RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer.

OBJECTIVE: To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS: The mRNA and protein levels of RhoA in matched sets of tumour, non-tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS: The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non-tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan-Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease-free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease-free and overall survival (both P < 0.05). CONCLUSIONS: These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.

The rho/rho-kinase pathway is involved in the progression of testicular germ cell tumour.

OBJECTIVE: To clarify the role of one of the downstream effectors of Rho (Rho-kinase) in testicular germ cell tumour (GCT) by quantifying mRNA expression for Rho-kinase in patients with this disease. MATERIALS AND METHODS: The mRNA levels of the RhoA and Rho-kinase genes were analysed in surgical specimens of testicular GCT tissues from 57 consecutive Japanese patients, and in the corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. The expression levels of these genes were compared between the tissues and the relationship between their expression levels evaluated within tumours and with tumour stage. The difference in the expression levels of the mRNAs of RhoA and Rho-kinase genes were also assessed between tumours that were seminoma only and mixed tumours of seminoma and nonseminoma. RESULTS: RhoA and Rho-kinase mRNAs were more abundant in tumour tissue than in non-tumour tissue (P < 0.01 and < 0.05, respectively). High RhoA and Rho-kinase mRNA expressions were related to tumour stage (P < 0.05 and < 0.01, respectively). The mRNA levels of RhoA and Rho-kinase in mixed tumours were higher than in tumours with seminoma only (P < 0.01 and < 0.05, respectively). There was a positive relationship between expression levels of mRNAs of RhoA and Rho-kinase in tumour tissues (P < 0.001). CONCLUSIONS: These findings suggest that the RhoA/Rho-kinase pathway is involved in the progression of testicular GCT. This pathway might be a molecular target for new treatment strategies for this disease.

Rat cardiac contractile dysfunction induced by Ca2+ overload: possible link to the proteolysis of alpha-fodrin.

The aim of the present study was to examine the mechanisms of Ca2+ overload-induced contractile dysfunction in rat hearts independent of ischemia and acidosis. Experiments were performed on 30 excised cross-circulated rat heart preparations. After hearts were exposed to high Ca2+, there was a contractile failure associated with a parallel downward shift of the linear relation between myocardial O(2) consumption per beat and systolic pressure-volume area (index of a total mechanical energy per beat) in left ventricles from all seven hearts that underwent the protocol. This result suggested a decrease in O(2) consumption for total Ca2+ handling in excitation-contraction coupling. In the hearts that underwent the high Ca2+ protocol and had contractile failure, we found marked proteolysis of a cytoskeleton protein, alpha-fodrin, whereas other proteins were unaffected. A calpain inhibitor suppressed the contractile failure by high Ca2+, the decrease in O(2) consumption for total Ca2+ handling, and membrane alpha-fodrin degradation. We conclude that the exposure to high Ca2+ may induce contractile dysfunction possibly by suppressing total Ca2+ handling in excitation-contraction coupling and degradation of membrane alpha-fodrin via activation of calpain.

Decreasing of p27(Kip1)and cyclin E protein levels is associated with progression from superficial into invasive bladder cancer.

The p27(Kip1)(p27) protein is a cyclin-dependent kinase inhibitor of the transition from G1 to S phase. It has been reported that decreased p27 protein level is a negative prognostic indicator in human tumours including bladder cancer. We studied the relationship between protein levels of p27, cyclin E and Ki-67 and clinicopathological features of 145 consecutive Japanese patients with transitional cell carcinoma of the bladder using immunohistochemical staining. Low protein levels of p27 were associated with low staining of cyclin E (P = 0.0302), high Ki-67 index (P = 0.0306), poorly differentiated grade (P = 0.0006), muscle invasion (P = 0.0019) and lymph node metastsis (P = 0.0002). Low staining of cyclin E and high Ki-67 index correlated with poorly differentiated grade, muscle invasion and lymph node metastsis. Cyclin E protein levels was inversely related with Ki-67 index (P = 0.0002). Kaplan-Meier plots of survival rate in patients with low versus high p27 staining showed that low protein levels of p27 were associated with a shortened disease-free and overall survival (P< 0.0001 and P< 0.0001, respectively). Similarly, low staining of cyclin E and high Ki-67 index correlated with a shortened disease-free and overall survival. On multivariate analysis using Cox proportional hazards model, low protein levels of p27 and high Ki-67 index were independent predictors of shortened disease-free (P< 0.0001, P = 0.0031, respectively), and low protein levels of p27, low staining of cyclin E and high Ki-67 index of overall survival (P = 0.0017, P = 0.0009, P = 0.0003, respectively). In superficial bladder tumours (Ta, T1; 86 patients), significant correlations were observed between low p27 staining and high Ki-67 index and early recurrence (P = 0.0048, P = 0.0178, respectively). Among the recurrenced superficial tumours (35 patients), the tumours which remained at a low stage showed high protein levels of p27 and cyclin E, and the tumours which progressed to invasive disease showed a gradual decrease in p27 and cyclin E protein levels over time. Our findings suggest that decreased protein levels of p27 and cyclin E play a role in the progression of bladder cancer and to evaluate these protein levels may be useful in management of the diseases.

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

OBJECTIVES: To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival. PATIENTS AND METHODS: The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. RESULTS: Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05). CONCLUSIONS: These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.

An operon for a putative ATP-binding cassette transport system involved in acetoin utilization of Bacillus subtilis.

The ytrABCDEF operon of Bacillus subtilis was deduced to encode a putative ATP-binding cassette (ABC) transport system. YtrB and YtrE could be the ABC subunits, and YtrC and YtrD are highly hydrophobic and could form a channel through the cell membrane, while YtrF could be a periplasmic lipoprotein for substrate binding. Expression of the operon was examined in cells grown in a minimal medium. The results indicate that the expression was induced only early in the stationary phase. The six ytr genes form a single operon, transcribed from a putative sigma(A)-dependent promoter present upstream of ytrA. YtrA, which possesses a helix-turn-helix motif of the GntR family, acts probably as a repressor and regulates its own transcription. Inactivation of the operon led to a decrease in maximum cell yield and less-efficient sporulation, suggesting its involvement in the growth in stationary phase and sporulation. It is known that B. subtilis produces acetoin as an external carbon storage compound and then reuses it later during stationary phase and sporulation. When either the entire ytr operon or its last gene, ytrF, was inactivated, the production of acetoin was not affected, but the reuse of acetoin became less efficient. We suggest that the Ytr transport system plays a role in acetoin utilization during stationary phase and sporulation.

Prognostic significance of p27Kip1 and Ki-67 expression in carcinoma of the renal pelvis and ureter.

OBJECTIVE: To determine the significance of p27(Kip1) (p27) for tumour behaviour and prognosis of patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter. PATIENTS AND METHODS: Using immunohistochemical staining, the relationship was evaluated between p27 protein level (low < 50%, high > 50%) and the Ki-67 labelling index (low < 30%, high > 30%) and clinicopathological features of 37 consecutive Japanese patients with TCC of the renal pelvis and ureter. RESULTS: Low levels of p27 correlated with higher tumour stage (P < 0.05) and positive lymph node metastases (P < 0.05). There was no significant association between p27 staining and the grade and tumour proliferation as assessed by the Ki-67 index. A high Ki-67 index correlated with higher grade and stage (P < 0.05). Kaplan-Meier plots of survival rate in patients with low or high p27 staining showed that low levels correlated with a shorter disease-free and overall survival (P < 0.001 and P < 0.01, respectively). Similarly, patients with a high Ki-67 index had lower disease-free and overall survival than those with a low Ki-67 index (P < 0.01 and P < 0.05, respectively). The Cox proportional hazards model showed that a low level of p27 was an independent predictor of a shorter disease-free (P < 0.01) and overall survival (P < 0.05) on univariate analysis, but not of overall survival on multivariate analysis. A high Ki-67 index was an independent prognostic marker for shorter disease-free survival on univariate and multivariate analysis (P < 0.01) and for overall survival on multivariate analysis (P < 0.05). In those with a high Ki-67 index, increased p27 staining was associated with a better prognosis than decreased staining for disease-free and overall survival (log-rank test, P < 0. 01 and P < 0.05, respectively). CONCLUSIONS: The finding that a low level of p27 is associated with tumour invasion and unfavourable prognosis indicates that p27 may be a useful prognostic marker for survival in upper urinary tract cancer.

Preliminary report of the clinical performance of a new urinary bladder cancer antigen test: comparison to voided urine cytology in the detection of transitional cell carcinoma of the bladder.

We compared the ability of a new urinary bladder cancer antigen (UBC) test with conventional cytology for the detection of transitional cell carcinoma of the bladder using voided urine samples. The UBC was measured and corrected for the creatinine concentration in the urine of 61 patients with transitional cell carcinoma of the bladder (group 1), 23 patients without recurrent bladder tumors during follow-up (group 2), 28 patients with benign prostatic hyperplasia (group 3), nine patients with prostate cancer (group 4), and 90 healthy volunteers free of urological diseases (group 5). The UBC concentrations were 408.8+/-578.5, 18.8+/-26.6, 23.9+/-32.7, 17.5+/-18.6 and 4.6+/-6.7 ngmg(-1) creatinine (mean+/-S. D.) for groups 1-5, respectively. The level for group 1 was significantly higher than for any other group. The sensitivity and specificity, which were optimized using receiver-operating characteristic curves for groups 1 and 2 were 82.0% and 82.6%, respectively, at a threshold value of 39 ngmg(-1) creatinine. The sensitivity and specificity of cytology for these same groups were 60.7% and 86.9%, respectively. The sensitivity of the UBC was significantly higher than that of cytology, not only for total bladder tumors (82.0% vs. 60.7%, P<0.02) but also for grade I transitional cell carcinoma of the bladder (76.5% vs. 11.8%, P<0. 001). While offering a similarly high specificity, the UBC test might have an advantage over cytology in terms of superior sensitivity, particularly for low-grade tumors.

CAG repeat length in the androgen receptor gene is enhanced in patients with idiopathic azoospermia.

OBJECTIVES: To determine whether the number of CAG repeats in the androgen receptor gene is enhanced in patients with idiopathic azoospermia. METHODS: Using the polymerase chain reaction, the number of CAG repeats was assayed in 41 patients with idiopathic azoospermia and in 48 normozoospermic fertile men. RESULTS: In the control group, the CAG repeat length ranged from 17 to 30 (mean 23.9 +/- 2.9); in the azoospermic group, the CAG repeat length ranged from 20 to 34 (mean 26.5 +/- 3.5). The difference between the two groups was statistically significant (P = 0.0013). None of the men in the control group had a CAG repeat length greater than 31; four of the azoospermic men had 34 CAG repeats. CONCLUSIONS: Results suggest that an increase in the number of CAG repeats in the androgen receptor gene to 31 or greater may be associated with the etiology of at least some cases of idiopathic azoospermia.

Interaction of a repressor and its binding sites for regulation of the Bacillus subtilis iol divergon.

Transcription of the Bacillus subtilis iol divergon is negatively regulated by a repressor encoded by iolR, which belongs to the DeoR family of bacterial regulators. Gel retardation analysis involving the IolR protein synthesized in Escherichia coli revealed that IolR bound specifically and independently to each of the iol and iolRS promoter regions, with higher affinity to iol. DNase I footprinting revealed that IolR affected DNase I sensitivity either in the iol promoter region between nucleotides -46 and +51 or in iolRS between -79 and -2 (+1 is the transcription initiation nucleotide of both iol and iolRS), indicating its interaction with the extended regions of the iol and iolRS promoters. Deletion analysis indicated that the iol region between -23 and +21 is involved mainly in IolR binding and negative regulation, while the iolRS region between -70 and -44 comprises at least part of the cis-acting sequences for IolR binding and negative regulation. Sequence examination of the extended regions revealed that a tandem direct repeat consisting of two relatively conserved 11-mer sequences, WRAYCAADARD (where D is A, G or T; R is A or G; W is A or T; and Y is C or T), found in each of the iol and iolRS regions might be a determinant sequence for the IolR-DNA interaction. Actual involvement of the direct repeats in the IolR-DNA interaction was shown by the deficiency of IolR-binding and negative regulation that was caused by substitution of the conserved bases within the conserved sequences. These results imply a unique mode of interaction of IolR with the target DNA.

Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

Organization and transcription of the myo-inositol operon, iol, of Bacillus subtilis.

Previous determination of the nucleotide sequence of the iol region of the Bacillus subtilis genome allowed us to predict the structure of the iol operon for myo-inositol catabolism, consisting of 10 iol genes (iolA to iouJ); iolG corresponds to idh, encoding myo-inositol 2-dehydrogenase (Idh). Primer extension analysis suggested that an inositol-inducible promoter for the iol operon (iol promoter) might be a promoter-like sequence in the 5' region of iolA, which is probably recognized by sigmaA. S1 nuclease analysis implied that a rho-independent terminator-like structure in the 3' region of iolJ might be a terminator for iol transcription. Disruption of the iol promoter prevented synthesis of the iol transcript as well as that of Idh, implying that the iol operon is most probably transcribed as an 11.5-kb mRNA containing the 10 iol genes. Immediately upstream of the iol operon, two genes (iolR and iolS) with divergent orientations to the iol operon were found. Disruption of iolR (but not iolS) caused constitutive synthesis of the iol transcript and Idh, indicating that the iolR gene encodes a transcription-negative regulator (presumably a repressor) for the iol operon. Northern and S1 nuclease analyses revealed that the iolRS genes were cotranscribed from another inositol-inducible promoter, which is probably recognized by sigmaA. The promoter assignments of the iol and iolRS operons were confirmed in vivo with a lacZ fusion integrated into the amyE locus.

A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.

Cytokines and various cellular stresses are known to activate c-Jun NH2-terminal kinase (JNK), which plays a role in conveying signals from the cytosol to the nucleus. Here we investigate the translocation and activation of JNK1 during ischemia and reperfusion in perfused rat heart. Ischemia induces the translocation of JNK1 from the cytosol fraction to the nuclear fraction in a time-dependent manner. Immunohistochemical observation also shows that JNK1 staining in the nucleus is enhanced after ischemia. During reperfusion after ischemia, further nuclear translocation of JNK1 is apparently inhibited. In contrast, JNK1 activity in the nuclear fraction does not increased during ischemia but increases significantly during reperfusion with a peak at 10 min of reperfusion. The activation of JNK1 is confirmed by the phosphorylation of endogenous c-Jun (Ser-73) with similar kinetics. The level of c-jun mRNA also increases during reperfusion but not during ischemia. Based on fractionation and immunohistochemical analyses, an upstream kinase for JNK1, SAPK/ERK kinase 1 (SEK1), is constantly present in both the nucleus and cytoplasm throughout ischemia and reperfusion, whereas an upstream kinase for mitogen-activated protein kinase, MAPK/ERK kinase 1, remains in the cytosol. Furthermore, phosphorylation at Thr-223 of SEK1, necessary for its activation, rapidly increases in the nuclear fraction during postischemic reperfusion. These findings demonstrate that JNK1 translocates to the nucleus during ischemia without activation and is then activated during reperfusion, probably by SEK1 in the nucleus.

Mitogen-activated protein kinase translocates to the nucleus during ischaemia and is activated during reperfusion.

Growth factors and various cellular stresses are known to activate mitogen-activated protein (MAP) kinase, which plays a role in conveying signals from the cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. Immunohistochemical observation shows that MAP kinase staining in the nucleus is enhanced after ischaemia for 40 min. Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates from the cytosol to the nucleus. During reperfusion (0-30 min), after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear fraction is increased with a peak at 10 min of reperfusion. The activation is confirmed by MAP kinase activity with similar kinetics to the tyrosine phosphorylation. However, the amount of MAP kinase in the fraction is almost constant during reperfusion for 10 min. Although an upstream kinase for MAP kinase, MAP kinase/extracellular signal-regulated kinase kinase (MEK)-1, remains in the cytosol throughout ischaemia and reperfusion, MEK-2, another upstream kinase for MAP kinase, is constantly present in the nucleus as well as in the cytoplasm, based on analyses by fractionation and immunohistochemistry. Furthermore, MEK-2 activity in the nuclear fraction is rapidly increased during post-ischaemic reperfusion. These findings demonstrate that nuclear MAP kinase is activated by tyrosine phosphorylation during reperfusion, probably by MEK-2.

Study of the structure of struvite stones with scanning electron microscopy and energy-dispersive X-ray microanalysis.

Topographic features of eight struvite calculi were investigated with scanning electron microscopy (SEM) equipped with energy-dispersive X-ray microanalysis (EDX). Perpendicularly cracked fragments showed concentric laminations composed of compact and loosely packed strata alternately. Magnesium and phosphorus were detected in the compact strata with their characteristic dispersive X-ray spectra. There existed numerous spherular crystals with smooth or porous surfaces and scattered penta- or hexa-hedral coffin-lid shaped crystals in the loosely packed strata. The former crystals showed the dispersive X-ray spectra of calcium and phosphorus, and were estimated to be calcium phosphate (CaP). The latter ones were presumed to be magnesium ammonium phosphate (MAP) with EDX. The surfaces of the fragments were cracked like eggshells and displayed numerous CaP crystals and scattered MAP crystals in most cases, while in only 1 case some faces of pieces demonstrated wavy MAP phases, sundry areas which were rimmed with aggregated CaP spherulites. The mean molar ratios of Mg/P and Ca/P in each case were 0.88-1.03 and 1.25-1.52, respectively. Though EDX was inadequate to determine the accurate chemical formula of CaP and MAP crystals by detecting their molar ratios of Ca/P and Mg/P with EDX, SEM/EDX is useful to observe these urolith crystals and to surmise them to be CaP or MAP crystals by detecting their atomic elements with EDX.

[Epidemiological study on sexually transmitted diseases in Saitama Prefecture--mainly study of male urethritis].

Epidemiological studies on sexually transmitted diseases (STDs) in Saitama Prefecture, from 1989 through 1991, were performed and the following results were obtained. The number of patients was 1,833 (male: 1,532, female: 30) cases in 1989, 1,294 (male: 1,163, female: 131) cases in 1990, and 1,672 (male: 1,478, female: 149) cases in 1991. Male patients in their twenties or thirties were often affected by STDs. The order of frequency of STDs was roughly as follows; non-gonococcal and non-chlamydial urethritis, gonococcal urethritis, chlamydial rethritis, condyloma acuminatum, genital herpeic infection and syphilis. Concerning the criteria of the diagnosis on chlamydial urethritis, cases diagnosed by only clinical findings decreased markedly from 1989 through 1991, cases diagnosed by the combination of the antibody of C. trachomatis and clinical findings increased, and cases diagnosed by the detection of C. trachomatis were always about 70%. Male patients were mostly infected from prostitutes. Many patients with STDs were often infected in Taiwan, the Philippines, the Kingdom of Thailand and Republic of Korea.

Comparative studies on the properties of purified gamma-glutamyl transferase from human reproductive system and the kidney.

Gamma-glutamyl transferase (GGT) of the human seminal plasma and reproductive tissues was purified and its properties were compared to those of the enzyme from kidney. A single band of GGT was obtained by polyacrylamide gel electrophoresis. Purification was 1080-fold for seminal plasma, 206-fold for prostate, 608-fold for testis and 382-fold for kidney. Similar Km value (0.87-1.06 mM) and optimum pH (8.2-8.5) were obtained for the enzymes of the four different sources. Their thermal stabilities were identical. However, inhibitions by Zn2+ and Cu2+ were different between kidney and reproductive system GGT. Molecular mass of the native enzyme was 78 kDa for seminal plasma, prostate and testis and 79 kDa and 105 kDa for kidney. The subunit molecular masses of the enzymes from seminal plasma, prostate and kidney consisted of three proteins, suggesting the precursor form, and the heavy and light subunits of the mature form.

[A study on acute renal damage from percutaneous nephrolithotomy assessed by urinary NAG and gamma-GTP activities].

We performed percutaneous nephrolithotomy (PNL) on 49 patients between May, 1986 and March, 1987. To investigate acute renal damage from PNL, we measured urinary NAG (N-acetyl-beta-D-glucosaminidase) and gamma-GTP (gamma-glutamyl transpeptidase) activities before PNL and for 6 days after PNL in 24 patients. The NAG activities elevated beyond normal level in 23 patients and gamma-GTP activities in 15 patients. NAG activities showed a peak level in the third day after PNL and gamma-GTP activities in the next day of PNL. After the peak both enzyme activities got down gradually. There was no difference in NAG and gamma-GTP activities between nephrostomy and lithotripsy in 2 staged patients. And the intrapelvic pressure during operation was at the normal level in 5 patients. Therefore, we think that the cause of NAG and gamma-GTP activity elevation is a mechanical damage, not an influence of the irrigation fluid. Large stones, long operation time and 2 stage procedure were the factors that produced high enzyme activities, because, we guess, the frequency of mechanical damages to the kidney increase in such cases. Postoperative pyrexia caused a slight increase in enzyme activities but preoperative hydronephrosis exerted no influence on both enzyme activities. We also measured creatinine clearance before and after PNL but no significant change was obtained. PNL causes only slight mechanical damage to the operated kidney which is reversible when assessed by NAG and gamma-GTP activities and the glomerular function is not affected. Therefore, we conclude that PNL is a safe treatment for upper urinary tract stones.