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Biomedical subjects

M Garcia

Publications and source records attributed to M Garcia.

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

Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview.

A short review of the literature first confirms the clinical value of cathepsin D as a prognostic marker in breast cancer, when using well standardized assays. We then summarize results of studies, mostly performed in our laboratory, aimed at understanding the effect of cathepsin D overexpression on metastasis and the molecular mechanisms involved. Cathepsin D-cDNA transfection increases tumor cell proliferation in vitro and the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when injected in vivo into nude mice. The mechanism by which cathepsin D increases the incidence of clinical metastasis involves increased cell growth and decreased contact inhibition rather than escape of cancer cells through the basement membrane. Different mechanisms are considered to explain this mitogenic activity. Cathepsin D could act as a protease following its activation at an acidic pH, or as a ligand of different membrane receptors at a more neutral pH. In this case cathepsin D can displace IGFII from the mannose-6-phosphate/IGFII receptor to the IGFI receptor or activate another membrane receptor to be identified. The nature of the mechanisms involved in vivo may depend on the micro environment of the tumor cells. These studies should guide in the development of new therapies aimed at inhibiting the deleterious effect of overexpressed cathepsin D.

Animals↗
PubMed2000

Protection against diverse highly pathogenic H5 avian influenza viruses in chickens immunized with a recombinant fowlpox vaccine containing an H5 avian influenza hemagglutinin gene insert.

A recombinant fowlpox vaccine with an H5 hemagglutinin gene insert protected chickens against clinical signs and death following challenge by nine different highly pathogenic H5 avian influenza viruses. The challenge viruses had 87.3 to 100% deduced hemagglutinin amino acid sequence similarity with the recombinant vaccine, and represented diversely geographic and spatial backgrounds; i.e. isolated from four different continents over a 38 year period. The recombinant vaccine reduced detectable infection rates and shedding titers by some challenge viruses. There was a significant positive correlation in hemagglutinin sequence similarity between challenge viruses and vaccine, and the ability to reduce titers of challenge virus isolated from the oropharynx (r(s)=0.783, P=0.009), but there was no similar correlation for reducing cloacal virus titers (r(s)=-0.100, P=0.78). This recombinant fowlpox-H5 avian influenza hemagglutinin vaccine can provide protection against a variety of different highly pathogenic H5 avian influenza viruses and frequent optimizing of the hemagglutinin insert to overcome genetic drift in the vaccine may not be necessary to provide adequate field protection.

Animals↗
PubMed2000

Insulin-like growth factor-I reverts testicular atrophy in rats with advanced cirrhosis.

The pathogenesis of hypogonadism in cirrhosis is not completely understood. The levels of insulin-like growth factor-I (IGF-I), an anabolic factor with trophic actions on testes, are reduced in cirrhosis. This study was undertaken to evaluate whether rats with advanced cirrhosis develop hypogonadism and whether the administration of IGF-I exerts beneficial effects on testicular structure and function. Wistar rats with ascitic cirrhosis induced with CCl(4) were allocated into 2 groups (n = 10, each) to receive recombinant IGF-I (20 microg x kg(-1) x d(-1), subcutaneously) or vehicle for 3 weeks. Healthy rats receiving vehicle were used as the control group (n = 10). At baseline, both cirrhotic groups showed similar deterioration of liver function tests. Compared with controls, nontreated cirrhotic rats showed decreased serum levels of IGF-I (P <.05), reduced testicular size and weight (P <.001), and intense histopathological testicular abnormalities, including reduced tubular diameters (P <.001), loss of the germinal line (P <. 001), and diminutions in cellular proliferation, spermatogenesis (P <.001), and testicular transferrin expression (P <.001). In addition, low serum testosterone (P <.01) and high serum LH (P <.01) were present in untreated cirrhotic animals. Cirrhotic rats that received IGF-I showed full recovery of testicular size and weight and of all histopathological abnormalities (P <.001 to <.01 vs. nontreated cirrhotic rats; P = ns vs. controls). Serum levels of sex hormones tended to normalize. In conclusion, IGF-I deficiency may play a pathogenetic role in hypogonadism of cirrhosis. Low doses of IGF-I for a short period of time revert testicular atrophy and appear to improve hypogonadism in advanced experimental cirrhosis.

Animals↗
PubMed2000

Nutritional condition affects the hepatic antioxidant systems in steers.

The objectives of this study were to evaluate the activity of antioxidant systems in the hepatic tissues of steers experimentally subjected to a restricted diet. Hence, the activities of superoxide dismutase (SOD) and reduced glutathione (GSH) and lipid peroxide levels were measured. Nine male Holstein steers were used. They were separated in two groups: three steers in group 1 (control) and six steers in group 2, which were subjected to a restricted diet that covered only 60% of the maintenance requirements. After 30 days, the animals in both groups were killed and studies were completed. Both the CuZn-SOD and the glucose-6-phosphate dehydrogenase activities were significantly decreased (p < 0.05) in group 2, reaching 68% and 60%, respectively, of the concentrations found in group 1. The concentration of GSH in group 2 was 6.71+/-0.9 nmol/mg protein, which was significantly lower (p < 0.01) than that of the controls, 25.7+/-2.4 nmol/mg protein. In addition, the lipid peroxide levels were significantly increased (p < 0.01) in group 2, being 50-60% higher than that in group 1. These results showed that the poor nutritional status caused modifications to the enzymatic antioxidant systems, with a lower ability to reduce oxidative compounds and a state of lipid peroxidation.

Animal Feed↗
PubMed2000

Regulation of somatotroph cell function by the adipose tissue.

Obese subjects exhibit a marked decrease in plasma growth hormone (GH) levels. However, the mechanisms by which increased adiposity leads to an impairment of GH secretion are poorly understood. Recent evidence suggests that the adipose tissue can markedly influence GH secretion via two different signals, namely free fatty acids (FFA) and leptin. FFA appear to inhibit GH secretion mainly by acting directly at pituitary level. Interestingly, reduction in circulating FFA levels in obese subjects led to a marked increase in GH responses to different GH secretagogues. This indicates that FFA exert a tonic inhibitory effect that contributes to blunted GH secretion in obese subjects. Recent data have shown that leptin is a metabolic signal that regulates GH secretion, since the administration of leptin antiserum to adult rats led to a marked decrease in spontaneous GH secretion. However, leptin prevents,the inhibitory effect exerted by fasting on plasma GH levels. The effect of leptin in adult rats appears to be exerted at hypothalamic level by regulating growth hormone releasing hormone (GHRH), somatostatin and neuropeptide Y (NPY)-producing neurones. In addition, during fetal life or following the development of pituitary tumors, leptin can also act directly at the anterior pituitary.

Adipose Tissue↗
PubMed2000

Effects of ionizing radiation on oocytes of prepubertally irradiated rats.

PURPOSE: To characterize the effects of ionizing radiation on the immature oocytes of prepubertal rats aged 16-20 days old. MATERIALS AND METHODS: The abdomen of Sprague Dawley (SD) female rats was exposed to 0, 1 and 2 Gy of X-rays. The effects were analysed when the animals became adults (80 days old) using as parameters the number of implantation sites, embryonic loss, dominant lethality and the synaptonemal complex (SC) analysis of F1 female foetuses. RESULTS: A statistically significant decrease in the fertility of the 2 Gy irradiated rats was observed. However, the SC analysis of F1 female foetuses showed no cytogenetic damage that could be attributed to radiation. CONCLUSIONS: A reproductive effect was demonstrated but no inherited genetic damage was detected by SC analysis in female foetuses of irradiated mothers.

Animals↗
PubMed2000

Validation of the Minnesota Leisure Time Physical Activity Questionnaire In Spanish Women. Investigators of the MARATDON Group.

PURPOSE: Regular physical activity (PA) is associated with lower risk for several chronic diseases. It is important to validate PA measurement instruments in different populations. The objective was to validate the Minnesota leisure time PA questionnaire among Spanish women. METHODS: A cross-sectional study with quota sampling was designed. Two PA groups (active, expending less than 301 MET-min x d(-1) in PA, and very active, expending more than 300 MET-min x d(-1)) and two age groups (18-40 and 41-60 yr) were defined. The Minnesota questionnaire was administered to obtain total energy expenditure in leisure time PA (EEPAtotal) and classified according to the intensity of the different types of PA (EEPAheavy, EEPAmoderate, and EEPAlight). The 250 women recruited performed an exercise test to assess fitness. RESULTS: Spearman correlation coefficients among EEPAtotal, EEPAheavy, EEPAmoderate, EEPAlight, and fitness were 0.39, 0.51, 0.13, and 0.02, respectively. Multiple linear regression model adjusted by the different EEPAs and age accounted for 46% of fitness variability. Besides age, only EEPAmoderate and EEPAheavy were associated with fitness. CONCLUSION: The Spanish version of the Minnesota questionnaire is a valid instrument for measuring leisure time PA performed in the last year in Spanish women aged 18-60 yr. Moderate and heavy physical activity are adequately assessed whereas light physical activity practice assessment may be questionable.

Adolescent↗
PubMed2000

Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I.

The intestine is an important target organ for insulin-like growth factor-I (IGF-I), an anabolic hormone synthesized in the liver upon growth hormone (GH) stimulation. Levels of IGF-I are reduced in cirrhosis, and altered GH/IGF-I axis may contribute to malnutrition in cirrhotic patients. Our aim was to study Na(+)-dependent jejunal transport of amino acids (L-leucine, L-proline, L-glutamic acid, and L-cysteine) in cirrhotic rats and to analyze the effect of IGF-I on this function. IGF-I or saline was administered for 2 wk to rats with CCl(4)-induced cirrhosis and saline was administered to healthy control rats. Transport of amino acids was assessed in brush-border membrane vesicles (BBMV) using (14)C- or (35)S-labeled amino acids, and the kinetic constants V(max) and K(t) were determined. Na(+)-independent uptake of L-leucine, L-proline, L-glutamic acid, and L-cysteine by BBMV was similar in all groups. Na(+)-dependent uptake of all four amino acids was significantly diminished in cirrhotic rats compared with both controls and IGF-I-treated cirrhotic rats. The latter two groups exhibited similar V(max) and K(t), whereas untreated cirrhotic rats had reduced V(max) and increased K(t) compared with normal controls and IGF-I-treated cirrhotic animals. In conclusion, the transport of all four tested amino acids by BBMV is impaired in cirrhotic rats, and low doses of IGF-I can correct this defect.

Amino Acids↗
PubMed2000

Unliganded and liganded estrogen receptors protect against cancer invasion via different mechanisms.

While estrogens are mitogenic in breast cancer cells, the presence of estrogen receptor a (ERalpha) clinically indicates a favorable prognosis in breast carcinoma. To improve our understanding of ERalpha action in breast cancer, we used an original in vitro method, which combines transient transfection and Matrigel invasion assays to examine its effects on cell invasiveness. ERalpha expression in MDA-MB-231 breast cancer cells reduced their invasiveness by 3-fold in the absence of hormone and by 7-fold in its presence. Integrity of hormone and DNA-binding domains and activating function 2 were required for estradiol-induced inhibition, suggesting that transcriptional activation of estrogen target genes was involved. In contrast, these domains were dispensable for hormone-independent inhibition. Analysis of deletion mutants of ERalpha indicated that amino acids 179-215, containing the N-terminal zinc finger of the DNA-binding domain, were required for ligand-independent receptor action. Among different members of the nuclear receptor family, only unliganded ERalpha and ERbeta reduced invasion. Calreticulin, a Ca2+-binding protein that could interact with amino acids 206-211 of ERalpha, reversed hormone-independent ERalpha inhibition of invasion. However, since calreticulin alone also inhibited invasion, we propose that this protein probably prevents ERalpha interaction with another unidentified invasion-regulating factor. The inhibitor role of the unliganded ER was also suggested in three ERalpha-positive cell lines, where ERalpha content was inversely correlated with cell migration. We conclude that ERalpha protects against cancer invasion in its unliganded form, probably by protein-protein interactions with the N-terminal zinc finger region, and after hormone binding by activation of specific gene transcription.

Amino Acid Sequence↗
PubMed2000

Entanglement of guide wires by vena cava filters during central venous catheter insertion: report of three cases and a review of the literature.

Since 1993, 14 cases of central line guide wires becoming entangled with vena cava filters have been reported. We present three additional cases and review the 14 cases in the literature. Obtaining a detailed patient history is important in identifying patients with a vena cava filter. A low threshold of suspicion is needed and immediate radiograph obtained. Entangled guide wires required fluoroscopic manipulation and or retrieval of the dislodged filter. Of all reported cases, only one sustained an arrhythmia. With no signs and symptoms, conservative management of the dislodged filter is a viable option.

Adult↗
PubMed2000

[Use of echocardiography in the diagnosis of carcinoid tumors. Report of 4 cases].

Carcinoid tumours are the most common neuro-endocrine tumours but cardiac involvement is rarely symptomatic although often observed at post-mortem and rarely revelatory of the disease. The authors report 4 cases in which echocardiographic detection of characteristic right ventricular involvement led to the confirmation of the diagnosis of carcinoid tumour leading to the secondary diagnosis of the primary carcinoid tumour. The clinical, physiopathological echocardiographic and therapeutic characteristics of this condition are discussed.

Aged↗
PubMed2000

HER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer, and ovarian cancer.

HER-2/neu is overexpressed in most epithelial malignancies. Lung cancer, prostate cancer, and ovarian cancer are common epithelial tumors in which clinical trials are currently in progress to explore the potential therapeutic role for monoclonal antibodies to HER-2/neu (trastuzumab [Herceptin; Genentech, Inc, South San Francisco, CA]). In preclinical studies with tumor cell lines, trastuzumab was found to have additive and synergistic effects with some chemotherapeutic agents. Clinical trials investigating combination chemotherapy with trastuzumab and a variety of chemotherapeutic agents are already in progress in lung cancer.

Animals↗
PubMed1999

An autosomal genomic screen for autism. Collaborative linkage study of autism.

Autism is a severe neurodevelopmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood. The etiology of idiopathic autism is strongly genetic, and oligogenic transmission is likely. The first stage of a two-stage genomic screen for autism was carried out by the Collaborative Linkage Study of Autism on individuals affected with autism from 75 families ascertained through an affected sib-pair. The strongest multipoint results were for regions on chromosomes 13 and 7. The highest maximum multipoint heterogeneity LOD (MMLS/het) score is 3.0 at D13S800 (approximately 55 cM from the telomere) under the recessive model, with an estimated 35% of families linked to this locus. The next highest peak is an MMLS/het score of 2.3 at 19 cM, between D13S217 and D13S1229. Our third highest MMLS/het score of 2.2 is on chromosome 7 and is consistent with the International Molecular Genetic Study of Autism Consortium report of a possible susceptibility locus somewhere within 7q31-33. These regions and others will be followed up in the second stage of our study by typing additional markers in both the original and a second set of identically ascertained autism families, which are currently being collected. By comparing results across a number of studies, we expect to be able to narrow our search for autism susceptibility genes to a small number of genomic regions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:609-615, 1999.

Adolescent↗
PubMed1999

A randomized study comparing instruments for measuring health-related quality of life in HIV-infected patients. Spanish MOS-HIV and MQOL-HIV Validation Group. Medical Outcomes Study HIV Health Survey.

OBJECTIVE: To compare the feasibility, reliability, validity and sensitivity to change of the MOS-HIV and MQOL-HIV in order to determine their suitability for use in clinical research. METHODS: Five hundred and fifty-eight HIV-infected patients and 80 healthy blood donors were randomly assigned to receive the MOS-HIV or MQOL-HIV. Test-retest reliability was assessed in 98 clinically stable patients, and responsiveness in 296 patients initiating or switching anti-retroviral treatment. Feasibility was assessed using mean time of administration and percentage of missing responses. Reliability was assessed using Cronbach's alpha and the intraclass correlation coefficient (ICC). Construct validity was assessed by correlating questionnaire scores with EuroQol-5D scores, number of symptoms, CD4 cell count and viral load. The area under the curve (AUC) was used for discrimination between patients and healthy donors, and HRQoL scores were compared across disease stage. Responsiveness was assessed by calculating the standardized effect size (SES). RESULTS: Mean administration time was 16 minutes for both questionnaires. On the MOS-HIV 18.9% patients had missing responses compared with 33.6% on the MQOL-HIV. Cronbach's alpha values were higher for MOS-HIV sub-scales (0.78-0.89) than MQOL-HIV sub-scales (0.44-0.82), and neither instrument showed good test-retest reliability (ICC values of 0.24-0.85 for MOS-HIV versus 0.48-0.82 for MQOL-HIV). AUC values for the MOS-HIV were 0.6-0.86, compared with 0.5-0.79 for the MQOL-HIV, and the MOS-HIV had higher correlations with symptoms (r = -0.28 to 0.79) and EuroQol scores (r = 0.4-0.66) than the MQOL-HIV (r = -0.15 to 0.42 and r = -0.11 to 0.59, respectively). Neither instrument discriminated well between disease stages. Eight of 11 MOS-HIV sub-scales and the Mental Health Summary Score were responsive to change (SES, 0.18-0.36), compared with six of 10 MQOL-HIV sub-scales and MQOL Index (SES, 0.16-0.27). CONCLUSIONS: Neither instrument demonstrated completely satisfactory psychometric properties for use in clinical research, although the MOS-HIV performed slightly better on feasibility and validity and the MQOL-HIV on test-retest reliability.

Adolescent↗
PubMed1999

Baculovirus-derived hemagglutinin vaccines protect against lethal influenza infections by avian H5 and H7 subtypes.

Baculoviruses were engineered to express hemagglutinin (HA) genes of recent avian influenza (AI) isolates of the H5 and H7 subtypes. The proteins were expressed as either intact (H7) or slightly truncated versions (H5). In both cases purified HA proteins from insect cell cultures retained hemagglutination activity and formed rosettes in solution, indicating proper folding. Although immunogenic in this form, these proteins were more effective when administered subcutaneously in a water-in-oil emulsion. One or two-day-old specific pathogen free (SPF) White Rock chickens, free of maternal AI antibodies, responded with variable serum HI titers, but in some cases the titers were comparable to those achieved using whole virus preparations. Vaccination of three-week-old chickens with 1.0 microg of protein per bird generated a more consistent serum antibody response with an average geometric mean titer (GMT) of 121 (H5) and 293 (H7) at 21 days postvaccination. When challenged with highly pathogenic strains of the corresponding AI subtypes, the vaccinated birds were completely protected against lethal infection and in some cases exhibited reduced or no cloacal shedding at 3 days postinfection. Vaccine protocols employing these recombinant HA proteins will not elicit an immune response against internal AI proteins and thus will not interfere with epidemiological surveys of natural influenza infections in the field.

Amino Acid Sequence↗
PubMed1999

Development of a database management/analysis system for field research activities within a coordinated research project.

There are several ways a database/analysis system can assist a scientist engaged in field research. Specifically, it can assist the scientist with accurate data collection and more rigorous data analyses. The database management portion of this system allows accurate data collection and provides easy data entry through the use of forms. In addition, it can provide the scientist with structured methods of error checking data entry and checking for implausible values and false zeros. The system can also assist the scientist with the organization of the data and provide easy methods of sorting, grouping, and selecting data for analysis. Data can then be exported to a data analysis program where the first step is data validation. A menu of analyses using examples from the coordinated research project (CRP) are demonstrated using statistical methods that test continuous and categorical data.

Analysis of Variance↗