Search PubMed⌕ Search

Biomedical subjects

M Tani

Publications and source records attributed to M Tani.

At least 37 records · Page 2Linked to original sources
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

Adequate endoscopic mucosal resection for early gastric cancer obtained from the dissecting microscopic features of the resected specimens.

BACKGROUND: We have employed endoscopic mucosal resection (EMR), using a cap-fitted panendoscope (EMRC), for early gastric cancer since 1992. The presence of an adequate surgical margin is a requirement because of the radicality of EMR, and dissecting microscopic examination is useful in regard to the diagnosis of spread of the disease. METHODS: To devise an adequate method of EMR that allows no lateral residue, we examined gastric mucosal specimens obtained by EMRC. One hundred and sixty-seven specimens from 97 lesions in 85 patients treated by EMRC were examined in regard to characteristic features, the recovery of marks made around the lesion, and the frequency of residue, and comparisons were made between the dissecting microscopic and histopathological findings. RESULTS: The first specimen obtained with a large cap under full suction was a circular shape measuring 21 x 19mm. The second specimen from fractionated resection was a half-moon or crescent shape, and the third specimen had a ginkgo leaflike or irregular shape. In the elevated lesions, coincidence regarding the spread, as determined by dissecting microscopy and histopathology, was present in 62 (93%) of the 67 lesions. In 16 (53%) of 30 flat or depressed lesions, there was a difference of 2 to 5 mm between the spread determined by these two examinations. CONCLUSION: It is important to place an adequate number of marks around the lesion and recover all marks by resection. When an elevated lesion measures 15mm or more, and a flat or depressed lesion is not clearly demarcated, aggressive use of planned fractionated resection seems to be the best way to prevent a lateral residue in EMR.

Aged↗
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

Mechanisms of Ca2+ overload induced by extracellular H2O2 in quiescent isolated rat cardiomyocytes.

Rat cardiomyocytes were exposed to H2O2 (1-100 micromol/L) for 10 min with washout for 10 min. Intracellular Ca2+ concentration ([Ca2+]i) was measured using fluo-3. [Ca2+]i increased with 100 micromol/L H2O2 and further increased during washout, causing irreversible contracture in one-half of the cells. The increase in [Ca2+]i with 10 micromol/L H2O2 was modest with few cells showing irreversible contracture and attenuated by caffeine, and [Ca2+]i gradually decreased during washout and this decrease was accelerated by a calcium-free solution, while 1 micromol/L H2O2 did not have any effects on [Ca2+]i or cell viability. Ca2+ overload caused during exposure to 100 micromol/L H2O2 was attenuated by caffeine with improved cellular viability but not by chelerythrine, KB-R7943 or nifedipine. With 100 micromol/L H2O2 calcium-free solution attenuated the increase during exposure and washout while KB-R7943 or chelerythrine partly attenuated further increase during washout but not improved cell viability, but chelerythrine did not have additional effect on calcium-free treatment. Catalase abolished the effects of H2O2. We concluded that the increased [Ca2+]i during exposure to 100 micromol/L H2O2 was caused both by release of Ca2+ from the intracellular store sites including the sarcoplasmic reticulum and by influx through route(s) other than the voltage-dependent Ca2+ channels or Na+/Ca2+ exchanger, although the Na+/Ca2+ exchanger or protein kinase C-mediated mechanism was partly responsible for a further increase during washout.

Alkaloids↗
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

Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon.

Most large bowel cancers are moderately to well-differentiated adenocarcinomas comprised chiefly or entirely of glands lined by tall columnar cells. We have identified a subset of poorly differentiated colon carcinomas with a distinctive histopathological appearance that we term large cell minimally differentiated carcinomas (LCMDCs). These tumors likely include a group of poorly differentiated carcinomas previously described by others as medullary adenocarcinomas. To better understand the pathogenesis of these uncommon neoplasms, we compared molecular features of 15 LCMDCs to those present in 25 differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for alterations commonly seen in typical colorectal carcinomas, including increased p53 and beta-catenin immunoreactivity, K-ras gene mutations, microsatellite instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and 18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a homeobox protein whose expression in normal adult tissues is restricted to intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs had the high-frequency microsatellite instability phenotype (P = 0.002). Our findings provide support for the hypothesis that the molecular pathogenesis of LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch repair defects have particularly prominent roles in the development of LCMDCs.

Adaptor Proteins, Signal Transducing↗
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

Very low dose of the Na(+)/Ca(2+) exchange inhibitor, KB-R7943, protects ischemic reperfused aged Fischer 344 rat hearts: considerable strain difference in the sensitivity to KB-R7943.

OBJECTIVE: Decreased ischemic tolerance in the aged myocardium is associated with accelerated intracellular Ca(2+) overload. However, few drugs have been shown to attenuate reperfusion injury in aged hearts. Because the Na(+)/Ca(2+) exchanger (NCX1) has been reported to play an important role in Ca(2+) overload during reperfusion, we investigated whether KB-R7943 (KB-R), a novel inhibitor of the reverse mode of Na(+)/Ca(2+) exchange, can protect aged rat hearts against reperfusion injury. METHODS: In the pilot study, isolated hearts from young Sprague-Dawley (SD) rats (12 weeks old), and young (12 weeks old) and aged (78 weeks old) Fischer 344 (F) rats were subjected to 25 min of global ischemia followed by 10 min of reperfusion with various concentrations of KB-R (0, 1 nM, 0.1 microM, 10 microM) and additional 20 min of reperfusion without agent. In subsequent studies with the same protocol in aged F rats, we added a protective dose of KB-R (1 nM) during the initial 10 min of reperfusion. In addition, we compared the amount of NCX1 and the sensitivity of the reverse mode of Na(+)/Ca(2+) exchange to KB-R under extracellular Na(+)-free condition in F rats with young SD rats. RESULTS: In the pilot study, protective effects were elicited with 1 nM of KB-R in both young and aged F rats, while 10 microM KB-R was needed for SD rats. In subsequent studies using aged F rats, there was better recovery of LV systolic function and high-energy phosphates with reduced creatine kinase release and the duration of reperfusion arrhythmias. 45Ca(2+) uptake via the reverse mode of Na(+)/Ca(2+) exchange was also inhibited with 1 nM of KB-R in young F rats, but not in young SD rats. Although the amount of NCX1 was not different among young SD, young F, and aged F rat hearts. CONCLUSIONS: These results demonstrated that KB-R could protect aged F rat hearts as well as young hearts of both strains against ischemia-reperfusion injury. Moreover, the sensitivity to KB-R is very different between these strains, suggesting serious caution when the agent is applied to human beings.

Adenosine Triphosphate↗
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

Effects of stereotactic radiosurgery on metastatic brain tumors of various histopathologies.

Although reports have been published describing clinical results in a large series of patients with metastatic brain tumors treated by stereotactic radiosurgery (SRS), clinical neuropathological correlation has rarely been available. The present paper describes three autopsy cases and one surgical case treated with linear accelerator based radiosurgery. The cases comprised a lung cancer, a rectal cancer, an osteosarcoma, and a malignant melanoma. Histological sections of each tumor were analyzed by light microscopy based on the Ohosi and Shimosato's histopathological classification of the effects of radiation therapy. In three cases (pulmonary squamous cell carcinoma, rectal adenocarcinoma and osteosarcoma), a large area of the tumors consisted of coagulation necrosis and non-viable tumor cells, while coagulation necrosis and non-viable tumor cells comprised a very small part of the malignant melanoma. Histopathological type of the metastatic brain tumor may be one of the factors influencing outcome after SRS.

Adenocarcinoma↗
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

Differences in the expression of protein kinase C isoforms and its translocation after stimulation with phorbol ester between young-adult and middle-aged ventricular cardiomyocytes isolated from Fischer 344 rats.

It is known that the tolerance against ischemia-reperfusion and the effects of preconditioning decrease in aged hearts, but the mechanisms responsible for this diminished ischemic tolerance and reduced efficacy of preconditioning remain unknown. To determine the age-related changes in these mechanisms, protein kinase C (PKC) isoform expression and its translocation by phorbol ester were analyzed because PKC is believed to be involved in preconditioning. Immunoblotting and immunostaining analysis were performed with isoform-specific PKC antibodies using cardiomyocytes isolated from young-adult (12-week-old: 12W) and middle-aged (50-week-old: 50W) Fischer 344 rats. There was significantly greater PKC-delta expression in both the cytosolic and membrane fractions of 12W cardiomyocytes than in 50W ones. Exposure of cardiomyocytes to 100 nmol/L 4-beta-phorbol 12-myristate 13-acetate (PMA) caused translocation of PKC-delta from the cytosol to the membrane in the 12W group, whereas in the 50W group, the translocation was attenuated. Immunostaining confirmed the PKC-delta translocation in the 12W cardiomyocytes. Oil pellet examination showed that the translocation of PKC-delta induced by preconditioning was associated with cell protection from ischemic injury in the 12W group only. Age-related changes in PKC isoform expression and activation in cardiomyocytes might be responsible for the reduced ischemic tolerance and less efficient preconditioning that accompanies aging.

Aging↗
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

Rapid improvement of icterus and pruritus by the oral administration of colestimide in two cases of drug-induced hepatitis.

We report two cases of drug-induced hepatitis refractory to therapy of ursodeoxycholic acid and prednisolone, who were relieved of icterus and pruritus immediately by the oral administration of colestimide. Their liver dysfunction was not improved, by withdrawal of causative drugs or by treatment with prednisolone and ursodeoxycholic acid. Colestimide (3.0 g/day), a strong basic anion-exchange resin, was orally taken before breakfast and evening meal, leading to rapid and complete relief of icterus and pruritus. These cases suggested that colestimide would be useful for patients with cholestasis in drug-induced hepatitis, because this agent has few side effects and it is easy to take.

Adult↗