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K M Ataya

Publications and source records attributed to K M Ataya.

At least 19 recordsLinked to original sources
PubMed1996

Gonadotropin-releasing hormone agonist influences absolute levels of lymphocyte subsets in vivo in male mice.

Our earlier studies have demonstrated that gonadotropin-releasing hormone (GnRH) agonists suppress immune system function in female mice. No systematic studies regarding the effect of gender on immune system function following GnRH agonist treatment, however, have been reported. This study, therefore, investigated sequential changes in lymphocyte subsets in 3- and 10-week-old male mice following agonist or placebo administration. Changes in immunophenotypic expression of lymphocytes from thymus, bone marrow, spleen, and blood were analysed at periodic intervals. Upon agonist administration, plasma testosterone levels were significantly increased in pre-pubertal mice, but were significantly decreased in post-pubertal males. Absolute thymic weights, thymocytes and T subsets were significantly increased from the third week regardless of gonadal status. Blood lymphocyte subsets showed a decreasing trend after agonist administration in pre-pubertal males, whereas no differences were observed in post-pubertal males. No significant differences were observed in spleen cells after agonist administration. These studies, together with earlier observations in female mice indicate that GnRH agonist effects on the immune system, are independent of steroid hormone levels. In contrast to suppressive effects in females, GnRH agonist induce no change or ultimately enhanced lymphocyte counts in males, indicating differential effects on the immune system between males and females. This may have important implications for the treatment of various diseases.

Animals↗
PubMed1996

Euprolactinemic Galactorrhea. Response of bioassayable prolactin to thyrotropin-releasing hormone.

OBJECTIVE: To define whether the pathophysiology of euprolactinemic galactorrhea (EuG) involves hyperresponsiveness to thyrotropin-releasing hormone (TRH). STUDY DESIGN: Basal and TRH-induced prolactin (PRL) patterns were examined in women with EuG (n = 7) and compared to those in controls (n = 10) with normal menstrual cycles. PRL activity was measured by radioimmunoassay (RIA) and Nb2 lymphoma cell bioassay (BA). The response of BA-PRL, RIA-PRL, the BA/RIA-PRL ratio and lactogenic activity to TRH given intravenously were studied. RESULTS: The response of RIA-PRL, BA-PRL, lactogenic activity (representing both PRL and growth hormone in the Nb2 lymphoma cell bioassay) and BA/RIA-PRL ratio were not significantly different in EuG as compared to controls. In both groups the combined BA/ RIA-PRL ratio increased at 15 (P = .006), 30 (P = .011), and 90 minutes (P = .022) after TRH injection as compared to zero time. The level of serum progesterone at the time of TRH stimulation did not affect the response of any parameter studied. CONCLUSION: The response of BA-PRL, RIA-PRL and the BA/RIA-PRL ratio to TRH was not significantly different in EuG as compared to controls. The mechanism of EuG did not involve hyperresponsiveness of BA-PRL, RIA-PRL, the BA/RIA-PRL ratio or lactogenic activity to TRH.

Adult↗
PubMed1995

Hematopoietic stem cell antigen-1 (Sca-1) expression in different lymphoid tissues of female mice treated with GnRH agonist.

PROBLEM: Our earlier studies have demonstrated a general suppression of leukocyte maturation upon GnRH agonist treatment in mice and suggested a potential effect at an early stem cell stage of leukocyte development. METHOD: Three-week old Balb/c and C57BL/6 female mice received 50 micrograms injections of Lupron depot or placebo. Sequential changes in Sca-1+ cells in the bone marrow, thymus, blood and spleen were studied by flow cytometry. RESULTS: In bone marrow, the absolute numbers of Sca-1+ cells were significantly decreased at 2 weeks in C57BL/6 mice whereas a decreasing trend was noted in Balb/c mice following agonist administration. Concomitantly, thymocytes expressing Sca-1+ cells were significantly increased at 2 weeks in C57BL/6 mice, but were significantly decreased in Balb/c mice. Significant decreases in Sca-1+ cells were also observed in spleen and blood in Balb/c mice whereas no significant differences were observed in C57BL/6 mice. CONCLUSIONS: These data suggest GnRH agonists affect hematopoietic stem cell development in mice. The effects observed vary with different genetic backgrounds. In Balb/c mice these effects are more pronounced, and appear to result in the inhibition of stem cell maturation. In contrast, GnRH agonist enhances stem cell maturation in C57BL/6 mice.

Animals↗
PubMed1994

Effects of GnRH antagonist on lymphocyte subpopulations in primary and secondary lymphoid tissues of female mice.

PROBLEM: GnRH analogs are playing an increasing role in the treatment of many clinical disorders. Recent studies have indicated that GnRH agonists suppress immune function in mice in vivo. The present study investigated the effects of GnRH antagonist of functional lymphocyte subsets of mice in vivo. METHOD: Three- and 10-wk old female mice received 10 micrograms of Nal-Glu daily for 15 and 30 days; changes in the immunophenotypic expression of lymphocytes from thymus, bone marrow, spleen and blood were analyzed by flow cytometry. RESULTS: The administration of GnRH antagonist to pre- and postpubertal female mice induced slight increases in lymphocyte subpopulations in primary and secondary lymphoid tissues. These effects are opposite those obtained with GnRH agonist in our earlier studies in mice. CONCLUSIONS: Assuming similar effects in humans and rodents, the gonadal steroid suppression achieved by GnRH antagonist treatment has no apparent suppressive effects on the immune system.

Amino Acid Sequence↗
PubMed1993

Alterations in thymic and bone marrow lymphocyte subpopulations in GnRH agonist treated prepubertal female mice.

Complex endocrine relationships exist among the hypothalamus, pituitary, ovaries and thymus. There is also considerable evidence showing gonadotropin releasing hormone (GnRH) involvement in modulating immune system functions. The present study investigated the sequential changes in functional lymphocyte subsets in primary lymphoid tissues of prepubertal female mice in vivo following GnRH agonist treatment in slow release microcapsule formulation. A direct two color immunofluorescence staining followed by flow cytometry was employed. Single i.m injection of agonist significantly decreased both absolute and relative thymic weights and absolute thymocyte counts. No differences, however, were observed in the percentage of thymocytes expressing Thy 1.2, CD4 and CD8. Absolute levels of thymic T cells, CD8 positive cells, immature cells expressing both CD4 and CD8, and immature subsets differentiating toward CD4 were significantly reduced two weeks after agonist treatment. The percentage of bone marrow B cells was also significantly decreased at the second and third weeks following agonist administration. Functional studies to determine in vivo cell-mediated immune function also indicated a significant suppression following agonist administration. These data, together with our earlier observations on secondary lymphoid tissues, suggest a general suppression of lymphocyte maturation at an early stem cell stage of development in prepubertal female mice in vivo.

Animals↗
PubMed1993

GnRH agonist induces suppression of lymphocyte subpopulations in secondary lymphoid tissues of prepubertal female mice.

PROBLEM: Gonadotropin-releasing hormone (GnRH) agonists are playing an increasing role in the medical management of a variety of diseases. Recent evidence also indicates GnRH immune system interactions. METHOD: The present study investigated the sequential changes in lymphocyte subpopulations in secondary lymphoid tissues of prepubertal female mice in vivo following Lupron depot administration. A direct two-color immunofluorescence staining followed by flow cytometric analysis was employed. RESULTS: Following agonist administration, white blood cell counts decreased significantly with decreases in both granulocyte and lymphocyte counts. Blood T-cell and B-cell subsets were also reduced although B cells decreased more markedly. In the spleen, B cells were again reduced more than T cells. There was no selective loss of either CD4 or CD8 subpopulations at any time point, in both spleen and blood. There were no differences in the percentage of lymph node subsets except that B cells decreased in the second week. CONCLUSIONS: These data indicate that GnRH agonist alters specific lymphocyte subpopulations and, therefore, have the potential for affecting immune system function in vivo.

Animals↗
PubMed1993

Urethral stones in women. A case report.

Urethral stones are encountered rarely in the urethra in women. We report the clinical and urodynamic findings and the management of 17 stones in a urethral diverticulum.

Cystoscopy↗
PubMed1992

Effects of oocyte exposure to local anesthetics on in vitro fertilization and embryo development in the mouse.

The effect on fertilization and development of local anesthetics routinely used during ultrasound-guided oocyte retrieval in women undergoing in vitro fertilization was examined in a mouse in vitro fertilization system. Mouse oocytes were exposed in vitro to lidocaine, chloroprocaine, and bupivacaine at concentrations of 0 (control), 0.01, 0.1, 1.0, 10.0, 100.0 micrograms/mL for 30 min, washed, and then inseminated. In vitro oocyte fertilization at 24 and 48 h and embryo development at 72 h were determined. Bupivacaine adversely affected mouse in vitro fertilization and embryo development only at the highest exposure concentration, 100 micrograms/mL, while lidocaine and chloroprocaine produced adverse effects at concentrations as low as 1.0 and 0.1 microgram/mL, respectively. Furthermore, an adverse dose-related effect on fertilization and embryo development was shown for lidocaine and chloroprocaine, but not for bupivacaine. These data demonstrate that the local anesthetics, lidocaine (L), chloroprocaine (C), and bupivacaine (B), adversely affect mouse in vitro fertilization and embryo development in the order of C greater than L greater than B.

Anesthetics, Local↗
PubMed1991

Effect of cyclophosphamide on mouse oocyte in vitro fertilization and cleavage: recovery.

To investigate the mechanism of cyclophosphamide (CTX)-induced ovarian failure, we previously reported that CTX metabolites added in vitro inhibit mouse oocyte fertilization and embryo development. In this study, we injected CTX (100 mg/kg) intraperitoneally in female mice at 0, 1, 4, 14, 18, and 24 h before sacrifice. Mice were superovulated with PMSG and hCG. Oocytes were recovered, washed, and fertilized with sperm obtained from nontreated proven breeders, and incubated for 3 days in 5% CO2 in air. CTX reduced oocyte fertilization and early cleavage rates. To examine the recovery process, CTX was injected at 0, 1, 3, 7, and 14 days before sacrifice. The most pronounced adverse effects on oocyte number and function were observed 1 and 3 days after exposure to CTX. Evidence of partial recovery was observed one week after CTX treatment. The data demonstrate that exposure of oocytes to CTX metabolites in vivo adversely effects oocyte function. This process, however, appears to be partially reversible. The oocytes may be involved in the mechanism of CTX-induced ovarian failure.

Animals↗
PubMed1991

The gonadotropin-releasing hormone agonist leuprolide affects the thymus and other non-reproductive systems of female rats.

To evaluate the effects of a gonadotropin-releasing hormone agonist on non-reproductive systems, we administered [D-Leu6,Des-gly10]-GnRH ethylamide (leuprolide; 5 micrograms/day) for 21 days to female Sprague-Dawley rats. In Experiment 1, continuous infusion (Alzet minipumps sc) was compared to injection. Increased thymus and body weights and decreased estradiol and uterine weights were noted for both administration methods. Spleen weight increased only in rats treated by continuous infusion. Ovary, kidney and liver weights did not change. Only leuprolide-injected rats had elevated LH with decreased corticosterone and ACTH levels, possibly related to the injection process. Glucose, insulin, progesterone, FSH and corticosterone/ACTH were not different. In Experiment 2, intact and ovariectomized rats were implanted with minipumps delivering leuprolide or 0.9% NaCl. Body and thymus weights increased, whereas uterine weight and estradiol declined in both leuprolide-treated and ovariectomized rats. No synergism between leuprolide and ovariectomy was noted. Thymosin alpha 1, but not thymosin beta 4, increased in leuprolide-treated ovariectomized rats. Peripheral white blood cell count was elevated in leuprolide-treated intact rats and ovariectomized rats. In bone marrow, non-nucleated cell count declined in leuprolide-treated intact rats, contributing to the decreased total cell count in this group. Nucleated cell count was unaffected. Therefore, thymus weight gain was accompanied only in some cases by functional changes. Our results demonstrate that leuprolide affects non-reproductive systems, in a similar manner to ovariectomy. We suggest that such alterations may be due to the hypoestrogenic environment produced by leuprolide.

Adrenocorticotropic Hormone↗
PubMed1990

The effect of "activated" cyclophosphamide on human and rat ovarian granulosa cells in vitro.

We investigated the mechanism of cyclophosphamide (CTX) induced ovarian toxicity by studying the effect of an activated form, 4-hydroperoxycyclophosphamide (PCTX), on human and rat granulosa cell function in vitro. In previous experiments we demonstrated that in short-term incubations with rat granulosa cells, high (greater than or equal to 100 micrograms/mL) but not low (less than or equal to 10 micrograms/mL) PCTX concentrations inhibited progesterone accumulation in vitro. In this study, human granulosa cells were obtained from patients undergoing follicle puncture for in vitro fertilization. PCTX at 10, 100, and 500 micrograms/mL, but not at 1 micrograms/mL, resulted in a dose-related reduction in progesterone accumulation in short-term human granulosa cell cultures. Rat granulosa cells were obtained from PMSG-primed immature rats and incubated for 24 h with PCTX concentrations of 1, 5, and 10 micrograms/mL. Ovine LH (10 ng/mL) was added in selected tubes. In comparison to control, progesterone accumulation was significantly reduced by PCTX concentration of 10 micrograms/mL. The above findings demonstrate that cyclophosphamide metabolites, at concentrations achievable in vivo during CTX therapy, decrease rat and human granulosa cell function in vitro. The effect of PCTX on granulosa cells is dependent on PCTX concentration and duration of exposure, as well as the species from which granulosa cells are obtained.

Animals↗
PubMed1990

Vinblastine reduces progesterone and prostaglandin E production by rat granulosa cells in vitro.

To elucidate the possible mechanism(s) of vinblastine-induced premature ovarian failure, we studied the effect of vinblastine (VLB) on progesterone (P) and prostaglandin E (PGE) production by rat granulosa cells in vitro. Granulosa cells obtained from immature, pregnant mares' serum gonadotrophin-primed rats were incubated for 5 h in modified Medium 199 +/- LH (10 ng/mL) with varying concentrations of VLB (0.001 to 10.0 micrograms/mL) and cells plus media were assayed for total P and PGE. VLB reduced production of both basal and LH-stimulated P in granulosa cells, with VLB at a concentration of 0.1 micrograms/mL showing the first significant difference from control. This dose also suppressed basal and LH-stimulated PGE. Granulosa cell survival was similar for all groups. Thus VLB, an agent known to disrupt microtubular function, reduced granulosa cell production of both P and PGE. Our results suggest that at a concentration (0.1 micrograms/mL) lower than that routinely achieved during chemotherapy (0.3 micrograms/mL), VLB depresses rat granulosa cell function in vitro. This system appears to be a valid model for preliminary assessment of the cytotoxic effects of chemotherapy on an ovarian component.

Animals↗
PubMed1989

Effect of cyclophosphamide on the immature rat ovary.

To investigate the early ovarian changes after cyclophosphamide treatment, immature rats primed for 48 h with pregnant mare serum gonadotropin were given injections i.p. of cyclophosphamide (100 mg/kg) at 1, 2, 4, 16, and 24 h before decapitation. Serum estradiol dropped significantly after 24 h of exposure to cyclophosphamide (P less than 0.001). Following 16 and 24 h of cyclophosphamide exposure, (a) the number of granulosa cells expressed from each ovary decreased (P less than 0.05 and P less than 0.01, respectively); (b) the number of nucleated bone marrow cells decreased (P less than 0.01 and P less than 0.01), and their median nuclear size was significantly reduced (P less than 0.05 and P less than 0.05) as measured by Coulter Counter and C-256 channelyzer (Hialeah, FL); and (c) the mean follicular diameter and the number of follicles with diameters greater than 300 microns were significantly lower than in control. After 4, 16, and 24 h of exposure, median granulosa cell nuclear size significantly increased (P less than 0.05, P less than 0.01, and P less than 0.01, respectively). DNA cross-links in granulosa cells, measured by alkaline elution, reached a maximum at 2 h of exposure and decreased thereafter. The above findings demonstrate that cyclophosphamide has significant effects on the rat ovary structure and function and that the granulosa cell is an important target of cyclophosphamide-induced ovarian toxicity.

Animals↗
PubMed1989

Effect of GnRH agonists on the thymus in female rats.

The potential clinical applications of GnRH agonists are growing. We studied the effects of two GnRH agonists on the adult female rat thymus in 4 experiments. GnRH agonists administered sc and continuously significantly increased wet and dry thymic weights (absolute and relative). Thymic enlargement was related to the duration of treatment with GnRH agonists. The maximum increase in thymic weight occurred at approximately 18 days following initiation of treatment with GnRH agonists. Thymic enlargement does not appear to involve enhanced mitotic activity as measured by incorporation of tritiated thymidine into thymic tissue and thymic DNA. Histologic examination and computer-assisted morphometric analysis of thymuses indicated an increase in cortex to medulla ratio most pronounced at 10 and 18 days of GnRH agonist treatment. No consistent increases in splenic weight or bone marrow cell counts were observed. Thymosin alpha-1 but not thymosin beta-4 increased in GnRH agonist-treated rats. Thymic weight correlated negatively with ovarian and uterine weights, relative adrenal weight, serum estradiol, LH, and positively with thymosin alpha-1. Exogenous estrogen administration reversed GnRH agonist-induced thymic weight increase. Whether GnRH agonists have direct thymic effects remains to be determined.

Animals↗
PubMed1989

Postabortal paracervical abscess as a complication of paracervical block anesthesia. A case report.

A paracervical abscess occurred after paracervical block anesthesia was administered for induced abortion in an 18-year-old multigravida. She presented with vaginal, low abdominal and low back pain and with nausea, vomiting, chills and fever. Incision and drainage of the abscess were performed and a vaginal drain inserted under antibiotic coverage. Cultures of the abscess contents revealed multiple anaerobic organisms. Laparoscopy showed normal pelvic organs, and the peritoneal fluid cultures were negative. Postoperatively the patient became afebrile and was discharged after three days on antibiotics. To our knowledge, this case report is the first one on paracervical abscess as a complication of induced abortion with paracervical block anesthesia.

Abortion, Induced↗
PubMed1988

Inhibition of rat ovarian [3H]thymidine uptake by luteinizing hormone-releasing hormone agonists: a possible mechanism for preventing damage by cytotoxic agents.

To investigate the mechanism involved in luteinizing hormone-releasing hormone (LHRH) agonists' protective effects against chemotherapy-induced ovarian damage, female rats were either implanted with 1-mg pellets of LHRH agonist Zoladex (LHRHz) or sham operated. All rats were implanted with osmotic minipumps loaded with [3H]thymidine 48 h before sacrifice in diestrus. Ovaries were combusted in a biological material oxidizer. Tritiated water was recovered in a special cocktail, and ovarian tritiated thymidine uptake (3HTU) was calculated. In five experiments, LHRHz significantly reduced ovarian 3HTU. This was observed 5 days after implanting LHRHz pellets. Ovarian 3HTU correlated significantly with serum estradiol, LH, and ovarian and uterine weights. Autoradiography showed that almost all ovarian 3HTU is by granulosa cells. These data suggest that LHRHz suppresses ovarian mitotic activity. Since cytotoxic agents preferentially destroy rapidly dividing cells, our findings may represent a mechanism for ovarian protection.

Animals↗
PubMed1988

The effect of "activated" cyclophosphamide on rat granulosa cells in vitro.

We investigated the mechanism of cyclophosphamide (CTX)-induced ovarian toxicity by studying the effect of an activated form, 4-hydroperoxycyclophosphamide (PCTX), on rat granulosa cells in vitro. Cells were obtained from PMSG-primed immature rats and incubated with PCTX at concentrations of 1, 10, 100, and 500 micrograms/mL. Ovine LH (10 ng/mL) was added in selected tubes. Cell viability before and after seven hours incubation was determined. Progesterone and prostaglandin E accumulation were measured by radioimmunoassay. Granulosa cell viability was significantly decreased at PCTX concentrations of 10 micrograms/mL or higher in a dose-related manner. PCTX at concentrations of 100 micrograms/mL and 500 micrograms/mL significantly decreased basal and LH-induced progesterone and prostaglandin E accumulation. The above findings demonstrate that cyclophosphamide metabolites decrease granulosa cell survival and function in vitro. These direct effects suggest a possible mechanism for CTX-induced premature ovarian failure.

Animals↗