Biomedical subjects

D S Torry

Publications and source records attributed to D S Torry.

25 records · Page 2Linked to original sources

PubMed1988

Effects of serum versus plasma on agglutination of antibody-coated indicator cells by human rheumatoid factors.

Plasma and serum contain an inhibitor (I) of the agglutination of rabbit IgG-coated sheep erythrocytes by human rheumatoid factor (RF). Plasma but not serum contains an inhibitor of the inhibitor (I/I) which allows RF to interact with its target. In normal blood, there is more I than I/I, and I can be removed by solid-phase chromatography through concanavalin A (Con A). Plasma I/I is heat labile being eliminated by heating at 56 degrees C for 30 min. Addition of exogenous calcium clots EDTA plasma, causing an irreversible loss of I/I, and suggesting its involvement in the clotting cascade. The absence of I/I from Factor V-deficient plasma and destruction of I/I by Russell's viper venom indicate I/I either is associated with or is a part of Factor V. These findings suggest a balanced interplay between I and I/I, and indicate results of immunological tests done in vitro may not accurately reflect immune function in vivo. This seems to represent an unexplored link between hemostasis and immunity.

Agglutination Tests↗

PubMed1988

Trophoblast antigens in human seminal plasma.

Secondary recurrent spontaneous (2 degrees) aborters manifest persistent IgG, which show differential cytotoxicity patterns with lymphocytes from many donors. These are non-HLA-directed antibodies, which react allotypically with both trophoblast and lymphocytes. The antigens they recognize are designated trophoblast-lymphocyte crossreactive (TLX) antigens. Xenogeneic anti-TLX sera were studied with the use of enzyme-linked-immunosorbent (ELISA) and immunochemical assays to determine the TLX status of seminal plasma. The results showed 1) allotypic TLX antigens are present in seminal plasma; 2) seminal plasma TLX antigens may be membrane associated; 3) by immunoblotting, the molecular weights of antigens reactive with TLX antisera are 15, 22, 28, 33 kD and a smear between 180 and 340 kd; 4) by isoelectric focusing, TLX antigens show pI 4.0, 5.35, 5.9, 6.5, 6.8, and 7.2. Allotypic seminal plasma TLX antigens may provide the antigenic stimuli for persistent maternal humoral immunity.

Abortion, Habitual↗

PubMed1987

Characterization of immunoglobulin class and subclass responses in secondary aborter sera.

Sera from secondary (2 degrees) aborters exhibit persistent, high-titred cytotoxicity against paternal as well as HLA dissimilar non-paternal lymphocytes. The majority of antipaternal complement-dependent cytotoxicity (CDC) and complement-independent antibody dependent cellular cytotoxicity (ADCC) was recovered in IgG enriched fractions following ion-exchange chromatography of 2 degrees aborter sera. The IgG subclasses mediating antipaternal reactivity were determined using murine anti-human IgG subclass specific monoclonal antibodies and Protein A affinity chromatography (SPA). Inhibition of paternal CDC by the anti-subclass reagents showed 75-90% of the reactivity mediated by maternal IgG1 antibodies. Anti-IgG3 inhibited 15-30% whereas anti-IgG2 produced little inhibition. SPA chromatography of 2 degrees aborter IgG supported the monoclonal antibody results in that greater than 80% of the CDC activity was recovered in the IgG1, 2, and 4 containing eluate and 20% was found in the IgG3 enriched effluent. Although the anti-IgG subclass specific monoclonals did not inhibit antipaternal ADCC, IgG3 did not appear to mediate this cytotoxicity as the ADCC was recovered in the eluate and not the effluent following SPA chromatography of 2 degrees aborter IgG enriched serum fractions. These data indicate that the humoral antipaternal and polyspecific CDC immune reactivities of 2 degrees aborters are due to the production of IgG1 and IgG3 antibodies.

Abortion, Habitual↗

PubMed1986

Differences in immunoglobulin subclasses between dye exclusion and 51Cr release complement-dependent lymphocytotoxicity assays.

Paradoxical differences previously noted between lymphocytotoxicity detected by dye exclusion at room temperature (CDCE) or by 51Cr release (CDC51Cr) at 37 degrees C in maternal antipaternal complement-dependent lymphocytotoxicity have suggested that CDCE and CDC51Cr at 37 degrees C, but not at 20 degrees C, may detect different immunological antibody-antigen interactions. Reactions in the two test systems against the same target cells were compared in sera from known immune dialysis patients, secondary aborting women, and refractory platelet recipients before and after heat treatment of sera, absorption with solid-phase heparin, anti-light-chain augmentation, and the addition of murine monoclonal anti-IgG subclass antibodies. The results demonstrate significant differences between the two tests using the same target and sera. Further, the results imply the presence of an inhibitor and an inhibitor of inhibitor in sera. The involvement of different immunoglobulin subclasses was shown in the two tests. These data demonstrate the necessity for further study of the nature of the differences in the mechanisms of these clinically important antibody-detecting systems.

Abortion, Spontaneous↗

PubMed1986

Inhibitors of complement-mediated cytotoxicity in normal and secondary aborter sera.

Sera from patients with secondary (2 degrees) spontaneous abortions contain complement-dependent cytotoxic (CDC) antibodies with specificity for paternal lymphocytes. These lymphocytotoxins are not anti-HLA (human lymphocyte antigen) as shown by their polyspecificity on HLA select cell panels and by their removal following absorption with HLA-negative trophoblast membranes. They are predominantly IgG and have been designated as trophoblast-lymphocyte cross-reactive (TLX) antibodies. Normal and homologous 2 degrees aborter sera contain a CDC inhibitor that does not bind to paternal cells and must be present when complement is added to antibody. The inhibitor does not manifest anticomplement effects and appears to be species specific. Inhibitory capacity is increased by heating (56 degrees C for 30 min) and by absorption with heparin. When chromatographed on G-200 Sephadex, inhibitor appears in the void volume, suggesting a molecular weight of more than 250,000. It can be isolated from diethylaminoethyl cellulose into an euglobulin fraction that does not contain IgG, but does contain IgM, though no studies indicate the inhibitor to be IgM. We suggest that the inhibitor is under the control of a regulator molecule, probably an inhibitor-of-inhibitor, and that in 2 degrees aborter sera the equilibrium is unbalanced between antibody, inhibitor, and regulator.

Abortion, Habitual↗

PubMedDate not supplied

Regulation of immunity to extraembryonic antigens in human pregnancy.

Pregnancy results in the immunologic challenge of the female to a wide variety of allogeneic antigens. Particular attention has been given to antibodies directed to allotypic trophoblast antigens (TLX), for trophoblast form the true allograft interface between mother and fetus. Studies found that antibodies to paternal TLX allotypes are produced in women suffering from secondary recurrent abortions. These TLX antibodies are not directed to classical HLA private epitopes. In this report, treatment of lymphocytes with papain to remove HLA Class I did not decrease TLX antigen densities. These results suggest TLX antibodies are not directed to Class I epitopes, public or private. The allotypic nature of TLX antigens requires that a pregnant female must be able to regulate TLX immune responses to avoid rejection of the conceptus. One mechanism to specifically and systemically regulate TLX immunity is the idiotype anti-idiotype network. We provide preliminary evidence in this report for the presence of TLX idiotype network in a normal primigravida. Initially, no antipaternal TLX antibodies were detected in the serum of the primigravida, suggesting no TLX immunization had occurred. However, separation of Ab1 from Ab2 by absorption of primigravida serum with 2 degrees aborter Ab1 resulted in seroconversion. The primigravida's Ab1 was cytotoxic for paternal and 3rd-party lymphocytes in a non-HLA-restricted pattern. Primigravida's Ab2 was recovered from the Ab1 matrix by competitive elution by using platelets as source of TLX antigen. The Ab2 was found to inhibit cytotoxicity by 2 degrees aborter Ab1 as well as primigravida Ab1. This is evidence that the Ab2 recognizes a cross-reactive idiotype (CRI) on TLX antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗

PubMedDate not supplied

Proto-oncogenes and germ-cell differentiation.

Oncogenes are identified functionally by their ability to induce neoplastic transformation of susceptible cells. The first oncogenes to be characterized were isolated from acutely transforming retroviruses. Subsequently, it was determined that the retroviral oncogenes were formed from normal, progenitor genes. These cellular homologs of the viral oncogenes are termed proto-oncogenes. The derivation of oncogenes from proto-oncogenes is the consequence of mutations that remove regulatory constraints from the proto-oncogene. The ability of oncogenes to induce transformation implies that proto-oncogenes may function in growth and differentiation pathways in normal cells. Although many proto-oncogenes have been defined, the normal physiological function of most is not known. Studies of proto-oncogene expression during normal gametogenesis have determined that some genes are expressed in a stage-specific manner. The use of germ cells to provide homogeneous and defined normal cell populations facilitates identifying the roles proto-oncogenes have in regulating cell growth and differentiation.

Animals↗