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Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 181 records · Page 10Linked to original sources

Haemophilus influenzae has a GM1 ganglioside-like structure and elicits Guillain-Barré syndrome.

The authors report a patient with an axonal Guillain-Barré syndrome (acute motor axonal neuropathy) associated with anti-GM1 antibody after Haemophilus influenzae infection. The result of ELISA inhibition studies and cytochemical staining with cholera toxin suggest the presence of a GM1-like structure on the surface of H. influenzae isolated from the patient. A particular strain of H. influenzae may have a GM1-like structure and may elicit an axonal Guillain-Barré syndrome.

Adult↗

Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution.

BACKGROUND: Pulmonary reimplantation response, presenting lung edema, is a major obstacle of lung transplantation. Transalveolar fluid absorption mechanism, regulated by active transalveolar Na+ transport via Na+ channel and Na+-K+-ATPase, is considered to be essential for resolution of lung edema. We investigated the effect of lung preservation on this fluid transport mechanism. METHODS: The rat lungs were flushed and preserved with either EP4 solution (EP4) or Euro-Collins solution (EC). First, we determined the basal transalveolar fluid movement by calculating alveolar fluid clearance (AFC) after pulmonary flushing, 24- and 72-hr preservation. Then, we assessed the effects of Na+ channel blocker, amiloride, and Na+-K+-ATPase inhibitor, ouabain, on AFC after 24-hr preservation. We further measured lung ATP content and Na+-K+-ATPase activity after 24-hr preservation to evaluate cellular metabolism and enzymatic activity during preservation. RESULTS: We found that the lungs preserved with EC showed significantly lower AFC and less inhibitory effects of both blockers than with EP4 after 24-hr preservation. Na+-K+-ATPase activity was significantly lower with EC than with EP4, even though lung ATP content was not affected by preservation solution. CONCLUSIONS: EP4 preservation provides a better environment for maintaining transalveolar fluid absorption mechanism than EC preservation. Therefore, lung preservation with EP4 may ensure more reliable ability in resolving pulmonary edema.

Adenosine Triphosphate↗

Plasma membrane recruitment of RalGDS is critical for Ras-dependent Ral activation.

In COS cells, Ral GDP dissociation stimulator (RalGDS)-induced Ral activation was stimulated by RasG12V or a Rap1/Ras chimera in which the N-terminal region of Rap1 was ligated to the C-terminal region of Ras but not by Rap1G12V or a Ras/Rap1 chimera in which the N-terminal region of Ras was ligated to the C-terminal region of Rap1, although RalGDS interacted with these small GTP-binding proteins. When RasG12V, Ral and the Rap1/Ras chimera were individually expressed in NIH3T3 cells, they localized to the plasma membrane. Rap1Q63E and the Ras/Rap1 chimera were detected in the perinuclear region. When RalGDS was expressed alone, it was abundant in the cytoplasm. When coexpressed with RasG12V or the Rap1/Ras chimera, RalGDS was detected at the plasma membrane, whereas when coexpressed with Rap1Q63E or the Ras/Rap1 chimera, RalGDS was observed in the perinuclear region. RalGDS which was targeted to the plasma membrane by the addition of Ras farnesylation site (RalGDS-CAAX) activated Ral in the absence of RasG12V. Although RalGDS did not stimulate the dissociation of GDP from Ral in the absence of the GTP-bound form of Ras in a reconstitution assay using the liposomes, RalGDS-CAAX could stimulate it without Ras. RasG12V activated Raf-1 when they were coexpressed in Sf9 cells, whereas RasG12V did not affect the RalGDS activity. These results indicate that Ras recruits RalGDS to the plasma membrane and that the translocated RalGDS induces the activation of Ral, but that Rap1 does not activate Ral due to distinct subcellular localization.

3T3 Cells↗

Identification of DERMO-1 as a member of helix-loop-helix type transcription factors expressed in osteoblastic cells.

Several members of the basic helix-loop-helix (bHLH) type of transcription factors have now been reported, and almost every member of this class has been implicated in transcriptional regulation in cell type determination and differentiation. Previously, we reported that dominant negative HLH proteins are involved in osteoblastic phenotype expression, such as osteocalcin, and hence differentiation (Tamura and Noda [1994] J. Cell Biol. 126:773-782). In this work, we used degenerate PCR cloning in order to identify cDNA clones encoding bHLH proteins expressed in osteoblastic osteosarcoma ROS17/2.8 cells. Sequence analyses of the 47 clones revealed that 11 clones encoded products with a characteristic motif of the bHLH transcription factor family. Of these clones, sequences in the amplified region of seven clones were homologous to the mouse twist, and three clones were homologous to the mouse twist-related HLH protein, Dermo-1. To confirm Dermo-1 mRNA expression in osteoblastic cells, we performed reverse transcription polymerase chain reaction (RT-PCR) analysis using mRNA from ROS17/2.8 cells and MC3T3-E1 cells by Dermo-1 specific primers and Northern blot analysis. These analyses demonstrated that Dermo-1 mRNA was expressed in these osteoblast-like cell lines. Nucleotide sequence analysis of the partial rat Dermo-1 cDNA cloned from ROS17/2.8 library revealed that it has the highest degree of homology with the mouse Dermo-1 cDNA, and the partial amino acid sequence deduced from the obtained rat Dermo-1 was identical with the corresponding region of the mouse Dermo-1 amino acid sequence. To further examine the role of Dermo-1 in the regulation of osteoblastic differentiation, we examined mRNA levels of Dermo-1 and twist in C3H10T1/2 cells treated with recombinant human bone morphogenetic protein (rhBMP)-2. Using the RT-PCR method, the mRNA levels of Dermo-1 and twist were found to be decreased by the treatment with rhBMP-2 in C3H10T1/2 cells. We also observed that the mRNA level of Dermo-1 was decreased about fourfold by the treatment with rhBMP-2 in C3H10T1/2 cells by Northern blot analysis. Moreover, Dermo-1 mRNA was detected at lower levels in 21-day-old differentiated MC3T3-E1 cells compared with 3-day-old undifferentiated MC3T3-E1 cells. These results suggested that Dermo-1 could be involved in the osteoblastic differentiation in a negative manner.

Amino Acid Sequence↗

Effects of GDF7/BMP12 on proliferation and alkaline phosphatase expression in rat osteoblastic osteosarcoma ROS 17/2.8 cells.

Growth and differentiation factor 7(GDF7), also later called as bone morphogenetic protein (BMP)12, is a new member of the BMP superfamily, which induces formation of tendon-like tissue formation in the ectopic implantation experiments. We examined the effect of BMP12 on proliferation and expression of phenotype-related genes in rat osteoblastic osteosarcoma ROS17/2.8 cells. BMP12 treatment enhanced proliferation of ROS17/2.8 cells within 3 days and this effect was observed at least up to day 6 of the treatment. The cell number was increased by about 50% on day 3 and about two-fold by day 6. These effects were observed at the dose range between 40 and 1,000 ng/ml. Treatment with BMP12 also enhanced alkaline phosphatase activity by about 50% in ROS17/2.8 cells within 24 h of the treatment. The effect peaked at 48 h and was still observed at 72 h. The enhancing effect of BMP12 on alkaline phosphatase was observed similarly at the doses ranging from 40 to 1,000 ng/ml. These data indicate that BMP12 has positive effects on proliferation and phenotypic expression of ROS 17/2.8 cells.

Alkaline Phosphatase↗

Levels of expression of pleiotrophin and protein tyrosine phosphatase zeta are decreased in human colorectal cancers.

Pleiotrophin (PTN) and midkine (MK) form a distinct family of heparin binding growth factors. In a variety of human cancers, MK mRNA levels have been found to be increased as compared to adjacent non-cancerous tissues. We examined the expression of PTN, its putative receptor, namely protein tyrosine phosphatase zeta (PTPzeta, also known as RPTPbeta), and a related protein, receptor-type protein tyrosine phosphatase gamma (RPTPgamma), in human colorectal cancers and the adjacent normal mucosae. PTN and PTPzeta mRNA levels were generally decreased in colorectal cancers as compared to those in adjacent normal mucosae, while the RPTPzeta level was not significantly different between them.

Aged↗

Up-regulated cytoplasmic expression, with reduced membranous distribution, of the src substrate p120(ctn) in gastric carcinoma.

p120(ctn) is a substrate of the tyrosine kinase pp60 src. Tyrosine kinases such as src localize to the adherens junctions and phosphorylate junctional proteins in both normal and transformed cells.(1) p120(ctn) forms a complex with E-cadherin at the adherens junction and is phosphorylated by ligands such as epidermal growth factor receptor as well as pp60 src. Phosphorylation of p120(ctn) has been shown to correlate with cell transformation. The aim of this study was to investigate in vivo expression of p120(ctn) in gastric carcinoma and to examine any relationship to pathological characteristics and patient survival. Immunohistochemical staining for p120(ctn) was performed in 68 gastric carcinoma specimens (19 diffuse, 49 intestinal type), in 22 lymph node metastases, and in gastric mucosal biopsies from 16 patients with gastric dysplasia and ten healthy controls. Up-regulation of p120(ctn) cytoplasmic staining was seen in six (37 per cent) of the gastric dysplasia cases and in 45 (66 per cent) tumours (89 per cent of diffuse and 57 per cent of intestinal tumours). Loss of membranous distribution of staining for p120(ctn) was seen in 22 (32 per cent) tumours (52 per cent of diffuse and 24 per cent of intestinal tumours). The staining pattern in the primary tumour showed no correlation with tumour type, grade, or stage, or patient survival. Of 22 lymph node metastases examined, 13 (60 per cent) showed loss of membranous staining. In conclusion, staining for p120(ctn) in gastric carcinoma and dysplasia revealed marked up-regulation of cytoplasmic staining, sometimes associated with reduced membranous expression. Up-regulation of expression of p120(ctn) has not previously been described in human epithelial malignancy. The significance of these findings is uncertain, but they may reflect a change in tyrosine kinase signal transduction pathways, and a role for p120(ctn) in ligand-induced mitogenic signalling and cell transformation.

Adult↗

Current trends in restorative proctocolectomy: introduction of an ultrasonically activated scalpel.

PURPOSE: We evaluated the usefulness of an ultrasonically activated scalpel (Harmonic Scalpel) for mucosal proctocolectomy and ileal J-pouch-anal anastomosis. METHODS: Seventy-four patients with ulcerative colitis (70 patients) and familial adenomatous polyposis (4 patients) underwent mucosectomy using the Harmonic Scalpel since 1997. We compared the clinical and functional results with those of the monopolar electrocoagulator (forceps coagulation technique, 86 patients with colitis and 7 with polyposis). RESULTS: We performed graduated mucosal proctectomy by using the Harmonic Scalpel. The operative time (Harmonic Scalpel, 42 minutes vs. forceps coagulation technique, 85 minutes) and blood loss (Harmonic Scalpel, 33 ml vs. forceps coagulation technique, 86.8 ml) were significantly reduced by this method. The Harmonic Scalpel enabled restorative proctocolectomy by the synchronous approach within three hours. The functional results and complications were not significantly different between the two groups. CONCLUSION: The Harmonic Scalpel shortened the operative time, decreased blood loss, and was useful for restorative proctocolectomy in our study.

Adult↗

Functional evaluations for pulmonary resection for lung cancer in octogenarians. Investigation from postoperative complications.

We have reviewed the records of our twenty-four patients aged 80 years or older who underwent lung resections for bronchogenic carcinoma between 1983 and 1997 in our department. Eighteen patients were male and six were female. Adenocarcinoma was the histology in more than half of the cases (13 patients), along with 8 squamous cell carcinoma, 2 large cell carcinoma, and one small cell lung carcinoma. More than single lobectomy was performed in each patient. Unilateral pulmonary occlusion tests were employed in patients with impairment in pulmonary functions. Every patient, who underwent the unilateral pulmonary occlusion test, was certified that the total pulmonary vascular resistance index during unilateral pulmonary arterial occlusion test was less than 700 dyne.sec.cm-5.m2. Postoperative cardiovascular complications, such as paroxysmal atrial tachycardia, premature atrial contraction, premature ventricular contraction or atrial fibrillation, were seen in 10 patients. Postoperative respiratory complications, namely, sputa retention, retained secretions or atelectasis, were seen in 7 patients. The extent of dissection of mediastinal lymph node was not correlated to the postoperative pulmonary complications. However, the incidence of arrhythmias in the patients who received R2 mediastinal lymphnode dissection was much higher than in those who received R1 or R0 dissection. Complete blood counts and serum biochemical analysis performed at about three weeks after operations revealed leukocytosis and increases in levels of serum transaminase. These phenomena in leukocytosis and increases in the levels of serum transaminase in these patients were similar to those in younger patients. There was no operative death. We conclude that some patients over 80 years are candidates for lung resection after careful preoperative cardiopulmonary evaluation.

Adenocarcinoma↗

A comparison of methods for detecting bacteria in root canal exudate.

This study compared the ability of bacterial detection from intracanal exudate by two different methods. One is a conventional method (i.e. the samples were transported into anaerobic chambers immediately after sampling and then moved to an outside laboratory for identification of bacteria). Another is a preculture method (i.e. the samples were inoculated into semisolid medium immediately after sampling, incubated for 24 h under anaerobic conditions, and then moved to the laboratory for bacterial identification). In 22 cases, the preculture method detected bacteria in 18 of 22 cases, whereas the conventional method detected bacteria in 6 of 22 cases. The preculture method showed significantly higher frequency of bacterial detection (p = 0.0003). Gram-positive cocci (alpha-Streptococcus, Enterococcus, etc.) were detected in many cases. These results suggested that the preculture method could be helpful in detecting root canal bacteria and enhance antibiotic treatment of endodontic disease.

Adult↗

Glutamate release from microglia via glutamate transporter is enhanced by amyloid-beta peptide.

In the present study, we found that amyloid-beta peptide enhanced glutamate release from primary cultured rat microglia via the Na+-dependent glutamate transporter, which was activated by extracellular K+. Glutamate transport current was measured by a conventional whole-cell patch recording mode under voltage-clamp conditions. With the pipette solution containing 10 mM glutamate and 100 mM Na+, an increase of the external K+ concentration from 0 to 10 mM evoked an outward current, resulting from co-extrusion of glutamate and Na+. The inward current, reflecting forward glutamate transport, was also activated by external glutamate. Both these reverse and forward glutamate transport currents were three-fold greater in microglia incubated with a relatively low concentration of amyloid-beta peptide (25-35) (5 microM) for four days. The glutamate-activated inward current was blocked by D,L-threo-beta-hydroxyaspartate in a dose-dependent manner (ranging from 0.001 to 1 mM), but not by a high concentration of kainate (1 mM). The glutamate concentration released from microglia upon high-K+ stimulation was also significantly increased (up to 170 microM) after treatment with amyloid-beta peptide (25-35). These results suggest that, at the pathological sites where extracellular K+ concentration may increase, the activation of microglia by amyloid-beta peptide causes an increase in extracellular glutamate concentration via reverse glutamate transporter, and therefore this mechanism may contribute to the pathogenesis of neuronal dysfunction and death in Alzheimer's disease.

ATP-Binding Cassette Transporters↗

Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines.

Dysfunction of the cadherin-catenin complex, a key component of adherens junctions, is thought to confer invasive potential to cells. The aim of this study is to examine the expression and function of the E-cadherin/catenin complex in gastric carcinoma cell lines. Expression of E-cadherin, alpha, beta and gamma-catenin and p120ctn, and of the adenomatous polyposis coli protein (APC), together with function of the cadherin-catenin complex was examined in a panel of gastric carcinoma cell lines, using immunocytochemistry, Western blotting and a cell-cell aggregation assay. Protein interactions were examined by sequential immunoprecipitation and immunoblotting with antibodies to E-cadherin, alpha, beta and gamma-catenin, p120ctn and APC. Abnormalities of E-cadherin, alpha- and beta-catenin expression, were associated with disturbance of E-cadherin-catenin complex composition, loss of membranous localization and loss of calcium-dependent aggregation in six gastric carcinoma cell lines. APC protein expression and interaction with beta-catenin was preserved in five cell lines. We demonstrate frequent abnormalities of expression and function of E-cadherin and catenins, and associated disturbance of E-cadherin-mediated intercellular adhesion in gastric carcinoma cell lines. These findings support the tumour suppressor role of the E-cadherin and its contribution to the development and progression of the neoplastic phenotype in gastric carcinoma.

Animals↗

Regulatory interrelations among topographic molecules CBF1, CBF2 and EphA3 in the developing chick retina.

It has been shown that topographic expression of two winged-helix transcription factors, CBF1/c-qin and CBF2, and a receptor tyrosine kinase EphA3 (Mek4/Cek4) play important roles in establishing the topographic retinotectal projection map along the rostrocaudal axis. The interrelationship among these topographic molecules in the chick retina was studied during development. The topographic expression of CBF1 and CBF2 preluded the graded expression of EphA3, but their precise expression profiles did not exactly fit together. However, interestingly, CBF1 and CBF2 were properly expressed, together with EphA3, in immortalized cell lines derived from the quail retina, which maintained position-specific characteristics. The expression of another topographic molecule SOHo-1, the sensory organ homeobox-1 transcription factor, was separate from EphA3 expression. Ectopic expression of CBF1 using in ovo electroporation repressed the expression of CBF2, and misexpression of CBF2 influenced the graded localization of EphA3 in the retina, albeit imperfectly. Taken together, it is suggested that retinal cells first begin to express CBF1 or CBF2 according to their topographic positions, generate cellular descendants in which the expression of CBF1 and CBF2 is maintained cell-autonomously, and then establish the nasotemporal gradient of EphA3 under the control of CBF2, although indirect.

Alkaline Phosphatase↗

Specific expression of ezrin, a cytoskeletal-membrane linker protein, in a subset of chick retinotectal and sensory projections.

Lamina-specific neuronal connections are a fundamental feature in many parts of the vertebrate central nervous system. In the chick, the optic tectum is the primary visual centre, and it has a multilaminated structure consisting of 15 laminae, of which only three or four receive retinal projections. Each of the retinorecipient laminae establishes synaptic connections selectively from one of a few subsets of retinal ganglion cells (RGCs). We have generated a series of monoclonal antibodies that appear to stain only one of the retinorecipient laminae. One of these, TB4, stained lamina F which receives inputs from a subpopulation of approximately 10-20% of RGCs which express the presynaptic acetylcholine receptor beta2-subunit. TB4 recognized a single 79-kDa protein on immunoblotting. cDNA cloning and immunochemical analysis revealed that the TB4 antigen molecule was ezrin, a cytoskeletal-membrane linker molecule belonging to the ezrin-radixin-moesin family. Unilateral enucleation of the eye, both prior to and after the establishment of retinotectal projections, attenuated the lamina-selective staining with TB4 in the contralateral tectum, suggesting that ezrin is anterogradely transported from RGCs to lamina F. Ezrin was thus expressed in a subset of RGCs that project to lamina F. Similar subset-selective expression and resultant lamina-selective distribution of ezrin were also observed in the lamina-specific central projections from the dorsal root ganglia. The staining pattern with TB4 in the dorsal root ganglia and spinal cord indicated that high expression of ezrin was restricted in cutaneous sensory neurons, but not in muscle sensory neurons. Since ezrin modulates cell morphology and cell adhesion profiles by linking membrane proteins with the cytoskeleton, it was suggested that ezrin is involved in the formation and/or maintenance of lamina-specific connections for neuronal subpopulations in the visual and somatosensory systems.

Amino Acid Sequence↗

The interaction between F3 immunoglobulin domains and protein tyrosine phosphatases zeta/beta triggers bidirectional signalling between neurons and glial cells.

F3, a mouse glycosyl-phosphatidylinositol anchored molecule of the immunoglobulin superfamily, is known to influence axonal growth and fasciculation via multiple interactions of its modular immunoglobulin-like domains. We prepared an Fc chimeric molecule (F3IgFc) to identify molecules interacting with these domains and characterize the functional impact of the interactions. We affinity-isolated tenascin-C and isoforms of the proteoglycan-type protein tyrosine phosphatases zeta/beta (PTPzeta/RPTPbeta) from extracts of developing mouse brain. We showed that both PTPzeta/RPTPbeta and tenascin-C can bind directly to F3, possibly in an exclusive manner, with the highest affinity for the F3-PTPzeta/RPTPbeta interaction. We observed a strong binding of F3IgFc-coated fluorospheres to astrocytes in neural primary cultures and to C6 astrocytoma cells, and demonstrated, in antibody perturbation experiments, that F3-Ig binding on astrocytes depends on its interaction with PTPzeta/RPTPbeta. We also found by confocal analysis that tenascin-C and PTPzeta/RPTPbeta were colocalized on astrocytes which suggests a complex interplay of interactions between PTPzeta/RPTPbeta, tenascin-C and F3. We showed that the interaction between PTPzeta/RPTPbeta and F3-Ig-like domains can trigger bidirectional signalling. C6 glia-expressed PTPzeta/RPTPbeta stimulated neurite outgrowth by cortical and cerebellar neurons, whereas preclustered F3IgFc specifically modified the distribution of phosphotyrosine labelling in these glial cells. Both effects could be prevented and/or mimicked by anti-F3 and anti-6B4PG antibodies. These results identify F3 and PTPzeta/RPTPbeta as potential mediators of a reciprocal exchange of information between glia and neurons.

Animals↗

Effect of candesartan cilexetil (TCV-116) in rats with chronic renal failure.

BACKGROUND: Inhibition of the renin-angiotensin system by both angiotensin II type 1 receptor antagonists (AT1As) and angiotensin I-converting enzyme inhibitors (ACEIs) shows renoprotective effects in rats with chronic renal failure when treatment is started in the early phase of renal injury. In this study, we examined the renal protective effects of candesartan cilexetil (TCV-116), an AT1A, and enalapril, an ACEI, in the progressive phase of renal injury in 5/6 nephrectomized rats. METHODS: Candesartan cilexetil (1 mg/kg/day) and enalapril (10 mg/kg/day) were orally administered once a day for 4 weeks (the short-term experiment) or 16 weeks (the long-term experiment) to 5/6 nephrectomized rats beginning 15 weeks after the nephrectomy, that is, after they had already showed marked proteinuria. RESULTS: In vehicle-treated rats, proteinuria, glomerulosclerosis, and interstitial fibrosis developed. Moreover, enhanced expression of transforming growth factor-beta1 (TGF-beta1) in the injured glomeruli was observed. These adverse changes progressed with time, and in the short-term experiment, both drugs inhibited them. In the long-term experiment, the progressive proteinuria and the elevation of blood pressure were similarly attenuated by both drugs. However, candesartan cilexetil significantly inhibited the progression of glomerulosclerosis, the expression of TGF-beta1, and interstitial fibrosis, whereas enalapril did not. CONCLUSION: These results indicate that candesartan cilexetil shows potent and long-term preventive effects against the progression of previously developed renal injury.

Angiotensin Receptor Antagonists↗