U Jonas

Evangelisches Krankenhaus Oberhausen, Oberhausen, North Rhine-Westphalia, Germany

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Publications (550)1128.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina. To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured. The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 µM) on the tension induced by 0.1 µM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 µM, 0.1 µM, 1 µM) and the production of cAMP and cGMP determined by means of radioimmunoassays. Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated. RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119-fold in the presence of CNP or BK, respectively. Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways.
    Journal of Sexual Medicine 01/2011; 8(1):35-43. · 3.51 Impact Factor
  • European Urology Supplements - EUR UROL SUPPL. 01/2010; 9(2):89-90.
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    ABSTRACT: To investigate the symptomatic and quality of life (QoL) response to treatment with tolterodine extended release (ER) in subgroups of male patients with Overactive Bladder Syndrome (OAB) and LUTS suggestive of non-obstructive benign prostatic hyperplasia (BPH) according to age, symptom severity, diabetes mellitus status, and concomitant treatment for LUTS. Patients treated with tolterodine ER 4 mg/day for OAB symptoms, alone or added to unsuccessful alpha-blocker treatment of > or =6 weeks duration, and presumed non-obstructive BPH (Q (max) > or = 15 ml/s) were observed for 12 weeks in a non-interventional study. Patients completed the International Prostate Symptom Score (IPSS) and Overactive Bladder Questionnaire (OAB-q) at baseline and after 12 weeks. 52.4% of 741 patients were aged < or =65 years; 4, 64, and 32% had mild, moderate, and severe symptoms, respectively, according to IPSS; 14% had diabetes mellitus, and in 42% tolterodine was added to alpha blockers. In the various subgroups, mean IPSS total scores improved by 2.8-11.1 points, IPSS QoL scores by 1.8-2.4 points, and all OAB-q subscores by more than 14 points. Only IPSS and OAB-q baseline scores had a relevant impact on changes during treatment, benefits were greatest in patients with more severe symptoms and bother. In men with symptoms of OAB and LUTS suggestive of non-obstructive BPH of all IPSS severity classes, aged < or =65 years or above, with or without concomitant diabetes or alpha-blockers, symptoms and QoL improved markedly during treatment with tolterodine ER.
    World Journal of Urology 12/2009; 28(3):353-7. · 2.89 Impact Factor
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    ABSTRACT: It has been suggested that serotonin re-uptake inhibitors (SRIs) may retard the ejaculatory response by acting directly on the seminal vesicle (SV) and ductus deferens smooth muscle. However, until now, only a very few experimental studies have investigated such potential local (peripheral) effects. To elucidate the effects of serotonin (5-HT) and the SRIs clomipramine, fluoxetine and imipramine on the tension induced by norepinephrine (NE) of isolated human SV smooth muscle, as well as on the production of tissue cyclic AMP and cyclic GMP. To measure the inhibition exerted by serotonin and SRIs clomipramine, fluoxetine, and imipramine on the contractile response of isolated SV tissue. In addition, the effects of the drugs on the turn-over of cyclic nucleotides cAMP and cGMP were also elucidated. The effects of the cumulative addition of serotonin and the SRIs clomipramine, fluoxetine and imipramine (1 nM-10 microM) on the tension induced by the alpha(1)-adrenoceptor agonist NE (10 microM) of SV strip preparations were studied using the organ bath technique. Cyclic AMP and cyclic GMP were measured by means of specific radioimmunoassays. The tension induced by NE was dose-dependently reversed by the drugs tested. The rank order of efficacy was: imipramine > or = fluoxetine > or = clomipramine > serotonin. Mean reversion of tension was measured between 66 +/- 6.6% and 52 +/- 6.6%. These effects were paralleled by a 1.3-fold to 2.7-fold increase in tissue cAMP in response to exposure to the drugs. In contrast, no significant enhancement in cGMP was noted. The findings, for the first time, present evidence that SRIs may antagonize the sympathetic contraction of SV smooth muscle via stimulation of tissue cyclic AMP.
    Journal of Sexual Medicine 08/2009; 6(10):2672-9. · 3.51 Impact Factor
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    ABSTRACT: The first theoretical reflections concerning the relation of hormone production with the ageing process stemmed from Charles Edouard Brown-Séquard (1817 1894). At the age of 72 years he experimented on himself with an injection of animal testicular extract. The Viennese physiologist Eugen Steinach (1861 1944) gained world-wide acknowledgement for his theory of 'autoplastic' treatment of ageing. He deduced that after vasoligation, an increased incretory hormonal production would ensue following the cessation of the secretory output of the gonads. The first operation was performed in 1918 and resulted in a vasectomy boom over the next two decades. The Russian Serge Voronoff (1866 1951), working in Paris, was one of the first to transplant testicular tissue from a monkey into a human reproductive gland in 1920. Five years later he had already performed this procedure on 300 patients and attracted patients from all over the world. In America early efforts of human testicular transplantation were performed by Frank Lydston and V.D. Lespinasse. Steinach's vasoligation was taken over by many American doctors, e.g., Harry Benjamin and Charles H. Chetwood. Among the patients who underwent a rejuvenation operation according to Steinach's method were Sigmund Freud (1856 1939) and the Irish poet and Nobel Prize winner William Butler Yeats (1865-1939). Two caricatures from the German magazine Simplicissimus published in 1927, confirm that the rejuvenation operations were constantly in the limelight of the printed media. From 1935 onwards rejuvenation operations gradually lost their appeal due to the introduction of artificial androgens.
    Andrologia 01/2009; 29(6):351-5. · 1.75 Impact Factor
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    ABSTRACT: Laparoscopic techniques have dramatically influenced urologic surgery in the past 2 decades. A questionnaire was distributed in 2006 to analyse laparoscopic practice patterns in Germany. The results were compared with a survey performed in 2002. In 2006, 324 German urology departments received a detailed, anonymous, and self-administered questionnaire regarding demographic data, current use, and attitudes concerning laparoscopy. Quantitative evaluation of laparoscopic procedures was performed for 20 indications. The response rate was 73% (238 of 324 institutions). Thirty-two responders were affiliated with universities; 95 responders were affiliated with urban hospitals; 101 responders were affiliated with general hospitals; and 9 responders were affiliated with private hospitals. Laparoscopy had been implemented as a standard operating procedure in 82% of the departments, an increase of 28% compared with the 2002 questionnaire. Forty-eight percent of participants expected a similar operating time to that of open surgery, an increase of 16% compared with the 2002 questionnaire. Concerns about the learning curve dropped from 92% in 2002 to 80% in 2006, and concerns about economic disadvantages dropped from 70% in 2002 to 45% in 2006. Criticism regarding lack of sufficient scientific data decreased from 76% in 2002 to 13% in 2006. Laparoscopic radical prostatectomies (>40 per year) were performed in 30 hospitals in 2006, an increase of 27% over 2002. Laparoscopic radical nephrectomy was performed 16-40 times per year in 33 of the responding institutions, an increase of 29% over 2002, and laparoscopic radical nephrectomy was performed >40 per year in 10 of the institutions, an increase of 9% over 2002. Laparoscopic pyeloplasty had a reported frequency of 16-40 procedures per year in 11 of the responding institutions, an increase of 10% over 2002, and laparoscopic pyeloplasty had a frequency between 5 and 15 procedures per year in 42 institutions, an increase of 37% over 2002. Only four hospitals performed cystectomy with ileum conduit and with orthotopic bladder substitute (5-15 cases per year). The results demonstrate the rising acceptance of laparoscopy in urologic surgery (an increase of 28% more departments performing laparoscopy) and an increasing interest in these techniques (an increase of 12% in the response rate). Their value is still limited by the response rate of only 73%. This survey demonstrates the increasing impact of laparoscopy on surgical patterns in urology and the increasing acceptance of laparoscopic techniques concerning operating time, learning curve, and scientific approval.
    European Urology 10/2008; 56(6):1074-80. · 10.48 Impact Factor
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    ABSTRACT: Detrusor overactivity is one known cause of lower urinary tract symptoms and has been linked to bladder storage symptoms (urgency, frequency, or urge incontinence). To determine clinical and urodynamic parameters associated with detrusor overactivity in patients with suspected benign prostatic hyperplasia. During 1993-2003, urodynamic investigations were performed in patients aged 40 yr or older and with lower urinary tract symptoms, benign prostatic enlargement, and/or suspicion of bladder outlet obstruction (maximum flow rate < 15 ml/s or postvoid residual urine > 50 ml). Detrusor overactivity was defined according to the new International Continence Society classification (2002) as involuntary detrusor contractions during cystometry, which may be spontaneous or provoked, regardless of amplitude. The Schäfer algorithm was used to determine bladder outlet obstruction. In total, 1418 men were investigated (median age: 63 yr) of whom 864 men (60.9%) had detrusor overactivity. In univariate analysis, men with detrusor overactivity were significantly older, more obstructed, had larger prostates, higher irritative International Prostate Symptoms Score subscores, a lower voiding volume at free uroflowmetry, and a lower bladder capacity at cystometry. The prevalence of detrusor overactivity rose continuously with increasing bladder outlet obstruction grade. Multivariate analysis showed that only age and bladder outlet obstruction grade were independently associated with detrusor overactivity. After age adjustment, the odds ratios of detrusor overactivity compared to Schäfer class 0 were 1.2 for class I, 1.4 for class II, 1.9 for class III, 2.5 for class IV, 3.4 for class V, and 4.7 for class VI. In patients with clinical benign prostatic hyperplasia, detrusor overactivity is independently associated with age and bladder outlet obstruction. The probability of detrusor overactivity rises with increasing age and bladder outlet obstruction grade.
    European Urology 09/2008; 54(2):419-26. · 10.48 Impact Factor
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    ABSTRACT: To date, there is an increasing interest in the nitric oxide (NO) pathway as a potential pharmacological target to treat male lower urinary tract symptomatology (LUTS). In the transition zone of the human prostate, a dense nitrinergic innervation has been shown of the fibromuscular stroma, glandular epithelium and blood vessels. The expression of key proteins of the NO pathway, such as the endothelial and neuronal nitric oxide synthase (eNOS, nNOS), cGMP-degrading phosphodiesterase type 5 (PDE5) and cGMP-binding protein kinase (cGK), has also been demonstrated. The hypothesis that an impaired NO/cGMP-signaling may contribute to the pathophysiology of benign prostatic hyperplasia (BPH) is supported by the results from randomized, placebo-controlled clinical studies, indicating that NO donor drugs and PDE5-inhibitors sildenafil, tadalafil and vardenafil may be useful to treat storage and voiding dysfunctions resulting from LUTS in men. Thus, given a potential role of the NO-pathway in the prostate and/or in other parts of lower urinary tract (e.g. bladder), the enhancement of the NO signaling by NO donor drugs, PDE5 inhibitors or activators of the soluble guanylyl cyclase (sGC) may represent a new therapeutic strategy for the treatment of LUTS. This review serves to focus on the role of NO and the NO-dependent signaling in the control of smooth muscle function in the human prostate. Results from clinical trials in men with LUTS/BPH are also discussed.
    World Journal of Urology 08/2008; 26(6):603-9. · 2.89 Impact Factor
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    ABSTRACT: To further evaluate the mechanism of action of phosphodiesterase (PDE) inhibitors on the human prostate, the effects of PDE4 and PDE5 inhibitors on the tension induced by norepinephrine (NE) and on the intracellular levels of cyclic nucleotides in isolated human prostatic tissue were investigated. Using the organ bath technique, the effects of increasing concentrations (1 nM to 10 microM) of the PDE5 inhibitors sildenafil, tadalafil, and vardenafil and the PDE4 inhibitors rolipram and RP 73401 on the tension induced by NE (40 microM) of prostate strip preparations were investigated. The accumulation of cyclic guanosine monophosphate and cyclic adenosine monophosphate in response to drug exposure was determined by radioimmunoassays. The tension induced by NE was dose dependently reversed by the drugs with the following rank order of efficacy: tadalafil greater than RP 73401 greater than rolipram greater than or equal to vardenafil greater than sildenafil. The maximal reversion of tension values ranged from 52.3% (tadalafil) to 17% (sildenafil). Of the PDE inhibitors, only tadalafil induced a 50% reversion of the initial tension. The most prominent enhancement in tissue cyclic adenosine monophosphate was registered in response to RP 73401 (11-fold), and cyclic guanosine monophosphate levels were significantly elevated by tadalafil, vardenafil, and sildenafil (28-fold, 12-fold, and 3-fold, respectively). Our results have demonstrated that drugs interfering with the cyclic nucleotide-mediated pathways can reverse the tension induced by NE in isolated prostatic tissue and elevate cyclic adenosine monophosphate and cyclic guanosine monophosphate. Our findings serve to explain how PDE inhibitors can affect symptoms of lower urinary tract symptoms and benign prostatic hyperplasia.
    Urology 04/2008; 71(3):526-30. · 2.42 Impact Factor
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    ABSTRACT: To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI. In all, 111 patients with a >50% reduction in UI symptoms during a percutaneous nerve evaluation test qualified for surgical implantation of SNM. Patients were categorized in two subgroups, i.e. those with UI with or without confirmed detrusor overactivity (DO) at baseline. At the 6-month follow-up all patients had a second urodynamic investigation, with the stimulator switched on. At baseline, there was urodynamically confirmed DO in 67 patients, while 44 showed no DO. A review of filling cystometry variables showed a statistically significant improvement in bladder volumes at first sensation of filling (FSF) and at maximum fill volume (MFV) before voiding for both UI subgroups, compared with baseline. In 51% of the patients with UI and DO at baseline, the DO resolved during the follow-up. However, those patients were no more clinically successful than those who still had DO (P = 0.73). At the 6-month follow-up, 55 of 84 implanted patients showed clinical benefit, having a >or=50% improvement in primary voiding diary variables. Patients with UI but no DO had a higher rate of clinical success (73%) than patients with UI and DO (61%), but the difference was not statistically significant. These urodynamic results show a statistically significant improvement in FSF and MFV in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical improvement in both groups, patients with UI but no DO are at least as successful as patients with UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for using SNM.
    BJU International 03/2008; 101(3):325-9. · 3.05 Impact Factor
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    ABSTRACT: To evaluate non-genomic effects of testosterone and dihydrotestosterone (DHT) on isolated human cavernosal arteries (HCA) and corpus cavernosum (HCC) using organ-bath studies and radio-immunoassays (RIA), as non-genomic effects of androgens are reported for vascular smooth musculature and there is evidence that the relaxant response involves a modulation of cyclic nucleotide tissue levels. The relaxation induced by the cumulative addition of testosterone and DHT (0.01-10 microm) was studied using circular segments of HCA and strip preparations of HCC. To evaluate the effects of testosterone and DHT on tissue levels of cAMP and cGMP, specimens were exposed to increasing concentrations of the hormones. Forskolin and sodium nitroprusside (SNP) served as reference compounds. Testosterone and DHT dose-dependently reversed the noradrenaline-induced tension of vascular segments and HCC strips. At the maximum concentration, testosterone and DHT reduced the mean (sd) tension to 79.8 (4.43)% and 83.9 (10.94)%, respectively. SNP and forskolin significantly stimulated the production of cGMP and cAMP. No effects of testosterone and DHT on cGMP and cAMP levels were detected. Rapid androgen-induced relaxation of HCA and HCC occurs via non-genomic mechanisms. In penile erectile tissue, non-genomic relaxant effects of testosterone and DHT are not mediated via modulation of cyclic nucleotide tissue levels. Additional studies are required to establish if non-genomic relaxant effects are important in ensuring a basal level of perfusion to maintain overall penile function.
    BJU International 02/2008; 101(1):71-5; discussion 75. · 3.05 Impact Factor
  • Journal of Urology - J UROL. 01/2008; 179(4):235-235.
  • European Urology Supplements - EUR UROL SUPPL. 01/2008; 7(3):185-185.
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    ABSTRACT: Deregulation of the canonical Wnt/beta-catenin-pathway is known to play an important role in the progression of various tumour cell types including prostate cancer (PCa). Recently, the tumour-suppressor p53 was shown to down-regulate beta-catenin-signalling in colon cancer. As p53 is frequently mutated in late stage PCa we investigated the effect of wild-type p53 (p53wt) as well as p53-mutants on beta-catenin-signalling in PCa-cell lines. The effects of p53wt and p53-mutants on Wnt/beta-catenin-signalling were studied using reporter gene assays. Expression of beta-catenin levels was monitored by Western blotting. Overexpression of p53wt as well as p53(249Ser) (a structural mutant) and p53(273His) (a DNA-contact-mutant) almost completely inhibited beta-catenin-mediated transcriptional activity of the T-cell factor (TCF) whereas p53(175His), a structural mutant, and a p53-mutant with a C-terminal deletion in the tetramerization domain (Deltap53) were unable to do so. Co-transfection experiments with p53wt and a dominant negative p53-mutant reversed the down-regulation of TCF-signalling, while Deltap53 was unable to interfere with p53wt-function. Down-regulation of TCF-signalling by p53wt and p53(273His) was accompanied by a reduction in beta-catenin protein level. p53wt, p53(273His)- and p53(249Ser)-mutants are able to down-regulate beta-catenin-signalling in PCa-cells probably via degradation of beta-catenin. The degradation of beta-catenin in PCa by p53 is not linked to transcriptional activity of p53. So far the mechanism how p53 interferes with beta-catenin-signalling is unknown. For the first time we provide experimental evidence that the C-terminus of p53 plays an important role in the down-regulation of beta-catenin-mediated TCF-signalling in PCa-cell lines possibly via p53 transrepressional function.
    The Prostate 01/2008; 67(16):1751-60. · 3.84 Impact Factor
  • Journal of Urology - J UROL. 01/2008; 179(4):452-452.
  • European Urology Supplements - EUR UROL SUPPL. 01/2008; 7(3):187-187.
  • European Urology Supplements - EUR UROL SUPPL. 01/2008; 7(3):216-216.
  • Journal of Urology - J UROL. 01/2008; 179(4):280-281.
  • European Urology Supplements - EUR UROL SUPPL. 01/2008; 7(3):185-185.
  • European Urology Supplements - EUR UROL SUPPL. 01/2008; 7(3):257-257.

Publication Stats

7k Citations
1,128.58 Total Impact Points

Institutions

  • 2008–2009
    • Evangelisches Krankenhaus Oberhausen
      Oberhausen, North Rhine-Westphalia, Germany
  • 1988–2009
    • Hannover Medical School
      • • Institute for Clinical Pharmacology
      • • Department of Nuclear Medicine
      • • Clinic for Urology
      Hannover, Lower Saxony, Germany
    • Universitair Medisch Centrum Groningen
      Groningen, Groningen, Netherlands
  • 2007
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2004–2007
    • University of Tuebingen
      • Department of Urology
      Tübingen, Baden-Wuerttemberg, Germany
    • University of Leipzig
      • Klinik und Poliklinik für Urologie
      Leipzig, Saxony, Germany
  • 2006
    • University of Cologne
      • Department of Neurology
      Köln, North Rhine-Westphalia, Germany
  • 2005
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2002
    • Universität Bremen
      Bremen, Bremen, Germany
    • University of Iowa
      • Department of Urology
      Iowa City, IA, United States
  • 2001
    • Maastricht University
      • Neurologie
      Maastricht, Provincie Limburg, Netherlands
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 2000
    • University of Wuerzburg
      Würzburg, Bavaria, Germany
  • 1998
    • Lower Saxony Institute for Historical Coastal Research
      Wilhelmshaven, Lower Saxony, Germany
  • 1997
    • Hochschule Hannover
      Hanover, Lower Saxony, Germany
  • 1991–1994
    • Hanover Hospital
      Hanover, Pennsylvania, United States
    • Universitätsklinikum Jena
      • Division of Anesthesiology
      Jena, Thuringia, Germany
    • Lund University
      • Department of Clinical Pharmacology
      Lund, Skane, Sweden
    • University of the Ryukyus
      • Department of Urology
      Okinawa, Okinawa-ken, Japan
  • 1985–1989
    • Leiden University Medical Centre
      • Department of Urology
      Leiden, South Holland, Netherlands
  • 1987–1988
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1984–1988
    • CSU Mentor
      Long Beach, California, United States