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Biomedical subjects

K Hirose

Publications and source records attributed to K Hirose.

At least 145 records · Page 8Linked to original sources
PubMed1999

3D electron microscopy of the interaction of kinesin with tubulin.

We have studied the structure of microtubules decorated with kinesin motor domains in different nucleotide states by 3D electron microscopy. Having docked the atomic coordinates of both dimeric ADP.kinesin and tubulin heterodimer into a map of kinesin dimers bound to microtubules in the presence of ADP, we try to predict which regions of the proteins interact in the weakly binding state. When either the presence of 5'-adenylyimidodiphosphate (AMP-PNP) or an absence of nucleotides puts motor domains into a strongly-bound state, the 3D maps show changes in the motor domains which modify their interaction with beta-tubulin. The maps also show differences in beta-tubulin conformation compared with undecorated microtubules or those decorated with weakly-bound motors. Strongly-bound ncd appears to produce an identical change.

Adenosine Diphosphate↗
PubMed1999

A formal total synthesis of (-)-cephalotaxine.

A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.

Acetylation↗
PubMed1999

Functional recovery after coronary artery bypass grafting in patients with severe left ventricular dysfunction and preserved myocardial viability in the left anterior descending arterial territory as assessed by thallium-201 myocardial perfusion imaging.

To evaluate the functional recovery after coronary bypass surgery in patients with severe left ventricular (LV) dysfunction (ejection fraction (EF) < or = 35%), 100 consecutive patients with viable myocardium in the territory supplied by the left anterior descending artery (LAD) underwent coronary bypass grafting. In addition, cardiac catheterization and single-photon emission computed tomography (SPECT) perfusion imaging with thallium-201 were repeated 1-year postoperatively. Although 12 patients with severe LV dysfunction were preoperatively in a worse New York Heart Association functional class (3.1+/-0.7 vs 2.4+/-0.8; p<0.01), had a higher incidence of heart failure (10/12 vs 14/88; p<0.001) and had a worse LVEF (29+/-5 vs 61+/-14%; p<0.001) compared with 88 patients without severe LV dysfunction, the operative mortality was similar in the 2 groups (1/12 vs 2/88; p=NS). The postoperative NYHA functional class in the patients with severe LV dysfunction was similar to that in the patients without such dysfunction (1.6+/-0.7 vs 1.3+/-0.6; p=NS). In addition, the 1-year postoperative study revealed a significant improvement in the thallium defect score in both the LAD territory (1.7+/-1.2 to 0.7+/-1.0, p=0.01) and all the territories (5.2+/-2.2 to 3.2+/-1.9, p=0.002) in patients with severe LV dysfunction, whereas no improvement in defect score was found in either of these territories in those without severe LV dysfunction (LAD: 0.6+/-1.4 to 0.4+/-1.2, p=NS; All: 1.9+/-2.2 to 1.8+/-2.0, p=NS). Furthermore, a marked 1-year postoperative improvement (15-24%; 95% confidence interval) in LVEF (29+/-5 to 48+/-10%, p<0.001) was demonstrated in patients with severe LV dysfunction, but not in those without such dysfunction (60+/-13 to 61+/-11%, p=NS). These results indicate that myocardial viability in the LAD territory, as demonstrated by thallium-201 SPECT perfusion imaging, predicts a significant improvement in functional class and LVEF of at least 10% or more after coronary artery bypass grafting in patients with severe LV dysfunction.

Adult↗
PubMed1999

Decrease in hepatic CYP2C11 mRNA and increase in heme oxygenase activity after intracerebroventricular injection of bacterial endotoxin.

We previously reported (Arch. Toxcol. 1998, 72, 492-498) that the differential decrease in the levels of hepatic cytochrome P450 (CYP) isozymes in rats was observed 24 hr after intracerebroventricular (i.c.v.) injection of bacterial lipopolysaccharide (LPS) at the dose ineffective (0.1 microgram) when injected intraperitoneally (i.p.). Among CYP isozymes we examined, the male specific CYP isozyme, CYP2C11 was most severely affected by i.c.v. injection of LPS. In this study, we examined the gene expression of CYP2C11, the total P450 contents, the CYP2C11-dependent activity of imipramine N-demethylase (IMND) and protein of CYP2C11 10 hr after i.c.v. or i.p. injections of LPS. Intracerebroventricular injection of LPS significantly decreased the level of CYP2C11 mRNA (to 63% of saline i.c.v. control), the total P450 contents (to 70% of saline i.c.v. control), the IMND activity (to 74% of saline i.c.v. control), but not protein of CYP2C11 in rat liver. In contrast, i.p. injection of LPS at the same dose as i.c.v. did not significantly affect these parameters. Since CYP is a heme protein, we also measured the activity of heme oxygenase (HO) using the same rat liver microsomes. The HO activity was increased to 166% by i.c.v. injection of LPS and 135% by i.p. injection of LPS compared to corresponding saline control. It is suggested that i.c.v. injection of LPS down-regulates the expression of CYP2C11 at transcriptional level and that both the decrease in CYP2C11 mRNA and the increase in heme degradation may be involved in the decreased level of protein and activity of CYP2C11 by i.c.v. injection of LPS in rat liver.

Adrenergic Uptake Inhibitors↗
PubMed1999

Granulocyte colony stimulating factor-producing diffuse malignant mesothelioma of pleura.

We report the rare case of a 61-year-old man with a diffuse malignant mesothelioma of mixed subtype which produced granulocyte colony-stimulating factor (G-CSF). The white blood cell (WBC) was elevated to 85,100/mm3 without any evidence of infection, and the G-CSF level in the pleural effusion was also increased at 13,200 pg/ml. The lobes of the lung were encased in a tumor. Histopathologically, the tumor cells were of a polymorphous morphology with an epithelial and sarcomatoid mixed pattern. Immunohistochemistry showed that the tumor cells were positive for vimentin, cytokeratin, epithelial membrane antigen, thrombomodulin, and G-CSF, and negative for carcinoembryonic antigen (CEA), CD34, and surfactant apoprotein-A.

Diagnosis, Differential↗
PubMed1999

Effect of life styles on the risk of subsite-specific gastric cancer in those with and without family history.

To evaluate a combined effect of gastric cancer family history (GCFH) and selected living habits on the subsite-specific of gastric cancer, a hospital-based case-referent study was conducted in Tokai area of Japan. The study subjects were 850 newly diagnosed gastric cancer (GC) patients and 28,619 cancer-free first-visit outpatients. Odds ratios (ORs) of all subsites of GC in subjects with both GCFH and habitual smoking were significantly higher (OR = 4.22) compared with those with merely GCFH (OR = 1.81) or habitual smoking (OR = 2.83). When positive GCFH subjects frequently consumed raw vegetable, the risk of GC decreased in cardia (OR = 0.68), antrum (OR = 0.43) and all subsites (OR = 0.74). Our findings provided evidence that GCFH and habitual smoking increased the risk of GC with family history, while frequent intake of raw vegetable decreased the risk and it was modified by other environmental factors.

Adult↗
PubMed1999

[Correlation between CTG triplet repeat length and the extent of multisystesmic disorders in myotonic dystrophy].

We investigated whether the degree of (CTG)n expansions is correlated with the extent of multisystemic disorders in 40 patients with myotonic dystrophy (DM). We examined the endocrinological disorders with both the Ellsworth-Howard(EH) test and thyrotropin releasing hormone (TRH) tolerance test. His-ventricular(HV) interval on the His bundle electrogram was analyzed as one of the cardiac conduction disorders. Serum IgG levels and the proliferative response of lymphocyte to concanavalin(Con). A mitogen were investigated as the immunological disorders and both intelligence quotient (IQ) and apnea index(AI) also as the disorders of central nervous systems. Moreover, the extent of muscular involvement was evaluated by muscle disability score, horizontal saccadic velocity using ENG, myopathy index(MI) estimated by quantitative EMG, and pulmonary function test consisting of % vital capacity (% VC) and peak flow. Southern blot were made of the DNAs as described previously. Briefly, the genomic DNAs extracted from the leukocytes were digested with Eco RI then hybridized with a 32P-labeled cDNA25 probe. The results of the EH test (p < 0.05), TRH tolerance test (p < 0.01), HV interval (p < 0.01), serum IgG levels (p < 0.05), and the proliferative response to Con A mitogen (p < 0.01) were all significantly correlated with (CTG)n length. The values of AI (p < 0.01) and IQ (p < 0.01) were significantly correlated with (CTG)n length. In addition, the extent of muscular involvement based on the disability score (p < 0.001), horizontal saccadic velocity (p < 0.001). MIs of Tibialis anterior (p < 0.05), and Biceps brachii (p < 0.02), % VC (p < 0.05) and peak flow (p < 0.01) also was significantly correlated with (CTG)n length. From the above results, it was considered that (CTG)n length was well correlated with disease severity in DM.

Apnea↗
PubMed1999

[Prosthetic valve replacement in children].

Between 1975 and 1998, 27 patients aged 3 months to 14 years underwent replacement of the aortic, mitral, tricuspid, and pulmonary valves. Five different types of prosthetic valves were used; three were mechanical valves and two were bioprosthetic valves. There were 3 hospital deaths. Among the 24 survivors there were 4 late deaths. Arrhythmia requiring pacemaker implantation occurred in 2 cases after AVR and TVR. Thromboembolic events occurred in 3 patients, all with mechanical valves in pulmonary position. Infective endocarditis occurred in 1 patient after PVR with a mechanical valve. No bleeding complication occurred among the patients on a regimen of Coumadin and Dipyridamole. Two patients, both with Hancock bioprosthesis, required a second valve replacement on account of severely calcified changes. Mechanical valves in left side heart had a satisfactory long-term performance. One patient who had undergone MVR for congenital parachute mitral valve received reoperation for growth. A larger sized prosthetic valve should be used at the first replacement, and special procedures including supra-annular positioning or annular augmentation are recommended for MVR or AVR respectively.

Adolescent↗
PubMed1999

[Assessment of internal thoracic artery grafts using duplex scanning].

In an effort to develop a noninvasive method to evaluate flow characteristics of the internal thoracic artery grafts (ITAG) after coronary artery bypass grafting, we performed duplex scanning of ITAGs of 51 patients who underwent bypass grafting. The ITAG was visualized with a duplex scanner of 7.5 MHz through the first or second left intercostal space. The visualization of the ITAG was adequate to make reliable measurements in 47 patients (92.2%). The diameter of the vessel, systolic peak velocity, and diastolic peak velocity were recorded, and systolic flow volume, diastolic flow volume, velocity ratio, flow volume ratio, and diastolic flow volume fraction were calculated. The velocity ratio, flow volume ratio, and diastolic flow volume fraction were markedly higher in the unstenotic subjects than in the stenotic subjects. In the group in which severe LAD stenosis were recognized preoperatively, both systolic and diastolic flow volumes were increased compared with moderately stenotic group. No differences in flow characteristics could be demonstrated between the subjects with old anterior myocardial infarction and without it. In 10 patients in whom flow pattern was abnormal or not identified, angiography revealed graft stenosis or predominant native coronary arterial flow. Duplex scanning is thought to be a reliable, sensitive, and noninvasive technique for the assessment of the ITAG.

Adult↗
PubMed1999

[Meige's syndrome].

Explore the source record for details and available documents.

Botulinum Toxins, Type A↗
PubMed1998

Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2.

The ryanodine receptor type 2 (RyR-2) functions as a Ca2+-induced Ca2+ release (CICR) channel on intracellular Ca2+ stores and is distributed in most excitable cells with the exception of skeletal muscle cells. RyR-2 is abundantly expressed in cardiac muscle cells and is thought to mediate Ca2+ release triggered by Ca2+ influx through the voltage-gated Ca2+ channel to constitute the cardiac type of excitation-contraction (E-C) coupling. Here we report on mutant mice lacking RyR-2. The mutant mice died at approximately embryonic day (E) 10 with morphological abnormalities in the heart tube. Prior to embryonic death, large vacuolate sarcoplasmic reticulum (SR) and structurally abnormal mitochondria began to develop in the mutant cardiac myocytes, and the vacuolate SR appeared to contain high concentrations of Ca2+. Fluorometric Ca2+ measurements showed that a Ca2+ transient evoked by caffeine, an activator of RyRs, was abolished in the mutant cardiac myocytes. However, both mutant and control hearts showed spontaneous rhythmic contractions at E9.5. Moreover, treatment with ryanodine, which locks RyR channels in their open state, did not exert a major effect on spontaneous Ca2+ transients in control cardiac myocytes at E9.5-11.5. These results suggest no essential contribution of the RyR-2 to E-C coupling in cardiac myocytes during early embryonic stages. Our results from the mutant mice indicate that the major role of RyR-2 is not in E-C coupling as the CICR channel in embryonic cardiac myocytes but it is absolutely required for cellular Ca2+ homeostasis most probably as a major Ca2+ leak channel to maintain the developing SR.

Animals↗
PubMed1998

Family history and subsite of gastric cancer: data from a case-referent study in Japan.

A comparative case-referent study was conducted using data from the Hospital-Based Epidemiologic Research Program at Aichi Cancer Center (HERPACC) (Nagoya, Japan), with the aim of clarifying the effect of family history on gastric cancer by subsite. Our study comprised 995 histologically confirmed gastric cancer cases (180 cardia, 430 middle, 365 antrum and 20 unclassified) and a total of 43,846 non-cancer outpatients at Aichi Cancer Center Hospital between 1988 and 1995. Logistic regression was used to calculate odds ratios (ORs) for family history of gastric cancer and other cancers, adjusted for age, year and season at first hospital visit, habitual smoking, habitual alcohol drinking, regular physical exercise, preference for salty food and raw vegetable intake. In both genders, a positive family history of gastric cancer was associated with a moderate, but statistically significant increase in risk of gastric cancer [OR = 1.51, 95% confidence interval (95% CI) = 1.29-1.76], while no association was observed between the risk of gastric cancer and a family history of other cancers [OR = 0.97, 95% CI = 0.84-1.13]. OR increased for the middle and antrum parts of gastric cancer, but an increment for the cardiac part was observed only in those with a maternal history of gastric cancer. Our results suggest that the risk of gastric cancer in relation to family history varies by subsite and, furthermore, that the subsite-specific risk of gastric cancer is linked to a maternal history of gastric cancer.

Adult↗
PubMed1998

Nucleotide-dependent structural changes in dimeric NCD molecules complexed to microtubules.

Complexes consisting of motor domains of the kinesin-like protein ncd bound to reassembled brain microtubules were visualised using cryoelectron microscopy and helical image reconstruction. Different nucleotide-associated states of a dimeric construct (NDelta295-700) of ncd were analysed to reveal ADP-containing, AMP.PNP-containing and empty (rigor) conformations. In these three states, each thought to mimic a different stage in ATP turnover, the double-headed motors attach to the microtubules by one head only, with the free head tethered in relatively fixed positions. The three structures differ both in the way the attached heads interact with tubulin and in the position of the tethered heads. In the strongly binding rigor and AMP.PNP (ATP-like) states, the attached head makes close contact with both subunits of a tubulin heterodimer. In the weakly bound ADP state, the contact made by the attached head with the monomer closer to the plus end appears to be more loose. Also, in the ATP-like state, the free head tilts nearer to the plus end than in the other two states. The data argue against model mechanisms in which a conformational change in the bound head guides the free head closer to its next binding site; on the contrary, the transition from ADP-filled via rigor to the AMP.PNP (ATP-like) state of the bound head produces a small motion of the free head in the counter-productive direction. However, the observation that the tethered head points towards the minus end, in all three states, is consistent with the idea that the relative arrangement of the heads in a dimer is a major determinant of directionality.

Adenosine Diphosphate↗
PubMed1998

Vi-deficient and nonfimbriated mutants of Salmonella typhi agglutinate human blood type antigens and are hyperinvasive.

We generated nonfimbriated mutants from both Vi-positive and -negative Salmonella typhi to analyze the role of type 1 fimbriae and Vi-antigen in bacterial invasion. A Vi-defective mutant of S. typhi GIFU 10007-3 was more invasive than the wild-type strain GIFU 10007. The wild-type strain expressing Vi-antigen did not agglutinate both Saccharomyces cerevisiae and human erythrocytes but Vi-defective mutants were able to agglutinate S. cerevisiae and human erythrocytes. Nonfimbriated mutants from Vi-negative GIFU 10007-3 lost the ability to adhere to S. cerevisiae but still could agglutinate human erythrocytes. The Vi-negative mutant increased secreted proteins and became 5-fold more invasive than the wild-type strain. Nonfimbriated Vi mutants became 50-120-fold more invasive than the wild-type GIFU 10007. To determine why nonfimbriated Vi mutants still agglutinate human red blood cells, we searched bacterial proteins that could bind human blood-type antigens. We finally identified a candidate 37 kDa outer membrane protein that recognized fucosyl-galactose, a structure common to blood type A, B and H antigens.

ABO Blood-Group System↗
PubMed1998

Salmonella typhi rpoS mutant is less cytotoxic than the parent strain but survives inside resting THP-1 macrophages.

Transcription of the stationary-phase sigma factor RpoS of Salmonella typhi increased in the macrophage. A single rpoS mutant of S. typhi was constructed to analyze the role of RpoS in intracellular multiplication of the bacterium and host cell killing. This mutant was sensitive to starvation, low pH and hydrogen peroxide; however, it could still multiply inside resting macrophages and was less cytotoxic than the wild-type strain. Therefore, S. typhi might produce RpoS-dependent factors which could contribute to host cell death.

Bacterial Proteins↗
PubMed1998

Allosteric regulation by cytoplasmic Ca2+ and IP3 of the gating of IP3 receptors in permeabilized guinea-pig vascular smooth muscle cells.

1. The potentiation by Ca2+ of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied by measuring luminal Ca2+ concentrations of the Ca2+ stores using a fluorescent Ca2+ indicator, furaptra, in permeabilized smooth muscle cells. 2. Ca2+ release at 10 microM IP3 was potentiated by an increase in the cytoplasmic Ca2+ concentration in the presence of 10 mM EGTA. This effect was not due to the pharmacological effect of EGTA, because changes in the EGTA concentration at a constant Ca2+ concentration had no effect on the Ca2+ release rate. 3. With an increase in the cytoplasmic Ca2+ concentration from 30 to 630 nM, the Ca2+ release rate at a saturating IP3 concentration increased 110-fold and the EC50 for IP3 increased from 0.07 to 1.0 microM. It was also indicated that the relationship between Ca2+ concentration and Ca2+ release rate was shifted towards higher Ca2+ concentrations at higher IP3 concentrations. 4. These results suggest that IP3 and submicromolar concentrations of Ca2+ allosterically lower the affinity of the IP3 receptor for each other and are both required for IP3 receptor activation. These properties enable the IP3 receptors to detect simultaneous increases in IP3 and Ca2+ concentrations.

Action Potentials↗