Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 289 records · Page 16Linked to original sources

PubMed1997

[Role of leukotriene B4 in monocrotaline-induced pulmonary hypertension].

Monocrotaline (MCT) causes lung inflammation and chronic pulmonary hypertension associated with lung vascular thickening in rats. We hypothesized that leukotriene B4 (LTB4) and LTB4-induced accumulation of leukocytes in the lung play a role in MCT-induced lung disease, and therefore measured LTB4 and myeloperoxidase (MPO) levels in lung tissue of MCT-treated rats. Next, we examined the effect of an orally active LTB4 receptor antagonist (ONO4057) on MPO levels in lung tissue, on pulmonary hypertension, and on pulmonary vascular remodeling induced by MCT. Lung LTB4 and MPO levels had increased by 3 days after MCT injection. In the ONO4057-treated MCT rats, lung MPO levels were significantly lower than in the rats given MCT but not ONO4057. By the third week after injection. MCT had caused increases in mean pulmonary arterial pressure, in the ratio of right ventricular weight to left ventricle+septum weight (RV/[VS + S]), and in media wall thickness of the muscular arteries of the lung. Treatment with ONO4057, either for 3 weeks or during the first week after MCT injection, significantly reduced pulmonary hypertension, right ventricular hypertrophy, and lung vascular thickening induced by MCT. These results indicate that ONO4057 reduces both the accumulation of leukocytes in lung tissue and the chronic pulmonary hypertension induced by MCT, and they suggest a role for LTB4 in the inflammatory process that contributes to pulmonary hypertension and lung vascular remodeling induced by MCT in rats.

Animals↗

PubMed1997

[Early postirradiation changes in Na+ and fluid transport across alveolar epithelium in rats].

To study changes in Na+ and fluid transport that occur soon after irradiation of the thorax, we used fluid-filled isolated rat lungs. Irradiation 15 Gy of 60Co doubled the fluid absorption rate across the alveolar epithelium within 2 weeks, but fluid absorption had returned to the baseline values by 3 weeks after irradiation. The timing of this change in fluid absorption was parallel to the time course of Na+ escape across alveolar epithelium and the two correlated closely. These data suggest that a dysfunction of alveolar epithelial Na+ transport is involved in the development of pulmonary edema after irradiation of the thorax.

Animals↗

PubMed1997

[Effect of thoracoscopic procedure versus standard posterolateral/muscle-sparing thoracotomy on pulmonary lung function].

To understand the effects of thoracoscopic approach to thoracotomy on lung function, we investigated the changes in lung function after thoracoscopic operation (n = 7) and compared them to those after standard posterolateral (n = 5) or muscle-sparing thoracotomy (n = 6). In 18 patients with benign lung tumor in which surgical treatment resected in partial resection of the lung tissue, we measured TLC, VC, RV, FEV1.0, FEV1.0%, Peak Flow and DLco preoperatively and at 2, 4 weeks postoperatively. In the standard posterolateral or muscle-sparing thoracotomy groups, FVC, TLC, FEV1.0 and Peak Flow decreased to about 80% of preoperative value at 2 weeks. At 4 weeks after operation, these values showed to increase some what, but did not reach to the preoperative value. Whereas, the thoracoscopic procedure group, did not show the decrease in lung function through the time course. There was not significant different between standard posterolateral and muscle-sparing thoracotomy. We conclude that thoracoscopic approach is an useful technique to thoracotomy because of its minimizing after thoracotomy effect of lung function loss.

Adult↗

PubMed1997

[A case of bronchial stenosis due to postoperative inflammation treated with expandable metallic stent].

We presented a 61-year-old man who had undergone a left sleeve upper resection because of a squamous cell carcinoma of the upper lobe of the left lung. At 5 weeks after the operation, the anastomosis between the left main bronchus and the left lower bronchus became stenotic, therefore pneumonitis occurred below the anastomosis. Because of the inflammatory granulo stenosis for short time, we used an expandable metallic stent to save a residual lung function of the operated side. The anastomosis between the left main bronchus and the left lower bronchus was kept open satisfactorily, and in the late postoperative periods the residual lung function recovered until the levels of predicted residual lung function.

Anastomosis, Surgical↗

PubMed1997

Possible involvement of MSX-2 homeoprotein in v-ras-induced transformation.

A truncated MSX-2 homeoprotein was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in untransformed cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a full-length human MSX-2 cDNA and tested its activities in two cell systems: fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated MSX-2 cDNA interfered with the transforming activities of both v-Ki-ras and v-raf oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and truncated MSX-2 cDNA was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that the truncated version MSX-2 may act as a dominant suppressor of intact MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.

3T3 Cells↗

PubMed1997

Characterization of a mammalian cell death gene Nedd2.

Through subtraction cloning approach, we have identified a set of mouse genes with developmentally down-regulated expression in brain. One such gene, termed Nedd2, was found to encode protein similar to the mammalian interleukin-1b-converting enzyme (ICE) and the product of the nematode (C. elegans) cell death gene ced-3. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.

Animals↗

PubMed1997

Activation of the JAK1-STAT5 pathway by binding of the Friend virus gp55 glycoprotein to the erythropoietin receptor.

Friend spleen focus forming-virus (F-SFFV) induces acute erythroleukemia in susceptible mice. Initiation of the erythroleukemia is due to binding of the env-related glycoprotein gp55 encoded by F-SFFV to the erythropoietin receptor (EPOR). The gp55/EPOR interaction induces prolonged and growth factor independent proliferation in a factor-dependent cell line. In erythropoietin (EPO) signaling, the JAK2/STAT5 pathway was shown to be activated downstream of the EPOR to transmit the signal to the cells. To determine members of the JAK family and the STAT transcription factor family involved in the gp55/EPOR signaling, we examined tyrosine phosphorylation of JAKs and STATs in F-SFFV-infected erythroid or erythroleukemic cells. JAK1 and STAT5 were constitutively tyrosine-phosphorylated but the DNA binding activity of STAT5 was not induced without EPO stimulation in erythroblastoid cells from spleens of F-SFFV-infected mice and erythroleukemia cell lines derived from gp55-transgenic mice. These results indicate that JAK1 is involved in the gp55/EPOR signaling but STAT5 is not playing an essential role in the growth of those erythroid cells.

Animals↗

PubMed1997

[Increase in pulmonary vascular permeability caused by increased expression of Mac-1 on the surface of polymorphonuclear leukocytes].

We studied the expression of adhesion molecules on the surface of human polymorphonuclear leukocytes (PMNs). The effects of mechanical stimulation were measured with a flow cytometer and pulmonary vascular injury due to accumulation of PMNs in the lungs was assessed by a gravimetric method. The accumulation of PMNs in the lungs was studied by measuring the amount of myeloperoxidase. PMNs were stimulated by gentle agitation in a glass container for 10 s. Mac-1 (CD11b/CD18) was upregulated on the surface of PMNs that were mechanically stimulated. When unstimulated PMNs were exposed to isolated rat lungs, the filtration coefficient did not change from that under baseline conditions. However, when mechanically stimulated PMNs were exposed to isolated rat lungs, the filtration coefficient was about 5 times higher than that measured at baseline. When mechanically stimulated PMNs treated with anti-CD18 antibody were used, the increase in the filtration coefficient was completely blocked. The assay of myeloperoxidase revealed that PMNs stuck to isolated rat lungs only after stimulated PMNs were added. We conclude that when the adhesiveness of PMNs is increased by mechanical stimulation, these cells adhere to pulmonary vessels and increase pulmonary vascular permeability.

Animals↗

PubMed1997

Molecular and genetic analysis of two patients with Bernard-Soulier syndrome--identification of new mutations in glycoprotein Ib alpha gene.

We investigated two unrelated patients with Bernard-Soulier syndrome (BSS) by performing molecular and genetic analysis. A flow cytometric and immunoblotting analysis showed GP Ib alpha to be absent from the platelet membrane of both patients. Other glycoproteins that formed GP Ib/IX/V complex were present on the platelets, but in decreased amounts. Therefore, GP Ib alpha gene from both cases was sequenced after PCR amplification and subcloning. We identified a homozygous mutation of a dinucleotide deletion within the TGTG repeat at cDNA number 972 to 975 in GP Ib alpha gene from Case 1. In Case 2, compound heterozygosity was demonstrated in GP Ib alpha gene; an insertion of a single base (T) at cDNA number 1,418 in one allele, and a deletion of a single base (A) within the 7-adenine repeat at cDNA number 1,438 to 1,444 in another allele. The three new mutations in both patients appeared to cause a frameshift, which created a new termination codon shortly thereafter, and thus lead to a GP Ib alpha deficiency on the platelet membrane. Truncated mutant proteins could be detected in the plasma and platelets of Case 2, but not of Case 1. According to these findings, it is thus supposed that the properties and conformation of additional COOH-terminal peptides, which were supposedly synthesized as results of the mutations, may have an important role on the processing of mutant GP Ib alpha in megakaryocytes and platelets.

Adult↗

PubMed1997

[Prediction of postoperative pulmonary hemodynamics for the second lobectomy after the contralateral lobectomy].

We presented 7 cases who were performed the second lobectomy for the second lung cancer after the first successful lobectomy on the contralateral lung (3 cases for right upper lobectomy + left lower lobectomy and 4 cases for right upper lobectomy + left lower lobectomy). In 6 patients, the predicted postoperative FEV1 estimated by multiplying the preoperative FEV1 by the fraction of perfusion to the contralateral lung was less than 800 ml/m2BSA, which is our first cut-off for identifying lung resection candidates. Unilateral pulmonary arterial occlusion test (UPAO) revealed that total pulmonary vascular resistance (TPVRI) in 3 of those 6 patients was lower than 700 dyne.sec.cm-5/m2BSA, our second cut-off for lung resection. More precise postlobectomy pulmonary hemodynamics in another 3 of those 6 patients were then estimated by adapting selective pulmonary occlusion test (SPAO). Since TPVRI during SPAO was lower than the cut-off value, it was suggested that second lobectomy would be feasible with low incidence of post operative cardiopulmonary complication. There was no serious complications in all 7 cases during their postoperative course. We believe that more precise prediction of postoperative pulmonary hemodynamics by adapting UPAO and SPAO could be one of the tools to minimumize postoperative cardiopulmonary complications in those patients needed second lobectomy for the second lung cancer after the first successful lobectomy on the contralateral lung even though their impaired lung fung function.

Aged↗

PubMed1997

[Video-assisted thoracoscopic surgery of bilateral dissemination of invasive thymoma: report of a case].

Eight years ago, A 29-year-old woman was admitted by complaining with facial edema and dyspnea. A chest x-ray film and computed tomography showed an anterior mediastinal tumor that invaded to the superior vena cava and the trachea. A bronchoscopic biopsy revealed that the tumor was a thymoma. We performed radiotherapy and chemotherapy because a surgical operation was not possible. The size of the tumor was slightly reduced after those therapies roentgenographically. We followed up the subsequent of history of the patient. Eight years later, July, 1995, chest computed tomography showed bilateral disseminations of invasive thymoma. The disseminated tumors were removed by two-stage video assisted thoracoscopic surgery (VATS), to preserve collateral veins so that collateral venous circulations were preserved. She discharged 20 days after second VATS uneventfully.

Adult↗

PubMed1997

Effects of candesartan cilexetil (TCV-116) and enalapril in 5/6 nephrectomized rats.

The renal protective properties of candesartan cilexetil (TCV-116), an angiotensin II type 1 receptor antagonist (AT1A), and enalapril, an angiotensin I converting enzyme inhibitor (ACEI), were investigated in 5/6 nephrectomized (NX) rats. Candesartan cilexetil (1 mg/kg/day) and enalapril (10 mg/kg/day) were administered orally to 5/6 NX rats for four weeks (during the early phase of disease development) or 16 weeks (through the late phase). In vehicle-treated rats, proteinuria, glomerulosclerosis, interstitial mononuclear cell (MNC) infiltration and interstitial fibrosis developed. Moreover, immunohistological studies showed enhanced expression of transforming growth factor-beta 1 (TGF-beta 1) in the injured glomeruli. Both drugs inhibited these adverse changes in the early phase. In the late phase, the progressive proteinuria, interstitial MNC infiltration were attenuated by both drugs. However, candesartan cilexetil significantly inhibited the progression of glomerulosclerosis, the expression of TGF-beta 1 and the interstitial fibrosis, while enalapril did not. Candesartan cilexetil and enalapril showed comparable hypotensive effects after the 16-week administration. These results indicate that candesartan cilexetil shows a more potent protective effect than enalapril against the progression of renal injury in the late phase. Thus, an AT1A might be more useful than an ACEI for the treatment of patients with chronic renal failure.

Angiotensin II↗

PubMed1996

Cleavage of single- and double-stranded DNAs containing an abasic residue by Escherichia coli exonuclease III (AP endonuclease VI).

The Escherichia coli exonuclease III (AP endonuclease VI) is a DNA-repair enzyme that hydrolyzes the phosphodiester bond 5' to an abasic site in DNA. To study how the enzyme recognizes the abasic site, we used oligonucleotides containing a synthetic abasic site at any desired position in the sequence. We prepared oligonucleotides containing an abasic residue such as 2'-deoxyribosylformamide, 2'-deoxyribose, 1',2'-dideoxy ribofuranose or propanediol. Duplex oligonucleotides containing an abasic residue used in this study were cleaved on the 5' side of the abasic site by exonuclease III in spite of the varieties of the bases opposite and adjacent to the abasic site. In addition, we observed that the enzyme cleaved single-stranded oligonucleotides containing an abasic site on the 5' side of the abasic site. These findings suggest that the enzyme may principally recognize the DNA-pocket formed at an abasic site. The indole ring of the tryptophan 212 residue of the exonuclease III is probably intercalated to the abasic site. The tryptophan in the vicinity of the catalytic site is conserved in the type II AP endonuclease from various organisms.

DNA, Bacterial↗

PubMed1996

Characterization of mutations induced by 300 and 320 nm UV radiation in a rat fibroblast cell line.

The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at four wavelengths (254, 290, 300 and 320 nm) were determined using a rat fibroblast cell line CREF stably infected with a retroviral vector carrying the neo and HSV-tk markers. In this system, mutations can be positively detected as acyclovir-resistant colonies. Although the action spectra for these activities closely fit some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing and mouse skin carcinogenesis, they diverge at 320 nm from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of the HSV-tk mutants detected after irradiation with 300 and 320 nm UV revealed (1) CC dimers and C oligomers as predominant targets at both wavelengths; (2) increased incidence of relatively large deletions at 300 nm; and (3) greatly increased frequency of tandem double mutations at both wavelengths and of clustered multiple mutations at 320 nm. These results suggest the involvement of distinct mechanisms specifically operating, or becoming evident, in UV-mediated mutagenesis at these different wavelengths in mammalian cells.

Acyclovir↗

PubMed1996

6B4 proteoglycan/phosphacan, an extracellular variant of receptor-like protein-tyrosine phosphatase zeta/RPTPbeta, binds pleiotrophin/heparin-binding growth-associated molecule (HB-GAM).

A major chondroitin sulfate proteoglycan in the brain, 6B4 proteoglycan/phosphacan, corresponds to the extracellular region of a receptor-like protein-tyrosine phosphatase, PTPzeta/RPTPbeta. Here, we purified and characterized 6B4 proteoglycan-binding proteins from rat brain. From the CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid) extract of brain microsomal fractions, 18-, 28-, and 40-kDa proteins were specifically isolated using 6B4 proteoglycan-Sepharose. N-terminal amino acid sequencing identified the 18-kDa protein as pleiotrophin/heparin-binding growth-associated molecule (HB-GAM). Scatchard analysis of 6B4 proteoglycan-pleiotrophin binding revealed low (Kd = 3 nM) and high (Kd = 0.25 nM) affinity binding sites. Chondroitinase ABC digestion of the proteoglycan decreased the binding affinities to a single value (Kd = 13 nM) without changing the number of binding sites. This suggested the presence of two subpopulations of the proteoglycan with different chondroitin sulfate structures. Heparin potently inhibited binding of 6B4 proteoglycan to pleiotrophin (IC50 = 3.5 ng/ml). Heparan sulfate and chondroitin sulfate C inhibited moderately (IC50 = 150 and 400 ng/ml, respectively), but, in contrast, chondroitin sulfate A and keratan sulfate were poor inhibitors (IC50 > 100 microg/ml). Immunofluorescence and immunoblotting analyses indicated that both 6B4 proteoglycan and PTPzeta are located on cortical neurons. Anti-6B4 proteoglycan antibody added to the culture medium suppressed pleiotrophin-induced neurite outgrowth of cortical neurons. These results suggested that interaction between 6B4 proteoglycan and pleiotrophin is required for the action of pleiotrophin, and chondroitin sulfate chains on 6B4 proteoglycan play regulatory roles in its binding.

Amino Acid Sequence↗

PubMed1996

The S29 ribosomal protein increases tumor suppressor activity of K rev-1 gene on v-K ras-transformed NIH3T3 cells.

The human S29 ribosomal protein (S29 rp) cDNA has been isolated from differential hybridization screening of a colon carcinoma cDNA library. Northern blot analysis showed that the level of S29 rp mRNA was higher in undifferentiated HT29 human colon carcinoma cells than in a morphologically differentiated subclone under the same growth condition. Furthermore, the level of S29 rp mRNA was downregulated in rapidly proliferating HT29 cells, as compared to the contact inhibited cells. Interestingly, the amount of Krev-1 mRNA was inversely correlated with respect to the amount of S29 rp mRNA in these cells. To examine a functional link between S29 rp and Krev-1 protein, we co-transfected the expression vectors containing wild-type or mutant S29 rp and mutationally activated Krev-1(63E) cDNAs into the v-Ki-ras-transformed NIH3T3 (DT) cells, and observed the induction of flat revertants. Krev-1(63E) induced a certain amount of flat colonies, while S29 rp alone also induced flat colonies at low frequencies. Interestingly, revertant-inducing activity of Krev-1(63E) was significantly enhanced by S29 rp. We have also demonstrated that a zinc finger-like domain of S29 rp indeed has a zinc binding activity and a derivative, S29 rp(ms), which was unable to bind zinc ion but still retained revertant inducing activity by itself, could not functionally interact with Krev-1(63E) protein.

3T3 Cells↗

PubMed1996

Visual projection map specified by topographic expression of transcription factors in the retina.

Topographical maps of neuronal connectivity occur in various brain regions. In the visual system of birds, retinal ganglion-cell axons from the anterior retina connect to a posterior part of the optic tectum, and posterior retinal axons connect to the anterior part, thereby establishing a point-to-point projection map. The chemoaffinity theory predicts that the orderly retinotectal projection is generated by a topographical arrangement of molecules. We report here that we have found several genes topographically expressed along the nasotemporal (anterior-posterior) axis in the embryonic chicken retina. Among these, two transcriptional regulators, belonging to the winged-helix family are expressed in a mutually exclusive manner in either the nasal or temporal part of the retina. Misexpression of each factor causes misprojection on the tectum along the rostrocaudal axis, showing that topographical expression of these transcription factors controls formation of the retinotectal map.

Alkaline Phosphatase↗

PubMed1996

Characterization of a human MSX-2 cDNA and its fragment isolated as a transformation suppressor gene against v-Ki-ras oncogene.

A cDNA (termed CT124) encoding a carboxyl-terminal fragment of the human homeobox protein MSX-2 was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in NIH3T3 cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a near full-length human MSX-2 cDNA and tested its activities in two cell systems, i.e. fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated CT124 cDNA interfered with the transforming activities of v-Ki-ras oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and CT124 was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that CT124 may act as a dominant suppressor of MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.

3T3 Cells↗