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Biomedical subjects

M Hirai

Publications and source records attributed to M Hirai.

At least 19 recordsLinked to original sources

Diagnostic usefulness of postexercise systolic blood pressure response for detection of coronary artery disease in patients with electrocardiographic left ventricular hypertrophy.

Patients with left ventricular (LV) hypertrophy often have a positive result on exercise testing despite a normal coronary arteriogram. This indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. We evaluated the usefulness of the postexercise systolic blood pressure (BP) response for detection of CAD in 51 patients with both electrocardiographic evidence of LV hypertrophy and positive ST depression on treadmill exercise testing. Coronary cineangiograms showed normal coronary arteries in 23 patients (45%) (group 1) and significant CAD in 28 patients (55%) (group 2). The systolic BP ratio (systolic BP at 3 minutes of recovery divided by systolic BP at peak exercise) was significantly higher in group 2 than in group 1 (1.01 +/- 0.19 vs 0.80 +/- 0.09; p < 0.001). Analysis of the relative cumulative frequency revealed that a systolic BP ratio of 0.86 was the cutoff point for distinguishing a patient with CAD from one with normal coronary arteries. The sensitivity, specificity, and accuracy of a systolic BP ratio > or = 0.86 for detection of CAD in patients with LV hypertrophy were 79%, 83%, and 82%, respectively. Our results suggest that the use of an abnormal BP ratio, in combination with ST depression, improves the accuracy of treadmill exercise testing for detecting CAD in patients with electrocardiographic evidence of LV hypertrophy.

Adult

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

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

[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

Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.

We expressed human MDR1 cDNA isolated from the human adrenal gland in porcine LLC-PK1 cells. A highly polarized epithelium formed by LLC-GA5-COL300 cells that expressed human P-glycoprotein specifically on the apical surface showed a multidrug-resistant phenotype and had 8.3-, 3.4-, and 6.5-fold higher net basal to apical transport of 3H-labeled cortisol, aldosterone, and dexamethasone, respectively, compared with host cells. But progesterone was not transported, although it inhibited azidopine photoaffinity labeling of human P-glycoprotein and increased the sensitivity of multidrug-resistant cells to vinblastine. An excess of progesterone inhibited the transepithelial transport of cortisol by P-glycoprotein. These results suggest that cortisol and aldosterone are physiological substrates for P-glycoprotein in the human adrenal cortex and that substances that efficiently bind to P-glycoprotein are not necessarily transported by P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem

Effects of simulated left bundle branch block on QRST time-integral values of 12-lead electrocardiograms in patients with and without prior anterior wall myocardial infarction.

The effects of right ventricular pacing, which simulated left bundle branch block (BBB), on QRST time-integral values of 12-lead electrocardiograms (ECGs) were examined, and the clinical usefulness of QRST values for estimating the severity of left ventricular wall motion abnormalities due to a prior anterior wall myocardial infarction (MI) in the setting of left BBB were evaluated. Digitized ECGs were recorded during normal sinus rhythm and simulated left BBB in 38 patients (24 with and 14 without prior anterior wall MI). QRST values were calculated in each lead point of 12-lead ECGs. Data from 608 normal subjects were used as control values; the mean +/- 2 SD of these values was regarded as the normal range. The parameter sigma DE was defined as the sum of the differences between the normal mean QRST value and the QRST values of a given patient in leads where the QRST value was less than the normal range. The correlation coefficient of sigma DE for the 2 activation sequences was highly significant. Although small but significant changes were seen in QRST values in leads I, II, III, aVR, aVF and V1 during simulated left BBB, left precordial leads showed no significant changes in QRST values. A criterion of sigma DE > 40 mV.ms for detecting an anterior wall MI showed a sensitivity of 88%, a specificity of 93%, and a diagnostic accuracy of 89%. The sigma DE was significantly (p < 0.001) correlated with the asynergy index calculated from left ventriculograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Bundle-Branch Block

Expression of renal organic cation transporter in Xenopus laevis oocytes.

The expression of the organic cation transport system of rat renal proximal tubules has been studied in Xenopus laevis oocytes injected with poly(A)+ RNA from the rat renal cortex. The effectiveness of the technique was confirmed by examining expression of the Na+/D-glucose co-transporter. Compared with water-injected and non-injected oocytes, the injection of total poly(A)+ RNA resulted in about a 3-fold increase in tetraethylammonium (TEA) uptake activity. TEA uptake by poly(A)(+)-RNA-injected oocytes was time-dependent and was inhibited by cimetidine and HgCl2, but not by p-aminohippurate. After size-fractionation on a sucrose density gradient, a 1.4-2.4 kb poly(A)+ RNA fragment was identified that expressed the organic cation transport system in oocytes. These results demonstrate that the renal organic cation transporter was expressed in oocytes and that this expression system can provide an effective assay procedure for cloning of the organic cation transporter.

Animals

Serum granulocyte colony-stimulating factor in patients with repeated infections.

We have already reported significant elevation of serum granulocyte colony-stimulating factor (G-CSF) in the acute phase of infection. In this study, we compared the responses to infection between patients with frequently repeated infection (repeaters) and others (non-repeaters). We examined the clinical data and serum G-CSF levels in 48 patients with acute infections. Serum G-CSF levels were significantly lower in repeaters than in non-repeaters (197.7 +/- 370.0 vs. 1014.1 +/- 924.4 pg/ml. P less than 0.001). There were no significant differences in age, serum total protein, or cholinesterase between the groups, but serum albumin was significantly lower in repeaters than in non-repeaters (2.87 +/- 0.5 vs. 3.31 +/- 0.4 g/dl. P less than 0.005). It is suggested that administration of recombinant G-CSF may be useful for patients with repeated infections.

Aged

Relationship of QRST isointegral maps during simulated left bundle branch block to impairment of left ventricular function due to myocardial infarction.

The clinical usefulness of QRST isointegral maps for assessing left ventricular (LV) dysfunction due to myocardial infarction (MI) in patients with MI in the setting of simulated left bundle branch block (LBBB) was investigated. Isointegral maps were recorded during sinus rhythm and right ventricular pacing, which simulated LBBB, in 62 patients with MI and 26 patients without MI. An abnormal decrease in the QRST value in the isointegral map was assessed by the difference map that indicated a "-2 SD area" where the QRST integral value was less than the normal range (mean - 2 SD) calculated from 608 normal individuals. The isointegral maps during the two activation sequences were similar in patients with and without MI (r = 0.87 and 0.92, respectively). The sum of QRST integral values less than the normal range (sigma DM) during simulated LBBB correlated significantly with the asynergy index, derived from left ventriculographic data (r = 0.81, p < 0.01). LV dysfunction (asynergy index > or = 2) was diagnosed in simulated LBBB with a sensitivity of 81%, specificity of 77%, and diagnostic accuracy of 80% when the criterion that LV dysfunction is present if the number of lead points in the -2 SD area exceeds 4, and a sensitivity of 71%, specificity of 81%, and diagnostic accuracy of 74% if sigma DM exceeds 200 mVms was used. The findings demonstrate that isointegral maps may be useful in assessing LV dysfunction due to MI in patients with MI and LBBB in addition to detecting the presence and site of MI in these patients.

Adult

Small differences among body surface and epicardial QRST integral maps recorded during normal activation and experimentally simulated left bundle branch block or preexcitation in canine hearts.

QRST integral maps were constructed from 87-lead body surface electrocardiograms (ECGs) and from 45-lead epicardial electrograms during artificial pacing, which simulated left bundle branch block (LBBB) and Wolff-Parkinson-White syndrome in 12 dogs. Although the ECGs and electrograms differed in configuration for each conduction model, the body surface and the epicardial QRST integral maps showed only small differences. Correlation coefficients (r) and root mean square differences (rms) were calculated to assess quantitatively the similarities in the QRST integral maps among the different conduction models. Mean r values between the normal conduction and the left bundle branch block models were 0.95 in the body surface maps and 0.89 in the epicardial maps. Mean r values between the normal conduction and the Wolff-Parkinson-White ECG models were 0.97 in the body surface maps and 0.91 in the epicardial maps, and rms values were small enough. The small differences were also verified by the difference maps and by paired t tests. QRST integral maps on the epicardium and on the body surface were largely independent of altered activation sequences in both the left bundle branch block and the Wolff-Parkinson-White ECG models.

Animals

Sequence and chromosome assignment to 11p13-p12 of human RAG genes.

The recombination-activating genes RAG-1 and RAG-2 are required for V(D)J DNA rearrangements at loci for immunoglobulin and T cell receptor genes. We isolated the human RAG-2 gene and determined its nucleotide sequence. Mapping analysis of RAG-1 and RAG-2 genes on human chromosomes by fluorescence in situ hybridization indicated that the genes are located on chromosome 11p13-p12. RAG-1 and RAG-2 do not seem to be linked to any of the primary immunodeficiencies for which defective genes have already been mapped.

Amino Acid Sequence

Distribution of cells containing progesterone receptor mRNA in the female rat di- and telencephalon: an in situ hybridization study.

In an attempt to examine regional synthesis of the progesterone receptor (PR) in the brain, the distribution of mRNA encoding PR was investigated in the female adult rat di- and telencephalon by in situ hybridization using T7 RNA polymerase transcripts of a 320 base pair rat PR cDNA clone. The rat PR cDNA had been partially cloned and sequenced by using the reverse transcription-polymerase chain reaction (RT-PCR) method. The primer set corresponds to a part of the progesterone binding domain of human PR cDNA. Large numbers of strong labeling were observed in the arcuate nucleus, medial preoptic nucleus, and ventrolateral part of the ventromedial nucleus which are relative to sexual behavior. Moderate labeling was found in layers II and IV of the isocortex, in the pyramidal layer of the CA1 and CA3 fields of the hippocampal formation, in the cortical nucleus of the amygdala, in the nucleus of the diagonal band, and in the anterior periventricular nucleus. Weak labeling was found in many other regions. These results were largely in agreement with the distribution of PR previously reported by ligand binding assay and autoradiographic studies. This present in situ hybridization study may provide a useful tool for the analysis of the regional regulation of PR synthesis in the rat brain.

Animals

Expression of estrogen receptor in the rat brain: detection of its mRNA using reverse transcription-polymerase chain reaction.

Reverse transcription-polymerase chain reaction (RT-PCR)-Southern blotting was employed for biochemical detection and measurement of the estrogen receptor messenger ribonucleic acid (ERmRNA) in various parts of the Wistar strain female rat brain. Total RNA extracted from the tissues was subjected to RT-PCR using the primer set which flanked the part(287bp) of the estrogen binding domain-corresponding region of the rat ERcDNA. It was confirmed that the RT-PCR product corresponded to the part of the ERcDNA by direct nucleotide sequencing of the product. Moreover, the level of ERmRNA could be determined by Southern blotting which was highly sensitive and produced quantitative results. The RT-PCR product of about 290 bp, corresponding in length to the distance between two primers, was generated from RNA of all the tissues examined. The levels of the product were as follows; anterior hypophysis greater than hypothalamus and preoptic area, amygdala much greater than cerebral cortex, cerebellum. These results indicate that ERmRNA is widely distributed in the whole brain, implying some physiological action of estrogen on target and 'non-target' brain regions.

Animals

Expression of progesterone receptor in the neonatal rat brain cortex: detection of its mRNA using reverse transcription-polymerase chain reaction.

Our previous reports have revealed the postnatal developmental pattern of progesterone receptor (PR) in the rat cerebral cortex, but little is known about PRmRNA changes in the tissue so far. In the present study, we have attempted to detect and quantify PRmRNA in the tissue by the use of the reverse transcription-polymerase chain reaction (RT-PCR)-dot blot analysis. Cerebral cortical tissues were dissected from female Wistar rats at 2 and 8 days of age. Total RNA extracted from the tissues was reverse transcribed, followed by PCR. The PCR primer set, whose sequence was derived from the human clone, flanked the part (320 bp) of the human PRcDNA which corresponded to the progesterone binding domain. The 320 bp of the RT-PCR product was generated from rat uterine RNA. The amino acid sequence deduced from the nucleotide sequence of the product had a 95.5% identity with the corresponding region in human PR, confirming that the product had originated from the rat PRmRNA. Moreover, a highly sensitive and quantitative assay for rat PRmRNA had been developed by the use of RT-PCR-dot blotting. The PRmRNA was detectable in the cerebral cortex of both 2- and 8-day-old rats by the assay. Furthermore, the level of cortical PRmRNA of the 8-day-old rats were greater than the 2-day-old rats. These results indicate that the RT-PCR assay is useful for detection and quantification of PRmRNA in the neonatal rat cerebral cortex, and that increment of the cortical PRmRNA in the 8-day-old rat is associated with a drastic change of the level of the cortical PR around day 10.

Aging

Molecular cloning and chromosomal mapping of a cDNA encoding human 80K-L protein: major substrate for protein kinase C.

We have isolated and sequenced complementary DNA (cDNA) for the human 80K-L protein, a major substrate for protein kinase C and the human homologue of an 80- to 87-kDa bovine protein named MARCKS (myristoylated alanine-rich C kinase substrate). The human 80K-L cDNA encodes a protein of 332 amino acids with a calculated molecular weight of 31,534. Homology comparisons of the nucleotide sequences of the cDNAs indicated that their 3'-untranslated regions are more homologous than the coding regions. Spot blot hybridization using flow-sorted human chromosomes indicated that the gene encoding the 80K-L protein, designated MACS, maps to the q15----qter region of human chromosome 6, and it also suggested that a genomic region with a sequence homologous to the 3'-untranslated region of the 80K-L mRNA exists on chromosome 21.

Amino Acid Sequence

An epidemiological study on hyponatremia in psychiatric patients in mental hospitals in Nara Prefecture.

Hyponatremia occurs often in mental illness. The frequency was not noticed because of the uncharacteristic symptoms of mild hyponatremia. Of the 1,114 psychiatric inpatients retrospectively surveyed, 10.5% had hyponatremia. Not only patients with schizophrenia, but also patients with other mental illness, especially with epilepsy, having hyponatremia were confirmed. An early onset, a long duration of psychiatric disorder and a prolonged admission were statistically significant factors. Nicotine abuse was not a significant factor. It was suggested that the pathogenesis of hyponatremia in psychiatric patients might be involved in a chronic course of psychiatric disorders and poor response to psychopharmacotherapy.

Adult

Degradation of hydrogen sulfide by Xanthomonas sp. strain DY44 isolated from peat.

Xanthomonas sp. strain DY44, capable of degrading H2S, was isolated from dimethyl disulfide-acclimated peat. This bacterium removed H2S either as a single gas or in the presence of the sulfur-containing compounds methanethiol, dimethyl sulfide, and dimethyl disulfide. The maximum specific H2S removal rate, obtained in the late stationary phase, was 3.92 mmol g of dry cells-1 h-1 (6.7 x 10(-16) mol cell-1 h-1) at pH 7 and 30 degrees C through a batch experiment in a basal mineral medium. Since Xanthomonas sp. strain DY44 exhibited no autotrophic growth with H2S, the H2S removal was judged not to be a consequence of chemolithotrophic activity. By using X-ray photoelectron spectroscopy, the metabolic product of H2S oxidation was determined to be polysulfide, which has properties very similar to those of elemental sulfur. Autoclaved cells (120 degrees C, 20 min) did not show H2S degradation, but cells killed by gamma-irradiation and cell extracts both oxidized H2S, suggesting the existence of a heat-labile intracellular enzymatic system for H2S oxidation. When Xanthomonas sp. strain DY44 was inoculated into fibrous peat, this strain degraded H2S without lag time, suggesting that it will be a good candidate for maintaining high H2S removability in the treatment of exhaust gases.

Biodegradation, Environmental

A novel cDNA clone for acid invertase in tomato fruit.

The sequence of a novel cDNA clone, Aiv-1, for tomato acid invertase was similar to that of TIV1 (Klann et al., 1992) for the enzyme except for a unique intron-like insertion. It is considered that Aiv-1 is derived from either an alternatively spliced mRNA for an isozyme or a pre-mRNA of TIV1.

Amino Acid Sequence