Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 145 records · Page 8Linked to original sources

PubMed2000

Impact of sequential grafting of the internal thoracic or right gastroepiploic arteries on multiple coronary revascularization.

OBJECTIVE: The aim of the study is to clarify the efficacy of the sequential anastomotic technique of the arterial conduits for multiple coronary revascularization. BACKGROUND: The internal thoracic artery (ITA) is now widely accepted as a durable conduit for myocardial revascularization. The right gastroepiploic artery (GEA) has been developed as a third in situ arterial graft with an outcome similar to that of the ITA. MATERIAL AND METHOD: One hundred and forty five consecutive patients (116 male, 29 female, mean age 60.4yr) who received sequential grafting of either the ITA or GEA or both were retrospectively analysed. RESULTS: Sequential anastomoses were performed in 121 in situ left ITAs, 36 in situ GEAs and 12 composite right ITAs. No in situ right ITA was anastomosed sequentially. Two to six vessels (mean 3.8) were revascularized for each patient. Of the total 543 bypassed vessels, 432 (79.6%) were reconstructed with the arterial grafts. In 85 patients with quadruple bypass or more, the arterial grafts were able to reconstruct 266 out of 360 (74.0%) target vessels. Seventy one patients (49.0%) were revascularized without venous grafts. The arterial grafts could revascularize 293 out of 310 vessels (94.5%) in the LAD approximately Diagonal region, 83 out of 113 (73.4%) in the distal RCA or Cx region. There were no cardiac events responsible for the arterial grafts in the follow up period. CONCLUSION: In light of our experience, multiple revascularization with in situ arterial sequential grafts is feasible. Aggressive application of this technique provides patients requiring multiple coronary revascularization with favorable long-term results.

Abdomen↗

PubMed2000

Identification of a novel HLA-B46 allele, B*4602, in Japanese.

The B*4602 was identified in a healthy Japanese donor. The B46 variant antigen differed serologically from B46. The nucleotide sequence of B*4602 differed from that of B*4601 by a single base (from A to G) at position 293 in exon 2. The substitution changed the amino acid Asp at position 74 to Gly. The gene frequency of B*4602 in the Japanese population is extremely low. The presumed haplotype of B*4602 was HLA-A2-Cw1-B*4602-DRB1*09. This is the first report of polymorphism of the B46 antigen.

Alleles↗

PubMed2000

Pulsed field ionization-ZEKE spectroscopy of cresoles and their aqueous complexes: internal rotation of methyl group and intermolecular vibrations

Pulsed field ionization-ZEKE photoelectron spectroscopy and (1 + 1) R2PI spectroscopy have been applied to the cis- and trans-m-cresol.H2O clusters. The internal rotational structure in the S1 state has been re-assigned, and the potential curve has been determined for the cluster. The PFI-ZEKE spectra of the cis- and trans-isomers show low-frequency bands up to 1000 cm-1 above the adiabatic ionization potential IP0. The low-frequency bands are assigned to the internal rotation of the methyl group, the intermolecular stretching and their combination bands in the m-cresol.H2O cluster cation. Level energies and relative transition intensities are reproduced well by a one-dimensional rotor model with a three-fold axis potential. Potential curves for the internal rotation have been determined for both cis- and trans-isomers of m-cresol.H2O cations. The effect of the cluster formation upon the internal methyl rotation, and the interaction between the methyl rotation and the intermolecular vibration are discussed.

Journal Article↗

PubMed2000

Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma.

Three different membrane-type matrix metalloproteinases (MT-MMPs) activate in vitro the latent form of matrix metalloproteinase-2 (MMP-2), which is one of the key proteinases in invasion and metastasis of various cancers. We examined the mRNA expression of MT1, 2, and 3-MMPs and MMP-2 in cell lines of head and neck squamous cell carcinoma (HNSCC) and quantitated the relative expression levels in human HNSCC tissues by Northern blotting. The tissue localization of MT1-MMP and MMP-2 was determined by immunohistochemistry and in situ hybridization. Their implications in clinicopathologic factors were statistically evaluated. All cell lines examined consistently expressed MT1-MMP and MMP-2, but not MT2, 3-MMP. In the clinical specimens, there was a significant correlation in coexpression of messenger of RNA (P = .0005) and colocalization by immunohistochemistry (P < .0001) for MT1-MMP and MMP-2. Relative mRNA expression levels of MT1-MMP and MMP-2 in the carcinoma tissues were significantly higher than those of the control tissues (P = .0045 and P = .0122, respectively). Both mRNA expression level and immunopositivity of MT1-MMP significantly correlated with lymph node metastasis (P = .0081 and P = .0193, respectively), which was confirmed by multivariate logistic regression analysis. Immunoreaction of MT1-MMP and its mRNA expression were observed in both carcinoma cells and stromal cells. The localization of MMP-2 closely corresponded to that of MT1-MMP. These observations suggest that MT1-MMP possesses a role as a determinant of lymph node metastasis in HNSCC, and that concurrent expression of MT1-MMP and MMP-2 are involved in progression of HNSCC.

Blotting, Northern↗

PubMed2000

Is extended lymph node dissection necessary for gastric cancer in elderly patients?

OBJECTIVE: To compare the outcome after limited and extended gastric resections to find out whether extended lymph node dissection is indicated for gastric cancer in elderly patients. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 182 patients over 75 years of age with gastric cancer who had gastric resections from 1980 to 1995. INTERVENTIONS: 161 patients had limited lymph node dissection (limited group) and 21 had extended lymph node dissection (extended group). MAIN OUTCOME MEASURES: Histopathological features, morbidity, mortality, and long-term survival. RESULTS: Postoperative morbidity was 27% (n = 44) in the limited group and 57% (n = 12) in the extended group, and postoperative mortality was 1% (n = 2) in the limited group and 10% (n = 2) in the extended group; these differences are significant (p = 0.005 and p = 0.002). The 5-year survival did not differ significantly between the two groups. Only the T classification and presence of lymph node metastases had a significant influence on the outcome of gastric cancer in elderly patients. CONCLUSIONS: The presence of lymph node metastases is a critical factor in the prognosis of gastric cancer, and extended lymph node dissection has therefore been recommended. However, extended lymph node dissection in elderly patients did not influence the 5-year survival; in addition, the mortality and morbidity in the extended group were higher than in the limited group. Extended lymph node dissection is therefore usually not indicated for gastric cancer in elderly patients.

Gastrectomy↗

PubMed2000

Synthesis and properties of novel acyclic nucleotides.

Acyclic adenosine and thymidine analogs derived from L- and D-threonie were synthesised and incorporated into oligonucleotides by automated protocols using a standard phosphoramidite method. UV melting experiments with thus obtained oligonucleotides showed that incorporation of those acyclic nucleosides did not destabilize the hybrid duplexes and that the stabilities of them are influenced by the stereochemical structures of acyclic analogs. Modification of 3'-end of oligonucleotide with acyclic analogs protected the oligonucleotide against 3'-exonuclease.

Adenosine↗

PubMed2000

Structure and affinity of DNA binding peptides.

Artificial peptides designed to form alpha-helical, beta-turn, antiparallel beta-sheet and beta-hairpin structures which are among the motifs most frequently found in natural DNA/RNA binding proteins were synthesized and their characteristic features were examined in the presence or absence of double or triple stranded DNA by means of UV melting experiments, CD spectra, SPR measurements. It was revealed that amphiphilic character arising from the specific secondary structures and positive charge in the hydrophobic face of peptides played an important role in the interaction with DNA, and that hybrid duplex and triplex were intensively stabilized by the cationic amphiphilic peptides. It was also found that these peptides could protect dsDNA against DNase 1 digestion. These results indicate that structurally designed amphiphilic peptides synthesized in the present study can be powerful tools for antisense and antigene strategies.

Amino Acid Sequence↗

PubMed2000

Design and synthesis of curcumin-bioconjugates to improve systemic delivery.

Di-O-glycinoyl curcumin (I), di-O-glycinoyl-C4-glycyl-curcumin (II), 5'-deoxy-5'-curcuminyl thymidine (5'-cur-T) (III) and 2'-deoxy-2'-curcuminyl uridine (2'-cur-U) (IV) have been synthesized and characeterised by elemental analysis & 1H NMR. The antibacterial activities of these four bioconjugates has been tested particularly for multiresistant micro-organisms. Best results are shown by I & IV. These bioconjugates serve dual purpose of systemic delivery as well as therapeutic agents against viral diseases.

Anti-Infective Agents↗

PubMed2000

Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression.

The neurotrophins and the tyrosine kinase (Trk) B receptor may play a protective role in the pathophysiology of cerebral ischemia. In this study, the authors investigated whether reducing endogenous expression of TrkB-binding neurotrophins modifies the susceptibility to ischemic injury after 1-hour middle cerebral artery occlusion followed by 23 hours of reperfusion in a filament middle cerebral artery occlusion model. Mice lacking both alleles for neurotrophin-4 (nt4-/-) or deficient in a single allele for brain-derived neurotrophic factor (bdnf+/-) exhibited larger cerebral infarcts compared to wild-type inbred 129/SVjae mice (68% and 91%, respectively, compared to controls). Moreover, lesions were larger (21%) in nt4-/- mice after permanent middle cerebral artery occlusion. Hence, expression of both NT4 and BDNF, and by inference the TrkB receptor, confers resistance to ischemic injury.

Animals↗

PubMed2000

Significant roles of endothelin-A- and -B-receptors in renal function in congestive heart failure.

Endothelin-1 (ET-1) not only causes potent vasoconstriction but also leads to fluid retention, both actions mediated by ET(A)- and/or ET(B)-receptors. Selective ET(A)- and combined ET(A)/ET(B)-receptor antagonists improve hemodynamics in heart failure; however, it is also important to evaluate the effects of these antagonists on urine output in heart failure. We administered an acute dose of either the selective ET(A)-receptor antagonist FR139317 (FR, n=5, 1 and 3 mg/kg) or the mixed ET(A)/ET(B)-receptor antagonist TAK-044 (TAK, n = 5, 1 and 3 mg/kg) to dogs with heart failure induced by rapid ventricular pacing. Renal hemodynamic and tubular functions were subsequently investigated. FR increased urinary excretion in association with increased renal plasma flow (RPF) and glomerular filtration rate (GFR) with no significant changes in the fractional reabsorption of water distally (FRWD). In contrast, despite increased GFR, TAK did not alter urine volume or RPF with significantly increased FRWD. The increase of GFR and RPF induced by FR was significantly larger than that of TAK. These findings indicate that ET(B)-receptor activation may result in diuresis by renal vasodilatation and reduction of water reabsorption in the distal tubules and collecting ducts. Acute ET(A)-receptor antagonism may therefore be more beneficial to diuresis than dual ET(A)/ET(B)-receptor inhibition in heart failure.

Animals↗

PubMed2000

Chronic effects of an orally active selective endothelin-B-receptor antagonist in experimental congestive heart failure.

Endothelin-B- (ETB) receptors located in vascular beds mainly mediate vasorelaxation, however, long-term treatment with a mixed ETA/ETB receptor antagonist has been shown to improve the survival rate of rats with heart failure in a similar way to ETA-receptor inhibitors. The inhibition of ETB-receptor-mediated action should therefore be beneficial in preventing the deterioration seen in heart failure, despite various adverse hemodynamic effects. We administered K-8794 (Kowa Co. Ltd, Japan, 2mg/kg/day, n = 6), an orally active selective ETB-receptor antagonist, to dogs with heart failure induced by rapid right ventricular pacing for 14 days, commencing 8 days after pacing. Control dogs were given a placebo (n = 6). Mean arterial pressure decreased and systemic vascular resistance increased in both groups at the end of the protocol. In the K-8794 group, however, those values were higher than in the control group. Cardiac output decreased in both groups, but there were no significant differences observed between the two groups. Plasma renin activity and aldosterone increased in both groups at the end of the protocol, however levels in the K-8794 group were significantly lower than those in the control group. In the K-8794 group, it was quite interesting to note that Na excretion and urine flow rate were higher than in the control group. Our findings thus suggest that, although ETB-receptor antagonism produces some hemodynamic disadvantages, it can successfully prevent body fluid retention through the suppression the activation the renin-angiotensin-aldosterone system in dogs with heart failure.

Administration, Oral↗

PubMed2000

Intractable epilepsy associated with multiple cavernous malformations: case report.

OBJECTIVE AND IMPORTANCE: Epilepsy associated with cavernous malformations is often effectively controlled by lesionectomy alone. Detailed preoperative evaluation is necessary if the lesions are multiple and the seizures are medically intractable. We report on a patient with multiple cavernous malformations associated with medically intractable seizures who became seizure-free after a single gyrus resection. The importance of electroencephalography with video monitoring is emphasized. CLINICAL PRESENTATION: The patient was a 25-year-old man with a 10-year history of complex partial and generalized convulsions. Magnetic resonance imaging revealed more than 10 cavernous malformations. Video-electroencephalographic monitoring indicated that seizures originated from either the frontal or temporal lobe of the right hemisphere. INTERVENTION: Subdural electrodes were implanted, covering both frontal and both temporal lobes. The seizures originated in the right frontal lobe. The gyrus, including a calcified cavernous malformation, was removed, and multiple subpial transections of the surrounding cortices were performed. The patient has been free of seizures for 22 months after surgery. CONCLUSION: Medically intractable seizures associated with multiple cavernous angiomas can be controlled by a single resective procedure.

Adult↗

PubMed2000

Clinicopathological significance of expression of CD44 variants in head and neck squamous cell carcinoma.

Splice variants of the cell surface glycoprotein CD44 have been reported to be associated with the progression of various human tumors. The aim of this study is to determine the correlation between the expression of CD44 isoforms, especially CD44 variant 2 (CD44v2), and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs). The expression of CD44 isoforms was evaluated immunohistochemically in paraffin-embedded tissues from 89 primary lesions, using monoclonal antibodies against CD44 standard (CD44st), CD44 variant 6 (CD44v6) and CD44v2. Cancer tissues from 89 (100%), 85 (95.5%) and 59 (66.3%) patients showed positive immunoreactivity for CD44st, CD44v6 and CD44v2, respectively. A significant correlation was observed between the down-regulation of CD44v2 and poorer differentiation of the tumor cells (P = 0.02). We could not find any significant correlation between the expression of CD44v2 and T stage or N stage (lymph node status). However, the rate of positive cervical lymph node metastasis tended to increase with reduced expression of CD44v2 (P = 0.08). Down-regulation of CD44v2 expression was correlated with shorter overall survival (P = 0.01). Furthermore, Cox's multivariate analysis revealed that only CD44v2 expression and lymph node status were independent prognostic factors. These findings suggest that down-regulation of CD44v2 expression may be one of the biological markers for the degree of malignancy in HNSCCs.

Adult↗

PubMed2000

Prevalence of GB virus C/Hepatitis G virus infection among various populations in Surabaya, Indonesia, and identification of novel groups of sequence variants.

A molecular epidemiological study was performed to investigate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection among various populations in Surabaya, Indonesia. The prevalence of GBV-C/HGV RNA, determined by reverse transcription-PCR for a portion of the NS3 region of the viral genome, was 2.7% (4 of 150) among randomly collected blood donor sera, which were all negative for both hepatitis B virus surface antigen and antibodies against hepatitis C virus (HCV). On the other hand, the prevalence among anti-HCV-positive blood donors was 17.8% (13 of 73), with the ratio being significantly higher than that observed with the anti-HCV-negative blood donors (P < 0.001). A high prevalence of GBV-C/HGV infection was also observed among patients with chronic liver disease, such as chronic hepatitis (5.7%), liver cirrhosis (11. 5%), and hepatocellular carcinoma (7.0%), and patients on maintenance hemodialysis (29.0%). No correlation was observed between GBV-C/HGV viremia and serum alanine aminotransferase levels in the populations tested, suggesting the possibility that GBV-C/HGV does not cause apparent liver injury. Phylogenetic analysis of sequences of a portion of the 5' untranslated region and the E1 region of the viral genome identified, in addition to a previously reported then novel group of GBV-C/HGV variants (group 4), another novel group of variants (group 5). This result suggests that GBV-C/HGV can be classified into at least five genetic groups. GBV-C/HGV isolates of group 4 and group 5 were each shown to comprise approximately 40% of the total Indonesian isolates.

5' Untranslated Regions↗

PubMed2000

Preparation of griseofulvin for topical application using N-methyl-2-pyrrolidone.

We attempted to prepare a new griseofulvin formulation for topical application using N-methyl-2-pyrrolidone (NMP). Griseofulvin dissolves poorly in both water and oil, but dissolves in NMP to a concentration of about 100 mg/ml. A soybean oil-water emulsion with soybean lecithin and NMP as emulsifier and co-solvent, respectively, was prepared using a Microfluidizer, a high-pressure homogenizer. The size of the droplets in emulsion was about 200 nm, and the emulsion was stable for over 3 months. The skin permeation of griseofulvin through Yucatan micropig skin was studied in vitro using vertical type cells under donor phase open conditions. The permeation of griseofulvin from the NMP-water mixture (0-40%) into the skin tended to increase with increasing NMP concentration, although this finding was not statistically significant. Permeation from emulsion (oil phase, 20%; NMP 10-40%) was significantly higher than that from the water-NMP mixture. Permeation from the oil-NMP mixture was highest among the formulations investigated, and permeation from emulsion under donor phase closed conditions was significantly lower than that under open conditions. We believe that the evaporation of water from the emulsion after application to the skin was an important factor in skin permeation enhancement. When the emulsion containing 3% l-menthol was applied, a sufficient skin concentration (47 microg/cm3 in dermis) was obtained.

Administration, Topical↗

PubMed2000

Effect of tranilast oily gel on carrageenin-induced granulation in rats.

Tranilast (TL) oily gels consisting of hydrogenated soybean phospholipid and fatty-acid ester were prepared, and the inhibitory effect of the gels on the growth of granulation tissue were evaluated in a carrageenin-induced rat granulation model. By the application of 0.1 and 0.2% TL oily gel, the weight of granulation tissue was significantly reduced to 64 and 55%, respectively, of control value. Furthermore, these gels reduced their respective hydroxyproline content to 64 and 51% of the control. On the other hand, the inhibitory effect of 10% TL ointments, which are clinically used for the treatment of keloids and hypertrophic scars as hospital preparations, was much lower than that of the oily gels. In addition, the application of 0.1 and 0.2% oily gel led to high concentration (0.1% gel, 168+/-18 microg/g; 0.2% gel, 221+/-16 microg/g) of TL in the dermis as compared with the 10% TL ointments. These results suggest that TL oily gels may be a useful topical formulation for the treatment of keloids and hypertrophic scars.

Administration, Topical↗

PubMed2000

A novel class of inhibitors for human steroid 5alpha-reductase: synthesis and biological evaluation of indole derivatives. II.

In a search for novel nonsteroidal inhibitors of human prostatic 5alpha-reductase, we found a new series of indole derivatives that showed potent inhibitory activities for the human enzyme. Among them, 4-[(1-benzyl-1H-indol-5-yl)oxyl-3-chlorobenzoic acid (2d, YM-32906) showed more potent inhibitory activity than finasteride with an IC50 value of 0.44 nM. 3-Chloro-4-[[1-(4-phenoxybenzyl)-1H-indol-5-yl]oxy]benzoic acid (2m) showed inhibitory activities for both human and rat prostatic 5alpha-reductase with IC50 values of 2.1 and 73 nM, respectively. The synthesis and structure-activity relationships of these indole derivatives are presented.

5-alpha Reductase Inhibitors↗

PubMed2000

Role of off-pump coronary artery bypass grafting in patients with malignant neoplastic disease.

Although the long-term benefits of conventional coronary artery bypass grafting (CABG) are obvious, postoperative morbidity and mortality and the length of recovery associated with cardiopulmonary bypass are the main concerns of cardiac surgeons and cardiologists. The aim of this study was to demonstrate the effectiveness and advantage of the off-pump CABG for patients with concomitant malignant disorders requiring myocardial revascularization. From March 1997 to February 1999, 51 patients underwent off-pump CABG. Of these, there were 9 patients who had concomitant malignant disease requiring noncardiac surgery: gastric cancer (4), urinary bladder cancer (2), cholangioma (1), lung cancer (1) and colon cancer (1). Off-pump CABG was performed through a sternotomy, left thoracotomy or subxiphoid incision. Five patients received single grafting and 4 received double. The mean operative time for the off-pump CABG was 167 min. The total amount of bleeding during the off-pump CABG was 450-890 ml. Simultaneous noncardiac operations were carried out in 5 patients. The other 4 patients underwent subsequent operations for the malignancy uneventfully. In contrast, of the 4 patients with concomitant malignant disorders who underwent standard CABG during the period before the use of off-pump CABG, 2 died without undergoing the subsequent noncardiac operation. Off-pump CABG is quite efficient and is of great advantage in patients with malignancy who require myocardial revascularization in addition to noncardiac surgery for the cancer.

Aged↗