[Behavior of Trp-P-1 and its metabolites in rat excreta].

To study of the behavior of Trp-P-1 and its metabolites in rat feces and urine, rats were orally administered with Trp-P-1 (750, 1,500 and 2,500 micrograms/rat), and excreted Trp-P-1 was analyzed using HPLC assay and bacterial mutagenicity assay. The extraction of Trp-P-1 from urine was performed by using the chloroform extraction method, and blue rayon was used for the extraction from feces. When Trp-P-1 was added to rat feces and urine, the recoveries of Trp-P-1 were 85.9 +/- 3.9% and 91.3 +/- 3.7%, respectively. The extracts of feces and urine from rats administered with Trp-P-1 were individually fractionated by thin layer chromatography on C18 gel. The major mutagenic zone corresponding to Trp-P-1 was found at Rf 0.09 in both extracts, while the feces extract gave two additional mutagenic zones at Rf 0.15 and 0.20. More than 97% of the fecal mutagenic activity was due to unchanged Trp-P-1. In rats administered with 750 micrograms of Trp-P-1, the amount of extracted Trp-P-1 and the number of His+ colonies induced by whole excreta were 81.6 +/- 7.1 micrograms (n = 6) and (432 +/- 77) x 10(4) for feces, and 28.7 +/- 4.9 micrograms and (171 +/- 28) x 10(4) for urine. The recoveries of Trp-P-1 in the feces and urine were 10.8 +/- 0.9% and 3.8 +/- 0.7% by HPLC analysis, and 11.1 +/- 2.0% and 4.4 +/- 0.7% by mutagenicity assay respectively. The results of the two assays seemed to show similar patterns of recovery.

Are alpha-blockers involved in lower urinary tract dysfunction in multiple system atrophy? A comparison of prazosin and moxisylyte.

Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple system atrophy (MSA). alpha1-Adrenergic receptors are present in the proximal urethra where impaired relaxation may be responsible for voiding difficulty and a large amount of residual urine. An open study was designed to evaluate whether the blockade of these receptors by prazosin (a nonselective alpha1 blocker) and moxisylyte (an alpha1A-selective blocker) would improve bladder emptying in patients with MSA. Post-micturition residual volumes and clinical symptoms of 49 patients with MSA were evaluated at trial entry and after 4 weeks (prazosin; n=21 and moxisylyte; n=28). The respective means for the prazosin and moxisylyte groups were 38.1% and 35.2% reductions in residual urine volume (P<0.05), and there was lessening of urinary symptoms. Side effects due to orthostatic hypotension were seen in 23.8% of the prazosin group but in only 10.7% of the moxisylyte group. These effects were common in patients with postural hypotension of more than -30 mmHg at trial entry (P<0.05). Modulation of alpha1-receptors may function in the management of lower urinary tract dysfunction in MSA.

Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria.

UNLABELLED: Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria. BACKGROUND: Cystinuria is an inheritable amino aciduria and has been classified into three subtypes: I, II, and III. One of the genes responsible for cystinuria has recently been identified as SLC3A1 or rBAT, but only type I cystinuria seems to be caused by genetic alterations in rBAT. To our knowledge, thus far 38 mutations in rBAT gene have been described. In this study, we investigated rBAT mutations in Japanese patients and compared the results with the previously reported mutations in other races. METHODS: We investigated 36 Japanese cystinuria patients by mutational analysis of rBAT gene. To identify newly mutated alleles, genomic DNA was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). When an abnormal migration was observed on SSCP, a nucleotide sequence determination was performed. RESULTS: Five novel mutations were identified in five patients, three with missense mutations (L346P, I445T, C673R), one with a 1 bp deletion (1820delT), and one with a 2 bp insertion (1898insTA), and we detected three previously reported polymorphisms. Three of the mutations were homozygous, in whom parents had intermarried, and two were heterozygous for each mutations. Analysis of rBAT in family of the 1898insTA patient revealed that the patient had inherited the mutated allele from his parents. CONCLUSION: Five novel mutations in the rBAT gene have been identified in Japanese patients with cystinuria. A racial difference was not apparent in the position and frequency of the mutations.

Advances in genetic aspects of cystinuria.

Cystinuria has been clinically classified into three subtypes (I, II, and III) by Rosenberg and associates. In 1994, the SLC3A1 (rBAT) genes which is one of the genes responsible for cystinuria, was located on chromosome 2(2p21). However, it was demonstrated that rBAT is responsible only for Type I cystinuria. At present, 43 mutations, including 5 discovered in our laboratory, have been reported in the rBAT gene of patients with cystinuria. Recent studies suggest that the rBAT-encoded protein was not a transporter itself; rather, the protein represented a specific "guidance molecule" for a selected amino acid transporter. In 1999, the SLC7A9 (BAT1) gene was located on chromosome 19(19q13) by us and by a European group. It seemed that the BAT1 gene is responsible for non-Type I cystinuria and that its protein was a subunit linked to the rBAT protein via a disulfide bond. Mutational, structural, and functional analyses of the gene have been performed by several groups, including our laboratory. It is expected that the roles of these genes in cystinuria will be clarified further, and genetic diagnosis and therapy of patients with cystinuria may be facilitated in the future.

[The evaluation of methods for determinations of urinary oxalate].

BACKGROUND: Estimation of urinary oxalate is one of important tools for the diagnosis and treatment of urolithiasis. And more precise, simple and inexpensive method is desirable. In the present study, we evaluated three methods which were clinically well-used. METHODS: From October 1996 to June 1997, 146 acidified urine samples were collected for 24 hours from 144 urolithiasis patients. We determined the urinary oxalates by three methods; the colorimetric method, the enzymic method and the ion chromatography (IC method). And we evaluated the correlations of these methods. RESULTS: Correlation coefficients in the urine oxalate concentration were, 0.86 with the colorimetric method and the IC method, 0.91 with the enzymic method and the IC method, 0.90 with the colorimetric method and the enzymic method. The coefficients in the 24 hours-urinary excretion of oxalate (0.76, 0.87, 0.82) were lower than those in the urine oxalate concentration. The correlation coefficients with the colorimetric method and the IC method were, 0.58 in hyperoxaluric group, 0.34 in normooxaluric group. The coefficients with the enzymic method and the IC method, 0.93 in hyperoxaluric group, 0.71 in normooxaluric group. CONCLUSION: The colorimetric method is least expensive, but is less useful. The enzymic method is less expensive, and is as useful as the IC method.

The long-term outcome of cystinuria in Japan.

Recurrence of growth of urinary stone is frequently observed during the clinical course of cystinuria patients. The aim of the present study is to examine the long-term outcome of cystinuria in Japan and clarify the effects of medical treatment on urinary stone. Thirty-one patients with cystinuria who had been followed up longer than 6 months were included. The follow-up period was 6-264 months with a mean of 89.5 months. Stone event was defined as appearance of new stone or radiological evidence of stone growth. All patients were managed with forced hydration and urine alkalization. Twenty-eight patients were treated with administration of thiol such as D-penicillamine or alpha-mercaptopropionylglycine. Stone events per year ranged from 0 to 1.09 with a median of 0.09. Stone events per patient-year was 0.19 for all patients. The average urinary cystine concentration during treatment in the favorable outcome group (stone events per year < 0.3) was lower that that in the unfavorable outcome group (stone events per year >/=0.3); 221.2 +/- 75.2 vs. 303.3 +/- 93.5 mg/l, although the difference was not statistically significant. Prognosis of urinary stone in Japanese patients with cystinuria was relatively good with large variation. The medical treatment to reduce urinary cystine concentration would be useful for the management of cystinuria.

11-Deoxycorticosterone-producing adrenocortical carcinoma.

A woman presented with a history of weight loss and muscle weakness. A laboratory test revealed hypokalemia and elevation of plasma 11-deoxycorticosterone (DOC). CT showed a left adrenal mass. A left adrenalectomy was performed. The histological and immunohistochemical diagnosis showed a DOC-producing adrenocortical carcinoma. This cancer is very rare; only 10 cases including the present case have appeared in the literature.

[Analysis of 42 patients with renal trauma--radiographic assessment of surgical application].

We treated 42 patients with renal trauma between 1988 and 1994. There were 18 cases of renal contusion, 12 of minor laceration, 6 of major laceration, 5 of renal rupture and 1 of major laceration with pedicle injury. Thirty-two patients were treated by conservative management, 10 were treated surgically, 9 by simple nephrectomy and 1 by partial nephrectomy. Excretory urography was performed in 27 patients. For stage evaluation, these cases were classified into 4 groups. I: The renal pelvis and calices were clearly enhanced. II: The renal pelvis was enhanced but part of the calix was not. III: The renal pelvis was not clearly enhanced and only some calices were enhanced. IV: The renal pelvis and calices were unenhanced. In addition, computerized tomography was carried out in 24 patients. We believe that cases with classification as III or IV in excretory urography, incomplete enhancement by computerized tomography, and recognized extravasation should be treated operatively.

[Assessment of quality of life after transurethral resection of prostate for benign prostatic hyperplasia].

The quality of life (QOL) after transurethral resection of the prostate (TURP) was studied. A total of 113 patients were operated and released, and 86 (76%) cases responded to the TURP follow-up survey. The average age was 69 years and the average time elapsed after the operation was 220 days. Data regarding the patients undergoing TURP was gathered from a questionnaire consisting of 22 questions concerning the preoperative condition and 28 about the post-operative state. Performance status was not changed post-TURP. The patients showed improvements in nocturia, pollakisuria and dysuria. These urological symptoms were in accordance with the findings of uroflowmetry and American Urological Association Symptom Index. Ten questions addressing the patients mental and physical conditions revealed that good quality was generally retained. Sexual activity showed a tendency of gradual decrease in relation to increasing age. Ejaculatory function and actual satisfaction with the sexual act were obviously damaged by the operation. TURP showed no changes in regard to morning erection, sexual desire in an arousing atmosphere, penile hardness at sex and total satisfaction with the sexual life. Social life, family life and mental status were not influenced, but the physical status of 21 (26%) of the patients was decreased by the operation and hospital stay. Over all, 78% of the patients could maintain a good quality of life in post-TURP.