PubMed Health⌕ Search

Biomedical subjects

Wolfgang Weidner

Publications and source records attributed to Wolfgang Weidner.

At least 19 recordsLinked to original sources
PubMed2006

Acetylcholine and molecular components of its synthesis and release machinery in the urothelium.

OBJECTIVES: Previous studies provided indirect evidence for urothelial synthesis and release of acetylcholine (ACh). We aimed to determine directly the ACh content in the urothelium and to characterize the molecular components of its synthesis and release machinery. METHODS: The study was performed on mouse bladder and abraded urothelium, and human mucosal bladder biopsies. ACh content was measured by high-performance liquid chromatography-electrochemical. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry served to investigate expression of ACh-synthesizing enzymes-choline acetyltransferase (ChAT) and carnitine acetyltransferase (CarAT)-vesicular ACh transporter (VAChT), and polyspecific organic cation transporters (OCTs; isoforms 1-3). Transfected cells served to investigate whether the anticholinergic drug trospium chloride interferes with ACh-transporting OCTs. RESULTS: ACh is present in the urothelium in a nanomolar range per gram of wet weight. RT-PCR data support the presence of CarAT but not ChAT. VAChT, used by neurons to shuffle ACh into synaptic vesicles, is detected in subepithelial cholinergic nerve fibres, but not by RT-PCR or immunohistochemistry in the urothelium. OCT1 and OCT3 are expressed by the urothelium. The quarternary ammonium base trospium chloride inhibits cation transport by OCTs with a potency rank order of OCT2 (IC(50)=0.67+/-0.42micromol/l)>OCT1 (IC(50)=6.2+/-2.1micromol/l)>OCT3 (IC(50)=871+/-177micromol/l). CONCLUSIONS: This study demonstrates a urothelial non-neuronal cholinergic system that differs widely from that of neurons with respect to molecular components of the ACh synthesis and release machinery. Consequently, these two systems might be differentially targeted by pharmacologic approaches.

Acetylcholine↗
PubMed2006

DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular cancer.

DNA methylation catalyzed by DNA methyltransferases (DNMTs) and histone deacetylation catalyzed by histone deacetylases (HDACs) play an important role for the regulation of gene expression during carcinogenesis and spermatogenesis. We therefore studied the cell-specific expression of DNMT1 and HDAC1 for the first time in human testicular cancer and impaired human spermatogenesis. During normal spermatogenesis, DNMT1 and HDAC1 were colocalized in nuclei of spermatogonia. While HDAC1 was additionally present in nuclei of Sertoli cells, DNMT1 was restricted to germ cells exhibiting a different expression pattern of mRNA (in pachytene spermatocytes and round spermatids) and protein (in round spermatids). Interestingly, in infertile patients revealing round spermatid maturation arrest, round spermatids lack DNMT1 protein, while pachytene spermatocytes became immunopositive for DNMT1. In contrast, no changes in the expression pattern could be observed for HDAC1. This holds true also in testicular tumors, where HDAC1 has been demonstrated in embryonal carcinoma, seminoma and teratoma. Interestingly, DNMT1 was not expressed in seminoma, but upregulated in embryonal carcinoma.

DNA (Cytosine-5-)-Methyltransferase 1↗
PubMed2006

Alterations in the transforming growth factor (TGF)-beta pathway as a potential factor in the pathogenesis of Peyronie's disease.

OBJECTIVES: The development of fibrotic diseases is associated with alterations in the transforming growth factor beta (TGF-beta) pathway. We have investigated the expression and activity of Smad transcription factors of the TGF-beta pathway in primary tunical fibroblasts derived from patients with Peyronie's disease and from controls. METHODS: Primary fibroblasts were established from biopsies obtained from plaques of 16 patients with Peyronie's disease or the tunica albuginea of 8 control patients. The expression and activity of Smad transcription factors in control and TGF-beta-stimulated primary fibroblasts were investigated at the RNA and protein level by reverse transcription-polymerase chain reaction, Western blotting, and immunofluorescence. RESULTS: RNA expression levels of Smad3 and Smad4 were significantly increased in fibroblasts from patients with Peyronie's disease. When stimulated with TGF-beta1, fibroblasts showed rapid nuclear translocation of Smad2/3, as soon as 15 min after stimulation. This effect was more pronounced and exhibited an earlier onset in fibroblasts from patients with Peyronie's disease, compared with controls. In addition, an increased nuclear retention time of Smad4 was observed in fibroblasts from patients with Peyronie's disease. CONCLUSIONS: The expression and activity of Smad transcription factors of the TGF-beta pathway is increased in fibroblasts of patients with Peyronie's disease. Alterations in the TGF-beta pathway seem to be a pathogenetic factor in the development of Peyronie's disease.

Cell Nucleus↗
PubMed2006

Genetic imprinting during impaired spermatogenesis.

Disorders in genetic imprinting are discussed as potential genetic risk in assisted reproduction technology (ART), where most of the natural selection mechanisms are bypassed. As currently only limited information about genomic imprinting in disruptive spermatogenesis is available, we analysed the imprinting state of the paternally methylated gene H19 in various germ cell populations derived from seminiferous tubules exhibiting impaired spermatogenesis. Different germ cell types were isolated by laser microdissection from human testicular paraffin sections. Although the methylation state of the maternally imprinted gene SNRPN was investigated by methylation-specific PCR (M-PCR) to establish the isolation method, methylation of H19 was analysed by a single-strand conformation-based method. Contamination by somatic Sertoli cells was excluded because of Sertoli cell-specific vimentin immunohistochemistry before germ cell laser microdissection. We demonstrate correct genetic imprints for H19 even in spermatogonia selected from seminiferous tubules exhibiting spermatogenic arrest at the level of spermatogonia, providing no evidence for incorrect genomic imprinting in spermatozoa from infertile men used for ICSI.

Autoantigens↗
PubMed2006

A critical analysis of nonsurgical treatment of Peyronie's disease.

OBJECTIVE: Because the efficacy of nonsurgical therapy of Peyronie's disease is controversial, this review analyses the current status of conservative therapy of Peyronie's disease. METHOD: A systematic survey on results of studies published as original papers in peer-reviewed journals is provided. RESULTS: Oral drug therapies include potassium para-aminobenzoate (Potaba), vitamin E, colchicine, tamoxifen, propoleum, acetyl-L-carnitine, and propionyl-L-carnitine. Verapamil, interferon-alpha2a and interferon-alpha2b, collagenase, cortisone, hyaluronidase, and superoxide dismutase are considered intralesional therapies that have had various degrees of success. Other treatments include local gels, iontophoresis, extracorporeal shock wave therapy, and radiation. CONCLUSION: This review analyses the current status of the conservative therapy of Peyronie's disease, because the efficacy of the nonsurgical therapy is controversial.

Administration, Oral↗
PubMed2006

Validation of the German prostate-specific module.

Theoretically, all patients newly diagnosed with prostate cancer are faced with a choice of treatment options: radical prostatectomy or radio therapy. Although these different treatments may have no differences in terms of survival, they may have very different consequences on the subsequent quality of life (QoL). Prerequisite to analyze QoL is a reliable and valid instrument to assess these differences not only in terms of general QoL (EORTC QLQ-C30) but prostate specific symptoms with a prostate specific module as well. Therefore, the aim of this study was a psychometric evaluation (validation) of the prostate-specific module (PSM). Five historical cohort studies were put together for an empirical meta-analysis. The main objective was to analyze the module's psychometric properties. The total sample consisted of 1,185 patients, of whom 950 completed the QoL questionnaires (EORTC QLQ-C30 and a prostate specific module developed by Kuechler et al.). First step of analysis was a principal component analysis that revealed the following scales: urinary problems, incontinence, erectile dysfunction, sexual problems, problems with partner, pain, heat, nutrition, and psychic strain. The module showed good reliability and concurrent validity and very good construct validity, since the module is able to discriminate between different treatment regimes, tumor stages and age. The German PSM is a reliable, valid and applicable tool for QoL in patients with prostate cancer.

Adaptation, Psychological↗
PubMed2006

Chlamydial infections in urology.

Chlamydia trachomatis is the most frequent cause for sexually transmitted diseases in European countries. The organism has an intracellular habitat with a very specific life cycle. A variety of diagnostic tests have been developed with different sensitivity and specificity. Interpretation of these tests can sometimes be difficult. Diseases caused by C. trachomatis in men comprise urethritis, prostatitis, epididymitis, infertility and reactive arthritis. Especially in prostatitis, the exact role of C. trachomatis is still under debate for the technical difficulties localizing the pathogen to the prostate. For treatment, only some antibiotics are effective because of the intracellular habitat of the pathogen. Prevention of infection comprises treatment and screening efforts.

Adolescent↗
PubMed2006

Chronic pelvic pain syndrome/chronic prostatitis affect the acrosome reaction in human spermatozoa.

Male genital tract inflammations constitute an important factor of male subfertility in which different mediators are discussed damaging sperm membranes. As acrosome reaction (AR) is ultimately a membrane function, this study aimed at investigating the effects of the chronic pelvic pain syndrome on AR. In a total of 56 patients with chronic pelvic pain syndrome NIH IIIA and NIH IIIB, AR, concentration of leucocytes in ejaculate and urine after prostate massage, sperm concentration, motility, vitality and morphology were determined. The control group (n = 95) consisted of patients with normozoospermia and proven absence of signs of inflammation. Compared to the control, both patients groups showed poorer sperm morphology (P < 0.0001) and sperm concentration (P < 0.002). In addition, while maximum AR was not affected, inducibility of AR was significantly lower (P < 0.004) and spontaneous AR increased (P < 0.02). Our data clearly demonstrate a significant influence of the inflammation on acrosomal functionality, which could be mediated by inflammatory mediators like ROS.

Acrosome Reaction↗
PubMed2006

Prescription practice for LH-RH analogs and androgen receptor antagonists in the treatment of advanced prostate cancer in Germany (1993-2003).

INTRODUCTION: Nearly 80% of the patients suffering from advanced stages of prostate cancer in Germany are treated currently with luteinizing hormone-releasing hormone (LH-RH) analogs alone or in combination with androgen receptor antagonists. The aim of this study was to assess whether the prescription practice for LH-RH analogs and direct antiandrogens between 1993 and 2003 parallels the rise in the incidence rates for prostate cancer associated with the proportional rise in daily doses. METHODS: Between 1993 and 2000 a yearly randomly selected number of receipts has been evaluated from official pharmacies in Germany which have been billed to public health insurance companies. Data concerning drug use, number of daily doses, and total cost of the respective drugs have been calculated by the Research Institute of the AOK (Wissenschaftliches Institut der AOK, WIdO). These prescription data have been related to incidence and mortality rates of patients with prostate cancer. RESULTS: Between 1993 and 2003 the age-standardized incidence rate of carcinomas of the prostate has risen by 180%, while the disease-specific mortality practically has remained nearly at the same level. The daily prescribed doses of LH-RH analogs have risen by a factor of 8.5 from 3.9 to 33.5 million daily doses during this time. In contrast, the daily doses of androgen receptor antagonists have remained unchanged between 1997 and 2001, followed by a rise of 50% between 2001 and 2003. CONCLUSIONS: The first analysis of the prescription practice of antiandrogens in the treatment of prostate cancer with respect to the incidence rates in Germany could only be facilitated by the fact that these medications are in exclusive use for this indication in Germany. The rise in prescriptions may be explained by the therapy shift from surgery to LH-RH application until the year 2000; the reasons for a further rise since 2000 remain speculative. In conclusion, only prevalence data would allow the exact calculation of medication needs among prostate cancer patients.

Aged↗
PubMed2006

Giant urethral diverticulum: unusual complication following ventral buccal mucosa onlay graft urethroplasty.

During the past 10 years, buccal mucosa grafting for urethroplasty has gained widespread acceptance. In general the reported success rates are 80% and higher. Typical complications are recurrent strictures, fistula, and, especially when the technique of ventral onlay urethroplasty has been used, sacculations that are of little clinical significance in most cases. The development of large diverticula has not been described yet. We report on the case of a 63-year-old man who developed a giant diverticulum of the urethra 1 year after a ventral buccal mucosa onlay graft urethroplasty for recurrent bulbar urethral strictures had been worked out.

Diverticulum↗
PubMed2005

Potassium paraaminobenzoate (POTABA) in the treatment of Peyronie's disease: a prospective, placebo-controlled, randomized study.

PURPOSE: The aim of this study was to investigate the effect of potassium paraaminobenzoate (Potaba) in Peyronie's disease in a prospective, randomized, double-blind, placebo-controlled, multicentre study during a 12-months period of treatment. PATIENTS AND METHODS: 103 patients with Peyronie's disease and a history <12 months, non-calcified plaques and without pre-treatment were included. 51 were randomized to potassium paraaminobenzoate, 52 to placebo receiving 4 x 3g/day for 12 months. Follow-up was performed during the treatment period. Response has been defined as regression in plaque-size and/or reduction in penile curvature of at least 30%. Data analysis was focussed on 75 patients who completed the study [valid-cases (VC)]. RESULTS: No severe adverse events occurred. Response rates were 74.3% on potassium paraaminobenzoate and 50.0% on placebo (p=0.016). Mean plaque-size decreased from 259 mm(2) to 142 mm(2) in the treatment arm. In the placebo group, plaque-size aggravated from 259 mm(2) to 303 mm(2) after 6 months but improved slightly to 233 mm(2) after 12 months. Differences between the groups were significant (p=0.042). Pre-existing curvature did not improve under the drug (p=0.066) but comparing the development of new curvature or deterioration of pre-existing curvature under potassium paraaminobenzoate penile deviation remained stable. However, under placebo penile curvature deteriorated significantly in 32.5% of the cases (p<0.001). No significant differences concerning decrease of pain could be observed between the two groups (82.6% vs. 77.3%). CONCLUSIONS: The results of this study indicate a significant plaque-related effect of potassium paraaminobenzoate. There was no relevant difference with regard to improvement of pre-existing penile deviation. However, under potassium paraaminobenzoate a significant protective effect on deterioration of penile curvature could be demonstrated. Potassium paraaminobenzoate appears to be useful to stabilize the disorder and prevent progression of penile curvature.

4-Aminobenzoic Acid↗
PubMed2005

Apoptosis: a key effector mechanism of lymphocyte action in human nonseminomatous testicular carcinoma?

OBJECTIVE: To correlate the number of tumour-infiltrating T lymphocytes (TILs) with the extent of apoptosis in testicular germ cell tumours, as TILs are considered to be a favourable prognostic factor of human testicular tumours, especially of seminomas, but the mechanism by which TIL contribute to an improved outcome is unclear. MATERIALS AND METHODS: Tissue samples from 47 patients with nonseminomatous germ cell tumour (NSGCT) and 15 with seminomatous GCT were investigated immunohistochemically for lymphocyte infiltration and apoptosis. The apoptotic index (AI) was assessed in various categories (DNA condensation and fragmentation) using in-situ end-labelling to identify typical apoptotic DNA strand breaks, and nuclear staining to identify typical apoptotic morphology. RESULTS: In seminomatous GCT there was no correlation between the number of TILs and any AI. In NSGCT there was only a relationship between lymphoid infiltration and those AIs showing morphological criteria of apoptosis in a small subgroup of NSGCT, i.e. metastasized embryonal cell carcinomas. Only 1.2% (AI, chromatin condensation) and 0.8% (AI, fragmentation and condensation) of all tumour cells showed these features of apoptosis. The overall AI in NSGCT was 7.9%. CONCLUSIONS: TILs do not seem to induce apoptosis in testicular tumours. Embryonal cell carcinomas might be susceptible to lymphocyte attack, resulting in apoptosis of the tumour cell. The mechanisms of interaction between lymphocytes and testis tumour cells need further investigation.

Apoptosis↗
PubMed2005

Emerging drugs for bacterial urinary tract infections.

Bacterial urinary tract infections (UTIs) are frequent infections in the outpatient as well as in the nosocomial setting. The stratification into uncomplicated and complicated UTIs has proven to be clinically useful. Bacterial virulence factors on the one side and the integrity of the host defence mechanisms on the other side determine the course of the infection. In uncomplicated UTIs, Escherichia coli is the leading organism, whereas in complicated UTIs, the bacterial spectrum is much broader, including Gram-negative, Gram-positive and often multiresistant organisms. The therapy of uncomplicated UTIs is almost exclusively antibacterial, whereas in complicated UTIs the complicating factors also have to be treated. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTIs: i) rapid and effective response to therapy and prevention of recurrence of the individual patient treated; and ii) prevention of emergence of resistance to chemotherapy in the microbial environment. The aim of this review is to highlight the existing, and to describe emerging, treatment options for UTIs.

Anti-Bacterial Agents↗
PubMed2005

Asymptomatic bacteriuria in elderly patients: significance and implications for treatment.

Asymptomatic bacteriuria (ASB) is frequent in elderly patients and even more prevalent in residents of long-term care facilities. Furthermore, because more and more people are reaching advanced age and the need for care increases with age, ASB is becoming increasingly important. There are several definitions for ASB, all of which require positive urine cultures and place little or no importance on accompanying pyuria. Most ASB is associated with complicating factors, as might be found in complicated urinary tract infections (UTIs). Thus, the bacterial spectrum associated with ASB is comparable to that seen in complicated UTIs. A variety of complicating factors are more frequently found in elderly patients with ASB, such as hormonal factors (e.g. estrogen decrease), certain anatomical factors (e.g. prostate obstruction), metabolic factors (e.g. diabetes mellitus), functional alteration of the urinary bladder, immunological changes and a high rate of indwelling-catheter use. Screening for ASB in elderly people is limited to those undergoing invasive urological procedures and surgical procedures with implant material. In other situations, examination of the urine is not recommended if signs or symptoms in the urinary tract are absent. Treatment of ASB is recommended only before urological procedures. Pyuria accompanying ASB is not an indication for antimicrobial treatment. If antimicrobial treatment is considered, concomitant factors that occur frequently in elderly people, such as renal insufficiency, must be taken into account. Although ASB is apparently a benign condition, prevention in elderly people is important. The degree of pathogenicity of bacteria causing ASB has not yet been satisfactorily elucidated. Therefore, until the implications of the bacteria involved in ASB are fully understood, implementing the same hygienic precautions as are used in individuals with symptomatic UTIs should at least be undertaken.

Aged↗
PubMed2005

INSL3 in the benign hyperplastic and neoplastic human prostate gland.

The human prostate gland is a well known source of H1 and H2 relaxin but information is lacking on the expression and potential role of the INSL3 peptide hormone within the prostate gland. In the present study we have investigated the expression of human INSL3 in patients with benign prostate hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate carcinoma tissues. Of the prostate epithelial cells, strongest INSL3 expression was detected in the basal epithelial cell compartment. Weaker INSL3 mRNA expression and immunoreactive INSL3 production were observed in secretory epithelial cells and in interstitial smooth muscle cells. Prostate epithelial cells were also a source for transcripts encoding the INSL3 receptor LGR8 suggesting the presence of an autocrine/paracrine INSL3-LGR8 ligand-receptor system within the human prostate. Three human prostate carcinoma cell lines displayed differential gene activity for INSL3 and LGR8. While LNCaP was devoid of INSL3, the androgen-insensitive PC-3 and the stromal prostate cell line hPCP co-expressed INSL3 and LGR8 transcripts. In addition to expressing INSL3 mRNA, the LGR8-negative DU-145 also expressed an INSL3 splice form formerly demonstrated in thyroid carcinoma cells. When incubated with recombinant INSL3, PC-3 cells showed significantly increased intracellular cAMP levels indicating functional LGR8 receptors. INSL3 did not alter the proliferative or metabolic activity of PC-3 carcinoma cells. Instead, PC-3 responded to INSL3 with significantly enhanced tumor cell motility and a transcriptional down-regulation of ErbB receptors and EGF. All-trans-retinoic acid was demonstrated in PC-3 to up-regulate LGR8 gene activity in a dose- and time-dependent manner while having no effect on INSL3 gene activity. In conclusion, we have identified a functional INSL3-LGR8 ligand-receptor system in human prostate carcinoma cells.

Cell Line, Tumor↗