Heparanase 2 and Urofacial Syndrome, a Genetic Neuropathy.

Urofacial syndrome (UFS) is a rare but potentially devastating autosomal recessive disease. It comprises both incomplete urinary bladder emptying and a facial grimace upon smiling. A subset of individuals with the disease has biallelic mutations of HPSE2, coding for heparanase-2. Heparanase-2 and the classical heparanase are both detected in nerves in the maturing bladder, and mice mutant for Hpse2 have UFS-like bladder voiding defects and abnormally patterned bladder nerves. Other evidence suggests that the heparanase axis plays several roles in the peripheral and central nervous systems, quite apart from UFS-related biology. Some individuals with UFS lack HPSE2 mutations and instead carry biallelic variants of LRIG2, encoding leucine-rich-repeats and immunoglobulin-like-domains 2. Like heparanase-2, LRIG2 is detected in bladder nerves, and mutant Lrig2 mice have urination defects and abnormal patterns of bladder nerves. Further work is now needed to define the precise roles of heparanase-2 and LRIG2 in normal and abnormal neural differentiation.

A mouse model of urofacial syndrome with dysfunctional urination.

Urofacial syndrome (UFS) is an autosomal recessive disease with severe dysfunctional urination including urinary incontinence (UI). Biallelic mutations of HPSE2 are discovered from UFS patients, suggesting that HPSE2 is a candidate disease gene. Here, we show that deletion of Hpse2 is sufficient to cause the UFS-like phenotype in mice. Hpse2 knockout mutants display a distended bladder (megacystis) phenotype and abnormal voiding behavior similar to that found in patients. While Hpse2 is largely dispensable for detrusor smooth muscle and urothelial cell fate determination, the mutants have significantly lower rates of cell proliferation than wild-type littermate controls. All Hpse2 mutants have a growth retardation phenotype and die within a month after birth. Comprehensive blood chemistry and urinalysis indicate that Hpse2 mutants have renal dysfunction and malnutrition. We provide evidence that transforming growth factor beta (Tgfß) signaling is attenuated at birth. However, Tgfß activity is significantly enhanced at later stages when the urological phenotype is severe, and the mutant bladders have accumulated excessive amount of fibrotic tissue. Together, these findings strongly suggest that Hpse2 is a causative gene of human UFS and further uncover unexpected roles of Hpse2 in bladder physiology, tissue remodeling and Tgfß signaling.

PDE5 inhibitor treatment options for urologic and non-urologic indications: 2012 update.

Phosphodiesterase (PDE) enzymes are widely distributed throughout the body, having numerous effects and functions. The use of on demand PDE5 inhibitors (-Is) for the treatment of erectile dysfunction (ED) has recently obtained approval for chronic daily dosing for the same indication. There are published data supporting the use of PDE5-Is for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Additional reports suggest benefit by these agents in patients with chronic heart failure, pulmonary hypertension, essential hypertension, and for the treatment of ischemia. Various central nervous system disorders have been described as targets by PDE5-Is. Sildenafil may have a potential therapeutic indication as a cognitive enhancer in age-related cerebral conditions. There is preclinical evidence for further investigation of the use of PDE5A -Is to improve recovery of cerebral function in humans after stroke by enhancing angiogenesis, neurogenesis and improving neurologic function. Sildenafil delays intestinal ulceration by an increase in the secretion of mucus/fluid and a decrease in hypermotility, and has a protective effect in reducing gastric damage. Larger scale, well designed clinical trials are needed to ascertain the safety, efficacy and cost-effectiveness of PDE5-Is in the future treatment of both urologic and non-urologic diseases. In this review, potential applications of PDE5-Is on urologic, cardiovascular, gastrointestinal, and central nervous system disorders will be updated.

Phosphodiesterase type 5 inhibitors in the management of non-neurogenic male lower urinary tract symptoms: critical analysis of current evidence.

CONTEXT: A large body of epidemiologic data suggests a causal relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). Recently reported studies on phosphodiesterase type 5 inhibitors (PDE5-Is) and LUTS have further contributed to the understanding of mechanisms involved in this relationship and of potential treatment options. OBJECTIVE: A nonsystematic descriptive review was performed to summarize the literature concerning the role of PDE5-Is in men with LUTS, particularly looking at data derived from clinical trials in relation to the different PDE5-Is or their association with α-blockers. EVIDENCE ACQUISITION: A comprehensive electronic search was conducted in October 2010 using the Medline database to identify all publications relating to ED and BPH and treatment with sildenafil, vardenafil, tadalafil, udenafil, UK-369003, and combination therapy with alfuzosin and tamsulosin. EVIDENCE SYNTHESIS: In studies in which either ED or LUTS was the entry criterion, sildenafil appears to improve both erectile function and LUTS in subjects with ED. Placebo-controlled trials of tadalafil and vardenafil showed improvement of LUTS secondary to benign prostatic hyperplasia (BPH), but none of the studies showed a significant effect on urodynamic measures. Exploratory studies with UK-369003 showed improvements in LUTS and ED. Sildenafil or tadalafil associated with alfuzosin or tamsulosin showed greater benefits for the combination therapy for both LUTS and ED. The coadministration of udenafil and an α-blocker in patients with BPH and ED also appeared to improve both LUTS and ED severity. CONCLUSIONS: Consistent evidence of improvements in LUTS has been shown with PDE5-Is, either alone or in combination with α-blockers. However, effects on urodynamics or objective measures of urinary flow are lacking. Further areas of research include investigation of mechanism of PDE5-Is, urodynamic studies, identification of new efficacy end points, head-to-head comparison with standard of care, potential benefit of add-on treatment, and long-term outcomes.

Exome capture and massively parallel sequencing identifies a novel HPSE2 mutation in a Saudi Arabian child with Ochoa (urofacial) syndrome.

We describe a child of Middle Eastern descent by first-cousin coupling with idiopathic neurogenic bladder and high-grade vesicoureteral reflux at 1 year of age, whose characteristic facial grimace led to the diagnosis of Ochoa (urofacial) syndrome at age 5 years. We used homozygosity mapping, exome capture and paired-end sequencing to identify the disease causing mutation in the proband. We reviewed the literature with respect to the urologic manifestations of Ochoa syndrome. A large region of marker homozygosity was observed at 10q24, consistent with known autosomal recessive inheritance, family consanguinity and previous genetic mapping in other families with Ochoa syndrome. A homozygous mutation was identified in the proband in HPSE2: c.1374_1378delTGTGC, a deletion of 5 nucleotides in exon 10 that is predicted to lead to a frameshift followed by replacement of 132 C-terminal amino acids with 153 novel amino acids (p.Ala458Alafsdel132ins153). This mutation is novel relative to very recently published mutations in HPSE2 in other families. Early intervention and recognition of Ochoa syndrome with control of risk factors and close surveillance will decrease complications and renal failure.

Rho-kinase, a common final path of various contractile bladder and ureter stimuli.

Normal urinary bladder function is based on the proper contraction and relaxation of smooth muscle (SM), which constitutes the majority of the bladder wall. The contraction and relaxation of all SM involves a phosphorylation-dephosphorylation pathway involving the enzymes smooth muscle myosin light chain kinase (SMMLCK) and smooth muscle myosin light chain phosphatase (SMMLCP), respectively. Although originally thought to function just as a passive opposition to SMMLCK-driven SM contraction, it is now clear that SMMLCP activity is under an extremely complex molecular regulation via which SMMLCP inhibition can induce "calcium sensitization." This review provides a thorough summary of the literature regarding the molecular regulation of the SMMLCP with a focus on one of its major inhibitory pathways that is RhoA/Rho-kinase (ROK) including its activation pathways, effector molecules, and its roles in various pathological conditions associated with bladder dysfunction. Newly emerging roles of ROK outside of SM contractility are also discussed. It is concluded that the RhoA/ROK pathway is critical for the maintenance of basal SM tone of the urinary bladder and serves as a common final pathway of various contractile stimuli in rabbits, rats, mice, and pigs as well as humans. In addition, this pathway is upregulated in response to a number of pathological conditions associated with bladder SM dysfunction. Similarly, RhoA/Rho-kinase signaling is essential for normal ureteral function and development and is upregulated in response to ureteral outlet obstruction. In addition to its critical role in bladder SM function, a role of ROK in the urothelium is also beginning to emerge as well as roles for ROK in bladder infection and invasion and metastasis of bladder cancer.

[The role of mutation of gene cyp1A1 and benzapilene in cytogenetic changes of urinary tract epitheliocytes in oil industry workers employed in the oil fields of the North of West Siberia].

The examination of 477 oil industry workers and office personnel (control) employed in the oil fields of the North of Tomsk and Tyumen regions has detected increased number of epithelyocytes with micronuclei and an elevated urine level ofbenzapilene in workers employed in oil production. Especially pronounced changes of the above parameters were observed in men with mutant alleles Val of CYP1A1 gene. An enhanced mutation process in oil production workers may be due to a resultant action of different factors on human genome. Involved may be both mutagens and factors of comutagenic nature. The results obtained in this study suggest a conclusion about urgent need of introduction of new scientifically validated criteria of selection of personnel for oil production in the North of the West Siberia. Health examination of the applicants must include genotyping.

Prenatal urinary matrix metalloproteinase profiling as a potential diagnostic tool in fetal obstructive uropathy.

BACKGROUND/PURPOSE: The diagnostic evaluation, patient stratification, and prenatal counseling for congenital obstructive uropathy remain sub-optimal. Matrix metalloproteinase (MMP) expression profiles are emerging as a valuable diagnostic tool in assorted disease processes. We sought to determine whether congenital obstructive uropathy impacts MMP expression in fetal urine. METHODS: Fetal lambs (n = 25) were divided in two groups: group I (n = 12) underwent a sham operation and group II (n = 13) underwent creation of a complete urinary tract obstruction. Gelatin zymography panels for 4 MMP species were performed on fetal urine in both groups at comparable times post-operatively. Statistical analysis was by the Fisher's exact test (P < .05). RESULTS: Overall fetal survival was 80% (20/25). A variety of significant differences in MMP expression between the two groups were identified. The following profiles were present only in obstructed animals: any MMP other than MMP-2 (P = .029), including any MMP other than 63 kDa and 65 kDa (P = .009); 2 or more MMPs excluding MMP-2s (0.029); and 3 or more MMPs (P = .029). CONCLUSIONS: Limited matrix metalloproteinase expression is present in the urine of normal ovine fetuses. Fetal obstructive uropathy impacts urinary MMP expression in various distinguishable patterns. Prenatal urinary MMP profiling may become a practical and valuable diagnostic tool in the evaluation of congenital obstructive uropathy.

Validated questionnaires for assessing sexual dysfunction and BPH/LUTS: solidifying the common pathophysiologic link.

Erectile dysfunction (ED) and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) share many epidemiologic and clinical similarities. First-line therapy for both conditions include oral medications (alpha blockers, phosphodiesterase inhibitors). The impetus to develop and use questionnaires to characterize these two conditions is based on the trend away from invasive diagnostic testing to the use of patient-reported outcomes or validated self-administered questionnaires. The International Prostate Symptom Score, the International Index of Erectile Function, the Male Sexual Health Questionnaire (MSHQ) and the MSHQ short form are similar patient-reported assessment questionnaires used for research or clinical evaluation of BPH/LUTS, ED and ejaculatory dysfunction. These patient-based self-administered questionnaires are likely to assume an ever increasing important role in the future, as oral BPH therapies are considered for the treatment of ED and oral ED therapies are considered for the treatment of BPH/LUTS.

PDE5 inhibitors beyond erectile dysfunction.

The phosphodiesterase type-5 (PDE5) inhibitors sildenafil, vardenafil and tadalafil are widely used first-line therapy for erectile dysfunction (ED). Since the advent of sildenafil in 1998, more than 40 million men worldwide have been successfully treated with these compounds. The safety and high tolerability of PDE5 inhibitors make them an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. As cGMP is a key component of intracellular signaling this may provide novel therapeutic opportunities beyond ED even for indications in which chronic administration is necessary. The approval of sildenafil for the treatment of pulmonary hypertension in 2005 was a notable success in this area of research. A number of other potential new indications are currently in various phases of preclinical research and development. In recent years, extensive but very heterogeneous information has been published in this field. The aim of this review is to summarize existing preclinical and clinical knowledge and critically discuss the evidence to support potential future indications for PDE5 inhibitors.

Inflammatory myofibroblastic tumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma.

Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities. We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC. Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences). Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months. In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but none of our typical cases metastasized, although they can rarely arise contemporaneously with sarcomatoid urothelial carcinomas. For these reasons, close follow-up is warranted.

Five-alpha-reductase expression in benign and malignant urothelium: correlation with disease characteristics and outcome.

OBJECTIVES: To evaluate 5-alpha-reductase (5alphaR) expression in benign and malignant urothelium and to assess the relationship between 5alphaR expression and tumor stage, tumor grade, and clinical outcome in patients with urothelial carcinoma/transitional cell carcinoma. METHODS: We performed immunohistochemistry for 5alphaR on 53 urothelial specimens from 36 patients with transitional cell carcinoma treated at our institution between June 2002 and July 2003. For each tumor and the adjacent nontumor urothelium, a semiquantitative staining score was calculated. We used t tests and analysis of variance to compare the staining score across groups. Kaplan-Meier and logistic regression analyses were performed to assess the relationship between 5alphaR expression and clinical outcome. RESULTS: 5alphaR was expressed throughout the non-neoplastic urothelium. Nontumor urothelium had greater mean staining scores than did tumor specimens (160.1 versus 105.5, P <0.01). Low staining scores were associated with high grade (P <0.05), Stage pT3, pT4, and pTis (P <0.05), and disease progression (P <0.05). A staining score less than the median was a risk factor for progression (odds ratio 6.2, P <0.01) on univariate regression analysis. Patients with a staining score less than the median had a greater likelihood of disease progression (log-rank P <0.05) and cause-specific mortality (log-rank P <0.05). CONCLUSIONS: We demonstrated 5alphaR expression in human urothelium and found that expression is decreased in transitional cell carcinoma in relation to tumor grade and stage. Decreased 5alphaR expression was associated with disease progression and cause-specific mortality.

Angiotensin converting enzyme gene polymorphism in Asian Indian children with congenital uropathies.

PURPOSE: To evaluate the role of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism as a risk factor for progressive renal damage in Asian Indian children with congenital uropathies. MATERIALS AND METHODS: ACE I/D polymorphism was determined by polymerase chain reaction in 84 children with congenital uropathies and 80 unrelated healthy controls. The study group included primary vesicoureteral reflux (29 patients), pelviureteral junction obstruction (21) and posterior urethral valves (34). Mean patient age was 69.4 +/- 4.5 months, and mean followup period was 7.2 +/- 1.5 years. Serum creatinine, ultrasound, voiding cystourethrogram and dimercaptosuccinic acid scans were done to evaluate renal function. RESULTS: The ACE I/D genotype distribution was similar in the 84 patients, II in 37 (44%), DI in 30 (35.7%) and DD in 17 (20.2%), and 80 controls, II in 36 (45%), DI in 30 (37.5%) and DD in 14 (17.5%), chi-square 0.00, p = 1.0). Renal scarring was seen in 49 of 84 patients (58.3%), with D allele present in 35 of 49 (71.4%), compared to 12 of 84 patients (34.2%) in the nonscarring group (chi-square 4.2, p = 0.02). Progressive scarring and renal failure were seen in 23 (27.3%) and 26 (31%) of patients, respectively, with D allele present in 21 of 23 (91.3%) and 21 of 26 (81%), respectively (chi-square 5.4, p = 0.001). Multivariate analysis showed that D allele is an independent risk factor for renal damage. CONCLUSIONS: The presence of D allele in I/D polymorphism of angiotensin converting enzyme gene is associated with progressive deterioration of renal function in congenital uropathies. The D allele was also significantly associated with renal scarring independent of known risk factors such as grade of reflux, age at diagnosis, gender and urinary tract infection.

Tissue polypeptide antigen (TPA) in comparison with mutations of tumour suppressor gene P53 (TP53) in patients with bladder cancer.

BACKGROUND: Tissue polypeptide antigen (TPA) is a circulating complex of polypeptide fragments from cytokeratins 8, 18 and 19. It is a tumour-related protein. TPA is an indicator of higher cell proliferation. One function of TP53 is the suppression of apoptosis. TP53 mutations are frequently correlated with tumour development in bladder cancer. One function of TP53 is the suppression of apoptosis. We compared TPA expression and TP53 mutation analysis in tumour-free and bladder cancer patients. MATERIALS AND METHODS: We examined 93 patients with bladder cancer, 24 patients with benign urological diseases and a control group of 18 healthy individuals. TPA concentration was measured by immunoluminometric assay with LIA-mat TPA-M Prolifigen. The normal cut-off value was defined at 47 U/I for serum and at 60 U/mmol for creatinine. Screening for TP53 mutations in tissue and urine sediment, amplification of the TP53 gene by polymerase chain reaction (PCR) for the exons 5, 6, 7 and 8 and temperature gradient gel electrophoresis (TGGE) were used to analyse the mutations. Statistical analysis included ROC, Mann-Whitney U-Test and Pearson's correlation. RESULTS: For superficial bladder cancer the mutation frequency in TP53 was 44.8%. We found elevated TPA levels in 45.5% in serum and 36.1% in urine. For invasive bladder cancer the mutation frequency in TP53 was 79.2%. Elevated TPA levels were found in 57.7% in serum and in 58.3% in urine. TPA has a sensitivity of 48.9% in serum and 40.4% in urine; the specificity of TPA is 83% in serum and 100% in urine in comparison with healthy individuals. We found no correlation between TPA level and the inflammation status of the patient. CONCLUSION: This study demonstrated that TP53 mutation frequently occurs in higher stages of bladder tumours. There was no TPA level difference between superficial and invasive bladder cancer. TPA is significantly higher in serum (p = 0.012) and in urine (p = 0.002) in patients with bladder cancer in comparison with control group. TPA in serum is significantly higher in patients with mutation of TP53 (p = 0.046) but not in urine (p = 0.173) in comparison with patients with wild-type TP53.

Determination of pyruvate kinase type tumor M2 in human renal cell carcinoma: a suitable tumor marker?

Renal cell carcinoma (RCC) expresses an isoform of the glycolytic enzyme pyruvate kinase (type M2). The dimeric form (TuM2-PK) is over expressed in tumor cells and is detectable in blood with a sensitive enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for RCC. The TuM2-PK concentration in EDTA-plasma was determined quantitatively and immunologically using an ELISA. We measured the TuM2-PK plasma levels of 83 patients before and after surgery. Ninety-seven patients with various non-malignant diseases were also recruited as a control group. The control group displayed mean levels of 11.37 U/ml of TuM2-PK. Values were elevated in patients with RCC prior to surgery (mean 21.88 U/ml). The plasma levels increased after surgery until day 5 (mean 53.97 U/ml). At day 10, marker levels started to decrease without reaching preoperative values (mean 43.5 U/ml). Plasma levels in the renal vein (obtained during surgery) were not different from those in the peripheral blood. Follow-ups after 2-6 months showed a decrease to below preoperative levels (mean 16.3 U/ml). A significant difference was obtained by comparing the patients according to their Robson score. We found a significant difference (P < 0.01, Wilcoxon's two-sample test) in TuM2-PK levels between patients with RCC and the control group. Nevertheless, using the manufacturer's recommended cut-off value (15 U/ml), sensitivity was only 50.6% and specificity was 80.4%. Our results suggest that TuM2-PK is not a suitable tumor marker for RCC.

Use of serum gamma-enolase and aldolase A in combination as markers for renal cell carcinoma.

To clarify whether measurement of serum gamma-enolase and aldolase A in combination is useful for diagnosis and prediction of prognosis in cases of renal cell carcinoma (RCC), levels of both markers were evaluated by enzyme immunoassay in 132 patients with RCC. Serum gamma-enolase was elevated in 53 of the cases (40%) whereas serum aldolase A was elevated in 45 (34%). At least one of the two markers was elevated in 54% of the patients (71/132), this value being significantly higher than the positive rates for either gamma-enolase (40%) or aldolase A (34%) evaluated singly. Expression of the two markers assessed in combination became more positive with stage progression, values being 37% in stage I, 59% in stage II, 72% in stage III, and 74% in stage IV. In contrast, patients with benign urological diseases demonstrated positive rates for gamma-enolase and aldolase A as low as 3% and 6%, respectively. Increase in serum gamma-enolase was correlated with stage, tumor size, and histological grade, whereas elevated levels of serum aldolase A were associated only with advancing stage. In 15 patients with recurrent diseases, 11 (73%) had elevated levels of gamma-enolase and 5 (33%) had elevated levels of aldolase A, indicating that gamma-enolase is the more sensitive of the two for detection of recurrence. Patients with elevated levels of both gamma-enolase and aldolase A had less favorable survival than those expressing no or only one of the markers, indicating that simultaneous measurement of the two markers provides information directly relevant to prognosis in cases of RCC.

Determination of soluble interleukin-2 receptor in human seminal plasma.

Following lymphocyte activation a soluble form of TAC antigen is released. This soluble molecule (soluble interleukin-2 receptor, SIL-2R) seems to corresponds to a truncated extracellular part of the membrane-bound TAC antigen, being smaller than its cellular counterpart. SIL-2R was determined and correlated with PMN elastase levels in the seminal plasma of 79 adult men having different concentrations of PMN elastase (0-700 micrograms/L). The normal level of SIL-2R was detected in the seminal plasma of 15 healthy men. The mean +/- SEM was 101 +/- 29 units/mL. The relation between PMN elastase in human seminal plasma as an index for the state of lymphocyte activity and the sperm motility is also investigated.

[Clinical evaluation of urinary glycyl-prolyl dipeptidyl aminopeptidase in patients with urological disease].

Urinary glycyl-prolyl dipeptidyl aminopeptidase (GP-DAP) activity was measured in 18 healthy adults and 252 patients with urological diseases. The GP-DAP activity was significantly higher in patients with prostatic cancer, bladder cancer or renal cancer and also in patients with acute prostatitis or pyelonephritis than in healthy adults. GP-DAP activity was also studied during anticancerous chemotherapy and proved to be a sensitive parameter for renal damage as are urinary N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, beta 2-microglobulin, alpha 1-microglobulin, and albumin. The analysis of tissue activities suggested that GP-DAP was located not only in the renal parenchyma but also in the prostate and seminal vesicles.

[Studies of enzymuria and proteinuria: Report 1: N-acetyl-beta-glucosaminidase in urological diseases].

N-Acetyl-beta-glucosaminidase (NAG) exists in renal tubules and seminal tract. We measured the NAG level in patients with urinary tract and seminal tract diseases and evaluated its clinical significance. The urinary NAG level was high in renal tubular function disorders such as glomerulonephritis, diabetic nephropathy and hydronephrosis. In these patients, NAG-isoenzyme studies indicated that the A-type isoenzyme decreased while the B-type isoenzyme increased. On the other hand, in the seminal tract disease patients, the urinary NAG level was high in benign prostatic hypertrophy with a catheter indwelling and in prostatitis. Urinary and seminal NAG-isoenzymes were measured in normal subjects. The isoenzyme patterns for urinary NAG and seminal NAG differed. The urinary NAG isoenzymes were measured in acute prostatitis patients, we found that the A-type isoenzyme decreased and the B type increased. In conclusion, when the A/B ratio of the NAG-isoenzyme is close to 24.9/75.0 in the urine, the presence of urological diseases in which seminal plasma could be mixed in, especially prostatic diseases, should be suspected.