Search PubMed⌕ Search

Biomedical subjects

C Perez

Publications and source records attributed to C Perez.

At least 91 records · Page 5Linked to original sources
PubMed1997

Carboxymethylethanolamine, a biomarker of phospholipid modification during the maillard reaction in vivo.

Nepsilon-(Carboxymethyl)lysine (CML) is a stable chemical modification of proteins formed from both carbohydrates and lipids during autoxidation reactions. We hypothesized that carboxymethyl lipids such as (carboxymethyl)phosphatidylethanolamine (carboxymethyl-PE) would also be formed in these reactions, and we therefore developed a gas chromatography-mass spectrometry assay for quantification of carboxymethylethanolamine (CME) following hydrolysis of phospholipids. In vitro, CME was formed during glycation of dioleoyl-PE under air and from linoleoylpalmitoyl-PE, but not from dioleoyl-PE, in the absence of glucose. In vivo, CME was detected in lipid extracts of red blood cell membranes, approximately 0.14 mmol of CME/mol of ethanolamine, from control and diabetic subjects, (n = 22, p >> 0.5). Levels of CML in erythrocyte membrane proteins were approximately 0.2 mmol/mol of lysine for both control and diabetic subjects (p >> 0.5). For this group of diabetic subjects there was no indication of increased oxidative modification of either lipid or protein components of red cell membranes. CME was also detected in fasting urine at 2-3 nmol/mg of creatinine in control and diabetic subjects (p = 0.085). CME inhibited detection of advanced glycation end product (AGE)-modified protein in a competitive enzyme-linked immunosorbent assay using an anti-AGE antibody previously shown to recognize CML, suggesting that carboxymethyl-PE may be a component of AGE lipids detected in AGE low density lipoprotein. Measurement of levels of CME in blood, tissues, and urine should be useful for assessing oxidative damage to membrane lipids during aging and in disease.

Adult↗
PubMed1997

Preparation and anti-HIV activity of N-3-substituted thymidine nucleoside analogs.

A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045-0.082 microM range. The analogs 12d, 12e, 12q, 15, and 19 were active at <0.5 microM concentration. Compound 18 in which two molecules of AZT are connected at N-3 via a two-carbon link and "dimer" 11 also displayed significant activity. To obtain information concerning the mechanism of RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT(12-18)] and poly(C)-oligo[dG(12-18)] template-primers. In contrast to AZT-TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequisite for activity.

Anti-HIV Agents↗
PubMed1997

Antifungal activity of plant extracts against Candida albicans.

In previous papers, we reported the antimicrobial activity of plants used in Argentine folk medicine against different micro-organisms. The present study deals with the screening of 11 of these plants against the opportunistic pathogen fungus Candida albicans. Aqueous extracts 6% p/v (6 mg dry plant per 100 ml of water) were checked against fungus cultures by the agar-well diffusion method. Five extracts showed antifungal activity.

Candida albicans↗
PubMed1997

Use of bronchoalveolar lavage semiquantitative cultures in cystic fibrosis.

To assess bronchoalveolar lavage (BAL) in adult CF patients with respiratory symptoms, we studied BAL fluid (BALF) culture results from 28 bronchoscopies in 11 patients. Patients were asked to provide sputum for culture. All but two patients were receiving antibiotics at the time of bronchoscopy, with 13 bronchoscopies done on patients who had been receiving antibiotics for more than 10 d. Gram stain of the BALF was positive in 18 cases. In all but one BALF, > 10,000 colony-forming units per milliliter (cfu/ml) BALF of one or more pathogens was identified. The final case grew Burkholderia cepacia, which was not grown in the sputum. In only six cases (21%) were the sputum and BALF culture results the same. Prior to 11 bronchoscopies, the sputum was not adequate. The remaining 11 cases either had different pathogens in the BAL (six cases), or had some but not all of the BALF pathogens in the sputum. BALF cultures changed therapy in 13 (48%) of cases. Semiquantitative culture of BALF was a useful diagnostic tool in CF in patients in whom empiric therapy failed.

Adult↗
PubMed1996

Involvement of heregulin-beta2 in the acquisition of the hormone-independent phenotype of breast cancer cells.

The erbB-2 receptor plays an important role in the prognosis of breast cancer. Amplification or overexpression of the erbB-2 proto-oncogene has been detected in 30% of breast cancers and is associated with poor patient prognosis. The significance of erbB-3 and erbB-4 in breast cancer is not yet known. The discovery of the growth factor heregulin (HRG) has allowed us to investigate a number of biological events that are regulated by erbB-2, -3, and -4 signal transduction. To determine the role of HRG in breast cancer tumor progression, we have developed an in vitro/in vivo model. We transfected HRG cDNA into the estrogen receptor (ER)-positive breast cancer cell line, MCF-7, and studied these cells as they progressed from a hormone-dependent to -independent phenotype. The biochemical and biological characteristics presented here demonstrate that overexpression of HRG induces morphological changes in MCF-7 cells as well as erbB-2, erbB-3, and erbB-4 autophosphorylation. MCF-7/ heregulin-transfected cells, which express relatively high levels of HRG, developed estrogen independence and resistance to antiestrogens in vitro and in vivo. This is consistent with a more aggressive hormone-independent phenotype. In contrast with control parental/wild-type cells, estradiol-mediated down-regulation of erbB-2 expression is blocked completely in this particular model system. These results indicate that HRG plays a role in the disruption of ER function. When a transient transfection with an ERE-CAT construct was introduced into these HRG-transfected MCF-7 cells, we observed that the ER was transcriptionally inactive. This suggests that ER signaling is altered in HRG-transfected cells. We observed that overexpression of HRG induces a more aggressive, hormone-independent phenotype that is most likely directly related to the constitutive activation of the erbB-2, erbB-3, and erbB-4 receptor signaling cascade. The data presented here suggest a close cross-regulation between the erbB-2/4 receptors and ER and provide new insights into the mechanism by which breast cancer cells acquire a hormone-independent phenotype.

Breast Neoplasms↗
PubMed1996

Differentiation of U-937 promonocytic cells with mitomycin C or cis-diamminedichloroplatinum II.

Administration of 0.3 microM mitomycin C (MMC) or 2.0 microM cis-diamminedichloroplatinum II (CDDP) decreased the growth activity and induced the differentiation of U-937 human promonocytic cells, as shown by nitroblue tetrazolium reduction and an increase in surface expression of the leukocyte integrins CD11b/CD18 and CD11c/CD18. Expression of these differentiation markers started to be significant at 48 hr of treatment. These concentrations resulted in little cell damage (determined by Trypan blue exclusion) and slightly induced apoptosis (determined by DNA degradation and changes in nuclear morphology). The treatments induced a transient increase in c-fos and c-jun mRNA levels, with maximum values at 1-6 hr; a transient increase in collagenase mRNA level, with a maximum value at 48 hr; and a progressive increase in vimentin and lamin A and C mRNA levels. These changes were qualitatively similar to those produced by 12-0-tetradecanoylphorbol 13-acetate. CDDP and MMC also caused a transient increase of total AP-1 binding activity, as determined by gel retardation assays. The drugs produced an early transient activation (3-6 hr) of membrane-bound protein kinase C, followed by a later activation (48 hr) of both the membrane and the cytosolic enzyme. These results suggest that protein kinase C and AP-1-dependent gene expression could be involved in myeloid cell differentiation by alkylating agents.

Antibiotics, Antineoplastic↗
PubMed1996

The significance of heregulin in breast cancer tumor progression and drug resistance.

The erbB-2 receptor plays an important role in the prognosis of breast cancer and is expressed at high levels in nearly 30% of tumors in breast cancer patients. While evidence accumulates to support the relationship between erbB-2 overexpression and poor overall survival in human breast cancer, understanding of the biological consequence(s) of erbB-2 overexpression remains elusive. The discovery of heregulin has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through the erbB-2/4 receptor. These endpoints of growth, invasiveness, and differentiation have clear implications for the emergence, maintenance, and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in human breast cancer. Preliminary studies in vitro have shown that heregulin induces a biphasic growth effect on cells with erbB-2 overexpression. Interestingly, we observed that expression of heregulin correlates with a more aggressive/invasive, vimentin-positive phenotype in breast cancer cells lines. Therefore, we have postulated that heregulin is involved in breast cancer tumor progression. We have shown that heregulin induces in vitro chemoinvasion and chemotaxis of breast cancer cells as well as growth in an anchorage dependent and independent manner. Interestingly, a heregulin neutralizing antibody inhibits chemotaxis and results in cell growth inhibition and blockade of the invasive phenotype. Strikingly, genetically engineered cells which constitutively express heregulin demonstrate critical phenotypic changes that are associated with a more aggressive phenotype. Specifically, these cells are no longer dependent on estrogen for growth and are resistant to tamoxifen in vitro and in vivo, and moreover these cells metastasize to lymph nodes in athymic nude mice. These tumors appear to have lost bcl-2 expression as compared with the control tumors. In addition, presumably by activation/regulation of topoisomerase II, the heregulin-transfected cells become exquisitely sensitive to doxorubicin and VP-16. Clearly, mechanistic aspects of the erbB-2/4 and heregulin interaction need to be understood from a therapeutic standpoint which could provide additional insights into synergistic treatments for certain patients, or improve treatment regimens for a large number of women. The study of heregulin and its co-expression with erbB-2/4 receptor and the assessment of its involvement in the progression from the in situ stage of breast tumors to the invasive one will additionally increase the relevance of heregulin as a prognostic/diagnostic factor. We believe that our studies provide new insights into breast cancer diagnosis, prognosis, and treatment.

Breast Neoplasms↗
PubMed1996

Meconium obstruction in markedly premature infant.

Markedly premature infants may present with intestinal obstruction and perforation secondary to inspissated meconium in the absence of cystic fibrosis. Between 1990 and 1994, 13 patients were treated for intestinal obstruction secondary to inspissated meconium. The average birth weight was 760 g. Prenatal and postnatal risk factors were identified, and included intrauterine growth retardation, maternal hypertension, prolonged administration of tocolytics, patent ductus arteriosus, hyaline membrane disease, and intraventricular hemorrhage. Stooling was absent or infrequent during the first 2 weeks of life. Surgical presentation consisted of distension and/or perforation between days 2 and 17 of life. Twelve patients required operative intervention. Findings invariably included one or more obstructing meconium plugs with proximal distension and frequent necrosis of the dilated segments. Surgical options consisted of resection or enterotomy, accompanied by primary closure or by distal irrigation and exteriorization. Irrigation led to iatrogenic bowel injury in two patients. One patient was managed successfully with oral and rectal gastrograffin and oral acetylcysteine. Ten patients were discharged, all of whom had normal stooling patterns and tested negatively for cystic fibrosis. Three patients died, two from the primary disease. The markedly premature infant is at risk for obstruction and eventual perforation secondary to meconium plugs, presumably formed in conjunction with intestinal dysmotility. Prompt diagnosis and timely intervention require a high index of suspicion, attention to stooling patterns and abdominal examinations, and screening radiographs when indicated.

California↗
PubMed1996

Minority use of community long-term care services: a comparative analysis.

A series of national surveys since 1982 have examined health needs of elders. Small proportions of minority elders in each sample have limited our understanding of service use by minorities. This research sought to determine (1) the extent to which minorities have restricted use of community long-term care services as a result of socioeconomic status, family structure, and health status, and (2) the replicability and validity of results across three national surveys: Supplement on Aging, National Long-Term Care, and National Medical Expenditure. Results indicate no bivariate or multivariate differences between African American, Hispanic, or White frail older persons in use of community long-term services. Living arrangements, Medicaid use, and overall health and functional status were primary predictors of service use. Taking methodological limitations into account, the results suggest similarity in processes influencing use of community long-term care services for African American and White older persons.

Black or African American↗
PubMed1996

The novel use of Rh(I) complexes with naphthyridine ligands and poly(oxyethylene) as antitumorals.

Rh(I) complexes adsorbed on polymers, as a way to improve their transport and solubility properties, were studied as antitumor agents. The binding constants of the complexes to the polymer were evaluated in order to determine the conditions for maximum association to the vehicle. The toxicity of the pure complexes and those bound were determined in vivo using female mice. [Rh(NBD)(2,4N)]CIO4, complex A; where NBD = norbornadiene, (2,4N) = 3,3'-dimethylene-2,2'-di-1,8-naphthyridine, was investigated on primary solid tumors and ascitic tumors. [Rh(NBD)(3,4N)]CIO4, complex B; where (3,4N) = 3,3'-trimethylene-2,2'-di-1,8-naphthyridine, was investigated on ascitic tumors. These Rh(I) complexes appear to be promising drugs because of their solubility in aqueous polymer, which make them easier to handle in comparison with the neutral species. These complexes show a similarity to cisplatin by reducing tumor growth and by increasing the survival life span of mice. Poly (oxyethylene) was used to solubilize these poorly water-soluble compounds and to stabilize the compounds in the solution before injection. These studies suggest that both complexes, A and B, are good candidates for tumor control growth and increase the survival time.

Animals↗
PubMed1996

Comparative evaluation of blood culture using the Vital automated system and the Becton-Dickinson Septi-Chek BHI-S biphasic and Sch bottles.

A comparative study was performed using 1,168 aerobic and anaerobic blood culture pairs from 395 patients, during which 5-10 mL of blood were collected in both Septi-Chek BHI-S biphasic and Septi-Chek Sch bottles (Becton-Dickinson, Meylan, France) and Vital AER and Vital Ana bottles (bioMérieux, Marcy-l'Etoile, France). The bottles were analyzed by using a 7-day protocol for Vital and a 12-day protocol for Septi-Chek. The Vital bottles revealed negative were all subcultured at the end of the protocol. Of the 374 positive Septi-Chek bottles, only 202 bottles gave a positive subculture. Of the 245 positive Vital bottles, 223 bottles led to the isolation of a microorganism. Thirty-five septic episodes were detected by Septi-Chek compared to 38 by the Vital system (only clinically significant isolates were taken into consideration). Four septic episodes were detected by Vital only (one episode implicating coagulase-negative Staphylococcus, one Streptococcus pneumoniae, one Pseudomonas aeruginosa and one Candida albicans, involving a total of 15 bottles). One septic episode implicating Bacteroides fragilis was detected by Septi-Chek only (five bottles). Among the negative Vital bottles, only six bottles gave a positive terminal subculture. This study validates the reliability of the Vital system to detect positive blood cultures.

Bacteria↗
PubMed1996

Pharmacokinetics of vancomycin in patients with severely impaired renal function.

The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure. Serum vancomycin levels were determined by fluorescence polarization immunoassay. After single dose of vancomycin peak concentrations ranged from 37.8 microg.ml-1 to 109.3 microg.ml-1 (mean 64.9 +/- 21.7 microg.ml-1). Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 microg.ml-1 to 11.42 microg.ml-1 (mean 6.55 +/- 2.8 microg.ml-1). The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time. Three-compartment parameters obtained from the 8 patients were t1/2 alpha = 0.312 +/- 0.242 h, t1/2 beta 6.012 +/- 5.36 h, and t1/2 gamma = 131.0 +/- 46.7 h. Vd = 0.158 +/- 0.121 1.kg-1, Vdss = 0.920 +/- 0.248 1.kg-1 and total Cl = 0.10 +/- 0.049 1.h-1 per kg of weight. Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis. The dialysis clearance of vancomycin ranged from 50.6 ml.min-1 to 76.8 ml.min-1 (average: 62.4 +/- 10.4 ml.min-1. However, after dialysis plasma concentrations returned to pre-dialysis values. In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min-1.

Adult↗
PubMed1995

Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using microscopic image analysis: a preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07.

PURPOSE: We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations. METHODS AND MATERIALS: Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique. RESULTS: Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor. CONCLUSION: Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Acid Phosphatase↗
PubMed1995

Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype.

Direct MHC binding assays with radiolabeled peptides and HLA class I-expressing mammalian cells such as EBV-transformed B cell lines and PHA-activated blasts have been developed. Significant binding of the radiolabeled probe could be obtained if the target cells were preincubated overnight at 26 degrees C in the presence of beta 2-microglobulin. Under these conditions, up to a few percent of the HLA molecules expressed by either cell type could be bound by the labeled peptides. With these assays, the degree of cross-reactivity of the A*0201-restricted hepatitis B virus core 18-27 peptide with other A2 subtypes was examined. It was determined that this peptide epitope also binds the A*0202, A*0205, and A*0206 but not A*0207 subtypes. Inhibition experiments with panels of synthetic peptide analogues underlined the similar ligand specificities of the HLA-A*0201, A*0202, and A*0205 alleles. Analysis of the polymorphic residues that help form the B and F pockets of various HLA alleles allowed prediction of binding of the hepatitis B virus core 18-27 epitope to two other HLA alleles (HLA-A*6802 and A*6901). Thus, it appears that a family of at least six different HLA-A molecules may share overlapping ligand specificities (aliphatic residues in position 2 and at the C termini). These results suggest that broadly cross-reactive peptide epitopes can be identified and greatly enhance the prospective feasibility of peptide-based vaccination approaches.

Amino Acid Sequence↗
PubMed1995

Sperm morphology analysis (strict criteria) in male infertility is not a prognostic factor in intrauterine insemination with husband's sperm.

OBJECTIVE: To assess the prognostic value of strict sperm morphology analysis in intrauterine insemination with husband's sperm (IUI) cycles performed because of male infertility. DESIGN: Prospective study. SETTING: Academic tertiary hospital. PATIENTS: Seventy-four consecutive couples subjected to 271 IUI cycles because of male infertility. MAIN OUTCOME MEASURE: Strict morphology analysis 1 month before the beginning of IUI following the criteria of Kruger et al. RESULTS: Pregnancy and no pregnancy couples were similar regarding strict normal forms (2.85% +/- 2.07% versus 3.13% +/- 2.63%), slightly amorphous forms, and the morphology index (11.79 +/- 6.06 versus 12.04 +/- 7.13). Pregnancy rates (PRs) were similar when normal forms were <4% (39.1%) or > 4% (35.7%). The PR, although higher in the group with morphology index > 10% (41.4%) than in the group < 10% (33.3%), lacked statistical significance. In pure male infertility group, mean values of morphology were similar in pregnancy and nonpregnancy group. A not significant trend was detected toward higher PRs in morphology index > 10% (50.0%) than in the group < 10% (33.3%). CONCLUSION: Strict morphology analysis 1 month before the beginning of IUI is not a useful prognostic factor in IUI performed because of male infertility.

Adult↗