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Biomedical subjects

E Nomura

Publications and source records attributed to E Nomura.

At least 19 recordsLinked to original sources

Plasma total homocysteine levels are associated with advanced leukoaraiosis but not with asymptomatic microbleeds on T2*-weighted MRI in patients with stroke.

Both leukoaraiosis and asymptomatic microbleeds are associated with small-artery diseases. Although an association between hyperhomocysteinemia and leukoaraiosis has been reported, no studies have evaluated the association between total homocysteine (tHcy) level and presence of microbleeds in stroke patients. We evaluated the association between tHcy level and leukoaraiosis or microbleeds in stroke patients. In 102 patients with stroke (69.5 +/- 10.3 years old, 54 men and 48 women), microbleeds on T2*-weighted MR images were counted, leukoaraiosis on T2-weighted images was graded and fasting plasma tHcy concentrations were measured. Plasma tHcy level was significantly higher in patients with advanced leukoaraiosis than in those without advanced leukoaraiosis (13.9 +/- 4.6 micromol/l vs. 10.2 +/- 3.4 micromol/l, P < 0.0001). Plasma tHcy level was not significantly different in patients with microbleeds and those without microbleeds (11.3 +/- 4.1 micromol/l vs. 11.4 +/- 4.3 micromol/l, P = 0.9441). Elevated tHcy level is significantly and independently associated with advanced leukoaraiosis [odds ratio (OR), 1.330; 95% CI, 1.130-1.565] but not with the presence of microbleeds. Elevated tHcy level appears to be associated with ischemic small-artery disease rather than with bleeding-prone small-artery disease.

Aged↗

Both N-terminal and C-terminal regions of steroid sulfatase are important for enzyme activity.

Steroid sulfatase (STS) is localized in the endoplasmic reticulum and catalyzes desulfation of 3beta-hydroxysteroid sulfates. X-linked ichthyosis (XLI) is an inherited skin disorder caused by deficiency of STS enzyme activity. We previously reported a case in which XLI with a one-base change in the STS gene and variation in amino acid Q560P developed. In this study, we performed molecular analysis to determine the importance of terminal regions of STS and the effect of mutant STS on STS enzyme activity. To examine the effect of terminal truncated STS on the enzyme activity, N- and C-terminal truncated STS expression vectors were transfected into COS-1 cells. The activity of truncated STS lacking the N-terminal regions declined, and the activity of C-terminal-truncated STS declined with extension of the truncated C-terminal region. Although the results of pulse-chase experiments showed that a one-base mutant STS (Q560P) and C-terminal-truncated STS (deltaC2 (1-559)) had no effects on protein synthesis and degradation, the mutant STS and C-terminal-truncated STS have dominant negative effect on STS enzyme activity when the STS mutant or truncated STS protein and a wild-type STS protein coexist in cells. Results of coprecipitation of the truncated STS with an STS-FLAG fusion protein showed that STS formed a dimer conformation in cells. In this study, we have shown that both the N-terminal region and C-terminal region are important for STS enzyme activity. The C-terminal mutant has a dominant negative effect on wild-type STS.

Amino Acids↗

Combinations of the presence or absence of cerebral microbleeds and advanced white matter hyperintensity as predictors of subsequent stroke types.

BACKGROUND AND PURPOSE: Previous studies have shown microbleeds to be a risk factor for intracerebral hemorrhage and white matter hyperintensity (WMH) to be a risk factor for ischemic stroke. This study was performed to determine whether combinations of the presence or absence of microbleeds and advanced WMH are risk factors for subsequent recurrent stroke types. METHODS: In 266 patients with stroke, microbleeds on T2*-weighted MR images were counted, and WMH on T2-weighted images was graded. Patients were divided into 4 groups by the combinations of the presence or absence of microbleeds and advanced WMH and were followed up for stroke recurrence. RESULTS: During a mean follow-up period of 564.8 +/- 220.5 days, 26 patients developed recurrent strokes, including 10 intracerebral hemorrhages and 16 ischemic strokes. Patients with microbleeds without advanced WMH (n = 42) developed only intracerebral hemorrhages (n = 8), and the recurrence rate of intracerebral hemorrhage in those patients estimated by the Kaplan-Meier method was the highest in the 4 groups (14.3% in 1 year and 21.2% in 2 years). In contrast, patients with advanced WMH without microbleeds (n = 39) developed only ischemic strokes (n = 6), and the estimated recurrent rate of ischemic stroke in those patients was the highest in the 4 groups (10.5% in 1 year and 17.4% in 2 years). Cox proportional hazards regression analysis revealed that microbleeds were associated with intracerebral hemorrhage (hazard ratio [HR], 85.626; 95% confidence interval [CI], 6.344-1155.649) and that advanced WMH was negatively associated with intracerebral hemorrhage (HR, 0.016; 95% CI, 0.001-0.258). Advanced WMH was associated with ischemic stroke (HR, 10.659; 95% CI, 2.601-43.678). CONCLUSION: It appears that patients at high risk of subsequent intracerebral hemorrhage or ischemic stroke can be identified by combinations of the presence or absence of microbleeds and advanced WMH.

Aged↗

Second-look arthroscopy of cartilage changes of the patellofemoral joint, especially the patella, following acute and recurrent patellar dislocation.

OBJECTIVE: The purpose of this study was to clarify some pathogenesis of the cartilage changes of the patellofemoral joint in patellar dislocation knees. METHODS: A first arthroscopy was performed in a total of 60 knees, including 30 knees of acute patellar dislocation (APD) and 30 knees of recurrent patellar dislocation (RPD). At the time of the first arthroscopy, 58 knees sustained open medial patellofemoral ligament repair/reconstruction, and 2 knees had only arthroscopy examination. In APD knees, the second-look arthroscopy was performed 16.7 months after the first arthroscopy, and in RPD knees, 25.2 months after the first arthroscopy. RESULTS: In most APD knees, cracking primarily on the central dome of the patella did not have a remarkable change but in several knees that had a high number of cracking or interlaced cracking, cracking became worse with fibrillation. Osteochondral defect site primarily on the medial facet showed fibrillation and/or ulceration (erosion). In most RPD knees, fissuring primarily on the central dome did not have a remarkable change, and fibrillation and/or erosion mainly on the medial facet also did not have a remarkable change. However, in four knees with the continuation of patellar dislocation, the patellar cartilage changes had definitely worsened. On the other hand, in the first and second-look arthroscopy, most APD and RPD knees had no remarkable cartilage lesions or cartilage changes of the femoro-trochlear aspect. CONCLUSIONS: One of the pathogenesis of fissuring in RPD knees seems to be cracking occurring at the time of APD. Two of the pathogenesis of fibrillation may result from the reparative reaction of the cartilage in osteochondral defect site and the cartilage change due to a high degree of cracking damage mainly on the central dome in APD injury. The continuation of patellar dislocation definitely makes the patellar cartilage lesions worse.

Acute Disease↗

Ultrastructural study of the extra-articular Leeds-Keio ligament prosthesis.

BACKGROUND: There have been several histological studies of the Leeds-Keio ligament in anterior cruciate ligament reconstruction, but there have been few of the Leeds-Keio ligament in the extra-articular portion. AIMS/METHODS: To report the histological and ultrastructural findings of two cases of medial patellofemoral ligament reconstruction using the Leeds-Keio ligament, removed 6.1 years and 8.7 years after implantation. RESULTS: In both cases, the tissue over the Leeds-Keio ligament was a ligament-like tissue. Electron microscopy showed that the diameter of the collagen fibrils in the tissue over the Leeds-Keio ligament was unimodal in the case investigated 6.1 years after implantation but bimodal in the case investigated after 8.7 years. CONCLUSIONS: The tissue over the Leeds-Keio ligament may continue to grow with prolonged periods of mechanical stress.

Adolescent↗

Laparoscopic approach for early gastric cancer within a paraesophageal hiatal hernia.

We present a case of early gastric cancer located in gastric volvulus associated with paraesophageal hiatal hernia. Two lesions of EGC were diagnosed in the distal third of the stomach, most of which had herniated into the left chest through a large hiatal defect in an organoaxial fashion. Routinely, laparoscopic-assisted distal gastrectomy (LADG) is our preferred approach for EGC, and the presence of hiatal hernia in this case did not alter our approach. Laparoscopic repair of hiatal hernia was performed successfully followed by LADG. A review of the literature supports a minimally invasive approach for both procedures and shows it to be safe, effective, and technically feasible. Further, LADG is shown to be oncologically adequate in terms of tumor margins and lymph node dissection, but its relevance to long-term disease-free survival still needs to be studied in well-designed prospective trials.

Gastrectomy↗

Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice.

Antioxidant activity and biological properties of ferulic acid (FA) are well recognized. This study was designed to estimate the potential utility of FA administered orally at low dosage for improvement of hyperglycemia in diabetes. With this aim we have evaluated the hypoglycemic effect of FA in two type diabetic animal models: (1) streptozotocin (STZ)-induced diabetic mice, a model of insulin-dependent diabetes mellitus (IDDM); (2) KK-Ay mice, a model of non-insulin dependent diabetes mellitus (NIDDM). In addition, we measured the production of thiobarbituric acid-reactive substances (TBARS) in brown adipose tissues of diabetic mice at the end of FA feeding experiment. FA at 0.01% and 0.1% of basal diet showed to suppress significantly blood glucose levels in STZ-induced diabetic mice. In KK-Ay mice 0.05% FA suppressed effectively blood glucose levels. In addition, FA inhibited the lipid peroxidation in brown adipose tissue of diabetic mice. Taken together, these findings suggest that dietary FA may be useful in alleviating oxidative stress and attenuating the hyperglycemic response associated with diabetes.

Animals↗

Characterization of binding between SF-1 and Sp1: predominant interaction of SF-1 with the N-terminal region of Sp1.

The transcription factor specificity protein 1 (Sp1) binds to GC boxes and interacts with many transcription factors to regulate gene expression. Steroidogenic factor-1 (SF-1) is an orphan nuclear receptor and plays a major role in regulation of the human steroidogenic acute regulatory (StAR) gene. We demonstrated that there is interaction between SF-1 and Sp1 on the human StAR promoter. In the present study, we examined the mechanism of the interaction between Sp1 and SF-1 on the human StAR gene promoter. Results of glutathione S-transferase (GST) pull-down assays and a mammalian two-hybrid assay showed that SF-1 interacted with Sp1 through the N-terminal domains of Sp1. Results of electrophoretic mobility shift assays using nuclear extracts showed that Sp1 is associated with SF-1-DNA complex formation. The density of SF-1-DNA complex was much greater when recombinant Sp1 was added to the incubation mixture. These results suggest that Sp1 interacts with SF-1 and that Sp1 enhances SF-1-DNA complex formation to regulate human StAR transcription.

Animals↗

Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis.

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

Adult↗

Significance of serum soluble thrombomodulin level in acute cerebral infarction.

The purpose of the present study was to investigate sequential changes in serum soluble thrombomodulin (sTM) concentrations in patients with acute cerebral infarction (ACI), and to correlate sTM concentrations with the severity of ACI evaluated by Japan Stroke Scale. Eighty-three consecutive patients with ACI were enrolled, and blood examinations were carried out soon after admission and 1 month after. sTM concentrations at admission in patients with cardioembolic infarction (3.2 +/- 1.2 ng/ml) were significantly lower than those of lacunar infarction (3.9 +/- 1.2) (P < 0.05). Serial examinations revealed that sTM concentrations increased significantly 1 month after admission (3.8 +/- 1.2), compared with those at admission (3.6 +/- 1.2) (P = 0.02). Of three ACI subtypes, sTM concentrations during 1 month significantly increased in atherothrombotic infarction (P = 0.002) or, not significantly, in cardioembolic infarction (P = 0.09). The sTM concentrations at admission showed a significant inverse correlation with the severity of ACI (P = 0.04). Although sTM concentrations serve as a useful marker for endothelial cell damage, they are decreased in patients with severe ACI, especially in atherothrombotic and cardioembolic infarctions. Lower sTM concentrations may play some important role in disease progression or in the recurrence following ACI, although the exact mechanism of this unique result should be clarified.

Acute Disease↗

Expression of enzyme associated with steroid hormone synthesis and local production of steroid hormone in endometrial carcinoma cells.

Endometrial carcinoma is a common malignancy of the genital tract. In the present study, we examined the expression of human steroidogenic acute regulatory (StAR) protein, P450 side-chain cleavage enzyme (P450 scc), 17alpha-hydroxylase/17,20-desmolase (P45017alpha) and aromatase (P450 arom) in endometrial carcinoma cells to clarify the ability of these cells to produce steroid hormones. The results of RT-PCR analysis showed that StAR, P450 scc and P45017alpha genes were expressed in endometrial carcinoma cells. To examine the protein expression of StAR and P450 scc, we performed Western blotting using extracts from carcinoma cells. StAR protein and P450 scc were detected in both HHUA and HOUA-1 cells. The production of pregnenolone in HHUA cells increased 2.4-fold with transfection of a StAR expression vector and 4.3-fold with transfection of an F2 side-chain cleavage system. The RT-PCR product of 3beta-hydroxysteroid dehydrogenase was present in endometrial carcinoma cells. In endometrial carcinoma cells, the production of progesterone also increased with over-expression of StAR and the F2 system. Results of steroid metabolic assays showed that endometrial carcinoma cells produced not only 17alpha-hydroxyprogesterone but also androstenedione. Endometrial carcinoma cells express enzymes that are associated with the production of steroid hormones. Locally produced steroid hormones may have effects on tumor proliferation and tumorigenesis.

17-alpha-Hydroxyprogesterone↗

Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB).

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

Animals↗

Sentinel node detection using 99mTc-rhenium sulphide colloid in breast cancer patients: evaluation of 1 day and 2 day protocols, and a dose-finding study.

Sentinel node (SN) biopsy is a promising replacement for standard axillary lymph node dissection for the staging of early breast cancer, and various techniques have been studied to identify SNs with dye or radioactive colloid. This study assesses the effect of the dose of radioactivity and the time before biopsy in order to set standards for the use of 99mTc-rhenium sulphide for the detection of SNs in breast cancer patients. Sixty patients with stage T1-2 N0 M0 breast cancer underwent SN biopsy, which was immediately followed by standard axillary dissection to confirm the SN results. For SN biopsy, 99mTc-rhenium colloid was injected peritumorally. A 1 day (morning injection and afternoon surgery) or 2 day (day before afternoon injection and morning surgery) protocol was applied. A dose-finding study was performed simultaneously using 7.4-37 MBq for the 1 day protocol and 37-74 MBq for the 2 day protocol. A scintigram was taken at 2 h for the 1 day protocol and 16 h for the 2 day protocol. After the injection of blue dye, SN biopsy was performed with a gamma probe, followed by standard axillary node dissection. The radiation exposure received by the surgical team during the operation was monitored. Histopathological comparison between SNs and axillary nodes was performed. Patient characteristics that might affect the radiocolloid uptake by SNs were assessed. SNs were identified in all patients regardless of the dose or administration protocol used. Two patients showed false negative pathological SN results, and the negative predictive value was 96% and the positive predictive value was 100%. In addition, radiation exposure to the surgical team and the amount of radioactive surgical waste were low, especially at lower doses. Two groups of patient characteristics were related to SN uptake. One was the body mass index (BMI) and the other was the age or menopausal status. Patients with a larger BMI tended to take up a smaller amount of 99mTc colloid. Older or post-menopausal patients showed lower SN uptake. 99mTc-rhenium sulphide colloid is an efficient radiopharmaceutical for SN detection. Both 1 day and 2 day protocols have equally good efficacy, and the recommended dose is 7.4 MBq for the 1 day protocol and 37 MBq for the 2 day protocol. Patients with larger BMI and older or post-menopausal patients tend to take up less 99mTc colloid.

Adult↗

Correlation of MR imaging findings and open exploration of medial patellofemoral ligament injuries in acute patellar dislocations.

The purpose of this investigation was to correlate magnetic resonance (MR) images of medial patellofemoral ligament (MPFL) injuries with gross macroscopic findings. Twenty-seven knees with MPFL injury following an initial patellar dislocation were examined using axial proton-density and T2-weighted fast spin-echo MR imaging. MR findings were subsequently correlated with open exploration. MPFL injury was observed in 26 (96%) of the 27 knees. From the MR images, discontinuity, irregularity and/or high-signal intensity changes anterior to the femoral attachment were seen in 13 (82%) of the 16 knees with substantial-tear type injuries of the MPFL. In 8 (80%) of the 10 knees with avulsion-tear type injuries, detachment of the MPFL from the femoral attachment, accompanied with or without high-signal intensity changes, was confirmed. MPFL injury types could be accurately diagnosed on 21 (81%) out of 26 knees using MR imaging. MR imaging was an acceptable method in diagnosing MPFL injury types.

Acute Disease↗

Analysis of microsatellite polymorphism around the HLA-B locus in Iranian patients with Behçet's disease.

We have previously suggested that in a Japanese population the susceptible locus for Behçet's disease (BD) is HLA-B51 itself. To confirm this finding in another population, we performed HLA class I typing using the PCR-SSP method and analyzed eight polymorphic markers distributed within 1100 kb around the HLA-B gene using automated sequencer and subsequent automated fragment detection by fluorescent-based technology with the DNA samples of 84 Iranian patients with BD and 87 healthy ethnically matched controls. As a result, three microsatellite alleles (MICA-A6, MIB-348, C1-4-1-217) and HLA-B51 were found to be strongly associated with BD. Of these alleles HLA-B51 is the most strongly associated allele. There were no alleles that were increased in allele frequency at any microsatellite loci centromeric of MICA or telomeric of HLA-B51. Therefore, HLA-B51 was confirmed to be by far the most strongly associated gene with BD in an Iranian population.

Behcet Syndrome↗

Synthesis and conformational property of tannin-like p-tert-butylcalix[4]arene 1,3-diesters stabilized by intramolecular hydrogen bonds.

Tannin-like p-tert-butylcalix[4]arene 1,3-digallate was synthesized, and its conformational property was investigated by dynamic (1)H NMR and X-ray crystallography. It was found that the 3-OH (or 5-OH) group of the galloyl group in p-tert-butylcalix[4]arene 1,3-digallate is placed at the position where an unusual nonbonded close contact is observed between the OH group and the aromatic ring of the galloyl group facing each other. The calixarene 1,3-diesters of various hydroxybenzoic acids were also prepared, and the conformational properties of those calixarenes were compared with that of p-tert-butylcalix[4]arene 1,3-digallate. A significant contribution of the 3- and 5-OH groups in pendant groups toward the close contact was found. It was suggested that the conformation of p-tert-butylcalix[4]arene 1,3-digallate was stabilized by intramolecular hydrogen bonds including OH.O and OH-pi interactions.

Calixarenes↗