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Biomedical subjects

T Harada

Publications and source records attributed to T Harada.

At least 19 recordsLinked to original sources

Glucocorticoid-induced diabetes mellitus: prevalence and risk factors in primary renal diseases.

BACKGROUND/AIMS: In patients with primary renal diseases the current knowledge of hyperglycemia associated with corticosteroid therapy is limited. We therefore examined the prevalence and risk factors of glucocorticoid-induced diabetes mellitus (DM) in primary renal diseases. METHODS: Patients were recruited with primary renal diseases who were started on corticosteroids between April 2002 and June 2005. In patients with DM, an impaired fasting glucose level and/or positive urinary glucose analyses before corticosteroids therapy were excluded. RESULTS: During corticosteroid therapy (initial dose: prednisolone 0.75 +/- 0.10 mg/kg/day), DM was newly diagnosed in 17 (40.5%) of 42 patients. All of the 17 patients were diagnosed as having DM by postprandial hyperglycemia at 2 h after lunch, although they had normal fasting blood glucose levels. Age (OR 1.40, 95% CI 1.06-1.84) and body mass index (OR 1.87, 95% CI 1.03-3.38) were determined as independent risk factors for glucocorticoid-induced DM. CONCLUSION: Over 40% of patients with primary renal disease developed DM during treatment with corticosteroids. A high age and high body mass index are the independent risk factors for glucocorticoid-induced DM. 24-hour urinary glucose analyses and postprandial plasma glucose are useful for detecting glucocorticoid-induced DM.

Adult↗

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the beta4 integrin and the PI3k pathway.

Pancreatic ductal adenocarcinoma is a devastating disease, characterized by a rapid progression and poor treatment response. Using gene expression profiling of pancreatic cancer tissues, we previously identified periostin as a potential diagnostic and therapeutic target. In this study, we report the overexpression of periostin in a larger set of pancreatic cancer tissues and show that although the periostin transcript is exclusively expressed in tumour cells, the protein product is only detected in the extracellular matrix adjacent to cancer cells. Using an enzyme-linked immunosorbent assay (ELISA) assay, we show significantly increased levels of periostin in the sera of pancreatic cancer patients compared to non-cancer controls. We demonstrate that periostin promotes the invasiveness of tumour cells by increasing the motility of cells without inducing expression of proteases, and enhances the survival of tumour cells exposed to hypoxic conditions. At the molecular level, we provide evidence that the alpha(6)beta(4) integrin complex acts as the cell receptor of periostin in pancreatic cancer cells and that interaction promotes phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT) though activation of the PI3 kinase pathway, but not the RAS/MEK/ERK pathway. These findings suggest an important role of periostin in pancreatic cancer and provide a rationale to study periostin for diagnostic and therapeutic applications.

Apoptosis↗

Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury.

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.

Adenosine↗

Identification of arginase in human placental villi.

l-Arginine is the common substrate for arginase and nitric oxide synthase (NOS). Arginase converts l-arginine to urea and ornithine, which is the principal precursor for production of polyamines required for cell proliferation. Human placenta expresses endothelial NOS (eNOS) in syncytiotrophoblasts, but the expression of arginase has not been fully elucidated. Our aim was to investigate the expression and distribution patterns of arginase-I (A-I) and arginase-II (A-II) in human placental villi in the first trimester and at term using immunohistochemistry, RT-PCR and Western blot analysis. The arginase enzyme activity in placental villi was also measured. Immunohistochemistry showed different distribution patterns of the arginase isoforms during gestation: A-I was observed only in cytotrophoblasts, while A-II was observed in both cytotrophoblasts and syncytiotrophoblasts. RT-PCR and Western blot analysis showed expression of A-I and A-II in the first trimester and at term in human placental villi. Expression of A-II and arginase activity was greater in the first trimester than at term. Differentiation of cytotrophoblasts into syncytiotrophoblasts may be associated with l-arginine metabolism through modulation of l-arginine availability for eNOS and A-I. And elevated arginase activity in the early gestational period may be responsible for proliferation of trophoblasts by increasing polyamines production. These results suggest that the l-arginine-ornithine-polyamine and l-arginine-nitric oxide pathways play a role in placental growth and development.

Arginase↗

The effect of oral splint devices on sleep bruxism: a 6-week observation with an ambulatory electromyographic recording device.

This study investigated the effect of stabilization splint (SS) and palatal splint (PS), which had the same design as SS except for the elimination of the occlusal coverage, on sleep bruxism (SB) using a portable electromyographic (EMG) recording system. Sixteen bruxers participated in this study. The EMG activities of the right masseter muscle during sleep were recorded for three nights each in the following five recording periods: before, immediately after, and 2, 4 and 6 weeks after the insertion of the splint. The crossover design, in which each splint was applied to each subject for 6 weeks with an interval of 2 months for a washout period, was employed in this randomized-controlled study. The number of SB events, duration and total activities of SB were analysed. The number of SB events before the insertion of splints (baseline) was 2.98 +/- 1.61 times h(-1). Both splints significantly reduced SB immediately after the insertion of devices (P < 0.05, one-way repeated-measures anova followed by Dunnett); however, no reduction was observed in 2, 4 or 6 weeks (P > 0.05). There was no statistical difference in the effect on SB between the SS and PS (P > 0.05, two-way repeated-measures anova). Both splints reduced the masseter EMG activities associated with SB; however, the effect was transient.

Adult↗

A case of primary extragonadal seminoma arising in the perineum.

We report the first case of primary extragonadal seminoma arising in the perineum. A 34-year-old-man presented with a 2-cm painless mass in the perineum. He underwent surgical resection, and histology showed poorly differentiated adenocarcinoma. Three months later, local recurrence occurred. Whole evaluation including ultrasound and MRI of the testes were normal, so he underwent surgical wide excision, and pathology showed the tumor was pure seminoma. He received two courses of bleomycin, etoposide and cisplatin (BEP) therapy, and there has been no evidence of recurrence for 1 month.

Adult↗

Bacterial luciferase activity and the intracellular redox pool in Escherichia coli.

In this study, we analyzed the activity of a bacterial luciferase (LuxAB of Vibrio fischeri) expressed under the control of a consensus-type promoter, lacUV5, in Escherichia coli, and found that activity declines abruptly upon entry into the stationary growth phase. Since this decline was reproducibly observed in strains cultured in various growth media, we refer to this phenomenon as ADLA (Abrupt Decline of Luciferase Activity) and define the time point when activity begins to decline as T (0). Because the levels of luciferase proteins (LuxA and LuxB) remained constant before and after T (0), ADLA cannot be due to the repression of luciferase gene expression. Further analyses suggested that a decline in the supply of intracellular reducing power for luciferase was responsible for ADLA. We also found that ADLA was alleviated or did not occur in several mutants deficient in nucleoid proteins, suggesting that ADLA is a genetically controlled process involved in intracellular redox flow.

Aliivibrio fischeri↗

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent fertility outcomes in couples with infertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 2 March 2004), MEDLINE (1966 to Mar 2004), EMBASE (1980 to Mar 2004), Biological Abstract (1980 to Mar 2004) and reference lists of articles. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eleven randomised controlled trials were identified and included in this review. All trials were assessed for quality criteria. The studied primary outcome was live birth (and ongoing pregnancy), with secondary outcomes pregnancy, miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention (three trials including 381 participants) was associated with a significant increase in the odds of live birth (Peto OR 2.98, 95%CI 1.40 to 6.37) and of pregnancy (Peto OR 3.30, 95%CI 2.00 to 5.43). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. For the comparison of tubal flushing with oil-soluble media versus tubal flushing with water-soluble media (six trials including 1,483 participants), the increase in the odds of live birth for tubal flushing with oil-soluble versus water-soluble media (Peto OR 1.49, 95%CI 1.05 to 2.11) was based on two trials where statistical heterogeneity was present and the higher quality trial showed no significant difference; there was no evidence of a significant difference in the odds of pregnancy (Peto OR 1.24, 95%CI 0.97 to 1.57). The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone; three trials including 555 participants) showed no evidence of a significant difference in the odds of pregnancy (Peto OR 1.18, 95%CI 0.82 to 1.70) or live birth (Peto OR 1.06, 95%CI 0.64 to 1.77). Adverse event data were only available for the comparison OSCM versus WSCM: OSCM carried a significantly higher chance of intravasation (Peto OR 5.41, 95%CI 2.57 to 11.37) but a significantly lower chance of immediate pain (Peto OR 0.53, 95%CI 0.34 to 0.84), prolonged pain (Peto OR 0.26, 95%CI 0.15 to 0.45) and post-procedure bleeding (Peto OR 0.22, 95%CI 0.15 to 0.31), and no serious adverse events were reported. AUTHORS' CONCLUSIONS: There is evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy and live birth versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing water-soluble media versus no intervention, would be a useful further guide to clinical practice. Further research is merited to ascertain the mechanism of the fertility enhancing effect of oil-soluble media, as to whether this is a 'tubal flushing' phenomenon, an effect on the intraperitoneal environment, or an implantation enhancing effect on the endometrium.

Contrast Media↗

Changes in histology and expression of cytokines and chemokines in the rat lung following exposure to ovalbumin.

Brown Norway (BN) and Fischer 344 (F344) rats were exposed to aerosol of 1% ovalbumin (OVA) solution for 30 min at 1 week after the second sensitization with 1 mg of OVA at 2-week intervals. Changes in the histology and expression of cytokines and chemokines in the lung were examined for up to 96 h after the exposure. The lung weight significantly increased in BN rats but not in F344 rats. Histologically, in the lung of BN rats, multiple foci of hemorrhage in the alveolar space with infiltration of eosinophils and macrophages in the surrounding alveolar septa were first observed. Thereafter, granulomatous lesions developed in the preexisting hemorrhagic foci, finally resulting in formation of multiple eosinophilic granulomas. On the other hand, in F344 rats, infiltration of eosinophils and macrophages was observed around the vessels and bronchi. Thereafter it progressed gradually, resulting in mild thickening of alveolar septa. The levels of Th1- (interferon-gamma and interleukin 2 (IL-2)) and Th2-related cytokines (IL-4 and IL-5) and chemokines (eotaxin and monocyte chemoattractant protein-1) mRNAs measured by reverse transcription-polymerase chain reaction method were elevated in the lung of both strains, and the levels were higher in BN rats than in F344 rats. These results suggest that BN rats are more sensitive to OVA-sensitization/inhalation than F344 rats and that the difference in the severity of lung lesions between BN and F344 rats may reflect the difference in the expression levels of cytokines and chemokines between these two strains.

Animals↗

Inheritance of the Md-ACS1 gene and its relationship to fruit softening in apple ( Malus x domestica Borkh.).

The 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene is a member of the ACS gene family that is involved in apple ( Malus x domestica Borkh.) fruit ripening. Presence of an allele ( Md-ACS1-2) of this gene is associated with low internal ethylene concentration in some apple cultivars. In this study, inheritance of Md-ACS1 was determined for 50 apple cultivars/advanced selections and 101 F(1) seedlings from five populations. Following this, the softening pattern of apples stored at 20 degrees C for up to 40 days was examined using 35 fruiting cultivars/selections of defined Md-ACS1 status. Md-ACS1 is inherited in a Mendelian fashion and was found to be linked to fruit softening. Maturity season of genotypes also significantly affected fruit softening. Late-season genotypes in the Md- ACS1-2/2 class had the slowest rate of softening, while early-season Md- ACS1-1/1 genotypes had the most rapid softening rate. The implications of these results are discussed in relation to parental selection and breeding for storage ability in apple.

Alleles↗

A probative approach for noninvasive evaluation of airway hyperresponsiveness and remodeling in adult asthmatics.

We propose a probative approach for noninvasive evaluation of airway hyperresponsiveness (AHR) and remodeling to investigate their outcome in adult asthmatics treated according to the Global Initiative for Asthma (GINA) guideline. Pulmonary function and AHR to methacholine were measured twice with an interval of 24.3 +/- 3.4 months in 18 adult asthmatics during the ongoing treatments. Mathematical formulas previously used in an animal model were applied in human asthmatics to eliminate the effect of airway wall thickening on respiratory resistance (Rrs), calculating indices for the proportional changes with time in airway wall thickness (PW(1)/PW(0)) and airway smooth muscle shortening (PMS(1)/PMS(0)), respectively. The minimum cumulative dose of methacholine (Dmin), an ordinary index of AHR measured with the oscillometry Asthograph, correlated with the asthma severity. The disease periods significantly correlated with the indices of airflow limitation. While there was no change in PW(1)/PW(0) (1.00 +/- 0.07) during the assessment periods, methacholine-induced airway smooth muscle shortening was attenuated by 46% (PMS(1)/PMS(0)=0.54 +/- 0.16). Less improvement in PMS(1)/PMS(0) was seen with a correlation to the disease periods, but PMS(1)/PMS(0) improved correlating to the relative length of the assessment period with ongoing treatments in the disease period. In conclusion, this probative approach may be useful to investigate the outcome of AHR and remodeling in human asthmatics, and shows that remodeling may get worse with time or may halt and AHR may improve with a stepwise, early intervention and prolonged treatment given according to the GINA guideline.

Administration, Inhalation↗

Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.

Dieulafoy's lesion is an arterial malformation in the subumucosal layer of the gastrointestinal tract that can cause massive bleeding. The esophagus is not a common location for this lesion. We present here a first report of Dieulafoy's lesion of the esophagus correctly diagnosed and successfully treated by the endoscopic injection of N-butyl-2-cyanoacrylate.

Aged↗

Different clinicopathological courses of two recipients of kidneys retrieved from the same non-heart beating donor.

We report the clinicopathological courses of two recipients of kidneys retrieved from the same non-heart beating donor (NHBD). A 52-year-old man received a renal transplant from an NHBD. The donor was a 66-year-old woman who died of subarachnoid haemorrhage. The recipient was immunosuppressed by basiliximab, tacrolimus (TAC), mycophenolate mofetil (MMF), methyl prednisolone (MP), and antilymphocyte globulin (ALG). On post-operative day (POD) 21, haemodialysis therapy was withdrawn, however, their serum creatinine (s-Cr) level failed to improve. Four transplant biopsies were performed (1 h and POD 46, 74, and 114). The biopsy showed tubular degeneration but no evidence of TAC nephrotoxicity. The last biopsy after discontinuation of TAC demonstrated acute rejection of borderline grade. The s-Cr level at discharge was 5.0 mg/dL. The contra-lateral kidney was transplanted into a 31-year-old female and showed early functioning, with an s-Cr level at discharge of 1.8 mg/dL. Biopsy examination on POD 38 showed a recovery of tubular degeneration. The causes of delayed graft function and persistently high level of s-Cr in Case 1 remain unclear. Various factors, including donor-related factors, recipient-related factors, TAC nephrotoxicity, acute rejection, and urinary tract infection could all be associated with this condition.

Adult↗

Activation of nuclear factor-kappa B in the conjunctiva with the epithelial scraping of the mouse cornea and human epidemic keratoconjunctivitis.

AIM: To examine the expression of p65, one of nuclear factor-kappa B (NF-kappa B), in the conjunctival epithelium of the C57Bl6 mouse and a patient with epidemic keratoconjunctivitis (EKC). METHODS: Normal and epithelial scraped cornea obtained 6 hours after the injury were processed for paraffin section. Samples of a normal and an EKC conjunctival epithelium were obtained using impression cytology. Both samples were analysed by immunocytochemistry using anti-p65 antibody. RESULTS: Immunocytochemistry with the anti-NF-kappa B p65 antibody revealed that p65 was localised in the cytoplasm of the conjunctival epithelium in the C57Bl6 mouse without the treatment. Six hours after the scraping of the cornea, p65 protein was expressed in the nuclei of the conjunctival epithelium. p65 was localised in the cytoplasm of the conjunctival epithelium in the human normal eye. p65 protein was expressed in the nuclei of the conjunctival epithelial cells in the EKC patient. CONCLUSION: These findings suggest that NF-kappa B was activated in the conjunctiva in the epithelial scraping of the mouse cornea and in human EKC.

Animals↗

Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer.

If oesophageal carcinoma is detected in the superficial stage, the prognosis is better than for advanced oesophageal carcinoma. But the factors which predict the prognosis and treatment policy remain unclear. Matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) have been reported to have close associations with tumour invasion and metastasis. In this study, we retrospectively studied the relations between MMP-7 and MMP-9 expression in immunohistochemistry, clinicopathologic factors, and prognosis in 55 superficial oesophageal carcinomas. MMP-7 and MMP-9 expression occurred in 23.6% and 47.3% of the patients, respectively. MMP-7 expression was significantly correlated with the presence of nodal metastasis (P=0.004). MMP-9 expression was significantly correlated with the depth of tumour invasion (P=0.004), lymphatic permeation (P=0.001), nodal metastasis (P=0.049), and pathologic differentiation grade (P=0.003). By the log-rank test, MMP-7 expression and MMP-9 expression on the invasive front were related to the prognosis. In multivariate analysis, MMP-9 expression on the invasive front was an independent prognostic indicator. The combined expression of MMP-7 and MMP-9 may be a good marker for the degree of malignancy of oesophageal cancer and for the presence of lymphatic metastasis.

Adenocarcinoma↗