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Biomedical subjects

H Fukui

Publications and source records attributed to H Fukui.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2001

Concurrent occurrence of gastric adenocarcinoma and duodenal neuroendocrine cell carcinoma: a composite tumour or collision tumours ?

BACKGROUND: Neuroendocrine cell (NEC) carcinoma is occasionally accompanied by adenocarcinoma but the relationship between these two morphologically distinct tumours is unclear. Two hypotheses have arisen regarding the mechanism for the association of adenocarcinoma and NEC carcinoma. One is that both are derived from a common multipotential epithelial stem cell. The second hypothesis is that adenocarcinoma and NEC carcinoma arise from a multipotential epithelial stem cell and a primitive NEC, respectively. AIMS: To elucidate the relationship between the two histologically distinct tumours, adenocarcinoma of the stomach and NEC carcinoma of the duodenum. PATIENT/METHODS: We present a case in which the tumour extended across the pyloric ring, the gastric portion of which revealed adenocarcinoma while the duodenal portion showed argyrophil NEC carcinoma. The two histologically distinct lesions of the tumour were examined by immunohistochemistry and genetic analysis of p53. RESULTS: The gastric region was negative for chromogranin A staining but positive for carcinoembryonic antigen (CEA) staining. In contrast, the duodenal region was positive for chromogranin A but negative for CEA. All tumour regions showed a point mutation in p53 gene at exon 7 (GGC (glycine)-->GTC (valine) at codon 245). The distal portion of the duodenal tumour showed an additional point mutation in p53 gene at exon 5 (GCC (alanine)-->GTC (valine) at codon 129). CONCLUSIONS: The two histologically distinct tumours, adenocarcinoma of the stomach and NEC carcinoma of the duodenum, appear to be derived from a common epithelial cell.

Adenocarcinoma↗
PubMed2001

Enhanced activity of the purine nucleotide cycle of the exercising muscle in patients with hyperthyroidism.

Myopathy frequently develops in patients with hyperthyroidism, but its precise mechanism is not clearly understood. In this study we focused on the purine nucleotide cycle, which contributes to ATP balance in skeletal muscles. To investigate purine metabolism in muscles, we measured metabolites related to the purine nucleotide cycle using the semiischemic forearm test. We examined the following four groups: patients with untreated thyrotoxic Graves' disease (untreated group), patients with Graves' disease treated with methimazole (treated group), patients in remission (remission group), and healthy volunteers (control group). To trace the glycolytic process, we measured glycolytic metabolites (lactate and pyruvate) as well as purine metabolites (ammonia and hypoxanthine). In the untreated group, the levels of lactate, pyruvate, and ammonia released were remarkably higher than those in the control group. Hypoxanthine release also increased in the untreated group, but the difference among the patient groups was not statistically significant. The accelerated purine catabolism did not improve after 3 months of treatment with methimazole, but it was completely normalized in the remission group. This indicated that long-term maintenance of thyroid function was necessary for purine catabolism to recover. We presume that an unbalanced ATP supply or conversion of muscle fiber type may account for the acceleration of the purine nucleotide cycle under thyrotoxicosis. Such acceleration of the purine nucleotide cycle is thought to be in part a protective mechanism against a rapid collapse of the ATP energy balance in exercising muscles of patients with hyperthyroidism.

Adenosine Monophosphate↗
PubMed2001

Inhibition of oxotremorine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

The aim of this study was to investigate the differences between oxotremorine-induced and acetylcholine (ACh)-induced desensitization, particularly under Ca2+-free conditions, in guinea-pig ileal longitudinal muscle, and to elucidate the different mechanisms of desensitization that might exist between these two muscarinic agonists. Pretreatment of the tissue with 10(-7)-10(-5) M oxotremorine (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses to ACh, as did the desensitizing treatment with ACh. However, Ca2+-free conditions significantly reduced oxotremorine-induced desensitization, contrary to the previous findings that Ca2+-free conditions enhanced ACh-induced desensitization. The desensitizing treatment with oxotremorine caused suppression of the responses to high K+ (tonic phase), as did the ACh treatment. Ca2+-free conditions removed this suppression, whereasthis condition enhanced ACh-induced suppression of the K+ response. A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (10(-4) M) had no effect on oxotremorine-induced desensitization of the ACh response. The results suggest that a voltage-gated Ca2+ channel was involved in oxotremorine-induced desensitization, as in ACh-induced desensitization, but that the process of inactivation of Ca2+ channels was different between oxotremorine and ACh, and that oxotremorine-induced desensitization was due not only to Ca2+ channel, but also to other unknown factors. Protein kinase C did not participate in oxotremorine-induced desensitization.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Characterization of polymorphs of a novel quinolinone derivative, TA-270 (4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone).

The polymorphic forms and amorphous form of TA-270 (4-hydroxy-1-methyl-3-octyloxy-7-sinapinoylamino-2(1H)-quinolinone), a newly developed antiallergenic compound, were characterized by powder X-ray diffractometry, thermal analysis, infrared spectroscopy and solid state 13C-NMR. The intrinsic dissolution rates of polymorphic forms were measured using the rotating disk method at 37 degrees C. The dissolution rates correlated well with the thermodynamic stability of each polymorphic form. These dissolution properties were clearly reflected in the oral bioavailability of TA-270 in rats. The transition behavior for each polymorph and for the amorphous form was studied under the high temperature and humidity conditions. The beta- and delta-forms were transformed into the alpha-form by heating. The amorphous form was also easily crystallized into alpha-form by heating, however it was relatively stable under humidified conditions. The internal molecular packing of each polymorph was estimated from IR and solid state NMR spectral analysis.

Absorption↗
PubMed2001

NMR determination of the absolute configuration of a macrophomate synthase inhibitor by using an axial chiral reagent.

Macrophomate synthase catalyzes an extraordinary four-step transformation from oxalacetate and 2-pyrone to macrophomic acid by an intermolecular Diels-Alder reaction. The absolute configuration of the most potent macrophomate synthase inhibitor; (-)-2-carboxylmethyl-1-methoxybicyclo[2.2.2]oct-5-ene-2-carboxylic acid, was determined to be (1S, 2R, 4R) by using an axial chiral reagent.

Carboxylic Acids↗
PubMed2001

Analysis of the KAL1 gene in 19 Japanese patients with Kallmann syndrome.

Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia. The KAL1 gene is responsible for the X-linked form of Kallmann syndrome. We analyzed the KAL1 gene in 19 Japanese patients with Kallmann syndrome, including 3 patients reported previously, using PCR-direct sequencing method. All of 19 patients were sporadic, except for 2 monozygotic twins. In this study, there were 3 kinds of mutations in the KAL1 gene. One of them was a novel mutation consisting of a G to A substitution in the acceptor site at the junction of intron 6/exon 7. None of the mutations have been reported in countries other than Japan. In male sporadic patients with Kallmann syndrome, the incidence of mutations in Japanese patients (14%: 2 of 14 cases) was slightly higher than that in patients in USA (8%). Also, we found 2 polymorphisms, which were always found together in 6 patients. The severity of hypogonadism was not related to the presence of mutations. Unilateral renal aplasia and mirror movement, which are frequently found in patients with the KAL1 gene mutation, were not related to the sites of mutations.

Adolescent↗
PubMed2001

Rhythmic spontaneous contractions in the rat proximal colon.

C-kit immunoreactive cells are known to be interstitial cells of Cajal (ICCs), and they generate pacemaker activity of the gastrointestinal tract. Recently a large number of special smooth muscle cells corresponding to c-kit immunoreactive cells were found in the proximal colon of the guinea pig. We learned that the rat proximal colon showed tetrodotoxin-insensitive regular rhythmic spontaneous contractions (RSCs) and hypothesized that RSCs are generated and/or regulated by ICCs. To prove our hypothesis, we investigated whether RSCs are absent in homozygous Ws/Ws mutant rats, since c-kit positive ICCs along the submucosal surface of the circular muscle (ICC(SM)) and myenteric plexus (ICC(MY)) are lacking. In contrast to our hypothesis, we found that RSCs were still present in the proximal colon of the Ws/Ws mutant rats. A recent study has reported that c-kit negative ICC(SM) remains in Ws/Ws mutant rats. Taken together, RSCs may be generated by c-kit negative ICC(SM) in the rat proximal colon. The blockade of sarcoplasmic reticulum Ca(2+)-ATPase by cyclopiazonic acid (CPA) (10(-6)M) or by thapsigargin (10(-6)M) increased the frequency of RSCs. The increasing effects of CPA on the frequency of RSCs were more prominent in Ws/Ws mutant rats than in +/+ rats. We concluded that the functional coordination between c-kit negative ICC(SM) and other mutationally impaired c-kit positive ICC(MY) and ICC(SM) may be required for moderate regulation in the frequency of spontaneous activity.

Animals↗