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Biomedical subjects

J A McIntyre

Publications and source records attributed to J A McIntyre.

At least 91 records · Page 5Linked to original sources
PubMed1991

Serological markers of sexually transmitted diseases associated with HIV-1 infection in pregnant black women.

While the prevalence of HIV-1 is increased in women attending sexually transmitted diseases (STD) clinics, in South Africa little is known about STD risk factors in women infected with HIV-1 in the general population. Serological markers of STDs were investigated in a cohort of 21 pregnant women, who were found to be carriers of HIV-1, and in 42 age- and residentially matched uninfected pregnant women. The rapid plasma reagin test (RPR) was positive in 33% of the HIV-1- infected women (P less than 0.05 compared with controls). The specific treponemal fluorescent antibody absorbed test (FTA-abs) was positive in 43% of the HIV-1-infected women (P less than 0.05 compared with controls). Similarly the prevalence of chlamydial IgG antibodies as measured by enzyme-linked immunosorbent assay was 95% (P = 0.026 compared with controls). Markers of hepatitis B infection were similar to both groups. Pregnant women with HIV-1 infection in the Johannesburg area have an increased seroprevalence of markers of STDs and more data are required on the attitudes and sexual activity of these women in order to target AIDS and education information.

Adult↗
PubMed1991

Immunogenetic studies of soluble Fc receptor (CD16) antigens in human seminal plasma.

Two forms of CD16 Fc receptors (FcRIII) have been defined on human leukocytes. Type 1, present on polymorphonuclear neutrophils (PMN), expresses the NA alloantigen system and type 2, present on natural-killer (NK) cells and macrophages, has no known polymorphic variations. We have described the presence of soluble FcRIII antigens in human seminal plasma (SP). These SP antigens retain an affinity for IgG-Fc and are biochemically distinct from leukocytic FcRIII. Their origin within the male reproductive tract and how they relate to FcRIII types 1 and 2 were not known. By using monoclonal antibodies CLB/Gran 11 and Leu 11c that differentially react with FcRIII type 1 and type 2 from different individuals, we studied how SP FcRIII antigens relate to leukocytic FcRIII. CLB/Gran 11 and Leu 11c reactivities with PMN and NK cells from a selected panel of male donors were compared with enzyme-linked immunosorbent assay reactivities of CLB/Gran 11 and Leu 11c with SP samples from these donors. The reactivity pattern with SP samples was shown to be different from findings with donors' PMN, but it corresponded with their NK cells. Our results indicate that SP FcRIII antigens do not manifest the polymorphic variations that are detected by CLB/Gran 11 and Leu 11c on PMN. These findings suggest that SP FcRIII antigens do not originate from PMN.

Adult↗
PubMed1991

Occurrence of other reproductive failures among women with recurrent spontaneous abortion.

We have previously reported an association between recurrent spontaneous abortion and ectopic pregnancy. We now report that not only ectopic pregnancy, but also other reproductive failures including hydatidiform moles, preterm births, and stillbirths are also associated with recurrent spontaneous abortion. The obstetrical histories of 455 women who had experienced two or more consecutive spontaneous abortions were studied for the occurrence of term births, preterm births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. The observed frequencies of these reproductive outcomes were compared with the expected frequencies of 920 term births, 80 preterm births, five stillbirths, 150 spontaneous abortions, 14.5 ectopic pregnancies and 0.5 molar pregnancies per 1,000 livebirths. The 455 women had experienced 1,968 pregnancies of which 184 were term births, 30 were preterm births, 16 were stillbirths, 1,669 were spontaneous abortions, 63 were ectopic pregnancies, and six were molar pregnancies. The ratio of observed to expected values was term births 0.1, preterm births 1.6, stillbirths 14.0, spontaneous abortion 6.6, ectopic pregnancy 2.6, and molar pregnancy 7.1. The gravid specific proportions of reproductive outcomes were constant suggesting comorbidity or common cause(s). The commonality that links these types of reproductive failure will provide insight into the mechanisms of reproductive wastage.

Abortion, Habitual↗
PubMed1991

Trophoblast immunity in human pregnancy defined by antiidiotype.

Successful reproduction in mammals requires the mother to immunologically accept genetically disparate tissues. Allotypic trophoblast antigens (TLX) are thought to be responsible for influencing maternal acceptance of the feto-placental graft, and faulty regulation of immunity to TLX antigens has been associated with recurrent pregnancy losses. In this report, rabbit antiidiotype (RAb2) was produced to a human TLX antibody (Ab1). This RAb2 detected TLX cross-reactive idiotypes (CRI) on antitrophoblast IgG from women with normal and abnormal pregnancies. These findings support an hypothesis that women respond immunologically to allotypic trophoblast antigens, and that idiotype-antiidiotype regulation of this response is characteristic of normal pregnancy.

Abortion, Spontaneous↗
PubMed1991

Antigens of immunoglobulin G-Fc receptor III in human male reproductive tract accessory glands.

We have documented the presence of soluble antigens of immunoglobulin (Ig)G-Fc receptor type III (FcRIII) in human seminal plasma that retain an affinity for the Fc fragment of IgG. The origin of these FcRIII antigens within the male reproductive tract was not known. By using polyclonal and monoclonal antibodies directed against different epitopes on FcRIII molecules, we demonstrated FcRIII reactivity in human prostate and seminal vesicle epithelial cells as well as in their glandular secretions. The FcRIII monoclonal antibody reactivity was removed by absorption with either seminal plasma or polymorphonuclear leukocytes that express FcRIII. Absorption of FcRIII monoclonal antibody with polymorphonuclear leukocytes also removed the reactivity with seminal plasma and vice versa. These data show for the first time that male accessory glands are a source of soluble FcRIII antigens.

Adult↗
PubMed1990

Immunohistologic evidence that villitis in human normal term placentas is an immunologic lesion.

Villitis of unestablished origin is a lesion in placentas from normal and high-risk pregnancies. We have studied villitis areas in 25 normal term placentas for immune cells, coagulation components, and endothelial markers. Villitis areas were filled with activated (HLA-DR, HLA-DP, and HLA-DQ reactive) macrophages. B lymphocytes were not identified, and T lymphocytes were of the helper (CD4) phenotype. Antibodies to coagulation components revealed perivascular and trophoblastic basement membrane deposits of factor IX, increased numbers of platelets, and fetal stem vessels that did not react with endothelial markers. These findings suggest helper T lymphocytes activate macrophages that mediate coagulation activation and alter endothelium. This combination of immunologic events results in tissue changes that are histologically diagnosed as villitis. It is not known what triggers these immunologic events, but the finding of villitis in normal placentas suggests the causative factor(s) is present in all pregnancies.

Adult↗
PubMed1990

Lactoferrin binding molecules in human seminal plasma.

During ejaculation, the iron binding protein lactoferrin binds to sperm and forms a major component of sperm-coating antigens. Physicochemical properties of lactoferrin in seminal plasma (SP) and on sperm differ from those of purified lactoferrin. These differences have been attributed to the binding of unknown seminal macromolecules to lactoferrin. We have studied lactoferrin binding molecules in SP. The SP samples were coated onto microtiter plates and tested for binding of biotinylated lactoferrin. SP was found to specifically bind biotinylated lactoferrin. This binding was competitively inhibited by coincubation with unlabeled lactoferrin but was not affected by control incubations done with human IgG or transferrin. Lactoferrin binding molecules in SP were biochemically characterized by using SDS-PAGE and ligand blotting. Biotinylated lactoferrin bound to SP molecules of approximately 120, 60 and 30 kDa. No binding was observed with biotinylated transferrin. The presence of molecules that associate with lactoferrin in SP was further studied by using crossed immunoelectrophoresis. Lactoferrin in SP immunoprecipitated as two peaks, one of which corresponded to purified lactoferrin. These results suggest that some lactoferrin molecules in SP are free and that others are associated with lactoferrin binding molecules. Binding of lactoferrin to lactoferrin binding molecules appears to change its physicochemical properties and thus could influence its biologic activity and its affinity to sperm.

Carrier Proteins↗
PubMed1990

Heat treatment of serum and plasma induces false positive results in the antiphospholipid antibody ELISA.

We found that levels of antiphospholipid antibodies (aPLA), measured with an ELISA increase if serum or plasma samples are heated. The phenomenon is dependent on duration and degree of heating, optimum levels being reached at 3 h at 56 degrees C. Negative samples become positive after heating. The heating effect is more pronounced for IgG-aPLA than for IgM-aPLA and is not observed for adsDNA, atetanus or lymphocytotoxic antibodies. The presence of serum/plasma components in addition to IgG is essential for the phenomenon to occur. Ultracentrifugation and mixing experiments with isolated IgG did not enable us to explain our observations. Nevertheless, knowledge of this phenomenon is of practical importance.

Abortion, Habitual↗
PubMed1990

Preliminary clinical study of transferrin-adriamycin conjugate for drug delivery to acute leukemia patients.

Seven patients with acute leukemia were treated intravenously with low doses of transferrin-Adriamycin conjugate. The total amount of drug given each patient was far below known toxicity levels for free Adriamycin. The number of tumor cells in peripheral blood diminished in treated patients, and bone marrow aspirates showed no evidence of disease progression. Two patients gave a febrile response and no hypersensitivity reactions were observed. Results of parallel basic research have shown that transferrin receptors on acute leukemia cells bind transferrin-Adriamycin conjugates, and kill by mechanisms at either the plasma membrane or nuclear levels, or both. Such conjugates may provide an alternative to monoclonal antibody drug targeting.

Acute Disease↗
PubMed1989

Soluble antigens of IgG receptor Fc gamma RIII in human seminal plasma.

Human seminal plasma (SP) has been shown to affect several immunologic reactions in vitro. This might be due in part to the presence of proteins that specifically bind the Fc domain of IgG. By using mAb Leu 11a, Leu 11b, Leu 11c, and 3G8 we showed that the Fc binding of SP is associated with a molecule that antigenically resembles Fc gamma RIII. This molecule manifests specific affinity for solid phase-coupled IgG-Fc, and appears not be be cell membrane-associated. When compared with serum or blood plasma, its highest concentration was found in SP. Western blot analysis of SP performed with mAb Leu 11a, Leu 11b, Leu 11c, and 3G8 showed distinct bands at approximately 70 and 35 kDa, which contrasts with the broad area of electrophoretic mobility reported for membrane-bound Fc gamma RIII. These molecules in SP could influence maternal immune responses to paternal Ag during fertilization and pregnancy.

Antibodies, Monoclonal↗
PubMed1989

Villitis in normal term human placentae: frequency of the lesion determined by monoclonal antibody to HLA-DR antigen.

Chronic villitis is a placental lesion of unestablished etiology. It is characterized by destruction of chorionic villi with a mononuclear infiltrate and focal areas of fibrinoid necrosis. The lesion frequently is seen in normal placentae, yet more lesions have been reported in placentae from abnormal pregnancies. We measured the extent of villitis in 25 normal term placentae by using both light microscopy and immunocytology for class II (HLA-DR) antigens of the major histocompatibility complex. HLA-DR antigens were found to be characteristic of villitis areas. Normal placentae showed striking variations in the incidence of villitis, but these variations did not correlate with clinical outcome.

Adult↗
PubMed1989

Seminal vesicles: a source of trophoblast lymphocyte cross-reactive antigen.

Maternal recognition of allotypic trophoblast lymphocyte cross-reactive (TLX) antigens is proposed to be involved in immunologic acceptance of the allogeneic fetus. The presence of TLX antigens in seminal plasma suggests that sensitization can occur before fertilization and implantation. In this study, the origin of TLX antigens within the male reproductive tract was investigated. Analysis of split ejaculates and immunohistological examinations of male accessory gland tissues showed the luminal epithelium of seminal vesicles as the source of seminal plasma TLX antigens. This finding suggests that seminal vesicles may play a role in the immunology of human reproduction.

Animals↗
PubMed1989

Hemostasis and fibrinolysis in renal transplantation.

Results of histologic, biochemical, and immunologic studies suggest that coagulation and fibrinolysis are possibly important in kidney graft rejection, but there is no information about how or why they are involved. The touchstones of their importance are histologic reports of platelet-fibrin thrombi in glomerular vessels of rejecting kidneys. Most of the nonhistologic studies have made use of functional assays aimed at measuring coagulation changes in blood. Little use has been made of immunoassays, and there are almost no studies of recently described anticoagulant systems, such as the protein C pathway. Endothelial cells form the interface between donor and recipient tissues. Antibody or thrombin-stimulated endothelium produces PAF, and thrombin-stimulated endothelium produces both plasminogen activators and plasminogen-activator inhibitors. As important as these reactions might be, information about them has been obtained with the use of either in vitro experiments or artificial systems, and there is no direct evidence that they are relevant to transplantation. However, these observations do show that tissue factor, PAF and fibrinolytic activities can be immunologically triggered. This opens the possibility that allogeneic recognition may initiate the triggering process. The clotting and fibrinolytic phenomena discussed in this overview were consequences of allogeneic recognition. Such recognition reactions cause monocytes and macrophages to produce tissue factor, which is a potent initiator of coagulation. Endothelial cells also can be stimulated to elaborate tissue factor by immune complexes, interleukin-1, or endotoxin. These observations give cause to speculate that the link between immunity and coagulation in kidney transplantation could be products of allogeneic recognition that activate Factor VII and lead to fibrin deposition. If true, this suggests new approaches to the old problems of diagnosis and treatment of rejection reactions in organ transplantation.

Fibrinolysis↗
PubMed1989

Immunological studies of trophoblast antigens: no evidence for human leucocyte antigen (HLA) linkage.

Parental disparity for trophoblast-lymphocyte crossreactive (TLX) antigens may promote successful pregnancy. A TLX antigen system has been defined on peripheral blood lymphocytes by heteroantisera. More recently, we have reported additional activity against antigens on B lymphocytes alone termed trophoblast-B lymphocyte crossreactive (TBX) antigens. In the present study we have investigated ten TLX sera in order to determine if their target antigens are linked to the human leucocyte antigen (HLA) gene complex. The sera showed no selective activity when tested against target B lymphocytes from ten normal donors. Cytotoxic activity of TLX antisera against peripheral blood lymphocytes from six normal donors was not reduced when the class I HLA antigens of the target cells were blocked with a monoclonal antibody (PA 2.6). Similarly the cytotoxic activity of both TBX antisera against B lymphocytes from six normal donors was not decreased when class II HLA antigens were blocked by a monoclonal antibody (FMC 4). Within a family the cytotoxic activity of the TLX antisera was absorbed equally by lymphocytes from siblings who shared neither HLA haplotype. Antibody content in TLX and TBX antisera is not directed toward the classically defined HLA class I or class II antigens and is not linked to the HLA gene complex.

Animals↗