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Biomedical subjects

K Hirata

Publications and source records attributed to K Hirata.

At least 289 records · Page 16Linked to original sources

A case of nocturnal polyuria in olivopontocerebellar atrophy.

We report a case of olivopontocerebellar atrophy without sleep apnea syndrome who presented nocturnal polyuria. It is considered that a disturbance in the circadian rhythm for arginine vasopressin secretion due to degeneration of suprachiasmatic nuclei and marked increase in the secretion of atrial natriuretic peptide due to abnormal diurnal variation in blood pressure may be involved in the mechanism of nocturnal polyuria.

Arginine Vasopressin↗

Disappearance of rhythmic involuntary movements during sleep in a case of olivopontocerebellar atrophy.

We report on a 54-year-old woman with an 8 or so year history of olivopontocerebellar atrophy associated with the rhythmic involuntary movements of the left upper and lower limbs, and cervical region. Surface electromyogram of the left upper limb revealed rhythmicity (about 3 Hz) and reciprocity between antagonistic muscles, which disappeared on polysomnography at all sleep stages including rapid eye movement sleep without atonia. These were characterized by the co-existence of rhythmic skeletal myoclonus and parkinsonian tremor. These findings suggest that a disturbance of the striatonigral system as well as the dentato-rubro-olivary circuit may be involved in these movements. It also seems that their fate is dependent on the level of wakefulness and that the ascending reticular activating system also plays a role in the development of these movements.

Cerebellar Nuclei↗

Proteins recognized by antibodies against isolated cytological heterochromatin from rat liver cells change their localization between cell species and between stages of mitosis (interphase vs metaphase).

Heterochromatin in the cell nucleus seems to concentrate various proteins, such as Drosophila heterochromatin protein 1, which maintain the repressed state of gene expression. However, it still remains obscure how protein composition related to chromatin structure is different between heterochromatin and euchromatin in interphase nuclei. We isolated cytological heterochromatin from sonicated interphase nuclei obtained from rat liver cells and prepared antisera against it. The dense heterochromatic bodies seen in the preparation of intact nuclei were duplicated in a relatively pure form during the preparation of heterochromatin. In the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, differences between the fractions of heterochromatin and euchromatin were noted by their protein composition. Isolated heterochromatin was then digested by DNase after partial digestion with trypsin and its dense structure changed to become highly sensitive to DNase. The prepared antibodies reacted with the heterochromatin region of rat liver cell nuclei and isolated cytological heterochromatin; however, they did not react with euchromatin. Using immunohistochemistry, the antibodies bound to each cell nucleus in all tissues observed; some cell types were distinguished by their differential stainability (e.g. staining in the cytoplasm). Staining of the mitotic cells showed that the proteins recognized by the antibodies were localized in the cytoplasm and, in part, on the chromosomes. Based on the results of molecular cloning from rat liver cDNA library using the antibodies as a probe, it seemed that the antibodies mainly recognized two proteins similar to arginase and general vesicular transport factor p115, respectively. The results obtained from these experiments reveal that some proteins located in the heterochromatin of interphase liver cell nuclei seem to play important roles in condensing a portion of the chromatin structure during interphase and suggest that proteins composing heterochromatin might be changed according to cell types or the stage of the cell cycle.

Animals↗

Longitudinal instability for a purely inductive wake function.

A purely inductive wake function was the only known case where a solution of the Haissinski equation did not exist beyond a certain threshold. This is due to the ill-defined treatment of the wake function. The solution is proved to exist beyond the threshold, if we define the wake function physically. The threshold of the stability for the solution exists but is lower than the former "threshold."

Journal Article↗

Coupled map car-following model and its delayed-feedback control.

This paper proposes a coupled map car-following traffic model, which describes a dynamical behavior of a group of road vehicles running in a single lane without overtaking. This model consists of a lead vehicle and following vehicles, which have a piecewise linear optimal velocity function. When the lead-vehicle speed is varied, we can observe a traffic jam in the group of the vehicles. We derive a condition under which the traffic jam never occurs in our model. Furthermore, in order to suppress the traffic jam, for each vehicle we use a dynamic version of decentralized delayed-feedback control proposed in [Konishi, Hirai, and Kokame, Phys. Rev. E 58, 3055 (1998)], and provide a systematic procedure for designing the controller.

Journal Article↗

Effects of nicotinamide-related agents on the growth of primary rat hepatocytes and formation of small hepatocyte colonies.

AIMS/BACKGROUND: We report in this study that, 10 mM nicotinamide can stimulate the proliferation of primary rat hepatocytes in serum-free Dulbecco's modified Eagle's medium supplemented with 10 ng/ml epidermal growth factor and that small hepatocyte colonies appear from 4 to 5 days after plating. We examined the effects of nicotinamide-related agents on the growth and differentiation of primary rat hepatocytes and on the appearance of small hepatocyte colonies. METHODS: As nicotinamide is an aqueous vitamin named niacin and known to act as an inhibitor of poly (ADP-ribose) polymerase (PARP), we therefore chose to examine the effects on hepatocytes of three nicotinamide-related agents, nicotinic acid (NA) which is also a niacin, 3-aminobenzamide (3-AB) which is a strong inhibitor of PARP but is not a niacin, and 3-acetylpyridine (3-AP) which is a weak inhibitor of PARP and also not a niacin. To examine their effects on the growth of the cells and on the formation of the colony, immunocytochemistry for BrdU was carried out. Expression of albumin, tryptophan 2,3-dioxygenase (TO), and connexin 32 (Cx32) mRNAs were used as marks of hepatic differentiation. Intracellular NAD+ content was also measured. RESULTS: At concentration of 10 mM, NA could not enhance the proliferation of mature hepatocytes but induced the appearance of small hepatocyte colonies. At concentration of 5 mM, 3-AB enhanced the proliferation of the hepatocytes but did not induce small hepatocyte colonies. On the other hand, although 10 mM 3-AP remarkably inhibited the DNA synthesis of the cells, the expression not only of albumin but also of TO and Cx32 mRNAs in the cells was well maintained for more than one week. The intracellular NAD+ concentration was correlated with the proliferation of the hepatocytes. CONCLUSION: These results suggest that the intracellular NAD+ content may be correlated with the proliferation of primary hepatocytes and that the supplementation of niacin in the medium may be important for the appearance of small hepatocyte colonies.

Albumins↗

Changes in intestinal absorption of 5-fluorouracil-treated rats.

5-Fluorouracil chemotherapy is often accompanied by gastrointestinal toxicity. In this study, we investigated the effect of 5-fluorouracil on the epithelial barrier function of rat small intestine by examining the absorption of a poorly absorbable marker, fluorescein isothiocyanate-labelled dextran (molecular weight 4,400). We further evaluated the intestinal absorption of 5-fluorouracil in rats treated orally with 5-fluorouracil once daily for 4 days. The small intestinal absorption of fluorescein isothiocyanate-labelled dextran and 5-fluorouracil was tested using in situ closed loop intestine technique and in vitro everted intestine technique, respectively. After administration of 5-fluorouracil to rats for 4 days, the body weight of rats decreased significantly and the fluorescein isothiocyanate-labelled dextran concentration in plasma increased significantly, compared with that of control rats to which the saline solution alone was administered. Moreover, the intestinal absorption of 5-fluorouracil in the 5-fluorouracil-treated rats was enhanced significantly, compared with that of control rats. The administration of 5-fluorouracil to rats caused body weight loss and epithelial barrier dysfunction of the small intestine in rats as shown by the increased permeation of the high molecular weight compound, fluorescein isothiocyanate-labelled dextran. The increased absorption of 5-fluorouracil after this treatment suggest that the 5-fluorouracil toxicity might be amplified by its treatment.

Animals↗

Antiganglioside antibody in patients with Guillain-Barré syndrome who show bulbar palsy as an initial symptom.

OBJECTIVES: To identify valuable antiganglioside antibodies that support the diagnosis of Guillain-Barré syndrome (GBS) and its variants in patients showing bulbar palsy as an initial symptom. METHODS: Medical records of 602 patients with GBS or its variants were reviewed. Fifteen patients had bulbar palsy as an initial symptom. Serum antibodies against GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, and GQ1b were examined in 13 of them. RESULTS: Serum antiganglioside antibodies were positive in 11 (85%) patients. IgG anti-GT1a (n=8; 62%) and anti-GM1b (n=7; 54%) antibodies were often present, whereas all the patients had low or no anti-GM1 antibody activity. High anti-GD1a and anti-GQ1b IgG antibody titres were also present in some patients, but most had higher IgG antibody titres to GM1b or GT1a. All five patients with high IgG antibody titre to GM1b or GT1a only had had antecedent diarrhoea. Some patients with pharyngeal-cervical-brachial weakness (PCB) had IgG antibody to GT1a which did not cross react with GQ1b. Other patients with PCB had antibody to GT1a which cross reacted with GQ1b or antibody to GM1b, but anti-GM1b and anti-GT1a antibodies were not associated with the presence of bulbar palsy. All the patients who had no IgG antiganglioside antibodies recovered completely. CONCLUSIONS: Measurement of serum IgG anti-GT1a and anti-GM1b antibodies gives helpful support for the diagnosis of GBS and its variants when there is early involvement of the oropharyngeal function independently of other neurological findings which appear as the illness progresses.

Adolescent↗

Bilateral ballism in a patient with overlapping Fisher's and Guillain-Barré syndromes.

A 29 year old woman developed diplopia and ataxic gait. Neurological examination showed total ophthalmoplegia, cerebellar ataxia, and areflexia. Moreover, there was muscle weakness in all four limbs. An overlap of Fisher's and Guillain-Barré syndromes was dignosed. On day 5 she suddenly developed involuntary flinging movements that affected the face and four limbs. Surface EMG showed 1.5-2 Hz rhythmic grouping discharges. The involuntary movements were considered ballism. This is the first report of a patient with Guillain-Barré syndrome and a related disorder who showed ballism.

Adult↗

Anatomical Study of the Distal Radioulnar Joint: Degenerative Changes and Morphological Measurement.

A study of the degenerative changes in the distal radioulnar joint compared with morphological measurement of that joint using 91 joints of the hand from 51 systemic anatomy cadavers was conducted. X-ray images of the joints of the hand were taken followed by measurement of radial inclination, ulnar variance, volar tilt, sigmoid notch inclination and ulnar seat inclination. Macroscopic observations of the ulnar notch of the radius and surface of the distal radioulnar joint of the ulnar head were made by dividing them into six and nine areas, respectively. These were then used to classify the degree of cartilage degeneration. In addition, the status of the triangular fibrocartilage complex (TFCC) was also observed. Arthropathic changes of the distal radioulnar joint were associated with factors including TFC degeneration and UV(+), SNI(-) and USI(+).

Journal Article↗

Administration of SIN-1 induces guinea pig airway hyperresponsiveness through inactivation of airway neutral endopeptidase.

BACKGROUND: Peroxynitrite plays an important role in the pathogenesis of airway inflammation. We have already found that peroxynitrite may contribute to decreased beta(2)-adrenoceptor responses in airway smooth muscle. However, it is not known whether peroxynitrite can alter neutral endopeptidase (EC 3.4.24.11; NEP) activity in the airways. This study was designed to determine whether peroxynitrite induces airway hyperresponsiveness to substance P (SP) and endothelin-1 (ET-1) through the inactivation of airway NEP. METHODS: We examined whether the administration of S-morpholinosydnonimine (SIN-1), a compound that releases peroxynitrite, increased bronchoconstrictor responses to SP and ET-1 in anesthetized guinea pigs. In addition, we assayed NEP activity in the airways of SIN-1-exposed guinea pigs. RESULTS: Though SIN-1 (10(-7) M) alone had no effect on pulmonary resistance, pretreatment with SIN-1 significantly enhanced SP- and ET-1-induced bronchoconstriction. Pretreatment with phosphoramidon, an NEP inhibitor, also enhanced SP- and ET-1-induced bronchoconstriction. However, simultaneous administration of phosphoramidon and SIN-1 had no additive effect on SP- and ET-1-induced bronchoconstriction. Peroxynitrite formation by SIN-1 was completely inhibited by N-acetylcysteine (NAC) and glutathione (GSH) in vitro, and pretreatment with NAC and GSH significantly reversed the potentiation by SIN-1 of SP-induced bronchoconstriction. In addition, the NEP activity of the trachea after SIN-1 exposure was significantly reduced compared to the level in control guinea pigs (solvent for SIN-1: 30.0+/-4.2 fmol.min(-1).mg tissue(-1); 10(-7) M SIN-1; 15.5+/-4.5 fmol.min(-1).mg tissue(-1), p<0.05). CONCLUSIONS: These findings suggest that peroxynitrite induces airway hyperresponsiveness to SP and ET-1 through the inactivation of airway NEP, and that peroxynitrite is an important mediator of the alterations in airway functions.

Animals↗

Plasma endothelin-1 level in chronic obstructive pulmonary disease: relationship with natriuretic peptide.

BACKGROUND AND OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). METHOD: We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). RESULTS: Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = -0. 503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0. 533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01). CONCLUSION: We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

Aged↗

Guinea pig airway hyperresponsiveness induced by blockade of the angiotensin II type 1 receptor. Role for endogenous nitric oxide.

Losartan is the first angiotensin II type 1 (AT1) receptor antagonist to become available for the treatment of hypertension. However, recent reports have revealed several cases of losartan-induced bronchoconstriction. We investigated to determine the mechanism of losartan-induced bronchoconstriction, considering in particular the involvement of endogenous nitric oxide (NO). In this study, we examined the effects of losartan on airway obstruction and endogenous NO production using anesthetized guinea pigs and cultured airway epithelial cells. Five minutes after administration of angiotensin II (Ang II), the bronchoconstriction induced by acetylcholine was not changed. In contrast, Ang II in the presence of losartan caused a significant increase in the acetylcholine responsiveness. Pretreatment with L-N omega-nitroarginine-methylester (L-NAME) potentiated acetylcholine-induced bronchoconstriction 5 min after administration of Ang II, and L-arginine reversed this action of L-NAME on the acetylcholine responsiveness. Moreover, Ang II administration increased NO concentration in expired air (12.5 +/- 1.5 ppb for saline, 40 +/- 5 ppb for Ang II, p < 0.01), and losartan significantly inhibited Ang II-stimulated NO release (20 +/- 3.5 ppb) from guinea pig airway. In cultured airway epithelial cells, Ang II also increased NO release (160 +/- 25 nM), and the effect of this Ang II-induced NO release was significantly inhibited by pretreatment with losartan (25 +/- 8 nM, p < 0.01). These findings suggest that losartan-induced bronchoconstriction may result from inhibition of endogenous NO release in the airway.

Acetylcholine↗

Inhibition of bronchoprotective effects of beta2-adrenoceptor agonists by peroxynitrite in guinea pig airways.

Peroxynitrite plays an important role in the pathogenesis of inflammatory diseases, including those affecting the lung. In inflamed airways, simultaneous cellular production of superoxide anion (.O2-) and nitric oxide (NO) may occur, potentially resulting in continuous formation of peroxynitrite. However, because peroxynitrite has a short half-life, its in vivo physiologic effects in the airways may not be sufficiently evaluated with a single administration. Accordingly, this study was designed to use 3-morpholinosydnonimine (SIN-1), a compound that releases peroxynitrite, to determine whether peroxynitrite could alter airway beta2-adrenoceptor (beta2-AR) function in anesthetized guinea pigs. Though SIN-1(10(-)7 M) alone had no effect on pulmonary resistance, pretreatment with SIN-1 significantly attenuated isoprenaline- and salbutamol-induced bronchoprotection against acetylcholine. Pretreatment with SIN-1 also attenuated forskolin-induced bronchoprotection. S-Nitroso-N-acetylpenicillamine (SNAP), a potent NO donor, did not have the same effect as SIN-1. N-Acetylcysteine and glutathione each significantly reversed the inhibitory effect of SIN-1 on isoprenaline-induced bronchoprotection in a dose-dependent manner. These striking findings suggested that peroxynitrite, but not NO, is an important mediator of alteration of beta2-AR function in airway smooth muscle. Additionally, the action of peroxynitrite seems to be directed either at adenylate cyclase activity or at effects downstream of such activity.

Acetylcholine↗

A case of diffuse pulmonary arteriovenous fistula.

A 30-year-old Japanese woman was admitted to hospital for dyspnea. She had a history of corrective surgery for a large atrial septal defect and partial anomalous pulmonary venous drainage, which had produced cyanosis in her infancy. However, her cyanosis continued postoperatively. Angiography revealed a double inferior vena cava (IVC), with the left IVC connected with the hemiazygos vein and the right IVC with the left atrium through a very small orifice. Most of the blood from the 2 IVCs flowed into the superior vena cava via the distended azygos and hemiazygos veins. Pulmonary arteriography revealed no abnormal structures. Pulmonary arterial pressure was normal. There was marked pulmonary venous oxygen desaturation. Perfusion lung scintigraphy revealed multiple segmental perfusion defects. These findings suggested the presence of diffuse microscopic pulmonary arteriovenous fistulas bilaterally in the lungs. The patient appears to be the first reported adult case of microscopic and diffuse arteriovenous fistulas. Neither resection of the arteriovenous fistulas nor corrective surgery for the diversion was indicated, and heart-lung transplantation might be the only treatment able to relieve her dyspnea.

Adult↗