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S Harada

Publications and source records attributed to S Harada.

At least 145 records · Page 8Linked to original sources
PubMed1999

Mutations in the exons and exon-intron junction regions of human cytochrome P-4502E1 gene and alcoholism.

Cytochrome P-4502E1 (CYP2E1) is a major component of the microsomal ethanol-oxidizing system (MEOS) and is also involved in the metabolism of a variety of foreign compounds, including carcinogens. It has been shown that there are interindividual variations in the expression of human CYP2E1. Gene-environmental interactions have been suggested to account for the difference. In this study, we screened nine exons and exon-intron junctions of the human CYP2E1 gene for detecting allelic variants in genomic DNA samples obtained from 115 Japanese controls, 96 alcoholics, and 44 patients with alcoholic liver diseases. A novel missense mutation in exon 2 (V72L) was found in Japanese controls, but the frequency was low (2.6%). In addition, two novel silent mutations (T303T and F420F), together with one mutation in intron 2, were found. However, no association of these mutations with alcoholism and alcoholic liver diseases was found. Our data indicate that nucleotide replacement in the open reading frame of CYP2E1 gene is not a major factor for interindividual differences in expression of CYP2E1 and susceptibility to alcohol-related disorders.

Alcoholism↗
PubMed1999

Differential modulation of the tyrosine phosphorylation state of the insulin receptor by IRS (insulin receptor subunit) proteins.

In response to insulin, tyrosine kinase activity of the insulin receptor is stimulated, leading to autophosphorylation and tyrosine phosphorylation of proteins including insulin receptor subunit (IRS)-1, IRS-2, and Shc. Phosphorylation of these proteins leads to activation of downstream events that mediate insulin action. Insulin receptor kinase activity is requisite for the biological effects of insulin, and understanding regulation of insulin receptor phosphorylation and kinase activity is essential to understanding insulin action. Receptor tyrosine kinase activity may be altered by direct changes in tyrosine kinase activity, itself, or by dephosphorylation of the insulin receptor by protein-tyrosine phosphatases. After 1 min of insulin stimulation, the insulin receptor was tyrosine phosphorylated 8-fold more and Shc was phosphorylated 50% less in 32D cells containing both IRS-1 and insulin receptors (32D/IR+IRS-1) than in 32D cells containing only insulin receptors (32D/IR), insulin receptors and IRS-2 (32D/IR+IRS-2), or insulin receptors and a form of IRS-1 that cannot be phosphorylated on tyrosine residues (32D/IR+IRS-1F18). Therefore, IRS-1 and IRS-2 appeared to have different effects on insulin receptor phosphorylation and downstream signaling. Preincubation of cells with pervanadate greatly decreased protein-tyrosine phosphatase activity in all four cell lines. After pervanadate treatment, tyrosine phosphorylation of insulin receptors in insulin-treated 32D/IR, 32D/ IR+IRS-2, and 32D/IR+IRS-1F18 cells was markedly increased, but pervanadate had no effect on insulin receptor phosphorylation in 32D/IR+IRS-1 cells. The presence of tyrosine-phosphorylated IRS-1 appears to increase insulin receptor tyrosine phosphorylation and potentially tyrosine kinase activity via inhibition of protein-tyrosine phosphatase(s). This effect of IRS-1 on insulin receptor phosphorylation is unique to IRS-1, as IRS-2 had no effect on insulin receptor tyrosine phosphorylation. Therefore, IRS-1 and IRS-2 appear to function differently in their effects on signaling downstream of the insulin receptor. IRS-1 may play a major role in regulating insulin receptor phosphorylation and enhancing downstream signaling after insulin stimulation.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Casein kinase II (CK-II)-mediated stimulation of HIV-1 reverse transcriptase activity and characterization of selective inhibitors in vitro.

The physiological significance of the casein kinase II (CK-II)-mediated phosphorylation of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on its three enzymatic activities [RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP) and ribonuclease H (RNase H)] was investigated in vitro. It was found that (i) the purified recombinant RT (rRT) functioned as an effective phosphate acceptor for CK-II; (ii) the RDDP, DDDP and RNase H activity of rRT was stimulated about 2.8-, 4.1- and 3.9-fold, respectively, after full phosphorylation by CK-II; and (iii) this stimulation was selectively inhibited by potent CK-II inhibitors, such as neocarzinostatin-chromophore (NCS-chrom) and three polyphenol-containing anti-oxidant compounds [quercetin, epigallocatechin gallate (EGCG) and 8-chloro-3',4',5,7-tetrahydroxyisoflavone (8C-3',4',5,7-THI)]. These results suggest that (i) CK-II may be responsible for activation of RT in HIV-1-infected cells; and (ii) the selective inhibition of CK-II-mediated activation of HIV-1 RT by potent CK-II inhibitors may be involved in the mechanism of their anti-HIV-1 effects at the cellular level.

Anti-HIV Agents↗
PubMed1999

Amelioration of acromegaly after pituitary infarction due to gastrointestinal hemorrhage from gastric ulcer.

We report a rare case of acromegaly in which pituitary infarction possibly developed in a GH-producing pituitary adenoma following gastrointestinal bleeding from peptic ulcer. In this case, pituitary infarction resulted in spontaneous remission of acromegaly associated with diabetes mellitus. In addition, detailed histological investigation revealed that clinically silent pituitary apoplexy was mainly an acute ischemic event which occurred recently in a GH-producing adenoma. This event led to massive coagulation necrosis of the tumor and endocrinological improvement.

Acromegaly↗
PubMed1999

Giant cell arteritis associated with rheumatoid arthritis monitored by magnetic resonance angiography.

A 57-year-old Japanese woman with well controlled rheumatoid arthritis visited our hospital with a severe bitemporal headache and marked fatigue. Based on the classification criteria by the American College of Rheumatology, she was diagnosed as having giant cell arteritis. Magnetic resonance (MR) angiography was performed, from which stenotic changes in the bilateral superficial temporal arteries were strongly suspected. Corticosteroid therapy was quickly started. The patient followed an uneventful course with no complications. Therapeutic effect was confirmed by MR angiographic findings obtained 4 weeks after the initiation of therapy.

Anti-Inflammatory Agents↗
PubMed1999

Bullous pemphigoid IgG2 and IgG4 antibodies have a capability to inhibit a transient increase of intracellular Ca2+ induced by bullous pemphigoid IgG1 antibody.

To elucidate the role of Bullous pemphigoid (BP) IgG subclasses in the transmembrane signal transduction of keratinocytes, we examined whether BP IgG2 or IgG4 inhibits the intracellular Ca2+ concentration ([Ca2+]i) increase induced by BP IgG1. IgG2 from one of five BP patients inhibited the increase of [Ca2+]i in human squamous cell carcinoma cell line; DJM-1 cells induced by BP IgG1. IgG4 from two of four BP patients inhibited the increase of [Ca2+]i induced by BP IgG1. In addition, a two fold quantity of IgG2 inhibited the increase of [Ca2+]i induced by BP IgG1. A two fold quantity of IgG4 from two of five BP patients inhibited the increase of [Ca2+]i induced by BP IgG1. These results indicate that BP IgG2 and IgG4 have a capability to inhibit the increase of [Ca2+]i induced by BP IgG1.

Autoantibodies↗
PubMed1999

Microsatellite instability as a potential marker for poor prognosis in adult T cell leukemia/lymphoma.

Microsatellite instability (MSI) represents a replication error resulting from the dysfunction of mismatch repair gene products. In this study, MSI was analyzed in 18 patients with various subtypes of adult T cell leukemia/lymphoma (ATL/L). Using six different microsatellite loci, we defined MSI as positive when replication errors were observed in at least two loci. The MSI was positive in four cases (22.2%)with acute type ATL, who tended to show more prognostically unfavorable factors and shorter overall survival. These results suggest that genomic instability may be associated with tumor progression rather than the development of ATL/L itself. In addition, the presence of the MSI at initial presentation could appear to warrant consideration as an additional prognostically unfavorable factor.

Adult↗
PubMed1999

Neuropathology of human immunodeficiency virus 1 infection. Significance of studying in forensic autopsy cases at Dar es Salaam, Tanzania.

OBJECTIVE: In sub-Saharan Africa, only a few studies of neurologic complications of human immunodeficiency virus 1 (HIV-1) infection have been done. The authors studied neuropathology of HIV-1 infection in Tanzania. DESIGN: Forensic autopsy study at Dar es Salaam, Tanzania. SETTING: A joint research project between Dar es Salaam, Tanzania, and Kumamoto, Japan. PATIENTS: Thirty patients with risk factors for HIV-1 infection. MAIN OUTCOME MEASURES: Human immunodeficiency virus 1 infection was evaluated by HIV-1 antibody test on postmortem serum samples. The brains of HIV-1-infected persons were studied histopathologically. RESULTS: Infection with HIV-1 was identified on postmortem serum samples in 10 of 30 forensic autopsy cases. Neuropathologic changes of the brain were observed in 8 of the 10 HIV-1-infected persons; these changes consisted of lymphocytic meningitis, bacterial meningoencephalitis, cryptococcal meningoencephalitis, tuberculous meningitis with brain abscesses, and intracerebral hemorrhage. CONCLUSIONS: Because none of the persons studied was suspected to have had brain diseases before autopsy, the results suggest that brain diseases of HIV-1-infected patients are likely to go unrecognized in Tanzania. In addition, the high incidence of neuropathologic findings in HIV-1-infected persons indicates that HIV-1-related brain diseases are common in Tanzania, as they are in developed countries. Further forensic autopsy study will determine the range and prevalence of brain complications and have immediate impact on the management of HIV-1-infected patients in Tanzania and other developing countries.

AIDS Dementia Complex↗
PubMed1999

Factors influencing arteriovenous fistula dysfunction in Japanese patients on chronic hemodialysis.

Arteriovenous fistula dysfunction is a constant problem in chronic hemodialysis patients. We investigated the factors influencing fistula dysfunction in 184 patients on chronic hemodialysis. Stepwise regression analysis and Cox proportional hazards model were used to assess the relationship between fistula dysfunction and age, sex, duration of hemodialysis, diabetes mellitus, hematocrit, serum creatinine, blood urea nitrogen, Kt/V, prothrombin time, blood pressure, anticoagulant therapy, dose of erythropoietin, calcium channel blocker therapy, and angiotensin-converting enzyme inhibitor therapy. Fistula dysfunction showed a significant relationship with a low systolic blood pressure, a low hematocrit, the presence of diabetes mellitus, and angiotensin-converting enzyme inhibitor therapy. These results suggested that treatment with angiotensin-converting enzyme inhibitors may help to prevent fistula dysfunction.

Adult↗
PubMed1999

Multiple myeloma preceding the development of chronic myelogenous leukemia.

A case of a 70-year-old man who first developed multiple myeloma and then chronic myelogenous leukemia (CML) within a 3-year period is documented. The patient, with monoclonal hypergammopathy, was diagnosed with smoldering myeloma with IgG-kappa and Bence Jones protein kappa paraproteinemia. No chemotherapy was given for the myeloma until progressive leukocytosis developed after approximately 3 years. This was found to be due to Philadelphia chromosome positive CML. A reverse transcription-polymerase chain reaction assay did not reveal BCR/ABL mRNAs when the myeloma was first diagnosed. The occurrence of 2 distinct hematologic malignancies in the same patient suggests either a different clonal evolution from a common pluripotent malignant stem cell since the CML stem cell also involves the B-lymphoid lineage, a coincident complication of the 2 hematological malignancies, or the coexistence of 2 distinct malignancies due to the same genetic background and/or exposure to similar carcinogenic agents. The literature provides support for the existence of a relationship between multiple myelomas and CML.

Aged↗
PubMed1999

[Relationship between ALDH2 genotypes and choice of alcoholic beverages].

There are obviously individual differences in the choice for many kinds of alcoholic beverages such as beer, wine, whisky, sake, cocktail and so on. It is generally believed that these differences are related to acquired preferences in taste and smell, in addition to life style. However, the basis of these acquired preferences is not yet understood. It has been shown that around half of Japanese show a marked sensitivity to alcoholic beverages because of aversive reactions due to a catalytic deficiency in ALDH2 isozyme. Therefore, differences in ALDH2 genotypes may possibly influence the choice of alcoholic beverages because the individuals possessing the ALDH2*2 gene may prefer the alcoholic beverages containing lower concentrations of alcohol. A large population survey (320 males, 132 females) was conducted using questionnaires to investigate the relationship between ALDH2 genotypes and the choice of alcoholic beverages. Individuals with the homozygote of ALDH2*1 generally showed more preference for alcoholic beverages containing a higher concentration of alcohol than those with the heterozygote or the homozygote of ALDH2*2. It was noted that the latter groups preferred whisky and water, and sweet cocktails. Also, the choices for beer, whisky, and sake were significantly different between both genders. Our data suggested that individuals with ALDH2*2 prefer beverages with lower concentrations of alcohol due to an aversive reaction after drinking, and that there are obvious gender differences in the consumption as well as the choice for many alcoholic beverages.

Adult↗
PubMed1999

A novel polymorphism (-357 G/A) of the ALDH2 gene: linkage disequilibrium and an association with alcoholism.

BACKGROUND: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads to ALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported. METHODS: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North-American Caucasians using single-strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing. RESULTS: A novel polymorphism at -357 with a G to A substitution was found in all the population groups, including North-American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2*2 allele is linked to the G promoter allele, and theALDH2*1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2*1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A chi2 test for the entire 3 x 2 table indicated significant variations in the three genotypes (chi2 = 6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed. CONCLUSION: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.

Adult↗
PubMed1999

A case of antiphospholipid antibody syndrome diagnosed after thrombosis of an arteriovenous shunt.

A 32-year-old male dialysis patient with lupus nephritis was admitted because of shunt obstruction. The arteriovenous fistula was reconstructed, but obstruction recurred twice within several hours after surgery. A high blood level of anticardiolipin beta2-glycoprotein I antibody suggested that shunt obstruction was caused by a thrombotic tendency related to the antiphospholipid antibody syndrome. Accordingly, for the third shunt procedure, antiplatelet therapy (which had been commenced for systemic lupus erythematosus) was combined with dalteparin sodium from before surgery and warfarin was added postoperatively. This regimen prevented shunt obstruction. In conclusion, hemodialysis patients who suffer repeated shunt obstruction should be examined for antiphospholipid antibody syndrome.

Adult↗
PubMed1999

[Relationship between alcoholism and HTR2 MspI polymorphism].

We investigated the human serotonin receptor, HTR2 genotype among 73 alcoholics. We found that there might not be a significant difference between alcoholics and controls in the frequency of HTR2 C1/C2 gene (MspI polymorphism). This result suggested that the HTR2 C1/C2 gene might not be associated with the risk factor for developing alcohol dependence. Further studies are required to determine whether or not a novel serotonin receptor polymorphism reflects pathogenesis of alcoholism.

Adult↗
PubMed1999

[A clinicobacteriologic study on clavulanic acid/amoxicillin in pediatric acute otitis media].

We carried out clinical and bacteriological studies on clavulanic acid/amoxicillin and amoxicillin in pediatric acute otitis media at 14 general practice settings. The results are summarized as follows. 1. The major isolated organisms from content of middle ear effusion were Streptococcus pneumoniae 31.8%, Haemophilus influenzae 35.8% and Moraxella subgenus Branhamella catarrhalis 1.5%. Similar results were observed for the major isolates organisms from content of nasopharynx Streptococcus pneumoniae 31.1%, Haemophilus influenzae 33.9% and Moraxella subgenus Branhamella catarrhalis 19.2%. 2. 42.2% of S. pneumoniae isolated from middle ear effusion were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. 3. 46.7% of S. pneumoniae isolated from nasopharyngeal swab were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. The incidence of drug resistant S. pneumoniae isolated from all cases and organisms were 26.3% and 14.5%, respectively. 4. On MIC90, antimicrobial activity of CVA/AMPC against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis was superior to SBTPC. 5. In the evaluation of clinical efficacy, bacteriological efficacy and utility, CVA/AMPC-treated group was significantly superior to AMPC-treated group. 6. Adverse reactions were observed in 22% of CVA/AMPC-treated group, involving diarrhea and loose stool.

Acute Disease↗
PubMed1999

[A clinicobacteriologic study on clavulanic acid/amoxicillin in pediatric sinusitis].

We carried out clinical and bacteriological studies on clavulanic acid/amoxicillin and amoxicillin in pediatric sinusitis at 11 general practice settings. The results are summarized as follows. 1. The major isolated organisms from content of middle meatus were Streptococcus pneumoniae 32.2%, Haemophilus influenzae 32.0% and Moraxella subgenus Branhamella catarrhalis 25.1%. Similar results were observed for the major isolates from nasopharynx. 2. 62.1% of S. pneumoniae isolated were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. 3. Drug resistant S. pneumoniae was isolated from 38.6% of all cases. 4. Regarding MIC90, CVA/AMPC showed superior antimicrobial activity against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis. 5. The clinical efficacy, bacteriological efficacy and utility of CVA/AMPC-treated group were 78%, 58% and 72.8%, respectively, and they were significantly superior to AMPC-treated group. 6. Adverse reactions were observed in 11.2% of CVA/AMPC group, involving diarrhea and stool loose and there was no statistical deference from those of AMPC group.

Amoxicillin↗
PubMed1999

[In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates].

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.

Ampicillin↗