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Y Imamura

Publications and source records attributed to Y Imamura.

At least 55 records · Page 3Linked to original sources

[Strain-, sex- and species-related differences of acetohexamide reductase and 20 beta-hydroxysteroid dehydrogenase activities in liver microsomes of experimental animals].

We examined physiological and genetic factors affecting acetohexamide reductase (AHR) and 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) activities in liver microsomes of experimental animals. Pronounced strain-related differences were found in both activities of AHR and 20 beta-HSD present in liver microsomes of male rats. Among rat strains tested in this study, even though a Wistar-Imamichi (WIM) rat strain was taken to lack AHR activity, it exhibited a significant 20 beta-HSD activity. These findings appeared to be in conflict with our conclusion reported so far, which AHR and 20 beta-HSD present in liver microsomes of male rats are identical enzymes. Thus the reason for this discrepancy was discussed. Furthermore, AHR and 20 beta-HSD activities were little or not observed in liver microsomes of female rats or male experimental animals other than the rat, indicating the existence of sex- and species-related differences in these two enzyme activities.

20-Hydroxysteroid Dehydrogenases↗

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↗

Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer.

In order to identify the prognostic factors that significantly influence the disease-free survival rate after surgical resection of primary breast cancers, we determined tumour and lymph node grades, and immunohistochemical staining for estrogen and progesterone receptors (ER and PR), c-erbB-2, p53, bcl-2, bax and PCNA in 76 patients. Univariate analysis showed that increased grade of tumour and lymph nodes, negative immunostaining for ER, positive immunostaining for c-erbB-2, and a high PCNA index (> or = 30%) negatively influenced the disease-free survival rate, but PR, p53, bcl-2 and bax had no predictive value. Although p53 was not an independent prognostic factor by itself, the combination of p53, bcl-2, and bax proved to correlate with the disease-free survival, with the best prognosis noted in tumours negative for p53 and positive for both bcl-2 and bax, intermediate prognosis in tumours negative for p53 and positive for either bcl-2 or bax and worst prognosis in tumors negative for p53 as well as bcl-2 and bax. Tumour grade correlated positively with PCNA index, while positive staining for ER correlated negatively with tumour grade as well as with PCNA index, although this was statistically insignificant. Immunostaining of breast cancers for bcl-2 correlated negatively with tumour grade and PCNA index. Immunostaining for c-erbB-2 correlated positively with PCNA but not with tumour grade. Immunostaining for p53 tended to correlate positively with PCNA, but not with tumour grade. Immunostaining for PR and bax did not correlate with tumour grade and PCNA index. These results suggest that in addition to tumour size and lymph node involvement, immunostaining for ER, c-erbB-2, and a high PCNA index are important prognostic factors in human breast cancer. Wild-type p53 with preserved bcl-2 and bax gene products is also a favorable prognostic factor indicating breast cancer at an early stage of cancer progression.

Adult↗

Comparative histochemical study of Bowen's disease and actinic keratosis: preserved normal basal cells in Bowen's disease.

The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test) has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen's disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen's disease were completely negative. Compatible with this result, the basal cells in Bowen's disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 beta E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14), which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen's disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen's disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 beta B4 (monoclonal antibody against cytokeratin 1), which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen's disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen's disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly indicate that the basal cells in Bowen's disease are normal. In support of this conclusion, the same cells showed normal morphology on electron microscopy with preserved basement membrane, although the latter was often damaged in actinic keratosis.

Actins↗

Clonal evolution and progression of 20-methylcholanthrene-induced squamous cell carcinoma of mouse epidermis as revealed by DNA instability and other malignancy markers.

We examined the clonal evolution of skin malignant lesions by repeated topical applications of 20-methylcholanthrene (20-MC) to the skin, which induces hyperplastic epidermis, papillomatous lesion and invasive carcinoma in mice. The lesions were examined histologically and immunohistochemically with anti-single-stranded DNA after acid hydrolysis (DNA-instability test), p53, VEGF, DFF45, PCNA and AgNORs parameters analyses. Multiple clones with increased DNA instability comparable to that of invasive carcinoma were noted in early-stage (2-6 weeks) hyperplastic epidermis, and their number increased in middle (7-11 weeks), and late-stages (12-25 weeks) of hyperplastic epidermis, indicating that they belong to the malignancy category. All papillomatous lesions and invasive carcinomas showed a positive DNA-instability test. Positive immunostaining for various biomarkers and AgNORs parameters appeared in clones with a positive DNA-instability test in early-or middle-stage hyperplastic epidermis, and markedly increased in late-stage hyperplastic epidermis, papillomatous lesions and invasive carcinomas. The percentage of PCNA-positive vascular endothelial cells was significantly higher in VEGF-positive lesions with a positive DNA-instability test and became higher toward the late-stage of progression. Cut-woundings were made to papillomatous and invasive carcinoma lesions, and the regeneration activity of vascular endothelial cells was determined by using flash labeling with tritiated thymidine (3H-TdR). In small papillomatous lesions, vascular endothelial cells showed regenerative response, but the response was weak in large lesions. No such response was noted in invasive carcinomas; rather, cut-wounding induced collapse of blood vessels, which in turn induced massive coagulative necrosis of cancer cells. These responses can be interpreted to reflect exhausted vascular growth activity due to excessive stimulation by VEGF-overexpression, which was persistently seen from hyperplastic epidermis to invasive carcinoma.

Animals↗

Immunohistochemical detection of early-stage carcinogenesis of oral leukoplakia by increased DNA-instability and various malignancy markers.

The degree of DNA instability as determined by immunohistochemical staining with anti-single-stranded DNA antibody after acid hydrolysis (the DNA instability test) was used as a marker of malignancy. The test was applied to tissues of oral leukoplakia assessed histopathologically as hyperplasia (38 cases), mild (12 cases), moderate (11 cases) and severe (8 cases) dysplasia, and invasive squamous cell carcinoma (SCC, 20 cases). Tissues were subjected to immunohistochemical staining for proliferating cell nuclear antigen (PCNA), p53, DNA-fragmentation factor 45 (DFF45), analysis of various AgNORs parameters, and triple immunostaining for vascular endothelial growth factor (VEGF), CD34, and PCNA. The DNA instability test was positive in 20 (100%) SCC cases, 8 (100%) severe dysplasia cases, 8 (72.7%) moderate dysplasia cases, 6 (50.0%) mild dysplasia cases, and 9 (23.7%) hyperplasia cases, indicating malignancy. The proportion of lesions positive for PCNA, p53, DFF45, and values of AgNORs parameters steadily increased from hyperplasia to mild, moderate and severe dysplasia, and SCC, especially in those showing positive DNA instability test, indicative of malignancy. Based on these results, 44.9% of leukoplakia were malignant tissues, namely carcinoma in situ. The proportion of PCNA-positive vascular endothelial cells in the vicinity of VEGF-positive epithelial lesion was significantly higher than that of negative DNA instability lesions, as revealed by immunohistochemical triple staining for VEGF, CD34, and PCNA. Our results suggest that increased DNA instability, enhanced proliferative activity, p53 mutation, and induction of DFF45 and VEGF may allow cancer cell proliferation, enhance their survival by escaping apoptosis, and provide abundant nutrients during early-stage carcinogenesis of oral leukoplakia.

Antigens, CD34↗

Coronary artery disease as a definitive risk factor of short-term outcome after starting hemodialysis in diabetic renal failure patients.

Cardiovascular disease is a major cause of morbidity and mortality in patients with diabetes who are receiving dialysis. It is known that cardiac mortality is high in the first year of hemodialysis (HD). The purpose of this study was to clarify the prevalence of coronary artery disease (CAD) in patients with diabetes at the initiation of HD, and to investigate the relationship between short-term outcomes after starting hemodialysis and CAD. We performed coronary angiography (CAG), whether or not patient had angina, within one month of initiation of maintenance HD in 17 of 34 consecutive unselected diabetic patients. We studied the two-year survival rate of those with CAD. Eleven patients (65%) were classified CAD-positive. Nine (82%) of these 11 had multivessel disease. Clinical and hematologic factors did not differ significantly between the groups with and without CAD. During the two-year follow-up period, 28 (82%) of 34 patients survived. In patients with CAD the two-year survival rate was 60%. None of the patients without CAD died within 2 years after starting HD. These results suggest that the presence of CAD at the initiation of HD may play a critical role in short-term outcomes after starting HD. We believe that an evaluation of CAD should be performed at the initiation of HD.

Chi-Square Distribution↗

Absorption in the visible region of YSZ implanted with Ag ions.

Ag ions were implanted into YSZ (yttrium-stabilized (cubic) zirconia) single crystals in two different energy regimes: kiloelectron volt and megaelectron volt. Optical absorption spectra were measured in the visible region at each stage in the annealing process of the sample. Depth profiles of Ag for the samples implanted at the energy of 20 keV were measured by X-ray photoelectron spectroscopy (XPS). For the samples implanted with Ag at the low energy of 20 keV, one large absorption peak appeared in the wavelength ranging from 470 to 536 nm, depending on the dose of Ag ions. As the sample was heated to 1000 degrees C, the intensity of the absorption peak decreased gradually, but a small, broad peak remains even at the temperature of 1000 degrees C. For the samples implanted with 2.8x10(16) Ag ion cm(-2) at the high energy of 3 MeV, one broad absorption peak was observed at around 470 nm. As the sample was heated sequentially to high temperatures, the peak gradually decreased and almost disappeared at 400 degrees C. When the sample was further heated to even higher temperatures, the absorption peak at 514 nm reappeared at 1000 degrees C and grew with heating time.

Journal Article↗

Increased secretory leukoprotease inhibitor in patients with nonsmall cell lung carcinoma.

BACKGROUND: It is well known that acute pulmonary inflammation, such as that observed in pneumonia, elevates secretory leukoprotease inhibitor (SLPI) levels in serum. A previous report indicated that serum SLPI levels in lung carcinoma patients with concurrent pneumonia were significantly higher than in those in patients whose disease was unaccompanied by pneumonia or in healthy subjects. The authors hypothesized that serum SLPI may increase in patients with lung carcinoma, even carcinoma occurring without pneumonia, and that cells in lung carcinoma might produce SLPI. METHODS: Serum SLPI levels in 58 patients with primary lung carcinoma unaccompanied by pneumonia and in 42 healthy subjects were measured by an enzyme immunoassay. Twenty-four specimens from 24 of the patients with primary lung carcinoma also were examined immunohistochemically using the rabbit antihuman SLPI antibody. RESULTS: The results of the current study confirmed that the serum levels of SLPI in patients with primary lung carcinoma were higher than those in healthy subjects, and further found there was no significant correlation between serum SLPI levels and C-reactive protein in lung carcinoma patients without pneumonia. When classifying primary lung carcinoma by its histology, SLPI levels in patients with adenocarcinoma and squamous cell carcinoma were significantly higher than in those in patients with small cell lung carcinoma (SCLC). In patients with nonsmall cell lung carcinoma (NSCLC), the SLPI levels in the advanced group (International Union Against Cancer Stages III and IV disease; n = 35) were significantly elevated compared with the nonadvanced group (Stages I and II disease; n = 12), and such elevated SLPI levels were reduced in some cases by an efficient response to surgical therapy or chemotherapy. Immunohistochemical studies showed that all the NSCLC tissues were stained with anti-human SLPI antibody, whereas staining was not noted in any of the SCLC tissues. CONCLUSIONS: The authors believe that the findings of the current study demonstrate that cells of NSCLC produce SLPI. Furthermore, they suggest that serum SLPI levels in serum may be a helpful marker in patients with NSCLC unaccompanied by pneumonia, and that SLPI also could be used as an immunohistochemical marker to distinguish between NSCLC and SCLC.

Aged↗

Bone morphogenetic protein-1 processes probiglycan.

Bone morphogenetic protein-1 (BMP-1) is a metalloprotease that plays important roles in regulating the deposition of fibrous extracellular matrix in vertebrates, including provision of the procollagen C-proteinase activity that processes the major fibrillar collagens I-III. Biglycan, a small leucine-rich proteoglycan, is a nonfibrillar extracellular matrix component with functions that include the positive regulation of bone formation. Biglycan is synthesized as a precursor with an NH(2)-terminal propeptide that is cleaved to yield the mature form found in vertebrate tissues. Here, we show that BMP-1 cleaves probiglycan at a single site, removing the propeptide and producing a biglycan molecule with an NH(2) terminus identical to that of the mature form found in tissues. BMP-1-related proteases mammalian Tolloid and mammalian Tolloid-like 1 (mTLL-1) are shown to have low but detectable levels of probiglycan-cleaving activity. Comparison shows that wild type mouse embryo fibroblasts (MEFs) produce only fully processed biglycan, whereas MEFs derived from embryos homozygous null for the Bmp1 gene, which encodes both BMP-1 and mammalian Tolloid, produce predominantly unprocessed probiglycan, and MEFs homozygous null for both the Bmp1 gene and the mTLL-1 gene Tll1 produce only unprocessed probiglycan. Thus, all detectable probiglycan-processing activity in MEFs is accounted for by the products of these two genes.

Animals↗

Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme.

Influenza virus replication has been effectively inhibited by antisense phosphothioate oligonucleotides targeting the AUG initiation codon of PB2 mRNA. We designed RNA-cleaving DNA enzymes from 10-23 catalytic motif to target PB2-AUG initiation codon and measured their RNA-cleaving activity in vitro. Although the RNA-cleaving activity was not optimal under physiological conditions, DNA enzymes inhibited viral replication in cultured cells more effectively than antisense phosphothioate oligonucleotides. Our data indicated that DNA enzymes could be useful for the control of viral infection.

Animals↗

Further studies on 20beta-hydroxysteroid dehydrogenase with carbonyl reductase-like activity present in liver microsomes of male rats.

Further characterizations of 20beta-hydroxysteroid dehydrogenase (20beta-HSD) present in liver microsomes of male rats were examined. A significant relationship was observed between 20beta-HSD and acetohexamide reductase (AHR) activities in liver microsomes of male rats. The hepatic microsomal 20beta-HSD and AHR preferentially required NADPH as a cofactor. When NADPH was replaced by NADH, NADP or NAD at the same concentration, these reductase activities were little detected. The hepatic microsomal 20beta-HSD and AHR activities in streptozotocin-induced diabetic rats were much lower than those in the corresponding controls. The hepatic microsomal 20beta-HSD and AHR activities appeared as one main peak, respectively, on DEAE-Sephacel column chromatography, and the peak of 20beta-HSD activity was in good agreement with that of AHR activity. Based on these results, we conclude that 20beta-HSD present in liver microsomes of male rats functions as AHR, and exhibits a carbonyl reductase-like activity.

Alcohol Oxidoreductases↗

Cytokine-inducing macromolecular glycolipids from Enterococcus hirae: improved method for separation and analysis of its effects on cellular activation.

Previously, we showed that several minor macromolecular glycolipids accounting for less than 5% of the lipoteichoic acid (LTA) fraction from Enterococcus hirae ATCC 9790 possess cytokine-inducing activity, whereas the purified LTA does not. In other words, the immunobiological activity of the LTA fraction reported in the 1980s was not attributable to LTA itself, but to other glycolipids coexisting in the fraction. In the present study, we improved the procedure of separation of the active glycolipids and evaluated their effects on cellular activation. The immunobiologically active glycolipids were separated from the crude glycolipid fraction obtained by hot phenol-water extraction of the cells. The total yield of active glycolipids was about fivefold higher than that separated by the previous method. Interleukin-6-inducing activities of the active glycolipids from 1,25-dihydroxy vitamin D(3)-differentiated human monocytic leukemia cells, THP-1, were inhibited by anti-CD14 mAbs in a dose-dependent manner. Macrophages from Toll-like receptor (TLR)-2-deficient or -4-deficient mice completely lacked the ability to produce tumor necrosis factor-alpha on stimulation with active glycolipids. These observations indicated that the cellular activation by the active glycolipids from E. hirae is mediated by CD14 and by both TLR2 and TLR4.

Animals↗

The pro-alpha3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains.

The low abundance fibrillar collagen type V is widely distributed in tissues as an alpha1(V)(2)alpha2(V) heterotrimer that helps regulate the diameters of fibrils of the abundant collagen type I. Mutations in the alpha1(V) and alpha2(V) chain genes have been identified in some cases of classical Ehlers-Danlos syndrome (EDS), in which aberrant collagen fibrils are associated with connective tissue fragility, particularly in skin and joints. Type V collagen also exists as an alpha1(V)alpha2(V)alpha3(V) heterotrimer that has remained poorly characterized chiefly due to inability to obtain the complete primary structure or nucleic acid probes for the alpha3(V) chain or its biosynthetic precursor, pro-alpha3(V). Here we provide human and mouse full-length pro-alpha3(V) sequences. Pro-alpha3(V) is shown to be closely related to the alpha1(V) precursor, pro-alpha1(V), but with marked differences in N-propeptide sequences, and collagenous domain features that provide insights into the low melting temperature of alpha1(V)alpha2(V)alpha3(V) heterotrimers, lack of heparin binding by alpha3(V) chains and the possibility that alpha1(V)alpha2(V)alpha3(V) heterotrimers are incorporated into heterotypic fibrils. In situ hybridization of mouse embryos detects alpha3(V) expression primarily in the epimysial sheaths of developing muscles and within nascent ligaments adjacent to forming bones and in joints. This distribution, and the association of alpha1(V), alpha2(V), and alpha3(V) chains in heterotrimers, suggests the human alpha3(V) gene COL5A3 as a candidate locus for at least some cases of classical EDS in which the alpha1(V) and alpha2(V) genes have been excluded, and for at least some cases of the hypermobility type of EDS, a condition marked by gross joint laxity and chronic musculoskeletal pain. COL5A3 is mapped to 19p13.2 near a polymorphic marker that should be useful in analyzing linkage with EDS and other disease phenotypes.

Amino Acid Sequence↗

(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity.

We investigated the mechanism of the hypoglycemic effect of (R)-4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzene-sulfonamide [(R)-acetoxyhexamide; (R)-ACX], a new sulfonylurea compound. (R)-ACX potently stimulated the release of insulin from cultured pancreatic beta-cells (HIT T15 cells), established from hamster islet cells SV40-transformed. When (R)-ACX was orally administered to fasted rats, it decreased the plasma glucose level in a dose-dependent manner. The hypoglycemic effect of (R)-ACX was quick and short lasting, as compared to that of acetohexamide and glibenclamide. The quick and short-lasting hypoglycemic effect of (R)-ACX was thought likely to result from rapid absorption of (R)-ACX and rapid elimination of (R)-ACX and its metabolite, (R)-hydroxyhexamide. Furthermore, (R)-ACX was found to suppress the increase of blood glucose level due to starch loading in fasted mice. (R)-ACX may be useful in the control of postprandial hyperglycemia to patients with non-insulin-dependent diabetic mellitus.

Acetohexamide↗

Strictureplasty for short duodenal stenosis in Crohn's disease.

Involvement of the gastroduodenum is extremely rare in Crohn's disease. For obstructing duodenal Crohn's disease, bypass procedures have traditionally been selected. However, more recently, strictureplasty has become an acceptable surgical option. We treated two Crohn's disease patients with short proximal duodenal stenosis, using Finney-type strictureplasty. Their postoperative courses were uneventful and they have remained asymptomatic during follow-up periods of more than 5 years, and 4 months, respectively. Owing to the good clinical results of our two patients, we consider strictureplasty to be indicated for short proximal duodenal stenosis in Crohn's disease.

Adult↗

Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis.

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1:160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind.

Adult↗