Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Comparison of amino acid sequences of the alpha-chain fragment of human C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 in which the aspartic acid-histidine substitution at position 1106 may be related to the amide and ester bond forming properties of these molecules. Peptides containing twelve amino acid residues of the C4A- or C4B-specific sequences were synthesized and injected into female Balb/c mice. Serum from 2 mice, one immunized with the C4A-specific peptide and the other with the C4B-specific peptide, gave strong isotype-specific responses in an enzyme-linked immunosorbent assay against affinity-purified C4A3 and C4B2B1. Spleen cells from these mice were fused with the mouse myeloma SP2/0-Ag 14, and two cloned cell lines, AII-1 and BII-1, were established from hybrids. Enzyme-linked immunosorbent assay and western blotting of monoclonal antibodies AII-1 and BII-1 show that the former reacts with the C4A but not with the C4B alpha-chain and the latter with C4B but not with the C4A alpha-chain. Furthermore, immunoblotting of C4 allelic variants showed that AII-1 reacted with all C4A allotypes tested, including A6, A4, A3 and A2, whereas BII-1 reacted with all C4B allotypes tested, including B5, B3, B2, and B1.
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PMID:Monoclonal antipeptide antibodies against amino acid residues 1101-1106 of human C4 distinguish C4A from C4B. 204 34

Spleen cells from Balb/c mice immunized with HCG were subjected to the normal hybridoma procedures. The resulting MCA's (from 78 clones) were evaluated in radioimmunoassay, haemagglutination and enzyme immunoassay with whole HCG. The RIA analysis was extended to include HCG subunits and intact LH. The alpha-chain of HCG was found to be strongly immunodominant, as shown by the very high frequency (46 of 78) of MCA's directed at the alpha-chain epitopes. These antibodies would bind luteinizing hormone as well as HCG. Only 1 of the 78 clones was specific for the B subunit of HCG, in RIA. This clone was later found to be positive for LH in EIA, thus making the derivation of antibodies specific for this B-epitope extremely difficult. Most MCA's were found to be applicable in the three types of assay systems (48 of 78), but some were compatible in just one or two of the systems. These differences are believed to be due to epitope masking resulting from the way in which the antigen was handled and presented in the different systems.
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PMID:Epitope masking and immunodominance--complications in the selection of monoclonal antibodies against HCG. 244 90

Spleen cells of BALB/c mice, immunized with fragments Y of normal human fibrinogen, were fused with P3 X 63 Ag 8653 myeloma cells. A clone was found which produces monoclonal antibodies (Mab-Y18) of the IgM kappa type. Mab-Y18 is immunoreactive with normal human fibrinogen, and its fragments X, Y, N-terminal disulphide knot, A alpha-chain, and A alpha stretch 1-51. The immunoreactivity with these same fragments disappears upon treatment with thrombin or arvin. This strongly suggests that fibrinopeptide A is an essential component of the Mab-Y18 epitope. This is supported by the finding that Mab-Y18 prolongs the thrombin and arvin clotting times of human fibrinogen by inhibition of the fibrinopeptide A release. More detailed information about the nature of the Mab-Y18 epitope was obtained from studies with genetic variants of human fibrinogen (especially fibrinogen Metz) and with fibrinogens from other mammalian species. These studies show that amino acid residue A alpha 16 (arginine) of fibrinopeptide A is essential for the Mab-Y18 epitope. Mab-Y18 does not react with free fibrinopeptide A.
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PMID:A monoclonal antibody, specific for human fibrinogen, fibrinopeptide A-containing fragments and not reacting with free fibrinopeptide A. 404 Jul 83

SJL/J (H-2 (8)) lymphocytes, primed in vitro against primary, cultured, and transplantable syngeneic reticulum cell sarcomas (RCS) were found to recognize and bind to the tumor without subsequent cytolysis. Additional data showed that the recognition was also directed against Ia molecules of the H-2(d), but not H-2(k), haplotype. Normal spleen cells of DBA/2, B 10.D2, and B 10.OL mice were bound, whereas those of CBA, B 10.BR, B 10.A, B 10.GD, and D2.GD were not. Furthermore, the Ia molecules were in the form of a hybrid, because spleen cells from F(1) progeny of a B10.A and a B10.GD parent were recognized and bound as effectively as the RCS. Recognition was not restricted solely to the H-2(d) haplotype. Spleen cells from B10.S(9R) mice were also significantly bound. This result suggested that the RCS expresses a hybrid Ia molecule containing a beta-chain of the H-2(8) haplotype. Recognition of this hybrid Ia molecule by the host resulted in a cross- reactive recognition of H-2(d) specificities. Further analysis revealed that the RCS express on their cell surface an alpha-chain of the hybrid Ia molecule which is involved in host anti-tumor recognition. Preincubation of the RCS with monoclonal antibody directed against the Ia.7 specificity on the alpha-chain could block lymphocyte-to-tumor cell binding. The blocking activity could be removed by preabsorption of the antibody on the RCS, as well as normal Ia.7-bearing lymphocytes, but not on lymphocytes that do not express Ia.7, such as SJL/J. The data suggest that the hybrid Ia molecules expressed on the RCS, and recognized by tumor-primed syngeneic lymphocytes, are composed of both a syngeneic and an alien chain. The component alien to the SJL/J host is the Ia.7-bearing alpha-chain. Normal SJL/J cells synthesize but do not express the beta-chain. In the RCS, however, alien alpha-chain synthesis permits expression of the syngeneic beta-chain in the form of a hybrid Ia molecule.
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PMID:Expression of hybrid Ia molecules on the cell surface of reticulum cell sarcomas that are undetectable on host SJL/J lymphocytes. 616

Analysis of cytokine (receptor) mRNA levels has been suggested to be a sensitive technique for predicting the immunomodulatory potential of drugs and chemicals. Furthermore, this type of analysis is thought to be important in unraveling mechanisms of immunotoxicity. To study these issues, male Wistar rats were exposed to the immunotoxic environmental contaminants bis(tri-n-butyltin) oxide (TBTO; 5, 20, or 80 mg/kg diet for 6 weeks), hexachlorobenzene (HCB; 50, 150, or 450 mg/kg diet for 6 weeks), or benzo(a)pyrene (B(a)P; 3, 10, 30, or 90 mg/kg body wt for 5 weeks by a daily (5 times a week) oral intubation). Spleen cells were cultured with Con A and analyzed by dot blot hybridization for IL-2, IFN-gamma, IL-2 receptor alpha-chain (IL-2R alpha; CD25), and IL-4 mRNA levels. In addition, spleen and thymus sections of TBTO-exposed animals were assayed immunohistochemically for CD25 expression. Exposure to TBTO resulted in a dose-dependent decrease in IL-2R alpha mRNA levels from 5 mg/kg, a dose-dependent increase in IFN-gamma mRNA levels from 20 mg/kg, and increased IL-2 mRNA levels at 80 mg/kg diet. Exposure to HCB resulted in a dose-dependent increase in IL-2 and IFN-gamma mRNA levels from 150 mg/kg and increased IL-2R gamma mRNA levels at 450 mg/kg diet. Exposure to B(a)P resulted in a dose-dependent increase in IL-2 and IFN-gamma mRNA levels from 10 mg/kg and increased IL-2R alpha mRNA levels at 90 mg/kg body wt. No effects were seen on IL-4 mRNA levels. Spleen and thymus sections of TBTO-exposed animals showed reduced CD25 expression from 5 mg/kg diet. These results show that (1) the correlation between altered cytokine (receptor) mRNA levels and functional endpoints is variable, depending on the type of functional endpoint tested and the compound studied, (2) these assays are among the most sensitive ones for TBTO and HCB immunotoxicity, and among the more sensitive ones for B(a)P immunotoxicity, and (3) for TBTO, these assays provide a possible clue to a mechanism for thymus atrophy, resulting from exposure to this compound: reduced IL-2R expression may impede thymocyte maturation, resulting in thymus atrophy.
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PMID:Effects of in vivo exposure to bis(tri-n-butyltin)oxide, hexachlorobenzene, and benzo(a)pyrene on cytokine (receptor) mRNA levels in cultured rat splenocytes and on IL-2 receptor protein levels. 946 72

Factor I (FI) is a regulatory serine protease of the complement system which cleaves three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. The human protein and the recently characterized mouse factor I are heterodimers of about 88,000 MW which consist of a non-catalytic heavy chain of 50,000 MW which is linked to a catalytic light chain of 38,000 MW by a disulphide bond. For the screening of a rat liver cDNA library we used a hybridization probe produced by polymerase chain reaction (PCR) using degenerated primers which corresponded to conserved parts of the human and the murine factor I nucleotide sequences. One of the identified sequences, which had a length of 2243 base pairs (bp), contained the complete coding region and the whole 3' untranslated region. The length of the coding region in rat consisted of 1812 bp followed by a 3' untranslated region of 207 bp including the polyadenylation signal and the beginning of the poly A tail. Comparison of the rat cDNA-derived coding sequence revealed identities of 87% to the mouse and of 78% to the human FI nucleotide sequence. The translation product of rat FI mRNA was 604 amino acid residues (aa) in length with an identity of 85% to the mouse (603 aa) and 69% to the human protein (583 aa). The comparison of the molecular mass predicted by the primary structure and derived from rat FI isolated from rat serum as detected in immunoblot analyses suggested a glycosylation of more than 20% of the total mass of the FI protein. Expression studies using reverse transcription (RT)-PCR assays indicated that FI-specific mRNA could neither be identified in B cells, nor in T cells, monocytes or granulocytes from rat and human peripheral blood nor in rat peritoneal macrophages. These data were in agreement with the results of RT-PCR obtained with several human lymphoma cell lines (Jurkat, MOLT-4, HUT102, Wil 2-NS, Ramos, Raji, U937) all of which were devoid of FI-specific mRNA. In accord with our data from two rat hepatoma cell lines (FAO and H4IIE) and one from man (HepG2) only isolated rat hepatocytes (HC) but neither Kupffer cells (KC), hepatic stellate cells (HSC; Ito cells) nor sinusoidal endothelial cells (SEC) expressed FI-specific mRNA. FI mRNA was also detected in human umbilical vein endothelial cells (HUVEC) and in the uterus and small intestine of the rat. Spleen and lymph nodes did not contain any detectable FI-specific mRNA.
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PMID:Rat complement factor I: molecular cloning, sequencing and expression in tissues and isolated cells. 1058 9