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M Higashiyama

Publications and source records attributed to M Higashiyama.

At least 91 records · Page 5Linked to original sources
PubMed1997

Extracellular ATP promotes cellular growth of renal inner medullary collecting duct cells mediated via P2u receptors.

The present study was undertaken to determine whether extracellular adenosine 5'-triphosphate (ATP) promotes cellular proliferation of cultured rat renal inner medullary collecting duct cells. Extracellular ATP increased inositol 1,4,5-triphosphate (IP3) production and cellular free calcium concentration - [Ca2+]i - in a dose-dependent manner. ATP also caused a transient cellular acidification. Extracellular ATP activated mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation in a dose-dependent manner. However, such effects were not obtained with adenosine 5'-diphosphate, adenosine monophosphate, and adenosine. In addition, uridine triphosphate, a P(2u) purinergic agonist, increased IP3 production and activated MAP kinase. 2-Methylthio ATP, a P(2y) purinergic agonist, also increased IP3 production, but did not affect the MAP kinase activity. We also examined the effect of arginine vasopressin on cellular growth. Arginine vasopressin did not alter MAP kinase activity and [3H]thymidine incorporation in cultured rat renal inner medullary collecting duct cells. These results indicate that extracellular ATP activates phospholipase C mediated through P(2u) and P(2y) purinergic receptors and promotes cellular proliferation mediated through P(2u) purinergic receptors in renal inner medullary collecting duct cells.

Adenosine Triphosphate↗
PubMed1997

Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)

We report a patient with herpetiform pemphigus (HP) who showed reactivity only with pemphigus vulgaris (PV) antigen but not with pemphigus foliaceus (PF) antigen. Direct and indirect immunofluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid-separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV, in addition to PF, with unique clinical and histological features.

Autoantigens↗
PubMed1996

Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.

As part of our evaluation of members of the transmembrane 4 super-family as possible prognostic predictors, we performed a retrospective study on the expression of the recently identified KAI1 gene by tumors of the lung. This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression. We used reverse transcription-PCR to analyze tumor tissues from 151 lung cancer patients; 74 tumors were stage I, 17 were stage II, and 60 were stage III. Our results indicate that while 35 patients had tumors in which the KAI1/CD82 gene was conserved (positive), 116 patients had tumors with reduced gene expression (negative). The overall survival rate of patients with KAI1/CD82-positive tumors was significantly higher than that of patients with KAI1/CD82-negative tumors (77.4% versus 38.5%; P=0.002). Furthermore, the overall survival rate of patients with KAI1/CD82-positive adenocarcinoma was also much higher than that of individuals whose adenocarcinoma had reduced KAI1/CD82 expression (73.4% versus 27.1%;P=0.009). Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status. Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis. These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis. This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.

Age Factors↗
PubMed1996

Ectopic primary pleural thymoma: report of a case.

We herein report an 83-year-old man who presented with a pleural tumor in the right thorax. The tumor was surgically resected and histopathologically diagnosed as ectopic primary pleural thymoma lacking any evidence of a mediastinal tumor. The clinicopathological aspects of this unusual thymoma are also discussed.

Aged↗
PubMed1996

Analysis of antigens recognized by autoantibodies in herpes gestationis. Usefulness of immunoblotting using a fusion protein representing an extracellular domain of the 180 kD bullous pemphigoid antigen.

Herpes gestationis (HG) is a rare pregnancy-associated disease. The aim of this study was to compare various immunohistochemical and immunobiochemical techniques with respect to their diagnostic sensitivity for HG. We studied 43 HG sera; only half of these reacted with the basement membrane zone (BMZ) with both indirect immunofluorescence (IF) and complement IF of normal human skin. 81% of the sera reacted with the epidermal side of 1 M NaCl-split skin. In general, titers of anti-BMZ antibodies in HG sera were lower than those in bullous pemphigoid (BP) sera. Immunoblot analysis of human epidermal extracts showed that 51% of HG sera recognized the 180 kD BP antigen (BP180) and 26% recognized the 230 kD BP antigen (BP230). We also studied the reactivity of HG sera with fusion proteins representing either the NC16a domain of human BP180 or the C-terminal region of mouse BP230. Whereas 79% of HG sera reacted with the BP180 fusion protein, only 5% recognized the BP230 fusion protein. Our results suggest that indirect IF of 1 M NaCl-split skin and immunoblotting of a fusion protein representing the BP180 NC16a domain are more sensitive techniques for the diagnosis of HG than conventional and complement IF or immunoblotting of crude epidermal extracts.

Animals↗
PubMed1996

Cellular signaling and proliferative action of AVP in mesangium of SHR: effect of low density lipoprotein.

The present study was undertaken to determine whether low density lipoprotein (LDL) modulates the cellular action of arginine vasopressin (AVP) in cultured glomerular mesangial cells of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The AVP-induced cellular signal transduction, including inositol 1,4,5-trisphosphate (IP3) production, fura-2 intracellular calcium measurements and cellular alkalinization, was significantly greater in cells of SHR than those of WKY. This is based on an increase in AVP V1 receptor number in cells of the SHR. Also, the AVP activation of mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation was significantly exaggerated in cells of SHR compared with those of WKY. LDL at a concentration of 10 micrograms/ml augmented the cellular signaling and proliferative action of AVP in cells of WKY, but not in those of SHR. Since [3H]AVP receptor binding was not affected by the LDL pretreatment, LDL modulates the signal transduction between a location distal to the AVP receptors and proximal from the production of IP3 and diacylglycerol. These results indicate that an increase in AVP receptor capacity has a profound effect on the AVP-induced cellular signaling and proliferation, and that LDL has a slight alteration on the action of AVP in glomerular mesangial cells of SHR.

Animals↗
PubMed1996

Specific detection of anti-cell surface antibodies in herpes gestationis sera.

We examined 42 herpes gestationis sera with immunofluorescence of normal human skin sections, and found that anti-keratinocyte cell surface antibodies were detected specifically in 10 herpes gestationis sera. The diagnosis of these herpes gestationis cases was confirmed by detecting antibodies against the 180 kD bullous pemphigoid antigen with immunoblotting of its fusion protein. The results of immunoadsorption assay using baculoproteins of both pemphigus vulgaris and pemphigus foliaceus antigens indicated that the herpes gestationis sera did not recognize common pemphigus antigens. Immunoblotting of human epidermal extracts and immunofluorescence of various tissues also suggested that the sera did not recognize any other desmosomal components or paraneoplastic pemphigus antigens. The significance of this reactivity is unclear. However, because no control bullous pemphigoid sera showed this reactivity, it may suggest a different pathophysiology between herpes gestationis and bullous pemphigoid.

Antigens, Surface↗
PubMed1996

Bcl-2 oncoprotein expression is increased especially in the portion of small cell carcinoma within the combined type of small cell lung cancer.

Immunohistochemical analysis of Bcl-2 oncoprotein, one of the oncogenes associated with the regulation of programmed cell death, was performed on 12 surgically resected tumors of the combined type of small-cell lung cancer. Ten cases (83%) expressed Bcl-2 oncoprotein within the tumor tissues. Two of them showed its expression in both the small cell carcinoma and non-small cell carcinoma types, and 7 cases exhibited Bcl-2 expression only in the portion of the small cell carcinoma. Considering previous reports indicating a high prevalence of Bcl-2 oncoprotein expression in small cell lung cancer, it is suggested that Bcl-2 oncoprotein even in the combined type of lung cancer may play an important role in tumorigenesis and tumor development and ensuing histological alterations between small cell carcinoma and non-small cell carcinoma types.

Aged↗
PubMed1996

The activation of phospholipase D participates in the mitogenic action of arginine vasopressin in cultured rat glomerular mesangial cells.

The present study was undertaken to determine whether phospholipase D participates in the mitogenic action of arginine vasopressin (AVP) in cultured rat glomerular mesangial cells. AVP promptly increased the phosphatidylethanol formation in a concentration-dependent manner, which indicates the activation of phospholipase D. When cells were preincubated with 2,3-diphosphoglycerate or carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), inhibitors of phospholipase D, the 1 x 10(-7) M AVP-produced phosphatidylethanol was significantly attenuated. Also, inhibitors of protein kinase C, staurosporine and calphostin C, reduced the AVP-induced increase in phosphatidylethanol. AVP activated mitogen-activated protein (MAP) kinase in a concentration-dependent manner. Such an activation was significantly reduced by 2,3-diphosphoglycerate, zLYCK, or staurosporine. Also, AVP stimulated [3H]thymidine incorporation, an effect significantly less in the presence of 2,3-diphosphoglycerate or zLYCK. Similar results were obtained with exogenous bacterial phospholipase D. Both MAP kinase and [3H]thymidine incorporation were not altered by 2,3-diphosphoglycerate or zLYCK per se. These results indicate that AVP activates phospholipase D and promotes cellular growth mediated through phospholipase D, in addition to a phospholipase C-dependent signal transduction, in glomerular mesangial cells.

2,3-Diphosphoglycerate↗
PubMed1996

Inhibition by adrenomedullin of arginine vasopressin-activated mitogen-activated protein kinase in rat glomerular mesangial cells via cAMP production.

The present study was undertaken to determine whether adrenomedullin modulates the arginine vasopressin (AVP)-activated mitogen-activated protein (MAP) kinase in cultured rat glomerular mesangial cells. AVP dose-dependently increased cellular free calcium, and this increase was unaffected by adrenomedullin. Adrenomedullin increased cellular cAMP production in a dose-dependent manner and AVP activated MAP kinase in a dose-dependent manner. When cells were preincubated for 15 min with adrenomedullin at concentrations of 1 X 10(-8) M or higher, the AVP-activated MAP kinase was significantly reduced. In addition, the activation of MAP kinase by phorbol-12-myristate-13-acetate (PMA) was significantly inhibited by adrenomedullin. Similarly, forskolin also diminished the activation of MAP kinase by AVP and PMA. The inhibition by adrenomedullin or forskolin of AVP-activated MAP kinase disappeared when cells were preexposed to H-89, an inhibitor of protein kinase A. These results indicate that adrenomedullin inhibits the AVP activation of MAP kinase mediated through cAMP in glomerular mesangial cells and that the site of action of adrenomedullin is behind the site of activation of protein kinase C.

Adrenomedullin↗
PubMed1995

Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.

Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to demonstrate that the level of MRP-1/CD9 expression was inversely related to the clinical stage of a given carcinoma of the breast. In addition, we found that the primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than their respective metastatic lymph nodes. In consideration of these findings, we have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP-1/CD9-positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than did other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence.

Antigens, CD↗
PubMed1995

Alpha-1-antichymotrypsin expression in lung adenocarcinoma and its possible association with tumor progression.

BACKGROUND: Alpha-1-antichymotrypsin (ACT) is a serine protease inhibitor, expression of which has been shown in various tumor types, but its biologic and clinical implications in tumor tissues are obscure. The authors examined ACT expression in lung adenocarcinoma to determine its clinicopathologic and prognostic significance. METHODS: First, reverse transcriptase-polymerase chain reaction (RT-PCR) using oligonucleotide primers specific for ACT and Western blotting and immunohistochemical methods using anti-ACT antibodies were performed in several lung adenocarcinoma cell lines. Secondly, ACT expression in clinical materials was examined immunohistochemically. RESULTS: By RT-PCR, Western blotting, and immunohistochemical methods, ACT synthesis was confirmed in several lung adenocarcinoma cell lines. Seventy-five (52%) of 170 surgically resected lung adenocarcinomas showed positive staining for ACT mainly in the cytoplasm, and the incidence of ACT expression was significantly higher in advanced T classification tumors (P = 0.009) or large sized tumors (P = 0.004). Tumors with a higher rate of mitosis were significantly positive for ACT expression (P = 0.023). Patients with ACT-positive adenocarcinoma had a shorter disease free survival (DFS) and a poor prognosis compared with those who were ACT-negative, most significantly among Stage I tumors (DFS, P = 0.003; overall survival, P = 0.006). In a multivariate analysis, the P value of ACT expression status in Stage I tumors was marginally significant (overall survival; P = 0.058). CONCLUSIONS: These results using cell lines suggest the potential productivity of ACT by lung adenocarcinoma cells. The data in clinical materials, combined with results of the previous report that ACT in breast cancer acts as a minor growth factor-like substance, suggest that ACT expression in lung adenocarcinoma also may be associated closely with tumor progression and especially with tumor growth. Alpha-1-antichymotrypsin expression status in Stage I tumors may be a potential independent prognostic factor.

Adenocarcinoma↗
PubMed1995

A new approach for performing a one-stage operation through the mediastinum to resect bilateral lung metastases: report of a case.

We describe herein a new operative technique for reaching the opposite lung from the thoracotomy site through the mediastinum. This procedure was successfully performed on a 76-year-old woman with bilateral lung metastases whose case is presented. After resection of the right lower lobe which contained two metastases, the anterior mediastinum was opened, and contralateral metastasis located in the lingular segment was resected using a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. A chest drainage tube was inserted through the mediastinal window. This transmediastinal approach seems to be a feasible technique for preserving the respiratory function of the chest wall in patients with imbalanced bilateral metastases.

Aged↗
PubMed1995

Lymphoepithelioma-like carcinoma of the lung: analysis of two cases for Epstein-Barr virus infection.

Lymphoepithelioma-like carcinoma, which is an uncommon histological type of epithelial tumor, has been described as being closely associated with Epstein-Barr virus (EBV) infection in organs other than the lung. Recently, we experienced two surgically resected cases of pulmonary tumors mimicking lymphoepithelioma-like carcinoma. Both cases contained EBV DNA genomes as shown by polymerase chain reaction (PCR) using EBV DNA-specific primers, one positive for EBV DNA in virtually all cancer cells, and the other showing positive hybridization in a small number of cancer cells by in situ hybridization (ISH) using digoxigenin-labeled olignucletide probes for each of EBV DNA for EBV DNA. EBV-encoded RNA-1 (EBER-1) was typically detected in one case. These results are highly suggestive of EBV-associated tumors in one of the current cases, although in the other case, no such close association was determined. It seems that lymphoepithelioma-like pulmonary carcinoma, which seems extremely unusual, may be closely associated with EBV infection in tumorigenesis.

Adenocarcinoma↗
PubMed1995

Adenomyoepithelioma of the lung.

A 66-year-old man with an extremely rare neoplasm of the lung, adenomyoepithelioma, is described. The tumor was a well-circumscribed lesion that showed solid, glandular, and papillary growth patterns and was composed of two types of cells, inner epithelial cells and outer myoepithelial cells. This bidirectional differentiation was confirmed immunohistochemically. The inner epithelial cells were positive for carcinoembryonic antigen and epithelial membrane antigen, while the outer myoepithelial cells were S-100 protein-positive. Electron microscopically, the tumor was characterized by a large amount of microfilaments in the cytoplasm and layers of basement membrane-like material in the intercellular spaces. Some glycogen granules were detected.

Adenomyoma↗
PubMed1995

Three cases of chemotherapy-induced acral erythema.

Three cases of chemotherapy-induced acral erythema are reported. All the patients had received cyclophosphamide, vincristine, adriamycin, prednisolone, and granulocyte-colony stimulating factor (G-CSF) for the treatment of leukemia or malignant lymphoma. From 35 to 45 days after the start of chemotherapy, painful erythematous lesions developed on their palms, soles, fingers, and toes, resulting in blister formation and desquamation. The recent higher incidence of chemotherapy-induced acral erythema may be correlated with the popularity of G-CSF, which allows the use of higher doses of chemotherapeutic drugs.

Adult↗
PubMed1995

p53 immunostaining in combined type small cell lung cancer. Brief report.

Abnormalities of the p53 oncogene in lung cancer have recently been reported to be more frequent in small cell lung cancer (SCLC) than in non-small cell lung cancer (non-SCLC), but their status in combined type SCLC is as yet unknown. In this study, immunohistochemical analysis using a polyclonal antibody against p53 protein was performed in 12 surgically resected specimens of combined type SCLC. Immunoreactivity of the p53 protein was found in 5 (42%) of the 12 cases, and the immunostaining pattern of the p53 protein in areas of the non-small cell carcinoma type was the same as in those of the small cell carcinoma type. Thus, it seems that the incidence of p53 abnormalities in combined type SCLC is slightly lower than in ordinary type SCLC. It is also suggested that abnormalities of the p53 oncogene in this histological type may not be a specific event related to the morphological difference between small cell carcinoma and non-small cell carcinoma.

Aged↗