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Biomedical subjects

Y Tagawa

Publications and source records attributed to Y Tagawa.

At least 91 records · Page 5Linked to original sources

Fisher syndrome associated with IgG anti-GQ1b antibody following infection by a specific serotype of Campylobacter jejuni.

OBJECTIVE: The purpose of the study was to describe clinical and serologic features of Fisher syndrome associated with IgG anti-GQ1b ganglioside antibody following Campylobacter jejuni enteritis. DESIGN: A clinical trial. PARTICIPANTS: Four consecutive patients with Fisher syndrome were studied. INTERVENTION: Samples of sera from four patients were tested for reactivity to GQ1b ganglioside by enzyme-linked immunosorbent assay (ELISA). Campylobacter jejuni strains isolated from samples of stool from three patients were serotyped by the method of Penner and Hennessy and that of Lior. MAIN OUTCOME MEASURES: Serum IgG anti-GQ1b antibody titer and serotypes of C. jejuni. RESULTS: Diplopia occurred 8 to 14 days after the onset of diarrhea. Campylobacter jejuni was isolated from samples of stool from all of the patients. ELISA revealed a high serum IgG anti-GQ1b antibody titer for all four patients. Two patients had high serum titers of other antiganglioside antibodies frequently related to Guillain-Barré syndrome. These two patients developed limb weakness following the onset of ophthalmoplegia. The C. jejuni serotype was Penner's serotype 2 for all three of the patients tested. CONCLUSIONS: These findings suggest that C. jejuni, especially Penner's serotype 2, enteritis could trigger development of Fisher syndrome associated with IgG anti-GQ1b antibody.

Adolescent↗

Endothelin in liver cell injury and regeneration after 70% hepatectomy with portal ischemia.

Hepatic ischemia-reperfusion (IR) injury caused by portal vein clamping is a common problem in hepatobiliary surgery. Endothelin (ET) is a potent vasoconstrictor and is associated with IR injury. This study evaluated the effect of ET on liver cell injury and hepatic regeneration after hepatectomy with IR. The portal veins of rats were clamped for 20 min, then unclamped and a 70% partial hepatectomy was performed. TAK-044 (TAK), the nonselective ETA/ETB receptor antagonist, was administered s.c. 30 min before laparotomy [TAK(+)]. Portal blood ET-1, GOT levels, hepatic blood flow, histologic change, DNA synthesis of hepatocytes, and the relationship of Ito cells and perisinusoidal cells were evaluated. ET-1 concentration increased after IR and was significantly higher in the TAK(+) group owing to the blockade of ET receptors. Increased GOT levels and sinusoidal congestion were reduced, but DNA synthesis of hepatocytes and hepatic blood flow did not change in the TAK(+) group. Changes in desmin staining showed that Ito cells might be related to IR injury. In conclusion, ET-1 was associated with IR injury and TAK-044 reduced but did not affect hepatocyte DNA synthesis after partial hepatectomy.

Animals↗

Induction of granulomas in interferon-gamma gene-disrupted mice by avirulent but not by virulent strains of Mycobacterium tuberculosis.

To gain a better understanding of the pathological role of interferon-gamma (IFN-gamma) in specific granuloma formation, IFN-gamma gene-deficient mice (BALB/c and C57BL/6) were produced. The IFN-gamma gene in embryonic stem (ES) cells was disrupted by inserting the beta-galactosidase gene (lacZ) and the neomycin resistance gene (neo) at the translation initiation site in exon 1 by homologous recombination. Six-week-old IFN-gamma-deficient and wild-type mice were inoculated with 10(3)-10(7) bacilli of various strains of Mycobacterium tuberculosis (Kurono, H37Rv, H37Ra and BCG Pasteur) through their tail veins. The mice were examined 7 weeks later for granuloma formation. The avirulent BCG Pasteur and H37Ra strains (10(3)-10(4) bacilli/ml) induced granulomas in the spleen, liver and lungs of IFN-gamma-deficient mice. The granulomas consisted of epithelioid macrophages and Langhans multinucleate giant cells, but lacked caseous necrosis. The virulent Kurono and H37Rv strains induced disseminated abscesses but not granulomas in various organs of IFN-gamma-deficient mice and Mac-3-positive macrophages were not detected in the abscess lesions. These results suggest that IFN-gamma may be primarily responsible for macrophage activation and that other factor(s) may be involved in the granuloma formation mechanism.

Animals↗

Murine coronavirus-induced subacute fatal peritonitis in C57BL/6 mice deficient in gamma interferon.

Gamma interferon-deficient (IFN-gamma-/-) mice with a C57BL/6 background were infected intraperitoneally with mouse hepatitis virus strain JHM (JHMV). In contrast to IFN-gamma-+/- and IFN-gamma+/+ mice, JHMV persisted in IFN-gamma-/- mice and induced death during the subacute phase of the infection. Unexpectedly, infected IFN-gamma-/- mice showed severe peritonitis accompanying the accumulation of a viscous fluid in the abdominal and thoracic cavities in the subacute phase. Destructive changes of hepatocytes were not observed. Administration of recombinant IFN-gamma protracted the survival time of IFN-gamma-/- mice after JHMV infection. These results demonstrate that IFN-gamma plays a critical role in viral clearance in JHMV infection. They also show that a resultant persistent JHMV infection induces another form of disease in IFN-gamma-/- mice, which bears a resemblance to feline infectious peritonitis in cats.

Alanine Transaminase↗

Minimal number of plasma exchanges needed to reduce immunoglobulin in Guillain-Barré syndrome.

Plasma exchange (PE) in Guillain-Barré syndrome (GBS) probably removes pathogenic antibodies. Results of a recent clinical study by the French Cooperative Group suggest that at least two sessions of PE are required. As an alternative procedure, we examined the effect of the number of PEs on the reduction of immunoglobulins in 11 patients. A significant immunoglobulin decrease was obtained in the first two sessions but not in subsequent ones. Based on the French trial results and our findings, we conclude that at least two PEs are needed for treating GBS.

Gangliosides↗

Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells.

We studied the effects of bafilomycin A1, a potent and specific inhibitor of vacuolar H+ ATPase (V-ATPase), on the process of autophagy in rat hepatoma cell line, H-4-II-E cells. To induce autophagy, cells were transferred from Dulbecco's modified Eagle medium containing 12% fetal calf serum into Hanks' balanced salt solution. When bafilomycin A1 was added to Hanks' balanced salt solution, endogenous protein degradation was strongly inhibited and numerous autophagosomes accumulated in H-4-II-E cells, whereas autolysosomes decreased in number. Acid phosphatase activity was not detected in the autophagosomes which accumulated in the presence of bafilomycin A1, suggesting that fusion between autophagosomes and lysosomes was disturbed by this drug. Inhibition of the fusion was reversible, and the autophagosomes changed into autolysosomes after the removal of the inhibitor. Bafilomycin A1 also prevented the appearance of endocytosed HRP in autophagic vacuoles. These results suggested that acidification of the lumenal space of autophagosomes or lysosomes by V-ATPase is important for the fusion between autophagosomes and lysosomes.

Amino Acids↗

Frequency of chromosome 7 gain in human breast cancer cells: correlation with the number of metastatic lymph nodes and prognosis.

Trisomy 7 has been reported in various malignant neoplasms, but there are no reports in breast cancer. In order to evaluate the contribution of chromosome 7 gain to breast cancer, we investigated the relationship of numerical abberation of chromosome 7 with clinicopathological variables and prognosis in seventy-nine breast cancer cases (invasive carcinomas) using the technique of fluorescence in situ hybridization (FISH) on paraffin-embedded sections. A significant correlation of the frequency of cells with extra copies of chromosome 7 (percent polysomy 7 cell score) was found with tumor size, regional lymph node status, tnm stage, histological extension, estrogen receptor (ER), and DNA ploidy. The number of metastatic lymph nodes was positively correlated with percent polysomy 7 cell score (correlation coefficient=0.623, p < 0.01). Furthermore, cases with a high percent polysomy 7 cell score had a shorter disease-free survival and overall survival times, especially in the lymph node-positive group. It was demonstrated that percent polysomy 7 cell value was closely associated with lymph node metastasis and prognosis and might be a useful prognostic predictor of breast cancer patients.

Adenocarcinoma↗

[Analysis of drug-induced apoptosis in human leukemic cell line (HL-60)].

Cell death plays an essential role in cell homeostasis and the pathological process in cancer. Apoptosis has been identified by the internucleosomal DNA cleavage which appears to be associated with endonuclease activation. Proteolysis is considered to be an early event in apoptosis. We studied the effects of proteolysis on early apoptotic events, such as chromatin condensation, nuclear breakdown, DNA breakage and sensitivity to denaturation induced by anticancer drugs (camptothecin: CAM, 5-azacytidine: AZA) on HL-60 cells. CAM induced apoptosis on S phase and AZA on G1 phase. The internucleosomal DNA cleavage shown by both the presence of DNA fragments during gel electrophoresis and a large number of in situ DNA strands breaks (revealed in high intensity fluorescence FITC of cells in the TdT reaction) was prevented by the protease inhibitor, TPCK (N-tosyl-L-phenylalanine chlorometyl-ketone), as well as by an inhibitor of the apoptosis-associated endonuclease, ZnSO4. The protective effects were observed under conditions in which apoptosis was induced by agents with a different mechanism of action, such as the DNA damaging drug. CAM (topo-isomerase inhibitor), and an RNA antimetabolite, AZA. The protease inhibitor inhibits early events of apoptosis such as chromatin condensation, nuclear breakdown, DNA breakage and sensitivity to denaturation, which have different structures and a different mechanism of interaction with drugs. The results suggest that control of protease inhibitor may be a useful strategy to treat cancers.

Antimetabolites, Antineoplastic↗

[Long-term survival in terms of DNA-RNA contents in breast cancer].

Fifty-nine primary breast cancers were analyzed by flow cytometric cellular DNa-RNA contents stained by acridine orange simultaneous DNA-RNA double staining. Forty-three cases (72.9%) out of 59 had abnormal stemlines (DNA aneuploidy), and 16 normal ones (DNA diploidy). RNA indices widely ranged from 1.41 to 9.02 (2.99). There was no correlation between DNA indices and RNA indices. The patients with DNA diploidy had a better prognosis than those with DNA aneuploidy, but the differences were not significant. The patients with a high RNA index of more than 4.0 had a significantly poorer prognosis than those with an index of less than 4.0. Those results suggest that RNA contents, and DNA contents are independent prognostic factors, and especially RNA contents may be a good prognostic factor in long-term survival in breast cancer.

Breast Neoplasms↗

Biomechanical effect and clinical application of the hip joint moment reduction brace.

A new brace, the hip joint moment reduction brace, has been designed and constructed. The basic construct of the brace incorporates only the thigh, and it minimally restricts one's activities of daily living. The concept of the brace is to reduce the frontal plane moment of the applied force against which the abductor muscle must contract to balance, and this reduction of the frontal plane moment results in reduction of the abductor muscle force. The brace uses the mechanism of the ischial weightbearing and lessens the abductor moment by transmitting load from the ischium through the condyle of the femur. In gait testing, the maximum ischial load taken up by the brace was 36.9% of the ground reaction force in the late stance phase, and the integrated electromyogram of the abductor muscle was reduced by 32.6% during the whole stance phase using this brace. These findings confirmed a reduction in the frontal plane moment of the hip joint and the potential for reduction in the load on the hip joint. The hip joint moment reduction brace is recommended as effective conservative management of hip disorders, such as coxarthrosis, that are caused or worsened by biomechanical insufficiency.

Adult↗

Disposition of the new antirheumatic agent ethyl 4-(3,4-dimethoxyphenyl)- 6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (TAK-603) in rats and dogs.

The disposition of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4- triazol-1-ylmethyl) quinoline-3-carboxylate (CAS 158146-85-1, TAK-603) after single oral dosing of 14C-labeled TAK-603 ([14C]TAK-603) at 10 mg/kg to rats and dogs was studied. In rats, the concentration of unchanged drug in plasma reached a peak (Cmax, 0.31 microgram/ml) 2 h (Tmax) after dosing of TAK-603 and declined biphasically with apparent half-lives (t 1/2 alpha, t 1/2 beta) of 1.5 and 3.6 h. In dogs, Tmax, Cmax, T 1/2 alpha, and t 1/2 beta were 1.7 h, 0.36 microgram/ml, 1.2, and 10.8 h, respectively. [14C]TAK-603 dosed orally was absorbed quantitatively in rats, while the extent of absorption in dogs was 54%. The bioavailability of TAK-603 was 53% and 42% in rats and dogs, respectively. In rats, 14C was distributed widely in various tissues, with relatively high concentrations in the liver, adrenal gland, and gut. The elimination of 14C from the thyroid was slower than that from other tissues. Unchanged TAK-603 and its pharmacologically active metabolite, M-I, which has the same potency as TAK-603, were distributed in articular soft tissues and synovial fluids, as target tissues, in rats and dogs, respectively. After oral administration of [14C]TAK-603, most of the 14C dosed was excreted within 48 h in rats and within 96 h in dogs. In both animals, a greater amount of the 14C dosed was excreted in feces than in urine. In biliary duct cannulated rats given [14C]TAK-603 intraduodenally, 69% of the dose was excreted in bile, and biliary 14C in part underwent enterohepatic circulation.

Administration, Oral↗

[Clinical utility of measurement for anti-GM1 and anti-GQ1b antibodies].

Gangliosides, important constituents of the plasma membrane, are particularly abundant in the nervous system. Some patients develop Guillain-Barré syndrome after the administration of bovine brain gangliosides. We previously showed existence of molecular mimicry between GM1 ganglioside and lipopolysaccharide of Campylobacter jejuni isolated from the patients with Guillain-Barré syndrome, and that between GQ1b and C. jejuni isolated from Fisher's syndrome patients. Moreover, the anti-ganglioside antibody can cause motor nerve dysfunction in vitro. These support the pathogenic significance of anti-ganglioside antibodies. To clarify clinical utility of measurement for anti-GM1 and anti-GQ1b antibodies, we investigated sera from 429 patients with immunoneurological diseases included Fisher's syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoparesis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and controls by enzyme-linked immunosorbent assay. We found very high titers of IgM anti-GM1 antibody in serum from a patient who had been diagnosed as having motor neuron disease. By further electrophysiological study, the patient was diagnosed as having multifocal motor neuropathy. Presence of high IgG anti-GM1 antibody titers was useful for supporting diagnosis of Guillain-Barré syndrome, IgG anti-GQ1b antibody was detected in patients who had paresis of extraocular muscles in Fisher's syndrome, Guillain-Barré syndrome, Bickerstaff's brainstem encephalitis, and acute ophthalmoparesis. This study showed that the measurement for anti-GM1 and anti-GQ1b antibodies are very useful.

Adolescent↗

Transformation of a virulence associated gene of Haemophilus somnus into a strain lacking the gene.

The role of a 76 kDa surface antigen (p76) of Haemophilus somnus in virulence was investigated. The p76 gene from a virulent isolate of H. somnus (strain 2336) was introduced into an asymptomatic carrier strain (129Pt) lacking this gene. This was accomplished by the development of a system for genetic exchange in H. somnus. The cloned p76 gene was inserted into the broad host range vector pLS88, electroporated into H. influenzae for modification and then into the H. somnus strain 129Pt. The recombinant plasmid was characterized from selected transformants and expression of the p76 protein was demonstrated by Western immunoblotting. However, transformants were not serum resistant and surface exposure of the recombinant protein could not be detected, suggesting that additional genetic elements might be required for export.

Antigens, Bacterial↗

Suppression of concanavalin A-induced hepatitis in IFN-gamma(-/-) mice, but not in TNF-alpha(-/-) mice: role for IFN-gamma in activating apoptosis of hepatocytes.

Con A-induced hepatitis (Con A-hepatitis) is a hepatitis model in which hepatic injury is supposed to be caused by cytokines from activated T cells. To elucidate the pathogenesis of this disease, we analyzed the roles of IFN-gamma and TNF-alpha using deficient mice of these cytokines. Development of hepatitis was reduced significantly in IFN-gamma(-/-) mice, while susceptibility of TNF-alpha(-/-) mice was not changed. Interestingly, apoptotic cell death was observed in the affected livers of control or TNF-alpha(-/-) mice, but not in those of IFN-gamma(-/-) mice. Fas mRNA expression was increased in the livers of hepatitis mice, but less abundantly in those of IFN-gamma(-/-) mice. Since apoptosis of liver cells was rarely observed in Con A-treated lpr/lpr mice, involvement of the Fas-Fas ligand system in this apoptotic process was suggested. These observations suggest that IFN-gamma plays a central role in Con A-hepatitis by activating Fas-induced apoptosis of liver cells.

Animals↗

Differences in spatial localization and chromatin pattern during different phases of cell cycle between normal and cancer cells.

We studied differences in chromatin patterns and the spatial localization of centromeres of chromosome 11 during the cell cycle between normal peripheral blood lymphocytes (PBL) and human promyelocytic leukemia cells (HL-60) using fluorescence in situ hybridization. The pericentromeres in both cells were located at the periphery during Gq (quiescent) phase, but moved towards the nuclear center in G1 and mid-S phase. During G2, the pericentromeres of PBL continued to move towards the nuclear center whereas those of HL-60 returned to the periphery. The angle defining the spatial location of two pericentromeres, in reference to the center of the nucleus, increased in PBL cells from a mean of 67 degrees during Gq phase to 106 degrees during G1 phase (P < 0.01), and the two pericentromeres remained wide apart throughout the entire cell cycle. In HL-60, the angle also increased during G1, but then decreased during mid-S and G2 phases. Both cells exhibited pericentromeric signals during Gq that were round and compact, and the entire chromatin was loosely condensed. The signal became more loose and dispersed during the G1 and mid-S phases. The pericentromere signal varied during G2 and was generally rod-like or bipartite with condensation of the entire chromatin or chromosome-like. Our results suggest that subtle but important differences in spatial localization of pericentromeres are present during the interphase between normal PBL and HL-60 cells.

Cell Cycle↗

Dominant negative mutant of ionotropic glutamate receptor subunit GluR3: implications for the role of a cysteine residue for its channel activity and pharmacological properties.

We reported that a 33-amino-acid deletion (from tyrosine-715 to glycine-747) in a putative extracellular loop of GluR3 produced a mutant that exhibited dominant negative effects upon the functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [Sekiguchi et al. (1994) J. Biol. Chem. 269, 14559-14565]. In this study, we searched for a key residue in the dominant negative effects to explore the mechanism and examined the role of the residue in the function of the AMPA receptor. We prepared 20 GluR3 mutants with amino acid substitutions within the 33-amino-acid-region, and dominant negative effects were tested electrophysiologically in Xenopus oocytes co-expressing the mutant and normal subunits. Among the mutants, only a GluR3 mutant in which an original cysteine (Cys)-722 was replaced by alanine exhibited a dominant negative effect comparable with that of the original mutant in which the entire 33-amino-acid segment is deleted. The co-expression of the Cys-722 mutant did not inhibit the translation of normal subunits in oocytes. The Cys-722 mutant formed a functional homomeric receptor with significantly higher affinity for glutamate or kainate than a homomeric GluR3 receptor. The Cys-722 mutation greatly enhanced the sensitivity of GluR3 for aniracetam, which alters kinetic properties of AMPA receptors. The kainate-induced currents in oocytes expressing the Cys-722 mutant alone showed strong inward rectification. These results suggest that the Cys-722 in GluR3 is important for dominant negative effects and plays a crucial role in the determination of pharmacological properties in AMPA receptor function.

Amino Acid Sequence↗