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Biomedical subjects

K Fukutake

Publications and source records attributed to K Fukutake.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1996

Factor VIII inhibitor antibodies with C2 domain specificity are less inhibitory to factor VIII complexed with von Willebrand factor.

In order to clarify the potential role of von Willebrand factor (vWf) in attenuating the inactivation of factor VIII (fVIII) by those antibodies with C2 domain specificity, we investigated a panel of 14 human antibodies to fVIII. Immunoblotting analysis localized light chain (C2 domain) epitopes for four cases, heavy chain (A2 domain) epitopes in five cases, while the remaining five cases were both light and heavy chains. The inhibitor titer was considerably higher for Kogenate, a recombinant fVIII concentrate, than for Haemate P, a fVIII/vWf complex concentrate, in all inhibitor plasmas that had C2 domain specificity. In five inhibitor plasmas with A2 domain specificity and in five with both A2 and C2 domain specificities, Kogenate gave titers similar to or lower than those with Haemate P. The inhibitory effect of IgG of each inhibitor plasma was then compared with recombinant fVIII and its complex with vWf. When compared to the other 10 inhibitor IgGs, IgG concentration, which inhibited 50% of fVIII activity (IC50), was remarkably higher for the fVIII/vWf complex than for fVIII in all the inhibitor IgGs that had C2 domain reactivity. Competition of inhibitor IgG and vWf for fVIII binding was observed in an ELISA system. In 10 inhibitors that had C2 domain reactivity, the dose dependent inhibition of fVIII-vWf complex formation was observed, while, in the group of inhibitors with A2 domain specificity, there was no inhibition of the complex formation except one case. We conclude that a subset of fVIII inhibitors, those that bind to C2 domain determinants, are less inhibitory to fVIII when it is complexed with vWf that binds to overlapping region in the C2 domain.

Antibody Specificity↗
PubMed1995

Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex.

To determine the difference in reactivity of factor VIII (FVIII) inhibitor to FVIII/von Willebrand Factor (vWF) complex and FVIII free of vWF, an autoantibody to FVIII light chain was tested. A patient (1-3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (I-3 IgG) was shown to be the C2 domain of FVIII light chain (2170-2332) by Western blotting using recombinant FVIII deletions expressed in Escherichia coli. The inhibitory effect on FVIII procoagulant activity (VIII:C) of I-3 IgG was tested against a conventional FVIII concentrate; Haemate P, a monoclonal antibody-purified FVIII concentrate; Hemofil M, and a recombinant FVIII (rFVIII); Kogenate. I-3 IgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mgIgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the I-3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVIII by forming a complex with vWF from 22 BU/mgIgG to 0.5 BU/mgIgG. Fab from the I-3 IgG had the same effect. In addition, vWF showed a protective effect on FVIII inactivation by the I-3 IgG in a dose dependent manner. Fifty-nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with I-3 IgG. These results suggested that vWF could compete with the I-3 IgG for binding to FVIII.

Adult↗
PubMed1995

Factor VIII inhibitor developed in a 60-year-old patient with mild hemophilia A after surgery for colon cancer.

Most factor VIII inhibitors are developed at an early age and in patients with severe type of hemophilia A. We report a case of newly developed factor VIII inhibitor in a 60-year-old patient with mild hemophilia A who had been treated with several kinds of factor VIII concentrates. The patient was treated with a total of 103,580 units of recombinant factor VIII concentrate by continuous and bolus infusions for the open surgery of sigmoid colon cancer. On the 95th postoperative day, the patient had right low limb muscle bleeding and was infused with 1,000 units of recombinant factor VIII concentrate for three days. Subsequently, the level of factor VIII inhibitor in the patient's plasma was 2 Bethesda units (BU)/ml. Since then numerous subcutaneous hemorrhages developed, but an adequate hemostatic effect was not obtained even with the administration of a high dose of recombinant factor VIII concentrate. The patient was switched to bypass therapy using human plasma-derived factor VIIa concentrate, which showed a favorable hemostatic effect.

Adenocarcinoma↗
PubMed1995

Platelets with 10% of the normal amount of glycoprotein VI have an impaired response to collagen that results in a mild bleeding tendency.

Platelet glycoprotein VI (GPVI), a 62kD membrane protein, has been identified as one of the platelet receptors for collagen, since GPVI-deficient platelets exhibit abnormal responses to collagen and an abnormal bleeding tendency. We report a female patient with a mild bleeding history whose platelets expressed 10% GPVI of normal platelets. Shape change, aggregation and ATP release of the patient's platelets were completely absent in response to 1-5 micrograms/ml collagen but present normally in response to ADP and Ca2+ ionophore A23187. Adhesion of the patient's platelets to coated collagen was mildly affected (40-60% of normal platelets) in spite of only 10% expression of GPVI. Flow cytometrical studies revealed that the patient's platelets expressed normal amounts of the GPIa/IIa complex. These results suggest that platelet GPVI is less involved in adhesion to collagen than shape change and aggregation induced by collagen.

Adenosine Diphosphate↗
PubMed1995

[Two cases of sensory neural hearing loss as a manifestation of HIV infection].

In patients with HIV infection, oral and pharyngeal pathology frequently occurs, but there have been no reports on cases of deafness in Japan. Herein, the authors report two cases of sensory neural hearing loss in hemophilia A patients infected with HIV through factor VIII concentrates. Case 1 was a 16-year-old male with hemophilia A. He had been administered factor VIII concentrates starting at 6 months after birth. At 8 years of age, HIV antibodies were positive. He was diagnosed as having AIDS after suffering from pneumocystis carinii. He complained of right otalgia and slight vertigo during treatment for a relapse of the pneumocystis carinii. He underwent otological examinations at our department. The right tympanic membrane showed opacification and serous otorrhea was noted. Acute otitis media was diagnosed and tympanotomy was conducted. Afterwards, the right tympanic membrane developed a large perforation and sensory neural hearing loss occurred. Case 2 was a 49-year-old male with hemophilia A. He had been administered factor VIII concentrates from the age of 23 years. At 48 years of age, HIV antibodies were positive. The patient complained of sudden deafness in the right ear and slight vertigo. He underwent otological examinations at our department. The tympanic membrane was normal bilaterally, but sensory neural hearing loss was found in the right ear. It was presumed that acute otitis media directly involving the inner ear had caused a perceptive disorder in case 1 while a pattern of sudden onset of deafness was apparent in case 2.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Enzyme immunoassay of blood coagulation and fibrinolysis factors].

Various types of immunoassays are at present applied to inspection items in clinical aspect of blood coagulation and fibrinolysis, in which EIA is acting as one of the major methods. Commercial EIA kits, available in Japan, can be itemized into categories of blood coagulation, fibrinolysis, endothelial cell injury, and platelet activation systems, along with other types of immunoassays and enzymatic activity assays, itemized for comparison. Assay methods suitable for an objective antigen should be selected, based on its biological, biochemical characteristics, such as plasma concentrations, and even clinical demands. The matters to be solved range over making reliable standard materials, using monoclonal antibody to detect absolute concentrates of specific antigen, and then further discovery of molecular markers that specifically reflect coagulative or fibrinolytic activation, leading to thrombotic or bleeding tendency.

Biomarkers↗
PubMed1995

[Massive and progressive hepatosplenomegaly caused by disseminated nontuberculous mycobacteriosis in a patient with acquired immunodeficiency syndrome].

A 28-year-old hemophilia A patient was admitted to our hospital in July, 1991 because of high fever, chronic diarrhea and anemia. The patient had been recognized as a asymptomatic carrier of human immunodeficiency virus (HIV) in 1985 and had developed Pneumocystis carinii pneumonia and had been diagnosed as acquired immunodeficiency syndrome (AIDS) in 1990. Hematologic laboratory examinations on admission revealed pancytopenia and a CD4+ cell count of 3/mm3. X-ray findings of chest and abdomen were normal and bacterial cultures of sputum, urine, blood, stool, cerebrospinal fluid and bone marrow yielded no pathogenic microorganisms. Microscopical examination of the stained specimens showed no acid-fast bacilli. On his fifth hospital day, his liver and spleen enlarged markedly and an abdominal CT scan obtained on the 13th day revealed high-grade hepatosplenomegaly. Administration of several kinds of antibiotics, antifungal agents, antiviral agents, antituberculous agents and gamma-globulin medicines did not relieve the symptoms. On the 28th day the patient had developed a subarachnoid hemorrhage and died five days later. Retrospectively all cultures for acid-fast bacilli of the specimens on his admission yielded nontuberculous mycobacteria. The bacteria were identified as Mycobacterium avium by polymerase chain reaction and his disease was eventually diagnosed as disseminated Mycobacterium avium complex (MAC) infection. The liver and spleen weighed 2,660 g and 1,840 g respectively at autopsy. Although hepatosplenomegaly is commonly recognized in AIDS patients with disseminated MAC infection, such massive and rapid enlargement has been rarely observed. This case study emphasize the importance of diagnosis and rapid treatment at the early stage of MAC infection.

AIDS-Related Opportunistic Infections↗