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41.
NUMB and NUMBL are implicated in cell fate determination through the inhibition of Notch signaling. LNX, binding to NUMB and CXADR (CAR), functions as E3 ubiquitin ligase at least for NUMB. LNX is the paralog of PDZRN1 (PDZ domain containing RING finger 1). Here, we identified two novel homologs of LNX and PDZRN1 by using bioinformatics, which were designated PDZRN3 (LNX3 or SEMCAP3) and PDZRN4 (LNX4 or SAMCAP3L), respectively. KIAA1095 cDNA (AB029018) was the representative PDZRN3 cDNA. Complete coding sequence of PDZRN4 cDNA was determined by assembling nucleotide sequences of ESTs (BF059062 and AW297403), FLJ33777 cDNA (AK091096) and IMAGE5767589 cDNA (BC040922). PDZRN4 gene, consisting of 11 exons, was found to encode two isoforms with N-terminal divergence (PDZRN4 and PDZRN4S) due to an alternative promoter. PDZRN3-CNTN3 locus at human chromosome 3p13-p12.3 and PDZRN4-CNTN1 locus at human chromosome 12q12 were paralogous regions within the human genome. PDZRN3 (1066 aa) and PDZRN4 (1036 aa) showed 59.9% total-amino-acid identity. Two bipartite nuclear localization signals (NLS) were located within the C-terminal region of PDZRN3 and PDZRN4. PR34H1 and PR34H2 domains were identified as the regions conserved among PDZRN3, PDZRN4 and Drosophila CG1783. PDZRN3 and PDZRN4 consist of RING, two PDZ, PR34H1, PR34H2 domains and two NLS, while PDZRN1 and LNX consist of RING and four PDZ domains. PDZRN family proteins were classified into the LNX-PDZRN1 subfamily and the PDZRN3-PDZRN4 subfamily. This is the first report on the PDZRN3 and PDZRN4 genes. 相似文献
42.
Kojima M Nakamura S Ban S Inagaki M Sugihara S Yoshida K Masawa N 《Pathology, research and practice》2002,198(10):685-688
We report a case of primary pulmonary low-grade marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type with prominent sclerosis, which morphologically resembled pulmonary hyalinizing granuloma (PHG) or inflammatory pseudotumor (IPT) of the lung. The patient, a 66-year-old Japanese female with a history of Sj?gren's syndrome and primary biliary cirrhosis, presented with a lower left lobe mass 6.8 cm in diameter. Histologically, the lesion is characterized by dense bundles of collagen with scattered plasma cells, mature small lymphocytes, and histiocytes among the collagen bundles. Only the peripheral area of the nodule contained dense lymphoplasmacytoid and histiocytoid infiltrates. A few centrocyte-like cells were obscured by the numerous plasma cells and plasmacytoid cells. In addition, lymphoepithelial lesions and colonalized lymphoid follicles were identified by immunohistochemistry alone. Although PHG and IPT are unlikely to be confused with pulmonary MALT-type lymphomas, the present case suggests that MALT-type lymphoma should be added to the list of differential diagnoses for PHG and IPT. 相似文献
43.
Otsuka Y Ito M Yamaguchi M Saito S Uesu K Kasai K Abiko Y Mega J 《Mechanisms of ageing and development》2002,123(6):663-674
It is well known that Down syndrome (DS) is a premature ageing syndrome. Periodontal disease in individuals with DS develops rapidly and extensively in a relatively younger age bracket compared with that in healthy controls. The mechanisms involved in the periodontal inflammatory processes in DS patients are not fully understood. In the present study, the non-inflamed gingival fibroblasts isolated from seven patients with DS (DGF) and seven healthy controls (NDGF) were stimulated with lipopolysaccharide (LPS) derived from Actinobacillus actinomycetemcomitans (A. a.). We measured the level of prostaglandin E2 (PGE2) production by DGF and NDGF by radioimmunoassay, and also measured the mRNA expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) by using the real-time PCR method. We found the higher levels of LPS-stimulated COX-2 mRNA expression and PGE2 production in DGF when compared with those in NDGF. This study may indicate that overexpression of LPS-stimulated COX-2 induced a greater ability of DGF to produce PGE2, and that these phenomena may be responsible for the severer periodontal disease in DS patients. 相似文献
44.
Array CGH combined with mRNA microarray analyses was successfully applied for genome-wide screening of proto-oncogenes and tumor suppressor genes in 2002. The CCND1-ORAOV1-FGF19-FGF4-FGF3-FLJ10261-FADD-PPFIA1-EMS1 locus on human chromosome 11q13 is one of the most frequently amplified regions within the human genome. Here, we identified and characterized mouse Ppfia1 gene by using bioinformatics. Nucleotide sequence of mouse Ppfia1 cDNA was determined in silico by assembling nucleotide sequences of ESTs BY727670, CA327608, BU708520, BQ886535, and a 5'-truncated partial cDNA BC038349. Mouse Ppfia1 gene, consisting of 28 exons, was located between Fadd and Ems1 (also known as Cttn) genes on mouse chromosome 7. Mouse Ppfia1 (1201 aa) and human PPFIA1 (1202 aa), showing 95.8% total-amino-acid identity, were found to consist of MAH (myosin heavy chain tail and ATPase homologous) domain and three SAM (sterile alpha motif) domains. MAH domain is implicated in the homo- or hetero-oligomer formation through the coiled-coil interaction, while SAM domain is implicated in the interaction with other proteins. Mouse Ccnd1-Ems1 locus and human CCND1-EMS1 locus were evolutionarily conserved in the order and the orientation of genes therein. Nucleotide and amino-acid substitution rates of Ccnd1, Ppfia1 and Ems1 genes located near both ends of the Ccnd1-Ems1 locus were relatively lower than those in the middle part of the locus. This is the first report on mouse Ppfia1 gene as well as comprehensive comparison of CCND1-EMS1 locus within the human and mouse genomes. 相似文献
45.
Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor protein transgenic mice show accelerated diffuse beta-amyloid deposition
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Yamamoto M Horiba M Buescher JL Huang D Gendelman HE Ransohoff RM Ikezu T 《The American journal of pathology》2005,166(5):1475-1485
Microglia accumulation at the site of amyloid plaques is a strong indication that microglia play a major role in Alzheimer's disease pathogenesis. However, how microglia affect amyloid-beta peptide (Abeta) deposition remains poorly understood. To address this question, we developed a novel bigenic mouse that overexpresses both amyloid precursor protein (APP) and monocyte chemotactic protein-1 (MCP-1; CCL2 in systematic nomenclature). CCL2 expression, driven by the glial fibrillary acidic protein promoter, induced mononuclear phagocyte (MP; monocyte-derived macrophage and microglial) accumulation in the brain. When APP/CCL2 transgenic mice were compared to APP mice, a fivefold increase in Abeta deposition was present despite increased MP accumulation around hippocampal and cortical amyloid plaques. Levels of full-length APP, its C-terminal fragment, and Abeta-degrading enzymes (insulin-degrading enzyme and neprilysin) in APP/CCL2 and APP mice were indistinguishable. Sodium dodecyl sulfate-insoluble Abeta (an indicator of fibrillar Abeta) was increased in APP/CCL2 mice at 5 months of age. Apolipoprotein E, which enhances Abeta deposition, was also increased (2.2-fold) in aged APP/CCL2 as compared to APP mice. We propose that although CCL2 stimulates MP accumulation, it increases Abeta deposition by reducing Abeta clearance through increased apolipoprotein E expression. Understanding the mechanisms underlying these events could be used to modulate microglial function in Alzheimer's disease and positively affect disease outcomes. 相似文献
46.
Yasuni Nakanuma Goroku Ohta Haruo Takeshita Yoshikiyo Yamazaki Kenji Doishita Masaru Shimizu 《Pathology international》1983,33(6):1095-1104
Intrahepatic biliary tree with either florid duct lesions or a moderate to severe degree of the duct loss in four livers with chronic hepatic diseases other than primary biliary cirrhosis were studied with histometric and serial section observations. Florid duct lesions, distributed segmentally in the liver, were found in one case with incomplete septal cirrhosis and one case with idiopathic portal hypertension. The florid duct lesions including marked plasma cell infiltration and occasional periductal granulomas, were not associated with any bile duct loss in the two cases. The duct lesions were reversible in one case during a long clinical course. On the other hand, a moderate to severe bile duct loss with biliary epithelial degeneration and necrosis was associated with no or little periductal inflammatory cell infiltration in one other case with chronic intrahepatic cholestasis, probably drug-induced, and in one case with idiopathic portal hypertension. Although florid duct lesions and bile duct loss were important diagnostic features of primary biliary cirrhosis, one of them was observed to develop independently in severely diseased livers, not consistent with a diagnosis of primary biliary cirrhosis, sclerosing cholangitis or intrahepatic bile duct paucity syndrome. 相似文献
47.
Effects of ruthenium red on membrane ionic currents in urinary bladder smooth muscle cells of the guinea-pig 总被引:2,自引:0,他引:2
Masaru Hirano Y. Imaizumi Katsuhiko Muraki A. Yamada Minoru Watanabe 《Pflügers Archiv : European journal of physiology》1998,435(5):645-653
Three major ionic currents, Ca2+-dependent K+ current (I
K-Ca), delayed rectifier type K+ current (I
kd) and Ca2+ current (I
Ca), were activated by depolarization under whole-cell clamp in single smooth muscle cells isolated from guinea-pig urinary
bladder. Externally applied ruthenium red (RuR) reduced the amplitude of I
K-Ca and I
Ca at 0 mV (IC50 values were 4.2 and 5.6 μM, respectively), but did not affect I
Kd. Spontaneous transient outward currents (STOCs) and caffeine-induced outward currents (I
caf) at –30 mV were reduced by external 10 μM RuR. When 10 μM RuR was added to the pipette solution, I
K-Ca during depolarization, STOCs and I
caf significantly decreased with time. RuR did not change the unitary current amplitude of the large-conductance Ca2+-dependent K+ (BK) channels, but reduced the open probability of the channel under excised patch-clamp recording mode. RuR reduced the
channel activity more effectively from the cytosolic face than from the other. This inhibition decreased when the cytosolic
Ca2+ concentration was increased. These results indicate that RuR blocks BK and Ca2+ channels in urinary bladder smooth muscle cells. The decrease in I
K-Ca, STOCs and I
caf by RuR is attributable to the direct inhibition of BK channel activity, probably in addition to the inhibition of Ca2+ release from storage sites. The direct inhibition of BK channel activity by RuR may be related to the interaction of RuR
with the Ca2+-binding sites of the channel protein.
Received: 15 October 1997 / Received after revision and accepted: 25 November 1997 相似文献
48.
Masaru Enomoto Akihiro Tamori Madoka Toyama Kohmoto Takehiro Hayashi Hisato Jomura Daiki Habu Hiroki Sakaguchi Tadashi Takeda Norifumi Kawada Shuichi Seki Susumu Shiomi Noritoshi Koh Shuhei Nishiguchi 《Journal of interferon & cytokine research》2007,27(3):201-207
Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response. 相似文献
49.
50.
Qunn L Takemura T Ikushima S Ando T Yanagawa T Akiyama O Oritsu M Tanaka N Kuroki T 《Virchows Archiv : an international journal of pathology》2002,441(3):271-278
Seventy-two cases of idiopathic pulmonary fibrosis (IPF) were examined from 2856 consecutive autopsy cases at the Japanese Red Cross Medical Center in Tokyo from 1973-1996. Primary lung cancer had arisen in 31 of 72 cases of IPF (43%), significantly higher than the incidence in cases without IPF (8.1%) and in the cases with non-IPF chronic lung diseases (11.9%). Hyperplastic epithelial foci in the honeycomb lesions of IPF cases were significantly more prominent in the lower than in the upper lobe, in cases with or without lung cancer, and they were more prominent in the lower lobe of IPF with than in those without cancer. The length of hyperplastic epithelial foci in the lower lobe of IPF cases was longer than that in interstitial pneumonia-associated with collagen vascular diseases. There was a higher PCNA labeling index of hyperplastic epithelial foci in IPF cases than in cases of interstitial pneumonia-associated with collagen vascular diseases. The PCNA labeling index was almost the same between smokers and nonsmokers with IPF. Overexpression of p53 was observed in hyperplastic epithelial foci in honeycomb lesion of IPF. DNA ploidy analysis of hyperplastic epithelial foci in the paraffin sections of 12 IPF cases revealed aneuploidy patterns in eight cases. These results strongly suggest that accelerated cell proliferation occurs in the honeycomb lesion of IPF, and that regenerative epithelia becomes susceptible to carcinogenic agents in addition to the smoking effect. 相似文献