Biomedical subjects

M Tani

Publications and source records attributed to M Tani.

At least 73 records · Page 4Linked to original sources

PubMed2000

Solid and cystic tumor of the pancreas: clinicopathologic and genetic studies of four cases.

BACKGROUND: Solid and cystic tumor (SCT) of the pancreas can be distinguished from other pancreatic neoplasms by its nearly exclusive occurrence in young women, and its favorable prognosis after complete resection. METHODS: We experienced four cases with SCT of the pancreas, and analyzed these tumors by immunohistochemical and electron microscopic studies, as well as genetic analysis of ras oncogene mutation. RESULTS: The presented cases expressed the neuron-specific enolase in two cases, alpha1-antitrypsin and alpha1-antichymotrypsin in two cases, and vimentin in one case, which indicated that this tumor originates from pleuripotential embryonic stem cells. No patients had mutations of K-ras gene in codon 12, and further genetic analysis is required to predict the malignant potential. CONCLUSION: SCT of the pancreas appears to have limited malignant potential and the metastatic ratio is not high, although the tumor has local invasion. Therefore, an aggressive surgical approach seems fully justified.

Adult↗

PubMed2000

Catheter-delivered in vivo gene transfer into rat myocardium using the fusigenic liposomal mediated method.

We compared the efficacy of four different in vivo hemagglutinating virus of Japan (HVJ)-liposome gene transfer methods, i.e., direct myocardial injection (i.m.), injection into the left ventricular cavity (LV), infusion at the level of the coronary cusps (CI), or injection into the left ventricular cavity with a balloon catheter blocking aortic flow (LV+B) to transfer beta-galactosidase, FlTC-labeled oligodeoxynucleotide (ODN), and/or luciferase genes into the rat heart. I.m. caused highly efficient gene transfer in the limited area around the injection site, which suggests that i.m. may be a suitable method for targeted treatment of focal lesion. In the LV+B group, all rats had myocardial beta-galactosidase staining and fluorescence of FITC-labeled ODN in the nuclei of cardiac myocytes around the coronary arteries and the vasa vasorum, and some transfected myocytes were observed in the middle of the myocardium without any evidence of injury. In contrast, in the CI group, only half of the animals had myocardial expression of beta-galactosidase. In contrast, fluorescence or luciferase activity was present throughout the left ventricle in the LV+B group. However, the percentage of myocytes that exhibited fluorescence was less than 1% of the total ventricular myocyte population and luciferase activity in the LV+B group was 1.6% of that in the i.m. group. No evidence of luciferase expression was observed in brain, lung, liver, kidney, or testis in either the i.m. or LV+B group. These results suggest that HVJ-liposome gene transfer into the myocardium through the coronary arteries using a balloon-catheter technique is safe and has the potential for causing widespread transgene expression with organ-specificity, although the efficiency of gene transfer should be improved.

Animals↗

PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 4). Fadrozole hydrochloride: an oral 2/4-week male reproductive organ toxicity study.

Doses of 0, 30 and 60 mg/kg/day of fadrozole hydrochloride (Afema: non-steroidal aromatase inhibitor, antitumor agent) were given perorally by gavage to HanIbm WIST male rats from 6 or 8 weeks of age for 2 weeks, and from 6 weeks of age for 4 weeks. In all treatment groups, reduced weights of seminal vesicle, prostate and epididymis, and degeneration/necrosis of the pachytene spermatocytes in stages VII or VIII seminiferous tubules, were dose-relatedly observed. Effects could also be assessed quantitatively by staging analysis with the result of a reduction in the numbers of stage VII pachytene spermatocytes at 30 and 60 mg/kg/day. Epididymal sperm examination revealed no treatment-related changes in any groups. The effects of 4-week treatment on male reproductive organs were similar to those of 2-week treatment at the same dose levels, except for the weights of seminal vesicle and prostate, which were more reduced by 4-week treatment than by 2-week treatment. There was no notable difference in detectability of toxicity in male reproductive organs between 2-week treatment from 6 weeks of age and 2-week treatment from 8 weeks of age. It was concluded that the changes observed in the rat male reproductive organs following 4 weeks of treatment with fadrozole hydrochloride could be detected also with 2 weeks of treatment.

Administration, Oral↗

PubMed2000

[Comparison of complications in colonoscopic treatment in elderly and young subjects].

PURPOSE: Owing to a recent increase in incidence of colonic adenoma and adenocarcinoma, colonoscopic treatments for elderly subjects are performed more frequently. We analyzed differences in complications between elderly and young subjects. OBJECT AND PROCEDURE: Subjects that had been treated with colonoscopy at Keio Cancer Center, were divided into two groups: one group (436) consisting of subjects below the age of 65, the other (176) consisting of subjects 65 and over. We analyzed differences in symptoms, complications and pathological findings. RESULT: No significant statistical differences were found in the occurrence of adenoma and adenocarcinoma between the young and the elderly group. COMPLICATIONS: Pain occurred in 9.4% of the young group and 10.2% of the elderly group, showing no significant difference between the two groups. Bleeding occurred in 0.7% of the young group and 3.8% of the elderly group and ulcerative scars were found in two of the latter. CONCLUSION: In the elderly the regenerative capacity of damaged blood vessels and tissues is greatly reduced, therefore bleeding and ulceration occurred more frequently. It was thus concluded that it is very important for elderly group to rest after endoscopical mucosal resection, polypectomy and biopsy in order to minimize the risk of bleeding in the digestive tract.

Adenocarcinoma↗

PubMed2000

[The problem of a long-term follow up in patients with renal cell carcinoma].

PURPOSE: We investigated on a problem of long-term follow up in patients with renal cell carcinoma. PATIENTS AND METHODS: A total of 287 patients with renal cell carcinoma treated in Nara Medical University and affiliated facilities from January 1980 to December 1990 were examined. And we investigated the trend of explanation to patients including 287 patients from 1991 to 1995. RESULTS: Up to December 1995, there are 76 patients (26.5%) unable to be followed and 211 patients able to be followed. The former group patients were less declared cancer rather than the latter group patients. Of 76, 22 patients (28.9%) might misunderstand completely recovering from the cancer disease. For the recent 5 years, those patients who were declared cancer increased, and those patients who were explained benign disease decreased. CONCLUSION: These results suggested that declaration of cancer is important for patients with renal cell carcinoma to be followed for a long-term.

Aged↗

PubMed2000

Efficacy of the VBM regimen in the treatment of elderly patients with Hodgkin's disease.

BACKGROUND AND OBJECTIVES: No specific chemotherapy regimens have yet been recommended for elderly Hodgkin's disease (HD) patients. We investigated the therapeutic efficacy and toxicity of the three-drug-combination VBM (vinblastine, bleomycin, and methotrexate) regimen in a group of 19 elderly HD patients. DESIGN AND METHODS: Vinblastine (6 mg/m(2) i.v.), bleomycin (10 mg/m(2) i.v.) and methotrexate (25 mg/m(2) i.v.) were administered on days 1 and 8. Chemotherapy was repeated every 28 days for a total of 6 cycles. Local radiotherapy was given only to patients who presented bulky disease at the time of diagnosis. Of the 19 patients, 13 patients had stage II, 2 stage III, and 4 stage IV disease; the median age was 68 years (range 60 to 75). RESULTS: Of the 19 patients, 15 (79%) achieved complete response (CR) and 3 (16%) partial response, while the remaining patient showed no benefit from the treatment. With a median follow-up of 48 months, the estimated 5-year relapse-free survival was 79%, and overall survival was 64%. Hematologic grade 3-4 toxicity was seen in only 1 (5%) patient; no severe non-hematologic side effects or deaths were associated with the administration of the VBM regimen. INTERPRETATION AND CONCLUSIONS: These preliminary data indicate that the VBM regimen provides a safe and effective therapeutic option for elderly patients with untreated HD.

Age Factors↗

PubMed2000

Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans.

To identify which cytochrome P-450 (CYP) isoform(s) are involved in the major pathway of disopyramide (DP) enantiomers metabolism in humans, the in vitro formation of mono-N-desalkyldisopyramide from each DP enantiomer was studied with human liver microsomes and nine recombinant human CYPs. Substrate inhibition showed that SKF 525A and troleandomycin potently suppressed the metabolism of both DP enantiomers with IC50 values for R(-)- and S(+)-DP of <7.3 and <18.9 microM, respectively. In contrast, only weak inhibitory effects (i.e., IC50 > 100 microM) were observed for five other representative CYP isoform substrates [i.e., phenacetin (CYP1A1/2), sparteine (CYP2D6), tolbutamide (CYP2C9), S-mephenytoin (CYP2C19), and p-nitrophenol (CYP2E1)]. Significant correlations (P <.01, r = 0.91) were found between the activities of 11 different human liver microsomes for mono-N-dealkylation of both DP enantiomers and that of 6beta-hydroxylation of testosterone. Conversely, no significant correlations were observed between the catalytic activities for DP enantiomers and those for the O-deethylation of phenacetin, 2-hydroxylation of desipramine, hydroxylation of tolbutamide, and 4'-hydroxylation of S-mephenytoin. Further evidence for involvement of CYP3A P450s was revealed by an anti-human CYP3A serum that inhibited the mono-N-dealkylation of both DP enantiomers and 6beta-hydroxylation of testosterone almost completely (i.e., >90%), whereas it only weakly inhibited (i.e., <15%) CYP1A1/2- or 2C19-mediated reactions. Finally, the recombinant human CYP3A3 and 3A4 showed much greater catalytic activities than seven other isoforms examined (i.e., CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1, and 3A5) for both DP enantiomers. In conclusion, the metabolism of both DP enantiomers in humans would primarily be catalyzed by CYP3A4, implying that DP may have an interaction potential with other CYP3A substrates and/or inhibitors.

Aged↗

PubMed2000

Tobacco smoking, occupational exposure and chronic respiratory disease in an Italian industrial area.

Tobacco smoking and occupational exposure are the major factors responsible for chronic obstructive pulmonary disease (COPD) worldwide. The prevalence of this disease and its main risk factors were investigated in an area characterized by a high density of iron- and steelworking factories in North Italy. A total of 1,497 subjects (50% male) aged 40-59 yrs underwent an interview and a physical assessment, and 1,244 of them also underwent spirometry. The prevalences of COPD and asthma were 16.1 and 5.2% among males and 4.4 and 4.0% among females. COPD and respiratory symptoms were associated with both smoking and occupational exposure in males: the odds ratios for having been occupationally exposed among males were 2.3 (95% confidence interval 1.4-3.7) for COPD and 1.7 (1.2-2.6) for respiratory symptoms. No association was found between asthma and tobacco smoking or occupational exposure. The forced expiratory volume in one second and forced vital capacity were associated negatively with smoking and not associated with occupational exposure. In females, lesser effects of cigarette smoking on both self-reported respiratory diseases and lung function tests were found. The attributable risks of chronic obstructive pulmonary disease for smoking and occupational exposure among males were 52.9 and 8.8%, respectively, and 60.3% when considered together, whereas 18.8% of chronic obstructive pulmonary disease cases among females were attributable to smoking.

Adult↗

PubMed2000

Long-term follow-up of hairy cell leukemia patients treated with 2-chlorodeoxyadenosine.

BACKGROUND AND OBJECTIVES: The management of patients with hairy cell leukemia (HCL) has evolved significantly over the past two decades. In fact, both 2'-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-CdA) induce complete response (CR) in the majority of the patients with HCL. However, fewer data exist on the long-term follow-up of patients who have undergone the characteristically brief exposure to 2-CdA therapy. Thus, it is important to evaluate such long-term outcome data in order to increase understanding of the efficacy of this agent in the management of HCL. DESIGN AND METHODS: We reviewed the long-term follow-up data of 23 HCL patients pretreated with a-interferon and then treated with 2-CdA administered as a single continuous IV infusion for 7 days at the dose of 0.1 mg/kg/day in our institute between January 1991 and February 1992. RESULTS: Of 23 patients, 19 (83%) achieved a CR and 4 (17%) a partial response (PR), with an overall response rate of 100%. After a median follow-up of 102 months (range: 96-108), there have been 9 (39%) relapses. In the PR subset 100% of patients relapsed within the first 45 months of follow-up. In the group of patients who obtained a CR, 26% relapsed; all these relapses occurred between 54 and 86 months. Overall, the median time to relapse was 54 months (range: 16-86). All relapsed patients were re-treated with 2-CdA at the dose of 0.15 mg/kg/day for 5 days in a 2-hour infusion, and 67% and 22% then obtained CR or PR, respectively. The median duration of this second response was 48 months (range: 22-80). All but one of these patients are still maintaining the second response to 2-CdA. The 9-year overall and the relapse-free survivals are 91% and 70%, respectively. INTERPRETATION AND CONCLUSIONS: In HCL patients a single dose of 2-CdA induces a long-term CR with a 9-year survival > 90%. Over 50% of patients appear to be clinically cured by this procedure, but the lack of a long-term plateau in the relapse-free survival curve means caution on this point is still warranted.

Adult↗

PubMed2000

Value of gemcitabine treatment in heavily pretreated Hodgkin's disease patients.

BACKGROUND AND OBJECTIVES: To assess the efficacy and the toxic profile of gemcitabine, a novel pyrimidine antimetabolite active against several solid tumors, we carried out a study in heavily pretreated Hodgkin's disease (HD) patients. DESIGN AND METHODS: From May 1997 to January 1999, 14 pretreated patients (10 relapsed and 4 refractory to previous treatments) were enrolled in a phase II trial and treated with gemcitabine. The drug was given on days 1, 8 and 15 of a 28-day schedule at a dose of 1,200 mg/m2 intravenously for a total of 6 cycles. RESULTS: Two (14%) patients achieved complete remission (CR) and 4 (29%) had partial responses (PR), giving an overall response rate of 43%. In the relapsed subset there was an overall response rate of 50% with 2 CR and 3 PR. Among the refractory patients there was only 1 PR (25%). Both patients who had relapsed after autologous bone marrow transplant achieved a response (1 CR and 1 PR). No major toxic effects were recorded. INTERPRETATION AND CONCLUSIONS: These data suggest that gemcitabine is an effective drug with a low toxicity profile in patients with heavily pretreated HD. Further trials using gemcitabine in combination with other conventional drugs are needed.

Adult↗

PubMed2000

Long-term follow-up after fludarabine treatment in pretreated patients with chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: A study update to assess long-term survival following fludarabine salvage treatment in previously treated patients with chronic lymphocytic lymphoma (CLL). DESIGN AND METHODS: From September 1992 to December 1995, 74 patients with advanced, relapsing B-cell CLL were enrolled in the study. Fludarabine was given for 5 consecutive days at the dose of 25 mg/m2/day in a 30 min infusion. Treatment was repeated every 28 days for a maximum of 6 courses.E RESULTS. Nineteen (26%) patients achieved a complete response (CR) and 20 (27%) patients had a partial response (PR), giving an overall response rate of 53%. The median overall survival was 68 months, and there was a strong negative correlation with the number of previous treatments. The median time to progression was 18 months for patients who achieved a CR and 12 months for those with a PR. INTERPRETATION AND CONCLUSIONS: The results obtained with fludarabine alone in this subset of CLL patients indicate the existence of a conspicuous disease-free survival period. This time window could be used to consolidate the initial response with either biological approaches or high-dose therapeutic strategies such as autologous bone marrow transplantation, with the aim of eventual eradication of the disease.

Actuarial Analysis↗

PubMed2000

[New therapeutic strategy against colon cancer based on a tumor-specific approach].

To develop a new therapy against colon cancer, we investigated two kinds of strategy using a cancer-specific approach. First, we employed the Cre/loxP regulation system to enhance the specific expression by carcinoembryonic antigen (CEA) promotor in CEA-producing tumor cells, and examined whether sufficient enhancement to transcriptional activity of CEA promotor, which maintains its specificity in vitro and in vivo, could be obtained. Next, using dendritic cells pulsed with HLA-A24 epitope peptides of CEA, we performed a Phase I study of active immunotherapy in patients with advanced colon cancer. These results suggest that the newly developed therapy for colon cancer is a promising strategy; however, minor modification may be necessary.

Antigen-Presenting Cells↗

PubMed1999

The autocrine motility factor receptor gene encodes a novel type of seven transmembrane protein.

Autocrine motility factor receptor (AMFR) is a cell surface glycoprotein of molecular weight 78,000 (gp78), mediating cell motility signaling in vitro and metastasis in vivo. Here, we cloned the full-length cDNAs for both human and mouse AMFR genes. Both genes encode a protein of 643 amino acids containing a seven transmembrane domain, a RING-H2 motif and a leucine zipper motif and showed a 94.7% amino acid sequence identity to each other. Analysis of the amino acid sequence of AMFR with protein databases revealed no significant homology with all known seven transmembrane proteins, but a significant structural similarity to a hypothetical protein of Caenorhabditis elegans, F26E4.11. Thus, AMFR is a highly conserved gene which encodes a novel type of seven transmembrane protein.

Amino Acid Sequence↗

PubMed1999

Circadian variation of idiopathic ventricular tachycardia originating from right ventricular outflow tract.

We determined circadian variation of isolated ventricular premature complexes (VPCs), 2 to 4 consecutive VPCs, and ventricular tachycardia (5 consecutive VPCs) originating from the right ventricular outflow tract in patients without apparent structural heart diseases. There was apparent circadian variation with 2 prominent peaks for these ventricular arrhythmias, and blockade abolished ventricular tachycardia and attenuated the circadian variation of consecutive VPCs.

Adult↗

PubMed1999

Treatment with BBB022A or rolipram stabilizes the blood-brain barrier in experimental autoimmune encephalomyelitis: an additional mechanism for the therapeutic effect of type IV phosphodiesterase inhibitors.

We examined the treatment effects of two structurally distinct phosphodiesterase type IV (PDE IV) inhibitors, BBB022 and rolipram, in murine and rat models of experimental autoimmune encephalomyelitis (EAE). Based on our data, we propose a mechanism of action which may supplement immunomodulatory effects of PDE IV inhibitors. In particular, PDE inhibitors promote elevation of intracellular cAMP levels, increasing the electrical resistance of endothelial monolayers by stabilizing intercellular junctional complexes. Such an effect on central nervous system (CNS) vascular endothelium has the potential to reduce disease severity in EAE, because both inflammatory cells and humoral factors readily cross a disrupted blood-brain barrier (BBB). In this report, we demonstrate the capacity of BBB022 and rolipram to decrease clinical severity of EAE. further, PDE IV inhibitors significantly reduced BBB permeability in the spinal cords of mice with EAE. These results provide evidence that PDE IV-inhibitors may exert therapeutic effects in EAE by modifying cerebrovascular endothelial permeability, reducing tissue edema as well as entry of inflammatory cells and factors.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1999

P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer.

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Endosonography during endoscopic mucosal resection to enhance its safety: a new technique.

BACKGROUND: We have performed endoscopic mucosal resection of the esophagus (172 cases), stomach (102 cases), and colon (28 cases) using a transparent plastic cap. Because the lesion-bearing mucosa is suctioned up inside the cap under endoscopic suction, the mucosa should be dissected sufficiently from the proper muscle layer to prevent perforation. METHODS: To avert the risk of perforation, we introduced endosonographic assessment of submucosal dissection (47 cases). In all cases, just keeping the ultrasonic probe on the surface of the mucosa allowed us to evaluate whether the mucosal lesion was lifted up sufficiently from the proper muscle layer after local saline injection. RESULTS: It was possible to confirm that the muscle layer was kept outside the strangulating snare by the same procedure (32 of 37 cases, 86.5%). CONCLUSIONS: We experienced five muscular resections in cases without the ultrasonic probe and no muscular resection with the ultrasonic probe. Thus we recommend endosonographic assessment during endoscopic mucosal resection to enhance its safety.

Colonic Neoplasms↗

PubMed1999

Loss of protection by hypoxic preconditioning in aging Fischer 344 rat hearts related to myocardial glycogen content and Na+ imbalance.

OBJECTIVES: The objective of this study was to determine whether hypoxic preconditioning (HP) could lessen the myocardial increase in [Na+]i, thus protecting the aging myocardium against ischemia. BACKGROUND: A decrease in ischemic tolerance with aging is associated with an accelerated increase in [Na+]i during ischemia. Ischemic preconditioning fails to protect the middle-aged and senescent myocardium against ischemia. METHODS: Isolated hearts of young adult (12-week-old), middle-aged (50-week-old) and senescent (100-week-old) Fischer 344 rats were subjected to 25 min of ischemia with or without HP followed by 30 min of reperfusion. Left ventricular (LV) function, myocardial energy metabolites and [Na+]i were measured. RESULTS: In the older groups, the recovery of LV function and high-energy phosphates (HEPs) was lower with an increased release of creatine kinase (CK) during reperfusion than in the young group. The increased [Na+]i at the end of ischemia was greater in the former groups than in the young group. HP decreased myocardial glycogen and lessened the increased [Na+]i in the young group, resulting in an improved recovery of LV function and HEPs, as well as decreased CK release. However, the levels of glycogen before HP in the older groups were higher than in the young group and its levels after HP were similar to that before HP in the young group. HP did not affect the [Na+]i, exacerbated CK release and inhibited the recovery of LV function and HEPs in the older groups. CONCLUSIONS: HP failed to lessen the increased [Na+]i or to protect the aging hearts, probably due to the preexistence of increased glycogen level.

Aging↗