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Biomedical subjects

K Matsuura

Publications and source records attributed to K Matsuura.

At least 19 recordsLinked to original sources

Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy.

Bcl-2 is an oncoprotein that plays a critical role in inhibiting apoptotic cell death in the mitochondria-dependent pathway in cancer chemotherapy. As a strategy for blocking Bcl-2 for enhancement of the chemotherapeutic effect, antisense Bcl-2 (AS Bcl-2; G3139, oblimersen sodium, Genasense) has shown promise, and there are several ongoing clinical studies with hematological malignancies as well as solid tumors. Although several preclinical and clinical studies have shown the therapeutic efficacy of Bcl-2 in combination with an anticancer drug as a chemosensitizer, in clinical trials the downregulation of Bcl-2 has not been observed with a high frequency in tumor cells. Nevertheless, previous studies showed nonantisense effects such as production of reactive oxygen species and immunostimulatory action through cytosine-phosphate-guanosine-motif in the antisense oligodeoxynucleotides. Further, Bcl-2 is able to inhibit Beclin 1-dependent autophagic cell death, which is a nonapoptotic cell death. The current status and future directions of AS Bcl-2 and the potential mechanisms for multiple roles that Bcl-2 has in cancer therapy are reviewed.

Clinical Trials as Topic↗

Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer.

PURPOSE/OBJECTIVE: To evaluate the outcome of cervical cancer patients unable to undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). METHODS AND MATERIALS: We reviewed the records of 7 patients who had received definitive radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and 2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment time was 42 days. RESULTS: Median follow-up for survival patients was 17 months. Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was 100%. The 2-year local control rate was 85.7%. Of these patients, 5 are alive without disease and 1 is alive with lung metastasis. CONCLUSIONS: Our outcomes suggest that 3DCRT using AHF may be a promising as a definitive treatment for cervical cancer when ICBT is not able to be performed.

Aged↗

Assessment of efficacy of a live oral poliovirus vaccine for virulent Sabin-like poliovirus 1 strains in Japan.

Virulent Sabin-like poliovirus (VSLP) was isolated from river and sewage waters between October 1993 and September 1995 in Toyama Prefecture, Japan (Yoshida et al., Lancet 356, 1461-1463, 2000). In this study, to assess the possibility of an epidemic of poliomyelitis caused by a VSLP in Japan under the current vaccination policy of administration of live attenuated oral poliovirus vaccine (OPV), we determined titers of serum neutralizing antibodies to poliovirus 1 (PV-1) strains Sabin (vaccine strain), Mahoney (wild-type strain) and G4-12 (VSLP) in various groups of residents of Toyama Prefecture, Japan. The seropositivity and geometric mean neutralizing antibody titers against these strains in the individuals who obtained two doses of OPV were 99.1%, 94.5% and 95.5%, respectively, and 564, 186 and 194, respectively. Although the antibody titers to G4-12 were lower compared with those to Sabin, these results indicate that the OPV vaccination policy in Japan has been effective in preventing poliomyelitis caused by VSLPs. These results also suggest that (i) an epidemic of poliomyelitis caused by a VSLP has not occurred in Japan due to herd immunity, and (ii) the possibility of reemergence of VSLPs will be prevented if sufficient herd immunity is acquired immediately after completion of the OPV vaccination in accordance with the poliomyelitis eradication program.

Adolescent↗

Insulin regulates the expression of the enhancer of split- and hairy-related protein-2 gene via different pathways in 3T3-L1 adipocytes and L6 myotubes.

We investigated the effect of insulin on the expression of the enhancer of split- and hairy-related protein-2 gene in 3T3-L1 adipocytes and L6 myotubes. The level of enhancer of split- and hairy-related protein-2 mRNA was increased by insulin in both cells. While both wortmannin and LY294002 blocked the increase in 3T3-L1 adipocytes, and only PD98059 was effective in L6 myotubes. Although the increase by insulin in these cells was inhibited by treatment with actinomycin D, this was enhanced by treatment with cycloheximide. Furthermore, cyclic AMP increased the level of enhancer of split- and hairy-related protein-2 mRNA in both cells in an additive manner. Thus, we conclude that insulin and cyclic AMP induce the expression of the enhancer of split- and hairy-related protein-2 gene in both 3T3-L1 adipocytes and L6 myotubes, and that the gene expression enhanced by insulin is regulated by the cell type-specific pathway. The former requires a phosphoinositide 3-kinase pathway and the latter a mitogen-activated protein kinase pathway.

3T3 Cells↗

Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience).

PURPOSE: This study aimed to compare the effects of computer-assisted, text-based and computer-and-text learning conditions on the performances of 3 groups of medical students in the pre-clinical years of their programme, taking into account their academic achievement to date. A fourth group of students served as a control (no-study) group. METHOD: Participants were recruited from the pre-clinical years of the training programmes in 2 medical schools in Japan, Jichi Medical School near Tokyo and Kochi Medical School near Osaka. Participants were randomly assigned to 4 learning conditions and tested before and after the study on their knowledge of and skill in performing an abdominal examination, in a multiple-choice test and an objective structured clinical examination (OSCE), respectively. Information about performance in the programme was collected from school records and students were classified as average, good or excellent. Student and faculty evaluations of their experience in the study were explored by means of a short evaluation survey. RESULTS: Compared to the control group, all 3 study groups exhibited significant gains in performance on knowledge and performance measures. For the knowledge measure, the gains of the computer-assisted and computer-assisted plus text-based learning groups were significantly greater than the gains of the text-based learning group. The performances of the 3 groups did not differ on the OSCE measure. Analyses of gains by performance level revealed that high achieving students' learning was independent of study method. Lower achieving students performed better after using computer-based learning methods. CONCLUSION: The results suggest that computer-assisted learning methods will be of greater help to students who do not find the traditional methods effective. Explorations of the factors behind this are a matter for future research.

Abdomen↗

Release of short and proline-rich antihypertensive peptides from casein hydrolysate with an Aspergillus oryzae protease.

Angiotensin-I converting enzyme inhibitory activities were measured after hydrolysis of casein by 9 different commercially available proteolytic enzymes. Among these enzymes, a protease isolated from Aspergillus oryzae showed the highest angiotensin-I converting enzyme inhibitory activity per peptide. The A. oryzae peptide also showed the highest antihypertensive effect in spontaneously hypertensive rats when the systolic blood pressure was measured 5 h after oral administration of 32 mg/kg of various enzymatic hydrolysates. Significant antihypertensive effects were observed with dosages of 9.6, 32, and 96 mg of the A. oryzae peptide/kg of body weight (BW), and the effects were dependent on these peptide dosages. Analysis of peptide length showed the A. oryzae hydrolysate was the shortest of all tested casein hydrolysates; the peptide mixture had an average value of 1.4 amino acids (AA) in the sequence. To further characterize the A. oryzae hydrolysate, we analyzed the AA sequence of the whole peptide mixture. Various AA were detected at the first AA position, however, an increased number of Pro residues were observed at the second and third position of the A. oryzae hydrolysate. No strong signals were detected after the fourth AA position of the A. oryzae hydrolysate. These results suggest that the casein hydrolysate of A. oryzae, which expressed potent antihypertensive effects in spontaneously hypertensive rats, mainly contain short peptides of X-Pro and X-Pro-Pro sequences.

Amino Acid Sequence↗

Regulation of circulating immune complexes by complement receptor type 1 on erythrocytes in chronic viral liver diseases.

BACKGROUND AND AIM: Complement receptor type 1 (CR1) is a transmembrane protein, and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating immune complexes (IC) from the circulation to the reticuloendothelial system, including the liver and spleen. In chronic viral hepatitis, increased levels of IC containing viral particles and an association with various extrahepatic manifestations have been reported. However, regulatory mechanisms for IC levels are not fully understood. PATIENTS/SUBJECTS AND METHODS: We analysed IC, E-CR1, and quantitative polymorphism of the CR1 gene in 149 patients with chronic viral liver diseases and in 64 normal blood donors using an enzyme linked immunosorbent assay, radioimmunoassay, and polymerase chain reaction-restriction fragment length polymorphism, respectively. We also analysed the effect of CR1 gene polymorphism on IC binding to E-CR1 using molecular methods. RESULTS: E-CR1 levels in patients with chronic hepatitis and chronic viral liver diseases as a whole correlated inversely with increased levels of IC. Moreover, significantly high levels of IC were observed in patients with chronic hepatitis C (CH-C) who were homozygous for the E-CR1 low density allele. We also found low levels of E-CR1 in liver cirrhosis and CH-C but not in CH-B. Low levels of E-CR1 in CH-C were observed, even after considering the polymorphism of the CR1 gene. Finally, we demonstrated CR1 gene polymorphism dependent binding of hepatitis virus containing IC. CONCLUSIONS: Our results emphasise the important role of E-CR1 in clearance of IC from the circulation and the acquired, rather than inherited, decrease in E-CR1 in chronic viral liver diseases, especially of type C.

Adult↗

In vitro and in vivo electron transfer to the triheme cytochrome subunit bound to the photosynthetic reaction center complex in the purple bacterium Rhodovulum sulfidophilum.

The cytochrome subunit bound to the photosynthetic reaction center (RC) complex in Rhodovulum sulfidophilum lacks one heme-binding motif (CXXCH) out of four motifs found in other purple bacteria resulting in the absence of the most distal heme from the RC-core complex (S. Masuda et al., J. Biol. Chem. 274 (1999) 10795). Cytochrome c(2), which acts as the electron donor to the RC was purified, and its gene was cloned and sequenced. The redox midpoint potential of cytochrome c(2) was determined to be E(m)=357 mV. The photo-oxidation and re-reduction of purified cytochrome c(2) were observed in the presence of membrane preparations. Flash-induced photo-oxidation and re-reduction of the RC-bound cytochrome were also observed in intact cells. Despite the unusual nature of the RC-bound cytochrome subunit, the cyclic electron transfer system in Rdv. sulfidophilum was shown to be similar to those in other purple bacteria.

Amino Acid Sequence↗

Different mechanisms of the binding of soluble electron donors to the photosynthetic reaction center of Rubrivivax gelatinosus and Blastochloris viridis.

The tetraheme cytochrome subunits of the photosynthetic reaction centers (RCs) in two species of purple bacteria, Rubrivivax gelatinosus and Blastochloris (Rhodopseudomonas) viridis, were compared in terms of their capabilities to bind different electron-donor proteins. The wild-type RCs from both species and mutated forms of R. gelatinosus RCs (with amino acid substitutions introduced to the binding domain for electron-donor proteins) were tested for their reactivity with soluble cytochromes and high potential iron-sulfur protein. Cytochromes from both species were good electron donors to the B. viridis RC and the R. gelatinosus RC. The reactivity in the R. gelatinosus RC showed a clear dependence on the polarity of the charges introduced to the binding domain, indicating the importance of the electrostatic interactions. In contrast, high potential iron-sulfur protein, presumed to operate according to the hydrophobic mechanism of binding, reacted significantly only with the R. gelatinosus RC. Evolutionary substitution of amino acids in a region of the binding domain on the cytochrome subunit surface probably caused the change in the principal mode of protein-protein interactions in the electron-transfer chains.

Bacterial Proteins↗

Effect of Sotalol in the prevention of atrial fibrillation following coronary artery bypass grafting.

OBJECTIVE: We assessed the efficacy of postoperatively administered oral Sotalol in preventing the occurrence of postoperative atrial fibrillation. METHODS: Subjects were 80 consecutive patients undergoing coronary artery bypass grafting (CABG) randomized alternately into a Sotalol group (40 patients) administered 80 mg of oral Sotalol daily starting on the postoperative day 1 and continued for 14 days, and a control group (40 patients) matched for age and gender. RESULTS: The incidence of postoperative atrial fibrillation (21 patients) was significantly lower in the Sotalol group (6/40 patients; 15%) than in controls (15/40; 37.5%) (p < 0.05). Significant bradycardia or hypotension, necessitating drug withdrawal, occurred in 3 of 40 (7.5%) patients in the Sotalol group. None in the Sotalol group developed Torsardes de Pointes or sustained ventricular arrhythmias or other severe side effects. The sinus heart rate increased in both groups but less in the Sotalol group. QT, QRS, and QTc durations did not differ between groups. Postoperative hospital stay did not differ between groups. CONCLUSIONS: Oral Sotalol administration of 80 mg daily was associated with a significant decrease in postoperative atrial fibrillation in patients undergoing CABG without appreciable side effects. Sotalol should thus be considered in preventing postoperative atrial fibrillation in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.

Administration, Oral↗

Horizontal transfer of the photosynthesis gene cluster and operon rearrangement in purple bacteria.

A 37-kb photosynthesis gene cluster was sequenced in a photosynthetic bacterium belonging to the beta subclass of purple bacteria (Proteobacteria), Rubrivivax gelatinosus. The cluster contained 12 bacteriochlorophyll biosynthesis genes (bch), 7 carotenoid biosynthesis genes (crt), structural genes for photosynthetic apparatuses (puf and puh), and some other related genes. The gene arrangement was markedly different from those of other purple photosynthetic bacteria, while two superoperonal structures, crtEF-bchCXYZ-puf and bchFNBHLM-lhaA-puhA, were conserved. Molecular phylogenetic analyses of these photosynthesis genes showed that the photosynthesis gene cluster of Rvi. gelatinosus was originated from those of the species belonging to the alpha subclass of purple bacteria. It was concluded that a horizontal transfer of the photosynthesis gene cluster from an ancestral species belonging to the alpha subclass to that of the beta subclass of purple bacteria had occurred and was followed by rearrangements of the operons in this cluster.

Amino Acid Sequence↗

Expression of monocyte chemoattractant protein-1 in peritoneal endometriotic cells.

It is well known that the number of peritoneal macrophages is increased in patients with pelvic endometriosis. We measured the concentration of monocyte chemoattractant protein-1 (MCP-1) using an enzyme-linked immunosorbent assay (ELISA) in the peritoneal fluid of women with and without endometriosis. The expression of MCP-1 in pelvic endometriotic lesions obtained from the peritoneum was also examined using immunohistochemistry and nonradioactive in situ hybridization. The mean concentration of MCP-1 in the peritoneal fluid was significantly higher in the patients with endometriosis (P<0.05). The most significant elevation, compared with non-endometriosis patients, was found in stage I of the disease (P<0.05). However, no statistically significant difference was found among endometriosis stages I, II, III, and IV. Immunohistochemical staining revealed that MCP-1-positive cells were localized in the glandular epithelium of the endometriotic lesions and in the stromal macrophages distributed in those lesions, but normal peritoneal cells were negative. The in situ hybridization method demonstrated expression of MCP-1 mRNA on the endometriotic glandular epithelium and stromal macrophages. These findings suggest that MCP-1 may be involved in the histogenesis and early development of peritoneal endometriosis.

Ascitic Fluid↗

Intracystic carcinoma of the male breast: report of a case.

We experienced a very rare case of male intracystic breast carcinoma. A 66-year-old man presented at our hospital because of a palpable mass in his right breast. The imaging diagnosis was an intracystic carcinoma with hemorrhagic fluid and two mural nodules. Modified radical mastectomy was performed under general anesthesia. The pathological examination revealed the intracystic papillary carcinoma with foci of microinvasion. The findings of power Doppler ultrasonography and dynamic magnetic resonance imaging were very useful for the differential diagnosis of our case.

Aged↗

Barotraumatic blowout fracture of the orbit.

We report a rare case of a barotraumatic blowout fracture of the orbit. A 32-year-old woman presented with sudden swelling of the right orbital region after vigorous nose blowing. Computed tomography scan revealed a blowout fracture of the medial wall of the right orbit with orbital emphysema and herniation of the orbital soft tissue. She was treated with prednisolone and an antibiotic, and did not show diplopia or visual disturbance. Three different theories have so far been proposed to explain the mechanism of blowout fractures, globe-to-wall contact theory, hydraulic theory, and bone conduction theory. The present case indicates that blowout fractures of the orbit can be induced solely by a sudden change of pressure, thereby suggesting the validity of the hydraulic theory.

Adult↗

Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and hippocampal lesions during kainic acid-induced seizures in newborn rabbits.

We examined the effects of 7-nitroindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg, i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, regional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously monitored throughout the experiment lasting at least 60 min after the KA administration. There was a significant increase in NO generation in the brain during KA-induced seizures, which was inhibited by a pre-treatment with 7-NI or L-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME. L-NAME pre-treatment caused a significant decrease in HbO2 and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities and Neuronal damages in the hippocampus were significantly lower in 7-NI- and L-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, L-NAME, attenuated both. These findings suggest that NO, probably originating from eNOS, may play an important role in the cerebral circulation. Both 7-NI and L-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less damage to the hippocampus.

Animals↗

Management of posterior capsule rupture during phacoemulsification using the dry technique.

To manage posterior capsule rupture during phacoemulsification, we use a dry technique in which all procedures are performed without an irrigation/aspiration system. The dry technique is characterized by (1) continuous viscoelastic injection instead of fluid irrigation to maintain anterior chamber depth with the posterior capsule and vitreous located posteriorly and (2) static removal of most residual lens material by viscoexpression and/or manual small incision extracapsular cataract extraction without aspiration and dynamic water flow. In 16 cases of posterior capsule rupture managed using the dry technique, the residual nucleus and cortex were readily removed with minimum extension of the ruptured area and new vitreous loss. Although large amounts of viscoelastic material (mean 5.8 mL) were required, rapid and stable visual recovery was comparable to that in patients having uneventful surgery. The dry system is a safe and reliable technique for managing posterior capsule rupture during phacoemulsification.

Eye Injuries↗