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Biomedical subjects

T Uchida

Publications and source records attributed to T Uchida.

At least 649 records · Page 36Linked to original sources

A study on cerebral nicotine receptor distribution, blood flow, oxygen consumption, and other metabolic activities--a study on the effects of smoking on carotid and cerebral artery blood flow.

We investigated middle cerebral artery flow velocity (MCA-FV) by a noninvasive method to determine whether or not smoking causes an increase in cerebral blood flow (CBF). Furthermore we determined sequentially the changes in CBF caused by smoking in order to evaluate changes in responses at different times in daily activities and the effect from meals. The subjects were 25 healthy individuals ranging in age from 20 to 36 yr. MCA-FV was measured by a transcranial Doppler system. They smoked a filtered cigarette for 5 min at 1 P.M., 3 P.M., 6 P.M., 8 P.M., 10 P.M., 8 A.M., and 11 A.M. Results (1) Smoking caused increases in both common carotid artery flow volume and MCA-FV, and the percentage increase of these parameters showed a good correlation (r = 0.809). (2) MCA-FV increased significantly during the first (by 6.6%) and second halves (by 5.4%) of the smoking period. (3) The change in MCA-FV after meals was slight. (4) Smoking tended to increase MCA-FV during each smoking session but the changes were not significant. The pulsatility index reduced significantly during almost every smoking session. These results lead to the conclusion that smoking reduces vascular resistance in cerebral arteries and increases CBF.

Adult↗

Severe flare-up in a prostate cancer patient treated with luteinizing hormone-releasing hormone analogue depot.

A 65-year-old man with advanced prostate cancer was treated with a luteinizing hormone-releasing hormone (LH-RH) analogue. Four days after the initial injection of 3.6 mg of goserelin acetate, severe dyspnea developed due to worsening pleuritis carcinomatosa, which was considered as a flare-up. Chest drainage was required to save his life. Therefore, we emphasize the importance of treatment to prevent tumor flare during LH-RH analogue therapy.

Adenocarcinoma↗

[Two cases of bladder cancer in patients with chronic renal failure].

We report here two cases of bladder cancer in patients with chronic renal failure who had been treated with hemodialysis. Case 1: A 58-year-old male on hemodialysis for 3 years visited with a complaint of gross hematuria. Transurethral resection of the bladder tumor (TUR-Bt) was performed and histopathological examination showed grade 1, stage pTa transitional cell carcinoma (TCC). The patient was followed for 4 years postoperatively without recurrence. Case 2: A 64-year-old male with hemodialysis for 1 week was referred to our department with a gross hematuria. TUR-Bt was conducted and histopathological findings showed grade 2, stage pT1b TCC. In April, 1992, he revisited our hospital with bladder tamponade due to massive hematuria, and TUR-Bt was performed. Histopathologically, the tumors were grade 2, stage pT2 TCC. He was followed for 1 year without recurrence.

Carcinoma, Transitional Cell↗

A granulocytic population with rearranged immunogenotype in chronic myelocytic leukemia blast crisis and Philadelphia-chromosome-positive acute leukemia with cross-lineage nature.

Two patients with chronic myelocytic leukemia (CML) mixed crisis and one with Philadelphia-chromosome-positive (Ph1 +) acute lymphoblastic leukemia (ALL) with cross-lineage nature had a considerable number of granulocytes with monoclonally rearranged immunogenotype. The gene configurations of immunoglobulin heavy chain (IgH), T-cell receptor beta chain (TCR beta), and gamma chain (TCR gamma) in the granulocytic cells were identical to those in the blasts, indicating that both the blasts and the granulocytes were derived from common leukemic progenitors with the IgH gene rearrangements. In a colony assay of cells from in the Ph1 + ALL patient, the leukemic cells showed the potential to differentiate into granulocytes in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). Interleukin 7 (IL-7) exerted synergistic effects on colony and cluster formation in cultures with these cytokines. Further, IL-3, GM-CSF, and G-CSF receptor gene expression was found in the leukemic cells. Our findings indicate that the Ph1 + common progenitors in these three patients preserved the potential for granulocytic differentiation even after the occurrence of the Ig (and TCR) gene rearrangements as the first genomic event in lymphocyte differentiation. The phenomenon of cross-lineage in leukemic cells, at least in Ph1 + leukemia, can be considered to demonstrate the potential of leukemic progenitors to differentiate in multiple directions.

Base Sequence↗

[A new cell line derived from a nude mouse resembling human large cell lung cancer].

Tumor cells derived from a metastatic mediastinal lymph node of a thirty six year old man with large cell lung cancer were transplanted into the subcapsule of the kidney of a nude mouse. The growing tumor was transplanted into a nude mouse twice and, thereafter, cultured in vitro. After the twelfth passage in vitro, the cell (NUTIY) was transplanted into subcutaneous tissue of a nude mouse and formed a rapidly growing tumor, showing the histological pattern similar to the large cell lung cancer of the patient. However, the chromosomal analysis revealed only murine chromosomes for NUTIY and any transfected human genes were not found in the genes of NUTIY by means of Alu probe. H-ras oncogene of NUTIY was amplified 4 folds, but that of the primary lung cancer and the metastatic lymph node of the patient was on a level with normal cells. NUTIY might be a cancer cell which a murine cell had been transformed into by some carcinogen in vitro.

Adult↗

[Effect of prostaglandin E2 on the proliferation of cultured guinea pig gastric mucous cells].

To understand the mechanism by which prostaglandins (PGs) preserve gastric mucosal integrity, we established a primary cultured monolayer of guinea pig gastric mucous cells, and by using this culture system, we studied whether endogenously released PGE2 could influence the proliferation of the mucous cells. By the histochemical and morphological analysis at 24h of the culture periods, the cells were recognized to contain PAS-positive mucous granules with only 3% of them being parietal cells. Although the cells which were simultaneously labeled with [3H] arachidonic acid in 0.5% serum-containing medium synthesized and released radiolabeled PGE2, PGI2 and PGA2, the release of PGE2 was more markedly observed and was partially dependent upon arachidonic acid added to the culture medium. By radioimmunoassay of the culture media, the mucous cells were found to release PGE2 in a time-dependent manner in response to 10% serum. Pretreatment of the cells with 10(-4)M indomethacin not only inhibited PGE2 release but also inhibited increase in cell number. However, the addition of PGE2 dose-dependently restored the indomethacin-induced inhibition of cell growth with the maximal increase almost to the control level at 10(-6)M PGE2. These results suggest that PGE2 endogenously released from the cells may exert a proliferative effect on gastric mucous cells.

Animals↗

Mechanical properties of artificial teeth.

In selecting the teeth for fabrication of complete or partial dentures, each patient's anatomic and physiologic requirements and the properties of the artificial teeth themselves should be taken into consideration. The purpose of this study was to evaluate the mechanical properties of the artificial teeth by the static compression test and the impact test. Specimens were the lower first molar porcelain and resin teeth (Livdent FB-20 teeth by G. C. Co., Tokyo, Japan). All were of the same shape. In the static compression test, the fracture load and deformation of the artificial teeth were measured with an Instron-type universal testing machine at a cross-head speed of 1.0 mm/min. Elastic modulus, ultimate strength and absorbed energy were calculated. In the impact test, the acceleration of a falling impactor was measured with a drop impact apparatus. The load applied to the specimen was equivalent to 300N. Absorbed energy and deformation were calculated. The resin teeth showed a lower elastic modulus, higher fracture toughness and shock-absorbing ability than the porcelain teeth. Resin teeth should be selected when the first requisite is high shock-absorbing ability, and porcelain teeth should be selected when the first requisite is high masticating efficiency.

Dental Porcelain↗

[Cloning and sequencing of cDNA of the hepatitis E virus genome--application to diagnosis].

Hepatitis E is endemic, often provoking epidemics in many developing countries. The hepatitis E virus has been molecularly cloned and sequenced and has a single-stranded, positive-sense RNA genome, 7,194 nucleotides, followed by a poly(A) tail. There are three open reading frames. The non-structural gene, approximately 5 kb, is located at the 5' end, while the structural gene, approximately 2 kb, is located at the 3' end of the genome. There is low level nucleotide variation among hepatitis E virus strains isolated from Myanmar and China.

Animals↗

Thrombopoietic effects of interleukin-6 in long-term administration in mice.

To further investigate the thrombopoietic and adverse effects of interleukin-6 (IL-6), 2 or 10 micrograms/day of recombinant human (rh) IL-6 was administered intraperitoneally (i.p.) to mice for up to 30 days. IL-6 increased platelet count, which plateaued at a level 30 to 40% higher than control after 5 days of treatment. This cytokine also maintained the high platelet count for the duration of treatment. The count exceeded normal levels 7 days after cessation of the 30-day treatment. IL-6 also induced a remarkable increase in the size but not the frequency of megakaryocytes in bone marrow sections. The number of bone marrow colony-forming units megakaryocyte (CFU-MK) and colony-forming units granulocyte-macrophage (CFU-GM) was not augmented by the administration of IL-6 in this protocol, while spleen progenitors were significantly stimulated. Small but significant increases did occur in the number of bone marrow megakaryocytes and CFU-MK, and in the proportion of CFU-MK in the DNA synthetic phase in mice treated with 10 micrograms/day of IL-6 for 30 days. Electron microscopic examination of bone marrow demonstrated that IL-6 remarkably developed the distribution of the demarcation membrane system (DMS) in mice treated for 30 days, with little change in mice treated for 5 days. The administration of 2 micrograms/day for 30 days induced a 2.2-fold increase in fibrinogen. No changes were observed in the hepatic or renal functions. Histologic and immunofluorescence studies on the kidneys revealed no significant changes compared with controls, indicating that proliferation of the glomerular mesangium did not occur. No neutralizing antibodies were detected in mice treated for 30 days. We conclude that the long-term administration of IL-6 in mice stimulates megakaryocyte maturation and platelet production with few adverse effects, and that this cytokine may be a candidate for the treatment of thrombocytopenia in humans.

Animals↗

Phosphorylation sites on tau by tau protein kinase I, a bovine derived kinase generating an epitope of paired helical filaments.

Tau protein kinase I (TPKI) isolated from bovine brain has been determined to phosphorylate tau at four distinct sites by detecting modified Ser and Thr residues with protein sequencer. Ser199, Thr231, Ser396 and Ser413 were all found to have been phosphorylated by TPKI (numbering of amino acids was done in relation to the longest human tau [Neuron, 3 (1989) 519-526]). These phosphorylations generate an epitope of PHF (paired helical filaments) and eliminate the recognition of tau by the monoclonal antibody, tau-1. These results suggested that TPKI might be responsible for at least some of the phosphorylation of tau to induce PHF formation.

Amino Acid Sequence↗

Single crystal structure of a mixed-chain triacylglycerol: 1,2-dipalmitoyl-3-acetyl-sn-glycerol.

The mixed chain triacylglycerol 1,2-dipalmitoyl-3-acetyl-sn-glycerol was synthesized and its crystal structure was determined to a final reliability factor (R) of 0.11. Two molecules are present in the monoclinic unit cell: space group P2(1); a = 5.375(1), b = 8.286(2), c = 42.96(1) A; beta = 93.30(2) degrees, V = 1910 A3, rho = 1.065 g/cm3, and mu = 5.7 cm-1. The structure is a trilayer: a bilayer of palmitate chains packed in the beta mode (T parallel) and an interdigitated monolayer of acetates. The glycerol backbone and acetate extend roughly linearly from the sn-1 chain. The sn-2 chain bends around the C-2 carbon to lie next to the sn-1 chain. Analysis of the torsion angles indicate that the glycerol conformation of 1,2-dipalmitoyl-3-acetyl-sn-glycerol is markedly different from single acid triacylglycerols and from 1,2-diacyl-sn-glycerols but very similar to 1,2-dimyristoyl-sn-glycero-3-phosphocholine.

Crystallography↗

Expression of two types of neurofibromatosis type 1 gene transcripts in gastric cancers and comparison of GAP activities.

To understand the molecular mechanism of gastric tumorigenesis, the status of neurofibromatosis type 1 (NF1) gene was analyzed in human gastric cancer cell lines. Although the sequencing of the GTPase activating protein (GAP)-related region of NF1 (NF1-GRD) revealed no apparent mutation, the NF1-GRD transcript (type I) and that containing an additional 63 bp insert in the center of NF1-GRD (type II) were equally expressed in most gastric cancer cells. By contrast, type II was predominantly expressed in normal stomach mucosa. When these two types of NF1-GRD were bacterially expressed and their GAP activities were tested, both types of NF1-GRD similarly stimulated ras GTPase activity. However, arachidonic acid inhibited GAP activities of two types of NF1-GRD to different extents. These results suggest that the increased expression of type I NF1 protein may modulate ras-related signal transduction and it may be related to the control of the gastric cellular proliferation.

Arachidonic Acid↗

p53 gene mutations in human gastric cancer: wild-type p53 but not mutant p53 suppresses growth of human gastric cancer cells.

To further investigate the role of p53 gene inactivation in gastric tumorigenesis, the mutational status of the p53 gene in primary human gastric cancer samples was examined. Reverse transcriptase polymerase chain reaction and subsequent direct sequencing of the p53 gene from gastric cancer samples revealed frequent point mutations of the p53 gene: some of these coincided with those previously identified in gastric cancer cell lines. In addition, both allelic deletion analysis using pYNZ 22 and polymerase chain reaction-restriction fragment length polymorphism analysis demonstrated an allelic deletion of the p53 gene in cancer tissue which contained a point mutation of the p53 gene in the remaining allele. Transfection of the wild-type or mutant p53 genes into gastric cancer cells showed that the wild-type but none of the mutated p53 genes suppressed the colony formation of gastric cancer cells. Furthermore, the incorporation of thymidine into DNA was reduced in cancer cells expressing the wild-type p53 gene. The glutathione S-transferase-wild type p53 fusion protein bound to simian virus 40 large T antigen in COS-1 cell lysate. None of the p53 fusion proteins containing mutations at codons 143, 175, 248, or 273 bound to simian virus 40 large T antigen. By contrast, two different mutant p53 fusion proteins containing mutations specifically observed in gastric cancer bound to simian virus 40 large T antigen. These results indicate that inactivation of the p53 gene through mutations and the allelic deletion may play an important role in gastric tumorigenesis. These mutations may cause a conformational change in the p53 protein resulting in the loss of the suppression by p53 of the growth of gastric cells, partly through disruption of the association of p53 protein with a cellular component.

Antigens, Viral, Tumor↗

Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments.

From bovine brain microtubules we purified tau protein kinase I (TPKI, Mr 45,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tau protein kinase II (TPKII) whose activity was attributed to a 30-kDa protein on SDS-PAGE by affinity-labeling using an ATP analog. Both kinases were activated by tubulin. TPKII, but not TPKI, phosphorylated tau fragment peptides previously used for detection of a Ser/ThrPro kinase activity. Therefore, TPKII was considered to be the Ser/ThrPro kinase. TPKI was more effective than TPKII for producing the decrease of tau-1 immunoreactivity and mobility shift of tau on SDS-PAGE. Moreover, TPKI, but not TPKII nor other well-known protein kinases, generated an epitope present on paired helical filaments. These findings suggested that tau phosphorylated by TPKI resembled A-68, a component of paired helical filaments.

Affinity Labels↗

Molecular cloning, characterization, and expression in Escherichia coli of a cDNA encoding mammalian choline kinase.

A rat liver lambda gt11 cDNA library was screened with antibody against rat liver choline kinase. One of the putative phage clones obtained was found to express choline kinase activity in infected Escherichia coli cells and used for the isolation of fully extended cDNA clones by hybridization. The obtained clones had identical overlapping nucleotide sequences and gave a composite cDNA sequence of 2540 bases. Poly(A)+ tails were found at three different sites of the cDNA sequence. Within the sequence there was a large open reading frame encoding 435 amino acids with a molecular mass of 49,743 Da. When this open reading frame was placed after the trc promoter and introduced into E. coli cells, fully active choline kinase was produced. This enzyme was partially purified using a published choline kinase purification method and was found to mediate the phosphorylation of choline, N,N-dimethylethanolamine,N-monomethylethanolamine, and ethanolamine. Similar to the case with choline kinases from various sources, Km decreased as the number of N-methyl groups increased. The deduced amino acid sequence significantly resembled the yeast choline kinase sequence. It also showed local sequence similarity to protein kinases and some bacterial phosphotransferases. Northern blot analysis revealed that the cDNA probe hybridized to 2.8- and 1.8-kilobase RNA in various rat tissues. The sizes of the transcripts were fairly consistent with that of cDNA. The order of mRNA abundance was testis, brain, lung, kidney, and liver, but did not coincide with the order of the activity levels in these tissues. These results show that the cloned cDNA encodes one of the choline kinase isoforms present in mammalian tissues.

Amino Acid Sequence↗