Background Gastrin/cholecystokinin type B receptors (CCKBRs) can be found on parietal cells and smooth muscle cells and are the predominant brain CCK receptors. Recent cloning studies indicate that this receptor type might also be expressed in the kidney. Materials and methods We used Northern blot analysis in guinea pig. kidney and reverse transcriptase polymerase chain reaction (RT‐PCR) in several murine kidney cell lines to evaluate this organ for the expression of the CCKBRs. The receptor was pharmacologically characterized by displacement experiments using [125I]‐BH‐CCKs and various agonists and antagonists. Polyclonal antibodies vs. the CCKBRs were raised in chicken, and immunohistochemistry on tissue sections was used to localize the receptor within the organ. The effect of gastrin on renal cell growth was measured using proximal tubulus (MCT) cells, which were cultured with gastrin (10−9 M) for 24–72 h. Cell counts and [3H]‐thymidine incorporation experiments were performed. Results CCKBR transcripts can be detected in kidney RNA (tubules > glomeruli > interstitium). RT‐PCR revealed CCKBR transcripts in proximal tubules (MCT cells) and in mesangium (MMC). The medullary thick ascending limb of Henle's loop and several control tissues such as liver and muscle were negative. Displacement experiments using [125I]‐BH‐CCK and various agonists and antagonists identified binding sites with typical CCKBR pharmacology. CCKBRs were localized in the proximal tubulus, distal collecting ducts and mesangium cells. Treatment of rested MCT cells with gastrin 17‐1 induced cell proliferation and [3H]‐thymidine incorporation by at least 40% compared with normal growth (P < 0.05). Conclusion These results show for the first time that CCKBRs are present in selected areas of the kidney, and strongly confirm our previous observation that this organ expresses binding sites for [125I]‐gastrin. Furthermore, gastrin might act as a growth factor in the kidney.
Objective To correlate the immunohistochemically of decreased E-cadherin expression for the long-term or recurrence-free survival of patients, using a threshold detected loss of E-cadherin expression with patient age, clinical and biological variables, and to investigate value of 40% for the relative amount of positively stained tumour cells, or for any other threshold value the prognostic value of these variables for the relapsefree and overall survival of patients with diCerent calculated (25%, 60% or 75%). However, comparing a follow-up of 16 months in patients with <40% stages of newly diagnosed prostate cancer. Patients and methods Sixty-seven patients (median age positivity and 46 months in patients with Á40% positivity, those patients retaining E-cadherin 63 years, range 48-78) undergoing radical prostatectomy for the treatment of primary prostate cancer expression had a significantly longer recurrence-free interval after radical prostatectomy (P<0.01). were assessed to determine whether age, tumour stage, histological grading, serum levels of prostate specific Conclusion The value of E-cadherin expression as an additional independent prognostic variable for patients antigen and prostatic acid phosphatase, regional lymph node status and E-cadherin expression were with primary prostate cancer is questionable. Keywords E-cadherin, expression, prostate cancer, radprognostic factors for relapse-free and overall survival. Results With a median (range) follow-up of 54 (3-193) ical prostatectomy, clinical prognosis months, there was no independent prognostic value brane 120 kDa glycoprotein belonging to the group of
Objective To evaluate the outcome of a new modification of percutaneous needle suspension, using a bone anchor system for fixing the suture at the pubic bone, and to compare the results with those published previously. Patients and methods From March 1996, 37 patients with stress urinary incontinence (>2 years) were treated using a bone anchor system. On each side the suture was attached to the pubocervical fascia and the vaginal wall via a broad ‘Z’‐stitch. A urodynamic investigation performed preoperatively in all patients confirmed stress incontinence and excluded detrusor instability. The outcome was assessed either by a clinical follow‐up investigation or using a standardized questionnaire, over a mean follow‐up of 11 months (range 6–18). Results In the 37 patients, the procedure was successful in 25 (68%), with 16 (43%) of the patients completely dry and nine (24%) significantly improved. Removal of the bone anchor and suture was necessary in two patients, because of unilateral bacterial infection in one and a bilateral soft tissue granuloma in the other. One bone anchor became dislocated in a third patient. In two cases where the treatment failed, new detrusor instability was documented urodynamically. Minor complications were prolonged wound pain in 10 (26%) and transient urinary retention or residual urine in 12 patients (32%). Conclusion The poor success rate in this study corresponds with the long‐term results of conventional or modified needle suspension procedures and does not reinforce the optimistic results of bone anchoring published recently. Because of the poorer long‐term results from percutaneous needle suspension than from other techniques of open retropubic bladder neck suspension, it remains questionable whether percutaneous needle suspension should be considered a first‐line procedure for the treatment of female stress urinary incontinence.
Objectives To evaluate the long-term continence rate, frequency of complications other than urinary retention was significant during and after surgery, at 27%, including subjective satisfaction and therapyassociated morbidity, of patients undergoing Stamey and in accord with the complication rate reported in earlier studies. bladder neck suspension. Patients and methods Eighty-five women (median ageConclusions Compared with other bladder neck suspension procedures, e.g. Burch colposuspension, the 55 years, range 30-85) with urinary stress incontinence treated by Stamey bladder neck suspension at Stamey procedure appears to be associated with a higher frequency of postoperative recurrent urinary our institution between 1987 and 1995 were evaluated using an anonymous questionnaire over a mean stress incontinence. Therefore, the Stamey procedure should only be used if the patient demands a minimally (range) follow-up of 61 (13-93) months. Results Of the 85 patients, 44 (52%) reported an invasive surgical procedure for bladder neck suspension. Although #60% of patients were satisfied with improvement in clinical symptoms at the evaluation and 29 (34%) were completely continent after the the durable improvement in clinical symptoms, it is appropriate to inform patients before surgery of the Stamey procedure. However, 53 (62%) patients reported subjective satisfaction with the result, because high recurrence rate after Stamey bladder neck suspension. they had a durable improvement in continence for a mean (range) of 44 (10-79) months. There was noKeywords Stamey bladder neck suspension, questionnaire-based analysis, long-term continence, compli-correlation between the number of previous urogynaecological operations undergone by the patients and cations, subjective satisfaction the success of the Stamey procedure. However, the like colporrhaphy or pubococcygeal plasty are associated
Growth differentiation factor 15 (GDF15) is a stress-induced cytokine that modulates food intake and energy metabolism. Until now, most mechanistic studies on GDF15 rely on pharmacological interventions using exogenous GDF15, but little is known about its mode of action when induced both chronically and endogenously. Mitochondrial stress is one of the most described physiological conditions that induces GDF15, and therefore an important model to study the underlying mechanisms of endogenous GDF15 action. Here, using a mouse model of mitochondrial dysfunction via elevated respiratory uncoupling in skeletal muscle, we show a circadian oscillation of muscle-derived GDF15 to promote a daytime-restricted anorexia without signs of nausea or reduced physical activity, contrary to findings using recombinant GDF15. We find that mitochondrial stress-induced GDF15 associates with increased anxiety and hypothalamic corticotropin releasing hormone (CRH) induction, without further activation of the hypothalamic-pituitary-adrenal (HPA) axis and corticosterone response. Strikingly, the daytime-restricted anorexia, lean phenotype, systemic shift in substrate metabolism and anxiety-like behavior are completey abolished in conditions of mitochondrial stress coupled with genetic ablation of the GDF15 receptor GDNF receptor alpha-like (GFRAL), which is predominantly expressed in the hindbrain. Finally, we demonstrate that stress-induced GDF15-GFRAL signaling is required for hypothalamic CRH induction to control diurnal food intake in a CRH-receptor 1 (CRHR1)-dependent manner. With this, we uncover for the first time a molecular target of the GDF15-GFRAL axis that links anxiolytic and anorectic behavior as downstream effects of the chronic activation of this pathway by mitochondrial stress.
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