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Biomedical subjects

S Naito

Publications and source records attributed to S Naito.

At least 19 recordsLinked to original sources

Serodiagnosis of hepatitis C virus infection by ELISA for antibodies against the putative core protein (p20c) expressed in Escherichia coli.

The putative core gene of hepatitis C virus (HCV) was incorporated into a plasmid vector (pCC5-J4), and expressed in Escherichia coli. The product of 180 amino acids (p20c) was purified by gel electrophoresis in the presence of sodium dodecyl sulfate, and used in enzyme-linked immunosorbent assay for antibodies against the putative core protein of HCV (anti-p20c). Anti-p20c was detected in 13 (1.5%) of 873 apparently healthy blood donors. It was detected in 205 (86.5%) of 237 patients with acute or chronic non-A, non-B (NANB) hepatic disease, significantly more frequently (p less than 0.01) than antibodies against the C100-3 protein encoded by nonstructural regions of HCV (anti-C100-3) that was found in 178 (75.1%). Anti-p20c developed in the circulation of a patient with acute NANB hepatitis much earlier than anti-C100-3. HCV RNA was detected by polymerase chain reaction in serum samples from blood donors positive for anti-p20c in high titers, one of which was negative for anti-C100-3. These results indicated that anti-p20c would be useful in complementing anti-C100-3 for the diagnosis of NANB hepatitis and further decreasing the incidence of posttransfusion NANB hepatitis.

Adolescent

Adjuvant chemotherapy with early intravesical instillation of adriamycin and long-term oral administration of 5-fluorouracil in superficial bladder cancer. The Kyushu University Urological Oncology Group.

A randomized controlled trial was performed to study the efficiency of adjuvant chemotherapy with early intravesical instillation of Adriamycin and long-term oral administration of 5-fluorouracil in 275 patients with superficial bladder cancer. All of the patients were randomized into four groups. Group A received early (immediately and 2 days after transurethral resection) instillation of Adriamycin alone; Group B received early instillation of Adriamycin with oral administration of 5-fluorouracil; Group C received delayed (7 days after transurethral resection) instillation of Adriamycin alone; and group D received delayed instillation of Adriamycin with oral administration of 5-fluorouracil. All patients subsequently received instillations weekly for 2 weeks and then every 2 weeks for a further 14 weeks. After 4 months, they received monthly instillations for 8 months. 5-Fluorouracil (groups B and D) was given daily p.o. for 1 year. Evaluation was possible in 187 patients. The postoperative follow-up period for determination of non-recurrence rates was 36 months, during which no significant difference was detected among the four groups. Moreover, no statistically significant difference was found between the early- and delayed-instillation groups. However, the non-recurrence rates obtained in the groups undergoing early instillation were higher than those determined in the delayed-instillation groups during the 36-month follow-up period, and this difference was especially significant at 4 and 5 months. In addition, the early-instillation groups showed significantly higher non-recurrence rates than did the delayed-instillation groups in terms of primary cases (P less than 0.01), tumor size of less than 1 cm (P less than 0.05), multiple tumors (P less than 0.01), pathological stage pTa (P less than 0.01), and histological grades G1 and G2 (P less than 0.05). Groups B and D, which were treated by intravesical instillation of Adriamycin with oral administration of 5-fluorouracil, showed no significant prophylaxis of recurrence during the 36-month follow-up as compared with groups A and C, which received intravesical instillations alone. The main side effect, which required discontinuation of the treatment, was bladder irritation. However, no significant difference in its incidence was found between the early- and delayed-instillation groups. No severe systemic side effect was encountered in this study. These results suggest that early as well as repeated intravesical instillation of Adriamycin is clinically tolerable and may be effective in preventing the recurrence of superficial bladder cancer.

Administration, Intravesical

Osteoclast-like giant cell tumour of the gallbladder.

We describe a rare carcinoma of the gallbladder containing osteoclast-like giant cells. Well-differentiated adenocarcinoma was found in the mucosa of the fundus, and osteoclast-like giant cells were present mainly in a haemorrhagic mass protruding from the mucosal surface. The metastatic hepatic tumour was composed chiefly, if not exclusively, of osteoclastoma-like cells, but minute carcinomatous elements were also present. There was an apparent transition between the giant cells and tubular structures in both the gallbladder tumour and hepatic tumour. However, ultrastructural study did not reveal any evidence of epithelial differentiation in the giant cells. Immunohistochemical studies suggested that the mononuclear and giant cells were mesenchymal and histiocytic in nature (vimentin and factor XIIIa positive). A few exceptional giant cells transforming from the fine tubular structure were positive for epithelial membrane antigen. In conclusion, the osteoclast-like giant cell tumour component was thought to represent mesenchymal metaplasia in pre-existent adenocarcinoma.

Adenocarcinoma

Cytologic findings of fine needle aspirates in chronic prostatitis.

Cytologic studies in patients with prostatic infection, primarily those with chronic prostatitis, were conducted on samples obtained by the fine needle aspiration method. Infiltration of inflammatory cells such as polymorphonuclear leukocytes and macrophages was observed to a greater extent in patients with chronic bacterial prostatitis as compared to those with chronic nonbacterial prostatitis or prostatodynia. The pathogen was isolated in only one out of 28 patients with chronic bacterial prostatitis. We concluded that fine needle biopsy is useful for assessing patients with prostatic inflammation, but not for detecting microorganisms because of focal colonization of the organisms in the glands.

Bacterial Infections

An HLA study on 149 Japanese patients with Crohn's disease.

To search for possible immunogenetic roles in the pathogenesis of Crohn's disease, we examined the HLA-A, -B, -C, -DR and -DQ locus antigens in 149 Japanese patients with Crohn's disease. All patients were living on Kyushu island. We also examined the HLA of 136 healthy controls who resided in Kyushu. The results were compared with both controls throughout Japan and Kyushu controls. In Japanese patients with Crohn's disease, HLA-DR4, especially -DR4.1, and -DQ4 were more frequent than in the controls throughout Japan and in Kyushu. In light of these observations, an immunogenetic factor may have some role in the development of Crohn's disease. The susceptibility to Crohn's disease may relate to HLA-DR4, especially -DR4.1, and -DQ4, in Japanese patients.

Crohn Disease

Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.

Adolescent

Establishment and characterization of doxorubicin-resistant human bladder cancer cell line, KK47/ADM.

A human bladder cancer cell line resistant to doxorubicin, KK47/ADM has been established in vitro by exposing KK47 parent cells to progressively higher concentrations of the drug over a period of 16 months. The KK47/ADM was 271 times more resistant to doxorubicin than the KK47 parent. The KK47/ADM exhibited cross-resistance to doxorubicin derivatives (pirarubicin, epirubicin), vinca alkaloids (vinblastine, vincristine) and etoposide, but not to cisplatin, carboplatin, mitomycin C, peplomycin and methotrexate. Unlike the KK47 parent, about 70% of the KK47/ADM cells showed a positive reaction with monoclonal antibody against P-glycoprotein, MRK16. Uptake and efflux studies with [14C]doxorubicin indicated that the resistance exhibited by the KK47/ADM line was mainly due to a lower accumulation of the drug caused by an increased active efflux, and these were reversed in the presence of verapamil. Although verapamil enhanced doxorubicin sensitivity of KK47/ADM, a complete overcoming of the resistance could not be obtained. These two lines with different chemosensitivity are thus considered to be a useful model for developing new chemotherapeutic strategies against multidrug resistant bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem

Analysis of HLA class II genes in Japanese patients with idiopathic membranous glomerulonephritis.

Thirty unrelated Japanese adult patients with idiopathic membranous glomerulonephritis (IMG) and 50 unrelated Japanese normal controls were examined for HLA class II genes. Both the 3.0 kb DQB and the 6.2 kb DQA restriction fragments were simultaneously identified in 86.7% of the patients. These were significantly different from the 14% frequency of the fragments in controls (relative risk = 39.9; P = 1.7 x 10(-10)). The haplotype DR2-DQwl associated with IMG seemed to be Dw2 which was essentially different from the haplotype common to the normal Japanese population. Dw12. This was because most of the restriction fragment length polymorphism (RFLP) of DQB and DQA of the patients coincided with that of homozygous cell lines with Dw2. The DRB probe showed no significant differences in the hybridization patterns between the patient group and HLA-matched controls. These findings indicate that the specific HLA-DQ polymorphism correlates primarily with Japanese IMG.

Adult

Analysis of complement C4 loci in Caucasoids and Japanese with idiopathic membranous nephropathy.

Deletion of the HLA class III complement gene, C4A, has been linked with susceptibility to a number of autoimmune diseases. In this study, we show a strong positive association between C4A gene deletion and development of idiopathic membranous nephropathy (IMN) in European Caucasoids [patients, 17/27 (63%); healthy controls, 13/65 (20%); RR 6.8; P = 0.003]. To clarify whether C4A deletion is an independent risk factor for IMN or is increased secondarily to the Caucasoid HLA A1, B8, DR3 extended haplotype, we examined the frequency of C4A deletion in Japanese patients, in whom the disease is associated with another HLA haplotype (DR2-DQw1). Analysis of 31 Japanese patients and 46 healthy controls showed that C4A deletion was present in only one patient (3%) and one control (2%). In addition, examination of the C4B locus in Japanese patients showed that there was no significant increase in the estimated frequency of C4B deletion in patients against controls (31 vs. 27%) and no difference in the frequency of the C4B long gene (73 vs. 87%) or C4B short gene (77 vs. 78%). We conclude that although C4A deletion confers significant risk of IMN in Caucasoids, there is no significant association between C4 polymorphism, as detected here, and risk of IMN in Japanese. This suggests that either C4A deletion is irrelevant to the pathogenesis of IMN or that more than one genetic mechanism is involved.

Asian People

Analysis of intergenic spacer regions in the nuclear rDNA of Pharbitis nil.

The nucleotide sequence of a 4.2-kb EcoRI fragment from the intergenic region between the genes for 25S and 18S ribosomal RNA of Pharbitis nil Choisy was determined. The region contained a unique repetitive family of DNA sequences, called the RsaI family, composed of 32-bp units. The 32-bp unit was tandemly repeated in the intergenic region, and four subfamilies of repeating units were clustered as discrete blocks. The RsaI family of repeats was shown to be specific to the genus Pharbitis by Southern blot hybridization.

Base Sequence

Intravesical therapy with adriamycin plus verapamil in patients with superficial bladder cancer: a pilot study.

Nineteen patients with histologically proven superficial bladder cancer (Ta, T1) were treated with intravesical instillation of 30 mg of adriamycin (ADM) dissolved in 24 ml physiological saline plus 15 mg of verapamil (VR) (6 ml) every day for 10 days. In spite of the short period of treatment, 6 of the 18 evaluable patients (33.3%) showed complete response (CR) and a further 5 (27.8%) showed partial response (PR). Five of the 6 patients with CR were recurrent cases who had previously received prophylactic intravesical instillation chemotherapy including ADM. Irritative urinary symptoms were observed in 11 of the 19 patients (57.9%). However, these symptoms were mild in the majority of patients and the treatment was completed without interruption in all but 1 patient. There was no significant absorption of ADM and VR into the systemic circulation. No clinical evidence of systemic toxicity was observed. These results suggest that combination of ADM and VR has a possibility to be a useful prophylactic intravesical instillation chemotherapy after endoscopic resection of not only primary but also recurrent chemoresistant bladder cancers.

Administration, Intravesical

Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract.

The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.

ATP Binding Cassette Transporter, Subfamily B, Mem

Bellini duct carcinoma of the kidney.

Human epithelial cells of the kidney present a wide spectrum of cytological and histological variation. The normal epithelium of the kidneys also includes a number of morphologically and functionally different cell types which are arranged along the nephrons and collecting ducts. Although renal carcinoma can involve any type of renal cell, the most common is renal cell carcinoma of the proximal tubuli. Here, we present the case of a 65-year-old Japanese patient with a renal cell carcinoma arising from Bellini duct epithelial cells. State-of-the-art techniques were used to establish the diagnosis and histogenesis of this renal cell carcinoma.

Aged

[Application of the limulus amebocyte lysate test to measurement of endotoxin in therapeutic human plasma protein fraction. Comparison with the rabbit pyrogen test].

We applied the limulus amebocyte lysate (LAL) test to the detection of bacterial endotoxins in therapeutic human plasma protein fraction (PPF) and compared the LAL-test with the rabbit pyrogen test. Two endotoxin-specific LAL-reagents were used for the colorimetric method and turbidimetric kinetic method. The amounts of added endotoxin to the PPF were correctly estimated by either method. The results of four independent assays for the 53 samples of PPF corresponded well with each other (correlation coefficient: 0.851-0.959, regression coefficient: 0.898-1.151). The amounts of endotoxin in the PPF estimated by the LAL-test significantly correlated with the rise of body temperature in rabbits (correlation coefficient: 0.547-0.642, and 0.911-0.934 for the endotoxin added samples). These results suggest that the LAL-test could be used as an alternative method for the rabbit pyrogen test to PPF.

Animals

Cellular and molecular bases for the immunopathology of the myocardial cell damage involved in acute viral myocarditis with special reference to dilated cardiomyopathy.

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of the myocardial cell damage involved in viral myocarditis. To investigate the cellular and molecular bases of both target cells and effector cells for cell-mediated cytotoxicity involved in viral myocarditis and dilated cardiomyopathy, we first examined the expression of major histocompatibility complex (MHC) antigens and a cell adhesion molecule, intercellular adhesion molecule-1 (ICAM-1) in myocardial cells of a murine model of viral myocarditis and in patients with acute myocarditis and dilated cardiomyopathy. Secondly, we analyzed the characteristics of the infiltrating cells in the heart, especially the expression of a cytolytic factor, perforin. We found that Coxsackievirus B3 (CVB3)-induced murine acute myocarditis resulted in enhanced expression of MHC (class I) antigens and ICAM-1 on myocardial cells, and that perforin was abundantly expressed in NK (natural killer)-like large granular lymphocytes (LGL), which represent the main infiltrating cell type in the early stage. Immunoelectron microscopic study showed killer cells directly damaging cardiac myocytes by the release of perforin. Perforin was also expressed in the infiltrating cells in the heart of a patient with acute myocarditis. Both MHC antigens and ICAM-1 were clearly expressed in the hearts of patients with acute myocarditis and dilated cardiomyopathy. These data provided direct evidence that cell-mediated cytotoxicity plays a critical role in the myocardial cell damage involved in viral myocarditis.

Acute Disease

[Spontaneous reversion to sinus rhythm in a case of lone atrial fibrillation of fifteen years duration].

A 69-year-old male visited our clinic in 1973 because of atrial fibrillation noted during an annual check-up for the aged. Blood pressure, heart rate and CTR in chest X-ray films showed 110/80 mmHg, 150/min and 55%, respectively. There were no signs of valvular heart diseases, and a diagnosis of lone atrial fibrillation was convincing. Since then, repeated ECGs recorded twice or more a year had shown atrial fibrillation until 1988, when sinus rhythm with both first degree AV block and low P-wave amplitude appeared. The motion pattern of the anterior mitral leaflet on M mode echocardiography was abnormal with almost complete disappearance of the A-wave, whereas the motion pattern of the tricuspid valve was normal.

Aged

[Recurrence following surgery for primary renal pelvic and ureter cancer--clinicopathologic analysis of distant metastasis].

A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer.

Adenocarcinoma

[DNA typing of HLA-class II genes in idiopathic nephropathy].

The association between idiopathic nephropathy and HLA-class II antigen has been reported in many ethnic groups. We attempted to ascertain the HLA regions more specifically, associated with Japanese idiopathic membranous nephropathy (IMN), IgA nephropathy (IgAN) and minimal change nephrotic syndrome (MCNS), by examining HLA-class II genes. DNA typing of HLA-class II genes showed that IMN was associated with HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602, IgA with HLA-DQA1*0301, and MCNS with DQB1*0302. We also found a common epitope of HLA-class II (at 38th amino acid position of HLA-DR beta in IMN, at 55th of HLA-DQ beta in MCNS) in Japanese and Caucasian patients. These particular epitopes seem to be important for the susceptibility to IMN or MCNS.

DNA