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Biomedical subjects

O Matsumoto

Publications and source records attributed to O Matsumoto.

At least 19 recordsLinked to original sources

X-ray structure of T4 endonuclease V: an excision repair enzyme specific for a pyrimidine dimer.

The x-ray structure of T4 endonuclease V, an enzyme responsible for the first step of a pyrimidine-dimer-specific excision-repair pathway, was determined at a 1.6-angstrom resolution. The enzyme consists of a single compact domain classified into an all-alpha structure. This single domain has two distinct catalytic activities; it functions as a pyrimidine dimer glycosylase and as an apurinic-apyrimidinic endonuclease. The amino-terminal segment penetrates between two major helices and prevents their direct contact. The refined structure suggests the residues involved in the substrate binding and the catalysis of the glycosylation reaction.

Amino Acid Sequence

Clinical and pathological evaluations of methotrexate, vinblastine, adriamycin and cisplatin chemotherapy for advanced urothelial cancers.

We have treated advanced transitional-cell carcinoma of the urothelial tract with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since July of 1985. We analyzed the effect of that chemotherapy in 26 patients with advanced urothelial cancer who were treated in our hospital and followed up. They were divided into two groups. Group 1 consisted of 15 patients with distant metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for metastatic lesions after surgical removal of the primary lesion, and the remaining 4 patients were not operable since they had very advanced-stage tumors; they received only M-VAC chemotherapy. Group 2 contained 11 patients who received M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1% and the mean duration of response was 12.6 months. In the 11 patients who had received M-VAC as adjuvant therapy after surgical removal of the primary tumor, the mean duration of response was 14.1 months. After M-VAC chemotherapy, six patients underwent surgical resection of metastatic lesions and restaging was done pathologically in these cases. The clinical response coincided with the pathological response in all six cases. In group 2, 5 of 11 patients experienced histological downstaging of the resected bladder. M-VAC chemotherapy combined with surgical resection of residual tumors has proved to be an effective option against advanced urothelial cancer.

Adult

Crystallization and preliminary X-ray studies of a Bacillus subtilis and Thermus thermophilus HB8 chimeric 3-isopropylmalate dehydrogenase and thermostable mutants of it.

A new type of chimeric 3-isopropylmalate dehydrogenase (2T2M6T) was produced by expressing the fused gene of Bacillus subtilis and Thermus thermophilus. The enzyme shows heat stability intermediate between those of the parents. The crystal of the enzyme belongs to the space group of P3(2)21, with cell dimensions of a = b = 78.9 A and c = 158.9 A. Two thermostable mutants of the chimeric enzyme were prepared by site-directed mutagenesis and then crystallized.

3-Isopropylmalate Dehydrogenase

Androgenic regulation of enzymes involved in DNA synthesis in epididymis of young rats.

In the epididymis of young rats, activities of DNA polymerases alpha, beta and gamma and DNA topoisomerase I decreased after castration. DNA polymerase alpha and gamma increased with androgen administration and activity reached 81.3% and 78.0%, respectively, of the activity in the sham-operated group on day 21. Activity of DNA polymerase beta remained at the activity of day 7 during androgen administration and was almost the same as that in the sham-operated group on day 21. DNA topoisomerase I activity showed a slight increase with androgen administration and reached 50.3% of that in the sham-operated group. The activities of these enzymes were not fully restored to those in the sham-operated group. These results indicate that in young rats activities of epididymal DNA polymerase alpha and gamma and DNA topoisomerase I are partially, and that of DNA polymerase beta wholly, dependent on androgens and may provide a means of investigating the regulation of epididymal cell proliferation.

Androgens

[Microsurgical autotransplantation of abdominal testis].

A 32-year-old man who had bilateral non-palpable testis underwent microsurgical orchidopexy of the right abdominal testis. Inferior epigastric vessels were used for the recipient vessels. Ischemic time during the operation was 40 minutes. Postoperative doppler readings revealed excellent blood flow to the testis, and HCG-stimulating test revealed good response. Now, 2 years after surgery, no sign of atrophy is found.

Adult

[A case of chronic scrotal hematocele and review of the literature].

A 38-year-old man visited our hospital because of swelling of left scrotal content. He had no history of trauma of scrotum, fever, pain or dysuria. Physical examination revealed a tumor larger than a fist in the left scrotum. Ultrasonography revealed an echogenic mass with echolucent area in the scrotum. Surgical extirpation of the left scrotal tumor was performed under the diagnosis of left testicular tumor. The mass was encapsulated by a white fibrous membrane and was 700 g in weight. The tumor contained 200 ml of dark brown pus-like material. Histological examination revealed deposition of cholesterine crista and infiltration of lymphocyte in tunica vaginalis with extremely atrophic testis, destructive spermatogenesis and atrophic epididymis. Twenty one cases of chronic scrotal hematocele have been reported in the Japanese literature. The age of the patients reported was 38 to 77 years old with a mean age of 65 years. Orchiectomy was done under the diagnosis of testicular tumor in 20 of the 21 cases. Our case was thought to be of an idiopathic chronic scrotal hematocele. The disease should be considered even in the absence of a particular cause such as injury and inflammation of scrotal content.

Adult

[Clinical study on surgical treatment of renal cell carcinoma with pulmonary metastases].

This study reviewed the surgical therapy for lung metastatic foci of renal cell carcinoma. During the 14 years from 1977 to 1991, lung metastatic foci were removed in 10 patients with renal cell carcinoma at our hospital. Six of them died of cancer and four are alive. The prognosis tended to be better the longer the interval from nephrectomy to lung metastasis. Neither the number of metastatic foci nor the surgical technique produced any difference in the prognosis. The prognosis tended to be better for patients with clear cell tumors than for those with granular cell tumors. For the treatment of lung metastasis of renal cell carcinoma, since we have no better therapy than surgical removal at the present, it is our duty to attempt to improve the prognosis of patients by the resection of metastatic foci whenever possible. However, the use of adjuvant therapy such as interferon should be considered, and the indications for operation and the timing of surgery reviewed.

Aged

[Usefulness of dipstick test for determining leukocytes and bacteria in urine].

The value of a simple dipstick test (BMtestLN, Boehringer Mannheim-Shionogi) for determination of leukocytes and bacteria in urine was examined. This test consisted of detection of esterase, an enzyme present in leukocytes and the nitrate reduced by bacteria. A total of 666 clinical urine specimens were tested with both tests. The evaluation of leukocytes in urine was compared with microscopic examination, and the identification and measurement of strains was performed using a semiquantitative plate culture method as a reference. The leukocyte esterase test had a sensitivity of 85.3%, a specificity of 67.3%, positive predictive value of 54.7% and negative predictive value of 90.8%. The range of the sensitivity value of nitrate test was 25.7% for the detection of bacteriuria (bacteria greater than or equal to 10(4) CFU/ml). This test had a specificity of 99.6%, positive predictive value of 94.8% and negative value of 82.9%. We concluded that this dipstick test is not useful for determination of the slight change of pyuria, but sensitive for the determination of acute and untreated urinary tract infections.

Bacteriuria

[A case of infected caliceal diverticulum].

A 60-year-old woman was admitted to our clinic with the chief complaint of high fever. Antibiotic therapy had produced no improvement in another hospital and she was referred to our hospital for further examination and treatment. Intravenous pyelography showed left non visualized kidney and a stone shadow in left ureter. Computed tomography showed a cystic lesion, 9 x 9 x 8 cm, in the upper pole of the left kidney. We punctured and drained 400 cc of turbid yellowish fluid by a transcutaneous route. The nephrostogram clearly showed a communication with infundibulum. A diagnosis of infected caliceal diverticulum was made. Further examination demonstrated no function of left kidney and we performed nephrectomy. She has reported no symptoms for 6 months after the operation.

Diverticulum

Testosterone dependent regulation of the enzymes involved in DNA synthesis in the rat ventral prostate.

The effects of testosterone on the activities of DNA polymerase alpha, beta, and gamma as well as topoisomerase I (all enzymes involved in DNA synthesis) were examined in the rat ventral prostate. The activities of these four enzymes decreased gradually after castration in comparison with normal controls, and continued to decrease until the 14th day. Enzyme activities were almost restored to normal within 48 to 72 hr. of the commencement of daily testosterone injections (0.3 mg./0.2 ml.), and increased successively until the 14th day. The wet weight, protein content, and DNA content of the rat ventral prostate decreased after castration, while following testosterone therapy all these parameters increased to equal or exceed the control levels. These results suggested that the activities of DNA polymerase alpha, beta, and gamma and topoisomerase I are at least partially regulated by testosterone, and that these enzymes play an important role in the regulation of prostatic cellular proliferation.

Animals

[Two case reports of eosinophilic cystitis--clinical review of 43 cases in Japan].

Two cases of eosinophilic cystitis are reported. Case 1 was a 7-year-old boy with pollakisuria and case 2 was a 20-year-old man with right lower abdominal pain. They were suspected of bladder sarcoma after the examinations by cystoscopy, IVP, ultrasonography, CT and NMR-CT. Transurethral, percutaneous and open biopsies were performed and histological examination revealed massive infiltration of eosinophils mainly in the vesical muscle layer without malignant cells. We could establish the diagnosis only by biopsy. In case 1, IgE RAST was positive for tick and case 2 seemed to be allergic to rare beef. We presumed that they caused eosinophilic cystitis.

Adult

[VAB-6 chemotherapy of advanced testicular cancers--its efficacy and limitation].

Fifteen patients with advanced testicular germ cell tumor were treated by VAB-6 chemotherapy after radical orchiectomy. CR was achieved in two (13.3%) and PR in nine (60.0%). The one, three and five year survival rates were 92.2, 64.2 and 51.4%, respectively. Nine patients (60.0%) remain with no evidence of disease (NED) after combined therapy (chemotherapy and surgery) with a median follow up of 4.3 months. We performed resection of the residual tumors and examined histologically. Out of 11 cases, four (36.3%) were with necrosis/fibrosis, two (18.2%) teratoma and five (45.5%) cancer. All of the six cases with non-cancerous tissues remain in NED. However, only two of the five cases with cancerous tissues remain in NED. We studied the NED rate based on four prognostic factors, (1) bulky abdominal diseases, (2) advanced lung diseases, (3) other metasteses, and (4) choriocarcinoma. In our analysis, advanced lung diseases and choriocarcinoma were poor prognostic factors. We should treat these poor prognostic cases initially with VP-16, ifosfamide, high doses cisplatin etc, which were used as salvaged drugs.

Adolescent

[A case of acquired cystic disease of bilateral kidneys with renal cell carcinoma following long-term hemodialysis].

We report a case of bilateral renal cell carcinoma which developed during about 14 years of hemodialysis. The patient of male was a 39-year-old with a chief complaint of macrohematuria 14 years prior to dialysis therapy. Computed tomography revealed multiple cystic changes of bilateral kidneys and a high density area in the right kidney. He was admitted to our department in April 1988. He was suspected of renal cell carcinoma of the right kidney and underwent transperitoneal radical nephrectomy on the right kidney. The left kidney was also resected simultaneously in part because it failed to function and in part because the long-term hemodialyzed patients are considered to have a complication of renal cell carcinoma at a high frequency. Pathological diagnosis was bilateral acquired cystic disease of the kidney (ACDK) with renal cell carcinoma. The kidney develops multiple cystic changes following long-term hemodialysis, which forms a high risk for development of renal cell carcinoma. This is a case of bilateral renal cell carcinoma which occurred after long-term hemodialysis, was reported with discussion and reference to the literature.

Adult

[Diagnosis of male infertility].

The diagnostic methods for male infertility in our clinic are reviewed, and the following are emphasized. In azoospermia, examinations for obstructive azoospermia such as testicular biopsy should be made focussing on patients with 10 ml or higher testicular volume and with 20 mIU/ml or lower serum FSH level. In hypospermic patients, examination of post-ejaculated urine and ultrasonotomography examination of prostate are necessary for the diagnosis of incomplete retrograde ejaculation and obstruction or stenosis of the ejaculatory ducts.

Algorithms

[Present status on bladder replacement--colon bladder replacement].

Bladder replacement using a detubularized right colonic segment was successfully performed on 22 male patients with bladder cancer after radical cystectomy. There were 10 early postoperative complications and one of them required reoperation. Urodynamic studies, performed on 16 patients, showed a low pressure reservoir at a large capacity without any involuntary spikes in every case. Of the 16 patients, 4 were nocturnally enuretic and 1 was partially continent. The other 11 patients (68.8%) were totally continent and voiding well, except one who was on intermittent self-catheterization. The incidence of urinary reservoir infections in patients treated with colon bladder replacement was investigated in 18 patients. The incidence rate of bacteriuria was 5.6% and the positive rate of pyuria was 27.8%. The detection rate of bacteriuria and pyuria was significantly low in patients after colon bladder replacement. These findings indicate that colon bladder replacement can be an ideal option for selected patients with bladder cancer.

Adult

Atomic structure of a pyrimidine-dimer specific excision-repair enzyme from bacteriophage T4.

T4 endonuclease V is an enzyme responsible for the first step of a pyrimidine-dimer specific excision-repair process. The three-dimensional structure of this enzyme has been determined at 1.6A resolution by X-ray crystallography. The enzyme consists of one single compact domain classified into the all alpha structure. This single domain possesses two distinct catalytic activities, a pyrimidine-dimer glycosylase and an apurinic/apyrimidinic endonuclease. The backbone of the enzyme represents a unique folding scheme incompatible with close packing of alpha-helices. The refined structure suggests possible residues that participate in interactions with DNA.

Amino Acid Sequence

[Clinical evaluation of terodiline hydrochloride in patients with urinary frequency or incontinence].

A clinical trial with the collaboration of 15 department of urology was performed to determine the usefulness of terodiline hydrochloride in 99 patients whose chief complaints were of pollakisuria or incontinence due to neurogenic bladder, psychogenic disease or chronic cystitis. The patients were orally given 24 mg once daily for 4 weeks. The final global improvement rate was 88.5% and the effective rates on subjective symptoms were; 66.2% for diurnal urinary frequency, 68.0% for nocturnal urinary frequency, 68.8% for urinary incontinence and 78.3% for nocturnal enuresis. Even for the cases having mild bladder outlet obstructive disease, the clinical effective rates were good. Mild side effects were observed in 10 patients, which were dry mouth and others. The results obtained from this trial suggest that terodiline hydrochloride may be useful for the treatment of urinary frequency and incontinence caused by detrusor instability.

Administration, Oral

[A study on the treatment duration of an antibacterial agent in complicated urinary tract infections. Utility and recurrence after 14-day treatment by fleroxacin].

In this study, fleroxacin (FLRX), a new quinolone derivative, was orally given at 300 mg once daily for 14 days to 102 patients with non-catheterized complicated urinary tract infections in order to determine the optimal treatment duration. We investigated its efficacy at day 5-7 and day 14, according to the criteria proposed by the Japanese UTI Committee, and also to the recurrence rate after the withdrawal. The results were as follows: 1. Overall clinical efficacy rates were 86% at day 5-7 and 84% at day 14. Both incidence of bacterial replacement in bacteriuria and normalization in pyuria were increased at day 14 as compared with those at day 5-7. 2. Bacteriological eradication rates were 91% at day 5-7 and 89% at day 14. 3. Clinical efficacy rates from physicians' evaluation were 86% at day 5-7 and 88% at day 14. 4. Incidence of side effects was 9.1%, and most of the cases were gastrointestinal symptoms which appeared within 4 days. Slight and transitory changes in laboratory findings were noted in 2.3% of evaluable cases. 5. With the occurrence of pyuria and bacteriuria as markers, the "no recurrence" rates were 63% at 1 week, 54% at 2 weeks, 61% at 3 weeks, 81% at 4-6 weeks after the withdrawal, and the "recurrence" rates were 4%, 4%, 6% and 5%, respectively. Remaining cases were judged as "reserved assessment". Generally, aggravation of bacteriuria was found but the aggravation of pyuria was observed in only few cases. 6. According to breakdown of cases with bacteriuria only, cure rate was 67% and recurrence rate was 33%. Re-infections were observed much more frequently than relapse based on the identification of infecting organisms. These results suggest that sufficient bacteriological eradication and clinical efficacy could be obtained by 14-day treatment of FLRX in non-catheterized complicated urinary tract infections. The efficacy of the treatment became evident around day 7. In approximately 30% of the cases in which eradication of the initial causative organisms was observed at day 14 reappearance of bacteriuria (greater than or equal to 10(3) CFU/ml) occurred after withdrawal of the antibiotic, but cases with pyuria were few, and the incidence of true recurrence was generally low. Onset of side effect after 5-day was not seen, hence FLRX seemed to be a safe agent.

Administration, Oral