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Biomedical subjects

A Yoshioka

Publications and source records attributed to A Yoshioka.

At least 145 records · Page 8Linked to original sources
PubMed1996

Measurement of anti-factor IX IgG subclasses in haemophilia B patients who developed inhibitors with episodes of allergic reactions to factor IX concentrates.

We have established a simple enzyme-linked immunosorbent assay (ELISA) for the detection of anti-factor IX IgG subclasses in haemophilia B patients with inhibitors. The assay was performed using immobilized purified factor IX. Specific IgG subclasses were detected by peroxidase-conjugated anti-human IgG1,2,3 and 4. Ten plasma samples from 6 haemophilia B patients with inhibitors ranging from 1.0 to 253 Bethesda Units/ml were analyzed. All samples were positive for IgG4. Six out of 10 samples were positive only for IgG4. Three samples were positive for IgG2. Five of the 6 patients had previously had allergic reactions to factor IX concentrates. Three patients had allergic episodes within the past month. Three samples from these latter patients taken on the day when the allergy had occurred showed positive also for IgG1. In later samples, however, taken at 4 days and 4 weeks respectively from two of these same patients. IgG1 was not detected. In two of the five patients in whom allergic reactions had occurred more than one month previously IgG1 was not detected. The results suggested that allergic reactions in patients with haemophilia B treated with factor IX concentrates were associated with the development of the specific IgG1 subclass of antibody to factor IX.

Adolescent↗
PubMed1996

Inhibition assay for the binding of biotinylated von Willebrand factor to platelet-bound microtiter wells in the presence of ristocetin or botrocetin.

We developed a solid-phase inhibition assay for the binding of biotinylated von Willebrand factor (vWF) to platelet glycoprotein (GP)Ib based on an enzyme-linked immunosorbent assay (ELISA) with platelet-bound microtiter wells. Washed platelets were immobilized onto the microplates via the anti-GPIIb/IIIa monoclonal antibody (mAb) VNR-5. In the presence of an antibiotic ristocetin (1 mg/ml, final) or the snake venom botrocetin (2 micrograms/ml, final), biotinylated vWF bound to the affixed platelets with half-maximal binding occurring at a vWF concentration of approximately 2 micrograms/ml. Several specific inhibitors of the binding of vWF to GPIb abolished the interaction of biotinylated vWF with GPIb in a dose-dependent fashion, with comparable protein concentrations to those seen in the liquid-phase inhibition assay using 125I-vWF. These inhibitors included mAb against vWF (NMC-4), mAb against GPIb (AP-1), and two vWF fragments containing vWF's putative GPIb-binding domain, namely a 39/34-kDa dispase-digested vWF fragment and a recombinant vWF fragment. Thus, this new assay is a convenient alternative to the conventional inhibition assay using 125I-vWF.

Anti-Bacterial Agents↗
PubMed1996

Factor VII binding to tissue factor in plasma from warfarin-treated individuals.

Using enzyme immunoassay, we measured the binding ability of artificial gamma-carboxyglutamic acid (Gla)-domainless-Factor VII (FVII) to tissue factor (TF) or of Factor VII in 44 patients stabilized by long term treatment with warfarin. Purified FVII digested with cathepsin G, that is Gla-domainless-FVII, showed a rapid loss in the binding ability of FVII to TF (FVII-TF binding). After adsorption with Al(OH)3 of plasma from 8 out of 44 warfarin-treated patients, no FVII clotting activity (FVII:c) was detected in the supernatant, whereas FVII antigen (FVII:ag) and FVII-TF binding remained 19.2% and 17%, respectively, as compared with those before adsorption. In the plasma from 44 warfarin-treated patients the FVII:c (mean +/- SD, 54.26 +/- 12.50%) was significantly lower than the FVII:ag (77.15 +/- 18.24%) (p < 0.001), although the FVII:c was significantly correlated with FVII:ag (r = 0.628). FVII-TF binding (68.27 +/- 21.16%) was significantly higher than FVII:c (p < 0.001), but not than FVII:ag (p > 0.05). The FVII-TF binding was significantly correlated with FVII:ag (r = 0.738), but somewhat poorly with FVII:c (r = 0.415). These results show that artificial Gla-domainless-FVII digested with cathepsin G loses both the clotting activity and the binding ability to TF. However, PIVKA-VII has little or no clotting activity but the binding ability to TF. This suggested that the low specific activity of FVII (FVII:c/FVII:ag) in the plasma of warfarin-treated patients would not entirely depend on the decreased FVII-TF binding.

Adsorption↗
PubMed1996

Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.

The sixth edition of the haemophilia B database lists in easily accessible form all known factor IX mutations due to small changes (base substitutions and short additions and/or deletions of <30 bp) identified in haemophilia B patients. The 1380 patient entries are ordered by the nucleotide number of their mutation. Where known, details are given on factor IX activity, factor IX antigen in circulation and origin of mutation. References to published mutations are given and the laboratories generating the data are indicated.

Databases, Factual↗
PubMed1996

Evaluation of patients with advanced neuroblastoma surviving more than 5 years after initiation of an intensive Japanese protocol: a report from the Study Group of Japan for Treatment of Advanced Neuroblastoma.

In January 1985, a single protocol consisting of cyclophosphamide, vincristine, tetrahydropyranyl adriamycin, and cis-platinum for the treatment of advanced neuroblastoma was begun nationwide in Japan and was found to improve clinical results significantly in terms of 2- or 3-year survival rate. Between January 1985 and December 1988, 113 eligible patients (7 infants younger than 12 months of age with stage IVA disease and 106 patients aged 12 months or older with stage III or IV disease) were enrolled and followed up for 5 years or more after initiation of treatment, as of March 1994. In this study, the usefulness of the protocol for the treatment of advanced neuroblastoma was evaluated with survival rates in relation to age, tumor site, stage, and N-myc amplification for patients surviving more than 5 years after initiation of the protocol. Fifty of the 113 patients were alive 5 years or more after initiation of the treatment, 39 without any episodes of disease recurrence. Fourteen (70%) of 20 patients with stage III, 6 (50%) of 12 with stage IVB, and 24 (30%) of 81 with stage IVA disease were alive and disease-free 5 years after initiation of the protocol. Twenty (56%) of 36 patients without N-myc amplification were alive at 5 years after initiation of the protocol. Only one patient who was alive without evidence of the disease at 5 years had recurrence afterward.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Hereditary partial deficiency of plasminogen activator inhibitor-1 associated with a lifelong bleeding tendency.

We report a family with a partial deficiency of plasminogen activator inhibitor-1 (PAI-1). The affected family members had had lifelong bleeding episodes, such as rebleeding after tooth extraction and trauma. This bleeding tendency in the propositus was autosomally transmitted from grandfather to son. The characteristic abnormalities of fibrinolysis in the patients were shortened eugloblin lysis time, low PAI activity with low antigen levels of plasminogen activator inhibitor-1 in plasma and serum. Furthermore, plasma 'active PAI' which indicates the quantity of plasminogen activator inhibitor-1 bound with plasminogen activator added was very low in these patients. These parameters were markedly low after the venous occlusion test. Moreover, two of the affected members had a much lower level of platelet PAI-1 than the normal controls. Tranexamic acid (Transamine) was useful to control bleeding in these patients.

Adolescent↗
PubMed1996

Changes in factor VIII binding capacity of von Willebrand factor and factor VIII coagulant activity in two patients with type 2N von Willebrand disease after hemostatic treatment and during pregnancy.

The changes of the FVIII binding capacity of vWF after the infusion of FVIII/vWF concentrate was studied in two patients with type 2N vWD, and also during pregnancy in one of them. After infusion of FVIII or DDAVP to the patients, FVIII:C in plasma increased as expected, but it then decreased, with a markedly short half-life, of about 2 h, due to the defect in the FVIII binding capacity of vWF in plasma. However, after infusion of FVIII/vWF concentrate (40 U of FVIII:C/kg), FVIII:C increased, from 4-6 to 100-160 U/dl, more than the expected values, and decreased with the half-life expected. The FVIII binding capacity of vWF in plasma changed in parallel with the concentration of exogenous normal vWF, with a half-life of more than 24 h. During pregnancy, no increase of FVIII:C was observed, although vWF:Ag increased from 40 (before pregnancy) to 90 U/dl in plasma at 35th week of gestation. The FVIII binding capacity of vWF in plasma showed no increase during pregnancy. Accordingly, the administration of FVIII/vWF concentrate to the patient at delivery resulted in adequate hemostasis.

Deamino Arginine Vasopressin↗
PubMed1996

Effect of depolymerized holothurian glycosaminoglycan (DHG) on the activation of factor VIII and factor V by thrombin.

Our previous study has shown that depolymerized holothurian glycosaminoglycan (DHG) has two different inhibitory activities in the blood coagulation cascade: heparin cofactor II-dependent thrombin inhibition; and antithrombin III- and heparin cofactor II-independent inhibition of the intrinsic factor Xase complex [Nagase et al. (1995) Blood 85, 1527-1534]. In the present study, the effect of DHG on the activation of factor VIII and factor V by thrombin was examined with purified human components. DHG inhibited the activation of factor VIII by thrombin at concentrations exceeding 80 nM, but not the activation of factor V by thrombin at concentrations of up to 8 mu M. On Western blot analysis, DHG inhibited the cleavage of factor VIII light chain at concentrations exceeding 0.8 mu M. The interaction between DHG and factors VIII and V and thrombin was examined with a DHG-cellulofine column. DHG had strong affinity for factor V and thrombin, but slight affinity for factor VIII. The interaction of DHG with thrombin was analyzed, using fluorescein isothiocyanate-labeled DHG. One mole of DHG bound 2 mol of thrombin, with a dissociation constant (Kd) of 3.04 x 10(-6) M. These results suggest that DHG interferes with the interaction between thrombin and factor VIII, probably by making a binary complex through the anionic binding exosite II of thrombin.

Animals↗
PubMed1996

Genotypes and multiple infections with hepatitis C virus in patients with haemophilia A in Japan.

Hepatitis C virus (HCV) RNA was tested for, and HCV genotypes determined, in 96 patients with haemophilia A in Japan. Of 88 patients aged > or = 10 years, 74 (84%) were positive for HCV RNA at a frequency higher than that in patients aged less than 10 years (one of eight, 13%, P < 0.001). Genotype I/1a was detected in 30(40%), II/1b in 12 (16%), III/2a in eight (11%), IV/2b in five (7%) and V/3a in 12 (16%); mixed infection with HCV of two different genotypes was identified in the remaining nine (12%). This distribution was markedly different from that in 767 Japanese HCV carriers without haemophilia, in whom II/1b accounted for the majority (68.7%), I/1a was rare (0.5%), V/3a was absent, and mixed infection was observed rarely (1.3%). Mixed infection was transient in all of the seven haemophilic patients who were followed for 1 to 7 years. One of them was infected with genotype II/1b and an unclassifiable genotype, which showed nucleotide sequence similarity to genotype 4c from Zaire (82% homology in the E1 gene) and to 4a from Egypt (91% homology in a part of the NS5b region). In this patient, HCV of genotype II/1b disappeared while that of group 4 survived during a 4-year observation period. These results indicate different epidemiology of HCV genotypes in Japanese haemophiliacs, attributable to HCV contaminating factor VIII imported in the past, and an increased opportunity in haemophiliacs for mixed infection with HCV of different genotypes.

Adolescent↗
PubMed1996

A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy.

A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-123I-iodoamphetamine (123 I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.

Adrenocorticotropic Hormone↗
PubMed1996

[A case of AIDS with intractable cryptococcal meningitis].

A 38-year-old hemophiliac, who had been infected with HIV by the administration of blood products and had been diagnosed as AIDS by the onset of Pneumocystis carinii pneumonia, was admitted to our hospital with the complaints of headache and vomiting. After he was diagnosed as cryptococcal meningitis using the microscopy, cryptococcal antigen detection and culture of cerebrospinal fluid, treatment with amphotericin-B and fluconazole was started. As there was no clinical improvement, spinal drainage was performed and acetazolamide administered in order to reduce the intracranial pressure. Treatment was changed from AMPH-B and FLCZ to a combined therapy of AMPH-B and itraconazole. As his clinical features showed improvement, he was discharged home on a maintenance dose of ITCZ and acetazolamide after having been hospitalized for three months. This case-report may be of use in the management of cryptococcal meningitis in patients with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pulmonary function is diminished in older asymptomatic smokers and ex-smokers with low attenuation areas on high-resolution computed tomography.

OBJECTIVES: The relation between pulmonary function and low attenuation areas (LAAs) on high-resolution computed tomography (HRCT) is not clear in subclinical pulmonary emphysema. Accordingly we examined pulmonary function and HRCT in asymptomatic community-based volunteers. DESIGN: The existence of LAAs on CT was evaluated independently by three respiratory physicians who were blind to the pulmonary function test data and smoking histories of the subjects. The LAA grade was assessed by a visual scoring method from 0 to 5, and the individual LAA score and the values of pulmonary function tests were compared. PARTICIPANTS: 57 subjects aged from 32 to 82 years [mean 62 +/- (SD) 11] years were enrolled in the study. RESULTS: LAAs were found in 20 of the 49 subjects who were current or ex-smokers but in none of the 8 who never smoked. LAAs observed were mostly less than 25% of the total areas of the lungs. Although all mean values were within normal limits, the forced expiratory volume in 1 s (%pred), maximal expiratory flow at 50% of forced vital capacity (%pred), diffusing capacity of the lungs for carbon monoxide (DLCO; %pred) and diffusing capacity for carbon monoxide per unit alveolar volume (DLCO/VA; %pred) were all significantly less in those with LAAs than in those without LAAs. There was also a significant tendency for DLCO %pred and DLCO/VA %pred to decrease as the LAA scores increased. CONCLUSION: Those who have LAAs on CT have a small but significant deterioration in pulmonary function tests even if the LAAs observed are minimal or mild in degree. Longitudinal studies will be necessary to determine whether LAAs on CT identify the subjects who will develop airflow obstruction over time.

Adult↗
PubMed1996

Thrombelastgram as a hemostatic monitor during recombinant factor VIIa treatment in hemophilia A patients with inhibitor to factor VIII.

Thrombelastgram (TEG) is an old but automated instrument that demonstrates changes occurring during blood coagulation and fibrinolysis. TEG was evaluated to be better than activated partial thromboplastin time (APTT) as a monitor of hemostatic effects when using recombinant factor VIIa (65-80 mu g/kg) in 3 hemophilia A patients with a high titer of factor VIII inhibitors. TEG was more suitable than APTT, because r, r + k and ma values of TEG were normalized at least for 4 h after the infusion, whereas APTT was variably shortened and was not always maintained at a normal level for 4 h.

Adult↗
PubMed1996

Elastin-derived peptides and neutrophil elastase in bronchoalveolar lavage fluid.

To evaluate effects of current smoking on the breakdown of lung elastin, we measured levels of elastin-derived peptides (EDP) in unconcentrated bronchoalveolar lavage (BAL) fluid from 42 community-based older asymptomatic volunteers (60 +/- 11 yr [mean +/- SD]) and examined the relationships of the concentrations of EDP with immunologically detected neutrophil elastase (NE) bound with alpha(1)-proteinase inhibitor and with esterolytic activity against the NE-sensitive synthetic substrate, methoxysuccinyl-alanyl-alanyl-prolyl-valyl paranitroanilide (MEOSAAPVNA). The measurement of EDP levels was carried out by an indirect, competitive ELISA, using a sheep IgG fraction generated against insoluble human lung elastin as a primary antibody. EDP concentrations were significantly elevated in current smokers (n = 24) compared with age-matched noncurrent smokers (n = 18) (29.9 +/- 3.5 [mean +/- SE] versus 17.0 +/- 1.8 ng/mg BAL fluid albumin, p < 0.01). We found weak but significant correlations of EDP levels with NE-alpha(1)-proteinase inhibitor complex (r = 0.38, p < 0.05) and with the esterolytic activity against the NE-sensitive synthetic substrate in BAL fluid (r = 0.65, p < 0.001). In addition, EDP levels in BAL fluid had a significant positive relationship with plasma cotinine concentrations (r = 0.53, p < 0.001), though not with pack-years of smoking (r = 0.1, NS). These data provide further evidence that the concentrations of EDP increase in BAL fluid from current smokers compared with noncurrent smokers and that enhanced breakdown of the lung elastin is associated with the increased load of NE in the lung.

Aged↗
PubMed1996

Safety profile of porcine factor VIII and its use as hospital and home-therapy for patients with haemophilia-A and inhibitors: the results of an international survey.

A multicentre retrospective survey was conducted to re-assess the use of porcine factor VIII (HYATE:C), its side effects and the selection of patients for regular or home-therapy. 15,152,000 units of HYATE:C were used by 154 patients. The median inhibitor cross-reactivity to porcine VIIIC of 137 patients was 15%, 27% of patients lacking cross-reactivity. An absent, intermediate or brisk specific antiporcine anamnestic response was observed in 29, 40 and 31% of patients respectively. Seven patients were treated on-demand as home-therapy for a median 6.2, range 1.5-13 years, 23 further patients were treated regularly in hospital for a median of 3, range 2-7 years. This group used 8,319,000 U of porcine VIIIC for 2,000 bleeding episodes. The incidence of transfusion reactions was 0.001%, 0.64% and 2.3%, for domiciliary infusions, infusions in multiply treated in-patients, and unselected in-patient infusions, respectively. The risk of reactions was dose-related. A post-infusion fall in platelet count was common, but usually transient and clinically insignificant. This was also dose-related (r = -0.64, p = 0.002). Marked reductions in platelet count were occasionally seen, usually with intensive replacement therapy. The relative lack of side effects observed amongst patients treated at home is attributable to the low, median 33 U/kg, dose used by this group. A subgroup of inhibitor patients, identifiable by their absent or modest anamnestic response to porcine factor VIII may be treated regularly and safely with this product in small doses, over a period of years.

Animals↗
PubMed1996

Genetic characterization of protein C deficiency in Japanese subjects using a rapid and nonradioactive method for single-stand conformational polymorphism analysis and a model building.

We studied the molecular basis of protein C deficiency in 28 Japanese families including 4 asymptomatic families. Two showed a decreased level of function with a normal antigen concentration consistent with type II protein C deficiency and the remaining 26 showed type I deficiency with decreases in both function and antigen level. All the exons and intron/exon junctions of the protein C gene were studied using a strategy combining polymerase chain reaction (PCR) amplification and rapid nonradioactive single-strand conformational polymorphism (SSCP) analysis. The PCR-amplified fragments with aberrant migration on SSCP analysis were sequenced. We identified 11 missense mutations, 1 nonsense mutation, 2 neutral polymorphisms, 1 frameshift deletion, 1 inframe deletion, and 1 splice site mutation. We also identified two different rare mutations in the 5'-untranslated region in the protein C gene that may be responsible for the phenotype. Of these molecular defects, ten were novel. From the results of genetic analysis of 47 Japanese families with protein C deficiency reported in this and previous studies, Phe139Val and Met364Ile substitutions and a G8857 deletion were only found in Japanese subjects and seem to be a founder effect. In contrast, Arg169Trp and Val297Met substitutions, both occurring at CG dinucleotides, were commonly observed in not only Japanese but also Western populations, indicating that these are hot spots for mutation in the protein C gene. These molecular defects were found in 22 families in total, accounting for 47% of Japanese families with protein C deficiency. The structural models of the second EGF and protease domains of activated wild-type and mutant human protein C suggest a possible substrate binding exosite on two loops; one from amino acid position 349 to 357 and the other from position 385 to 388, both of which are close to each other in the three-dimensional model.

Amino Acid Sequence↗