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Biomedical subjects

K Ohno

Publications and source records attributed to K Ohno.

At least 289 records · Page 16Linked to original sources
PubMed1997

Cell-specific targeting of Sindbis virus vectors displaying IgG-binding domains of protein A.

Sindbis virus can infect a broad range of insect and vertebrate cell types due to the widespread distribution of the cellular receptor for the virus. The development of Sindbis virus vectors that target specific cell types could have important implications for the design of gene therapy strategies. To achieve this goal we have designed and constructed Sindbis virus particles displaying the IgG-binding domain of protein A. The protein A-envelope chimeric Sindbis virus vector has minimal infectivities against baby hamster kidney and human cell lines. When used in conjunction with monoclonal antibodies that react with cell-surface antigens, however, the protein A-envelope chimeric virus was able to infect human cell lines with high efficiency. Infection rates were 90% or higher for human lymphoblastoid cells. A variety of cells could be targeted by changing the monoclonal antibody without generating a new recombinant virus.

Animals↗
PubMed1997

Mutation in the M1 domain of the acetylcholine receptor alpha subunit decreases the rate of agonist dissociation.

We describe the kinetic consequences of the mutation N217K in the M1 domain of the acetylcholine receptor (AChR) alpha subunit that causes a slow channel congenital myasthenic syndrome (SCCMS). We previously showed that receptors containing alpha N217K expressed in 293 HEK cells open in prolonged activation episodes strikingly similar to those observed at the SCCMS end plates. Here we use single channel kinetic analysis to show that the prolonged activation episodes result primarily from slowing of the rate of acetylcholine (ACh) dissociation from the binding site. Rate constants for channel opening and closing are also slowed but to much smaller extents. The rate constants derived from kinetic analysis also describe the concentration dependence of receptor activation, revealing a 20-fold shift in the EC50 to lower agonist concentrations for alpha N217K. The apparent affinity of ACh binding, measured by competition against the rate of 125I-alpha-bungarotoxin binding, is also enhanced 20-fold by alpha N217K. Both the slowing of ACh dissociation and enhanced apparent affinity are specific to the lysine substitution, as the glutamine and glutamate substitutions have no effect. Substituting lysine for the equivalent asparagine in the beta, epsilon, or delta subunits does not affect the kinetics of receptor activation or apparent agonist affinity. The results show that a mutation in the amino-terminal portion of the M1 domain produces a localized perturbation that stabilizes agonist bound to the resting state of the AChR.

Acetylcholine↗
PubMed1997

Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations.

We describe and functionally characterize six mutations of the acetylcholine receptor (AChR) epsilon subunit gene in three congenital myasthenic syndrome patients. Endplate studies demonstrated severe endplate AChR deficiency, dispersed endplate regions and well preserved junctional folds in all three patients. Electrophysiologic studies were consistent with expression of the fetal gamma-AChR at the endplates in one patient, prolongation of some channel events in another and gamma-AChR expression as well as some shorter than normal channel events in still another. Genetic analysis revealed two recessive and heteroallelic epsilon subunit gene mutations in each patient. One mutation in each (epsilonC190T [epsilon R64X], epsilon 127ins5 and epsilon 553del 7) generates a nonsense codon that predicts truncation of the epsilon subunit in its N-terminal, extracellular domain; and one mutation in each generates a missense codon (epsilon R147L, epsilon P245L and epsilon R311W). None of the mutations was detected in 100 controls. Expression studies in HEK cells indicate that the three nonsense mutations are null mutations and that surface expression of AChRs harboring the missense mutations is significantly reduced. Kinetic analysis of AChRs harboring the missense mutations show that epsilon R147L is kinetically benign, epsilon P245L prolongs burst open duration 2-fold by slowing the rate of channel closing and epsilon R311W shortens burst duration 2-fold by slowing the rate of channel opening and speeding the rate of ACh dissociation. The modest changes in activation kinetics are probably overshadowed by reduced expression of the missense mutations. The consequences of the endplate AChR deficiency are mitigated by persistent expression of gamma-AChR, changes in the release of transmitter quanta and appearance of multiple endplate regions on the muscle fiber.

Acetylcholine↗
PubMed1997

Transdiscal lumbar sympathetic block: a new technique for a chemical sympathectomy.

UNLABELLED: Genitofemoral neuritis, which occurs when the neurolytic solution spreads into the psoas muscle, is the most common complication after neurolytic lumbar sympathetic block. We developed a transdiscal approach for neurolytic lumbar sympathetic block to reduce the danger of genitofemoral neuritis by making a sympathectomy without penetration of the psoas muscle, through which the genitofemoral nerve passes. We attempted transdiscal lumbar sympathetic block in 14 patients for whom the last previous lumbar sympathetic block performed by using the conventional paravertebral method was unsuccessful. Under fluoroscopic guidance, the needle was inserted transdiscally at L2-3 and/or L3-4 and was advanced until its tip pierced the anterior longitudinal ligament. Radiography and computed tomography revealed that the injected contrast media spread along the anterolateral surface of the vertebral column without any flow into the psoas muscle. Alcohol was injected successfully in all patients. During the 1-mo follow-up period, no patients had any symptom of genitofemoral neuritis. Thirteen patients who had been suffering from lower extremity pain achieved partial or complete pain relief. One patient with plantar hyperhidrosis achieved persistent anhidrosis. These results suggest that the transdiscal approach can be a technical option for neurolytic lumbar sympathetic block. IMPLICATIONS: Neurolytic lumbar sympathetic block was performed with the needle advanced through the intervertebral disc. With this technique, the risk of genitofemoral neuritis, the most common complication after neurolytic lumbar sympathetic block, was reduced because the needle does not penetrate the psoas muscle, through which the genitofemoral nerve passes.

Adult↗
PubMed1997

Distribution of referred pain from the lumbar zygapophyseal joints and dorsal rami.

OBJECTIVE: The purpose of this study was to determine the distribution of referred pain from the lumbar zygapophyseal joints (L1/2 to L5/S1) and the medial branches of the lumbar dorsal rami (Th12 to L5) in a large number of patients with chronic low back pain. SETTING: This study was conducted at the pain clinics of Kanto Teishin Hospital and Hannan Central Hospital from March 1994 to May 1996. PATIENTS AND DESIGN: Chronic low back pain patients who underwent zygapophyseal joint injection or radiofrequency facet denervation were studied. Under fluoroscopic control, the joints from L1/2 to L5/S1 were stimulated by injection of contrast medium, and the lumbar medial branches of the dorsal rami from Th12 to L5 underwent electrical stimulation during radiofrequency facet denervation. OUTCOME MEASURES: If the injection or electrical stimulation reproduced the patient's usual pain, the distribution of induced pain was determined, and the sites of induced pain were divided into six areas. RESULTS AND CONCLUSIONS: A total of 71 joints and 91 medial branches were studied in 48 patients. The distribution of referred pain from the L1/2 to L5/S1 zygapophyseal joints, and the medial branches of the dorsal rami from L1 to L5 were similar for each level stimulated, and the overlap of referred pain between each level was considerable.

Adult↗
PubMed1997

Morphometric examination of the free scapular flap.

In this study we investigated the clinicoanatomic basis of the scapular flap by morphometric examinations of 42 cadavers. Our findings were as follows: With common-trunk type scapular vessels, the maximal lengths of arteries and veins that could be used for a flap pedicle were 93 and 91 mm. With direct-type scapular vessels, the maximal lengths were 95 and 71 mm. In common-trunk type vessels, the mean internal diameter 2 mm distal from the confluence of the scapular vessel was 2.8 mm for arteries and 3.3 mm for veins. In the direct-type vessels, the mean internal diameter 2 mm distal from the confluence of the circumflex scapular vessel was 1.8 mm for arteries and 3.3 mm for veins. The maximal superoinferior dimension of the scapular graft was 28 mm. The maximal lateral dimension of the scapular graft was 12 mm.

Adult↗
PubMed1997

Genetic mapping of genes regulating the thymus size in back-cross rats between the laboratory BUF/Mna strain and the MITE strain derived from the wild rat, Rattus norvegicus.

The thymoma prone BUF/Mna (B) rat is a useful model for studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at all stages of life. A locus, Ten-1, which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the locus, ¿B x(B x MITE)F1¿ BC rats were generated by crossing the B strain with the inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargement were found in genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11, and D1MIt6, by chi2-test and Student's t-test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1, in this region. Paradoxically, a suppressive locus, Tsu-1, to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT, D3MIt16, and D3MIt13. By analyses of MAPMAKER/EXP and MAPMAKER/QTL, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.

Animals↗
PubMed1997

[Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia].

This investigation was carried out to try the application of pilocarpine hydrochloride (PC) solid dispersion as sustained release dosage form. Four preparations of PC with ethylcellulose and/or hydroxypropylmethylcellulose phthalate were prepared by the organic solvent method. The preparation D including PC: ethylcellulose: hydroxypropylmethylcellulose phthalate (1:9:10 at weight ratio) showed the best sustained release behavior in dissolution test among four preparations. The preparation D was examined by powder X-ray diffractometry and differential scanning calorimetry, and confirmed to be solid dispersion. Saliva secretory effect of preparation D was examined in healthy male volunteers, and its effect for Xerostomia was showed.

Cellulose↗
PubMed1997

Apoptosis enhanced by soluble factor produced in feline immunodeficiency virus infection.

Feline immunodeficiency virus (FIV)-infected cells have been shown to undergo apoptosis by treatment with tumor necrosis factor alpha (TNF-alpha). This study detected a soluble factor which enhanced the apoptosis induced by TNF-alpha treatment. The sensitivity to TNF-alpha in the induction of apoptosis in a feline fibroblastoid cell line (CRFK) cells was significantly enhanced when the culture supernatant of FIV-infected CRFK cells or plasma samples from FIV-infected cats was added to the culture. These findings suggested that FIV infection induces production of a soluble factor which enhances CRFK cells sensitivity to TNF-alpha induction of apoptosis both in vitro and in vivo. This factor may contribute to the loss of lymphocytes in cats infected with FIV.

Animals↗
PubMed1997

[What children think about their growth: the sense of growth and Loevinger's ego developmental level].

This study concerns the sense of growth that children have of themselves, and attempted to show that differences in it can be explained in terms of ego developmental levels proposed by Loevinger. Seven hundred ninety-nine (799) children between 5th and 12th grades responded to a Sentence Completion Test (SCT) of ego development and sense of growth. Five ego developmental levels were identified: Impulsive, Self-Protective, Self-Protective/Conformist, Conformist, and the Self-Aware. The results confirmed the higher the age, the higher the ego developmental level, and the level affected what children thought about their growth. The answers to the SCT of low ego-development children had more overt characteristics such as physical development, whereas those of high children tended to include more covert aspects such as mental development.

Adolescent↗
PubMed1997

[Long-term effects of a selective alpha 1-adrenergic inhibitor on right and left ventricular masses in patients with chronic pulmonary disease].

We examined the effect of one year of treatment with the selective alpha 1-adrenergic inhibitor doxazosin on right ventricular mass (RV mass), left ventricular mass (LV mass), and arterial blood gases. The subjects were 24 outpatients (18 men and 6 women, mean age 68.3 +/- 9.4 years) with chronic pulmonary disease complicated by hypertension who were clinically stable. One year of drug therapy was associated with significant decreases both in systolic pressure (159 +/- 15.2 vs 125.8 +/- 14.1 mmHg, p < 0.05, n = 24), and in LV mass index (101.0 +/- 13.4 vs 97.6 +/- 11.8 gm-2, p < 0.05), n = 24). We obtained the RV mass index by multiplying the thallium score RV/LV count and the LV mass index obtained by echocardiography. One year of drug therapy was associated with a significant increase in RV mass index (42.9 +/- 31.2 vs 53.6 +/- 30.5 gm-2, p < 0.05, n = 8). Vital capacity decreased (2.18 +/- 1.95 vs 1.95 +/- 0.57 l, p < 0.05, n = 24), but PaO2 improved (77.3 +/- 17.2 vs 82.2 +/- 2.4 mmHg, p < 0.05, n = 24). These data indicate that doxazosin can decrease blood pressure and can depress the left ventricle with no adverse effect on oxygenation in patients with chronic pulmonary disease complicated by hypertension. The worsening of RV hypertrophy may have been caused by a mechanism different from the one that caused LV hypertrophy, and by an increase in the work load on the right ventricles secondary to lung deterioration.

Adrenergic alpha-Antagonists↗
PubMed1997

[Simultaneous ambulatory electrocardiography and pulse oximetry].

We developed a system for 24-hour ambulatory recording of blood oxygenation (SpO2) and electrocardiography (ECG). Using this system, we studied 10 healthy volunteers and 7 patients with chronic pulmonary diseases. The system incorporated a portable pulse oximeter (SM50) manufactured by Fukuda Denshi KK; the first and second channels were used to record ECG data and the third was used to record SpO2 data. An SpO2 sensor (Dispo-sensor D-25; Nellcor Inc.) was applied to the fourth of fifth finger. The SpO2 data (MicrO2; Siemens AG) were digitized and stored in the ambulatory recording device; the ECG was recorded simultaneously. The data were analyzed with a model DMW-9000H analyzer (Fukuda Denshi KK). A custom-designed program was also used, to remove noise errors. In the healty volunteers, SpO2 was at least 90% for the entire 24 hours. In all the patients, SpO2 fell below 90% at rest during the night or after a 15-minute walk. Transient atrial tachycardia was observed in 3 patients, and during the tachycardia the SpO2 was low. The number of extra ventricular beats divided by the total number of beats increased more in the patients than in the healthy volunteers (1.21 +/- 0.89 vs 0.6 +/- 0.3%, p < 0.05). SpO2 did not change significantly in the patients. In outpatients and in patients receiving home health care, the present system facilitates simultaneous diagnosis of respiratory failure an arrhythmias. In patients with chronic pulmonary diseases desaturation may cause transient atrial tachycardia.

Adult↗
PubMed1997

[Effect of percutaneous transluminal mitral commissurotomy on pulmonary function and on the pulmonary vasculature].

We evaluated the therapeutic effect of percutaneous transluminal mitral commissurotomy (PTMC) on pulmonary function, and the damage caused to pulmonary vasculature by transient occlusion of the mitral valve during PTMC in patients with mild mitral stenosis. Pulmonary function tests were done and serum thrombomodulin was measured in 6 patients before and after PTMC. The mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure decreased significantly from the control values, and the decreases were proportional to the increase in the area of the mitral valve. VC, %VC, and DLco were in the normal range before and after PTMC but PEFR, FEV1%, FEV1, V50, V25, and V50/V25 were significantly higher after PTMC. Change in the area of the mitral valve correlated with the changes in FEV1% (r = 0.841), in V50 (r = 0.624), and in V25 (r = 0.697). The serum thrombomodulin levels before and after PTMC did not differ. We conclude that pulmonary dysfunction in patients with mild mitral stenosis MS is mainly due to an obstructive ventilatory defect, and that PTMC can correct this dysfunction without damaging the pulmonary vasculature.

Aged↗
PubMed1997

[Dural arteriovenous fistula involving the superior sagittal and transverse-sigmoid sinuses, treated by thrombolysis: case report].

A rare case of dural arteriovenous fistula (DAVF) in the superior sagittal sinus (SSS), the transverse sinus and the sigmoid sinus is reported. A 64-year-old man, who had had an episode of temporary visual disturbance after moderate fever for a week about 20 years before, was aware of loss of visual acuity and reduced field of view in the right eye. When he was introduced to our outpatient service, increased intracranial pressure (ICP) was detected by lumbar puncture. Cerebral angiograms showed bilateral DAVFs both in the posterior fossa and the SSS concomitant with thrombosis in the transverse sinus, sigmoid sinus and SSS. Afterwards, endovascular transarterial embolization through bilateral occipital, posterior auricular and left middle meningeal, superior temporal arteries was carried out. In addition, transvenous thrombolytic therapy using a catheter inserted into SSS resulted in the improvement of his visual problems. Although he was discharged at once, he was readmitted to our department with Foster Kennedy syndrome and increased ICP. Cerebral angiograms showed recurrence of both DAVF and sinus thrombosis. Transarterial embolization was performed again resulting in a significant reduction of DAVF, and his visual acuity was recovered to a moderate degree. The origin of DAVF is still controversial. Although two theories, "congenital" and "acquired", are put forward, it has been thought that both factors play important roles. In our case, the patient had stenosis in the jugular canal portions of the sigmoid sinus. In addition, sinus thrombosis seemed to have occurred. It is thought that increased intrasinus pressure may have lead to communication with surrounding arteries through existing dural vessels. We applied transvenous thrombolytic therapy in this case. Our result suggests that we should consider this therapy for some cases of DAVF.

Arteriovenous Fistula↗
PubMed1997

[Evaluation on blood clearance and hepatic uptake of 99mTc-GSA in rats with blood flow conversion].

This study was aimed to clarify a contribution of the hepatic blood flow in hepatic accumulation of 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA). The experiment was performed in rats by the blood flow conversion with an external scintillation gamma camera and laser doppler flowmeter. Rats were divided into 4 groups: hepatic artery ligation (HAL, n = 10), portal vein ligation (PVL, n = 8), both hepatic artery and portal vein ligation (HAL+PVL, n = 9), and control (CONT, n = 10) groups. The scintigraphic data were obtained in each group for 10 minutes after intravenous injection of 99mTc-GSA (50 micrograms/100 g B.W). The regions of interest were assigned over the heart and whole liver and the time activity curves (TAC) were generated. Five parameters of HH 4, LHL 4, KH1, KH2, KL, were calculated as blood clearance and hepatic accumulation from TAC in each rat. HH4 as blood clearance index in CONT, HAL, PVL and HAL+PVL was 0.58 +/- 0.04 (mean +/- SE), 0.63 +/- 0.04, 0.85 +/- 0.04, 0.97 +/- 0.001, respectively. HH 4 between CONT vs PVL, HAL+PVL was statistically significant (p < 0.05). LHL 4 as hepatic uptake index in CONT, HAL, PVL and HAL+PVL was 0.96 +/- 0.001, 0.93 +/- 0.01, 0.71 +/- 0.07, 0.41 +/- 0.04, respectively. This parameter was also statistically significant between CONT vs PVL and HAL+PVL groups. Another parameter of KH1 for blood clearance and KL for hepatic uptake were also significant between CONT vs PVL and HAL+PVL groups. All parameters obtained in 99mTc-GSA study correlated well with the hepatic flow rate which was measured with a laser doppler flowmeter and reflected the reduction rate of the hepatic tissue blood flow 4 minutes after the ligation of target vessels. These result suggest that blood clearance and hepatic uptake of 99mTc-GSA are significantly affected by hepatic blood inflow. 99mTc-GSA scintigraphy may be useful in evaluating hepatic tissue blood flow.

Animals↗
PubMed1997

[Interdural dermoid cyst of the cavernous sinus presenting with oculomotor palsy: case report].

A 19-year-old female was admitted to our hospital because of diplopia. Neurological examination showed slight anisocoria (right > left), disturbance of ocular movement in upward, downward and medial directions on the right side, and diplopia on upward gaze. Computed tomography (CT) scan demonstrated a well-demarcated cystic lesion in the right parasellar region. The lesion showed non-homogeneous low intensity with a high intensity margin on T1-weighted imaging and high intensity with a low intensity margin on T2-weighted imaging in magnetic resonance image (MRI). The lesion showed enhancement by contrast media on neither CT nor MRI. Cerebral angiography revealed no tumor stains. The lesion was approached via right fronto-temporal craniotomy. The right optic nerve, oculomotor nerve and internal carotid artery were compressed medially by the tumor. The tumor contents appeared to be flaky and greasy containing motor-oil-like fluid, mineralized body, and a few hairs. The tumor was attached to the lateral wall of the right cavernous sinus (inner membranous layer), but was totally resected with careful microscopic dissection. The histopathological examination confirmed the diagnosis of dermoid cyst. The patient's complaint of diplopia showed gradual improvement postoperatively. Supratentorial intracranial dermoid cyst is a rare congenital tumor and, to our knowledge, only one case arising within the lateral wall of the cavernous sinus and presenting oculomotor palsy has been reported. Total removal is ideal and may be possible even when the tumor arises from the lateral wall of the cavernous sinus.

Adult↗
PubMed1997

[A mitochondrial DNA mutation in the heteroplasmic tRNA-Tyr gene associated with chronic progressive external ophthalmoplegia--clinical and molecular biological study].

Determination of the total mtDNA sequence of a 42 year-old female with chronic progressive external ophthalmoplegia (CPEO) revealed a heteroplasmic G-to-A transition at nt. 5877 in the tRNA-Tyr gene and a homoplasmic T-to-C transition in the tRNA-Gln gene at 4343. The former mutation was located in a highly conserved nucleotide in the DHU loop. This mutation by restriction enzyme analysis using Ddel was observed only in the blood of her two asymptomatic children and her mother. The tRNA-Gln mutation in the T psi C loop was found in a few controls and in all of her maternal relatives. The cybrid clones including tRNA-Tyr mutation showed decreased oxygen utilization and fragility against oxygen stress. This tRNA-Tyr mutation is tightly associated with CPEO.

Adult↗