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1.
So Jeong Park Doo Ri Park Deepak Bhattarai Kyeong Lee Jaesang Kim Yun Soo Bae Soo Young Lee 《Molecules and cells》2014,37(8):628-635
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity. 相似文献
2.
The role of the epidermal growth factor-1 and hydrophobic stack domains of human factor IX in binding to endothelial cells. 总被引:6,自引:0,他引:6
W F Cheung D L Straight K J Smith S W Lin H R Roberts D W Stafford 《The Journal of biological chemistry》1991,266(14):8797-8800
To determine the function and specificity in factor IX of the first epidermal growth factor (EGF)-like domain and the eight-amino acid hydrophobic stack encoded by exon C (residues 39-46), these domains were replaced by the corresponding polypeptide regions of factor X and chimeric proteins were produced in human embryo kidney cells. Both chimeras were activated by factor XIa at a rate similar to plasma factor IX and exhibited calcium-dependent fluorescence quenching similar to plasma factor IX. Both chimeras competed equally for binding to the endothelial cell receptor. Our findings make it unlikely that the first EGF-like domain or the hydrophobic stack of factor IX are responsible for the specific binding of factor IX to its endothelial cell receptor. 相似文献
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4.
Myeong Hee Kim Yee Hyung Kim So Young Kang Woo In Lee 《Indian journal of microbiology》2015,55(4):464-468
Non-tuberculous mycobacterium (NTM) lung disease is increasing in prevalence. We analyzed the frequency of NTM lung disease among patients who are suspected of tuberculosis. NTM was isolated from about one-fourth of the mycobacterium culture-positive patients and about half of these had NTM lung disease. Therefore, NTM isolates should be routinely identified at the species level for adequate treatment. 相似文献
5.
M. G. Rosenblum Lawrence Cheung S. K. Kim Kalpana Mujoo Nicholas J. Donato James L. Murray 《Cancer immunology, immunotherapy : CII》1996,42(2):115-121
The development of cellular resistance to immunotoxins has been demonstrated in a variety of models and can involve a number
of mechanisms. For the present study, an immunotoxin was utilized composed of an antimelanoma antibody ZME-018 recognizing
a 240-kDa surface glycoprotein (gp 240) and the plant toxin gelonin. Human melanoma cells (A375-M) were grown in the presence
of increasing amounts of ZME-gelonin and a clonal variant (A-375-ZR) was developed that was 100-fold resistant to ZME-gelonin
compared to parental cells. Scatchard analysis showed that the A375-M parental cells had 260×103 ZME-gelonin-binding sites/cell with relatively low affinity (5 nM). In contrast, resistant A375-ZR cells demonstrated a reduced
number of low-affinity sites (160×103/cell), but showed a small number (47×103) of higher-affinity sites (0.8 nM). Internalization rates and degradation rates of 125I-labeled ZME-gelonin were identical in both the parental and resistant cells. A375-ZR cells were found to be more resistant
to vincristine and doxorubicin than were parental cells. Both cell lines were almost equally sensitive to native gelonin,
5-fluorouracil (5-FU), cisplatin, melphalan, carmustine, interferon γ (IFNγ) and IFNα. In addition, both cell lines were equally
sensitive to another gelonin-antibody conjugate that binds to cell-surface, GD2 (antibody 14G2A). However, resistant cells were twice as sensitive to the cytotoxic effects of etoposide than were parental cells. Finally,
a variety of agents were tested in combination with ZME-gelonin against A375-ZR cells in an attempt to identify agents to
augment immunotoxin cytotoxic effects against resistant cells. The agents 5-FU, cisplatin, IFNγ, IFNα, and etoposide were
the most effective in augmenting the cytotoxicity of ZME-gelonin against resistant cells. These studies suggest that development
of resistance to one immunotoxin does not cause development of cross-resistance to other gelonin immunotoxins. Further, specific
biological response modifiers and chemotherapeutic agents may be effective in augmenting the effectiveness of immunotoxins
and specifically targeting or reducing the emergence of immunotoxin-resistant cells.
Received: 15 March 1995 / Accepted: 28 November 1995 相似文献
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8.
Thorsten Thye Genevieve Scarisbrick Edmund N. L. Browne Margaret Amanua Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Stefan Niemann Sabine Rüsch-Gerdes Christian G. Meyer Rolf D. Horstmann 《PloS one》2009,4(7)
The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (Pcorrected [cor] = 0.002, Pcor = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB. 相似文献
9.
R Cornett M O James G N Henderson J Cheung A L Shroads P W Stacpoole 《Biochemical and biophysical research communications》1999,262(3):752-756
Dichloroacetate (DCA) inhibits its own metabolism and is converted to glyoxylate by glutathione S-transferase zeta (GSTz). GSTz is identical to maleylacetoacetate isomerase, an enzyme of tyrosine catabolism that converts maleylacetoacetate (MAA) to fumarylacetoacetate and maleylacetone (MA) to fumarylacetone. MAA and MA are alkylating agents. Rats treated with DCA for up to five days had markedly decreased hepatic GSTz activity and increased urinary excretion of MA. When dialyzed cytosol obtained from human liver was incubated with DCA, GSTz activity was unaffected. In contrast, DCA incubation inhibited enzyme activity in dialyzed hepatic cytosol from rats. Incubation of either rat or human hepatic cytosol with MA led to a dose dependent inhibition of GSTz. These data indicate that humans or rodents exposed to DCA may accumulate MA and/or MAA which inhibit(s) GSTz and, consequently, DCA biotransformation. Moreover, DCA-induced inhibition of tyrosine catabolism may account for the toxicity of this xenobiotic in humans and other species. 相似文献
10.
Comparison of bone marrow extracellular matrices. 总被引:1,自引:0,他引:1
M Lee I P Christopherson J M Lehman C J Bennett H T Cheung 《Biochimica et biophysica acta》1999,1428(2-3):300-304
We have compared the structure and composition of adult and fetal bovine bone marrow extracellular matrices. In contrast to fetal bone marrow, adult bone marrow has more oval fenestration and accumulation of adipocytes as well as lower protein content. These differences could be due to remodeling of bone marrow tissue as it develops. Zymogram analysis of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) activities showed that fetal, but not adult bone marrow extract contained a 96-kDa MMP and TIMP-1 and -2. These activities may contribute to the structural differences between adult and fetal bone marrow tissues. 相似文献