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Takeo Kato

Publications and source records attributed to Takeo Kato.

At least 55 records · Page 3Linked to original sources
PubMed2003

Large-scale search of SNPs for type 2 DM susceptibility genes in a Japanese population.

The etiology of type 2 diabetes (DM) is polygenic. We investigated here genes and polymorphisms that associate with DM in the Japanese population. Single-nucleotide polymorphisms (SNPs) of 398 derived from 120 candidate genes were examined for association with DM in a population-based case-control study. The study group consisted of 148 cases and 227 controls recruited from Funagata, Japan. No evident subpopulation structure was detected for the tested population. The association tests were conducted with standard allele positivity tables (chi(2) tests) between SNP genotype frequency and case-control status. The independent association of the SNPs from serum triglyceride levels and body mass index was examined by multiple logistic regression analysis. A value of P<0.01 was accepted as statistically significant. Six genes (met proto-oncogene, ATP-binding cassette transporter A1, fatty acid binding protein 2, LDL receptor defect C complementing, aldolase B, and sulfonylurea receptor) were shown to be associated with DM.

ATP-Binding Cassette Transporters↗
PubMed2003

Immunological responses in acute low-tone sensorineural hearing loss and Ménière's disease.

OBJECTIVE: The autoimmune response appears to play an important role in some types of acute sensorineural hearing loss. Endolymphatic hydrops associated with fluctuating hearing loss has also been suggested to be caused by an immunological mechanism. Acute low-tone hearing loss (ALHL) associated with Ménière's disease (MD) is characterized by fluctuating hearing loss, and its etiology is thought to involve endolymphatic hydrops. The aim of this study was to attempt to determine the etiology of ALHL in MD. MATERIAL AND METHODS: A flow cytometer was used to analyze intracellular cytokine levels in peripheral blood from 19 patients with ALHL and 26 patients with MD and the data compared to those obtained from age- and gender-matched healthy volunteers. RESULTS: The patients with ALHL showed significantly increased levels of Th1 subsets (interferon-gamma-producing helper T cells) as compared to those in normal controls. The levels of Th2 (IL-4-producing helper T cells) subsets did not differ from those in the control group and thus Th1 predominated in ALHL patients. The patients with MD showed significantly increased natural killer cell activity but no Th1 dominance. These patients had no obvious systemic or local disease except in the inner ear. CONCLUSION: An abnormality of the Th1/Th2 balance in ALHL and increased natural killer cell activity in MD are thought to relate to inner ear disorder. These results are consistent with the possibility that the etiology of ALHL and MD involves an immune response.

Acute Disease↗
PubMed2003

The D allele of the angiotensin-converting enzyme insertion/ deletion (I/D) polymorphism is a risk factor for type 2 diabetes in a population-based Japanese sample.

The association of the ACE gene I/D polymorphism with type 2 diabetes (DM) was examined in a population-based Japanese sample. A total of 902 individuals (490 females and 412 males, age 58.8 +/- 12.2 yr) from a cohort population (n = 3,706) of the Funagata diabetes study were divided into three groups according to genotype: D/D (n = 104), I/D (n = 436) and I/I (n = 362). Chi-square test and ANOVA were used for association studies and to assess the differences in the traits' values, respectively. More individuals with the genotypes D/D and I/D were diabetic (8.7% and 4.1%, respectively) than those with the genotype I/I (2.8%, p = 0.008 and p = 0.032, respectively). The genotype D/D was a risk factor for DM (relative risk (RR) 3.13, 95% CI 1.31-7.51), and also for DM and IGT (RR 1.78, 95% CI 14-2.76). Multiple logistic regression analysis also showed that the genotypes with the D allele were risk factors for DM and IGT even when adjusting for age, sex, hypertension and serum total cholesterol levels (odds ratio 1.49, 95% CI 1.01-2.21). The D allele of the ACE gene I/D polymorphism is a risk factor for DM.

Aged↗
PubMed2003

Increased urinary levels of pentosidine, pyrraline and acrolein adduct in type 2 diabetes.

This study investigates whether urinary levels of pentosidine, pyrraline and acrolein adduct are increased in type 2 diabetes (DM), and whether these levels are correlated with glycemic control and clinical traits. Urinary levels of pentosidine, pyrraline and acrolein adduct in DM patients (n = 100) recruited from the outpatient clinic of our university hospital were compared with those of age- and sex-matched non-diabetic subjects (n = 50). The correlation of these urinary levels with the glycemic control and the clinical traits were examined. Furthermore, the influence of smoking habit on the levels of acrolein adduct was examined. Urinary levels of pentosidine, pyrraline and acrolein adduct were all significantly (p<0.001) higher in the DM group than in the non-DM group (pentosidine (log(pmol/mgCr)), 1.579 +/- 0.147 vs 1.427 +/- 0.142; pyrraline (log(nmol/mgCr)), 0.888 +/- 0.402 vs 0.581 +/- 0.336; acrolein adduct (log(nmol/mgCr)), 2.316 +/- 0.221 vs 2.051 +/- 0.201). Glycemic control parameters, such as fasting plasma glucose (FPG) and HbA1c, were significantly correlated with these urinary levels. Age was correlated with the urinary levels of pentosidine but not with those of pyrraline and acrolein adduct. The urinary albumin excretion rate did not correlate with any of these urinary levels. The levels of acrolein adduct were higher in the subjects with smoking habit than in those without the habit in the DM group as well as in the non-DM group (DM, 2.391 +/- 0.230 and 2.212 +/- 0.190, p=0.0004; Non-DM, 2.120 +/- 0.171 and 1.993 +/- 0.206, p=0.0503). The urinary levels of pentosidine, pyrraline and acrolein adduct were increased in DM and were significantly correlated with glycemic control levels. In addition, smoking habit seems to increase the urinary levels of acrolein adduct.

Acrolein↗
PubMed2003

The long, but not the short, presequence of human coproporphyrinogen oxidase is essential for its import and sorting to mitochondria.

Nucleotide sequence analyses of human coproporphyrinogen oxidase (CPO) have shown two possible translation initiation eodons (TICs) in the region upstream from the region coding the mature polypeptide. These TICs lead to the precursor polypeptides of CPO (long and short pCPOs), which have 110 and 10 amino acids (long and short) presequences, respectively. To determine which TIC is the real one, import reactions to mitochondria of the two pCPOs synthesized using in vitro transcription-translation system were analyzed. The results showed that the long pCPO was imported into mitochondria and sorted properly to the intermembrane space, whereas the short pCPO was not. We also found several miss-readings in the reported nucleotide sequence of mouse CPO gene. This correction revealed that mouse pCPO has also a longer presequence, which are very similar to the long presequence of human. These results indicate that the long, but not short, presequence is the real one.

5' Untranslated Regions↗
PubMed2003

Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study.

OBJECTIVE: To examine whether decreased serum levels of adiponectin are an independent risk factor for the progression to type 2 diabetes in a Japanese population. RESEARCH DESIGN AND METHODS: The serum levels of adiponectin and tumor necrosis factor-alpha (TNF-alpha) at baseline (from 1995 to 1997) were evaluated in 1,792 individuals (1,023 women and 769 men, aged 58.5 +/- 12.5 years) from a cohort population (n = 3,706) of the Funagata study. Glucose tolerance was evaluated at baseline and also at 5-year follow-up examinations (n = 978, follow-up rate, 54.6%) according to the 1985 World Health Organization criteria. The correlation of clinical traits with serum levels of adiponectin was examined. The association of the traits with the progression to type 2 diabetes at the 5-year follow-up was also examined. RESULTS: Among the traits examined, the correlation with aging was highest (r = 0.312, P < 0.001). Eighteen subjects with normal glucose tolerance (NGT) developed diabetes, and 709 remained NGT at the 5-year follow-up examinations. The subjects who became diabetic had decreased serum levels of adiponectin (7.29 +/- 2.35 vs. 9.13 +/- 2.35 10 x log microg/ml, P = 0.009). Multiple logistic regression analysis with age, sex, waist-to-hip ratio, and 2-h plasma glucose as the variables revealed that serum adiponectin level (odds ratio [per 0.1 log microg/ml] 0.766, P = 0.029) was an independent risk factor for the progression to type 2 diabetes. The subjects whose serum levels of adiponectin were in the lowest tertile were 9.320 times (95% CI 1.046-83.1) more likely to develop diabetes than those in the highest tertile (P = 0.046). CONCLUSIONS: Decreased serum adiponectin level is an independent risk factor for progression to type 2 diabetes.

Adiponectin↗
PubMed2003

Mechanism of an inhibitory effect of nipradilol on rat vascular smooth muscle cell growth.

The aim of this study was to clarify the mechanism of an inhibitory effect of nipradilol on cultured rat vascular smooth muscle cell (VSMC) growth. After being starved, cultured VSMCs were stimulated by 5% fetal bovine serum with various concentrations of nipradilol. Nipradilol dose-dependently decreased the values of [(3)H]-thymidine incorporation, cell numbers and total cellular protein content, and the levels of phosphorylated extracellular signal-regulated protein kinase 1/2 and p38. It also suppressed the level of proliferative cell nuclear antigen in a dose-dependent manner. In contrast, nipradilol did not change the level of the phosphorylated value of c-jun NH(2)-terminal protein kinase or cytoplasmic histone-associated DNA fragments in VSMCs. These results indicate that nipradilol suppresses cell growth without apoptosis in rat VSMCs, suggesting that it could be effective for preventing the progression of restenosis after angioplasty.

Adrenergic beta-Antagonists↗
PubMed2003

Clinical utility and approach to estimate postprandial hypertriglycemia by a newly designed oral fat-loading test.

The objective of this study was to estimate postprandial hypertriglycemia by a newly designed oral fat-loading test. Twenty-three healthy normolipidemic volunteers were orally administered a test meal consisting of a mixture of Telmeal 2.0 and 20 g of salt-free butter after fasting for 12 h. To measure the levels of total cholesterol (T-Cho), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), remnant-like particle-cholesterol (RLP-C), lipoprotein (a) [Lp (a)], free fatty acid, apolipoproteins (Apos), plasma glucose (PG), immunoreactive insulin (IRI), and high-sensitivity C-reactive protein (hs-CRP), venous blood samples were collected before the meal and at each hour until 9 h after fat-loading. The levels of both TG and RLP-C were drastically elevated at 2 h after fat-loading and these levels remained high until 4 h (p < 0.01). A significant correlation between TG and RLP-C was also observed at 2, 3 and 4 h, and the values of the correlation coefficients (r) were 0.837, 0.838, and 0.908, respectively. In contrast, the levels of T-Cho, HDL-C, Lp (a), Apos, PG, and hs-CRP did not change. Furthermore, there were no gastrointestinal symptoms during or after the study. These results strongly suggested that this newly designed fat-loading test was very useful for evaluating postprandial hypertriglycemia, including remnant concentrations.

Adult↗
PubMed2002

Topographical alterations of the midbrain and the substantia nigra following unilateral posteroventral pallidotomy in patients with Parkinson's disease using routine and multishot diffusion-weighted magnetic resonance imaging.

To determine whether posteroventral pallidotomy (PVP) induces topographical changes of the ipsilateral midbrain and degeneration of the substantia nigra in Parkinson's disease patients, we obtained magnetic resonance (MR) images of 18 patients who had undergone PVP and measured the width of the cerebral peduncle at the mid-point of the inner margin. Then, we assessed MR signal changes in the substantia nigra on T2-weighted images in all patients and on multishot diffusion-weighted images in seven patients. In MR images taken within 1 year of PVP, a comparison between the ratio of the ipsilateral side/contralateral side of the cerebral peduncle of patients after PVP and that of the unaffected side/affected side in the preoperative images revealed no significant difference ( P>0.05). In MR images 1 to 2 years after PVP, there was a significant difference in the ratio of the cerebral peduncle ( P<0.01). A significant difference was still evident in MR images more than 2 years after PVP ( P<0.001). On T2-weighted images obtained within 1 year of PVP, an area of patchy high signal appeared in the posterolateral region of the ipsilateral substantia nigra in six of 13 patients. However, there was no signal change in the substantia nigra in any T2-weighted images more than 1 year after PVP. Multishot diffusion-weighted images obtained from all six patients more than 1 year after PVP revealed an abnormal area of high signal in the posterolateral region of the ipsilateral substantia nigra, however, within 1 year of PVP such a signal change was not seen. PVP would induce degeneration of the ipsilateral substantia nigra and atrophy of the ipsilateral midbrain.

Aged↗
PubMed2002

Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese.

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.

Aged↗
PubMed2002

Subclinical central pontine myelinolysis following liver transplantation.

Central pontine myelinolysis (CPM) is a demyelinating disorder of unknown origin that almost exclusively affects the central portion of the basis pontis, and is one of the fatal neurological complications after liver transplantation. We describe two children with CPM detected incidentally after liver transplantation. To our knowledge, this is the first report of CPM diagnosed antemortem in children who had undergone liver transplantation. In our patients, there were no clinical manifestations associated with CPM. We conclude that, including silent cases such as our patients, CPM may be more prevalent than previously appreciated following liver transplantation.

Adolescent↗
PubMed2002

Secretion of a peripheral membrane protein, MFG-E8, as a complex with membrane vesicles.

MFG-E8 (milk fat globule-EGF factor 8) is a peripheral membrane glycoprotein, which is expressed abundantly in lactating mammary glands and is secreted in association with fat globules. This protein consists of two-repeated EGF-like domains, a mucin-like domain and two-repeated discoidin-like domains (C-domains), and contains an integrin-binding motif (RGD sequence) in the EGF-like domain. To clarify the role of each domain on the peripheral association with the cell membrane, several domain-deletion mutants of MFG-E8 were expressed in COS-7 cells. The immunofluorescent staining of intracellular and cell-surface proteins and biochemical analyses of cell-surface-biotinylated and secreted proteins demonstrated that both of the two C-domains were required for the membrane association. During the course of these studies for domain functions, MFG-E8, but not C-domain deletion mutants, was shown to be secreted as membrane vesicle complexes. By size-exclusion chromatography and ultracentrifugation analyses, the complexes were characterized to have a high-molecular mass, low density and higher sedimentation velocity and to be detergent-sensitive. Not only such a exogenously expressed MFG-E8 but also that endogenously expressed in a mammary epithelial cell line, COMMA-1D, was secreted as the membrane vesicle-like complex. Scanning electron microscopic analyses revealed that MFG-E8 was secreted into the culture medium in association with small membrane vesicles with a size from 100 to 200 nm in diameter. Furthermore, the expression of MFG-E8 increased the number of these membrane vesicle secreted into the culture medium. These results suggest a possible role of MFG-E8 in the membrane vesicle secretion, such as budding or shedding of plasma membrane (microvesicles) and exocytosis of endocytic multivesicular bodies (exosomes).

Animals↗
PubMed2002

The levels of mature glycosylated nicastrin are regulated and correlate with gamma-secretase processing of amyloid beta-precursor protein.

Nicastrin, a type-I transmembrane glycoprotein, is a necessary component of the high molecular weight presenilin (PS) complexes that mediate intramembranous cleavage of beta-amyloid precursor protein (betaAPP) and Notch. Nicastrin undergoes trafficking-dependent glycosylation maturation, and PS1 interacts preferentially with these maturely glycosylated forms of nicastrin. We investigated the effects of differing levels of the immature and mature endoglycosidase-H-resistant forms of nicastrin on Abeta40- and Abeta42-peptide secretion in several cell lines stably expressing a mutant nicastrin (D336A/Y337A) that increases Abeta secretion. There was no correlation between Abeta secretion and the level of over-expression of the immature forms of nicastrin. The total level of mature nicastrin remained constant, but mutant nicastrin replaced endogenous mature nicastrin in varying degrees. Differences in the levels of mature mutant nicastrin positively correlated with Abeta secretion, but did not influence either betaAPP trafficking or processing by alpha- and beta-secretases. Proper trafficking and terminal maturation of nicastrin is therefore a necessary event for the regulated intramembranous proteolysis of betaAPP.

Amino Acid Substitution↗
PubMed2002

Astrocytic deformity and globular structures are characteristic of the brains of patients with aceruloplasminemia.

Aceruloplasminemia is an interesting disease, the study of which helps elucidate how iron-induced oxidative stress is involved in neuronal cell death. In order to study the neuropathological characteristics associated with oxidative stress, we scrutinized the brains of 5 patients with aceruloplasminemia histopathologically and immunohistochemically. The pathological findings were essentially similar in all patients. In the frontal cortices, iron deposition and neuronal cell loss were trivial, but in the basal ganglia (especially in the caudate nucleus and putamen), severe iron overload and extensive neuronal loss were noted. Iron deposition was more prominent in the astrocytes than in the neurons in both regions. 4-hydroxynonenal (HNE), one of the most physiologically active lipid peroxides, was strongly detected on neurons and astrocytes by immunostaining. Markedly deformed astrocytes were observed in the striatum. These astrocytes were similar to Alzheimer type 1 astrocytes. Globular structures were seen in proportion to the degree of iron deposition. They clearly reacted with anti-glial fibrillary acidic protein (GFAP) and anti-S-100 antibodies and contained glial fibril-like filaments, but showed no or only faint immunoreactivity to antibodies for neuronal marker proteins, such as neurofilament and synaptophysin. Therefore, the globular structures presumably originated from astrocytes. The structures also reacted positively to anti-HNE and anti-ubiquitin antibodies. We conclude that astrocytic deformities and globular structures are characteristic neuropathological features of aceruloplasminemia and are closely linked to iron overload and subsequent oxidative stress.

Aldehydes↗
PubMed2002

Mechanisms of inhibitory effects of cerivastatin on rat vascular smooth muscle cell growth.

The aim of this study was to clarify the mechanism(s) of an inhibitory effect of cerivastatin on cultured rat vascular smooth muscle cell (VSMC) growth. After being starved, cultured VSMCs were stimulated by 5% fetal bovine serum with either various concentrations of cerivastatin or 10-4 M of mevalonate. Cerivastatin dose-dependently decreased the values of [3H]-thymidine incorporation and cell numbers and the level of phosphorylated extracellular signal-regulated protein kinase 1/2. It also suppressed the level of proliferative cell nuclear antigen in a dose-dependent manner. These reductions were abolished by the addition of mevalonate. Similarly, the level of phosphorylated p38 was also decreased by cerivastatin. In contrast, cerivastatin dose-dependently activated the phosphorylation of both c-jun NH2-terminal protein kinase and activating transcription factor-2, and these activations were abolished by the addition of mevalonate. The levels of phosphorylated Akt and p70 S6 kinase as well as those of Bcl-2 were dose-dependently reduced by cerivastatin, and these reductions were abolished by the addition of mevalonate. Cerivastatin could dose-dependently elevate the levels of CPP32/caspase-3 activity and cytoplasmic histone-associated DNA fragments in VSMCs without causing cytotoxicity. These results indicate that cerivastatin suppresses cell survival and activates the apoptotic cellular signaling in VSMCs, suggesting that it could be effective for preventing the progression of restenosis after angioplasty.

Analysis of Variance↗
PubMed2002

Cerebrovascular disease in acute leukemia: a clinicopathological study of 14 patients.

OBJECTIVE: Cerebrovascular disease (CVD) is a serious complication of acute leukemia, and the underlying conditions are different from the common risk factors for CVD. The aim of this study was to characterize the clinical and pathological features of CVD in patients with acute leukemia. PATIENTS OR MATERIALS: In our series of 116 autopsied cases of acute leukemia during the period between January 1978 and December 1998, we had 14 patients who had CVD during the course of acute leukemia. The neuropathological and clinical features of those patients were examined. RESULTS: Neuropathological examination showed hemorrhagic infarction due to disseminated aspergillosis or mucormycosis (5 cases), multiple hemorrhages due to leukemic cell infiltration (2 cases) and a single massive hemorrhage with petechial hemorrhages in various regions of the brain (4 cases). Three patients had CVD due to miscellaneous causes. Clinicopathological correlation revealed that fungal disseminations occurred under agranulocytosis, while leukemic cell infiltration occurred under a marked leukocyotosis (peripheral white blood cell count >100,000/microl). Four patients with coagulopathy, including three with disseminated intravascular coagulation (DIC) had a single massive hemorrhage. CONCLUSION: Our study demonstrated that there were at least three types of CVD with specific clinicopathological features. Hemorrhagic infarction under agranulocyotosis was due to disseminated aspergillosis or mucormycosis. Multiple cerebral hemorrhages under marked leukocyotosis was due to leukemic cell infiltration into the brain. Massive cerebral hemorrhage was associated with coagulopathy including DIC.

Acute Disease↗