Search PubMed⌕ Search

Biomedical subjects

N Nakashima

Publications and source records attributed to N Nakashima.

At least 19 recordsLinked to original sources
PubMed2006

The HAUSP gene plays an important role in non-small cell lung carcinogenesis through p53-dependent pathways.

Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild-type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53-dependent pathways.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

International transmission of uncompressed endoscopic surgery images via superfast broadband Internet connections.

BACKGROUND: Although telecommunication is increasing in popularity, poor-quality images sent through a narrowband network limit its use in the medical field. METHODS: Kyushu University Hospital in Japan and four hospitals in Korea were linked via superfast broadband Internet connection. The digital video transfer system, which can transmit digital videos without loss of image quality, was used, and the bandwidth was 30 Mbps per line. RESULTS: Of the 16 teleconferences conducted, 6 demonstrated real-time endoscopic surgery. In addition to the surgical images, preoperative diagnostic images, images of the operating room, and images of the staff in the conference room were transmitted to facilitate discussion. The network remained stable, and the sound delay was restricted to less than 0.3 s. In the other 10 teleconferences, recorded video images were used for discussion. CONCLUSIONS: The authors have established a high-quality, practical teleconference system that is economical and easy to use in clinical practice. This system shows promise for remote education beyond geographic borders.

Cholecystectomy, Laparoscopic↗
PubMed2005

The p53-Mdm2 association in epithelial cells in idiopathic pulmonary fibrosis and non-specific interstitial pneumonia.

BACKGROUND: Wild-type p53 is increased during cellular responses to various stresses. Mdm2, which is induced by p53, regulates p53 protein concentrations through the ubiquitin-proteasome pathway. AIM: To investigate whether the Mdm2 mediated ubiquitination of p53 is associated with epithelial cell apoptosis in idiopathic pulmonary fibrosis (IPF). METHODS: Immunohistochemistry and western blot analysis were carried out on lung samples obtained by lung biopsy from patients with IPF and non-specific interstitial pneumonia (NSIP). RESULTS: The expression of p53, phosphorylated p53, Mdm2, p21, and Bax was upregulated in epithelial cells from patients with IPF and NSIP compared with normal lung parenchyma. Except for p21, there was a significant increase in the expression of these factors in IPF compared with NSIP. In addition, the number of apoptotic cells and the number of p53 and Bax positive cells was increased compared with controls. p53 conjugated with Mdm2 was decreased in IPF compared with NSIP and controls. Ubiquitinated p53 was increased in both IPF and NSIP compared with controls. CONCLUSIONS: Signalling molecules associated with p53 mediated apoptosis may participate in epithelial cell apoptosis, and the attenuation of p53-Mdm2 conjugation and of p53 degradation may be involved in the epithelial cell apoptosis seen in IPF. Augmented epithelial apoptosis in IPF may lead to the poor prognosis compared with NSIP.

Adult↗
PubMed2004

Communication about the ending of anticancer treatment and transition to palliative care.

BACKGROUND: Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement. METHODS: A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%). RESULTS: Thirty-nine percent of the bereaved family members reported that they were 'very distressed' in receiving information about the ending of anticancer treatment, and 19% reported 'considerable' or 'much' improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions. CONCLUSIONS: In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

Aged↗
PubMed2004

Retinoic acid fails to reverse emphysema in adult mouse models.

BACKGROUND: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. METHODS: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-alpha transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. RESULTS: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-alpha transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-alpha transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. CONCLUSIONS: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.

Animals↗
PubMed2003

Involvement of cytotoxic granules in the apoptosis of aplastic anaemia.

To study the involvement of cytotoxic granules in apoptosis of aplastic anaemia (AA), we analysed bone marrow clot sections of AA for apoptosis and perforin, granzyme B and T-cell intracellular antigen-1 (TIA-1) expression. Perforin, TIA-1 expression and apoptosis were significantly increased in AA patients compared with control subjects, but granzyme B was not. TIA-1 was significantly correlated with apoptotic cells of AA. No correlation was found between perforin and apoptotic cells of AA. These results suggest that perforin and TIA-1 play a role in the pathogenesis of AA. TIA-1 is implicated as an effector in the apoptosis of AA.

Adolescent↗
PubMed2003

Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias.

Lung epithelial cells are a primary target for reactive oxygen species (ROS). ROS can cause oxidative deoxyribonucleic acid modification, such as 8-hydroxy-deoxyguanosine (8-OHdG). A human homologue of the MutT protein (hMTH1) prevents this modification. Mitochondria are the most important cellular source of ROS and may be susceptible to oxidative damage. The purpose of this study is to investigate oxidative stress and mitochondrial damage in lung epithelial cells from idiopathic interstitial pneumonias (IIPs). The authors analysed 8-OHdG, hMTH1, and mitochondrial proteins on lung specimens from 13 patients with IlPs consisted of eight patients with usual interstitial pneumonia and five patients with nonspecific interstitial pneumonia using Western blot analysis and immunohistochemistry. Immunoreactivity for 8-OHdG and hMTH1 was significantly increased in the lung epithelial cells from patients with IIPs compared with controls. The expression of hMTH1 was localised in the nuclear and cytoplasmic, but not the mitochondrial, fraction of lung homogenates. Immunoreactivity for mitochondrial protein and cytochrome c oxidase complex subunit IV was increased in the lung epithelial cells from patients with IIPs compared with controls. The current study concludes that oxidative stress may participate in epithelial cell damage in idiopathic interstitial pneumonia, and that increased mitochondrial mass may associate with increased reactive oxygen species production in idiopathic interstitial pneumonia.

Blotting, Western↗
PubMed2002

Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade.

AIMS: Abnormalities involving proliferation, apoptosis, and angiogenesis are important in tumorigenesis. The purpose of this study was to examine these three biological processes, and their relation with the clinical stage and cytological grade in multiple myeloma (MM). METHODS: Fifty four newly diagnosed patients with MM were studied by immunohistochemistry using bone marrow clot sections. Proliferation and apoptosis were evaluated for the proportion of MM cells (indicated by morphology and CD138 reactivity) positive for the Ki67 antigen and single stranded DNA (ssDNA), respectively. Angiogenesis was evaluated by measuring the intratumoral microvessel density (IMVD) and by assessing the immunoreactivity of vascular endothelial growth factor (VEGF). RESULTS: There were 30 men and 24 women (median age, 65 years; range, 37-84). At initial presentation, 15 (28%) were in Durie stage I, 15 (28%) in stage II, and 24 (44%) in stage III. Advanced clinical stage correlated with high cytological grade (p < 0.03). The medians for Ki67, ssDNA, and IMVD were 4.4% (range, 0-15%), 0.2% (range, 0-2.8%), and 15.5 (range, 0-63), respectively. Among these three continuous parameters, the only significant correlation was that between Ki67 and IMVD (p < 0.0001). Both Ki67 and IMVD also correlated with the clinical stage, cytological grade, and VEGF positivity (p <0.05). No correlation was found between ssDNA and all of the other parameters. CONCLUSIONS: These data suggest that proliferation is associated with angiogenesis in MM. Furthermore, proliferation and angiogenesis, but not apoptosis, may be important in disease progression. Lastly, increased production of VEGF may be one of the contributing factors to the increase in intratumoral vascularity seen in advanced MM.

Adult↗
PubMed2001

Molecular bilayer-based superstructures of a fullerene-carrying ammonium amphiphile: structure and electrochemistry.

The synthesis of a water-soluble C60-carrying single-chain ammonium amphiphile, 10- (N-methyl-2-fulleropyrrolidyl)decyltrimethylammonium bromide (1) as well as the characterization of aqueous solutions and cast films of 1 are described. X-ray diffraction study suggests that cast films of 1 form a multilayer structure based on biomembrane-like molecular bilayers. Electron microscopy has revealed that 1 produces both fibrous and disk-like aggregates with 10-12 nm of thickness through self-organization of 1 in aqueous solution. Differential scanning calorimetry, dynamic light scattering, FTIR, and UV-visible absorption studies were also carried out to characterize aqueous solutions and cast films of 1. Electrochemistry for an aqueous solution and for cast films of just 1 and 1 incorporated in lipid films on electrodes was conducted. It was found that films of just 1 and of 1/lipid cast on electrodes showed electron transfer reactions leading to the generation of the fullerene dianion or trianion. In contrast, electrochemistry of aqueous solution of 1 at a bare electrode gives a cathodic current near -0.5 to -0.6 V against SCE; however, an anodic current for the solution did not appear.

Carbon↗
PubMed2001

Saturated non-esterified fatty acids stimulate de novo diacylglycerol synthesis and protein kinase c activity in cultured aortic smooth muscle cells.

AIMS/HYPOTHESIS: Insulin resistance is linked with a cluster of multiple risk factors and excessive acceleration of atherosclerosis. The underlying mechanism is not, however, fully understood. METHODS: To determine the link between insulin resistance and altered vascular function, we focused on the effect of various non-esterified fatty acids on diacylglycerol-protein kinase C pathway and mitogen-activated protein kinase activity in cultured aortic smooth muscle cells. RESULTS: Incubation of the cells with saturated non-esterified fatty acids (200 micromol/l) for 24 h, such as palmitate or stearate, induced a significant increase in diacylglycerol concentrations by about fivefold or eightfold, respectively, whereas oleate induced a slight increase in diacylglycerol concentrations by 1.8-fold and arachidonate induced none. In addition, the increased diacylglycerol concentrations induced by palmitate were completely restored to control concentrations by triacsin C, acyl-CoA synthetase inhibitor. These results suggest that saturated non-esterified fatty acids may increase diacylglycerol concentrations through de novo pathway by stepwise acylation. In parallel with the increased diacylglycerol, incubation of the cells with saturated non-esterified fatty acids significantly induced the activation of protein kinase C and mitogen-activated protein kinase. The palmitate-induced increase in mitogen-activated protein kinase activity was restored to control concentrations by GF109203X (5 x 10(-7) mol/l), a specific protein kinase C inhibitor, suggesting a protein kinase C-dependent activation of mitogen-activated protein kinase. CONCLUSION/INTERPRETATION: Saturated non-esterified fatty acids induced an increase in de novo diacylglycerol synthesis and subsequent activation of protein kinase C and mitogen-activated protein kinase in cultured aortic smooth muscle cells. This could contribute to the altered vascular functions in the insulin resistant state.

Animals↗
PubMed2001

A tertiary structure model of the internal ribosome entry site (IRES) for methionine-independent initiation of translation.

Cricket paralysis-like viruses have a dicistronic positive-strand RNA genome. These viruses produce capsid proteins through internal ribosome entry site (IRES)-mediated translation. The IRES element of one of these viruses, Plautia stall intestine virus (PSIV), forms a pseudoknot immediately upstream from the capsid coding sequence, and initiates translation from other than methionine. Previously, we estimated that the IRES element of PSIV consists of seven stem-loops using the program MFOLD; however, experimental evidence of the predicted structures was not shown, except for stem-loop VI, which was responsible for formation of the pseudoknot. To determine the whole structure of the PSIV-IRES element, we introduced compensatory mutations into the upstream MFOLD-predicted helical segments. Mutation analysis showed that stem-loop V exists as predicted, but stem-loop IV is shorter than predicted. The structure of stem-loop III is different from predicted, and stem-loops I and II are not necessary for IRES activity. In addition, we identified two new pseudoknots in the IRES element of PSIV. The complementary sequence segments that are responsible for formation of the two pseudoknots are also observed in cricket paralysis virus (CrPV) and CrPV-like viruses such as Drosophila C virus (DCV), Rhopalosiphum padi virus (RhPV), himetobi P virus (HiPV), Triatoma virus (TrV), and black queen-cell virus (BQCV), although each sequence is distinct in each virus. Considering the three pseudoknots, we constructed a tertiary structure model of the PSIV-IRES element. This structural model is applicable to other CrPV-like viruses, indicating that other CrPV-like viruses can also initiate translation from other than methionine.

Base Pairing↗
PubMed2001

Localized amyloidosis and extramedullary plasmacytoma involving the larynx of a child.

Extramedullary plasmacytoma of the larynx and localized laryngeal amyloidosis are 2 uncommon disease entities that are exceedingly rare in children. We report a case of a 12-year-old girl presenting with progressive hoarseness who was subsequently found to have extramedullary plasmacytoma coexisting with localized amyloidosis involving the larynx. Results from the immunohistochemical and molecular studies showed that the tumor cells of the plasmacytoma were monoclonal (kappa-restricted), strongly supporting their neoplastic nature. The biochemical nature of the amyloid deposits was also shown to be of kappa immunoglobulin light chain, suggesting the pathogenetic relationship between the plasmacytoma and amyloid deposition in the larynx of this patient. There was no other evidence of malignancy or amyloidosis elsewhere. On a follow-up period of 4 years, this patient was well and asymptomatic. We believe that this represents the first case in the literature showing the coexistence of extramedullary plasmacytoma and localized amyloidosis of the larynx in children. This case also supports the concept that localized laryngeal amyloidosis may be a manifestation of low-grade B-cell neoplasms.

Amyloidosis↗
PubMed2001

Prognostic factors of patients with yolk sac tumors of the ovary.

OBJECTIVE: Our purpose was to evaluate the prognostic factors in yolk sac tumors of the ovary. STUDY DESIGN: We performed a retrospective review of 47 patients with yolk sac tumors of the ovary from 1979 to 1997. RESULTS: Twenty-two patients had pure yolk sac tumors and 25 had germ cell tumors with yolk sac tissue as a component of the disease. The 5-year survival rate in stages I, II, III, and IV was 95%, 75%, 30%, and 25%, respectively. Patients with stage I disease had a more favorable prognosis than those with stage III and IV disease (P <.001). All patients who did not respond to chemotherapy died of this disease within 36 months of the first treatment. Chemotherapy regimens that included cisplatin gave better results than those without cisplatin (P <.05). The difference in prognosis was significant in cases in which the size of residual tumor was <2 cm in diameter (P <.01) and in cases in which ascites was either absent or <100 mL in volume (P <.05). Coexistence of other components of ovarian germ cell tumors in histologic specimens, preoperative serum alpha-fetoprotein level, fertility-sparing surgery, dissection of intrapelvic nodes, and p53 status had no significant correlation with the prognosis in this study. CONCLUSIONS: Staging and tumor-reductive surgery strongly affected the prognosis of this disease. Tumor-reductive surgery is advisable when ascites is minimal. Cisplatin-based chemotherapy after surgery was superior to chemotherapy without cisplatin; however, p53 status seemed to have no impact on chemosensitivity in yolk sac tumors of the ovary.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Intraoperative ultrasonography by high-resolution annular array transducer for intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumors of the pancreas (IPMT) spread along the main pancreatic duct (MPD) or branch duct, or both. It is important to intraoperatively determine the extent of IPMT lesions in the MPD to perform a successful operation. METHODS: This study included 27 consecutive patients with IPMT who were referred for operation and who had undergone endoscopic ultrasonography, endoscopic retrograde pancreatography, and computed tomography as a diagnostic examination. Intraoperative ultrasonography with a 7.5-MHz annular array transducer and a 7. 5-MHz conventional transducer was performed. All patients underwent operation, and the pathology was confirmed. Endoscopic ultrasonography, endoscopic retrograde pancreatography, intraoperative conventional ultrasonography, and intraoperative annular array ultrasonography results were correlated with those from a pathologic examination of the resected specimens. The diagnostic accuracy of these 4 modalities in the detection of IPMT lesions in the MPD and the branch duct was confirmed. RESULTS: The diagnostic criterion of IPMT lesions by intraoperative annular array ultrasonography was the presence of echogenic masses with irregular margins in the MPD or branch duct, or both. An IPMT lesion in the MPD was found in 22 of the 27 patients. Intraoperative annular array ultrasonography detected 5 cases of IPMT lesions in the MPD that could not be detected by endoscopic ultrasonography or endoscopic retrograde pancreatography. In 3 of 5 patients, pancreatic resection was extended to remove IPMT lesions. Intraoperative annular array ultrasonography detected 3 multifocal lesions that could not be detected by preoperative examinations. For the diagnosis of IPMT lesions in the MPD, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 86%, 100%, and 89%; the respective values were 50%, 100%, and 59% for endoscopic retrograde pancreatography; 59%, 100%, and 67% for endoscopic ultrasonography, and 32%, 100%, and 44% for intraoperative conventional ultrasonography. For the diagnosis of IPMT lesions in the branch duct, the respective sensitivity, specificity, and overall accuracy of intraoperative annular array ultrasonography were 95%, 100%, and 96%. CONCLUSIONS: Intraoperative annular array ultrasonography is suitable for longitudinal scanning of the MPD, useful for accurate diagnosis of the extent of IPMT in the pancreas, and valuable for planning surgical strategy and successful operations for IPMT.

Adenocarcinoma, Mucinous↗
PubMed2001

Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in sputum from patients with bronchial asthma.

To examine a possibility that matrix metalloproteinases (MMPs) participate in the pathogenesis of asthma and/or the development of asthma attack, we measured the concentrations of MMP-2, MMP-9, and their respective tissue inhibitors of metalloproteinases (TIMP)-2 and TIMP-1, in induced sputa collected from 28 patients with moderate to severe bronchial asthma. Specimens were collected during both the attack and the remission from 15 age- and sex-matched healthy control subjects. The concentration of MMP-9 was significantly (p < 0.05) higher in the patients, even during the remission, as compared to that in healthy controls. The concentrations of MMP-9 (p < 0.05) and its specific inhibitor TIMP-1 (p < 0.01), and MMP-2 (p < 0.01) in these patients during the attack were significantly higher than those in healthy controls. In these patients, the MMP-9 concentration was significantly higher (p < 0.05) during the attack than during the remission. These results suggest that MMPs and TIMPs may be involved in the pathogenesis of bronchial asthma, and that the increased MMP-9 might be involved in the development of attack in patients with chronic asthma.

Adolescent↗
PubMed2001

The Saccharomyces cerevisiae small GTPase, Gsp1p/Ran, is involved in 3' processing of 7S-to-5.8S rRNA and in degradation of the excised 5'-A0 fragment of 35S pre-rRNA, both of which are carried out by the exosome.

Dis3p, a subunit of the exosome, interacts directly with Ran. To clarify the relationship between the exosome and the RanGTPase cycle, a series of temperature-sensitive Saccharomyces cerevisiae dis3 mutants were isolated and their 5.8S rRNA processing was compared with processing in strains with mutations in a S. cerevisiae Ran homologue, Gsp1p. In both dis3 and gsp1 mutants, 3' processing of 7S-to-5.8S rRNA was blocked at three identical sites in an allele-specific manner. In contrast, the 5' end of 5.8S rRNA was terminated normally in gsp1 and in dis3. Inhibition of 5.8S rRNA maturation in gsp1 was rescued by overexpression of nuclear exosome components Dis3p, Rrp4p, and Mtr4p, but not by a cytoplasmic exosome component, Ski2p. Furthermore, gsp1 and dis3 accumulated the 5'-A0 fragment of 35S pre-rRNA, which is also degraded by the exosome, and the level of 27S rRNA was reduced. Neither 5.8S rRNA intermediates nor 5'-A0 fragments were observed in mutants defective in the nucleocytoplasmic transport, indicating that Gsp1p regulates rRNA processing through Dis3p, independent of nucleocytoplasmic transport.

Active Transport, Cell Nucleus↗