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Y Hirano

Publications and source records attributed to Y Hirano.

At least 19 recordsLinked to original sources
PubMed1999

A new, simple method for measuring mucociliary clearance in guinea-pigs.

Airway mucociliary transport (MCT), which continuously removes inhaled particles and cellular debris from deep in the lung, is impaired in a number of diseases such as bronchitis and asthma. In order to determine the effects of candidate drugs on MCT function in the airway, a new in situ method to measure MCT function was established. MCT function is represented by the distance a gelatin solution containing Evans blue as a marker moves after injection into the trachea. The basal rate of dye transport in non-treated guinea-pigs was 4.4+/-0.2 mm/min. The beta2-adrenoceptor agonist salbutamol (2, 6, 10, 20 mg/kg, po), dose-dependently accelerated the basal MCT rate. However, its effect was completely inhibited by pretreatment with the non-selective beta -adrenoceptor antagonist, propranolol (1 mg/kg, iv). MCT function in guinea-pigs was significantly attenuated to 2.6+/-0.3 mm/min by SO2 gas exposure. Salbutamol failed to prevent MCT dysfunction in SO2-exposed animals at doses previously shown to accelerate basal MCT rate. This simple method is useful for estimating MCT function in several airway disease models and for examining new drugs designed to improve MCT function in airway diseases.

Adrenergic beta-Antagonists↗
PubMed1999

Emergence and spread of a new clone of M type 1 group A Streptococcus coincident with the increase in invasive diseases in Japan.

BACKGROUND: In Japan invasive group A streptococcal infections such as sepsis and toxic shock syndrome (TSS) have increased since 1992. As is the case in the United States and Europe, M1 serotype is predominant among the isolates from Japanese patients. METHODS: By restriction enzyme digestion and pulsed field gel electrophoresis, we investigated the whole genomic DNA profiles of 95 M type 1 group A streptococcal strains isolated from patients with serious diseases including sepsis, toxic shock syndrome, necrotizing fasciitis and nonsuppurative complications and with uncomplicated pharyngitis during 1979 through 1996 in Japan. RESULTS: The genome profiles among 8 of 10 isolates from patients with serious diseases in 1979 through 1991 were all the same and were shared by the profiles of the 35 of 48 isolates from patients with uncomplicated pharyngitis in 1982 through 1991. All 18 strains isolated from patients with invasive diseases in 1992 to 1996 had a unique profile, which was shared by the profiles of 18 of 19 isolates from uncomplicated pharyngitis during the same period. This genomic profile was distinct from the predominant or any other profiles before 1992, and it was found to be a new clone. CONCLUSIONS: The emergence and spread of this new clone of M type 1 Streptococcus after 1991 may be associated with the increase in invasive streptococcal infections that occurred during the same period in Japan. Genomic profiles as well as serotypes of streptococcal isolates are important for the epidemiology of clinical relevance in streptococcal diseases.

Child↗
PubMed1999

[Extended resection of the great vessels for primary lung cancer and mediastinal tumor].

From 1973 to 1998, we resected and reconstructed the great vessels in 44 patients with primary lung cancer or mediastinal tumor. Among them, 39 patients (28 with lung cancer and 11 with mediastinal tumor) and 5 patients (all with lung cancer) underwent reconstruction of the superior vena cava (SVC) and aorta, respectively. The SVC was repaired by expanded polytetrafluoroethylene (EPTFE) graft (n = 8), prosthetic patch (n = 5) or direct suture (n = 26). The aorta was repaired with temporary subclavian artery-descending aorta (n = 3), or left atrium-femoral artery bypass (n = 2). No complication or operative death occurred after surgery. The survival rate of the patients with lung cancer who underwent SVC reconstruction at 3 year and 5 year were 26.2% and 11.2%, respectively. Five of 11 (45.5%) patients with mediastinal tumor are alive at 5 years. We concluded that extended resection for primary lung cancer or mediastinal tumor invading the SVC is acceptable operation method for some patients.

Adult↗
PubMed1999

[Monozygotic twins with suspected hereditary sensory and autonomic neuropathy (HSAN) type V].

We report a pair of 1-year-5-month-old female monozygotic twins with generalized loss of pain sensation, but without impairment of other sensory modalities and the diaphoretic function. Routine electrophysiological investigations revealed no abnormalities. Morphometric analysis of biopsied sural nerve showed that the number of small myelinated fibers was reduced and that of unmyelinated fibers was normal or mildly reduced. On the basis of these findings, we suspected a diagnosis of a rare disorder, HSAN type V, which has not previously been reported in Japan.

Diseases in Twins↗
PubMed1999

[Endothelial-derived nitric oxide mediates the peripheral vasodilatory effects of amrinone in humans].

Amrinone, which is used for the treatment of acute congestive heart failure, has vasodilatory and positive inotropic effects through the increment of intracellular cyclic adenosine monophosphate. Recent in vitro investigations have shown that amrinone has an endothelium-dependent vasodilatory effect. The present study examined whether amrinone shows this endothelium-dependent vasodilatory effect in human peripheral vessels. Forearm blood flow during intra-arterial infusion of graded doses (12.5, 25, 50, 100, 200 micrograms/min) of amrinone was measured using plethysmography in 10 healthy subjects without organic vascular disease before and after nitric oxide synthase blocking with NG-monomethyl-L-arginine (L-NMMA, 400 mumol). The graded dose of amrinone produced progressive increases in amrinone plasma concentrations, and a dose over 100 micrograms/min caused amrinone plasma concentrations of more than 1.0 microgram/ml. The increase in forearm blood flow in response to amrinone was significantly depressed after L-NMMA doses of less than 100 micrograms/min, but the increase in forearm blood flow during infusion of higher doses (100, 200 micrograms/min) was not affected by L-NMMA. These results suggest that endothelial-derived nitric oxide may partially contribute to amrinone-induced vasodilation in humans. Thus, the vasodilatory effect of amrinone might be impaired in patients with endothelial dysfunction.

Adult↗
PubMed1999

Effect of overproduction of interleukin 5 on dinitrofluorobenzene-induced allergic cutaneous response in mice.

The effect of overproduction of interleukin (IL) 5 on the allergic cutaneous response was investigated in transgenic mice overexpressing IL-5. Five repeated topical applications of 2, 4-dinitrofluorobenzene (DNFB) to the ears of mice resulted in allergic dermatitis on the ears as well as significant elevation in dinitrophenol-specific IgE antibody and total IgE in the serum in both wild-type and transgenic mice. The development of dermatitis as measured by skin thickness and histopathological changes were potentiated in the transgenic mice. In IL-5 transgenic mice, significant accumulation of eosinophils in skin lesions was observed after five paintings of DNFB, and the magnitudes of eosinophilia and IL-5 messenger RNA expression were significantly higher than in wild-type mice. The dinitrophenol-specific and total IgE in the serum were higher in IL-5 transgenic mice. The late phase reaction of IgE antibody-mediated biphasic cutaneous response was potentiated in IL-5 transgenic mice. The magnitudes of vasopermeability increase by passive cutaneous anaphylaxis, serotonin, and platelet-activating factor were similar in both mice. These results indicate that overproduction of IL-5 resulted in the potentiation of DNFB-induced dermatitis by elevation of IgE production, IgE-mediated allergic late-phase cutaneous reaction, and eosinophilia in the skin lesion.

Animals↗
PubMed1998

Telomerase activity as an indicator of potentially malignant adrenal tumors.

BACKGROUND: Telomerase is an enzyme that adds repeated telomere sequences to the ends of chromosome arms. It helps maintain both the length of telomere and infinite cell proliferation. In recent years, telomerase activity has been considered an important characteristic that differentiates between normal and cancerous cells. Because the authors often encountered difficulties in distinguishing between benign and malignant adrenal tumors, they investigated whether the expression of telomerase activity could distinguish potentially malignant adrenal tumors. METHODS: The authors examined telomerase activity in 48 samples of adrenal tumor tissue and 27 samples of adjacent normal adrenal tissue. All samples were obtained from 48 patients who underwent surgery at Hamamatsu University Hospital in Hamamatsu, Japan. Based on the clinical and postoperative pathologic examinations, 45 samples were diagnosed as benign and 3 were diagnosed as malignant. Telomerase activity was examined using a telomerase repeat amplification protocol (TRAP) assay. RESULTS: Of the 48 adrenal tumor samples, 7 (14.6%) had telomerase activity. All adjacent normal adrenal tissues were negative for telomerase activity. Of the telomerase positive samples, two were clinically known adrenocortical carcinoma, and another was metastatic adrenal tumor from lung carcinoma. Four other telomerase positive samples were diagnosed as benign after clinical and initial pathologic examinations. However, two of the patients from whom these samples were taken developed metastatic lesions after adrenalectomy. CONCLUSIONS: A telomerase assay of adrenal tumors may help predict their malignant potential.

Adrenal Gland Neoplasms↗
PubMed1998

Effects of alpha1-adrenergic stimulation on L-type Ca2+ current in rat ventricular myocytes.

The effect of alpha1-adrenergic stimulation on L-type Ca2+ current (ICa,L) in adult rat ventricular myocytes was investigated using three different methods of current recording. During conventional whole-cell recordings with 5 mm-BAPTA included in the pipette solution, phenylephrine (20 microM) did not increase ICa,L after 10 min of application. With nystatin perforated-patch whole-cell recordings, phenylephrine potentiated ICa,L, although there were variations among myocytes. The most frequent response was a transient suppression of peak ICa,L at approximately 2 min of exposure followed by a sustained increase of current amplitude evident after 5-10 min exposure. The relative current amplitude 10 min after phenylephrine application was 1.08+/-0.05 compared to control (n=14 cells,P<0.05). During cell-attached single channel recordings, phenylephrine (1 microM) increased the L-type Ca2+ channel open probability (NPo) by 2.25+/-0.31-fold (n=21,P<0.01). It potentiated NPo by increasing the number of openings per sweep and also by promoting longer openings. These effects developed slowly in approximately 10 min. Phenylephrine had no on unitary current amplitude. The potentiation was also elicited by methoxamine (5 microM) and was blocked by prazosin (1 microM), indicating that it was mediated by alpha1-adrenergic receptor stimulation. The increase in NP(o) was suppressed by chelerythrine, a protein kinase C inhibitor. Our results demonstrate that ICa,L can be enhanced by alpha1-adrenergic stimulation, and stress the importance of not disturbing the intracellular environment during studies of the modulation of cardiac ICa,L by alpha1-adrenergic stimulation.

Adrenergic alpha-Agonists↗
PubMed1998

Role of cardiac chloride currents in changes in action potential characteristics and arrhythmias.

Various types of Cl- currents have been recorded in cardiac myocytes from different regions of the heart and in different species. With few exceptions, most of these currents are not active under basal conditions, but are activated under the influence of various agonists and by physical stress. These channels are distributed nonuniformly, depending on the cell type, tissue and region of the heart. Therefore, Cl- current activation may influence membrane potential and impulse formation differently in different cells, and may play a role in arrhythmogenesis. Among these Cl- currents, the protein kinase A-activated Cl- current (I Cl.PKA), the stretch- or swelling-activated Cl- current (I Cl.SWELL) and the Ca(2+)-activated Cl current (I Cl.Ca) comprise the major anion currents that modify cardiac electrical activity. These currents exhibit outward-going rectification, or are predominantly activated at depolarized voltages and, thus, contribute significantly to shortening of the action potential duration but little to diastolic depolarization. The action potential shortening by Cl- current activation may not only perpetuate reentry by shortening the refractory period in a reentry pathway, but may also prevent the development of early afterdepolarization and triggered activity caused by the prolongation of action potentials. I Cl.Ca contributes to delayed afterdepolarization at diastolic potentials in Ca(2+)-overloaded cells. Another factor limiting the influence of Cl- currents on diastolic potentials is the presence of a predominantly opposing background K+ current, except at the nodal regions that lack these K+ channels, or under conditions of decreased K+ conductance. Therefore, the contribution of Cl- currents to the genesis of arrhythmias may depend on their association with the conductance of other ions, especially that of K+.

Action Potentials↗
PubMed1998

Surgical trauma induces group II phospholipase A2 production by neutrophils at a local site after surgery.

OBJECTIVES: Group II phospholipase A2 (PLA2) regulates eicosanoids and platelet activating factor (PAF) production and plays an important role in regulating critical mediators in inflammatory diseases such as trauma, sepsis and multiple organ failure. To elucidate the local effect of surgical trauma, we investigated the production of group II PLA2 at a local site after surgery. DESIGN AND METHODS: We utilized a radioimmunoassay to measure group II PLA2 levels in peritoneal exudates from the operative field and blood in patients who underwent gastrectomy. We also investigated the production of group II PLA2 in cells from peritoneal exudates by Northern blotting and immunocytochemistry. RESULTS: Immunoreactive group II PLA2 levels were significantly increased from 3 h after surgery and peaked at 12 h peritoneal exudates. However, serum group II PLA2 levels peaked at 24-48 h and decreased gradually after surgery, findings similar to levels of postoperative serum C-reactive protein (CRP). There was no significant correlation between group II PLA2 levels in peritoneal exudates and those in blood. Group II PLA2 mRNA was expressed at high level in cells from peritoneal exudates, by Northern blot analysis, but not those from blood. The localization of group II PLA2 protein was intense in neutrophils, as determined by immunocytochemistry. No group II PLA2 expression was observed in corresponding peripheral blood cells. CONCLUSIONS: After surgery, group II PLA2 is increased in peritoneal exudates prior to elevation in the blood circulation and is produced by neutrophils recruited and activated at a local site. Group II PLA2 produced in peritoneal exudates by neutrophils has an important role in the physiological and pathological states at a local site, after surgery.

Adult↗
PubMed1998

Inhibition of NF-kappaB-dependent transcription of human immunodeficiency virus 1 promoter by a phosphodiester compound of vitamin C and vitamin E, EPC-K1.

We investigated the effect of EPC-K1, which is a phosphodiester compound of vitamin E and vitamin C, on NF-kappaB activity in human cultured astrocytoma cells T98G. In TNFalpha-stimulated T98G cells, treatment with EPC-K1 inhibited both DNA binding activity and transactivation of NF-kappaB in a dose-dependent manner, and the suppressive effect of EPC-K1 was stronger than either that of vitamin E or vitamin C. Moreover, we showed that in TNFalpha-stimulated T98G cells treatment with EPC-K1 repressed NF-kappaB-dependent activation of the human immunodeficiency virus 1 promoter. In contrast, TNFalpha-induced activation of the human immunodeficiency virus 1 promoter was not completely inhibited by either treatment with vitamin E or vitamin C. We, thus, suggest that EPC-K1 is considered to be one of the inhibitory agents of NF-kappaB.

Antioxidants↗
PubMed1998

Recurrent aciclovir-resistant herpes simplex in a child with Wiskott-Aldrich syndrome.

A boy with Wiskott-Aldrich syndrome suffered from thymidine kinase (TK)-altered and aciclovir-resistant herpes simplex virus type 1 (HSV-1) skin infections. He presented with severe herpes simplex around the left eye in March 1993 at the age of 8 years. HSV-1 strain TAS was isolated and was shown to be susceptible to aciclovir (50% inhibitory concentration (IC50) 0.23 microg/mL). He was treated with intravenous (i.v.) high dose aciclovir, 2 mg/kg per h, which produced an improvement. About 1 year later (May 1994), a severe herpes simplex infection appeared on his face, arm, genitalia, back and foot. Treatment with i.v. aciclovir, 2 mg/kg per h, was initiated, but the skin lesions did not improve. HSV-1 strain TAR was isolated and was shown to be resistant to aciclovir (IC50 36 microg/mL). HSV-1 TAR and TAS were susceptible to vidarabine (IC50 4. 4 and 2.9 microg/mL, respectively). The skin lesions were treated with i.v. vidarabine, 15-20 mg/kg per day, and healed satisfactorily. However, in March 1995, the patient again experienced a severe herpes simplex infection around the left eye. HSV-1 strain R95 was isolated and was shown to be resistant to aciclovir (IC50 36 microg/mL). Diminished sensitivity of HSV-1 TAR and R95 to aciclovir was associated with reduced viral TK activity and loss of aciclovir phosphorylation activity.

Acyclovir↗
PubMed1998

Denture mobility with six degrees of freedom during function.

The purpose of this study was (1) to assemble and verify a system to measure the three-dimensional (3-D) movement of the upper and lower complete dentures and the movement of the mandible simultaneously, and (2) to analyse the relation between denture movements and the path of closure of the mandible during function. A 3-D motion capture system with four infrared TV cameras was used for this purpose. The relation between the dentures and the mandibular movements was analysed through the change of the inner product of normal vectors of the denture occlusal planes and mandibular planes. The mandibular movements were classified into two types; the normal stroke (the path of closure was on the ipsilateral side of mastication) and the reverse stroke (on the contralateral side). The results showed that the system could measure the denture mobility within a 0.3 mm error. The mobility of the upper dentures had a correlation to the path of closure of the mandible regardless of the working side or nonworking side, and the lower dentures had a tendency to move toward the working side.

Aged↗
PubMed1998

[A patient with Streptococcus intermedius brain abscess treated with high dose penicillin G--susceptibility of the isolate to penicillin G and the concentration of penicillin G in cerebrospinal fluid].

We report here a 2-year-old boy with a Streptococcus intermedius brain abscess and bilateral ventriculitis successfully treated with a high dose penicillin G (200,000 U/kg/dose, 6 times a day, 1 hour continuous infusion). Although hydrocephalus residuced, the high dose penicillin G therapy cured his brain abscess and bilateral ventriculitis. The minimal inhibitory concentration of penicillin G to the isolate was 0.008 microgram/ml. The penicillin G concentration in the cerebrospinal fluid after 2 hours from the infusion was about 5 micrograms/ml. S. intermedius must be considered as one of the causative agents for brain abscess. High dose penicillin G therapy is one choice of treatment for brain abscess due to penicillin-susceptible streptococci.

Brain Abscess↗
PubMed1998

Functional interference of Sp1 and NF-kappaB through the same DNA binding site.

Gene activation by NF-kappaB/Rel transcription factors is modulated by synergistic or antagonistic interactions with other promoter-bound transcription factors. For example, Sp1 sites are often found in NF-kappaB-regulated genes, and Sp1 can activate certain promoters in synergism with NF-kappaB through nonoverlapping binding sites. Here we report that Sp1 acts directly through a subset of NF-kappaB binding sites. The DNA binding affinity of Sp1 to these NF-kappaB sites, as determined by their relative dissociation constants and their relative efficiencies as competitor DNAs or as binding site probes, is in the order of that for a consensus GC box Sp1 site. In contrast, NF-kappaB does not bind to a GC box Sp1 site. Sp1 can activate transcription through immunoglobulin kappa-chain enhancer or P-selectin promoter NF-kappaB sites. p50 homodimers replace Sp1 from the P-selectin promoter by binding site competition and thereby either inhibit basal Sp1-driven expression or, in concert with Bcl-3, stimulate expression. The interaction of Sp1 with NF-kappaB sites thus provides a means to keep an elevated basal expression of NF-kappaB-dependent genes in the absence of activated nuclear NF-kappaB/Rel.

Animals↗
PubMed1998

Structures of P-type transporting ATPases and chromosomal locations of their genes.

P-type ATPases (E1E2-ATPases) are primary active transporters which form phospho-intermediates during their catalytic cycle. They are classified into P1 to P4 based on the primary structure and potential transmembrane segments. Although the classic P-type ATPases are cation transporters, two new members have recently been found; one is a flippase catalyzing the flip-flop movement of aminophospholipids, but the substrate and function of the other one remain unknown. It would be interesting to determine whether the cations and aminophospholipids are transported by similar or different mechanisms. P-type ATPases are believed to have been derived from a common ancestor, and their genes are found to be distributed in various chromosomal loci. However, gene duplication events can be traced from the tandem arrangement of genes and their linkage map. Na+/K+- and H+/K+-ATPases have not only closely related a subunits but also similar beta subunits. Renal Na+/K+-ATPase has an additional subunit gamma. Similar small polypeptides (phospholemman, Mat-8 and CHIF), which induce Cl- and K+ currents, have been found. The idea of their functional and structural coupling with P-type ATPases, especially with H+/K+-ATPase, is intriguing. Each P-type ATPase must have specific domains or sequences for its intracellular trafficking (sorting, retention and recycling). Identification of such regions and studies on the molecules playing role in their recognition may facilitate the unveiling of various cellular processes regulated by P-type ATPases.

Adenosine Triphosphatases↗
PubMed1998

[The effects of YM26818: 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea and derivatives on pulmonary surfactant secretion and lung compliance].

To discover a novel compound which has an effect on pulmonary surfactant (PS) secretion, we studied the effects of various compounds on PS secretion by measuring the contents of PS in the bronchoalveolar lavage (BAL) fluid in guinea pigs. In the chemical modification study of ambroxol, which is known as a PS secretagogue, and a compound we discovered from our compounds library, 1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea: YM-26818 (the increasing effect on PS in BALF, 34.7% at 50 mg/kg, i.p.). In the surfactant deficient model induced by BAL in guinea pigs, YM-26818 (5 and 10 mg/kg, p.o.) significantly increased the contents of PS in the BAL fluid compared with that of control animals (5 mg/kg: 60.3 +/- 8.0, 10 mg/kg: 59.4 +/- 4.3% increase). Concomitantly by these effects, the recovery of lung compliance was observed in this model (AUC of lung volume, control: 560 +/- 15, YM-26818 5 mg/kg: 898 +/- 51, YM-2681 10 mg/kg: 956 +/- 11 ml.min). These results may indicate that YM-26818 is useful for the therapy of adult respiratory distress syndrome (ARDS) and obstructive pulmonary diseases.

Animals↗