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Biomedical subjects

H Tanimura

Publications and source records attributed to H Tanimura.

At least 19 recordsLinked to original sources
PubMed1992

Activation of human multidrug resistance-1 gene promoter in response to heat shock stress.

The multidrug resistance (MDR1) gene encodes a P-glycoprotein, which catalyzes the energy-dependent efflux of anticancer agents. Various environmental stresses including heat shock can induce the expression of endogenous MDR1 genes. In order to study the regulatory mechanisms of MDR1 gene expression, we have established human cancer KB cell lines which could stably integrate bacterial chloramphenicol acetyltransferase (CAT) gene driven by various lengths of the MDR1 promoter. Kst-6 has an integrated plasmid, pMDRCAT1, containing the human MDR1 promoter of -2 kilobases. The MDR1 gene promoter contains a typical heat shock element (HSE) motif located -152 bp to -178 bp from the initiation site. Heat shock at 45 degrees C for 90 min significantly induced CAT activity in Kst-6 cells. Northern blot analysis showed a 4-5 fold increase in CAT mRNA levels in Kst-6 cells. Deletion analysis of the MDR1 promoter demonstrated that the induction of CAT activity was observed in Kxh-14 cells containing a HSE-deleted MDR1 promoter construct, pMDRCAT7. However, further deletion analysis showed that heat shock could not induce CAT activity in Khp-1 cells containing -76 approximately +121 base sequence of the promoter, suggesting that a new heat shock responsible element was located at between -136 and -76. Gel shift assay showed that the heat shock factor (HSF) could bind to the HSE motif located at -152 bp to -178 bp in the MDR1 promoter. We also found that one distinct DNA-protein complex formed specifically within the MDR1 promoter region -99 to -66 was not significantly increased, but relatively more stabilized under mild denaturing condition in the nuclear extract of heat-shocked cells. In our present assay system, activation of the MDR1 promoter in response to heat shock appears to be mediated through both a new heat shock responsive element and MDR1 specific transcription factor.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Topical antibiotics in cholecystectomy for gallstone diseases.

Efficacy of topical antibiotics in cholecystectomy for gallstone disease was evaluated. Forty-four patients who accepted topical single administration of 1 or 2 g each of latamoxef, cefmenoxime, cefotiam or cefamandole during operation were compared with 36 patients with systemic administration of cefem antibiotics by intravenous drip at a dose of 1 or 2 g, twice daily for postoperative 4 to 7 consecutive days. In topical administration group, concentration of each antibiotic in the gallbladder and common duct bile, gallbladder tissue, parietal peritonea and intra- and postoperative peripheral blood exceeded mostly MIC80 against bacteria usually existing in bile by biliary tract infection or bacteria by wound infection. There was no difference between the two groups in postoperative clinical course. Thus, an adequate prophylactic effect can be expected by topical use of antibiotic during cholecystectomy.

Administration, Topical↗
PubMed1992

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients.

The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR-killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLR-killer cells against various tumor-cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumor-killing activity of AMLR-killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autotumor killing activity was decreased by the elimination of CD4+ cells, whereas the elimination of CD16+ cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non-specific killer cells which lysed K562 were different from the specific killer cells that lysed autotumor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non-specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.

Adult↗
PubMed1992

The human multidrug resistance 1 promoter has an element that responds to serum starvation.

We have previously demonstrated in transient expression assay systems that a human multidrug resistance 1 (MDR1) promoter can be directly activated by cytotoxic anticancer agents. In this study, we examined whether the MDR1 promoter could be regulated in response to growth arrest induced by serum starvation. We have established human and rodent cell lines which stably expressed the chloramphenicol acetyltransferase (CAT) gene driven by various lengths of the MDR1, the viral thymidine kinase (TK) and the simian virus 40 (SV40) promoters. Serum starvation caused enhanced expression of CAT gene with MDR1 promoter, but not with two viral gene promoters in human cancer KB cells. Hydroxyurea activated the MDR1 promoter, but not TK and SV40 promoters. By contrast, the DNA topoisomerase II inhibitor, etoposide, equally activated the MDR1, TK and SV 40 promoters. Increased CAT gene expression by serum starvation was also specifically observed in stable transfectants of human adrenal SW-13 cell lines, but not in stable transfectants of mouse fibroblast NIH3T3 and adrenal Y-1 cell lines when the human MDR1 promoter-CAT was introduced. Etoposide, however, effectively induced CAT activity in both human and rodent cells. Assays with deletion constructs of the MDR1 promoter showed that serum starvation activated the MDR1 promoter carrying -258 approximately +121 base sequence of the promoter, but not -198 approximately +121 of the promoter. These results suggest that the expression of the MDR1 gene induced by serum starvation is regulated at the transcriptional level in a promoter sequence-specific manner in human cells.

Animals↗
PubMed1992

Effects of proton pump inhibitor on gastric mucosa hemodynamics and tissue oxygenation in anesthetized rats.

Proton pump inhibitors have been reported to have a cytoprotective action in addition to the anti-secretory action of acid. The precise mechanism, however, remains obscure. In this study, the effects of proton pump inhibitors (omeprazole and NC-1300) on gastric mucosa hemodynamics and tissue oxygenation were investigated using organ reflectance spectrophotometry in a hemorrhagic shock-reperfusion model involving anesthetized rats. Neither drug affected gastric mucosa hemodynamics nor tissue oxygenation in the basal state before hemorrhage. During the hemorrhagic shock state, however, these drugs maintained tissue oxygenation and reduced ulcer formation, although they did not show a significant effect on gastric mucosa blood volume. The results suggest that both proton pump inhibitors have an anti-ulcer action by maintaining mucosal oxygenation in addition to the anti-secretory activity of acid.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged↗
PubMed1992

In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan.

The in vitro effect of lentinan in inducing activation of killer cells and cytotoxic macrophages has been examined. Human peripheral blood mononuclear cells were cultured with lentinan for 2, 4 and 8 days. After 4 days cytotoxicity was increased 4% by lentinan less than 1,000 ng/ml. After 8 days, it was increased 12% by 25 and 1,000 ng/ml lentinan. The phenotype of the killer cells induced by lentinan was CD2+, CD16+ and CD56+, suggesting that they were natural killer cells. Macrophages separated from the spleens of 6 patients with gastric cancer were cultured with lentinan for 7 days, and their cytotoxicity increased 19%. The optimal concentration of lentinan was from 25 to 100 ng/ml. The findings suggest that the antitumour effect of lentinan is due to the activation of killer cells in vivo, because the optimal concentration of lentinan for the induction of killer cells in vitro was equivalent to the plasma concentration obtained after clinical doses of this agent.

Antigens, Surface↗
PubMed1992

The promotive effect of interleukin 4 with interleukin 2 in the proliferation of tumor-infiltrating lymphocytes from patients with malignant tumor.

In adoptive immunotherapy, the number of effector cells is one of the major factors relating to the therapeutic efficacy. We demonstrated that tumor-infiltrating lymphocytes (TILs) were stimulated to proliferate by incubation with interleukin 2 (IL-2) plus interleukin 4 (IL-4). TILs cultured with IL-2 plus IL-4 increased 3.1-fold more than TILs cultured with IL-2 alone. However, IL-4 did not alter the cytotoxic activity of TILs against autologous tumor cells and established tumor cell lines. It is suggested that IL-2 receptor is related to the mechanism of the proliferation of activated TILs cultured by combination with IL-2 and IL-4. Thus, the combination of IL-2 and IL-4 may increase the efficacy of adoptive immunotherapy using activated TILs.

Cytotoxicity, Immunologic↗
PubMed1992

Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432.

We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.

Antigens, Neoplasm↗
PubMed1992

In vitro augmentation of the cytotoxic activity of peripheral blood mononuclear cells and tumor-infiltrating lymphocytes by famotidine in cancer patients.

We investigated the in vitro effects of famotidine on the cytotoxic activity of peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs). The cytotoxic activity of PBMC was augmented by famotidine at a concentration of 10 ng/ml, which is equivalent to the serum level achieved by the intravenous administration of a dose of 20 mg. This response to famotidine was seen only in cancer patients. Both the cytotoxic activity and DNA synthesis of activated TILs were increased by the combination of interleukin-2 and 1 microgram/ml of famotidine. Augmentation of cytotoxic activity by famotidine occurred independently of any decrease in the population of suppressor T-cells. Thus, famotidine may have the potential to be used in adoptive immunotherapy with TILs for cancer patients.

Antigens, CD↗
PubMed1992

Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay.

A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).

Adult↗
PubMed1992

[Chemotherapy of biliary tract infections (XXXVII). Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections].

Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections. 1. Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively. These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound. 2. The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg. The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated. 3. At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0%. 4. A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d. for 3-14 days. Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7%. 5. A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild. It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections.

Adult↗
PubMed1991

Augmentation of cytotoxic activity by combination with interleukin 2 and interferon gamma.

The synergy of cytotoxic activity by interleukin 2 (IL-2) and interferon gamma (IFN-gamma) was evaluated in human peripheral blood mononuclear cells (PBMC) and spleen cells. PBMC incubated with IL-2 (10 IU/ml) and IFN-gamma (200 IU/ml) for 4 days showed the stronger cytotoxic activity against K562, MOLT-4 and Daudi cells. Combination with IL-2 and IFN-gamma induced stronger activity than IL-2 or IFN-gamma alone. In order to investigate the sequential roles of IL-2 and IFN-gamma in the killer cell function, the cells were stimulated with IFN-gamma after washing of IL-2 or stimulated by IFN-gamma at various timing and duration without washing of IL-2. IL-2 was essential to induce the synergistic effect of IL-2 and IFN-gamma to cytotoxic activity. The similar augmentation of cytotoxic activity was observed by the addition of IFN-gamma at any incubation periods with IL-2, compared with stimulation with IL-2 or IFN-gamma alone. The phenotypes of the killer cells by stimulation with IL-2, IFN-gamma alone or IL-2 plus IFN-gamma were mainly CD2+, CD16+, indicating the activated natural killer cells.

Cytotoxicity, Immunologic↗
PubMed1991

[Nasobiliary drainage for spontaneous bile peritonitis due to cholangiocarcinoma].

We report a case of cholangiocarcinoma presented with bile peritonitis, in which endoscopic nasobiliary drainage (ENBD) as well as pleural and abdominal drainages improved the general condition leading to a radical operation. The case was a 79-year-old woman with the chief complaints of fever and right hypochondralgia due to pleural effusion and infected ascites contaminated with bile including E. coli. However gall-stones were not recognized in any biliary trees. US-guided drainage was performed into the pleural and abdominal cavities because of poor condition. After continuous drainages, peritonitis was improved, but hematoemesis and tarry stool appeared. Emergent endoscopy revealed a multiple gastric ulcer, and the bleeding was stopped by an injection of ethanol. ERCP findings revealed a cholangiocarcinoma in superior and middle portion of the bile duct obstructed nearly completely. After improvement in general condition by ENBD, cholecystectomy, resection of extrahepatic bile duct and subtotal gastrectomy were performed followed the reconstruction with Roux-en-Y method. Postoperative course was uneventful and the patient was discharged at the postoperative 35th day. Thus, the appropriate and opportune multiple biliary drainages can save a patient with cholangiocarcinoma in poor condition and lead to tolerate the operation even if he or she is suffering from severe bile peritonitis.

Adenoma, Bile Duct↗
PubMed1991

Beneficial effects of fructose-1,6-diphosphate infusion on liver regeneration after ischemic liver injury.

The effect of fructose-1,6-diphosphate (FDP) on cellular viability after partial hepatectomy in partial ischemic liver was investigated in rats. The administration of FDP did not increase blood flow in the hepatic tissue; however, it significantly suppressed the elevation of serum liver functions for 24 hours after partial hepatectomy. Levels of DNA synthesis, protein synthesis, and labeling index were significantly higher in the groups administered divided doses of FDP before and after partial hepatic ischemia than in the control group (P less than 0.01). Thus, these findings indicate that FDP has cytoprotective and hepatotrophic effects on liver with ischemic injury and that divided dose administration of FDP is more effective than bolus doses in decreasing damage following ischemic and reperfusion injury.

Animals↗
PubMed1991

Endoscopic microwave coagulation therapy for villous adenoma of the duodenum--a case report.

The effects of endoscopic microwave coagulation therapy on duodenal adenoma in a 58-year-old man are reported. The patient had a 35-mm sessile tubulo-villous adenoma in the duodenal bulb. Endoscopic polypectomy followed by microwave coagulation therapy for duodenal adenoma was performed to avoid a major surgical procedure which would disturb the physiological functions of the gastrointestinal tract. After partial polypectomy which included the core of the adenoma, the entire remaining adenoma was destroyed after three microwave therapy sessions. During a follow-up period of 14 months, neither endoscopic nor histologic evidence of recurrence has been noted. Endoscopic microwave coagulation therapy is considered to be useful in the treatment of large sessile duodenal villous adenoma, provided that repeated endoscopic follow-up surveillance is also performed.

Adenoma↗