Interaction of heparin with beta 2-glycoprotein I and antiphospholipid antibodies in vitro.
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Antibodies, Antiphospholipid↗
Biomedical subjects
J A McIntyre
Publications and source records attributed to J A McIntyre.
Glycosylation of membrane cofactor protein (CD46) in human trophoblast, kidney and platelets.
Many cell surface glycoconjugates are differentiation markers and are involved in cell-cell and intermolecular interactions in development, immunity and cancer. Membrane cofactor protein (MCP) comprises structurally related 65 and 55 kDa glycoproteins that bear O- and N-linked glycans. MCP prevents amplification of autologous complement action on human cells. We used immunoblotting with MCP-specific monoclonal antibody TRA-2-10 to determine lectin-binding properties and glycosidase sensitivities of MCP in a study of cell-specific variation in glycosylation of this protein. The results showed that N-linked glycans on placental syncytiotrophoblast and cytotrophoblast, kidney and platelet MCP are similar in binding to concanavalin A and Lens culinaris lectins, but are not bound by leucophytohemagglutinin. Lectin binding prior to and after neuraminidase digestion indicates that MCP from these sources is highly sialylated. 65 kDa MCP was confirmed to contain more O-linked glycans than 55 kDa MCP. A fraction of platelet 65 kDa MCP is distinct, however, in bearing peripheral fucose residues. Syncytiotrophoblast is unique in containing a 110 kDa form of MCP in non-reducing SDS-PAGE that resembles 65 kDa MCP in glycosylation. Chorion laeve MCP in 4 of 8 preparations was unusually heterogeneous and differed from syncytiotrophoblast MCP after neuraminidase digestion in the forms bound to peanut agglutinin and WGA. The results indicated for the first time, differences in O-linked glycosylation of MCP in chorion laeve cytotrophoblast relative to syncytiotrophoblast, platelet and kidney MCP. We conclude that structures of MCP glycans can differ between trophoblasts and other cell types.
Antigens, CD↗
Previous birth outcome of antenatal clinic attenders in northern KwaZulu--perinatal and infant mortality rates.
A questionnaire survey was undertaken among pregnant women presenting for the first time to antenatal clinics attached to Mosvold Hospital in rural northern KwaZulu. They were asked details of the outcome of their previous pregnancies and the survival of their last-born children. Of 2,388 mothers interviewed, 1,795 had given birth previously. Of these, 41% had had their last deliveries at home, 47% in hospital and 10% at clinics. The perinatal mortality rate was 38/1,000, with no significant differences between home and hospital or clinic births. The infant mortality rate for live-born children was 62/1,000. Fifty per cent of child deaths occurred at home. The study methodology was easily applied and provided an acceptable alternative technique for measuring child mortality rates, which are so difficult to obtain in rural areas in southern Africa.
Ambulatory Care Facilities↗
AIDS--the Baragwanath experience. Part I. Epidemiology of HIV infection at Baragwanath Hospital, 1988-1990.
This four-part series describes the experience with HIV infection at Baragwanath Hospital to December 1990. In this first part we give an overview of the emergence of this disease and of its impact on the hospital. From July 1988 to December 1990, 426 HIV-positive individuals were identified: 58 were women identified in surveys at antenatal and gynaecology clinics, 60 were parents of infected babies or sexual contacts of hospitalised patients, and 30 were not inpatients (mainly patients at Soweto clinics). Of the 278 inpatients, 16 were identified in the latter 6 months of 1988, 54 in 1989 and 208 in 1990. Fifty-one per cent of the patients were in the adult medical wards, 11% in surgery, 20% in paediatrics and 18% in other disciplines. One per cent of sera from Wassermann reaction-positive women in mid-1990 were HIV-positive; this also applied to 1% of antenatal women in late 1990 and 2.7% of women with pelvic inflammatory disease. The HIV antigen assay is a useful adjunctive assay in the evaluation of HIV-antibody-positive children. The false/true-positive ratio of a rapid HIV antibody test was 2:1 initially, but the specificity improved with experience. The use of rapid diagnostic assays for HIV must be restricted to laboratories with experience in reading assays and where definitive follow-up testing is assured.
Acquired Immunodeficiency Syndrome↗
AIDS--the Baragwanath experience. Part II. HIV infection in pregnancy and childhood.
By the end of 1990, 51 symptomatic children with perinatally acquired HIV infection had been admitted to Baragwanath Hospital. Of 42 children who were followed up for at least 3 months, 15 (35.7%) died and 16 (38.1%) were lost to follow-up. The case fatality rate for these children lies between 35.7% and 73.8%. Most children became symptomatic before the age of 6 months and presenting features seen in over 70% of cases included lymphadenopathy, failure to thrive and hepatomegaly. Surviving children had recurrent admissions to hospital, predominantly for respiratory distress. Many had bacterial pneumonias. Cardiac involvement (cardiomyopathy and cor pulmonale), recurrent serious bacterial infections and neurodevelopmental abnormalities were common. Our experience confirms that vertically acquired HIV infection has a relatively short incubation period and progresses rapidly with cardiorespiratory symptoms predominating. Five HIV seroprevalence studies have been conducted in pregnant women attending Baragwanath Hospital and the Soweto clinics since 1988. The calculated doubling time is between 7 and 21 months. At the end of 1990 the HIV seroprevalence rate in pregnant women was 0.82% (95% confidence limits 0.44-1.19%).
Adolescent↗
AIDS--the Baragwanath experience. Part IV. Counselling and ethical issues.
This fourth part of the series describes the setting up of counselling for HIV-positive patients in response to the need at Baragwanath Hospital. Nurse counsellors were trained and supervised. The work, extending over 2 1/2 years, raised a number of issues for patient care and also for wider community education. Brief reference is made to pertinent ethical and cultural issues.
Counseling↗
South African obstetricians' views on caesarean section.
The widespread increase in the rate of caesarean sections performed in the Western world has become a cause for concern. In this country, two systems of health care exist, one provided by the State and the other based on private practice. A high incidence of caesarean sections has been reported, especially among private practitioners. This study investigated doctors' perceptions of caesarean section practices and explored the availability of facilities which could help to reduce the high caesarean section rate. Questionnaires were mailed to all registered obstetricians. Of these 45.2% (233) responded. Findings indicate that private obstetricians are more likely to perform caesarean sections even though they do have good facilities available to monitor or assess difficult deliveries. Other factors influencing their practice are also explored.
Attitude of Health Personnel↗
Inhibition of immunoglobulin (Ig)G-Fc-mediated cytotoxicity by seminal plasma IgG-Fc receptor III antigens.
OBJECTIVE: To determine if the presence of soluble immunoglobulin (Ig)G-Fc receptor III (Fc gamma RIII) antigens in human seminal plasma interfere with IgG-Fc-mediated effector functions. DESIGN: An antibody-dependent cellular cytotoxicity (ADCC) assay was used as a model for IgG-Fc-mediated effector functions. Human red blood cells (RBC), labeled with 51Cr were sensitized with rabbit anti-RBC and used as targets for peripheral blood leukocyte (PBL) effector cells. Cytotoxicity was measured by assessing the release of 51Cr from RBC. INTERVENTIONS: (1) Seminal plasma was added at different concentrations to the ADCC, and inhibitory effects were measured. (2) The level of seminal plasma interaction in ADCC was studied by comparing ADCC results in the presence and absence of seminal plasma with findings of target and effector cells that had been preincubated with seminal plasma. (3) The role of seminal plasma Fc gamma RIII in inhibiting ADCC was studied by coincubating seminal plasma with monoclonal antibodies (MAs) Leu 11b that block Fc gamma RIII binding sites. Two isotype-matched MA controls were used at identical concentrations. RESULTS: (1) Seminal plasma dose dependently inhibits ADCC. (2) Seminal plasma inhibition of ADCC occurs at the level of IgG-Fc interaction with effector cell Fc gamma receptors. (3) Inhibitory effects of seminal plasma on ADCC can be specifically blocked by coincubating seminal plasma with MAs Leu 11b that block Fc gamma RIII binding sites. CONCLUSIONS: Seminal plasma Fc gamma RIII antigens interfere with IgG-Fc-mediated effector functions. This mechanism could play a beneficial role in controlling potentially harmful antipaternal immune responses.
Antibody-Dependent Cell Cytotoxicity↗
A vitronectin-receptor-related molecule in human placental brush border membranes.
The heterodimeric vitronectin receptor (VNR) and platelet glycoprotein IIb/IIIa (GPIIb/IIIa) are two members of the integrin family of cell adhesion receptors that share the same beta subunit (GPIIIa). These proteins are involved in binding to vitronectin, fibrinogen and fibronectin and in cytoskeleton-membrane interactions. The present study shows that the human placental syncytiotrophoblast brush border membrane contains a heterodimer of subunit Mr values of 140,000 and 90,000 (non-reduced) or 125,000 and 100,000 (reduced). This protein was recognized by a monoclonal antibody to GPIIIa, rabbit antisera to the VNR and a human alloantiserum to GPIIIa. Brush border VNR-related protein bound to an immobilized peptide containing the Arg-Gly-Asp sequence and, less avidly, to immobilized fibrinogen. Only a small fraction of brush border VNR was associated with a cytoskeleton fraction. Membrane-bound brush border GPIIIa was distinct from that of platelets in its resistance to digestion by trypsin and Staphylococcus aureus V8 protease, and had a slightly lower mobility on SDS/PAGE. In addition, lectin-binding studies indicate glycosylation differences between microvillar and platelet GPIIIa heterodimers. Thus, although placental syncytiotrophoblast expresses a beta 3 integrin in its apical brush border, differences in protease sensitivity and carbohydrate content suggest that it may lack or mask certain antigenic determinants. This may be beneficial in avoiding harmful maternal alloantibody responses during pregnancy. Immunohistology showed that the VNR was present in syncytiotrophoblast apical but not basal plasma membranes, and was absent from other forms of trophoblast. The brush border VNR could function in localizing Arg-Gly-Asp-sequence-containing plasma proteins to the materno-trophoblastic interface.
Blood Platelets↗
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↗
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↗
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↗
Immunotherapy for recurrent spontaneous abortion and its analogies to treatment for cancer.
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Abortion, Habitual↗
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↗
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↗
Interlaboratory inconsistencies in detection of anticardiolipin antibodies.
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Abortion, Habitual↗
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↗