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Biomedical subjects

H Husslein

Publications and source records attributed to H Husslein.

At least 19 recordsLinked to original sources

Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes.

Canonical Wingless (Wnt) signalling provoked by exogenous and endogenous Wnt ligands was recently shown to play a crucial role in the invasive differentiation of human trophoblasts. To gain insights into the expression pattern of the developmental regulators, we analysed all human Wnt ligands and their frizzled (FZD) receptors in the human placenta and different trophoblast model systems using semi-quantitative PCR. Fourteen out of 19 Wnt ligands and 8 out of 10 FZD receptors were detectable in placental tissues, however, expression patterns varied with gestational age and between different trophoblast subtypes suggesting cell-specific functions. Besides Wnt ligands acting through the canonical pathway, non-canonical ligands such as Wnt-5a, which may also activate alternative Wnt signalling pathways or inhibit canonical Wnt signalling, could be identified. Western blot analyses revealed secretion of Wnt-5a from primary trophoblast cultures and trophoblastic cell lines. To evaluate the potential role of Wnt-5a, SGHPL-5 trophoblast cells were transfected with luciferase reporter plasmids harbouring eight T-cell factor (TCF) DNA-recognition sequences which are exclusively activated through the canonical Wnt signalling pathway. Luciferase assays revealed that Wnt-3a-induced reporter activity was repressed by recombinant Wnt-5a indicating an antagonistic role in trophoblasts. The data suggest that a complex network of Wnt ligands and FZD receptors may regulate developmental processes of the human placenta.

Cells, Cultured↗

Tumour necrosis factor-alpha impairs chorionic gonadotrophin beta-subunit expression and cell fusion of human villous cytotrophoblast.

Growth factors expressed at the fetal-maternal interface modulate hormone expression of placental trophoblasts. The aim of this study was to investigate the effects of different cytokines on hCG subunit mRNA expression in differentiating villous cytotrophoblasts. Quantitative real-time PCR revealed a 1.8- and 6.9-fold increase of hCG-alpha and hCG-beta mRNA levels, respectively, between 36 and 60 h of term trophoblast syncytialization. Compared with controls, neither interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, IL-13 and IL-15 nor tumour necrosis factor (TNF)-alpha significantly altered hCG-alpha mRNA expression. Similarly, the ILs did not affect hCG-beta transcript levels. In contrast, TNF-alpha suppressed hCG-beta mRNA 3.8- and 1.8-fold at 36 and 60 h of term trophoblast differentiation. Accordingly, hCG secretion was impaired by TNF-alpha but not by the different ILs. Moreover, TNF-alpha reduced luciferase expression of reporter plasmids harbouring the proximal hCG-beta5 promoter to 35 and 77%, respectively, in primary term trophoblasts and trophoblastic SHGPL-5 cells. In addition, counting of nuclei in syncytialized, desmoplakin-negative areas revealed a 1.9-fold reduction of term trophoblast fusion in the presence of TNF-alpha. Similarly, floating explant cultures prepared from first trimester-denuded villi recovered the syncytium 2.8-fold less efficiently during 72 h of cytokine treatment. Concomitantly, TNF-alpha impaired induction of endogenous and secreted hCG-beta protein levels in these cultures. The data suggest that TNF-alpha decreases hCG-beta mRNA and protein expression by reducing gene transcription and trophoblast cell fusion. Suppression of these processes by TNF-alpha could partly explain the adverse effects of the cytokine on placental function and pregnancy outcome.

Cell Differentiation↗

Premalignant and malignant uterine changes in immunosuppressed renal transplant recipients.

29 female immunosuppressed renal transplant recipients were examined gynecologically. In 2 cases the epithelium of the portio was found to be dysplastic, while endometrial carcinoma was present in 1 patient. A review of the literature suggests that immunosuppressed patients are more likely to develop tumors than others. The authors stress the need for gynecological and cytological examinations at short intervals, to identify premalignant and early malignant uterine changes at a time at which these can readily be treated without discontinuation of the immunosuppressive therapy.

Adenocarcinoma↗

[Psychosomatic in gynecology and obstetrics--problems and difficulties (author's transl)].

The hypo-, hyper- and normogonadotropic amenorrheas (according to WHO nomenclature) are psychosomatic amenorrheas. The significance of the various psychic factors is pointed out initially. Especially with psychosomatic disorders in gynecology sexual factors play an important role. Adequate treatment of psychosomatic disorders is rendered difficult of the present state of medical education. Lectures in psychosomatics are not presented outside of psychiatry, the dialogue between doctor and patient is almost completely neglected within the medical training. Psychosomatic treatment in the office of patients with state medical insurance poses problems. At our clinic an outpatient department has been open for 2 years. 136 cases have been treated so far. Gynecologist and the psychosomatic specialist examine the patient simultaneously and define a joint treatment plan. Prevailing problems are conflicts with the partner (31%), , conflicts within the family (20%) and conflicts within the social environment (13%). Following adequate diagnostic clarification patients are treated once (19%) or several times (28%) or are referred to other outpatient clinics. A prolonged therapy in our own outpatient department is presently possible in only 2,5% of cases.

Amenorrhea↗

[A six-year review of patients attending the sterility clinic (author's transl)].

The paper reports the therapeutic results achieved in patients attending the sterility clinic over the period 1969-1974. Altogether 540 couples were examined and treated. The average age of the female patients in this series was 29,6 years; the length of time over which pregnancy had been attempted averaged 3.9 years. Sterility was attributable to the female partner in 54.3% of the cases, to the male partner in 32.4% and to both spoused in 3%. No apparent cause for the sterility was detected in 10.3% of the cases. 209 pregnancies occurred following treatment, corresponding to an overall success rate of 38.7%, or 40.6% when due allowance is made for the 27 cases in whom the outlook was certainly hopeless. 107 husbands were treated and in 22 cases (20.5%) their spouses became pregnant during the period of treatment. The following therapeutic measures proved successful in the females: clomiphene: 34 pregnancies in 82 patients; gonadotrophins (HMG), HCG): 13 pregnancies in 35 patients; 22 out of 66 patients becamse pregnant had been discontinued; treatment of luteal insufficiency with Duphaston resulted in 13 pregnancies among 43 women; tubal surgery led to eight pregnancies in 32 patients and uterine surgery to one pregnancy among five patients. The greatest number of pregnancies was achieved by simple therapeutic measures such as consultation, determination of the optimum time for conception, local treatment, and cervical dilatation.

Adolescent↗