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M Nishimura

Publications and source records attributed to M Nishimura.

At least 37 records · Page 2Linked to original sources
PubMed2006

Role of interleukin-17F in chronic inflammatory and allergic lung disease.

IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case-control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures.

Adolescent↗
PubMed2006

Pathology of fatal highly pathogenic H5N1 avian influenza virus infection in large-billed crows (Corvus macrorhynchos) during the 2004 outbreak in Japan.

Highly pathogenic H5N1 avian influenza viruses were isolated in 9 large-billed crows that died in Kyoto and Osaka prefectures in Japan from March to April in 2004. We studied 3 of the 9 crows using standard histologic methods, immunohistochemistry, and virus isolation. The most prominent lesions were gross patchy areas of reddish discoloration in the pancreas. The consistent histologic lesions included severe multifocal necrotizing pancreatitis, focal degeneration and necrosis of neuron and glial cells in the central nervous system, and focal degeneration of cardiac myocytes. All of these tissues contained immunohistochemically positive influenza viral antigens. The virus was isolated from the brain, lung, heart, liver, spleen, and kidney of the crows examined. Thus we concluded that highly pathogenic avian influenza virus was associated with clinical disease, severe pathologic changes, and death in the 3 crows.

Animals↗
PubMed2006

[Treatment for pinch-off syndrome using a video-assisted thoracoscopic surgery; report of a case].

Use of a central venous catheter (CVC) may be complicated by a catheter fracture, causing an embolism. Pinch-off syndrome is a recognized complication that develops from the use of implantable subclavian venous access devices. Although rare, as it occurs in only 0.8% of the reported cases, the condition can appear as a complication secondary to the insertion of a CVC. We experienced a case of CVC division in a 26-year-old male who had a CVC implanted through the subclavian vein. We failed in our attempt to remove the catheter fragment using video-assisted thoracoscopic surgery (VATS). If no complication occur over a long-term, it is highly possible that the catheter fragment will become adhered to the vessel wall. Therefore, it may not be necessary to remove the fragment in those cases.

Adult↗
PubMed2005

A nucleotide substitution responsible for the tawny coat color mutation carried by the MSKR inbred strain of mice.

"Tawny" is an autosomal recessive coat color mutation found in a wild population of Mus musculus molossinus. The inbred strain MSKR carries the mutation. The causative gene Mc1r(taw) of the tawny phenotype is the second recessive allele at the melanocortin 1 receptor locus and is dominant to the first recessive allele, "recessive yellow" (Mc1r(e)). The Mc1r(taw) gene has six nucleotide substitutions, and its forecasted transcript has three amino acid substitutions (i.e., V101A, V216A, W252C). Though the nucleotide substitutions leading to V101A and V216A exist in various mouse strains, the nucleotide substitution leading to W252C exists in only tawny-colored mice. Thus this substitution is considered to be responsible for the expression of the tawny coat color. The frequency of the allele having this nucleotide substitution was 9.21% in the wild M. m. molossinus population inhabiting Sakai City, Osaka Prefecture, Japan, where the ancestral mice of the MSKR strain were captured.

Amino Acid Sequence↗
PubMed2005

A defect in glyoxysomal fatty acid beta-oxidation reduces jasmonic acid accumulation in Arabidopsis.

The final steps of jasmonic acid (JA) biosynthesis are thought to involve peroxisomal beta-oxidation, but this has not been directly demonstrated. The last and key step in fatty acid beta-oxidation is catalyzed by 3-ketoacyl-CoA thiolase (KAT) (EC 2.3.1.16). A mutant of Arabidopsis thaliana ecotype Landsberg erecta, which lacks a functional KAT protein and is defective in glyoxysomal fatty acid beta-oxidation has been reported. In this study, the mutant was found to accumulate reduced level of JA in both its wounded cotyledons and leaves, while only the cotyledons accumulate 3-oxo-2-(pent-2'-enyl)-cyclopentane-1-octanoic acid (OPC-8:0). This indicates that a defect in one of the thiolase isoenzymes impairs beta-oxidation of OPC-8:0 to JA. The mutant had sufficient thiolase activity for the synthesis of JA in the unwounded but not in the wounded tissues. Activities of the enzymes in the JA pathway that catalyze the steps, which precede beta-oxidation were not altered by the mutation in a thiolase protein. Thus, reduced levels of JA in the wounded tissues of the mutant were attributed to the defect in a thiolase protein.

Acetyl-CoA C-Acyltransferase↗
PubMed2005

Promoter region polymorphism of macrophage migration inhibitory factor is strong risk factor for young onset of extensive alopecia areata.

We have demonstrated that serum macrophage migration inhibitory factor (MIF) was significantly elevated in patients with extensive alopecia areata (AA). Recently, functional polymorphisms have been identified in the MIF promoter region. To address the functional and prognostic relevance of the -173G/C and -794[CATT]5-8 repeat polymorphisms in MIF genes in patients with extensive AA, 113 patients with extensive AA and 194 healthy controls were genotyped. We found that MIF-173*C was a risk factor for early onset (<20 years) of extensive AA (odds ratio for GC heterozygotes with -173G/C was 4.88 (95% CI, 2.04-11.8), P=0.00038; odds ratio for CC homozygotes with -173G/C was 10.42 (95% CI, 2.56-43.5), P=0.0011). We found no statistically significant differences in the genotype frequencies of the -794[CATT]5-8 repeat polymorphism and extensive AA. These results suggest that polymorphisms within the MIF-173*C allele confer an increased risk of susceptibility to the extensive forms of AA, especially with an early onset of disease. MIF is therefore suggested to be closely implicated in the pathogenesis of the more extensive forms of AA.

Adolescent↗
PubMed2005

In vivo induction of human cytochrome P450 3A4 by rifabutin in chimeric mice with humanized liver.

The induction of human cytochrome P450 enzymes (CYPs) often poses a serious problem in clinical practice. The induction of CYP3A leads to a decrease in the pharmacological potency of drugs, since many drugs are substrates of CYP3A. The present study examined the in vivo induction potency of human CYP3A in chimeric mice with humanized liver, recently established in Japan, by a specific inducer of human CYP3A enzyme activity in this experimental condition, rifabutin, which is an analogue of rifampicin. The chimeric mice were treated intraperitoneally daily for 4 days with rifabutin (50 mg kg(-1) day(-1)). The mRNA, protein and enzyme activity in liver of the chimeric mice were measured by reverse-transcriptase polymerase chain reaction, Western blot analysis and high-performance liquid chromatography, respectively. In the chimeric mice, the human CYP3A4 mRNA expression, CYP3A4 protein content, testosterone 6ss-hydroxylase activity and dexamethasone 6-hydroxylase activity were increased 7.4-, 3.0-, 2.4- and 1.9-fold, respectively, by treatment with rifabutin. The mRNA expression of other human CYPs, transporters and nuclear receptors was not significantly changed by rifabutin. On the other hand, rifabutin was demonstrated not to increase the murine Cyp3a enzyme activities in the control mice. It was demonstrated that human CYP3A4 expressed in the chimeric mice with humanized liver was induced by rifabutin, suggesting that human CYP3A4 in the chimeric mice had induction potency. This chimeric mouse model may be a useful animal model to estimate and predict the in vivo induction of CYPs in human.

Animals↗
PubMed2005

Evaluation of mRNA expression of human drug-metabolizing enzymes and transporters in chimeric mouse with humanized liver.

The hepatic mRNA expression of human drug-metabolizing enzymes and transporters in chimeric mise with almost-completely humanized liver (replacement index: 71-89%) was investigated. The mRNAs of 58 human phase I enzymes, 26 human phase II enzymes, 23 human transporters, and five mouse Cyps were measured in the chimeric mice with humanized liver generated using hepatocytes from a Japanese donor. The mRNA expression of 52 human phase I enzymes, which includes 20 human CYPs, 26 human phase II enzymes and 21 human transporters was ascertained in the chimeric mouse liver. Among them, the expression of the target mRNAs vital for liver function such as the metabolism and secretion of endogenous compounds appeared to be maintained. The central value for the expression ratio in all target genes in chimeric mouse liver to the donor liver was 0.46, which was lower than the substitution rate of chimeric mouse liver by donor liver. The ratio of mouse Cyp mRNA expression of chimeric mouse liver to that of control mouse liver was 0.19 or less, except for that of Cyp2b10. There were good correlations between the mRNA expression levels of human hepatic albumin gene, the values of the rate of replacement of mouse liver by human liver, and the human blood albumin concentration in the chimeric mice. The chimeric mice with humanized liver may be a useful tool for the evaluation of drug-drug interactions such as the inhibition and induction of drug-metabolizing enzymes and transporters.

Animals↗
PubMed2005

Decrease of vascular endothelial growth factor in macrophages from long-term smokers.

Vascular endothelial growth factor (VEGF), a survival factor for endothelial cells and a promoter of angiogenesis, is reportedly expressed in alveolar macrophages (AMs). To investigate whether long-term smoking with age affects VEGF expression in AMs, bronchoalveolar lavage (BAL) was performed on 18 young and 23 older volunteers with various smoking histories. The expressions of VEGF and its functional receptor, fms-like tyrosine kinase (Flt)-1, were quantified in AMs by real-time RT-PCR and, further, the level of VEGF in BAL fluid was determined by ELISA. VEGF mRNA in AMs demonstrated a 1.8-fold reduction in current smokers compared with nonsmokers in older subjects and, furthermore, a 1.5-fold downregulation in those with emphysema, although there was no difference between current smokers and nonsmokers among the young subjects. The downregulation in total VEGF mRNA was supported by the substantial reduction of VEGF121 and VEGF165 isoforms. However, in contrast, Flt-1 mRNA did not differ within the older groups, whereas it was upregulated in young current smokers compared with age-matched nonsmokers. VEGF in BAL fluid is significantly decreased in current smokers compared with nonsmokers, regardless of their age. In conclusion, these data imply that the biological availability of vascular endothelial growth factor in alveolar macrophages is impaired in older current smokers with long-term smoking histories.

Adult↗
PubMed2005

[Traumatic rupture of the ascending aorta].

A 42-year-old male was diagnosed as having a traumatic rupture of the ascending aorta 24 hours after traffic accident. On admission, the patient was in a state of shock, but he was successfully treated by emergency surgery. Traumatic rupture of the ascending aorta is a serious condition and the mortality may be very high. Although physicians rarely encounter patients with this condition, it is relatively common among autopsy cases with multiple trauma. Urgent diagnosis and treatment are mandatory.

Adult↗
PubMed2004

Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation.

The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the dorsal surface of mice, in order to induce local inflammation. CS gel beads retaining PS were then implanted into the AP to investigate the therapeutic efficacy of sustained PS release against local inflammation. In vivo PS release from CS gel beads was governed by both diffusion of the drug and degradation of the gel matrix. Sustained drug release by CS gel beads allowed the supply of the minimum effective dose and facilitated prolonged periods of local drug presence. Inflammation indexes were significantly reduced after implantation of CS gel beads when compared with injection of PS suspension. Thus, extension of the duration of drug activity by CS gel beads resulted in improved therapeutic efficacy. These observations indicate that CS gel beads are a promising biocompatible and biodegradable vehicle for treatment of local inflammation.

Adjuvants, Pharmaceutic↗
PubMed2004

Smooth muscle hamartoma of the abomasum in a calf.

This report describes a case of smooth muscle hamartoma of the abomasum in a 6-month-old steer humanely killed because of severe pneumonia. At necropsy, marked thickening of the abomasal wall in the area of the pylorus was found. On cut section, the thickness of the submucosal layer, extending from the submucosa to the muscularis propria, was seen to be increased to 3 cm. The upper (i.e., nearest to the gut lumen) half of the sectioned thickening was composed mainly of adipose-like tissue and the lower half mainly of muscle-like tissue. Histologically, the submucosal layer was composed of fibroadipose tissue, within which were embedded, to varying degrees, numerous well-defined, haphazardly oriented, thin to thick bundles of smooth muscle fibres. This appears to be the first report of smooth muscle hamartoma of the stomach or abomasum in animals, including man.

Abomasum↗
PubMed2004

Allogeneic peripheral blood stem cell transplantation from two- or three-loci-mismatched related donors in adult Japanese patients with high-risk hematologic malignancies.

With the increasing frequency of haploidentical transplantation, it is becoming more important to establish the degree of HLA mismatch that can be accepted. We retrospectively analyzed clinical data of 50 adult Japanese patients with high-risk hematologic malignancies who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from two- or three-loci-mismatched related donors with HLA class I and II gene disparities in the graft-versus-host direction. They were treated at 20 transplant centers between 1996 and 2002. In all, 18 patients received unmanipulated PBSC, while 32 received purified CD34+ blood cells. Conventional (n=31) or reduced-intensity (n=19) conditioning regimens were used. Of the 39 patients (78%) who survived for > or =28 days after transplant, 37 (95%) achieved neutrophil engraftment, while graft failure and rejection occurred in two of 39 (5%) and three of 37 (8%) patients, respectively. Stepwise Cox regression analysis revealed a significantly lower incidence of grades II-IV acute GVHD in patients receiving purified CD34+ cells (hazard ratio 0.32; 95% CI 0.12-0.84; P=0.022). By 1 year post transplant, 28 patients (56%) had died of transplant-related problems, including infectious complications (30%). Although the number of patients is small, our data suggest that transplant-related problems, particularly infectious complications, are major obstacles to the success of this therapy.

Adolescent↗
PubMed2004

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Antifungal Agents↗
PubMed2004

Activation of polymorphonuclear neutrophils by immune complex: possible involvement in development of transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is a serious side-effect of transfusion. We presumed that immune complex (IC)-activated polymorphonuclear neutrophils (PMNs) are involved in the development of TRALI. The aim of this study is to examine the various effects of ICs on normal human PMNs. ICs used here were artificially formed by combining soluble human leucocyte antigen (HLA) class II-positive serum and anti-HLA class II antiserum. The abilities of ICs to trigger PMNs and induce the production of soluble mediators and the involvement of the Fc receptor (FcR) in the activation of PMNs by ICs were investigated. Moreover, the ability of the culture supernatant of PMNs incubated with ICs regarded to induce the apoptosis of lung microvascular endothelial (LME) cells was examined. The results proved that PMNs are triggered by ICs resulting in the acceleration of the production of tumour necrosis factor-alpha (TNF-alpha), perforin and Fas ligand, in which FcR on PMNs appears to be involved. Furthermore, the culture supernatants of PMNs cultured with ICs were revealed to induce the apoptosis of LME cells. In conclusion, the ICs used here were proved to induce PMNs to release cytotoxic factors upon activation. These results suggest that ICs are mediators of the development of TRALI.

Acute Disease↗
PubMed2004

Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth movement.

Previously, we discovered that RANKL expression is induced in compressed periodontal ligament cells, and that this promotes osteoclastogenesis on the compression side in orthodontic tooth movement. We hypothesized that local OPG gene transfer to the periodontium would neutralize the RANKL activity induced by mechanical compressive force, thereby inhibiting osteoclastogenesis and diminishing tooth movement. The upper first molars of six-week-old male Wistar rats were moved palatally by means of a fixed-orthodontic wire. A mouse OPG expression plasmid [pcDNA3.1(+)-mOPG] was constructed, and the production of functional OPG protein was confirmed in vitro. The inactivated HVJ envelope vector containing pcDNA3.1(+)-mOPG or PBS was injected periodically into the palatal periodontal tissue of upper first molars. When this local OPG gene transfer was performed, OPG production was induced, and osteoclastogenesis was inhibited. Local OPG gene transfer significantly diminished tooth movement. In this study, we report that OPG gene transfer to periodontal tissue inhibited RANKL-mediated osteoclastogenesis and inhibited experimental tooth movement.

Animals↗