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Biomedical subjects

L Kiesel

Publications and source records attributed to L Kiesel.

At least 19 recordsLinked to original sources
PubMed2001

Increased microvessel density in adenomyosis uteri.

OBJECTIVE: To investigate microvessel density in adenomyosis compared to the endometrium in patients with adenomyosis and in normal controls. DESIGN: Uterine paraffin-embedded histologic specimens were immunostained for CD34. The area with the highest microvessel density in adenomyosis and in the endometrium was evaluated. All microvessels in a specific field of view (x200 magnification) were counted. SETTING: The Department of Gynecological Endocrinology and the Institute of Clinical Pathology, Department of Gynecopathology, in an university hospital. PATIENT(S): Specimens of 53 patients with adenomyosis, who had undergone hysterectomy. Endometrial specimens of 17 women without uterine pathology were investigated as normal controls. MAIN OUTCOME MEASURE(S): Microvessel density in adenomyosis and in the endometrium. RESULT(S): The mean microvessel density was significantly higher in adenomyosis than in the endometrium of the same patients (33.5 +/- 14.6 vs. 19.5 +/- 12.5 microvessels/field; P<.001 sign test). No significant difference between the endometrium of patients and of normal controls was observed (P=.805). CONCLUSION(S): Adenomyosis exhibits angiogenic properties. However, the endometrium of patients with adenomyosis is not more prone to express angiogenic activity compared to the endometrium of normal controls.

Adult↗
PubMed2001

[Clinical experience with large-core needle biopsies of the breast and evaluation of histopathology].

OBJECTIVE: Interventional techniques allow a microinvasive diagnostic of breast lesions. We examined the reliability of large core needle biopsies for histologic diagnosis on breast lesions. MATERIAL AND METHODS: 143 ultrasound guided automated spring gun biopsies and 16 stereotactic guided vacuum-assisted device biopsies were analyzed. Indications included confirmation of malign or benign lesions and diagnosis of suspicious lesions. RESULTS: In 113 biopsies (71%) an invasive breast carcinoma was diagnosed, in 5 biopsies (3%) in situ/atypical lesions were seen and 38 cases (24%) showed benign lesions. Based on the bioptic results, 108 patients underwent subsequent surgery. An identical histology was seen in 100/108 patients (93%), 5 biopsies were false negative (5%) and 3 specimens yielded necrotic/insufficient material. The immunohistochemical results of percutaneous biopsies and surgical specimens were comparable. 17 out of 113 patients (15%) with biopsy proven carcinoma were treated with neoadjuvant therapy. 32/38 patients with benign lesions were follow-up clinically. CONCLUSION: Ultrasound- or stereotactic guided percutaneous biopsies are methods to confirm histological diagnosis. Based on the biopsy results the, number of surgical excisions can be reduced and treatment of biopsy proven carcinoma can be improved by individual presurgical planing.

Biomarkers, Tumor↗
PubMed2001

Regulation of estrogen receptor alpha and progesterone receptor (isoform A and B) expression in cultured human endometrial cells.

The effects of RU 486 together with estradiol and progesterone on estrogen receptor alpha and progesterone receptor (isoforms A and B) expression were studied in human endometrial long term cultures at the mRNA and protein level. We asked whether ligand induced receptor regulation, found in mammals in vivo, is also found in human cultured endometrial cells with special regard to the progesterone isoforms A and B. Endometrial cultures were maintained for 27 days. Media were supplemented with progesterone and/or estradiol alone or in combination with RU 486. Receptor expression (estrogen receptor alpha and progesterone receptor isoform A and B) was examined at the mRNA level by RT-PCR and at the protein level by western blot analysis. All receptor types examined were expressed in our culture model. Estradiol led to a general increase of receptor expression whereas treatment with estradiol in combination with progesterone down regulated receptor expression. The receptor down regulation was not found when RU 486 was additionally supplemented into the medium. Activation or inhibition of expression due to these treatments was similar for both PR isoforms. Our results (1) show that in our culture system estradiol induced up regulation of estrogen receptor and progesterone receptor A and B and suggest that the estrogen induced up regulation is prevented by progesterone (2) a clear cut antigestagenic effect of RU 486 and (3) suggest that both progesterone isoforms are analogously regulated in our culture model. We conclude that human endometrial cell cultures are suitable for the study of the dynamics of steroid receptor expression.

Blotting, Western↗
PubMed2001

Chemokine bioactivity of RANTES in endometriotic and normal endometrial stromal cells and peritoneal fluid.

Endometriotic lesions secrete chemokines that recruit immune cells into the peritoneal cavity. The accumulation of these immune cells, especially activated macrophages and T lymphocytes, is thought to mediate inflammatory symptoms associated with endometriosis. Previous studies have demonstrated that RANTES (regulated on activation, normal T cell expressed and secreted) is synthesized by endometriotic stromal cells and circulates in peritoneal fluid, commensurate with the stage of endometriosis. In the current studies, we used the human monocytic cell line, U937, to assay chemotactic activity in cell culture conditioned media and peritoneal fluid from patients with endometriosis and normal controls. We demonstrated expression of the human RANTES receptors CCR-1 and CCR-5 in U937 cells and peritoneal macrophages. Over a range of 0-1000 pg/ml recombinant human RANTES had a direct, linear effect on monocyte migration. Conditioned media and peritoneal fluid induced dose-dependent effects on monocyte migration that were correlated with concentrations of immunoreactive RANTES (as measured by enzyme-linked immunosorbent assay) and the severity of endometriosis. Heat denaturation of the RANTES protein or addition of anti-human RANTES antibodies neutralized the chemoattractant effects of conditioned media and peritoneal fluid. RANTES stimulation of monocyte recruitment may be an important pathogenetic target for the treatment of infertility and pain associated with endometriosis.

Ascitic Fluid↗
PubMed2001

Kallmann's syndrome: pregnancy through intracytoplasmic sperm injection and complicated by gestational diabetes.

Kallmann's syndrome is characterized by hypogonadotropic hypogonadism and anosmia. Assisted reproductive techniques such as intracytoplasmic sperm injection (ICSI) may be required to treat the infertile couple with oligozoospermia. Rare complications have been described in patients with Kallmann's syndrome, but gestational diabetes has not previously been reported. A case of Kallmann's syndrome with infertility is reported. Ovulation was successfully induced by human menopausal gonadotropin therapy, but pregnancy could not be achieved by artificial insemination or by conventional in vitro fertilization, although the husband had only moderate oligozoospermia. A high fertilization rate of the retrieved oocytes and successful pregnancy was achieved by ICSI. The pregnancy was complicated by gestational diabetes that was managed by insulin therapy. Successful ovulation induction in Kallmann's syndrome is not rare, but ICSI may be needed in selected cases. Some recent data have suggested that diabetes may occur in patients with Kallmann's syndrome, but further investigation is needed to establish whether gestational diabetes is associated with Kallmann's syndrome or is purely coincidental.

Adult↗
PubMed2000

Inhibition of proliferation and differentiation by RU 486 in human endometrial stromal and epithelial cells in vitro.

The effects of progesterone and RU 486 on cellular proliferation and differentiation in long term cultures of mixed human endometrial cells were studied. The endometrial tissue was obtained from women with normal menstrual cycles who were undergoing hysterectomy for benign growths. Estradiol supplemented cultures were treated with progesterone and/or RU 486 for 27 days. Cell number was measured by crystal violet assay, and prolactin secretion was used as a marker of differentiation. Progesterone doubled the rate of proliferation, but the addition of RU 486 reduced it to baseline again. The gestagen increased prolactin secretion up to 30 times, while the addition of RU 486 suppressed it to baseline levels. When administered to cells that were pretreated with progesterone for 15 days RU 486 abolished the progesterone effects. RU 486 alone was without any effect. Our results indicate that (1) in vitro progesterone is essential for the initiation and maintenance of proliferation and differentiation of endometrial cells and (2) RU 486 acts as a pure progesterone antagonist in our culture model.

Cell Differentiation↗
PubMed2000

Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis.

Our laboratories have focused recently on the production and localization of eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the chemoattraction of eosinophils. Given evidence of autoimmune activity in the endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be expressed in endometriosis. In histological sections, we observed eotaxin protein localized mainly in epithelial cells, with only very faint immunostaining in the surrounding stromal cells. Prominent eotaxin accumulation was noted in the luminal epithelium of secretory endometrium. Eotaxin distribution in endometriosis was similar to that seen in eutopic endometrium but with higher levels of eotaxin staining in the glandular epithelium. Peritoneal fluid concentrations of eotaxin were significantly higher in women with moderate or severe endometriosis than in women with minimal or mild endometriosis or no disease. The treatment of isolated human endometriosis epithelial cells with estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and interferon-gamma stimulated measurable eotaxin secretion into the conditioned media. The results indicate that eotaxin is produced in epithelial cells of normal endometrium and endometriosis tissues, varies across the menstrual cycle, and is elevated in women with endometriosis. We postulate that eotaxin, interacting with other known cytokines and immune cells, contributes to an inflammatory reproductive tract environment, leading to endometrial or blastocyst dysfunction.

Adult↗
PubMed1999

Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions.

We hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast.

Adult↗
PubMed1999

Add-back medrogestone does not prevent bone loss in premenopausal women treated with goserelin.

To investigate the effect of medrogestone on bone mineral density (BMD) and bone turnover under conditions of estrogen withdrawal, premenopausal women with endometriosis were treated with goserelin (Zoladex), combined with either placebo (group A, n = 12) or 10 mg medrogestone (Prothil, group B, n = 11) for six months, and followed for an additional six months. Lumbar spine BMD was measured at 0 and 6 month. Markers of bone turnover were serum bone alkaline phosphatase (sBAP) and osteocalcin (sOC) by ELISA, and urinary total pyridinoline (uPYD) and deoxypyridinoline crosslinks (uDPD) by HPLC. Patients in both groups had a similar and significant decrease in BMD after 6 months (4%, p < 0.01). The time course of changes in bone turnover, in contrast, was different in both groups. In group A, crosslink excretion increased from one month onwards, while no changes were seen in group B. In group A, sBAP levels rose during treatment, while in group B, this rise was delayed until treatment was terminated. Additionally, group B showed an initial suppression of sBAP and sOC. In both groups, sOC increased after treatment was discontinued. Medrogestone at 10 mg/d does not prevent lumbar bone loss in premenopausal women under estrogen deprivation. In the medrogestone add back group, the changes in bone turnover are compatible with low turnover bone loss,as ooposed to a state of high turnover seen in the unopposed goserelin group. This effect may be due to glucocorticoid receptor mediated actions of medrogestone on bone.

Adult↗
PubMed1999

Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium.

Besides being an antiprogestin, mifepristone (RU 486) was recently shown to antagonize oestrogen-dependent growth in the endometrium. To explore the molecular mechanisms for this phenomenon, we investigated whether or not the morphological effects of mifepristone are mediated by the progesterone receptor (PR) and whether mifepristone has disparate effects on the glandular epithelium and stroma. Six groups of hypogonadal, oestrogen-primed cynomolgus monkeys were treated for 2 weeks with: vehicle only (group I); mifepristone (group II); mifepristone plus progesterone at 0.2 mg/kg (group III), 1.0 mg/kg (group IV) or 5.0 mg/kg (group V); and progesterone only (5.0 mg/kg) (group VI). Histomorphological evaluation showed strikingly compacted stroma in the mifepristone-exposed endometria (group II), which was partially reversible by additional progesterone treatment (groups III-V). Glandular proliferation (pseudostratification, glandular mitoses) in mifepristone-treated monkeys was not significantly different from that in vehicle (oestradiol)-treated monkeys, but was inhibited by progesterone-only treatment. Cells containing vacuoles were scarce in the mifepristone-exposed endometrium, but detected frequently in progesterone-exposed endometria, indicating the strong antisecretory effect of mifepristone on glands. We conclude that oestrogen-dependent oedema in the stroma is antagonized by mifepristone. The reversal of this effect by progesterone suggests a PR-mediated mechanism. In glands, mifepristone is antiprogestogenic, but not antioestrogenic. Thus, stromal cells may be the target of antiprogestin-induced inhibition of oedema and endometrial growth.

Animals↗
PubMed1999

[In Process Citation]

The assessment of the activity of endometriosis provides a challenge during endoscopic procedures. Novel approaches can be developed in future based on more detailed understanding of the mechanisms of the pathogenesis of endometriosis. Angiogenic factors of local immunoreactions are important agents in the development and progression of the disease. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability and of the mitogenesis of endothelial cells. In endometriotic and endometrial tissues VEGF isoforms VEGF121, VEGF165, VEGF189 and VEGF206 are expressed. The amount of VEGF isoforms in the endometrium is regulated depending on the menstrual cycle. Macrophage recruitment by ectopic endometrial implants is an early step in the cascade of implantation and local peritoneal reaction. RANTES (Regulated upon Activation, normal T-cell-Expressed and Secreted) is a specific chemoattractant for monocytes and activated T-cells. Soluble products of activated macrophages play an important role in endometriosis associated infertility. The factors involved in angiogenesis and immune response are potential parameters to determine the activity of endometriotic implants and novel approaches for the treatment of endometriosis.

Journal Article↗
PubMed1998

Fetal sex determination by high resolution ultrasound in early pregnancy.

OBJECTIVE: Fetal sex determination by ultrasound, and its medical and ethical implications, has been predominantly discussed in mid and late gestation. The development of high resolution ultrasound equipment has provided the possibility of detailed visualization of the fetus in early pregnancy. The present prospective study investigates the feasibility and accuracy of fetal sex determination by transabdominal ultrasound in early pregnancy. METHODS: Sonographic determination of fetal sex was attempted prospectively prior to genetic amniocentesis in 173 fetuses from 11 to 16 weeks of gestation. The result of ultrasound examination was compared with the karyotype obtained from amniotic fluid cells. RESULTS: Sonographic sex determination was feasible in 80.3% of cases, and all these determinations proved to be correct. There was no difference in the identification rate between male (n=87) and female (n=86) sex. Fetal sex determination was also feasible and correct in all four sets of twins and in the one set of quadruplets. CONCLUSION: Fetal sex assignment in the late first and early second trimester can be useful in pregnancies at risk for severe sex-linked diseases, in fetal disorders involving the genitalia, and in the individual identification of multiple fetuses. Prenatal sex assignment in early pregnancy implicates also far-reaching ethical problems because of the potential risk of sex-selected abortion.

Ethics, Medical↗
PubMed1998

Human trophoblast cells are permissive to the complete replicative cycle of human cytomegalovirus.

Human trophoblast cells were permissively infected by human cytomegalovirus. The kinetics of viral immediate-early, early, and late gene expression was clearly delayed compared to that in fibroblasts. Productive infection was unequivocally proven by the detection of virion particles, infectious virus in trophoblast culture supernatant, and cell-to-cell spread of cytomegalovirus from infected trophoblasts to uninfected fibroblasts. These observations indicate that infected trophoblasts may be involved in maternofetal transmission of human cytomegalovirus.

Antigens, Viral↗
PubMed1997

Humoral immune response to membrane components of Chlamydia trachomatis and expression of human 60 kDa heat shock protein in follicular fluid of in-vitro fertilization patients.

Recent evidence suggests that Chlamydia trachomatis can persist in the female upper genital tract in an unculturable state. Since unsuspected C. trachomatis infection has been associated with adverse in-vitro fertilization (IVF) outcome we sought to detect further evidence of C. trachomatis in the genital tracts of women undergoing IVF. The prevalence and distribution of antibodies to the major structural proteins of C. trachomatis in paired follicular fluid and sera of women undergoing IVF were examined. Sera and follicular fluid samples from 149 women were assayed for immunoglobulin (Ig)G and IgA antibodies to two C. trachomatis antigens, the major outer membrane protein (MOMP) and a recombinant lipopolysaccharide (rLPS) fragment. Additionally, the expression of human 60 kDa heat shock protein (hsp 60) in follicular fluid was determined. All cervical and follicular fluid samples were negative for C. trachomatis by polymerase chain reaction, ligase chain reaction and DNA probe. Sera from 60% of the subjects were positive for antichlamydial rLPS IgG; 36% were positive for anti-MOMP IgG. Similarly, rLPS-directed and MOMP-directed IgA were detected in sera of 34 and 14% of the subjects respectively. IgG antibodies to MOMP and rLPS were detected in 42 and 41% of the follicular fluid examined respectively. Anti-MOMP IgA was identified in 8.7% of the follicular fluid while 27.5% were positive for anti-rLPS IgA. Human hsp 60 expression was documented in 11.6% of the follicular fluid tested. IgA antibodies to both MOMP (P = 0.03) and rLPS (P = 0.02) in follicular fluid were associated with a failure to become pregnant after embryo transfer. IgG antibodies in sera and follicular fluid and IgA antibodies in sera were unrelated to IVF outcome. Similarly only anti-MOMP IgA (P = 0.02) and anti-rLPS IgA (P = 0.04) in follicular fluid were correlated with human hsp 60 expression in follicular fluid. The unique association between IgA antibodies to two chlamydial antigens in follicular fluid and both hsp 60 expression and IVF failure provides further support for the possibility that a persistent upper genital tract chlamydial infection contributes to IVF failure in some women.

Antibodies, Bacterial↗
PubMed1997

Chromosomal findings in 150 couples referred for genetic counselling prior to intracytoplasmic sperm injection.

A total of 150 infertile couples underwent chromosome analysis and genetic counselling before intracytoplasmic sperm injection (ICSI). Chromosomal abnormalities, including low-level sex chromosome mosaicism, were detected in 12% of the men and an unexpectedly high 6% of the women. Chromosomal abnormalities included gonosomal mosaicism in 13 cases, Robertsonian translocations in four males, autosomal reciprocal translocations in five cases, reciprocal translocation involving a sex chromosome in one case, inversions in three cases and a marker chromosome in one male. Chromosomal variants found in 11 women and 13 men were not included in the above percentages. Couples with a chromosomal aberration in one partner received a second counselling. The different aspects of genetic counselling in these couples are discussed. In conclusion, we recommend genetic counselling and chromosomal analysis of men and women prior to ICSI therapy.

Adult↗
PubMed1997

Inhibitory effect of leukotrienes on luteinizing hormone release.

The aim of this work was to study the effect of high concentrations of leukotrienes on luteinizing hormone (LH) secretion in rat anterior pituitary cells. We also investigated the effect of leukotrienes in parallel with gonadotropin-releasing hormone (GnRH) action. Experiments were on cells gained from trypsinized pituitaries of female rats. Tests were performed by superfusion of the cells attached to cytodex-1 carrier beads. The LH content in samples of perfusate was estimated by radioimmunoassay. This work reports 48% inhibition of basic LH release by action of leukotriene C4 in superfused cells when applied continuously at a concentration of 100 nmol/l. Moreover, we have shown that leukotrienes suppressed GnRH-induced LH secretion in rat pituitary cells when applied in parallel to GnRH (1 nmol/l) as a 4-min pulse at a concentration of 0.1 nmol/l. GnRH-induced LH release was reduced to 66% of its value by leukotriene (LT) B4 (0.1 nmol/l) action; also to 54% by LTC4, 66% by LTD4 and 74% by LTE4 action. In contrast, arachidonic acid (50 pmol/l) and its other 5-lipoxygenase metabolites: 5-hydroperoxyeicosatetraenoic acid (5-HPETE) (50 pmol/l), or 5-hydroxyeicosatetraenoic acid (5-HETE) (50 pmol/l), had no inhibitory effect on GnRH-induced LH release. Arachidonic acid and 5-HETE potentiated GnRH-induced LH release up to 249% and 429%, respectively, when applied in parallel with GnRH (1 nmol/l) as a 4-min pulse at a concentration of 10 pmol/l. In our earlier work we have shown that several leukotrienes are potent stimulants of LH release. The present report documents the finding that the 5-lipoxygenase pathway is also involved in the inhibitory regulation of hormone release in anterior pituitary cells.

Animals↗
PubMed1996

Role of leukotriene C4 in follicle-stimulating hormone (FSH) secretion in female rat pituitary.

Leukotriene C4, at doses of 0.01 and 0.1 nmol/l added to superfused cells in pulse of 4-min duration, evoked follicle-stimulating hormone (FSH) release up to 12- to 26-fold of basal secretion. Higher and lower concentrations of leukotriene C4 were not able to induce FSH secretion. Gonadotropin-releasing hormone (GnRH)-induced FSH release was reduced by 38-57% by the leukotriene receptor antagonist FPL 55712 (10 mumol/l). Moreover, we have shown that FSH release occurs parallel to leukotriene C4 synthesis in rat anterior pituitary cells. Mellitin (100 nmol/l), an activator of phospholipase A2, induced FSH and radioactivity secretion in rat anterior pituitary cells previously preincubated for 24 h with [3H]arachidonic acid (AA).

Animals↗