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Biomedical subjects

S S Witkin

Publications and source records attributed to S S Witkin.

At least 19 recordsLinked to original sources
PubMed2004

Maternal serum levels of interferon-gamma and interleukin-2 soluble receptor-alpha predict the outcome of early IVF pregnancies.

BACKGROUND: Elevated maternal serum levels of interleukin-2 soluble receptor-alpha (IL-2 sRalpha), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been associated with pregnancy loss. The aim of our study was to evaluate the predictive value of these cytokines in the outcome of early IVF pregnancies. METHODS: One hundred and fifty-nine consecutive IVF patients who were subsequently diagnosed to have a biochemical pregnancy (n = 23), a first-trimester miscarriage (n = 19) or a normal term delivery (n = 117) were included in this study. Serum was collected from the initial pregnancy test, 11 days after a day 3 embryo transfer, and all samples were analysed for IL-2 sRalpha, TNF-alpha and IFN-gamma by commercially available enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: IL-2 sRalpha levels were significantly higher in patients with an early pregnancy loss compared with patients with a normal term delivery (849.5 +/- 69.6 versus 693.5 +/- 31.2 pg/ml, P = 0.02), and a cut-off point of IL-2 sRalpha >1000 pg/ml predicted a poor pregnancy outcome (44.4 versus 22.7% pregnancy loss, IL-2 sRalpha >or=1000 versus IL-2 sRalpha <1000 pg/ml; P = 0.02). IFN-gamma-positive patients had twice the risk for poor IVF pregnancy outcome compared with IFN-gamma-negative subjects (40.8 versus 20.0%, respectively; P < 0.02), including a significantly lower implantation rate (37.6 +/- 0.05 versus 50.0 +/- 0.03%, respectively; P = 0.02). There was no difference in pregnancy outcome based upon serum levels, or the ability to detect the presence of TNF-alpha. No differences in levels of these cytokines were found based on the aetiology of the patients' infertility. CONCLUSIONS: Elevated maternal serum levels of IL-2 sRalpha and IFN-gamma as early as 11 days after embryo transfer are associated with poor IVF pregnancy outcome.

Adult↗
PubMed2003

Involvement of interleukin-1 and the interleukin-1 receptor antagonist in in vitro embryo development among women undergoing in vitro fertilization-embryo transfer.

PURPOSE: To examine the roles of Interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1ra), in in vitro embryo development and subsequent pregnancy outcome. METHODS: Maternal serum utilized to supplement embryo growth in IVF cycles was analyzed for the presence of IL-1 cytokines. RESULTS: The maternal serum that was utilized to supplement the embryo media was found to have measurable amounts of IL-1beta and IL-1ra. CONCLUSIONS: Relative antagonism of the IL-1 system was positively associated with embryo development and pregnancy outcome.

Embryo Transfer↗
PubMed2001

Autologous endometrial coculture in patients with in vitro-fertilization (IVF) failure: correlations of outcome with leukemia inhibiting factor (LIF) production.

PROBLEM: To determine if LIF produced by autologous endometrial co-culture (ECC) was associated with outcome in 46 patients with a history of multiple IVF failures. METHOD OF STUDY: The conditioned media (CM) from ECC cells exposed or non-exposed to human embryos was analyzed for LIF. RESULTS: Exposure or non-exposure to an embryo did not result in differing levels of LIF in the CM. LIF levels were significantly greater in the CM than in the serum controls (LIF was not found in the serum controls). Embryos grown on ECC demonstrated a significant improvement in number of blastomeres and fragmentation when compared to embryos grown in conventional media without ECC (6.7 +/- 1.3 vs. 5.6 +/- 1.2 blastomeres and 17.6% +/- 9.3 vs. 26.4% +/- 9.8 fragmentation; P < 0.05). When LIF levels were detectable in the CM, the embryos grown in ECC were of improved quality as compared to the embryos grown only in conventional media and demonstrated a non-significant increase in pregnancy rates (60 vs. 48%, P = 0.50). CONCLUSIONS: We have demonstrated a significant improvement in embryo quality with ECC. The cells in the ECC express LIF. The presence of LIF in the CM was associated with embryonic development and clinical pregnancy.

Adult↗
PubMed2001

Interleukin-1 receptor antagonist gene polymorphism and circulating levels of human immunodeficiency virus type 1 RNA in Brazilian women.

Interleukin-1 receptor antagonist (IL-1ra) gene polymorphisms in 83 human immunodeficiency virus (HIV)-seropositive women were evaluated. Fourteen of the subjects (16.9%) were homozygous for IL-1ra allele 2 (IL-1RN*2). These women had a lower median level of HIV RNA than did women homozygous for allele 1 (IL-1RN*1) (P = 0.01) or heterozygous for both alleles (P = 0.04). Among 46 subjects not receiving antiretroviral treatment, HIV levels were also reduced in IL-1RN*2 homozygous individuals (P < 0.05). There was no relation between IL-1ra alleles and CD4 levels.

Female↗
PubMed2001

Differentiation between women with vulvovaginal symptoms who are positive or negative for Candida species by culture.

OBJECTIVE: To investigate whether clinical criteria could differentiate between women with vulvovaginitis who were culture positive or negative for vaginal Candida species. METHODS: Vulvovaginal specimens were obtained from 501 women with a vaginal discharge and/or pruritus. Clinical information and wet mount microscopy findings were obtained. All specimens were sent to a central laboratory for species identification. RESULTS: A positive culture for Candida species was obtained from 364 (72.7%) of the specimens. C. albicans was identified in 86.4% of the positive cultures, followed by C. glabrata in 4.5%, C parapsilosis in 3.9%, C. tropicalis in 2.7% and other Candida species in 1.4%. Women with a positive Candida culture had an increased utilization of oral contraceptives (26.1% vs. 16.8%, p = 0.02) and antibiotics (8.2% vs. 0.7%, p = 0.001), and were more likely to be pregnant (9.1% vs. 3.6%, p = 0.04) than the culture-negative women. Dyspareunia was more frequent in women without Candida (38.0% vs. 28.3%, p = 0.03) while vaginal erythema (p = 0.01) was more common in women with a positive Candida culture. CONCLUSIONS: Although quantitative differences were observed, the presence of vaginal Candida vulvovaginitis cannot be definitively identified by clinical criteria.

Adult↗
PubMed2001

Temperature stability of vaginal specimens for Chlamydia trachomatis detection by Amplicor polymerase chain reaction assay.

Vaginal introital specimens were collected from 17 women - 10 positive and 7 negative for Chlamydia trachomatis, and kept in Amplicor collection medium at ambient temperature. Aliquots were removed at intervals for up to 34 days and frozen at -80 degrees C. Samples were thawed and assayed for C. trachomatis by polymerase chain reaction (PCR). The results of all specimens remained unchanged over this time interval.

Chlamydia Infections↗
PubMed2001

Lipopolysaccharide stimulation of 70 kilo Dalton heat shock protein messenger ribonucleic acid production in cultured human fetal membranes.

OBJECTIVE: The 70 kilo Dalton heat shock protein is up-regulated when cells are under physiological stress. It prevents protein denaturation and incorrect polypeptide assembly, and inhibits apoptosis as well as the transcription of genes coding for pro-inflammatory cytokines. To evaluate if up-regulation of heat shock protein 70 can occur during pregnancy, we examined whether addition of bacterial lipopolysaccharide to human amniochorion membranes in vitro stimulated heat shock protein 70 gene transcription. MATERIALS AND METHODS: Amniochorionic membranes (n = 5), collected at the time of elective repeat cesarean section prior to labor from normal term gestations, were placed in an organ explant system. After 48 hour in culture, the membranes were stimulated with lipopolysaccharide for 24 hours. Total RNA was extracted and subjected to an oligo dT primed reverse transcriptase reaction followed by polymerase chain reaction (PCR) using heat shock protein 70 specific primers. PCR products were hybridized with biotinylated internal probes and identified by enzyme-linked immunosorbent assay (ELISA). Results were analyzed by Mann-Whitney U test. A p < 0.05 was significant. RESULTS: Heat shock protein 70 messenger RNA was expressed by all fetal membrane preparations both prior to and following in vitro culture. Addition of lipopolysaccharide increased the concentrations of heat shock protein 70 messenger RNA in each sample tested from a mean of 35.5 +/- 29.6 ng/milliliter (12.1-80.1 ng/milliliter) to 169.6 +/- 69.9 ng/ml (51.7-218.2 ng/milliliter) (p = 0.03). CONCLUSION: Human fetal membranes constitutively express heat shock protein 70 messenger ribonucleic acid. Bacterial lipopolysaccharide markedly stimulated heat shock protein 70 messenger RNA gene transcription in human fetal membranes. Thus, heat shock protein 70 is inducible in fetal membranes and may facilitate fetal survival under adverse conditions.

Cesarean Section↗
PubMed2001

Relationship of abnormal vaginal flora, proinflammatory cytokines and idiopathic infertility in women undergoing IVF.

OBJECTIVE: To investigate the prevalence of bacterial vaginosis (BV) and abnormal bacterial vaginal flora in an infertile population and correlate with cervical cytokine production and in vitro fertilization (IVF) outcome. STUDY DESIGN: In a blinded study, 331 asymptomatic IVF patients were evaluated for BV, abnormal vaginal flora and cervical cytokine production (interleukin 1 beta [IL-1 beta] and IL-8) on the day of oocyte retrieval. All patients received tetracycline prophylaxis at the time of oocyte retrieval. RESULTS: BV was identified in 4.2% (14/331) of the patients. Patients with idiopathic infertility were more likely to have BV than were women with other causes of infertility (P = .02 vs. male factor, P = .03 vs. tubal factor and P < .01 vs. endometriosis-associated infertility). Patients with abnormal vaginal flora had higher cervical IL-1 beta and IL-8 cytokine levels as compared to patients with normal vaginal flora. IL-1 beta and IL-8 levels in the study subjects correlated highly. No differences were detected in IVF outcome parameters based on the vaginal flora determined at the time of retrieval. CONCLUSION: Abnormal vaginal flora, including that causing BV, is associated with elevated cervical levels of IL-1 beta and IL-8. The induction of proinflammatory cytokines by an altered vaginal ecosystem may be a previously unrecognized cause of idiopathic infertility.

Adult↗
PubMed2001

Heat shock protein expression and immunity: relevance to gynecologic oncology.

Heat shock proteins function as molecular chaperones, guiding the transport, assembly and degradation of intracellular polypeptides. Under the influence of non-physiological conditions heat shock protein synthesis is accelerated to aid cell survival. Thus, over-production of heat shock proteins protects malignantly transformed cells from apoptotic cell death and fosters resistance to chemotherapeutic agents and irradiation. Individual heat shock proteins, such as the 27 kDa (hsp27) and 70 kDa (hsp70) heat shock proteins, their antibodies and/or genotypes of polymorphic genes may have diagnostic and prognostic value for different gynecologic malignancies. The possible exploitation of the properties of heat shock proteins for development of unique anti-cancer therapies in individuals resistant to traditional treatment is currently under active investigation.

Antigens, Neoplasm↗
PubMed2000

IgA antibodies to the 27-kDa heat-shock protein in the genital tracts of women with gynecologic cancers.

Heat-shock proteins promote cell survival under adverse environmental conditions. Synthesis of the 27-kDa (HSP27), 70-kDa (HSP70), and 90-kDa (HSP90) heat-shock proteins is increased in malignantly transformed cells and has been associated with tumor proliferation, metastasis, and resistance to chemotherapeutic agents. The increased expression of heat-shock proteins and their association with tumor-specific antigens may result in local immunity to the heat-shock proteins. We examined the occurrence of IgA antibodies to HSP27, HSP70, and HSP90 in the lower genital tracts of women with possible gynecologic cancers. Cervical samples were obtained from 119 consecutive women being evaluated for a gynecologic malignancy or returning for a follow-up examination following cancer treatment. Aliquots were tested for IgA anti-heat-shock protein antibodies by ELISA. Aliquots were also tested for IgG antibodies to HSP27 as well as for human papillomavirus. Anti-HSP27 IgA was detected in 85.7% of 21 women with endometrial cancer tested prior to diagnosis and in 41.1% of 17 women tested after treatment. In women with ovarian cancer, 77.8% of 9 women tested prior to diagnosis and 75.0% of 24 women evaluated after treatment were anti-HSP27 IgA-positive. Of 6 women with cervical cancer tested prior to diagnosis, 5 were positive for this antibody. None of 25 women with benign diagnoses or 46 healthy women were cervical IgA anti-HSP27-positive (P < 0.0001). In contrast, anti-HSP27 IgG was not associated with a gynecologic malignancy. HSP27 cervical antibodies were not associated with the presence of human papillomavirus. Cervical IgA antibodies to HSP90 were associated with ovarian cancer; antibodies to HSP70 were not cancer-associated. We conclude that cervical IgA antibodies to HSP27 may be indicators of a gynecologic malignancy.

Aged↗
PubMed2000

Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis.

OBJECTIVE: Vulvar vestibulitis is a chronic inflammatory syndrome of unknown cause and pathogenesis. We examined the relation between vulvar vestibulitis and polymorphisms in the gene coding for the interleukin 1 receptor antagonist, a naturally occurring down-regulator of proinflammatory immune responses. STUDY DESIGN: Cells from the lower genital tract of 68 women with vulvar vestibulitis, 343 women with no history of vulvodynia, and 40 women with human papillomavirus cervical infection were tested by polymerase chain reaction for the different alleles of the gene encoding for interleukin 1 receptor antagonist. The presence of human papillomavirus in the specimens was determined by polymerase chain reaction with the use of degenerate consensus primers to the conserved L1 gene. RESULTS: Allele 2 of the gene encoding the interleukin 1 receptor antagonist was present in homozygous form in 52.9% of women with vulvar vestibulitis. In marked contrast only 8. 5% of the control women and 2.5% of women with human papillomavirus were homozygous for this allele (P </=.0001). Among the women with vulvar vestibulitis, 57.5% of those without human papillomavirus, as well as 52.2% of those with human papillomavirus, were homozygous for allele 2 of the gene encoding interleukin 1 receptor antagonist. CONCLUSION: The unique distribution of interleukin 1 receptor antagonist alleles among women with vulvar vestibulitis suggests that polymorphism in this gene may be a factor influencing susceptibility to this syndrome, severity of symptoms, or both.

Alleles↗
PubMed2000

Testing for high-risk human papillomavirus types will become a standard of clinical care.

Testing for high-risk human papillomavirus types should become a standard of care for women in the United States because cervical cancer is an infectious disease. Current care is based on cytologic screening and a pathologic staging of cellular tissue changes. Before these cellular modifications, there is a demonstrable pattern of human papillomavirus infection. Human papillomavirus is the most frequently acquired sexually transmitted disease in women and is usually eliminated without treatment. Persistence of high-risk human papillomavirus types can lead to abnormal cervical cellular changes. When these cervical cellular changes occur, physician interventions hasten human papillomavirus elimination. Currently, adding human papillomavirus screening to the Papanicolaou smear identifies a population for closer follow-up studies. In the future a vaccine should be introduced to prevent infections, and medical treatments to hasten the elimination of high-risk human papillomavirus types should become part of standard medical practice.

Attitude of Health Personnel↗
PubMed2000

Vaginal colonization by Candida in asymptomatic women with and without a history of recurrent vulvovaginal candidiasis.

OBJECTIVE: The asymptomatic carriage of Candida in the vagina of women with a history of recurrent vulvovaginal candidiasis was compared with that of women with no such history. METHODS: Vaginal swabs from 50 women with a history of recurrent vulvovaginal candidiasis and 45 women with one or fewer episodes of candidal vaginitis within the past 12 months were evaluated for Candida by wet mount/Gram stain, culture, and polymerase chain reaction (PCR). All women were asymptomatic for at least 30 days. RESULTS: Candida was identified in 28 women by PCR, in 14 women by culture, and in 13 women by wet mount/Gram stain. Candida was identified by PCR in a similar proportion of patients with previous recurrent vulvovaginal candidiasis (30%) and in controls (28.8%). However, Candida was identified by culture in more women with previous recurrent vulvovaginal candidiasis (22%) than in controls (6.6%, P = .04); it also was identified by wet mount/Gram stain in more women with recurrent vulvovaginal candidiasis (22%) than in controls (4.4%, P = .01). For the recurrent vulvovaginal candidiasis patients, culture and wet mount/Gram stain had a sensitivity of 66.6% compared with PCR. For the controls, the sensitivity of the two former assays relative to PCR was only 15.3%. CONCLUSION: Women with a history of recurrent vulvovaginal candidiasis have more easily detectable Candida in their vagina, even when asymptomatic, than do other women. A relative inefficiency in regulating the proliferation of Candida in the vagina may increase susceptibility to periodic symptomatic recurrences.

Adult↗
PubMed2000

Individual immunity and susceptibility to female genital tract infection.

The responses to genital tract infection vary among different women to a far greater extent than has previously been appreciated. All women are not genetically identical and have not been exposed to identical environments; therefore it is naive to expect that a particular microorganism will elicit the identical response and have the identical sequelae for each infected individual. The genes inherited from one's parents, which contain specific polymorphisms in immune response genes, greatly influence the direction and magnitude of the immune response to microorganisms. Similarly, extrinsic variables, such as the type or quantity of a specific infection, whether there is a coinfection with another microorganism, such as an intracellular parasite, and whether an immediate hypersensitivity response is concurrently induced also determine the nature of the host response and thus the consequences of microbial exposure. Finally, factors such as the frequency of sexual intercourse and previous immune sensitization to spermatozoa or other components of a particular ejaculate also influence the outcome. An increased awareness of the uniqueness of each host will lead to the development of more precise individualized treatments and improvements in combating infectious diseases of the female genital tract.

Chlamydia Infections↗
PubMed2000

Serum antibodies to the 27-kd heat shock protein in women with gynecologic cancers.

OBJECTIVES: Among women the association between heat shock protein immunity and cancer has been examined primarily for breast cancer. Autoantibodies to the 27-kd heat shock protein were detected in some patients with breast cancer but not in control subjects, and the presence of these antibodies was correlated with improved survival. We examined the relationship between autoimmunity to heat shock proteins and the diagnosis of malignancies of the female genital tract. STUDY DESIGN: Serum samples from women seen for possible gynecologic malignancies or returning for evaluation after surgery, radiation, chemotherapy, or a combination for gynecologic cancers were tested for immunoglobulin G antibodies to the 27-kd, 60-kd, 70-kd, and 90-kd heat shock proteins by enzyme-linked immunosorbent assay with the purified recombinant proteins bound to wells of a microtiter plate. Serum samples from women with no history of malignancies served as control preparations. RESULTS: Antibodies to the 27-kd heat shock protein were detected in only 1 of 29 healthy control subjects (3.4%) and 1 of 23 women whose lesions were benign (4.3%). In marked contrast, 39 of 96 women with gynecologic cancers (40.6%) had positive antibody detection (P =.0004 vs benign). The percentages of positive results seen for ovarian (17/34, 50%), endometrial (13/34, 38.2%), cervical and uterine (3/10, 30%), vaginal and vulvar (3/5, 60%), and other (3/13, 23.1%) cancers were not significantly different from each other. Similar prevalences of antibodies to the 27-kd heat shock protein were seen among patients with cancer who had untreated active disease and after treatment. Unlike the results with antibodies to the 27-kd heat shock protein there was no relationship between antibodies to the other heat shock proteins and any gynecologic cancer. CONCLUSION: Circulating autoantibodies to the 27-kd heat shock protein were found to be associated with malignancies of the female genital tract.

Adult↗
PubMed2000

Indomethacin blocks interleukin 1beta-induced myometrial contractions in pregnant rhesus monkeys.

OBJECTIVE: We sought to determine whether blockade of prostaglandin synthesis with indomethacin prevents interleukin 1beta-induced increases in uterine contractions in a nonhuman primate model. STUDY DESIGN: Maternal and fetal vascular catheters, intra-amniotic fluid pressure catheters, and fetal electrocardiographic and myometrial electromyographic electrodes were implanted in 11 rhesus monkeys at 124 +/- 2 days' gestation (term, 167 days). After postsurgical stabilization (136 +/- 2 days) indomethacin 50 mg was administered orally twice daily for 5 days (n = 6). On day 3 human recombinant interleukin 1beta 10 microg was infused into the amniotic cavity over 2 hours. Five days after the last indomethacin dose the study was repeated without indomethacin treatment. Uterine activity was continuously monitored and quantified as the hourly contraction area (millimeters of mercury. seconds per hour) in the experimental group and a control group (n = 5) that received interleukin 1beta alone. At timed intervals amniotic fluid was sampled for leukocyte counts and assayed for prostaglandin E(2) and F(2alpha), the inflammatory cytokines interleukin 1beta, interleukin 6, interleukin 8, tumor necrosis factor alpha, and interleukin 1 receptor antagonist by specific assays. RESULTS: Uterine activity was increased severalfold from baseline after interleukin 1beta infusion alone and in the absence of indomethacin treatment (P <.05). There was no increase in uterine contractility when interleukin 1beta was infused concurrently with indomethacin treatment. Concentrations of amniotic fluid leukocytes and cytokines increased significantly after interleukin 1beta infusion in both the presence and absence of indomethacin. Amniotic fluid prostaglandins E(2) and F(2alpha) were suppressed during indomethacin treatment but rose significantly after interleukin 1beta infusion in the absence of indomethacin. Except for higher interleukin 6, cytokine levels were unaltered by indomethacin. CONCLUSIONS: After interleukin 1beta infusion, indomethacin blocked the development of uterine activity. Amniotic fluid prostaglandins were suppressed by indomethacin treatment, but cytokines and leukocytes were not. These results suggest that prostaglandins or possibly other indomethacin-suppressible compounds stimulate uterine activity after interleukin 1beta infusion in late-gestation rhesus monkeys or that indomethacin has direct tocolytic effects.

Amniotic Fluid↗
PubMed2000

Interleukin-1 levels in the supernatant of conditioned media of embryos grown in autologous endometrial coculture: correlation with outcome after in vitro fertilization.

PROBLEM: To determine if interleukin (IL)-1 produced by autologous endometrial coculture (AECC) was associated with outcome in patients with a history of multiple in vitro fertilization (IVF) failures. METHOD OF STUDY: The conditioned media (CM) from AECC cells exposed or non-exposed to human embryos was analyzed for IL-1. RESULTS: Embryos grown on AECC demonstrated a significant improvement in number of blastomeres and fragmentation (frag) when compared to embryos grown in conventional media without ECC (6.4 +/- 1.3 vs. 5.5 +/- 1.2 blastomeres and 14.6 +/- 9.3%, vs. 18.4 +/- 9.8% frag; P< 0.008 and 0.003, respectively). When IL-1alpha and IL-1beta were undetectable in the CM, the embryos grown in ECC were of improved quality as compared to the embryos grown only in conventional media. Conversely, IL-1ra levels in the CM were positively associated with embryo quality. Exposure or non-exposure to an embryo did not result in differing levels of IL-1alpha, IL-1beta, or IL-1ra in the CM. IL-1beta levels were negatively associated with clinical pregnancy outcome (3.3 pg/mL (pregnant, n = 12) vs. 27.1 pg/mL (not pregnant, n = 17); P = 0.008, Mann Whitney U-test). IL-1alpha and IL-1ra levels were not associated with outcome. CONCLUSIONS: We have demonstrated a significant improvement in blastomere number and frag with ECC. The presence of IL-1beta in the CM was negatively associated with embryonic development and clinical pregnancy. The presence of IL-1alpha in the CM was negatively associated with embryonic development and the presence of IL-1ra in the CM was positively associated with embryonic development. Whether IL-1beta itself interferes with successful outcome after embryo transfer or if it is a marker for undetected endometritis in the biopsy specimens remains to be determined.

Adult↗