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Biomedical subjects

H Fukui

Publications and source records attributed to H Fukui.

At least 343 records · Page 19Linked to original sources
PubMed1991

Intramedullary multiple hematomas in siblings with congenital alpha-2-plasmin inhibitor deficiency: orthopedic surgery with protection by tranexamic acid.

Congenital alpha 2-plasmin inhibitor deficiency is very rare, but causes bleeding problems similar to hemophilia. Three young Japanese sisters affected with congenital alpha 2-plasmin inhibitor deficiency have been reported by us earlier. Recently we encountered a particular form of intramedullary multiple hematomas in the long bones in all of them which was not reported previously. In 2 of the sisters orthopedic operations were successfully performed by using an antiplasmin reagent: tranexamic acid. In this paper we describe the characteristics of the hematomas and the hemostatic management with tranexamic acid.

Adolescent↗
PubMed1991

Antiplatelet glycoprotein Ib monoclonal antibody (OP-F1) totally abolishes ristocetin-induced von Willebrand factor binding, but has minimal effect on the botrocetin-induced binding.

We describe here a new antiplatelet glycoprotein (GP) Ib monoclonal antibody (MoAb) designated OP-F1 (IgG1 kappa). Both OP-F1 and a well-characterized anti-GPIb MoAb, AP-1, totally abolished ristocetin-induced von Willebrand factor (vWF) binding to platelets and desialylated vWF binding to platelets at an IgG concentration of 2-8 micrograms/ml. AP-1 also blocked snake venom botrocetin-induced vWF binding at a similar IgG concentration, whereas OP-F1 had a minimal effect on botrocetin-induced binding. At a higher IgG concentration (150 micrograms/ml), OP-F1 inhibited botrocetin-induced binding by 50%. AP-1 (IgG) did not interfere with binding of [125I]OP-F1 (IgG) to platelets. Thus, the epitope involved in the binding of OP-F1 or AP-1 appears to be quite different. These results suggest that the vWF binding site(s) on the GPIb molecule generated by these inducers is in close proximity but not completely identical.

Antibodies, Monoclonal↗
PubMed1991

Functional expression of H1-histaminergic receptors in Xenopus laevis oocytes injected with bovine adrenal medullary mRNA.

We prepared poly (A)+ mRNA from bovine adrenal medulla and electrophysiologically examined the expression of H1-histaminergic receptors in Xenopus laevis oocytes. Histamine dose-dependently induced inward currents in oocytes injected with the mRNA, but not in those injected with water or the non-injected oocytes. This response was also induced by H1-agonists and antagonized by H1-antagonists, while both an H2-agonist and an antagonist had no effect. These results clearly demonstrate that H1-histaminergic receptors are functionally expressed in oocytes injected with exogenous mRNA.

Adrenal Medulla↗
PubMed1991

[3H]mepyramine binding sites, histamine H1-receptors, in bovine retinal blood vessels.

The presence of histamine H1-receptors in the bovine retinal blood vessels was studied with a [3H]mepyramine binding assay. The membranes of purified vessels obtained from bovine retinas showed specific [3H]mepyramine binding sites with a dissociation constant (KD) of 2.78 +/- 0.32 nM. This was similar to values obtained from the retinal neuronal fractions. The binding capacity (Bmax) was 53.8 +/- 1.7 fmol/mg protein, which was about a half that of the retinal neuronal fractions (108.9 +/- 3.1 fmol/mg protein). Some H1-antagonists proved to be potent competitors for [3H]mepyramine binding sites in bovine retinal blood vessels. These results indicate that histamine H1-receptors exist in the retinal blood vessels which may be involved in the physiological and the pathological responses of blood circulation in retinas.

Animals↗
PubMed1991

[Histamine metabolism in the nasal tissue of human and nasal hypersensitive guinea-pig].

Histamine (HA) is the most important mediator of nasal allergy and nasal hypersensitivity. To investigate HA metabolism, HA content and activities of its synthetic enzyme, histidine decarboxylase (HDC) and degrading enzymes, histamine-N-methyltransferase (HMT) and diamine oxidase (DAO) in nasal mucosa of human and toluene diisocyanate (TDI) sensitized guinea-pigs were measured. In human nasal mucosa and nasal polyps, HA content and HDC activity were 80-200 nmol/g tissue, 20-30 fmol/min/mg protein respectively. Among two degrading enzymes, HMT activity was 20-200 times higher than that of DAO. In the nasal mucosa of guinea-pigs, HA content was significantly increased by TDI sensitization, and was decreased immediately after TDI provocation. In 24 hours after provocation, HA content recovered to 80% of pre-provocation level. HDC activity increased by TDI sensitization significantly. Though HMT activity increased slightly by TDI sensitization and provocation, DAO activity was unchanged. The data suggest that, increase in turnover rate of HA is present in allergic nasal mucosa.

Amine Oxidase (Copper-Containing)↗
PubMed1991

[Mouse fetal brain specific protein "GP68" is expressed in human tumor cells].

It is well known that some fetal antigens are expressed in malignant tumor cells. Likewise, brain tumors, especially histologically malignant cases, may have any antigenic relationships with fetal brain. So, we investigated the relationship by immunohistochemical technique, utilizing a polyclonal antibody to mouse fetal stage-specific polypeptide "GP68". We prepared GP68 from homogenate of head part of embryos at the 14th day of gestation mice by RCA-1 agarose column chromatography. And immunized it to Japanese white rabbits and the titer was measured by enzyme-linked immunosorbent assay. We analyzed operatively resected brain tumors and autopsy brain tissues. Frozen tissues were fixed in cold acetone and immunostained with anti-GP68 serum according to biotin-streptavidin peroxidase method. Remained tissues were homogenized in Laemmli's sample buffer and electrophoresed. The proteins were transferred to nitrocellulose membrane and immunostained with anti-GP68. Normal brain tissues were not positively stained, except for capillary endothelium which showed a weak staining. On the other hand, brain tumors of neuroectodermal origin were positively stained in varying degrees, and other tumors were negative. It is especially noteworthy that, in astrocytoma cases, there exists a definite correlation between the intensity of stain and the degree of histological malignancy. Immunoblot studies demonstrated a very weak band at 68 KD in normal brain and meningioma. In contrast, very strong band at the same position was seen in malignant astrocytomas. These results suggested that in brain tumors, especially those of neuroectodermal origin, GP68 antigen is expressed and the degree of expression is related to their histological malignancy. So this fetal antigen may be useful for evaluation of biological malignancy of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Murine anti-human IL-6 monoclonal antibody prolongs the half-life in circulating blood and thus prolongs the bioactivity of human IL-6 in mice.

Human interleukin-6 (hIL-6) injected into mice increases antigen-specific antibody production. In the present study, we examined the possibility that anti-hIL-6 murine monoclonal antibody (MH-166) could neutralize this hIL-6 activity in vivo. Although MH166 completely neutralized hIL-6 activity in vitro, treatment in vivo with hIL-6 and MH166 combined unexpectedly increased both anti-dinitrophenyl (DNP) and anti-sheep red blood cell (SRBC) antibody production more than treatment with IL-6 alone did. To explain this phenomenon, the serum hIL-6 level was monitored following the MH166 administration. The hIL-6 level was significantly higher in the mice treated with both hIL-6 and MH166 than in the mice treated with hIL-6 alone during the 24 hr following hIL-6 administration. These results indicate that MH166 prolongs half-life of a xenogeneic hIL-6.

Animals↗
PubMed1991

Epitope localization of monoclonal antibodies against factor VIII light chain which inhibit complex formation by factor VIII with von Willebrand factor.

We obtained three clones of monoclonal antibodies against factor VIII by immunization with purified human factor VIII. The anti-factor VIII procoagulant activity of these antibodies ranged from 2 to 53 Bethesda units/mg of IgG. According to an immunoblotting study, all antibodies reacted with the 80 kDa light chain but not with 72 kDa peptides derived from thrombin digestion of factor VIII. We attempted to localize the antigenic epitopes of these antibodies by a competitive blocking assay using synthetic peptides and recombinant fragments of the amino-terminal region of factor VIII light chain. In the former assay, a 50 microM peptide containing the fifteen amino acid residues from the Val1670-Glu1684 completely inhibited the binding of the three monoclonal antibodies to immobilized factor VIII. In the latter experiment, 13 reactive recombinant peptides were obtained. Sequences of these peptides revealed fourteen overlapped amino acid residues from Glu1675 to Pro1688. All three antibodies at a final concentration of around 10 micrograms/ml completely inhibited the binding of 125I-labelled factor VIII to immobilized von Willebrand factor (vWF). We conclude that ten amino acid residues, 1675EDFDIYDEDE1684 in the factor VIII light chain are important for complex formation with vWF.

Antibodies, Monoclonal↗
PubMed1991

Changes in polypeptide-specific factor VIII antigen levels during whole blood clotting.

The time-course of factor VIII (FVIII) proteolysis during whole blood coagulation was monitored using polypeptide-specific enzyme-linked immunosorbent assays (ELISAs) developed with monoclonal antibodies to FVIII. Such assays of whole blood from normal subjects revealed that, within 30 min after coagulation had started, levels of the amino-terminal region of FVIII light chain and in the middle region of FVIII heavy chain had decreased to baseline in parallel with factor VIII procoagulant activity, but that levels of the 70 kDa thrombin digest decreased more slowly, with 75 U/dl of FVIII antigen (FVIII:Ag) remaining even after 2 h. Similar analysis of the blood of a patient with congenital hypoprothrombinemia indicated a lag phase of 20 min before proteolysis started. No significant change was observed until 1 h after calcium chloride was added to prothrombin-depleted plasma. On the other hand, in the presence of tissue thromboplastin, levels of FVIII:Ag in all ELISAs decreased rapidly. These results indicate a requirement for thrombin generation in the proteolysis of FVIII during the process of whole blood clotting.

Blood Coagulation↗
PubMed1991

Clinical evaluation of recombinant human factor VIII (BAY w 6240) in the treatment of hemophilia A.

A pilot clinical trial was conducted in five patients with severe hemophilia A to evaluate the safety and efficacy of a recombinant human factor VIII preparation, BAY w 6240 (rFVIII). In a comparative pharmacokinetic study of rFVIII and a plasma-derived factor VIII preparation (pdFVIII), the mean t1/2 values for rFVIII at week 1 and week 13 were 16.8 and 14.4 h, while this value for pdFVIII at week -2 was 16.9 h. There were no statistical differences between these values. The mean in vivo recovery rates of rFVIII were comparable to those of pdFVIII. When rFVIII was administered prophylactically three times a week for 4 weeks, no bleeding episodes were observed. Seventy-four bleeding episodes were assessed during the 6-month treatment period. The efficacy rate of the hemostatic effect was confirmed to be 95.9%. No adverse reactions attributable to rFVIII were observed in a total of 178 infusions. Neither FVIII-inhibitors nor antibodies to foreign proteins were detected. Vital signs and laboratory findings showed no significant changes attributable to rFVIII. These results suggest that rFVIII is safe and efficacious as replacement therapy for hemophilia A.

Adult↗
PubMed1991

[Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases].

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-Galactosyl-Human-Serum-Albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver diseases. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images was not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku and PT values were more significantly decreased or prolonged in the patients with liver cirrhosis than those in the patients with chronic hepatitis. Kd, Ku and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degrees of hepatic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Histamine and its synthesis in mammalian retinas.

Histamine (HA) content and histidine decarboxylase (HDC) activity were studied in the sensory retinas of the rat, guinea-pig, rabbit, dog, monkey, bovine and pig. Using a highly sensitive and specific method developed for the determination of histamine using high-performance liquid chromatography, HA was detected in the retinas of all species examined. HA content ranged from 11 (bovine) to 540 pmole/g wet tissue (dog), and HDC activity ranged from 2 (rabbit) to 150 (dog) fmol HA synthesized/min/mg protein. With the exception of the dogs, the retinal values were one order lower than those in the brain in all species examined. The canine retinas had the high HA and HDC values among the species examined, and were approximately equal to those in the brain. However, the ratios of HDC activity to HA content ranged from 0.04/min to 0.51/min. These values resembled those in the brain and were much higher than those in mast cells. This suggests that histamine in the retinas exists mainly in the neurons even though the actual amounts are small and may be involved in the physiological and the pathological responses in mammalian retinas.

Animals↗
PubMed1991

Ethanol-induced focal cell necrosis via microcirculatory disturbance in the perfused rat liver.

In the perfused rat liver, infusion of ethanol induced an initial increase in portal pressure which is an indicator of vasoconstriction and a subsequent increase in lactic dehydrogenase (LDH) release, which is an indicator of cell damage in a dose-dependent fashion. Simultaneous infusion of sodium nitroprusside, a potent vasodilator, (100 microM) inhibited the increases in portal pressure and LDH release. Focal hepatocellular necrosis evidenced by trypan-blue stained cell nuclei were localized in midzonal and pericentral area of the liver lobules at 60 min after ethanol load. These ethanol-induced microcirculatory disturbance might be involved in the pathogenesis of alcoholic liver disease.

Animals↗
PubMed1991

[Domain structure of human von Willebrand factor, and its modulators involved in the platelet adhesion process in vitro].

von Willebrand factor (vWF), a macromolecular glycoprotein synthesized in endothelial cells and megakaryocytes circulates in blood as heterogenous multimers and plays a critical role in the formation of platelet plugs. vWF is composed of an identical subunit with a molecular weight (MW) of 270 kDa, which is held together by disulfide bonds. Functional domains of vWF for factor VIII, heparin, platelet glycoprotein (GP) Ib, collagen, and GP IIb/IIIa locate in this order from the N-to C-terminus of subunit. The GP Ib binding domain is cryptic in normal circulation and only becomes expressed when vWF is associated with the subendothelial matrix or with fibrin. In vitro, an antibiotic ristocetin or the snake venom botrocetin isolated from Bothrops jararaca mimics the active component of subendothelial matrix and causes the binding of vWF to GP Ib. To elucidate the mechanism of in vitro process of vWF-GPIb binding, we describe here the isolation and characterization of two distinct forms of botrocetin. Since ristocetin is a heavily glycosylated proteoid, it is hard to characterize the structure on the basis of amino acid analysis. The apparent MW of the one-chain botrocetin was 28 kDa before and 32 kDa after reduction of disulfide bonds, while that of the two-chain botrocetin was 27 kDa before and 15/14.5 kDa after reduction. Amino acid composition of the two species revealed a similar high content of potentially acidic residues (greater that 60 Asx and Glx residues/molecules) but significant differences in the content of Cys and Phe residues. The N-terminal sequence of the one-chain was Ile-Ile/Val-Ser-Pro-Pro-Val-Cys-Gly-Asn-Glu-.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Renal disease in an adult with type 1 glycogen storage disease.

The renal disease in an adult woman with Type 1 glycogen storage disease (GSD) is reported. Since she was 15 years old, several episodes of gouty arthritis had developed. At the age of 18, proteinuria was pointed out. Hepatomegaly, renomegaly out of proportion to the impairment of renal function, hyperuricemia, hyperlipidemia, fasting hypoglycemia and lactic acidemia were observed. The diagnosis of GSD was established on the basis of a glucose tolerance test, glucagon test and liver biopsy. The findings of renal biopsies performed at the ages of 24 and 27 years old suggested that glomerular damage might have preceded the tubulo-interstitial lesion.

Adult↗
PubMed1990

Immuno-cross-reactivity of histidine and dopa decarboxylases.

Immuno-cross-reactivity between histidine decarboxylase (HDC) and dopa decarboxylase (DDC) was investigated. By comparing the cDNA sequences of rat HDC with rat and guinea-pig DDCs, we found a region that may possibly be related to the cross-reactivity of anti-rat HDC antibody with guinea-pig DDC. The peptide encoded by this region was synthesized and anti-peptide antibody was prepared. We also purified HDC and DDC homogeniously from fetal rat liver and guinea-pig liver, respectively. On immunoblotting, anti-peptide antibody recognized both rat HDC and guinea-pig DDC. Anti-HDC polyclonal antibody which also recognizes both enzymes detected only rat HDC when it was absorbed by the peptide. This result indicates that this region is responsible for the immuno-cross-reactivity of anti-rat HDC antibody with guinea-pig DDC.

Amino Acid Sequence↗
PubMed1990

Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant Factor VIII Study Group.

BACKGROUND: Current treatment of hemophilia A, a hereditary disorder affecting approximately 1 in 10,000 males, relies on plasma-derived factor VIII concentrates. We tested the safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder. METHODS: We conducted the investigation in three stages: comparing the pharmacokinetics of plasma-derived and recombinant factor VIII, assessing the efficacy of recombinant factor VIII for home therapy, and assessing its efficacy for major surgical procedures and hemorrhage. A total of 107 subjects with hemophilia, 20 of whom had not been treated previously, enrolled in the investigation. RESULTS: The in vivo recovery and elimination half-lives of recombinant factor VIII equaled or exceeded those of plasma-derived factor VIII. Seventy-six subjects participated in a home-treatment program, using recombinant factor VIII for 69 to 807 days (median, 618); home diaries of 56 subjects treated for 5 months were analyzed. Of 540 bleeding episodes, 399 (73.9 percent) required only one treatment with recombinant factor VIII. The projected annual consumption of recombinant factor VIII was similar to that of plasma-derived factor VIII concentrate. Twenty-six subjects received recombinant factor VIII for 22 surgical procedures and 10 serious hemorrhages; hemostasis was excellent in all cases. De novo formation of inhibitors occurred in only 1 of 85 previously treated subjects. Inhibitor antibodies also developed in 6 of 21 children, 20 of whom had not previously been treated; 5 had low levels (less than or equal to 7.5 Bethesda units) despite continued treatment with recombinant factor VIII. There was no evidence of new formation of antibody to foreign proteins, and recombinant factor VIII was well tolerated. CONCLUSIONS: Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.

Adult↗