Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 37 records · Page 2Linked to original sources

PubMed2004

Serological and genetic characterisation of a unique strain of adenovirus involved in an outbreak of epidemic keratoconjunctivitis.

AIMS: To characterise a novel strain of adenovirus (Ad) type Ad8 (genome type Ad8I) involved in an epidemic keratoconjunctivitis (EKC) outbreak in Hiroshima city using serological testing and sequence analysis of the fibre and hexon gene. METHODS: A neutralisation test (NT) was performed in microtitre plates containing a confluent monolayer of A549 cells using 100 tissue culture infectious doses of virus and type specific antisera. The haemagglutination inhibition test was also carried out in microtitre plates with rat erythrocytes using four haemagglutination units of virus and twofold dilutions of serum. The fibre gene was sequenced by generating overlapping polymerase chain reaction products or by direct sequencing of genomic DNA. Primer selection was based on alignment of the fibre genes of human adenovirus serotypes Ad8, Ad19, Ad37, Ad9, and Ad15 available from Gene Bank. RESULTS: The virus strain was specifically neutralised by anti-Ad8 antibodies, although there was a major crossreaction with anti-Ad9 antibodies. Haemagglutination was equally inhibited by anti-Ad8 and anti-Ad9 antibodies. The predicted amino acid sequences of the hypervariable regions (HVRs) of the Ad8I hexon gene showed higher homology with Ad9 (83.3%) than with Ad8 (62.0%). However, the Ad8I fibre knob was more homologous to Ad8 (94.4%) than to Ad9 (91.6%). CONCLUSIONS: Ad8I is a unique strain of adenovirus because of its lower genomic homology with Ad8, major crossreactivity with Ad9 in NT, and mixed genetic organisation of HVRs of the hexon gene. These factors may have enabled the virus to circumvent acquired immunity, resulting in the outbreak.

Adenovirus Infections, Human↗

PubMed2003

Hg2+ and Ni2+ alter induction of heat shock protein-72 in THP-1 human monocytes.

The biological liabilities that result from the release of metal ions from biomedical alloys, particularly Ni(2+) and Hg(2+), continue to be a concern. Heat-shock proteins (HSP) are a class of molecular chaperones that may be induced under conditions of cellular stress, including oxidative stress. Our hypothesis was that because Hg(2+) and Ni(2+) alter other cellular stress responses such as glutathione levels and cytokine secretion, these metal ions may alter HSP induction in monocytes, which are key cells in the response of tissues to biomedical alloys. THP-1 monocytes were exposed to sublethal concentrations of Hg(2+) or Ni(2+) for 1 h with or without heat stress (43 degrees C), then allowed to recover at 37 degrees C for 2-6 h. HSP72 was measured using immunoblotting with phosphorimage quantification. Hg(2+) exposures of 2-10 micromol/L induced HSP72 without heat stress. With heat stress, HSP72 levels were altered by Hg(2+) versus heat stress alone. The response depended on the concentration of Hg(2+) and the recovery time. Hg(2+) at 10 micromol/L caused uniformly lower HSP72 levels. Ni(2+) exposures of 20-100 micromol/L did not induce HSP72 without heat stress, but significantly altered heat-induced HSP72 expression, with a significant increase in expression over heat alone at 40 and 100 micromol/L. Results from the current study support the hypothesis that these metal ions can, at concentrations relevant to those released from biomedical alloys, modulate HSP expression in human monocytes. The modulation of HSP expression indicates an early sign of cellular stress that may be important to the overall biological response to biomedical alloys containing and releasing these metal ions.

HSP72 Heat-Shock Proteins↗

PubMed2003

Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property.

Development of the musculoskeletal system requires coordinated formation of distinct types of tissues, including bone, cartilage, muscle, and tendon. Compared to muscle, cartilage, and bone, cellular and molecular bases of tendon development have not been well understood due to the lack of tendon cell lines. The purpose of this study was to establish and characterize tendon cell lines. Three clonal tendon cell lines (TT-E4, TT-G11, and TT-D6) were established using transgenic mice harboring a temperature-sensitive mutant of SV40 large T antigen. Proliferation of these cells was significantly enhanced by treatment with bFGF and TGF-beta but not BMP2. Tendon phenotype-related genes such as those encoding scleraxis, Six1, EphA4, COMP, and type I collagen were expressed in these tendon cell clones. In addition to tendon phenotype-related genes, expression of osteopontin and Cbfal was observed. These clonal cell lines formed hard fibrous connective tissue when implanted onto chorioallantoic membrane in ovo. Furthermore, these cells also formed tendon-like tissues when they were implanted into defects made in patella tendon in mice. As these tendon cell lines also produced fibrocartilaginous tissues in tendon defect implantation experiments, mesenchymal stem cell properties were examined. Interestingly, these cells expressed genes related to osteogenic, chondrogenic, and adipogenic lineages at low levels when examined by RT-PCR. TT-G11 and TT-E4 cells differentiated into either osteoblasts or adipocytes, respectively, when they were cultured in cognate differentiation medium. These observations indicated that the established tendon cell line possesses mesenchymal stem cell-like properties, suggesting the existence of mesenchymal stem cell in tendon tissue.

Adipocytes↗

PubMed2003

Possible involvement of Rap1 and Ras in glutamatergic synaptic transmission.

Rap1A, first identified as a suppressor of transformed phenotype induced by an activated ras oncogene, is abundantly expressed in the brain. Its neurophysiological function, however, is poorly understood. When an activated Rap1A mutant (Rap1-12V) or a dominant negative H-Ras mutant (Ras-17N) was expressed in CA1 neurons in cultured hippocampal slices using the sindbis virus-mediated gene transfer technique, NMDA receptor current in response to Schaffer collateral stimulation was suppressed. Expression of activated H-Ras mutant (Ras-12V) resulted in the elevation of both NMDA receptor current and AMPA receptor current. These results implicate counteracting functions of Ras and Rap1 in the regulation of NMDA receptor-mediated synaptic transmission and a positive regulatory role of Ras in AMPA receptor-mediated synaptic transmission.

Animals↗

PubMed2003

Mixed-ligand modification of polyamidoamine dendrimers to develop an effective scaffold for maintenance of hepatocyte spheroids.

Compared with a monolayer culture, hepatocyte spheroids are known to maintain liver function for long periods. We found that hepatocytes formed spheroids when cultured on polyamidoamine dendrimers modified with fructose. Because galactose is a ligand for the asialoglycoprotein receptor on the hepatocyte cytoplasmic membrane, it was chosen as another ligand for modification in order to maintain adhesion of spheroids for long periods. Simultaneous modification of dendrimers with fructose and galactose had a marked effect on the time length of spheroid adhesion. Suppression of apoptosis and necrosis was observed in hepatocyte spheroids cultured on a dendrimer modified with fructose and galactose (F/G dendrimer). Moreover, the hepatocyte spheroids cultured on the F/G dendrimer had higher activities of liver-specific functions, such as urea synthesis and albumin gene expression, than did those cultured on single-ligand-modified dendrimers. The expression of heat shock protein (HSP) genes was examined to evaluate the stress response of cells to scaffolds. The hepatocytes cultured on the F/G dendrimer had very low expression levels of both HSP60 and HSP70 mRNAs. Thus immobilization of mixed-ligand-modified dendrimers could generate a suitable surface for hepatocyte spheroid formation. These dendrimers could be a powerful tool for generating custom-made scaffolds for cells other than hepatocytes by selecting the ligands suitable for each cell type.

Animals↗

PubMed2003

Tissue reconstruction process in the area of peri-tumoural oedema caused by glioblastoma--immunohistochemical and graphical analysis using brain obtained at autopsy.

BACKGROUND: In the area of peri-tumoural oedema, proteolytic agents derived from the tumour cause tissue degradation, which promotes tumour cell invasion. METHOD: We investigated the biological processes in the area of peri-tumoural oedema, using a brain obtained at autopsy from a patient who died from glioblastoma. Immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF), c-myc, p53, paternally expressed gene-3 (PEG-3), transforming growth factor beta (TGFB), and tumour necrosis factor alpha (TNFA). The data were translated into colour graphics and the localization of these proteins was analyzed. FINDINGS: In the area of peri-tumoural oedema, Ki-67 and p53 positive cells were observed with TGFB expression. Moreover, c-myc, PEG-3, VEGF, and TNFA were also expressed strongly in the glial cells or extra-cellular spaces in the area of peri-tumoural oedema. INTERPRETATION: These data suggest that in the area of peri-tumoural oedema, tissue reconstruction processes take place with concomitant anti-tumour activities. The expression of c-myc, VEGF, and TNFA in the area of peri-tumoural oedema may indicate that these proteins are not utilized for tumour growth, but may be used to guard the brain against tumour invasion. Peri-tumoural oedema does not only indicate the tissue damage caused by tumour, but many tissue reconstruction processes take place in these areas against tumour cell invasion.

Adult↗

PubMed2003

Isolation of a set of genes expressed in the choroid plexus of the mouse using suppression subtractive hybridization.

The choroid plexus produces cerebrospinal fluid, providing a specialized environment for the CNS. We previously demonstrated that choroid plexus ependymal cells can enhance nerve regeneration in vivo and promote neurite outgrowth in vitro. To understand the molecular mechanisms of choroid plexus functions, we isolated genes predominantly expressed in the mouse choroid plexus using suppression subtractive hybridization. Out of the 49 complementary DNA (cDNA) fragments isolated in two types of screening, 43 matched known sequences in the database and six were novel. In one type of screening where choroid plexus cDNAs were subtracted with cerebral cortex cDNAs, transthyretin and phosphodiesterase I alpha were predominant. This is consistent with previous reports and supports the authenticity of our approach. In the other type of screening, cDNAs derived from the choroid plexus of neonatal (postnatal day 5) mice were subtracted with cDNAs from the choroid plexus of adult mice. RNA blot and/or in situ hybridization confirmed abundant expression, in the mouse choroid plexus, of the mRNA encoding gelsolin, phospholipid transfer protein, ATP-binding cassette transporter A8 (ABCA8), androgen-inducible aldehyde reductase, and Na(+)/sulfate cotransporter SUT-1. Also, one novel gene (FS88) was found to be expressed in the choroid plexus from neonatal mice. Our data suggest that the choroid plexus cells produce molecules involved in processes such as prevention of fibrillization of amyloid beta-protein (transthyretin and gelsolin), lipid metabolism (phospholipid transfer protein and ABCA8), and detoxification (androgen-inducible aldehyde reductase).

Animals↗

PubMed2003

Coordinated development of embryonic long bone on chorioallantoic membrane in ovo prevents perichondrium-derived suppressive signals against cartilage growth.

Perichondrium has been shown to elicit signals to suppress differentiation and proliferation of chondrocytes during endochondral bone formation based on in vitro organ culture. However, these in vitro organ cultures did not allow the growth of bone collar, and thus the effect of perichondrium in a normal environment where development of adjacent embryonic tissues, including bone collar, is taking place has not yet been fully understood. Therefore, we examined the effect of perichondrium on cartilage development using chicken long bone organ cultures on chorioallantoic membrane in ovo, which supported bone collar development. In contrast to previous observations in in vitro organ cultures, in ovo organ cultures prevented overgrowth of epiphyseal cartilage due to the removal of perichondrium. This prevention was associated with the suppression of aggrecan gene expression in the absence of perichondrium in ovo. These results indicated that the perichondrium-derived activity that was observed in vitro to suppress cartilage development could be counterbalanced in ovo, where culture conditions are closer to those in in vivo. TUNEL assay indicated enhanced apoptosis in the presence of perichondrium in vitro, and removal of the perichondrium suppressed apoptosis. No major apoptosis was observed in ovo regardless of the presence or the absence of perichondrium. Thus, chondrogenesis in long bone could be coordinately regulated through modulation of apoptosis by perichondrium and adjacent embryonic tissues, including bone collar, as revealed in in ovo assay.

Allantois↗

PubMed2003

Physical characteristics of low and medium energy collimators for 123I imaging and simultaneous dual-isotope imaging.

Septal penetration of high energy photons may degrade 123I images obtained with a low energy collimator. We evaluated the physical characteristics of a low energy, high resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium energy collimator for 123I studies. The cross-talk of 99mTc and 123I into the 201Tl window was also examined. Sensitivity and spatial resolution were measured with each collimator. Point sources of 99mTc and 123I were imaged at various source-collimator distances using multiple energy windows, and the effects of collimator choice on energy spectrum and spatial distribution of photopeak counts were assessed. For 99mTc, both sensitivity and resolution were similar with the low energy collimators, and higher sensitivity and lower resolution were observed with the medium energy collimator. For 123I, the full width at tenth maximum was larger for 123I than for 99mTc when using the LEHR collimator. Acquisitions with multiple energy windows revealed severe degradation due to septal penetration in imaging 123I with the LEHR collimator, especially at short distances. The degradation was reduced with the SLEHR collimator and further with the medium energy collimator. In both 99mTc and 123I imaging, cross-talk into the 201Tl window was larger at shorter distances and the largest with the LEHR collimator. In conclusion, variation in collimator geometry causes differences in the effect of septal penetration on 123I images and in cross-talk into the 201Tl window. The SLEHR collimator may be suitable for use in high resolution 123I imaging and simultaneous 99mTc/201Tl imaging. Use of the medium energy collimator appears to be preferable in quantitative 123I studies.

Equipment Failure Analysis↗

PubMed2003

Hedgehog signaling enhances core-binding factor a1 and receptor activator of nuclear factor-kappaB ligand (RANKL) gene expression in chondrocytes.

Hedgehog signaling is considered to play a crucial role in chondrogenesis by regulation through a network of cytokine actions, which is not fully understood. We examined the effect of hedgehog signaling on the expression of core-binding factor a1 (Cbfa1), a critical transcription factor for the development of bone and cartilage. Primary chondrocytes prepared from the costal cartilage of newborn mice were treated with N-terminal fragment of recombinant murine sonic hedgehog (rmShh-N). Northern blot analysis indicated that Cbfa1 mRNA expression levels in the chondrocyte cultures were elevated by the treatment with rmShh-N. rmShh-N treatment enhanced 1.8 kb Cbfa1 promoter activity in chondrocytes, suggesting the presence of transcriptional control. As Cbfa1-binding site(s) have been located in the promoter of the receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) gene, we also examined RANKL expression. rmShh-N treatment upregulated RANKL and RANK mRNA expression levels in chondrocytes. Interestingly, RANKL suppressed the hedgehog enhancement of alkaline phosphatase activity in chondrocytes, suggesting the presence of a link between these signaling molecules. We conclude that hedgehog signaling activates Cbfa1 gene expression through its promoter in chondrocytes, and also activates and interacts with RANKL to maintain cartilage development.

Analysis of Variance↗

PubMed2003

[The establishment of the styles of video-assisted thoracoscopic surgery for spontaneous pneumothorax].

Video-assisted thoracoscopic surgery (VATS) has been widely used in the treatment of a pneumothorax, but the high incidence of recurrence from spontaneous pneumothorax after VATS is an important problem. In this study, we classified the groups into two categories from the thoracoscopic observations, and discussed whether or not there was reappearance of pneumothorax. In addition, we examined whether adjunctive procedure contributes to recurrent of pneumothorax after operation or not. We concluded that there is a tendency to recurrence in the group with multiple and skip lesions in the lung, and then concluded that the cases apical covering with absorbable material sheet and the use of fibrin glue spray was thought to be effective of recurrence of pneumothorax in cases of multiple and skip lesions from the intraoperative findings through the thoracoscopes. Finally, we examined application of Foley catheter for spontaneous pneumothorax under VATS. It is possible that the application of Foley catheter to prevention against recurrence of pneumothorax is a valid method.

Adult↗

PubMed2002

Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.

Adiponectin (Ad) is a hormone secreted by adipocytes that regulates energy homeostasis and glucose and lipid metabolism. However, the signaling pathways that mediate the metabolic effects of Ad remain poorly identified. Here we show that phosphorylation and activation of the 5'-AMP-activated protein kinase (AMPK) are stimulated with globular and full-length Ad in skeletal muscle and only with full-length Ad in the liver. In parallel with its activation of AMPK, Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Blocking AMPK activation by dominant-negative mutant inhibits each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK. Our data may provide a novel paradigm that an adipocyte-derived antidiabetic hormone, Ad, activates AMPK, thereby directly regulating glucose metabolism and insulin sensitivity in vitro and in vivo.

Acetyl-CoA Carboxylase↗

PubMed2002

Clinical and pathologic characteristics of nontyphoidal salmonella encephalopathy.

OBJECTIVE: To investigate the clinical and pathologic characteristics of primary encephalopathy caused by nontyphoidal salmonellosis (NTS). METHODS: Case records of six Japanese hospitals from 1994 to 1999 were reviewed. Eight cases of primary NTS encephalopathy were identified based on strictly defined criteria: 1) encephalopathic feature defined as altered state of consciousness, altered cognition or personality, or seizures; 2) detection of nontyphoidal Salmonella species in stool; 3) absence of other viral or bacterial infection associated with CNS abnormalities; and 4) absence of alternative explanation by underlying neurologic or systemic disease. Three patients died, three had severe sequelae, and two recovered completely. The authors analyzed their clinical course, neurologic symptoms, and histopathologic findings. RESULTS: NTS encephalopathy was clinically characterized by diffuse and rapidly progressive brain dysfunction and circulatory failure that developed following enteritis. There was no evidence of severe dehydration or sepsis, and encephalopathy was rarely accompanied by abnormal laboratory data, except elevated CSF opening pressure, brain edema on CT, and slow waves on EEG. Pathologic findings included minimal ischemic damage and mild edema in the brain, microvesicular fatty change of the liver, severe enterocolitis but no evidence of dehydration, and no fatal organ damage including microvasculature and endothelial cells. CONCLUSION: Noninfectious encephalopathy associated with nontyphoidal salmonella infection is a distinctive clinical entity that can be differentiated from Reye's syndrome and Ekiri.

Adolescent↗

PubMed2002

Low-dose, long-term exposures of dental material components alter human monocyte metabolism.

The short-term degradation of dental polymers and alloys in biological environments has been well documented, but recent evidence indicates that oral tissues may be chronically exposed to low levels of these released components. The effect of these chronic exposures on the ability of cells to respond to a subsequent challenge is not known. To investigate this idea, we exposed human THP-1 monocytes to sublethal concentrations of HEMA, TEGDMA, Hg(2+), and Ni(2+) for 2 weeks and then assessed the monocytic response to subsequent 24-h challenge with the same components at higher concentrations. Chronic (2 week) exposures of monocytes to HEMA and both metal ions significantly altered monocyte response to short-term (24 h) secondary exposures, even when overt effects of the chronic exposures were not apparent. However, cellular responses were highly variable depending on the material and its concentrations. For TEGDMA, no effects were seen. These results demonstrate that the chronic effects of materials must be considered even when the chronic exposure has no initial overt effect. The effect on cells may only be apparent if the cell is challenged by a secondary exposure.

Cells, Cultured↗

PubMed2002

Ag, Cu, Hg and Ni ions alter the metabolism of human monocytes during extended low-dose exposures.

The monocyte and macrophage play an important role in the biological response to dental biomaterials. However, the effects of low-level, extended exposures of monocytes to metal ions which are known to be released from dental alloys is not known. Thus, in the current study we characterized the metabolic activity of monocytes in the presence of low doses of Ag, Cu, Hg and Ni ions for up to 4 weeks. THP-1 human monocytes were exposed in vitro to concentrations of metal ions at 1-10% of those known to be lethal during 24 h exposures. Mitochondrial function [succinic dehydrogenase (SDH) activity] and total cellular protein [bicinchoninic acid (BCA) assay] were assessed at weekly intervals during metal exposure. Each metal ion caused a unique pattern of effects from the monocytes. These effects were sometimes delayed until several weeks into the exposure (Cu, Ni). Large increases in total protein or SDH activity per cell were observed (Cu 150%, Hg 40-60%, Ni 50%), but these increases were always transient. The differences between concentrations with minimal effects and those which were lethal (8 versus 12 micromol L(-1) for Ag, 1.0 versus 1.5 micromol L(-1) for Hg) were small. Finally, concentrations which caused total suppression of cellular activity were sometimes preceded by an increased activity (Hg, Ni). We concluded that metal ions alter monocyte metabolic activity during extended exposures in vitro, but that the concentrations required are often near long-term lethal levels. Clinically, these results imply that the levels of metals released from dental alloys may be significant to monocytic function.

Cells, Cultured↗

PubMed2002

Components of dentinal adhesives modulate heat shock protein 72 expression in heat-stressed THP-1 human monocytes at sublethal concentrations.

Few studies have investigated the ability of dental resins to induce cellular stress at sublethal concentrations. Cellular stress, especially in immune cells such as monocytes, may modulate the biological response to materials or the host's ability to respond to bacterially mediated inflammation. The current study examined the ability of sublethal concentrations of 2-hydroxylethylmethacrylate (HEMA) and triethyleneglycol dimethacrylate (TEGDMA) to induce heat shock protein 72 (HSP72) in human monocytes. HEMA and TEGDMA significantly suppressed heat-induced HSP72 expression, even at sublethal levels, but did not induce HSP72 by themselves. The results of the current study suggest that components released from dental resin could modulate the HSP stress response without altering cellular metabolic activity.

Analysis of Variance↗

PubMed2002

Defects in growth and bone metabolism in klotho mutant mice are resistant to GH treatment.

Klotho mutant (kl/kl) mice exhibit growth retardation after weaning, and previous electron microscopic examination of GH-producing cells in pituitary glands revealed a reduction in GH granules. However, it has not been known whether growth retardation in klotho mutant mice is related to the loss of GH function. We therefore examined whether treatment with GH could rescue the retardation of growth. At the end of 3 weeks of treatment with human GH, the body weight of wild-type (WT) mice was increased. In contrast, body weight was not increased in klotho mutant mice even after the treatment with human GH. Another feature of klotho mutant mice is the presence of osteopetrosis in the epiphyses of long bones and vertebrae. Treatment with human GH increased trabecular bone volume in the epiphyseal region of WT tibiae. Interestingly, increase in trabecular bone volume by GH treatment was also observed in klotho mutant mice and, therefore, the phenotype of high bone volume in the klotho mice was further enhanced. These findings indicate that a GH receptor system in cancellous bones could operate in mutant mice. Thus, growth retardation in the klotho mutant mice is resistant against GH treatment even when these mice respond to GH treatment in terms of cancellous bone volume.

Animals↗

PubMed2002

Genetic effects on fatty acid composition of carcass fat of Japanese Black Wagyu steers.

Two hundred ninety-three Japanese Black Wagyu steers derived from 34 sires were used to investigate genetic effects on the fatty acid composition of carcass fat. All steers were fed identical diets for 365 d and slaughtered at similar ages. If the percentage of genetic contribution of sire A, B, or C was not lower than 25%, steers were classified into groups A, B, and C, respectively. Fatty acid compositions differed depending on deposit sites. Mean percentage of monounsaturated fatty acids (MUFA) tended to be higher in the outer parts than in the inner parts of the body. Percentage of MUFA in carcass fat was negatively correlated with withers height and BW and positively correlated with meat quality score and marbling score. Fatty acid compositions of the 34 sire groups varied, and mean percentages of MUFA in i.m. fat ranged from 47.71 to 54.77%. Steers in the C group grew larger than those in the A or B group. Mean percentages of MUFA for i.m. fat in the A, B, and C groups (52.83, 51.88, and 50.33%, respectively) differed (P < 0.05) from each other. Steers in the C group had higher (P < 0.05) percentages of saturated fatty acids than those in the A or B groups. Percentages of genetic contribution of sires B (P < 0.05) and C (P < 0.001) were negatively correlated with percentage of MUFA in i.m. fat. These results suggested that genetic factors affected fatty acid composition of carcass fat in Japanese Black Wagyu cattle and that some sires had potent genetic factors affecting this composition.

Adipose Tissue↗