Biomedical subjects

Francisco Garcia

Publications and source records attributed to Francisco Garcia.

17 recordsLinked to original sources

PubMed2006

Pilot study of a commercialized human papillomavirus (HPV) genotyping assay: comparison of HPV risk group to cytology and histology.

We evaluated a commercialized PCR assay, Linear Array, that detects 37 human papillomavirus (HPV) genotypes, using a sample of liquid cytology specimens (n = 534). We found a strong association of an increasing level of HPV risk (HPV type 16 [HPV16] > HPV18 > other carcinogenic types > noncarcinogenic types > negative specimens) with increasing severities of cytologic interpretations (P(Trend) < 0.0005) and histologic diagnoses (P(Trend) < 0.0005).

Cytodiagnosis↗

PubMed2006

High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping.

Array-CGH is a powerful tool for the detection of chromosomal aberrations. The introduction of high-density SNP genotyping technology to genomic profiling, termed SNP-CGH, represents a further advance, since simultaneous measurement of both signal intensity variations and changes in allelic composition makes it possible to detect both copy number changes and copy-neutral loss-of-heterozygosity (LOH) events. We demonstrate the utility of SNP-CGH with two Infinium whole-genome genotyping BeadChips, assaying 109,000 and 317,000 SNP loci, to detect chromosomal aberrations in samples bearing constitutional aberrations as well tumor samples at sub-100 kb effective resolution. Detected aberrations include homozygous deletions, hemizygous deletions, copy-neutral LOH, duplications, and amplifications. The statistical ability to detect common aberrations was modeled by analysis of an X chromosome titration model system, and sensitivity was modeled by titration of gDNA from a tumor cell with that of its paired normal cell line. Analysis was facilitated by using a genome browser that plots log ratios of normalized intensities and allelic ratios along the chromosomes. We developed two modes of SNP-CGH analysis, a single sample and a paired sample mode. The single sample mode computes log intensity ratios and allelic ratios by referencing to canonical genotype clusters generated from approximately 120 reference samples, whereas the paired sample mode uses a paired normal reference sample from the same individual. Finally, the two analysis modes are compared and contrasted for their utility in analyzing different types of input gDNA: low input amounts, fragmented gDNA, and Phi29 whole-genome pre-amplified DNA.

Cell Line, Tumor↗

PubMed2006

Evaluation of secondhand smoking characteristics in asthmatic children presenting to four emergency departments on O'ahu, Hawai'i.

Exposure to secondhand smoke causes adverse health outcomes particularly in vulnerable groups like children. This multi-centered prospective study examined the household exposure to secondhand smoke among asthmatic children presenting to emergency departments on O'ahu, Hawai'i. Findings revealed that asthmatic children of Samoan, Micronesian, Filipino, Part/Native Hawaiian and Other/Mixed Ancestry had a greater proportion of high exposure to secondhand smoke in the home compared to Japanese, Chinese and Caucasian ethnic groups. Asthmatic children with no insurance or with Medicaid had a greater frequency of high exposure to secondhand smoke in the home than those with private insurance. Additionally, an inverse relationship between caregiver educational level and exposure to secondhand smoke in the home was observed. Recommendations are provided to improve health outcomes and address the disproportionate burden of asthma in such children.

Adolescent↗

PubMed2005

Cactus pear: a natural product in cancer chemoprevention.

BACKGROUND: Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. METHOD: Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25%) to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycle changes were analyzed in the cultured cells; the suppression of tumor growth in nude mice was evaluated and compared with the effect of a synthetic retinoid N-(4-hydroxyphernyl) retinamide (4-HPR), which is currently used as a chemoprevention agent. Immunohistochemistry staining of tissue samples from animal tumors was performed to examine the gene expression. RESULTS: Cells exposed to cactus pear extracts had a significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner. It also affected cell cycle of cancer cells by increasing G1 and decreasing G2 and S phases. Both 4-HPR and cactus pear extracts significantly suppressed tumor growth in nude mice, increased annexin IV expression, and decreased VEGF expression. CONCLUSION: Arizona cactus pear extracts effectively inhibited cell growth in several different immortalized and cancer cell cultures, suppressed tumor growth in nude mice, and modulated expression of tumor-related genes. These effects were comparable with those caused by a synthetic retinoid currently used in chemoprevention trials. The mechanism of the anti-cancer effects of cactus pear extracts needs to be further studied.

Animals↗

PubMed2005

High-throughput SNP genotyping on universal bead arrays.

We have developed a flexible, accurate and highly multiplexed SNP genotyping assay for high-throughput genetic analysis of large populations on a bead array platform. The novel genotyping system combines high assay conversion rate and data quality with >1500 multiplexing, and Array of Arrays formats. Genotyping assay oligos corresponding to specific SNP sequences are each linked to a unique sequence (address) that can hybridize to its complementary strand on universal arrays. The arrays are made of beads located in microwells of optical fiber bundles (Sentrix Array Matrix) or silicon slides (Sentrix BeadChip). The optical fiber bundles are further organized into a matrix that matches a 96-well microtiter plate. The arrays on the silicon slides are multi-channel pipette compatible for loading multiple samples onto a single silicon slide. These formats allow many samples to be processed in parallel. This genotyping system enables investigators to generate approximately 300,000 genotypes per day with minimal equipment requirements and greater than 1.6 million genotypes per day in a robotics-assisted process. With a streamlined and comprehensive assay, this system brings a new level of flexibility, throughput, and affordability to genetic research.

DNA Methylation↗

PubMed2005

Comparison of type-specific human papillomavirus data from self and clinician directed sampling.

OBJECTIVE(S): To compare the type-specific human papillomavirus (HPV) recovery from physician and patient-collected samples. METHODS: Three hundred thirty-four (334) women attending colposcopy clinics in three countries were enrolled in this cross-sectional study. Cervicovaginal samples were collected by patients and physicians and processed with polymerase chain reaction and reverse line blot genotyping. McNemar's Chi-squared tests and Kappa statistics were utilized to determine statistical associations between physician- versus patient-collected samples. RESULTS: Oncogenic HPV infection was identified in 23.2% of patient-collected specimens compared to 34.9% of physician-collected specimens. Physician sampling detected significantly more infections with type 16 and 52 than did self-sampling and significantly more oncogenic HPV infection overall. For non-oncogenic HPV detection, there was no statistical difference between physician- and patient-collected samples. CONCLUSION(S): Patient sampling for HPV using a single vaginal brush does not identify all oncogenic HPV subtypes.

Colposcopy↗

PubMed2005

Effect of acculturation and income on Hispanic women's health.

This research examines how acculturation and income affect health care access, utilization, and prevention knowledge among a population of Hispanic women living along the U.S.-Mexico border in Yuma, Arizona, a rural agricultural county. A cross-sectional survey was conducted among 417 Hispanic women with mean age 61.3 years (s.d.=9.2). Most were long-term residents of Yuma County with some elementary and middle school education. Respondents had low monthly household incomes (average: USD $927.77, s.d.=550.40) and 10% reported current employment. The results show that income may be a more important predictor of actual utilization of health care services while acculturation may play a more prominent role with respect to provider preferences. A better understanding of the complex interplay between the individual and the society she inhabits is required in order to develop a meaningful public health intervention that will affect disease risk.

Acculturation↗

PubMed2005

Monitoring metals in the population living in the vicinity of a hazardous waste incinerator: concentrations in autopsy tissues.

This study is a part of a monitoring program for the determination of metals in various human tissues of the population living in the vicinity of a new hazardous waste incinerator (HWI) in Constantí (Tarragona County, Spain). Concentrations of arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn), thallium (Tl), and vanadium (V) were determined in brain, bone, kidney, liver, and lung autopsy samples collected in 2003 from 22 individuals who had been living for at least 10 yr in the area under evaluation. Results were compared with the metal levels obtained in a baseline study, which was performed during the construction of the HWI (1996--1998). In the present survey, As, Be, Tl, and V levels were not detected in any of the analyzed tissues, while Cr concentrations were very close to the limit of detection. The highest levels of Cd and Hg were found in kidney (17.46 microg/g and 0.23 microg/g, respectively), those of Mn in liver (1.07 microg/g), and those of Ni, Pb, and Sn in bone (1.16 microg/g, 2.11 microg/g, and 0.34 microg/g, respectively). In comparison to the results of the baseline study, a general reduction of most metal concentrations was observed in the current survey.

Arsenic↗

PubMed2004

Decoding randomly ordered DNA arrays.

We have developed a simple and efficient algorithm to identify each member of a large collection of DNA-linked objects through the use of hybridization, and have applied it to the manufacture of randomly assembled arrays of beads in wells. Once the algorithm has been used to determine the identity of each bead, the microarray can be used in a wide variety of applications, including single nucleotide polymorphism genotyping and gene expression profiling. The algorithm requires only a few labels and several sequential hybridizations to identify thousands of different DNA sequences with great accuracy. We have decoded tens of thousands of arrays, each with 1520 sequences represented at approximately 30-fold redundancy by up to approximately 50,000 beads, with a median error rate of <1 x 10(-4) per bead. The approach makes use of error checking codes and provides, for the first time, a direct functional quality control of every element of each array that is manufactured. The algorithm can be applied to any spatially fixed collection of objects or molecules that are associated with specific DNA sequences.

Algorithms↗

PubMed2004

Risk factors for squamous intraepithelial lesions (SIL) of the cervix among women residing at the US-Mexico border.

It is now well established that cervical cancer is caused by oncogenic human papillomavirus (HPV) infections that commonly infect women worldwide. What remains to be understood are the factors that contribute to cervical cancer in the presence of HPV infection. We conducted a case-control analysis of women recruited at the US-Mexico border to simultaneously evaluate factors associated with 3 cytologic outcomes: atypical squamous cells of undetermined significance or atypical glandular cells of undetermined significance (ASCUS/AGUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL). A cross-sectional binational study of 2059 women ages 15-79 years was conducted between 1997 and 1998. A significant difference in the distribution of cytologic categories by country was observed (3.0% vs. 0.7% HSIL among Mexican vs. US women, respectively). The only factors independently associated with all 3 cytologic outcomes were HPV infection and viral load. A linear increase in risk with increasing viral load was observed for each of the 3 outcome variables, with the strength of this association increasing with cytology abnormality. In addition to HPV infection, parity and Mexico as a country of residence appear to be associated with LSIL and HSIL, respectively. Factors associated with cytologic outcomes in analyses limited to women with HPV infection were similar to results obtained in models where HPV infection was included as a covariate. Future work is needed to evaluate the predictive value of HPV viral load utilizing more specific and quantitative measures.

Adolescent↗

PubMed2004

Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening.

Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. The conclusions of the workshop were that HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinicians in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments.

Adult↗

PubMed2004

ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial.

OBJECTIVE: The objective of this study was to assess the safety and efficacy of a novel therapeutic, ZYC101a, for the treatment of women with histologically confirmed cervical intraepithelial neoplasia (CIN) 2/3. ZYC101a contains plasmid-DNA-encoding fragments derived from the E6 and E7 proteins of human papillomavirus (HPV) 16 and 18, and is formulated within small biodegradable microparticles. METHODS: A multicenter, double-blind, randomized, placebo-controlled trial was conducted in a group of women with biopsy-confirmed CIN 2/3. Subjects were randomized to 3 intramuscular doses of either placebo or ZYC101a (100 or 200 microg). Six months after the first injection, subjects underwent cervical conization. The primary endpoint for this study was histologically confirmed resolution of CIN 2/3. A total of 161 subjects were randomized, dosed, and evaluated for safety. After central pathology review, 127 subjects were evaluable for efficacy. RESULTS: The most common adverse events were related to the injection site, were mild to moderate, and did not worsen at later treatments. The proportion of subjects who resolved was higher in the ZYC101a groups compared to placebo (43% versus 27%), but the difference was not statistically significant (P =.12). In a prospectively defined population of women younger than 25 years (n = 43), resolution was significantly higher in the combined ZYC101a groups compared to placebo (70% versus 23%; P =.007). ZYC101a activity was not restricted to HPV-16-or HPV-18-positive lesions. CONCLUSIONS: ZYC101a was shown to be well tolerated in all patients and to promote the resolution of CIN 2/3 in women younger than 25 years. LEVEL OF EVIDENCE: I

Adolescent↗

PubMed2003

Cross-sectional study of patient- and physician-collected cervical cytology and human papillomavirus.

OBJECTIVE: To compare the performance of patient- and physician-obtained cytology and human papillomavirus (HPV) testing for the detection of high-grade cervical intraepithelial neoplasia. METHODS: A cross-sectional study was performed involving 334 women seen at three colposcopy clinics (Tucson, Arizona; Hermosillo, Mexico; and Lima, Peru). All women used a cytobrush to self-collect specimens for cervical cytology and HPV testing. Subjects subsequently underwent physician collection for cytology and HPV, followed by a complete colposcopic evaluation with directed biopsy. Cytology was processed using thin-layer technology, and HPV was determined using the polymerase chain reaction technique. Test performance characteristics were determined using the histopathologic diagnosis as the reference standard and designating high-grade cervical intraepithelial neoplasia as clinically significant disease for the purpose of the analysis. RESULTS: The sensitivity of patient-collected cytology was significantly lower (55.0%) and specificity was significantly better (84.1%) than those of physician-directed sampling (85.2% and 73.4%, respectively). Patient-collected HPV had significantly lower sensitivity (49.0%) than physician sampling (82.2%), although specificity did not significantly differ. CONCLUSION: Patient collection is a feasible although inferior alternative to physician-collected cervical cytology and HPV testing.

Adolescent↗

PubMed2003

Identification of HLA-A*0201-restricted cytotoxic T-cell epitopes of Trypanosoma cruzi TcP2beta protein in HLA-transgenic mice and patients.

Trypanosoma cruzi-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of parasite growth and will play an important part in therapeutic and prophylactic T. cruzi vaccines. The identification of parasite-specific epitopes that are efficiently recognized by CTLs is the first step in the development of future vaccines. HLA-A2 transgenic mice (HHD) were shown to provide a powerful model for studying the induction of HLA-A*0201-restricted immune responses in vivo, since these mice are endowed with a CTL repertoire representative of HLA-A2.1 individuals. Here, we describe the immunological characterization of T-cell epitopes of the T. cruzi ribosomal P2 protein (TcP2beta) that are recognized by HLA-A*0201-restricted CTLs in HLA-transgenic mice and humans. Epitopes identified in the present study do not share sequence homology with the homologous human or murine counterparts and so they should not induce any autoreactive response. Moreover, HHD mice vaccinated with these peptide epitopes have reduced parasitemia after challenge with a lethal T. cruzi infection. Hence, these epitopes represent potential subunit components of multi-protein vaccines to prevent Chagas' disease.

Amino Acid Sequence↗

PubMed2003

Factors that affect the quality of cytologic cervical cancer screening along the Mexico-United States border.

OBJECTIVE: The purpose of this study was to identify the factors that affect the quality of cytologic cervical cancer screening conducted in public sector clinics in Sonora, Mexico. STUDY DESIGN: We assessed the quality of cervical cytology before and after a 2-hour training session and the implementation of cervical spatulas and endocervical brushes. Additionally, we conducted a cross-sectional study of reproductive aged women who attended public clinics in paired border communities in Sonora and Arizona. Cervical cytologic specimens (n=2436) were collected and compared for adequacy and cytologic diagnosis and for the prevalence of human papillomavirus infection. RESULTS: The training intervention achieved significantly improved the rates of satisfactory but limited smears and unsatisfactory smears. The cross-sectional study revealed comparable quality indicators for cytologic specimens that were collected in Sonora and Arizona clinics. CONCLUSION: A high-quality cytology-based cervical cancer screening program is possible in public sector clinics in Sonora, with indicators similar to those achieved in comparable Arizona clinics.

Adult↗

PubMed2003

Thin-layer cytology and histopathology in the evaluation of abnormal uterine bleeding.

OBJECTIVE: To compare thin-layer endometrial cytology to endometrial biopsy and surgical pathology in women with abnormal uterine bleeding. STUDY DESIGN: We performed a prospective study of 103 women. Patients underwent endometrial cytologic evaluation using an endometrial brush, followed by either endometrial biopsy, hysteroscopy with dilation and curettage, or hysterectomy, as clinically indicated. Test performance characteristics and adequacy of cytology and endometrial biopsy were assessed. Ki-67 immunocytochemical expression was evaluated in a random subset of 60 specimens. RESULTS: Cytologic sampling demonstrated a sensitivity of 78%, a specificity of 96%, a positive predictive value of 78% and a negative predictive value of 96% for the detection of endometrial abnormalities. The unsatisfactory rate of uterine cytology was 15% as compared to 26% for endometrial biopsy. Of adenocarcinoma cases, 83% expressed Ki-67, as compared to 30% in benign cases. CONCLUSION: Endometrial cytology may be useful in the detection of endometrial hyperplasia and neoplasia and provides adequate material for the assessment of Ki-67.

Adenocarcinoma↗

PubMed2002

Plasmodium falciparum and P. vivax gametocyte-specific exoantigens stimulate proliferation of TCR gammadelta+ lymphocytes.

Immune modulation of Plasmodium vivax and P. falciparum gametocytes occurs over the course of erythrocytic infection. The response is linked to proliferative and inflammatory responses, which may be stimulated by stage-specific gametocyte proteins. Stage-specific exoantigens were purified from supernatants of P. falciparum and P. vivax gametocyte cultures, and either primary or secondary postinfection lymphocytes were stimulated for proliferation. Five of 25 exoantigens purified from P. falciparum gametocyte cultures and 6 of 28 exoantigens isolated from P. vivax were gametocyte stage specific. Metabolic labeling of soluble P. falciparum gametocyte proteins confirmed synthesis and secretion of 5 stage-specific exoantigens, with molecular masses of 118, 62, 52, 37, and 33 kDa. Purified gametocyte exoantigens within the range of 50 to 100 kDa stage-specifically stimulated proliferation of lymphocytes from postprimary P. falciparum infections, and from postprimary and secondary P. vivax infection patients with homologous purified exoantigens. T-cell receptor (TCR)gammadelta+, and CD3+ CD8+ and CD3+ CD4- CD8- T cells were specifically upregulated from P. falciparum primary- and P. vivax secondary-infection lymphocytes, respectively, using gametocyte stage-specific exoantigens. CD25+ was the major activation marker expressed by CD3+ and gammadelta T cells when stimulated with gametocyte exoantigens. None of the T cell markers was significantly upregulated using gametocyte stage-specific exoantigens with primary-infection P. vivax lymphocytes.

Adolescent↗