Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 91 records · Page 5Linked to original sources

PubMed2002

Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema.

BACKGROUND: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid. METHODS: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B(4) (LTB(4)) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) which are predominantly chemotactic for mononuclear leucocytes. RESULTS: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-alpha(1) protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema. CONCLUSION: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined.

Bronchoalveolar Lavage Fluid↗

PubMed2002

Dissociation between airway responsiveness to methacholine and responsiveness to antigen.

Repeated aerosolized antigen challenges to brown Norway (BN) rats generate nonspecific airway hyperresponsiveness (AHR). On the other hand, some studies have demonstrated that repeated antigen challenge could attenuate antigen-specific AHR in BN rats. The authors questioned whether such dissociation in airway responses actually occurs when assessed in a single study in the same animals. The authors simultaneously measured AHR to methacholine and antigen-specific AHR in rats that were repeatedly exposed to aerosolized ovalbumin (OA) for 1 or 3 months after sensitization. Four days after the last challenge, airway responses to methacholine and OA, morphometry of the airways, the cell profile in bronchoalveolar lavage fluid, and cytokine messenger ribonucleic acid (mRNA) expression in the lungs were evaluated. The two types of AHR were modulated in opposite directions by repeated antigen challenges. The AHR to methacholine was significantly increased in the rats receiving antigen challenges compared with the control rats receiving saline challenges after sensitization; whereas, the antigen-specific AHR was significantly decreased. The number of alveolar macrophages in lavaged fluid and the expression of transforming growth factor-beta1 mRNA in lung tissue was significantly different between the antigen-challenged rats and the control rats. In conclusion, dissociation between nonspecific airway hyperresponsiveness and antigen-specific airway hyperresponsiveness in brown Norway rats after repeated antigen challenges was demonstrated. Sustained airway inflammation with macrophages and/or upregulation of transforming growth factor-beta1 messenger ribonucleic acid in the lung tissue may be responsible for this dissociation.

Aerosols↗

PubMed2002

Role of secretory leukocyte protease inhibitor in the development of subclinical emphysema.

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. In some chronic airway diseases, the level of SLPI is decreased in sputum, leading to the continuation of neutrophil inflammation. In this study, the role of SLPI in subclinical pulmonary emphysema was examined. Sequential bronchoalveolar lavage was performed in an attempt to separately evaluate the levels of SLPI in the large airways and in the peripheral airways for two groups of smokers. One group had subclinical emphysema by computed-tomography scans and one group did not. SLPI localized in alveolar macrophages (AM) was also assessed. The level of SLPI was significantly elevated in the peripheral airways from the subjects with emphysema compared to those without emphysema (1589.2+/-353.9 versus 729.1+/-31.0 ng x mL(-1)), although it was similar in the large airways (3442.3+/-499.6 versus 2535.7+/-578.8 ng x mL(-1)). There was a trend for higher amount of SLPI to be released from AM in subjects with subclinical emphysema, although this did not reach statistical significance. In conclusion, there is compensatory upregulation of secretory leukocyte protease inhibitor in peripheral airways in subclinical pulmonary emphysema, which is in sharp contrast to the decreased level of secretory leukocyte protease inhibitor reported in some chronic airway diseases.

Adult↗

PubMed2002

Minimally invasive direct coronary artery bypass for completely obstructed left anterior descending coronary artery.

BACKGROUND: We evaluated the efficacy of minimally invasive direct coronary artery bypass (MIDCAB) using the left internal thoracic artery (LITA) in patients with completely obstructed left anterior descending coronary artery (LAD). METHODS: Ten patients undergoing MIDCAB for LAD stenosis were enrolled in this study. These patients were all men aged 45 to 69 years, and were divided into two groups, one showing complete LAD obstruction (n=5, Group A), and one about 90% stenosis of the LAD (n=5, Group B). RESULTS: The internal size of the LAD at the anastomosis site was significantly smaller in Group A than in Group B, and the time required for graft anastomosis in Group A was significantly longer. Total operation time, intubation time after operation, perioperative bleeding, total blood transfusion, max CK-MB, and hospital stay did not significantly differ between the two groups. Postoperative coronary angiography revealed good graft patency in both groups, however, one Group A patient had graft obstruction. CONCLUSIONS: The MIDCAB procedure appears useful even in our patients with completely obstructed LAD, despite the long anastomosis time. However, the indications for this procedure are limited by any perceived difficulty in harvesting the LITA by indirect vision or in performing the anastomosis based on the size or quality of the LAD. Intensive preoperative angiography evaluation is essential and conversion to a median full-sternotomy is necessary for cases in which we cannot confirm the feasibility of MIDCAB.

Aged↗

PubMed2002

[Salvage operation for esophageal cancer after radical chemoradiotherapy].

We reviewed salvage surgery cases for esophageal cancer following radical chemoradiotherapy. From January 1998 through January 2001, 6 patients (4 men, 2 women) underwent salvage operation at our department. Mean age was 56 years (range: 46-66). According to the Japanese Society for Esophageal Diseases localization schema, there was one case in the upper third of the thoracic esophagus, 3 cases in the middle third and 2 cases in the lower third. The histology was squamous cell carcinoma in all cases. Our radical chemoradiotherapy regimen for esophageal cancer was fluorouracil (5-FU) 400 mg/m2/24 hours i.v. on days 1 to 5 and 8 to 12, cisplatin (CDDP) 40 mg/m2/2 hours i.v. on days 1 and 8, and concurrent radiation therapy (2 Gy/day on days 1 to 5, 8 to 12 and 15 to 19). This regimen was repeated in 5 weeks, followed by 5-FU 800 mg/m2/24 hours i.v. on days 1 to 5 and CDDP 80 mg/m2/2 hours i.v. on day 1, which was repeated in 4 weeks. After these chemoradiotherapy, patients who were confirmed to have local recurrence or esophagobronchial fistula underwent salvage operation. Postoperative complications were anastomosis leakage in 1 patient, and anastomosis stenosis in 2 and esophagobronchial fistula in 1. Although no postoperative hospitalized death occurred, 1 patient died because of empyema 3 months after salvage operation. Another patient died due to respiratory failure 15 months later. The salvage operation outcomes are not acceptable. Salvage procedure and indication for salvage intervention need to be changed.

Aged↗

PubMed2002

Importance of proinflammatory cytokines in synovial fluid from 121 joints with temporomandibular disorders.

The concentrations of cytokines were measured by an ELISA in the synovial fluid from 117 patients with temporomandibular disorders (TMD) and correlated with degenerative changes of the condyle and clinical symptoms.Fifty-seven patients had degenerative changes of the condyle. The fluid from seven healthy volunteers was used as controls. The concentrations of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly higher in the synovial fluid of patients than controls (P<0.05). The concentration of IL-6 was significantly higher in the patients with degenerative changes than in other patients (P<0.05). The detection of IL-8 correlated with the concentrations of IL-6 and TNF-alpha. However, there was no correlation between the concentrations of any cytokines and symptoms. In conclusion, the cytokines in the synovial fluid may participate in the pathogenesis of TMD. In particular, IL-6 is important and may be associated with the development of osteoarthritis.

Adult↗

PubMed2002

[Lymphoscintigraphy for chylothorax after replacement of descending thoracic aortic aneurysm].

A 77-year-old female with Stanford B chronic aortic dissection, received elective replacement of descending aorta. The aorta distal to the aneurysm was encircled with a tape, and replaced using the double barrel technique. After the operation, chest X-ray showed effusion on the bilateral side. The amount of milky fluid from drain increased to 2,000 ml per day. The chemical profiles of the fluids were compatible with chylothorax. The Thoracic duct near the diaphragm was closed through left mini-thoracotomy. But the leakage of chyle did not cease. The lymphoscintigraphy showed a leakage to right lower intrathorax near the diaphragm and native aorta. A defect of the thoracic duct was closed, and chylothorax was cured. This case shows that though detailed anatomical structure of thoracic duct is not revealed, lymphoscintigraphy is useful for the localization of leakage in patients with chylothorax of post-cardiovascular-surgery.

Aged↗

PubMed2001

Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice.

The disease outcome in malaria caused by the protozoan parasite Plasmodium is influenced by host genetic factors. To identify host genes conferring resistance to infection with the malaria parasite, we undertook chromosomal mapping using a whole-genome scanning approach in cross-bred mice. NC/Jic mice all died with high parasitemia within 8 days of infection with 1 x 10(5) parasitized erythrocytes. In contrast, 129/SvJ mice all completely excluded malaria parasites from the circulation and remained alive 21 days after infection. We performed linkage analysis in backcross [(NC/Jic x 129/SvJ)xNC/Jic] mice. The Pymr ( Plasmodium yoelii malaria resistance) locus was mapped to the telomeric portion of mouse Chromosome (Chr) 9. This locus controls host survival and parasitemia after infection. The Char1 locus ( P. chabaudi resistance locus 1), controlling host survival and peak parasitemia in P. chabaudi infection, was previously mapped to the same region. This host resistance locus mapping to Chr 9 may represent a ubiquitous locus controlling susceptibility to rodent malaria. Elucidation of the function of this gene will provide valuable insights into the mechanism of host defense against malaria parasite infection.

Animals↗

PubMed2001

Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice.

Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared with wild-type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were lower in the deficient mice than in the wild-type controls 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1beta was higher in the deficient mice than in the wild-type controls 9 h after LPS injection. Consistent with the regulatory roles of syndecan-4, its expression in monocytes and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. Although IL-1beta was produced to the same extent by macrophages from syndecan-4-deficient and wild-type mice after LPS stimulation, inhibition of its production by transforming growth factor-beta1 was impaired in the syndecan-4-deficient macrophages. These results indicate that syndecan-4 could be involved in prevention of endotoxin shock, at least partly through the inhibitory action of transforming growth factor-beta1 on IL-1beta production.

Animals↗

PubMed2001

Detection of lung tumor movement in real-time tumor-tracking radiotherapy.

PURPOSE: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. METHODS AND MATERIALS: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined "permitted dislocation." The value was set at +/-1 to +/-3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. RESULTS: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p = 0.007), y (p = 0.025), and z (p = 0.002) coordinates, respectively. CONCLUSION: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the "permitted dislocation" zone from the planned position.

Aged↗

PubMed2001

Tumor necrosis factor gene polymorphisms in patients with sporadic Parkinson's disease.

We studied promoter region polymorphisms in the tumor necrosis factor (TNF) gene at position -1031, -863, and -857, in 172 Japanese patients with sporadic Parkinson's disease (PD). The frequency of the -1031C allele, a high producer of TNF, increased significantly in early onset PD patients compared with controls. In addition, PD patients with the -1031C allele showed a significantly earlier onset than those without -1031C allele, after stratification of the data by an interleukin-1beta gene polymorphism. Our findings suggest that TNF might have a toxic effect in PD.

Adult↗

PubMed2001

Integrin-linked kinase controls neurite outgrowth in N1E-115 neuroblastoma cells.

Mouse N1E-115 cells grown on a laminin matrix exhibit neurite outgrowth in response to serum deprivation. Treatment of cells with an antibody against beta(1) integrin inhibits neurite outgrowth. Thus, beta(1) integrin is involved in the neuritogenesis of N1E-115 cells on a laminin matrix. Integrin-linked kinase (ILK), a recently identified cytoplasmic serine/threonine protein kinase that binds to the cytoplasmic domain of beta(1) integrin, has an important role in transmembrane signal transduction via integrins. We report that ILK is expressed in N1E-115 cells, the expression levels of which are constant under both normal and differentiating conditions. A stable transfection of a kinase-deficient mutant of ILK (DN-ILK) results in inhibition of neurite outgrowth in serum-starved N1E-115 cells grown on laminin. On the other hand, a transient expression of wild type ILK stimulated neurite outgrowth. The ILK activity in the parental cells was transiently activated after seeding on the laminin matrix, whereas that in the DN-ILK-transfected cells was not. These results suggest that transient activation of ILK is required for neurite outgrowth in serum-starved N1E-115 cells on laminin. Under the same conditions, p38 mitogen-activated protein (MAP) kinase, but neither MAP kinase/extracellular signal-regulated kinase kinase (MEK) nor extracellular signal-regulated kinases (ERK), was transiently activated after N1E-115 cell attachment to laminin, but not in the DN-ILK-expressed cells. The time course of p38 MAP kinase activation was very similar to that of ILK activation. Furthermore, a p38 MAP kinase inhibitor, SB203580, significantly blocked neurite outgrowth. Thus, activation of p38 MAP kinase is involved in ILK-mediated signal transduction leading to integrin-dependent neurite outgrowth in N1E-115 cells.

Animals↗

PubMed2001

Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis in cultured mouse astrocytes.

Riluzole is an antiexcitotoxic agent used for the treatment of amyotrophic lateral sclerosis, and reported to have neuroprotective effects in animal models of Parkinson's disease, Huntington's disease and brain ischemia. We investigated the effects of riluzole on synthesis of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in cultured mouse astrocytes. The protein and mRNA levels were measured by enzyme-linked immunosorbent assay and semiquantitative reverse transcription-polymerase chain reaction, respectively. Treatment with riluzole at 100 microg/ml (426 microM) for 24 h increased the contents of NGF, BDNF, and GDNF in the culture medium 109-fold, 2.0-fold and 3.1-fold over the control, respectively. The drug-induced relative mRNA levels of NGF, BDNF, and GDNF were 7.3-fold at 2 h, 2.1-fold at 4 h, and 1.9-fold at 2 h, respectively. These results indicate that riluzole stimulates synthesis of NGF, BDNF and GDNF in cultured astrocytes. Riluzole might exert neuroprotective effects, at least in part, via stimulation of neurotrophic factors.

Animals↗

PubMed2001

Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 scid mice.

Scid mice are defective in the ability to repair DNA double strand breaks and, as a consequence, their cells are radiosensitive. Further, they have been shown to be prone to develop thymic lymphomas (TLs) after small doses of ionizing radiation. Little is known, however, on the role of scid mutation in chemical carcinogenesis. To determine if scid mutation increased predisposition to chemical carcinogenesis, we examined both the susceptibility of scid mice to N-ethyl-N-nitrosourea (ENU)-induced lymphomagenesis and the involvement of ras gene activation. Adult female mice at 8 weeks of age were given ENU in their drinking water at 400 ppm for 2-10 weeks. Contrary to expectations, we observed a two to three-fold reduction in TL development in the scid mice. The highest incidence was achieved by ENU treatment for 8 weeks for scid and wild-type C.B-17 mice, of 42 and 85%, respectively (P<0.05). We investigated whether this was attributable to the usage of the ras mutation pathway. There was, however, no significant difference in the frequency and spectrum of K-ras mutation between the scid and wild-type C.B-17 mice. Most of the K-ras mutations were either GGT to GAT transition in codon 12 (11/23: 48%) or CAA to CCA transversion in codon 61 (8/23: 35%) that was independent of scid background. The incidence of N-ras mutation was very low. These results indicate that scid mice are less susceptible to ENU-induced lymphomagenesis and ras gene mutation frequently occurs in both scid and wild-type C.B-17 mice.

Animals↗

PubMed2001

Complete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7.

The complete genomic sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 which optimally grows at 80 degrees C, at low pH, and under aerobic conditions, has been determined by the whole genome shotgun method with slight modifications. The genomic size was 2,694,756 bp long and the G + C content was 32.8%. The following RNA-coding genes were identified: a single 16S-23S rRNA cluster, one 5S rRNA gene and 46 tRNA genes (including 24 intron-containing tRNA genes). The repetitive sequences identified were SR-type repetitive sequences, long dispersed-type repetitive sequences and Tn-like repetitive elements. The genome contained 2826 potential protein-coding regions (open reading frames, ORFs). By similarity search against public databases, 911 (32.2%) ORFs were related to functional assigned genes, 921 (32.6%) were related to conserved ORFs of unknown function, 145 (5.1%) contained some motifs, and remaining 849 (30.0%) did not show any significant similarity to the registered sequences. The ORFs with functional assignments included the candidate genes involved in sulfide metabolism, the TCA cycle and the respiratory chain. Sequence comparison provided evidence suggesting the integration of plasmid, rearrangement of genomic structure, and duplication of genomic regions that may be responsible for the larger genomic size of the S. tokodaii strain7 genome. The genome contained eukaryote-type genes which were not identified in other archaea and lacked the CCA sequence in the tRNA genes. The result suggests that this strain is closer to eukaryotes among the archaea strains so far sequenced. The data presented in this paper are also available on the internet homepage (http://www.bio.nite.go.jp/E-home/genome_list-e.html/).

Archaeal Proteins↗

PubMed2001

Suppressed gap junctional intercellular communication in carcinogenesis of endometrium.

To examine whether and at which stage of endometrial carcinogenesis decreased connexin expression occurs, we investigated changes in the expression of the gap junction proteins, connexin 26 (Cx26), Cx32 and Cx43, in human endometrial hyperplasia and cancer samples. Forty-eight endometrial tissue samples (15 endometrial hyperplasias and 33 endometrial cancers) were subjected to immunofluorescence and RT-PCR analysis. In endometrial hyperplasia, Cx26 was aberrantly expressed in all samples as revealed immunohistochemically. There was weak or negative expression in 12 samples (80.0%) and diffuse expression in cytoplasm in 3 samples (20.0%). Cx32 expression in those samples was similar to that of Cx26; there was weak or negative expression in 11 samples (73.3%) and diffuse expression in 4 samples (26.7%). In endometrial cancer, Cx26 was expressed weakly or negatively in 25 samples (75.8%), diffusely in 6 samples (18.2%) and normally in 2 samples (6.1%), while Cx32 was expressed weakly or negatively in 26 samples (78.8%), diffusely in 5 samples (15.2%) and normally in 2 samples (6.1%). It was confirmed that weak staining of Cx26 and Cx32 was due to poor expression of their mRNA. All samples showed weak Cx43 protein expression as revealed by immunohistochemical analysis. In the majority of samples, concomitant expression levels of Cx26 and Cx32 protein were observed, confirming our long-term hypothesis that Cx26 and Cx32 are both abnormally regulated in a coordinated fashion in the endometrium. Our results indicate that during endometrial carcinogenesis, loss of gap junctional intercellular communication (GJIC) may occur due to the suppressed expression and the aberrant localization of connexin at relatively early stages.

Adenocarcinoma↗

PubMed2001

Influence of interleukin-1beta gene polymorphism on age-at-onset of spinocerebellar ataxia 6 (SCA6) in Japanese patients.

An inverse correlation is observed between the expanded CAG repeat number and age-at-onset of spinocerebellar ataxia 6 (SCA6). To detect another modifying genetic factor for SCA6, we studied polymorphisms in the genes for interleukin (IL)-1beta and tumor necrosis factor in 122 Japanese patients with SCA6. No contribution of these polymorphisms to the variance in disease onset was observed by regression analysis or by ANOVA. The IL-1beta promoter polymorphism, however, significantly affected the age-at-onset, when adjusted for the CAG repeat number as a covariate (P=0.0004, by ANCOVA), suggesting that IL-1beta may be a genetic factor other than the SCA6 gene that modifies the age-at-onset of the disease.

Age of Onset↗

PubMed2001

Constitutive expression and delayed light response of casein kinase Iepsilon and Idelta mRNAs in the mouse suprachiasmatic nucleus.

Casein kinase Iepsilon (CKIepsilon) and casein kinase Idelta (CKIdelta) phosphorylate clock oscillating mPER proteins, and play a key role in the transcription (post)translation feedback loop that generates circadian rhythm. In the present study, the expression profiles of CKIepsilon and CKIdelta mRNAs were examined in the mice clock center, suprachiasmatic nucleus (SCN). Moderate levels of CKIepsilon and CKIdelta mRNAs were constantly expressed in the SCN in both light:dark and constant dark conditions. This finding supports the hypothesis that CKI may form a constant threshold to the nuclear entry of mPER proteins as in the Drosophila homologue, double-time. Further, we demonstrated that the light exposure at subjective night induced a delayed increase in CKIepsilon and CKIdelta mRNAs in the SCN. CKIepsilon and CKIdelta proteins may play a role on light-induced phase-shift.

Animals↗