Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 631 records · Page 35Linked to original sources

PubMed1997

Prognosis and clinical features of intractable epilepsy: a prospective study.

Of the epileptic patients who were treated for > or = 5 years until the end of 1990 and had more than four seizures in 1990, 63 patients had been treated without interruption until the end of 1995. We analyzed their clinical courses from 1990 to 1995 prospectively. More than half the subjects were diagnosed with temporal lobe epilepsy. Twenty cases had presumed etiology, and 32 had neuropsychiatric complications. Of the subjects whose seizures were not controlled with conventional antiepileptic drugs (AED), 11 cases demonstrated significant improvement when new AED; that is, lamotrigine, vigabatrin, clobazam, topiramate, tiagabine or CGP33101 were added. However, 10 patients did not respond to new AED. Presumed etiology, neuropsychiatric complications, multiple epileptic foci in EEG and abnormalities on head CT or MRI were characteristics of the patients whose seizures were resistant to new AED.

Adult↗

PubMed1997

Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation.

A rare case of carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation occurring in the gastric remnant is reported. A 69-year-old Japanese man who had undergone a partial gastrectomy for a duodenal ulcer 30 years earlier, presented with anemia, epigastralgia, and an abdominal mass. The diagnosis of gastric carcinosarcoma was made based on the findings of endoscopic biopsies. The patient was thus scheduled to undergo a surgical operation, but he died of respiratory failure. At autopsy, a huge polypoid tumor measuring 20 x 18 x 8 cm was located on the greater curvature of the gastric remnant. Microscopically, the tumor consisted of intimately mixed tubular adenocarcinoma and heterologous mesenchymal elements containing rhabdomyosarcoma and osteosarcoma. Between these components, a morphological transition from the adenocarcinoma element to the sarcomatous element was observed. Ultrastructually, rhabdomyoblastic differentiation was confirmed in the sarcomatous areas. Immunocytochemical expressions of epithelial markers including epithelial membrane antigen and cytokeratins (35bH11 and 34bE12) were recognized not only in the carcinomatous cells but also in the sarcomatous cells. These findings suggest that carcinomatous cells appear to transform into cells with sarcomatous features.

Aged↗

PubMed1997

Effects of 17beta-estradiol and progesterone on the adhesion of human monocytic THP-1 cells to human female endothelial cells exposed to minimally oxidized LDL.

It is known that hormone replacement therapy inhibits the progression of atherosclerosis in postmenopausal women. Focal attachment of monocytes to endothelial cells is observed in early atherosclerotic lesions. The aim of this study was to investigate the effects of 17beta-estradiol (E2) and progesterone on the adhesion of human monocytic THP-1 cells to human female aortic endothelial cells (HAECs) in vitro. Minimally oxidized low-density lipoprotein (LDL) significantly increased THP-1 cell adhesion to HAECs as compared with native LDL at the same concentration. Though E2 inhibited minimally oxidized LDL-induced THP-1 cell adhesion in a dose-dependent manner, progesterone had no significant effects. Preincubation of HAECs with tamoxifen significantly antagonized the inhibitory effect of E2. These findings suggest a beneficial effect of hormone replacement therapy on atherosclerosis.

Adult↗

PubMed1997

Clinical responses and platinum concentrations in tumors after intra-arterial and intravenous administration of cisplatin in the same patients with cervical cancer.

We evaluated 3 patients with advanced cervical cancer treated with cisplatin intra-arterially and intravenously. The dose of cisplatin was 50 mg/m2 in each infusion. Chemotherapy was repeated at 4-week intervals for three to four courses. The clinical response and the tumor concentration of platinum were evaluated in each course. All patients who received the intra-arterial infusion of cisplatin were judged to be responders, whereas none of them responded to the intravenous infusion. The platinum concentration in tumor tissue was significantly higher after intra-arterial infusion of cisplatin (1.97 +/- 0.04 vs. 2.86 +/- 0.10 microg/g). Although there were no apparent differences in side effects between intra-arterial and intravenous routes, 2 of 3 patients rejected an intra-arterial route. The present study suggests that intra-arterial administration of cisplatin may be useful in treating locally advanced cervical cancer.

Adult↗

PubMed1997

Combination effect of granisetron and methylprednisolone for preventing emesis induced by cytotoxic agents.

To evaluate the combined effect of granisetron and methylprednisolone against acute emesis induced by cytotoxic agents, we investigated the clinical response and the urinary excretion of 5-HIAA in 85 patients with ovarian cancer who received the same anticancer chemotherapeutic regimen in a prospective randomized trial. Each patient received one of three different regimens (granisetron alone, methylprednisolone plus granisetron, and metoclopramide alone). The combination therapy of granisetron and methylprednisolone is effective for preventing acute emesis induced by cytotoxic chemotherapy.

Adult↗

PubMed1997

Structural changes in oxidative modification of low-density lipoprotein: investigation using lipid peroxidation products, surface charge, and spectrophotometric patterns.

It is well recognized that oxidative modification of low-density lipoprotein (LDL) accelerates atherogenesis of the arterial vascular wall. In this study, we examined the relationship between various methods of measuring the extent of oxidation, namely lipid peroxidation products, surface charge, and spectrophotometric patterns. LDL was isolated from fresh human normal plasma by centrifugation and was oxidized by incubating with copper ions. Apolipoprotein B was isolated from the LDL solution. We also prepared artificial lipid particles composed of cholesterol linolenate, triolein, and phosphatidylcholine. Our results suggest that lipid peroxidation begins drastically in 30-60 min, while the abolition of the positive charge on apoliproproteins is accelerated after 60 min. We found a characteristic change in the spectrophotometric pattern during the process and conclude that the spectrophotometric absorption ration at 232 and 203 nm is a useful measure of in vitro oxidation of LDL.

Electrophoresis, Polyacrylamide Gel↗

PubMed1997

Studies on aromatase inhibitors. IV. Synthesis and biological evaluation of N,N-disubstituted-5-aminopyrimidine derivatives.

In order to study the potency of the 5-aminopyrimidine skeleton as an aromatase inhibitor, we synthesized various N,N-disubstituted-5-aminopyrimidine derivatives and evaluated their aromatase-inhibitory activity (in vitro) and their inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). Compounds with the fluoro-substituted benzyl group showed potent aromatase inhibition. Among them, 5-[(4-cyanophenyl)(3,5-difluorobenzyl)amino]pyrimidine (5w, YM553) was a highly potent compound with an IC50 value of 0.038 nM for aromatase from human placenta. Its inhibitory effect was approximately four times greater than that of YM511. In addition, YM553 was a weak inhibitor of other enzymes involved in steroid hormone synthesis. These results indicate that YM553, as well as YM511 (a 4-amino-4H-1,2,4-triazole derivative), is a promising agent for the treatment of estrogen-dependent diseases.

Animals↗

PubMed1997

Studies on aromatase inhibitors. II. Synthesis and biological evaluation of 1-amino-1H-1,2,4-triazole derivatives.

1-N,N-Disubstituted amino-1-H-1,2,4-triazole derivatives were prepared and evaluated for aromatase-inhibitory activity (in vitro) and for the inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). 1-N-para-Substituted benzylamino derivatives, having an electron-withdrawing group on the phenyl moiety, exhibited aromatase-inhibitory activity in vitro and in vivo. Among them, 1-[(4-nitrobenzyl)(4-nitrophenyl) amino]-1H,1,2,4-triazole (5b) was the most potent aromatase inhibitor. These 1-N-benzylamino derivatives also showed relatively strong inhibitory activity on aldosterone synthesis, indicating that the selectivity of these derivatives for aromatase inhibition was not sufficient in comparison with that of the 4-amino-4H-1,2,4-triazole derivatives.

Aldosterone↗

PubMed1997

Studies on aromatase inhibitors. III. Synthesis and biological evaluation of [(4-bromobenzyl)(4-cyanophenyl)amino]azoles and their azine analogs.

A series of [(4-bromobenzyl)(4-cyanophenyl)amino]azoles and their azine analogs, which have the side chain of the selective aromatase inhibitor YM511, were synthesized and evaluated for aromatase-inhibitory activity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis inhibitory activity (in vivo). Among these aza-heterocycles, the pyrimidin-5-yl derivative (6a) was the most potent aromatase inhibitor and its in vitro inhibitory activity was comparable to that of YM511. Compound 6a also showed weak inhibitory activity on aldosterone synthesis. These data indicated that the pyrimidin-5-yl moiety is useful as a new azole fragment in place of the 4H-1,2,4-triazol-4-yl moiety of the aromatase inhibitor YM511.

Aldosterone↗

PubMed1997

[Structure and metabolic fate of N-nitrosodialkylamines in relation to their organotropic carcinogenicity with special reference to induction of urinary bladder tumors].

The metabolic fates of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N,N-dibutylnitrosamine (DBN) were investigated in the rat and other animal species, to elucidate a possible relationship between metabolism and organotropic carcinogenicity to the urinary bladder of these N-nitrosamines. The principal urinary metabolite of BBN as well as of DBN in the rat was N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), which was demonstrated to be the active form of these compounds as bladder carcinogen. The species difference in response to BBN or DBN is discussed on the basis of the urinary excretion rate of BCPN. Metabolism in vivo and carcinogenicity of a number of BBN analogues were investigated in the rat and a general scheme for biotransformation of N-alkyl-N-(omega-hydroxyalkyl)nitrosamines is given. A possible correlation of structure and metabolism with organotropic carcinogenicity of BBN analogues is discussed, with special reference to selective induction of urinary bladder tumors.

Animals↗

PubMed1997

Influences of ovariectomy and continuous replacement of 17beta-estradiol on the tail skin temperature and behavior in the forced swimming test in rats.

The effect of ovariectomy and continuous subcutaneous replacement of 17beta-estradiol was examined in female Wistar rats. Tail skin temperature significantly increased in ovariectomized rats 6 days after ovariectomy, and the elevated level was sustained until 21 days after ovariectomy. 17beta-Estradiol at doses of 0.3 and 1.0 microg/body/day suppressed the increases in tail skin temperature. In the forced swimming test, the ovariectomized control rats showed significantly prolonged immobility time in comparison with sham-ovariectomized rats 14 days after ovariectomy. The duration of immobility of ovariectomized rats treated with 17beta-estradiol (0.3, 1.0, 3.0 microg/body/day) or maprotiline (0.6 mg/body/day) was significantly shorter than that of ovariectomized control rats.

Animals↗

PubMed1997

In vivo replication of porcine reproductive and respiratory syndrome virus in swine alveolar macrophages and change in the cell population in bronchoalveolar lavage fluid after infection.

Replication of porcine reproductive and respiratory syndrome (PRRS) virus in swine alveolar macrophages (AM) and cell population in broncho-alveolar lavage fluid (BALF) obtained from PRRS virus-infected pigs were investigated. BALF samples were periodically collected from 6 pigs infected with PRRS virus and 3 non-inoculated control pigs by means of fiber-optic bronchoscope between post-inoculation day (PID) 0 and 56. The mean ratio of macrophages in BALF collected from infected group was 92.7 +/- 3.2% before inoculation and gradually decreased from PID 14. On the other hand, the ratio of lymphocytes was 4.8 +/- 3.2% before inoculation and increased from PID 21 and indicated 41.8 +/- 9.1% on PID 28. After that, they decreased gradually and that of macrophages correspondingly increased. The ratio of neutrophils maintained between 0.7% and 5.1%. The ratios of macrophages, lymphocytes and neutrophils collected from control group were almost stable through the examination. Intracellular PRRS virus antigens in AM were detected from PID 2 by indirect immunofluorescence assay (IIFA). PRRS virus was first isolated from BALF samples collected from inoculated group between PID 2 and 49. From serum, virus was isolated between PID 2 and 21. Antibodies in sera measured by IIFA to PRRS virus were first detected on PID 14 and the antibody titer rose to 1:640 or 1:1,280. The results suggested that PRRS virus replicates in swine AM for a relatively long period.

Animals↗

PubMed1997

Effect of Bordetella bronchiseptica and serotype D Pasteurella multocida bacterin-toxoid on the occurrence of atrophic rhinitis after experimental infection with B. bronchiseptica and toxigenic type AP. multocida.

In efficacy tests, 7 primary specific-pathogen-free piglets vaccinated with the Bordetella bronchiseptica and type D Pasteurella multocida bacterin-toxoid were challenged with B. bronchiseptica and type A P. multocida. Severe or moderate nasal turbinate atrophy was produced in the non-vaccinated pigs, whereas, only one of the 4 pigs in the vaccinated group had slight turbinate atrophy. Other immune sera against crude toxin of P. multocida type A or D were cross neutralized. The results of the present study show that the P. multocida serotype D bacterin-toxoid is effective against atrophic rhinitis caused by toxigenic P. multocida serotype A as well as toxigenic P. multocida serotype D.

Animals↗

PubMed1997

Glycation and inactivation of aspartate aminotransferase in diabetic rat tissues.

Glycated cytosolic aspartate aminotransferase was detected in the liver and kidney of streptozotocin diabetic rats using a boronate affinity column for adjacent cis-hydroxyl groups and an immunoblotting technique. The enzymatic activity and amount of immunoreactive substance were determined in the liver, kidney, and erythrocytes of diabetic and control rats. The ratio of enzymatic activity to the amount of enzyme was lower in diabetic rat tissue than in that in the control rats. It has been suggested that there is an inactive aspartate aminotransferase molecule in the tissues of diabetic rats. We therefore suggest that the cytosolic aspartate aminotransferase was inactivated in the diabetic rat tissues by a glycation reaction, accompanied by an impairment in glucose utilization.

Alkaline Phosphatase↗

PubMed1997

Development of basophils in Mongolian gerbils: formation of basophilic cell clusters in the bone marrow after Nippostrongylus brasiliensis infection.

Development of basophilic leukocytes was studied in the Mongolian gerbil, Meriones unguiculatus, after infection with the nematode Nippostrongylus brasiliensis. After infection, peripheral blood basophilia developed and peaked at 2 weeks. In bone marrow sections, numbers of alcian blue+/safranine- basophilic cells were increased. These cells did not bind berberine sulfate and were clearly distinguishable from the bone marrow-resident mast cells, safranine+ and berberine sulfate+. Alcian blue+/safranine- cells were identified by electron microscopy as basophilic myelocytes in various stages of maturation. In the early period of infection, these cells had round-to-oval granules with a homogenous electron-dense matrix, a well-developed Golgi apparatus and rough endoplasmic reticulum, and a nonsegmented nucleus. By enzyme cytochemical analysis, intense peroxidase activity was demonstrated in all of the specific granules as well as in the rough endoplasmic reticulum and Golgi apparatus. Two weeks after infection, the number of bone marrow basophilic cells further increased, forming distinct clusters or islands composed of up to 100 cells each. On electron micrographs, the basophilic cells in these clusters appeared to be late-stage basophilic myelocytes, ie, having an increased number of granules, a less-conspicuous Golgi apparatus and rough endoplasmic reticulum, a horseshoe-shaped-to-lobulated nucleus, and reduced peroxidase activity. Eosinophils and mast cells were rarely found in the basophilic cell clusters. Four weeks after infection, the clusters had disappeared. These results show that gerbil basophilic myelocytes tend to form cell clusters in the bone marrow during their active proliferation. The comparative paucity of other cell lineages in basophilic cell clusters suggests that basophilia is generated from differentiation/proliferation of precommitted basophil progenitors independently from cells of other lineages.

Alcian Blue↗

PubMed1997

Effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid on ischemic brain damage induced by four-vessel occlusion in rats.

The effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was evaluated in a rat four-vessel occlusion model and compared to the effect of another NMDA antagonist (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intravenously immediately following occlusion. At 72 h after the ischemia, latency in the passive avoidance test was significantly shorter in ischemic control rats in comparison with sham-operated rats. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly lengthened the latency. At 2 weeks after ischemia, ischemic control rats showed no differences in latency compared to sham-operated rats. The number of survived neurons of control rats was significantly less than that of sham-operated rats at 72 h and 2 weeks after ischemia. CGP 40116 at the doses of 3 and 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly increased the number of survived neurons. Adenosine triphosphate (ATP) level in striatum of control rats was significantly lower than that of sham-operated rats at 24 h after ischemia when an acquisition trial was performed in the passive avoidance test. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg ameliorated the decrease. These results suggest that CGP 40116 might have an ameliorative effect on the memory deficits in the passive avoidance test after ischemic injuries through the suppression of changes in brain energy metabolism.

2-Amino-5-phosphonovalerate↗

PubMed1997

[Recent advance in laparoscopic-assisted colectomy for colon cancer].

Laparoscopic-assisted colectomy for colon cancer has been tried in these 5-6 years in Western countries. In Japan, this procedure has been used since about three years ago. In this country, the indication for laparoscopic-assisted colectomy has been either colonic adenomas or carcinomas in early stage which are not suitable for colonoscopic removal. The application of this procedure to more advanced carcinomas with invasion in the muscularis propria or invasion penetrating the muscularis propria is controversial. This is because of the technical difficulties involved in the lymph node dissection which is usual procedure for these invasive carcinomas in the usual laparotomy operation. We have carried out laparoscopic-assisted colectomy and lymph node dissection for colorectal carcinomas with invasion in the submucosa or deeper. In this study, we present the technical aspect of lymph node dissection in the laparoscopic procedure, and discuss the indication and technical problems in this procedure.

Adenocarcinoma↗

PubMed1997

Activation of the erythropoietin promoter by a point mutation from GATA to TATA in the -30 region.

We show here a role of the highly conserved GATA motif in the -30 region of the erythropoietin (Epo) promoter. Epo production is reduced in normoxia and activated in hypoxia to control the oxygen supply through erythropoiesis. Although the hypoxic inducibility has been analyzed, the molecular mechanism for the low basal activity in normoxia remained unclear. The GATA motif in the -30 region upstream of the transcription initiation site is highly conserved among the species. In many genes, the consensus motif in the -30 region is TATA. The GATA motif of the Epo promoter was mutated to TATA. The transcriptional activity of the mutant was enhanced even in normoxia. Binding assays showed that TATA-binding protein (TBP) could weakly bind to the wild-type GATA motif whereas TBP bound to the mutant TATA motif with high affinity. These results indicate that the highly conserved GATA motif in the -30 region of the Epo promoter can avoid binding and activation by TBP. This evidence is considered to be the molecular basis for the low physiological expression from the Epo promoter in normoxia.

Animals↗