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Biomedical subjects

K Furusho

Publications and source records attributed to K Furusho.

At least 19 recordsLinked to original sources
PubMed2003

A survey on awareness and utilization of new asthma management guidelines in Japan.

The present questionnaire survey, designed to interview Japanese internists and pediatricians who were specialists or nonspecialists in allergy or asthma, was conducted to determine the acceptance of "Asthma Prevention and Management Guidelines 1998" 1 year after release. The surveyor visited each physician and used the questionnaire form at the interview. Replies were obtained from a total of 5,963 physicians. The percentage of physicians who were aware of the guidelines was 96% among specialists and 68% among nonspecialists. Among the internists who were aware of the guidelines, the percentage of physicians giving a reply of "I refer to them often" or "I refer to them" in the actual diagnosis and management of asthma was 95% among specialists and 92% among nonspecialists. Therefore, reference was very high. Except for nonspecialists among pediatricians, not less than 60% of physicians expected that propagation of the present guidelines would allow a further decrease in asthma death and further improvement of patient's quality of life. The present survey revealed an increase in guideline awareness over the last several years, which was especially marked in nonspecialists. Furthermore, high reference and high expectancy also verified that physicians recognize the contents of the present guidelines as appropriate.

Asthma↗
PubMed2000

Tacrolimus and myocardial hypertrophy.

Tacrolimus has been used as an immunosuppressive agent in the transplantation of all solid organs. Tacrolimus-induced hypertrophic cardiomyopathy has been reported to be an unusual but serious complication. To elucidate the effects of tacrolimus on myocardial hypertrophy, we studied the relationship between the blood levels of tacrolimus and cardiac wall thickening. Our findings demonstrated that tacrolimus-induced myocardial hypertrophy correlated with tacrolimus blood levels, and that myocardial hypertrophy induced by tacrolimus was reversible. However, no patients developed clinically significant symptoms related to myocardial hypertrophy.

Adolescent↗
PubMed2000

Coronary risks after high-dose gamma-globulin in children with Kawasaki disease.

OBJECTIVES: The goals of the present study were to develop a predictive coronary risk scoring system after intravenous gamma-globulin (IVGG) therapy of any dose for the different preparations currently used in the treatment of children with Kawasaki disease and to determine the predictive value of the system. The previously reported scoring systems were based on treatment with high-dose IVGG therapy at limited doses and were determined using investigative methods. METHODS: Four hundred and fifty-one patients were randomized into one of three groups and received either i.v. polyethylene glycol-treated human immunoglobulin at a dose of either 200 (n = 147) or 400 mg/kg per day (n = 152) or freeze-dried sulfonated human immunoglobulin at 200 mg/kg per day (n = 152) for 5 consecutive days. We documented 31 cases of coronary abnormalities (CA). Univariate and multivariate logistic regression was performed using 49 clinical variables and the resulting predictive model was validated. RESULTS: The duration of fever (odds (I day)/odds (- 5 days)= 0.158; 95% confidence interval (CI) 0.0385-0.648), hemoglobin (odds (Q1 = 10.3)/odds (Q3 = 11.6) = 3.97; 95% CI 1.92-8.20), IgG (odds (Q1 = 1,900)/odds (Q3=2,658)=2.72, 95% CI 1.18-6.25) and IgA (odds (Q1 =72)/odds (Q3= 160) = 0.415; 95% CI 0.253-0.680) levels after completion of gamma-globulin infusion were independent predictors. The model is quasi-cross validated and has acceptable sensitivity and selectivity. The estimated risk and observed occurrence of CA coincide. CONCLUSIONS: Determinants of the risk of CA after IVGG therapy are a longer duration of fever, a lower IgG level, a higher IgA level and a lower hemoglobin level after IVGG infusion. This model is applicable for IVGG doses from 1 to 2 g/kg and for at least two different gamma-globulin preparations.

Child↗
PubMed1999

Hypomethylation of the proximal and intronic regulatory regions of the IFN-gamma gene is not essential for its transcription by naive CD4+ T cells cultured with IL-4.

Recently, long-term preculture with IL-4 or IL-7 has been reported to induce IFN-gamma-producing ability in naive CD4+ T cells without stimulation via TCR. The mechanism of IFN-gamma-transcription in naive CD4+ T cells precultured with IL-4 was analyzed and compared with that in typical Th1 cells by focusing on the TATA proximal and first intronic regulatory regions of the IFN-gamma gene. Both regulatory regions in these IL-4-primed naive CD4+ T cells, which produce a large amount of IFN-gamma upon stimulation with PMA and ionomycin, were completely methylated in contrast to the same hypomethylated regions in Th1 cells. DNase I hypersensitive site analysis suggested that both regulatory regions in IL-4-primed naive CD4+ T cells were not active for IFN-gamma-expression. Moreover, we demonstrated that the composition of transcriptional factors that can bind to the proximal regulatory region is different between IL-4-primed naive CD4+ T cells and Th1 cells. These results indicated that the transcriptional machinery involved in the expression of the IFN-gamma gene by CD4+ T cells varied depending on their modes of differentiation in both the responsive regulatory regions and the specific nuclear factors.

CD4-Positive T-Lymphocytes↗
PubMed1999

Relationships between atopy and lung function: results from a sample of one hundred medical students in Japan.

BACKGROUND: The prevalence of allergic diseases has been increasing dramatically and several studies have shown that atopy is related to asthmatic symptoms and bronchial hyperresponsiveness. OBJECTIVE: To observe the relationships between atopic status and asthmatic predisposition (obstructive change in lung function) in apparently healthy young adults in Japan. METHODS: A sample of 100 healthy Japanese medical students were subjected to a skin prick test for 11 common aeroallergens and food allergens, and their spirometric lung function was measured. RESULTS: Surprisingly, 90% of them showed a positive prick test result for at least one of the 11 allergens tested, and 59% of them showed allergic responses to more than three allergens. The positive rate for Dermatophagoidesfarinae (Der) was the highest (71.0%), followed by house dust (57.0%), Dactylois gloinerata (42.0%), Cryptomeria gromerata (Cry) (40.0%), and cat fur (39.0%). Furthermore, there was no statistical difference in the positive rates for Der and Cry between groups with and without either the present illness or past history of any of the three major allergic diseases: bronchial asthma (BA), atopic dermatitis (AD), or allergic rhinitis (AR). Compared with the positive rates for these aeroallergens, those for food allergens were much lower (4% to 9%). Several lung function parameters, including the levels of FEV1% and %V50 which reflect obstructive pulmonary changes, showed significant negative correlation to the number of skin prick test-positive allergens. The same correlation was observed for groups without either the present illness or past history of BA. CONCLUSION: These data suggest that those who are multi-allergic tend to feature subclinical asthma-like changes in their lung functions. Further studies are needed to determine whether this multi-allergic status can lead to future onset of asthma or other allergic diseases.

Adult↗
PubMed1999

Intrapulmonary shunting in biliary atresia before and after living-related liver transplantation.

BACKGROUND: Intrapulmonary shunting (IPS) is frequently observed and causes hypoxaemia in liver cirrhosis. This study investigated the prevalence, predictors of reversibility and the effect of living-related liver transplantation (LRLT) on IPS using contrast echocardiography in patients with end-stage biliary atresia. METHODS: Fifty consecutive patients with biliary atresia were examined for IPS using contrast echocardiography before and after LRLT until IPS disappeared. The severity of IPS was classified into five grades according to the extent of contrast in the left ventricle (0, none; 1, trivial; 2, apparent; 3, complete but less than in right ventricle; 4, as dense as in right ventricle). RESULTS: Thirty-two patients (grade 1, n = 15; grade 2, n = 7; grade 3, n = 4; grade 4, n = 6) had IPS before LRLT. Forty-four patients have survived for 9-26 months after LRLT. Among patients with grade 3 or 4 IPS (n = 8), there was a significant correlation between age at LRLT and the duration of IPS persistence after LRLT (P = 0.044). CONCLUSION: IPS takes longer to disappear in older children than in younger ones, but always disappears eventually. LRLT is an effective treatment for biliary atresia with IPS. Presented to the 31st annual meeting of the Pacific Association of Pediatric Surgeons, Maui, Hawaii, June 1998

Adolescent↗
PubMed1999

Existence of activated and memory CD4+ T cells in peripheral blood and their skin infiltration in CD8 deficiency.

CD8 deficiency is a rare primary immunodeficiency caused by the defect of a tyrosine kinase, ZAP-70, which transduces signals from the T cell receptor. We report here a case of CD8 deficiency, having CD4+ T cells with a unique phenotype. The patient's T cells did not respond to anti-CD3 stimulation in vitro, suggesting that they were naive. However, many CD4+ T cells with activated and memory phenotypes, which expressed CD45RO+, HLA-DR+ and CD25+, were present in the peripheral blood, and these cells accumulated in the perivascular area of his infiltrative erythematous skin lesions. The patient's T cells could be activated by a high concentration of phytohaemagglutinin (PHA), indicating the presence of an alternate signalling pathway which bypasses ZAP-70 and activates CD4+ T cells in vivo. The origin and role of activated CD4+ T cells in the pathogenesis involved in the skin lesions are discussed.

CD4-Positive T-Lymphocytes↗
PubMed1998

Biomarkers in long survivors of pediatric acute lymphoblastic leukemia patients: late effects of cancer chemotherapy.

In order to elucidate the late effects of cancer chemotherapy, mutant frequencies (Mfs) at the hypoxanthine phosphoribosyl transferase (hprt) locus were evaluated in pediatric patients with early pre-B acute lymphoblastic leukemia (ALL). Hprt-Mfs were measured at least 2 years after completion of chemotherapy. Ten out of 15 patients were found to have hprt-Mfs exceeding the 99% confidence limits as calculated from observations of healthy controls. Although there was some intraindividual variation, serial measurements of hprt-Mfs with intervals of more than 6 months revealed that hprt-Mfs were fairly stable. Patients with high Mfs tended to have sibling clones as detected by clonality analysis using the T-cell receptor (TCR) rearrangement pattern, but clonality did not have a major effect on the Mfs. On the other hand, Mfs at the TCR locus and sister chromatid exchange frequency were within the normal range in all patients. These data suggest that chemotherapy can cause persistent genotoxicity in vivo in a subset of pediatric ALL patients and that the hprt-Mf is a useful method for measuring such an effect.

Adolescent↗
PubMed1998

Living-related liver transplantation and neurological outcome in children with fulminant hepatic failure.

BACKGROUND: Fulminant hepatic failure (FHF) in children is associated with high mortality under medical management. Living-related liver transplantation (LRLT) is an accepted measure to treat the children with end-stage liver disease. Reversibility of hepatic encephalopathy is crucial for the quality of life among the survivors after transplantation. METHODS: A retrospective review was made of the records of children undergoing LRLT at this hospital between May 1992 and November 1996. RESULTS: Eleven children with FHF underwent emergency LRLT. The mean age was 5 years (range, 2 months to 15 years). The indication for transplantation was persistent or worsening hepatic encephalopathy and severe coagulopathy, despite repeated plasma exchanges or exchange transfusions. The cause of FHF was non-A, non-B hepatitis in seven children, hepatitis B in two children, herpes simplex virus hepatitis in one child, and fulminant Wilson's disease with intravascular hemolysis in one child. The grade of hepatic encephalopathy was II in four children, III in two, and IV in five. The actuarial survival rate was 73% after a mean follow-up of 28 months (range, 13-67 months). Short-term neurological morbidity was present in two children with grade IV encephalopathy who also showed brain edema on cranial computed tomography. Eight survivors exhibited no long-term neurological deficit; the mean intelligence or developmental quotient was 97 (range, 86-110) at the end of the follow-up period. CONCLUSIONS: LRLT is an effective option for the treatment of FHF in children. The long-term neurological status is satisfactory among survivors.

Brain Edema↗
PubMed1998

Evaluation of mutant frequencies at the hprt and the T-cell receptor loci in pediatric cancer patients before treatment.

Mutant frequencies (Mfs) at the two genetic loci, the hypoxanthine phosphoribosyl transferase (hprt) gene and the T-cell receptor (TCR) gene were evaluated in pediatric cancer patients before starting chemotherapy or radiotherapy. The study population consisted of 27 patients with various solid tumors (mean age +/- SD; 5.5 +/- 5.1 years, range; 0.2-14.5 years), 5 patients with acute leukemia (10.3 +/- 6.1, 1.3-17.0 years), and 26 healthy controls (11.6 +/- 4.0, 4.4-22.2 years). Although the age distributions were different, the mean Mf values of the hprt and the TCR loci were comparable among these three groups. On an individual basis taking the age factor into consideration, the hprt-Mfs of 3 patients with solid tumors, i.e., two patients with Hodgkin's disease and one patient with Askin tumor, were found to be well above the 95% confidence limit. There were no patients with a TCR-Mf exceeding the 95% confidence limit. These data suggest the possibility that some patients with solid tumors may be predisposed to mutational susceptibility before treatment. The assay of the hprt-Mf appears more sensitive than the TCR-Mf assay in distinguishing these patients.

Adolescent↗
PubMed1998

Increase in nitric oxide in the hypoxic-ischemic neonatal rat brain and suppression by 7-nitroindazole and aminoguanidine.

We measured the changes in nitric oxide (NO) metabolites in the brains of neonatal rats with hypoxic-ischemic damage. There were two peaks of NO metabolites in the lesioned side of the cortex without treatment: one during hypoxia and the other during the re-oxygenation period. Prehypoxic treatment with 7-nitroindazole, a selective neuronal NO synthase inhibitor, suppressed both peaks of NO metabolites, whereas prehypoxic treatment with aminoguanidine, a selective inducible NO synthase inhibitor, partially suppressed only the peak in the re-oxygenation period. These data suggest different roles of neuronal and inducible NO synthases in the pathogenesis of hypoxic-ischemic encephalopathy.

Animals↗
PubMed1998

Role of protein tyrosine phosphorylation in etoposide-induced apoptosis and NF-kappa B activation.

When a human myeloid cell line, U937, was incubated with etoposide (10 micrograms/mL), morphologically apoptotic cells first appeared at 3 hr and increased with time to 50% at 6 hr. Pretreatment of U937 cells for 30 min with a potent tyrosine kinase inhibitor, herbimycin A (10 microM), significantly suppressed the appearance of apoptotic morphological changes. Concomitantly, herbimycin A pretreatment prevented both high molecular weight and internucleosomal DNA fragmentation induced by etoposide. Two major bands at 30 and 66 kDa with enhanced tyrosine phosphorylation inhibited by herbimycin A were detectable after 30 min of incubation with etoposide. In addition, herbimycin A prevented etoposide-induced NF-kappa B activation. The expressions of Bcl-2 and Bax, on the other hand, were not affected by herbimycin A pretreatment. Herbimycin A was also found to inhibit 1-beta-D-arabinofuranosylcytosine-induced apoptotic changes and NF-kappa B activation. These results suggest that activation of tyrosine kinase(s) may play an important role in apoptotic processes induced by a variety of anti-cancer drugs.

Apoptosis↗
PubMed1998

Measurement of mutation frequency at the HPRT locus in peripheral lymphocytes. Is this a good method to evaluate a cancer risk in pediatric patients?

Validity of measurement of somatic cell mutation frequency (Mf) at the hprt locus for evaluating cancer risk of the given individual was determined in pediatric patients. Peripheral lymphocytes (PL) from patients with various diseases, including acute lymphoblastic leukemia (ALL) and Hodgkin's disease (HD), DNA repair deficient syndromes or short stature receiving growth hormone (GH), were isolated through Ficoll-Hypaque sedimentation with informed consent. Mf at the hprt locus of PL was determined by limiting dilution assay using 6-thioguanine (6-TG). Results were as follows. (1) ALL patients after chemotherapy had higher Mf than that of age-matched controls. (2) Patients with HD tended to have higher Mf after chemotherapy. (3) Among DNA-repair deficient syndromes, diseases which are susceptible to cancer (Xeroderma pigmentosum, Ataxia telangiectasia) have high Mf, but those without any cancer disposition (Cockayne syndrome, Rothmund-Thomson syndrome) have normal Mf. (4) GH-receiving patients have normal Mf, regardless of total doses of GH. Measurement of Mf at HPRT locus may be useful for evaluating cancer risk of pediatric patients.

Adolescent↗
PubMed1998

IL-4 and prostaglandin E2 inhibit hypomethylation of the 5' regulatory region of IFN-gamma gene during differentiation of naive CD4+ T cells.

We have previously shown that prostaglandin E2 (PGE2) and IL-4 inhibit the priming of IFN-gamma-production during the differentiation of naive CD4+ T cells from human cord blood by different signal-transducing mechanisms. To compare and analyse the molecular mechanisms by which PGE2 and IL-4 inhibit the priming of IFN-gamma production, we investigated the effects of PGE2 and IL-4 on the methylation of the IFN-gamma gene during the in vitro differentiation of naive CD4+ T cells. In human naive CD4+ T cells, which produce primarily IL-2 and a little amount of IFN-gamma, the IFN-gamma gene was methylated. After stimulation via TCR, CD4+ T cells produced IFN-gamma and the CpG dinucleotide contained within the TATA proximal regulatory element of the IFN-gamma gene was partially hypomethylated. Both IL-4 and PGE2 inhibited the hypomethylation of this site and the acquisition of IFN-gamma-producing ability. In contrast to the SnaBI site in the TATA proximal regulatory element, the HpalI site in the first intron of the IFN-gamma gene of the CD4+ T cells from cord blood was completely methylated even after stimulation via TCR. 5-azacytidine restored the IFN-gamma-producing ability of these cells treated with IL-4 and PGE2. These findings suggest that, although the signal transduction that inhibits the priming of IFN-gamma-production is different for each reagent, the protection from hypomethylation of the regulatory region of the IFN-gamma gene is involved in the molecular mechanisms by which these reagents inhibit the priming of IFN-gamma-production during the differentiation of human naive CD4+ T cells.

Azacitidine↗
PubMed1998

Dynamics of the carbohydrate chains attached to the Fc portion of immunoglobulin G as studied by NMR spectroscopy assisted by selective 13C labeling of the glycans.

A systematic method for 13C labeling of the glycan of immunoglobulin G for NMR study has been developed. A mouse immunoglobulin of subclass IgG2b has been used for the experiment. On the basis of chemical shift and linewidth data, it has been concluded that (1) the mobility of the carbohydrate chain in IgG2b is comparable to that of the backbone polypeptide chain with the exception of the galactose residue at the nonreducing end of the Man alpha 1-3 branch, which is extremely mobile and (2) agalactosylation does not induce any significant change in the mobility. The results obtained indicate that even in the agalactosyl from the glycans are buried in the protein. Biological significance of the NMR results obtained is also briefly discussed.

Animals↗
PubMed1998

X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It is X-linked and hemizygous new-born males usually suffer fatal hyperammonemia. In contrast, carrier females manifest variable phenotypes, ranging from asymptomatic carriers to those with severe hyperammonemia. In order to understand the correlation between X-inactivation status and the clinical phenotype of carrier females with this disorder, we analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and two daughters with severe manifestation. In addition, we obtained tissue samples from various parts of the liver of one of these daughters and analyzed X-inactivation patterns and the residual OTC activities. The X-inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype. However, the X-inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. Interestingly, the degree of X-inactivation varied considerably, even within the same liver.

Child↗