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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 685 records · Page 38Linked to original sources

Human P-glycoprotein transports cyclosporin A and FK506.

Cyclosporin A, a cyclic undecapeptide, and FK506 are efficient immunosuppressive agents. They also attract attention as effective P-glycoprotein modulators that inhibit P-glycoprotein from binding to anticancer drugs and overcome multidrug resistance. Cyclosporin A itself interacts with a common binding site of P-glycoprotein to which Vinca alkaloids and verapamil bind. We were interested to determine whether cyclosporin A and FK506 are substrates for P-glycoprotein to transport, and we studied their transcellular transport. In LLC-PK1 cells, derived from porcine kidney proximal tubule and forming a highly polarized epithelium, cyclosporin A was transported in a saturable manner. LLC-GA5-COL300, a transformant cell line derived by transfecting LLC-PK1 with human MDR1 cDNA isolated from normal adrenal gland, expresses P-glycoprotein specifically on the apical surface and shows a typical multidrug-resistant phenotype. LLC-GA5-COL300 cells showed increased transport of cyclosporin A from the basal to the apical side. Kinetic analysis showed that this transport was a typical saturable transport with the calculated apparent Michaelis constant (Kappm) and the maximum flux (Vmax) as 8.4 microM and 2.4 nmol/mg protein/h, respectively. LLC-GA5-COL300 also showed increased transport of FK506 from the basal to the apical side. These results indicate that P-glycoprotein transports the immunosuppressive agents cyclosporin A and FK506.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Mother-to-child transmission of human T-lymphotropic virus type I (HTLV-I): an extended follow-up study on children between 18 and 22-24 years old in Okinawa, Japan.

The significant difference observed between the seroprevalence of HTLV-I in adults and in children is as yet unexplained. To evaluate a hypothetical explanation of the existence of seroconversion cases of "seronegative carriers" for this phenomenon, 21 of 55 children who had been born to seropositive mothers and who remained seronegative until the age of 18 years were further followed up at the ages of 22 and/or 24 years. None of the 21 seronegative children born to seropositive mothers seroconverted, either at 22 years or at 24 years. In addition, the polymerase-chain-reaction (PCR) technique could not prove the existence of the HTLV-I provirus genome in peripheral mononuclear cells (PBMC) of 10 of these children. Our results fail to prove the possibility of viral latency of HTLV-I in mother-to-child transmission. Therefore, the hypothetical seroconversion of "seronegative carriers" after adulthood cannot be an explanation.

Adolescent↗

Frequent isolation of human herpesvirus 7 from saliva samples.

Human herpesvirus 7 (HHV-7) was isolated frequently from saliva specimens. The isolation rates were 81% (13/16) in adults, 70% (7/10) in children over 1 year old, and none (0/7) in children less than 1 year old, respectively, indicating that infection of HHV-7 occurs during early infancy and the virus shedding rate after infection is very high. Human herpesvirus 6 (HHV-6) was not isolated from saliva specimens although some studies on isolation of HHV-6 from saliva was reported previously.

Adult↗

Phylogenetic relationships of ferns deduced from rbcL gene sequence.

Part of the large subunit of the ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) gene (rbcL) was sequenced from three fern species: Adiantum capillus-veneris, Botrypus strictus, and Osmunda cinnamomea var. fokiensis. This region included 1,333 base pairs, about 90% of the gene. Maximum likelihood analysis of the deduced amino acid sequences indicated that (1) Botrypus (Ophioglossaceae) clustered monophyletically with other ferns (Adiantum, Angiopteris, Osmunda); the closest relative to Botrypus among the three species was Osmunda, which did not support the hypothesis that the Ophioglossaceae are linked to the progymnosperm-seed plant lineage. (2) Eusporangiate ferns containing Botrypus (Ophioglossaceae) and Angiopteris (Marattiaceae) were a paraphyletic group. (3) Seed plants and the four fern species examined formed a monophyletic group, but ferns and bryophytes (liverwort) did not. Variations in rates of substitution for synonymous and nonsynonymous codons were found in fern lineages.

Amino Acid Sequence↗

A case of cerebral glioblastoma with extensive cerebrospinal fluid dissemination: diagnostic value of immunohistochemical examination and MR imaging.

A 9-year, 6-month-old boy presented with peripheral-type multiple cranial nerve palsy due to extensive cerebrospinal fluid (CSF) dissemination of intracranial glioblastoma multiforme. Tissue obtained from biopsy did not stain for glial fibrillary acidic protein (GFAP). The relationship between GFAP-negative tumor cells and extensive CSF dissemination agreed with recent reports. Magnetic resonance imaging with gadolinium-DPTA enhancement clearly depicted not only the cranial meningeal dissemination but also spinal metastasis. Magnetic resonance imaging showed undoubted usefulness in demonstrating disseminated glioblastoma.

Brain↗

Prevalence of type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance in the Japanese general population: the Hisayama Study.

We determined the population-based prevalence of diabetes mellitus in members of the Japanese community, Hisayama aged 40-79 years old by a 75-g oral glucose tolerance test. The basic population used to calculate diabetic prevalence was 1,077 men (72.8% of the whole population in the same age range) and 1,413 women (80.8%) including ten diabetic patients on insulin therapy. In addition, we compared the prevalence of history of diabetes which was acquired by interview or questionnaire, between participants and non-participants in the 75-g oral glucose tolerance test, but they were not statistically different. The age-adjusted prevalence of diabetes to world population was 12.7% for men and 8.4% for women, and that of impaired glucose tolerance was 19.6% for men and 18.4% for women. These figures were much higher than those previously reported from several Japanese communities. The results obtained from the present study could reveal true prevalence of diabetes among the Japanese population. In addition, the reasons for the increasing prevalence of diabetes among the recent Japanese population are also discussed.

Adult↗

Discordance between thallium-201 scintigraphy and coronary angiography in patients with Kawasaki disease: myocardial ischemia with normal coronary angiogram.

To assess the usefulness of radionuclide tests in detecting coronary occlusive lesions in children with Kawasaki disease, we compared the results of stress thallium-201 myocardial single photon emission computed tomography with dipyridamole infusion and coronary angiography in 34 patients (19 males and 15 females). Perfusion defects on the stress image only were categorized as transient and were attributed to coronary vascular disease in the presence of redistribution on the delayed image. Others were classified as persistent, due to myocardial damage. Five of the seven children (71%) with severe stenosis on coronary angiography showed persistent and/or transient perfusion defects. However, six of the 11 children (55%) with aneurysms but no obvious stenosis, and four of the 16 children (25%) with normal angiography, showed persistent and/or transient defects. After analyzing 20 individual segments of perfusion defects in the 15 children, six segments (30%) were attributed to the stenosis of supplying coronary arteries, six segments (30%) were related to the coronary aneurysms, and eight segments (40%) were unrelated to any abnormalities on angiography. Thus, significant discordance between the radionuclide and angiographic studies was demonstrated. These results suggest that coronary lesions, as conventionally defined by angiography and supplemented by echocardiography, may not completely identify all Kawasaki patients who may develop myocardial ischemia in the future or who had ischemia in the past.

Adolescent↗

Histopathological and morphometric analysis of atypical adenomatous hyperplasia of human cirrhotic livers.

Atypical adenomatous hyperplasia (AAH) is a hyperplastic parenchymal nodular change in the cirrhotic liver, in which overt hepatocellular carcinoma (HCC) occasionally arises. AAH is defined as a sizable hepatocellular nodule with a variable degree of hepatocellular atypia not regarded as HCC, and is different from ordinary adenomatous hyperplasia in which hepatocellular atypia is absent. In the present study, we attempted to evaluate carcinogenetic processes and to find histological variables which indicate malignant transformation in AAH, using 49 surgically resected or autopsied nodules. AAH frequently showed morphological heterogeneity. Atypical lesions within AAHs were divisible into the following three categories from overall histopathological appearances: malignant (A), equivocal (B), or non-malignant (C) lesions. Analysis of combination of these three lesions, which were frequently intermixed in a given AAH, suggested that B lesions appear subsequent to C lesions, and A lesions finally appear in AAH nodules. Among the 14 histological variables, enlargement, hyperchromasia and irregular contour of nuclei were found to correlate well with A lesions. Increased nuclear density, iron resistance, reduction of reticulin fibres, clear cell change, sinusoidal dilatation and presence of abnormal arteries were suggestive of A or B lesions. Nuclear deviation toward the sinusoids, acinar and compact arrangements, fatty change and Mallory's hyaline alone were not useful indicators of A or B lesions. These results indicate that AAH is a preneoplastic or borderline lesion in which overt HCC is likely to evolve through several steps. Although a needle liver biopsy is a useful tool for diagnosis of benign, equivocal and malignant hepatocellular nodular lesions, the needle biopsy specimen should be carefully evaluated by considering the morphological heterogeneity of the AAH and a variable combination of 14 histological variables.

Aged↗

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease.

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scar-like fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.

Adenoma↗

Development of acute myocardial infarction associated with coronary collateral regression after reperfusion by percutaneous transluminal coronary angioplasty.

Clinical and experimental observations have suggested that newly developed collaterals usually remain even after successful revascularization. We present a patient in whom coronary collateral regression was angiographically demonstrated within about 1 month after percutaneous transluminal coronary angioplasty, which led to the development of acute myocardial infarction. This case suggests that there may be a possibility of unexplained clinically important anatomical or functional regression of collaterals after reperfusion.

Adult↗

An autopsy case of intracranial hemorrhage during tissue plasminogen activator infusion.

We describe an autopsy case of severe intracranial hemorrhage which occurred during the infusion of tissue plasminogen activator (t-PA) for acute myocardial infarction. A 75-year-old man was admitted with substernal chest pain of 3-h duration and electrocardiographic changes consistent with an acute inferior myocardial infarction. Physical examination was unremarkable, except for an initial blood pressure reading of 160/96 mmHg. The patient received 3,000 IU intravenous heparin followed by a 2.4 x 10(6) IU bolus dose of tissue plasminogen activator (t-PA) (Alteplase). This was followed by a drip infusion of 21.6 x 10(6) IU of t-PA over 1 h (total dose 41 mg). Thirty minutes after the infusion of t-PA was initiated, the patient suddenly lost consciousness and began to have violent convulsions, followed by cardiac arrest. Autopsy revealed massive hemorrhage in the bilateral cerebrum and brain stem. To our knowledge, this is the first case of sudden death during t-PA infusion therapy.

Aged↗

Hypergalactosaemia in a patient with portal-hepatic venous and hepatic arterio-venous shunts detected by neonatal screening.

Hypergalactosaemia was discovered in a newborn girl during routine metabolic screening. Hereditary enzyme deficiency was ruled out. She had multiple hepatic haemangiomas with portal-hepatic venous and hepatic arterio-venous shunts. Since she showed signs of high-output heart failure due to the arterio-venous shunt, hepatic artery embolization was performed at age 3 months. A galactose tolerance test was performed before and after embolization and when the haemangioma no longer appeared on ultrasonography. Even after embolization, the level of blood galactose was abnormally elevated in the galactose tolerance test, but the blood galactose was eliminated more rapidly than before embolization. When the hepatic haemangioma was no longer detected by ultrasonography, the peak galactose level decreased. We surmise that the hypergalactosaemia was due to these shunts. In cases of hypergalactosaemia of unknown cause; liver haemangioma with portal-hepatic venous shunting should be considered as a possible cause. If a hepatic arterio-venous shunt also exists, this may contribute to the effect of the portosystemic shunting.

Arteriovenous Malformations↗

Effects of cytokines on HLA class I antigen expression on Huh6 and HB611 cells.

This study investigated the expression of HLA class I antigens on Huh6 and HB611 cells induced by interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. All of these cytokines induced the antigens on both cells in a dose-dependent manner, with IFNs inducing much more expression than TNF-alpha or IL-1 beta. We have already reported that protein kinase C (PKC) is involved in the antigen expression induced by IFN-gamma on Huh6 cells. The antigen expression induced by IFN-alpha was also blocked by a PKC inhibitor, H-7. However, the antigen expression by TNF-alpha or IL-1 beta was not inhibited by H-7, by a protein kinase A inhibitor, HA1004, nor by a calmodulin antagonist, W-7. These results suggested that PKC, Ca(2+)-calmodulin, and cAMP are not involved in the induction of HLA class I antigens on both cells by TNF-alpha and IL-1 beta. We concluded that TNF-alpha and IL-1 beta induced much less expression of HLA class I antigens on both cells than IFNs and that this might be because the signaling pathway by TNF-alpha and IL-1 beta differed from that by IFNs.

Carcinoma, Hepatocellular↗

An experimental study of delay of flow-through venous flaps.

A delayed procedure was performed in flow-through venous flaps made in rabbits' ears. Compared with undelayed venous flaps, the delayed flaps at 7, 14 and 21 days after delay showed a distinct increase of survival area. This effect increased with the delay period.

Animals↗