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Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 19 recordsLinked to original sources

Clinical evaluation of cornea pseudoguttata.

AIM: To report on cornea pseudoguttata which occurred in 44 eyes from 40 patients. METHODS: In 3521 consecutive patients seen at a local eye clinic, eyes were examined with a slit-lamp biomicroscope in specular illumination. When guttate appearance was found, specular microscopy was performed. RESULTS: Cornea pseudoguttata was found in 44 eyes of 40 patients (1.1%). All patients had some form of anterior-segment ocular diseases, including keratitis (corneal infiltration) with contact lens wear (n = 16), epidemic keratoconjunctivitis (n = 8), corneal epithelial defect (n = 6), superficial punctate keratitis (n = 4), corneal foreign body (n = 3), keratitis of unknown causes (n = 3), corneal ulcer (n = 2), herpetic keratitis (n = 1), and iritis (n = 1). Six eyes were lost to follow-up, but in the remaining 38 eyes, cornea pseudoguttata completely resolved as the primary anterior-segment diseases subsided. Specular microscopy, measured after resolution of cornea pseudoguttata, showed that corneal endothelial cell density was not different between the affected and contralateral healthy eyes. CONCLUSION: Cornea pseudoguttata is commonly found in cases with corneal infiltration and inflammation. These results indicate that cornea pseudoguttata is reversible in its nature and resolves completely without any damage to the corneal endothelial cells.

Adolescent↗

Observation and control of transverse energy-transport barrier due to the formation of an energetic-electron layer with sheared ExB flow.

Off-axis electron-cyclotron heating in an axisymmetric barrier mirror produces a cylindrical layer with energetic electrons, which flow through the central cell and into the end region. The layer, producing a localized bumped ambipolar potential Phi(C), forms a strong shear of radial electric fields E(r) and peaked vorticity with the direction reversal of E(r)xB sheared flow near the Phi(C) peak. Intermittent vortexlike turbulent structures near the layer are suppressed in the central cell by this actively produced transverse energy-transport barrier; this results in T(e) and T(i) rises surrounded by the layer.

Journal Article↗

Epidemiology of needlestick and sharps injuries among nurses in a Japanese teaching hospital.

The epidemiology of needlestick and sharps injuries (NSIs) was investigated among a complete cross-section of 1,162 nurses from a large hospital in southern Japan (response rate 74.0%). Forty-six percent had experienced an NSI in the previous year. Most were caused by ampoules or vials, which injured 32.3% of all nurses and accounted for 42.9% of all NSI events. Twenty-two percent of all NSIs involved a device that had been used on a patient prior to the NSI (contaminated device), while the usage status of a further 2.8% of devices was unknown. Logistic regression indicated that nurses younger than 25 years of age were 2.18 times more likely to have sustained a single NSI in the past 12 months [odds ratio (OR) 2.18, 95% confidence intervals (CI) 1.15-4.17] and 2.39 times more likely to have sustained multiple NSIs (OR 2.39, 95% CI 1.08-5.34). Working mixed shifts (rotating day and night, as opposed to day shifts alone) was associated with a 1.67-fold increased risk of sustaining any NSI (OR 1.67, 95% CI 1.01-2.85) and a 2.72 times greater risk of sustaining an NSI from a contaminated device (OR 2.72, 95% CI 1.71-4.44). Nurses who reported significant fatigue after work were 1.87 times more likely to sustain multiple NSIs (OR 1.87, 95% CI 1.13-3.13) and 1.94 times more likely not to report their NSIs (OR 1.94, 95% CI 1.03-3.71). Perceived high mental pressure was associated with a 1.75-fold increased risk of sustaining an NSI from a contaminated device (OR 1.75, 95% CI 1.07-2.88). Nurses who reported suboptimal staffing levels in their wards were 2.21 times more likely not to report any NSIs they sustained in the previous year (OR 2.21, 95% CI 1.06-4.89). Overall, this study suggests that NSIs represent a complex and multi-faceted problem for Japanese nurses. Intervention strategies should consider the emerging complicity of psychosocial factors on NSI among hospital staff in Japan, as elsewhere.

Adult↗

Prednisolone inhibits hyperosmolarity-induced expression of MCP-1 via NF-kappaB in peritoneal mesothelial cells.

The mechanism of peritoneal fibrosis in patients on continuous ambulatory peritoneal dialysis (CAPD) is poorly elucidated. We investigated the cellular mechanism of high-glucose-induced expression of monocyte chemoattractant protein-1 (MCP-1), which is important in recruiting monocytes into the peritoneum and progression of peritoneal fibrosis, and examined the inhibitory mechanism of glucocorticoids. Rat peritoneal mesothelial cells were cultured in high-glucose-containing medium and then analyzed for phosphorylation levels of p42/44 and p38 mitogen-activated protein (MAP) kinases (MAPK), MAPK or extracellular signal-regulated kinase kinase (MEK)1/2, c-Jun N-terminal kinase (JNK)1/2, and protein kinase C (PKC) by Western blotting. Expression of MCP-1 was examined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. DNA-binding activity of nuclear factor (NF)-kappaB was measured by electrophoretic mobility shift assay. High glucose increased MCP-1 mRNA and MCP-1 protein expression. Although glucose increased phosphorylation of MEK1/2, p42/44 MAPK, p38 MAPK, JNK1/2, and PKC, and DNA-binding activity of NF-kappaB, its effect on MCP-1 expression was suppressed only by PKC and NF-kappaB inhibitors. Mannitol caused a similar increase in PKC and NF-kappaB activation and MCP-1 synthesis. Prednisolone increased I-kappaB-alpha expression and inhibited glucose/mannitol-induced NF-kappaB DNA binding and MCP-1 expression without affecting PKC phosphorylation. The inhibitory effects of prednisolone on MCP-1 expression were reversed by mifepristone, a glucocorticoid receptor antagonist. Our results indicate that glucose induces MCP-1 mainly through hyperosmolarity by activating PKC and its downstream NF-kappaB, and that such effect was inhibited by prednisolone, suggesting the efficacy of prednisolone in preventing peritoneal fibrosis in patients on CAPD.

Animals↗

Observation of the effects of radially sheared electric fields on the suppression of turbulent vortex structures and the associated transverse loss in GAMMA 10.

Vortexlike turbulent structures in hot-ion mode plasmas with several keV are observed in the case with a radially produced weak shear of electric fields E(r). However, a strong E(r) shear formation due to a high ion-confining potential phi(c) production clears up these vortices together with plasma-confinement improvement and disappearance of both drift-wave and turbulencelike Fourier spectral signals. These findings are based on three-time progress in phi(c) in comparison to phi(c) attained 1992-2002. The significant advance of phi(c) is well extended in line with proposed potential-formation physics scalings.

Journal Article↗

Molecular characterization and evolution of the repeating units of histone genes in Drosophila americana: coexistence of quartet and quintet units in a genome.

Quintet and quartet repeating units of the histone genes in Drosophila americana were cloned and characterized. Nucleotide sequence analysis of the units showed that a 3175 bp unit contained the core histone genes but lacked the H1 gene ('quartet unit') while a 5025 bp unit contained all five histone genes ('quintet unit'). Comparative analysis suggested that these repeating units diverged before the separation of D. americana and D. virilis. Multiple forms of H1 genes, differing by 5.8% of amino acids, were found in D. americana. The genomic organization of the histone gene family in D. americana was found to be very similar to that of D. virilis.

Amino Acid Sequence↗

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma.

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.

Adult↗

[The effect of multimodality induction therapy for locally advanced non-small cell lung cancer].

In this study we analyzed induction therapy for locally advanced non-small cell lung cancer. Eligible patients had mediastinoscopic proven N2 disease and T4 with mediastinal involvement. From January 1997 to May 2005, 56 patients entered the study. They received 2 cycle chemotherapy (platinums based 2 or 3 drugs), in 32 patients with concurrent radiotherapy followed by surgery. Response rates were 57.1%. Fifty-one patients underwent surgery. A radical resection was possible in 39 patients. Complication occurred in 14 patients (27.5%). Overall 5-year survival was 27.5%. In N2 disease, there was no statistically significant difference in survival between the induction group and the historical group. In T4 disease, overall 5-year survival was 30.2% for the induction group and 5.2% for historical group. There was significant difference in survival between the groups (p < 0.05).

Adult↗

Association between nasal respiratory obstruction and vertical mandibular position.

Vertical mandibular position is considered to have an effect on the patency of the upper airway, because mouth opening is associated with a backward and downward displacement of the mandible and tongue. This study was conducted to investigate the nature of mandibular displacement at rest and to determine whether or not different respiration modes and body postures influence the mandibular position. The mandibular position was measured by use of a newly developed system with magnets and magnetic sensors placed on the upper and lower first molars, respectively. Vertical mandibular position was significantly affected by the degree of nasal airway obstruction. The proportion of the duration of mouth opening from 0 to 2.5 mm was about 80% in the sitting and lateral recumbent positions and 55% in the supine position. The amount and duration of vertical mandibular displacement were thus significantly increased by experimentally induced nasal respiratory obstruction. Furthermore, it was demonstrated that the amount and duration of mouth opening were significantly greater in the supine posture than in the sitting and lateral recumbent positions. It is thus shown that nasal respiratory disturbance may be a key determinant for mouth opening and breathing and the resultant vertical mandibular displacement.

Adult↗

Clinical significance of tissue inhibitor of metalloproteinase and matrix metalloproteinase mRNA expression in thymoma.

BACKGROUND: Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade extracellular matrix and basement membrane. There is much evidence that their increased expression is correlated with tumor aggressiveness in various carcinomas. Tissue inhibitor of metalloproteinases (TIMPs) are the specific inhibitors of MMPs. MMPs and TIMPs are considered to play an important role in carcinoma invasion and metastasis. We hypothesized that MMPs and TIMPs also play an important role in thymoma. MATERIALS AND METHODS: This study included 34 thymoma cases. The mRNA levels of MMP-1, -7, and -9, TIMP-1 and -2, and GAPDH were quantified by real-time polymerase chain reaction using LightCycler. We also performed immunohistochemistry for TIMP-1. RESULTS: The TIMP-1/GAPDH mRNA expression level was significantly higher in invasive (stage II-IV) thymomas (means +/- SE, 81.4 +/- 28.1) than in noninvasive (stage I) thymomas (30.9 +/- 8.3, P = 0.026). The MMP-1/GAPDH mRNA expression level was also higher in invasive thymomas (19.7 +/- 7.5) than in non invasive thymomas (2.26 +/- 1.72, P = 0.020). Immunopositivity of TIMP-1 was localized in stromal cells adjacent to the advancing margin of the tumor. CONCLUSIONS: These findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.

Gene Expression↗

Integration of hepatitis B virus containing mutations in the core promoter/X gene in patients with hepatocellular carcinoma.

UNLABELLED: Integration of hepatitis B virus is thought to be an essential step in hepatitis B virus associated hepatocarcinogenesis. Mutations at nucleotides 1762 and 1764 in the hepatitis B virus, within a sequence encoding both the core promoter gene and the X gene, have been found frequently in patients with hepatocellular carcinoma. However, integration of these mutant sequences has not been reported to date. METHODS: A 228-base pair segment of the hepatitis B virus core promoter gene was amplified from hepatocellular carcinomas and adjacent non-tumourous liver tissue by nested PCR and sequenced. Integration of hepatitis B virus into human genomic DNA was investigated using the 'genome walking' method. RESULTS: Point mutations were found in both hepatitis B virus nucleotides 1762 and 1764 in 8 of 14 hepatocellular carcinoma tissues (57%) and in 11 of 14 adjacent non-tumourous liver tissues (79%). Three patients were evaluated using the 'genome walking' method; all were found to have hepatitis B virus DNA integrated in their hepatocellular carcinoma (two patients) and/or in their non-tumourous liver tissue (three patients). Integration occurred in all tissues near host genomic sites that are prone to integration. Hepatitis B virus was integrated at or near the hepatitis B virus DR1 site in all samples, and all contained truncated X gene sequences that have been reported to be capable of producing fusion transcripts with transactivation potential. CONCLUSIONS: Integrated hepatitis B virus DNA containing core promoter mutations at nucleotides 1762 and 1764 was found in hepatocellular carcinoma and/or adjacent non-tumourous liver tissue of three patients. These findings leave open the possibility that insertional mutagenesis or transactivation by fusion transcripts resulting from hepatitis B virus integration could play a role in hepatocarcinogenesis in some patients.

Aged↗

Airway-directed gene transfer of interleukin-10 using recombinant Sendai virus effectively prevents post-transplant fibrous airway obliteration in mice.

Bronchiolitis obliterans (BO) after lung transplantation prevents a satisfactory prognosis, and recent studies suggested that interleukin-10 (IL-10) gene transfer to distant organs could inhibit BO in rodent models. Although delivery of the therapeutic gene to a local airway would be favored to minimize systemic effects, current limitations include lower gene transfer efficiency to airway epithelium. As recombinant Sendai virus (SeV) can produce dramatically efficient gene transfer to airway epithelium, we determined if SeV-mediated IL-10 gene transfer to the local airway would inhibit bronchial fibrous obliteration in murine tracheal allografts. Administration of cyclosporine A (CsA) significantly promoted not only recovery of the injured airway epithelium but also SeV-mediated IL-10 expression (CsA- versus CsA+ =228+/-78 versus 3627+/-1372 pg/graft with 5 x 10(7) pfu), thereby suggesting the requirement of epithelia for efficient gene transfer. Even at the highest expression, no significant leakage of IL-10 was evident in the systemic circulation, and the induction of interferon-gamma was completely diminished on day 7 by IL-10 gene transfer. As a result, luminal loss was significantly prevented in allografts treated with SeV-IL-10 (luminal opening, all control groups: 0% respectively, and SeV-IL-10 5 x 10(7) pfu: 25.7+/-10.5%), an effect that was enhanced by short-term CsA treatment (SeV-IL-10 5 x 10(7) pfu with CsA: 63.7+/-12.7%). We propose that SeV is a useful vector that can target airway epithelium to prevent BO avoiding putative systemic effect.

Animals↗

Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery.

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5 x 10(5)) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 microg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.

Animals↗

Recombinant Sendai virus vectors for activated T lymphocytes.

T-lymphocyte-directed gene therapy has potential as a treatment of subjects with immunological disorders. One current limitation of this therapeutic strategy is low gene transfer efficiency, even when complex procedures are used. We report herein that a recombinant Sendai virus vector (SeV) was able to overcome this issue. Using jellyfish enhanced green fluorescent protein gene (EGFP), we found that SeV was able to transduce and express a foreign gene specifically and efficiently in activated murine and human T cells, but not in naive T cells, without centrifugation or reagents including polybrene and protamine sulfate; the present findings were in clear contrast to those demonstrated with the use of retroviruses. The transduction was selective in antigen-activated T cells, while antigen-irrelevant T cells were not transduced, even under bystander activation from specific T-cell responses by antigens ex vivo. Receptor saturation studies suggested a possible mechanism of activated T-cell-specific gene transfer, ie, SeV might attach to naive T cells but might be unable to enter their cytoplasm. We therefore propose that the SeV vector system may prove to be a potentially important alternative in the area of T-cell-directed gene therapy used in the clinical setting.

Animals↗

Effects of activator on masticatory muscle activity during daytime and sleep.

The purpose of this study was to investigate masticatory muscle activity with and without the use of an activator during daytime and sleep, and further to focus on the changes in muscle activity produced by the daytime use. The subjects in this study were 10 healthy males (mean age: 27.6 years). A portable electromyogram (EMG) recording device was used to record the activity from the right temporal, masseter and digastric muscles. After recording, the integrated EMG values (microV s) were measured. The muscle activity was lower during sleep than during daytime, irrespective of the use of the activator. In sleep-time, temporal and digastric muscle activity was significantly decreased, although masseter muscle activity presented no significant differences. With the activator in use, the digastric muscle activity tended to increase in comparison with the elevator muscles during daytime and sleep. Although the activity of both elevator muscles was diminished by use of the activator during sleep in all subjects, some subjects showed an increase during daytime. These results suggested that the activator should be used, if possible, not only during sleep, but also during daytime and clenched on consciously to obtain the adaptation and development of the masticatory muscles for the 're-training of the muscles' at a new favourable mandibular position.

Adult↗

Bestatin results in pathophysiological changes similar to preeclampsia in rats via induction of placental apoptosis.

OBJECTIVE: To establish a rat preeclampsia model with fetoplacental growth restriction caused by bestatin via induction of placental apoptosis. STUDY DESIGN: 200 mg/kg/day of bestatin or saline as a control were infused intraperitoneally into pregnant Wistar rats from 15 days' gestation. In the first experiment, maternal blood pressure and proteinuria were examined during the pre- and postpartum periods. In the second experiment, cesarean sections were performed at 20 days' gestation and the weights of pups and placentas, and levels of proteinuria and placental apoptosis were examined. RESULTS: Physiological decrease of blood pressure in late pregnancy was not detected in the bestatin group but proteinuria level at 20 days' gestation was elevated. The weights of pups and placentas in the bestatin group were significantly lower than those in the controls, bestatin strongly inducing apoptosis in the placenta. CONCLUSION: Bestatin may cause a preeclampsia-like condition through induction of placental apoptosis.

Animals↗