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Biomedical subjects

Joseph A Politch

Publications and source records attributed to Joseph A Politch.

10 recordsLinked to original sources
PubMed2007

T-lymphocyte profile and total and virus-specific immunoglobulin concentrations in the cervix of HIV-1-infected women.

BACKGROUND: The mucosal lymphocyte population is the largest in the body, and the gastrointestinal compartment has been well characterized in HIV infection. Much less is known about the effects of HIV on the genital tract. OBJECTIVE: : To examine the T-lymphocyte phenotype and receptor repertoire as well as total and virus-specific immunoglobulin concentrations in the endocervix of HIV-infected women at different stages of infection as compared with uninfected women. PATIENTS AND METHODS: Participants were 12 seronegative women, 10 HIV-infected "slow progressors" not taking antiretroviral therapy, and 9 HIV-infected women whose antiretroviral therapy was failing. We used multiparameter flow cytometry to enumerate T-cell populations on cytobrush-obtained cervical specimens, the immunoscope technique to determine the T-cell receptor (TCR) repertoire, and quantitative enzyme-linked immunosorbent assays for antibody determinations on cervical secretions absorbed onto ophthalmic sponges. Nonparametric statistical analyses were performed. RESULTS: We found marked depletion of leukocytes and CD4 T lymphocytes in the endocervix of HIV-infected women as compared with uninfected women; this was significant at more advanced disease stages. Naive T cells were rare in the endocervix of all groups. Activation marker expression was higher in endocervical T lymphocytes than in peripheral blood among control and slow-progressing HIV-infected women but not in women failing therapy. Endocervical T lymphocytes showed highly restricted utilization of Vbeta TCR families. Unlike other mucosal sites, the cervix contained IgG as the predominant immunoglobulin isotype. HIV-IgG was detected in the cervix of most HIV-infected women and in blood of all infected women. CONCLUSIONS: HIV infection induces substantial changes in the immune profile of the female genital tract. Further study of the implications of these findings for HIV acquisition and transmission is needed.

Adult↗
PubMed2005

Human immunodeficiency virus type-1 episomal cDNA in semen.

BACKGROUND: Episomal 2-long terminal repeat (LTR) HIV-1 cDNA, a by-product of HIV-1 infection, is used in clinical trials as a marker for ongoing viral replication. It would be useful to employ 2-LTR cDNA to monitor cryptic HIV-1 infection in the genital tract of men on antiretroviral therapy (ART) to predict the evolution of sexually transmissible drug-resistant HIV-1, but studies thus far have failed to detect this marker in semen. The objectives of this study were: 1) to use a technique that maximizes DNA recovery from HIV-1 infected white blood cells in semen to determine if episomal 2-LTR cDNA is detectable in semen of ART-naïve men with other evidence of genital tract HIV-1 infection, and 2) to compare levels of HIV-1 2-LTR cDNA, RNA, and proviral DNA in semen from HIV-1+ men on ART. RESULTS: Using a somatic cell DNA extraction technique, 2-LTR cDNA was detected by PCR/ELISA in 4 out of 8 semen samples from ART-naïve men selected for other signs of seminal HIV-1 infection (positive controls). Southern blot and DNA sequencing confirmed that the amplified sequences were HIV-1 2-LTR cDNA; copy numbers ranged from 55 to 504 copies/sample. Two semen samples from a cohort of 22 HIV-1-infected men on dual nucleoside therapy, one with and one without detectable seminal HIV-1 RNA, were 2-LTR cDNA positive (336 and 8,560 copies/sample). Following addition of indinavir to the therapy regimen, no semen samples from 21 men with controlled peripheral and seminal viral loads were 2-LTR cDNA positive at 1 and 6 month time points, despite the persistence of HIV-1 proviral DNA+ semen cells and seminal cytomegalovirus (CMV) shedding in some cases. However, one individual who failed indinavir therapy and later developed distinct protease inhibitor (PI) drug resistance mutations in semen, maintained elevated levels of HIV-1 RNA and 2-LTR cDNA in semen. CONCLUSION: 2-LTR HIV-1 cDNA is detectable in semen of HIV-1-infected men. Two men on ART had 2-LTR HIV-1 cDNA in semen, suggesting that this marker may prove to be useful to monitor HIV-1 infection in the genital tract of men on ART to predict the evolution of drug resistance mutations in semen.

Journal Article↗
PubMed2005

T-helper 2 and 3 type immunity to trophoblast in successful in vitro fertilization-embryo transfer.

OBJECTIVE: To determine whether peripheral blood mononuclear cell (PBMC) secretion of T-helper (Th)-1 type cytokines and Th-2 and Th-3 type cytokines in women undergoing in vitro fertilization-embryo transfer (IVF-ET) is associated with therapeutic failure and success, respectively. DESIGN: Cohort study. SETTING: Academic medical center. PATIENT(S): One hundred one women undergoing IVF-ET and 19 fertile controls. INTERVENTION(S): Peripheral blood was obtained from women undergoing IVF-ET before oocyte retrieval and from 19 nonpregnant fertile controls. The PBMCs were cultured in the presence or absence of a protein extract from either a trophoblast cell line or sperm membrane. MAIN OUTCOME MEASURE(S): Supernatants from PBMC cultures were tested by enzyme-linked immunoabsorbent assay (ELISA) for the Th-1 type cytokines tumor necrosis factor-alpha (TNF)-alpha) and interferon-gamma (IFN)-gamma), the Th-2 type cytokines interleukin (IL)-6 and IL-10, and the Th-3 type cytokine transforming growth factor (TGF)-beta1. RESULT(S): Levels of IL-6 and IL-10 were significantly higher in controls than in infertile women with endometriosis, and levels of IL-10 were higher in controls than in women with unexplained infertility. No differences were found in unstimulated levels of TNF-alpha, IFN-gamma, or TGF-beta1 between infertile patients and controls. In trophoblast-stimulated PBMC cultures, levels of TGF-beta1 were significantly lower in subjects who experienced failed compared with ongoing pregnancies. CONCLUSION(S): Baseline PBMC secretion of IL-6 and IL-10 is higher in fertile controls than in women with endometriosis, and IL-10 secretion is also higher than in women with unexplained infertility. Trophoblast-stimulated PBMC secretion of TGF-beta1 is positively associated with the establishment of successful pregnancy in women undergoing IVF-ET. Our study provides novel evidence to support a faciliatory role of Th-2 and Th-3 type responses to trophoblast in early pregnancy.

Analysis of Variance↗
PubMed2004

Separation of human immunodeficiency virus type 1 from motile sperm by the double tube gradient method versus other methods.

OBJECTIVE: To compare a new sperm-processing device, utilizing a double tube and gradient, with other commonly used sperm-processing methods for their abilities to exclude human immunodeficiency virus type 1 (HIV-1) from the motile sperm fraction while retaining maximum sperm yield. DESIGN: Laboratory experiments. SETTING: Academic research environment. PATIENT(S): Healthy HIV-1 seronegative men between the ages of 25 and 55. INTERVENTION(S): Semen samples were spiked with HIV-1 (MN HIV-1 strain; range of concentrations: 10(-1)-10(6) TCID(50)) and subjected to one of the following sperm-processing methods: double sperm tube with discontinuous gradient of sperm separation medium formed inside (double tube gradient), conventional single tube gradient, swim-up or single tube gradient followed by swim-up (gradient/swim-up), which is the method currently used to minimize HIV-1 in semen used for assisted reproductive technology (ART) procedures. For the gradient techniques, Percoll, ISolate, and PureSperm sperm separation media were compared for efficacy of HIV-1 removal. The amount of HIV-1 remaining in the motile sperm pellet after processing was measured by reverse transcription-polymerase chain reaction (RT-PCR), NucliSens assay, or quantitative HIV-1 culture. A hemacytometer was used to microscopically assess motile sperm count. MAIN OUTCOME MEASURE(S): HIV-1 RNA copy number, decrease in HIV-1 TCID(50), motile sperm yield. RESULT(S): The double tube gradient technique was significantly better than all other methods in the removal of HIV-1 from the motile sperm fraction, and produced significantly higher sperm yields in comparison with the gradient/swim-up method. CONCLUSION(S): The double tube gradient technique is a relatively simple and effective method that reduces the risk of infection by HIV-1 while producing good sperm recovery.

Adult↗
PubMed2004

Detection of implantation-related cytokines in cervicovaginal secretions and peripheral blood of fertile women during ovulatory menstrual cycles.

OBJECTIVE: To determine whether cytokines implicated in uterine receptivity are detectable in cervicovaginal secretions and/or serum of fertile women, and whether their concentrations undergo hormonal regulation during the menstrual cycle. DESIGN: Prospective, observational study. SETTING: Academic medical center. PATIENT(S): Six fertile volunteers studied over two menstrual cycles. INTERVENTION(S): Cervicovaginal lavages (CVLs) and peripheral blood specimens were obtained during the menstrual, proliferative, periovulatory, and midsecretory phases of the cycle. Endometrial biopsies were obtained during the midsecretory phase. MAIN OUTCOME MEASURE(S): Concentrations of leukemia inhibitory factor (LIF), macrophage-colony stimulating factor (M-CSF), interleukin-1beta (IL-1beta), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, and epidermal growth factor (EGF) in CVL and peripheral blood of fertile women; endometrial cytokine messenger (m)RNA levels in midsecretory phase; and serum E(2) and P levels throughout the menstrual cycle. RESULT(S): Macrophage-colony stimulating factor and EGF were detectable in all CVL samples. Macrophage-colony stimulating factor concentrations were positively correlated with serum E2 levels and the E2/P ratio. Whereas EGF concentrations in serum and CVL samples remained constant throughout the menstrual cycle, individual concentrations during the secretory phase of the menstrual cycle were positively correlated with endometrial EGF mRNA levels. Interleukin-1beta, TGF-beta1, and TGF-beta2 were detected in most CVL samples. Interleukin-1beta concentrations in CVL were significantly higher at menses than at the periovulatory stage of the menstrual cycle; TGF-beta2 levels were higher at menses than at the periovulatory and secretory stages. Leukemia inhibitory factor was undetectable in CVL except at menses. In serum, TGF-beta1, TGF-beta2, M-CSF, and EGF were detectable, but there was no menstrual cycle effect. There were no correlations between cytokine levels in CVL and serum. CONCLUSION(S): This study demonstrates that several endometrial cytokines that have been implicated in uterine receptivity are detectable in cervicovaginal secretions and peripheral blood of reproductive-aged women, and it provides normal concentration ranges of these cytokines in CVL and serum of fertile women at four stages of the menstrual cycle. Macrophage-colony stimulating factor and EGF warrant further study in CVLs of fertile and infertile women to determine their predictive value as minimally invasive markers of uterine receptivity.

Adult↗
PubMed2004

Implications of blood contamination for assessment of local cellular immunity in the endocervix.

Cervical cytobrushes provide a tool to sample endocervical T cells for assessment of local immunity. However, most previous studies in HIV-seropositive women have excluded samples containing blood and hence have analyzed selected populations of patients. As determined by multiple-parameter flow cytometric analysis of T lymphocytes from two sequential cytobrushes and concurrently collected blood samples, this study found a minimal effect of blood contamination on cervical T cell phenotypic parameters in normal women. The consequences of blood in endocervical samples will ultimately depend on the design and objective of each study, but these data suggest studies could be more inclusive and should not automatically discard samples that contain red blood cells.

Cervix Uteri↗
PubMed2003

Immunotherapy of human cervical high-grade cervical intraepithelial neoplasia with microparticle-delivered human papillomavirus 16 E7 plasmid DNA.

OBJECTIVE: The purpose of this study was to evaluate the safety of the administration of a bacterial expression plasmid encoding a 13 amino acid sequence that is highly homologous with human papillomavirus E7 within poly (lactide-co-glycolide) microparticles (ZYC101) in women with HLA A2+ antigen and persistent cervical intraepithelial neoplasia grade 2/3 and human papillomavirus 16. STUDY DESIGN: Fifteen women entered an institutional review board-approved dose-escalating phase I study with the use of three levels of blood monitoring and urine studies, Papanicolaou tests, and colposcopy. Escalation required no serious adverse events. Immunologic responses were evaluated in peripheral blood with the use of human papillomavirus peptide-stimulated interferon gamma enzyme-linked immunosorbent assay for T-cell reactivity. In cervical secretions, immunoglobulin A anti-human papillomavirus 16 E2 concentrations were measured. Three doses every 3 weeks were followed 4 weeks later by surgical excision. RESULTS: No serious adverse events occurred. Five women had complete histologic responses; 11 women had human papillomavirus-specific T-cell responses. Four of five complete histologic responses developed immunoglobulin A anti-E2-specific antibody. CONCLUSION: ZYC101 warrants further investigation because of a 33% complete histologic responses, a 73% immunologic response, and no serious adverse events.

Adult↗
PubMed2002

Conversion of high-response gonadotropin intrauterine insemination cycles to in vitro fertilization results in excellent ongoing pregnancy rates.

OBJECTIVE: To determine whether conversion of gonadotropin/IUI cycles at high risk of high-order multiple pregnancies to IVF yields a pregnancy rate high enough to warrant the added intervention. DESIGN: Case-control study. SETTING: Brigham and Women's Hospital assisted reproductive technology program. PATIENT(S): Seventy-seven patients converted from gonadotropin/IUI to IVF, 77 consecutive age and attempt number-matched controls (sequential controls [SCs]), and 77 consecutive age-, attempt-, and E(2)-matched controls (E(2) controls [ECs]). INTERVENTION(S): Gonadotropin/IUI cycles with exuberant responses were converted to IVF (cases) to avoid cycle cancellation and high-order multiple pregnancies. MAIN OUTCOME MEASURE(S): Pregnancy rates, delivery rates, E(2) levels, follicle and oocyte number, and fertilization and implantation rates. RESULT(S): Compared with SCs and ECs, cases had more follicles (16.3 +/- 0.6 vs. 13.3 +/- 0.9 and 14.4 +/- 0.9) and higher E(2) at hCG administration (1,951 +/- 93 vs. 1,568 +/- 96 and 1,939 +/- 89 pg/mL). Delivery rates among the three groups (45.5% vs. 32.5% and 39.0%) did not differ significantly. Despite the transfer of fewer embryos in cases than in controls (2.5 +/- 0.1 vs. 3.1 +/- 0.1 and 2.9 +/- 0.1), three triplet pregnancies occurred in cases and three in controls. CONCLUSION(S): Conversion of high responder gonadotropin/IUI patients to IVF is an effective alternative to cycle cancellation and offers a delivery rate as high or higher per cycle than that of planned IVF. Sample size limited the statistical power of the study.

Adult↗