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Biomedical subjects

H Fukui

Publications and source records attributed to H Fukui.

At least 55 records · Page 3Linked to original sources
PubMed2001

Histamine H1 receptor mRNA is expressed in capsaicin-insensitive sensory neurons with neuropeptide Y-immunoreactivity in guinea pigs.

Histamine H1 receptor mRNA-expressing sensory neurons in guinea pigs are unmyelinated and are not immunoreactive to substance P and calcitonin gene-related peptide (CGRP) [Mol. Brain Res. 66 (1999) 24], which are implicated in the nociceptive transmission of the primary sensory system. In this study, we examined whether these H1 receptor mRNA-expressing neurons are sensitive to capsaicin by using in situ hybridization histochemistry. Of lumbar dorsal root ganglion (DRG) neurons in control animals, 17% were positive for CGRP. In guinea pigs neonatally treated with capsaicin (50 mg/kg), few CGRP-immunoreactive neurons were seen in the DRGs. However, the percentages of H1 receptor mRNA-expressing neurons (15-20%) and the intensity of the mRNA signals in these neurons were not affected by neonatal capsaicin treatment. We also revealed the presence of both capsaicin-sensitive and insensitive neuropeptide Y (NPY)-immunoreactive neurons in the DRGs. These neurons were exclusively small. H1 receptor mRNA was expressed in NPY-immunoreactive neurons in naive guinea pig DRGs. These results suggest that H1 receptor mRNA is expressed in capsaicin-insensitive DRG neurons with NPY-immunoreactivity in guinea pigs.

Animals↗
PubMed2001

Evaluation of a floating dosage form of nicardipine hydrochloride and hydroxypropylmethylcellulose acetate succinate prepared using a twin-screw extruder.

A floating dosage form composed of nicardipine hydrochloride (NH) and hydroxypropylmethylcellulose acetate succinate (enteric polymer) was prepared using a twin-screw extruder. By adjusting the position of the high-pressure screw elements in the immediate vicinity of die outlet, and by controlling the barrel temperature, we were able to prepare a puffed dosage form with very small and uniform pores. It was found that the porosity and pore diameter could be controlled by the varying amount of calcium phosphate dihydrate. In the shaking test, the puffed dosage form was found to have excellent floating ability and mechanical strength in acid solution (JP First Fluid, pH 1.2). The dissolution profile of NH was controlled by the amount of wheat starch. In the dissolution test using JP Second Fluid (pH 6.8), rapid dissolution of NH and loss of buoyancy were observed. It was shown that the puffed dosage form, consisting of enteric polymer prepared using the twin-screw extruder, was very useful as a floating dosage form that was retained for a long period in the stomach.

Administration, Oral↗
PubMed2001

Structural changes of quartz-type crystalline and vitreous GeO2 under pressure.

Using a large volume high pressure apparatus, quartz-type crystalline GeO2 and Li2O-4GeO2 glass have been compressed up to 14 GPa at room temperature and their local structural changes have been investigated by an in-situ XAFS method. In quartz-type crystalline GeO2, the change of the coordination number from 4 to 6 begins above 8 GPa and finishes below 12 GPa. On decompression, reversal transition begins below 8 GPa and there is a large hysteresis. Almost no sixfold coordination of Ge is preserved after releasing pressure. Change of coordination number in vitreous Li2O-4GeO2 begins above 6 GPa and is completed below 10 GPa. Reversal transition begins below 10 GPa and the hysteresis is smaller than that of quartz-type GeO2. Change of coordination number in vitreous Li2O-4GeO2 is also reversal.

Journal Article↗
PubMed2001

Genetic analysis of a local recurrent tumor after colonic polypectomy.

After polypectomy, the cut end of the polyp is usually examined by light microscopy to assess the risk of recurrent cancer. Here, we report a recurrent tumor that appeared in the colon 6 years after polypectomy, although cancer cells were not observed in hematoxylin and eosin-stained sections of the cut end of the primary polyp. Retrospectively, the primary polyp and the recurrent tumor were analyzed for mutations of the p53 gene. We detected p53 mutations in the primary polyp, even in the cut end of the polyp. The same set of two p53 mutations was detected in the recurrent tumor. These observations indicate a common origin of the primary tumor and the recurrent tumor. We conclude that it is important to analyze p53 mutations in colonic polyps, especially when the cut end of the polyp is difficult to evaluate histologically, in order to predict recurrence.

Adenocarcinoma↗
PubMed2001

Microscopic polyangiitis complicated with massive intestinal bleeding.

Microscopic polyangiitis (MPA) is associated with renal dysfunction, in most cases, and occasionally with pulmonary hemorrhage. However, massive intestinal bleeding is a rare manifestation. We report a case of MPA in a man who developed arterial bleeding in the small intestine. A 74-year-old man was admitted after enduring a fever for 4 weeks. Laboratory examination revealed leucocytosis with neutrophil predominance, and renal dysfunction was noted. He did not respond to treatment with antibiotics, and the worsened renal function soon required hemodialysis. On the seventh hospital day, he suddenly developed massive melena. A colonoscopic examination suggested bleeding in the small intestine, and abdominal angiography demonstrated that the bleeding originated in a branch of the ileal artery. Hemostasis was achieved by transarterial embolization (TAE), but the patient suffered a massive pulmonary hemorrhage 2 days after the TAE. Although he responded well to a combination treatment with corticosteroid and cyclophosphamide, recurrence of pulmonary hemorrhage led to death, on the 87th hospital day. MPA in this patient was associated with three serious complications; deteriorating renal function, massive melena, and pulmonary hemorrhage. Of the various manifestations associated with MPA, arterial bleeding in the gastrointestinal tract, although rare, should be considered as one of the serious complications in MPA.

Aged↗
PubMed2001

Hepatic adenomas treated with percutaneous ethanol injection in a patient with glycogen storage disease type Ia.

We report a 20-year-old man with glycogen storage disease type Ia (GSD Ia) who presented multiple hepatocellular adenomas (HCAs) in 1993 and in whom percutaneous ethanol injection (PEI) was conducted as treatment for some enlarging tumors beneath the liver surface. In a 6-year follow-up period, we observed gradual enlargement of some of the HCAs, and the rapid growth of a newly developed tumor. In August 1996, one slow-growth HCA was 52 mm in diameter and was located beneath the surface of the liver. We conducted PEI therapy to prevent its spontaneous rupture. During the following year, another tumor developed beneath the liver surface, but showed extremely rapid growth, reaching 51 mm in diameter, from being undetectable, within 12 months. PEI therapy was again conducted for this newly developed tumor. Although additional PEI therapy was required for each tumor, because of suspected recurrence, no findings of discrete recurrence have been detected by computed tomography and magnetic resonance imaging for more than 2 years, up to the time of this study. We consider PEI to be a useful and effective therapeutic modality for individual HCAs in patients with GSD Ia.

Adenoma↗
PubMed2001

Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6-phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle.

Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1 expression, we analyzed the expression profiles of GFAT1 mRNA in various human tissues using reverse transcriptase-polymerase chain reaction. We report here the identification and cDNA cloning of a novel GFAT1 splice variant expressed abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L, contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L protein possessed functional GFAT activities and biochemical characteristics similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The identification of a novel GFAT1 subtype possessing functional enzymatic activity and tissue-specific expression should provide additional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications.

Alternative Splicing↗
PubMed2001

The impact of chronic renal failure on atherosclerosis of the internal thoracic arteries.

BACKGROUND: Little is known about the impact of renal failure on atherosclerotic changes in the internal thoracic artery (ITA). METHODS: A total of 20 consecutive patients on chronic dialysis who underwent coronary artery bypass grafting (CABG) during April 1998 through September 1999 were investigated. The 20 control patients were selected from the same interval to rigorously match risk factors. Atherosclerosis of the ITA collected from each patient was analyzed using the subjective evaluation proposed by Kay and colleagues. RESULTS: There were no cases of greater than 25% atherosclerotic luminal narrowing among a total of 35 ITA specimens from dialysis patients. The degree of atherosclerosis was not significantly different from that of the specimens from matched patients (p = 0.18). No calcification was found in ITA grafts either microscopically or macroscopically. The number of elastic lamellae, an index of the elasticity of the ITA graft, was not significantly different from those obtained from the matched patients. Analysis of preoperative coronary angiography revealed that coronary calcification was significantly more frequent in dialysis patients (15 patients, 75%) than in matched patients (p < 0.05). By analysis of postoperative angiography in dialysis patients, no evidence of atherosclerotic changes was found in 28 opacified ITAs. In addition, despite the presence of calcification in the native coronary, no calcification was evident along the entire length of the ITAs. CONCLUSIONS: This study revealed the minimal impact of chronic renal failure on atherosclerotic changes in the ITA. The results of this study support the continued use of ITA grafting in dialysis patients.

Aged↗
PubMed2001

Hydroxysesamone and 2,3-epoxysesamone from roots of Sesamum indicum.

A red naphthoquinone, named hydroxysesamone, was isolated from the roots of Sesamum indicum together with a known yellow naphthoxirene derivative, 2,3-epoxy-2,3-dihydro-5,8-dihydroxy-2-(3-methyl-2-butenyl)-1,4-naphthoquinone, named 2,3-epoxysesamone. The structure of the naphthoquinone was characterized as 2,5,8-trihydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone on the basis of spectral evidence. Full assignments of NMR resonances of 2,3-epoxysesamone were also confirmed by two-dimensional NMR spectroscopic experiments. Chlorosesamone, hydroxysesamone and 2,3-epoxysesamone all showed antifungal activities toward Cladosporium fulvum.

Antifungal Agents↗
PubMed2001

Endothelin-1 plays a major role in portal hypertension of biliary cirrhotic rats through endothelin receptor subtype B together with subtype A in vivo.

BACKGROUND/AIMS: Endothelin-1 has been suggested to play a key role in cirrhotic portal hypertension, but a role of its receptors in vivo is not fully elucidated. METHODS: Biliary cirrhosis was induced by bile duct ligation. Expressions of endothelin-1 and its receptors were evaluated by radioimmunoassay and/or reverse-transcription polymerase chain reaction. Hemodynamics were studied using endothelin receptor agonist or antagonist. RESULTS: Portal pressure and hepatic endothelin-1 concentrations progressively increased in parallel after bile duct ligation. Gene expression of hepatic prepro-endothelin-1 and endothelin B receptor enhanced after bile duct ligation, while that of endothelin A receptor was unchanged. Intraportal administration of endothelin-1 or endothelin B receptor agonist sarafotoxin 6c (0.5 nmol/kg, respectively) progressively raised portal pressure in both sham and cirrhotic rats. Portal hypertensive effect of sarafotoxin 6c was more intense in cirrhotic rats than sham animals. Neither endothelin A receptor antagonist FR139317 (1 mg/kg) nor endothelin B receptor antagonist BQ788 (1 mg/kg) alone ameliorated cirrhotic portal hypertension. Only the combined endothelin A and B blockade was associated with a decrease in portal pressure in cirrhotic rats. CONCLUSIONS: These results indicate that endothelin-1 plays a major role in cirrhotic portal hypertension through endothelin receptor subtype B together with subtype A in vivo.

Animals↗
PubMed2001

Gene therapy for hepatocellular carcinoma based on tumour-selective suicide gene expression using the alpha-fetoprotein (AFP) enhancer and a housekeeping gene promoter.

The aim of this study was to examine whether the human alpha-fetoprotein (AFP) enhancer could be used to induce hepatocellular carcinoma (HCC)-selective expression of the herpes simplex virus thymidine kinase (HSV-tk) gene which is under the control of the phosphoglycerate kinase (pgk) promotor. The human AFP enhancer was linked with the non-tissue-specific, human housekeeping pgk promoter in a retroviral vector. AFP-producing HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter were much more susceptible to the prodrug, ganciclovir (GCV), than those infected with the same retroviruses without the AFP enhancer. Non-HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter exhibited profoundly increased resistance to GCV compared with those infected with the same retroviruses without the AFP enhancer. Northern blot analysis revealed that the AFP enhancer caused enhanced HSV-tk expression in AFP-producing HCC cells and suppressed HSV-tk expression in non-HCC cells. Our results indicate that the AFP enhancer could give HCC selectivity to the pgk promoter, and that this novel strategy may be useful for HCC-selective cancer gene therapy.

Blotting, Northern↗
PubMed2001

Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis.

BACKGROUND/AIMS: Little is known about endotoxin clearance and secretion of cytokines from macrophages in liver cirrhosis. The aims of this study were to investigate the relationship of endotoxin clearance and release of tumor necrosis factor alpha by various macrophages to hepatic and renal disturbances in liver cirrhosis. METHODS: Male Sprague-Dawley rats were given 0.04% thioacetamide orally for 6 or 12 months. The organ distribution of infused [3H]-endotoxin (10 microg/kg b.w.) was analyzed at 30 min or at 24 h. Uptake of [3H]-endotoxin and secretion of tumor necrosis factor alpha by Kupffer cells, splenic macrophages and peripheral blood monocytes (1 x 10(4) cells/ml) from cirrhotic and control rats were determined. RESULTS: In cirrhotic rats, more endotoxin was left in the body and more endotoxin accumulated in the spleen and kidney, and thus was related to elevation of serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and tumor necrosis factor alpha. Endotoxin uptake and tumor necrosis factor alpha release by the Kupffer cells were decreased and those by the splenic macrophages and peripheral blood monocytes were increased in cirrhotic rats. CONCLUSIONS: In liver cirrhosis, impaired clearance of endotoxin together with increased secretion of tumor necrosis factor alpha by extrahepatic macrophages may play an important role in the progression of hepatic and renal disturbances.

Animals↗
PubMed2001

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon.

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.

Adult↗
PubMed2001

The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model.

The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation.

Animals↗
PubMed2001

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats.

The renin-angiotensin system (RAS) is frequently activated in patients with chronic liver diseases. Angiotensin-II (AT-II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up-regulates the transforming growth factor beta(1) (TGF-beta(1)) expression via AT-II type 1 receptor (AT(1)-R) in vitro. The aim of the present study was to examine the in vivo effect of candesartan (CA), a clinically used AT(1)-R blocker (ARB), and perindopril (PE), an angiotensin-converting enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development in rats. The clinically available comparable doses of CA and PE significantly attenuated the fibrosis development. These inhibitory effects of PE and CA were also found in the on-going liver fibrosis model. The hepatic hydroxyproline and serum fibrosis markers were significantly suppressed by CA and PE treatment. Furthermore, the alpha smooth muscle actin (alpha-SMA) positive cells in number were markedly suppressed by CA and PE treatment. Similarly, the hepatic TGF-beta(1) protein and messenger RNA (mRNA) levels were significantly suppressed. Our in vitro study showed that AT-II increased the TGF-beta(1) mRNA expression in the activated HSCs, and this effect was totally blocked by CA. These results suggested that the RAS, especially AT-II and AT(1)-R interaction plays a pivotal role in liver fibrosis development through HSC activation. Because both CA and PE are widely used in clinical practice without serious side effects, these drugs may provide an effective new strategy for anti-liver fibrosis therapy.

Angiotensin II↗
PubMed2001

A potential approach for electrochemotherapy against colorectal carcinoma using a clinically available alternating current system with bipolar snare in a mouse model.

BACKGROUND: Although electrochemotherapy appears promising for the treatment of superficial tumors, its usefulness against internal tumors, such as colorectal carcinoma (CRC), has not been well examined. Furthermore, since direct current electric pulses have been used for electropermeabilization of tumors in all in vivo electrochemotherapy studies, including clinical trials, the usefulness of alternating current systems has not been examined at all. In a mouse model it was examined whether the alternating current system with a bipolar snare, which has been employed already as a clinical endoscopic treatment modality, was useful for electrochemotherapy against CRC. METHODS: Murine CRC colon 26 cells were implanted subcutaneously into syngeneic BALB/c mice and electrochemotherapy with bleomycin (BLM) using the alternating current system was performed against established CRC tumors. RESULTS: Electrochemotherapy significantly suppressed the growth of established CRC tumors, resulting in significantly prolonged survival of animals with CRC. Histological examination revealed that electrochemotherapy caused massive necrosis of CRC tumors. Subsequent analysis revealed that the delivery of alternating current electric pulses to CRC tumors profoundly increased intratumoral amounts of BLM. CONCLUSIONS: Because the alternating current system using a bipolar snare has been used widely as an endoscopic treatment modality in clinical settings, these results indicate that electrochemotherapy using the alternating current system may be a promising approach for the treatment of CRC.

Adenocarcinoma↗
PubMed2001

Balloon catheter-assisted endoscopic sclerotherapy for gastric fundal varices using alpha-cyanoacrylate monomer.

We present two patients with bleeding episodes from gastric fundal varices. The gastric fundal varices were treated by balloon catheter-assisted endoscopic sclerotherapy using alpha-cyanoacrylate monomer. The varices were successfully obliterated with no complications or hemodynamic changes to the gastrorenal shunts. This procedure may be considered a novel, feasible approach to the treatment of gastric fundal varices in the future.

Aged↗