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Biomedical subjects

Y Ishihara

Publications and source records attributed to Y Ishihara.

At least 91 records · Page 5Linked to original sources
PubMed1997

[A case of traumatic extracranial internal carotid artery dissecting aneurysm treated by proximal ligation and STA-MCA bypass].

We present a case with the traumatic extracranial internal carotid artery dissecting aneurysm. A 21-year-old man was involved in a motorcycle accident, resulting in multiple injuries but no apparent head and neck injuries. Head CT was normal on his admission. He was discharged from his local hospital 3 weeks after the accident without any neurological deficits. Five weeks after the accident, he suddenly presented with a motor aphasia and a right hemiparesis. CT and MRI showed infarctions in the left para-Sylvian and the left angular areas. Angiography showed a left extracranial carotid artery dissecting aneurysm at the level of C1 vertebral arch. The patient was initially managed by an anticoagulant agent, but he suffered from another transient ischemic attack due to distal embolism from the aneurysm. Balloon occlusion test of the left ICA was performed under monitoring EEG, SEP. Mean stump pressure (MSP) revealed 60 mmHg. and MSP/Mean systematic blood pressure revealed 67%. We judged that the left ICA ligation was a safe method to treat this patient, however, considering the patient's age and the side of the lesion, left STA-MICA bypass and ligation of the left ICA were carried out in one stage. Postoperatively, the patient did not show any cerebral ischemic complications and angiography showed disappearance of the aneurysm and patency of the bypass. The left MCA territories were filled well by cross circulation and the bypass.

Accidents, Traffic↗
PubMed1997

Neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, in rats.

We examined the neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzaze pin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase (AChE) inhibitor in vitro and in vivo. TAK-147 showed a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC50 = 51.2 nM), and was 3.0- and 2.4-fold more potent than tacrine and physostigmine, respectively. By contrast, TAK-147 was the least potent inhibitor of butyrylcholinesterase activity in rat plasma (IC50 = 23,500 nM). Tacrine and physostigmine inhibited butyrylcholinesterase activity potently and nonselectively. TAK-147 showed a moderate inhibition of muscarinic M1 and M2 receptor binding with K(i) values of 234 and 340 nM, respectively. TAK-147 showed very weak or no inhibition of high-affinity choline uptake, nicotinic receptor binding and choline acetyltransferase activity. In ex vivo experiments, oral administration of TAK-147 at doses ranging from 1 to 10 mg/kg induced a statistically significant and dose-dependent decrease in AChE activity in the cerebral cortex. Of the monoaminergic systems, TAK-147 moderately inhibited uptake of noradrenaline and serotonin with IC50 values of 4020 and 1350 nM, respectively. TAK-147 also inhibited ligand binding at alpha-1, alpha-2 and serotonin 2 receptors with K(i) values of 324, 2330 and 3510 nM, respectively, whereas it showed only weak activities on D1, D2 and serotonin 1A receptor bindings. Oral administration of TAK-147 (3 mg/kg) significantly accelerated the turnover rates of dopamine, noradrenaline and serotonin in the rat brain. These results suggest that TAK-147 activates the central cholinergic system by specific inhibition of AChE activity without affecting peripheral butyrylcholinesterase activity, and that TAK-147 also moderately activates the monoaminergic systems.

Acetylcholinesterase↗
PubMed1996

Pretreatment with T cell receptor peptides using a conventional immunization protocol does not induce effective protection against autoimmune encephalomyelitis.

It was previously reported that vaccination with synthetic peptides corresponding to the CDR2 or CDR3 region of T cell receptor (TCR) protected susceptible animals from the development of experimental autoimmune encephalomyelitis (EAE). However, recent studies by several research groups have revealed that TCR peptide therapy often confers little or no protection from autoimmune disease. In the present study, we attempted to find more appropriate peptides that is capable of conferring effective protection against the development of EAE. Four peptides corresponding to parts of the V beta region (13-23, 24-36, 39-59, and 64-74) were selected by epitope scanning and hydrophilicity searching, and their protective abilities were tested. All these peptides were, however, ineffective in protecting rats from the disease. We also generated three different synthetic peptides corresponding to the TCR J region of encephalitogenic T cells. Vaccination with the J-region peptides did not protect animals from the development of EAE. Rather, one of the peptides (V beta-DSS-J beta 2.6) enhanced the clinical severity of EAE and induced fatal disease in some rats. Taken together, TCR peptide therapy appears to be generally ineffective and elucidation of the mechanism by which EAE is enhanced after TCR peptide vaccination should provide insight into the pathogenesis of this disease.

Amino Acid Sequence↗
PubMed1996

Characterization of CD4-CD8- T cell receptor alpha beta + T cells appearing in the subarachnoid space of rats with autoimmune encephalomyelitis.

Inflammation of the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) starts in the subarachnoid space (SAS) and spreads later to the adjacent CNS parenchyma. To characterize the nature of lesion-forming T cells in situ in more detail, T cells were isolated from the SAS and their surface phenotype and the nucleotide sequence of the junctional region of the T cell receptor (TCR) was determined and compared with those of the lymph node (LN) and spinal cord (SC) T cells. Characteristically, more than 70% of SAS TCR alpha beta + T cells isolated at the early stage of EAE lacked both CD4 and CD8 molecules, whereas those from LN and SC were either CD4+ or CD8+. Analysis of nucleotide sequences of the junctional region of TCR revealed that T cells bearing a sequence identical to that for encephalitogenic T cell clones were found in both SAS and SC. Furthermore, purified CD4-CD8- T cells expressed CD4 molecules after culture. At the same time, these T cells acquired reactivity to myelin basic protein and induced passive EAE in naive animals after adoptive transfer. Our results suggest that CD4-CD8- T cells in the SAS are precursors of lesion-forming T cells in the SC and that phenotype switching takes place during the process of T cell infiltration into the CNS parenchyma. The double-negative nature of these T cells may explain an escape of encephalitogenic T cells from negative selection in T cell differentiation.

Amino Acid Sequence↗
PubMed1996

Temperature mapping using water proton chemical shift obtained with 3D-MRSI: feasibility in vivo.

This article discusses the applicability to a living animal of the temperature mapping method using the water proton chemical shift obtained with three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). There are several sources of error in obtaining the spectra with 3D-MRSI: signal noise, limitation in the frequency resolution due to the finite signal length, intravoxel inhomogeneity in the static magnetic field, and variation in the magnetic field due to the eddy current magnetic field. A spectral estimation method called phase deduction complex Lorentzian fitting (PD-CLF) was proposed. Numerical simulations demonstrated that this method reduces the error in the chemical shift to one third of that obtained with the simple frequency subtraction method that uses zero-padded first Fourier transformation (FFT). The temperature images obtained using 3D-MRSI with PD-CLF clearly visualized the changes and distribution of temperature in an anesthetized rat.

Animals↗
PubMed1996

Suppression of Theiler's murine encephalomyelitis virus induced demyelinating disease by administration of gangliosides.

Intracerebral (i.c.) inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelinating disease. Gangliosides are membrane components of essentially all eukaryotic cells and are abundant in plasma membranes. Endogenous gangliosides have been implicated in cell recognition, cell adhesion, cell differentiation and neurite outgrowth. We studied the effect of gangliosides on TMEV-induced demyelinating disease (TMEV- IDD). We injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD. Gangliosides were injected subcutaneously and examined for various immunological indicators. The results show that when gangliosides were administered in the effector phase, TMEV-IDD was suppressed both clinically and histologically. Cellular immunity such as delayed-type hypersensitivity, and the proliferative response of T cells against TMEV and mitogens were decreased, and only in this group anti-TMEV IgG2a antibody was not detected. Taken together, these data suggest that administration of gangliosides suppressed the function of pathogenic Th1 cells and suppressed TMEV-IDD. Additionally, this study proposes the possibility of a new therapy in multiple sclerosis.

Animals↗
PubMed1996

Stimulation of acid secretion in rat stomach following exposure to taurocholate in the presence of the nitric oxide synthase inhibitor.

1. The role of nitric oxide (NO) in the acid secretory response of the rat stomach following damage was investigated. A rat stomach was mounted in an ex-vivo chamber, perfused with saline, and the potential difference (PD), luminal pH, acid and HCO3- responses were measured before and after the mucosal exposure to 20 mM taurocholate (TC) for 30 min, with or without pretreatment with NG-nitro-L-arginine methyl ester (L-NAME). 2. Exposure of the stomach to TC caused a reduction of PD, a decrease of acid secretion and an increase in luminal HCO-. Pretreatment with L-NAME did not affect such PD and HCO3- responses, but completely attenuated the decreased acid secretory response and rather enhanced this secretion. 3. These effects of L-NAME were significantly antagonized by the co-administration of L-arginine but not D-arginine. The enhanced acid secretory response in the presence of L-NAME was significantly inhibited by prior administration of cimetidine or FPL-52694 (a mast-cell stabilizer). 4. The mucosal exposure to TC significantly decreased the number of mucosal mast cells and increased the luminal histamine output. 5. Damage in the stomach may activate the histamine-dependent acid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, although the latter effect overcomes the former, resulting in a decrease of acid secretion. L-NAME unmasks the stimulation of acid secretion by suppressing the inhibitory pathway.

Animals↗
PubMed1996

The level of tumor necrosis factor-alpha producing cells in the spinal cord correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

The levels of tumor necrosis factor (TNF)-alpha producing cells were analyzed in mice with Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Using an ELISPOT assay, we demonstrate an increase in TNF-alpha producing cells in the spinal cords of TMEV-infected SJL/J mice, especially at an active disease stage. The numbers of TNF-alpha producing cells were extremely high in susceptible SJL/J mice compared with the numbers in resistant BALB/c and C57BL/6 mice. TNF-alpha producing cells were also immunohistochemically identified in active lesions of TMEV-IDD at acute as well as chronic stages. The percentage of TNF-alpha producing cells compared with the total number of cells isolated from spinal cords was higher in TMEV-infected SJL/J mice than resistant BALB/c and C57BL/6 mice. Correspondingly, the level of TNF-alpha was much higher in the culture supernatants of both infiltrating cells in the spinal cords and spleen cells from clinically affected animals than that from similarly treated resistant mice. Treatment of virus-infected mice with a mAb specific for TNF-alpha at the beginning of the onset of disease suppressed the development of the demyelinating disease. These findings suggest that TNF-alpha may play an important role in the pathogenicity of TMEV-IDD.

Animals↗
PubMed1996

Split posterior tibial tendon transfer for varus deformity of hindfoot.

Sixteen patients (23 feet) who underwent split posterior tibial tendon transfers were evaluated. The patients were seen on a followup basis for a minimum of 1 year postoperatively. The causes were spastic cerebral palsy in 13 feet, spastic-athetoid cerebral palsy in 3 feet, hydrocephalus in 3 feet, and other diseases in 4 feet. The indication for surgery was varus deformity during the stance phase of gait and increased varus deformity during the swing phase of gait because of spasticity of the posterior tibial muscle. Heel cord lengthening was done on 17 feet. Preoperative and postoperative gaits were evaluated while the patients were walking. Axial radiographs of the calcaneus and the tibia were taken of all patients while they were weightbearing. There were 15 excellent, 6 good, and 2 poor results. The poor ratings were assigned to patients who had recurrence of varus deformity; there were no cases of overcorrection. Split posterior tibial tendon transfer was effective for treating spastic varus deformity of the hind part of the foot. This treatment also could be considered for a patient with spastic-athetoid cerebral palsy, if the deformity was determined to be caused by overactivity of the tibialis posterior muscle.

Adolescent↗
PubMed1996

Expression of the fibroblast growth factor receptor-1 in human normal tissues and tumors determined by a new monoclonal antibody.

OBJECTIVE: To characterize the distribution of the receptor for the fibroblast growth factor in human normal tissues and tumors using a new monoclonal antibody. DESIGN: Monoclonal antibodies for a kinase-insert region of fibroblast growth factor receptor-1 (FGFR-1) were generated. We conducted an immunohistological analysis of FGFR-1 using a highly specific antibody we generated, and we examined the distribution of this receptor in normal human tissues and in tumors. RESULTS: Intense positivity of FGFR-1 was observed in astrocytes in the brain, smooth muscles in the uterus, cardiac myocytes, respiratory epithelium in the lung, tubular epithelium in the kidney, acinar cells in the pancreas, follicular cells in the thyroid, and ductal and lobular epithelium in the breast. We also observed FGFR-1 expression in the fibroblasts and the tissue microvasculature. In addition to some nonepithelial tumors, some epithelial tumors expressed FGFR-1, including pancreatic adenocarcinomas, thyroid papillary carcinomas, invasive ductal carcinomas of the breast, lung adenocarcinomas, renal cell carcinomas, and colonic adenocarcinomas. Although FGFR-1 was expressed in colonic adenocarcinomas, which have invasive potential, tubular adenomas, which are noninvasive, did not express FGFR-1. CONCLUSION: We have been able to define the distribution of FGFR-1 in human normal tissues and tumors. Especially in colonic tumors, FGFR-1 expression may lead adenoma cells to invade and grow in the surrounding tissue.

Amino Acid Sequence↗
PubMed1996

[The development of a new QOL Questionnaire on chemotherapy - induced emesis and vomiting--investigation of reliability and validity. Group for Investigation of QOL Questionnaire for Anti-Emetics Used in Cancer Chemotherapy. Joint Research Group for Tropisetron Double-Blind Comparative study].

A new questionnaire on QOL of patients with chemotherapy-induced emesis and vomiting was developed, and its reliability and validity were investigated in the present multi-center clinical trial. The questionnaire consisted of 15 items which included descriptive questions on appetite, feeling, sleep, mental fatigue, anxiety, pain, sputum, respiratory distress, nausea, vomiting, abdominal condition, daily life in a hospital and relationship with family, a linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours, and a face scale as the global scale. Data from 98 patients with cancer were analyzed by principal component analysis and correlation analysis. The results were summarized as follows: 1) Recollect rate was 78.1% and complete response rate was 86.0% in this QOL measurement. 2) A clear correlation was observed between appetite, feeling, nausea, vomiting and the physiological scale, between sleep, mental fatigue, anxiety, pain, abdominal condition and the psychological scale, between sputum, respiratory distress and the respiratory condition related scale, between daily life in hospital and the active scale, between relationship with family and the social relation scale. These results satisfied internal consistency. 3) As for test-retest reliability, the total score of 13 descriptive items between the day before and two days before the start of chemotherapy showed no significant difference. 4) The 13 items were grouped into physiological, the psychological, the respiratory condition related, the active and the social relation scales, and these scales belonged to a different dimension. 5) The linear analogue scale, the face scale and the total scores of 13 descriptive items correlated respectively with all of items except item of, relationship with family. 6) As for concurrent validity, vomiting frequency, severity of nausea and anorexia correlated with the physiological scale. Severity of nausea and anorexia also correlated with the psychological and active scales. 7) As a result of investigation of sensitivity, the total score of the 13 descriptive items, the linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours and the face scale revealed the poorest levels 2-3 days after chemotherapy but recovered thereafter. The aggravation of QOL of patients treated with chemotherapy was reduced in the anti-emetic administration group compared with the placebo administration group. These results suggested that this new questionnaire developed for chemotherapy-induced emesis and vomiting had sufficient validity and reliability to reflect the effects of anti-emetic drug.

Aged↗
PubMed1996

[Effects of an anti-emetic tropisetron capsule on QOL of patients with delayed nausea and vomiting induced by cancer chemotherapy. Group for Investigation of QOL Questionnaire for Anti-Emetics used in Cancer Chemotherapy. Joint Research Group for Tropisetron Double-Blind Comparative Study].

We have reported our "new questionnaire of QOL (quality of life) in anti-emetic therapies during cancer chemotherapy" and demonstrated its reliability and validity. In the present study we investigated the utility of tropisetron capsules for delayed nausea and vomiting induced by cancer chemotherapies with CDDP single administration in a placebo-controlled double-blind comparative study using the questionnaire. The questionnaire was composed of the following scales: a physiological scale (appetite, feeling, vomiting, nausea), a psychological scale (sleep, mental fatigue, anxiety, pain, abdominal condition), a respiratory condition related scale (sputum, respiratory distress), an active scale (daily life in a hospital), a social relation scale (understanding of the family), a linear analogue scale for evaluation of the influence of nausea and vomiting in patient's life during 24 hours, and a face scale as the global scale. First, all patients were administered a preventive dose of tropisetron capsule on day 1 (the day of CDDP administration) and then allotted to once-daily oral administration of either a tropisetron (T group) or a placebo (P group) capsule during days 2 to 5 by a double-blind method. Chronological changes of QOL during the study period were measured by the area under the curve (AUC) generally used for calculation of blood levels of drugs. The maximum fluctuation (Difmax) of QOL scores throughout the whole study period was also evaluated. The data were collected from 114 cases, and 98 cases (51 in P group, 47 in T group) were analyzed. 1) The total score or 13 items (a modified linear analogue scale with 5 graduations), the face scale and linear analogue scale of T group were higher (better) than those of P group. 2) As for the total score of each scale, the physiological, psychological and active scales in the T group showed higher (better) levels than the P group. 3) As for the AUC values, the T group was lower (better) than the P group in most items. In AUC of the total score of 13 items, the face scale, the physiological and the psychological scales, the T group was significantly superior to the P group. 4) AUC levels of each item belonged to the physiological and the psychological scales in the T group tended to be lower (better) than the P group, and "sleep" and "pain" in the psychological scale were significantly lower (better) in T group than P group. 5) In Difmax values, all scales except respiratory condition related scale showed lower levels (better) in T group and the total score of 13 items, the face scale and the physiological and psychological scales showed significantly lower levels than P group. 6) Difmax values in each item belonging to the physiological and psychological scales showed lower levels in the T group, while "appetite" and "vomiting" in the physiological scale and "sleep" in the psychological scale showed significantly lower levels (better) than those of the P group. 7) In the stratified analysis performed for patients without nausea and vomiting on the 1st day of chemotherapy, there was no significance in AUC levels of all items in both groups. In patients with nausea and vomiting on the 1st day, the total score of 13 items, the face scale, the physiological and the psychological scales in the T group were significantly better than in the P group. 8) It was suggested that the anti-emetic efficacy of tropisetron for delayed nausea and vomiting might reduce the undesirable influence of chemotherapy on QOL, especially on the physiological and the psychological effects. These results suggested that this new questionnaire is applicable for evaluation of the utility of anti-emetics in patients in cancer chemotherapy, and that tropisetron capsules could reduce the decrease of QOL in delayed nausea and vomiting induced by chemotherapy.

Adolescent↗
PubMed1996

Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models.

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.

Acetylcholinesterase↗