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Biomedical subjects

Y Hirano

Publications and source records attributed to Y Hirano.

At least 19 recordsLinked to original sources
PubMed1999

Multicenter study of paroxysmal dyskinesias in Japan--clinical and pedigree analysis.

To investigate the clinical features of paroxysmal dyskinesias and carry out a pedigree analysis, we conducted a multicenter survey in Japan. A questionnaire was mailed to 229 medical institutions. A total of 150 patients with paroxysmal kinesigenic choreoathetosis (PKC), including 53 sporadic cases and 97 affected individuals from 32 pedigrees, were identified. The mean age of onset of PKC was 8.8 years, and 80% of the cases were men. Of the 32 pedigrees with familial occurrence, 18 (56%) were compatible with an autosomal-dominant inheritance (AD) with complete penetrance, and seven (22%) had AD with incomplete penetrance; the remaining seven were sibling recurrence cases with apparently healthy parents. In six of seven familial cases with incomplete penetrance, the disease gene was thought to be transmitted by clinically unaffected females. Paroxysmal dystonic choreoathetosis (PDC) was found in five cases, including two sporadic cases and three affected individuals from two pedigrees; the mean age of onset was 0.6 years, and a male predominance was noted (male:female = 4:1). There was one case of paroxysmal hypnogenic dyskinesia and one case of paroxysmal exertion-induced dyskinesia. There is an unexplained male predominance for paroxysmal dyskinesias. When the genetic defect of patients with paroxysmal dyskinesias is identified, the pathophysiology of the disease will become more clear.

Adolescent↗
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

The change of bone mineral density in secondary osteoporosis and vertebral fracture incidence.

Causes of secondary osteoporosis are diverse, and bone changes in this condition have been elucidated less than those in primary osteoporosis. In this study, bone mineral density (BMD) was measured in the lumbar spine, distal and proximal sites of the radius, and calcaneus in representative disorders that cause secondary osteoporosis to evaluate its changes. Also, the incidence of nontraumatic vertebral fracture was examined. The subjects were 80 patients with rheumatoid arthritis, 50 patients undergoing glucocorticoid (steroid) therapy, 20 patients with chronic hepatitis, 24 patients with liver cirrhosis, 14 patients with primary biliary cirrhosis (PBC), 26 patients with diabetes mellitus, and 20 postgastrectomy patients; all were ambulatory female outpatients. Two hundred females with primary osteoporosis were examined as a control group. The reproducibility of the measurement of the BMD was satisfactory at about 3% by all methods of measurement employed. Concerning changes in BMD, periarticular trabecular bone density was most markedly reduced in the rheumatoid arthritis group. The patients receiving steroid therapy showed the greatest decreases in the trabecular bone mineral density at the distal 4% of the radius and lumbar spinal BMD. In addition, the threshold of vertebral fracture was higher in those undergoing steroid therapy than in those with primary osteoporosis. The patients with PBC showed the greatest decreases in BMD among patients with chronic liver disorders, and no decrease in BMD was noted in the chronic hepatitis group. BMD was reduced only in the radius in the patients with diabetic mellitus, and it was generally reduced in the postgastrectomy patients. BMD of the calcaneus was not reduced in any group.

Adrenal Cortex Hormones↗
PubMed1999

Potentiation of recombinant L-type Ca channel currents by alpha1-adrenoceptors coexpressed in baby hamster kidney (BHK) cells.

In cardiac myocytes, the effect of alpha1-adrenergic stimulation on L-type Ca current remains to be clarified. We examined this issue by the transient coexpression of alpha1-adrenoceptors on BHKC12 cells, where recombinant Ca channels composed of cardiac alpha1 subunit and skeletal beta, gamma, alpha2/delta subunits were stably expressed. After transfection of plasmid DNA encoding bovine alpha1C-adrenoceptors, bath-applied phenylephrine potentiated the cloned Ca channel current during perforated-patch whole-cell recording by 26+/-6% in 6 out of 12 cells. The potentiation was elicited also by methoxamine, and was blocked by prazosin. Phenylephrine also increased the channel open probability during cell-attached single channel recording in 7 out of 15 cells. The ratio of successful modulation of Ca channels was in accordance with the ratio of successful expression of alpha1-adrenoceptors, as estimated by beta-galactosidase staining. These results suggest that the stimulation of alpha1C-adrenoceptors is linked to potentiation of cardiac L-type Ca current. BHK cells provide a valuable expression system to study the modulation of Ca channels evoked by a receptor stimulation.

Animals↗
PubMed1999

Preparation of poly(ethylene glycol)-polystyrene block copolymers using photochemistry of dithiocarbamate as a reduced cell-adhesive coating material.

This article reports a novel preparation method of poly(ethylene glycol) (PEG)-polystyrene (PST) amphiphilic block copolymers with well-defined block lengths by using photopolymerization of an iniferter, benzyl N,N-diethyldithiocarbamate. PEG macroiniferters, which were prepared by end-capping of PEG monomethyl ethers with benzyl N,N-diethyldithiocarbamate group at one end, were irradiated with UV light in the presence of styrene (ST). NMR analyses showed that the PST block was chain-extended from the PEG block, resulting in the preparation of PEG-PST block copolymers. The number-average molecular weights of the copolymers increased almost linearly with irradiation time, light intensity, and concentration of ST. The polydispersities of the copolymers remained relatively small throughout the reaction (Mw/Mn approximately 1.3). The composition of two PEG-PST block copolymers thus obtained was as follows: PEG (Mn; 1.9 x 10(3) gmol(-1))-PST (3.0 x 10(3) gmol(-1)) and PEG (4.9 x 10(3) gmol(-1))-PST (2.6 x 10(3) gmol(-1)). These copolymers were coated onto a poly(ethylene terephthalate) film surface. X-ray photoelectron spectroscopy analyses and water wettability measurements showed that the PST block was enriched at the outermost layer as cast in air, whereas upon immersion into water, the PEG block was oriented toward water. Enhanced wettability was observed for the diblock copolymer with a higher PEG content. Significantly reduced cell adhesion was observed on both the coated surfaces. Thus, the PEG-PST block copolymer may function as a cell adhesion-resistant coating which reduced cell-substrate interaction.

Animals↗
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

Study on the early-onset variant of benign childhood epilepsy with occipital paroxysms otherwise described as early-onset benign occipital seizure susceptibility syndrome.

PURPOSE: We studied the early-onset variant of benign childhood epilepsy with occipital paroxysms (EVBCEOP) proposed by Panayiotopoulos, to confirm whether his five criteria are sufficient to delineate EVBCEOP as a new epileptic syndrome, as well as to predict a good outcome prospectively at the time of the first examination. SUBJECTS: The subjects were 649 children with localization-related epilepsies (LREs) observed in our hospital for >4 years. METHODS: We applied the International Classification of Epilepsies and Epileptic Syndromes to the 649 patients and identified patients who had EVBCEOP from among those with nonspecific idiopathic LRE. The inclusion criteria were to satisfy all five criteria and all but one criterion (i.e., either ictal vomiting or occipital EEG paroxysms). We were blind as to the outcomes and selected patients who satisfied the following three of the five criteria at the time of the first examination, (a) normal development before the onset, (b) epilepsy onset age between 2 and 8 years, and (c) occipital EEG foci. We attempted to determine whether the outcome can be predicted prospectively, and whether the presence or absence of ictal vomiting affects the prognosis. RESULTS: We identified 19 patients who satisfied all five criteria, 22 who exhibited all but occipital EEG foci, and 21 who exhibited all but ictal vomiting. The incidence of status convulsivus was higher in those with ictal vomiting than in those without ictal vomiting (p < 0.05). Interictal EEG performed every 6 months showed shifting and multiplication of EEG foci in 42 and 52% of all subjects, respectively. We identified 57 patients, 42 (74%) of whom were in remission by age 12 years. The number of patients who experienced remission did not differ significantly between those with (76%, n = 25) and without (72%, n = 32) ictal vomiting (p > 0.05). CONCLUSIONS: Nosologically, EVBCEOP appears to constitute the earliest form of idiopathic epileptic syndrome different from classic BCEOP. However, its clinical spectrum, ranging from the absence of ictal vomiting to a combination of extraoccipital and multifocal EEG foci, is broad, such that further prospective study is expected to reveal the exact prerequisite criteria for determining the border of this epileptic syndrome and for clarifying the clinical spectrum within this syndrome.

Adolescent↗
PubMed1999

Prepulse-induced mode 2 gating behavior with and without beta-adrenergic stimulation in cardiac L-type Ca channels.

Mode 2 gating of L-type Ca channels is characterized by high channel open probability (NPo) and long openings. In cardiac myocytes, this mode is evoked physiologically in two apparently different circumstances: membrane depolarization (prepulse facilitation) and activation of protein kinase A. To examine whether the phosphorylation mechanism is involved during prepulse-induced facilitation of cardiac L-type Ca channels, we used isolated guinea pig ventricular myocytes to analyze depolarization-induced modal gating behavior under different basal levels of phosphorylation. In control, NPo measured at 0 mV was augmented as the duration of prepulse to +100 mV was prolonged from 50 to 400 ms. This was due to the induction of mode 2 gating behavior clustered at the beginning of test pulses. Analysis of open time distribution revealed that the prepulse evoked an extra component, the time constant of which is not dependent on prepulse duration. When isoproterenol (1 microM) was applied to keep Ca channels at an enhanced level of phosphorylation, basal NPo without prepulse was increased by a factor of 3.6 +/- 2.2 (n = 6). Under these conditions, prepulse further increased NPo by promoting long openings with the same kinetics of transition to mode 2 gating (tau congruent with 200 ms at +100 mV). Likewise, recovery from mode 2 gating, as estimated by the decay of averaged unitary current, was not affected after beta-stimulation (tau congruent with 25 ms at 0 mV). The kinetic behavior independent from the basal level of phosphorylation or activity of cAMP-dependent protein kinase suggests that prepulse facilitation of the cardiac Ca channel involves a mechanism directly related to voltage-dependent conformational change rather than voltage-dependent phosphorylation.

Adrenergic beta-Agonists↗
PubMed1999

MR imaging of hepatic injury in the LEC rat under a high magnetic field (7.05 T).

Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T1 and T2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the T1 and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.

Animals↗
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

Nucleotide sequence of thymidine kinase gene of sequential acyclovir-resistant herpes simplex virus type 1 isolates recovered from a child with Wiskott-Aldrich syndrome: evidence for reactivation of acyclovir-resistant herpes simplex virus.

Recurrent acyclovir (ACV)-resistant (ACV-r) herpes simplex virus type 1 (HSV-1) infections occurred in a patient with Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency syndrome composed of three clinical characteristics of immunodeficiency, thrombocytopenia, and an eczematous dermatitis. The patient had severe and recurrent ACV-r herpes simplex and was treated with vidarabine in a satisfactory manner from 1993 to 1997. During the 4-year observation period, two ACV-sensitive (ACV-s) HSV-1 isolates and five ACV-r HSV-1 isolates were recovered. The nucleotide sequence of the thymidine kinase (TK) gene from these sequential ACV-r isolates was compared with the ACV-s isolates. A single nucleotide deletion of cytosine (C) from homopolymer stretch of four C residues between nucleotide 1061 and 1064 of the open reading frame was found in all ACV-r isolates. No other differences were observed in the TK nucleotide sequence between ACV-s and ACV-r isolates. The TK nucleotide sequences of the two ACV-s isolates were identical to each other and those of the five ACV-r isolates were identical to one another. These results suggest that the ACV-r HSV-1 might have derived from the ACV-s strain in the patient body and that TK-associated ACV-r HSV-1 can reactivate from latency.

Acyclovir↗
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↗