PubMed Health⌕ Search

Biomedical subjects

J A McIntyre

Publications and source records attributed to J A McIntyre.

At least 37 records · Page 2Linked to original sources
PubMed2000

Risk of early renal allograft failure is increased for patients with antiphospholipid antibodies.

Renal allograft thrombosis can cause transplant failure. Because antiphospholipid antibodies (aPA) are associated with thrombosis, we investigated pretransplant sera from patients with early renal allograft failure to determine if aPA were present. Fifty-six final cross-match (FxM) sera from patients whose transplant failed within 16 days were compared to FxM sera from the next sequential transplant patients. The sera were tested for IgG, IgM, and IgA antibodies to cardiolipin, phosphatidylserine, and phosphatidylethanolamine. aPA were identified in 57% of FxM sera from patients with early non-function versus 35% of FxM sera from patients with functioning grafts (P = 0.02). Historical sera from 11 aPA-positive patients contained aPA up to 18 months prior to transplantation. Since aPA were present in historical sera, testing for aPA can identify certain patients at risk for early allograft failure. The involvement of aPA in early allograft loss is supported by studies demonstrating aPA recovery from an explanted failed transplant.

Antibodies, Antiphospholipid↗
PubMed2000

Immunochemical analysis of polyspecific antibodies in patients exposed to bovine fibrin sealant.

BACKGROUND: Patients exposed to bovine thrombin preparations in fibrin sealant often develop antibodies to bovine coagulation proteins, which cause significant bleeding by cross-reacting with human homologues. Recipients of our left ventricular assist system (LVAS) routinely are exposed to fibrin sealant; therefore, we determined whether they developed antibodies. METHODS: We compared sera from 6 LVAS recipients exposed to fibrin sealant (THROMBOGEN, Johnson & Johnson, Arlington, TX ) during LVAS placement to that of 5 nonexposed LVAS recipients. Pre-LVAS and weekly post-LVAS sera were tested for immunoglobulin (Ig)G, IgA, and IgM reactivity to THROMBOGEN by enzyme-linked immunosorbent assay. Peak IgG and IgA reactive sera were characterized by immunoblotting. RESULTS: All patients exposed to THROMBOGEN developed antibodies: 5 developed IgG, 4 IgA, and 3 IgM. In contrast, nonexposed patients did not develop antibodies. Only some antibody reactivity was contributed by antithrombin or antifactor V antibodies. Silver stain sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses of THROMBOGEN showed more than 18 bands, many of which were recognized in Western blot by positive patient sera. CONCLUSIONS: We found both IgG and IgA polyspecific antibody responses in patients exposed to bovine thrombin preparations.

Adult↗
PubMed2000

Changes in platelet activation associated with left ventricular assist system placement.

BACKGROUND: Thromboembolic and hemorrhagic complications are common in patients after left ventricular assist system (LVAS) placement. Platelet physiology may be involved in these complications. METHODS: Using flow cytometry, expression of CD62P and CD63 were analyzed as markers of platelet activation. Binding of annexin V was analyzed to determine platelet membrane asymmetry. Results from two patients who received a Novacor LVAS as a bridge to transplantation are reported. RESULTS: Patients' platelets showed increased CD62P and CD63 expression, yet annexin V binding was not increased. They also revealed suppression of thrombin activation following LVAS placement, which approached normal after transplantation. Heparin suppressed thrombin activation, whereas aspirin or dipyridamole did not. Suppression was attenuated by protamine sulfate and heparinase. CONCLUSIONS: Following LVAS placement, resting platelets demonstrate increased expression of activation markers.

Annexin A5↗
PubMed1999

Antiphospholipid antibodies are a risk factor for early renal allograft failure.

BACKGROUND: Biopsy specimens of transplanted kidneys that fail to function reveal cellular infiltrates, infarcts, and thrombi. Because antibodies to phospholipids (aPA) and/or phospholipid-binding proteins have been associated with thrombosis, we asked whether aPA are a risk factor for early allograft failure. METHODS: Final crossmatch sera from 56 patients with primary nonfunctioning renal allografts were tested for aPA. Serum from the next consecutive patient to undergo transplantation served as transplantation controls. Both groups were compared with aPA values obtained from testing 252 control individuals. The ELISA was designed to detect IgG, IgM, and IgA antibodies to phosphatidylserine, cardiolipin, and phosphatidylethanolamine. RESULTS: Patients were evaluated based upon the aPA ELISA findings. aPA were present in 57% of the patients with early nonfunction renal allografts and 35% of the patients with functioning grafts (P=0.0234). aPA in previously hemodialyzed patients did not predict allograft failure or success (P=0.3766). In contrast, all nonhemodialysis patients who had aPA at the time of transplantation experienced early allograft failure (P=0.0022). CONCLUSIONS: These data show that aPA are an important risk factor for early renal allograft failure. Furthermore, aPA-positive patients who have no history of hemodialysis are at the greatest risk. Pretransplantation aPA screening of renal transplant candidates forewarns of early graft failure and indicates which patients may benefit from anticoagulant therapy.

Animals↗
PubMed1999

Platelet membrane early activation markers during prolonged storage.

The relationship between platelet aging and early markers of membrane activation have not been defined clearly. Activation markers expressed during prolonged storage are similar if not identical to those that appear after exposure to thrombin. Using flow cytometry, we investigated platelet membrane expression of CD62P, CD63, and annexin V binding (i.e., loss of membrane asymmetry) in platelets stored for up to 11 days under standard blood banking conditions. We compared five apheresis platelets to two random donor platelet concentrates, and to one pooled platelet preparation from six single platelet concentrates before and after exposure to thrombin. CD62P, CD63 expression, and annexin V binding increased during storage albeit with different kinetics. The differential increments observed between resting and thrombin (1 unit/ml) activated platelets showed an inverse correlation to storage time for CD62P, CD63, and annexin V binding, which was identical to published survival curves. A difference between apheresis platelets and platelet concentrates was observed only on day 1. Our data indicate that the in vitro platelet reserve activity to thrombin activation mirrors that of radiolabeled platelet survival in vivo and that platelet cross-sectional residual life span can explain their diminished capacity to respond to thrombin as a function of viability.

Annexin A5↗
PubMed1999

Development of optimal techniques for cryopreservation of human platelets. I. Platelet activation during cold storage (at 22 and 8 degrees C) and cryopreservation.

Using the current blood bank storage conditions at 22 degrees C, the viability and function of human platelets can be maintained for only 5 days. This does not allow for the necessary and extensive banking of platelets needed to treat patients afflicted with thrombocytopenia, a side effect of many invasive surgeries such as cardiopulmonary bypass or bone marrow transplantation. The development of optimal techniques for long-term cryopreservation and banking of human platelets would provide the ability to greatly extend the viable life of the platelet and would fulfill an increasing and urgent need in many clinical applications. To determine the optimal techniques for platelet preservation, the expression of an activation marker, phosphatidylserine, on the platelet membrane during storage at 22 and 8 degrees C as well as during the different freezing preservation processes was examined using flow cytometry and annexin V binding assay. Human platelets were identified by both CD41 and light scatter in flow cytometry. In cryopreservation experiments, effects of the following factors on platelet activation were evaluated: (a) cryoprotective agents (CPAs) type: dimethyl sulfoxide (Me2SO), ethylene glycol (EG), and propylene glycol (PG), (b) CPA concentration ranging from 0 to 3 M, and (c) ending temperatures of a slow cooling process at -1 degrees C/min. Our results demonstrated that (a) approximately 50% of platelets were activated on days 7 and 16 at 22 and 8 degrees C, respectively; (b) platelets were not significantly activated after 30-min exposure to 1 M Me2SO, EG, and PG at 22 degrees C, respectively, and (c) there was a significant difference in cryoprotective efficacy among these three CPAs in preventing platelets from cryoinjury. After being cooled to -10 degrees C, 74% of the cryopreserved platelets survived (nonactivated) in 1 M Me2SO solution, while in 1 M EG and 1 M PG solutions, 62 and 42% of the platelets survived, respectively. Using the information that Me2SO consistently yields higher percentages of nonactivated platelets and does not seem to be cytotoxic to platelets for 30-min exposure time, this was found to be the optimal cryoprotective agent for platelets. In addition, significant Me2SO toxicity to platelets was not noted until Me2SO concentrations exceeded 2 M. Finally, a concentration of 1 M Me2SO proved to be the most effective at all cryopreservation ending temperatures tested (-10, -30, -60, and -196 degrees C). In conclusion, under the present experimental conditions, a storage temperature of 8 degrees C appeared to be much better than 22 degrees C. Although the potential chemical toxicity of 1 M Me2SO, EG, or PG is negligible, 1 M Me2SO was found to be optimum for cryopreservation of human platelets. PG has the least cryoprotective function for low-temperature platelet survival.

Blood Platelets↗
PubMed1999

Unique epitopes of lactoferrin expressed in human cytotrophoblasts involved in immunologic reactions.

OBJECTIVE: Lactoferrin is an iron-binding protein that has been implicated in protection against infections and allogeneic recognition reactions and in the control of cell growth. We studied the biochemical characteristics and expression of the unique lactoferrin epitopes (LF(1)) in human placentas. STUDY DESIGN: Immunohistologic studies of normal human term placentas were done by using monoclonal antibodies to LF(1). Double-antibody experiments were done by using monoclonal antibodies to markers of inflammation (macrophages, human leukocyte antigen [HLA-DR]). LF(1) was studied immunochemically by using lactoferrin fragments produced by the reaction of lactoferrin with trypsin or N-glycanase. RESULTS: Anti-LF(1) monoclonal antibodies reacted with most interstitial cytotrophoblasts in the basal plate and with villous cytotrophoblasts of some but not all chorionic villi. Cytotrophoblasts expressing LF(1) were associated with large numbers of HLA-DR-reactive macrophages. Anti-LF(1) monoclonal antibodies reacted with 2 distinct tryptic fragments of lactoferrin, and these reactivities were not affected by treatment with N-glycanase. CONCLUSION: Placental cytotrophoblasts express unique epitopes of lactoferrin (LF(1)). Such expression is increased in the presence of activated macrophages. This expression could be an extraembryonic response to inflammation and maternal allogeneic recognition as an effort to protect trophoblastic cells. The LF(1) epitopes might represent conserved polypeptide epitopes on 2 homologous lobes of lactoferrin.

Amidohydrolases↗
PubMed1999

Increased incidence of antiphospholipid antibodies in left ventricular assist system recipients.

BACKGROUND: Antiphospholipid antibodies are associated with thrombosis. Because thromboembolic complications are often observed in recipients of a left ventricular assist system, we questioned if antiphospholipid antibodies were present in these patients. We report results from 10 patients who received a Novacor left ventricular assist system. METHODS: Serum samples were collected before left ventricular assist system placement and weekly thereafter until discharge after cardiac transplantation. Samples were tested for IgG, IgA, and IgM antiphosphatidylserine, anticardiolipin, and antiphosphatidylethanolamine using an enzyme-linked immunosorbent assay. RESULTS: Development of phospholipid-binding plasma protein-dependent antiphospholipid antibodies was observed in 9 of the 10 patients. Before placement of the assist system, 3 patients had IgG antiphospholipid antibodies, and 9 were positive after placement. None had IgA antiphospholipid antibodies before placement, whereas 5 seroconverted for IgA after placement. One patient had IgM antiphospholipid antibodies before placement, and 1 additional patient became positive after placement. In patients with a preexisting antibody, increased titers and additional specificities developed subsequent to placement. CONCLUSIONS: All but 1 patient showed development of phospholipid-binding plasma protein-dependent antiphospholipid antibodies after left ventricular assist system placement.

Adult↗
PubMed1999

Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses.

OBJECTIVE: To describe the prevalence of antiphospholipid antibodies to both anionic and zwitterionic phospholipids in women with early recurrent pregnancy losses (RPLs). DESIGN: Retrospective data analysis. SETTING: Tokai University Hospital, Kanagawa, Japan. PATIENT(S): One hundred thirty-nine patients with unexplained early RPLs. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assays were used to measure autoantibodies to phosphatidylethanolamine, cardiolipin, and phosphatidylserine. RESULT(S): Twenty-eight (20.1%), 17 (12.2%), and 2 (1.4%) patients of the 139 total patients were positive for immunoglobulin (Ig) G, IgM, and IgA antiphosphatidylethanolamine antibodies, respectively. Because 3 patients had two isotypes, 44 (31.7%) of the patients were positive for antiphosphatidylethanolamine antibodies. Six patients (4.3%) and 1 patient (0.7%) were positive for IgG and IgM antiphosphatidylserine antibodies, respectively. Seven patients (5%) were positive for beta2-glycoprotein I-independent anticardiolipin IgG, and 1 patient was positive for beta2-glycoprotein I-dependent anticardiolipin IgG. Two patients (1.4%) had lupus anticoagulant. CONCLUSION(S): Our data show a statistically stronger association between RPLs and antiphosphatidylethanolamine antibodies than between RPLs and antibodies to anionic phospholipids for early gestational losses. Our data suggest that antiphosphatidylethanolamine antibodies may be a risk factor in patients with early RPLs.

Abortion, Habitual↗
PubMed1999

Immunohistochemical analysis of vascular prostheses implanted with the left ventricular assist system.

BACKGROUND: Dacron vascular prostheses are associated with thromboembolic complications and inflammatory responses; impregnation with bovine collagen reportedly stimulates additional inflammatory/immunologic complications. The Novacor (Baxter Healthcare Corp., Oakland, CA, USA) left ventricular assist system uses Dacron inflow and collagen-impregnated Dacron outflow prostheses. METHODS: Explanted inflow and outflow prostheses were evaluated for inflammatory/immunologic, hemostatic, anticoagulant, and fibrinolytic pathways. Non-implanted prostheses immersed in whole blood or plasma were used as controls. RESULTS: Immunoglobulins and complement components were observed in all prostheses with activated macrophages being present only in implanted prostheses. Antithrombin III was observed in all prostheses whereas fibrin, tissue plasminogen activator, and alpha-2 plasmin inhibitor were present only in implanted prostheses. Endothelial and smooth muscle cells associated with vascular structures containing collagen type IV and laminin were observed solely in implanted prostheses. CONCLUSION: An inflammatory response occurs and key components of hemostatic, anticoagulant, and fibrinolytic pathways are present within implanted prostheses. These processes are accompanied by endothelial and smooth muscle cell infiltration which appear to lay the foundation for neovessel development.

Antithrombin III↗
PubMed1999

Qualitative and quantitative studies of autoantibodies to phospholipids in diabetes mellitus.

Diabetes mellitus is associated with vascular and neurological complications. We have investigated the presence of antibodies to phospholipids and to phospholipid binding plasma proteins in blood samples collected from 68 clinically and biochemically characterized type I and type II diabetic patients and from 252 healthy blood donor controls. Each sample was analysed for antibodies to three phospholipids (cardiolipin, phosphatidylserine and phosphatidylethanolamine), the antibody isotypes (IgA, IgG and IgM), and whether antibody activity was plasma protein-dependent. Patients were considered to have anti-phospholipid antibodies when one or more of these 18 tests was found above predetermined control values. The results of these experiments revealed an increased incidence of anti-phospholipid antibodies in diabetic patients compared with control subjects. The incidence of IgA isotype to phosphatidylethanolamine was higher than the incidence of other isotypes to other phospholipids, and their reactivities were independent of phospholipid-associated proteins. In addition, these antibody findings were studied for associations with prothrombin degradation products, activated factor VII and activated protein C, and with the incidence of diabetic complications. The anti-phosphatidylethanolamine antibody association with proliferative retinopathy was significant.

Adult↗
PubMed1998

The pre-conditioning incidence of antiphospholipid antibodies is not significantly increased in patients with bone marrow transplant-related organ dysfunction.

Hepatic dysfunction resulting from hepatic veno-occlusive disease (VOD) is a common complication of bone marrow transplantation (BMT). Some investigators believe that hepatic dysfunction, along with pulmonary and central nervous system (CNS) dysfunction, is part of a systemic disorder called multiple organ dysfunction syndrome (MODS). Endothelial damage by pretransplant chemo-radiation and activation of hemostasis are considered early events in the development of hepatic VOD. The pathological mechanism leading to fibrous obliteration of hepatic vessels may also take place in pulmonary and CNS vessels. Since antiphospholipid antibodies (aPA) are associated with venous and arterial thrombosis, which can lead to vessel occlusion, we asked if the incidence of aPA before conditioning was greater in patients who developed MODS following BMT. Samples drawn before pretransplant chemo-radiation from 57 patients who subsequently developed MODS and 55 control patients who did not develop MODS were studied blindly for aPA by ELISA. The number of aPA-positive patients who developed MODS (10/57), compared to the number of aPA-positive patient controls who did not develop MODS (7/55) was not statistically significant (P = 0.48). Our data indicate that the incidence of aPA before conditioning was not greater in patients who developed MODS, including hepatic VOD, following BMT.

Antibodies, Antiphospholipid↗
PubMed1998

Uteroplacental vascular involvement in recurrent spontaneous abortion.

Spontaneous abortion is common in human pregnancy. Recent advances in pregnancy immunology and vascular biology are reviewed with emphasis upon the events associated with recurrent fetal losses. Certain treatment options used to alleviate or prevent some miscarriages are presented and discussed.

Abortion, Habitual↗
PubMed1998

Compliance and use behaviour, an issue in injectable as well as oral contraceptive use? A study of injectable and oral contraceptive use in Johannesburg.

This study examines the compliance, use behaviour and knowledge of method of women using injectable and oral contraceptives in two clinic sites in the Johannesburg area, South Africa. An interviewer administered questionnaire was used to collect information in the clients' home language. A total of 400 women were interviewed in the clinics. The mean age of clients was 26.2 years (range 13 to 43 years). Of the clients not wanting to get pregnant, 30.4 per cent of injectable users and 18.4 per cent of oral contraceptive (OC) users had stopped using their method temporarily before returning to the same method (called the nonuse segment) and had not used any other form of contraception during this time. Almost one third of injectable users (31.2 per cent) had been late for their next injection at least once. Although nearly all women using injectables had experienced some menstrual disturbances, over one third (38.5 per cent) had not been informed by the providers about the possibility of these changes. Many women gave the disruption of their menstrual cycle as the reason for the nonuse segment. The majority of OC users lacked information on how to use their method correctly. Nearly all women expressed an interest in obtaining more information on their current method and other available methods. This study shows that compliance is an issue in injectable as well as OC users.

Adolescent↗
PubMed1997

Identification of structural mutations in the fifth domain of apolipoprotein H (beta 2-glycoprotein I) which affect phospholipid binding.

Apolipoprotein H (apoH), also known as beta 2-glycoprotein-I, is considered to be a cofactor for the binding of certain antiphospholipid autoantibodies to negatively charged phospholipids. Genetically determined structural abnormalities in the lipid binding domain(s) of apoH can affect its ability to bind lipid and consequently the production of the autoantibodies. In this study we have identified two common structural mutations at codons 316 and 306 in the fifth domain of apoH which rendered apoH unable to bind to negatively charged phosphatidylserine (PS). The missense mutation at codon 316 (TGG --> TCG) replaces Trp316 with Ser316 and disrupts the integrity of four highly conserved hydrophobic amino acids sequence at positions 313-316, which is a potential protein-lipid hydrophobic interaction site. The missense mutation at codon 306 (TGC --> GGC) involves the substitution of Cys306 by Gly306 which causes the disruption of a disulfide bond between Cys281 and Cys306 and affects the normal configuration of the fifth domain of apoH that appears to be critical for clustering positively charged amino acids along with four hydrophobic amino acids sequence. ApoH from the two homozygotes (Ser316/Ser316) and all seven compound heterozygotes (Ser316/Gly306) failed to bind to PS; all heterozygotes at one or the other sites and wild type showed normal PS binding. These data indicate that the fifth domain of apoH harbors the lipid binding region. An estimated 2 million Caucasians in the United States, who are compound heterozygotes for the two mutations, may be precluded from producing apoH-dependent antiphospholipid autoantibodies.

Alleles↗
PubMed1997

DQB1*0202 and the new DQB1*0203 allele: a fourth pair of DQB1 alleles differing only at codon 57.

Amino acid 57 of DQ beta chains is of functional importance as it influences peptide binding, is part of B and T cell epitopes, and is associated with susceptibility and resistance to insulin-dependent diabetes mellitus and humoral immunodeficiencies. Polymorphism of codon 57 is conserved in primates and in HLA class II B genes implying that balancing selection operates on this residue. Previously, three DQB1 allele pairs have been described, that only differ at residue 57. In an African-American Black individual with the HLA phenotype A23.30;B58,63;Cw6;DR18,12;DR52;DQ5,2, we found a fourth example of this dimorphism: the new DQB1*0203 allele, that was identical to DQB1*0202 except for codon 57, which encodes aspartic acid and alanine respectively in the two alleles. The class II haplotype carrying the new allele was deduced to be DRB1*0302,DRB3*0101,DQA1*05011,DQB1*0203.

Alleles↗
PubMed1997

Analyses of HLA-DQ alleles in recurrent spontaneous abortion (RSA) couples.

PROBLEM: The influence of HLA sharing on pregnancy outcome is controversial. In renal transplantation, HLA-DQB1 donor-recipient mismatches have been shown beneficial for long-term transplant success. Since pregnancy is defined as Nature's allograft, we investigated the relevance of HLA-DQ mismatching in normal reproducing couples compared to couples experiencing RSA. METHOD: Unexplained RSA couples referred to our laboratory for immunological testing were classified by immunological findings and obstetrical history. Primary RSA couples shared > or = 2 HLA-A, B, or DR antigens, had no cytotoxic anti-paternal antibodies, and no gestation beyond 20 weeks. Secondary RSA couples had cytotoxic anti-paternal antibodies and RSA after a live birth. HLA-DQA1 and DQB1 alleles were identified by PCR-SSP. RESULTS: No differences in DQA1 and DQB1 mismatch were observed among RSA patients and controls. DQA1-DQB1 haplotype mismatches were not different among the three groups of couples. CONCLUSIONS: In contrast to renal transplant, HLA-DQ incompatibility did not differ among RSA couples compared with successful reproducing couples.

Abortion, Habitual↗