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Biomedical subjects

Shotai Kobayashi

Publications and source records attributed to Shotai Kobayashi.

At least 19 recordsLinked to original sources

Differentiating Alzheimer's disease from subcortical vascular dementia with the FAB test.

BACKGROUND: The frontal assessment battery (FAB) test is a composite tool for assessing executive functions related to the frontal lobe. Neuropsychological and blood-flow studies indicate distinct patterns of deterioration of anterior and posterior cortical function in Alzheimer's disease (AD) and subcortical vascular dementia (VD) patients. We predict that the FAB score may be useful for discriminating VD from AD. OBJECTIVE: To evaluate the clinical usefulness of the FAB test for differential diagnosis of AD and VD. METHODS: We compared FAB scores in 25 patients with AD, 27 patients with VD, and 80 age-matched normal control subjects. The AD group was matched for age, education and MMSE score with the VD group. The subtest scores in FAB were also compared among the three groups. RESULTS: The FAB scores were significantly decreased in both the AD and VD groups compared to the control group, and the reduction were greater in the VD group. Among the FAB subtests, mental flexibility (phonological verbal fluency) was the only subtest that significantly discriminated VD from the other two groups. CONCLUSIONS: The FAB test can provide useful information for differentiating AD and VD at the bedside.

Aged↗

Somatosensory disinhibition and frontal alien hand signs following medial frontal damage.

We report augmentation of somatosensory evoked potentials (SEP) in a patient with frontal alien hand signs after left medial frontal lobe damage. The SEP components occurring later than 30 msec post stimuli were enhanced over the parietal and frontal scalp sites of the lesioned hemisphere. This finding suggests that deficits in inhibitory control of somatosensory processing in parietal and frontal lobes contributes in some way to frontal alien hand signs.

Aged, 80 and over↗

Surgery for spontaneous intracerebral hemorrhage has greater remedial value than conservative therapy.

BACKGROUND: The aim of this study was to compare the efficacy of surgery for spontaneous intracerebral hemorrhage with that of medical treatment, based on data from the Japan Stroke Registry Study. METHODS: From 1999 to 2001, 1010 patients with spontaneous intracerebral hemorrhage were registered in the Japan Standard Stroke Registry Study from 45 stroke center hospitals in Japan. The National Institutes of Health Stroke Scale (NIHSS), Japan Stroke Scale (JSS), and modified Rankin Scale scores were used to compare severity and improvement in patients given surgical and medical treatment. CONCLUSIONS: Surgically treated patients, especially those with cerebellar hemorrhage, had significantly greater improvement in NIHSS or JSS score compared with medically treated patients. Our findings indicated that the patients who underwent surgery appeared to have better outcomes. But, because the study was not randomized, this observation cannot be interpreted as indicating that surgery is advantageous.

Adult↗

Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase.

In the present study, we investigated the expression of protease-activated receptors (PARs), receptors for thrombin, in substantia nigra pars compacta (SNpc) of Parkinson disease (PD) brains and cultures of human neurons, astrocytes, oligodendrocytes, and microglia as determined by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of PAR-1 was demonstrated only in glial fibrillary acidic protein-positive astrocytes in SNpc, and the number of astrocytes expressing PAR-1 increased in SNpc of PD as compared with nonneurologic control brain. Immunoreactivity for thrombin and prothrombin was stronger in astrocytes and the vessel walls in SNpc of PD brains. PAR-1 was expressed in human astrocytes and neurons, but not in oligodendrocytes or microglia as determined by RT-PCR. We investigated thrombin-mediated activation of human astrocytes. Thrombin treatment activates human astrocytes and induces morphologic change and a marked increase in proliferation of astrocytes. Increased expression of glial cell line-derived growth factor and glutathione peroxidase (GPx) but no change in the expression of nerve growth factor and inflammatory cytokines/chemokine (IL-1beta, IL-6, IL-8, MCP-1) was found in thrombin/PAR-activated astrocytes. Next, we studied the neuroprotective effect exerted by thrombin-activated astrocytes in human cerebral neuron x human neuroblastoma hybrid neurons. Although thrombin showed neurotoxicity against human hybrid neurons in a dose-dependent manner, the conditioned media derived from thrombin-pretreated astrocyte cultures promoted the survival of human hybrid neurons. The protective effect was completely inhibited with a GPx inhibitor, mercaptosuccinic acid, indicating that GPx released from thrombin/PAR-activated astrocytes is responsible for neuroprotection of hybrid neurons against thrombin cytotoxicity. The present study suggests that the increased expression of PAR-1 in astrocytes in SNpc of PD brain is the restorative move taken by the brain to provide neuroprotection against neuronal degeneration and cell death of dopaminergic neurons caused by noxious insults during the progression of PD pathology.

Aged↗

[Effect of sarpogrelate in enteral feeding of patients with gastroesophageal reflux (GER)].

AIM: Enteral feeding of patients who are unable to eat or drink because of neurological disorders finally undergo percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Their most common serious complication is aspiration pneumonia. Our objectives were to evaluate the effect of sarpogrelate (a 5-HT2A receptor blocker) on gastroesophageal reflux (GER) in these patients. METHODS: This study was performed in 5 elderly patients, aged 70-87 years with neurological disorders (stroke 4, post herpes encephalitis 1), on PEG or nasogastric feeding for 5 weeks-1 year. A 48-hour esophageal pH study was performed using the Degitrapper pH400 (Medtronic Co.). The pH monitor catheter was passed into the esophagus transnasally and positioned with the pH electrode 5cm above the lower esophageal sphincter. During the first 24 hours drug no drug was given, and during the next 24 hours we gave 100mg sarpogrelate 3 times. We analyzed the frequency of acid reflux (when the pH in the esophagus become less than 4.0 for more than 5 seconds, we defined this is 1 episode of acid reflux), frequency of acid reflux and mean pH values between drug-on and drug-off periods. An upright position was maintained for two hours after each meal. RESULTS: When the results of pH monitoring during two half days (from 7 pm to 7 am: 12 hours) was compared between drug-on term and drug-off term, mean pH value was statistically elevated from 6.0 +/- 0.2 (drug-off) to 6.5 +/- 0.4 (drug-on) (mean +/- SD, p< 0.05). Frequency and the total time of acid reflex showed no difference between the two periods. CONCLUSION: Treatment with sarpogrelate might be effective in patients with GER by blocking activated serotonin receptor in the gastrointestinal system.

Aged↗

[Clinical characteristics and prognosis in stroke patients with diabetes mellitus: retrospective evaluation using the Japanese Standard Stroke Registry database (JSSRS)].

We studied clinical characteristics and prognosis in acute stoke patients with diabetes mellitus registered on the Japanese Standard Stroke Registry database. A total of 16,630 acute stroke patients admitted to 56 hospitals in Japan. They were examined as to their stroke types, risk factors, their severity of stroke according to the NIH Stroke Scale (NIHSS) and Japan Stroke Scale (JSS), and outcomes by the modified Rankin Scale (m-RS). The incidence of subarachnoid hemorrhage was relatively high in the group of patients who had neither hypertension nor diabetes, and the incidence of brain hemorrhage was higher in the group of patients who had hypertension without diabetes. The frequencies of lacunar infarct and atherothrombotic infarct were also higher in the group of patients who had both hypertension and diabetes. In the diabetic group without hypertension, there were less numbers of hemorrhagic stroke. The ratio of good prognosis (m-RS 0-1) was significantly smaller in the diabetic patients with lacunar infarction, cardioembolic infarction, and subarachnoid hemorrhage. Additionally, there was significantly more stroke recurrence in the diabetic patients (33.0% vs. 26.9%, p<0.0001). The diabetic patients who received insulin therapy (-0.8 +/- 7.4), diet therapy (-0.4 +/- 9.4), or oral medicine (-0.9 +/- 7.2), showed significantly less improvements in the NIHSS compared to the non-diabetic patients (-1.6 +/- 8.2), respectively. Moreover, the poor-management diabetic patients showed significantly less improvements in the JSS compared to non diabetic patients (3.8 +/- 7.7 vs. 4.8 +/- 8.6, p<0.005). In conclusions, stroke patients with diabetes mellitus showed more stroke recurrence and resulted in poorer functional recovery compared to patients without diabetes.

Aged↗

Neuronal cell death induced by cystatin C in vivo and in cultured human CNS neurons is inhibited with cathepsin B.

Cystatin C, a cysteine protease inhibitor, is implicated in pathogenesis of late-onset Alzheimer's disease and other neurological disorders. Our recent study showed that cystatin C injection into rat hippocampus induced neuronal cell death in granule cell layer of dentate gyrus in vivo. We further confirmed that cystatin C neurotoxicity was inhibited by simultaneous coapplication of cathepsin B, a cysteine protease. In vitro cytotoxicity was also studied in cultures of human CNS neurons, mixed cultures with astrocytes and A1 human hybrid neurons. Cystatin C induced neuronal cell death in a dose-dependent manner, which accompanied increased number of TUNEL (+) cells, up-regulation of active caspase-3 and DNA ladder. The results of the present study indicate that cystatin C participates in the process of apoptotic neuronal cell death in experimental conditions by means of inhibitory activity of cysteine proteases, and that cystatin C might be involved in the pathogenesis in human neurological disorders including Alzheimer's disease.

Animals↗

Immortalized human microglial cell line: phenotypic expression.

Microglia are a major neuroglial component of the CNS, playing an important role as resident immunocompetent and phagocytic cells in the CNS in the event of injury and disease. To understand the role of microglia in the CNS in health and diseases, we have recently established an immortalized clonal cell line of human microglia, HMO6, from human embryonic telencephalon tissue by using a retroviral vector encoding v-myc. This immortalized microglia HMO6 cell line exhibits cell-type-specific antigens for microglia, including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and RCA-1 lectin, and actively phagocytoses latex beads.

Animals↗

Event-related potentials for response inhibition in Parkinson's disease.

This study investigated inhibitory function in patients with Parkinson's disease (PD) by recording event-related brain potentials (ERPs) during a Go/NoGo task. Fourteen healthy volunteers and 13 patients with PD without dementia performed a cued continuous performance test that included Go and NoGo trials. The peak latency, amplitude, and topographic distributions of the ERPs to Go and NoGo stimuli were analyzed. Cognitive function was evaluated using the Wisconsin Card Sorting Test (WCST), Kana Pick-out Test, and Verbal Fluency Test (VFT). Performances in the WCST and VFT were significantly impaired in the PD group as compared with the control group. The PD group had significantly higher rates of omission and commission errors during the ERP task. The ERP study found no differences in the latency and amplitude of the Go-P3 between the two groups. By contrast, the NoGo-P3 latency was significantly longer in the PD group than in the control group. The amplitudes of the NoGo-P3 and NoGo-N2 were also significantly smaller in the PD group than in the control group. The NoGo-P3 latency was significantly correlated with the Kana Pick-out Test and VFT scores. The NoGo-P3 amplitude was significantly correlated with the WCST and VFT scores, as well as with the number of commission errors. There were no significant correlations between the cognitive function tests and either the Go-P3 or NoGo-N2 measures. The behavioral and ERP data suggest that there is selective impairment of inhibitory function in PD and that this deficit may be related to impaired inhibitory executive function in the frontal lobe.

Aged↗

Clinical characteristics of first-ever atherothrombotic infarction or lacunar infarction with hyperlipidemia (J-STARS-C): an analysis of data from the stroke data bank of Japan.

OBJECTIVE: The clinical trial, Japan Statin Treatment Against Recurrent Stroke (J-STARS), is being carried out to investigate the efficacy of statin treatment against recurrent stroke. To participate in J-STARS, patients must have a past history of ischemic stroke excluding cardioembolic events, and must be clinically diagnosed with hyperlipidemia (HL). Before starting J-STARS, we needed to be aware of the clinical characteristics of the patients who were eligible to participate in this study. METHODS: Between 1999 and 2002, 7,149 patients with ischemic stroke were enrolled in a stroke data bank developed by the Japan Standard Stroke Registry Study Group. From this, we acquired the data on 1,487 patients with first-ever atherothrombotic infarction (ATI) or lacunar infarction (LI) with a satisfactory functional outcome on discharge. RESULTS: Patients with HL were significantly younger (65.3+/-11.0 vs 68.4+/-10.9, p<0.0001) and showed a higher frequency of concomitant hypertension (70.9% vs 61.0%, p=0.0002), diabetes mellitus (42.2% vs 25.7%, p<0.0001) or both (31.7% vs 16.4%, p<0.0001) compared to those without HL. The ratio of ATI to LI and the frequency of prior ischemic heart disease (IHD) did not differ between the 2 groups. Among 467 patients with HL, 52.7% did not receive treatment on admission. CONCLUSION: ATI or LI patients with HL had an earlier age of onset and higher frequency of other lifestyle-related diseases, and this probably includes many with metabolic syndrome, whereas the frequency of IHD was not different between these 2 groups.

Aged↗

[Management of hypertension in elderly patients with stroke].

Hypertension is the most significant risk factor for stroke. Recently, many mega-studies have been shown that antihypertensive therapy reduced the incidence of stroke not only for normal elderly but also for patients with a past history of stroke. To prevent the recurrences of stroke, tighter control of blood pressure is thought to be required than used to be. According to the recent Japanese guidelines for hypertension, desirable blood pressure should be 140/90 mmHg or less for the patients with stroke.

Aged↗

Evaluation of applied cases of thrombolytic therapy against ultra-acute ischemic stroke. Using the Japanese Standard Stroke Registry Database.

BACKGROUND: A retrospective evaluation was made concerning thrombolytic therapy for ultra-acute ischemic stroke patients, using a recombinant tissue plasminogen activator (rt-PA), which is not yet approved as a drug for brain infarction in Japan. The evaluation was implemented using the database of patients that suffered acute strokes as collected by the Japanese Standard Stroke Registry Study (JSSRS). METHODS: The thrombolytic therapy group, selected from among the registered 6,090 cases of brain infarction patients, was divided into two groups, namely, a group of patients who were admitted in the hospital within 3 hours of the onset (86 cases, average age 69.6) and the other group who were admitted after 3 hours from the onset (28 cases, average age 66.8). Using a Multiple Logistic Regression Analysis adapted for modified Rankin scale (mRS) regarding each group, the clinical effects of thrombolytic therapy for functional outcome and presence or absence of dementia at the time of hospital discharge were examined. Among the 467 cases of patients (average age 74) who were admitted within 3 hours of the onset and for whom the NIH Stroke Scale (NIHSS) was between 6 and 29 at the time of admission, intravenous or intra-arterial thrombolytic therapy was conducted in 88 cases. Then, a case-control study and Multiple Logistic Regression Analysis was implemented for subject groups matched according to the gender, age and severity at the time of admission, and the effects on early-admitted patients were examined. Also, for two rehabilitation patient groups: one whose rehabilitation started within 7 days (216 cases; average age 73) and the other whose rehabilitation started after 7 days (56 cases, average age 76), the effects of early rehabilitation were examined using Multiple Logistic Regression Analysis. Moreover, the effects of thrombolytic therapy on a group of patients who were admitted early and for whom rehabilitation started early (215 cases; average age 73) were examined in the same way. RESULTS: In the comparison between the thrombolytic therapy groups, the functional outcome of the group of patients admitted within 3 hours of the onset at the time of discharge (mRS 0-1) was significantly better compared with that of the group after 3 hours from the onset (OR 2.79, 95% CI: 1.06-7.32). Regarding the comparison between the early admitted patients, the frequency of poor functional outcomes (mRS 2-6) at the time of discharge was significantly lower in the thrombolytic therapy group (OR 0.55, 95% CI 0.31-0.98), and the frequency of dementia was also significantly lower (OR 0.37, 95% CI 0.17-0.86). In the case control study, a significant difference was noted for the presence of dementia. In the group rehabilitation was started early, the frequency of poor functional outcomes was significantly lower (OR 0.33, 95% CI 0.11-0.98), and the frequency of dementia was also significantly lower (OR 0.41, 95% CI 0.19-0.89). As for the comparison of the groups admitted early and for which rehabilitation started early, the frequency of poor functional outcomes at the time of discharge was significantly lower in the thrombolytic therapy group (OR 0.38, 95% CI 0.16-0.86). CONCLUSIONS: From the present analysis, in spite of being a retrospective analysis based on comparatively small number of patient cases from the stroke database, it is concluded that the clinical application of thrombolytic therapy for ultra-acute ischemic strokes was effective. Moreover, it was demonstrated that, if it is possible to start rehabilitation early, a dramatic improvement of the effects might be expected.

Aged↗

[Acute divergence paralysis in the Miller Fisher syndrome].

We experienced a 53-year-old man diagnosed as Miller Fisher syndrome (MFS) associated with anti-GQ1b and anti-GT1a antibodies. He presented acute divergence paralysis, bulbar palsy, ascending hyperesthesia, areflexia and diminished vibration sense. External ophthalmoplegia and convergence paralysis were not seen, but he noticed double vision when looking at an object from the distance of more than 70 cm away on a day 10 of hospitalization. Hess chart test revealed an esotropic pattern, so the diagnosis of divergence palsy was made. Brain MRI was normal. Neurological deficits were treated with plasma exchange, resulting in favorable outcome. Divergence paralysis could be one of the clinical manifestations for MFS and might be due to nuclear or supranuclear damge of vergence-related neurons.

Acute Disease↗

[Intravenous tissue plasminogen activator (t-PA) for acute ischemic stroke in a local university hospital].

Thrombolytic therapy for ischemic stroke has not been approved in Japan yet. However, we have used intravenous t-PA for acute ischemic stroke patients. We reviewed the clinical data on patients who were treated with intravenous t-PA and entered in the stroke registry of our hospital between April 1999 and March 2004. Of 408 acute ischemic stroke patients, 20 patients (mean age 73.6 +/- 10.9, male 15, female 5) were given intravenous t-PA (alteplase in 18 patients and monteplase in two patients). The baseline NIH Stroke Scale (NIHSS) and Japan Stroke Scale (JSS) scores were 17.5 (median) and 13.3 +/- 7.6 (mean), respectively. The NIHSS and JSS at discharge were 12.5 and 12.1 +/- 11.8, respectively. Symptomatic intracerebral hemorrhage occurred in one patient. The rate of favorable outcome (mRS 0-3) at 90 days was 40%. The rate of favorable outcome at 90 days in our study was lower than that in reported randomized trials of intravenous t-PA, such as the NINDS study or the ATIANTIS trial, perhaps because age and baseline severity were higher in our patients than in the subjects in these trials. Another reason may be the dose of t-PA. As we concerned about the occurrence of symptomatic intracranial hemorrhage and there are no data on appropriate dose of t-PA for Japanese patients, the dose of t-PA that we used was 0.4 mg/kg in most patients. Although five patients died in our study, the cause of death in four patients was not hemorrhagic transformation but deteriorating ischemic infraction. The dose of t-PA that we used may have been safe but a little low for thrombolysis.

Age Factors↗