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K Fukutake

Publications and source records attributed to K Fukutake.

At least 19 recordsLinked to original sources
PubMed1999

Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression.

RANTES (regulated on activation normal T cell expressed and secreted) is one of the natural ligands for the chemokine receptor CCR5 and potently suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Previous studies showed that peripheral blood mononuclear cells or CD4(+) lymphocytes obtained from different individuals had wide variations in their ability to secrete RANTES. These findings prompted us to analyze the upstream noncoding region of the RANTES gene, which contains cis-acting elements involved in RANTES promoter activity, in 272 HIV-1-infected and 193 non-HIV-1-infected individuals in Japan. Our results showed that there were two polymorphic positions, one of which was associated with reduced CD4(+) lymphocyte depletion rates during untreated periods in HIV-1-infected individuals. This mutation, RANTES-28G, occurred at an allele frequency of approximately 17% in the non-HIV-1-infected Japanese population and exerted no influence on the incidence of HIV-1 infection. Functional analyses of RANTES promoter activity indicated that the RANTES-28G mutation increases transcription of the RANTES gene. Taken together, these data suggest that the RANTES-28G mutation increases RANTES expression in HIV-1-infected individuals and thus delays the progression of the HIV-1 disease.

Base Sequence↗
PubMed1999

[Suggestions and propositions to resolve some issues for standardization of prothrombin time and activated partial thromboplastin time].

Prothrombin time (PT) and activated partial thromboplastin time (APTT), popularized as a routine assay for screening blood coagulation disorders and monitoring anticoagulant therapy, still involve some issues regarding standardization. In this lecture, we present propositions to resolve these problems in respective laboratory. Although international normalized ratio (INR) calculated by international sensitivity index (ISI) of PT reagent seems to improve discrepancy of sensitivity between reagents, local calibration of sensitivity of PT reagent in respective laboratories (local SI) is reasonable to make INR/ISI system more useful. However, local calibration of reagent is not easy by WHO recommended method in a small size laboratory. By using AK calibrant (IMMUNO AG), one of calibration plasma for INR, we investigated its possibility to calibrate local SI in four different reagents, compared with the recommended methodology. The results led the following process to determine reagent and calibrate local SI for practical use of INR/ISI system. (a) Use PT reagent of which ISI is close to 1.0 if possible, and utilize manufacture's ISI as is for INR. (b) Select PT reagent labeled specific ISI for an instrument as the same as used in the lab., and use the manufacture's ISI as is, if impossible to choose small ISI reagent. (c) If use a reagent of which ISI is close to 2.0 and shown no specific ISI for used detector, adjustment of local SI by commercial calibration plasma is recommended when unavailable warfarinized patient plasma. In APTT, we attempted to evaluate sensitivity between five different APTT reagents with a patient model by hemophilia A plasma contained various FVIII: C. This model reflected difference of sensitivity between reagents in results. Because standardization of APTT is not improved in this point, certification of APTT pattern in each laboratories with patient models is required for not only monitoring of heparinization, but also screening of typical coagulation disorders such as hemophilia and von Willebrand disease.

Humans↗
PubMed1998

A sole del(15q) anomaly in post-myelodysplasia acute myeloid leukemia.

We report the second case of post-myelodysplasia acute myeloid leukemia (post-MDS AML) with a sole chromosome change del(15q). This anomaly is rarely seen. To our knowledge, only seven cases so far have been reported in human neoplasias, including one case each of acute myeloid leukemia (AML), acute lymphoid leukemia, post myelodysplasia AML, myelodysplastic syndrome, myelofibrosis, macroglobulinemia, Hodgkin's lymphoma and uterine leiomyoma. This case suggests that del(15q) is related to lympho-myeloproliferative disorders. Moreover, we speculate that certain oncogene(s) located on 15q might have some role in the progression of the disease, since the del(15q) anomaly appeared only in the AML phase in this case.

Acute Disease↗
PubMed1998

[Prospective matched control study concerning the treatment and quality of life of hemophiliacs with inhibitors].

Factor VIII (IX) inhibitors represent one of the most serious problems for the treatment of patients with hemophilia. The Blood Products Research Organization (Japan) has supported a study group for treatment of hemophiliacs with inhibitors. In 1995 the study group started a prospective matched control study of hemophiliacs with and without inhibitors and compared such factors as quality of life and economic cost. Each inhibitor patient was matched with a control patient in terms of age, type of hemophilia, and severity of hemophilia. A total of 136 patient-pairs were enrolled. Bleeding episodes were more frequent in the control group than in the inhibitor group. Days of hospitalization, days in wheelchairs, and the number of impaired joints were significantly higher for the inhibitor group. Number of blood-product infusions, days of bed rest at home, and days of brace use were the same for both groups. Blood-product expenditures were significantly higher for the inhibitor group than for the control group (yen 10,872,283/patient/year vs. yen 4,327,542/patient/year). Our study highlighted the higher cost of treatment and lower quality of life for hemophiliaes with Factor VII inhibitors.

Adult↗
PubMed1998

[Hemophilia A].

Explore the source record for details and available documents.

Hemophilia A↗
PubMed1997

Factor VIII Ise (R2159C) in a patient with mild hemophilia A, an abnormal factor VIII with retention of function but modification of C2 epitopes.

We found a patient with mild hemophilia A who had no detectable factor VIII antigen (FVIII:Ag), as shown by two-site ELISA using inhibitor alloantibodies (TK). We then analyzed A2, A2/B, and C2 antigen of the patient's DDAVP-induced FVIII using several anti-FVIII monoclonal antibodies. Factor VIII activity (FVIII:C) was increased from 12 to 42 U/dl by the administration of DDAVP. The DDAVP-induced increases in the A2 and A2/B antigens were 40 and 36 U/dl, respectively. However, the increase in the C2 antigen was only 7.5 U/dl. SSCP analysis and subsequent sequencing demonstrated an Arg to Cys transition at codon 2159. The anti-FVIII:C titer of monoclonal antibody, NMC-VIII/5 which recognized the C2 domain, against normal plasma was 450 Bethesda U/mg of IgG. However, the titer against DDAVP-treated patient's plasma was only 15 Bethesda U/mg. We also tested DDAVP-induced increase in the FVIII:Ag in another mild hemophilia A patient with the same mutation at Arg2159. Increase in his C2 antigen levels was only 19% of those in the A2 and A2/B antigen. We designate this abnormal FVIII as FVIII Ise. Our results show that a missense mutation at Arg2159 to Cys modifies the antigenicity of the C2 domain.

Adolescent↗
PubMed1997

[Serum levels of soluble tumor necrosis factor receptors as markers for disease progression of human immunodeficiency virus infection].

We studied whether the serum levels of soluble tumor necrosis factor receptor(sTNFR) type I or II correlate with clinical progression of human immunodeficiency virus type 1(HIV-1) infection. Serum levels of sTNFR type I and II were measured by an enzyme-linked immunosorbent assay in sixty five patients with HIV-1 infected hemophiliacs and 10 healthy controls. In a longitudinal study, we assessed whether the decline of CD4+ lymphocyte counts were associated with increased serum concentrations of sTNFRs. Elevated serum concentrations of sTNFRs were found among the HIV-1 infected patients and higher in patients with advanced clinical stage. We noticed there were two distinct patient groups in change of CD4+ lymphocyte count when twenty-eight patients were followed retrospectively for a median period of 65 months. 14 patients represented stable CD4+ lymphocyte counts, but another 14 patients had more than 40% decrease of CD4+ lymphocyte counts over the course of this study. Serum sTNFR type II levels were 3.49 +/- 0.71 to 3.11 +/- 0.31 ng/ml in the former group, and 4.88 +/- 0.91 to 4.26 +/- 0.71 ng/ml in the latter group during the study. Significantly higher levels of sTNFR type II were already revealed at early time in the latter group. There was, however, no significant difference in the level of sTNFR type I between the two. These results suggest that serum levels of sTNFR type II provided useful information as a predictor of disease progression related to the decline of CD4+ lymphocyte counts.

Adult↗
PubMed1996

Heterozygote for plasmin inhibitor deficiency developing hemorrhagic tendency with advancing age.

A heterozygote for congenital deficiency of plasma plasmin in inhibitor had hemorrhagic episodes repeatedly after the age of 79. Before the age of 79, he had not exhibited any hemorrhagic tendency and did not have abnormal bleeding even after surgical operations. Although heterozygotes for congenital deficiency of this inhibitor usually have no or only a mild hemorrhagic tendency, this case suggests that they may exhibit severe hemorrhagic tendency when they reach advanced ages because of age-related vascular changes producing hemostatic imbalance.

Aged↗
PubMed1996

[Cytomegalovirus retinitis and Pneumocystis carinii choroidopathy in a patient with AIDS].

A case of Pneumocystis carinii (P. carinii) choroidopathy is reported. The patient was a 17-year-old man with acquired immunodeficiency syndrome (AIDS) who developed bilateral, multifocal, yellow-white, round, flat choroidal lesions ranging in size from 1/8 to 1/6 of the disc diameter while undergoing treatment for cytomegalovirus retinitis. He had had P. carinii pneumonia 43 months previously, and received inhaled pentamidine as suppressive therapy. Over a 4-week period of observation, the choroidal lesions appeared to enlarge slowly and increased in number in the posterior pole, with no clinical evidence of intraocular inflammation and retinal involvement. He was diagnosed as having P. carinii choroidopathy and treated with intravenous pentamidine. Three months after systemic pentamidine therapy was begun the choroidal lesions disappeared. Despite the fact that P. carinii choroidopathy is a rare opportunistic ocular infection, ophthalmic manifestations may be an important initial marker of extrapulmonary disseminated infection in some patients. Therefore we recommend ophthalmologic examinations in patients with AIDS who receive long-term aerosolized pentamidine prophylaxis for pneumonia.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Analysis of factors which affect the measurement of factor VIII inhibitor by Bethesda method].

Factor VIII neutralizing antibody (factor VIII inhibitor) sometimes develops in the patients with hemophilia A who are treated with factor VIII concentrates and more rarely in non-hemophilic individuals as auto antibody. Factor VIII inhibitor titer is most commonly measured by Bethesda method in which the sample is mixed with normal pooled plasma as a source of factor VIII for 2-hour incubation followed by measurement of residual factor VIII activity. Because of its simplicity and accessibility of normal pooled plasma, Bethesda method is widely used in clinical laboratories. However, the reproducibility of the assay is not generally considered to be satisfactory and measurement of inhibitor units varies among laboratories. In the present study, the factors which affect the measurement of Bethesda method were assessed. The reproducibility of Factor VIII activity showed better in a factor VIII dose dependent manner and varies according to clotting threshold of the sample that is analyzed by an automated coagulation equipment and a desktop computer. The reproducibility of inhibitor measurement was worse in the inter-assay than in the intra-assay. The assay fluctuation of the measurement of lower inhibitor units tends to be more evident when the sample of 0.39 to 2.39 BU/ml were tested. The factor VIII content in the normal pooled plasma did not affect the measurement of factor VIII inhibitor units in the range of 0.8 to 1.2 U/ml. The buffers retained factor VIII in the control sample during the 2-hour incubation better in the order of imidazole buffer, bernard buffer, Tris-HCl buffer and saline.

Adult↗
PubMed1996

[Mutation detection enhancement (MDE) gel electrophoresis method for analysis of the von Willebrand factor gene].

We conducted electrophoresis using Mutation Detection Enhancement (MDETM) gel (AT Biochem) on the von Willebrand factor (vWF) gene from three unrelated patients with type 2A von Willebrand disease and one type 3 patient whose point mutations we had identified earlier. The mutations were located on the 3'region of exon 28 in the vWF gene in which three known polymorphisms were included. To eliminate any influence of the polymorphisms, 671bp including two AluI sites amplified by polymerase chain reaction (PCR) from the region of the vWF gene was digested with the restriction enzyme AluI and three fragments (283, 148, and 240bp) were obtained. Three polymorphisms were contained in the 283bp fragment and four mutations were found in the remaining fragments. Following MDETM gel electrophoresis, three of the four cases showed heteroduplex formations. One mutation was not detected, although the mutation was found to be heterozygous by the restriction analysis of MspI. Failure to detect this mutation may be attributed to the fact that it was located on the extreme end of the 148bp fragment of the 5' region. The results of this study suggest the MDETM gel electrophoresis method is useful in detecting gene mutations or polymorphisms in heterozygous subjects. Furthermore, this technique is more convenient than other methods for a base mismatch detection since specific apparatus or radioisotopes are not required.

Electrophoresis↗
PubMed1996

[Sulfamethoxazole-trimethoprim-induced pneumonitis in a patient with hemophilia B who was infected with the human immunodeficiency virus].

Severe cellular immunosuppression developed in a 25-year-old man with hemophilia B who was infected with the human immunodeficiency virus (HIV). Four days after administration of sulfamethoxazole-trimethoprim (SMX-TMP) for prophylaxis against Pneumocystis carinii pneumonia (PCP), diffuse uptake of both lungs was confirmed on a 67Ga scintigram. Reticular shadows were also seen throughout both lung fields on a chest CT scan. These findings were compatible with PCP, according to the guidelines for presumptive diagnosis of the acquired immunodeficiency syndrome, published by the Centers for Disease Control and Prevention. The dose of SMX-TMP was increased, but interstitial pneumonitis worsened and was accompanied by fever, skin rash, and liver dysfunction, which are common in HIV-infected patients receiving SMX-TMP. No evidence of PCP or of any other opportunistic infection was found by bronchoalveolar lavage. Adverse reactions diminished after SMX-TMP administration was stopped. The 67Ga scintigram and chest CT findings also returned to normal. We concluded that the interstitial pneumonitis was induced by SMX-TMP. SMX-TMP is the first choice anti-PCP drug, but a high incidence of adverse reactions in patients with HIV infection has been reported. Therefore the possibility of SMX-TMP-related pulmonary toxicity must be considered in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Changes of factor XIII a and b subunit in patients with disseminated intravascular coagulation syndrome].

Factor XIII is composed of two distinct proteins, a and b subunit. The dimers of each subunit form a tetrameric complex of a2b2 in plasma. Two separate ELISA systems were developed to measure either factor XIII a or b subunit in plasma. Sensitivity of the ELISAs was 3.0% of factor XIII a and b subunit in normal plasma. The ELISA for factor XIII b subunit quantitate free b2 and a2b2 complex in a equimolar manner. In order to evaluate the changes of each factor XIII subunit in a state of hypercoagulation, 16 plasmas from proteins with disseminated intravascular coagulation syndrome (DIC) were examined. Factor XIII a and b subunit showed 56.5 +/- 30.5% and 63.4 +/- 22.5%, respectively in the DIC subjects compared to normal pooled plasma as 100%. The ratio of factor XIII a and b subunit (a/b ratio) were between 0.5 and 1.0 in DIC cases which improved after treatment. However, the ratios were less than 0.5 in the cases with DIC which deteriorated in spite of the treatment. These results suggest that the a/b ratio would indicate the prognosis of patients with DIC.

Biomarkers↗
PubMed1996

A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.

Genetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEII.

Arginine↗