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Biomedical subjects

M Ishii

Publications and source records attributed to M Ishii.

At least 163 records · Page 9Linked to original sources
PubMed2000

Prevalence of mitochondrial gene mutations among hearing impaired patients.

The frequency of three mitochondrial point mutations, 1555A-->G, 3243A-->G, and 7445A-->G, known to be associated with hearing impairment, was examined using restriction fragment length polymorphism (RFLP) analysis in two Japanese groups: (1) 319 unrelated SNHL outpatients (including 21 with aminoglycoside antibiotic injection history), and (2) 140 cochlear implantation patients (including 22 with aminoglycoside induced hearing loss). Approximately 3% of the outpatients and 10% of the cochlear implantation patients had the 1555A-->G mutation. The frequency was higher in the patients with a history of aminoglycoside injection (outpatient group 33%, cochlear implantation group 59%). One outpatient (0.314%) had the 3243A-->G mutation, but no outpatients had the 7445A-->G mutation and neither were found in the cochlear implantation group. The significance of the 1555A-->G mutation, the most prevalent mitochondrial mutation found in this study of a hearing impaired population in Japan, among subjects with specific backgrounds, such as aminoglycoside induced hearing loss, is evident.

Aminoglycosides↗
PubMed2000

Psoriasis in a patient with juvenile rheumatoid arthritis.

A 20-year-old woman had polyarticular-onset type of juvenile rheumatoid arthritis with a chronic and destructive course since 6 years of age. She had developmental retardation, deformity and disability. Asymptomatic erythematous scaly plaques developed on the trunk. A skin biopsy specimen revealed psoriasis. This is the first report of psoriasis developing in a patient with juvenile rheumatoid arthritis.

Adult↗
PubMed2000

Angiotensin-(1-7) attenuates vasoconstriction evoked by angiotensin II but not by noradrenaline in man.

Angiotensin-(1-7) has been suggested to be a novel vasodilating peptide. We investigated the direct vascular effect of angiotensin-(1-7) in human forearm resistant vessels, particularly with regard to the interaction with angiotensin II, in healthy normotensive men by strain-gauge venous occlusion plethysmography with intra-arterial infusions of peptides. Intra-arterial infusion of angiotensin-(1-7) at 0.1 to 2000 pmol/min did not cause vasodilatation but rather reduced forearm blood flow by approximately 10% at the highest dose. A placebo-controlled study showed that angiotensin-(1-7) at 0.5 to 40 nmol/min caused weak but significant vasoconstriction (P=0.0016 by ANOVA). Angiotensin-(1-7) at 100 pmol/min, but not at 10 pmol/min, significantly shifted the angiotensin II dose-response curve toward the right (mean+/-SD of percent changes in forearm blood flow: -19+/-17%, -33+/-22%, -55+/-12%, -63+/-10%, and -68+/-5% at 5, 10, 25, 50, and 100 pmol/min of angiotensin II, respectively, with saline; 5+/-13%, 0. 9+/-18%, -40+/-16%, -54+/-9%, and -61+/-6% with angiotensin-(1-7), P=0.0021 by ANOVA). Angiotensin-(1-7) did not affect the dose-response curve of noradrenaline [3+/-12%, 5+/-16%, -20+/-22%, -31+/-18%, and -40+/-12% at 25, 50, 100, 300, and 600 pmol/min of noradrenaline, respectively, with saline; -4+/-15%, -2+/-23%, -29+/-22%, -34+/-16%, and -42+/-9% with angiotensin-(1-7)]. Our results suggest that angiotensin-(1-7) antagonizes vasoconstriction by angiotensin II in human resistant vessels and might act as an endogenous angiotensin II antagonist.

Angiotensin I↗
PubMed2000

Catalytic mechanism of class A beta-lactamase. I. The role of Glu166 and Serl30 in the deacylation reaction.

The tetrahedral intermediate formation process, which is the first step in the deacylation reaction by class A beta-lactamase, was investigated by the ab initio molecular orbital method. In this study, benzyl penicillin was used as the substrate. From the results of our molecular dynamics study of the structure of beta-lactam antibiotics-beta-lactamase complex, the substrate, Ser70, Lys73, Ser130, Glu166 and a water molecule for the deacylation reaction were considered for construction of a model for calculation. The calculation results indicated that Glu166 plays a role in holding a water molecule, which is necessary for the deacylation reaction, and that the hydrogen bond network among Lys73Nzeta, Ser130Ogamma, and the carboxyl group of the beta-lactam antibiotics was formed by the uptake of beta-lactam antibiotics by beta-lactamase. The activation energy for this reaction was 33.3 kcal/mol, and it is very likely that the reaction occurred at body temperature. Subsequent calculation results obtained by using the model excluding Ser130 and the carboxyl group of the substrate indicated that the activation energy for this reaction was 40.8 kcal/mol, which is 7.5 kcal/mol higher than that of the previous reaction. It was found that the hydrogen bond network plays an important role in decreasing the activation energy for the tetrahedral intermediate formation reaction. Lys73Nzeta, which is located at the edge of the hydrogen bond network, played a role in forming a hydrogen bond with Glu166Oepsilon in order to help the deacylation reaction. The role of amino acid residues around the active site of class A beta-lactamase was also discussed.

Acylation↗
PubMed2000

Purification and characterization of membrane-bound hydrogenase from Hydrogenobacter thermophilus strain TK-6, an obligately autotrophic, thermophilic, hydrogen-oxidizing bacterium.

A membrane-bound hydrogenase was purified to electrophoretic homogeneity from the cells of Hydrogenobacter thermophilus strain TK-6, an obligately autotrophic, thermophilic, hydrogen-oxidizing bacterium. Solubilization and purification were done aerobically in the presence of Triton X-100. Three chromatography steps were done for purification; Butyl-Sepharose, Mono-Q, and Superose 6, in this order. Purification was completed with 6.73% yield of total activity and with 21.4-fold increase of specific activity when compared with the values for the membrane fraction. The purified hydrogenase was shown to be a tetramer with alpha2beta2 structure, with a molecular mass of 60,000 Da for the large subunit and 38,000 Da for the small subunit. The purified hydrogenase directly reduced methionaquinone with an apparent Km of around 300 microM and with a turnover number around 2900 (min(-1)). Metal analysis and EPR properties of the hydrogenase have shown that the enzyme is one of the [NiFe]-hydrogenases. Also, optimum pH and temperature for reaction, thermal stability, and electron acceptor specificity were reported. Finally, a model is presented for energy and central metabolism of H. thermophilus strain TK-6.

Amino Acid Sequence↗
PubMed2000

Control of blood pressure and lifestyle-related risk factors in elderly Japanese hypertensive subjects.

The aim of this study was to analyze the treatment of elderly hypertensive patients by Japanese physicians specializing in hypertension. We enrolled 939 patients with hypertension who were treated in the outpatient clinics of 11 hospitals in 1995; 793 of these patients (388 men and 405 women; mean age, 66.6+/-9.0 years) received follow-up examinations in 1996, and the data on these patients was used for the present analysis. Blood pressure (BP), body mass index, lifestyle, and laboratory data were analyzed in all patients. The average BP was 143+/-16/81+/-10 mmHg in 1995 and 142+/-15/80+/-10 mmHg in 1996. The patients whose baseline BP was at the level of Grade 2 or 3 in the WHO-ISH classification (n=117) were characterized by a higher women-to-men ratio, higher age, a higher serum total cholesterol concentration, and higher QRS voltage. In these patients, from 1995 to 1996, the average BP significantly decreased, whereas fasting plasma glucose, serum total cholesterol and serum creatinine concentrations showed only negligible changes. In 220 patients (28%), BP was <140/<90 mmHg at both the initial and the follow-up examinations, whereas 351 patients (44%) were hypertensive in both 1995 and 1996. Thirty-three percent of the patients were smokers. More smokers than nonsmokers had had prior cardiovascular events, diabetes mellitus, or overt proteinuria. In conclusion, the average BP level among the patients treated by Japanese physicians specializing in hypertension was somewhat higher than that recommended by WHO-ISH Guidelines (1999). Patient education to control lifestyle-related risk factors, particularly to stop smoking, should be emphasized.

Aged↗
PubMed2000

Effectiveness of the fold plication method in lung volume reduction surgery.

OBJECT: The fold plication method is a new operative procedure for lung volume reduction surgery whereby the target area is obliterated by plicating the folded tissue using a knifeless stapler, without the use of bovine pericardium. The effectiveness of this new method was evaluated in patients with advanced pulmonary emphysema. PATIENTS AND METHODS: Two weeks before and 6 months after surgery, pulmonary function, static lung compliance, maximal esophageal pressure, maximal inspiratory and expiratory mouth pressures, 6-min walking distance and the Borg scale were determined in twenty consecutive patients who underwent video-assisted thoracoscopic unilateral surgery. RESULTS: There was an increase in forced expiratory volume in one second (31%), forced vital capacity, peak expiratory flow rate and maximal voluntary ventilation, and a decrease in functional residual capacity (-16%) measured by plethysmograph. Static lung compliance decreased, and maximal esophageal pressure, and maximal inspiratory and expiratory mouth pressures increased. The 6-min walking distance increased (20%) and the Borg scale decreased (5.9 to 3.5). CONCLUSION: The results compare favorably with those obtained with other methods. Thus, the fold plication method could be considered an alternative procedure for lung volume reduction surgery.

Aged↗
PubMed2000

[Ocular counter-rolling after prolonged alteration in the direction of gravity].

To investigate the dynamics of otolith and oculomotor function, we subjected volunteers to a lateral body tilt for a period of two hours and analyzed ocular counter-rolling. Six healthy adult volunteers were roll-tilted along the naso-occipital axis at a speed of 0 degree/sec. from the 0 degree earth vertical position to the 90 degrees lateral tilt position. After two hours, the volunteers were returned to the 0 degree earth vertical position. Ocular counter-rolling was recorded using an infrared CCD camera. The video recordings were made in the dark while the volunteers had their eyes open. Recordings were obtained (1) as the volunteers was moved from the 0 degree earth vertical position to the 90 degrees lateral position, (2) 5 minutes after reaching the lateral position, (3) during the roll-back from the 90 degrees lateral position to the 0 degree upright position, two hours after the lateral tilt loading, and (4) 5 minutes after reaching the final upright position. The occurrence of ocular counter-rolling between the 0 degree upright position and the 30 degrees tilt position was confirmed during both roll movements from 0 degree to 90 degrees and from 90 degrees to 0 degree. The counter-rolling was most noticeable between the 0 degree and the 30 degrees positions. No differences in ocular counter-rolling during the roll-tilt and the roll-back situations were observed. These results indicate that the two-hour lateral tilt position did not produce any functional changes in the hair cells and/or the otolith-oculomotor system. All of the subjects exhibited ocular counter-counter-rolling during the initial stage of their roll-back to a normal upright position. This phenomenon might result from the additional bending of the hairs by inertia during the initiation of the backward roll motion.

Adult↗
PubMed2000

Genomic structure and mapping of human orphan receptor LXR alpha: upregulation of LXRa mRNA during monocyte to macrophage differentiation.

In order to identify changes in the gene expression profile during human monocyte/macrophage differentiation in the presence of GM-CSF, the expression level of various mRNA was studied using DNA microarray technology. We found LXR alpha (LXRa) to be the most highly induced transcriptional regulator during macrophage differentiation. The LXRa mRNA level was induced 40 fold which ranked it as the 10th highest among the approximately 5,600 genes studied. Although only restricted hepatic expression of LXRa mRNA had been reported, the macrophage expressed the highest level of LXRa among the nine human tissues and cultured cells studied. To further investigate transcriptional control, we have characterized the genomic structure of the human LXRa gene and determined the structure of its promoter region. The human LXRa gene consists of eleven exons, and analysis of the promoter region indicated the presence of conserved binding sites for myeloid zinc finger protein 1, which may be related to the extrahepatic expression of LXRa. LXRa is known to be activated by oxysterols, and the induced expression of the gene may be related to the foam cell formation in atherosclerotic lesions.

Base Sequence↗
PubMed2000

Gene expression induced by BO-653, probucol and BHQ in human endothelial cells.

2, 3-Dihydro-5-hydroxy-2, 2-dipentyl-4, 6-di-tert-butylbenzofuran (BO-653) and probucol, which act as radical scavenging antioxidants, were developed as anti-atherosclerotic medicines. In order to investigate the effect of these antioxidants on cell functions, we analyzed their ability to regulate gene expression in cultured human umbilical vein endothelial cells (HUVECs) using an oligonucleotide chip. Among 6,416 genes, 17 genes including those encoding mitochondrial proteins and proteins related to oxidative stress response were induced more than 3 fold by BO-653, probucol and tert-butylated hydroquinone (BHO). On the other hand, genes of three subunits of proteasome (PSMA2, PSMA3, PSMA4) were down-regulated by these antioxidants. A gene of cytochrome P-450 1A1 isozyme, a drug-metabolizing phase I enzyme, was expressed only by BHQ treatment. These results suggested that anti-atherogenic antioxidants affected gene expression in HUVECs by which they might regulate cell functions against oxidative stress.

Antioxidants↗
PubMed2000

The gene expression profile of human umbilical vein endothelial cells stimulated by tumor necrosis factor alpha using DNA microarray analysis.

Stimulation of vascular endothelial cells by tumor necrosis factor alpha (TNFalpha) plays a critical role in the pathogenesis of inflammation and vascular diseases. Changes in the gene expression profile in cultured human umbilical vein endothelial cells (HUVEC) treated with TNFalpha was analyzed with high-density oligonucleotide arrays comprised of 35,000 genes. TNFalpha stimulation profoundly induced genes involved in signal transduction, leukocyte adhesion and chemoattraction. ICAM-1 mRNA (fold change 111.9) was most profoundly induced followed by TNFalpha receptor-associated factor 1 (TRAF1) (95.5), Bcl3 (71.8), IL8 (65.4), fractalkaine (62.4), E-selectin (48.0), lymphotoxin beta (41.3) and VCAM-1 (31.7). In addition to these previously known genes, 18 poorly characterized or novel genes known as ESTs profoundly induced by TNFalpha. Initial sequencing analysis identified three of these the genes for squalene epoxydase, chromodomain helicase DNA binding protein 4, and CLP respectively. Further analysis of these genes will provide important information about TNFalpha signaling and function in vascular endothelial cells.

Cell Line↗
PubMed2000

A novel zinc finger protein mRNA in human umbilical vein endothelial cells is profoundly induced by tumor necrosis factor alpha.

Zinc finger proteins are known to mediate various transcriptional control mechanisms and other cellular functions in human cells. Tumor necrosis factor alpha (TNFalpha) induces a variety of genes in human endothelial cells including A20, an antiapoptotic zinc finger protein. In order to identify other zinc finger protein genes induced by TNFalpha, we studied the gene expression profile of human umbilical vein endothelial cells (HUVECs) stimulated by TNFalpha by means of oligonucleotide microarrays. Among the 155 genes encoding zinc finger motif, the level of EST M88357 mRNA encoding a novel designated EZFIT (endothelial zinc finger protein induced by TNFalpha) was induced most profoundly (>19 fold). The EZFIT gene is located on the chromosome 19q13.4. Isolation of the full length cDNA coding sequence by PCR using primers architected from the genomic sequence revealed that EZFIT has 490 amino acids which contain 13 C2H2 zinc finger motifs. Among 24 human organs and cell types studied, EZFIT mRNA was found to be most highly expressed in the placenta followed by the brain, testis, pancreas, heart, small intestine, muscle, uterus, prostate and peripheral blood leukocytes. EZFIT mRNA was not detected in the liver, lung, colon, stomach, the salivary gland or the thyroid gland.

Amino Acid Sequence↗
PubMed2000

[Depression during interferon therapy in renal cell cancer patients--comparison with chronic hepatitis C patients].

BACKGROUND AND PURPOSE: Depression is well known as one of the psychiatric complications of interferon (IFN) therapy in patients with chronic active hepatitis C. We compared the psychiatric status during interferon therapy between patients with renal cell cancer (RCC) and those with chronic active hepatitis C. METHODS: The psychiatric status of 40 patients with renal cell cancer, 36 who were subjected to radical nephrectomy and 4 who were not because of the presence of distant metastasis and other complicated underlying diseases, was assessed by psychiatrists before and at 2, 4, 12 and 24 weeks after the start of IFN therapy according to the major depressive episode diagnostic criteria listed in the DSM-III-R and the Hamilton Depression Scale (HDS). The mental aspect was measured using the Eysenk Personality Questionnaire (EPQ) before IFN therapy, and the results were compared with those obtained in 85 hepatitis C patients evaluated according to the same protocol for psychiatric assessment. RESULTS: Eight of the 40 patients were diagnosed as having depression before IFN therapy and 5 of them became even more depressed 2 weeks after the start of IFN therapy. Nine patients were found to be depressed after the start of IFN therapy, 7 of them were diagnosed before 4 weeks of therapy. All the patients needed treatment for depression: discontinuation of IFN therapy in 4, decrement of the IFN dose in 8, and psychiatric drug medication in 13. The patients who suffered from depression had significantly higher scores in neuroticism (EPQ) before IFN therapy than those who did not become depressed. There was no difference in age, sex or cancer stage between the two groups. The occurrence of depression in RCC patients was the same as that observed in hepatitis C patients receiving IFN therapy. But in RCC patients the depressive state was diagnosed earlier and was more severe than that observed in hepatitis C patients. CONCLUSION: Urologists should be aware of the psychiatric symptoms of RCC patients under IFN therapy just as in hepatitis patients. The depression in RCC patients was considered to be related to the cancerous disease itself which may explain its higher degree of severity, as compared to hepatitis C patients.

Aged↗
PubMed2000

Purification and characterization of factor VII inhibitor found in a patient with life threatening bleeding.

We recently observed a patient with acquired inhibitor-induced F.VII deficiency whose plasma level of F.VII was < 1.0%. However, the biochemical nature of the inhibitor has not yet been clarified. In the present study, we purified the F.VII inhibitor from the patient's plasma by using activated F.VII (F.VIIa)-conjugated gel and characterized the inhibitor. The results showed that the inhibitor comprised two kinds of antibodies: one was eluted with EDTA (antibody 1) and the other with glycine-HCl buffer (pH 2.3) (antibody 2) from the F.VIIa affinity gel. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis of these inhibitors demonstrated that both antibodies had features of immunoglobulin G1 (IgG1) with kappa and lambda-light chains. Antibody 1 bound to the immobilized F.VIIa with a high affinity in the presence of calcium ion, while antibody 2 bound to the F.VIIa very weakly and the binding was independent of calcium ion. Immunoblotting analysis demonstrated that antibody 1 bound to the light chain of F.VIIa after reduction with 2-mercaptoethanol, while it did not react with either the gamma-carboxyglutamic acid (Gla)-domainless light chain of F.VIIa or the heavy chain with the protease domain. Antibody 1 markedly inhibited the activity of tissue factor-F.VIIa complex. Based on these observations, it is suggested that F.VIIa autoantibody (antibody 1) recognizes the calcium-dependent conformation within or near the Gla domain and inhibits F.VIIa activity by interacting with the light chain.

Antibodies↗
PubMed2000

Three-dimensional helical computed tomographic angiography in neonates and infants with complex congenital heart disease.

BACKGROUND: For the clinical management of patients with complex congenital heart disease (CHD), accurate evaluation of their morphologic conditions is critical. Three-dimensional (3D) helical computed tomography (CT) angiography has been used to assess the vascular system in adult patients; the indication for complex CHD, especially in the neonatal period, has not yet been defined. Therefore the purposes of our study were to determine the quality and limitations of current 3D helical CT angiography for neonates and infants with complex CHD and to assess the clinical utility of this technique. METHODS AND RESULTS: 3D helical CT angiography was performed in 17 patients with various types of complex CHD. Their median age was 41 days (range 3 days to 9 months), and mean body weight was 3.6 kg (range 2.2 to 8.5 kg). All 3D images were produced with the 3D reconstruction algorithm of shaded-surface display. Oral sedation was required in only 4 infants during the procedure. 3D helical CT angiography clearly demonstrated the shape and spatial relation of great arteries, proximal branch pulmonary arteries, anomalous pulmonary venous connections, the patent ductus arteriosus, and a shunt. The 3D information of extracardiac morphologic characteristics and 3D anatomic relation of each extracardiac structure were easily recognized by this imaging process. However, intracardiac structure could not be visualized because of blurred and/or unclear edges of the ventricular wall caused by respiratory movement. CONCLUSIONS: 3D helical CT angiography represents an important additional diagnostic tool and may become an alternative method to angiography or other noninvasive techniques used in the evaluation of extracardiac anomalies in neonates and infants with complex CHD.

Adult↗
PubMed2000

[Activities of antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group].

The surveillance study was conducted to determine the antimicrobial activity of fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other 20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. The resistance to fluoroquinolones was remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas aeruginosa from UTI. However, many of the common pathogens such as Streptococcus pneumoniae including penicillin-resistant isolates, methicillin-susceptible Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae, Haemophilus influenzae including ampicillin-resistant isolates have been kept to be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI were susceptible to fluoroquinolones. In conclusion, the results from this surveillance study suggest that fluoroquinolones are useful in the treatment of various bacterial infections including respiratory infections.

Anti-Infective Agents↗