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Biomedical subjects

M Oka

Publications and source records attributed to M Oka.

At least 181 records · Page 10Linked to original sources
PubMed1999

Synthesis and muscarinic activity of novel aniline derivatives with a 1-azabicyclo[3.3.0]octane moiety.

In order to develop drugs effective against Alzheimer's disease, we synthesized a series of aniline derivatives having a characteristic cyclic amine, 1-azabicyclo[3.3.0]octane ring, and evaluated their binding affinity for the central muscarinic cholinergic receptor. Among these compounds which showed high affinity to the M1 receptor, N-[2-(1-Azabicyclo[3.3.0]octan-5-yl)ethyl]-2-nitroaniline (9f fumarate, SK-946) showed the highest affinity. The ability of this compound to improve cognitive function was assessed using the passive avoidance test in scopolamine-induced dementia mice. Some anilines with a 1-azabicyclo[3.3.1]nonane ring were also synthesized by the ring expansion of the 1-azabicyclo[3.3.0]octane ring, and showed a high affinity for the central muscarinic cholinergic receptor.

Aniline Compounds↗
PubMed1999

Natural antioxidant, chlorogenic acid, protects against DNA breakage caused by monochloramine.

Chlorogenic acid prevented a stepwise conversion of plasmid pUC18 DNA, from I-->form II-->form III, induced by 3 mM monochloramine with a half inhibition of 67.4 microM. Chlorogenic acid reacted with monochloramine in a time-dependent manner, and the reaction rate increased with decreasing pH. These results suggest that chlorogenic acid prevents genotoxicity of monochloramine in gastric mucosa.

Ammonium Chloride↗
PubMed1999

Bronchoscopic therapy for mucosa-associated lymphoid tissue lymphoma of the trachea.

The tracheal tumor of a 74-year-old female was detected on bronchoscopy and histologically diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma. We successfully treated the tumor with endoscopic neodyminum-yttruim-aluminium-garnet (Nd-YAG) laser photoresection followed by local ethanol injection. This is the first case in which tracheal MALT lymphoma was successfully treated with bronchoscopy. Bronchoscopic therapy seems to be one of the most valuable strategies for treatment of MALT lymphomas of the central airway.

Aged↗
PubMed1999

Vasospastic angina likely related to cisplatin-containing chemotherapy and thoracic irradiation for lung cancer.

Vasospastic angina is rarely observed during cancer treatment. The present report describes two males with lung cancer, aged 73 and 61, who developed vasospastic angina during combination treatment of cisplatin-containing chemotherapy and thoracic irradiation. As both patients have smoked and their ages are typical for patients with coronary artery disease, such events may be incidental. However, oncologists should be aware of the possible development of myocardial ischemia during or following administration of antineoplastic agents, especially in elderly patients with pre-existing coronary risk factors or a history of thoracic radiotherapy.

Adenocarcinoma↗
PubMed1999

Repair of osteochondral defects with autogenous callo-osseous grafts.

A new method of biological repair of osteochondral defects is presented. An osteochondral defect in the rabbit knee was reconstructed with an autogenous callo-osseous graft made of a superficial sheet of medullary fracture callus attached to a base of cancellous bone. The reparative tissues were evaluated for 24 weeks by histology, analysis of uronic acid contents, and immunohistochemical staining of collagen constituents. The callo-osseous graft provided significantly faster and better repair of the articular surface than an untreated defect or a callo-osseous graft in which the cells had been devitalized by irradiation prior to transplantation. The results indicate that the callo-osseous graft contributes to the repair process via providing both favorable extracellular matrices and pluripotential mesenchymal cells.

Animals↗
PubMed1999

Possible involvement of proteolytic degradation of tyrosinase in the regulatory effect of fatty acids on melanogenesis.

The purpose of this study was to investigate the mechanism of fatty acid-induced regulation of melanogenesis. An apparent regulatory effect on melanogenesis was observed when cultured B16F10 melanoma cells were incubated with fatty acids, i.e., linoleic acid (unsaturated, C18:2) decreased melanin synthesis while palmitic acid (saturated, C16:0) increased it. However, mRNA levels of the melanogenic enzymes, tyrosinase, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2), were not altered. Regarding protein levels of these enzymes, the amount of tyrosinase was decreased by linoleic acid and increased by palmitic acid, whereas the amounts of TRP1 and TRP2 did not change after incubation with fatty acids. Pulse-chase assay by [35S]methionine metabolic labeling revealed that neither linoleic acid nor palmitic acid altered the synthesis of tyrosinase. Further, it was shown that linoleic acid accelerated, while palmitic acid decelerated, the proteolytic degradation of tyrosinase. These results suggest that modification of proteolytic degradation of tyrosinase is involved in regulatory effects of fatty acids on melanogenesis in cultured melanoma cells.

Animals↗
PubMed1999

[A rare case of lung adenocarcinoma in cavity wall of pulmonary aspergilloma].

A 67-year-old man was admitted with the complaint of hemosputum. Chest X-ray films resulted in a diagnosis of pulmonary aspergilloma, and treatment with intravenous amphotericin B was initiated. However, therapy was discontinued due to renal insufficiency, an adverse effect of amphotericin B. The size of the fungus ball and cavity increased despite treatment with oral itraconazole (200 mg/day). Cavernostomy was performed and the fungus ball was removed from the upper lobe of the left lung. Computed tomographic scans disclosed thickening of the remaining wall of the cavity, with destruction of the ribs. The patient experienced worsening respiratory distress and died. Necropsy revealed adenocarcinoma of the left lung.

Adenocarcinoma↗
PubMed1999

[Study of continuous arterial infusion chemotherapy with low-dose cisplatin and 5-fluorouracil for patients with hepatocellular carcinoma].

Seven patients with postoperative recurrence of hepatocellular carcinoma (HCC) and four patients who underwent absolute non curative resection for HCC were treated with continuous arterial infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (250 mg/body/day). This infusion chemotherapy was continued for five days and discontinued for two days, repeated over four weeks as one course. The response rate in patients with postoperative recurrence was 42.9%, while that in patients who underwent reduction surgery for multiple HCC was 75%. Continuous arterial infusion of low-dose CDDP/5-FU may be effective in patients with multiple small intrahepatic metastases.

Aged↗
PubMed1999

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel].

Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.

Adenocarcinoma, Scirrhous↗
PubMed1999

Depressed cytotoxic activity of hepatic nonparenchymal cells in rats with obstructive jaundice.

BACKGROUND: The nonparenchymal cells (NPC) of the liver have strong cytotoxic activity. Our hypothesis is that their activity may be imparted by obstructive jaundice and show recovery after biliary drainage. METHODS: In Donryu rats, we performed either a sham operation (group C; n = 5), production of irreversible obstructive jaundice (group J; n = 5), or production of reversible obstructive jaundice for 7 days, with biliary drainage then provided for 3 days (group Ds; n = 5) or for 14 days (group Dl; n = 5). Natural killer (NK)-cell activities shown against YAC-1 lymphoma cells of hepatic NPC and peripheral blood mononuclear cells were assessed. We then measured the growth of experimental liver metastases 13 days after inoculation of a tumor cell line (AH130) into the portal vein of rats that had undergone similar biliary manipulations (group mC, group mJ, group mDs, and group mDl; n = 5 in each group). RESULTS: The highest number of NK activities by NPC in group J (11.5%) and group Ds (37.7%) were significantly lower than those in group C (68.8%) and group Dl (90.5%; effector/target ratios, 40:1; P < .01). NK activity of peripheral blood mononuclear cells was similar among groups. Metastatic liver tumors in group mJ (10.2% +/- 2.6%) and group mDs (5.4% +/- 1.5%) were significantly larger than in group mC (0.4% +/- 0.1%) and group mDl (0.5% +/- 0.3%; P < .02). CONCLUSIONS: Obstructive jaundice depressed the NK activity of hepatic NPC and enhanced the growth of liver metastases. To counter this depression, adequate biliary drainage was required. These results suggest that preoperative biliary drainage to relieve obstructive jaundice might help to prevent liver metastases after surgery for biliary tract or pancreatic tumors.

Animals↗
PubMed1999

Phase I study of irinotecan combined with carboplatin in previously untreated solid cancers.

Irinotecan (CPT-11) and carboplatin have broad anti-tumor activities. We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer. The aim of the study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this regimen. In addition, we prospectively evaluated the Chatelut formula for predicting carboplatin clearance. Patients with advanced cancer were treated with CPT-11 (days 1, 8, and 15) and carboplatin (day 1) of a fixed-target area under the concentration-time curve (AUC) of 5 mg x min/ml. Carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The CPT-11 dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2. A total of 27 patients, 26 lung cancer patients and 1 colon cancer patient, were enrolled in this study. Dose-limiting leukoneutropenia, thrombocytopenia, and diarrhea, including one treatment-related death, were observed at 60 mg/m2 CPT-11, indicating that this level was the MTD. In 11 patients, the actual AUCs of carboplatin almost achieved the target AUC of 5. Fifteen (60%) of 25 evaluable patients showed an objective response, with an 85% response rate [11 of 13 patients (complete response, 31%; partial response, 54%)] in small cell lung cancers and a 36% response rate (4 of 11 patients) in non-small cell lung cancers. Neutropenia, thrombocytopenia, and diarrhea were the dose-limiting toxicities in this regimen. CPT-11 (50 mg/m2) under the carboplatin target AUC of 5 using the Chatelut formula was the recommended dose for further Phase II study, and this regimen seems to be active for small cell lung cancer.

Adult↗
PubMed1999

Treatment of cholecystoduodenal fistula by laparoscopy.

We describe a patient with cholecystoduodenal fistula treated by a laparoscopic approach. Use of a flexible videoscope, flexible retractor, and endoscopic transecting stapler allows for laparoscopic treatment of cholecystoenteric fistulae.

Biliary Fistula↗
PubMed1999

Laparoscopic distal pancreatectomy with preservation of the spleen.

We describe a case of chronic pancreatitis treated by laparoscopic distal pancreatectomy with conservation of the spleen involving the resection of the splenic vessels. A proximal ligation of the splenic artery and vein was performed, followed by transection of the body of the pancreas. Retroperitoneum was dissected to the left by mobilizing the stump of the transected pancreas. The entire distal pancreas was freed posteriorly. The distal splenic artery and vein were ligated and divided individually adjacent to the tail of the pancreas at the hilum of the spleen. The points of this operation were to ligate the splenic artery and vein at both sides of the resected pancreas and to save the spleen with the blood supply continuing through the short gastric vessels and the splenocolic ligament. This operation with splenic preservation is more suitable for a patient who is a candidate for laparoscopic distal pancreatectomy, which will minimize the operation time, preserve the useful immunologic role of the spleen, and obtain the intact resected specimen. Furthermore, this procedure is useful in chronic pancreatitis patients because it avoids the difficult dissection of the posterior pancreas off of the splenic vessels.

Aged↗
PubMed1998

Hepatocyte growth factor activator: a possible regulator of morphogenesis during fetal development of the rat gastrointestinal tract.

The role played by the hepatocyte growth factor activator (HGFA) during morphogenesis of the gastrointestinal tract was investigated in fetal rats between days 16 and 21 of gestation. By our recently established method using chelation and dissecting microscope, samples could be separated into epithelium and mesenchyme, essentially without cross-contamination. The expression of the gene for HGFA together with those for hepatocyte growth factor (HGF) and its receptor, c-met, was investigated in each tissue element by RT-PCR. In the fetal rat gastrointestinal tract, mRNA signals for the HGFA gene were observed only in epithelia expressing c-met mRNA. In contrast, expression of HGF mRNA was limited to the mesenchymal elements, indicating the presence of a local HGF system in the gastrointestinal tract; an inactive form of HGF (proHGF) is secreted from the mesenchyme and then cleaved into the active form by HGFA secreted by the target epithelia. During the period of morphogenesis and histodifferentiation in the gastrointestinal tract, enhanced expression of the genes for HGF and its receptor/c-met was evident, with elevated HGFA mRNA level observed throughout the gastrointestinal tract except in the forestomach, where mRNA expression was barely detectable. These results strongly suggest the possibility that morphogenesis of the gastrointestinal tract is regulated not only by a local increase in production of HGF, but also by enhanced proteolytic activation of proHGF. Thus, it is probable that locally synthesized HGFA plays a significant role as a regulator of the morphogenic action of HGF during gastrointestinal tract development.

Animals↗
PubMed1998

Slowly progressive L-DOPA nonresponsive pure akinesia due to nigropallidal degeneration: a clinicopathological case study.

We report an autopsy case of a 51-year old man who showed slowly progressive pure akinesia: freezing phenomenon and festination during 21 years of illness without tremor, rigidity, upward gaze palsy, bradykinesia and dementia, which were not responded to L-DOPA clinically. Neuropathological findings revealed the circumscribed regions in the substantia nigra and middle portion of the internal globus pallidus (GPi), without neurofibrillary tangles, neuropil threads, and glial fibrillary tangles. So this case was clearly distinguished with progressive nuclear palsy and pallidonigroluisian atrophy. It was first reported to describe that L-DOPA nonresponsive pure akinesia can arise from nigopallidal atrophy.

Disease Progression↗
PubMed1998

Loss of Hsp70-Hsp40 chaperone activity causes abnormal nuclear distribution and aberrant microtubule formation in M-phase of Saccharomyces cerevisiae.

The 70-kDa heat shock proteins, hsp70, are highly conserved among both prokaryotes and eukaryotes, and function as chaperones in diverse cellular processes. To elucidate the function of the yeast cytosolic hsp70 Ssa1p in vivo, we characterized a Saccharomyces cerevisiae ssa1 temperature-sensitive mutant (ssa1-134). After shifting to the restrictive temperature (37 degreesC), ssa1-134 mutant cells showed abnormal distribution of nuclei and accumulated as large-budded cells with a 2 N DNA content. We observed more prominent mutant phenotypes using nocodazole-synchronized cells: when cells were incubated at the restrictive temperature following nocodazole treatment, viability was rapidly lost and abnormal arrays of bent microtubules were formed. Chemical cross-linking and immunoprecipitation analyses revealed that the interaction of mutant Ssa1p with Ydj1p (cytosolic DnaJ homologue in yeast) was much weaker compared with wild-type Ssa1p. These results suggest that Ssa1p and Ydj1p chaperone activities play important roles in the regulation of microtubule formation in M phase. In support of this idea, a ydj1 null mutant at the restrictive temperature was found to exhibit more prominent phenotypes than ssa1-134. Furthermore, both ssa1-134 and ydj1 null mutant cells exhibited greater sensitivity to anti-microtubule drugs. Finally, the observation that SSA1 and YDJ1 interact genetically with a gamma-tubulin, TUB4, supports the idea that they play a role in the regulation of microtubule formation.

Adenosine Triphosphatases↗
PubMed1998

A leukotriene receptor antagonist, ONO-1078, modulates drug sensitivity and leukotriene C4 efflux in lung cancer cells expressing multidrug resistance protein.

ONO-1078 is a new class of peptide leukotriene receptor antagonist, and multidrug resistance protein (MRP) is a membrane tranporter of multiple anticancer drugs and endogenous leukotriene C4 (LTC4). We investigated the effects of ONO-1078 on drug sensitivity and LTC4-efflux in MRP-expressing lung cancer cells. Drug sensitivity, intracellular vincristine accumulation, and intracellular and extracellular LTC4 concentrations were measured with or without ONO-1078. The effect of ONO-1078 on MRP-mediated calcein-efflux was determined by flow cytometry. ONO-1078 (1 to 10 microM) dose-dependently enhanced the sensitivity of NCI-H520 cells to vincristine with the reduced accumulation, and also enhanced the sensitivity to doxorubicin and etoposide. ONO-1078 inhibited both LTC4- and calcein-efflux from the cells with increased intracellular accumulations. Our findings indicate that ONO-1078 modulates multidrug resistance and inhibits LTC4-efflux in lung cancer cells, by inhibition of MRP function.

ATP-Binding Cassette Transporters↗