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Biomedical subjects

T Ohira

Publications and source records attributed to T Ohira.

At least 19 recordsLinked to original sources

Crystallographic characterization of Pap1-DNA complex.

Pap1 is a fission yeast transcription factor that activates genes related with resistance against staurosporine, a potent inhibitor of protein kinase C, and has been shown to be involved in cell growth, cell cycle, carcinogenesis and differentiation. Pap1 has the bZIP DNA-binding domain but binds to non-consensus DNA sequences for the bZIP motif. Highly ordered crystals of the DNA-binding domain complexed with a DNA fragment that has an ATF/CREB-like non-consensus sequence have been obtained. The crystals grew by the vapor-diffusion technique with polyethylene glycol 6000 and belong to space group R3 with a = b = 240.78, c = 43.85 A. A 2.0 A resolution data set was collected with a cryo-crystallographic technique.

Basic-Leucine Zipper Transcription Factors

New system for linear accelerator radiosurgery with a gantry-mounted video camera.

PURPOSE: We developed a positioning method that does not depend on the positioning mechanism originally annexed to the linac and investigated the positioning errors of the system. METHODS AND MATERIALS: A small video camera was placed at a location optically identical to the linac x-ray source. A target pointer comprising a convex lens and bull's eye was attached to the arc of the Leksell stereotactic system so that the lens would form a virtual image of the bull's eye (virtual target) at the position of the center of the arc. The linac gantry and target pointer were placed at the side and top to adjust the arc center to the isocenter by referring the virtual target. Coincidence of the target and the isocenter could be confirmed in any combination of the couch and gantry rotation. In order to evaluate the accuracy of the positioning, a tungsten ball was attached to the stereotactic frame as a simulated target, which was repeatedly localized and repositioned to estimate the magnitude of the error. The center of the circular field defined by the collimator was marked on the film. RESULTS: The differences between the marked centers of the circular field and the centers of the shadow of the simulated target were less than 0.3 mm.

Computer Terminals

Crystallographic Characterization of the DNA-Binding Domain of Interferon Regulatory Factor-2 Complexed with DNA.

Interferon regulatory factors (IRFs) are transcription factors for interferon-related genes, which manifest both antiviral and tumor-suppressor activities and regulate cell growth in response to DNA damage. For the transcription initiation of the interferon-beta gene, IRFs form a macromolecular assembly bound to the promoter DNA, referred to as an enhancesome, together with several other transcription factors and DNA-binding proteins. The three-dimensional structure of IRF-DNA complex would provide insights into the structure and function of the enhancesome. In this study, we crystallized the DNA-binding domain of interferon regulatory factor-2 complexed with a DNA fragment. The crystals reproducibly grew by the vapor diffusion technique with 2-methyl-pentanediol from solutions containing small detergents, such as n-octyl-beta-d-glucoside. Cryocrystallographic experiments showed that crystals belong to space group P212121 with a = 90.66 Å, b = 101.01 Å, c = 171.58 Å and diffract up to 2.8 Å resolution. The absorption measurements of a solution in which the crystals were dissolved indicate that the DNA-binding domain binds to the DNA as a dimer. The calculated values of the solvent contents suggest that the protein-DNA complexes form a multimer in the crystal. These features may reflect the association of the complexes in the enhancesome. Copyright 1998 Academic Press.

Journal Article

Generation of far field potentials from the trigeminal nerve in the cat.

This study provides evidence that far field potentials (FFPs) are generated from the trigeminal nerve in the cat. By stimulating the main mental nerve, three components (component 1, 0.59 +/- 0.06 ms; component 2, 0.81 +/- 0.06 ms; and component 3, 0.98 +/- 0.07 ms) were identified from surface electrodes. These three components were thought to be positive and negative FFPs because each component had a stationary peak and was distributed on the head being divided into positive and negative fields. Results of a study of lesions and recording compound action potentials (CAPs) defined the neural origins of those potentials as follows: component 1, the mandibular nerve at the mandibular foramen; component 2, the mandibular nerve at the foramen ovale; and component 3, somewhere between the gasserian ganglion and the trigeminal root. The amplitude of component 2 decreased when the mandibular nerve at the foramen ovale was immersed in cerebrospinal fluid (CSF) after opening the foramen and recovered to the prior level after closing the foramen with beeswax. We concluded that this transformation resulted in the change in electrical resistance of the volume conductor around the nerve.

Action Potentials

Long-latency response to transcranial magnetic stimulation in patients with hemifacial spasm.

OBJECTIVE: We studied the long-latency response of the orbicularis oris muscle elicited with transcranial magnetic stimulation in patients with hemifacial spasm (HFS) and evaluated the excitability of the facial nucleus. METHODS: We compared the thresholds on both sides in 8 normal volunteers and 7 patients with hemifacial spasm. The thresholds were determined as the lowest intensity required to produce motor evoked potentials with an amplitude of at least 50 microV in the orbicularis oris muscle. Average values were given as means +/- standard deviation. Wilcoxon's rank sum test was used for comparisons between the sides of normal subjects and of patients with HFS with respect to the threshold stimulus. RESULTS: There was no significant difference between the thresholds on the two sides of the normal subjects (mean 1.88+/-5.30%, P > 0.05). In patients with HFS, there was a significant difference between the thresholds on the spasm side and the normal side (mean 20.7+/-13.0%, P < 0.05) In one patient studied after MVD, the difference between both sides disappeared. CONCLUSION: The difference between the thresholds in patients with HFS and the normalization in threshold after MVD suggested that the mechanism of HFS was hyperexcitability of the facial nucleus.

Adult

Transcranial magnetic stimulation of the oculomotor and abducens nerves: determining the site of excitation in the cat.

The authors have attempted to stimulate the feline oculomotor and abducens nerves using a magnetic coil (MC) and to determine the optimal reliable MC position for eliciting motor evoked potentials. The authors have also determined the site of excitation to analyze the validity and potential advantages of this technique as a means of neurophysiologically studying the oculomotor and abducens nerves. The potentials of both of these muscles are evoked by MC placed to be symmetrical to the line connecting the vertex and the center of the eyeball on the side being examined, as the coil center corresponds to the midpoint of this line. The latencies of the motor responses of the superior rectus and lateral rectus were 1.08 +/- 0.22 and 1.02 +/- 0.21 msec, respectively, suggesting that magnetic stimulation excites both the oculomotor and the abducens nerve at the superior orbital fissure.

Abducens Nerve

[Is medical linac suitable for high-precision stereotactic irradiation?: investigations in geometrical accuracies of gantry and couch].

Linac-based radiosurgery has many advantages over the gamma knife, including low initial cost and no need of source replacement. On the other hand, most of the medical linacs currently in use were not originally designed to be applied for radiosurgery, and, therefore, careful quality assurance programs are required. In the gantry-head of a linac, a small CCD video camera is mounted in a position optically identical to that of the x-ray source. The video signal from the camera was digitalized to be evaluated for geometrical errors. A metal ball fixed to the stereotactic base frame via XYZ-sliding rods was used as a simulated target. Displacements of the target from the isocenter were measured during rotation of the gantry. Displacements in the gantry-rotation plane were satisfactorily small, while those perpendicular to it were maximal at gantry position angles of 0 degree and 180 degrees. This error night be caused by gravitational vending of the heavy gantry head. Although other major errors of the linac were within one millimeter, the center of coach rotation around the isocenter did not coincide with the center of gantry rotation, probably owing to gravitational vending. Special care should be taken when very small collimators are employed.

Quality Control

[The relation between platelet aggregation and constitutional and lifestyle variables in two Japanese communities].

To investigate the contribution of the platelet aggregation in the development of cardiovascular diseases, we examined the relation of constitutional and lifestyle variables with platelet aggregation for a total of 306 males aged 50 to 70 in Ikawa town, Akita prefecture (n = 163) and Noichi town, Kochi prefecture (n = 143). The examination of platelet aggregation was completed within 3 hours of obtaining blood samples. We used ADP (Adenosine 5'-diphosphate) as an agonist and obtained PATI (the platelet aggregatory threshold index) by nephelometry. Platelet count, mean platelet volume, white blood cell count, serum fatty acid compositions were also examined and dietary intake of fish, seafood and soy bean foods were inquired using one-week dietary records. PATI indicated a logarithmic normal distribution in both Ikawa and Noichi. The mean of logarithmic transformed PATI (log PATI) was higher in Ikawa than in Noichi. Thus platelet aggregation was lower in Ikawa than in Noichi. According to multiple regression analysis, age, platelet count in platelet rich plasma, mean platelet volume in platelet rich plasma, and white blood cell count were inversely associated with log PATI. Serum arachidonic acid composition tended to be inversely related with log PATI. Serum n3-polyunsaturated fatty acid composition was positively related with log PATI, and log gamma-GTP tended to be positively associated with log PATI. Soy protein intake and cigarette smoking showed no consistent associations with log PATI. This cross-sectional study suggests that serum n3-polyunsaturated fatty acid, and gamma-GTP, as an index of alcohol intake, reduce platelet aggregation while age, white blood cell count, platelet count, mean platelet volume, and serum arachidonic acid raise platelet aggregation.

Age Factors

[Survival and disability in stroke by stroke subtype based on computed tomographic findings in three rural Japanese communities].

PURPOSE: We conducted an epidemiological study of survival and disability in stroke in three Japanese communities to seek community strategies for improvement in survival and disability. METHODS: A total of 297 first-ever strokes were identified between 1988 and 1992 in three rural communities (total population = 47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of daily living by sex, age-group and stroke subtypes. Successful review of computed tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and the data were used for subtype analyses. RESULTS: For all strokes (n = 297) survival rates were 85% for 30 day, 70% for one year, 62% for three year. The rates tended to be lower in women than in men. The rates were lowest in ages less than 60 at thirty day, and in ages 80 and older at the end of the first and third year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage and cortical cerebral infarction had lower survival rates than intracerebral hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80 in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar infarction. The proportion of stroke survivors who need assistance from others in the first and third years tended to be higher in women than in men. The proportion was higher in older patients than in the younger, and higher for intracerebral hemorrhage with ventricular rupture and cortical cerebral infarction than in other subtypes of stroke. From logistic regression analysis, the odds ratio for disability in the first year was 6.55 for ages 80 and older compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage with ventricular rupture, 4.53 for cortical cerebral infarction compared with lacunar infarction. In the third year the odds ratio was significant for ages 70-79, and decreased for intracerebral hemorrhage with ventricular rupture (odds ratio = 2.98), and increased for cortical cerebral infarction (odds ratio = 6.06). CONCLUSIONS: Survival and disability in stroke depended on age and stroke subtypes. Even after age adjustment, stroke subtypes with large cerebral involvement had worse prognosis than stroke subtypes. Community-based hypertension control programs are important to prevent any subtypes of stroke. Stroke subtypes as well as age should be taken into account to develop effective care and medical treatments for strokes.

Activities of Daily Living

Genetic immunotherapy by intrapleural, intraperitoneal and subcutaneous injection of IL-2 gene-modified Lewis lung carcinoma cells.

The induction and augmentation of tumor non-specific immunity and of tumor-specific immunity by intrapleural, intraperitoneal and subcutaneous injection of interleukin-2 (IL-2) gene-modified Lewis lung carcinoma (LLC) cells (LLC-IL2) was tested in C57BL/6 mice. Intrapleural injection of LLC cells induced lung tumors with a malignant effusion, intraperitoneal injection induced peritoneal tumors with ascites and subcutaneous injection induced subcutaneous tumors. Intrapleural injection of irradiated LLC-IL2 cured pre-existing lung LLC tumors and extended the survival of the mice but did not affect survival of mice with pre-existing peritoneal tumors nor did it affect the growth of s.c. tumors. Intraperitoneal injection of irradiated LLC-IL2 cured pre-existing LLC peritoneal tumors and extended the survival of the mice but did not affect survival of mice bearing lung tumors nor did it affect the growth of s.c. tumors. Subcutaneous injection of irradiated LLC-IL2 did not affect the growth of preexisting s.c. tumors and also did not improve survival of mice bearing the lung or peritoneal tumors. Injection with irradiated LLC-IL2 by all routes, i.e., intrapleural, intraperitoneal and s.c., protected against subsequent re-challenge with LLC. Eight days after the initial immunization (early stage of immunization), non-adherent mononuclear cells in the peritoneal cavity of the mice treated with intraperitoneal injection of irradiated LLC-IL2 displayed enhanced cytotoxicity against LLC, B16-F10 and P815 cells, while the cytotoxic activity of spleen cells in the same mice did not change. The efficiency of induction of tumor-specific immunity was the strongest after intraperitoneal immunization and weakest after s.c. immunization. In vitro analysis using the spleen cells of mice immunized with irradiated LLC-IL2 suggested that CD8+ T cells play a key role in tumor-specific immunity.

Animals

A new method for estimating spinal cord function. Refractory period of conductive spinal cord evoked potentials.

STUDY DESIGN: This study was designed to examine the possibility of a new spinal cord monitoring method using measurement of the refractory period to monitor spinal cord function. OBJECTIVES: To determine whether measuring the refractory period and the recovery rate of conductive spinal cord evoked potential is a useful method for estimating spinal cord function. BACKGROUND: Measuring the refractory period and constructing the recovery curve have been used to investigate peripheral nerve function. Spinal cord evoked potential elicited by the single stimulus usually is used to evaluate spinal cord function, and it has been said that 50% attenuation of the amplitude is the critical alarm level. METHODS: In anesthetized cats, amplitude, area, and latency were measured on a personal computer from subtracted data collected with a paired-stimulation technique. The authors constructed recovery curves of ascending and descending conductive spinal cord evoked potentials and measured the refractory period during spinal cord compression. RESULTS: When the amplitude of the ascending spinal cord evoked potential began to decrease during spinal cord compression, the amplitude of the response elicited by the second stimulus with interstimulus intervals of 0.8 msec and 1.0 msec decreased more significantly. When the amplitude of the ascending spinal cord evoked potential decreased to 50% of the precompression amplitude, the mean value of the absolute refractory periods of the ascending and descending spinal cord evoked potentials became prolonged from 0.40 +/- 0.007 msec to 0.53 +/- 0.014 msec, and the mean values of their amplitude and area recovery rates decreased from 75% +/- 1% to 35% +/- 2% (interstimulus interval, 0.8 msec) and from 81% +/- 1% to 46% +/- 2% (insterstimulus interval, 1.0 msec). CONCLUSIONS: The change of the responses elicited by the paired stimuli is more sensitive than those elicited by the single stimulus in the spinal cord evoked potentials. The absolute refractory periods and the recovery rate during 50% attenuation of the precompression amplitude is the critical alarm level in spinal cord monitoring.

Animals

Acute popliteal artery occlusion after total knee arthroplasty.

We describe the case of a 71-year-old man with calcium pyrophosphate dihydrate crystal deposition disease who developed acute popliteal artery occlusion immediately after total knee arthroplasty. Reperfusion was achieved thanks to the early diagnosis and thrombolytic therapy with urokinase. Arterial occlusion occurring after total knee arthroplasty is a rare but serious complication. Detailed preoperative evaluation of the peripheral arterial circulation and an early diagnosis seem to be important.

Acute Disease

Effects of spinal cord ischemia on the refractory period of descending spinal cord evoked potential.

The recovery cycle, following the conduction of action potentials along a nerve fiber, consists of the absolute refractory period (ARP), the relative refractory period (RRP) and the supernormal period (SNP). The recovery cycle of the descending conductive spinal cord evoked potential (SCEP) was shown during normal state, ischemia and after ischemia using paired stimuli in cats. During ischemia the refractory period revealed a trend towards increment. Five minutes after reperfusion the refractory period decreased transiently compared with the normal level and within 30 min the refractory period returned to the normal level. The recovery curve of the 2nd potential showed different pattern compared with that of the 1st potential. Moreover, during ischemia, firstly the 3rd potential and secondly the 2nd potential of the SCEP elicited by the 2nd stimulus were disturbed. These results demonstrated that there is increased excitability of the spinal cord to the second stimulus after a brief period of ischemia, and that the 2nd and 3rd potentials are evoked synaptically and easily disturbed during ischemia. Measuring the SCEP elicited by paired stimuli or constructing the recovery curve of the SCEP is useful for the electrophysiological assessment of spinal cord function.

Action Potentials

Prediction of consistency of meningiomas with preoperative magnetic resonance imaging.

BACKGROUND: The consistency of a meningioma is one of the important factors in determining the surgical outcome. If the surgeon is aware of the consistency of a meningioma preoperatively, the surgical plans will be influenced. A few papers have described the correlation between consistency of meningiomas and their magnetic resonance imaging (MRI) findings. However, prediction of consistency with MRI is still difficult. We have tried to predict the consistency of meningiomas with MRI findings more precisely. METHODS AND RESULTS: Fifty patients diagnosed as having intracranial meningiomas were studied with 1.5 Tesla MRI. We compared the MRI findings with tumor consistency. The intensities of the tumors were categorized into three grades (low, iso, and high) compared to that of the gray matter. T1-weighted images had no specifics, but T2-weighted images and proton density images were useful for the prediction of tumor consistency. Hyperintensity on protein density (PD) and T2-weighted images was a sign of a soft tumor. CONCLUSION: We presume that T2 and PD are useful for predicting consistency of meningiomas, and their water content is one of the main factors in their consistency. Histology may be one of the factors helpful in defining the consistency of a tumor. In this series, we found no relationship between histology and MRI findings, nor between histology and consistency. If the meningioma is believed to be hard, preoperative endovascular embolization is beneficial, which will induce necrosis of the meningioma and make it soft enough to be removed more easily and safety.

Adult

Bony foramina facilitate magnetic stimulation: an experimental cat sciatic nerve model.

We have established an experimental bony foramen model in vivo using a cat sciatic nerve, a section of skull bone and a column made from methylmethacrylate. In each model, a foramen-like slit or fissure was created. Motor responses of the cat right gastrocnemius were elicited with a figure-of-8-shaped magnetic coil. Very high intensities of magnetic stimulation were necessary to evoke motor responses with the coil placed on the thigh. However, when the bone section or methylmethacrylate column was placed under the thigh muscle layer with the sciatic nerve fitted into the foramen-like slit or fissure, motor responses could be elicited with a smaller intensity of magnetic stimulation. Despite changes in stimulation intensity or shifts in the magnetic coil, the latency of the motor responses remained constant. By comparing the latency with the electrical recording, the site of excitation was predicted to be at the exit of the foramen. Our studies have confirmed that bony structures, especially bony foramina, facilitate excitation of the nerve by magnetic stimulation and that the exit of the foramen could be the preferential site for magnetic stimulation.

Animals

Fundamental electrophysiologic investigation of spinal cord: refractory period of feline conductive spinal cord evoked potential.

Refractory periods and recovery curves have been used to investigate the physiologic importance and disturbance of peripheral nerves, but the refractory periods of the central nervous system (CNS) have seldom been investigated. We estimated the refractory periods and the recovery curves of the ascending and descending conductive spinal cord evoked potentials (SCEP) in cats. The absolute refractory period of the first and second potentials of both the ascending and descending SCEP was approximately 0.4-0.5 ms. The amplitudes of the first potentials of the ascending and descending SCEP elicited by test stimuli exhibited significant differences, but their latencies did not differ significantly except at the interstimulus interval (ISI) of 1.5 ms, which implies that the same type of fibers was stimulated in the first potentials of the ascending and descending SCEP. The second potential of the descending SCEP elicited by test stimulus showed > 100% amplitude and a maximal recovery of 200% when the ISI was 3.0 ms. The third potential was produced in the test response more easily when a lower vertebral level (L4) was used as the recording site and the ISI was between 1.0 and 4.0 ms. We consider these phenomena to be the result of elimination of the synaptic inhibitory influence by the conditioning stimulus of the paired stimuli for the descending SCEP.

Action Potentials

Computed tomographic analysis of hemifacial spasm: narrowing of the posterior fossa as a possible facilitating factor for neurovascular compression.

Hemifacial spasm can be caused by vascular compression of the facial nerve at the root exit zone from the brainstem. Several case reports suggest that narrowing of the cerebellopontine angle cistern caused by Paget's disease, abnormal elevation of the petrous bone caused by hyperplasia, or contralateral acoustic neurinoma may increase the chance of vascular compression of the facial nerve. Therefore, posterior fossa narrowness has been evaluated in 34 patients with hemifacial spasm by measuring the petrous angle and pons diameter index to elucidate whether narrowing of the posterior fossa can act as a facilitating factor for neurovascular compression. The petrous angle in the hemifacial spasm group was significantly smaller than that in the control group, which consisted of 33 patients with an unruptured supratentorial aneurysm, and the pons diameter index in the hemifacial spasm group was significantly greater than that in the control group. These results indicate that the cerebellopontine angle cistern of patients with hemifacial spasm is narrower resulting in more crowded cranial nerves and vascular structures compared with patients without hemifacial spasm. The narrowness of the cerebellopontine angle cistern may be a possible factor in facilitating neurovascular compression in hemifacial spasm.

Adult