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Biomedical subjects

T Strowitzki

Publications and source records attributed to T Strowitzki.

At least 37 records · Page 2Linked to original sources

Decreased suppression of antibody-dependent cellular cytotoxicity by seminal plasma in unexplained infertility.

OBJECTIVE: To determine whether seminal plasma (SP) from unexplained infertile males has different suppressive activity on antibody-dependent cellular cytotoxicity (ADCC) than SP from fertile males or SP from males of couples with known infertility factor. DESIGN: Comparative clinical/experimental study. SETTING: In vitro fertilization program in a university hospital and a hospital research laboratory. PATIENT(S): A total of 245 SP samples from 174 infertile and 16 fertile couples were compared. INTERVENTION(S): SP suppression of ADCC was measured by using human 51chromium-labeled red blood cells (RBC), sensitized with IgG-rabbit-anti-human-RBC as targets and peripheral blood lymphocytes as effector cells. MAIN OUTCOME MEASURE(S): Suppressive activity of each sample was determined by calculating 51Cr-release in the presence and absence of SP. RESULT(S): When analyzed with respect to sperm number, motility, and morphology, suppressive activities of samples with normal semen analyses (n = 142) were significantly higher (x = 37% +/- 14%) than suppressive activities of abnormal samples (n = 103; x = 32% +/- 13%). There was no strong correlation of suppressive activity to other semen parameters. Within the andrologically normal males, SP from the unexplained infertile couples (n = 15) showed significantly lower suppressive activity (x = 24% +/- 11%) compared with the SP from fertile males (n = 16; x = 35% +/- 13%) and from couples with female infertility factor (n = 65; x = 39% +/- 14%). CONCLUSION(S): Loss of suppressive activity is associated with unexplained infertility, even in male patients who previously were considered normal by traditional methods of semen analysis.

Antibody-Dependent Cell Cytotoxicity↗

Endometrial osteopontin, a ligand of beta3-integrin, is maximally expressed around the time of the "implantation window".

OBJECTIVE: To analyze endometrial mRNA and protein expression of osteopontin and its receptor, beta3-integrin, throughout the menstrual cycle. DESIGN: Study by immunohistochemistry, RNase protection assay, and ELISA. SETTING: Academic research unit. PATIENT(S): Forty-five regularly cycling women without endometrial pathology. INTERVENTION(S): Expression of endometrial osteopontin and beta3-integrin mRNA was analyzed by RNase protection assay in endometrium, endometrial epithelial cells, stromal cells, and endometrial leukocytes (CD45) and by immunohistochemistry in frozen sections of endometrium throughout the menstrual cycle. Concentration of osteopontin was studied in uterine secretions by ELISA. MAIN OUTCOME MEASURE(S): mRNA and protein expression of osteopontin and beta3-integrin. RESULT(S): Osteopontin mRNA and protein was weakly expressed in the proliferative phase and maximally expressed in the mid to late secretory phases in endometrium, endometrial epithelial cells, and endometrial leukocytes and in uterine secretions. Beta3-integrin mRNA and protein were expressed in stromal cells throughout the menstrual cycle and were maximally expressed in epithelial cells in the mid to late secretory phases. CONCLUSION(S): Expression of osteopontin and its receptor, beta3-integrin, in human endometrial glands and osteopontin secretion into the uterine cavity around the time of the "implantation window" suggest a role for these proteins in endometrial function and implantation.

Adult↗

Relationship of seminal plasma interleukin (IL) -8 and IL-6 with semen quality.

The concentration of interleukin (IL) -8 and IL-6 was determined in seminal plasma (SP) samples from 137 randomly chosen subfertile males to evaluate the relationship with other potential parameters of subclinical infection/inflammation such as seminal leukocytes, and with semen quality in a prospective study. All patients were asymptomatic for genital tract infection. A comprehensive semen evaluation included sperm analysis, sperm migration testing, antisperm antibody screening, immunocytochemical round cell differentiation to determine seminal leukocytes counts and the leukocyte ratio, complement fraction C(3) (C(3c)) determination, and semen cultures, in aliquots of the same ejaculates. The SP concentration of IL-8 was inversely related to semen quality, e.g. to the total number of motile spermatozoa or to the outcome of the sperm migration test (motile sperm harvested after a swim-up procedure). IL-8 concentrations were significantly correlated with leukocyte counts per ml (P < 0.0001) and per ejaculate (P < 0.0001), and with the leukocyte ratio (P < 0.001). All leukocytospermic samples had high IL-8 concentrations (< or =2 ng/ml). The SP concentration of IL-6 was much lower, but was significantly correlated with IL-8 (P < 0.0001). Both IL-8 and IL-6 were significantly related with the C(3c). No association of interleukin concentrations with the bacterial colonization of semen samples was found. The results indicate a marked relationship of some pro-inflammatory cytokines with semen quality. The significant association with seminal leukocytes and other potential inflammation markers suggests that IL-8 might be used as sensitive marker for silent male genital tract infection.

Adult↗

Synthetic estrogens-mediated activation of JNK intracellular signaling molecule.

Signal transduction pathways regulate the transmission of specific signals to the cells from the surface to the nucleus. Activation of protein kinases such as JNKs (c-jun amino-terminal kinase), a subgroup of the mitogen activated protein kinase (MAPK) family, results in regulation of important cellular functions like cell growth and differentiation. The involvement of estrogens in stimulation of growth of already transformed breast cancer cells in vivo and in vitro accompanied with activation of JNKs prompted us to investigate the role of synthetic estrogens in the regulation of JNK expression. T 47D breast cancer cells were incubated with the synthetic estrogens, ethinylestradiol (10(-9)M) and 17 beta-estradiol valerate (10(-9)M), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen, 17 beta-estradiol (10(-9)M), for 5 minutes. The same experiments were repeated after pretreatment of the cells with ICI 182780 for 24 hours. EGF as well as natural and synthetic estrogens stimulated proliferation. This effect was reversed by the estrogen receptor blocker ICI 182780, but only in the case of both natural and synthetic estrogen. Like 17 beta-estradiol, synthetic estrogens induced a rapid and transient activation of JNK kinase. ICI 182780 blocked this effect, but not that mediated by EGF. Ethinylestradiol used in oral contraceptives, and 17 beta-estradiol and 17 beta-estradiol valerate for hormone replacement therapy, are able to activate JNK. The estrogen receptor is necessary for JNK activation upon estrogen stimulation.

Blotting, Western↗

Expression of glucose transporter 1 in human endometrial and decidual tissue.

Regulation of endometrial glucose transport is important for the decidualization process. Therefore, we have examined the expression of the glucose transporter protein isoform 1 (GLUT1) in endometrial samples during the menstrual cycle and in decidual tissue by immunohistochemistry, and GLUT1 mRNA by RNase protection assays. GLUT1 protein was not detected in proliferative endometrial samples, but was highly expressed in decidual tissue. Placental tissue was highly positive. GLUT1 mRNA could be detected in endometrial samples with an increase in endometria of the late secretory phase (day 25-28) and maximum concentration in the decidua of the 9th-10th week of gestation. Our results show that GLUT1 is differentially expressed in the different phases of the human endometrium with a maximum in the human decidua. Therefore, GLUT1 may be an important marker for endometrial differentiation.

Adult↗

Herpes simplex virus infection of the uterine cervix--relationship with a cervical factor?

OBJECTIVE: To determine the prevalence of genital herpes simplex virus (HSV) in women of reproductive age and to evaluate a potential relation of asymptomatic HSV shedding with a cervical factor. DESIGN: Prospective study. SETTING: Outpatient infertility clinic of a university hospital. PATIENT(S): Randomly chosen asymptomatic women (n = 1,262) with a median age of 30 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of cervical HSV, cervical index parameters, and other variables of CM quality, including CM penetrability in vivo and in vitro. RESULT(S): The prevalence of HSV infection of the uterine cervix was 5.2% (identified with cell culture). There was a tendency toward increased viscosity of the CM in HSV-positive women, but no significant relation with the other variables of CM quality (amount, spinnbarkeit, ferning, cervical appearance, and cellularity of the CM), or with the summarized Insler score or the cervical index according to World Health Organization guidelines. Postcoital testing and the in vitro penetration test, using either partners' or donors' semen, showed that the penetrability of the CM did not differ significantly between women with and without cervical HSV shedding. Asymptomatic cervical HSV infection was not significantly associated with bacterial colonization of the lower genital tract, with leukocyte counts in cervical secretions, with the pH of the CM or the vaginal fluid, or with antisperm antibodies in the CM. CONCLUSION(S): The results suggest that in asymptomatic women under controlled endocrine conditions, cervical HSV infection is not a significant cause of impaired quality and penetrability of the CM.

Adult↗

Antimicrobial activity of human cervical mucus.

The antibacterial activity of human cervical mucus (CM) was examined on standardized microbial colonized agar plates (agar diffusion test). In parallel, the lysozyme content of CM was determined by means of a turbidimetric test system in aliquots of the same CM specimens. Suspensions of living lyophilized Micrococcus lysedeikticus were used as bacterial substrate. Testing was performed in a total of 133 CM samples, obtained at mid-cycle from sexually active women from unselected infertile couples with a median age of 30 (range 21-42) years. All mucus specimens showed considerable antibacterial activity with clearly visible circular inhibition zones around the CM-filled holes in the colonized agar plates. Related to the effect of hen's egg white (HEW)-lysozyme on the same plates, the median activity of the CM specimens in the agar diffusion test was equivalent to 33.0 (range 6.4-391.4) microg/ml HEW-lysozyme. However, there was a wide inter-individual range of antibacterial effects of cervical secretions. The cervical index did not significantly influence the outcome of either test. The pH of the endocervical CM also was not correlated with the antibacterial effect. Sexual activity leading to the presence of spermatozoa in CM considerably increased its antibacterial effect. The activity was markedly higher in samples obtained within hours after intercourse compared with those taken after sexual abstinence of >/=5 days (P < 0.05). In microbially colonized CM specimens compared to sterile CM, all obtained under hormonally standardized conditions, the antibacterial activity in the agar plate test was significantly lower (P < 0.05). The results of this pilot study demonstrate the considerable antibacterial activity of human CM.

Adult↗

Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion.

It is widely assumed that, after ovulation, the human endometrium undergoes specific changes and becomes receptive to the implantation of embryo during the mid-secretory phase. When implantation does not take place, further changes occur which eventually result in the shedding of human endometrium. The present study was carried out to examine whether there are changes in the cytokine gene expression in human endometrium which are correlated with endometrial function in various phases of the menstrual cycle. The RNase protection assay was performed on carefully dated endometria from normal subjects to characterize the expression of cytokines which potentially contribute to endometrial function. These included: tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6, IL-8, leukaemia inhibitory factor (LIF), transforming growth factor beta1 (TGF-beta1), macrophage colony stimulating factor (MCSF or colony stimulating factor-1), and vascular endothelial growth factor (VEGF) mRNAs. A low level of expression of these cytokine mRNAs was found during the proliferative and early secretory phase. Expression of cytokine mRNA increased during the mid-secretory phase and rose to a peak in the late secretory phase. The level of cytokine mRNA expression during gestation was most akin to that observed during the mid-secretory phase. Individuals with habitual abortion presented with an abnormal expression of IL-1beta and IL-6 mRNA in endometrium, during the mid-secretory phase. Taken together, these findings are consistent with a progressive rise in the expression of cytokines in human endometrium during the secretory phase in natural cycles. Furthermore, the findings show that habitual abortion is associated with the abnormal expression of IL-1beta and IL-6 in the mid-secretory phase.

Abortion, Habitual↗

Cycle modulation of insulin-like growth factor-binding protein 1 in human endometrium.

Endometrium is one of the fastest growing human tissues. Sex hormones, estrogen and progesterone, in interaction with several growth factors, control its growth and differentiation. Insulin-like growth factor 1 (IGF-1) interacts with cell surface receptors and also with specific soluble binding proteins. IGF-binding proteins (IGF-BP) have been shown to modulate IGF-1 action. Of six known isoforms, IGF-BP-1 has been characterized as a marker produced by endometrial stromal cells in the late secretory phase and in the decidua. In the current study, IGF-1-BP concentration and affinity in the proliferative and secretory phase of the menstrual cycle were measured. Endometrial samples were from patients of reproductive age with regular menstrual cycles and taking no steroid hormones. Cytosolic fractions were prepared and binding of (125)I-labeled IGF-1 performed. Cross-linking reaction products were analyzed by SDS-polyacrylamide gel electrophoresis (7.5%) followed by autoradiography. (125)I-IGF-1 affinity to cytosolic proteins was not statistically different between the proliferative and secretory endometrium. An approximately 35-kDa binding protein was identified when (125)I-IGF-1 was cross-linked to cytosol proteins. Secretory endometrium had significantly more IGF-1-BP when compared to proliferative endometrium. The specificity of the cross-linking process was evaluated by the addition of 100 nM unlabeled IGF-1 or insulin. Unlabeled IGF-1 totally abolished the radioactivity from the band, indicating specific binding. Insulin had no apparent effect on the intensity of the labeled band. These results suggest that IGF-BP could modulate the action of IGF-1 throughout the menstrual cycle. It would be interesting to study this binding protein in other pathologic conditions of the endometrium such as adenocarcinomas and hyperplasia.

Affinity Labels↗

Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.

This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene (EE/GSD) or 150 micrograms of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.

Adolescent↗

Does growth hormone-releasing factor assist follicular development in poor responder patients undergoing ovarian stimulation for in-vitro fertilization?

Treatment with growth hormone-releasing factor (GRF) has been reported to improve the ovarian response to gonadotrophins in women who respond poorly to ovarian stimulation during in-vitro fertilization (IVF). The efficacy and tolerability of GRF were studied in a randomized, double-blind, placebo-controlled trial involving 196 patients. Following down-regulation with a gonadotrophin-releasing hormone agonist (GnRHa), patients were randomized to receive GRF (500 microg twice daily; n = 96) or placebo (n = 100) in addition to follicle stimulating hormone (FSH); treatment was continued until human chorionic gonadotrophin was given, or for a maximum of 14 days. GRF had no significant effect on the mean number of follicles with a diameter of >/=16 mm (GRF: 3.26 +/- 2.29; placebo: 3.27 +/- 2.30; P = 0.95), the number of FSH ampoules required to achieve ovarian stimulation (GRF: 55.2 +/- 16. 4; placebo: 54.9 +/- 17.2; P = 0.50), or on secondary measures of ovarian response and treatment outcome. There were, however, significant increases in circulating growth hormone (GH) and insulin-like growth factor (IGF)-1 concentrations. GRF was well tolerated. It is concluded that, despite producing significant increases in GH and IGF-1, concomitant treatment with GRF does not improve the ovarian response to FSH in poorly responsive women undergoing IVF.

Adolescent↗

Regulation of TNF-alpha mRNA expression in endometrial cells by TNF-alpha and by oestrogen withdrawal.

During each menstrual cycle, the human endometrium undergoes a series of orchestrated and well controlled changes in anticipation of the arrival of the blastocyst. In the absence of implantation, the endometrium is shed. The underlying basis of the menstrual bleeding is not clear, however, it seems to be related to steroid hormone withdrawal. We showed that tumour necrosis factor-alpha (TNF-alpha) is released by human endometrium and that endometrial epithelial cells are a major source of TNF-alpha mRNA and protein. We show here that TNF-alpha mRNA shows a specific menstrual cycle-dependent expression. The expression of TNF-alpha is mostly minimal throughout the proliferative, early and mid-secretory phases. Expression of TNF-alpha mRNA, however, is increased in the human endometrium in the late secretory phase and during endometrial bleeding. Such a menstrual cycle-dependent expression suggests that specific signals regulate the expression of TNF-alpha mRNA in the human endometrium. In vitro, the expression of TNF-alpha mRNA in endometrial epithelial cells could be regulated by exogenous TNF-alpha. This induced expression was both time- and dose-dependent. In vitro, the TNF-alpha mRNA expression was not altered by oestrogen, progesterone, or both, in the endometrial epithelial cells under conditions that maintain the steroid hormone receptors. However, in vivo, oestrogen withdrawal led to an enhanced expression of TNF-alpha in endometrial epithelial cells. These findings suggest that the up-regulation of TNF-alpha in human endometrium in the late secretory phase may be related to the falling serum oestrogen concentration at the end of the menstrual cycle as well as the potentiating effect of released TNF-alpha on its own mRNA expression.

Adult↗

Low-dose FSH stimulation in polycystic ovary syndrome: comparison of 3 FSH-preparations.

In patients with PCOS low dose administration of follicle stimulating hormone is accepted as a safe treatment modality with low risk for an ovarian hyperstimulation syndrome or a multiple pregnancy. In this study we have retrospectively compared the efficacy of 3 different FSH preparations in low dose protocols-urinary FSH (FSH), highly purified urinary FSH (FSHHP) and recombinant FSH (rec. FSH). A total of 68 PCOS-patients, 36 lean and 32 moderately obese patients, were treated in 116 stimulation cycles. The mean age did not differ between the groups. A mean number of 1.7 cycles per patient was performed. PCOS was diagnosed in all patients by hormonal and sonographic means. Treatment was performed with daily injections of one ampoule FSH from day 3 onwards. Ovulation was induced with 10,000 IU HCG, when the leading follicle exceeded 16 mm in diameter and no more than 3 follicles were seen. The rate of monofollicular cycles was lowest in obese patients after FSHHP stimulation (30%) and after rec. FSH (66.6% in lean and 58.3% in obese patients, respectively). The number of FSH ampoules did not differ significantly between the groups. No severe hyperstimulation syndrome was registered. 21 pregnancies were achieved without significant differences between the different FSH preparations. Besides two abortions and one ectopic implantation, 12 pregnancies were ongoing singleton pregnancies, 3 twin pregnancies and 3 sets of triplets were noted. In conclusion, low-dose stimulation with FSH offers a safe and successful treatment option in patients with PCOS with an acceptable risk for multiple gestations.

Adult↗

Flow cytometric detection and binding studies of human endometrial stromal cell epidermal growth factor receptor in monolayer culture: influence of progesterone.

Epidermal growth factor (EGF) has been shown to modulate endometrial differentiation in vivo and in vitro. Therefore, endometrial stromal cell EGF receptors were characterized in intact endometrial stromal cells, cultured in vitro. The methods used for characterization were flow cytometry, binding and displacement studies, and gel electrophoresis followed by autoradiography. In flow cytometry the histogram of labelled stromal cells was identical to Caski cells, which served as a positive control. EGF binding revealed the typical binding hierarchy for EGF receptors. The Scatchard analysis showed a curvilinear plot with a calculated dissociation constant of 0.36 nM for high affinity binding sites. In autoradiography a band of approximately 170 kDa was visualized corresponding to the known size of the EGF receptor. The intensity of this band was increased by pretreatment of stromal cells with 10 nM progesterone for 4 days. Furthermore, stimulation with progesterone led to an increase in specific EGF binding activity of stromal cells by 21% compared to control. These data indicate that intact stromal cells in monolayer culture maintain specific EGF receptors, which are up-regulated by progesterone.

Adult↗

Increase in serum leptin concentrations in women undergoing controlled ovarian hyperstimulation for assisted reproduction.

The ob gene product might influence the hypothalamo-pituitary axis and ovarian function directly via specific ovarian receptors. Premenopausal women have higher leptin concentrations compared to postmenopausal controls. In this study, we determined changes in leptin serum concentrations under the influence of supraphysiological estradiol levels during controlled ovarian hyperstimulation. In a prospective study of 20 patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), morning blood samples were collected to determine leptin and estradiol concentrations on day 3 and day 9 of the stimulation cycle and on alternate days until ovulation induction. There was a significant increase in serum leptin concentrations from day 3 to day 9 (9.87 +/- 1.5 ng/ml on day 3 and 13.8 +/- 2.1 ng/ml on day 9 respectively). No further increase in leptin was observed until the day of ovulation induction. These data further underline the role of leptin as a hormone of reproduction.

Adult↗

[Hormonal treatment of proximal tubal pathology with the GnRH analogue leuprorelin].

In proximal tubal occlusions (PTO) the microsurgical anastomosis or in case of extensive tubal damage the in vitro-fertilisation (IVF) are the treatment modalities of choice. Aim of our study was to evaluate the effectivity of GnRH-analogues in the treatment of PTO. In 23 patients with repeatedly proven proximal tubal occlusion the GnRH-analogon Leuprorelin was applied for a 3 month period. 20 out of 23 patients completed the entire study including a further tubal patency test. 10 patients showed open tubes on both sides and in 2 cases one oviduct was patent. In 8 patients no effect of the hormonal treatment was found. Following the therapy 4 pregnancies occurred, 2 were located ectopically. Regarding tubal patency we could demonstrate a significant effect of hormonal treatment in proximal tubal occlusions (PTO). However, in respect to the pregnancy rate the results were not satisfactory. Therefore, the hormonal treatment of PTO by GnRH-analogues is limited to certain cases and doesn't represent a standard therapy.

Adult↗