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Biomedical subjects

T Nishioka

Publications and source records attributed to T Nishioka.

At least 19 recordsLinked to original sources

Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice.

Tenascin-C (TNC), an extracellular matrix glycoprotein, is upregulated in chronic liver disease. Here, we investigated the contribution of TNC to liver fibrogenesis by comparing immune-mediated hepatitis in wild-type (WT) and TNC-null (TNKO) mice. Eight-week-old BALB/c mice received weekly intravenous injections of concanavalin A to induce hepatitis, and were sacrificed one week after the 3rd, 6th, 9th, and 12th injections. In WT livers, immunohistochemical staining revealed a gradual increase in TNC deposition. TNC mRNA levels also increased sequentially and peaked after the 9th injection. Collagen deposition, stained with picrosirius red, was significantly less intense in TNKO mice than in WT mice, and procollagen I and III transcripts were significantly upregulated in WT mice compared with TNKO mice. Inflammatory infiltrates were most prominent after the 3rd-6th injections in both groups and were less intense in TNKO mice than in WT mice. Interferon-gamma, tumour necrosis factor-alpha, and interleukin-4 mRNA levels were significantly higher in WT mice than in TNKO mice, while activated hepatic stellate cells (HSCs) and myofibroblasts, a cellular source of TNC and procollagens, were more common in WT livers. Transforming growth factor (TGF)-beta1 mRNA expression was significantly upregulated in WT mice, but not in TNKO mice. In conclusion, TNC can promote liver fibrogenesis through enhancement of inflammatory response with cytokine upregulation, HSC recruitment, and TGF-beta expression during progression of hepatitis to fibrosis.

Animals↗

Caspase-dependent cell death involved in brain damage after acute subdural hematoma in rats.

Traumatic brain injury is associated with acute subdural hematoma (ASDH) that worsens outcome. Although early removal of blood can reduce mortality, patients still die or remain disabled after surgery and additional treatments are needed. The blood mass and extravasated blood induce pathomechanisms such as high intracranial pressure (ICP), ischemia, apoptosis and inflammation which lead to acute as well as delayed cell death. Only little is known about the basis of delayed cell death in this type of injury. Thus, the purpose of the study was to investigate to which extent caspase-dependent intracellular processes are involved in the lesion development after ASDH in rats. A volume of 300microL blood was infused into the subdural space under monitoring of ICP and tissue oxygen concentration. To asses delayed cell death mechanisms, DNA fragmentation was measured 1, 2, 4 and 7 days after ASDH by TUNEL staining, and the effect of the pan-caspase inhibitor zVADfmk on lesion volume was assessed 7 days post-ASDH. A peak of TUNEL-positive cells was found in the injured cortex at day 2 after blood infusion (53.4+/-11.6 cells/mm(2)). zVADfmk (160ng), applied by intracerebroventricular injection before ASDH, reduced lesion volume significantly by more than 50% (vehicle: 23.79+/-7.62mm(3); zVADfmk: 9.06+/-4.08). The data show for the first time that apoptotic processes are evident following ASDH and that caspase-dependent mechanisms play a crucial role in the lesion development caused by the blood effect on brain tissue.

Amino Acid Chloromethyl Ketones↗

Can monitoring of serum 8-OHdG level for 2 hours after renal transplantation predict prognosis of the graft?

8-Hydroxy-2'-deoxyguanosine (8-OHdG) is an oxidant of deoxyguanosine, a base in the construction of DNA. We examined the extent of DNA damage to the graft through oxidative stress after renal transplantation. Seven renal transplant patients were enrolled in this study. Before reperfusion of the grafts, the level of serum 8-OHdG was measured using enzyme-linked immunosorbent assay. No relationship was found between the level of serum 8-OHdG just before reperfusion and the postoperative course. In all cases, the level of serum 8-OHdG increased after reperfusion and decreased within 2 hours. In six cases, it remained almost the same as the preoperative level. A faster rate of decrease from the first peak of serum 8-OHdG was associated with a lower nadir serum creatinine and reduced occurrence of acute rejection. This study suggested that immediate calming of the oxidative stress following reperfusion may potentially have a positive influence on graft prognosis. In addition, biomarkers of oxidative stress may predict graft prognosis.

8-Hydroxy-2'-Deoxyguanosine↗

Creatol, an oxidative product of creatinine in kidney transplant patients, as a useful determinant of renal function: a preliminary study.

Creatol (CTL, 5-hydroxycreatinine) is a creatinine (Cr) oxidative metabolite, which was originally isolated from the urine of patients with chronic renal failure, representing a candidate for a uremic toxin. The effectiveness of CTL as an indicator of oxidative stress after kidney transplantation has not been reported. Therefore, we examined the relation between the change in oxidative stress (using CTL) in renal transplant patients and their change in renal function (using Cr). The serum Cr and serum and urine CTL were examined in five renal transplant patients. Serum CTL closely correlated with serum Cr. Serum CTL also correlated with urine CTL, but in some cases there was a time lag. Both the ratio of CTL/(Cr) and serum CTL observed in patient 2 were slow to improve after transplantation. The process through which oxidative stress was reduced was shown by the index of renal damage correlated with kidney function oxidative stress (using serum CTL) after transplantation. Our data suggested that CTL/Cr may be a good indicator of graft prognosis.

ABO Blood-Group System↗

Pattern of local relapse of maxillary sinus carcinoma.

Maxillary sinus carcinoma (MSC) is a rare disease with a variety of treatment options. The present study was undertaken to review the outcome of patients with treated MSC in order to clarify the factors related to local recurrence by analyzing CT findings. The study group comprised of 47 cases, 40 males and 7 females with a median age of 61 years (range, 40- 84 years) treated between 1988 to 1996 at the department of radiotherapy. CT was taken with a slice thickness of 5 mm and contrast material was routinely used. The mean follow-up period for the group was 45.0 months (range, 3-125 months). The treatment policy was either preoperative radiotherapy of 40Gy/16fr followed by maxillectomy or radical radiotherapy of 65Gy/26fr with partial maxillectomy during the course of radiotherapy. By using CT-simulation, wedge pair techniques were used in most patients with Cobalt or 6MV X-ray machines as treatment sources. Tumor extension was categorized into the following anatomical sites: orbital contents, other paranasal sinuses, posterior wall of the maxillary sinus, pterygoid plate/muscle, nasopharynx, infra-temporal fossa, base of the skull, anterior wall of the maxillary sinus, subcutaneous tissue, cheek mucosa, hard palate and alveolar bone. Local control was computed by using the Kaplan-Meier method and p value was measured by using Chi-squared test. The 5-year overall local control rates for all patients were 56%. The local recurrence was found in 19 of 47 patients (40.4%). Tumors extending to pterygoid plates (n=13) and pterygoid muscles (n=10) showed higher rate of local recurrences as compared to those without extensions (9/13 [69%] vs 10/34 [29%], p<0.02 and 7/10 [70%] vs 12/37 [32%], p<0.05, respectively). Extensions to nasopharynx (6/9, 66%) and base of skull (4/6, 66%) also showed higher rates of recurrence; however, those were not statistically significant. More than 80% of the relapse became manifest within 12 months of diagnosis and isolated local failure was the most common pattern. This analysis indicates that tumor extension to pterygoid plate/muscles, results in higher rates of recurrences. This may due to the difficult surgical accessibility of the tumor. During radiotherapy planning, special emphasis should be given to this sites of tumor extension to avoid possible local recurrence.

Adult↗

[Coronary artery bypass grafting in a patient with right aortic arch; report of a case].

A 60-year-old man was admitted to another hospital because of chest oppression on effort. Chest X-ray showed radiographic evidence of a right aortic arch and double vessel coronary artery disease with 50% stenosis in the left main trunk was diagnosed by coronary angiography. He was transferred to our institute for surgical treatment of angina pectoris. Preoperatively, multi-detector row computed tomography (CT) was performed and it revealed a right aortic arch and an aberrant left subclavian artery with narrow left internal thoracic artery. A right internal thoracic artery was well demonstrated. Therefore, conventional coronary artery bypass grafting using a right internal thoracic artery and a saphenous vein graft was performed and his postoperative course was uneventful.

Aorta, Thoracic↗

Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.

Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.

Adolescent↗

Keratan sulphate levels in mucopolysaccharidoses and mucolipidoses.

The mucopolysaccharidoses (MPS) is characterized by accumulation of glycosaminoglycans (GAGs), and mucolipidosis (ML) by accumulation of GAGs and sphingolipids. Each type of MPS accumulates specific GAGs. The lysosomal enzymes N-acetylgalactosamine-6-sulphate sulphatase and beta-galactosidase involve the stepwise degradation of keratan sulphate (KS). Deficiency of these enzymes results in elevation of KS levels in the body fluids and in tissues, leading to MPS IV disease. In this study, we evaluated blood and urine KS levels in types of MPS and ML other than MPS IV. Eighty-five plasma samples came from MPS I (n = 18), MPS II (n = 28), MPS III (n = 20), MPS VI (n = 3), MPS VII (n = 5) and ML (n = 11) patients while 127 urine samples came from MPS I (n = 34), MPS II (n = 34), MPS III (n = 32), MPS VI (n = 7), MPS VII (n = 9) and ML (n = 11) patients. KS levels were determined using the ELISA method. Plasma KS levels varied with age in both control and patient populations. In all age groups, the mean values of plasma KS in MPS and ML patients were significantly higher than those in the age-matched controls. Plasma KS values in four newborn patients were above the mean + 2SD of the age-matched controls (mean, 41 ng/ml). Overall, 85.9% of individual values in non-type IV MPS and ML patients were above the mean + 2SD of the age-matched controls. For urine KS levels, 24.4% of individual values in patients were above the mean + 2SD of the age-matched controls. In conclusion, KS in blood is elevated in each type of non-type IV MPS examined, in contrast to the conventional understanding. This finding suggests that measurement of KS level provides a new diagnostic biomarker in a wide variety of mucopolysaccharidoses and mucolipidoses in addition to MPS IV.

Adolescent↗

Root fracture in immature anterior teeth followed for 15 years.

We report a case of injury to an immature tooth, observed over a period of 15 years. In 1987, a 9-year-old boy fell down in a schoolyard. The right central incisor demonstrated palato-version and radiographic observations revealed that the roots of both central incisors were incomplete. Further, a root fracture in the apical region of the central incisors was observed. During the first treatment visit, the right central incisor was repositioned and both teeth splinted. After confirming that the line of fracture was aligned, the fixation was continued for 2 months. The teeth were examined periodically for the next 15 years. Both teeth had favorable outcomes with continued root development of both the apical and coronal segments with good apposition of the fracture lines.

Child↗

[Beating heart surgery for ischemic mitral regurgitation: report of a case].

A 51-year-old man was admitted to our hospital because of dyspnea. Coronary angiography revealed triple vessel disease and echocardiography demonstrated severe mitral regurgitation with poor left ventricular function. Under a diagnosis of ischemic mitral regurgitation, on-pump beating mitral annuloplasty and coronary artery bypass grafting using the normothermic retrograde continuous coronary sinus perfusion of oxygenated blood was performed in order to prevent reperfusion injury. The patient was easily weaned from cardiopulmonary bypass and his postoperative course was uneventful. Because of the advantages of this procedure (e.g., no reperfusion injury, testing of the mitral valve repair is done in real physiologic conditions with beating tonus), on-pump beating heart surgery seems a good surgical option for ischemic mitral regurgitation with poor left ventricular function.

Heart-Lung Machine↗

Electrocardiographic Q-waves as a predictor of mortality in patients with cerebral infarction.

OBJECTIVE: To determine whether abnormal EKG findings could be predictive factors for death after a stroke event. METHODS: Patients with acute cerebral infarction who were 35 to 98 years old during April 1996 through November 2000 were analyzed (n = 216). A standard 12-lead EKG was recorded for each patient after acute cerebral infarction. The authors prospectively investigated the association between abnormal EKG findings and the risk for death after stroke over a 1-year period. RESULTS: Using multivariate Cox proportional hazards models, the authors found age (hazard ratio of mortality per year 1.10, 95% CI 1.06 to 1.15, p < 0.001), sex (female; hazard ratio of mortality 3.42, 95% CI 1.43 to 8.19, p = 0.006), and the presence of Q-waves in more than two leads (hazard ratio of mortality 2.75, 95% CI 1.23 to 6.14, p = 0.013) were independently associated with death after stroke. CONCLUSION: The presence of Q-waves in more than two leads could be a predictive factor for death after acute cerebral infarction.

Adult↗

Cis-acting effect of the IL1B C-31T polymorphism on IL-1 beta mRNA expression.

Since the effect of IL1B polymorphisms on IL-1beta production is still controversial, we selected two polymorphisms to test their cis-acting effect on IL-1beta mRNA expression by means of the allele-specific transcript quantification and the haplotype analysis. As for the C-31T polymorphism, we found that expression of the -31T allele was 2.2 times of the -31C allele. This higher transcription efficiency may correspond to the fact that C-31T is located in a TATA box. The other polymorphism, C+3954T, did not alter the levels of transcription. The use of the allele-specific transcript quantification enables us to exclude trans-acting effects of polymorphisms on the gene expression and contributes to understanding the roles of the IL1B polymorphisms in susceptibility to multifactorial diseases.

Cell Line↗

[One-staged operation for mitral regurgitation and annuloaortic ectasia without aortic regurgitation with Marfan syndrome; report of a case].

A 32-year-old man with Marfan syndrome was admitted to our hospital for detail examination of congestive heart failure. Doppler echocardiography showed severe mitral regurgitation due to prolapse of posterior mitral leaflet. Annuloaortic ectasia without aortic regurgitation was also detected by aortography. Considering the future operative need for aortic root and ascending aorta, we performed mitral valve replacement with a mechanical valve and preventive concomitant aortic root replacement with a composite valve graft. His postoperative course was uneventful. Optimal surgical treatment of mitral regurgitation and annuloaortic ectasia in Marfan syndrome is controversial because the underlying connective tissue defect theoretically might compromise repair durability. Several surgical options for mitral regurgitation and annuloaortic ectasia in Marfan syndrome are discussed.

Adult↗

Postrenal acute renal failure during pregnancy 20 years after antireflux surgery.

We report that a 27-year-old woman with bilateral severe hydronephorosis during pregnancy 20 years after antireflux surgery. The patient developed postrenal acute renal failure due to obstruction of the lower ureter. This patient could safely give birth after bilateral percutaneous nephrostomy through joint management with the obstetrics and gynecology staff. We describe that stenosis of the lower ureter is a late complication of antireflux surgery.

Acute Kidney Injury↗

The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein-Barr virus-transformed lymphoblastoid cells.

The effects of the SDF1-3'A on AIDS progression have been attributed to the altered amount of stromal cell-derived factor 1 (SDF-1). However, the contribution of the SDF1-G801A polymorphism to SDF-1 expression is still unclear. In contrast to fresh peripheral blood mononuclear cells (PBMCs), Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) express the SDF-1 mRNA. Using EBV-transformed LCLs from 42 individuals with different genotypes, we investigated the SDF-1 mRNA levels and methylation status in the SDF1 gene. Both in PBMCs and in EBV-transformed LCLs, CpG dinucleotides in the 5' region of the SDF1 gene were unmethylated. As for the 3' untranslated region (3'UTR), by contrast, CpG dinucleotides were methylated in PBMCs, whereas site-specific demethylation around the polymorphic site was detected in EBV-transformed LCLs. The levels of the demethylation were correlated with the SDF-1 mRNA levels. However, the genotype for the SDF1-G801A polymorphism did not significantly alter the SDF-1 mRNA levels. The allele preferences in transcription and methylation were also absent in the heterozygous cells. In conclusion, this study suggested a contribution of site-specific demethylation in the 3'UTR to the SDF1 gene expression, but did not show any evidence for the contribution of the SDF1-G801A polymorphism to the amount of the SDF-1 mRNA.

Alleles↗

Molecular characterization of a membrane-bound cGMP dependent protein kinase from the silk moth Bombyx mori.

The cGMP signalling pathway has been suggested to be involved in the signal transduction of various physiological functions in insects; olfaction, antidiuresis and eclosion. However, the cGMP signalling mechanism has remained elusive. We isolated two cDNAs of the cGMP dependent protein kinase, designated BmPKG-Ialpha and BmPKG-Ibeta. The deduced amino acid sequences indicate that both BmPKG-Ialpha and BmPKG-Ibeta appear to consist of an amino terminal region, a cGMP binding domain and a protein kinase domain. Transcripts of BmPKG-Ialpha and BmPKG-Ibeta were detected in various tissues: flight muscles, antennae, midgut, legs, head, thoracic ganglia and Malphighian tubules. Recombinant BmPKG-Ialpha bound to lipid membranes, while BmPKG-Ialpha with a deleted amino terminal region failed to bind to lipid membranes.

Amino Acid Sequence↗