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Biomedical subjects

K Isoe

Publications and source records attributed to K Isoe.

At least 19 recordsLinked to original sources

Production of dopaminergic neurons for cell therapy in the treatment of Parkinson's disease.

Dopaminergic cell therapy is a potential viable treatment for Parkinson's disease. However, lack of a well-characterized cell preparation of known phenotypic composition containing a high percentage of dopaminergic neurons, has prevented a definitive, controlled, pilot clinical trial from being conducted. We report the successful in vitro expansion of rat E12 mesencephalic progenitors to produce 5-fold the normal number of dopaminergic neurons. The expanded neurons (MAP2+) were detached, resuspended, and formed into small aggregates of 10-200 neurons containing 25-50% of dopaminergic neurons (TH+) that will likely be optimal for use in successful cell therapy. After storage in DPBS, in 0 mM Ca(2+) for up to 24 h at room temperature, aggregated cells were still 90% viable. These results demonstrate that it might be feasible to use a similar protocol to expand human dopaminergic progenitors in vitro. If successful, the requisite large numbers of dopaminergic neurons required to conduct a pilot clinical trial for Parkinson's disease will be produced in vitro. Indications are that the cells can be maintained at optimal viability for the duration of the neural transplantation procedure, under real operating conditions.

Animals↗

Longitudinal study of cerebrospinal fluid levels of tau, A beta1-40, and A beta1-42(43) in Alzheimer's disease: a study in Japan.

To clarify the alterations of tau, amyloid beta protein (A beta) 1-40 and A beta1-42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non-AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme-linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the A beta1-42(43) levels and a significant increase of the ratio of A beta1-40 to A beta1-42(43) were observed in the AD patients. The longitudinal AD study showed continuous low A beta1-42(43) levels and an increase of the ratio of A beta1-40 to A beta1-42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of A beta1-42(43) and the ratio of A beta1-40 to A beta1-42(43) may start at early stages in AD. The assays of CSF tau, A beta1-40, and A beta1-42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of A beta1-40 to A beta1-42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.

Aged↗

Presenilin-1 polymorphism in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia in Japanese population.

We investigated the genetic association between intronic polymorphism in Presenilin-1 (PS-1) gene and patients with various types of dementia such as Alzheimer's disease (AD), vascular dementia (VD) and alcohol associated dementia (ALD), in Japanese population. Homozygosity for allele 1 of the PS-1 polymorphism was significantly increased in late-onset sporadic AD, but not in early-onset sporadic AD, familial AD, VD and ALD. When late-onset sporadic AD patients were divided on the basis of apolipoprotein E (APOE) genotype, homozygosity for the allele 1 of the PS-1 polymorphism was significantly increased in patients with late-onset sporadic AD without APOE epsilon 4 allele, but not in those with APOE epsilon 4 allele. Intronic mutation in PS-1 gene may be specific and one of the genetic risk factor for late-onset sporadic AD.

Age of Onset↗

[A case of supranuclear hypoglossal nerve palsy with Avellis' syndrome due to a medullary infarction].

We reported a 72-year-old man with left supranuclear hypoglossal nerve palsy and right Avellis' syndrome due to a medullary small infarction. On admission, he showed slight disturbance of consciousness, ocular lateropulsion to the right side, rotatory nystagmus, dysarthria, absent right gag reflex, curtain sign, absent right palatal reflex, deviation of the uvula toward the left side, raise of only the left palate when the patient attempted to utter, paralysis of the right vocal cord and deviation of the tongue toward the left side. Neither atrophy nor fasciculation was observed on the tongue. 124 days after the onset, he had only the left supranuclear hypoglossal nerve palsy and right Avellis' syndrome. MRI showed a small lesion in the medulla, so lateral area of the medulla and a part of the reticular formation medial to the nucleus ambiguous presumed to be involved. These findings suggest that supranuclear pathway to the hypoglossal nucleus of the opposite side exists in the reticular formation near nucleus ambiguous.

Aged↗

[A case of dissecting aneurysm of the basilar artery presented as superior pons type of Foville's syndrome].

Here we report a 47-year-old man with dissecting aneurysm of the basilar artery who developed Foville's syndrome due to upper pons involvement. At first he had an abrupt onset of dysarthria and weakness in his left upper and lower extremities during his work. Neurological examination on admission revealed mild disturbance of consciousness, absent light reaction on the left side, hypesthesia of the left face, absent gag reflex, dysarthria, and left hemiparesis with ataxia. On the second hospital day he developed paralysis of conjugate eye movement to the right, left central facial palsy, and left hemiplegia, and hyperhidrosis of the left side of the body. He was diagnosed to have superior pons type of Foville's syndrome. Computed tomography showed low density area in the right upper pons, and the basilar artery had marked lateral shift, dilatation, and calcification. Vertebral angiography demonstrated dissecting aneurysm of the basilar artery. Although it is very rare that dissecting aneurysm of the basilar artery causes the brain stem symptoms, its possibility should be considered when computed tomography shows marked lateral shift, dilatation, and/or calcification of the basilar artery.

Aortic Dissection↗

[A case of pontine supranuclear facial palsy].

A 56-year-old hypertensive man suddenly developed difficulty in speaking and numbness in the right hand. On admission, he showed moderate right supranuclear facial palsy and right clumsy hand. Three weeks later, he was discharged with only right supranuclear facial palsy. MRI revealed a small infarction in the middle pons. The lesion was situated in the paramedian borderzone between the base and tegmentum. These findings suggest that supranuclear fibers to the facial nucleus descend as a separate bundle from the main pyramidal tract at the mid-pontine level.

Cerebral Infarction↗

[A case of cerebral pedunclar infarction presenting with pure motor hemiparesis].

Left pure motor hemiparesis occurred in a 42-year-old woman with a history of hypertension and diabetes mellitus. The left hemiparesis affected the arm and leg equally. The face was almost spared, with only a very slight facial asymmetry. Brain CT and MRI showed a small infarction located in the external 2/3 of the right cerebral peduncle. Cerebral angiography did not reveal significant abnormalities.

Adult↗

[The efficacy of X-ray signs for differential diagnosis of small lung cancer and tuberculoma. Committee for Lung Cancer Mass Screening, JATA].

In order to evaluate the efficacy of X-ray signs for the differential diagnosis of small lung cancer from tuberculoma, a cooperative study was carried out. X-ray films of 64 cases (lung cancer 35, tuberculoma 29) were read by 11 experienced chest physicians independently. The positivity of various X-ray signs were assessed respectively and obtained data were analysed with ROC analysis method. "Ill defined contour", "unevenness of density", "paleness" were proved to be relatively useful as a diagnostic tool, but "notch", "pleural indentation" were not useful in differentiating lung cancer from tuberculoma. It was also noted that great interindividual variations existed on the judgements of X-ray signs among chest specialists, and the conquest of which may be a crucial key for the universal validity of these signs.

Diagnosis, Differential↗

Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia.

The phenotypes of apolipoprotein E (ApoE) in the plasma of patients with dementia of the Alzheimer type (DAT) and vascular dementia (VD) were determined by the isoelectric focusing method. The ApoE mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the control subjects, the frequency of the ApoE epsilon 4 allele was significantly higher in the DAT group as well as the VD group, but was not significantly different in the cerebrovascular disease without dementia (CVD) group. The skin fibroblast ApoE mRNA level in the DAT group and the VD group was significantly lower than that in the control group. These findings suggest that the phenotype of ApoE is associated with DAT and VD, and that the lower level of ApoE mRNA may play an important role in the development of DAT as well as VD.

Aged↗

The expression of presenilin-1 mRNA in skin fibroblasts from Alzheimer's disease.

The presenilin-1 (PS-1) gene was recently identified as one of the causative genes in the early onset of familial Alzheimer's disease (AD). Analysis of the PS-1 gene is thought to be useful in clarifying the pathogenesis of AD. However, there have been few reports about the expression of the PS-1 gene in AD. In this study, we analyzed the expression of PS-1 mRNA in cultured skin fibroblasts taken from living patients with AD by Northern blot analysis. The subjects consisted of 18 cases with AD and 10 cases of neurological patients without dementia (CTL). We found that the PS-1 mRNA levels in AD were significantly higher than those in CTL (p < 0.01). Moreover, we found that the PS-1 mRNA level increases in the early stages of AD and tends to decrease in the advanced stages. These findings suggest that high levels of PS-1 mRNA may play an important role in developing AD.

Adult↗

Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease.

Apolipoprotein E sigma4 allele (ApoE sigma4) is associated with Alzheimer's disease (AD) in familial and sporadic cases, but the associations of ApoE sigma4 allele and vascular dementia (VD) and/or ischemic cerebrovascular disease (ICVD) are still controversial. To clarify the associations of ApoE polymorphism with AD, VD and ICVD in Japanese, we examined ApoE polymorphism in samples of 255 patients with AD, 87 patients with VD, and 123 patients with ICVD, as compared with 117 age-matched healthy control subjects (CTL). The frequency of the ApoE sigma4 allele was significantly higher in the VD group (0.21), the ICVD group (0.15) as well as in the AD group (0. 26) than in the CTL subjects (0.08). These findings suggest that the genotype of ApoE sigma4 is associated with not only AD but also VD and ICVD, and that ApoE sigma4 plays an important role in the development of dementia and ICVD.

Aged↗