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Biomedical subjects

A Hobisch

Publications and source records attributed to A Hobisch.

77 records · Page 5Linked to original sources
PubMed1993

Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone.

Structural changes of the androgen receptor (AR) may contribute to the development of resistance to endocrine therapy in prostatic carcinoma. We have isolated AR cDNA fragments from seven tumor specimens derived from patients with advanced metastatic prostatic tumors. In one specimen obtained from a patient who failed to respond to endocrine and cytotoxic therapy we have detected a point mutation in the hormone-binding domain of the receptor. This AR mutation is a guanine-to-adenine transition at nucleotide 2671 that leads to substitution of methionine for the wild type valine at position 715. It is a somatic mutation because it was not present in the AR genomic DNA fragments isolated from prostatic and testicular tissues of the same patient. The mutant AR was recreated in an expression vector and transiently expressed in COS-7 and CV-1 cells. Hormone-binding assays revealed that the mutant receptor does not differ from the wild type receptor in its ability to bind androgen. The dissociation constant for the synthetic androgen mibolerone was 3 nM for both receptors. There was also no significant difference in binding of other steroids and nonsteroidal antiandrogens as revealed by competition binding assays. However, transfection experiments to determine the trans-activation potential of the mutant receptor produced differences in the action of this receptor compared to the wild type receptor. Dihydrotestosterone and the synthetic androgens methyltrienolone (R1881) and mibolerone were equally proficient in conferring trans-activation activity to both the mutant and wild type receptors. Adrenal androgens such as dehydroepiandrosterone and androstenedione, as well as progesterone mediated a higher trans-activation through the mutant than through the wild type receptor. These data demonstrate that the exchange of a single valine into methionine at position 715 in the AR promoters trans-activation not only by testicular but also by adrenal androgens and progesterone. This pattern of ligand-dependent trans-activation may have significance in the process controlling the progression of prostatic carcinoma.

Adrenal Glands↗
PubMed1993

[Modified retroperitoneal lymph node excision in testicular tumors. Anatomy, surgical technique and results].

Between January 1988 and June 1992, 56 patients suffering from malignant testicular tumors underwent nerve-preserving retroperitoneal lymphadenectomy at the University Hospital in Innsbruck. The tumors were staged according to the nomenclature recommended by the Workshop for Staging and Treatment of Testicular Cancer (Lugano 1979). According to this nomenclature 23 patients had stage I and 33 patients stage II. Thirty-nine patients presented with malignant teratoma, 3 with seminoma and 14 with teratoma and seminoma. The patients with stage I tumors were treated after orchiectomy with nerve-preserving retroperitoneal lymphadenectomy according to the dissection fields of Weissbach et al. In cases of nodal involvement in the retroperitoneum (stage IIa and IIb) a retroperitoneal modified lymphadenectomy according to the margins of Colleselli et al was performed. Patients with stage IIc tumors were treated with three cycles of polychemotherapy. Subsequently, the residual tumor was removed and, if possible, a nerve-sparing lymphadenectomy was performed. Since the nerve-preserving technique was modified in accordance with the tumor stage, antegrade ejaculation could be preserved in 47 of the 56 patients. In 22 patients exocrine testicular function was assessed by sperm analysis. The findings for the patients with stage I and IIa were considerable. The patients who had undergone induction chemotherapy for stage IIb and IIc had poor exocrine testicular function. The follow-up time was 29 months. At follow-up none of the patients presented with recurrent retroperitoneal tumor. Only one patient was found to have tumor progression (solitary pulmonary metastasis 1.7%). These results show that nerve-preserving retroperitoneal lymphadenectomy is the treatment of choice in stage I non-seminomatous testicular tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Urethral rupture--primary repair and reconstruction].

Whether the posterior urethra can successfully be reconstructed depends mainly on the primary care, especially in the case of strictures secondary to trauma. Prior to surgery, primary care of the lesion is mandatory, including open suprapubic fistula, drainage of the cavum retii and of the perineal space, repositioning of the urethra and immediate stabilization of the pelvic ring by means of elastic procedures. In a second step, between 1978 and 1990 we performed bulbo-prostatic surgery in 27 patients with traumatic rupture of the posterior urethra. Based on extensive anatomic be studies on the relationship of the membranous urethra to the pelvic floor and to the arteries, veins and nerves, an operative approach via the perineal body was developed. Of 18 patients followed up, only 4 had flow rates of less than 15 ml/s. Retrograde urethrograms and micturition cystograms showed good results.

Adolescent↗
PubMed1992

[Correlation of vesico-ureteral reflux and recurrent urinary tract infections with increased bacterial adherence].

Unimpeded urinary flow and voiding of the bladder without residual urine are essential for the prevention of urinary tract infections. Therefore, recurrent urinary tract infections are most commonly found in patients with functional and anatomic disorders of the urinary tract. Children suffering from vesico-ureteral reflux are especially susceptible to recurrent urinary tract infections. The interaction between germ and target cell, i.e. between antigen and receptor, is another important factor in the development of urinary tract infections. This so-called bacterial adherence is variable and depends upon receptor density as well as the affinity of the germ to the receptor. However, our study showed that this bacterial adherence plays a minor role in the development of recurrent urinary tract infections secondary to vesico-ureteral reflux.

Adolescent↗