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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 253 records · Page 14Linked to original sources

Endogenously generated nitric oxide by nitric-oxide synthase gene transfer inhibits cellular proliferation.

We investigated whether endothelial nitrite oxide synthase (NOS) gene transfer inhibited cellular proliferation. Endothelial NOS and endothelin type A receptor genes were transferred into 293 cells, a human embryonic kidney cell line, by calcium-phosphate coprecipitation. The cytosolic free Ca(2+) levels ([Ca(2+)](i)) of transfected cells were estimated with fura-2 fluorescence. Thymidine incorporation was increased by endothelin-1 in type A receptor-transfected cells. The endothelial NOS gene transfer did not affect endothelin-1-induced increase in [Ca(2+)](i) of type A receptor-transfected cells, but markedly inhibited mitogen-activated protein kinase and c-fos promoter activities. The endothelial NOS gene transfer also inhibited thymidine incorporation into type A receptor-transfected cells in response to endothelin-1, which was abolished in the presence of the NOS inhibitor N(G)-monomethyl-L-arginine acetate. The endothelin-1-induced increase in cell number was significantly suppressed by endothelial NOS gene transfer as well as by the mitogen-activated protein kinase inhibitor PD98059. These results indicate that endothelial NOS gene transfer inhibits cellular proliferation via inhibition of the mitogen-activated protein kinase cascade.

Calcium↗

Gender effects on age-related changes in brain structure.

BACKGROUND AND PURPOSE: Previous reports have suggested that brain atrophy is associated with aging and that there are gender differences in brain atrophy with aging. These reports, however, neither exclude silent brain lesions in "healthy subjects" nor divide the brain into subregions. The aim of this study is to clarify the effect of gender on age-related changes in brain subregions by MR imaging. METHODS: A computer-assisted system was used to calculate the brain matter area index (BMAI) of various regions of the brain from MR imaging of 331 subjects without brain lesions. RESULTS: There was significantly more brain atrophy with aging in the posterior parts of the right frontal lobe in male subjects than there was in female subjects. Age-related atrophy in the middle part of the right temporal lobe, the left basal ganglia, the parietal lobe, and the cerebellum also was found in male subjects, but not in female subjects. In the temporal lobe, thalamus, parieto-occipital lobe, and cerebellum, brain volume in the left hemisphere is significantly smaller than in the right hemisphere; sex and age did not affect the hemisphere differences of brain volume in these regions. CONCLUSION: The effect of gender on brain atrophy with aging varied in different subregions of the brain. There was more brain atrophy with aging in male subjects than in female subjects.

Adult↗

[Support with residential facilities].

In Western countries many residential institutions for the mentally retarded have been built since the end of 19th century. Some large-scaled public facilities accommodated as much as 5,000 to 8,000 residents. This trend persisted the middle of this century. However, institutionalism has been abandoned since the latter half of 1960's. In Japan the law for the welfare of persons with mental retardation was enacted in 1960. Thereafter the most important subject was the construction of residential institutions. Thus, Japan lags behind the United States and European countries by nearly half a century as far as the policy for the mentally retarded is concerned. International Year of Persons with Disabilities in 1981 and subsequent United Nations Decade of Persons with Disabilities provided us with motivation to change the social welfare services in Japan under the concept of normalization. At present Japanese social welfare systems are changing to community-oriented services, such as community residential facilities and day-activity centers.

Adolescent↗

[A comparison between three methods to investigate falls among the elderly living in the community].

PURPOSE: Interview survey is the often selected method to investigate falls among the elderly. However, the reliability of data obtained by that method has not be confirmed. The aim of this study is to clarify the number of intervals of recollection that should be specified to ensure accurate data when we investigate falls by using interview surveys among the elderly. METHODS: We carried out a total health survey among the elderly in Shigenobu town, and reported about the frequency of falls and its relating factors. Sex, age, walking ability over a distance of 1 km and hospitalization experience for past 1 year were related to falls significantly. In this study, we set 3 groups matching for the above factors in addition to history of falls during the preceding a year, and for one year we asked about falls every month for the first group (116 participants), every 3 months for the second group (116 participants) respectively. The third group (118 participants) was asked once at the end of this study. These three groups totaled 350 persons who were participants of physical fitness measurements that we carried out in Shigenobu town. The existence of falls was investigated by mail, and the nonrespondents were questioned by direct telephone calls. RESULTS: For reasons such as death, moving out, hospitalization and answer denial, persons whose answer was not obtained were excluded from the analysis. Finally, 87.1% in the 1st group, and 89.7% in the 2nd group and 96.6% in the 3rd group were analyzed. Statistically significant difference for the above factors related to falls did not exist among the 3 groups. Annual incidence for falls tended to be more frequent in the 1st group that in the 3rd group (20.5% in the 1st group, 15.9% in the 2nd group and 6.4% in the 3rd group) in males. In females, such a difference was not observed. (26.3% in the 1st group, 18.3% in the 2nd group and 20.9% in the 3rd group). CONCLUSIONS: There were no significant differences for the factors related to falls in 3 groups, therefore, the groups had almost similar backgrounds. In men, the difference of annual reported incidence between the 1st group and the 3rd group may be due to differences in the method of recollection.

Accidental Falls↗

Tissue selectivity of KMD-3213, an alpha(1)-adrenoreceptor antagonist, in human prostate and vasculature.

PURPOSE: We evaluated the binding and functional affinity of KMD-3213 and other alpha 1-adrenoceptor (AR) antagonists such as prazosin or tamsulosin, to compare the tissue selectivity of these antagonists between human prostate and vasculature. MATERIALS AND METHODS: In the binding experiments, saturation experiments using [3H]-KMD and [3H]-prazosin (PZ) were performed, and competition of [3H]-PZ binding by antagonists was also examined in human prostatic and aortic membranes. In the functional study, contractile responses to noradrenaline were evaluated in human prostate and mesenteric artery. RESULTS: [3H]-PZ bound to human prostatic and aortic membranes with subnanomolar affinity. [3H]-KMD also bound to human prostate, with higher affinity than [3H]-PZ; whereas it did not bind sufficiently to human aorta. Competition of [3H]-PZ binding revealed that KMD-3213 had more than 200-fold higher affinity for human prostate than for aorta. Binding profiles of antagonists revealed that human prostate predominantly expressed alpha 1A-AR, whereas human aorta expressed alpha 1B-AR mainly. In functional experiments, KMD-3213 potently inhibited the noradrenaline-induced contraction in human prostate as potently as tamsulosin, although prazosin showed relatively low affinity. Comparing these functional affinities with those in the mesenteric artery, only KMD-3213 exhibited substantial tissue selectivity, showing more than 100-fold higher affinity for human prostate than for mesenteric artery. Functional affinity of each antagonist suggested that noradrenaline-induced contractions were mainly mediated by alpha 1L-AR in the human prostate and by alpha 1B-AR in the mesenteric artery. CONCLUSION: These results suggest that KMD-3213 is a substantially prostate-selective alpha 1-AR antagonist in human tissues compared with other alpha 1-AR antagonists.

Adrenergic alpha-Antagonists↗

Regulating actin dynamics in neuronal growth cones by ADF/cofilin and rho family GTPases.

Growth cone motility and navigation in response to extracellular signals are regulated by actin dynamics. To better understand actin involvement in these processes we determined how and in what form actin reaches growth cones, and once there, how actin assembly is regulated. A continuous supply of actin is maintained at the axon tip by slow transport, the mobile component consisting of an unassembled form of actin. Actin is co-transported with actin-binding proteins, including ADF and cofilin, structurally related proteins essential for rapid turnover of actin filaments in vivo. ADF and cofilin activity is regulated through phosphorylation by LIM kinases, downstream effectors of the Rho family of GTPases, Cdc42, Rac and Rho. Attractive and repulsive extracellular guidance cues might locally alter actin dynamics by binding specific GTPase-linked receptors, activating LIM kinases, and subsequently modulating the activity of ADF/cofilin. ADF is enriched in growth cones and is required for neurite outgrowth. In addition, signals that influence growth cone behavior alter ADF/cofilin phosphorylation, and overexpression of ADF enhances neurite outgrowth. Growth promoting effects of laminin are mimicked by expression of constitutively active Cdc42 and blocked by expression of the dominant negative Cdc42. Repulsive effects of myelin and sema3D on growth cones are blocked by expression of constitutively active Rac1 and dominant negative Rac1, respectively. Thus a series of complex pathways must exist for regulating effectors of actin dynamics. The bifurcating nature of the ADF/cofilin phosphorylation pathway may provide the integration necessary for this complex regulation.

Actin Depolymerizing Factors↗

[A case of G-CSF-producing large cell carcinoma of the lung with gastric metastasis].

We report a rare surgically-treated case of G-CSF-producing large cell carcinoma of the lung with gastric metastasis. A 65-year-old male was admitted to our hospital because of fever, anemia and epigastralgia. Chest X-ray examination and CT scanning revealed a round mass shadow (8 cm) in contact with the chest wall in the right upper lung field and metastasis to the mediastinal lymph nodes. Laboratory examination showed a WBC of 16,800/mm3, CRP of 11.6 mg/dl, and a serum G-CSF of 90 pg/ml. Upper gastrointestinal series and gastroscopy showed an ulcerating submucosal tumorous lesion in the pyloric antrum. The lung carcinoma was treated by right upper lobectomy with chest wall resection. After 1 month, gastrectomy was performed. After the operation, the WBC normalized, and the CRP and serum G-CSF levels decreased. Histopathological examination demonstrated a poorly differentiated large cell carcinoma in the lung and a metastatic lesion in the stomach. Immunohistochemical staining with anti-G-CSF mono-clonal antibody showed negative results in the lung but positive results in the stomach. He was discharged 3 weeks after gastrectomy but died of aggravation of the general condition associated with local recurrence in the chest wall 2 months after discharge.

Aged↗

Frequency of apoptosis of tumor-infiltrating lymphocytes induced by fas counterattack in human colorectal carcinoma and its correlation with prognosis.

We investigated apoptosis in tumor-infiltrating lymphocytes (TILs) obtained from 41 colorectal carcinomas by in situ nick translation (ISNT). When the ISNT labeling index (LI) was determined as the number of positive nuclei per 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2-30). The ISNT LI of colorectal carcinoma with lymph node metastasis was higher than that of colorectal carcinoma without metastasis. The cases with a high LI of 212.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequently in FasL-positive cases than in FasL-negative ones. These findings indicate that the FasL expressed in colorectal carcinoma cells may kill the Fas-positive immune effective TILs by means of a Fas-FasL system termed Fas counterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.

Adult↗

Comparison between short-term food restriction and exercise on whole body glucose disposal in high-fat rats.

High-fat diets induce whole-body insulin resistance. The aim of this study was to compare effect of two interventions: 3-day food restriction (66% of ad libitum fed) and 3-day exercise training (voluntary running wheels), on decreased insulin-mediated whole body glucose uptake in high-fat fed rats (5 mo old) using the hyperinsulinemic euglycemic clamp procedure. The control group was maintained on rat chow alone. After high-fat feeding for 2 wk, insulin-stimulated whole body glucose utilization was significantly decreased by 26%. The exercise training was more effective than food restriction in lowering plasma concentrations of insulin and triacylglycerol and tissue concentrations of triacylglycerol in soleus muscles. Diminished whole-body glucose uptake resulting from high-fat feeding was reversed completely by exercise training, but only partially by food restriction. The time course of starvation on insulin-stimulated glucose uptake was also observed in high-fat fed rats. Although the extension of starvation time to 48 h resulted in decreased plasma glucose, insulin and triacylglycerol concentrations, whole body glucose uptake did not increase further. These findings suggest that short-term exercise has a higher restorative effect on insulin sensitivity in high-fat fed rats than food restriction, in spite of the same loss in body weight, presumably due in part to improved local lipid availability.

Animals↗

Ruptured sinus valsalva with infectious endocarditis: a technique of defect closure with an autologous-xenologous pericardial sandwich patch.

We report a case of ventricular septal defect with acquired rupture of sinus Valsalva induced by infectious endocarditis. After irrigati on of all infectious tissues, the defect was closed twice using two different patches. One was an autologous pericardial patch from the right ventricle and the other was a composite patch made of an autologous pericardium and axenologous pericardium from the left ventricle. As a result, the xenologous pericardium was sandwiched between autologous pericardiums. We thought that this "sandwiched patch" would compensate for the shortcomings of each type of pericardium and resist left ventricular pressure and infection. Despite the development of antibiotic therapy, infectious endocardit is (IE) is still one of the most difficult disease to cure. In the case of a rupture of sinus Valsalva, because of the rapid spread of infection into any of the cardiac chambers, surgical intervention is necessary. In this report, we describe a case treated successfully.

Adult↗

Results of filtering surgery in young patients with aniridia.

To evaluate whether filtering surgery is effective in controlling the intraocular pressure of young aniridic patients with glaucoma, we retrospectively reviewed the charts of aniridic patients with glaucoma under the age of 40 years. We defined a good intraocular pressure control period as the time from surgery until IOP exceeded 20 mm Hg, with or without glaucoma medication. Twenty filtering surgeries (17 trabeculectomies and 3 trabeculectomies with mitomycin C) were performed on 10 eyes in 6 patients for more than 20 years. The mean good intraocular pressure control period after the filtering surgery was 14.6 months (range, 2 to 54 months). Aside from mild choroidal detachment, no other serious complications were encountered. We believe that filtering surgery is efficacious for control of intraocular pressure of young aniridic patients with glaucoma.

Adult↗

[Diagnosis of acute cerebral infarction using diffusion-weighted imaging by low field (0.2 T) magnetic resonance image].

The purpose of this study is to confirm the diagnosis of acute cerebral infarction on diffusion-weighted imaging using low field (0.2 T) magnetic resonance image(MRI). Acute cerebral infarctions in 51 patients were examined on diffusion-weighted imaging using low field MRI within 48 hours after clinical symptoms. Diffusion-weighted imaging was examined using line scan method. Twenty-four cases were cortical infarction, and twenty-two cases were perforating infarction. In five cases out of 51 cases, ischemic regions were not detected as abnormal high signal intensity area on diffusion-weighted imaging. Four cases of no abnormal detection were transient ischemic attack, and the other one was a perforating infarction. The earliest detection time in cortical infarction cases was 1 hour and 20 minutes. On the other hand, the earliest detection time in perforating infarction cases was 3 hours. Detective ability for acute cerebral infarction on diffusion-weighted imaging by low field MRI was depending on both size and lesion of infarction. That is to say, either small size or brain stem infarction was hard to detect. Thin slice and vertical slice examination for the infarction may improve to diagnose in low field MRI. Our conclusion is acute cerebral infarction was able to be diagnosed on diffusion-weighted imaging by low field as well as high field MRI.

Acute Disease↗

[Evaluation of hepatic resection following hepatic arterial infusion chemotherapy for colorectal liver metastases].

We evaluated the significance of hepatectomy following hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. The prognosis of 4 cases with initially resectable tumors was discouraging, indicating no benefit of preoperative HAI for resectable tumors. The 2- and 3-year survival of patients who underwent hepatectomy after downstaging by HAI of originally unresectable metastases were 100% and 67%, respectively, suggesting that hepatectomy combined with HAI is a promising modality for those patients. However, it seems that the control of extrahepatic disease and decision making for the timing for surgical therapy are issues requiring improvement.

Aged↗