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Biomedical subjects

H Niwa

Publications and source records attributed to H Niwa.

At least 19 recordsLinked to original sources

Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein. Identification of essential domains for nuclear localization and DNA excision repair.

We showed previously that the xeroderma pigmentosum group A complementing (XPAC) protein involved in the DNA excision repair pathway contains a zinc-finger motif and is localized in the nucleus of normal human cells. For detailed structural and functional analyses of the XPAC protein, we constructed various XPAC cDNAs by site-directed mutagenesis and isolated permanent cell lines expressing mutant proteins. Immunofluorescent analysis of these lines indicated that the nuclear localization signal is located in the region encoded by Exon 1, especially centered at amino acids 30-42. A UV survival study showed that regions from Exons 2 through 6 were essential for DNA repair function, but that Exon 1 was not. Interestingly, deletion of the glutamic acid cluster in the region encoded by Exon 2 resulted in a dramatic loss of DNA repair activity. Furthermore, replacements of each of the 4 cysteines supposed to form a zinc-finger structure in the region encoded by Exon 3 by serine or glycine resulted in similar levels of loss of repair activity. These results suggest that all 4 cysteines forming a zinc-finger structure and also the glutamic acid cluster are important for DNA repair function.

Amino Acid Sequence

QT interval shortening and ST elevation in intracoronary ECG during PTCA.

Percutaneous transluminal coronary angioplasty (PTCA) can provide a unique model of transient and reversible myocardial ischemia. The aim of this study was to assess the serial changes in QT interval during elective PTCA-induced transient ischemia. The serial changes in QT interval before, during, and after PTCA of the left anterior descending artery (LAD) were measured in patients who showed ST elevation in intracoronary electrocardiogram. Twelve consecutive patients who showed ST-segment elevation during PTCA-induced ischemia anterior precordial leads of the electrocardiogram (ECG) were enrolled in the present study. Target lesions for PTCA were all in the LAD. There were six patients with angina pectoris, two with non-Q-wave infarction, and four with Q-wave myocardial infarction. During balloon inflation, QTc interval shortened in both intracoronary ECG (ic-ECG) (0.472 +/- 0.013 vs 0.436 +/- 0.014) and surface ECG (0.462 +/- 0.012 vs 0.438 +/- 0.011). However, a significant shortening of the QT interval was more rapidly observed in the ic-ECG (20 s) than in the surface ECG (40 s). We conclude that the QT interval in both ic-ECG and surface ECG becomes shortened in PTCA-induced myocardial ischemia, and that the ic-ECG might be a good probe for detecting survived viable myocardium in the infarcted zone.

Aged

The effect of furosemide on evoked otoacoustic emissions in guinea pigs.

After recording transiently evoked otoacoustic emissions (TEOAEs) to a click stimulus in guinea pigs by using the IL088 which was developed by Bray and Kemp (1987) for easy recording and analysis of TEOAE, the changes after intravenous administration of furosemide (30 mg/kg or 50 mg/kg) were examined. The wave of the TEOAE could be detected from 20 of 24 ears (83%). After the i.v. injection of furosemide (30 mg/kg), TEOAE powers (total echo power and highest peak power in FFT pictures) decreased quickly and showed minimum values after 5-10 min. Then they increased rapidly and recovered normally within 60 min after injection. However, no ears showed TEOAEs during the 5- to 10-min period following the injection of the 50-mg/kg dose of furosemide. They then recovered slowly as compared with the group treated with the lower dose of furosemide (30 mg/kg). These changes are similar to those of the endocochlear potential (EP) after furosemide injection. These data support the notion that the EP can contribute to the mechanism of TEOAE generation.

Acoustic Stimulation

Clinical use of new video-endoscopes (EVIS 100 and 200).

The authors report on their clinical experience with two new videoendoscopes developed in cooperation with Olympus Co. One of them is an instantaneous image method videoendoscope (EVIS 100), the other produces sequential images (EVIS 200). EVIS 100 is as compact as a fiberscope; EVIS 200 has the special advantages of electronic magnification, the use of infrared rays and image display of hemoglobin concentration in the tissue. In clinical application in 245 patients examined with EVIS 100 and 30 cases with EVIS 200, both instruments were found to be satisfactory in terms of daily use; EVIS 200 could be applied in further endoscopic research. In our opinion videoendoscopes will replace conventional fiberscopes in the future.

Endoscopes, Gastrointestinal

The optical resolution of racemic chlorpheniramine and its stereoselective pharmacokinetics in rat plasma.

An ovomucoid-conjugated column has been developed for the chiral stationary-phase liquid chromatographic resolution of racemic chlorpheniramine with a quantitation limit of 0.05 microgram mL-1. The assay was used to study the stereoselective kinetics of chlorpheniramine enantiomers in rats. After bolus intravenous administration of racemic chlorpheniramine maleate (20 mg kg-1), plasma concentration of the (-)-form was higher than that of the (+)-form. In the elimination phase, the concentrations of (+)- and (-)-chlorpheniramine in the plasma declined biexponentially with half-lives of 18.2 and 50.0 min, respectively. Although there was no significant difference in blood-to-plasma concentration ratio of both enantiomers, the apparent total blood clearance of (+)-chlorpheniramine was twice as large as that of the (-)-isomer. Binding of (-)-chlorpheniramine to rat plasma protein was stronger than that of (+)-chlorpheniramine suggesting stereoselective pharmacokinetics may be due to a difference in the plasma protein binding.

Animals

Nephrotoxicity of germanium compounds: report of a case and review of the literature.

A 55-year-old woman was admitted to our hospital, complaining of general malaise, muscular weakness, anorexia and weight loss. She had a history of ingesting of a certain germanium (Ge) compound over the preceding 19 months, with a total dose of 47 g as Ge element. She was found to have renal failure (blood urea nitrogen, 44 mg/dl; serum creatinine, 2.6 mg/dl) without abnormal findings in urinalysis, and muscular and nervous damage. Initially, polymyositis was diagnosed and prednisolone administered. However, no improvement was seen, and neuromuscular symptoms and signs steadily worsened, ending in death. Microscopic study of the kidney showed that lipofuscin granules increased in the cells of the thick ascending limb of Henle's loop to the distal convoluted tubule accompanying mild tubular atrophy and that some of the tubules of these segments had vacuolar degeneration or desquamation. No apparent glomerular and vascular changes were observed. High Ge content was found in serum, urine and various tissues, e.g., spleen, liver, kidney, adrenal gland and myocardium, while in controls Ge could not be detected in sera, urine or tissues. We also review case reports about Ge toxicity, and discuss the pathogenesis of renal failure induced by Ge compounds.

Acute Kidney Injury

[Magnified tomography for identification of ceramic prostheses].

Recently, ceramic prostheses for ossicular replacement have become very popular in middle ear surgery. These prostheses have a good affinity with the surrounding tissue. But, it is difficult to identify the position of these prostheses postoperatively. We used magnified tomography in order to identify the implanted ceramic prostheses, and to determine whether these prostheses were in the appropriate position. In the case of patients without stapes, we usually use Apaceram type T, which restores ossicular continuity to the inner ear. When the shaft of the ceramic prosthesis is placed on the oval window niche, the overhanging Fallopian canal obstructs the tip of the prosthetic shaft to obtain the appropriate place in the oval window. The angle of the shaft should be slightly tilted inferiorly against the medial wall of the middle ear cavity.

Adult

Postnatal changes in development of serotonin-, neuropeptide Y-, Leu-enkephalin- and substance P- terminals in the rat locus coeruleus; a quantitative immunohistochemical study.

Postnatal developmental changes were investigated in afferent terminals immunoreactive to serotonin (5-HT), neuropeptide Y (NPY), Leu-Enkephalin (ENK) and substance P (SP) within the locus coeruleus from postnatal rat from day 1 (1 D) to 9 week (9 W) adult using immunohistochemical techniques. Quantitative study using a light microscopic image analyzing system revealed that the number of immunoreactive terminals increased after birth to reach a peak at 5 W, then decreased by 26% of this value and stabilized at 7 W; terminals immunoreactive to 5-HT or NPY increased gradually after birth, while those immunoreactive to ENK or SP increased suddenly at 3 W. Electron microscopic analysis revealed similar changes in the total terminal number during development. Synaptic terminals, on the other hand, increased sharply from 1 D to 3 W, then gradually until 5 W, and remained stable thereafter. These results suggest that surplus afferent terminals are eliminated prior to the establishment of afferent innervation and that 5 W postnatal is the critical time for maturation of the afferent system. Electron microscopy also demonstrated morphological characteristics of terminals immunoreactive to each peptide or 5-HT and developmental changes in their characteristics.

Aging

[The influence of proton-pump inhibitors on the healing process of peptic ulcers--electronic endoscopic study].

It is highly important to analyze the of protonpump inhibitors on the healing process of peptic ulcers endoscopically since the use of proton-pump inhibitors is restricted in their period of usage. It is however, too early to evaluate proton-pump inhibitors as equal to or comparable to the many H2 blockers which have been tested basically and clinically. From the view-point of the number of clinical cases too, it is too early to conclude that the protonpump inhibitors are superior to previous H2 blockers. Most of the ear electronic endoscopic studies are highly conducted with the stereo-type electronic endoscopes except that on the regenerative epitheliums. The pictorial management of the regenerative epitheliums and intramucosal blood volume are not discussed in this paper, but results are expected to in the near future.

Adenosine Triphosphatases

[The general aspects of the treatment of irritable bowel syndrome].

Irritable bowel syndrome (I.B.S.) is treated with medication, change of life style, various psychotherapies, oriental medicine, and etc., But no specific therapy is recognized useful for all the symptoms derived from I.B.S.. In fact the combination of these therapies are useful. When the therapeutic schedule is planned for individuals, we must keep it in mind that the relief from the symptoms is most important for patients.

Anti-Anxiety Agents

[Postoperative management in neonate after open cardiac surgery].

Recent advances in diagnostic method and preoperative care have allowed us to perform surgical repair in neonate. Important to the successful outcome of open cardiac surgery in neonate is cautious management in postoperative period. So we investigated the hemodynamics in the first 72 hours following open heart surgery for TAPVC, TGA and PAIVS. The hemodynamics in acute period are different according to patient age. Especially, early neonates under 14 days present low systemic blood pressure and high central venous pressure. So we must manage them according to their hemodynamic characteristics.

Blood Pressure

[An experience of rapid, two-stage arterial switch operation for transposition of the great arteries and intact ventricular septum beyond the neonatal period].

A 2-month-old girl with transposition of the great arteries and intact ventricular septum was successfully repaired by rapid, two-stage arterial switch operation. Balloon atrioseptostomy and ligation of the ductus arteriosus was done elsewhere on 14th and 29th day after birth. On her first admission to our hospital at 2 months of age, left ventricular-right ventricular pressure ratio (LVp/RVp) was almost 0.5 and left ventricular posterior wall thickness (LVPWT) by echo cardiography was 3.5 mm. Because of these date, we selected rapid, two-stage arterial switch operation. On 74 days, the first-stage preparatory operation (pulmonary arterial banding and right modified Blalock-Taussig shunt) was undergone with the resultant LVp/RVp of 0.97. During a few days after the first-stage operation, left ventricular ejection fraction (LVEF) by echocardiography was reduced to nearly 30%. But after this phase left ventricular function recovered rapidly and LVp/RVp, LVPWT and LVEF was 1.18, 6.3 mm and 66% on the 7th day. On the 9th day, the second-stage arterial switch operation was undergone as usual as in neonatal period without hard adhesion. Her postoperative course was uneventful.

Cardiac Surgical Procedures

[Operative indications for tracheobronchomalacia].

Tracheobronchomalacia in 3 children and 4 adults was reviewed, and operative indications were investigated. Tracheobronchomalacia in children differed from that in adults in that the lesion was localized and spontaneous healing was effected by cartilage growth and hardening. In adults, tracheobronchomalacia was characterized by a notch on the expiratory flow volume curve and higher V peak of inspiratory flow volume curve than that of expiratory curve. Operative indications for tracheobronchomalacia are BP higher than 28.2 cmH2O and delta CT higher than 15.4 cmH2O. Of 2 patients with tracheobronchomalacia in whom airway pressure was measured, one was a candidate for operation, and in the other, surgery was contraindicated because of low BP due to chronic obstructive pulmonary disease.

Adult

[The effects of isosorbide dinitrate spray on the coronary artery and its modification by the preceding chronic oral therapy with long acting isosorbide dinitrate].

The vasodilatory effect of a new formula of isosorbide dinitrite (ISDN) spray on the left coronary artery was studied by comparing its effects in 46 consecutive patients who subsequently received intracoronary injection with ISDN (2.5 mg). In addition, the influence long acting and ISDN for chronic cases on the vasodilatory effects of ISDN spray and on subsequent intracoronary injection of ISDN was investigated. The patients were divided into two groups, those who had had chronic oral ISDN (Group N; 29 patients) and those who had not (Group O; 17 patients). The vasodilatory effect of ISDN spray was evaluated in segments; 5, 6, 8, 11 and 12 by AHA classification and it dilated those segments by 9.9%, 13.2%, 21.5%, 15.6% and 23.5% respectively. Subsequent intracoronary injection of ISDN dilated those segments by 10.4%, 14.0%, 27.2%, 17.9% and 29.1% respectively. The differences in the degree of vasodilation caused by ISDN spray and that caused by injection in segments 8, 11, 12 were statistically significant. However, the per cent dilation of ISDN spray in segments 5 in group N was 5.9%, and 18.4% in group O, revealing a significant difference depending on previous chronic administration of long acting ISDN. We conclude that ISDN spray did dilate the coronary artery, and subsequent intracoronary administration of ISDN dilated it further in the distal portions of the left coronary artery. Long acting oral ISDN for chronic cases seemed to attenuate the vasodilatory action of ISDN.

Administration, Oral

Basic fibroblast growth factor promotes proliferation of rat glomerular visceral epithelial cells in vitro.

Glomerular visceral epithelial cells (vGEC) play an important role in the synthesis of the glomerular basement membrane (GBM), and together with glomerular endothelial cells and the GBM, in glomerular ultrafiltration. Therefore clarification of the properties of vGEC is essential to investigations of glomerular morphology and function in both physiologic and pathologic conditions. This article demonstrates that basic fibroblast growth factor (bFGF) is mitogenic to vGEC in vitro. Its effect was found at concentrations as low as 1.25 ng/ml, and was synergistic with epidermal growth factor (EGF). In contrast, EGF by itself had no demonstrable mitogenic effect at concentrations of 1.25-100 ng/ml. In addition, mRNA for bFGF was identified in cultured vGEC by the method of reverse transcriptase polymerase chain reaction and the immunoreactivity of bFGF was found in GEC of the Sprague-Dawley rat kidney. These results suggest that bFGF stimulates the proliferation of vGEC in an autocrine manner in vivo. A unique relationship similar to that observed in endothelial cells may also exist among bFGF, vGEC, and the extracellular matrix (ECM). In a word, bFGF may be produced by vGEC and stored in the ECM, that is the GBM, and may be one factor that stimulates vGEC to proliferate when vGEC are injured and lost in vivo.

Animals