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Biomedical subjects

M Oda

Publications and source records attributed to M Oda.

At least 289 records · Page 16Linked to original sources
PubMed1995

Neutrophilic eccrine hidradenitis: report of two cases.

BACKGROUND: Neutrophilic eccrine hidradenitis (NEH) is an uncommon, self-limited dermatosis usually attributed to anti-cancer chemotherapy. It is characterized histologically by necrosis of the eccrine gland and neutrophilic infiltrate. OBSERVATIONS: We saw NEH in a 5-year-old boy with acute lymphoblastic leukemia and a 4-year-old girl with acute monocytic leukemia. NEH developed after the anti-leukemic chemotherapy including high dose cytarabine. The eruption was composed of vesicles, papules, and plaques. CONCLUSIONS: Histological findings were compatible with those described in the literature. NEH in our two patients could be attributed to high doses of cytarabine.

Child, Preschool↗
PubMed1995

Effect of KBT-3022, a new diphenylthiazole derivative, on platelet functions.

The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.

Adenosine Diphosphate↗
PubMed1995

Thermally gelling poloxamine Synperonic T908 solution as a vehicle for rectal drug delivery.

Thermally reversible gels of the block copolymer, Synperonic T908, have been evaluated as vehicles for the rectal administration of indomethacin. Prolonged plasma levels of indomethacin following rectal administration in such gels was observed with the 40% w/w Synperonic T908 gels when compared with commercial suppositories. The release rate decreased with an increase in gel concentration over the range 30% to 40% w/w. Histological observation showed no damage to the rectal mucosal membrane in animals at 6 h after the administration of a 40% w/w gel.

Animals↗
PubMed1995

[Inhibitory effects of sepimostat mesilate (FUT-187) on the activities of trypsin-like serine proteases in vitro].

Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 microM for trypsin, 0.029 microM for pancreatic kallikrein, 0.61 microM for plasma kallikrein, 0.57 microM for plasmin, 2.5 microM for thrombin, 20.4 microM for factor Xa and 6.4 microM for C1r. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for C1s, and Ki values for these proteases were 0.021 and 0.18 microM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 microM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 microM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 microM, while camostat revealed no inhibition by concentrations up to 1 microM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 microM, respectively, the corresponding values for camostat being 350 and 150 microM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and C1s in complement pathway.

Animals↗
PubMed1995

[The uptake of nalidixic acid and enoxacin by rat renal cortical slices in rat].

The mechanisms involved in the renal excretion of quinolone and new quinolone antibacterial drugs are still incompletely understood. The purpose of this study was to examine the renal handling of nalidixic acid (NA) and enoxacin (ENX), using the renal cortical slices uptake techniques in rats. It was demonstrated that both NA and ENX were taken against a concentration gradient by a saturable processes resulting from the ratio of slice to medium (ratio of S/M) being dependent on the time and the concentration. It was indicated that the inhibition of uptake by 2,4-dinitrophenol, ouabain and sodium cyanate was shown to be an energy dependence. Probenecid and cimetidine exhibited that they might inhibit NA uptake slightly. ENX uptake was inhibited by probenecid, cimetidine, guanidine and disopyramide, suggesting that ENX might possess an affinity for both anionic and cationic transport mechanisms.

Animals↗
PubMed1995

Anti-thrombotic activity of KBT-3022 in experimental models of thrombosis.

In this study, we investigated the effects of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate) , a potent and long-lasting anti-platelet agent, in several experimental thrombosis models and compared them with those of other anti-platelet drugs. Oral administration of KBT-3022 prevented arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022, and ticlopidine hydrochloride (TP) showed no such effect in these models. In a guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus formation on a silk thread inserted into the shunt was dose-dependent and 300 and 30 times more potent than the inhibition obtained with ASA and indomethacin, respectively. In a model of aortic thrombosis induced by perivascular application of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had no effect. However, in a stasis-induced venous thrombosis model in guinea pigs, TP inhibited thrombus formation significantly, but KBT-3022 and ASA were ineffective. These results suggest that KBT-3022 may be a useful drug for the treatment and/or prophylaxis of thrombus formation in shunts and aortic thrombosis.

Animals↗
PubMed1995

Inhibitory effect of KBT-3022, a new anti-platelet agent, on infiltration of polymorphonuclear leukocytes induced by leukotriene B4 or formyl-methionyl-leucyl-phenylalanine in mice.

We devised a method for evaluating polymorphonuclear leukocyte (PMN) infiltration in vivo employing an air bleb technique combined with measurement of myeloperoxidase (MPO) activity, and the effects of some anti-platelet agents were evaluated. KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and cilostazol inhibited the increase in MPO activity in the connective tissue around the air bleb induced by leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine (fMLP). Indomethacin inhibited only the fMLP-induced increase in MPO activity, but ticlopidine hydrochloride and acetylsalicylic acid had no effect. Histologic observation confirmed the inhibition of PMN infiltration by KBT-3022. These results indicate that KBT-3022 may be a potent inhibitor of both LTB4- and fMLP-induced infiltration of PMNs.

Animals↗
PubMed1995

Protective effect of KBT-3022, a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia.

The protective effect of KBT-3022 (ethyl 2-[4,5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) , a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia was studied and compared with those of indomethacin and acetylsalicylic acid (ASA). Oral administration of KBT-3022 (3-100 mg/kg) and indomethacin (3 and 10 mg/kg) significantly prevented KCN-induced death in mice, while ASA (100 mg/kg) had no effect. KBT-3022 (3 and 10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) significantly prolonged the survival time of mice subjected to normobaric hypoxia, while ASA (100 mg/kg, p.o.) had no effect. KBT-3022 (3-30 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly ameliorated delayed neuronal death in the gerbil hippocampal CA1 sector after occlusion of bilateral carotid arteries for 5 min, while ASA (300 mg/kg, p.o.) had no effect. KBT-3022 (10 mg/kg, p.o.) significantly inhibited ATP depletion in the gerbil hippocampus after a 1-min occlusion of bilateral carotid arteries, but had no effect on ATP depletion after a 5-min occlusion and the recovery during recirculation. These results show that KBT-3022 exerts protective effects against cerebral anoxia and hypoxia and ameliorates delayed neuronal death in the hippocampus. KBT-3022 may therefore be useful for prophylaxis of ischemic cerebrovascular disorders.

Adenosine Triphosphate↗
PubMed1995

A case of acute lymphoblastic leukemia accompanied with the production of parathyroid hormone-related protein.

Hypercalcemia accompanied with malignant tumors is generally classified into two categories, namely with or without bone metastasis. As for the latter, bone resorption-stimulating factors produced by tumor cells, such as parathyroid hormone-related protein (PTHrP), show hormone-like effects and promote a bone resorption. Many cases have been reported regarding the production of TPTHrP in adult T cell leukemia (ATL), but few have been reported with acute lymphoblastic leukemia (ALL). We report here a similar case with ALL. A 12-year-old male presented with fever, petechiae and thrombocytopenia, and was diagnosed as ALL. We started the induction therapy and confirmed complete remission. Later, he relapsed 3 times without symptoms apart from hypercalcemia at the beginning. Elevation of the serum calcium level followed by a rise of lymphoblastic cells was recognized. Bone metastasis was excluded since bone mineral density and serum mid region PTH were normal and no abnormal findings were noticed on X rays and 99mTc bone scintigraphy. However, his urinary PTHrP level was high, and his lymphoblastic cells staining immunocytochemically with the monoclonal antibodies against the C-terminal region of PTHrP showed a positively brownish color. Finally, he died of pulmonary aspergillosis. Hypercalcemia was not related to serum PTH or bone metastasis. ATL viral infection reported as a cause of PTHrP production was also excluded from several experimental data. Therefore, we concluded that lymphoblastic cells directly produced PTHrP, and that this PTHrP played an important role in the induction of hypercalcemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

The effects of KBT-3022, a new anti-platelet agent, on hemorheological properties in guinea pigs.

Using guinea pigs, a study was conducted on the effects of KBT-3022, a new anti-platelet agent, on hemorheological properties in various tests including blood filterability, blood viscosity, shear stress-induced red blood cell (RBC) deformability and contents of ATP and 2,3-diphosphoglycerate (2,3-DPG). Oral administration of KBT-3022 at 1 and 10 mg/kg significantly increased blood filterability, and significantly reduced blood viscosity at 10 mg/kg without changing the hematocrit, plasma fibrinogen concentration or plasma viscosity. KBT-3022 (10 mg/kg, p.o.) improved RBC deformability in response to shear stress, which was evoked by passing the blood through a thin tube. This dose of KBT-3022 also increased the contents of ATP and 2,3-DPG in RBC. These findings indicate that KBT-3022 may reduce blood viscosity as a sequel to improvement of RBC deformability through direct action on RBC. The increase in the intracellular levels of ATP and 2,3-DPG was considered to be involved in this improvement of hemorheological properties. These hemorheological effects of KBT-3022 appear to be promising for the treatment of patients with ischemic vascular disease.

2,3-Diphosphoglycerate↗
PubMed1995

Uptake site of lansoprazole, a proton pump inhibitor, in human fundic mucosa: possible relevance with fibroblast and Helicobacter pylori.

To clarify the mechanism of the effect of lansoprazole in the healing of human gastric ulcer, the uptake sites of lansoprazole were studied using endoscopically biopsied specimens from the margin of the gastric ulcer. The specimens were incubated in a medium containing 3H-lansoprazole for 5 or 15 min., postfixed with 1% osmic acid and embedded in Epon. The semithin or ultrathin sections were made and radioautographic emulsion films were applied by the wire-loop method. 30 days after the incubation, the sections were developed, fixed and observed by light and electron microscopy. As a result, the uptake sites of lansoprazole were accumulated on the fibroblasts located near the tip portion of the gastric mucosa and on the unmyelinated nerve fibers as well as on the parietal cells. Some of the uptake sites were also observed near the plasma membrane of the bacteria in the gastric lumen. From these observations, lansoprazole uptake sites were not only on the parietal cells but on the fibroblasts and the bacteria, suggesting that the effect of lansoprazole was exerted partly through the influence on the mesenchymal cells and Helicobacter pylori-related organisms.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[Reoperation for recurrent and second primary lung cancer].

Thirty patients have undergone multiple resections for non-small cell lung cancer from 1973 to July 1994, constituting 2.6% of 1,153 who had undergone pulmonary resection for such tumor. In the 22 patients for recurrent cancer, 15 resections of the ipsilateral lung and 9 of the contralateral lung were performed with no operative death. The survival rate following second resection in 22 patients was 33.8% at 3 years and 13.5% at 5 years. Survival rate was poor in patients with DNA aneuploid primary tumor and there was not a patients of 5 years survival. Three out of the 5 patients which had a diploid pattern in the primary tumor, showed an aneuploid pattern in the recurrent tumor. Long survival patients were founded only in the patients which had a diploid primary tumor. In the 8 patients for second primary lung cancer, 4 resections of the ipsilateral lung and 4 of the contralateral lung were performed, including two bronchoplastic surgery for early hilar squamous cell carcinoma. The survival rate following second resection in 8 patients was 64.2% at 5 years with good result. We concluded that an aggressive surgical approach is safe and warranted in patients with second primary lung cancer.

Adenocarcinoma↗
PubMed1995

Increased immunoreactivity and concentration of basic fibroblast growth factor in lansoprazole-treated gastric mucosa.

The purpose of this study was to clarify the effect of lansoprazole on basic fibroblast growth factor (bFGF) during the healing of gastric ulcers in comparison with famotidine and rebamipide. Alteration of the localization and concentration of bFGF was examined in gastric mucosa obtained endoscopically from ulcer patients. The bFGF content was estimated by enzyme-linked immunosorbent assay and the localization of bFGF immunoreactivity was determined by indirect immunohistochemical study using monoclonal antibodies. In the lansoprazole-treated cases, the content and the histochemical immunoreactive area of bFGF significantly increased 4 weeks after the treatment, compared with the group treated with rebamipide and the control group. In the famotidine-treated group, the concentration of bFGF significantly increased, compared with the rebamipide-treated group, and not with control. The number of binding sites for [125I]bFGF, as determined by in vitro autoradiography, also significantly increased in the lansoprazole-treated group. Therefore, an increase in bFGF concentration and receptor distribution was shown to be brought about by treatment with lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Primary thymic carcinoma: a clinicopathological and immunohistochemical study.

During the treatment of five cases of thymic carcinoma, we conducted a clinicopathological and immunohistochemical study. The patients included four males and one female, whose ages ranged from 50 to 69 years. The histologic breakdown was squamous cell carcinoma in four and small cell carcinoma in one. Immunohistochemically, the squamous cell carcinomas were positive for cytokeratin (intermediate molecular weight) and keratin. However, staining was negative for Leu-7 and chromogranin. A complete resection was achieved in only one case. In all four of the remaining cases, the resection was incomplete due to invasion into adjacent organs and disseminated lesions. Thymic carcinoma is a tumor for which a higher response rate can be expected from multidisciplinary therapy than that for lung cancer. Therefore, it is desirable, from the clinical view, to determine clinical staging and to establish standard operative procedures comprising mediastinal lymph node dissection as well as effective chemotherapy. With respect to pathology, it is hoped that an improved histologic classification will be developed.

Carcinoma, Small Cell↗
PubMed1994

Contact granulomas of the larynx.

Ten cases of intubation granulomas and eight cases of contact granulomas not related to intubation were reviewed for the purpose of clinical analysis and pathological investigation. Granulomas were located primarily at the vocal process of the arytenoid cartilage. Additionally, 58 hemilarynges obtained from 37 cadavers with intubation granulomas were evaluated grossly and histopathologically. The intubation granulomas had no side predilections. All eight contact granulomas occurred in males and had a higher incidence of recurrence (three of eight cases) despite complete removal with laser surgery. In an attempt to explain recurrences of these contact granulomas, all three cases were studied clinically and pathologically. Results indicated that they recurred in singers and vocal abusers, and presumably resulted from the continued hammering of one vocal process against the other. Analysis also demonstrated that vocal rehabilitation was essential prior to or immediately after removal of the granuloma to prevent its recurrence. Pathological evaluation of the contact granulomas revealed focal ulceration and a covering of necrotic tissue with desquamating epithelium. The propria mucosa was edematous and infiltrated by chronic inflammatory cells and neutrophils forming focal granulation tissue in a stroma containing proliferated capillaries. Pathological features around local ulcerations were typical of a secondary granuloma while underlying arytenoid cartilage was partially necrotic.

Adult↗