共查询到20条相似文献,搜索用时 15 毫秒
1.
Navin Reddy Gaik Lin Ong T. M. Behr Robert M. Sharkey David M. Goldenberg M. J. Mattes 《Cancer immunology, immunotherapy : CII》1998,46(1):25-33
We reported previously that the blood clearance of injected mouse IgG2a was extremely rapid in many strains of nude and nu/+ mice. In an attempt to determine the cause of this phenomenon, the levels of endogenous IgG2a in the blood of these mice
was assayed. It was found that the serum level of IgG2a was extremely low in many of these mice, below 50 μg/ml, which is
20–100 times lower than the expected normal value. Great heterogeneity between individual mice was observed in their blood
level of IgG2a, and there was an excellent correlation between low blood IgG2a levels and rapid clearance of injected IgG2a.
Thus, the blood IgG2a levels are so low that a novel, previously undescribed effect occurs, namely the rapid clearance of
small amounts of injected IgG2a. The clearance is due primarily to binding sites in the spleen and liver. The low level of
endogenous IgG2a is not due to the lack of a thymus, since it occurs in nu/+ as well as nude mice, but can probably be attributed to the very clean environment in which these mice are raised. In assays
of sera from approximately 50 mouse strains, low IgG2a levels were found in all nude colonies and also in some normal mouse
strains. Some nude mice displayed relatively normal IgG2a clearance rates despite having low levels of endogenous IgG2a. In
repeated bleedings of individual mice, IgG2a levels were found to fluctuate greatly. A similar clearance effect was observed
with a human IgG1 Ab injected into mice. This rapid clearance of injected IgG, of certain subclasses, represents a practical
problem for many experiments in which antibodies are used for diagnosis or therapy, and several methods of circumventing the
problem are discussed.
Received: 15 August 1977 / Accepted: 14 October 1997 相似文献
2.
Sylvia Kirsch Ruediger Jankowsky Peter Leibnitz Hartmut Spies B. Johannsen 《Journal of biological inorganic chemistry》1999,4(1):48-55
The monooxo rhenium(V) complexes of cysteine (complex 1) and cysteine methyl ester (complex 2) were synthesised via a ligand exchange reaction starting from gluconatooxorhenium(V). Unexpectedly, the obtained oxorhenium(V)
complex with cysteine methyl ester (2) was partially saponified. Both complexes were characterised by common analytical techniques in their solid state. Thus,
an octahedral complex structure with 2(NH2,S) co-ordination in the equatorial plane and one carboxyl group bound trans to the oxo group is proven for complex 2 by X-ray diffraction. Furthermore, the existence of a dioxo species at higher pH was proven for the first time with this
type of ligand by determining the nearest co-ordination sphere of the rhenium centre in solution at a pH of 12 using extended
X-ray absorption fine structure spectroscopy.
Received: 20 July 1998 / Accepted: 2 December 1998 相似文献
3.
S. Lausson B. Fournes C. Borrel G. Milhaud F. Treilhou-Lahille 《Cancer immunology, immunotherapy : CII》1996,43(2):116-123
The existence of inherited aggressive forms of medullary thyroid carcinoma (MTC), and their resistance to all classical therapies,
make it a prime candidate for adoptive immunotherapy. As a prelude to a vaccine for the protection of family members at risk
of developing the disease, we investigated the immunological antitumour response provoked by the 6/23 rMTC cell line, compared
to that of the same cells engineered to secrete interleukin-2 (rMTC-IL2), in an animal model of familial human MTC, the inbred
strain of Wag/Rij rats. The rMTC cells developed a tumour that invaded the whole neck 15 days after orthotopic injection (into
the thyroid), while the rMTC-IL2 cells were progressively rejected. Co-injection of rMTC-IL2 with the parental cells induced
the rejection of the rMTC transplants. When injected, both tumoral cell types showed a similar positive immunoreaction with
anti-MHC class I (major histocompatibility complex class I) antibodies. They both recruited natural killer cells and eosinophils
at the site of injection. In addition, CD8+ T lymphocytes infiltrated the rMTC-IL2 cells, and eosinophil recruitment was amplified. Neutrophils, macrophages and CD4+ T lymphocytes were scarce. Our results suggest that the CD8+ T lymphocytes are implicated in the antitumour reaction elicited by the Il-2-transfected cells. As these effectors are known
to induce a specific immunological response, including memory, such a protocol should be tested as a vaccine on the young
population genetically at risk of developing a MTC.
Received: 18 December 1995 / Accepted: 21 August 1996 相似文献
4.
X.-L. Zhang Y. Komada Yan-Wen Zhou Tong-Xin Chen Haruko Sakai Eiichi Azuma Masaru Ido Minoru Sakurai 《Cancer immunology, immunotherapy : CII》1997,44(1):41-47
Peripheral blood lymphocytes obtained from children with acute lymphoblastic leukemia (ALL) at onset were studied for the
expression of interleukin-2 (IL-2) receptor α-chain (CD25) by two-color flow-cytometric analysis. Stimulated with anti-CD3
monoclonal antibody (mAb) alone, CD25 expression was significantly suppressed in CD4+ T cells from 27 of 48 (56.3%) cases and in CD8+ T cells from 29 of 48 (60.4%) cases. When stimulated with anti-CD3 mAb plus phorbol 12-myristate 13-acetate (PMA), CD25 expression
was clearly restored in certain cases of ALL. When PMA plus ionomycin were used for stimulation of T cells, CD25 was inducible
in a majority of cases. Interestingly CD25 expression upon anti-CD3 mAb stimulation was recovered after complete remission
had been achieved. These observations suggest the presence in ALL children at onset of an in vitro defect in the signal transduction
pathway of the T-cell-receptor/CD3 complex, resulting in inefficient CD25 expression. However, immune-staining analysis indicated
that protein kinase C was normally translocated from the cytosol fraction to the cell membrane fraction. The mobilization
of cytoplasmic free calcium is also normal.
Received: 27 March 1996 / Accepted: 23 December 1996 相似文献
5.
Stephan Paxian Susanne Liptay Guido Adler Horst Hameister R. M. Schmid 《Immunogenetics》1999,49(9):743-750
NFKB2 is a member of the NFKB/Rel gene family, which is known to be a pivotal regulator of the acute phase and immune responses. NF-κB2 is initially synthesized
as a ∼100 000 M
r protein which needs to be processed in order to bind DNA, either as homodimer or as heterodimer with other members of the
NF-κB/Rel family. The unprocessed form of NF-κB2 acts as an IκB-like protein. Therefore, NF-κB2 has a dual function. In this
report we describe the genomic structure, expression pattern, and chromosomal localization of mouse NFKB2. Genomic clones were isolated, which span the entire gene of approximately 8.5 kilobases (kb) including 1.5 kb of the promoter
region. Comparison to its human and avian homologues revealed a strong evolutionary conservation of the gene structure including
the exon/intron borders, sequence, and position of the nuclear localization signal, the glycine-hinge region, and the ankyrin
repeats. By fluorescence in situ hybridization, mouse NFKB2 was mapped to Chromosome (Chr) MMU 19C3-D2, which is homologous to human Chr 10q24, at which position the human NFKB2 was previously located. NFKB2 is ubiquitously expressed, highest in lymph nodes and thymus, underlining its role in the immune function.
Received: 14 January 1999 / Revised: 29 March 1999 相似文献
6.
To avoid destruction by complement, normal and malignant cells express membrane glycoproteins that restrict complement activity.
These include decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and protectin (CD59), which are
all expressed on colonic adenocarcinoma cells in situ. In this study we have characterised the C3/C5 convertase regulators
DAF and MCP on the human colonic adenocarcinoma cell line HT29. DAF was found to be a glycosyl-phosphatidylinositol-anchored
70-kDa glycoprotein. Blocking experiments with F(ab′)2 fragments of the anti-DAF monoclonal antibody BRIC 216 showed that DAF modulates the degree of C3 deposition and mediates
resistance to complement-mediated killing of the cells. The expression and function of DAF were enhanced by tumour necrosis
factor α (TNFα) and interleukin-1β (IL-1β). Cells incubated with interferon γ (IFNγ) did not alter their DAF expression. Two
MCP forms were expressed, with molecular masses of approximately 58 kDa and 68 kDa, the lower form predominating. MCP expression
was up-regulated by IL-1β, but not by TNFα or IFNγ. Expression of DAF and MCP promotes resistance of colonic adenocarcinoma
cells to complement-mediated damage, and represents a possible mechanism of tumour escape.
Received: 18 July 1995 / Accepted: 4 January 1996 相似文献
7.
Peter Taylor Marlene Gerder Zoila Moros Marc Feldmann 《Cancer immunology, immunotherapy : CII》1996,42(3):179-184
The neu proto-oncogene encodes a plasma membrane protein belonging to the epidermal growth factor receptor family. The cell line
B104, derived from a BDIX rat neuroblastoma, carries a point mutation in neu, and forms a tumor when injected into these rats. The human homologue of the neu oncogene (here called HER2) is overexpressed in certain types of cancer. Rats were immunized with HER2 protein (HER2) to investigate a possible cross-reaction between the homologous proteins which could protect them against
subsequent inoculation with B104. Specific antibody in the serum was measured by cell-based enzyme-linked immunosorbent assay
and fluorescence immunocytochemistry, and delayed-type hypersensitivity by an ear assay. Sera from animals immunized with
the HER2 extracellular domain (HER2-ECD) reacted with both HER2- and neu-expressing cells. In the ear assay, a significant cellular response to both HER2-ECD (P <0.05) and neu protein (P <0.001) was observed in HER2-ECD-immunized rats. However, the growth of B104 tumors in rats was not affected by preimmunization
with HER2-ECD. The results indicate that an autoreactive immune response to neu was induced by immunization with HER2-ECD, but was too weak to affect the growth of the neu-bearing tumor.
Received: 9 November 1995 / Accepted: 2 February 1996 相似文献
8.
R. Senekowitsch-Schmidtke Kurt Steiner Jutta Haunschild Sigrun Möllenstädt Regine Truckenbrodt 《Cancer immunology, immunotherapy : CII》1996,42(2):108-114
In order to study the potential of non-invasive scintigraphic evaluation of the epidermal growth factor (EGF) receptor status
in vivo, the biokinetics and tumor binding of 125I-EGF and anti-(EGF receptor) mAb 425 were investigated in nude mice bearing human tumor xenografts with different EGF-receptor
densities as determined by a radioreceptor assay. The results demonstrated a tumor uptake for both substances depending on
the receptor level. The EGF receptor status, however, was reflected slightly better by the binding of EGF to tumor tissue
compared to the mAb. The rapid blood clearance of EGF with a plasma half-life of less than 1 min led to a tumor-to-blood ratio
of approximately 3 within 6 h after injection in tumors with a high receptor expression. A similar ratio for the mAb was not
obtained before day 6 after injection. The absolute concentration of EGF, however, was low compared to the mAb. Therefore,
it can be concluded that the EGF receptor status as a target for (radio)immunotherapy can be evaluated in vivo with EGF labeled
with a short-life positron-emitting radionuclide or with monoclonal antibodies to the EGF receptor or their fragments.
Received: 14 September 1995 / Accepted: 6 December 1995 相似文献
9.
Y. Kikuchi Eiji Imaizumi Yoshitaka Kataoka Junko Hirata Tsunekazu Kita Takehiko Tode Ichiro Nagata 《Cancer immunology, immunotherapy : CII》1997,43(5):257-261
The aim of this study was to elucidate the effect of intraperitoneal (i.p.) instillations of granulocyte-colony-stimulating
factor (G-CSF) and/or interleukin-2 (IL-2) on ascites formation and the survival time of nude mice with malignant ascites,
produced by i.p. inoculation of human ovarian cancer cells. When the nude mice were treated with medium alone, ascites was
observed in all mice 28 days after tumor inoculation. When the mice were treated with cis-diamminedichloroplatinum(II) (cisplatin) alone, G-CSF alone or IL-2 alone, it took 35 days for the ascites to form in all
mice. When cisplatin was combined with G-CSF or IL-2, one of ten mice did not form ascites during the observation period.
Surprisingly, when G-CSF and IL-2 were simultaneously administered, ascites formation was not observed in any mice. Although
i.p. treatment with cisplatin alone significantly prolonged the survival time, compared to medium alone, the lytic activity
of spleen cells against HRA cells was significantly suppressed. When G-CSF or IL-2 was combined with cisplatin, the suppression
by cisplatin was eliminated and subsequently resulted in a prolongation of the survival time. When G-CSF was combined with
IL-2, both the peritoneal and splenic macrophages/monocytes were stimulated and the splenic lytic activity was about double
that following treatment with G-CSF alone on IL-2 alone, suggesting that complete inhibition of ascites formation results
not only from a significant increase of the peritoneal macrophages but also from enhancement of the lytic activity. Two mice,
died from dissemination of tumor in the abdominal cavity, but eight mice survived without tumor for more than 90 days. As
confirmed by monitoring body weight and hematocrit, G-CSF and IL-2 seemed to have no adverse effect. From these results, we
conclude that a combination therapy with G-CSF and IL-2 might be of clinical use for inhibiting large amounts of ascites,
which may inhibit therapeutic effects for ovarian cancer patients.
Received: 20 May 1996 / Accepted: 19 September 1996 相似文献
10.
Christine Hicks Elizabeth Keoshkerian Leonie Gaudry Robert Lindeman 《Cancer immunology, immunotherapy : CII》2001,50(4):173-180
Acute myeloid leukaemia (AML) blasts rarely express the B7 family of co-stimulatory molecules and do not elicit a clinically significant autologous T-lymphocyte anti-tumour response. The aim of this study was the in vitro modification of AML blasts to an antigen-presenting cell phenotype characterised by upregulated expression of the co-stimulatory molecule CD80 (B7-1). Circulating AML cells were induced to undergo partial differentiation in culture with the cytokines IL-3, IL-6 and GM-CSF; they exhibited variable upregulation of CD80 and continued to express MHC class I and II. These cells remained viable to day 20, in contrast with normal peripheral blood mononuclear cells (PBMNC), which did not survive under the culture conditions. In contrast to unmanipulated blasts, cultured leukaemic cells expressed B7-1. Where initial cytogenetic abnormalities were present, they were also seen in flow-sorted CD80-expressing cells after culture in cytokines, indicating their malignant origin. The immunogenic potential of these cultured cells was highlighted by allogeneic and autologous mixed lymphocyte reactions, in which both differentiated, but not unmanipulated, blasts produced expansion of T-lymphocyte numbers. Autologous cytotoxic T-lymphocyte (CTL) assays indicated specific killing of B7-1+ leukaemic cells, which was greatly enhanced after priming of the T-lymphocytes by B7-1+ blasts prior to the CTL assay, then enabling the CTL to lyse both unmanipulated and differentiated leukaemic cells. 相似文献
11.
12.
Penichet ML Dela Cruz JS Challita-Eid PM Rosenblatt JD Morrison SL 《Cancer immunology, immunotherapy : CII》2001,49(12):649-662
In the present study we describe a novel murine tumor model in which the highly malignant murine B cell lymphoma 38C13 has
been transduced with the cDNA encoding human tumor-associated antigen HER2/neu. This new cell line (38C13-HER2/neu) showed stable surface expression but not secretion of human HER2/neu. It also maintained expression of the idiotype (Id) of the surface immunoglobulin of 38C13, which serves as another tumor-associated
antigen. Surprisingly, spontaneous tumor regression was observed following s.c. but not i.v. injection of 38C13-HER2/neu cells in immunocompetent syngeneic mice. Regression was more frequently observed with larger tumor cell challenges and was
mediated through immunological mechanisms because it was not observed in syngeneic immunodeficient mice. Mice that showed
complete tumor regression were immune to challenge with the parental cell line 38C13 and V1, a variant of 38C13 that does
not express the Id. Immunity could be transferred with sera, suggesting that an antibody response mediated rejection and immunity.
Continuously growing s.c. tumors as well as metastatic tumors obtained after the i.v. injection of 38C13-HER2/neu maintained expression of human HER2/neu, which can serve as a target for active immunotherapy. As spontaneous tumor regression has not been observed in other human
murine models expressing human HER2/neu, our results illustrate the enormous differences that can exist among different murine tumors expressing the same antigen.
The present model provides a useful tool for the study of the mechanisms of protective immunity to B cell lymphoma and for
the evaluation of different therapeutic approaches based on the stimulation or suppression of the immune response.
Received: 2 August 2000 / Accepted: 20 September 2000 相似文献
13.
M. Motiur Rahman Takatsugu Hirokawa Daisuke Tsuji Jun Tsukimoto Seiji Hitaoka Tatsusada Yoshida Hiroshi Chuman Kohji Itoh 《Biochemistry and Biophysics Reports》2015
Human cytosolic sialidase (Neuraminidase 2, NEU2) catalyzes the removal of terminal sialic acid residues from glycoconjugates. The effect of siastatin B, known as a sialidase inhibitor, has not been evaluated toward human NEU2 yet. We studied the regulation of NEU2 activity by siastatin B in vitro and predicted the interaction in silico. Inhibitory and stabilizing effects of siastatin B were analyzed in comparison with DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) toward 4-umbelliferyl N-acetylneuraminic acid (4-MU-NANA)- and α2,3-sialyllactose-degrading activities of recombinant NEU2 produced by E. coli GST-fusion gene expression. Siastatin B exhibited to have higher competitive inhibitory activity toward NEU2 than DANA at pH 4.0. We also revealed the stabilizing effect of siastatin B toward NEU2 activity at acidic pH. Docking model was constructed on the basis of the crystal structure of NEU2/DANA complex (PDB code: 1VCU). Molecular docking predicted that electrostatic neutralization of E111 and E218 residues of the active pocket should not prevent siastatin B from binding at pH 4.0. The imino group (1NH) of siastatin B can also interact with D46, neutralized at pH 4.0. Siastatin B was suggested to have higher affinity to the active pocket of NEU2 than DANA, although it has no C7–9 fragment corresponding to that of DANA. We demonstrated here the pH-dependent affinity of siastatin B toward NEU2 to exhibit potent inhibitory and stabilizing activities. Molecular interaction between siastatin B and NEU2 will be utilized to develop specific inhibitors and stabilizers (chemical chaperones) not only for NEU2 but also the other human sialidases, including NEU1, NEU3 and NEU4, based on homology modeling. 相似文献
14.
Takashi Miwa Mayumi Nonaka Noriko Okada Shigeharu Wakana Toshihiko Shiroishi H. Okada 《Immunogenetics》1998,48(6):363-371
Human membrane cofactor protein (MCP, CD46) is widely distributed and is one of the plasma membrane complement inhibitors.
We isolated cDNA clones encoding genetic homologues of human MCP from a rat testis cDNA library. Northern blot analysis indicated
that rat MCP is preferentially expressed in testis, similar to what is found with guinea pig MCP. We identified several different
cDNAs, which were presumably generated by alternative splicing from a single-copy gene. The most prevalent isoform corresponded
to the Ser/Thr/Pro-rich C type of human MCP. Mouse MCP cDNA was cloned by polymerase chain reaction based on the nucleotide
sequence of rat MCP. The deduced amino acid sequence showed 77.8% identity to rat MCP. Mouse MCP was also preferentially expressed
in testis. Unique expression in testis in rat and mouse as well as guinea pig suggests that MCPs in these species not only
act as complement regulatory proteins but may also have more specialized functions in fertilization or reproduction. Genetic
mapping by linkage analysis indicated that the mouse Mcp gene is located on distal chromosome 1, closely linked to the complement receptor 2 (Cr2) gene.
Received: 24 February 1998 / Revised: 11 May 1998 相似文献
15.
Expression and function of the B and T lymphocyte attenuator (BTLA/CD272) on human T cells 总被引:5,自引:0,他引:5
Otsuki N Kamimura Y Hashiguchi M Azuma M 《Biochemical and biophysical research communications》2006,344(4):1121-1127
Co-signal receptors provide crucial activating or attenuating signals for T cells. The B and T lymphocyte attenuator (BTLA/CD272) is a third member of co-inhibitory receptors, which belongs to the CD28 immunoglobulin-superfamily. Using monoclonal antibodies (mAbs) against human BTLA, we show that BTLA is constitutively expressed on most CD4+ and CD8+ T cells and its expression progressively decreases upon T cell activation. Polarized Th1 and Th2 cells contained both BTLA-positive and BTLA-negative populations, but the extended culture diminished BTLA expression. Cross-linking BTLA with an agonistic mAb inhibited T cell proliferation and the production of the cytokines IFN-gamma and IL-10 in response to anti-CD3 stimulation. BTLA-mediated inhibition of T cell activation occurred during both primary CD4+ T cell responses and secondary CD4+ and CD8+ T cell responses, suggesting that BTLA ligation sends a constitutive "off" signal to T cells and thus might play an important role in the maintenance of T cell tolerance. 相似文献
16.
Jaspreet Singh Mushfiquddin KhanInderjit Singh 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(4):747-758
X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene. Accumulation of very long chain fatty acids (VLCFA) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity are the hallmark of the disease. Overexpression of ABCD2 gene, the closest homolog of ABCD1, has been shown to compensate for ABCD1, thus correcting the VLCFA derangement. The accumulation of VLCFA leads to a neuroinflammatory disease process associated with demyelination of the cerebral white matter. The present study underlines the importance of caffeic acid phenethyl ester (CAPE) in inducing the expression of ABCD2 (ALDRP), and normalizing the peroxisomal β-oxidation as well as the levels of saturated and monounsaturated VLCFAs in cultured human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1), was also reduced by CAPE treatment. Importantly, CAPE upregulated Abcd2 expression and peroxisomal β-oxidation and lowered the VLCFA levels in Abcd1-deficient U87 astrocytes and B12 oligodendrocytes. In addition, using Abcd1/Abcd2-silenced mouse primary astrocytes we examined the effects of CAPE in VLCFA-induced inflammatory response. CAPE treatment decreased the inflammatory response as the expression of inducible nitric oxide synthase, inflammatory cytokine, and activation of NF-κB in Abcd1/Abcd2-silenced mouse primary astrocytes was reduced. The observations indicate that CAPE corrects both the metabolic disease of VLCFA as well as secondary inflammatory disease; therefore, it may be a potential drug candidate to be tested for X-ALD therapy in humans. 相似文献
17.
Kam H. Leung 《Cancer immunology, immunotherapy : CII》1991,34(1):31-36
Summary We have shown that depletion of monocytes from human peripheral blood mononuclear cells (PBMC) byl-phenylalanine methyl ester (PheOMe) enhanced lymphokine-activated killer cell (LAK) generation by recombinant interleukin-2 (rIL-2) at high cell density. In this study, we have investigated the mechanism of action of PheOMe on LAK activation by using trypsin, chymotrypsin, tosylphenylalaninechloromethanol (TPCK, a chymotrypsin inhibitor), tosyl-l-lysinechloromethane (TLCK, a trypsin inhibitor), phenylalaninol (PheOH), and benzamidine. PBMC were treated with 1–5 mM PheOMe for 40 min at room temperature in combination with the various agents, washed and assessed for their effects on natural killer (NK) activity against K562 cells and monocyte depletion. The treated cells were then cultured with or without rIL-2 for 3 days. LAK cytotoxicity was assayed against51Cr-labeled K562 and Raji tumor target cells. TPCK at 10 µg/ml partially inhibited depletion of monocytes by PheOMe. TLCK did not prevent depletion of monocytes nor inhibition of NK activity induced by PheOMe. TPCK and TLCK inhibited NK activity by themselves. TPCK but not TLCK inhibited rIL-2 induction of LAK cells. On the other hand, PheOH and benzamidine (analogs of PheOMe) lacked any effect on monocyte depletion but abrogated the inhibitory effect of PheOMe on NK activity. They had no effect on rIL-2 activation of LAK activity enhanced by PheOMe. Trypsin potentiated the inhibitory effect of PheOMe on NK activity and monocyte depletion. Trypsin partially inhibited IL-2 activation of LAK activity enhanced by PheOMe. Chymotrypsin had little effect on NK activity but prevented the inhibitory effect of PheOMe on NK activity. It had little effect on monocyte depletion induced by PheOMe. PheOMe was hydrolysed by monocytes and chymotrypsin to Phe and methanol as determined by HPLC. TPCK inhibited hydrolysis of PheOMe by monocytes. Our data suggest that the effects of PheOMe on monocytes, NK cells and LAK activation involve protease activities of monocytes. 相似文献
18.
Cheon MS Kim SH Ovod V Kopitar Jerala N Morgan JI Hatefi Y Ijuin T Takenawa T Lubec G 《Amino acids》2003,24(1-2):127-134
Summary. Down syndrome (DS) is the most frequent genetic disorder with mental retardation and caused by trisomy 21. Although the gene
dosage effect hypothesis has been proposed to explain the impact of extra chromosome 21 on the pathology of DS, a series of
evidence that challenge this hypothesis has been reported. The availability of the complete sequences of genes on chromosome
21 serves now as starting point to find functional information of the gene products, but information on gene products is limited
so far. We therefore evaluated expression levels of six proteins whose genes are encoded on chromosome 21 (synaptojanin-1,
chromosome 21 open reading frame 2, oligomycin sensitivity confering protein, peptide 19, cystatin B and adenosine deaminase
RNA-specific 2) in fetal cerebral cortex from DS and controls at 18–19 weeks of gestational age using Western blot analysis.
Synaptojanin-1 and C21orf2 were increased in DS, but others were comparable between DS and controls, suggesting that the DS
phenotype cannot be simply explained by gene dosage effects. We are systematically quantifying all proteins whose genes are
encoded on chromosome 21 in order to provide a better understanding of the pathobiochemistry of DS at the protein level. These
studies are of significance as they show for the first time protein levels that are carrying out specific function in human
fetal brain with DS.
Received August 12, 2002 Accepted September 12, 2002 Published online January 30, 2003
Authors' address: Prof. Dr. Gert Lubec, CChem, FRSC (UK) Department of Pediatrics, University of Vienna, Waehringer Guertel 18, A-1090 Vienna,
Austria, Fax: +43-1-40400-3194, E-mail: gert.lubec@akh-wien.ac.at
Abbreviations: ADAR2, adenosine deaminase RNA-specific 2; C21orf2, chromosome 21 open reading frame 2; DS, Down syndrome; NSE, neuron specific
enolase; OSCP, oligomycin sensitivity conferring protein; PEP-19, peptide 19 相似文献
19.
Reactive oxygen species (ROS) generation is linked to dynamic actin cytoskeleton reorganization, which is involved in tumor
cell motility and metastasis. Thus, inhibition of ROS generation and actin polymerization in tumor cells may represent an
effective anticancer strategy. However, the molecular basis of this signaling pathway is currently unknown. Here, we show
that the Ecklonia cava-derived antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family
verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse melanoma cells. Steady-state intracellular
ROS levels were higher in malignant B16F10 cells than in parental, nonmetastatic B16F0 cells. Elevation of ROS by H2O2 treatment increased migration and invasion ability of B16F0 cells to level similar to that of B16F10 cells, suggesting that
intracellular ROS signaling mediates the prometastatic properties of B16 mouse melanoma cells. ROS levels and the cell migration
and invasion ability of B16 melanoma cells correlated with Rac1 activation and WAVE2 expression. Overexpression of dominant
negative Rac1 and depletion of WAVE2 by siRNA suppressed H2O2-induced cell invasion of B16F0 and B16F10 cells. Similarly, dieckol attenuates the ROS-mediated Rac1 activation and WAVE2
expression, resulting in decreased migration and invasion of B16 melanoma cells. In addition, we found that dieckol decreases
association between WAVE2 and NADPH oxidase subunit p47phox. Therefore, this finding suggests that WAVE2 acts to couple intracellular Rac1/ROS signaling to the invasive migration of
B16 melanoma cells, which is inhibited by dieckol. 相似文献
20.
Bromidge SM Dabbs S Davies DT Davies S Duckworth DM Forbes IT Gadre A Ham P Jones GE King FD Saunders DV Thewlis KM Vyas D Blackburn TP Holland V Kennett GA Riley GJ Wood MD 《Bioorganic & medicinal chemistry》1999,7(12):2767-2773
A model series of 5-HT2C antagonists have been prepared by rapid parallel synthesis. These N-substituted phenyl-N′-pyridin-3-yl ureas were found to have a range of 5-HT2C receptor affinities and selectivities over the closely related 5-HT2A receptor. Extrapolation of simple SAR, derived from this set of compounds, to the more active but synthetically more complex 1-(3-pyridyl-carbamoyl)indoline series allowed us to target optimal substitution patterns and identify potent and selective 5-HT2C/2B antagonists. 相似文献