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1.
Br J Dermatol ; 180(6): 1449-1458, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30431148

RESUMEN

BACKGROUND: Cutaneous viral infections and immune suppression are risk factors for some forms of nonmelanoma skin cancer; however, their interrelationship is poorly understood. OBJECTIVES: To examine cross-sectional associations between cutaneous viral infections and circulating forkhead-box P3 (FOXP3)-expressing T-regulatory (Treg) cells, suppressive cells that dampen effective antitumour immunity. MATERIALS AND METHODS: Blood, eyebrow hair (EBH) and skin swab (SSW) samples were collected from 352 patients 60 years and older undergoing skin screening, without prevalent skin cancer, while participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five human polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg-cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4high Treg cells, both previously associated with cutaneous diseases. Age- and sex-adjusted associations between circulating T-cell populations and infection were estimated using logistic regression. RESULTS: Total Treg-cell proportion in peripheral blood was not associated with ß HPV or HPyV infection. However, the proportion of circulating CLA+ Treg cells was inversely associated with γ HPV EBH infection [odds ratio (OR) 0·54, 95% confidence interval (CI) 0·35-0·84]. Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27- CD45RA- FOXP3+ CD4+ ) were also inversely associated with γ HPV infection in SSW (OR 0·55, 95% CI 0·30-0·99) and EBH (OR 0·56, 95% CI 0·36-0·86). CONCLUSIONS: Inverse associations between circulating Treg cells and γ HPV infection suggest that localized viral infection may promote immunosuppressive cell migration into skin.


Asunto(s)
Gammapapillomavirus/aislamiento & purificación , Tolerancia Inmunológica , Infecciones por Papillomavirus/inmunología , Enfermedades Cutáneas Virales/inmunología , Linfocitos T Reguladores/inmunología , Anciano , Carcinogénesis/inmunología , Estudios Transversales , ADN Viral/aislamiento & purificación , Cejas/inmunología , Cejas/virología , Femenino , Gammapapillomavirus/genética , Gammapapillomavirus/inmunología , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/virología , Poliomavirus/genética , Poliomavirus/inmunología , Poliomavirus/aislamiento & purificación , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/virología , Estudios Prospectivos , Piel/inmunología , Piel/virología , Enfermedades Cutáneas Virales/sangre , Enfermedades Cutáneas Virales/virología , Neoplasias Cutáneas/inmunología , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virología
2.
Oral Dis ; 22(8): 781-790, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27470907

RESUMEN

OBJECTIVES: This cross-sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men. METHODS: Extracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA-based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively. RESULTS: Among men aged 18-73 years, the median SLPI concentration was 492.0 ng ml-1 (range: 2.3-1919.9). In multivariable modeling, men in Brazil and younger men (18-30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94-7.59, and aOR 3.84; 95% CI: 1.98-7.43, respectively]. Men with a self-reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1-7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15-0.79). Similar results were observed for linear regression models. CONCLUSIONS: Secretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.


Asunto(s)
Saliva/química , Inhibidor Secretorio de Peptidasas Leucocitarias/análisis , Adolescente , Adulto , Factores de Edad , Anciano , Estudios Transversales , Gingivitis/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de Transmisión Sexual/metabolismo , Adulto Joven
3.
Epidemiol Infect ; 140(6): 1087-94, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21875452

RESUMEN

The Poisson model can be applied to the count of events occurring within a specific time period. The main feature of the Poisson model is the assumption that the mean and variance of the count data are equal. However, this equal mean-variance relationship rarely occurs in observational data. In most cases, the observed variance is larger than the assumed variance, which is called overdispersion. Further, when the observed data involve excessive zero counts, the problem of overdispersion results in underestimating the variance of the estimated parameter, and thus produces a misleading conclusion. We illustrated the use of four models for overdispersed count data that may be attributed to excessive zeros. These are Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial models. The example data in this article deal with the number of incidents involving human papillomavirus infection. The four models resulted in differing statistical inferences. The Poisson model, which is widely used in epidemiology research, underestimated the standard errors and overstated the significance of some covariates.


Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Factores de Riesgo , Adulto Joven
4.
Tissue Antigens ; 77(2): 143-8, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21214526

RESUMEN

Current methodologies for the analysis of the killer-cell immunoglobulin-like receptor (KIR) locus utilize specific primer-directed polymerase chain reaction (SSP-PCR), which require a wide range of DNA input, multiple reaction conditions, and up to 16 individual reactions. We have developed and validated a multiplex SSP-PCR method for the genetic analysis of the KIR locus. Design and optimization of four multiplex groups targeting 14 genes and their alleles on the KIR locus has been completed. Each multiplex group contains PCR products that differ in size by a minimum of 15 bp to allow sufficient fragment length resolution for size discrimination by gel electrophoresis. This assay allows for efficient genotyping of the KIR locus while requiring a minimum amount of DNA input, utilizing the simplicity of SSP-PCR.


Asunto(s)
Reacción en Cadena de la Polimerasa , Receptores KIR/genética , Bioensayo , Cartilla de ADN/química , Genotipo , Humanos
5.
Hum Vaccin Immunother ; 14(2): 396-403, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29211620

RESUMEN

A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type 6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age, including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and women 16-26 years of age, showed that the 9vHPV vaccine was generally well tolerated. Additional safety analyses were conducted to include the results of new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine recipients from 1 randomized controlled trial) was evaluated. Vaccine was administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse events (AEs) were monitored. The most common AEs were injection-site events (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively), the majority of which were mild. Discontinuations due to an AE were rare (0.2% and 0.0% among prior qHPV vaccine recipients and young men, respectively). In young men, the AE profile of the 9vHPV vaccine was generally similar to that of the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients and in young men, with an AE profile generally consistent with that previously reported with the broader clinical program.


Asunto(s)
Vacunas contra Papillomavirus/efectos adversos , Vacunas contra Papillomavirus/inmunología , Adolescente , Adulto , Niño , Método Doble Ciego , Femenino , Humanos , Masculino , Infecciones por Papillomavirus/prevención & control , Vacunación/efectos adversos , Adulto Joven
6.
Int J STD AIDS ; 16(3): 247-51, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15829027

RESUMEN

The incidence of cervical cancer increases with age among USA Hispanics and women living in Latin America starting in the fourth decade of life. We conducted a study of women > or = 40 living at the USA-Mexico border to determine the prevalence and risk factors for human papillomavirus (HPV) infection detected by polymerase chain reaction. In all, 9.2% of participants tested HPV positive. Compared with women aged 50-59, odds ratios of 8.82 and 6.67 were observed for women > or = 60 and 40-49, respectively. Among women aged 40-49, both oncogenic and non-oncogenic HPV infections were detected; however, women > or = 60 were positive for predominantly oncogenic genotypes. HPV risk significantly increased with > or = 2 lifetime sexual partners in adjusted models. These data suggest that the prevalence of HPV infection may have a second peak among post-menopausal Hispanic women.


Asunto(s)
Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , ADN Viral/análisis , Femenino , Humanos , México/epidemiología , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , Estados Unidos/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal
7.
Clin Microbiol Infect ; 21(5): 502-9, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25698660

RESUMEN

Human papillomavirus (HPV) infections are associated with the development of anogenital lesions in men. There are no reports describing the distribution of non-α HPV types in the anal canal of a sexually diverse group of men. The HPV Infection in Men (HIM) Study is a multicentre study on the natural history of HPV infection in Brazil, Mexico, and the USA. At baseline, 12% of anal canal PCR HPV-positive specimens were not typed by the Roche Linear Array, and were considered to be unclassified. Our goals were to characterize HPVs among these unclassified specimens at baseline, and to assess associations with participant socio-demographic and behavioural characteristics. Unclassified HPVs were typed by sequencing of amplified PGMY09/11 products or cloning of PGMY/GP + nested amplicons followed by sequencing. Further analysis was conducted with FAP primers. Of men with unclassified HPV in the anal canal, most (89.1%) were men who have sex with women. Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. Eighteen, 26 and three different α-HPV, ß-HPV and γ-HPV types were detected, respectively. α-HPVs were more commonly detected among young men (18-30 years) than among older men (45-70 years), whereas ß-HPVs were more frequent among mid-adult men (31-44 years). ß-HPVs were more common among heterosexual men (85.0%) than among non-heterosexual men. All ß-HPVs detected among non-heterosexual men were ß2-HPV types. The high prevalence of ß-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile-anal intercourse.


Asunto(s)
Canal Anal/virología , Variación Genética , Genotipo , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Adolescente , Adulto , Anciano , Conducta , Brasil/epidemiología , Estudios Transversales , Demografía , Femenino , Técnicas de Genotipaje , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Epidemiología Molecular , Análisis de Secuencia de ADN , Estados Unidos/epidemiología , Adulto Joven
8.
Vaccine ; 33(48): 6892-901, 2015 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-26144901

RESUMEN

OBJECTIVES: This study was designed to evaluate the immunogenicity and tolerability of a prophylactic 9-valent HPV (types 6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine in young men 16-26 years of age in comparison to young women 16-26 years of age (the population that was used to establish 9vHPV vaccine efficacy). Safety and immunogenicity data from this study will be used to bridge 9vHPV vaccine efficacy findings in 16-26 year old women to 16-26 year old men. METHODS: This study enrolled 1106 heterosexual men (HM) and 1101 women who had not yet received HPV vaccination. In addition, 313 men having sex with men (MSM) were enrolled and were evaluated separately for immunogenicity because previous results showed that antibody responses to quadrivalent HPV (types 6/11/16/18) VLP (qHPV) vaccine were lower in MSM than in HM. All subjects were administered a 3-dose regimen (Day 1, Month 2, Month 6) of 9vHPV vaccine. Serum samples were collected for anti-HPV assays. Safety information was collected for ∼ 12 months. RESULTS: The geometric mean titers (GMTs) for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 for HM were non-inferior to those of women at Month 7. For all vaccine HPV types, Month 7 GMTs were numerically lower in MSM than in HM. Over 99.5% of subjects were seropositive at Month 7 for each vaccine HPV type. Administration of 9vHPV vaccine to both 16-26 year old men and women was generally well tolerated. CONCLUSIONS: These results support bridging the efficacy findings with 9vHPV vaccine in young women 16-26 years of age to men 16-26 years of age.


Asunto(s)
Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Vacunas contra Papillomavirus/inmunología , Adolescente , Adulto , Femenino , Humanos , Esquemas de Inmunización , Masculino , Vacunas contra Papillomavirus/administración & dosificación , Resultado del Tratamiento , Adulto Joven
9.
Am J Clin Nutr ; 66(1): 52-61, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9209169

RESUMEN

Normal lactating mothers were administered a single dose of 60 or 210 mg beta-carotene and changes in serum and milk retinol, alpha-tocopherol, and carotenoids were monitored for 8 d. Average serum beta-carotene concentrations increased 4.1- and 4.0-fold after the 60- and 210-mg doses, respectively. Milk beta-carotene concentrations increased 4.1- and 3.0-fold after the 60- and 210-mg doses, respectively. Maximum serum concentrations were reached 24 h after both supplements, although concentrations of milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene concentrations remained about twofold higher than baseline concentrations. Increases in serum or milk beta-carotene concentrations were not dose-dependent. Initial serum and milk concentrations of beta-carotene predicted increases after supplementation, and increases in serum beta-carotene concentrations predicted those in milk. Concentrations of milk carotenoids were less than one-tenth their respective concentrations in serum. Lutein, beta-cryptoxanthin, lycopene, alpha-carotene, retinol, and alpha-tocopherol concentrations in serum or milk did not change significantly after beta-carotene supplementation. Retinol esters account for most of the retinol equivalents in the milk of well-nourished mothers. Initial and maximum concentrations of beta-carotene in serum and milk were strongly correlated for individual mothers. Collectively, the data showed that a single 60-mg supplement of beta-carotene sustained elevated beta-carotene concentrations in serum and milk for > 1 wk in normal mothers but did not affect concentrations of other major carotenoids, retinol, or alpha-tocopherol.


Asunto(s)
Antioxidantes/metabolismo , Leche Humana/metabolismo , beta Caroteno/metabolismo , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/farmacocinética , Carotenoides/análisis , Carotenoides/sangre , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Lactancia/metabolismo , Leche Humana/química , Vitamina A/análisis , Vitamina A/sangre , Vitamina E/análisis , Vitamina E/sangre , beta Caroteno/administración & dosificación , beta Caroteno/sangre , beta Caroteno/farmacocinética
10.
Am J Clin Nutr ; 67(2): 276-83, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9459376

RESUMEN

Changes in concentrations of milk and serum carotenoids, retinol, and alpha-tocopherol of five healthy, well-nourished, lactating women were measured over a 28-d supplementation trial with 30 mg beta-carotene and for 4 wk thereafter. Beta-carotene supplementation increased mean beta-carotene concentrations in milk and serum 6.4- and 7.4-fold, respectively. Concentrations of other major carotenoids, retinol, and alpha-tocopherol did not change substantially in either milk or serum. Uptake of beta-carotene into both serum and milk followed apparent first-order kinetics, occurring more rapidly into serum (t(1/2) = 5.5 d) than into milk (t(1/2) = 9 d). After supplementation, milk and serum beta-carotene concentrations decayed slowly, reaching approximately twofold initial concentrations by 4 wk. Kinetics of uptake and decay in milk beta-carotene concentrations paralleled those in serum. The data show that short-term supplementation of healthy, lactating mothers with purified beta-carotene at approximately fivefold the average daily dietary intake substantially increased milk and serum beta-carotene concentrations while not interfering with concentrations of other carotenoids, retinol, or alpha-tocopherol in milk or serum. Thus, an increased intake of beta-carotene by healthy, lactating women increases the supply of milk beta-carotene available to their breast-feeding infants.


Asunto(s)
Carotenoides/metabolismo , Lactancia/metabolismo , Leche Humana/metabolismo , beta Caroteno/farmacocinética , Adulto , Antropometría , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Vitamina A/sangre , Vitamina A/metabolismo , Vitamina E/sangre , Vitamina E/metabolismo , beta Caroteno/administración & dosificación , beta Caroteno/sangre
11.
Cancer Epidemiol Biomarkers Prev ; 8(7): 615-20, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10428199

RESUMEN

Minority women in the United States experience a disproportionately high burden of the more than 2 million yearly cases of squamous intraepithelial lesions of the cervix. Risk factors for squamous intraepithelial lesions of the cervix are infection with the sexually acquired human papillomavirus (HPV), an early age at first intercourse, history of multiple sexual partners, oral contraceptive use, high parity, lower socioeconomic status, poor diet, immunosuppression, and promiscuous male sexual partners. Although Hispanics are the largest growing minority population in the United States, few HPV risk factor studies have either included or focused on Hispanics in the United States. To determine risk factors for HPV infection among Mexican-American women, we conducted a cross-sectional study from 1992-1995. Nine hundred and seventy-one women, 18-47 years of age, with cytology results were included in this analysis. Overall, 13.2% of participants were HPV positive by the Hybrid Capture tube method for high-risk types 16, 18, 31, 33, 35, 45, 51, 52, or 56. Age [adjusted odds ratio (AOR) = 0.3 for ages >36 years compared with ages 18-20] and duration of oral contraceptive use (AOR = 0.4 for > or =4 years relative to nonusers) were inversely associated with these high-risk types of HPV infection. Marital status (AOR = 1.9 among single women compared with married) and lifetime number of sexual partners (AOR = 2.3 for women > or =5 partners relative to monogamous women) were positively associated with an increased risk. Participants born in Mexico were significantly (P < 0.05) older, had fewer sex partners, and older age at first intercourse. Despite this lower behavioral risk profile, women born in Mexico were significantly more likely (AOR = 1.9; CI = 1.2-3.2) to have an HPV infection compared with United States-born, Mexican-American women after adjustment for potential confounders. Collectively, these results suggest that an unmeasured factor, such as the sexual behavior of the male partner, may be influencing HPV risk. Further research is needed to define this factor and to assess cultural norms of sexual behavior.


Asunto(s)
Americanos Mexicanos/estadística & datos numéricos , Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Infecciones Tumorales por Virus/epidemiología , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adolescente , Adulto , Arizona/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/transmisión , Factores de Riesgo , Conducta Sexual , Infecciones Tumorales por Virus/transmisión , Neoplasias del Cuello Uterino/etiología , Frotis Vaginal , Displasia del Cuello del Útero/etiología
12.
Cancer Epidemiol Biomarkers Prev ; 6(11): 917-23, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9367065

RESUMEN

Research from the past several years has definitively shown intermediate and high risk-type human papillomavirus (HPV) infection to play a significant role in cervical carcinogenesis. Persistent compared with intermittent infection appears to confer an elevated risk, and cofactors may be necessary to allow the virus to progress to cervical cancer. We explored the association between circulating concentrations of the antioxidant nutrients (alpha- and beta-carotene, lutein, lycopene, beta-cryptoxanthin, alpha-tocopherol, gamma-tocopherol, and ascorbate) and persistent HPV infection among 123 low-income Hispanic women who were all nonsmokers and were not currently using vitamin and mineral supplements. In addition, the association between these nutrients and grade of cervical pathology, independent of HPV status, was assessed. Intermediate and high risk-type HPV infection was assessed by the Digene Hybrid Capture System at two time points, 3 months apart. At the second interview, cytology, colposcopy, and a fasting blood draw were conducted. Mean concentrations of serum and plasma antioxidant nutrients were calculated within categories of HPV status (two times HPV negative, one time HPV positive, and two times HPV positive) and colposcopy. Adjusted mean concentrations of serum beta-carotene, beta-cryptoxanthin, lutein, and alpha- and gamma-tocopherol were on average 24% (P < 0.05) lower among women two times HPV positive compared with either two times HPV negative or one time HPV positive. Independent of HPV status, alpha-tocopherol was significantly inversely associated with grade of cervical dysplasia (normal, 21.57 microM; cervical intraepithelial neoplasia III, 17.27 microM). The results obtained in this study need to be confirmed in larger cohort studies with a longer follow-up period.


Asunto(s)
Antioxidantes/metabolismo , Papillomaviridae , Infecciones por Papillomavirus/sangre , Infecciones Tumorales por Virus/sangre , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/virología , Adulto , Ácido Ascórbico/sangre , Biomarcadores/sangre , Carotenoides/sangre , Enfermedad Crónica , Femenino , Hispánicos o Latinos , Humanos , Funciones de Verosimilitud , Modelos Logísticos , Luteína/sangre , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/etnología , Infecciones por Papillomavirus/patología , Factores de Riesgo , Infecciones Tumorales por Virus/etnología , Infecciones Tumorales por Virus/patología , Neoplasias del Cuello Uterino/etnología , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Vitamina E/sangre , Displasia del Cuello del Útero/sangre , Displasia del Cuello del Útero/etnología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología
13.
Cancer Epidemiol Biomarkers Prev ; 7(10): 901-6, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9796635

RESUMEN

We have shown previously that DNA hypomethylation is significantly associated with grade of cervical intraepithelial neoplasia (CIN; Y.I. Kim et al., Cancer, 74: 893-899, 1994). The objective of this study was to further describe this relationship and to investigate the role of folate in the observed association of DNA hypomethylation and CIN. Eighty-three patients with abnormal PAP smear results were referred to the Cervical Dysplasia Clinic at the University of Arizona for colposcopic examination and biopsy. Patients completed a short questionnaire and provided a nonfasting serum sample. DNA hypomethylation was assessed by incubating DNA extracted from biopsy samples with [3H]methyl-S-adenosylmethionine and Sss 1 methylase. Cervical tissue and serum folate concentrations were assessed using a microbiological assay. All folate levels were log transformed prior to statistical analysis. The histological distribution of the samples was: 7 adjacent normal, 30 CIN I, 18 CIN II, 13 CIN III, and 11 carcinoma in situ (CIS). The mean age of participants was 29.8 +/- 9.6 years. DNA hypomethylation was significantly different between select histological levels. Both cervical tissue folate and serum folate levels were significantly correlated to methylation level (P = 0.0211 and P = 0.0569, respectively). Smoking, hormonal contraceptive use, parity, and human papillomavirus infection were not associated with DNA hypomethylation or folate status. The current use of vitamins was significantly associated with serum folate level but not with methylation or cervical folate levels. These data extend our earlier findings that DNA hypomethylation is an early event in cervical carcinogenesis. To conclude that the folate level is significantly related to DNA hypomethylation, further investigation of DNA hypomethylation of specific genes is required.


Asunto(s)
Metilación de ADN , Deficiencia de Ácido Fólico/sangre , Deficiencia de Ácido Fólico/complicaciones , Displasia del Cuello del Útero/etiología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/patología , Adolescente , Adulto , Anciano , Biopsia , Cuello del Útero/química , Femenino , Ácido Fólico/análisis , Ácido Fólico/sangre , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Paridad , Factores de Riesgo , Fumar/efectos adversos , Encuestas y Cuestionarios , Vitaminas/uso terapéutico
14.
Cancer Epidemiol Biomarkers Prev ; 10(11): 1129-36, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11700260

RESUMEN

The United States-Mexico border is a region comprised of a country with one of the highest rates of invasive cervical cancer (Mexico) and a country with one of the lowest rates (United States). Recent evidence clearly indicates that human papillomavirus (HPV) infection is the cause of cervical cancer. The distribution of specific types of HPV is known to vary in different regions of the world, as do the cofactors that may inhibit or promote HPV carcinogenesis. Estimating the prevalence of oncogenic HPV is needed for guiding vaccine development. The purpose of this study was to determine the prevalence of oncogenic and nononcogenic HPV types and risk factors for HPV among women residing along the United States-Mexico border. A cross-sectional study of 2319 women, ages 15-79 years, self-referring for gynecological care was conducted between 1997 and 1998. HPV was detected by PCR using the PYGMY 09/11 L1 consensus primer, and HPV genotyping was conducted using the reverse line blot method. Overall, the HPV prevalence was 14.4% with no significant differences observed by country after adjustment for age. HPV 16 was the most commonly detected HPV type in both the United States and Mexico. Among women with high-grade squamous intraepithelial lesions, HPV types 58, 45, 51, 31, 35, 55, and 73 were most common in Mexico, and HPV types 18, 31, 35, 51, 52, and 58 were most common in the United States. In both countries, HPV prevalence declined linearly with age from 25% among women ages 15-19 years to 5.3% among women 56-65 years. Factors significantly independently associated with HPV infection were older age [adjusted odds ratio (AOR) = 0.15 for ages 56-65 years compared with those 15-19 years], a marital status other than married (AOR = 1.58-3.29), increased numbers of lifetime male partners (AOR = 3.8 for > or =10 partners compared with 1 partner), concurrent infection with Chlamydia trachomatis (AOR = 1.79), ever use of Norplant (AOR = 2.69), and current use of injectable contraceptives (AOR = 2.29). Risk factors for HPV infection did not differ by country. Results from this study suggest that in addition to HPV 16 and 18, HPV types 31, 45, 51, and 58 should be considered for inclusion in an HPV prevention vaccine for distribution in Mexico.


Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus/epidemiología , Infecciones Tumorales por Virus/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Genotipo , Humanos , México/epidemiología , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Factores de Riesgo , Estados Unidos/epidemiología , Neoplasias del Cuello Uterino/prevención & control
15.
Ann Epidemiol ; 10(8 Suppl): S22-34, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11189089

RESUMEN

Overall, participation rates in cancer clinical trials are very low, ranging from 3 to 20% of eligible participants. However, participation rates are especially low among the socially disadvantaged and racial/ethnic minority groups that have been historically underrepresented in clinical research. Structural factors such as study duration, treatment or intervention schedule, cost, time, followup visits, and side effects represent more of a barrier to participation among these groups compared with white, non-Hispanics. Attitudes, beliefs, perceptions, and knowledge regarding clinical research, and cultural characteristics of underrepresented minorities pose additional barriers to participation. This article focuses on the structural, cultural, and linguistic factors that affect participation in clinical cancer research for each major U.S. racial/ethnic group. Low socioeconomic status, speaking a primary language other than English, differences in communication styles, mistrust of research and the medical system, fear, embarrassment, and lack of knowledge about the origin of cancer appear to have a negative impact on clinical cancer research participation rates. Much of the information about these factors comes from studies of cancer screening because little data is available on the factors that prevent and facilitate participation of minorities in clinical cancer trials specifically. Such research is needed, and, given the heterogeneity within and between minority populations, should occur in several different geographic settings and with as many different minority subpopulations as possible.


Asunto(s)
Etnicidad/estadística & datos numéricos , Grupos Minoritarios/estadística & datos numéricos , Neoplasias/etnología , Selección de Paciente , Investigación/estadística & datos numéricos , Adolescente , Adulto , Anciano , Niño , Características Culturales , Recolección de Datos , Femenino , Humanos , Lenguaje , Persona de Mediana Edad , Estados Unidos
16.
Nutr Rev ; 56(1 Pt 1): 9-16, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9481113

RESUMEN

Invasive cervical cancer accounts for 11.6% of all cancers worldwide and is the second most common cancer among women. It is the most common cancer among women living in less developed countries. Although infection with oncogenic-type human papillomaviruses (HPV) is associated with most cases of cervical cancer, HPV infection alone is an insufficient cause of cervical cancer. Research from the last two decades suggests a role for nutrients in the prevention of cervical cancer. However, results from phase III folic acid and beta-carotene chemoprevention trials have been negative. Potential reasons for the lack of treatment effect are discussed within the context of cervical carcinogenesis.


Asunto(s)
Suplementos Dietéticos , Ácido Fólico/administración & dosificación , Tretinoina/administración & dosificación , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , beta Caroteno/administración & dosificación , Femenino , Ácido Fólico/uso terapéutico , Humanos , Resultado del Tratamiento , Tretinoina/uso terapéutico , Displasia del Cuello del Útero/dietoterapia , Neoplasias del Cuello Uterino/dietoterapia , beta Caroteno/uso terapéutico
17.
J Pharm Sci ; 84(4): 410-4, 1995 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-7629729

RESUMEN

The overall objective of this research was to identify enhancers of calcium transport using an in-vitro Caco-2 cell monolayer model. The enhancers studied were medium-chain triglycerides (MCT) and acylcarnitines (AC). The extent of cell damage associated with the use of these enhancers was determined by monitoring the release of cellular lactate dehydrogenase (LDH). The effect of chain-length and concentration dependence of these agents on enhancement were also determined. The effects of ACs were found to be superior to those of MCTs. However, the ACs elicited a greater release of LDH than the MCTs. The possible mechanisms of enhancer-mediated increase in calcium transport and the potential significance of this study with regard to the prevention of osteoporosis are discussed.


Asunto(s)
Calcio/metabolismo , Transporte Biológico Activo , Carnitina/farmacología , Línea Celular , Humanos , L-Lactato Deshidrogenasa/metabolismo , Triglicéridos/farmacología
18.
J Pharm Sci ; 84(3): 269-74, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7542333

RESUMEN

The overall objective of this study was to determine the mechanisms of acylcarnitine-mediated enhancement of calcium transport across Caco-2 cells. The different mechanisms of enhancement postulated are (a) loosening of tight junctions, thereby promoting paracellular transport; (b) opening of calcium channels, thus increasing calcium entry; and (c) stimulation of the basolateral Ca-ATPase pump, thereby aiding calcium extrusion. Although the existence of calcium channels and the reversal of verapamil-mediated inhibition of calcium uptake by acylcarnitines were demonstrated for the first time in Caco-2 cells, the channels do not appear to be a major contributing factor to the enhancement of calcium transport by acylcarnitines. Calmidazolium, a potent Ca-ATPase pump inhibitor in tissues such as rat intestinal segments, failed to inhibit this pump in Caco-2 cells. Thus, the predominant mechanism of enhancement of calcium transport by acylcarnitines in the Caco-2 model appears to be via promotion of paracellular transport.


Asunto(s)
Calcio/metabolismo , Carnitina/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Transporte Biológico , Canales de Calcio/efectos de los fármacos , Canales de Calcio/metabolismo , Línea Celular , Relación Dosis-Respuesta a Droga , Cinética , Nifedipino/farmacología , Factores de Tiempo , Verapamilo/farmacología
19.
Int J STD AIDS ; 14(12): 800-4, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14678586

RESUMEN

Association between the p53 codon 72 polymorphism and cervical cancer remains unresolved. We determined the association between the polymorphism and risk of human papillomavirus (HPV) persistence. The polymorphism was detected by restriction enzyme digestion following p53 amplification and HPV detection by the PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples were analysed. HPV persistence was assessed on a subset of samples collected at baseline, four and 10 months (n =442). Highly significant differences were observed between ethnic groups (P <0.005). No associations were found between P53 arginine and cytological grade in women infected with any HPV or any oncogenic HPV, despite adjustment for ethnicity. These results were sustained even when HPV-negative women were used as controls. Persistence for any or oncogenic HPV infection was not associated with the polymorphism, irrespective or ethnicity adjustment. Our findings do not support a role for this polymorphism conferring elevated risk for HPV-related disease.


Asunto(s)
Codón/genética , Etnicidad/genética , Infecciones por Papillomavirus/genética , Polimorfismo Genético , Proteína p53 Supresora de Tumor/genética , Neoplasias del Cuello Uterino/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/etnología , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Infecciones Tumorales por Virus/etnología , Infecciones Tumorales por Virus/genética , Estados Unidos , Neoplasias del Cuello Uterino/etnología , Neoplasias del Cuello Uterino/virología
20.
Int J STD AIDS ; 15(12): 815-21, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-15601488

RESUMEN

Few studies have reported on sexually transmitted infections at the US-Mexico border, so the prevalence of Chlamydia trachomatis in this population remains uncertain. This binational project investigated the prevalence of, and risk factors for, C. trachomatis among women along the Arizona, US-Sonora, Mexico border. Women who self-referred for routine gynaecological care were invited to complete an interviewer-administered questionnaire and to undergo a Pap smear, C. trachomatis test, and HPV test. In 2270 women, C. trachomatis prevalence overall was 8.2% as measured by hybrid capture and 2.6% by enzyme immunoassay. Infection was associated with young age, a history of new sexual partner(s) in the previous three months, HPV infection, and proximity of clinic to the international border. Antibiotic use in the previous 30 days was associated with decreased odds of infection. Women in Arizona-Sonora border communities are at increased risk for C. trachomatis infection compared to women attending clinics in non-border locations.


Asunto(s)
Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis , Internacionalidad , Enfermedades Bacterianas de Transmisión Sexual/epidemiología , Adolescente , Adulto , Anciano , Arizona/epidemiología , Infecciones por Chlamydia/diagnóstico , Femenino , Humanos , México/epidemiología , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Enfermedades Bacterianas de Transmisión Sexual/diagnóstico , Estados Unidos/epidemiología
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