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Biomedical subjects

S Shoji

Publications and source records attributed to S Shoji.

At least 19 recordsLinked to original sources
PubMed1998

Downbeat nystagmus in two siblings with spinocerebellar ataxia type 6 (SCA 6).

We report two siblings with spinocerebellar ataxia type 6 (SCA 6), both showing downbeat nystagmus (DBN) as a predominant clinical feature. Familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA-2) and SCA 6 are allelic disorders, and interestingly, the occasional presence of DBN in EA-2 was reported. Our observations suggest that common molecular mechanisms might underlie DBN in FHM, EA-2 and SCA 6. Then, these disorders should be kept in mind in diagnosing patients with DBN.

Adult↗
PubMed1998

Essential roles of Lyn in fibronectin-mediated filamentous actin assembly and cell motility in mast cells.

Although the requirement for c-Src in extracellular matrix (ECM)-mediated fibroblast motility has been well established, the roles of hemopoietic Src family protein tyrosine kinases in leukocyte migration have not been fully elucidated. To address the issue, we analyzed fibronectin (Fn)-mediated adhesion signaling in rat basophilic leukemia (RBL) 2H3 cells overexpressing 1) Csk, 2) a membrane-anchored, gain-of-function Csk (mCsk), and 3) a kinase-defective mCsk (mCsk(-)). Parent RBL2H3 cells, expressing autoactivated c-kit, readily adhered to Fn-coated surface, developed typical leukocyte adhesion machinery (podosome), and migrated toward Fn without cytokine priming, thus provided a simple experimental system to analyze Fn-mediated outside-in signaling. While overexpression of Csk or the Csk mutants did not significantly affect cell adhesion to the Fn surface or alpha5 integrin recruitment to the attachment sites, Csk suppressed and mCsk almost abolished Fn-mediated tyrosine phosphorylation of paxillin, filamentous actin assembly to podosomes, and cell migration, but mCsk(-) did not. Coexpression of LynA devoid of C-terminal negative regulatory tyrosine in mCsk cells successfully restored Fn-mediated podosome formation and cell migration. Coexpression of c-Src lacking the C-terminal tyrosine reconstructed podosomes, but could not restore the cell migration regardless of its expression level. Collectively, these observations provide evidence that Src family protein tyrosine kinases are required, and that Lyn could transmit sufficient signal for Fn-mediated cytoskeletal changes leading to cell locomotion in RBL2H3 cells, and they suggest that Lyn and c-Src are differentially involved in cell motility.

Actins↗
PubMed1998

An allosteric drug, o,o'-bismyristoyl thiamine disulfide, suppresses HIV-1 replication through prevention of nuclear translocation of both HIV-1 Tat and NF-kappa B.

The efficacy of o,o'-bismyristoyl thiamine disulfide (BMT) was examined in detail against HIV-1 laboratory isolates (HTLV-IIIB, JRFL, and MN), primary isolates (KMT and KMO), and simian immunodeficiency virus (SIVmac251) in vitro. BMT inhibited the replication of HIV-1 in both laboratory and primary isolates in vitro. In addition, BMT exhibited antiviral activity against SIVmac251. Minimizing energy studies of BMT structure reveal that a trans-disulfide of thiamine (holo drug) disulfide (TDS, protodrug) is allosterically transited to the reactive twisted disulfide of BMT (allo drug) by o,o'-bismyristoyl esterification of TDS. BMT inhibits nuclear translocation of both HIV-1 transactivator (TAT) and the cellular transcriptional nuclear factor-KB (NF-kappa B), resulting in the suppression of HIV-1 replication.

Allosteric Site↗
PubMed1998

Emergence of immunoreactivities for phosphorylated tau and amyloid-beta protein in chronic stage of fluid percussion injury in rat brain.

Head injury is one of the potential environmental factors in Alzheimer's disease (AD). To study the chronic stage of concussive brain injury, histological analyses were performed 2-6 months after right lateral fluid percussion (FP) brain injury (3.6-4.8 atm) in rats. Six months after injury, numerous normal-looking neurons in the telencephalon and brain stem were immunoreactive with either antibody to phosphorylated tau or with four antibodies to beta-amyloid protein. Neuronal counts in the cortices were gradually decreased after injury, up to 42% loss at 6 months after injury. These neuropathological changes suggest that this animal model could serve as a good animal model of neurodegenerative diseases such as AD.

Amyloid beta-Peptides↗
PubMed1998

Horner's syndrome associated with mononeuritis multiplex due to cytomegalovirus as the initial manifestation in a patient with AIDS.

We report on a 60-year-old male with AIDS who presented Horner's syndrome that was associated with mononeuritis multiplex due to cytomegalovirus (CMV) infection. This is the first case who presented Homer's syndrome in the course of AIDS. Horner's syndrome associated with mononeuritis multiplex in this patient was the initial manifestation without any opportunistic infections. Since Horner's syndrome and mononeuritis multiplex in the present case were both improved by ganciclovir, it is important to consider CMV infection when Horner's syndrome or mononeuritis multiplex is observed in immunocompromised patients, such as those with HIV-1 infection or AIDS, even if they do not show any other opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1998

Identification of a single nucleotide insertion polymorphism in the upstream region of the insulin promoter factor-1 gene: an association study with diabetes mellitus.

Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of insulin gene expression and for the development of the pancreas. In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide insertion polymorphism was found in a guanine triplet at 108 bp upstream of the translation start site. The G insertion allele (G4 allele) was found to be common in the Japanese population, at a frequency of 0.50. The prevalence of G3 homozygotes was higher in IDDM patients (35%) and lower in NIDDM patients (17%) than in normal control subjects (28%, p=0.049). In the NIDDM group, the ratio of insulin treatment tended to be higher in subjects homozygous for the G3 allele, although the genotype was not significantly associated with basal C-peptide levels. The polymorphism is unlikely to be a major contributor to the insulin deficiency of diabetes. However, the polymorphic locus, or an unknown mutation which is in linkage disequilibrium with the polymorphism, could be involved in the pathophysiology of diabetes. The high heterozygosity may be useful for genetic linkage studies of other mutations within and near the IPF1 gene.

Adolescent↗
PubMed1998

Amyloid-beta-protein isoforms in brain of subjects with PS1-linked, beta APP-linked and sporadic Alzheimer disease.

To determine whether similar abnormalities of various soluble full-length and N-terminal truncated Abeta peptides occur in postmortem cerebral cortex of affected PS1 mutation carriers, we examined the amounts of two amyloid species ending at residue 40 or at residues 42(43) using sandwich ELISA systems. Our results indicate that PS1 mutations effect a dramatic accumulation in brain of the highly insoluble potentially neurotoxic long-tailed isoforms of the Abeta peptide such as Abeta1-42(43) and Abetax-42(43). This enhancing effect of PS1 mutation on Abetax-42(43) deposition was highly similar to that of a betaAPP mutation (Val717Ile) but the effects on Abetax-40 production were significantly different between these two causal genes. In contrast to previous studies of soluble Abeta in plasma and in supernatants from cultured fibroblasts of subjects with PS1 mutations, our studies also show that there is an increase in insoluble Abetax-40 peptides in brain of subjects with PS1 mutations.

Adult↗
PubMed1998

CYFRA 21-1, a cytokeratin subunit 19 fragment, in bronchoalveolar lavage fluid from patients with interstitial lung disease.

1. It has been suggested that CYFRA21-1, a cytokeratin subunit 19 fragment, is potentially useful for diagnosis and monitoring of lung carcinoma. However, serum levels of CYFRA21-1 are also increased in a high proportion of patients with interstitial lung disease. In this study we measured CYFRA21-1 levels in bronchoalveolar lavage fluid from 10 normal subjects, 18 patients with idiopathic pulmonary fibrosis and 14 patients with sarcoidosis, and determined whether any relationship exists between CYFRA21-1 levels in bronchoalveolar lavage fluid and clinical parameters. 2. CYFRA21-1 levels in bronchoalveolar lavage fluid were significantly higher in patients with sarcoidosis (mean value 8.3 ng/ml, P < 0.01) and idiopathic pulmonary fibrosis (42.5 ng/ml, P < 0.005) than in normal controls (1.0 ng/ml). Moreover, higher CYFRA21-1 levels in bronchoalveolar lavage fluid were found in sarcoidosis patients in radiological stage 2 or 3 than in those in stage 1. In patients with idiopathic pulmonary fibrosis, there was a significant correlation between CYFRA21-1 levels, and percentage of inflammatory cells in bronchoalveolar lavage fluid (r = 0.56, P < 0.05) and the magnitude of the alveolar--arterial oxygen pressure difference [P(A-a)O2] gradient (r = 0.66, P < 0.01). 3. Serial bronchoalveolar lavage samples were obtained from six patients with clinically active pneumonitis after they had undergone systemic corticosteroid therapy. CYFRA21-1 levels were significantly lower after these patients exhibited clinical improvement (P < 0.05). 4. These findings suggest that the level of CYFRA21-1 in bronchoalveolar lavage fluid is a useful marker for the clinical diagnosis of pneumonitis, and is also adequate for the evaluation of disease activity, especially over the course of treatment.

Adrenal Cortex Hormones↗
PubMed1998

Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Though direct measurement of endogenous NO has been difficult in humans, we have recently found that measurement of NO derivatives in induced sputum may be useful for assessing airway inflammation in asthmatic patients. OBJECTIVE: This study was designed to determine the direct in vivo evidence of increased production of endogenous NO in patients with bronchial asthma and chronic obstructive pulmonary disease (COPD). METHODS: We have investigated simultaneous assessment of NO using two non-invasive methods, such as NO level in exhaled air and induced sputum, in these patients. We determined the concentration of stable end-products of NO (nitrite plus nitrate) in induced sputum and exhaled NO concentration using a chemiluminescence analyser in 10 normal controls, 10 asthmatic patients and 11 patients with COPD, and evaluated whether endogenous NO levels correlate with percentage of neutrophils and interleukin-8 (IL-8) level in induced sputum in patients with COPD. RESULTS: We found significantly higher concentrations of exhaled NO in patients with bronchial asthma (25.1 [5.1] p.p.b.) than in patients with COPD (12.1 [1.9] p.p.b.) and normal controls (5.2 [1.4] p.p.b.). However, higher concentrations of NO derivatives in induced sputum were found in patients with bronchial asthma (1190 [106] micromol/L) and COPD (950 [105] micromol/L) than in normal controls (514 [30] micromol/L). In patients with asthma, but not in those with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with concentrations of exhaled NO (r = 0.64, P < 0.05). Moreover, in patients with COPD, concentrations of NO derivatives in induced sputum were significantly correlated with percentage of neutrophils (r = 0.71, P < 0.05) and IL-8 level (r = 0.80, P < 0.01). CONCLUSION: We conclude the increased production of endogenous NO in patients with asthma and COPD, and that NO derivatives in induced sputum are more valuable than exhaled NO in assessing airway inflammation in patients with COPD.

Adult↗
PubMed1998

Polymyalgia rheumatica in a patient with acute tubulointerstitial nephritis due to Sjögren's syndrome.

A 68-year-old Japanese woman with polymyalgia rheumatica associated with acute tubulointerstitial nephritis and subclinical Sjögren's syndrome is described. Gallium scintigraphy showed marked accumulation in both kidneys and the salivary glands. Renal biopsy revealed lymphocytic infiltration in the tubulointerstitium. She was treated with intravenous high-dose methylprednisolone followed by oral prednisolone. Her clinical symptoms improved. This is the first report of this particular association.

Aged↗
PubMed1998

Developmental malformations and intrauterine deaths in gamma-ray-irradiated scid mouse embryos.

PURPOSE: To examine the induction by radiation of developmental malformations and intrauterine deaths in severe combined immunodeficiency (scid) mice. MATERIALS AND METHODS: The scid embryos, as well as those of C.B-17 control mice, were irradiated with graded doses of 60Co gamma-rays on gestation day 8. RESULTS: Intrauterine deaths in scid mice increased with radiation dose, and their frequency was substantially higher than in C.B-17 mice. The LD50 for intrauterine death in scid mice was 0.58 Gy and 1.25 Gy in C.B-17 mice. In addition, after irradiation scid mice showed several types of developmental malformations, including meningoencephalocele, spina bifida, eye defects, tail defects and oedema. Malformation incidences were higher in scid than in C.B-17 mice: 33.3% in scid mice irradiated with 0.75 Gy and 13.0% in C.B-17 mice irradiated with 1.0 Gy. However, when malformation incidences were plotted against intrauterine deaths, all the data, irrespective of the type of mouse, essentially fell along a single straight line. CONCLUSIONS: These results suggest that some mechanism common to both scid and normal mice induces developmental malformations. This mechanism involves cell killing. Residual DNA damage, such as double-strand breaks, could be associated with radiation-induced teratogenesis.

Abnormalities, Radiation-Induced↗
PubMed1998

Characterization of gyrA, gyrB, grlA and grlB mutations in fluoroquinolone-resistant clinical isolates of Staphylococcus aureus.

The distribution of fluoroquinolone resistance-associated point mutations in genes encoding the subunits of DNA gyrase and DNA topoisomerase i.v. was examined in 110 clinical isolates of Staphylococcus aureus. Point mutations were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis and mutations were further characterized by sequencing of PCR products. Mutations at Ser84 of GyrA were widely distributed among isolates exhibiting various degrees of fluoroquinolone resistance, and border zones between mutant and non-mutant strains based on drug susceptibility were generally distinct. Mutations at Ser80 of GrlA were also widely distributed, but border zones between mutant and non-mutant isolates were in this case less distinct and several GrlA mutants were highly susceptible to sparfloxacin and tosufloxacin. Only two gyrB mutants and one grlB mutant were observed among the isolates: all contained a previously unreported mutation. GyrA and grlA mutations thus appear to impart high levels of fluoroquinolone resistance in many S. aureus clinical isolates.

Anti-Infective Agents↗
PubMed1998

Eosinophil degranulation in the presence of lung fibroblasts.

BACKGROUND: Although eosinophils (Eos) and fibroblasts (Fb) are closely approximated in the bronchial submucosae of asthmatics, and are believed to play important roles in the pathogenesis of bronchial asthma, the interaction between Eos and Fb has not been thoroughly elucidated. In this study, we have examined eosinophil cationic protein (ECP) release from human Eos cultured in the presence of human lung Fb. METHODS: Eos from healthy donors were cultured with or without C5a for 16 h in the presence of human fetal lung Fb which had previously been incubated with or without some cytokines for 4 h. ECP in supernatants was measured by RIA. RESULTS: ECP release was potentiated only when both Eos and Fb were activated by C5a and TNF, respectively, while it was not significantly potentiated when either Eos or Fb were activated. ECP release from Eos activated by C5a was also potentiated when Fb were stimulated by IL-1beta. The enhancement of ECP release in cocultured Eos and Fb with stimulation was partly inhibited by monoclonal antibodies against GM-CSF and was accompanied by the enhancement of adhesion of Eos to Fb. CONCLUSIONS: This study shows that the stimulation of both Eos and Fb increases ECP release. It is suggested that Fb may influence Eos degranulation and play a role in the pathogenesis of bronchial asthma.

Asthma↗
PubMed1998

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma.

Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

Adolescent↗
PubMed1998

Caenorhabditis elegans anti-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells.

ced-9, a member of the bcl-2 gene family in Caenorhabditis elegans plays a central roles in preventing cell death in worms. Overexpression of human bcl-2 can partially prevent cell death in C. elegans. However, it remains to be elucidated whether ced-9 can regulate cell death when expressed in other organisms. We demonstrated that the CED-9 protein is co-localized with BCL-2 in COS cells and Drosophila Schneider's L2 (SL2) cells, suggesting that the site of CED-9 action is located to specific cytoplasmic compartments. Overexpression of ced-9 only poorly protected cells from the death induced by ced-3 in HeLa cells, but ced-9 significantly reduced the cell death induced by ced-3 in Drosophila SL2 cells. Furthermore, apoptosis of SL2 cells that was induced by a Drosophila cell-death gene, reaper, was shown to be partially prevented by ced-9, bcl-2 and bcl-xL. These results suggest that the signaling pathway that is required for the anti-apoptotic function of bcl-2 family members, including ced-9, is conserved in Drosophila cells. In addition, SL2 cells provide a unique systems for dissecting the main machinery of cell death.

Animals↗