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M Hirai

Publications and source records attributed to M Hirai.

At least 235 records · Page 13Linked to original sources

A gene outside the human MHC related to classical HLA class I genes.

By presenting antigenic peptides to T lymphocytes, major histocompatibility complex (MHC) class I molecules play important roles in the human immune system. Knowledge is limited on the evolutionary history of human MHC class I-related molecules. An expressed class I gene, MR1, has now been identified on human chromosome 1q25, outside the MHC. In contrast to other known human divergent class I genes, MR1 encodes peptide-binding domains similar to those encoded by human leukocyte antigen (HLA) class I genes on chromosome 6 and by nonmammalian classical MHC class I genes. This gene may thus contribute to understanding the evolution of the MHC.

Amino Acid Sequence↗

Cloning and characterization of MST, a novel (putative) serine/threonine kinase with SH3 domain.

Protein kinases play a key role in cell growth regulation. We have isolated a cDNA fragment of the MST gene from the MKN28 gastric cancer cell line cDNA pool by degenerate polymerase chain reaction. MST-cDNAs were cloned from the human brain cDNA library. Nucleotide sequence analysis indicated that the MST gene encodes a novel putative non-receptor type of serine/threonine kinase with Src homology 3 (SH3) domain, two leucine zipper domains and proline rich domain. The deduced amino acid sequence corresponding to a part of kinase domain and leucine zipper domains of MST (amino acid codons 244-461) is almost identical to the published partial amino acid sequence of MLK2. MST is the first non-receptor type of serine/threonine kinase containing SH3 domain, leucine zipper domain and proline rich domain other than PTK1/Sprk. The MST gene was moderately expressed in brain, skeletal muscle and testis as a 3.8 kb mRNA, and the MST gene has been mapped to human chromosome 19q13.1-q13.2.

Amino Acid Sequence↗

Evaluation of QRST isointegral maps in detecting posterior myocardial infarction with and without conduction disturbance.

We investigated the usefulness of QRST isointegral maps (I-maps) for detecting posterior myocardial infarction (MI) with and without conduction disturbance. The I-maps were recorded during sinus rhythm and right ventricular (RV) pacing, which simulated left bundle-branch block (LBBB) in 19 patients with and in 20 patients without MI. Data on 608 normal subjects were used as controls. The "-2 SD area," where the QRST integral value was less than the lower limit of the normal range, was assessed by sigma DM (sum of QRST integral values below the normal range). Posterior MI was diagnosed with a sensitivity of 84%, a specificity of 90%, and a diagnostic accuracy of 87%, assuming that MI was present if sigma DM exceeded 50 mVms. During simulated LBBB, when the criterion sigma DM more than 250 mVms was used, the sensitivity, specificity, and diagnostic accuracy were 79, 75, and 77%, respectively. Thus, I-maps may be useful in detecting posterior MI in patients with and without an intraventricular conduction disturbance.

Adult↗

A proton pump inhibitor, E3810, has antibacterial activity through binding to Helicobacter pylori.

Helicobacter pylori infection is causally related to atrophic gastritis, and it may also be associated with peptic ulcer and gastric carcinoma. Eradication of H.pylori is recommended in patients with such diseases, especially in those with peptic ulcer. A new potent proton pump inhibitor, E3810, had an antibacterial effect on H. pylori, as has been reported for omeprazole and lansoprazole, two other proton pump inhibitors. The minimum inhibitory concentration of E3810 was 1.57-3.13 micrograms/ml, lower than that of omeprazole or lansoprazole. To clarify the mechanism of the antibacterial effect of E3810, we analyzed the characteristics of E3810 binding to H. pylori. Scatchard plot analysis of this binding showed a curvilinear profile, indicating the presence of several molecules with different affinities to E3810 on H. pylori. The binding capacity of E3810 to H. pylori was calculated to be about 2 x 10(6) sites/cell. These results suggested that E3810 has an antibacterial effect against H. pylori and that the effect may be mediated through direct binding to H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

QRST time integral values in 12-lead electrocardiograms before and after radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

OBJECTIVES: We investigated the usefulness of QRST values obtained from 12-lead electrocardiograms (ECGs) for identification of repolarization abnormalities before and after radiofrequency ablation in patients with Wolff-Parkinson-White syndrome. BACKGROUND: Marked T wave abnormalities often appear after ablation and have been attributed to a continuation of repolarization abnormalities present before ablation (cardiac memory). However, to our knowledge repolarization properties before and after ablation have not been assessed quantitatively. METHODS: We calculated the ECG QRST values from 53 patients with Wolff-Parkinson-White syndrome and compared these values before, immediately after and 1 day and 1 week after successful ablation in 25 patients. RESULTS: QRST values were abnormally high in lead V1 in 7 of 28 patients with a left-sided accessory pathway and abnormally low in leads III and aVF and high in lead aVL in 12, 9 and 10 of 20 patients, respectively, with a right-sided accessory pathway. Preexisting QRST abnormalities were still present immediately and 1 day after ablation but were usually absent by 1 week after ablation. QRST values before, immediately after and 1 day after ablation were not significantly different in any lead. In 14 patients with ablation of a left-sided accessory pathway, QRST values before, immediately after and 1 day after ablation in lead V1 and immediately after ablation in leads I, aVR and V2 were significantly different from QRST values in those leads 1 week after ablation. In six patients with ablation of a right-sided accessory pathway, QRST values before, immediately after and 1 day after ablation in leads III, aVL and aVF and immediately after ablation in lead II were significantly different from QRST values in those leads 1 week after ablation. CONCLUSIONS: Electrocardiographic QRST values may provide useful quantitative information with respect to repolarization properties before and after ablation in patients with Wolff-Parkinson-White syndrome that is otherwise difficult to obtain by conventional ECG analysis.

Adult↗

Lansoprazole treatment of Helicobacter pylori-positive peptic ulcers.

Forty-nine patients with Helicobacter pylori (Hp)-positive gastric ulcer (GU) and 39 patients with Hp-positive duodenal ulcer (DU) were studied. Before the trial and every 3 or 4 weeks, phenol red dye spraying endoscopy, the rapid urease test, biopsy specimen histology, and culture were performed to assess the ulcer stage and to detect Hp. Patients were divided into three groups: group I received lansoprazole 30 mg/d; Group II received dual therapy of lansoprazole 30 mg/day and amoxicillin (AMPC) 1 g/day or clarithromycin (CAM) 400 mg/day; and Group III received combination therapy of lansoprazole 30 mg/day, AMPC 1 g/day, or CAM 400 mg/day, and metronidazole 500 mg/day. Patients with GU received lansoprazole for 8 weeks and patients with DU received lansoprazole for 6 weeks. The other agents were administered for 2 weeks at the beginning of the trial. There were no differences in ulcer healing among the three treatment groups in patients with GU or DU, but there were significant differences in the eradication of Hp. No side effects were observed in any of the patients. We conclude that combination therapy is likely to be most effective and is harmless for Hp-persistent patients with peptic ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Multidrug resistance-associated protein-mediated multidrug resistance modulated by cyclosporin A in a human bladder cancer cell line.

A doxorubicin-resistant subline (5637/DR5.5) from human bladder cancer cells (5637) was induced by stepwise increase in the doxorubicin concentration. 5637/DR5.5 cells were cross-resistant to vinblastine and etoposide but not to mitomycin C and cisplatin. We analyzed the mdr1, MRP (multidrug resistance-associated protein), and DNA topoisomerase II gene expression using the reverse transcription polymerase chain reaction assay (RT-PCR) and investigated possible differences in the accumulation and efflux of radiolabeled daunorubicin. 5637/DR5.5 cells do not express the mdr1 gene, but the expression levels of MRP are markedly higher than in drug-sensitive 5637 cells. The intracellular accumulation of radiolabeled daunorubicin was markedly decreased in the 5637/DR5.5 cells in comparison with the parent cells. This reduced drug accumulation was associated with an enhanced drug efflux, but was reversed when cells were incubated with cyclosporin A. Cyclosporin A at the concentration of 5 microM caused 3.4-fold enhancement of daunorubicin-sensitivity in the 5637/DR5.5 cells. On the other hand, there was no difference in DNA-topoisomerase II activity between the parent and resistant cells. The resistance of the 5637/DR5.5 cells is therefore associated with an enhanced drug efflux mediated by the MRP gene overexpression, as distinct from P-glycoprotein, and is modulated by cyclosporin A.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Establishment and characterization of IRTA17 and IRTA21, two novel acute non-lymphocytic leukaemia cell lines with t(16;21) translocation.

The t(16;21)(p11;q22) translocation is an infrequent chromosomal abnormality, but seems specific to acute non-lymphocytic leukaemia (ANLL). We established two cell lines with t(16;21)(p11;q22) from the bone marrow of a patient with ANL in relapse. Their morphological, karyotypic, immunohistochemical and genetic features are examined. Although both cell lines show monocytoid features morphologically, they express only CD13 (My7) and CD34, and neither expressed monocytoid or lymphoid markers. Reverse transcription-polymerase chain reaction showed that both cell lines expressed a similar TLS-ERG chimaeric mRNA as a result of the t(16;21)(p11;q22) translocation. As far as we know, there is no report of a leukaemia cell line with t(16;21). These cell lines represent a useful tool for leukaemia research.

Adult↗

A high-resolution cytogenetic map of human chromosome 2: localization of 434 cosmid markers by direct R-banding fluorescence in situ hybridization.

We have constructed a high-resolution cytogenetic map of human chromosome 2 with 434 newly isolated cosmid markers by means of direct R-banding fluorescence in situ hybridization. Two markers were mapped to the centromeric region, 173 to the short arm, and 259 to the long arm. The clones were evenly distributed along the entire chromosome, although a tendency toward clustering in R-positive bands was observed. The mapped cosmids provide useful landmarks for construction of a contig map and for positional cloning of cancer-associated genes, as well as genes responsible for hereditary diseases.

Animals↗

Effects of suprachiasmatic lesions on circadian rhythms of blood pressure, heart rate and locomotor activity in the rat.

To determine whether the circadian rhythms in blood pressure (BP), heart rate (HR) and locomotor activity are controlled by an internal biological clock located in the suprachiasmatic nucleus (SCN), we continuously measured these parameters in SCN-lesioned rats using a newly developed implantable radiotelemetry device and a computerized data collecting system. Although SCN-lesioned rats showed a weak but significant 24-h periodicity in BP and HR under light-dark (LD) cycles, BP, HR and locomotor activity became completely aperiodic under constant dark (DD) conditions. The amount of locomotor activity was significantly reduced in SCN-lesioned rats compared to that in intact rats. BP tended to be higher in SCN-lesioned rats, but the differences were significant only in the comparison of systolic blood pressure (SBP) under LD and DD (p < 0.05) and of mean blood pressure (MBP) under LD (p < 0.05). HR in SCN-lesioned rats was significantly lower under LD (p < 0.05), but not under DD. The standard deviation and the variation coefficient of MBP, as indices of short-term variability of this parameter, were significantly larger in SCN-lesioned rats than in intact rats, while those of HR and locomotor activity did not differ significantly between SCN-lesioned and intact rats. These results indicate that the SCN is important not only for generating circadian rhythms of BP, HR and locomotor activity, but also for buffering the short-term variability of BP in rats.

Animals↗

[Plasma concentration of cytosine arabinoside (Ara-C) in the elderly patients with hematological malignancy treated by Ara-C or cytarabine ocfosfate (SPAC)].

Plasma concentration of cytosine arabinoside (Ara-C) was determined in elderly patients with myelodysplastic syndromes or acute myelocytic leukemia who were treated with subcutaneous injection of Ara-C (Ara-C s.c.; 10 mg/m2/12 hr, 14-21 days), continuous drip infusion of Ara-C (Ara-C d.i.v.; 20 mg/m2/day, 24 hr 14 days) and/or oral administration of cytarabine ocfosfate (SPAC) (SPAC p.o.; 100 mg-300 mg/body/day, 14 days) by radioimmunoassay. In the Ara-C s.c. patients, the peak plasma level (Cmax) of Ara-C was 103 ng/ml and the time to reach Cmax was 15 min. The elimination half-like (t1/2) was 25 min and no accumulation was detected after 14 days of consecutive Ara-C s.c. administrations. In the SPAC p.o. patients, Cmax of Ara-C was 3-8 ng/ml and it took 3-5 days to reach Cmax. The plasma concentration level of Ara-C remains almost at the Cmax level during the SPAC p.o. administration and it remained higher than 0.32 ng/ml for as long as 15 days after the end of administration. In a Ara-C d.i.v. patient, plasma level of Ara-C was detected 4-7 ng/ml during the administration (day 7 through day 14). In all patients bone marrow suppression was observed after chemotherapy regardless of regimen, and there was no significant difference between nadir peripheral cell blood counts of Ara-C s.c. patients and SPAC p.o. patients.

Administration, Oral↗

Transvaginal pulsed and color Doppler sonography for the evaluation of adenomyosis.

In an earlier paper, we reported our scoring system for the diagnosis of adenomyosis by gray scale transvaginal sonography. In this study we evaluated 44 benign uterine masses (adenomyosis and myomas) and seven uterine malignancies. We used transvaginal color and pulsed Doppler imaging to determine whether this technique is useful to differentiate adenomyosis from uterine malignancies. The peak systolic velocity and the resistive index of intratumoral vessels were studied. The differences in these parameters for adenomyosis and uterine malignancies were statistically significant. Our results suggest that this technique is useful to differentiate adenomyosis from uterine malignancies.

Adult↗

[A case report of prosthetic valve replacement for malfunction of the Hancock valve in mitral position associated with recurrent peptic ulcer and renal dysfunction].

A 62-year-old woman was admitted with malfunction of the Hancock valve in mitral position. She had been suffering from gastroduodenal ulcer for about ten years. She couldn't take warfarin after 5 years later of the initial operation due to recurrent gastrointestinal bleeding. Judging from her age and renal dysfunction, we preferred mechanical valve to avoid the risks for the reoperation. After confirming the healed ulcer with administering omeprazole, we performed prosthetic valve replacement with SJM 29 M successfully. Postoperative course was uneventful and recurrence of the ulcer was not observed.

Female↗

[A case report of bentall type operation for annuloaortic ectasia with anomalous origin of the right coronary artery complicated by aortic dissection].

A 49-year-old woman of Marfan's syndrome, who had undergone replacement of the thoracoabdominal aorta for Stanford B type aortic dissection at 47 years of age, developed Stanford A type aortic dissection with annulo-aortic ectasia and aortic regurgitation. At the time of operation, anomalous origin of the right coronary artery from the left sinus of Valsalva and near site of the left coronary orifice were found. Then, composite graft replacement of the ascending aorta and aortic valve, in which a single graft of 16 mm in diameter was interposed between the coronary ostia and composite graft, was performed. Anomalous origin of the right coronary artery from the left sinus of Valsalva is a rare congenital abnormality. It is a matter how to reconstruct the coronary circulation for this type of operation. This technique was useful to reconstruct the aortic root even when an anomalous origin of the coronary artery existed.

Aortic Dissection↗

Cepharanthin, a multidrug resistant modifier, is a substrate for P-glycoprotein.

P-glycoprotein modulators are respected to be multidrug resistance reversing agents in cancer chemotherapy. Some calcium channel blockers, calmodulin inhibitors or immunosuppressive agents have been used in clinical studies, although the dose of these drugs required to test in vitro experimental data might cause potent pharmacological effects which are not desirable in patients. By using LLC-GA5-COL150 cells that express P-glycoprotein specifically on the apical membranes, we examined the transport of anticancer drugs mediated by P-glycoprotein. Cepharanthin, a biscoclaurine alkaloid, potently inhibits the transport of vinblastine and daunorubicin, both commonly used anticancer agents. The 50% inhibitory concentration of cepharanthin on daunorubicin transport was 2.06 microM. Combined inhibitory effects on daunorubicin transport were observed when cepharanthin was used together with cyclosporin A, a potent immunosuppressive agent and P-glycoprotein modulator. Cepharanthin itself was transported by P-glycoprotein. Transcellular transport of cepharanthin across LLC-GA5-COL150 cell monolayers was saturable when its concentration was under 5 microM, and the transport was inhibited by P-glycoprotein modulators. These results indicate that cepharanthin can reverse multidrug resistance, and proper combination with other P-glycoprotein modulators could potentiate its inhibitory effect on expelling the anticancer drugs out of the cell via P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗