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H Saito

Publications and source records attributed to H Saito.

At least 55 records · Page 3Linked to original sources
PubMed2004

Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's disease induced by the Japanese encephalitis virus.

We previously reported that exogenously administered isatin, an endogenous monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was developed as a MAO-B inhibitor more than 30 years ago and widely used in the treatment of Parkinson's disease. Effects of isatin or selegiline were investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test for detecting motor activity and by the determination of biogenic amine levels. Motor activity of JEV-induced rats receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg per day for 1 week, i.p.) was significantly improved compared with that of untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not by selegiline. These results suggested that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

Animals↗
PubMed2004

Comparative roles of macrophages and NK cells in the host innate resistance of mice to Mycobacterium fortuitum infection.

OBJECTIVES: Profiles of host innate resistance to Mycobacterium fortuitum (MFT) infection in mice and the roles of macrophages (Mphis) and NK cells in host resistance to MFT infection were studied. METHODS: MFT-infected mice with or without the treatments to reduce Mphis and NK cells were examined for survival and the bacterial loads in the kidneys during the course of infection. RESULTS: A unique profile of strain difference was found in the innate resistance of mice to MFT. A/J, C3H/He and DBA/2 mice were susceptible, while BALB/c, B10A and C57BL/6 mice were resistant, in terms of survival after MFT infection. Such profiles of host resistance to MFT were essentially correlated with the ability of individual strain mice to prevent the bacterial growth in the early periods after infection. These profiles were different from the strain difference controlled by Bcg gene. Studies using carrageenan, anti-asialo GM1 antibody, and NK cell-deficient beige mice indicated the important roles of Mphis and NK cells in the host innate defense against MFT. CONCLUSIONS: These findings suggest that Bcg gene does not control the host resistance to MFT and that both Mphis and NK cells play crucial roles in the host innate resistance to MFT infection.

Animals↗
PubMed2004

TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways.

We previously reported the fusion of the TEL gene to the Syk gene in myelodysplastic syndrome with t(9;12)(q22;p12). TEL-Syk fusion transformed interleukin-3 (IL-3)-dependent murine hematopoietic cell line BaF3 to growth factor independence. Here, we investigate the intracellular signal transduction of the stable transfectants. TEL-Syk fusion protein was associated with the p85 subunit of phosphatidyl inositol 3 kinase (PI3-K) followed by the activation of Akt in the absence of IL-3. Vav, phospholipase C-gamma2 and mitogen-activated protein kinase (MAPK) were also constitutively activated. TEL-Syk also activated the signal transducer and activator of transcription 5 (STAT5) in the absence of Janus kinase 2 activation. None of these kinases were phosphorylated in the BaF3 cells transfected with TELDeltaPNT-Syk in which the oligomerization domain of TEL was deleted. Inhibitor analysis showed that the MAPK pathway was important in TEL-Syk-mediated cell proliferation. The immunofluorescence technique revealed that the TEL-Syk fusion protein was located in the cytoplasm. These data suggest that TEL-Syk fusion protein in the cytoplasm leads to the constitutive activation of PI3-K/Akt, MAPK and STAT5 signal pathways, which are closely involved in IL-3-independent cell proliferation of BaF3 cells.

Amino Acid Substitution↗
PubMed2004

Rapid-sequence phosphorus-31 magnetic resonance spectroscopy of the human heart using a 1.5-T clinical system.

PURPOSE: To compare a 'standard' slow phosphorus-31 magnetic resonance spectroscopy (31P-MRS) sequence with two faster sequences in phantoms and healthy volunteers using a 1.5-T clinical system. MATERIAL AND METHODS: Complete 3D localization was performed using a 2D phosphorus chemical-shift imaging sequence in combination with 30-mm axial slice-selective excitation. Two 31P-MRS rapid sequences (RS8-4: 8 x 8 phase-encoding, with an average of 4 acquisitions, and RS16-1: 16 x 16 phase-encoding, 1 acquisition) were compared with the standard sequence (StdP: 16 x 16 phase-encoding, with an average of 8 acquisitions) in phantom and healthy volunteers. RESULTS: Acquisition time for the 31P-MRS procedure with StdP, RS8-4, and RS16-1 in the healthy volunteer studies ranged from 30 to 45, 3 to 5, and 3 to 5 minutes, respectively. Metabolite measurements of healthy volunteers obtained from 31P-MRS using RS8-4 correlated with values obtained using StdP (PCr r2=0.63, P<0.001; ATP r=0.41, P<0.01 and PCr/ATP ratio r2=0.25, P<0.05). There was no correlation between StdP and RS16-1 for either ATP or the PCr/ATP ratio (r2=0.03, P=0.60, and r2=0.11, p=0.26, respectively). Reproducibility (intensity of phosphorus signal) with RS16-1 was worse than that of RS8-4 or StdP. CONCLUSION: 31P-MRS using RS8-4 may be a valid diagnostic tool for patients with cardiac diseases.

Adult↗
PubMed2004

High prevalence rate of Helicobacter pylori resistance to clarithromycin during long-term multiple antibiotic therapy for chronic respiratory disease caused by non-tuberculous mycobacteria.

BACKGROUND: Helicobacter pylori resistance to clarithromycin, probably due to the frequent use of this antibiotic for the treatment of other diseases, is the greatest obstacle against its eradication. AIM: To clarify the prevalence of clarithromycin-resistant H. pylori in patients with non-tuberculous mycobacterial lung disease receiving multiple antibiotic treatment, including clarithromycin. METHODS: We enrolled 88 patients with non-tuberculous mycobacterial lung disease; 29 underwent upper gastrointestinal endoscopy for the diagnosis of H. pylori infection prior to treatment, and 60 underwent it during treatment. The diagnosis of H. pylori infection was confirmed by histological examination, urease test and microaerobic bacterial culture. The minimum inhibitory concentration of clarithromycin was determined and the DNA was analysed for each of the isolated H. pylori strains. RESULTS: Patients during the treatment had a high prevalence rate of clarithromycin-resistant H. pylori (100%). Analysis of DNA of the clarithromycin-resistant H. pylori isolates revealed point mutations at A2142G or A2143G. Moreover, a linear correlation was found between the total cumulative dose of clarithromycin and the minimum inhibitory concentration. CONCLUSION: All patients with non-tuberculous mycobacterial lung disease being treated long-term with multiple antibiotics, including clarithromycin, harboured clarithromycin-resistant H. pylori in the stomach. Therefore, eradication of H. pylori before commencement of long-term therapy including clarithromycin should be recommended.

Anti-Bacterial Agents↗
PubMed2004

Polymorphisms of NS5B protein relates to early clearance of hepatitis C virus by interferon plus ribavirin: a pilot study.

Although randomized trials have shown enhancement of efficacy for combination therapy with interferon (IFN) alpha-2b and ribavirin compared with IFN monotherapy as first-line treatment for chronic hepatitis C, infection with genotype 1b and high viremia are still associated with significantly low response rates compared with non-1 genotypes and low viremia. We analysed amino acid sequences of the viral RNA-dependent RNA polymerase (RdRP) or nonstructural protein 5B (NS5B), responsible for ribavirin misincorporation into RNA products in patients with genotype 1b-related chronic hepatitis C and high viremia, and examined the relationship between such RdRp polymorphisms, and the initial decline in viral load induced by combination therapy with IFN-alpha and ribavirin. Substitution of glutamic acid to lysine at the 124th position (E124K) and of isoleucine to valine at the 85th position (I85V) were found to be closely associated with a potent decline of viral load and viral clearance at 8 weeks of treatment (five of five patients, coincidence rate 100%). In conclusion, our results suggest that the polymorphisms of E124K and I85V identified in NS5B protein are crucial for early viral clearance in patients with genotype 1b and high viremia by combination therapy with IFN and ribavirin, and that detection of amino acid sequence motifs might enable prediction of clinical efficacy.

Aged↗
PubMed2004

Human mast cells express receptors for IL-3, IL-5 and GM-CSF; a partial map of receptors on human mast cells cultured in vitro.

BACKGROUND: Mast cells have long been recognized as the principal cell type that initiates the inflammatory response characteristic of acute allergic type 1 reactions. Our goal has been to further characterize maturation of progenitors to mast cells. METHODS: Mast cells were cultured from human cord blood derived CD133(+) progenitors. Mast cell function was tested using histamine release. During differentiation mast cells surface marker expression was monitored by flow cytometry. RESULTS: CD133(+) progenitors expressed the early haematopoietic and myeloid lineage markers CD34, CD117, CD13 and CD33. Mature mast cells expressed CD117, CD13 and CD33, and expression of the high affinity immunoglobulin E receptor FcepsilonRI increased during culture. Cytokine receptors interleukin (IL)-5R, IL-3R, granulocyte-macrophage-colony stimulating factor (GM-CSF)R and IL-18R were expressed at high levels during maturation. Chemokine receptors CXCR4 and CXCR2 were highly expressed on both newly purified CD133(+) cells and mature cells. CONCLUSION: Human mast cells can be cultured from a CD34(+)/CD117(+)/CD13(+)/CD33(+) progenitor cell population in cord blood that is tryptase and chymase negative. Developing and mature mast cells express a wide range of chemokine and cytokine receptors. We found high levels of expression of CD123, IL-5R and GM-CSF receptors, also found on eosinophils and basophils, and high levels of expression of the receptor for the inflammatory cytokine IL-18.

AC133 Antigen↗
PubMed2004

[Mitral regurgitation due to sole punched out lesion of the mitral anterior leaflet in infective endocarditis; report of a case].

Mitral regurgitation (MR) due to only punched out lesion is extremely rare in infective endocarditis. A 31-year-old male was admitted to our hospital due to unusual cause of MR. Echocardiography showed MR due to punched out lesion of the mitral anterior leaflet, which is extremely rare. A round shape punched out lesion (about 16 mm in size) was found intraoperatively in the anterior leaflet of the mitral valve. The surface around the punched out lesion was smooth, and the leaflet displayed good movability. Neither vegetation nor calcification was found. Punched out lesion was successfully closed with autologous pericardial patch and annuloplasty was performed.

Adult↗
PubMed2003

Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected mesencephalic dopaminergic cells.

Ginsenosides Rb1 and Rg1 are the main active ingredients of Panax ginseng C.A. Meyer (Araliaceae). They appear to exert protection against ischaemia and anoxic damage in animal models, suggesting an antioxidative and cytoprotective role. In our study, primary cultures from embryonic mouse mesencephalon are applied to examine the effects of these two ginsenosides on neuritic growth of dopaminergic cells and their survival affected by 1-methyl-4-phenylpyridinium-iodide (MPP(+)). Ginsenoside Rb1 (at 10 microM) enhanced the survival of dopaminergic neurons by 19% compared to untreated control. MPP(+) (at 1 microM) significantly reduced the number of dopaminergic neurons and severely affected neuronal processes. Both ginsenosides counteracted these degenerations and significantly protected lengths and numbers of neurites of TH(+) cells. Both compounds however could not prevent the cell loss caused by MPP(+). Our study thus indicates partial neurotrophic and neuroprotective actions of ginsenosides Rb1 and Rg1 in dopaminergic cell culture.

1-Methyl-4-phenylpyridinium↗
PubMed2003

Prevention of advanced colorectal cancer by screening using the immunochemical faecal occult blood test: a case-control study.

To evaluate colorectal cancer screening with faecal occult blood testing (FOBT) in terms of prevention of advanced cancers, we conducted a case-control study in the areas where an annual screening programme with immunochemical FOBT has been offered to all inhabitants aged 40 years or over. Cases were 357 consecutive patients in the study areas clinically diagnosed as having advanced colorectal cancer or a tumour invading the muscularis propriae or deeper, that is, T(2)-T(4) in TNM classification. Three controls were selected for each case matched by gender, age, residential area and exposure status to screening within 1 year before case diagnosis. The odds ratios (ORs) of developing advanced cancer were calculated using conditional logistic regression analyses. The OR for those screened within 3 years before the diagnosis vs those not screened was 0.54 (95% confidence interval (CI) 0.29-0.99). The ORs were lower for rectum than for colon (0.32-0.73 and 0.84-1.18 for rectum and colon, respectively). For those screened within the past 3 years, OR of developing advanced cancer in the rectum was 0.32 ( 95%CI: 0.12-0.84). A screening programme with immunochemical FOBT can be effective for prevention of advanced colorectal cancer. Risk reduction appears to be larger for rectal than for colon cancer. British Journal of Cancer (2003) 89, 23-28. doi:10.1038/sj.bjc.6601002 www.bjcancer.com

Adult↗
PubMed2003

Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype.

OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. RESULTS: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. CONCLUSIONS: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.

Adult↗
PubMed2003

Room-temperature ferromagnetism in a II-VI diluted magnetic semiconductor Zn(1-x)Cr(x)Te.

The magnetic and magneto-optical properties of a Cr-doped II-VI semiconductor ZnTe were investigated. Magnetic circular dichroism measurements showed a strong interaction between the sp carriers and localized d spins, indicating that Zn(1-x)Cr(x)Te is a diluted magnetic semiconductor. The Curie temperature of the film with x=0.20 was estimated to be 300+/-10 K, which is the highest value ever reported for a diluted magnetic semiconductor in which sp-d interactions were confirmed. In spite of its high Curie temperature, Zn(1-x)Cr(x)Te film shows semiconducting electrical transport properties.

Journal Article↗
PubMed2003

S-allyl-L-cysteine selectively protects cultured rat hippocampal neurons from amyloid beta-protein- and tunicamycin-induced neuronal death.

S-allyl-L-cysteine (SAC), one of the organosulfur compounds found in aged garlic extract, has been shown to possess various biological effects including neurotrophic activity. In our previous experiments, we found that SAC could protect against amyloid beta-protein (Abeta)- and tunicamycin-induced cell death in differentiated PC12 cells. In the study described here, we characterized the neuronal death induced by Abeta, 4-hydroxynonenal (HNE), tunicamycin, and trophic factor deprivation, and investigated whether and how SAC could prevent this in cultured rat hippocampal neurons. Treatment with SAC protected these cells against Abeta- and tunicamycin-induced neuronal death, which is mediated predominantly through caspase-12-dependent pathway in a concentration-dependent manner. In contrast, it afforded no protection against HNE- and trophic factor-deprivation-induced cell death, which has been shown to be mediated by caspase-3-dependent pathway. SAC also attenuated the Abeta-induced increase of intracellular reactive oxygen species in hippocampal neurons. SAC had no effect on Abeta-induced cell death in cultured cerebellar granule neurons, which was prevented by a caspase-3 inhibitor. These results suggest that SAC could protect against the neuronal cell death that is triggered by ER dysfunction in the hippocampus, and that it has no effect on neuronal cell death that is dependent upon the caspase-3 mediated pathway.

Amyloid beta-Peptides↗
PubMed2003

Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications.

Atherosclerotic vascular diseases are frequently associated with diabetes mellitus. There has been increasing evidence showing that the atherosclerotic diseases in diabetic patients are distinct from diabetic microvascular complications as to their pathophysiology and epidemiology. However, we have no information on the prevalence of asymptomatic atherosclerosis in diabetic patients before the onset of microvascular diseases. In the present investigation, we aimed to evaluate risk factors for the atherosclerosis in type 2 diabetic patients without the microvascular diseases. For this purpose, we evaluated atherosclerotic change of carotid arteries in 125 Japanese type 2 diabetic patients who had neither atherosclerotic vascular diseases nor diabetic microvascular complications. When atherosclerotic change was defined as the mean intima-media thickness (IMT) of >/= 1.1 mm and/or the presence of plaque lesion, 50% of patients had atherosclerosis of the carotid arteries. Risk factors for the carotid atherosclerosis were age, low-density lipoprotein (LDL)-cholesterol, hypertension, and diabetes treatment. Age and LDL-cholesterol were associated with mean IMT. Age, diabetes treatment, LDL-cholesterol, and hypertension were positively associated with plaque lesion, while high-density lipoprotein (HDL)-cholesterol was negatively associated with it. Fasting plasma glucose, glycosylated hemoglobin (HbA(1c)), and known diabetes duration remained unassociated with any parameters of asymptomatic atherosclerosis of the carotid arteries. These results indicate that glycemic control is unrelated with asymptomatic atherosclerosis in type 2 diabetic patients without diabetic microvascular complications. Conventional risk factors and diabetes treatment are independently associated with atherosclerosis of the carotid arteries in these patients.

Aged↗
PubMed2003

Sustained activation of c-jun-terminal kinase (JNK) is closely related to arsenic trioxide-induced apoptosis in an acute myeloid leukemia (M2)-derived cell line, NKM-1.

High concentrations (greater than 5 microM) of arsenic trioxide (As(2)O(3)) have been reported to be able to induce apoptosis in several malignant cells. We explored cell lines in which apoptosis was induced with a therapeutic concentration (1-2 microM) of As(2)O(3), and found that 1 microM of As(2)O(3) induced apoptosis in the NKM-1 cell line, which was established from a patient with acute myeloid leukemia (M2). Apoptosis induced by 1 microM of As(2)O(3) in NKM-1 cells was accompanied by an increased cellular content of H(2)O(2), a decreased mitochondrial membrane potential (Deltapsim), and activation of caspase-3. C-Jun-terminal kinase (JNK) was activated only in NKM-1 cells and arsenic-sensitive NB4 cells, but not in arsenic-insensitive HL-60 cells. Activation of JNK in NKM-1 was sustained from 6 to 24 h after As(2)O(3) treatment, and preceded changes in cellular H(2)O(2), Deltapsim, and caspase-3 activation. Moreover, addition of a JNK inhibitor reduced the percentage of apoptotic cells after the As(2)O(3) treatment. Taken together, in the M2 cell line NKM-1, 1 microM of As(2)O(3) induced sustained activation of JNK and apoptosis. This finding may provide a basis to select a subgroup other than acute promyelocytic leukemia, which can benefit from As(2)O(3) treatment.

Acute Disease↗
PubMed2003

Analysis of gene expression in peripheral blood eosinophils from patients with atopic dermatitis and in vitro cytokine-stimulated blood eosinophils.

Investigation of differentially expressed genes in eosinophils of patients with allergic diseases such as atopic dermatitis (AD) will provide important information for elucidating possible mechanisms of pathology. To identify novel genes that are expressed in AD, we compared gene expression in samples of peripheral blood eosinophils from AD patients and healthy volunteers. RNA was extracted from peripheral blood eosinophils. The expression of various genes, such as those for cytokine receptors, eosinophil activation marker, platelet activating factor (PAF) receptor, eosinophil-specific granular proteins and apoptosis-related genes, was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood eosinophils of healthy volunteers were also isolated and stimulated for introduction of various cytokines. RNA was extracted and gene expression was monitored. Several genes, such as those for cytokine receptors (granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha and beta chain and interleukin (IL)-3 receptor alpha chain), CD44 and PAF receptor were expressed at significantly higher levels in AD patients than in healthy volunteers. In addition, the anti-apoptotic genes, bcl-2 and bcl-xL, were expressed at increased levels in AD patients. No single gene expression correlated with clinical markers, such as eosinophil count or IgE levels. Expression of GM-CSF receptor beta chain and IL-3 receptor alpha chain in isolated blood eosinophils of healthy volunteers was stimulated by IL-5, IL-4, interferon (IFN)-gamma and GM-CSF. Expression of bcl-2 and bcl-xL was also increased after stimulation with IL-5, IL-4 or IFN-gamma. The in vitro enhancement of cytokine-stimulated gene expression correlated well with the enhancement observed in clinical samples of eosinophils, suggesting that cytokines may affect gene expression in vivo in eosinophils of patients with AD.

Adolescent↗