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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
PubMed2004

Adrenomedullin contributes to vascular hyporeactivity in cirrhotic rats with ascites via a release of nitric oxide.

BACKGROUND: Plasma levels of adrenomedullin, a potent vasodilator peptide, are increased in cirrhotic patients, whereas its role in vascular hyporeactivity in cirrhosis has not been clarified. METHODS: Adrenomedullin expression was evaluated by radioimmunoassay and reverse-transcription polymerase chain reaction. Vascular reactivity to phenylephrine, alpha-adrenoceptor agonist, was investigated in the aortic rings from control rats and CCl-induced cirrhotic rats with ascites in the presence of the neutralizing antibody against adrenomedullin, human adrenomedullin and/or N-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor. RESULTS: Plasma adrenomedullin levels were significantly higher in cirrhotic rats than in controls (16.3 +/- 2.9 versus 7.4 +/- 1.7 fmol/mL, P < 0.05) and correlated negatively with systemic arterial pressure (r = -0.62, P < 0.05). Gene expression of adrenomedullin in various organs (liver, kidney, lung) and vessels (portal vein, aorta) was enhanced in cirrhotic rats compared with controls. Neutralizing antibody against adrenomedullin ameliorated the blunted contractile response to phenylephrine in cirrhotic aorta (Rmax: 1.5 +/- 0.1 versus 1.0 +/- 0.1 g/mg tissue, P < 0.05), whereas contraction remained unchanged in control aorta (Rmax: 1.9 +/- 0.2 versus 1.9 +/- 0.2 g/mg tissue). Intravenous infusion of human adrenomedullin induced a reduction of mean arterial pressure together with an increase of serum nitrate levels, which was abolished by neutralizing antibody against adrenomedullin. Human adrenomedullin caused a blunted contractile response to phenylephrine in both control and cirrhotic aortas, which was not observed in the presence of N-nitro-L-arginine methyl ester. CONCLUSIONS: These findings indicate that the overproduction of adrenomedullin may contribute to vascular hyporeactivity in cirrhosis via a release of nitric oxide.

Adrenergic alpha-Agonists↗
PubMed2004

Pacemaker activity from submucosal interstitial cells of Cajal drives high-frequency and low-amplitude circular muscle contractions in the mouse proximal colon.

The present study was aimed at elucidating how pacemaker activity (plateau potentials) (mean frequency: 15.9 +/- 2.8 times min(-1)) from submucosal interstitial cells of Cajal (ICC-SM) control spontaneous contractions in the mouse proximal colon. Mechanical activities in the circular muscle direction showed high-frequency (mean frequency: 15.6 +/- 2.7 times min(-1)) and low-amplitude (mean amplitude: 0.01 +/- 0.005 g) (HFLA) rhythmic contractions. Simultaneous recordings of circular muscle mechanical activity and electrical activity from ICC-SM revealed that HFLA contractions were synchronized with plateau potentials (mean frequency: 15.9 +/- 2.8 times min(-1)). Although low-frequency (3.5 +/- 2.1 times min(-1)) and high-amplitude (0.12 +/- 0.03 g) (LFHA) contractions in both longitudinal and circular muscle directions were synchronized with burst of action potentials in both muscle cells, these LFHA contractions were not synchronous with plateau potentials. Intracellular Ca2+ release from the internal stores through IP3 receptors is not a major factor to generate both action potentials differently from plateau potentials. Neither tetrodotoxin nor atropine affected the plateau potentials. The results reveal that the pacemaker activity from ICC-SM drives only the spontaneous HFLA (one-tenth amplitude of the LFHA circular and longitudinal muscle contractions) circular muscle contractions without control by enteric nerves.

Animals↗
PubMed2004

Review of combination of peritoneal dialysis and hemodialysis as a modality of treatment for end-stage renal disease.

Because the contribution of residual renal function (RRF) to total solute clearance is often significant in continuous ambulatory peritoneal dialysis (CAPD), loss of RRF over time can lead to inadequate dialysis if appropriate prescription management strategies are not pursued. Additionally, declines in ultrafiltration caused by increases in peritoneal permeability may limit continuation of CAPD therapy. Peritoneal dialysis and hemodialysis (PD + HD) combination therapy (complementary dialysis therapy) is an alternative method. This therapy allows the patient to maintain daily activities, as with CAPD, while undergoing once-a-week HD supplements for the insufficient removal of solutes and water. This therapy allows for the continuation of PD without shifting to total HD in PD patients who continue to have uremic symptoms even after individualization of the PD prescription. This treatment option is psychologically more acceptable to patients and may be expected to provide such accompanying beneficial effects as peritoneal resting, improvement of QOL and reduction in medical cost.

Combined Modality Therapy↗
PubMed2004

Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

Adult↗
PubMed2004

Repeated adenoviral administration into the biliary tract can induce repeated expression of the original gene construct in rat livers without immunosuppressive strategies.

BACKGROUND: Systemic adenoviral readministration appears to be limited by immunogenicity. AIMS: We examined the feasibility of repeated adenovirus mediated gene transfer into the liver via the biliary tract. METHODS: Recombinant adenoviruses carrying a reporter lacZ gene were infused retrogradely into the common bile duct of rats. Transduction efficiency of the lacZ gene was estimated histochemically and quantitatively. RESULTS: Retrograde administration of recombinant adenoviruses into the common bile duct of rats resulted in efficient transgene expression in the liver, specifically in hepatocytes, but not in biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral administration was not substantially different from that induced by intraportal adenoviral infusion. Transgene expression in the liver was however transient, and development of neutralising antibodies against adenovirus was observed in serum but not in bile. When adenoviruses were readministered into the common bile duct, successful re-expression of the transgene in the liver was achieved despite the existence of neutralising antibodies in serum. Interestingly, although proliferation of adenovirus specific T cells in response to adenoviral readministration was suppressed significantly by immunosuppressive FK506 treatment, levels of transgene expression in the liver achieved by intrabiliary adenoviral readministration were not significantly different between animals treated with and without FK506. Furthermore, third adenoviral administration into the common bile duct also induced successful transgene expression in the liver. CONCLUSIONS: These results suggest that adenovirus mediated gene transfer into the liver may be repeatable without immunosuppressive strategies in clinical settings by means of endoscopic retrograde cholangiography.

Adenoviridae↗
PubMed2003

Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative.

OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.

Algorithms↗
PubMed2003

Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis.

BACKGROUND: It has been shown that expression of the potent angiogenic factor, vascular endothelial growth factor (VEGF), and its receptors, flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), increased during the development of liver fibrosis. AIMS: To elucidate the in vivo role of interaction between VEGF and its receptors in liver fibrogenesis. METHODS: A model of CCl(4) induced hepatic fibrosis was used to assess the role of VEGFR-1 and VEGFR-2 by means of specific neutralising monoclonal antibodies (R-1mAb and R-2mAb, respectively). R-1mAb and R-2mAb were administered after two weeks of treatment with CCl(4), and indices of fibrosis were assessed at eight weeks. RESULTS: Hepatic VEGF mRNA expression significantly increased during the development of liver fibrosis. Both R-1mAb and R-2mAb treatments significantly attenuated the development of fibrosis associated with suppression of neovascularisation in the liver. Hepatic hydroxyproline and serum fibrosis markers were also suppressed. Furthermore, the number of alpha-smooth muscle actin positive cells and alpha1(I)-procollagen mRNA expression were significantly suppressed by R-1mAb and R-2mAb treatment. The inhibitory effect of R-2mAb was more potent than that of R-1mAb, and combination treatment with both mAbs almost completely attenuated fibrosis development. Our in vitro study showed that VEGF treatment significantly stimulated proliferation of both activated hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). VEGF also significantly increased alpha1(I)-procollagen mRNA expression in activated HSC. CONCLUSIONS: These results suggest that the interaction of VEGF and its receptor, which reflected the combined effects of both on HSC and SEC, was a prerequisite for liver fibrosis development.

Animals↗
PubMed2003

Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor.

The role of various protein kinases in the downregulation of histamine H(1) receptors was studied by using their inhibitors and activators. Human histamine H(1) receptors (H(1)Rs) expressed in CHO cells were downregulated by histamine in a dose- and time-dependent manner, and this downregulation continued to increase over a 24-h period. KT5823, an inhibitor of protein kinase G, remarkably but not completely reversed the histamine-induced H(1)R downregulation over 24 h. HA1004, another inhibitor of protein kinase G, showed a similar inhibitory effect. However, both 8-Br-cGMP and 8-pCPT-cGMP, membrane-permeable analogues of cGMP, did not show any effects on H(1)R downregulation in the absence or presence of histamine. Ro 31-8220, an inhibitor of protein kinase C (PKC), did not affect histamine-induced downregulation of H(1)R; nor did phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester. Similarly, histamine-induced downregulation of H(1)R was unaffected by either H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable analogue of cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2003

Direct phosphorylation of histamine H1 receptor by various protein kinases in vitro.

Phosphorylation of G protein-coupled receptors (GPCRs) by various kinases is suggested to be an important step in initiating receptor desensitization. Some reports have indirectly demonstrated the involvement of protein kinase C (PKC)-mediated receptor phosphorylation in the desensitization of the histamine H1 receptor (H1R). In this study, human c-myc-epitope-tagged H1R (hm mcH1R) was expressed in Sf9 cells, and an in vitro approach was taken to obtain direct evidence that H1R could be phosphorylated by various kinases. When hm mcH1R, which had been immunoprecipitated with anti-c-myc antibody from Sf9 cell membranes, was incubated with PKC, cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinase II (CaMKII) or cGMP-dependent protein kinase (PKG), the immunoprecipitated receptor was phosphorylated by these kinases. Membrane-bound hm mcH1R, whose conformation is closer to its physiological state than that of the immunoprecipitated receptor, was also phosphorylated by PKC, PKA, CaMKII and PKG. Phosphorylation of immunoprecipitated and membrane-bound hm mcH1R was inhibited by kinase inhibitors. These data are the first demonstration of the phosphorylation of H1R by four protein kinases, i.e., PKC, PKA, CaMKII and PKG, and provide fundamental information to help us further understand the relationship between H1R phosphorylation and desensitization of this receptor.

Animals↗
PubMed2003

[Thoracoscopic resection of localized fibrous tumor of the pleura; report of a case and review of the Japanese literature].

A 61-year-old female was admitted with abnormal shadow on chest X-ray. Chest computed tomography (CT) showed a clearly localized flat tumor at the peripheral region of the left lung. We suspected localized fibrous tumor of the pleura (LFTP) and performed video-assisted thoracic surgery (VATS). Under the thoracoscopy, the tumor was connected to the visceral pleura with a short pedicle and completely resected with safety margin. Pathological findings, including immunohistochemical examination, definitely revealed benign LFTP. VATS is a good indication for the diagnosis and treatment of LFTP. This case was reported together with some reviews of the literature.

Female↗
PubMed2003

[A resected case of malignant fibrous histiocytoma of the chest wall].

We report a 74-year-old woman with malignant fibrous histiocytoma (MFH), treated successfully by radiation and followed with chest wall resection and reconstruction. The patient suffered from right back pain and her chest X-ray showed a clear round shadow in the middle field of the right lung. Chest computed tomography (CT) showed a 5 x 5 cm tumor in diameter, involving the right 8 rib with destructive changes. After radiation therapy of total 30 Gy to the tumor to obtain the safety surgical margin, we widely resected 10 x 9 cm chest wall with 3 ribs in area under thoracoscopy and performed reconstruction using GORE-TEX Soft Tissue Patch. The pathological and immuno-histochemical diagnosis showed pleomorphic type of MFH. Final result of the tumor negative in surgical margin manifested that our technique of chest wall resection and reconstruction using thoracoscope after the irradiation to the tumor was very safe and useful.

Aged↗
PubMed2003

[Inflammatory pseudotumor diagnosed by thoracoscopic resections; report of a case].

A 65-year-old woman was referred to our hospital because of cough and sputum. Chest CT scan revealed a coin lesion (about 1.5 cm diameter) with slight speculation at the right upper lobe. We suspected a lung cancer and performed video assisted thoracic surgery (VATS). Under the thoracoscopy, the tumor was completely extirpated with safety margin by the partial resection of the right upper lobe. Pathological findings definitely revealed inflammatory pseudotumor, fibrohistiocytic variant type. VATS is a good indication for the diagnosis and treatment of inflammatory pseudotumor. This case was reported together with some reviews of the literature.

Aged↗
PubMed2002

A case of aceruloplasminaemia: abnormal serum ceruloplasmin protein without ferroxidase activity.

A 34 year old diabetic man with a complete deficiency of serum ferroxidase activity, regardless of the presence of serum ceruloplasmin (Cp), a multicopper ferroxidase protein, is described. The patient had had diabetes mellitus for 13 years, and was also found to have retinal degeneration accompanied by the development of a hearing disturbance of unknown aetiology. Laboratory examination showed markedly increased serum ferritin and low serum iron. Magnetic resonance imaging showed a pronounced hypointensity in the putamen, caudate, cerebellar dentate, and thalamus on T2 weighted images, and also disclosed a low level signal in the liver, suggesting the accumulation of some magnetic substances in the brain and liver. Liver biopsies histochemically identified iron deposition in the hepatocytes. Most of these findings were consistent with the newly established autosomal recessive disease "aceruloplasminaemia", except for the presence of serum Cp and the lack of apparent neurological symptoms. Interestingly, no ferroxidase activity was detected in the patient's serum, whereas suppressed ferroxidase activity was found in his mother's serum. A nucleotide sequence analysis of the Cp gene showed two mutations; a C to T substitution at nucleotide 2701 in exon 16, resulting in a nonsense mutation at amino acid 882 (Arg882ter), and a T to G substitution at nucleotide 2991 in exon 17, resulting in an amino acid alternation at amino acid 978 (His978Gln). The second mutation was also found in the patient's mother. The absence of serum ferroxidase activity despite the presence of serum Cp protein in this compound heterozygote was considered to be due to the production of a non-functional Cp harbouring no ferroxidase activity.

Adult↗
PubMed2001

The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells.

Angiogenesis is now recognized as a crucial process in tumor development, including hepatocellular carcinoma (HCC). Since HCC is known as a hypervascular tumor, anti-angiogenesis is a promising approach to inhibit the HCC development. Trientine dihydrochloride (trientine) is used in clinical practice as an alternative copper (Cu)-chelating agent for patients with Wilson's disease of penicillamine intolerance. In our study, we examined the effect of Cu-chelating agents on tumor development and angiogenesis in the murine HCC xenograft model. Although both trientine and penicillamine in the drinking water suppressed the tumor development, trientine exerted a more potent inhibitory effect than penicillamine. In combination with a Cu-deficient diet, both trientine and penicillamine almost abolished the HCC development. Trientine treatment resulted in a marked suppression of neovascularization and increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. In vitro studies also exhibited that trientine is not cytotoxic for the tumor cells. On the other hand, it significantly suppressed the endothelial cell proliferation. These results suggested that Cu plays a pivotal role in tumor development and angiogenesis in the murine HCC cells, and Cu-chelators, especially trientine, could inhibit angiogenesis and enhance apoptosis in the tumor with consequent suppression of the tumor growth in vivo. Since trientine is already used in clinical practice without any serious side effects as compared to penicillamine, it may be an effective new strategy for future HCC therapy.

Animals↗
PubMed2001

Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in spontaneously diabetic rats.

Changes in enteric neurons containing various neurotransmitters in the colon have been described in diabetic rats; however, how these changes are related to colonic motility disorders remains unclear. Nitric oxide (NO) is known to be an important inhibitory neurotransmitter in the enteric nervous system. In the present study, we investigated the peristaltic reflex using our modified Trendelenburg's method to evaluate the differences in enteric nitrergic neurons of the distal colon between spontaneously diabetic rats and their sibling control rats. We measured maximum intraluminal pressure, threshold pressure and propagation distance of the reflex contraction. These diabetic rats showed a greater maximum intraluminal pressure than that in the control rats. NG nitro-L-arginine methyl ester (L-NAME) significantly increased the maximum pressure in the control rats. Although L-arginine did not change the maximum pressure, sodium nitroprusside (SNP) significantly decreased it in these diabetic rats. Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reactivities in the myenteric plexus were much weaker in the diabetic rats than those in the control rats. These results indicate that the colonic peristaltic reflex is enhanced by impairment of enteric nitrergic inhibitory neurons in spontaneously diabetic rats.

Animals↗
PubMed2001

Specific recognition of cytosolic thymidine kinase in the human lung tumor by monoclonal antibodies raised against recombinant human thymidine kinase.

Anti-TK monoclonal antibodies (mAbs) were raised against recombinant human cytosolic thymidine kinase (rhTK) and characterized by Western immunoblotting, enzyme-linked immunosorbent assay (ELISA) and immunostaining of tumor cells. Twenty-three clones of TK mAbs were characterized to recognize specifically not only rhTK produced by Escherichia coli but also TK subunit of 25 kDa in human lung cancer. The anti-TK mAbs reacted specifically with cytosolic TK but not with mitochondrial TK. Only one clone of the mAbs inhibited the catalytic activity of TK. By solid phase sandwich enzyme immunoassay using these mAbs, we could quantitate the cytosolic TK content in tissues. Immunohistochemical staining analysis using one of the TK mAbs showed that human lung adenocarcinoma and squamous cell carcinoma exhibited much higher staining intensity than stromal cells. These mAbs are useful for biochemical studies on the regulation of human TK in proliferating cells such as tumor cells and for diagnosis of highly proliferating tumors.

Adenocarcinoma↗