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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 703 records · Page 39Linked to original sources
PubMed1996

Purification and characterization of a p13suc1-bound serine/threonine kinase that is expressed in mature rat brain.

We previously reported that the histone-H1 kinase activity bound to p13suc1 increased dramatically during development of the rat brain. In the present work, an in situ kinase assay in an SDS/polyacrylamide gel that contained substrate proteins was employed to characterize the enzyme. Two major proteins of 45 kDa and 100 kDa were found to have p13suc1-bound histone-H1 kinase activity. The former (p45) exhibited strong activity towards histone H1 and had weak autophosphorylation activity, whereas the latter (p100) acted on myelin basic protein or histone H1, and underwent autophosphorylation. p45 was further purified from the nuclear-enriched fraction of rat brain to near homogeneity through sequential column chromatographies. The purified enzyme retained its ability to bind specifically to p13suc1, which suggests that this binding does not require a cofactor. The immunochemical and enzymatic properties of p45 revealed that it differs from Cdk that are known to bind to p13suc1 with high affinity. However, in vitro p45 acted on the peptide motif that is conserved among substrates for cyclin-dependent kinases (Cdk) and mitogen-activated protein kinases, which implies that this protein might belong to the large family of proline-directed kinases. The evidence obtained in this study suggest that p45 is a nuclear p13suc1-bound kinase that has unique functions in the mature brain.

Acrylic Resins↗
PubMed1996

Rapid purification of human complement receptor type 1 (CD35, CR1).

We established a rapid purification procedure for complement receptor type 1 (CR1, CD35). Human erythrocyte stromata were solubilized, and the extract was directly applied to a Red-Sepharose column. The eluate was diluted 2-fold, then subjected to an immunoaffinity column, anti-CR1 (named 31R)-conjugated to Sepharose. More than 50% of CR1 was recovered with purity of > 90%. The CR1 preparation showed sufficient cofactor activity for factor I as compared to that prepared by the conventional method. Since 31R recognizes a single epitope in CR1 including its rare variants and soluble forms, this method will allow us to recover with high efficiency these forms of CR1 which have been detected especially in some disease states.

Antibodies, Monoclonal↗
PubMed1996

Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction.

We measured serum hepatocyte growth factor (HGF) in patients with acute myocardial infarction, angina pectoris, and other heart diseases. In patients with acute myocardial infarction, blood was collected at the time of admission. Serum HGF was elevated within 3 hours in 8 of 10 patients (80%) with acute myocardial infarction after onset of chest pain (9.4 +/- 3.2 ng/mL, mean +/- SEM, values in normal subjects <0.39 ng/mL). Mean value of serum HGF was 11.0 +/-2.6 ng.mL (n=11) in patients who admitted to the hospital between 6 and 9 hours and 13.1 +/- 5.7 ng.mL between 12 and 24 hours after onset. Elevated HGF levels were significantly more frequent than those of creatine kinase within 3 hours, and elevated levels correlated well with those of serum creatine kinase at 6-9 hours after onset of acute myocardial infarction. No increase in serum HGF value was found in patients with angina pectoris or other heart diseases. Thus, measurement of HGF is a sensitive method for early diagnosis of acute myocardial infarction.

Aged↗
PubMed1996

Novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonists: synthesis and structure-activity relationships of 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione and related compounds.

We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-substituted 2,3(1H,4H)-pyrido[2,3-b]pyrazinedione derivatives 4, 7-1-, 13, 15 and 16 showed some differences in comparison with those of the corresponding substituted quinoxalinediones, including 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione (1) (YM90K). The X-ray study exhibited that conformation of the 7-nitro group of 1.HCl was nearly coplanar with the quinoxaline ring, whereas the 6-imidazol-1-yl group was rotated with respect to the aromatic ring. From the glycine site on NMDA receptor binding study, it is indicated that bulkiness of 6-substituents on pyridopyrazinediones may be responsible for the selectivity against the glycine site. Among the series of azaquinoxalinediones, 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione (8c) exhibited a combination of the best affinity to AMPA receptors with a Ki value of 0.14 microM and selectivity against the glycine site (no affinity at 10 microM). In vivo, 8c also protected against sound-induced seizure in DBA/2 mice (minimum effective dose, 10 mg/kg ip).

Animals↗
PubMed1996

Depolarization-induced tyrosine phosphorylation of paxillin in PC12h cells.

Treatment of PC12h cells with a high concentration of KC1 induces depolarization of the plasma membrane and Ca2+ influx into the cells. We have previously shown that KC1 induced tyrosine phosphorylation of cellular proteins of 120, 110, 68, 44 and 42 kDa. In the present study, we found that the 68-kDa protein is paxillin, a tyrosine kinase substrate associated with the actin cytoskeleton. A calcium ionophore, A23187, also induced tyrosine phosphorylation of the 68-kDa protein, while KC1 did not in the presence of EGTA or nifedipine, indicating that the effect of KC1 was due to the Ca2+ influx into the cells. Tyrosine phosphorylation of paxillin was also induced by nerve growth factor and epidermal growth factor, but its migration patterns on an SDS/polyacrylamide gel were different, that is, nerve growth factor and epidermal growth factor caused upward shifts of the bands, while KC1 did not. However, both forms could associate with Csk and Crk. The effect of KC1 was blocked by cytochalasin D, indicating that tyrosine phosphorylation required the integrity of actin filaments. These results suggest that tyrosine phosphorylation of paxillin may be involved in Ca2+ -dependent events in neuronal and neuroendocrine cells.

Animals↗
PubMed1996

Proto-oncogene expression in human glomerular diseases.

The expression of the protein products and mRNA of c-fos, c-myc, p53, and c-raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c-fos and c-myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.

Cell Nucleus↗
PubMed1996

Laparoscopic-assisted colectomy with lymph node dissection for invasive carcinoma of the colon.

The results of performing laparoscopic-assisted colectomy in 20 patients with invasive carcinoma of the colon were analyzed in this study. The site of the lesion was the right colon in 5 patients, the transverse colon in 1, the left colon in 13, and the rectosigmoid in 1. In 2 patients, the laparoscopic procedure needed to be converted to an open laparotomy. Limited lymph node dissection (R1+, R2) was carried out in 10 patients and extensive node dissection (R3) was carried out in 9 patients. The histological depth of invasion in the 18 patients who underwent laparoscopic-assisted colectomy was the submucosa in 9, the muscularis propria in 2, and the extramuscular layer in 7. There were 3 patients who developed postoperative complications, 1 of whom underwent reoperation due to perforation of the colon. The postoperative course of the patients who underwent laparoscopic surgery was compared with that of a retrospectively selected control group of patients who had undergone open laparotomy. The postoperative recovery of the patients who underwent laparoscopic surgery was significantly faster than that of those who had undergone open laparotomy. Thus, we consider that laparoscopic-assisted colectomy with lymph node dissection is technically feasible provided that patients are properly selected. This procedure may be indicated not only for colonic carcinoma in the early stage, but also for that with invasion of the muscularis propria or the extramuscular layer.

Aged↗
PubMed1996

Effects of fructose ingestion on sorbitol and fructose 3-phosphate contents of erythrocytes from healthy men.

To investigate the effect of fructose ingestion on sorbitol and fructose 3-phosphate (F3P) in erythrocytes, we administered 50 g fructose with and without treatment with an aldose reductase inhibitor, epalrestat, to seven healthy, normal-glucose-tolerant, male volunteers aged 20-43 years. The same subjects were given 50 g glucose on another day. The sorbitol and F3P contents in their erythrocytes increased significantly, reaching peak levels at 60 min and 180 min, respectively, following fructose in gestion. On the other hand, glucose ingestion did not cause any statistically significant change in sorbitol content in their erythrocytes, although it significantly elevated their F3P content. Treatment with epalrestat had no significant effect on incremental changes in erythrocyte sorbitol and F3P content following fructose ingestion. This suggests that oral fructose may be converted directly to sorbitol and F3P in erythrocytes instead of being converted via glucose. Thus, the dietary intake of fructose may affect the concentrations of sorbitol and F3P in erythrocytes in normal men.

Adult↗
PubMed1996

Right-sided ulcerative colitis.

This report describes a case of right-sided ulcerative colitis in which multiple shallow ulcers and erosion with symmetric luminal stenosis were distributed segmentally from the ascending colon to the cecum, with a skip lesion composed of superficial erosions in the right half of the transverse colon. Both the rectum and the left colon were spared at the time of onset. Biopsies taken from the lesions showed non-specific inflammation, while those from the rectum and sigmoid colon showed no abnormal findings. A 5-year follow-up study was made based on radiography and endoscopy. Other inflammatory bowel diseases, such as Crohn's disease, tuberculosis, Yersinosis, Behçet's disease, and ischemic colitis were all ruled out, based on the macroscopic and microscopic findings as well as the clinical course. To our knowledge, this is the first report of right-sided ulcerative colitis that has been followed for a long period.

Adult↗
PubMed1996

Effect of the eradication of Helicobacter pylori on duodenal ulcer healing and ulcer relapse: randomized controlled study in Japan.

To investigate the effect of the eradication of Helicobacter pylori on the healing and relapse of duodenal ulcers. 50 patients with active duodenal ulcer and H. pylori infection were randomly allocated to two treatment groups. One group (cimetidine group) received cimetidine 400 mg twice daily for 6 weeks and the other group (double-therapy group) received 300 mg amoxicillin granules and 250 mg metronidazole thrice daily for 2 weeks, in addition to the same regimen of cimetidine as the cimetidine group. Forty-two patients completed the study. After confirmation of ulcer scar, all patients were followed up for 6 months while receiving treatment with teprenone, an agent that does not affect acid secretion or the eradication of H. pylori. The healing rates at 6 weeks were 90% in the cimetidine group and 95.5% in the double-therapy group. H. pylori eradication occurred in 0% of the cimetidine group and in 73.7% of the double-therapy group (P = 0.004). The cumulative relapse rates in the two groups at 6 months were 64.3% and 11.1%, respectively (P = 0.0007). In the double-therapy group, the cumulative relapse rate at 6 months in the patients in whom H. pylori persisted was 50% (2/4); the rate was 0% (0/14) in the patients in whom H. pylori had been eradicated (P = 0.005). Histological gastritis significantly improved compared with the baseline in the double-therapy group, but no such improvement was seen in the cimetidine group. White scarring was found in 7.1% of the cimetidine group and in 83.3% of the double-therapy group after 6 months (P < 0.0001). The eradication of H. pylori markedly decreased the relapse rate in duodenal ulcer patients, and it significantly improved both the grade of gastritis and the quality of the ulcer scar.

Adult↗
PubMed1996

Saponins from the root of Bupleurum falcatum.

Three new saponins and nine known saponins were isolated from the dried roots of Bupleurum falcatum. On the basis of chemical and spectral analyses, the structures of new compounds, named 4''-O-acetylsaikosaponin d and hydroxysaikosaponins a and c, were established. In aqueous acidic conditions, saikosaponins a and d were converted into not only known compounds, saikosaponins b1 and b2, but also hydroxysaikosaponins a and d, respectively. Furthermore, quantitative analysis of the decoction of Bupleuri Radix itself by HPLC exhibited that it contained saikosaponins a, c and d, and hydroxysaikosaponins a, c and d.

Carbohydrate Sequence↗
PubMed1996

The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats.

The purpose of this study was to investigate whether chronic administration of docosahexaenoic acid is able to reduce spatial cognitive deficit following transient ischemia in rats. In addition, we investigated whether the chronic treatment of docosahexaenoic acid is able to protect the hippocampal neuronal damage induced by either hypoxia in vitro or cerebral ischemia in vivo. A chronic administration of 200 mg/kg/day docosahexaenoic acid over 21 days did not affect the content of docosahexaenoic acid in the hippocampus, but did tend to increase it in the frontal cortex. On the other hand, this chronic administration decreased the content of arachidonic acid significantly both in the hippocampus and the frontal cortex. Under hypoxic conditions, the onset of the increase in the NADH fluorescence in the hippocampal slice was made significantly slower relative to the control by the chronic administration of docosahexaenoic acid. Rats were subjected to 10 min of transient forebrain ischemia by the method of four-vessel occlusion and were tested in a radial eight-arm maze task after cerebral reperfusion. Docosahexaenoic acid was administered either once 1 h before occlusion or daily for 21 days before occlusion. The single treatment of docosahexaenoic acid (1, 10, 100 or 200 mg/kg) did not significantly affect any aspect of the spatial learning deficit following occlusion. On the other hand, chronic treatment with docosahexaenoic acid (10, 100 or 200 mg/kg/day) significantly improved the spatial learning deficit following occlusion. A comparison of the neuronal densities in the hippocampal CA1 region of the chronically docosahexaenoic acid-treated (200 mg/kg/day) rats with those of the ischemic control revealed a significant neuronal preservation. From these results, it appears that chronic administration of docosahexaenoic acid may be valuable in ameliorating the spatial cognitive deficit induced by transient forebrain ischemia. In addition, docosahexaenoic acid might contribute to the protection of hippocampal neuronal damage caused by either hypoxia or ischemia.

Animals↗
PubMed1996

Myelodysplastic changes in three cases within 100 days after allogeneic bone marrow transplantation.

Three patients with severe aplastic anemia, acute promyelocytic leukemia (M3) and chronic myelogenous leukemia, developed myelodysplastic changes with trilineage morphological abnormalities in a few months following allogenic bone marrow transplantation (BMT). Morphologically dysplastic changes associated with moderate-severe anemia, leukopenia and/or thrombocytopenia appeared on day 40, day 62 and day 68 after BMT. A ferrokinetics study clearly showed ineffective erythropoiesis in one patient. Hematopoietic cells were shown to be of donor-origin in all three cases. The levels of vitamin B12 and folic acid were normal. Laboratory tests showed no signs of hemolysis or fragmentation of red blood cells. Although the cause of aberrant hematopoiesis compatible with MDS within 100 days post-BMT remains to be determined, cytomegalovirus infection, ganciclovir and/or graft-versus host disease (GVHD) might be associated with this myelodysplasia following allogeneic BMT.

Adolescent↗
PubMed1996

A rare case of multiple atherosclerotic aneurysms involving the femoral artery.

Atherosclerotic aneurysm of the deep femoral artery is a rare peripheral aneurysm that is likely to have associated aortoiliac aneurysms. The case of a patient who had five atherosclerotic aneurysms located in the abdominal aorta, bilateral common iliac arteries, and the left common femoral and deep femoral arteries is reported. He underwent a semi-emergency operation for the aneurysm of the deep femoral artery, followed by a two-stage operation for the aortoiliac aneurysms. The aneurysm of the deep femoral artery was repaired, and reconstruction of the distal deep femoral artery successfully performed with direct anastomosis to the superficial artery. In this report, the clinical presentation of multiple atherosclerotic aneurysms and the details of surgical reconstruction are described.

Aged↗
PubMed1996

Magnetic resonance imaging and serum CA-125 in evaluating patients with endometriomas prior to medical therapy.

OBJECTIVE: To determine whether magnetic resonance imaging (MRI) and serum levels of CA-125 can be used to evaluate patients with endometriomas before initiating medical treatment. DESIGN: Comparative study before and after medical treatment. SETTING: Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Eleven consecutive patients with at least one endometrioma > 10 mm in maximal diameter that was diagnosed by laparoscopy and treated with 900 micrograms/d buserelin acetate for 6 months. INTERVENTIONS: Magnetic resonance imaging and blood sampling was performed < 2 weeks before laparoscopy. MAIN OUTCOME MEASURES: Signal intensity of edometrioma/signal intensity of gluteus maximum muscle on T2-weighted image (T2SI:MSI); volume of endometrioma and serum CA-125. RESULTS: There was a positive linear correlation (r = 0.787) between T2SI:MSI before treatment and the extent of decrease in the volume of endometrioma. There was a negative linear relationship between serum CA-125 before treatment and the mean extent of decrease in the cyst volume (r = 0.678). The reduction in volume of endometrioma and T2SI:MSI before treatment related to the outcome of patients. CONCLUSION: The T2SI:MSI on MRI and serum CA-125 may be useful for estimating the outcome of patients with endometriomas before initiating medical treatment.

Adult↗