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Biomedical subjects

H Fukui

Publications and source records attributed to H Fukui.

At least 19 recordsLinked to original sources
PubMed1992

Re-examination of [3H]mepyramine binding assay for histamine H1 receptor using quinine.

[3H]Mepyramine, a potent antagonist of the histamine H1 receptor, has been widely used as a radioligand binding assay for the H1 receptor. Previously, we purified a mepyramine binding protein (MBP) from rat liver, but found that its partial amino acid sequences were very similar to those of debrisoquine 4-hydroxylase isozymes (P450 db1 and db2), which are members of the superfamily of cytochrome P450. Using cloned histamine H1 receptor cDNA, we found that [3H]mepyramine could bind only the H1 receptor and did not bind MBP in the presence of 10(-5) M quinine, an inhibitor of debrisoquine 4-hydroxylase isozymes. We developed a method to determine the contents of the H1 receptor and MBP separately using [3H]mepyramine and quinine and found that MBP is abundant in certain areas of bovine brain.

Animals↗
PubMed1992

The interaction of botrocetin with normal or variant von Willebrand factor (types IIA and IIB) and its inhibition by monoclonal antibodies that block receptor binding.

We have recently shown the existence of two distinct forms of botrocetin (one-chain and two-chain), and demonstrated that the two-chain species is approximately 30 times more active than the one-chain in promoting von Willebrand factor (vWF) binding to platelet glycoprotein (GP) Ib. The N-terminal sequence of two-chain botrocetin is highly homologous to sea-urchin Echinoidin and other Ca(2+)-dependent lectins (Fujimura et al., Biochemistry 1991; 30: 1957-64). Present data indicate that purified two-chain botrocetin binds to vWF from plasmas of patients with type IIA or IIB von Willebrand disease and its interaction is indistinguishable from that with vWF from normal individuals. However, an "activated complex" formed between botrocetin and IIB vWF expresses an enhanced biological activity for binding to GP Ib whereas the complex with IIA vWF has a decreased binding activity. Among several anti-vWF monoclonal antibodies (MoAbs) which inhibit ristocetin-induced platelet aggregation and/or vWF binding to GP Ib, only two MoAbs (NMC-4 and RFF-VIII RAG:1) abolished direct binding between purified botrocetin and vWF. This suggests that they recognize an epitope(s) on the vWF molecule in close proximity to the botrocetin binding site.

Antibodies, Monoclonal↗
PubMed1992

Histamine N-methyltransferase from rat kidney. Cloning, nucleotide sequence, and expression in Escherichia coli cells.

Complementary DNA clones encoding rat kidney histamine N-methyltransferase have been isolated using synthetic oligonucleotide probes based on partial amino acid sequences of tryptic peptides of the purified enzyme. The 1.3-kilobase cDNA consisted of a 5'-noncoding region of 8 nucleotides, a coding region of 885 nucleotides, and a 3'-noncoding region of 369 nucleotides. The encoded protein of 295 amino acid residues had a calculated molecular weight of 33,940.2. After introduction of a prokaryotic expression vector containing the isolated cDNA, Escherichia coli cells expressed histamine N-methyltransferase activity. The enzyme expressed in these cells was isolated and purified as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whose mobility was identical to the natural enzyme purified from rat kidney. The recombinant enzyme had Vmax and Km values for both histamine and S-adenosylmethionine identical to those of the natural enzyme. All of the inhibitors of the natural enzyme tested showed similar Ki values on both recombinant and natural enzyme.

Amino Acid Sequence↗
PubMed1992

D-galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes.

Specific bindings of [3H]prostaglandin E1 ([3H]PGE1), 125I-glucagon and [3H]norepinephrine to D-galactosamine (GalN)-treated rat hepatocytes in primary culture were investigated. After a two hour-treatment with GalN (1 and 10mg/ml), hepatocytes showed an enhanced specific binding to [3H]PGE1, whereas 125I-glucagon binding was little affected and [3H]norepinephrine binding was strongly diminished. Scatchard plot analysis indicated an increase of binding sites of [3H]PGE1. This unusual manner of [3H]PGE1 binding is suggested to indicate a special property of PGE1 receptor and may be associated with the cytoprotective effect of prostaglandins.

Alprostadil↗
PubMed1992

Type-1 and type-2 astrocytes are distinct targets for prostaglandins D2, E2, and F2 alpha.

Accumulating evidence has revealed that astrocytes are potential targets for various neurotransmitters. Here we investigated the effects of prostaglandins (PGs) on signal transduction in purified primary cultures of rat type-1 and type-2 astrocytes. PGF2 alpha, PGD2, and 9 alpha,11 beta-PGF2, a metabolite of PGD2 and a stereoisomer of PGF2 alpha, evoked a rapid rise in the intracellular Ca2+ concentration ([Ca2+]i) in type-1, but not in type-2, astrocytes. STA2, a stable analogue of thromboxane A2, was less effective, and PGE2 showed little effect. The PG-induced rise in [Ca2+]i was not blocked by an antagonist of either PGD2 receptor or thromboxane A2 receptor. PGF2 alpha and 9 alpha,11 beta-PGF2 stimulated rapid formation of inositol trisphosphate followed by inositol bisphosphate and inositol monophosphate. On the other hand, PGE2 increased the intracellular level of cyclic AMP in type-2 astrocytes, rather than in type-1 astrocytes. The potency of PGs for cyclic AMP formation was in the following order: PGE2 greater than PGE1 greater than or equal to STA2 much greater than iloprost, a stable analogue of PGI2. PGD2 and PGF2 alpha had no effect on cyclic AMP formation. These results demonstrate that type-1 astrocytes preferentially express PGF2 alpha receptors, the activation of which leads to phosphoinositide metabolism and [Ca2+]i elevation, whereas type-2 astrocytes possess PGE receptors that are linked to cyclic AMP formation.

Animals↗
PubMed1992

Hepatic tissue oxygenation as a predictive indicator of ischemia-reperfusion liver injury.

The purpose of this study was to determine whether hepatic tissue oxygenation after ischemia-reperfusion procedures is an indicator for later liver injury. Partial ischemia in the liver was induced by ligating the left pedicles. Rats were divided into two groups according to duration of ischemia: group A (30-min ischemia) and group B (60-min ischemia). Indices of blood oxygenation and blood volume in regional hepatic tissue, serum ALT levels and histological appearance of livers were evaluated. Twenty-four hours after ischemia and reflow, all rats in group A were alive, whereas only 67% survived in group B. Blood-oxygenation index and blood-volume index in group A rats rebounded quickly after reperfusion. In group B, blood-oxygenation index and blood-volume index remained significantly lower than in group A after reperfusion. Serum ALT levels at 60 and 120 min after reperfusion in group B were significantly higher than those in group A. Blood-oxygenation index measured at 5 and 60 min of reperfusion showed significant correlation with serum ALT levels at 120 min of reperfusion. When the percentage recovery of blood-oxygenation index at 5 and 60 min after reperfusion was more than 75%, all rats survived. No obvious signs of hepatocellular degeneration were observed histologically 5 min after reperfusion; however, substantial hepatocellular degeneration had occurred at 120 min of reperfusion in groups A and B. These data indicate that a decline in hepatic tissue oxygenation during the early phase of reperfusion (even when no obvious hepatocellular degeneration has been observed) can be a predictor of subsequent liver injury and prognosis.

Alanine Transaminase↗
PubMed1992

Immunomodulatory effects of ursodeoxycholic acid on immune responses.

Ursodeoxycholic acid was recently recognized as an effective agent in the treatment of primary biliary cirrhosis. Experimental evidence supporting the usefulness of ursodeoxycholic acid as a potentially beneficial therapeutic agent for primary biliary cirrhosis has been reported from the biochemical and physiological aspects. In this study, we investigated the direct effects of ursodeoxycholic acid on immunoglobulin and cytokine production in vitro using plaque-forming cell assay and enzyme-linked immunosorbent assay. It was demonstrated that ursodeoxycholic acid suppressed the production of IgM, IgG and IgA induced by Staphylococcus aureus Cowan I in peripheral blood mononuclear cells derived from healthy subjects and patients with primary biliary cirrhosis and also in human B lymphoma cell lines. Furthermore, ursodeoxycholic acid suppressed interleukin-2 and interleukin-4 production induced by concanavalin A and interferon-gamma production induced by polyinosinic-polycytidylic acid, but it did not affect interleukin-1 and interleukin-6 production induced by lipopolysaccharide in peripheral blood mononuclear cells. In addition, ursodeoxycholic acid suppressed the concanavalin A-induced thymocyte proliferation mediated by interleukin-1. Cytotoxicity against lymphocytes was not observed at the concentrations of ursodeoxycholic acid used. These results suggest that the beneficial effect of ursodeoxycholic acid in primary biliary cirrhosis is mediated in part by immunosuppression.

Adjuvants, Immunologic↗
PubMed1992

Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat.

This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1992

Ethanol-induced vasoconstriction causes focal hepatocellular injury in the isolated perfused rat liver.

The role of microcirculation in the pathogenesis of alcoholic liver injury was investigated in isolated perfused livers from fed rats. Infusion of ethanol into the portal vein at concentrations ranging from 25 to 200 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately on initiation of ethanol load and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase, an indicator of cell injury, into the effluent perfusate began to increase after 20 to 30 min of ethanol infusion and continued to increase until the end of the experiment (60 min after the initiation of ethanol infusion). The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 22 +/- 3 IU/L; 50 mmol/L, 51 +/- 11 IU/L; 100 mmol/L, 60 +/- 7 IU/L; 200 mmol/L, 120 +/- 7 IU/L). Simultaneous infusion of sodium nitroprusside (100 mumol/L), a known vasodilator, inhibited significantly the ethanol-induced increases in portal pressure and lactate dehydrogenase release by abolishing hepatic vasoconstriction. In histological examinations focal hepatocellular necrosis, evidenced by trypan blue staining of cell nuclei, was detected predominantly in midzonal and pericentral areas of the liver lobule after 60 min of ethanol infusion. Change in portal pressure during 60 min of ethanol infusion correlated significantly with levels of lactate dehydrogenase after ethanol infusion (r = 0.82; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Assessment of portosystemic shunting from superior mesenteric vein by duodenal administration of iodoamphetamine I123.

Portosystemic shunting (PSS) from the superior mesenteric vein (SMV) was evaluated with the duodenal administration of iodoamphetamine I123 (IMP) in patients with chronic hepatitis and liver cirrhosis. After duodenal intubation, IMP was administered through a tube, and then scintigraphy including the pulmonary and hepatic regions was performed. In all patients, images of the liver and/or lungs were observed within 10 min and became clear with time, due to a good absorption of IMP from the intestine. On the other hand, IMP appears not to be absorbed from the stomach. The portosystemic shunt index was calculated by dividing counts of lungs by counts of liver and lungs. The shunt index (mean +/- SE) was 1.5% +/- 0.8%, 12.6% +/- 3.7% and 28.3% +/- 4.5% in chronic hepatitis, compensated cirrhosis and decompensated cirrhosis, respectively. This index was significantly higher in cirrhosis, especially in decompensated cirrhosis. Therefore, transintestinal portal scintigraphy with IMP could be a useful method for the non-invasive and quantitative evaluation of PSS from the SMV in portal hypertension.

Amphetamines↗
PubMed1992

Aphidicolin inhibits DNA polymerizing activity but not nucleolytic activity of Escherichia coli DNA polymerase II.

We have purified the DNA polymerase II of Escherichia coli from the recombinant strain carrying the plasmid which encodes the polB gene. We confirmed that the purified protein, of molecular weight 90,000, possesses a 3'----5' exonuclease activity in addition to DNA polymerizing activity in a single polypeptide. Its DNA polymerizing activity was sensitive to the drug aphidicoline, which is a specific and direct inhibitor of the alpha-like DNA polymerases including eukaryotic replicative DNA polymerases. Aphidicolin had no detectable effect on the 3'----5' exonuclease activity. The inhibition by aphidicolin on the polymerizing activity of polymerase II was competitive with respect to dNTP and uncompetitive with respect to template DNA. This mode of action is the same as that on eukaryotic DNA polymerase alpha. The apparent Ki value calculated from Lineweaver-Burk plots was 55.6 microM.

Aphidicolin↗
PubMed1992

Portal vein aneurysm demonstrated by blood pool SPECT.

Portal vein aneurysms are rare and are occasionally suggested by ultrasound and usually confirmed by invasive angiography. Such a case was diagnosed by scintigraphic studies, most importantly blood pool SPECT, which clearly separates it from hepatic cysts.

Adult↗
PubMed1992

A monoclonal antibody (NMC-VIII/10) to factor VIII light chain recognizing Glu1675-Glu1684 inhibits factor VIII binding to endogenous von Willebrand factor in human umbilical vein endothelial cells.

The monoclonal antibody NMC-VIII/10 is a neutralizing antibody which recognizes the Glu1675-Glu1684 sequence of the factor VIII light chain and inhibits factor VIII (FVIII) binding to immobilized von Willebrand factor (vWf). In this study we immunohistochemically determined, using human umbilical cord tissue, whether or not NMC-VIII/10 has an inhibitory effect on FVIII binding to endogenous vWF in endothelial cells. Tissue sections were reacted with purified FVIII followed by peroxidase-conjugated monoclonal antibody (C5) recognizing the 54 kD fragment of the FVIII heavy chain. The labelling pattern of bound FVIII was similar to that of endogenous vWF and appeared as a fine granular deposit in the endothelial cells. Addition of purified vWF completely inhibited the binding of FVIII to endothelial cells. Furthermore, FVIII did not bind to endothelium in the presence of 0.25 M CaCl2, and similarly, thrombin-treated FVIII did not bind to the vascular site. These findings suggested that FVIII was bound to endogenous vWF in the endothelial cells. The binding reaction was completely inhibited by NMC-VIII/10, confirming that the monoclonal antibody recognizes the specific epitope responsible for FVIII binding to endogenous vWF.

Antibodies, Monoclonal↗
PubMed1992

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma). A case report.

True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma) originating in the right lower lobe in a 62-year-old Japanese male is reported. The tumor, measuring 5.5 x 3.5 x 3.5 cm, was markedly necrotic and its apex protruded into the bronchial lumen. Light microscopy showed that the tumor was composed of squamous cell carcinoma with sarcomatous spindle or polygonal cell proliferation and true chondrosarcoma. Immunohistochemically, the cytoplasm of numerous cells of the squamous cell carcinoma component was stained with anti-cytokeratin (PKK 1) and the cytoplasmic membrane with anti-epithelial membrane antigen (EMA). Although sarcomatous regions were stained with anti-vimentin (vimentin) and no tumor cells were reactive for EMA, a few tumor cells were positive for PKK 1. The cytoplasm of numerous chondrosarcoma cells was positively stained for vimentin and S-100 protein. Based on these findings, we concluded that the present tumor was a true carcinosarcoma composed of squamous cell carcinoma with sarcomatous regions and true chondrosarcoma.

Aged↗
PubMed1992

Vagal afferent fibers and peripheral 5-HT3 receptors mediate cisplatin-induced emesis in dogs.

The involvement of visceral afferent fibers and 5-HT3 receptors in the emesis induced by cisplatin was studied in beagle dogs. The emesis induced by cisplatin (3 mg/kg, i.v.) was inhibited by the intravenous administration of ICS205930 (2 x 0.01 or 2 x 0.1 mg/kg) and MDL72222 (2 x 0.5 mg/kg), 5-HT3 receptor antagonists, but not by the intravenous administration of metoclopramide (2 x 0.5 mg/kg), a dopamine D2 receptor antagonist. The cisplatin-induced emesis was also suppressed by the intravenous administration of para-chlorophenylalanine (300 mg/kg/day for 3 days), an inhibitor of 5-HT synthesis. On the other hand, the administration of ICS205930 into the IVth ventricle (2 x 0.01 mg/animal) had no effects on the cisplatin-induced emesis. The cisplatin-induced emesis was completely inhibited by abdominal vagotomy and splanchnicectomy, but not by splanchnicectomy alone. On the contrary, the emesis induced by apomorphine was suppressed by the intravenous (0.1 mg/kg) or intracerebroventricular (0.05 mg/animal) administration of metoclopramide, but not by visceral nerve section. These results strongly suggest that cisplatin evokes emesis mainly by acting on the vagal afferent terminals through the release of 5-HT and that peripheral 5-HT3 receptors are involved in this action.

Afferent Pathways↗
PubMed1992

Chronic active Epstein-Barr virus infection in an adult.

We report a rare adult case of chronic active Epstein-Barr virus (EBV) infection. A 54-year-old woman was admitted to our hospital with intermittent fever, weight loss, hepatosplenomegaly, pancytopenia and liver disturbance. In serological tests for EBV, anti-virus capsid antigen (VCA)-IgG antibody and anti-early antigen (EA)-IgG antibody were markedly elevated and anti-EBV nuclear antigen (EBNA) antibody was negative. EBV genome was detected in the bone marrow nucleated cells and peripheral lymphocytes by Southern blot hybridization. The patient developed left facial edema, bilateral breast tumor and pneumonia. She died one year after admission in spite of the administration of prednisolone, interferon and acyclovir.

Acyclovir↗
PubMed1992

Effects of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs.

Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis.

Animals↗