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排序方式: 共有90条查询结果,搜索用时 31 毫秒
1.
Identification and sequence of the VH gene elements encoding a human anti-DNA antibody 总被引:12,自引:0,他引:12
Antibodies to DNA similar to those found in patients with systemic lupus erythematosus (SLE) and autoimmune mice can be derived from the lymphocytes of normal individuals. It is not known whether these normal derived anti-DNA antibodies are made from the same VH gene elements as the anti-DNA antibodies made by SLE patients. To begin to answer this question, we examined mu chain cDNA clones from human hybrid clone C6B2 producing anti-DNA antibodies. The sequence of the 500 base pair restriction fragment containing the variable region (5' terminus) was determined and was sequenced. This antibody uses a VHII heavy chain subgroup gene, a J3 joining segment, a hitherto unknown D segment, and a previously reported leader sequence. Significant homology was found to a mouse anti-DNA antibody sequence in the use of VH subgroup in J3, and in the hypervariable regions with a shared Ser-Tyr construction in CDR1 and an identical five amino acid residue stretch in CDR2. Comparison with the limited sequence data of published SLE monoclonal anti-DNA antibodies, both human and mouse, suggests that this shared Ser-Tyr may be important in some but not all antibodies to DNA. Comparison of C6B2 antibody is made with other known antibody sequences with identification of those residues likely to be part of the antigen binding site. 相似文献
2.
Phylogenetic distribution in the genus Mus of t-complex-specific DNA and protein markers: inferences on the origin of t-haplotypes 总被引:8,自引:0,他引:8
Delarbre C; Kashi Y; Boursot P; Beckmann JS; Kourilsky P; Bonhomme F; Gachelin G 《Molecular biology and evolution》1988,5(2):120-133
We have examined the phylogenetic distribution of two t-specific markers
among representatives of various taxa belonging to the genus Mus. The
centromeric TCP-1a marker (a testicular protein variant specific for all
t-haplotypes so far studied) has also been apparently detected in several
non-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolor
species. By contrast, a t-specific restriction- fragment-length
polymorphism allele (RFLP) of the telomeric alpha- globin pseudogene DNA
marker alpha-psi-4 was found only in animals belonging to the M.
musculus-complex species either bearing genuine t- haplotypes or, like the
M. m. bactrianus specimen studied here, likely to do so. This t-specific
alpha-psi-4 RFLP allele was found to be as divergent from the RFLP alleles
of the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, or
M. spretus ones. These results suggest the presence of t-haplotypes and of
t-specific markers in populations other than those belonging to the M. m.
domesticus and M. m. musculus subspecies, implying a possible origin for
t-haplotypes prior to the radiation of the most recent offshoot of the Mus
genus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago.
相似文献
3.
Specificity analysis of human anti-DNA antibodies 总被引:6,自引:0,他引:6
Human hybrids producing anti-DNA antibodies were generated by the fusion of pokeweed mitogen-stimulated splenic lymphocytes from a child with sickle cell anemia to GM4672. Of 19 hybrids, three (15%) produced anti-DNA antibody as detected by an enzyme linked immunosorbent assay. One subclone from each of these three hybrids was then characterized. All produced IgM antibody in large amounts ranging from 22 to 266 micrograms/ml per million cells per 24 hr. All three antibodies bound both double- and single-stranded DNA. Competitive inhibition assays revealed the greatest inhibition of DNA binding with the ribohomopolymers polyinosinic and polyguanylic acid. A complex pattern of cross-reactivity with various other polynucleotides and with some phospholipids was observed. Subtle differences were found among the three antibodies in light chain class and some of the binding specificities. By using a modified Farr assay, all three monoclonals were found to be of low to intermediate affinity. These results confirm that anti-DNA antibodies apparently equivalent to those seen in patients with SLE can be derived from "normal" nonautoimmune individuals. 相似文献
4.
The contractile basis of amoeboid movement: V. The control of gelation, solation, and contraction in extracts from dictyostelium discoideum 总被引:29,自引:22,他引:7
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Motile extracts have been prepared from Dictyostelium discoideum by homogenization and differential centrifugation at 4 degrees C in a stabilization solution (60). These extracts gelled on warming to 25 degrees Celsius and contracted in response to micromolar Ca++ or a pH in excess of 7.0. Optimal gelation occurred in a solution containing 2.5 mM ethylene glycol-bis (β-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA), 2.5 mM piperazine-N-N'-bis [2-ethane sulfonic acid] (PIPES), 1 mM MgC1(2), 1 mM ATP, and 20 mM KCI at ph 7.0 (relaxation solution), while micromolar levels of Ca++ inhibited gelation. Conditions that solated the gel elicited contraction of extracts containing myosin. This was true regardless of whether chemical (micromolar Ca++, pH >7.0, cytochalasin B, elevated concentrations of KCI, MgC1(2), and sucrose) or physical (pressure, mechanical stress, and cold) means were used to induce solation. Myosin was definitely required for contraction. During Ca++-or pH-elicited contraction: (a) actin, myosin, and a 95,000-dalton polypeptide were concentrated in the contracted extract; (b) the gelation activity was recovered in the material sqeezed out the contracting extract;(c) electron microscopy demonstrated that the number of free, recognizable F-actin filaments increased; (d) the actomyosin MgATPase activity was stimulated by 4- to 10-fold. In the absense of myosin the Dictyostelium extract did not contract, while gelation proceeded normally. During solation of the gel in the absense of myosin: (a) electron microscopy demonstrated that the number of free, recognizable F- actin filaments increased; (b) solation-dependent contraction of the extract and the Ca++-stimulated MgATPase activity were reconstituted by adding puried Dictyostelium myosin. Actin purified from the Dictyostelium extract did not gel (at 2 mg/ml), while low concentrations of actin (0.7-2 mg/ml) that contained several contaminating components underwent rapid Ca++ regulated gelation. These results indicated : (a) gelation in Dictyostelium extracts involves a specific Ca++-sensitive interaction between actin and several other components; (b) myosin is an absolute requirement for contraction of the extract; (c) actin-myosin interactions capable of producing force for movement are prevented in the gel, while solation of the gel by either physical or chemical means results in the release of F-actin capable of interaction with myosin and subsequent contraction. The effectiveness of physical agents in producting contraction suggests that the regulation of contraction by the gel is structural in nature. 相似文献
5.
Cholecystokinin (CCK) has been implicated as a signal for the syndrome of satiety in a variety of species. Several lines of evidence point to a peripheral site of action for the behavioral effects of CCK. Peripheral CCK receptors appear to activate a gut-brain pathway involving the sensory fibers of the vagus nerve. To investigate the central anatomical substrate of this visceral-behavioral control system, the terminal regions of the sensory tract of the vagus were lesioned. Radiofrequency lesions of the nucleus tractus solitarius abolished the effects of acute doses of CCK on exploratory behaviors. Sham lesions had no effect on baseline exploratory behaviors and did not influence the ability of CCK to decrease spontaneous exploratory behaviors. These findings delineate the first central site along the ascending sensory pathway which appears to mediate the satiety-related behavioral effects of CCK. 相似文献
6.
The observation that increased muscular activity leads to muscle hypertrophy is well known, but identification of the biochemical and physiological mechanisms by which this occurs remains an important problem. Experiments have been described (5, 6) which suggest that creatine, an end product of contraction, is involved in the control of contractile protein synthesis in differentiating skeletal muscle cells and may be the chemical signal coupling increased muscular activity and the increased muscular mass. During contraction, the creatine concentration in muscle transiently increases as creatine phosphate is hydrolyzed to regenerate ATP. In isometric contraction in skeletal muscle for example, Edwards and colleagues (3) have found that nearly all of the creatine phosphate is hydrolyzed. In this case, the creatine concentration is increased about twofold, and it is this transient change in creatine concentration which is postulated to lead to increased contractile protein synthesis. If creatine is found in several intracellular compartments, as suggested by Lee and Vissher (7), local changes in concentration may be greater then twofold. A specific effect on contractile protein synthesis seems reasonable in light of the work of Rabinowitz (13) and of Page et al. (11), among others, showing disproportionate accumulation of myofibrillar and mitochondrial proteins in response to work-induced hypertrophy and thyroxin-stimulated growth. Previous experiments (5, 6) have shown that skeletal muscles cells which have differentiated in vitro or in vivo synthesize myosin heavy-chain and actin, the major myofibrillar polypeptides, faster when supplied creatine in vitro. The stimulation is specific for contractile protein synthesis since neither the rate of myosin turnover nor the rates of synthesis of noncontractile protein and DNA are affected by creatine. The experiments reported in this communication were undertaken to test whether creatine selectively stimulates contractile protein synthesis in heart as it does in skeletal muscle. 相似文献
7.
The results described in the accompanying article support the model in
which glucosylphosphoryldolichol (Glc-P-Dol) is synthesized on the
cytoplasmic face of the ER, and functions as a glucosyl donor for three
Glc-P-Dol:Glc0-2Man9-GlcNAc2-P-P-Dol glucosyltransferases (GlcTases) in the
lumenal compartment. In this study, the enzymatic synthesis and structural
characterization by NMR and electrospray-ionization tandem mass
spectrometry of a series of water-soluble beta-Glc-P-Dol analogs containing
2-4 isoprene units with either the cis - or trans - stereoconfiguration in
the beta-position are described. The water- soluble analogs were (1) used
to examine the stereospecificity of the Glc-P-Dol:Glc0-2Man9GlcNAc2-P-P-Dol
glucosyltransferases (GlcTases) and (2) tested as potential substrates for
a membrane protein(s) mediating the transbilayer movement of Glc-P-Dol in
sealed ER vesicles from rat liver and pig brain. The Glc-P-Dol-mediated
GlcTases in pig brain microsomes utilized [3H]Glc-labeled Glc-P-Dol10,
Glc-P-(omega, c )Dol15, Glc-P(omega, t,t )Dol20, and Glc-P-(omega, t,c
)Dol20as glucosyl donors with [3H]Glc3Man9GlcNAc2-P-P-Dol the major product
labeled in vitro. A preference was exhibited for C15-20 substrates
containing an internal cis -isoprene unit in the beta-position. In
addition, the water-soluble analog, Glc-P-Dol10, was shown to enter the
lumenal compartment of sealed microsomal vesicles from rat liver and pig
brain via a protein-mediated transport system enriched in the ER. The
properties of the ER transport system have been characterized. Glc-
P-Dol10was not transported into or adsorbed by synthetic PC-liposomes or
bovine erythrocytes. The results of these studies indicate that (1) the
internal cis -isoprene units are important for the utilization of Glc-P-Dol
as a glucosyl donor and (2) the transport of the water- soluble analog may
provide an experimental approach to assay the hypothetical "flippase"
proposed to mediate the transbilayer movement of Glc-P-Dol from the
cytoplasmic face of the ER to the lumenal monolayer.
相似文献
8.
Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects
Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects. 相似文献
9.
C57Bl/6 mice with the lpr mutation of Fas (CD95) were tested for deviation from the genetically restricted antibody response to the hapten 4-hydroxy-3-nitrophenyl acetyl (NP). lambda1+ germinal centers (GC) with the canonical v186.2 V(H) gene element develop in lpr/lpr mice with the same time course as in wild-type (+/+) mice. In contrast to +/+ mice, however, lambda1+ GC persist in the spleens of lpr/lpr mice 25 days after immunization. Virtually all of the lambda1+ GC are reactive with NP 10 days after immunization. Sixteen days after immunization, however, many of the lambda1+ GC are not reactive with NP, and few of the lambda1+ GC are reactive with NP 25 days after immunization. The V(H) gene elements of three lambda1+NP- GC 25 days after immunization are derived by somatic mutation of v186.2, but have lost reactivity with NP. The mutated VDJs from these GC react with cells in spleen sections from +/+ and lpr/lpr mice, indicating that they represented secondary antibody responses induced by self antigens that are available as presented antigen. These data indicate that Fas-mediated apoptosis serves to eliminate a (limited) population of B cells that acquire reactivity to "self antigens" by somatic mutation of VDJs in the GC. 相似文献
10.
Presence or absence of N-acetylneuraminic acid (Neu5Ac) can change a
sialylated glycoprotein's serum half-life and possibly its function. We
evaluated the linearity, sensitivity, reproducibility, and accuracy of a
HPAEC/PAD method to determine its suitability for routine simultaneous
analysis of Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). An effective
internal standard for this analysis is 3-deoxy-d-glycero-d-
galacto-2-nonulosonic acid (KDN). We investigated the effect of the Au
working electrode recession and determined that linear range and
sensitivity were dependent on electrode recession. Using an electrode that
was 350 &mgr;m recessed from the electrode block, the minimum detection
limits of Neu5Ac, KDN, and Neu5Gc were 2, 5, and 2 pmol, respectively, and
were reduced to 1, 2, and 0.5 pmol using a new electrode. The response of
standards was linear from 10 to 500 pmol (r2>0.99) regardless of
electrode recession. When Neu5Ac, KDN, and Neu5Gc (200 pmol each) were
analyzed repetitively for 48 h, area RSDs were <3%. Reproducibility was
unaffected when injections of glycoprotein neuraminidase and acid
digestions were interspersed with standard injections. Area RSDs of Neu5Ac
and Neu5Gc improved when the internal standard was used. We determined the
precision and accuracy of this method for both a recessed and a new working
electrode by analyzing Neu5Ac and Neu5Gc contents of bovine fetuin and
bovine and human transferrins. Results were consistent with published
values and independent of the working electrode. The sensitivity,
reproducibility, and accuracy of this method make it suitable for direct
routine analysis of glycoprotein Neu5Ac and Neu5Gc contents.
相似文献