Left ventricular hypertrophy demonstrated by four-dimensional myocardiography by helical computed tomography.
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Cardiomyopathy, Hypertrophic↗
Biomedical subjects
T Mochizuki
Publications and source records attributed to T Mochizuki.
Functional domains of the LIM homeodomain protein Xlim-1 involved in negative regulation, transactivation, and axis formation in Xenopus embryos.
The Xenopus LIM homeodomain protein Xlim-1 is specifically expressed in the Spemann organizer region and assumed to play a role in the establishment of the body axis as a transcriptional activator. To further elucidate the mechanism underlying the regulation of its transcriptional activity, we focused on the region C-terminal to the homeodomain of Xlim-1 (CT239-403) and divided it into five regions, CCR1-5 (C-terminal conserved regions), based on similarity between Xlim-1 and its paralog, Xlim-5. The role of Xlim-1 CT239-403 in the Spemann organizer was analyzed by assaying the axis-forming ability of a series of CCR-mutated constructs in Xenopus embryos. We show that high doses of Xlim-1 constructs deleted of CCR1 or CCR2 initiate secondary axis formation in the absence of its coactivator Ldb1 (LIM-domain-binding protein 1), suggesting that CCR1 and CCR2 are involved in negative regulation of Xlim-1. In contrast, while Xlim-1 is capable of initiating secondary axis formation at low doses in the presence of Ldb1, deletion of CCR2 (aa 275-295) or substitution of five conserved tyrosines in CCR2 with alanines (CCR2-5YA) abolished the activity. In addition, UAS-GAL4 one-hybrid reporter assays in Xenopus showed that CCR2, but not CCR2-5YA, with its flanking regions (aa 261-315) functions as a transactivation domain when fused to the GAL4 DNA-binding domain. Finally, we show that none of the known transcriptional coactivators tested (CBP, SRC-1, and TIF2) interacts with the Xlim-1 transactivation domain (aa 261-315). Thus, Xlim-1 not only contains a unique tyrosine-rich activation domain but also contains a negative regulatory domain in CT239-403, suggesting a complex regulatory mechanism underlying the transcriptional activity of Xlim-1 in the organizer.
Amino Acid Sequence↗
Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to alpha and gamma isoforms of peroxisome-proliferator-activated receptors by competing with agonists.
Peroxisome-proliferator-activated receptors (PPARs) alpha and gamma are ligand-dependent transcription factors that are key regulators of lipid and carbohydrate homoeostasis. Fatty acids bind to the ligand-binding domains (LBDs) of PPARalpha and PPARgamma and activate these receptors. To clarify whether fatty-acyl-CoAs interact directly with the LBDs of PPARalpha and PPARgamma, we performed a competition binding assay with radiolabelled KRP-297, a known dual agonist for these receptors. We show here that fatty-acyl-CoAs bind directly to PPARalpha and PPARgamma. Interestingly, fatty-acyl-CoAs, unlike fatty acids, failed to recruit steroid receptor co-activator 1 (SRC-1), on the basis of conformational changes in the LBDs of PPARalpha and PPARgamma. Moreover, fatty-acyl-CoAs also markedly inhibited agonist-induced recruitment of SRC-1. These findings demonstrate that fatty-acyl-CoAs have a novel function in the signalling pathways of PPARalpha and PPARgamma.
Acyl Coenzyme A↗
Twenty-four-hour Tl-201 delayed scan underestimates myocardial viability in patients with acute myocardial infarction after percutaneous transluminal coronary angioplasty.
BACKGROUND: Myocardial viability in area at risk of acute myocardial infarction (AMI) after reperfusion therapy may be underestimated by the 24-hour images due to reverse redistribution (r-RD). METHODS: Subjects were 37 AMI patients in whom Tc-99m pyrophosphate (PYP)/Tl-201 dual-isotope SPECT was positive. The 24-hour delayed scan was performed with only a Tl window. One month later, follow up rest Tl SPECT was performed to evaluate myocardial viability. In early (at PYP/Tl-201 dual-isotope SPECT), 24-hour, and one month follow up Tl studies, Tl uptake in the area of AMI was scored into four grades: 3 as normal to 0 as severely reduced. The scores were evaluated. RESULTS: Among the 37 AMI lesions, there were 16 r-RD, 3 RD, 16 fixed defect (FD) and 2 normal (positive PYP and normal Tl). Mean Tl scores were early; 1.4 +/- 1.1, 24-hr; 0.9 +/- 0.9 and one month; 1.3 +/- 1.1. The 24-hour Tl score was lower than the early and one month Tl scores (p < 0.01). CONCLUSION: Reverse redistribution is frequently observed in an area at risk where PYP SPECT was positive. Nuclear medicine physicians should be aware of the existence of frequent r-RD in Tl scan to avoid the underestimation of myocardial viability in the acute phase after PTCA.
Aged↗
Effects of insulin and glucose loading on FDG uptake in experimental malignant tumours and inflammatory lesions.
Fluorine-18 2-deoxy-2-fluoro-D-glucose (FDG) accumulation in tumours has been well investigated, but much less is known regarding FDG accumulation in inflammatory lesions. In this study, we determined the effects of hypo- and hyperglycaemia on FDG uptake in inflammatory lesions of infectious and non-infectious origin and compared them with those in malignant tumours in rats, to provide a biological basis for differentiating malignant lesions from benign lesions by means of FDG-PET. Rats were inoculated with a suspension of allogenic hepatoma cells (KDH-8) or Staphylococcus aureus, or with turpentine oil into the left calf muscle. Two weeks after KDH-8 inoculation and 1 week after S. aureus and turpentine oil inoculations, the rats were divided into three subgroups: insulin-loaded (2 U/kg body weight, i.p.), glucose-loaded (1.2 g/kg body weight, p.o.) and control groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. Intraperitoneal injection of insulin and oral administration of glucose induced hypoglycaemia and hyperglycaemia, respectively. In the control animals, tumours showed a level of FDG uptake which was 2.2 and 3.0 times higher than the levels in the inflammatory lesions induced by S. aureus and turpentine oil, respectively (P<0.0001). There was no significant difference in the level of FDG uptake between the two inflammatory lesions of infectious and non-infectious origin. Insulin loading significantly decreased the level of FDG uptake in tumours and in both types of inflammatory lesion to approximately one-half of the control values (P=0.001 in the tumour group and P<0.0001 in the two inflammatory lesion groups). In the glucose-loaded group, the level of FDG uptake in both types of inflammatory lesion decreased significantly to 50%-61% of the control value (P=0.0002 in the S. aureus group and P<0.0001 in the turpetine group), while the tumour uptake did not decrease significantly (86% of the control value) (P=NS). It is concluded that FDG uptake in both types of inflammatory lesion was significantly impaired in rats with hyperglycaemia induced by glucose loading, while tumour uptake of FDG was not significantly affected. These results indicate that glucose loading has greater effects on FDG uptake in inflammatory lesions than in tumours, providing a biological basis for differentiation of malignant lesions from benign lesions by FDG-PET in a clinical setting.
Animals↗
Reproducibility of the brain perfusion index for measuring cerebral blood flow using technetium-99m compounds.
We previously developed an alternative method for estimating the brain perfusion index (BPI) using technetium-99m compounds and spectral analysis (SA) for quantification of cerebral blood flow (CBF). In this study, we investigated the reproducibility of the BPI values obtained by SA (BPIS) using a double injection of technetium-99m ethyl cysteinate dimer without any intervention, and compared it with that of the BPI values obtained by graphical analysis (BPIG). The BPIS values in the first (x) and second sessions (y) correlated closely (y=0.921x+0.036; r=0.962; n=64; s.e.e.=0.058 min-1). Although the BPIG values in the first (x) and second sessions (y) also correlated (y=0.942x+0.040; r=0.916; n=64; s.e.e.=0.061 min-1), the correlation coefficient for BPIS was significantly higher than that for BPIG. The reproducibility was dependent on the injection dose ratio of the second session to the first (R). The difference in BPI between the first and second sessions tended to be smaller when 1.5<R<2.5 than when 0<R<1.5 or 2.5<R. These results suggest that the reproducibility of BPIS is satisfactory and that it can be applied to two sequential measurements of CBF using a double injection of 99mTc compounds. When applying our method to such measurements, it is recommended that R is taken as approximately 2.0.
Aged↗
Mutational analysis within the 3' region of the PKD1 gene in Japanese families.
Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that causes renal failure. One of the genes that is responsible for this disease, PKD1, has been identified and characterized. Many mutations of the PKD1 gene have been identified in the Caucasian population. We investigated the occurrence of mutations in this gene in the Japanese population. We analyzed each exon in the 3' single copy region of the gene between exons 35 and 46 in genomic DNA obtained from 69 patients, using a PCR-based direct sequencing method. Four missense mutations (T3509M, G3559R, R3718Q, R3752W), one deletion mutation (11307del61bp) and one polymorphism (L3753L) were identified, and their presence confirmed by allele-specific oligonucleotide (ASO) hybridization. These were novel mutations, except for R3752W, and three of them were identified in more than two families. Mutation analysis of the PKD1 gene in the Japanese population is being reported for the first time.
Alleles↗
An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons.
Considerable evidence indicates that adenosine may be an endogenous somnogen, yet the mechanism through which it promotes sleep is unknown. Adenosine may act via A1 receptors to promote sleep, but an A2a receptor antagonist can block the sleep induced by prostaglandin D(2). We previously reported that prostaglandin D(2) activates sleep-promoting neurons of the ventrolateral preoptic area, and we hypothesized that an A2a receptor agonist also should activate these neurons. Rats were instrumented for sleep recordings, and an injection cannula was placed in the subarachnoid space just anterior to the ventrolateral preoptic area. After an 8-10-day recovery period, the A2a receptor agonist CGS21680 (20 pmol/min) or saline was infused through the injection cannula, and the animals were killed 2 h later. The brains were stained using Fos immunohistochemistry, and the pattern of Fos expression was studied in the entire brain. CGS21680 increased non-rapid eye movement sleep and markedly increased the expression of Fos in the ventrolateral preoptic area and basal leptomeninges, but it reduced Fos expression in wake-active brain regions such as the tuberomammillary nucleus. CGS21680 also induced Fos in the shell and core of the nucleus accumbens and in the lateral subdivision of the central nucleus of the amygdala. To determine whether these effects may have been mediated through A1 receptors, an additional group of rats received subarachnoid infusion of the A1 receptor agonist N(6)-cyclopentyladenosine (2 pmol/min). In contrast to CGS21680, infusion of N(6)-cyclopentyladenosine into the subarachnoid space produced only a small decrease in rapid eye movement sleep, and the pattern of Fos expression induced by N(6)-cyclopentyladenosine was notable only for decreased Fos in regions near the infusion site. These findings suggest that an adenosine A2a receptor agonist may activate cells of the leptomeninges or nucleus accumbens that increase the activity of ventrolateral preoptic area neurons. These ventrolateral preoptic area neurons may then coordinate the inhibition of multiple wake-promoting regions, resulting in sleep.
Adenosine↗
Molecular epidemiology of Arthroderma benhamiae, an emerging pathogen of dermatophytoses in Japan, by polymorphisms of the non-transcribed spacer region of the ribosomal DNA.
In Japan, several isolates of Arthroderma benhamiae, a teleomorphic member of Trichophyton mentagrophytes complex, which were not found by earlier mating studies, have recently been recovered from human and animal dermatophytoses. In the present study, intraspecies polymorphism of A. benhamiae isolated in Japan was investigated using restriction fragment length polymorphisms (RFLP) of the non-transcribed spacer (NTS) region of the ribosomal DNA (rDNA), a method introduced to detect intraspecies polymorphisms of other dermatophyte species, such as T. rubrum. Based on their restriction profiles, there were five DNA types out of eight strains of A. benhamiae isolated in Japan. None of the five DNA types were found among the registered tester strains of A. benhamiae. Therefore, several different strains of A. benhamiae may have been brought into Japan separately.
Arthrodermataceae↗
A close relationship of triplet repeat polymorphism in MHC class I chain-related gene A (MICA) to the disease susceptibility and behavior in ulcerative colitis.
Major histocompatibility complex (MHC) class I chain-related gene A (MICA) has been found near the HLA-B gene. The MICA molecule is exclusively expressed on gastrointestinal epithelium and recognized by intestinal epithelial gamma delta T cells, where it exhibits a triplet repeat polymorphism in the transmembrane region. We investigated the possible correlation between MICA genetic polymorphism and ulcerative colitis (UC). Eighty-three patients with UC and 132 unrelated controls were included in this study. All subjects were Japanese. A triplet repeat polymorphism in the transmembrane region of the MICA was determined by direct sequencing procedures after amplification by a polymerase chain reaction. A significantly higher allele and phenotype frequencies of MICA A6 allele were observed in patients with UC than controls (allele frequency: P(c)=0.000011, phenotype frequency: P(c)=0.0049 odds ratio=2.62). A6 homozygous patients with UC showed significantly earlier onset of UC than patients without the A6 allele ((P)c=0.0042). Phenotypes of MICA A6 allele in Japanese are closely related to the disease susceptibility and behavior in UC. Examinations of MICA polymorphism in other ethnic groups may provide important information about the locus of primary responsible gene for UC.
Adolescent↗
Stratification analysis of MICA triplet repeat polymorphisms and HLA antigens associated with ulcerative colitis in Japanese.
We previously reported a conserved haplotype of HLA B52-DR2 and a significantly high frequency of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane-short tandem repeat (TM-STR) 6 allele in Japanese patients with ulcerative colitis (UC). To examine the predominance of the MICA TM-STR 6 allele as a marker of the susceptibility to UC within the susceptible haplotype, the association of each allele with UC was estimated following stratification of the patients to control for any possible confounding effects of other alleles positively associated with UC. Sixty-four patients with UC and 236 unrelated healthy controls were included in this study. All subjects were Japanese. HLA-A, -B, -C, and -DR antigens were determined serologically. A triplet repeat polymorphism of the MICA was determined by direct sequencing. To control for the effect of linkage disequilibrium, Mantel-Haenszel weighed odds ratios were calculated. Significantly higher phenotype frequencies of B52, MICA TM-STR 6, and DR2 were observed in patients with UC. Linkage disequilibria among alleles associated with UC revealed that a B52 - MICA TM-STR 6 - DR2 haplotype was conserved in patients with UC, as in controls. When the association of HLA-B52 was estimated after patient stratification for the possible confounding effect of MICA TM-STR 6 or DR2, a strong significant association of B52 with UC was still observed. In contrast, no association with UC was observed for MICA TM-STR 6 or DR2, after stratification of the possible confounding effect of HLA-B52. These results imply that the significant increase in MICA TM-STR 6 in Japanese patients with UC is attributable to linkage disequilibrium with HLA-B52.
Colitis, Ulcerative↗
An anisotropic diffusion method for denoising dynamic susceptibility contrast-enhanced magnetic resonance images.
The purpose of this study was to present an application of a novel denoising technique for improving the accuracy of cerebral blood flow (CBF) images generated from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). The method presented in this study was based on anisotropic diffusion (AD). The usefulness of this method was firstly investigated using computer simulations. We applied this method to patient data acquired using a 1.5 T MR system. After a bolus injection of Gd-DTPA, we obtained 40-50 dynamic images with a 1.32-2.08 s time resolution in 4-6 slices. The dynamic images were processed using the AD method, and then the CBF images were generated using pixel-by-pixel deconvolution analysis. For comparison, the CBF images were also generated with or without processing the dynamic images using a median or Gaussian filter. In simulation studies, the standard deviation of the CBF values obtained after processing by the AD method was smaller than that of the CBF values obtained without any processing, while the mean value agreed well with the true CBF value. Although the median and Gaussian filters also reduced image noise, the mean CBF values were considerably underestimated compared with the true values. Clinical studies also suggested that the AD method was capable of reducing the image noise while preserving the quantitative accuracy of CBF images. In conclusion, the AD method appears useful for denoising DSC-MRI, which will make the CBF images generated from DSC-MRI more reliable.
Aged↗
Accumulation of Tc-99m HMDP in ovarian serous papillary adenocarcinoma reflecting ongoing calcification.
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Adenocarcinoma, Papillary↗
Influence of interleukin-10 on the interleukin-1 receptor antagonist/interleukin-1 beta ratio in the colonic mucosa of ulcerative colitis.
A decrease in the ratio of IL-1ra/IL-1 beta produced regionally by the colonic mucosa of patients with ulcerative colitis (UC) is believed to play a role in the pathogenesis of UC. To investigate factors influencing intramucosal IL-1ra/IL-1 beta ratios, we evaluated polymorphism of the IL-1ra gene and the production of mucosal cytokines in Japanese patients with UC. Colonic biopsy specimens of mucosal tissue were placed in organ cultures for 24 h. Then, the supernatant concentrations of IL-1 beta, IL-1ra, IL-8, IL-4, IL-10, and TGF-beta were assayed by ELISA. Genomic DNA was extracted from patient peripheral blood samples, then IL-1ra gene polymorphism was determined using PCR amplification. The mucosa from patients with active stage UC showed a tendency toward a decreased IL-1ra/IL-1 beta ratio. In the resolving stage, IL-1ra/IL-1 beta ratios increased with increasing IL-10 and TGF-beta concentrations. The addition of human recombinant IL-10 to the culture supernatants produced concentration-dependent inhibition of IL-1 beta. In Japanese patients with UC, the IL-1ra allele gene 2 phenotype had no effect on the IL-1ra/IL-1 beta ratio. Our findings suggest that a relative deficiency of IL-10 in patients with UC may contribute to persistent inflammatory changes.
Adult↗
Prognostic value of iodine-123-metaiodobenzylguanidine imaging and cardiac natriuretic peptide levels in patients with left ventricular dysfunction resulting from cardiomyopathy.
This study assessed the prognostic value of Iodine-123-metaiodobenzylguanidine (MIBG) imaging and of the plasma level of cardiac natriuretic peptides in patients with left ventricular dysfunction resulting from cardiomyopathy. Predictors of cardiac death or hospitalization related to progressive heart failure were examined in 171 patients with chronic heart failure (96 patients with idiopathic cardiomyopathy and 75 patients with ischemic cardiomyopathy). All patients underwent MIBG imaging at rest and other hemodynamic studies. During a mean (+/-SD) follow-up period of 27+/-11 months, 11 patients died from heart failure and 16 required hospitalization. High MIBG washout was an independent predictor of cardiac death (relative risk [RR] = 1.158, p<0.0001) whereas the plasma level of brain natriuretic peptide (BNP: relative risk [RR] = 1.005, p<0.0001) and high MIBG washout (relative risk [RR] = 1.094, p<0.0001) were predictors of progressive heart failure (ie, combined cardiac death and hospitalization). Accelerated myocardial adrenergic nerve activity as assessed by MIBG imaging and the plasma levels of BNP are powerful predictors of the patient's prognosis.
3-Iodobenzylguanidine↗
Methane fermentation of bean curd refuse.
The methane fermentation of bean curd refuse was studied in a 1 l reactor with a draft tube which was operated in a fed-batch mode with a once-a-day feeding cycle using two kinds of methanogens. The effects of substrate loading rate on the methane yield and on the behaviors of the product species were examined. A unified approach was employed for the material balance between the substrate (reactant) and product species based on the elemental carbon content in the species being considered. The classified product species are methane and carbon dioxide in the gas phase, soluble TOCs excluding VFAs, ICs and VFAs in the liquid phase and cells, and the unconverted substrate in the solid phase. It is found that the methane yield increases with the increasing substrate loading rate, reaches a maximum and then decreases with a further increasing loading rate. The maximum methane yield is found to be as high as 53.7% which is very close to the theoretical yield of 55%. It is also found that there is a critical substrate loading rate beyond which the operation becomes impossible due to excessive accumulation of unconverted solids.
Journal Article↗
Production of anti-Gordonia amarae mycolic acid polyclonal antibody for detection of mycolic acid-containing bacteria in activated sludge foam.
Mycolic acid-containing actinomycetes (mycolata) are considered the causative agents of foaming of activated sludge and scum formation in activated sludge treatment plants. In this study, the production of anti-Gordonia amarae mycolic acid polyclonal antibodies was investigated. Rabbits were immunized with a conjugate of keyhole limpet hemocyanin and mycolic acids of G. amarae, which contained 48 to 56 carbon atoms (average, 52.0). Enzyme-linked immunosorbent assay (ELISA) demonstrated that the polyclonal antibodies could recognize cells of G. amarae ranging from 0.1 to 10 microg. The antibodies also reacted with other tested mycolata strains belonging to the genera Nocardia, Rhodococcus, Dietzia, Mycobacterium and Tsukamurella. However, reactivities against other gram-positive and gram-negative bacteria not containing mycolic acid were negligible or much lower. The results indicate that the anti-G. amarae mycolic acid antibodies show a reactivity selective for a group of mycolata involved in the foaming of activated sludge.
Journal Article↗
Intestinal absorbability of wheat allergens, subunits of a wheat alpha-amylase inhibitor, expressed by bacteria.
Wheat CM2, CM3 and CM16 proteins are known as subunits of the tetrameric alpha-amylase inhibitor as well as major allergens to baker's asthma. The purpose of this study is to produce these CM proteins by bacteria in a quantity adequate for studying the penetration characteristics of the CM proteins through intestinal mucosa in rats and Caco-2 cells. cDNAs encoding the mature proteins were expressed in Escherichia coli and purified by an Ni2+-chelating column. The recombinant proteins were radioiodinated and admministered orally to rats or applied to the apical site of the Caco-2 cell monolayer. The radioactivity in the trichloroacetic acid-insoluble fraction, which was mainly composed of peptides with molecular mass less than that of the intact CM proteins, in the serum and the basolateral medium was highest in recombinant CM3. Accordingly, the intestinal absorption of these three proteins in the form present in wheat should be evaluated.
Allergens↗