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M Tani

Publications and source records attributed to M Tani.

At least 19 recordsLinked to original sources
PubMed2001

Strain variation in renal carcinogenesis by N-ethyl-N-hydroxyethylnitrosamine in F1 (Wistar-Fischer) rats.

The present study was conducted to compare the incidences of renal tumors in Wistar (W), Fischer (F) and F1 rats (WF: female Wistar rats x male Fischer rats; FW: female Fischer rats x male Wistar rats) induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN). Levels of 8-OHdG in renal DNA were also investigated in Wistar and Fischer rats. After 2000 ppm of EHEN was administered orally for 2 weeks, the animals were fed basal diet until week 32. Wistar males and females demonstrated significantly higher sensitivity regarding induction of renal lesions, while both WF and FW rats had similar incidences, generally intermediate between those for the two parent strains. The formation of 8-OHdG was maximal 60-180 min after an intraperitoneal dose of 750 mg/kg to Wistar and Fischer rats, which correlates with the increase tending to the incidence of renal tumors in male and female Wistar and Fischer rats. The results suggest that EHEN induction of renal tumors is related to oxygen radical damage and that the genes in the Wistar strain responsible for the sensitivity are not inherited in a sex-dependent fashion, despite the male being more susceptible.

Animals↗
PubMed2001

Enhancement of OGG1 protein AP lyase activity by increase of APEX protein.

8-Hydroxyguanine (oh(8)G) is a major form of oxidative DNA damage produced by reactive oxygen species (ROS). The human OGG1 gene encodes a DNA glycosylase that excises oh(8)G from double-stranded DNA. In this study, we investigated a mode of interaction between OGG1 and APEX proteins in the repair of oh(8)G under oxidative stresses. DNA cleavage assay using oh(8)G-containing oligonucleotides showed that the phosphodiester bond on the 3'-side of oh(8)G was cleaved by the AP lyase activity of GST-OGG1 protein and the phosphodiester bond on the 5'-side of oh(8)G was cleaved by the DNA 3'-repair diesterase activity of APEX protein. Gel mobility shift assay showed that the complex of GST-OGG1 protein and oh(8)G-containing oligonucleotides mostly changed into the complex of APEX protein and oligonucleotides by addition of APEX protein into the reaction mixture. We next analyzed alterations in the amount of 8-hydroxydeoxyguanosine (oh(8)dG) in DNA and the levels of OGG1 and APEX expression in HeLa S3 cells treated with 2mM hypochlorous acid, a kind of ROS. An approximately four-fold increase in the amount of oh(8)G was detected by the HPLC-ECD method. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses indicated that the level of APEX expression increased approximately four-fold, whereas the level of OGG1 expression was unchanged. However, in the DNA cleavage assay, the AP lyase activity of GST-OGG1 protein was significantly increased in the presence of a molar excess of APEX protein. These results indicate that, under severe oxidative stresses, OGG1 mRNA is not induced and the amount of OGG1 protein is not remarkably increased, but the activity of OGG1 protein is enhanced by the increase of APEX protein in the cells.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Purification, characterization, molecular cloning, and subcellular distribution of neutral ceramidase of rat kidney.

Previously, we reported two types of neutral ceramidase in mice, one solubilized by freeze-thawing and one not. The former was purified as a 94-kDa protein from mouse liver, and cloned (Tani, M., Okino, N., Mori, K., Tanigawa, T., Izu, H., and Ito, M. (2000) J. Biol. Chem. 275, 11229--11234). In this paper, we describe the purification, molecular cloning, and subcellular distribution of a 112-kDa membrane-bound neutral ceramidase of rat kidney, which was completely insoluble by freeze-thawing. The open reading frame of the enzyme encoded a polypeptide of 761 amino acids having nine putative N-glycosylation sites and one possible transmembrane domain. In the ceramidase overexpressing HEK293 cells, 133-kDa (Golgi-form) and 113-kDa (endoplasmic reticulum-form) Myc-tagged ceramidases were detected, whereas these two proteins were converted to a 87-kDa protein concomitantly with loss of activity when expressed in the presence of tunicamycin, indicating that the N-glycosylation process is indispensable for the expression of the enzyme activity. Immunohistochemical analysis clearly showed that the ceramidase was mainly localized at the apical membrane of proximal tubules, distal tubules, and collecting ducts in rat kidney, while in liver the enzyme was distributed with endosome-like organelles in hepatocytes. Interestingly, the kidney ceramidase was found to be enriched in the raft microdomains with cholesterol and GM1 ganglioside.

Amidohydrolases↗
PubMed2001

Diagnostic potential of short echo time MR spectroscopy of gliomas with single-voxel and point-resolved spatially localised proton spectroscopy of brain.

Accurate neuroimaging grading of gliomas is useful for management, but techniques such as MRI and CT are not sufficiently reliable. Necrosis is a consistent, decisive prognostic factor and the key diagnostic criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows noninvasive measurement of metabolites in brain tumours and mobile lipids reflect necrosis. However, short echo-time (TE) spectroscopy has been required for reliable assessment of lipids, since their relaxation times are very short. Recent advances have made it possible to perform short-TE MRS. We attempted to evaluate the significance of short TE spectroscopy as part of routine imaging for diagnosis and grading of gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II six; grade III three; grade IV, 16) and in 19 areas of healthy white matter using proton brain examination/single voxel (PROBE/SV) and point-resolved spatially localised spectroscopy (PRESS). With short-TE spectroscopy, lipid signals were detected in all 16 tumours of grade IV, one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms MRS, carried out in 20 of these cases, showed lipid signals in only four of 14 grade IV tumours and in none of the other six. N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in healthy tissues and less than 1.0 in all but one of the gliomas. The mean creatine (Cr)/Cho ratio in each tumour grade was significantly lower than in the healthy tissues. The mean Cr/Cho ratio was also significantly lower in grade IV than in grade II tumours (P < .0005). Considerable overlap in Cr/Cho ratio was observed between grade II and grades III and IV gliomas at long but less so at short-TE MRS. We conclude that short-TE MRS with PROBE/SV and PRESS is of value in grading gliomas.

Adolescent↗
PubMed2001

Adult T-cell leukemia associated with gastric carcinoma: report of a case.

A 67-year-old man was admitted to our hospital with nausea and epigastralgia, and a diagnosis of smoldering type adult T-cell leukemia (ATL) associated with advanced gastric carcinoma was made. The gastric carcinoma had caused pyloric stenosis, and investigations revealed regional lymph node metastasis. The patient underwent total gastrectomy, splenectomy, cholecystectomy, and lymph node dissection with a Roux-en-Y anastomosis. Histological examination of the regional lymph nodes revealed not only metastases of gastric carcinoma, but also of ATL lymphoma, indicating a final diagnosis of advanced gastric carcinoma with locoregional lymph node due to both metastasis of the gastric carcinoma and the ATL lymphoma. Despite the administration of postoperative adjuvant chemotherapy comprised of cisplatin/adriamycin/5-fluorouracil in combination with oral etoposide and immunotherapy using ubenimex, paraplegia suddenly developed caused by the metastasis of ATL to the epidural space. Resection of this metastatic tumor for decompression of the spinal cord resulted in resolution of the paraplegia; however, the patient died about 1 month later from rapid systemic tumor growth.

Adenocarcinoma↗
PubMed2001

Direct activation of mitochondrial K(ATP) channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts.

OBJECTIVES: This study is aimed to determine whether loss of preconditioning (IP) effects in the middle-aged hearts (MA) is due to the failure of protein kinase C (PKC) activation and, if so, whether direct activation of mitochondrial ATP-sensitive potassium channels (m-K(ATP)) or PKC mimics IP. BACKGROUND: PKC is a mediator and m-K(ATP) may be its downstream effector of IP in young adult hearts (YA), but we have demonstrated that IP is not effective in MA. METHODS AND RESULTS: Isolated hearts from YA (12-week) and MA (50-week) Fischer 344 rats were preconditioned by three cycles of ischemia and reperfusion (5 min each), and the translocation of PKC isoforms and the effects on reperfusion injury were assessed. In some hearts activation of m-K(ATP) or PKC by diazoxide or 1, 2-dioctanoyl glycerol (DOG) was performed before 25 min of global ischemia/30 min of reperfusion. IP could improve the recovery of LV function and resulted in higher content of ATP after reperfusion in YA but these beneficial effects of IP was not found in MA. The effects of IP in YA were abolished by 5-hydroxydecanoate. In YA but not in MA, immunohistochemical analysis revealed that IP translocated PKC-alpha and delta from the cytosolic or membrane to the perinuclear region but immunoblotting analysis showed translocation of PKC-alpha, delta and epsilon to the membrane fraction. Pretreatment with diazoxide or DOG mimicked IP and decreased the creatine kinase release in YA. Diazoxide was also effective but effects of DOG were less in MA as compared with in YA. CONCLUSIONS: IP is not effective in MA hearts partly due to failure of translocation of PKC isoforms. Moreover, less efficacy of PKC activation by DOG as compared with activities of m-K(ATP) by diazoxide in MA may suggest that defect(s) of cell signaling downstream to PKC may also be involved in the loss of IP effects in MA.

Aging↗
PubMed2001

Local chemotherapy with interferon-alpha for conjunctival mucosa-associated lymphoid tissue lymphoma: a preliminary report.

OBJECTIVE: To evaluate the efficacy of subconjunctival interferon-alpha for the treatment of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN: Small, noncomparative, interventional case series. PARTICIPANTS: Five patients with histologically proven conjunctival MALT lymphoma were studied prospectively. METHODS: Patients were given 1,500,000 international units (IU) of interferon-alpha (IFN-alpha) (Roferon-A) subconjunctivally inside the lesion, three times a week for four weeks. If there was even a minimal response, a further cycle of 1,000,000 IU three times a week for four weeks was administered. Patients received a maintenance dose of 1 million IU, every 15 days for 4 times, after clinical resolution of the lesion. MAIN OUTCOME MEASURES: Patients were followed clinically, with slit lamp examination, for evidence of tumor disappearance or recurrence. RESULTS: Complete response was obtained in all patients. The lesion resolved completely by the eighth week. Four patients did not show any local recurrence with a median follow-up of 21 months (12-36 months). One patient presented with a recurrence after 11 months, in association with systemic lymphoma progression. CONCLUSIONS: Local chemotherapy with IFN-alpha seems to be an effective treatment modality, alternative to radiotherapy, for conjunctival MALT lymphomas.

Adult↗
PubMed2001

Improvement in right lung atelectasis (middle lobe syndrome) following administration of low-dose roxithromycin.

Middle lobe syndrome is a distinct clinical entity characterized by right middle lobe atelectasis. Prompt diagnosis and initiation of medical therapy including the administration of antibiotics and the avoidance of irritating agents may be effective. However, abnormal shadows on chest radiography remain unchanged even when acute symptoms have disappeared, suggesting latent lesional inflammation or recurrence. We describe 2 cases of atelectasis in the middle lobe of the right lung which resolved completely after administration of low-dose roxithromycin. Thus, low-dose therapy with a macrolide could be of interest or some value in these cases, but it is too early to draw a definite conclusion.

Aged↗
PubMed2001

Complete response of highly advanced gastric cancer with peritoneal dissemination after new combined chemotherapy of S-1 and low-dose cisplatin: report of a case.

TS-1(S-1) has been developed as a new oral anticancer drug based on the biological modulation of 5-fluorouracil. We treated a patient with highly advanced gastric carcinoma with a new combination chemotherapy of S-1 and low-dose cisplatin. Remarkable tumor reduction was observed after two cycles of this therapy in the primary tumor and metastatic lymph nodes, and the ascites disappeared. This was concluded to be a partial response. The only adverse effect was skin pigmentation of the fingers (grade 1), leading to early timing of operation after chemotherapy. The gastric tumor showed evident invasion to the serosa. Lymph nodes around the stomach were swollen. Peritoneal dissemination was also recognized in the omentum and mesocolon. Total gastrectomy with regional lymph node dissection was performed. Disseminated tumors were all resected. Histological examination showed that no tumor cells were detected in the gastric primary lesion, metastatic lymph nodes or disseminated peritoneal tumors, suggesting pathological complete remission. It was suggested that this regimen could be a potent combined therapy for the treatment of patients with highly advanced gastric carcinoma, and it could be useful as neoadjuvant chemotherapy. Further studies are necessary to evaluate the efficacy of this therapy.

Adenocarcinoma↗
PubMed2001

Radiofrequency ablation at the coronary sinus ostium interrupts the vagal efferent input to the atrioventricular node in the canine heart.

The fat pad at the junction of the inferior vena cava and inferior left atrium is the area of convergence of vagal projections into the atrioventricular node (AVN) region. The present study investigated whether radiofrequency (RF) ablation applied to the area around the coronary sinus (CS) ostium would impair vagal input to the AVN in the canine heart. Twenty-four dogs were anesthetized by sodium pentobarbital and RF energy was delivered at 20W for 5-10s. In the baseline state without vagal stimulation (10Hz, 2ms), the electrophysiological variables did not change significantly after RF ablation. Vagally induced changes in the sinus cycle length and effective refractory period of the right atrium and left ventricle did not differ after RF ablation. However, the effects of vagal stimulation on the AVN function were impaired after RF ablation to the CS area from the ostium to 10mm within the ostium. After ablation was applied to the fast pathway area, the vagally induced changes in the AVN function decreased, but these changes were not affected after RF ablation in the slow pathway area. RF ablation in the vicinity of the CS would attenuate vagal input to the AVN.

Animals↗
PubMed2001

The expression of a barley HvNAS1 nicotianamine synthase gene promoter-gus fusion gene in transgenic tobacco is induced by Fe-deficiency in roots.

Nicotianamine (NA) is a precursor for mugineic acid-family phytosiderophores, which are a critical component of the Fe aquisition process in graminaceous plants. In addition, nicotianamine synthase (NAS) is strongly induced in these plants by Fe deficiency. NA is essential for Fe metabolism also in dicots, but NAS is not induced by Fe deficiency. We introduced a barley HvNAS1 promoter-gus fusion gene into tobacco. GUS activity was induced in the roots of these plants by Fe deficiency, and was constitutively expressed at a low level in their leaves.

Alkyl and Aryl Transferases↗
PubMed2001

Adenosquamous carcinoma of the pancreas: successful treatment with extended radical surgery, intraoperative radiation therapy, and locoregional chemotherapy.

BACKGROUND: Adenosquamous carcinoma of the pancreas is a rare tumor with an extremely poor survival rate. No obvious evidence that multidisciplinary treatments improves the prognosis and survival has been reported. PATIENT AND RESULTS: A 63-yr-old female with adenosquamous carcinoma of the pancreas underwent extended radical surgery, intraoperative radiation therapy, postoperative intraarterial chemotherapy, and external beam radiation therapy. The patient is alive at 40 mo after surgery with no recurrence. CONCLUSIONS: Multidisciplinary treatments including aggressive surgery, intraoperative radiation therapy, and locoregional chemotherapy might improve the survival of patients with adenosquamous carcinoma of the pancreas to inhibit liver metastasis and local recurrence.

Antineoplastic Agents↗
PubMed2001

Role of CYP2C19 in stereoselective hydroxylation of mephobarbital by human liver microsomes.

The 4-hydroxylation of mephobarbital enantiomers was investigated by using human liver microsomes from the extensive metabolizers (EM) and poor metabolizers of CYP2C19. The 4-hydroxylase activity of R-mephobarbital in the EM microsomes was >10 times higher than that of S-mephobarbital. In the poor metabolizer microsomes, the 4-hydroxylase activity of R-mephobarbital was much lower than that in the EM microsomes, and the ratio of 4-hydroxylase activity of R-mephobarbital to that of S-mephobarbital was also lower than that in the EM microsomes. Moreover, the 4-hydroxylase activity of R-mephobarbital showed a high correlation (r = 0.985, p<0.001) with the 4'-hydroxylase activity of S-mephenytoin in a panel of nine human liver microsomes. Anti-CYP2C antibody inhibited R-mephobarbital 4-hydroxylase activity by 85% of the control activity. R-Mephobarbital competitively inhibited S-mephenytoin 4'-hydroxylase activity (K(i) = 34 microM), while S-mephenytoin inhibited R-mephobarbital 4-hydroxylase activity (K(i) = 103 microM). Among the seven cDNA-expressed CYPs studied, only CYP2C19 catalyzed R-mephobarbital 4-hydroxylation. These findings suggest that the 4-hydroxylation of mephobarbital catalyzed by CYP2C19 is preferential for R-enantiomer in human liver microsomes.

Aryl Hydrocarbon Hydroxylases↗
PubMed2001

Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy.

BACKGROUND AND OBJECTIVES: Primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis has recently been recognized as a specific clinical and pathologic entity for which the best therapeutic approach seems to be a combination of chemotherapy and radiotherapy. DESIGN AND METHODS: Between 1989 and 1998, 89 previously untreated patients with PMLBCL with sclerosis were treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal radiation therapy. The response evaluations were examined after chemotherapy and at the end of radiotherapy. RESULTS: Twenty-three (26%) patients achieved a complete response (CR) and 59 (66%) obtained a partial response (PR) after the MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%) patients were non-responders. Among the 78 patients who obtained a CR there were 7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9 months); the other 71 patients are currently in continuous CR with a median follow-upof 45 months (range, 4-110 months). Projected overall survival was 86% at 9 years; the relapse-free survival curve of the 78 patients who achieved CR was 91% at 9 years. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and radiation therapy induces a good remission rate with the patients having a greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often plays a pivotal role in obtaining CR status.

Adolescent↗
PubMed2001

[Prostatic cancer developing after transurethral resection of the prostate for benign prostatic hyperplasia].

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.

Aged↗
PubMed2001

Efficacy of vinorelbine, epirubicin and prednisone combination regimen in pretreated elderly patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: To assess the efficacy and toxic profile of the NAEPP protocol, a regimen including vinorelbine, epirubicin and prednisone, in a particularly troublesome subset of patients: pretreated elderly patients with aggressive non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: From November 1998 to January 2000, 20 pretreated patients who had all relapsed after first-line VNCOP-B chemotherapy were enrolled in a phase II trial and treated with the NAEPP regimen: vinorelbine (25 mg/m(2) i.v. on days 1 and 8), epirubicin (40 mg/m(2) i.v. on days 1 and 8), and prednisone (40 mg/m(2) on days 1 and 8) with granulocyte colony-stimulating factor administered at 5 mg/kg/day on days 2-5 and days 9-12. Chemotherapy was repeated every 4 weeks for a total of 6 cycles. RESULTS: Six (30%) patients achieved complete remission (CR) and 7 (35%) had partial responses (PR), giving an overall response rate of 65%. The response rate was not affected either by type of relapse presentation (nodal versus nodal plus extranodal), presence of bulky disease, or time of relapse. No major toxic effects were recorded. INTERPRETATION AND CONCLUSIONS: These preliminary data suggest that the NAEPP regimen is an effective combination with a low toxicity profile in elderly pretreated patients with aggressive NHL. Further trials using NAEPP as a consolidation phase following first-line treatment are needed to establish the advantage in terms of CR rate and relapse-free survival in these patients.

Aged↗
PubMed2001

[Combination effect of arbekacin and cefepime on mixed culture of MRSA and P. aeruginosa].

We investigated the in vitro combination effects of arbekacin (ABK), vancomycin (VCM) or teicoplanin (TEIC) and cefepime (CFPM) on methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa isolated from various clinical specimens. Using checkerboard titration technique by agar dilution, combinations of ABK, VCM or TEIC and CFPM exhibited synergistic effects on 25 MRSA strains. The similar effects were also observed on ABK-resistant MRSA. Combination of ABK and CFPM exhibited a good effect on P. aeruginosa, but combinations of VCM or TEIC and CFPM exhibited no synergistic effect on P. aeruginosa. In vitro bactericidal activities of ABK, VCM or TEIC and CFPM against mixed cultures of MRSA with P. aeruginosa were examined at concentration of each drug that corresponds to the serum concentration at 3 hours after the usual therapeutic dosage. VCM or TEIC alone showed bacteriostatic effects against MRSA, and no enhancements were observed when combined with CFPM. ABK alone showed good bactericidal activity against MRSA and combination with CFPM enhanced the bactericidal activity. Against P. aeruginosa, ABK or CFPM alone showed the bactericidal activity, and strong bactericidal activity was induced by the combination of ABK and CFPM. VCM and TEIC showed no bactericidal activities against P. aeruginosa. When CFPM combined with VCM or TEIC, the bactericidal activity of CFPM was not enhanced against P. aeruginosa.

Aminoglycosides↗