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Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mechanism of the photocatalytic inactivation of Lactobacillus casei phage PL-1 by titania thin film.

The mechanism of the inactivation of Lactobacillus casei phage PL-1 suspended in a phosphate buffer by black-light (BL) -catalytic titanium dioxide (TiO2) thin film was studied. Generation of both superoxide anions (O2-) and hydroxyl radicals (*OH) was confirmed in the aqueous medium in which TiO2 film was settled with BL irradiation under gentle shaking. With BL-irradiation alone without TiO2 film, only O2- was generated to some extent. The genome DNA inside the phage particles was found to be fragmented by the treatment of PL-1 phages with BL-catalytic TiO2 film. The phage inactivation by BL-catalytic TiO2 film was inhibited by the addition of albumin in a concentration-dependent manner. BL-catalytic TiO2 film was considered to cause primarily the damage to the capsid protein through the generation of active oxygen species such as *OH, followed by damage to the genome DNA inside the phage particles.

Antiviral Agents↗
PubMed2001

Flexor digitorum longus accessorius in the club foot of an infant with Nager syndrome.

The case of a male infant is reported who had club foot on the right side and pes adductus on the left side in combination with acrofacial dysostosis; he also demonstrated preaxial anomalies of the upper limbs indicative of Nager syndrome. In addition, an unusual aberrant muscle was discovered during surgical correction of the right club foot.

Abnormalities, Multiple↗
PubMed2001

Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

Adult↗
PubMed2001

Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha release by human monocyte/macrophages in vitro.

Periprosthetic membranes commonly observed at sites of total joint implant loosening exhibit abundant macrophages and particulate debris. Macrophages phagocytose orthopedic debris and release the pro-inflammatory mediators interleukin-1, interleukin-6, tumor necrosis factor-alpha, and prostaglandin E2. Populations of activated lymphocytes are often seen in periprosthetic membranes. These lymphocytes may modulate the monocyte/macrophage response to particulate debris and influence aseptic loosening. In addition, other immunologic agents, such as interleukin-10, are present in tissues harvested from the bone-implant interface of failed total joint arthroplasties. The present study examined the effects of interleukin-10 on polymethylmethacrylate (PMMA) particle challenged human monocyte/macrophages in vitro. Human monocyte/macrophages isolated from buffy coats of five healthy individuals were exposed to 1-10 microm PMMA particles. Interleukin-10 was added to the monocyte/macrophages with and without the addition of PMMA particles. Interleukin-10-induced alterations in monocyte/macrophage metabolism were determined measuring interleukin-6 and tumor necrosis factor-alpha release by the cells following exposure to PMMA particles. Exposure of the monocyte/macrophages to PMMA particles resulted in a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha at 48 h. Interleukin-10 reduced the levels of interleukin-6 and tumor necrosis factor-alpha release by macrophages in response to PMMA particles in a dose-dependent manner. At 48 h, particle-induced interleukin-6 release was inhibited by 60 and 90% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. At 48 h, particle-induced tumor necrosis factor-alpha release was inhibited by 58 and 88% with 1.0 and 10.0 ng/ml treatments of interleukin-10, respectively. Interleukin-10 challenge alone did not significantly alter basal interleukin-6 or tumor necrosis factor-alpha release relative to control cultures. The data presented in this study demonstrate that the anti-inflammatory cytokine, interleukin-10, inhibits monocyte/macrophage release of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in response to PMMA particle challenge in vitro.

Biocompatible Materials↗
PubMed2001

A selective ROCK inhibitor, Y27632, prevents dimethylnitrosamine-induced hepatic fibrosis in rats.

BACKGROUND: p160ROCK is a direct Rho target which mediates Rho-induced assembly of focal adhesions and stress fibers. We previously reported that Rho signaling pathways are involved in the activation of hepatic stellate cells (HSC) in vitro. The aim of the present study was to test the hypothesis that an inhibitor specific for p160ROCK (Y27632) could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Y27632 was given orally at 30 mg/kg daily for 4 weeks after the first injection of DMN. The degree of fibrosis was evaluated by image analysis and also by measurements of collagen and hydroxyproline content in the liver. The expression of alpha-smooth muscle actin (alpha-SMA) in the liver and in the primary cultured HSC was also evaluated. Semi-quantitative RT-PCR was performed to evaluate the expression of type I collagen mRNA in the liver. RESULTS: Y27632 treatment significantly decreased the occurrence of DMN-induced hepatic fibrosis and reduced the collagen and hydroxyproline content and alpha-SMA expression in the liver. The expression of alpha-SMA in HSC was also suppressed in vitro. CONCLUSIONS: These findings indicate that inhibitors of the Rho-ROCK pathway might be useful therapeutically in hepatic fibrosis.

Actins↗
PubMed2001

Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in non-small cell lung cancer.

Inhibition of programmed cell death (apoptosis) is associated with increased tumor aggressiveness. We hypothesized that a novel apoptosis inhibitor gene, antiapoptosis clone 11 (AAC-11), may be expressed in tumors of patients with non-small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of AAC-11 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 94 non-small cell lung carcinomas and adjacent histologically normal lung samples. The data was analyzed in reference to clinicopathological and survival data. AAC-11 transcripts were detected in 12 (12.7%) of the tumor samples, although five of paired normal lung samples showed very weak expression. There was no relationship between AAC-11 gene expression and age, gender, N or T-status. AAC-11 was preferentially expressed in squamous cell carcinoma (26.9% of squamous cell carcinoma vs. 7% of adenocarcinoma). The NSCLC patients with AAC-11 expression had significantly poor survival than the patients without AAC-11 expression (P=0.0360). Although the AAC-11 gene was not expressed in a majority of NSCLC tumors, we suggest that AAC-11 may predict poor survival.

Adenocarcinoma↗
PubMed2001

Activation of hypothalamic neuronal nitric oxide synthase in lithium-induced diabetes insipidus rats.

The expression of the neuronal nitric oxide synthase (nNOS) gene in the paraventricular (PVN) and supraoptic nuclei (SON) in rats with lithium (Li)-induced polyuria was examined by using in situ hybridization histochemistry. The state of the thyroid axis in these rats was also examined by in situ hybridization histochemistry for thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) mRNAs and radioimmunoassay for circulating thyroid hormones. Adult male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed remarkable polyuria. The urine in the Li-treated rats was hypotonic and had a large volume and low ionic concentration. The nNOS mRNA in the PVN and SON was significantly increased in the Li-treated rats in comparison with that in control. The increased levels of the nNOS mRNA in the PVN and SON were confirmed by NADPH-diaphorase histochemical staining. There were no differences of TRH mRNA in the PVN, TSH mRNA in the anterior pituitary and plasma concentrations of free T3 and free T4 between Li-treated rats and control rats. These results suggest that Li-induced diabetes insipidus may activate nNOS in the PVN and SON without change of the thyroid axis.

Animals↗
PubMed2001

Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury.

OBJECTIVES: In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue injury. Degradation of the basement membrane, which is composed of extracellular matrix (ECM) molecules, is necessary for neutrophil migration. Matrix metalloproteinases (MMPs) might play a role in ECM degradation in lung ischemia-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressions using rat lung transplantation models. METHODS: We divided animals into 4 groups. Groups I and II served as control groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Group II). Groups III and IV received lung grafts after 24-hour cold preservation. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (Group IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2, MMP-9, and TIMP-1 gene expression using biplex reverse transcriptase-polymerase chain reaction method. RESULTS: In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression were low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion. CONCLUSIONS: Matrix metalloproteinase 9, but not MMP-2, may play an important role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.

Animals↗
PubMed2001

Guar gum reduces trichloroethylene accumulation in the body by reducing TCE absorption and fat tissue mass.

Two studies were conducted regarding the effects of guar gum on accumulation and metabolism of trichloroethylene (TCE). In study 1, 6- and 14-weeks-old rats were given a single oral dose of 100 mg of trichloroethylene (TCE). Ten hours after administration of TCE, a marked positive correlation was noted between relative fat tissue weights and TCE distribution in fat tissues. Therefore, a small mass of fat tissue apparently limited TCE accumulation. In study 2, each of four groups of rats was fed one of four diets: cellulose-soybean oil, cellulose-docosahexaenoic acid (DHA), guar gum-soybean oil, or guar gum-DHA for 3 weeks and then all were given TCE as in study 1. The rate of decrease of TCE distributed in fat tissues of groups fed guar gum compared with corresponding groups fed cellulose was greater than the rate of decrease in relative weight of these tissues. TCE absorption by groups fed guar gum decreased 12% compared with TCE absorption of corresponding groups fed cellulose. Therefore, guar gum decreased TCE accumulation in the body by reducing TCE absorption and fat tissue mass.

Adipose Tissue↗
PubMed2001

Presumed interference colours at the level of the human anterior lens capsule.

PURPOSE: To assess the incidence and related factors of the presumed interference colour phenomenon at the anterior lens capsule. METHODS: In 274 eyes of 137 normal subjects, ranging in age from 4 to 83 years old (50.1 +/- 24.9 years, mean +/- standard deviation), the anterior lens capsule was observed with slit-lamp microscopy under specular conditions to assess the presence and degree of presumed interference colours. RESULTS: The colouring phenomenon, which was thought to be relevant to the interference phenomenon induced at the level of the anterior lens capsule, was found in 67.5% of eyes. Typically, there was a colour spectrum with a greenish tint in the central area and a reddish tint at the periphery, which coincided with the area of capsular shagreen. Multiple regression analysis revealed a signigificant positive correlation between the degree of the interference colour phenomenon and the age of the subjects (r = 0.45, p < 0.0001, R2 = 0.713). CONCLUSION: Presumed interference colours are frequently seen at the human anterior lens capsule. Interference colours and capsular shagreen seem to reflect age-related changes in the lens.

Adolescent↗
PubMed2001

Pirfenidone inhibits dimethylnitrosamine-induced hepatic fibrosis in rats.

1. In the present study, we investigated the preventive effects of pirfenidone (PFD), an antifibrotic agent, on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. 2. Treatment with DMN caused a significant decrease in bodyweight and liver weight. Oral PFD (500 mg/kg daily for 4 weeks) essentially prevented this DMN-induced loss in bodyweight and tended to suppress the loss in liver weight. There were no significant differences in liver weight and serum L-alanine aminotransferase levels between PFD-treated and -untreated groups. Pirfenidone has no major side effects in vivo. 3. Pirfenidone suppressed the induction of hepatic fibrosis determined by histological evaluation and reduced hepatic hydroxyproline levels. Expression of mRNA for type I collagen and transforming growth factor-beta in the liver was also suppressed by PFD treatment. 4. Because hepatic stellate cells (HSC) are the major cellular source of extracellular matrix in hepatic fibrosis, we examined the effects of PFD on type I collagen production in vitro using rat primary HSC cultures. Pirfenidone inhibited collagen production in HSC culture in a dose-dependent manner. 5. These results demonstrate that the inhibitory effects of PFD against hepatic fibrosis may be due, at least in part, to blockade of collagen production by HSC and suggest that PFD may be potentially useful in the prevention of the development of hepatic fibrosis.

Animals↗
PubMed2001

Pressure-induced expression of monocyte chemoattractant protein-1 through activation of MAP kinase.

BACKGROUND: In glomerular hypertension, mesangial cells (MC) are subjected to at least two physical forces: a high pressure and mechanical stretch. In 5/6 nephrectomized rat, a model of progressive glomerular sclerosis associated with glomerular hypertension, monocyte chemoattractant protein-1 (MCP-1) is expressed in glomeruli, suggesting the possible role of MCP-1 in the pathogenesis of glomerular sclerosis; however, whether pressure directly affects MCP-1 expression remains undetermined. Here we examined the effects of pressure on MCP-1 expression in cultured rat MC and the signal transduction pathways that lead to MCP-1 expression. METHODS: Pressure was applied to MC by instilling compressed helium gas into sealed plates. MCP-1 mRNA and protein levels in MC were detected by reverse transcription-polymerase chain reaction (RT-PCR) or Northern blotting and ELISA or Western blotting, respectively. Mitogen-activated protein (MAP) kinase activity was measured with the catalytic activity of p42/p44 MAP kinase and anti-phospho p42/p44 MAP kinase antibody. A transient transfection assay that specifically modulates MAP kinase kinase (MEK) activity was carried out. RESULTS: MCs subjected to external pressure expressed MCP-1 mRNA rapidly and transiently with the peak level noted at 10 minutes and 80 mm Hg pressure. MCP-1 protein levels in cell lysates and culture medium also significantly increased after pressure loading. Pressure rapidly increased the phosphorylation level and activity of p42/p44 MAP kinase. Treatment of MC with a MAP kinase kinase (MEK) inhibitor, PD98059, suppressed levels of both pressure-induced MAP kinase activities and MCP-1 mRNA expression. The constitutively activated type of MEK1 induced MCP-1 expression (13.7-fold) even in non-pressurized MC. CONCLUSIONS: Our results indicate that pressure per se can induce MCP-1 via activation of MAP kinase pathway, suggesting that glomerular hypertension might be involved in the progression of renal diseases through the expression of MCP-1 in MC.

Animals↗
PubMed2001

Increased Fas antigen in uremia accelerates adhesion of mononuclear cells to endothelial and sinovial cells via stimulated hyaluronan production.

We examined influences of increased soluble Fas (sFas) and hyaluronan in uremia on apoptosis and peripheral blood mononuclear cell (MNC) adhesiveness. Synovocytes, human umbilical cord endothelial cells (HUVEC), human coronary artery smooth muscle cells (CASMC), and MNC were prepared in this study. In cultures of synovocytes, HUVEC, and CASMC, sFas or high molecular hyaluronan was added to media at medium change. After 1 day, Fas-positive cells were calculated by fluorescence-activated cell sorting. Uremic level of sFas enhanced Fas-positive cells in all cell lines (P < 0.01) not in CASMC. On the contrary, hyaluronan inhibited Fas expression in all cell lines (P < 0.05). In culture with uremic serum, Fas were induced in all cell lines. At this time, the hyaluronan levels of the supernatant were measured and hyaluronan production was estimated. In contrast to the results using sFas supplement, hyaluronan production was increased in culture with sFas and uremic sera. MNC adhesiveness was increased in synovocytes and HUVEC lines by adding hyaluronan or sFas. Higher adherent cell numbers were recognized when both sFas and hyaluronan were added to the media. A most remarkable increase in cell numbers was observed in uremic MNC suspension as compared with that of MNC from healthy subjects. In conclusion, these results indicate that increased sFas in uremia stimulates apoptosis and hyaluronan production. Both sFas and hyaluronan are responsible for accelerated MNC adhesiveness in uremia.

Adhesiveness↗
PubMed2001

Immunohistologic study on the expressions of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma.

Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P <.05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue-PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP-negative cases, tissue-AFP-positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP-positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II-positive.

Adult↗
PubMed2001

Expression of the protein gene product 9.5, PGP9.5, is correlated with T-status in non-small cell lung cancer.

BACKGROUND: In a tumor, increased deubiquitination of cyclins by a protein gene product gene, PGP9.5, could contribute to the uncontrolled growth of somatic cells that is a hallmark of cancer. We hypothesized that PGP9.5 may be expressed in tumors of patients with non-small cell lung cancer (NSCLC). METHODS: Expression of PGP9.5 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 95 non-small cell lung carcinomas and adjacent histological normal lung samples. The data were analyzed with reference to clinicopathological factors. RESULTS: PGP9.5 transcripts were detected in 18 (12.8%) of the tumor samples, although some of paired normal lung samples showed very weak expression. There was no relationship between PGP9.5 gene expression and age, gender, N-status or pathological subtype. PGP9.5 gene was preferentially expressed in T3/T4 NSCLC (12/41, 29.3%) compared with T1/T2 NSCLC (6/54, 11.1%) (p = 0.0482). CONCLUSIONS: Although the PGP9.5 gene was not expressed in a majority of NSCLC tumors, we suggest that PGP9.5 may correlate with tumor invasion or progression of NSCLC.

Adult↗
PubMed2001

Synergistic interaction of integrin and angiotensin II in activation of extracellular signal-regulated kinase pathways in vascular smooth muscle cells.

Integrins, major adhesion receptors and angiotensin II activate extracellular signal-regulated kinase (ERK) pathways and result in a mitogenic response such as the proliferation of vascular smooth muscle cells (VSMCs). We investigated mechanisms of collaboration or synergism between integrins and angiotensin II involving ERK pathways in VSMCs. Integrin activation by cell adhesion to fibronectin increased the phosphorylation level of focal adhesion kinase (FAK) upstream of the ERK pathway. angiotensin II induced a high increase in the phosphorylation level of FAK with integrin activation, but not in suspended cells. Integrin activation increased phosphorylation levels of ERK kinase (MEK) and ERK phosphorylation as well. Angiotensin II-induced MEK and ERK phosphorylation were retained even in suspended cells. Furthermore, with integrin activation, angiotensin II induced a much larger increase in the phosphorylation levels of MEK and ERK. These results suggest that simultaneous stimulation of integrin and angiotensin II receptors cause synergistic interaction in the activation of ERK pathway, possibly via phosphorylation of FAK, which may play a critical role in angiotensin II-mediated mitogenic response in VSMCs.

Angiotensin II↗