Biomedical subjects

Kyoko Okada

Publications and source records attributed to Kyoko Okada.

At least 19 recordsLinked to original sources

PubMed2006

Decreased serum levels of transforming growth factor-beta1 in patients with autism.

BACKGROUND: The neurobiological basis for autism remains poorly understood. Given the key role of transforming growth factor-beta1 (TGF-beta1) in brain development, we hypothesized that TGF-beta1 plays a role in the pathophysiology of autism. In this study, we studied whether serum levels of TGF-beta1 are altered in patients with autism. METHODS: We measured serum levels of TGF-beta1 in 19 male adult patients with autism and 21 age-matched male healthy subjects using enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum levels (7.34+/-5.21 ng/mL (mean+/-S.D.)) of TGF-beta1 in the patients with autism were significantly (z=-5.106, p<0.001) lower than those (14.48+/-1.64 ng/mL (mean+/-S.D.)) of normal controls. However, there were no marked or significant correlations between serum TGF-beta1 levels and other clinical variables, including Autism Diagnostic Interview-Revised (ADI-R) scores, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), aggression, Theory of Mind, and Intellectual Quotient (IQ) in patients. CONCLUSIONS: These findings suggest that decreased levels of TGF-beta1 may be implicated in the pathophysiology of autism.

Adolescent↗

PubMed2006

Aip1 and cofilin promote rapid turnover of yeast actin patches and cables: a coordinated mechanism for severing and capping filaments.

Rapid turnover of actin structures is required for dynamic remodeling of the cytoskeleton and cell morphogenesis, but the mechanisms driving actin disassembly are poorly defined. Cofilin plays a central role in promoting actin turnover by severing/depolymerizing filaments. Here, we analyze the in vivo function of a ubiquitous actin-interacting protein, Aip1, suggested to work with cofilin. We provide the first demonstration that Aip1 promotes actin turnover in living cells. Further, we reveal an unanticipated role for Aip1 and cofilin in promoting rapid turnover of yeast actin cables, dynamic structures that are decorated and stabilized by tropomyosin. Through systematic mutagenesis of Aip1 surfaces, we identify two well-separated F-actin-binding sites, one of which contributes to actin filament binding and disassembly specifically in the presence of cofilin. We also observe a close correlation between mutations disrupting capping of severed filaments in vitro and reducing rates of actin turnover in vivo. We propose a model for balanced regulation of actin cable turnover, in which Aip1 and cofilin function together to "prune" tropomyosin-decorated cables along their lengths. Consistent with this model, deletion of AIP1 rescues the temperature-sensitive growth and loss of actin cable defects of tpm1Delta mutants.

Actin Cytoskeleton↗

PubMed2006

Twinfilin is an actin-filament-severing protein and promotes rapid turnover of actin structures in vivo.

Working in concert, multiple actin-binding proteins regulate the dynamic turnover of actin networks. Here, we define a novel function for the conserved actin-binding protein twinfilin, which until now was thought to function primarily as a monomer-sequestering protein. We show that purified budding yeast twinfilin (Twf1) binds to and severs actin filaments in vitro at pH below 6.0 in bulk kinetic and fluorescence microscopy assays. Further, we use total internal reflection fluorescence (TIRF) microscopy to demonstrate that Twf1 severs individual actin filaments in real time. It has been shown that capping protein directly binds to Twf1 and is required for Twf1 localization to cortical actin patches in vivo. We demonstrate that capping protein directly inhibits the severing activity of Twf1, the first biochemical function ascribed to this interaction. In addition, phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] inhibits Twf1 filament-severing activity. Consistent with these biochemical activities, a twf1Delta mutation causes reduced rates of cortical actin patch turnover in living cells. Together, our data suggest that twinfilin coordinates filament severing and monomer sequestering at sites of rapid actin turnover and is controlled by multiple regulatory inputs.

Actin Capping Proteins↗

PubMed2006

Effect of probucol on elderly hypercholesterolemic patients in the FAST study.

The present study involved a detailed post hoc comparison of the efficacy and safety of lipid-lowering therapy in elderly hypercholesterolemic patients from the Fukuoka Atherosclerosis Trial (FAST). The FAST cohort of 246 hypercholesterolemic patients included 76 patients who were (75 years old. Patients were randomized to receive probucol (500 mg/day) or pravastatin (10 mg/day) therapy, or to a control group (diet alone), and then were followed for 2 years. In patients > or = 75 years old, either probucol or pravastatin achieved a significant reduction of carotid intima-media thickness (IMT). In patients <75 years old, lipid-lowering therapy also achieved a significant reduction of IMT. In patients > or = 75 years old receiving probucol, the relative risk (95% confidence interval) of all-cause mortality was 0.15 (0.02 to 1.28) and that for major coronary events was 0.12 (0.02 to 1.04). In conclusion, probucol reduced the incidence of cardiovascular disease in elderly hypercholesterolemic patients as well as younger patients.

Adult↗

PubMed2006

Both hepatitis C virus and Chlamydia pneumoniae infection are related to the progression of carotid atherosclerosis in patients undergoing lipid lowering therapy.

Recent experimental and epidemiological findings suggest that infectious agents may play a role in the development and progression of atherosclerosis. We previously reported that Chlamydia pneumoniae (C. pneumoniae) infection reduces the effectiveness of lipid-lowering therapy for carotid atherosclerosis and that this micro-organism may play a role in the progression of atherosclerosis. In this study, we investigated the possible association between hepatitis C virus (HCV) infection and carotid arteriosclerosis. A total of 165 asymptomatic hypercholesterolemic patients were randomized to receive probucol (500 mg/day, n=82) or pravastatin (10 mg/day, n=83) and were followed for 2 years. The 2-year change of the maximum common carotid artery intima-media thickness (Max-IMT) was the primary endpoint, while the Max-IMT and the incidence of major cardiovascular events were secondary endpoint. All serum samples were tested for antibody to HCV (anti-HCV) by enzyme-linked immunosorbent assay (ELISA), and all anti-HCV-positive samples were assayed for HCV RNA. Patients without HCV infection (n=25) showed a significant reduction of Max-IMT (-10.9%) (p<0.0001), while a small decrease of Max-IMT was noted in the patients with HCV infection (n=25) (-0. 3%). Significant differences in the reduction of serum total cholesterol and LDL cholesterol were found between patients with and without HCV infection (both p<0.0001). No significant difference in therapeutic effect was noted between the probucol and the pravastatin groups. After adjustment for confounding risk factors, both C. pneumoniae infection and anti-HCV positivity were associated with a greater risk of an increase in Max-IMT (8.5635 [1.3738-15.7532], p<0.05, 9.5040 [0.2886-18.7194], p<0.05, respectively). These findings suggest that both chronic HCV infection and C. pneumoniae infection can reduce the effectiveness of lipid-lowering therapy for carotid atherosclerosis, and that the HCV may play a role in the progression of atherosclerosis in HCV infected patients.

Adult↗

PubMed2005

Association between fast-migrating low-density lipoprotein subfraction as characterized by capillary isotachophoresis and intima-media thickness of carotid artery.

BACKGROUND: A mildly modified LDL subfraction that is characterized by an increased negative charge exists in plasma. This electronegative LDL separated by ion-exchange chromatography has been shown to be inflammatory and its proportion is increased in patients with hyperlipidemia and diabetes mellitus. The present study examined the association between the level of fast (f)-migrating LDL subfraction characterized by capillary isotachophoresis (cITP) and carotid-artery intima-media thickness (CA-IMT). METHODS AND RESULTS: This study included 469 subjects who underwent a physical examination. CA-IMT was determined by high-resolution B-model ultrasonoraphy. Levels of charge-based LDL subfractions were measured by cITP on a Beckman P/ACE MDQ system. An increased serum LDL-C level and cITP fLDL level were associated with increased CA-IMT after adjusting for age. The extent of the associations between cITP fLDL and CA-IMT and between LDL-C and CA-IMT were similar as assessed by a receiver-operating characteristic curve analysis. LDL-C, triglyceride, and remnant-like particle cholesterol levels were independently correlated with cITP fLDL, and the LDL-C level had the strongest correlation with cITP fLDL. The association between the cITP fLDL level and CA-IMT was significant in the high LDL-C stratum but not in the low stratum, indicating that it is modified by the LDL-C level. The high-LDL-C-high-fLDL group had the highest relative risk for a high CA-IMT among the groups with each combination of LDL-C and cITP fLDL level. CONCLUSION: The cITP fLDL level was associated with CA-IMT and its combination with the LDL-C level is a stronger indicator for a high CA-IMT.

Adult↗

PubMed2005

'Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer'.

Seprase is a membrane-bound serine proteinase with gelatinase activity, which may be involved in cancer invasion and metastasis. We examined seprase expression in colorectal cancer specimens obtained from 109 patients. Seprase immunoreactivity was found in cancer cells and adjacent stromal cells. Immunoblotting showed higher levels of seprase protein in colorectal cancer tissue than in normal colorectal tissue. A semiquantitative assessment of the immunohistochemistry results revealed a significant correlation between seprase expression and lymph node metastasis. These results suggested that an abundant expression of seprase in colorectal cancer tissue is associated with lymph node metastasis.

Adult↗

PubMed2005

Amelioration of extrapontine myelinolysis and reversible parkinsonism in a patient with asymptomatic hypopituitarism.

A 37-year-old woman with a history of transphenoidal surgery and gamma knife treatment for prolactinoma was admitted because of pneumoniae with hyponatremia (Na 109 mmol/l). After the careful correction of the serum sodium level within 15 mmol/l/day, the patient developed parkinsonism. MRI of the brain disclosed a signal increase in the bilateral basal ganglias on T2-weighted images, a finding consistent with extrapontine myelinolysis (EPM). Interestingly, the parkinsonism fully disappeared after the replacement therapy of hydrocortisone for adrenal insufficiency due to hypopituitarism, and MRI 5 months later showed complete disappearance of the lesions, indicating the patient had ameliorated from the EPM.

Adult↗

PubMed2005

Pravastatin improves insulin resistance in dyslipidemic patients.

To evaluate the effect of pravastatin on both lipid and glucose metabolism, twenty-two consecutive dyslipidemic patients treated with pravastatin at 10 mg/day for one year were enrolled in this study. The meal test, which consisted of 115 g of cookies (energy 560 kcal; glucose 75 g; protein 7 g; fat 24 g), was conducted before and after one year of treatment. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR), by the area under the IRI curve (AUC-IRI), and by the formula AUC-IRI x AUC-PG. After one year of treatment with pravastatin, the plasma glucose (PG), immunoreactive insulin (IRI) and C-peptide levels were unchanged after fasting and at 120 minutes after the meal test; however, PG, IRI and C-peptide levels at 60 minutes after the meal were all significantly decreased from baseline (p < 0.05). AUC-IRI and AUC-IRI x AUC-PG were also significantly decreased (p < 0.05). HOMA-IR was reduced by 26.8%, but the reduction was not significant. The triglyceride (TG) level was decreased after fasting and increased at 60 and 120 minutes after the meal test, but not significantly. This study demonstrated that pravastatin not only reduced serum lipids, but also improved the glucose metabolism, including insulin resistance, of dyslipidemic patients.

Aged↗

PubMed2004

Carotid atherosclerosis and cardiovascular risk factors: a comparison of residents of a rural area of Okinawa with residents of a typical suburban area of Fukuoka, Japan.

Areas of Japan are known worldwide for the longevity of their residents. Okinawa has the highest longevity in Japan and a low rate of death due to cardiovascular disease. We investigated carotid atherosclerotic (CA) risk factors in islands of I city in Okinawa prefecture and compared them with K town, a suburban area of Fukuoka prefecture in Kyushu, to determine the relationship between cardiovascular risk factors and carotid atherosclerosis. We investigated conventional cardiovascular risk factors in 1078 I city residents (375 men, mean age 63.7 and 703 women, mean age 60.0) in 2000 and 2364 K town residents (676 men, mean age 57.1 and 1688 women, mean age 53.0) in 1999. Carotid atherosclerosis was assessed by mean intima-media thickness (IMT) by B-mode ultrasound. The mean IMT was significantly lower in the residents of I city than in those of K town (P < 0.05). Total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels and smoking rate were also lower in I city than in K town. Body mass index (BMI) and triglyceride (TG) level were higher in I city than in K town. In I city, multiple regression analysis found independent relationships between carotid atherosclerosis and age, sex (male), hypertension, LDL cholesterol, high-density-lipoprotein cholesterol (HDL-C), and diabetes. The lower mean IMT is probably related to a lower lifetime burden of atherosclerotic risk factors, which may in turn be related to the longevity of Okinawa residents. BMI was not a cardiovascular risk factor, although LDL cholesterol was a common important risk factor.

Adult↗

PubMed2004

The influence of lifestyle modification on carotid artery intima-media thickness in a suburban Japanese population.

To evaluate the influence of lifestyle modification with and without lipid-lowering drug therapy on the carotid arterial wall, we did a 2 year prospective ultrasound study of carotid intima-media thickness (IMT) in 1390 male and female residents of a suburban Japanese town. According to total cholesterol (TC) level at baseline, subjects were classified into a lifestyle modification alone group (TC >/= 220 mg/dl, n = 437), a lifestyle modification with lipid-lowering drug group (TC >/= 220 mg/dl, n = 159), and a control group (TC < 220 mg/dl, n = 794). After 2 years of follow-up, both sexes of both treatment groups showed significant reductions of TC, low-density lipoprotein cholesterol (LDL-C), and IMT, although TC continued over 220 mg/dl in some subjects in the lifestyle modification group. The reduction of TC and LDL-C was significantly higher in the lifestyle modification with lipid-lowering drug group than in the lifestyle modification alone group. Although the IMT reduction was not statistically different between the treatment groups of either sex, the reduction of IMT was greater in the lifestyle modification with lipid-lowering drug group than in the lifestyle modification alone group. Our results indicate that comprehensive lifestyle modification can reduce carotid IMT in the general population, with or without the use of lipid-lowering drugs and that cholesterol reduction is of benefit even when TC level remain above the recommended level.

Adult↗

PubMed2004

The genetic properties of Streptococcus pyogenes emm49 genotype strains recently emerged among severe invasive infections in Japan.

Explore the source record for details and available documents.

Antigens, Bacterial↗

PubMed2003

Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer.

Adult↗

PubMed2003

Shear stress-induced collagen XII expression is associated with atherogenesis.

Fluid shear stress has been shown to modulate various endothelial functions. We selected a shear stress-specific clone, identified as collagen XII, from a bovine aortic endothelial cell (BAEC) cDNA library. We confirmed that shear stress induces collagen XII expression at both the mRNA and protein levels in cultured BAECs and human umbilical vein ECs (HUVECs) by stimulating transcription. When HUVECs were exposed to shear stress, they secreted collagen XII protein and it was deposited underneath them. Strong expression of collagen XII was found in the intima of human aortic wall lacking atherosclerotic lesions, whereas weak expression was seen in the intima of atherosclerotic plagues. Furthermore, the downstream portion of atherosclerotic plaques showed apparently weak collagen XII expression compared with the upstream portion. These results suggest that collagen XII expression induced by fluid shear stress may play a role in stabilizing the vascular structure and preventing the formation of atherosclerotic lesions.

Animals↗

PubMed2003

Association of Chlamydia pneumoniae antibody with the cholesterol-lowering effect of statins.

To investigate the association between Chlamydia pneumoniae (C. pneumoniae) infection and atherosclerosis, we compared the effect of lipid-lowering drugs on carotid intima-media thickness (IMT) between patients who were positive and negative for C. pneumoniae antibodies. A total of 165 asymptomatic hypercholesterolemic patients were randomized to probucol (500 mg per day, n = 82) or pravastatin (10 mg per day, n = 83) and followed for 2 years. The 2-year change of IMT in the common carotid artery was the primary endpoint, while mean IMT change and major cardiovascular events were secondary endpoints. C. pneumoniae antibodies (IgA and IgG) were measured by enzyme-linked immunosorbent assay. The 50 patients without C. pneumoniae antibodies showed significant reduction of IMT progression (-19%), while no significant change of IMT was noted in the 115 antibody-positive patients (-6%). Significant inverse associations were found between the reduction of IMT progression and the C. pneumoniae IgA- and IgG-antibody index (P < 0.01 and 0.01, respectively). No significant differences in the reduction of serum total-cholesterol and LDL-cholesterol were found between antibody-positive and -negative patients. There was no significant difference of efficacy between probucol and pravastatin. These observations suggest that C. pneumoniae infection reduces the effect of lipid-lowering therapy on carotid atherosclerosis and that this organism may play a role in the progression of atherosclerosis.

Adult↗

PubMed2003

Carotid artery lesions and atherosclerotic risk factors in Japanese hemodialysis patients.

To determine the prevalence and severity of carotid artery lesions and which risk factors might be responsible for atherosclerosis in end-stage renal disease (ESRD) patients, we tested for carotid atherosclerosis (CA) by ultrasonography and compared the CA prevalence with well-known or suspected atherosclerotic risk factors in 226 hemodialysis (HD) patients and 2410 healthy residents of Japan. The CA prevalence was higher in the HD patients than in the healthy residents. Univariate analysis showed that HD patients with CA had a higher frequency of diabetes mellitus and left ventricular hypertrophy, and were significantly older, had significantly higher systolic blood pressure and pulse pressure, and lower albumin levels than those without. Multivariate analysis showed that age, pulse pressure, phosphorus, duration of HD, and diabetes mellitus were independent, significant predictors for CA in the HD patients. Neither Chlamydia pneumoniae seropositivity nor elevated homocysteine level was independently, significantly associated with CA. Our results suggest that HD patients had more advanced CA than the healthy residents. CA in the HD patients may be associated not only with several conventional risk factors but also with non-conventional risk factors such as phosphorus and the HD procedure itself.

Adult↗

PubMed2003

Introduction of Wx transgene into rice wx mutants leads to both high- and low-amylose rice.

The Waxy (Wx) gene encodes a granule-bound starch synthase (GBSS) that plays a key role in the amylose synthesis of rice and other plant species. Two functional Wx alleles of rice exist: Wx(a), which produces a large amount of amylose, and Wx(b), which produces a smaller amount of amylose because of the mutation at the 5' splice site of intron 1. Wx(b) is largely distributed in Japonica cultivars, and high amylose cultivars do not exist in Japonica cultivars. We introduced the cloned Wx(a) cDNA into null-mutant Japonica rice (wx). The amylose contents of these transgenic plants were 6-11% higher than that of the original cultivar, Labelle, which carries the Wx(a) allele, although the levels of the Wx protein in the transgenic rice were equal to those of cv. Labelle. We also observed a gene-dosage effect of the Wx(a) transgene on Wx protein expression, but a smaller dosage effect was observed in amylose production with over 40% of amylose content in transgenic rice. Moreover, one transgenic line carrying eleven copies of the transgene showed low levels of Wx expression and amylose in the endosperm. This suggested that the integration of excessive copies of the transgene might lead to gene silencing.

Amylose↗

PubMed2003

Seprase, a membrane-type serine protease, has different expression patterns in intestinal- and diffuse-type gastric cancer.

OBJECTIVE: Seprase is an integral membrane serine proteinase with gelatinase activity that may be involved in cancer invasion and metastasis. However, the pathophysiologic significance of its expression in gastric cancer tissue has not been fully elucidated. METHODS: Seprase expression and distribution in gastric cancer specimens obtained from 133 patients were examined by immunohistochemistry and immunoblotting. RESULTS: Immunohistochemistry showed that in intestinal-type cancer, which includes well and moderately differentiated adenocarcinoma, seprase immunoreactivity was mainly recognized in the moderately differentiated cells and not in the well differentiated cells. In the diffuse type, which includes poorly differentiated adenocarcinoma and signet ring cell carcinoma, seprase immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The reactive pattern in the cells was different between moderately differentiated adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell membrane also apparently reacted in the former, while only the cytoplasm reacted diffusely in the latter. Seprase immunoreactivity was also recognized in endothelial cells and stromal cells especially adjacent to tumor nests. The immunoreactivity of the stromal cells was more abundant in the intestinal type than in the diffuse type, and these stromal expressions of seprase in the intestinal type correlated with the liver (13/13 = 100% of cases with metastases) or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting showed that the levels of seprase protein were higher in intestinal-type cancer than in diffuse-type cancer. CONCLUSION: These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer.

Aged↗