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Biomedical subjects

M Kitahara

Publications and source records attributed to M Kitahara.

At least 19 recordsLinked to original sources

Identification of the human ERK gene as a putative receptor tyrosine kinase and its chromosomal localization to 1p36.1: a comparative mapping of human, mouse, and rat chromosomes.

From a newly determined cDNA sequence of the human ERK gene, a highly hydrophobic portion was identified upstream of the putative tyrosine kinase domain. This is the first evidence that the ERK protein possesses a receptor-like membrane-spanning structure. Fluorescence in situ hybridization analysis of R-banded metaphase chromosomes revealed that the ERK gene is located in chromosome region 1p36.1. This locus is near the frequent translocation breakpoint or deletion region of neuroblastoma and some other cancers. A comparative mapping study of the mouse and rat homologues indicated that each counterpart maps to the mouse chromosome 4D2.2-D3 and rat chromosome 5q36.13 regions, both of which have conserved linkage homology to human chromosome 1p.

Amino Acid Sequence

CD27/CD70 interaction directly drives B cell IgG and IgM synthesis.

CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27+ B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM.

Adult

Frequently relapsing minimal change nephrotic syndrome with natural killer cell deficiency prior to the overt relapse of Hodgkin's disease.

A 15-year-old boy developed minimal change nephrotic syndrome (MCNS) during remission of Hodgkin's disease. Natural killer (NK) cell activity was practically absent at the onset of MCNS, with a value of 3% compared with the normal value of 44.1% +/- 7.8% (mean +/- SD). Treatment with prednisolone resulted in transient remission of MCNS and partial improvement of NK cell activity. Extensive investigations for Hodgkin's disease were performed at 1- to 3-month intervals; a relapse finally became apparent 25 months after the diagnosis of MCNS. Successful treatment of Hodgkin's disease resulted in complete disappearance of proteinuria and normalisation of NK cell activity. Frequently relapsing MCNS with NK cells deficiency during remission of Hodgkin's disease appears to imply its subclinical relapse.

Child

Effects of efonidipine hydrochloride on cholesterol esterification mediated by beta-very low density lipoprotein in J774 macrophages.

The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium antagonist, on the cholesterol ester metabolism induced by beta-migrating very low density lipoprotein (beta-VLDL) in J774 macrophages were studied. The cholesteryl ester content in the macrophages was increased by incubation with beta-VLDL, and the increase was inhibited by efonidipine. Oleic acid incorporation into cellular cholesteryl ester was increased by beta-VLDL in J774 macrophages. The incorporation at an early phase of beta-VLDL induction (0-3 hr) was inhibited by efonidipine. This inhibitory effect of efonidipine was greater at an early phase of beta-VLDL induction (0-3 hr) than at a late phase of the induction (8-11 hr). Pretreatment of the cells with efonidipine enhanced the inhibitory effect. Efonidipine also inhibited beta-VLDL degradation but not the binding and association in macrophages without pretreatment. beta-VLDL binding and association to macrophages were decreased by pretreatment of the cells with efonidipine. beta-VLDL metabolism was also decreased by dibutyryl cyclic AMP pretreatment. The decrease of beta-VLDL metabolism by efonidipine was prevented by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor. Furthermore, efonidipine increased the intracellular cyclic AMP content in J774 macrophages. These findings suggest that efonidipine suppresses cholesterol ester deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein metabolism and cholesterol esterification mainly through elevation of the cellular cyclic AMP level.

Animals

Air caloric test with continuous thermal change in patients with vestibular disorders.

In a previous report (1) the author described a new air caloric test with continuous thermal change. In this study, 19 patients with vestibular disorders were examined with this technique, and the results were compared with the results of the water caloric test (30 degrees C, 50 ml, 20 s) in the same subjects. A difference in interaural response to the air caloric test was noted in 9 of the 19 patients (47.4%), greater than with the water caloric test, 5 of 19 (26.3%). The detectability of vestibular disorders with the air caloric test (28 of 38 ears; 73.7%) was significantly higher than that with the water caloric test (8 of 38 ears; 21.1%) (p < 0.01). The air test appeared to estimate vestibular function more precisely, as stimulation by this method is too weak to cause vestibular recruitment.

Adult

Epidemiological and clinical characteristics of Menière's disease in Japan.

From 1975 to 1990, nationwide surveys on Menière's disease were performed three times by the Research Committee of Menière's disease (1975-76) and the Research Committee of Peripheral Vestibular Disorders (1982-84 and 1990) in Japan. Nine hundred and fifty-eight definite Menière cases, 520 in the 1st, 230 in the 2nd and 148 in the 3rd survey, were sampled by the members of the Committees. The epidemiological and clinical characteristics of Menière's disease were analyzed and compared with such control cases as other vertiginous patients, ENT patients without vertigo, and healthy subjects. In Menière's disease, the male to female ratio has changed from even to female predominance over the 15 years the study ran. The age distribution at onset peaked in the forties for males and thirties for females. Significant epidemiological results are summarized as follows: Definite Menière's disease has a higher incidence in married persons and in people with a nervous and precise character, whereas the incidence is lower in obese people. Physical and mental fatigue induced the onset of attacks. Menière's disease happened in day time in many cases, especially during the afternoon. As these epidemiological findings were commonly observed in all the surveys, the results are considered to be universal epidemiological characteristics of Menière's disease in Japan. In the same period, regional investigations were performed by Toyama Medical Association and our University. The male to female ratio in Toyama indicated a more significant female predominance than in the nationwide surveys. The prevalence of Menière's disease in Toyama Prefecture has been almost constant in all surveys, about 17/100,000 since 1974.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Clinical findings in Menière's disease with bilateral fluctuant hearing loss.

Our department conducted an examination of the clinical characteristics of Menière's disease with bilateral fluctuant hearing loss, using data obtained in a survey involving sixteen institutes associated with the Vestibular Disorder Research Committee, Japan. A total of 480 cases were surveyed, of which 204 showed normal hearing in the second ear, and were thus classified as unilateral Menière's disease, or Menière's disease with unilateral involvement; 135 cases showed fluctuating cochlear symptoms in the second ear, and were therefore classified as Menière's disease with bilateral fluctuant hearing loss or bilateral involvement. Our results show that patients with bilateral involvement experience increased disruption of daily life activities, and respond poorly to therapy with diuretics or steroids. Hospitalization is often considered for these patients. For these reasons it is especially important that bilaterality be diagnosed as early as possible, and that intensive treatment be carried out. ENT specialists must recognize the seriousness of bilateral involvement, and take particular precautions against its occurrence.

Activities of Daily Living

Epidemiological study of severe cases of Meniére's disease in Japan.

In order to clarify the characteristics of severe cases of Meniére's disease (MD), we analyzed various epidemiological factors such as sex ratio, past history, complication, cause of onset of vertiginous attacks, etc., in a series of 958 patients with definite MD. Data were obtained from the three Japan-wide surveys of MD conducted by the Meniére's Disease Research Committee of Japan (1975-76) and the Vestibular Disorders Research Committee of Japan (1982-84 & 1990). Following the ideas proposed by the members of the Vestibular Disorder Research Committee of Japan, we divided severe cases into three categories according to the following criteria i) bilateral MD cases (BMD), ii) unilateral MD cases with prolonged disabled vertigo (UPDV), iii) unilateral MD cases with profound hearing loss (UPHL). About 40% of the subjects were classified as severe cases (UPDV: 23%; BMD: 9%; UPHL: 6%). The ratio of otitis media in past history was statistically different between severe cases and non-severe patients (p < 0.05), suggesting that otitis media in the past may contribute to the severity of Meniére's disease.

Adolescent

[A case of ruptured true posterior communicating artery aneurysm thirteen years after surgical occlusion of the ipsilateral cervical internal carotid artery].

A case is presented of ruptured "true" posterior communicating artery aneurysm thirteen years after surgical occlusion of the ipsilateral cervical internal carotid artery. A 58-year-old female developed the sudden onset of blepharoptosis on the right side. She had had a right superficial temporal artery-middle cerebral artery anastomosis and a surgical occlusion of the right cervical internal carotid artery 13 years earlier for a subarachnoid hemorrhage that occurred as the result of a ruptured aneurysm of the right internal carotid artery. Neurological examination on admission revealed an occulomotor palsy on the right. Cerebral angiograms demonstrated an aneurysm arising from the right posterior communicating artery itself near the right posterior cerebral artery. Also, the right intracranial internal carotid artery was supplied through the right posterior communicating artery. Five days later she experienced the sudden onset of severe headache. CT scan showed subarachnoid hemorrhage in the ambient cistern. Neck clipping of the aneurysm was successfully performed by the contralateral zygomatic approach. The postoperative course was uneventful. It has been well known that internal carotid artery occlusion may be associated with cerebral aneurysm in some cases. However, it seems to be very rare that a "true" posterior communicating artery aneurysm should occur following the ipsilateral carotid artery occlusion. Hemodynamic factors were strongly suggested as the reason for aneurysmal formation in this case.

Aneurysm, Ruptured

Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta.

Lysophosphatidic acids (LPA) with a C18 fatty acyl group accelerated thymidine incorporation into cultured rat aortic vascular smooth muscle cells and stimulated their cell division. LPA acted synergistically with epidermal growth factor and fibroblast growth factor but additively with platelet-derived growth factor. The stimulatory actions of LPA were suggested to be rather specific from the following findings: 1) their stimulation of DNA synthesis increased with an increase in their acyl moiety; 2) lysophosphatidylcholine, a neutral lysophospholipid, had no mitogenic action but was cytotoxic at high concentrations; and 3) LPA induced a rapid external Ca(2+)-independent increase in intracellular Ca2+ concentration ([Ca2+]i) in single fura 2-loaded cells that resembled the receptor-mediated increases in [Ca2+]i triggered by different agonists, whereas lysophosphatidylcholine provoked a slow sustained increase in [Ca2+]i in an external Ca(2+)-dependent manner. These results are discussed in relation to the possible pathophysiological role of LPA.

Animals

[Effect of efonidipine hydrochloride (NZ-105), a new dihydropyridine calcium antagonist, on the experimental atherosclerosis in cholesterol-fed rabbits].

We studied the effect of efonidipine hydrochloride [NZ-105:(+-)-2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl )-3-pyridine-carboxylate hydrochloride ethanol], a newly synthesized dihydropyridine calcium antagonist, on atherosclerosis in 1% cholesterol-fed rabbits. NZ-105 (10, 30 and 100 mg/kg) was orally administered to the animals twice a day for 10 weeks. NZ-105 did not cause any significant change in the plasma lipid levels. The area of atherosclerotic lesion was reduced by 37% (P < 0.05) in the aortic arch and by 54% (P > 0.05) in the thoracic aorta of rabbits administrated 100 mg/kg of NZ-105. The content of cholesterol ester in the aorta was also reduced by 64% (P < 0.05) in the aortic arch and by 73% (P > 0.05) in the thoracic aorta. These results suggest that NZ-105 may suppress the development of atherosclerosis without affecting the plasma lipids.

Animals

The influence of middle ear pressure changes on the primary vestibular neurons in guinea pigs.

The responses of primary vestibular neurons and perilymphatic pressure changes to middle ear pressure stimuli in guinea pigs were investigated in order to clarify the direct effects of pressure stimulus on the vestibular apparatus. The vestibular response was related to the amount of middle ear pressure change applied at a rate of +/- 100 mmH2O/s. The neural response rates of vestibular units to positive pressure in the middle ear were significantly larger than those to negative pressure. The time course pattern of the perilymphatic pressure change resembled that of the response of the vestibular units, indicating that the vestibular response is elicited by middle ear pressure via the pressure transmitted in the inner ear.

Animals

The influence of vestibular and cochlear aqueducts on vestibular response to middle ear pressure changes in guinea pigs.

The responses of primary vestibular neurons and perilymphatic pressure changes to middle ear pressure were investigated in guinea pigs with obstructed vestibular or cochlear aqueduct (closed VA or closed CA group) in order to clarify the influence of VA and CA on pressure-induced vestibular response. Although the neural response rates and the amount of perilymphatic pressure change in the closed VA group resembled those in the control group, these values in the closed CA group were higher than in the control group. Patency of the CA had a more significant effect on the vestibular response to middle ear pressure change than patency of the VA.

Animals

Swimming test for evaluating vestibular function in guinea pigs.

A swimming test was used to evaluate vestibular function in guinea pigs. We first observed tracings of the swimming patterns of 20 healthy guinea pigs to establish the normal range. Then the same test was used in a group of 49 guinea pigs with endolymphatic hydrops induced by immunologic techniques. They did not show spontaneous nystagmus or body deviation while walking, but a total of 20 out of 49 animals displayed abnormal swimming patterns, with 8 swimming clockwise and 4 counterclockwise. This swimming test is easily able to detect mild vestibular dysfunction in guinea pigs, and can be repeated, so that we consider it useful for examining vestibular function in these animals.

Animals

Electrocochleography in experimental endolymphatic hydrops.

This study investigated whether dominant negative summating potential (DNSP) is absent at all stages of induced hydrops development, including the early stages of hydrops formations. Electrocochleography (ECoG) was done 3 days to 20 weeks after obliteration of the endolymphatic sac in guinea pigs, by electrodes attached to the cochlear bony wall on the scala vestibuli of the basal turn. DNSP was noticed only during the early stages of endolymphatic hydrops formation, before hydrops was fully developed. There was no DNSP when the distension of Reissner's membrane was marked. Increased endolymphatic pressure and/or changes in biochemical composition were thought to be the causes of DNSP.

Action Potentials

Endolymphatic sac blood flow versus cochlear blood flow following intravenous administration of isosorbide in guinea pigs.

Endolymphatic sac (ES) blood flow (ESBF) and cochlear blood flow (CBF) were measured in different groups of guinea pigs by laser-Doppler flowmetry (Advance Laser Flowmeter, Model ALF 2100) after the intravenous administration of 70% isosorbide (1.6 ml/kg). The measurements were made under general anesthesia with intraperitoneal pentobarbital sodium. Respiration was controlled by a respirator after tracheotomy, and blood pressure was monitored through the femoral artery (Gould Statham P23 ID Pressure Transducer). For ESBF measurements, a probe was placed on the right ES after entering the posterior cranial fossa via the dorsal approach. For CBF measurements, a probe was placed on the basal turn of the right cochlea via the ventral approach. Isosorbide was administered intravenously through the jugular vein for 60 s. Both ESBF and CBF increased immediately after administration, reached a peak within 3-6 min and decreased gradually to their initial baseline levels in 11-15 min. Both blood flow changes almost always corresponded to systemic blood pressure changes, although a slight delay was observed in blood pressure compared to the blood flow. The magnitude of the CBF response tended to be greater than that of the ESBF response (p < 0.1). This may result from the anatomical differences in the two blood supplies, i.e., from the vertebral artery (CBF) and the external carotid artery (ESBF).

Animals

Acceleration registrography of head movement during alternating inclination of the support platform.

The righting reflex, essential for maintaining equilibrium, keeps the head and trunk in a state of balance with regard to gravity. Because patients suffering from vestibular disorders almost always complain of dizziness during everyday movements such as rising and walking, the righting reflex should be evaluated within the context of these dynamic states. A new method of acceleration registrography was designed to enable the testing of this reflex as the subject stands upon a moving platform. Participating in the study were 49 normal control subjects and 80 patients with peripheral vestibular disorders. The test we devised proved to be more successful in detecting labyrinthine righting reflex dysfunction in patients than the tests of righting reflex and deviation evaluations used thus far, such as Romberg's, Mann's and the stepping test, and to more accurately represent the disequilibrium and/or dizziness experienced by patients in everyday movements.

Acceleration

Influence of passive and active pendular head rotation on horizontal optokinetic nystagmus.

The influence of pendular head rotation on optokinetic nystagmus was examined using a vestibulo-optic stimulator (pendular rotating chair with an optic cylinder) to study passive head rotation, and an optic cylinder which was rotated by a motor fixed to the head to study active head rotation. Pendular head rotation and optic stimuli were simultaneously and independently applied horizontally. The optic cylinder consisted of 12 vertical stripes rotating at a uniform velocity of 30 degrees/s or 90 degrees/s. Passive pendular head rotation was applied at a frequency of 0.1 Hz and a peak angular velocity of 30 degrees/s. Active head rotation was applied for a period of approximately 10 s, and at an amplitude of approximately 50 degrees. Optokinetic nystagmus was enhanced when the head was rotated in the opposite direction to the optic cylinder. However, when the head and the optic cylinder were rotated in the same direction, optokinetic nystagmus was inhibited. There was little difference between the effects of passive and active head rotation on enhancement. However, during active head rotation, optokinetic nystagmus was less inhibited than during passive head rotation.

Adult