[Polypoid lesion of the appendix].
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Appendiceal Neoplasms↗
Biomedical subjects
Y Muto
Publications and source records attributed to Y Muto.
[Lymphoid hyperplasia of the appendix].
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Appendix↗
[Development of a hybrid bio-artificial liver].
Despite recent advances in medical management, fulminant hepatic failure (FHF) is still associated with high mortality. Liver transplantation is currently the only effective therapy for patients with FHF in many countries, but not yet in Japan. Thus, it is needed to introduce a bioartificial liver (BAL) support system using hepatocytes that substitutes for insufficient metabolism until the liver can recover. To function as a surrogate liver, BAL must meet two metabolic criteria: the first criterion requires highly differentiated liver cells; the second requires a mass sufficient to support the needs of the patients. Cell-extracellular matrix interaction is biologically relevant to regulating gene expression and maintaining cell differentiation of hepatocyte through activating liver-enriched transcriptional factors, including hepatocyte nuclear factor-1 (HNF-1) and HNF-4. With the advance of biotechnology, clinical trials of BAL using porcine primary hepatocytes or human hepatoblastoma cell lines have been successfully performed in the United States. In the near future, a hybrid liver support system is expected to be widely used for treating patients with FHF.
Animals↗
[Impaired metabolism of amino acid and protein in patients with liver cirrhosis].
Patients with liver cirrhosis are characterized by impaired metabolism of amino acids, such as, increased plasma aromatic amino acid (AAA), methionine levels, and decreased plasma branched-chain amino acid (BCAA) levels. These abnormalities are also regarded to induce hepatic encephalopathy, ascitic retention and muscular waste. The etiology of such abnormal amino acid metabolism is multifactorial, i.e. inadequate nutritional intake or protein-restricted diet, disturbed intestinal absorption, hormonal abnormalities and hyperammonemia. In terms of therapy, decreased plasma BCAA level is particularly important, since it is mostly relating to the protein-energy malnutrition. BCAA supplementation seems to be useful to improve plasma amino acid imbalance, protein-energy malnutrition, and subsequently, survival rate of cirrhotic patients.
Amino Acids↗
[Recent advances in the treatment of decompensated liver cirrhosis].
Comprehensive care is required to treat decompensated liver cirrhosis. Fischer's solution and lactulose are usually administered to the patients with hepatic encephalopathy, and improve 98% of those with chronic recurrent type hepatic coma. Benzodiazepine receptor antagonist may be effective to prevent "sensitized brain" in cirrhotics. As to ascites, bed rest, administration of diuretics and albumin infusion improve 88% of the patients. Autoinfusion of filtered and concentrated ascites shows 40% efficacy in patients with ascites, which does not respond to conventional therapy, but is not effective when plasma total bilirubin level is higher than 10 mg/dl. To prevent the development of liver failure in cirrhotic, oral supplementation with branched-chain amino acids is particularly important, in addition to administration of lactulose and prevention of major gastrointestinal bleeding by histamin H2 receptor antagonist and sclerotherapy of esophageal varices.
Albumins↗
The three-dimensional structure of the colicin E3 immunity protein by distance geometry calculation.
The three-dimensional solution structure of the colicin E3 immunity protein (84 residues) was determined by distance geometry calculations. The hydrophilic side of a four-stranded antiparallel beta-sheet constitutes a part of the surface of the protein, and two loops lie on the hydrophobic side of the sheet. All the three specificity-determining residues, which are included in the center of the beta-sheet, display their side groups on the protein surface.
Amino Acid Sequence↗
Structure of novel gangliosides, deaminated neuraminic acid (KDN)-containing glycosphingolipids, isolated from rainbow trout ovarian fluid.
Two acidic glycosphingolipids were isolated and purified from rainbow trout ovarian fluid. They were designated as ovarian fluid gangliosides ofg-2a and ofg-2b. Both of these glycolipids were found to contain glucose, galactose, and N-acetylgalactosamine in a molar ratio of 1:2:1, but they differ by the presence of 2 mol of deaminated neuraminic acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in ofg-2a and 1 mol each of KDN and 9-O-acetyl-KDN in ofg-2b. On the basis of composition analysis, methylation analysis, mild acid hydrolysis, fast atom bombardment mass spectrometry (FABMS), 400-MHz 1H nuclear magnetic resonance spectroscopy, and immunochemical analysis using a monoclonal antibody (mAb.kdn3G), the complete structures of these gangliosides were determined to be KDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2a [(KDN)GD1a] and 9-O-AcKDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2b [(KDN)GD1a(OAc+)]. The ceramide moieties (Cer) in both ofg-2a [(KDN)GD1a] and ofg-2b [(KDN)GD1a(OAc+)] were found by combining of the results from fatty acid analysis and FABMS measurements to be made up of 4-sphingenine and mainly a C24:1 fatty acyl chain (nervonate). The structures of ofg-2a and ofg-2b are novel, and they represent the second example of naturally occurring KDN-gangliosides. Mild acid hydrolysis of both ofg-2a and ofg-2b resulted in formation of (KDN)GM1a.
Animals↗
Sequence-specific 1H and 15N resonance assignments and secondary structure of GDP-bound human c-Ha-Ras protein in solution.
All the backbone 1H and 15N magnetic resonances (except for Pro residues) of the GDP-bound form of a truncated human c-Ha-ras proto-oncogene product (171 amino acid residues, the Ras protein) were assigned by 15N-edited two-dimensional NMR experiments on selectively 15N-labeled Ras proteins in combination with three-dimensional NMR experiments on the uniformly 15N-labeled protein. The sequence-specific assignments were made on the basis of the nuclear Overhauser effect (NOE) connectivities of amide protons with preceding amide and/or C alpha protons. In addition to sequential NOEs, vicinal spin coupling constants for amide protons and C alpha protons and deuterium exchange rates of amide protons were used to characterize the secondary structure of the GDP-bound Ras protein; six beta stands and five helices were identified and the topology of these elements was determined. The secondary structure of the Ras protein in solution was mainly consistent with that in crystal as determined by X-ray analyses. The deuterium exchange rates of amide protons were examined to elucidate the dynamic properties of the secondary structure elements of the Ras protein in solution. In solution, the beta-sheet structure in the Ras protein is rigid, while the second helix (A66-R73) is much more flexible, and the first and fifth helices (S17-124 and V152-L171) are more rigid than other helices. Secondary structure elements at or near the ends of the effector-region loop were found to be much more flexible in solution than in the crystalline state.
Amino Acid Sequence↗
DNA replication of parvovirus B 19 in a human erythroid leukemia cell line (JK-1) in vitro.
A major limitation of studies on the parvovirus B 19, a causative agent of transient aplastic crisis, has been the absence of appropriate cell lines permissive for the virus. In the present study, a human erythroid leukemia cell line (JK-1) was shown to support B 19 virus DNA replication in vitro. Forty-eight hours after virus inoculation of JK-1 liquid cell cultures, the average number of B 19 genome copies was estimated at 3,000 per cell by DNA dot blot analysis. The addition of erythropoietin increased B 19 copy number to 10,000 per cell. The presence of replicative forms of the B 19 virus genome was genome was demonstrated by Southern blot analysis. Although persistent infection of B 19 virus was not observed in JK-1 cells, this culture system will be of value in elucidating the molecular basis of the erythroid specificity of parvovirus B 19.
DNA Replication↗
Operative transluminal laser angioplasty as the sole treatment for late stenoses of femorodistal artery bypass graft: experimental and clinical studies.
To determine the role of Nd:YAG laser thermal angioplasty as the sole treatment for late stenoses of femorodistal artery bypass graft, the lasing effect of a larger size of hot-tip probe (3, 4, and 5 mm) was experimentally studied in vitro. For an adequate lasing effect, 30 watts of laser power output for 3 seconds was needed for the 3 mm probe, 40 watts for the 4 mm probe, and 50 watts for the 5 mm probe, respectively. Based on these results, we used Nd:YAG laser thermal angioplasty alone for 25 grafts, including 16 polytetrafluoroethylene (PTFE) grafts, eight saphenous vein grafts, and one externally supported (EXS) Dacron graft in which the stenotic lesions were detected by deterioration of the Doppler flow waveform pattern or a significant fall in the ankle/brachial pressure index (ABPI). Follow-up was from 3 to 24 months (average of 9 months) for PTFE grafts, from 5 to 21 months (average of 11 months) for saphenous vein grafts, and 13 months for the EXS Dacron graft following femorodistal artery reconstructions. Stenotic lesions were most common in the distal anastomotic sites: 11 PTFE grafts, three saphenous vein grafts, and one EXS Dacron graft. Among these, 13 grafts showed a type II flow waveform pattern at the time of surgery. Clinical success was achieved in 12 of the PTFE grafts (75%), in five of the vein grafts (62.5%), and in the single EXS Dacron graft. Four PTFE and three saphenous vein grafts failed subsequent to repeat intraoperative balloon angioplasty in three and graft extension in three and one graft interposition.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Natural killer cell may impair liver regeneration in fulminant hepatic failure.
The authors established a new experimental model of fulminant hepatic failure (FHF) with prolonged hepatocellular necrosis and impaired liver regeneration, and evaluated the immunological mechanisms related to the impaired liver regeneration in this model. A novel lipid A analogue, FS-112, was injected intravenously into male Balb/c mice, followed by a 70% partial hepatectomy 2 days later. Serum levels of T.Bil. and ALT rose 7 days after the partial hepatectomy, as compared with controls. In mice pretreated with FS-112, labeling indices of both BrdU and PCNA 36 hrs after the partial hepatectomy were significantly lower than those in the controls. Splenic lymphocytes harvested from the FHF mice 1-5 days after the partial hepatectomy showed a cytotoxic activity against regenerating hepatocytes with a peak effect on day 5. Cytotoxic activity against YAC-1 cells was also found up to 5 days after the partial hepatectomy, and resembled that directed against the regenerating hepatocytes. On the 5th day of FS-112 administration, there was a marked rise in the production of IFN-gamma from splenocytes. When FK-506, an immunosuppressive agent, was given intracutaneously daily for 7 days, serum levels of T.Bil. and ALT significantly decreased, as compared with controls. Furthermore, the PCNA-labeling index 36 hrs after the partial hepatectomy was enhanced by the administration with FK-506 in the FHF mice. These results strongly suggest that the NK cells activated by IFN-gamma may be involved in killing the regenerating liver cells, and thus play a role in the pathogenesis of the impaired liver regeneration in FHF.2+ recovery from the impaired liver regeneration in FHF.
Animals↗
Present status of autoimmune hepatitis in Japan.
The clinical and biochemical features of patients with autoimmune hepatitis (AIH) in Japan during the 15-year period, 1975 to 1990, were evaluated by a nationwide survey using a questionnaire prepared by the Intractable Diseases Study Group organized by the Ministry of Health and Welfare. Data on a total of 866 cases with AIH were collected and analyzed, and of these, 632 cases underwent follow-up study. AIH was predominant in females, with a male:female ratio of approximately 2:19. Biochemical investigation on the occasion of the first examination showed abnormalities of liver function tests, including increased serum total bilirubin, transaminase activity and gamma-globulin levels. The main complications of autoimmune diseases were rheumatoid arthritis, Sjögren's syndrome and chronic thyroiditis. All patients with complications were female. Of 253 AIH patients, 50 were positive for anti-C100-3 antibody. ICG clearance and platelet count, which are stigmata of liver cirrhosis, were the main factors of prognostic importance in AIH. Therefore, early diagnosis prior to the development of liver cirrhosis is important to improve the prognosis of AIH.
Autoimmune Diseases↗
A 15N-1H nuclear magnetic resonance study on the interaction between isoleucine tRNA and isoleucyl-tRNA synthetase from Escherichia coli.
Imino 15N and 1H resonances of Escherichia coli tRNA(lIle) were observed in the absence and presence of E coli isoleucyl-tRNA synthetase. Upon complex formation of tRNA(lIle) with isoleucyl-tRNA synthetase, some imino 15N-1H resonances disappeared, and some others were significantly broadened and/or shifted in the 1H chemical shift, while the others were observed at the same 15N-1H chemical shifts. It was indicated that the binding of tRNA(lIle) with IleRS affect the following four regions: the anticodon stem, the junction of the acceptor and T stems, the middle of the D stem, and the region where the tertiary base pair connects the T, D, and extra loops. This result is consistent with those of chemical footprinting and site-directed mutagenesis studies. Taken together, these three independent results reveal the recognition mechanism of tRNA(lIle) by IleRS: IleRS recognizes all the identity determinants distributed throughout the tRNA(lIle) molecule, which induces changes in the secondary and tertiary structures of tRNA(lIle).
Base Sequence↗
Intratumoral heterogeneity of DNA ploidy and regional differences in epidermal growth factor and epidermal growth factor receptor of esophageal carcinoma.
Intratumoral regional differences in DNA ploidy patterns, and expression of epidermal growth factor (EGF) and EGF receptor (EGF-R) were studied to evaluate the biological and clinical significance of intratumoral DNA heterogeneity in 23 cases of esophageal carcinoma. Multiple specimens were subjected to histologic grading of carcinoma, DNA analysis and immunohistochemistry. DNA heterogeneity was found in 34.8% of the cases. Expression of EGF and EGF-R within a single tumor was observed in 69.6% and 73.9% of the lesions examined, respectively. A positive correlation was noted between the expression of EGF and that of the EGF-R. EGF expression showed positive correlation with the DNA index, but not with the proliferative index. There was no relationship between DNA heterogeneity and the degree of histopathological differentiation of carcinoma. Cases with DNA heterogeneity showed better prognosis than those with DNA homogeneity. The present study suggests that esophageal carcinoma consists of carcinoma cells with intratumoral regional polymorphism and variable types of clones. Furthermore, the autocrine mechanism of EGF and EGF-R could be one of the contributory factors on the development of DNA abnormalities during tumor proliferation.
Adult↗
The combined effects of all-trans retinoic acid and granulocyte colony-stimulating factor as a differentiation induction therapy for acute promyelocytic leukemia.
A 61-year-old male with acute promyelocytic leukemia (APL) had been in complete remission for the previous 15 months, but his APL relapsed with neutropenia. Although promyelocytes in bone marrow were reduced after administration of 60 mg all-trans retinoic acid (ATRA) daily, myelocytes were predominant on the myelogram and neutropenia did not recover. By adding 75 micrograms of granulocyte colony-stimulating factor (G-CSF) daily, neutrophils accounted for 35.0-55.5% of the myelogram, and the peripheral neutrophil count rose dramatically. Such morphological differentiation of myeloid series was also ascertained in terms of their functions of both neutrophil alkaline phosphatase activity and active oxygen producing capacity. This case supports the concept that G-CSF accelerates ATRA-induced neutrophilic differentiation of blast cells in APL.
Alkaline Phosphatase↗
Differentiation induction of human promyelocytic leukemia cells by acyclic retinoid (polyprenoic acid).
Acyclic retinoid (all-trans-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid) has a slightly different structure from all-trans retinoic acid (ATRA), while it binds cellular retinoic acid-binding protein with a similar binding affinity to that of ATRA. We studied the in vitro efficacy of acyclic retinoid for the differentiation induction of human promyelocyte-derived HL-60 cell line and primary cultured blast cells obtained from 8 patients with acute non-lymphocytic leukemia (ANLL) including 3 acute promyelocytic leukemia (APL) patients. HL-60 cells and ANLL cells were incubated with or without retinoids for 5 days. Acyclic retinoid induced the differentiation of HL-60 cells and APL cells at 10(-6) mol/l, while ATRA induced differentiation at 10(-7) mol/l. These concentrations were well below those that affected cell growth and viability. Although ATRA has an excellent capacity for differentiation induction of HL-60 and APL cells, it is also known to have severe, sometimes fatal, adverse effects, including retinoic acid syndrome. In contrast, acyclic retinoid is reported to have a much wider safety margin than that of ATRA. A clinical trial of acyclic retinoid for the differentiation induction therapy of APL may be worthwhile.
Adolescent↗
Flow cytometric determination of active oxygen (hydroperoxide) produced by peripheral blood neutrophils in patients with hematological disorders.
We analyzed active oxygen (hydroperoxide; H2O2) production by peripheral neutrophils in various hematological diseases by flow cytometry. One hundred microliters of heparinized fresh blood was sequentially incubated at 37 degrees C with 2',7'-dichlorofluorescein diacetate and with or without phorbol myristate acetate (PMA). After hemolysis, the pelleted white blood cells were subjected to flow cytometry, and the neutrophil fraction was gated on the cytogram. Production of H2O2 by the fraction was estimated by determining the increase in the relative intensity of fluorescence emitted from the fraction in response to stimulation by PMA. In controlled chronic myelogenous leukemia (CML) (WBC < 1 x 10(10)/1), H2O2 production was normal, while in uncontrolled CML (WBC > or = 1 x 10(10)/1), it was reduced. In myelodysplastic syndrome (MDS), H2O2 production was also reduced, but no significant difference was observed among FAB classification disease types in MDS patients. In untreated acute non-lymphocytic leukemia (ANLL), H2O2 production was reduced, while in the complete remission stage of ANLL, its level was normal, suggesting recovery from normal clones. In aplastic anemia, the H2O2 production level was normal. Steroid therapy might be responsible for the reduction of H2O2 production in non-Hodgkin's lymphoma and multiple myeloma. The production of H2O2 is closely related to the oxygen-dependent bactericidal activity of neutrophils, and, hence, can be utilized as an index to indicate susceptibility to infection. This neutrophil function can be determined easily in ordinary clinical facilities by using flow cytometry, and care should be taken to prevent infection when H2O2 production is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
[Cellular retinoid-binding proteins].
This paper will review the function of cellular retinoid-binding proteins and receptors (RAR), especially to address recent works on cellular uptake, intracellular transport, biosynthesis and metabolism of retinoids. Cellular retinol-binding protein (CRBP) binds retinol and retinal, cellular retinoic acid-binding protein (CRABP) binds retinoic acid, both of which have a molecular weight of 16 kDa, and cellular retinal-binding protein (CRALBP) binds retinal with a molecular weight of 36 kDa. CRBP (I) functions in cellular uptake of retinol from the plasma, solubilizes and renders retinol nontoxic in the aqueous system, and presents retinol to the appropriate enzymes to biosynthesize retinoic acid (an active form of retinoids) or retinyl esters (a storage form). CRBP (II) mainly distributes in the absorptive cell in the small intestine and functions in absorption of retinoids and carotenoids to biosynthesize retinyl esters present in the chylomicron. CRBP (III) is recognized as one of oncofetal proteins and binds both retinol and retinoic acid, the function of which still remains unclear. CRABP (I), previously recognized as a transport protein of retinoic acid to the nucleus, is now assumed to sequester retinoic acid from retinoic acid receptor(s) in the tissue where retinoic acid levels are required to be low. CRABP (I) also functions in the catabolism of retinoic acid to modulate its concentration in the cell. CRABP (II), expressed in the developmental stage of the fetus, is suggested to modulate the action of retinoic acid as a 'morphogen'.
Animals↗