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Biomedical subjects

H Miyahara

Publications and source records attributed to H Miyahara.

At least 37 records · Page 2Linked to original sources

Effect of intravenous vasopressin on endocochlear potential and systemic blood pressure in the guinea pig.

The effects of intravenous arginine-vasopressin (AVP) on the endocochlear potential (EP) and systemic blood pressure (BP) were examined in the guinea pig. Intravenous AVP (10(-7) M) elevated BP significantly but did not change EP. AVP (10(-8) M) produced a significant decrease in the amplitude of EP but did not change mean blood pressure significantly. AVP at 10(-9) M did not affect EP or BP. These results suggest that intravenous AVP might have an inhibitory effect on EP.

Animals↗

Selective expression of mercurial-insensitive water channel (AQP-4) gene in Hensen and Claudius cells in the rat cochlea.

We investigated the cellular localization of mercurial-insensitive water channel (MIWC) mRNA in the rat cochlea. MIWC gene expression was detected in the supporting cells in Corti's organ. The function of these supporting cells is not clear, but the results suggest that they reabsorb water and play a role in maintaining the ionic balance of inner ear fluids.

Animals↗

The neurosteroid pregnenolone sulfate excites medial vestibular nucleus neurons.

To examine the relationship between neurosteroids and vertigo we performed electrophysiological studies to determine whether pregnenolone sulfate (PS) affects the activity of medial vestibular nucleus (MVN) neurons in alpha-chloralose-anesthetized cats. Single neuronal activities in the MVN were recorded extracellularly using a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. 3 mM PS, 1 M glutamate and 3 mM NaCl were applied microiontophoretically in the immediate vicinity of the target neurons. The effects of these drugs were then examined on type I and type II neurons, identified by their responses to horizontal and sinusoidal rotations. The iontophoretic application of PS dose-dependently increased the spontaneous firing of both type I and type II neurons. The larger increase in firing was observed in type I neurons as compared with type II neurons following the PS application. These results suggest that PS excites types I and II neurons differentially, presumably resulting in a disturbance of harmony of the vestibulo-ocular reflex with ensuing development of vertigo.

Animals↗

Vestibular neuronal function of cats following unilateral vertebral artery occlusion.

Since vertigo is known to be caused by vertebrobasilar arterial occlusive disease (ex. vertebrobasilar insufficiency; VBI), an electrophysiological study was performed to examine the effects of a unilateral vertebral artery (VA) occlusion on the neuronal activities of the medial vestibular nucleus (MVN) and vestibular ganglion (VG) in alpha-chloralose-anesthetized cats. Single neuronal activity in the MVN and VG was recorded extracellularly with a glass-insulated silver wire microelectrode. When the unilateral VA was occluded for 5 min. the spontaneous firing rate in the MVN was altered as follows. The type A pattern exhibited a transient increase, followed by a decrease. The type B pattern showed a gradual decrease, and no further changes after the onset of occlusion. Type A and B patterns were observed respectively in MVN ipsi- and contra-lateral to the VA occlusion. In contrast, the VG neuronal firing rate was not affected by the occlusion. These results seem to support the clinical suggestion that the vertigo in VBI is produced by a difference in the function between the bilateral vestibular nuclei. rather than by the peripheral vestibular nerve.

Animals↗

Inner ear blood flow in the rat after unilateral arterial occlusion in the vertebrobasilar arterial system.

It is generally accepted that certain kinds of vertigo and hearing disturbances are caused by blood flow insufficiency in the vertebrobasilar arterial system. Using the microsphere method we investigated whether unilateral vertebral artery or unilateral posterior inferior cerebellar artery occlusion could cause an imbalance between right and left inner ear blood flow in rats. We also studied the differential vulnerability between blood flow in the cochlea and in the ampullae of the three semicircular canals. We counted the numbers of microspheres distributed to the cochlea (CO) and microspheres distributed to three ampullae of semicircular canals (SC) under a microscope with the surface preparation method. The results were as follows: i) no imbalances were observed between bilateral CO or SC even in animals with arterial occlusion, and ii) the CO/SCs of animals with arterial occlusion were not significantly different from that of the control animals. These findings suggest that total inner ear blood flow over a certain period of time was even between the ears bilaterally even in animals with arterial occlusion. The blood flow in the ampullae of the three semicircular canals was not more or less affected by arterial occlusion than the blood flow in the cochlea.

Animals↗

Four cases of vertebrobasilar insufficiency.

Four cases of vertebrobasilar insufficiency are reported. Case 1 was a 38-year-old man who felt a sudden onset of dizziness when he turned his head to the back. An abnormal positional nystagmus was observed when he rotated his head to the left. A magnetic resonance angiogram (MRA) demonstrated total occlusion of the left vertebral artery (VA). Case 2 was a 31-year-old woman who had a total occlusion of her left VA as observed in the MRA. Case 3 was a 68-year-old man who noted dizziness. The systolic blood pressure change on his Schellong test was 28 mmHg. On his MRA, severe displacement of the basilar and the vertebral arteries was visible. Case 4 was a 76-year-old woman who noted a blackout-like sensation. Optokinetic nystagmus was noted with a hyponystagmus pattern, and an eye tracking test showed a saccadic pattern. On her MRA, the vertebrobasilar system was narrowed. The arterial architecture and any stenosis of the blood vessels could be detected non-invasively by MRA.

Adult↗

MR-angiographic findings of patients with central vestibular disorders.

Magnetic resonance angiography (MRA) is a new, noninvasive, and useful method to estimate the posterior circulation in patients with vertigo. From June 1995 to May 1997, 180 patients were examined by magnetic resonance imaging (MRI) and MRA in our department. One hundred and forty-seven patients were vertiginous patients. We measured the displacement angle of the basilar artery with MRA, and examined the relationship between the findings from some neurological examinations and MRA findings in patients with vertigo and dizziness. One hundred and forty-seven patients with vertigo or dizziness were examined by MRI and MRA. They were diagnosed with MRI images in addition to several neurological examinations. MRA was not used for the diagnosis but rather for measuring the displacement angle of the basilar artery. Eighty-six cases with central vestibular disorders, 11 cases with vertebrobasilar insufficiency, and 26 cases with autonomic nerve disorders were recognized. In the cases of central vestibular disorders, the incidences of hyperlipidemia and hypotension were higher than the incidence of anemia. The average displacement angle of the basilar artery (n = 180) was 153.4 degrees +/- 39.4 degrees (mean +/- S.D.). MRA findings were classified into five categories. Ten patients were classified as category III, which represented unilateral partial vertebral artery stenosis. The detection rate for category III and IV abnormalities by neurological examination was higher than that for the other categories. MRI and MRA are important methods to examine patients with central nervous disorders. Distal vertebral artery stenosis may carry a higher risk of a stroke than brainstem infarction.

Autonomic Nervous System Diseases↗

Magnetic resonance imaging (MRI) test in hemodynamic vertebro-basilar insufficiency.

We investigated the efficiency of analysis by magnetic resonance imaging (MRI) in cases of hemodynamic vertebro-basilar insufficiency (VBI). We enrolled 76 cases of hemodynamic VBI who had visited our clinic in the Department of Otolaryngology, Nara Medical University, from 1994 to 1996. The evaluation of MRI was classified according to the degree of ventricular dilatation, callosal degeneration, and lacunar infarction, and the evaluation of MR angiography (MRA) was classified according to the degree of pathological change of the blood vessels. There was a significant difference in lacunar infarction on the MRI findings between VBI cases and normal controls, and there were also significant differences in side differences in the vertebral artery between VBI cases and peripheral vertigo and normal control patients. We propose an etiology for hemodynamic VBI: a functional cerebral circulation disorder causes ischemia of the basal ganglia and leads to lacunar infarctions; furthermore, the side difference between the two vertebral arteries causes a circulation disorder in the vertebrobasilar system.

Basilar Artery↗

Restricted TCR V alpha repertoire in the T cell response to a tolerogenic determinant of type II collagen.

Tolerization of B10.RIII mice (H-2r) with i.v.-injected type II collagen (CII) renders the animals resistant to induction of collagen-induced arthritis (CIA). The B10.RIII mouse is of particular interest, in that the T cell determinants that induce tolerance are different from those that induce arthritis. To characterize T cells that react with the tolerogenic determinant and play a role in regulation of arthritis, we have developed a panel of T cell hybridomas reactive with the tolerogenic T cell epitope, CII 607-621. None of the hybrids cross-reacted with either the arthritogenic CII 445-453 or murine CII. As determined by PCR and immunofluorescence, the T cell response to the tolerogenic determinant was oligoclonal, with evident preferential usage of V alpha. Through the analysis of a large panel of T cell hybridomas, preferential usage of V alpha2, J alpha44, J beta2.7, and D beta2.1 was observed. Characterization of T cells reactive with the immunodominant determinant, CII 607-621, responsible for the induction of tolerance should prove important in developing novel therapeutic approaches for the treatment of autoimmune diseases.

Amino Acid Sequence↗

Thrombin activates NF-kappa B through thrombin receptor and results in proliferation of vascular smooth muscle cells: role of thrombin in atherosclerosis and restenosis.

We investigated the role of thrombin in the pathogenesis in atherosclerosis and restenosis. First we examined the effect of thrombin on cultured human vascular smooth muscle cells (VSMC). We showed that thrombin acts as a mitogen on VSMC through thrombin receptor. The expression of thrombin receptor was increased in the cell lines of VSMC established from directional coronary atherectomy (DCA). This is more pronounced in the cells from patients with restenosis after PTCA. Next we investigated the signaling pathway from thrombin/thrombin receptor. Thrombin activates thrombin receptor resulting in the exposing of the agonist peptide domain (thrombin receptor agonist peptide, TRAP). The signal from thrombin/thrombin receptor activated protein C kinase, tyrosine kinase, and MAP kinase and resulted in NF-kappa B activation. Furthermore, treatment of the cells with antisense p65 oligodeoxynucleotides of NF-kappa B inhibited the thrombin-stimulated growth of VSMC in vitro. These results suggest that thrombin may have a role in the pathogenesis of atherosclerosis and restenosis after PTCA through the thrombin receptor.

Arteriosclerosis↗

Aberrant glycosylation based on the neo-expression of poly-N-acetyllactosamine structures in squamous cell carcinomas of the head and neck.

An immuno- and lectin-histochemical study was performed to investigate the aberrant expression of blood group-related antigens and poly-N-acetyllactosamine structures in squamous cell carcinomas of the maxillary sinus, the larynx, the apipharynx, the hypopharynx, the oral cavity, the parotid gland and the tonsil from 52 patients using monoclonal antibodies against A, B and H antigens, and six lectins, UEA-I, PNA, VVA-B4, PWM, LEA and DSA. In addition, GSA-II staining following endo-beta-galactosidase digestion procedure was also applied. A, B and H antigens were expressed in most normal epithelial cells of head and neck organs, and depended on the patient blood type. However, in squamous cell carcinoma, A antigen was not detected in eight out of 25 individuals of blood groups A and AB, although B antigen was consistently expressed in carcinoma cells from all the B and AB individuals. On the other hand, H antigen was expressed in carcinoma cells not only from all blood group O individuals, but from 32 out of 35 individuals of blood groups A, B and AB. T and Tn antigens, which are recognized by PNA and VVA-B4, were strongly expressed in carcinoma cells from 40 and 42 out of 52 individuals respectively. Reactivity with GSA-II staining following endo-beta-galactosidase digestion, which recognizes linear poly-N-acetyllactosamine structures, was found in a few malignant cells from 21 individuals. Staining with anti-A, -B and -H monoclonal antibodies and UEA-I lectin was diminished after endo-beta-galactosidase digestion in some cases. Lectins specific for poly-N-acetyllactosamine, such as PWM, LEA and DSA, exhibited reactivity in some malignant cells from 30, 22 and 32 out of 52 individuals respectively. These results suggested that the expression of the blood group-related antigens is suppressed and immature carbohydrate chains, that is H, T and Tn antigens, are accumulated in squamous cell carcinomas of the head and neck. The results further suggested that poly-N-acetyllactosamine structures are simultaneously synthesized along with the deletion of A antigen and the accumulation of precursors.

ABO Blood-Group System↗

Sulfidoleukotriene release test (CAST) in hypersensitivity to nonsteroidal anti-inflammatory drugs.

There is a great need to develop a method for making an accurate and reliable in vitro diagnosis of adverse hypersensitivity reactions to drugs. We measured the amount of sulfidoleukotriene (sLT) released from the peripheral blood leukocytes obtained from 25 patients who developed hypersensitivity reactions following the administration of nonsteroidal anti-inflammatory drugs (NSAIDs); 12 patients demonstrated reactions to Voltaren, 8 patients to Bufferin, and 5 patients to Sedes G. The stimulation index, the ratio of the amounts of sLT (pg/ml) incubated with and without drugs, was considerably higher in the patients than in the controls, which consisted of 5 nonallergic healthy subjects. The sensitivity of the CAST (cellular antigen stimulation test) was evaluated to range from 62.5 to 80%, while the specificity was 70-100%. The CAST may thus be useful as a novel in vitro test system in order to screen for possible hypersensitive reactions to NSAIDs with both reliability and safety.

Adult↗

ABR findings, electrocochleograms and caloric tests in vertebrobasilar ischemic rats.

In rats with ischemia induced by occlusion of the anterior inferior cerebellar artery (AICA) or vertebral artery (VA), we investigated the auditory brainstem response (ABR), electrocochleogram and caloric test result. Upon occlusion of the VA, there was no change of the ABR, whereas in the caloric test the duration of nystagmus upon stimulation of both ears shortened. Upon occlusion of the AICA, the cochlear blood flow (CoBF) showed one of three patterns of change no change: n = 5; decrease: n = 10; and transient decrease with recovery: n = 5. The cochlear potentials were dependent on the residual CoBF. In the caloric test, when the left AICA was occluded, the duration of nystagmus induced by stimulation of the left (ipsilateral) ear was shorter than that induced by the right (contralateral) ear. Based on the functional test results, we conclude that in this model of ischemia the function of the vestibular structures including the semicircular canals is more severely affected than is the hearing function.

Action Potentials↗

Arrhythmia curve interpretation using a dynamic system model of the myocardial pacemaker.

A problem of identifying the phase response curve of the myocardial pacemaker was investigated using a simple dynamic system model of cardiac arrhythmia. A hybrid optimization method of a genetic algorithm and a local optimization technique was employed to obtain a solution of the model fitting. The method was applied to two categories of arrhythmias, ventricular parasystole and high-degree AV block. The present study offered a new insight into the mechanism of cardiac arrhythmias.

Animals↗

Lack of p16/CDKN2 alterations in thyroid carcinomas.

Exons 1-3 of the p16/CDKN2 gene and exons 4-9 of the p53 gene were screened for mutations by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of PCR-amplified DNA from human primary thyroid carcinomas and thyroid carcinoma cell lines. The samples included 21 papillary carcinomas, 2 undifferentiated carcinomas, 1 follicular carcinoma, 1 medullary carcinoma and 2 cell lines originating from thyroid undifferentiated carcinomas. No homozygous deletions and mutations in the p16/CDKN2 were observed in any of the primary tumors or cell lined. In contrast, one of the two undifferentiated carcinomas an both cell lines demonstrated point mutations in the p53 gene. These results that p16/CDKN2 gene alteration is not required for malignant transformation in the thyroid, while p53 gene mutations may play a role in the progression from differentiated to undifferentiated carcinoma.

Adenocarcinoma, Follicular↗

Effect of IL-10 on collagen-induced arthritis in mice.

In the present study we investigated the effect of a potent anti-inflammatory cytokine, interleukin (IL)-10, on the development of collagen-induced arthritis (CIA) in mice. Each DBA1/J mouse was immunized with 200 micrograms of native collagen and followed by booster injections at 3 weeks. rmIL-10 was injected i.p. daily at a dose of 100 ng/mouse. Mice were divided into four groups according to the administration period of rmIL-10. As a result, a 48-day course of IL-10 treatment significantly suppressed the severity of arthritis. Among the 4 groups, the most pronounced suppression was observed in the group in which IL-10 was given from day 0 to 21. On the other hand, there were no significant differences in the serum IgG anti-type II collagen (CII) titers between the four groups. Moreover, the production of cytokines (IL-6 and tumor necrosis factor-alpha (TNF-alpha)) and other mediators (prostaglandin E2 (PGE2) and nitric oxide (NO)) by peritoneal macrophages seemed to show no clear correlation with the severity of arthritis in mice. These results raise the possibility that IL-10 might be a useful agent for suppressing the progression and the development of CIA in mice.

Analysis of Variance↗

Induction by chronic autoimmune arthritis in DBA/1 mice by oral administration of type II collagen and Escherichia coli lipopolysaccharide.

We have developed a new model of autoimmune arthritis in DBA/1 mice by feeding chick type II collagen (CII) for 2-3 week intervals over a 15 week period. Clinically evident arthritis occurred in 8/10 mice receiving native CII (nCII; 100 micrograms/mouse) alone at 9-13 weeks. Arthritis was aggravated by the further ingestion of CII, while remission occurred after withdrawal of the CII. Heat-denatured CII (dCII; 200 micrograms/mouse) was also arthritogenic if co-administered with ovoinhibitor (OVI; 2 mg/mouse), a proteinase inhibitor. Co-oral administration of lipopolysaccharide (LPS; 10 micrograms/mouse) with CII enhanced the antibody production and T-cell responses to CII, and induced a more chronic arthritis that progressed spontaneously without further administration of CII or LPS. Long-term oral administration of LPS alone also induced a mild arthritis characterized by destruction of bone rather than cartilage. These observations suggest that abnormal gastrointestinal absorption of dietary mimic antigens and intestinal bacterial toxins can potentially disrupt self-tolerance mechanisms, thereby precipitating or exacerbating autoimmune disease in genetically susceptible individuals.

Administration, Oral↗