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Takeo Kato

Publications and source records attributed to Takeo Kato.

At least 19 recordsLinked to original sources
PubMed2006

The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease.

Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of alpha-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with alpha-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. Genetic association study revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of alpha-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.

Aged↗
PubMed2006

Vogt-Koyanagi-Harada's disease presenting polymorphonuclear pleocytosis in the cerebrospinal fluid at the early active stage.

We report a 16-year-old woman with Vogt-Koyanagi-Harada's (VKH) disease, presenting polymorphonuclear pleocytosis in the cerebrospinal fluid (CSF) and neurological manifestation similar to meningoencephalitis. VKH disease, which has severe neurological manifestations including numerous CSF polymorphonuclear pleocytosis, should be considered as a differential diagnosis from infectious meningoencephalitis.

Adolescent↗
PubMed2006

A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells.

Although embryonic stem (ES) cells are capable of unlimited proliferation and pluripotent differentiation, effective preparation of neural stem cells from ES cells are not achieved. Here, we have directly generated under the coculture with dissociated primary neurosphere cells in serum-free medium and the same effect was observed when ES cells were cultured with conditioned medium of primary neurosphere culture (CMPNC). ES-neural stem cells (NSCs) could proliferate for more than seven times and differentiate into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. The responsible molecule in CMPNC was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, which turned out to be cystatin C. Purified cystatin C in place of the CMPNC could generate ES-NSCs efficiently with self-renewal and multidifferentiation potentials. These results reveal the validity of cystatin C for generating NSCs from ES cells.

Animals↗
PubMed2006

Alteration of familial ALS-linked mutant SOD1 solubility with disease progression: its modulation by the proteasome and Hsp70.

Accumulation of misfolded Cu/Zn superoxide dismutase (SOD1) occurs in patients with a subgroup of familial amyotrophic lateral sclerosis (fALS). To identify the conversion of SOD1 from a normally soluble form to insoluble aggregates, we investigated the change of SOD1 solubility with aging in fALS-linked H46R SOD1 transgenic mice. Mutant SOD1 specifically altered to insoluble forms, which were sequentially separated into Triton X-100-insoluble/sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble/formic acid-soluble species. In spinal cords, the levels of SDS-dissociable soluble SOD1 monomers and SDS-stable soluble dimers were significantly elevated before motor dysfunction onset. In COS-7 cells expressing H46R SOD1, treatment with proteasome inhibitors recapitulated the alteration of SOD1 solubility in transgenic mice. In contrast, overexpression of Hsp70 reduced accumulation of mutant-specific insoluble SOD1. SDS-soluble low molecular weight species of H46R SOD1 may appear as early misfolded intermediates when their concentration exceeds the capacity of the proteasome and molecular chaperones.

Age Factors↗
PubMed2006

Upper midbrain profile sign and cingulate sulcus sign: MRI findings on sagittal images in idiopathic normal-pressure hydrocephalus, Alzheimer's disease, and progressive supranuclear palsy.

PURPOSE: On magnetic resonance imaging (MRI) sagittal sections, we sometimes encounter abnormal aspects of the superior profile of the midbrain and the cingulate sulcus in patients with dementia. In this preliminary study, we refer to these findings as the "upper midbrain profile sign" and the "cingulate sulcus sign." We prospectively evaluated the usefulness of these signs for the diagnosis of idiopathic normal-pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). MATERIALS AND METHODS: We evaluated the upper midbrain profile sign and the cingulate sulcus sign on MRI sagittal images obtained from 21 people with headaches but no neurological deficit (controls), 10 iNPH patients, 11 AD patients, and 5 PSP patients. The upper midbrain profile sign indicated a concave shape to the superior profile of the midbrain on mid-sagittal images, and the cingulate sulcus sign indicated a narrow, tight aspect of the posterior part of the cingulate sulcus on paramedian-sagittal images. RESULTS: These signs were never seen in any images from the controls. The upper midbrain profile sign was seen in 7 of 10 patients with iNPH, 5 of 11 with AD, and 3 of 5 with PSP. The cingulate sulcus sign was seen in all 10 patients with iNPH but was never seen in any patient with AD or PSP. CONCLUSION: The upper midbrain profile sign could support a diagnosis of PSP but cannot discriminate among iNPH, AD, and PSP. In contrast, the cingulate sulcus sign has a very high sensitivity for iNPH and should facilitate the distinction of iNPH from other dementias. In the clinical setting, it is momentous to evaluate these signs easily by one simple MRI sequence.

Aged↗
PubMed2006

Correlation between change in body weight rather than current body weight and change in serum adiponectin levels in a Japanese population -- the Funagata study.

Serum adiponectin levels are decreased in obese subjects. We examined the association of current body weight (BW) and its change with a change in serum adiponectin levels. Serum adiponectin levels at the baseline (from 1995 to 1997) and the 5-year follow-up (from 2000 to 2002) examinations were evaluated in 1003 (M/F, 425/578; age at the baseline examinations, 58.3 +/- 11.7/57.5 +/- 11.0 years) Japanese subjects from a cohort population (N = 2013) of the Funagata study. Correlations and associations of BW at the baseline examinations and changes in BW between the baseline and the follow-up examinations (deltaBW) with changes in the serum adiponectin levels in the study period (deltaAdiponectin) were examined. Stepwise regression analyses revealed a significant correlation of the deltaBW (r = -0.233 and -0.204 for men and women, respectively; r = -0.324 for the upper tertile group divided based on their body mass index in women) with the deltaAdiponectin. However, the BW at the baseline examinations was not significantly correlated in both sexes. Multiple logistic regression analyses revealed that subjects who reduced their BW by 2 kg or more were 2.56 (95% confidence interval, 1.21-5.42; P = .014) and 8.24 times (95% confidence interval, 3.59-18.9; P < .001) more likely to be in the upper tertile of the deltaAdiponectin than those who increased their BW by 2 kg or more in men and women, respectively, independent of their BW at the baseline examinations. In conclusion, we showed here that the deltaBW was strongly associated with the deltaAdiponectin in both sexes, whereas the BW at the baseline examinations was not associated with the deltaAdiponectin, at least in women.

Adiponectin↗
PubMed2006

Cardiovascular risk factors and retinal microvascular signs in an adult Japanese population: the Funagata Study.

OBJECTIVE: To describe the prevalence of retinal vascular signs and their association with cardiovascular risk factors in a Japanese population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Adult persons aged 35 years or older from Funagata, Yamagata Prefecture, Japan (n = 1481). METHODS: The Funagata Study is a Japanese population-based study of persons aged 35 years or older, and included 1961 nondiabetic participants (53.3% of 3676 eligible subjects). A nonmydriatic retinal photograph was taken of 1 eye to assess retinal microvascular signs. Retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex) and retinopathy were assessed in 1481 participants without diabetes (40.3% of eligible persons) using a standardized protocol. Using a computer-assisted method, retinal vessel diameters were measured in 921 participants with gradable retinal image (25.1% of eligible persons). MAIN OUTCOME MEASURES: Prevalence of retinal microvascular signs and their association with cardiovascular risk factors. RESULTS: Moderate or severe focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex, and retinopathy were found in 8.3%, 15.2%, 18.7%, and 9.0%, respectively, of the study population. Mean (+/-standard error) values for retinal arteriolar diameter were 178.6+/-21.0 mum, and mean values (+/-standard error) for venular diameter were 214.9+/-20.6 mum. Older persons were more likely to have retinal arteriolar wall signs, retinopathy, and narrower retinal vessel diameters. After adjusting for multiple factors, each 10-mmHg increase in mean arterial blood pressure was associated with a 20% to 40% increased likelihood of retinal arteriolar signs and a 2.8-mum reduction in arteriolar diameter. Retinopathy was associated with higher body mass index and both impaired glucose tolerance and impaired fasting glucose. CONCLUSIONS: In nondiabetic Japanese adults, retinal arteriolar wall signs were associated with older age and increased blood pressure, whereas retinopathy was associated with older age, higher body mass index, impaired glucose tolerance, and impaired fasting glucose. These findings are comparable with data from white populations.

Adult↗
PubMed2006

[Trends in the incidence of stroke in Yamagata, Japan].

The purpose of this study was to clarify the incidence and features of acute cerebrovascular diseases in Yamagata Prefecture, by comparing with those in other prefectures reported in previous studies. Consecutive 13,639 cases of acute stroke were prospectively registered to Yamagata Society in Treatment for Cerebral Stroke (YSTCS) between January 1, 1998 and December 31, 2002. Cerebral infarction (CI), intracerebral hemorrhage (CH), subarachnoid hemorrhage (SAH) and transient ischemic attack (TIA) were observed in 58.4%, 25.8%, 11.4% and 4.4% of the patients, respectively. The frequencies of CH and SAH (37.2%) in Yamagata Prefecture were higher than those reported in other studies (p < 0.01). In addition, time from onset to admission in Yamagata Prefecture was longer than that reported in others(p< 0.01). This study was one of the largest stroke registration studies in Japan enrolling 13,639 patients. In addition, computed tomography (CT) and/or magnetic resonance image (MRI) was performed on admission in all patients. Diagnosis was made by a neurologist or a neurosurgeon based on CT and/or MRI findings. Our results might accurately reflect current status of stroke patients in Yamagata Prefecture.

Adult↗
PubMed2006

[A case of non-herpetic acute limbic encephalitis associated with a type-2 adenovirus infection].

This is a report of a 31-year-old woman with non-herpetic acute limbic encephalitis following a type-2 adenovirus infection. The patient was admitted to a hospital with high fever, severe liver dysfunction, and thrombocytopenia. Six days after admission, she became afebrile, and her liver dysfunction was normalized by conservative therapy. However, the patient started to experience generalized seizures that developed into status epileptics. The patient was then transferred to a referred hospital. Brain MR images revealed faint high-signal intensity in the bilateral limbic systems on FLAIR images. A CSF examination indicated mild pleocytosis. These findings suggested acute limbic encephalitis, which may have been mediated by an autoimmune reaction following some viral infection. Thus, steroid pulse therapy was started on the day of admission. The patient's condition, including the seizures and disturbances involving consciousness, improved gradually. The patient was discharged from the hospital in one month while still experiencing mild memory disturbances. Three months after onset of the illness, a T1-weighted MR image showed a linear high-signal intensity in the hippocampi, which indicated focal necrosis. Six months after onset, the patient's memory disturbance had been improved (her MMSE score was 28/30 points). We investigated the titers of many viruses that are known to cause liver dysfunction and found that a titer of the type-2 adenovirus was significantly elevated within three weeks. Although the anti-voltage-gated potassium channel (VGKC) antibody was not detected in the patient's serum, it seems that the autoimmune reaction after the type-2 adenovirus infection may have caused the acute limbic encephalitis.

Acute Disease↗
PubMed2005

Prospective characterization of neural stem cells by flow cytometry analysis using a combination of surface markers.

Neural stem cells (NSCs) with self-renewal and multilineage differentiation properties can potentially repair degenerating or damaged neural tissue. Here, we have enriched NSCs from neurospheres, which make up a heterogeneous population, by fluorescence-activated cell sorting (FACS) with antibodies against syndecan-1, Notch-1, and integrin-beta1, which were chosen as candidates for hematopoietic cell-or somatic stem cell-markers. Antigen-positive cells readily initiated neurosphere formation, but cells lacking these markers did so less readily. Doubly positive cells expressing both syndecan-1 and Notch-1 underwent neurosphere formation more efficiently than did singly positive cells. The progeny of sorted cells could differentiate into neurons and glial cells both in vitro and in vivo. These antibodies were also useful for isolating cells from the murine embryonic day 14.5 brain that efficiently formed neurospheres. In contrast, there was no distinct difference in neurosphere formation efficiency between Hoechst 33342-stained side population cells and main population cells, although the former are known to have a stem cell phenotype in various tissues. These results indicate the usefulness of syndecan-1, Notch-1, and integrin-beta1 as NSC markers.

Animals↗
PubMed2005

Association of the ABCA1 gene polymorphisms with type 2 DM in a Japanese population.

To examine the association of the ATP-binding cassette transporter 1 (ABCA1) gene with type 2 diabetes (DM), we studied genetic polymorphisms of the ABCA1 gene including its linkage disequilibrium (LD) and haplotype analyses using a Japanese population. A sample set (DM:72, IGT:75, and NGT:227) was genotyped with 34 SNPs distributed from the promoter region to the last exon of the ABCA1 gene. LD between SNPs was assessed in pairwise manner. Among 13 LD blocks constructed, an LD block at the 5'-region showed a significant difference in the haplotype distribution between the study groups (NGT vs. IGT + DM: overall p = 0.0180; NGT vs. DM: 0.0001). Fisher's exact probability test (NGT vs. DM) showed a significant association of the haplotype 2 of the LD block (p = 0.0001), with an odds ratio (OR) of 2.53 (95%CI:1.62-4.12). Diplotype analysis also showed a significant association of the diplotypes with the haplotype 2 (OR:2.59, 95%CI:1.48-4.54, p = 0.0013).

ATP Binding Cassette Transporter 1↗
PubMed2005

Neuroprotective effect of oxidized galectin-1 in a transgenic mouse model of amyotrophic lateral sclerosis.

Abnormal accumulation of neurofilaments in motor neurons is a characteristic pathological finding in amyotrophic lateral sclerosis (ALS). Recently, we revealed that galectin-1, whose oxidized form has axonal regeneration-enhancing activity, accumulates in the neurofilamentous lesions in ALS. To investigate whether oxidized galectin-1 has a beneficial effect on ALS, oxidized recombinant human galectin-1 (rhGAL-1/ox) or physiological saline was injected into the left gastrocnemius muscle of the transgenic mice over-expressing a mutant copper/zinc superoxide dismutase (SOD1) with a substitution of histidine to arginine at position 46 (H46R SOD1). The H46R SOD1 transgenic mice, which represented a new animal model of familial ALS, were subsequently assessed for their disease onset, life span, duration of illness, and motor function. Furthermore, the number of remaining large anterior horn cells of spinal cords was also compared between the two groups. The results showed that administration of rhGAL-1/ox to the mice delayed the onset of their disease and prolonged the life of the mice and the duration of their illness. Motor function, as evaluated by a Rotarod performance, was improved in rhGAL-1/ox-treated mice. Significantly more anterior horn neurons of the lumbar and cervical cords were preserved in the mice injected with rhGAL-1/ox than in those injected with physiological saline. The study suggests that rhGAL-1/ox administration could be a new therapeutic strategy for ALS.

Age of Onset↗
PubMed2005

Association of decrease in serum dehydroepiandrosterone sulfate levels with the progression to type 2 diabetes in men of a Japanese population: the Funagata Study.

Association of serum dehydroepiandrosterone sulfate (DHEAS) levels with insulin resistance and impairment of insulin secretion have been reported. We here examined the association of serum DHEAS levels with type 2 diabetes mellitus (DM) and the progression to DM. The serum DHEAS levels at baseline (from 1995 to 1997) were evaluated in 1709 individuals (998 women and 711 men) from a cohort population (n = 3706) of the Funagata Study. Glucose tolerance was evaluated at baseline as well as at 5-year follow-up examinations (n = 970, follow-up rate, 56.8%) according to the 1985 World Health Organization criteria. The statistical significance of the difference between any 2 groups was determined by the Student t test. Multiple logistic regression analysis determined the association of the traits with the progression to DM at the 5-year follow-up examinations. P < .05 was accepted as statistically significant. The serum DHEAS levels were significantly lower in DM than in normal glucose tolerance. However, this difference was not significant when adjusted for age. In men, the decrease in serum DHEAS levels by the 5-year follow-up examinations was significantly larger in the subjects who became diabetic than in the subjects who remained normal glucose tolerance, even when adjusted for age ( P = .0003). Multiple logistic regression analysis revealed a significant association of the decrease in serum DHEAS levels with the progression to DM, with an odds ratio (per 0.1 log ng/mL) of 1.410 (95% confidence interval [CI], 1.020-1.948, P = .038), independently from age, height, and 2-hour plasma glucose in men. A decrease in serum DHEAS levels seems to be associated with the progression to DM in Japanese men.

Aged↗