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Biomedical subjects

R S Mathur

Publications and source records attributed to R S Mathur.

At least 19 recordsLinked to original sources
PubMed2003

Serum IGF-1 concentrations following pituitary desensitization do not predict the ovarian response to gonadotrophin stimulation prior to IVF.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is known to play a role in ovarian follicular development augmenting the action of FSH. Low intrafollicular concentrations have been detected in women who respond poorly to gonadotrophins. This study addresses the relationship between serum IGF-1 levels following pituitary desensitization and ovarian response to gonadotrophin stimulation. METHODS: This is a case-control study of 78 patients undergoing IVF-embryo transfer treatment. Thirty-nine strictly-defined poor responder patients requiring 50 or more ampoules (75 IU FSH) to reach oocyte retrieval were compared with 39 age-matched normal responders, requiring fewer than 50 ampoules. IGF-1 concentrations were determined by extraction radioimmunoassay on serum samples obtained after pituitary desensitization but prior to gonadotrophin stimulation. RESULTS: Despite highly significant differences in measures of ovarian response between groups, the mean serum IGF-1 concentration was not statistically significantly different between poor and normal responders [(31.5 nmol/l [95% confidence interval (CI) 28.5-34.5] versus 34.5 nmol/l (95% CI 31.8-37.2)] respectively. No correlation between oocyte number or total gonadotrophin used and serum IGF-1 concentration was observed. CONCLUSION: Whilst IGF-1 influences ovarian follicular development this study suggests that serum IGF-1 does not predict ovarian response and does not differentiate between critically-defined poor and normal responders.

Adult↗
PubMed2002

Effect of adrenalectomy on rat epididymidis.

AIM: To investigate the effect of adrenalectomy (ADX) on the epididymidis of Sprague-Dawley rats. METHODS: The histological, biochemical (cholesterol protein, zinc, copper, alkaline and acid phosphatase aryl sulphatase, lactic dehydrogenase and leucine amino peptidase) and hormonal (FSH, LH and testosterone) changes of caput and cauda epididymis in ADX rats were observed. RESULTS: Organ wet weight, histological studies and morphometric measurements indicated a cellular degeneration in caput and cauda epididymis of ADX rats. Serum testosterone level was significantly lower in ADX than in sham-operated rats, while the serum FSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham-operated rats. Epididymal zinc level increased whereas copper level decreased in ADX rats compared to the sham-operated. CONCLUSION: Adrenalectomy leads to degeneration of caput and cauda epididymidis epithelial cells as a result of decreased supply of testosterone.

Acid Phosphatase↗
PubMed2001

Human papilloma virus (HPV)-E6/E7 and epidermal growth factor receptor (EGF-R) protein levels in cervical cancer and cervical intraepithelial neoplasia (CIN).

BACKGROUND: About 90% of cervical cancers and advanced cervical intraepithelial neoplasia (CIN II/III) are squamous epithelial cells with mRNA for human papillomavirus (HPV)16 and 18 and up-regulated epidermal growth factor receptor (EGF-R). Since presence of proteins rather than mRNA may be truly indicative of active infection or disease progression, establishing reliable methods for quantifying these proteins in cervical biopsies is important. METHOD: We have established an objective semi-quantitative immunofluorescent antibody assay to reliably assess the levels of HPV-E6/E7 and EGF-R proteins in the cervical biopsies from 12 normal women, five women with CIN I, 15 with CIN II/III and ten with cervical cancer. RESULTS: HPV-E6/E7 and EGF-R, when present, were specific to para-basal, basal and squamous epithelial cells (negative in stromal cells). Nine of ten women with cervical cancer and 15 (14 CIN II/III; 1 CIN I) of 20 women with CIN were positive for HPV-E6/E7. All 12 controls were HPV-negative. The controls and six women with CIN (four with CIN I) negative for HPV had low levels of EGF-R. The only exception was one woman with cervical cancer negative for HPV, with high levels of EGF-R. Levels of HPV-E6/E7 and EGF-R were significantly higher (P < 0.001 vs. controls) in women with advanced CIN II and III (P< 0.05 vs. controls in CIN I) and cervical cancer. The HPV-E6/E7 and EGF-R levels correlated significantly (r = 18.98; P < 0.001, by linear regression analysis). CONCLUSION: We have established a highly specific and sensitive semi-quantitative immunofluorescent antibody assay for measuring levels of HPV-E6/E7 proteins and EGF-R in archival cervical biopsies. Our data suggest an association between HPV-E6/E7 and EGF-R.

Carcinoma, Squamous Cell↗
PubMed2001

Effect of adrenalectomy and hydrocortisone on ventral prostate of rats.

AIM: To study the effects of adrenalectomy and hydrocortisone on the ventral prostate of SD rats. METHODS: In adrenalectomised (ADX) and ADX + hydrocortisone (1, 2, or 4 mg) treated rats, the prostatic histology and the cholesterol, protein, zinc, and copper levels and the enzymic profile (acid phosphatase, alkaline phosphatase, aryl sulphatase, lactic dehydrogenase, and leucine aminopeptidase) in the prostatic tissue were determined; the serum hormonal profile (testosterone, FSH and LH) was also assayed. RESULTS: Adrenalectomy caused a progressive degeneration in prostatic structure that was not reversed by hydrocortisone treatment. The serum testosterone were significantly lower in ADX than in sham operated rats and lower in ADX + hydrocortisone than in ADX-C rats (P < 0. 01). The serum FSH and LH were below the detection limit of 1 mIU/mL. The enzymatic activity was higher in ADX than in sham operated rats and higher in ADX + hydrocortisone than in ADX-C rats (P < 0.05-0.01). The prostatic zinc levels were significantly higher in sham operated than in ADX, and higher in ADX-C than in ADX + hydrocortisone rats (P < 0.05-0.01). The prostatic copper level was significantly lower in sham operated than in ADX, and lower in ADX-C than in the ADX + hydrocortisone rats (P < 0.01). CONCLUSION: In rats, adrenalectomy leads to pathological and functional changes of the prostate. Hydrocortisone treatment at the doses employed did not reverse these changes.

Adrenalectomy↗
PubMed2000

Distinction between early and late ovarian hyperstimulation syndrome.

OBJECTIVE: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. DESIGN: Prospective observational study. SETTING: University assisted conception service. PATIENT(S): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E(2)) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. RESULT(S): Women with early OHSS had significantly higher serum E(2) levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E(2) and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. CONCLUSION(S): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

Adult↗
PubMed2000

Periovulatory human oocytes, cumulus cells, and ovarian leukocytes express type 1 but not type 2 11beta-hydroxysteroid dehydrogenase RNA.

OBJECTIVE: To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11beta-hydroxysteroid dehydrogenase (HSD) messenger (m)RNA transcripts in oocytes; cumulus cells; granulosa cells; and CD45(+), CD15(+) leukocytes was assessed semiquantitatively. DESIGN: Controlled study using semiquantitative assessment of 11beta-HSD mRNA. SETTING: University IVF center. PATIENT(S): Twenty-six patients undergoing controlled ovarian hyperstimulation for assisted conception. INTERVENTION(S): Metaphase II oocytes; cumulus cells; granulosa cells, and CD45(+), CD15(+) leukocytes from individual follicular fluid aspirates. MAIN OUTCOME MEASURES: Semiquantitative analysis of PCR products after total RNA extraction and complementary DNA synthesis. RESULT(S): Periovulatory human oocytes; cumulus cells; CD45(+), CD15(+) leukocytes; and granulosa cells consistently express type 1 but not type 2 11beta-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11beta-HSD mRNA expression varies considerably in all cell types and among individual follicles and patients. CONCLUSION(S): These studies of mRNA expression suggest that the enzymes present both in and around the periovulatory oocyte will favor a high-cortisol environment.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF.

PROBLEM: Over-expression of epidermal growth factor-receptors (EGF-R) has been described in a variety of cancers, including cervical cancer. Nicotine may increase cellular proliferation rates through a mechanism involving EGF or EGF-R. In this study, we ascertain the effect of EGF antibodies on nicotine-enhanced proliferation rates in two cervical cancer cell lines. METHOD OF STUDY: We studied (a) nicotine-induced increase in the cellular expression of EGF-R in human papillomavirus (HPV)-positive ME-180 and HPV-negative HT-3 cervical cancer cell line cultures, using a semi-quantitative immunofluorescent antibody assay; (b) alterations in cellular proliferation in association with changes in EGF-R levels; and (c) the EGF-R mediation by EGF. RESULTS: Nicotine exposure at physiologically attainable plasma concentrations caused increased expression of EGF-R in both cervical cancer cell lines. Up-regulation of EGF-R was associated with increased cellular proliferation. Decreased expression of EGF-R was associated with decreased cellular proliferation. These data were consistent with EGF-R expression as a mechanism for the control of proliferation of the cervical cancer cells. The action of nicotine was abrogated when antibodies to EGF were added, implying that nicotine up-regulation of EGF-R may be mediated by EGF. CONCLUSIONS: Our data show that nicotine-induced proliferation of cervical cancer cells is mediated through EGF-R over-expression and that this action of nicotine utilizes EGF.

Cell Division↗
PubMed2000

Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer.

PROBLEM: To ascertain if cervical epithelial epidermal growth factor receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer. METHOD OF STUDY: We tested cervical biopsies obtained from 18 controls, 3 women with cervical intraepithelial neoplasia (CIN) I, 17 women with CIN II and III, and 12 women with cervical cancer for EGF-R using a quantitative immunofluorescent antibody assay. We measured serum IGF-II levels using an enzyme-linked immunosorbent assay in 20 controls, 26 CIN patients, 12 with cervical cancer before therapy, 5 with cervical cancer for < 1 year, and 9 others > 1 year after therapy. RESULTS: The levels of cervical EGF-R in women with CIN and cervical cancer were significantly higher (P<0.05 for CIN I; P<0.001 for patients with CIN II and III or cervical cancer) than in controls. Women with cervical cancer (P<0.001 vs. controls) or advanced CIN (P = 0.03) had elevated levels of serum IGF-II, while the women with CIN I had levels similar to controls. Women with cervical cancer in the post-therapy period had significantly lower serum IGF-II levels than the women with cervical cancer before therapy (P<0.001). CONCLUSION: Cervical epithelial EGF-R and serum IGF-II levels may be used for the diagnosis and prognosis of cervical cancer.

Biomarkers, Tumor↗
PubMed1999

Effect of hemodialysis on serum progesterone level in pregnant women.

The objective of this study is to evaluate the effect of chronic hemodialysis on serum progesterone level in pregnancy. Serum progesterone levels were measured predialysis and postdialysis using the radioimmunoassay technique in seven gravid women with renal failure requiring hemodialysis. Uterine contractions were measured before and after hemodialysis using home uterine activity monitoring (HUAM) in two patients. Thirty-three paired serum samples were obtained between 14 and 39 weeks' gestation. The mean change in serum progesterone level postdialysis throughout pregnancy ranged from -52.0% to +8.7% for each individual patient. The change in serum progesterone level was unrelated to gestational age. The woman experiencing the most significant decrease in serum progesterone level with dialysis continued her pregnancy to greater than 39 weeks. No significant increase in uterine contraction frequency was noted on HUAM postdialysis (P = 0.22), although both monitored patients experienced a small increase in serum progesterone levels. In conclusion, serum progesterone values showed a variable patient-specific response when measured predialysis and postdialysis in pregnancies complicated by renal failure. There was no significant increase in uterine activity noted postdialysis. Progesterone withdrawal does not appear to explain the increased frequency of preterm delivery in women after dialysis.

Female↗
PubMed1998

Presence of platelet-activating factor in squirrel monkey (Saimiri boliviensis) spermatozoa: seasonal differences.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphoryl-choline) (PAF) is a potent signaling phospholipid which has pleiotropic biological properties in addition to platelet activation. PAF has been detected in the spermatozoa in a number of species. The concentration of PAF is inversely related to human spermatozoa quality. There are no reports on the presence of PAF in nonhuman primate spermatozoa. Therefore, the primary objective of this study was to determine if PAF is present in the spermatozoa from the squirrel monkey (which is a seasonal breeder). A second objective was to determine if PAF levels change from the breeding to the nonbreeding season. Endogenous lipids were extracted from mature Bolivian squirrel monkeys (Saimiri boliviensis) spermatozoa and assayed for the presence of PAF by [125I] radioimmunoassay. PAF was detected in all samples assayed. PAF levels were significantly higher (P < 0.01) during the breeding season (mean: 3.58 ng/10(6) spermatozoa) than the nonbreeding season (mean: 0.76 ng/10(6) spermatozoa). The data demonstrate that PAF is present in squirrel monkey spermatozoa, with higher levels found during the breeding season. Additional studies are warranted to elucidate the role of PAF in spermatozoa function.

Animals↗
PubMed1998

Diagnostic role of Mantoux test site biopsy in neurosarcoidosis.

We discuss a patient with sarcoidosis presenting with cranial neuropathy and a cerebral mass lesion evident on imaging. Also, we review from the literature six patients with sarcoidosis presenting with cerebral mass lesion. We emphasize the diagnostic role of Mantoux test site biopsy in patients with dominant or isolated neurologic presentation because the involved sites are not easily accessible and Kveim's test antigen is not commercially available.

Biopsy↗
PubMed1998

Zinc, copper and hydrolytic enzymes in epididymis of hydrocortisone treated rat.

Administration of glucocorticoid (1, 2 and 4 mg) in excess leads to degeneration of epididymides as supported by cellular degeneration, sperm density and morphometric measurements. Zinc level increased statistically after 1, 2 and 4 mg hydrocortisone treatment while copper increased after 1 and 2 mg treatment. Cholesterol, protein and leucine aminopeptidase levels increased and decreased significantly in caput and cauda respectively. Activity of alkaline phosphatase reduced significantly while the treatment of hydrocortisone at different doses elevated acid phosphatase, aryl sulphatase and lactate dehydrogenase activities. Evidently, these changes are as a result of onset of cellular degeneration leading to impairment of metabolic/secretory activity of epididymal cells. The possible involvement of pituitary-testis axis in hydrocortisone induced epididymal degeneration and functional inhibition has been discussed.

Acid Phosphatase↗
PubMed1997

Intrauterine insemination: is it an effective treatment for male factor infertility?

Results were collected from 11 studies comparing intrauterine insemination (IUI) with intracervical insemination (ICI) of frozen donor semen, 10 studies comparing IUI with timed natural intercourse (NI) or ICI in couples with semen defects and seven studies comparing ICI with NI or ICI in couples with unexplained infertility. IUI significantly increased the pregnancy rate relative to favourably timed ICI in donor insemination (DI) with frozen semen both with and without gonadotrophin stimulation of the female partner (odds ratios (95% confidence interval) 1.92 (1.02-3.61) and 2.63 (1.52-4.54) respectively). The benefit of IUI tended to be less when the pregnancy rate for ICI was high and IUI had no benefit with fresh donor semen. Overall IUI was of significant benefit in the male factor couples compared with NI-ICI (odds ratio 2.20 (1.43-3.39) and the advantage appeared to be maintained when comparison was confined to properly timed ICI although the odds ratios were not significantly greater than 1. IUI had no benefit relative to favourably timed NI-ICI for couples with unexplained infertility; an apparent advantage overall was produced by studies where NI was late. None of the studies on male factor used a sperm function test to define male subfertility and three only included couples with good mucus penetration by sperm. The range of semen defects defined was such that many couples would have had a good chance of conceiving naturally given a normal female partner but nevertheless the overall pregnancy rate (4.8%) was considerably less than in the unexplained group (11.6%), suggesting that some sperm dysfunction was present. We conclude that the available evidence suggests that IUI is valuable for DI with cryopreserved semen and for couples with mild to moderately impaired semen quality and postulate that it overcomes failure to fertilize due to impaired mucus penetration and poor survival in the female reproductive tract.

Cryopreservation↗
PubMed1997

The possible role of the immune system in the aetiopathogenesis of ovarian hyperstimulation syndrome.

This review examines recent evidence suggesting a role for the immune system, in particular cytokines, in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Ovarian tissue is known to contain cells capable of producing a range of immunological mediators and the concentrations of these have been shown to be elevated in serum and ascitic fluid from women with established OHSS. Available evidence points to a role for vascular endothelial growth factor and interleukin-2, possibly acting through other intermediary cytokines, in the pathogenesis of OHSS. However, each individual has a unique cytokine profile and several cytokines may share biological actions, making it difficult to interpret data on isolated cytokine concentrations from relatively small numbers of patients. Improved understanding of the role of the immune system in the development of OHSS may have implications for the prediction, prevention and management of this iatrogenic condition.

Cytokines↗
PubMed1997

Gender-related differences in androgen regulation of thromboxane A2 receptors in rat aortic smooth-muscle cells.

Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. Aortas obtained from male rats are more sensitive to TXA2 mimetics compared with those obtained from females. A similar phenomenon has been reported in canine coronary arteries. To determine whether there is a gender-related difference in the regulation of TXA2 receptors by androgenic steroids, we determined the effect of testosterone and dihydrotestosterone (DHT) on TXA2 receptor density in cultured rat aortic smooth-muscle (RASM) cells and guinea pig coronary artery smooth-muscle (CASM) cells. TXA2 receptor density (B(max)) and dissociation constant (Kd) were determined by radioligand binding studies with (125)I-BOP, a TXA2 receptor agonist. Testosterone significantly (p < 0.05) increased TXA2 receptor density in cultured RASM cells and guinea pig CASM cells. DHT significantly (p < 0.005) increased the B(max) in male RASM cells (62 +/- 2 vs. 40 +/- 3 fmol/mg protein; n = 7; p < 0.005). DHT increased the B(max) values in both male and female RASM cells, but the increase was significantly (p < 0.05) less in female than in male RASM cells (57 +/- 10% increase for male and 31 +/- 5% for female). Androgen-receptor protein was detected in RASM cells by Western blot and was less in the female RASM cells than in the male. The results indicate that RASM cells possess an androgen receptor and that gender-related differences exist in the regulation of expression of TXA2 receptors by androgens.

Androgens↗