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Biomedical subjects

K Furukawa

Publications and source records attributed to K Furukawa.

At least 109 records · Page 6Linked to original sources
PubMed2000

Analysis of the role of egg integrins in sperm-egg binding and fusion.

Sperm-egg fusion is believed to be mediated via specific molecular interactions. Integrin alpha6beta1 is a strong candidate for a sperm receptor on the egg plasma membrane. However, the ability of the egg integrin alpha6beta1 to interact with molecules on intact sperm has not yet been proven. In this report, possible involvement of integrin alpha6beta1 in sperm-egg interactions was examined by biochemical and immunocytochemical analyses. To identify egg molecules that specifically interact with sperm, we first incubated sperm with biotin-labeled egg surface proteins. Under this condition, solubilized proteins from eggs inhibited sperm-egg fusion. Western blot analysis under reducing conditions indicated that a major-labeled band of 135 kDa bound to sperm. An immunodepletion experiment using the anti-integrin alpha6 antibody GoH3 indicated that the 135 kDa egg surface molecule that bound to sperm was the integrin alpha6 subunit. To investigate the potential involvement of integrin alpha6beta1 in sperm-egg fusion, we next examined the localization of integrin alpha6 and beta1 subunits before and after fertilization by confocal laser microscopy. At an early stage of sperm-egg fusion, the integrin alpha6 and beta1 subunits were accumulated at the sperm binding site. The frequency of cluster formation was closely related to that of sperm-egg fusion, indicating that integrin receptors are accumulated by sperm destined for fusion. Taken together, these results strongly suggest that the integrin alpha6beta1 is involved in sperm-egg binding leading to fusion via direct association of the integrin alpha6 with sperm.

Animals↗
PubMed2000

Clinical experience of Argatroban for anticoagulation in cardiovascular surgery.

PURPOSE: We have reviewed our experience with Argatroban-a direct thrombin inhibitor for anticoagulation--in a variety of cardiovascular operations, and in extracorporeal circulation, as a substitute for heparin. SUBJECTS AND METHODS: 60 patients receiving anticoagulation with Argatroban were classified into the following four groups. Group 1; 20 patients with anticoagulation therapy after cardiac surgery. Group 2; 8 patients with extracorporeal circulation for continuous hemofiltration for either pre- or post-operative control of acute renal failure. Argatroban was used alone or in combination with nafamostat mesilate. Group 3, one patient with replacement of the descending aorta with left heart assist and 15 patients with percutaneous cardiopulmonary support. And Group 4, 16 patients undergoing vascular surgery including the abdominal aorta. The target activated clotting time was individually set for each group. In Group 1, the coagulofibrinolytic activity and platelet function were measured precisely. Bleeding and complications were examined in all groups. RESULTS: Group 1; the targeted activated clotting time of 150-180 seconds was achieved by a dosage of 0.4-0.8 microgram/kg/min Argatroban. Group 2; the activated clotting time of 150-180 seconds was achieved by 0.05-1.6 micrograms/kg/min (concomitance), or by 0.02-2.5 micrograms/kg/min (alone). Group 3; the activated clotting time of 180-200 seconds by 0.05-3.86 micrograms/kg/min. And Group 4; the activated clotting time of around 150 seconds by 2.0 micrograms/kg/min with initial bolus infusion of 0.1 mg/kg. Argatroban did not promote post-surgery bleeding and had no unfavorable effect on coagulo-fibrinolysis or on platelet activity. CONCLUSION: Argatroban may be useful as an anticoagulant in the field of cardiovascular surgery as a substitute for heparin, without causing any post-surgery bleeding complication, or influencing the fibrinolytic activities or platelet functions.

Aged↗
PubMed2000

Profile of cytokine production during the inhibition of acute xenograft rejection.

Th2 cells have been shown to exert cell-mediated immune responses in vitro; therefore, the present study was conducted to investigate the cellular mechanisms of the long-term survival of cardiac xenografts by measuring cytokine production from recipient lymphocytes. Xenogeneic heart grafts from Lewis rats were transplanted into C57BL/6 mice, and the recipients were intravenously injected with H57-597 at the time of transplantation. The production of Th1 cytokines, namely, interleukin (IL)-2 and interferon (IFN)-gamma, and Th2 cytokines, namely, IL-4 and IL-10, from mixed lymphocyte culture cells was assayed by enzyme-linked immunosorbent assay. Splenocytes from the xenograft recipients treated with H57-597 produced significantly lower levels of IL-2, IFN-gamma, IL-4, and IL-10 than those from the untreated recipients, 100 days after transplantation. The findings of this study indicate that the long-term survival of cardiac xenografts induced by H57-597 is mediated by the inhibition of Th0, or both the Th1 and Th2 response.

Acute Disease↗
PubMed2000

Purification and some properties of a tetrodotoxin binding protein from the blood plasma of kusafugu, Takifugu niphobles.

A tetrodotoxin binding protein has been purified from the plasma of the puffer fish kusafugu, Takifugu niphobles, through DEAE-cellulose treatment, ammonium sulfate fractionation, Sephadex gelfiltrations and Sephacryl S-200 and Cellulofine A-500 column chromatography. Final purification by HPLC on a TSK G-3000 SL column yielded a protein which showed only a single protein peak. The molecular weight of the protein was estimated to be 116,000 and 91,000 by SDS-PAGE and mass spectrometry, respectively. A blast search on the amino-terminal amino acid sequence of the purified protein revealed that the protein had no homology to any other protein on data base.

Animals↗
PubMed2000

Chemokine- and cytokine-induced expression of endothelin 1 and endothelin-converting enzyme 1 in endothelial cells.

BACKGROUND: Endothelin 1 (ET-1) is a product of endothelial and many other cell types that possesses a wide range of actions, including vasoconstriction, bronchoconstriction, and mitogenic activity on smooth muscle cells and fibroblasts. ET-1 release and expression is induced in several disease conditions associated with inflammation and cellular injury. OBJECTIVE: The purpose of this study is to determine the effects of alpha-chemokines (IL-8 and melanoma growth-stimulating activator), beta-chemokines (monocyte chemotactic protein 1, macrophage inflammatory protein 1alpha [MIP-1alpha], MIP-1beta, and RANTES), and proinflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma) on the expression of both ET-1 and endothelin-converting enzyme 1 (ECE-1) by human umbilical vein endothelial cells. METHODS: Subconfluent monolayers of human umbilical vein endothelial cells were incubated with each chemokine individually for 24 hours or with a mixture (cytomix) of TNF-alpha, IL-1beta, and IFN-gamma for 6 and 24 hours. RESULTS: Incubation with the alpha-chemokines melanoma growth-stimulating activity and IL-8 did not significantly increase ET-1 and ECE-1 messenger (m)RNA expression and had no effect on ET-1 release. Monocyte chemotactic protein 1 exerted the most potent increase in ET-1 and ECE-1 mRNA and ET-1 release among all chemokines studied (P <.05). MIP-1alpha and RANTES exerted a moderate, but significant, increase on the ET system (P <.05). The cytomix resulted in a significant increase in ET-1 and ECE-1 mRNA expression (P <.05). CONCLUSION: These data demonstrate that, like cytokines, chemokines can induce endothelial ET-1 and ECE-1 in vitro and suggest a possible role for these inflammatory mediators in the induction of the ET system in inflammatory and vascular diseases.

Aspartic Acid Endopeptidases↗
PubMed2000

Cell surface expression of immature H glycoprotein in measles virus-infected cells.

Two forms of hemagglutinin (H) protein, one with an apparent molecular mass of 78 kDa (78K H protein) and the other with that of 74 kDa (74K H protein), are present in cells infected with measles virus (MV). We previously observed that only the mature 78K H protein, a completely glycosylated form of the 74K H protein, was expressed on the cell surface of the infected cells. In the present study, we detected transient expression of the 74K H protein on the cell surface of infected cells by pulse-chase studies, although the level of this expression was much lower than that of the 78K H protein. On the cell surface the 74K H protein was present as dimers and sensitive to endo-beta-N-acetylglucosaminidase H digestion. Treatment with brefeldin A, which blocks the transport of membrane and secretory proteins from the endoplasmic reticulum to the Golgi apparatus, inhibited the cell surface expression of the 78K H protein, but not that of the 74K H protein. These data suggest that a part of the MV 74K H proteins could be transported directly to the cell surface - probably via an alternative pathway - without processing to the complex form in the Golgi apparatus.

Animals↗
PubMed2000

Engineering dioxygenases for efficient degradation of environmental pollutants.

Dioxygenases have recently been engineered to improve their capabilities for environmental pollutant degradation. The techniques used to achieve this include in vitro DNA shuffling and subunit or domain exchanges between dioxygenases of different bacterial origins. Such evolved enzymes acquire novel and enhanced degradation capabilities of xenobiotic compounds, such as polychlorinated biphenyls, trichloroethylene and a variety of aromatic compounds. Hybrid strains in which the evolved genes are integrated into the chromosomal operons exhibit efficient degradation of xenobiotic chlorinated compounds.

Amino Acid Sequence↗
PubMed2000

Successful valve-sparing in aortic root reconstruction under endoscopic guidance.

OBJECTIVE: Aortic insufficiency (AI) associated with ascending aneurysm can be corrected by valve-sparing aortic root reconstruction ('David' reimplantation, 'Yacoub' remodeling). Intraoperative endoscopic evaluation in the aortic root may help to clarify the procedure and to access competence of the preserved valve. METHODS: Following cross-clamping of the ascending aorta, an endoscopy was inserted into the proximal aortic root. Perfusion of crystalloid cardioplegia enabled the visualization of the pressure-loaded valve in the closed position. Conventional macroscopic evaluation would have overlooked valve prolapse because of a release from perfusion pressure. Valve coaptation was imaged directly before and after the valve-sparing procedure. A total of 17 patients underwent aortic root reconstruction under endoscopic guidance. Indications of the valve-sparing were determined with endoscopic findings. The degree of AI before and after the surgery was evaluated by aortography and scored (0, none; 1 trivial; 2, mild; 3, moderate; 4, severe). RESULTS: Remodeling was employed to eight patients and reimplantation to four. The other five patients were replaced with prosthetic valved-conduit. There was no early and late mortality. Before and after the valve-sparing surgery, grades of AI were significantly reduced. Three patients who underwent reimplantation procedure required late valve replacement for late progression of AI, however, none of the patients with remodeling required reoperation. CONCLUSION: Introduction of an endoscopy successfully reduced postoperative AI and clarified indications and limitations of valve-sparing aortic root operations.

Aortic Dissection↗
PubMed2000

Contribution of the portal flow on hepatic tissue perfusion increases in reduced hepatic vascular bed.

Background: A hepatic artery-portal vein reciprocal response and hepatic hemodynamics have well been investigated under normal condition, but not under pathologic condition with decreased vascular bed. This study was designed to determine the hemodynamic changes in the hepatic blood flow, tissue perfusion and interrelationship between portal venous flow (PVF) and hepatic arterial flow (HAF) after inflow interruption in the various size of hepatic vascular bed. Methods: Anesthetized dogs were used to measure PVF and HAF using a transit time flow meter and hepatic tissue flow (HTF) using a laser Doppler flow meter before and after portal venous (PVO) or hepatic arterial occlusion (HAO) under various range of portal triad occlusion (PTO). Results: The ratio of HAF/TLF (total liver flow) was 38+/-14% under the basal condition. This ratio did not change under the 30% PTO where there was a similar decrease in PVF and HAF, but reduced to 25+/-12% under the 70% PTO where there was more selective reduction in HAF than PVF. Although a reciprocal HAF increase was observed under any conditions after PVO, the TLF and HTF decreases after PVO were largest under the 70% PTO with the highest PVF/TLF ratio. On the other hand, there was no reciprocal PVF increase in any conditions after HAO, and the TLF and HTF decreases after HAO were minimal under the 70% PTO with the lowest HAF/TLF ratio. Conclusions: With decreasing hepatic vascular bed, dependency of the remnant hepatic hemodynamics and tissue perfusion on the portal blood flow increased. These findings suggest that an integrity of portal venous flow becomes crucial in the remnant hepatic tissue perfusion after extensive hepatic resection.

Journal Article↗
PubMed2000

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury.

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringer's solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Journal Article↗
PubMed2000

'Adenomyomatous' hamartoma of the lung.

A 53-year-old man presented with a lung mass. A segmentectomy of the left lung was performed, and pathologic examination revealed an unusual hamartomatous lesion in the lung, named 'adenomyomatous hamartoma.' The tumor was composed of multicysts lined by ciliated pseudostratified bronchial epithelium and smooth muscle overgrowth. The authors have proposed that this is a distinct entity that has not previously been described in the English literature.

Actins↗
PubMed2000

Enhancement of rat hypoglossal nerve regeneration by chitin sheet plus gangliosides.

The effects of chitin sheet interposition with and without brain gangliosides on the regeneration of hypoglossal nerve fibres was studied in the rat following resection of a 5mm length of the nerve. At 10 weeks after operation, the number of horseradish peroxidase (HRP)-labelled motor neurones, indicative of the axonal repair process, on the side treated with chitin and gangliosides was higher than on the control side (where 5mm of the nerve was simply resected). The ratios of HRP-positive neurones in the right hypoglossal nucleus (treated side)/left hypoglossal nucleus (intact side) was 0 in the 5mm-resected group, 53% in the chitin-grafted group, 88% in the ganglioside (0.2 microg)-injected group, 90% in the ganglioside (2 microg)-injected group, 91% in the chitin with ganglioside (0.2mg)-injected group, 91% in the chitin with ganglioside (2 microg)-injected group and 85% in the autograft group, respectively. There were significant differences between the 5 mm-resected group and chitin-grafted group, ganglioside-injected group, chitin with ganglioside group and autograft group, and between the chitin-grafted group and ganglioside-injected, chitin with ganglioside and autograft groups (P< 0.005, respectively). Our results indicated that the use of chitin and gangliosides stimulated the regeneration of severed motor nerve fibres. These findings suggest that chitin and gangliosides might be therapeutically useful for treatment of neuronal degeneration.

Animals↗
PubMed2000

Lanoconazole, a new imidazole antimycotic compound, protects MAIDS mice against encephalitis caused by Cryptococcus neoformans.

The protective effect of a new antifungal compound, lanoconazole, against Cryptococcus neoformans infection in C57BL/6 mice exposed to LP-BM5 murine leukaemia virus (MuLV) (MAIDS mice) was investigated. Mice were infected intratracheally with C. neoformans, strain 613D, 40 days after infection with LP-BM5 MuLV. They were treated orally with various doses of lanoconazole or with fluconazole 10 mg/kg (a positive control) once daily beginning 1 day after the fungal infection and continuing until the end of the experimental period. The number of C. neoformans cells in the lungs and brains of infected mice was determined. Lanoconazole and fluconazole had a similar inhibitory effect on the growth of C. neoformans in the brains and lungs of normal mice. Whereas lanoconazole inhibited the growth of C. neoformans in the brains and lungs of MAIDS mice, the pathogen grew in the brains of MAIDS mice treated with fluconazole. Lanoconazole reduced the number of C. neoformans in the brains of normal mice treated with a type 2 cytokine mixture, whereas fluconazole did not. A predominance of type 2 T-cell responses was demonstrated in MAIDS mice. Splenic T cells from MAIDS mice, but not those from normal mice, released interleukins 4 and 10 into the culture medium when they were stimulated with an anti-CD3 monoclonal antibody. These results suggest that lanoconazole may have the potential to inhibit the growth of C. neoformans in AIDS patients with a predominance of type 2 T-cell responses.

Animals↗
PubMed2000

Effects of chronic neutral endopeptidase inhibition in rats with cyclosporine-induced hypertension.

OBJECTIVE: Cyclosporine (CysA), a potent immunosuppressant, is associated with hypertension and nephrotoxicity. Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides and endothelin-1 (ET-1). We conducted the present study to determine whether or not the NEP inhibitor, ecadotril, prevents cyclosporine-induced hypertension and to clarify the mechanisms responsible for the hypotensive effects of ecadotril. DESIGN AND METHODS: We studied the chronic effects of ecadotril (30 mg/kg per day) on blood pressure; the production of ET-1 and C-type natriuretic peptide (CNP); endothelial nitric oxide synthase (eNOS) activity; and the expression of messenger RNA (mRNA), for each substance in blood vessels of CysA-induced hypertensive rats. RESULTS: CysA (25 mg/kg per day) given for 4 weeks increased the blood pressure from 116 +/- 14 mmHg to 159 +/- 15 mmHg, in rats. This increase was blunted by the co-administration of ecadotril (blood pressure: 134 +/- 14 mmHg). CysA increased plasma NEP activity. CysA increased the production of ET-1 and the expression of ET-1 mRNA without affecting CNP synthesis and endothelin converting enzyme (ECE)-1 mRNA expression. CysA decreased the eNOS activity and eNOS mRNA levels. Addition of the NEP inhibitor decreased the synthesis of ET-1 and ET-1 mRNA levels and increased the eNOS activity and the eNOS mRNA levels. Vascular CNP synthesis and ECE-1 mRNA expression in rats treated with ecadotril did not differ from those in rats treated with CysA and ecadotril. CONCLUSION: These results indicate that chronic NEP inhibition may prevent the CysA-induced hypertension by decreasing local ET-1 synthesis and partly increasing vascular nitric oxide production.

Animals↗
PubMed2000

A 90-kilobase conjugative chromosomal element coding for biphenyl and salicylate catabolism in Pseudomonas putida KF715.

The biphenyl and salicylate metabolic pathways in Pseudomonas putida KF715 are chromosomally encoded. The bph gene cluster coding for the conversion of biphenyl to benzoic acid and the sal gene cluster coding for the salicylate meta-pathway were obtained from the KF715 genomic cosmid libraries. These two gene clusters were separated by 10-kb DNA and were highly prone to deletion when KF715 was grown in nutrient medium. Two types of deletions took place at the region including only the bph genes (ca. 40 kb) or at the region including both the bph and sal genes (ca. 70 kb). A 90-kb DNA region, including both the bph and sal genes (termed the bph-sal element), was transferred by conjugation from KF715 to P. putida AC30. Such transconjugants gained the ability to grow on biphenyl and salicylate as the sole sources of carbon. The bph and sal element was located on the chromosome of the recipient. The bph-sal element in strain AC30 was also highly prone to deletion; however, it could be mobilized to the chromosome of P. putida KT2440 and the two deletion mutants of KF715.

Base Sequence↗
PubMed2000

Left ventricular mass and global function in essential hypertension after antihypertensive therapy.

This study compares left ventricular global function in 55 patients (25 with hypertrophy and 30 without hypertrophy) with essential hypertension, whose blood pressure had been stable for longer than 1 year, with that in 35 healthy subjects. Left ventricular global function was calculated using the echocardiographic Doppler index as described by Tei et al. (Tei index). No significant differences were observed in echocardiographic left ventricular systolic function between the three groups. Left ventricular global function differed significantly between the three groups, however, suggesting impaired left ventricular global function even in the absence of left ventricular hypertrophy. Similar changes were observed in the ratio of peak velocity of atrial systole to peak velocity of early diastole during left ventricular inflow waveform (A/E), indicating that this disorder mainly reflects impaired left ventricular diastolic function. Unlike A/E, the Tei index is not affected by increasing age, and, therefore, is appropriate for evaluating left ventricular global function in hypertensive patients, most of whom are middle-aged or older. This index may be useful for determining treatment strategy and evaluating treatment effects.

Adrenergic beta-Antagonists↗
PubMed2000

Implantation of ultraflex nitinol stents in malignant tracheobronchial stenoses.

STUDY OBJECTIVE: To assess the uncovered Ultraflex nitinol stent (Boston Scientific; Natick, MA) for its efficacy and safety. DESIGN, SETTING, AND PATIENTS: Between October 1997 and October 1998, we carried out a prospective multicenter study at six hospitals in Japan. Fifty-four Ultraflex stents were inserted in 34 patients with inoperable malignant airway stenosis using a flexible and/or a rigid bronchoscope under fluoroscopic and endoscopic visualization. MEASUREMENTS AND RESULTS: Clinical, endoscopic examination, and pulmonary function on days 1, 30, and 60 after stent implantation showed improvement. In 19 patients (56%), stent implantation was performed as an emergency procedure because of life-threatening tracheobronchial obstruction. Immediate relief of dyspnea was achieved in 82% of the patients. The dyspnea index improved significantly after implantation (before vs. days 1, 30, and 60; p<0.001). Significant improvements were observed in obstruction of airway diameter (81+/-15% before vs. 14+/-17% on day 1, 12+/-12% on day 30, and 22+/-28% on day 60; p<0.001). Vital capacity (VC), FEV(1), and peak expiratory flow (PEF) increased significantly after stent implantation: before vs immediately after VC (p<0.01), FEV(1) (p<0.001), and PEF (p<0.05). The main complications were tumor ingrowth (24%) and tumor overgrowth (21%). After coagulation with an Nd-YAG laser or argon plasma coagulation, mechanical coring out using the bevel of a rigid bronchoscope was necessary in patients showing tumor ingrowth or overgrowth. Removal and reposition were possible in case of misplacement. There were no problems with migration and retained secretions. The median survival time of patients was 3 months. The 1-year survival rate was 25.4%. CONCLUSIONS: In this study of the Ultraflex nitinol stent, we have demonstrated that patients were relieved from dyspnea, which contributed to improved quality of life, with minimal complications. This stent can be used safely, even in the subglottic region. Owing to its excellent flexibility and biocompatibility, the stent is also indicated in certain complicated situations, eg, narrow stenosis, hourglass stenosis, curvilinear stenosis, bilateral mainstem bronchial stenoses, and long stenosis of varying diameters.

Adult↗