collapsed mean left ventricular pressure throughout the reperfusion period (3.6 +/- 1.3 mmHg) compared to the NS hearts and the control group (97 +/- 2.6 and 122 +/- 1.9 respectively), while the STH-1, UW-1 and UW-2 hearts showed an intermediate-range ventricular function (48 +/- 4; 39.9 +/- 4.1; and 69 +/- 1.8 respectively). Creatine kinase levels were higher in the STH-1 and NaCl groups (541.9 +/- 168 and 1,080.8 +/- 126.2 IU/L respectively). The energetic charge was significantly lower in the NaCl and UW-2 groups (P = 0.001) compared to the control, NS, STH-1 and UW-1 groups. CONCLUSION: It was found that the composition of the respective solutions had a major effect on the the quality of myocardial preservation. Compared to the other solutions tested in this study, the NS solution was found to be optimal for the preservation of isolated hypothermic rat hearts.

Animals↗
PubMed1999

17q21-q25 aberrations in breast cancer: combined allelotyping and CGH analysis reveals 5 regions of allelic imbalance among which two correspond to DNA amplification.

Chromosome 17q is frequently rearranged in breast cancer. Allelotyping studies have proposed the existence of at least four regions of allelic imbalance (AI). Here we present a study combining allelotyping using 19 CA repeat markers mapping in the 17q21-25 region and molecular cytogenetics (CGH and FISH). Allelotyping was undertaken on 178 pairs of cognate tumor and normal DNA in order to determine the number of regions of AI and define the shortest overlaps. AI ranged from 34-54% of the informative cases according to the marker and, overall, 66% of the tumors presented AI at one of the markers tested. Analysis of the patterns of imbalances revealed at least five common regions of imbalance respectively defined by markers: D17S855, which is intragenic of BRCA1 (SRO 1), D17S1607 (SRO 2), D17S1855 (SRO 3), between D17S789 and D17S785 (SRO 4) and D17S784 (SRO 5). In order to characterize the nature of the genetic events revealed by allelotyping we performed CGH analysis on a subset of 43 tumors presenting variable patterns of imbalance. CGH showed that AI at 17q could represent four different types of genetic events: loss of chromosome 17, gain of 17q, gain of 17q22-q24, loss of 17q11-q21 and/or 17q25-qter. Some of these anomalies could occur concomitantly within the same tumor. Since 35% of the tumors analysed by CGH presented gains, these data indicated that AI at 17q were not solely indicative of losses of genetic material and could also represent DNA amplification. Gains were most commonly observed in the 17q23-q24 regions. This suggested that AI in SRO 2 and SRO 3 corresponded to DNA amplification. To assess this, we isolated BAC clones by PCR screening for markers D17S1607 and D17S1855 and used these in FISH experiments on six breast tumor cell lines and 14 breast cancer specimens. FISH results showed that both D17S1607 and D17S1855 were frequently involved in DNA amplification (8-30 copies). Altogether, our data show that allelotyping can be efficiently used in amplicon mapping. Clinico-pathological correlations indicated that imbalance at 17q preferentially occurred in high grade, PR- and ERBB2 amplified tumors.

Adult↗
PubMed1999

Body-mass index and mortality in a prospective cohort of U.S. adults.

BACKGROUND: Body-mass index (the weight in kilograms divided by the square of the height in meters) is known to be associated with overall mortality. We investigated the effects of age, race, sex, smoking status, and history of disease on the relation between body-mass index and mortality. METHODS: In a prospective study of more than 1 million adults in the United States (457,785 men and 588,369 women), 201,622 deaths occurred during 14 years of follow-up. We examined the relation between body-mass index and the risk of death from all causes in four subgroups categorized according to smoking status and history of disease. In healthy people who had never smoked, we further examined whether the relation varied according to race, cause of death, or age. The relative risk was used to assess the relation between mortality and body-mass index. RESULTS: The association between body-mass index and the risk of death was substantially modified by smoking status and the presence of disease. In healthy people who had never smoked, the nadir of the curve for body-mass index and mortality was found at a body-mass index of 23.5 to 24.9 in men and 22.0 to 23.4 in women. Among subjects with the highest body-mass indexes, white men and women had a relative risk of death of 2.58 and 2.00, respectively, as compared with those with a body-mass index of 23.5 to 24.9. Black men and women with the highest body-mass indexes had much lower risks of death (1.35 and 1.21), which did not differ significantly from 1.00. A high body-mass index was most predictive of death from cardiovascular disease, especially in men (relative risk, 2.90; 95 percent confidence interval, 2.37 to 3.56). Heavier men and women in all age groups had an increased risk of death. CONCLUSIONS: The risk of death from all causes, cardiovascular disease, cancer, or other diseases increases throughout the range of moderate and severe overweight for both men and women in all age groups. The risk associated with a high body-mass index is greater for whites than for blacks.

Adult↗
PubMed1999

Loss of expression of the candidate tumor suppressor gene ZAC in breast cancer cell lines and primary tumors.

Loss of chromosome 6q21-qter is the second most frequent loss of chromosomal material in sporadic breast neoplasms suggesting the presence of at least one tumor suppressor gene on 6q. We recently isolated a cDNA encoding a new zinc finger protein which we named ZAC according to its functional properties, namely induction of apoptosis and control of cell cycle progression. ZAC is expressed in normal mammary gland and maps to 6q24-q25, a recognized breast cancer hot spot on 6q. In the present report, we investigated the possible inactivation of ZAC in breast cancer cell lines and primary tumors. We detected no mutation in ZAC coding region in a panel of 45 breast tumors with allelic imbalance of 6q24-q25. However, a survey of eight breast cancer cell lines showed a deeply reduced (three cell lines) or complete loss of (five cell lines) ZAC expression. Treatment of three of these cell lines with the methylation-interfering agent 5-azacytidine induced ZAC re-expression. In addition, Northern blot and RNase protection assay analysis of ZAC expression in 23 unselected primary breast tumors showed a reduced expression in several samples. Together with its functional properties and chromosomal localization, these findings substantiate ZAC as a good candidate for the tumor suppressor gene on 6q24-q25.

Breast↗
PubMed1999

Influence of a family history of cancer within and across multiple sites on patterns of cancer mortality risk for women.

A case-control study nested within a large cohort, the American Cancer Society Cancer Prevention Study-1, was conducted to test associations between a family history of cancer and cancer mortality in women. By using logistic regression, the authors analyzed family history, as reported by 429,483 women enrolled in 1959, relative to subsequent mortality through 1972 from cancer within and across multiple sites. The associations between family history and cancer mortality were generally stronger within cancer sites than across cancer sites. Within-site associations were found for breast cancer (odds ratio (OR) = 1.9), colorectal cancer (OR = 1.6), stomach cancer (OR = 1.9), and lung cancer (OR = 1.7). Across-site associations were observed for a family history of 1) breast cancer as a risk factor for ovarian cancer mortality (OR = 1.6), 2) stomach cancer as a risk factor for ovarian cancer mortality (OR = 1.5), and 3) uterine cancer as a risk factor for pancreatic cancer mortality (OR = 1.6). A general pattern of positive associations was observed between a family history of cancer at several sites and subsequent death from pancreatic cancer. These findings support the growing body of evidence from cancer genetics suggesting that inherited cancer-susceptibility genes increase the risk for cancer at many sites and are not specific to cancer risk within a single site.

Adult↗
PubMed1999

Ultrastructural confirmation of neuronal protection by melatonin against the neurotoxin 6-hydroxydopamine cell damage.

6-Hydroxydopamine (6-OHDA) is a neurotoxin used in the induction of experimental Parkinson's disease in both animals and cultured neuronal cells. Biochemical and molecular approaches showed previously that low doses of 6-OHDA induced apoptosis in PC12 cells, while high doses of this neurotoxin induced necrosis. Melatonin has been shown to protect against the neuronal programmed cell death induced by 6-OHDA, although it was not able to prevent the massive necrotic cellular death occurring after the addition of high doses of the neurotoxin. In the present work, we demonstrate by ultrastructural analysis that although low doses of 6-OHDA induced apoptosis in PC12 cells, it also damaged the non-apoptotic cells, morphologically corresponding this damage to incipient and reversible necrotic lesions. When the doses of the neurotoxin increase, there are still apoptotic cells, although most of the cells show necrotic irreversible lesions. We also found that melatonin partially prevents the incipient necrotic lesions caused by low doses of 6-OHDA. The fact that melatonin was shown in previous work to prevent apoptosis caused by low doses of 6-OHDA, but not necrosis induced by high doses of the neurotoxin, seemed to indicate that this agent is only able to protect against apoptosis. However, our present results, melatonin preventing also the incipient necrotic neuronal lesions, suggest that this hormone may provide a general protection against cell death, suggesting that higher doses should be tried in order to prevent the necrotic cell death induced by high doses of the neurotoxin.

Animals↗
PubMed1999

High-performance liquid chromatographic method for the comparison of the photostability of five sunscreen agents.

Sunscreen agents are commonly used in cosmetic products to filter out noxious radiation in sunlight. A convenient high-performance liquid chromatographic (HPLC) method for the quantification of five sunscreens after irradiation has been selected. We used this analytical method to compare the photostability of benzophenone-3, PEG-25 PABA, octyl dimethyl PABA, 4-methylbenzylidene camphor and butyl methoxydibenzoylmethane, at levels in the range of 25-60 microM. The assay was carried out, using a C8 column with a methanol--water mobile phase. The detector was set at a wavelength of 300 nm. The assay was linear with the following limits: 0.2 microgram ml-1 for benzophenone-3, 1 microgram ml-1 for PEG-25 PABA, 0.15 microgram ml-1 for octyl dimethyl PABA, 0.1 microgram ml-1 for methylbenzylidene camphor and 0.05 microgram ml-1 for butyl methoxydibenzoylmethane. The half-lives calculated indicate a very good photostability of the sunscreens studied and permit to classify amongst themselves.

4-Aminobenzoic Acid↗
PubMed1999

Factors related to quality of ambulatory blood pressure monitoring in a pediatric population.

To assess the factors related to the quality of ambulatory blood pressure monitoring in a pediatric population, we performed 24-h ambulatory blood pressure monitorings on 333 unselected children aged 3 to 18 years using a Spacelabs 90207 monitor. For each individual, the percentages of valid measurements (ratio between valid and total number of measurements, 76.4% +/-15.6%) and of successful measurements (percentage of valid preset measurements, 89.8% +/- 11.5%) were calculated. Two hundred eighty-one (84.1%) monitorings had a successful measurement rate of >80%. Two hundred thirteen (64%) were of excellent quality, as defined by the percentage of successful measurements being higher than or equal to 90%. Age (P < .0001) and 24-h systolic blood pressure (P < .04) were positively and independently associated (in multiple regression analysis) to the percentage of successful measurements, accounting for 8% of the variance. Furthermore, a significant negative correlation between causal pulse pressure and the number of erroneous measurements was observed (r = -0.18, P < .01). This study has shown that in a pediatric population, the quality of the monitoring depends only in part on age and ambulatory systolic blood pressure values when an oscillometric device is used. The results have demonstrated the important role pulse pressure amplitude plays when accounting for the number of erroneous measurements.

Adolescent↗
PubMed1999

Pharmacokinetics and bioequivalence of two suxibuzone oral dosage forms in horses.

A disposition and bioequivalence study with a suxibuzone granulated and a suxibuzone paste oral formulation was performed in horses. Suxibuzone (SBZ) is a nonsteroidal anti-inflammatory drug, which was administered to horses (n = 6) at a dosage of 19 mg/kg bwt by the oral route (p.o.) in a two period cross-over design. Suxibuzone is very rapidly transformed into its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ). Therefore plasma and synovial fluid concentrations of SBZ, PBZ and OPBZ were simultaneously measured by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Suxibuzone could not be detected in any plasma and synovial fluid samples (< 0.04 microgram/mL). Plasma PBZ and OPBZ concentrations were detected between 30 min and 72 h after granulate and paste administration. Mean plasma concentration of PBZ peaked at 5 h (34.5 +/- 6.7 micrograms/mL) and at 7 h (38.8 +/- 8.4 micrograms/mL), and mean area under the concentration-time curve (AUC0-->LOQ) was 608.0 +/- 162.2 micrograms.h/mL and 656.6 +/- 149.7 micrograms.h/mL after granulate and paste administration, respectively. Mean plasma concentration of OPBZ increased to 5-6.7 micrograms/mL, with the maximum concentration (Cmax) appearing between 9 and 12 h after administration of both formulations. The AUCs0-->LOQ for OPBZ were also similar (141.8 +/- 48.3 micrograms.h/mL granulate vs. 171.4 +/- 45.0 micrograms.h/mL paste). It was concluded that the suxibuzone products were bioequivalent with respect to PBZ. For OPBZ, the 95% confidence intervals of the pharmacokinetic parameters were within the acceptable range of 80-125%. The paste formulation provided greater bioavailability of PBZ and OPBZ.

Administration, Oral↗
PubMed1999

Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus.

We have previouslyreported that low doses of melatonin inhibit apoptosis in both dexamethasone-treated cultured thymocytes (standard model for the study of apoptosis) and the intact thymus. Here we elucidate the mechanism by which this agent protects thymocytes from cell death induced by glucocorticoids. Our results demonstrate an effect of melatonin on the mRNA for antioxidant enzymes in thymocytes, also showing an unexpected regulation by dexamethasone of these mRNA. Both an effect of melatonin on the general machinery of apoptosis and a possible regulation of the expression of the cell death related genes bcl-2 and p53 are shown not to be involved. We found melatonin to down-regulate the mRNA for the glucocorticoid receptor in thymocytes (glucocorticoids up-regulate their own receptor). The decrease by melatonin of mRNA levels for this receptor in IM-9 cells (where glucocorticoids down-regulate it) demonstrates that melatonin actually down-regulates glucocorticoid receptor. These findings allow us to propose the effects of melatonin on this receptor as the likely mediator of its thymocyte protection against dexamethasone-induced cell death. This effect of melatonin, given the oxidant properties of glucocorticoids, adds another mechanism to explain its antioxidant effects.

Animals↗
PubMed1999

Disposition and tolerance of suxibuzone in horses.

Suxibuzone (SBZ), a nonsteroidal anti-inflammatory drug, was administered to 6 horses at a dose rate of 7.5 mg/kg bwt by intravenous (i.v.) route. Plasma and synovial fluid concentrations of suxibuzone and its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ), were measured simultaneously by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Plasma SBZ concentrations rapidly decreased and were not detectable beyond 20 min after treatment. The parent drug was not detected in any synovial fluid samples. Average maximum plasma concentrations of PBZ (16.43 microg/ml) and OPBZ (2.37 microg/ml) were attained at 0.76 and 7.17 h, respectively. The mean residence time (MRT) of PBZ was 6.96 h in plasma. Oxyphenbutazone plasma concentrations were below those reached by phenylbutazone during the first 12 h after suxibuzone administration, even though its values were detectable for at least 24 h (MRT = 10.65 h). Plasma concentrations of PBZ and OPBZ exceeding EC50 and IC50 of TXB2 and PGE2 were reached by at least 12 h. Synovial fluid concentrations of PBZ and OPBZ were 2.87+/-0.37 microg/ml and 0.97+/-0.08 microg/ml at 9 h after suxibuzone administration and exceeded IC50 of PGE2 for at least this time. In the present study, suxibuzone was well tolerated following i.v. injection.

Animals↗
PubMed1999

Association between educational level and health related quality of life in Spanish adults.

OBJECTIVE: To analyse differences in health by educational level in Spanish adults by comparing the health dimensions of the SF-36 Heath Survey. DESIGN: Data were taken from the National Survey on Drug Use carried out in February 1996. The information was collected by home personal interview. In addition to measuring the use of legal and illegal drugs and their associated health risks, the health status of the Spanish population was analysed using the Spanish version of the SF-36 Health Survey. MAIN OUTCOME MEASURE: Absolute and standardised differences between mean score on each dimension of the SF-36 Health Survey in each educational group with respect to the group with the highest educational level. RESULTS: Perceived health status declines with decreasing educational level, except in women with second level education who have a higher mean rating than women with third level education on various health dimensions. The absolute differences in perceived health between the different categories of educational level and the reference category become larger with increasing age. The greatest differences by educational level in both men and women were found in mental health and general health among persons 25 to 44 years of age, and in physical function and general health among those 45 to 64 years. In persons aged 65 or older, the greatest differences are seen in physical function and vitality in men, and in bodily pain and emotional role in women. CONCLUSIONS: The influence of educational level on the different dimensions of perceived health may vary by sex.

Adolescent↗
PubMed1999

The magnitude of differences in perceived general health associated with educational level in the regions of Spain.

STUDY OBJECTIVE: To examine and compare the relation between inequalities in perceived general health and education in the 17 regions of Spain. DESIGN AND METHODS: Data were taken from the 1993 Spanish Health Interview Survey. For each region we calculated the magnitude of inequality in perceived general health in association with educational level by a measure of association or effect and by a relative index of inequality. Both measures are odds ratios and were estimated by logistic regression. The first is an odds ratio associated with one year less education, while the second represents the inequality in perceived general health between those at the bottom and those at the top of the educational hierarchy. MAIN RESULTS: The six regions with the highest relative indices of inequality also have the highest odds ratios associated with one year less education, and five of the six regions with the lowest relative indices of inequality have the lowest odds ratios associated with one year less education. Pearson's correlation coefficient between the odds ratio and the relative index of inequality is 0.94. CONCLUSIONS: Regional differences in levels of inequality in perceived general health are attributable exclusively to the effect of education on health and not to the distribution of the population among the different educational levels. It is not known why the magnitude of this effect of education on health varies from one area to another.

Adolescent↗