Filtering valve glaucoma implants.
Explore the source record for details and available documents.
Glaucoma↗
Biomedical subjects
J Freedman
Publications and source records attributed to J Freedman.
Thrombin binding to platelets and their activation in plasma.
The interactions of alpha-thrombin with platelets are critical in haemostasis and arterial thrombosis. This study established methods for characterizing the binding of alpha-thrombin to platelets and some of its consequences in platelet-rich plasma. The binding of alpha-thrombin to platelets and the subsequent platelet activation were quantified by flow cytometry, using affinity purified polyclonal antibodies to human alpha-thrombin and a monoclonal antibody to GMP-140, respectively. Dose-dependent binding of alpha-thrombin to platelets and their activation occurred in parallel, both reaching the maxima for each enzyme concentration within 10s after > or = 1.0 nM alpha-thrombin was added to recalcified PRP containing 1 microM recombinant tick anticoagulant peptide. The tick anticoagulant peptide abrogated prothrombin activation in the platelet-rich plasma. alpha-Thrombin binding to platelets, and their activation, were abrogated by a monoclonal antibody to the hirudin tail-like domain of the seven transmembrane thrombin receptor on platelets. Therefore this receptor represents an important site for alpha-thrombin binding to platelets suspended in plasma. D-Phe-Pro-ArgCH2-alpha-thrombin only bound to platelets when its concentration was > or = 100 nM, and it did so without inhibiting platelet activation by alpha-thrombin. Whereas concentrations of hirudin equimolar to those of alpha-thrombin failed to abrogate alpha-thrombin-mediated activation of platelets, a 10-fold molar excesses of hirudin over alpha-thrombin abrogated alpha-thrombin binding to platelets. The demonstration that > or = 1.0 nM alpha-thrombin can bind to platelets and initiate their activation raises the possibility that the levels of thrombin generated in venous and arterial thrombosis contribute to platelet activation in vivo.
Blood Platelets↗
The effect of rabbit antithymocyte serum (RATS) and OKT3 on peripheral blood mononuclear cell subsets following renal transplantation.
Fifty-five renal transplant recipients were studied prospectively for changes in monoclonal antibody-defined mononuclear cell subsets (MCS) over the first 45 days posttransplant. Patients received induction immunotherapy with either monoclonal OKT2(n = 29) or polyclonal RATS (n = 26) preparation. Sequential examinations showed characteristic patterns of MCS depletion, which differed according to the type of therapy received and which subset was examined. In general, induction therapy with RATS resulted in greater and more sustained reduction of most MCS than was seen with OKT3 therapy. In recipients who received OKT3 induction there was a correlation between allograft rejection and an increase in lymphocytes expressing pan-T cell markers and in natural-killer cells. In contrast, rejection episodes in patients receiving RATS were associated with increases in subpopulations of T cells including helper, inducer and suppressor/cytotoxic T-cell subsets. There was no correlation of rejection with B cells or T-cell activation markers. The different patterns of MCS depletion with different antilymphocyte preparations and the association between changes in different MCS and rejection warrant further investigation.
Animals↗
Idiopathic thrombocytopenia and neutropenia in childhood.
PURPOSE: Between 1975 and 1990, 13 patients seen at The Hospital for Sick Children, Toronto, Ontario, were noted to have concurrent idiopathic thrombocytopenia and neutropenia (ITN; platelet count < 150 x 10(9)/L; absolute neutrophil count < 1.5 x 10(9)/L). These patients all had normal marrow function and no evidence of systemic disease. PATIENTS AND METHODS: A detailed chart review was performed to define the clinical and laboratory features of these patients. RESULTS: Although this was a heterogeneous group of patients, they shared several common characteristics. The disease followed a chronic course with thrombocytopenia or neutropenia or both that persisted or recurred over the entire period of follow-up in all patients (18 months to 15 years). The disease was associated with splenomegaly in eight patients and lymphadenopathy in nine patients. Boys were affected more frequently than were girls (ratio 11:2). Thrombocytopenia improved temporarily during treatment with corticosteroids, i.v. immunoglobulin G, RhoGAM, and a variety of immunosuppressive agents; however, neutropenia tended to be much more resistant to these therapies. Splenectomy was ineffective in two children in whom the procedure was performed. Platelet of and neutrophil antibodies or both were detected in five of six patients who were tested, suggesting an autoimmune cause for the cytopenias. CONCLUSIONS: These findings suggest that ITN in childhood is distinct from immune thrombocytopenic purpura, particularly in terms of its chronicity and poor response to therapy.
Adolescent↗
Downregulation of the anti-HLA alloimmune response by variable region-reactive (anti-idiotypic) antibodies in leukemic patients transfused with platelet concentrates.
Approximately 30% to 40% of patients with acute leukemia receiving repeated pooled random-donor platelet transfusions develop anti-HLA alloantibodies. Over time, however, serum anti-HLA concentrations decrease in approximately 50% of these patients, despite continued exposure to platelet and/or red blood cell transfusions. Using an enzyme-linked immunosorbent assay to measure serum Igs, the present study demonstrates that the sera of 67% of 82 transfused patients exhibiting a decrease in anti-HLA contain antibodies (anti-idiotypes) that react with the variable (V) region of anti-HLA antibodies. Anti-HLA binding to platelet membranes could be inhibited by these serum antibodies in 36% of the patients, indicating they had paratope-related reactivity. Protein G sepharose absorption showed that the anti-HLA V region-reactive antibodies were IgG. Of the 43 patients who had a decrease in anti-HLA levels, that were 16 whose anti-HLA decreased to undetectable levels; 7 (44%) developed anti-idiotypic antibodies that could specifically inhibit their own previously anti-HLA-positive serum. In contrast, antibodies with reactivity to the V region of anti-HLA antibodies (anti-idiotypes) were not demonstrable in patients who developed anti-HLA that did not decrease or disappear. The findings suggest that the development of anti-HLA V region-reactive antibodies (anti-idiotypic antibodies) correlates with a decrease in anti-HLA antibody formation in patients multiply transfused with platelet concentrates. The observations indicate that anti-idiotypic antibodies may downregulate alloimmune responses in patients undergoing repeated allostimulation during platelet transfusion therapy.
Acute Disease↗
Rapid separation of CD4+ and CD19+ lymphocyte populations from human peripheral blood by a magnetic activated cell sorter (MACS).
Rapid purification of human lymphocyte subpopulations is an essential step in order to elucidate their interactions and/or contributions in various disease states. Cell purification using a Magnetic Activated Cell Sorter (MACS) is a relatively new technology which has been shown to be rapid and yield highly purified populations of cells. This report describes both a simple one-step positive selection method using the MACS to purify either human CD4+ or CD19+ lymphocytes from PBMC and a sequential separation of both CD4+ and CD19+ cell populations. These methods can separate the cell populations in approximately 4 h with yields > 90% and purity of 97 +/- 3% for CD4+ T cells and 92 +/- 5% for CD19+ B cells. In functional studies, purified CD19+ B cells secreted 13- and 24-fold more IgM and IgG, respectively, than the CD19- cell fraction in 10 day B cell stimulation assays. Purification of the two cell types did not cause any significant activation as shown by proliferation. Both cell types, however, were able to proliferate upon stimulation with interleukin-2.
Antigens, CD↗
Prenatal diagnosis of neonatal alloimmune thrombocytopenia using an allele-specific oligonucleotide probe.
The prediction of neonatal alloimmune thrombocytopenia (NAIT) in affected families is usually based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. Recently the use of allele-specific oligonucleotide probe typing for PlA (HPA-1) antigens has been described to determine the risk of second or subsequent fetuses in families where one infant had the diagnosis of anti-PlA1 (HPA-1a)-mediated NAIT (McFarland et al., 1991a). This paper describes the first case in which the prenatal diagnosis of PlA (HPA-1) antigen status was accomplished using this technology on genomic DNA derived from chorionic villus tissue in the first trimester, and presents the implications of these findings for the clinical management of this disorder.
Adult↗
Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects both CD4+ and CD8+ T cells.
To study the basis for immunological tolerance of peripheral tissue-specific antigens, a transgenic mouse line was established that expresses the influenza hemagglutinin (HA) on pancreatic islet beta cells (Ins-HA transgenic mice). When followed up to 14 months of age, Ins-HA transgenic mice did not develop spontaneous autoimmune disease. Upon immunization with HA-expressing viruses, high titers of HA-specific circulating antibody were detected; however, T cell responses by both the T helper and T cytolytic compartment were markedly reduced as compared with transgene-negative littermates, and no evidence could be found for islet infiltrates. Adoptive transfer of histocompatible lymphocytes from transgene-negative mice plus virus into irradiated Ins-HA hosts resulted in islet inflammation dominated by CD4+ T cells, indicating that the HA antigen was accessible to activated T cells. These results suggest that T cells can be rendered tolerant of antigens expressed outside the thymus.
Amino Acid Sequence↗
Effects of interpleural bupivacaine (0.5%) on canine diaphragmatic function.
Several authors have questioned the potential for phrenic nerve paralysis with interpleural analgesia. This study was designed to examine the potential for phrenic nerve paralysis with the use of interpleural bupivacaine in dogs. Seven dogs were anesthetized, tracheally intubated, and allowed to breathe spontaneously with halothane/oxygen while in the supine position. After a midline laparotomy, two wires were inserted into the costal portion of each hemidiaphragm for measurement of electromyographic (EMG) signals. A balloon catheter was placed in the abdominal cavity to measure abdominal pressure. The abdomen was then closed. Airway pressure was measured through a side port in the endotracheal tube. Bilateral interpleural catheters were inserted with the loss-of-resistance technique. Each dog was used for two experiments, one on each side, except for one animal. To assess the contribution of the ipsilateral diaphragm to total respiratory effort, the airway was occluded at functional residual capacity for three consecutive breaths, and EMG, airway pressure, and abdominal pressure were measured. In five of nine experiments with bupivacaine, there was complete loss of EMG activity on the side of the injection. In two dogs, there was partial loss of diaphragmatic function, and in the remaining two, there was no change in EMG. In the normal saline solution group (n = 4), there was no change in the EMG. Two dogs that received bilateral bupivacaine injections developed paradoxical respiration with negative inspiratory intraabdominal pressures. Phrenic nerve paralysis or paresis can occur with interpleural blockade. The factors affecting the occurrence of this complication remain to be elucidated.
Animals↗
Cellular immune mechanisms in chronic autoimmune thrombocytopenic purpura (ATP).
Chronic autoimmune thrombocytopenic purpura (ATP) is a common autoimmune-mediated bleeding disease in which autoantibodies are directed against platelets, resulting in their enhanced Fc-mediated destruction by macrophages in the spleen. While there has been extensive studies relating to the autoantibodies in this autoimmune disorder, relatively few have dealt with cell-mediated immunoregulation of the anti-platelet autoantibody response. Nonetheless, there is accumulating evidence that suggests the production of these anti-platelet autoantibodies is under the influence of several abnormal lymphocyte-mediated mechanisms, i.e. enhanced anti-platelet T helper cell activity with concomitant reduced T suppressor cell activity. This review focuses on these cellular events and presents a working model which attempts to explain their close interrelationships.
Autoantibodies↗
Clinical experience with the Molteno dual-chamber single-plate implant.
A Molteno dual-chamber single-plate implant was placed in 40 consecutive patients, who were followed for a minimum of 6 months. This implant is identical to the single-plate Molteno implant, except for the addition of a pressure ridge to the upper surface of the episcleral plate, which allows the episcleral tissues to function as a temporary, pressure-sensitive valve, limiting the escape of aqueous in the early postoperative period. Confirming earlier studies, we found that use of the modified implant reduced immediate postoperative hypotony, eliminated choroidal hemorrhage, and, by obviating ligature of the silicone tube, permitted immediate reduction of elevated intraocular pressure.
Choroid Hemorrhage↗
Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia.
Chronic autoimmune thrombocytopenic purpura (ATP) is a common hematologic disorder in which platelet-specific autoantibodies bind to platelets and enhance their destruction by the reticuloendothelial system. While there has been considerable investigation of the humoral immune abnormalities in ATP, little work has been performed on the cellular immunoregulatory aspects of this autoimmune disorder. We describe here that patients with ATP have lymphocytes that proliferate normally when stimulated by mitogens. However, when stimulated by normal control platelets in 7-day antigen-presenting cell cultures, peripheral blood mononuclear cells (PBMC) from patients with ATP proliferate at significantly higher levels (P less than .001) and their lymphocytes secrete significantly higher amounts of interleukin-2 (IL-2) (P less than .001) than do lymphocytes from control subjects. Depletion studies with monoclonal anti-CD8 and complement did not reduce the proliferative capacity of the responding PBMC population, indicating that CD4+ T-helper cells may be responsible for the response. Phenotypic analysis of peripheral blood lymphocyte subsets from patients with ATP showed that there was a significant reduction in CD4+Leu8+ T suppressor-inducer cells (P less than .001) and a concomitant increase in CD3+DR+ activated T cells (P less than .001) and CD19+ B cells (P less than .05). These data indicate that CD4+ T-helper cells from patients with ATP are stimulated by normal platelet antigen(s) to secrete IL-2 and may modulate the enhanced antiplatelet autoantibody response.
Adult↗
Molteno implants as a treatment for refractory glaucoma in black patients.
Eighty-two black patients with refractory glaucoma were treated with a single-plate Molteno implant inserted in a single-stage procedure. A successful outcome (intraocular pressure less than or equal to 21 mm Hg with or without adjunctive medical therapy) was achieved in 72% of the patients with a mean follow-up of 30 months. Success was achieved in 23 (73%) of the 31 patients with open angle glaucoma, 20 (83%) of the 24 patients with either aphakic or pseudophakic glaucoma, 12 (67%) of the 18 patients with neovascular glaucoma, four (80%) of the five patients with uveitic glaucoma, and two (50%) of the four patients with congenital glaucoma. All but four patients required additional medical therapy. Visual acuities remained the same or improved in 21 (68%) of the 31 patients with open angle glaucoma, 11 (61%) of the 18 with neovascular glaucoma, 19 (79%) of the 24 patients with aphakic/pseudophakic glaucoma, three (75%) of the four patients with congenital glaucoma, and four (80%) of the five patients with uveitic glaucoma. Complications included hyphema (18%), "kissing" choroidal effusion (6%), blocked tube (8%), flat anterior chamber (12%), cataracts (5%), Tenon's cyst (encapsulated bleb) (17%), uveitis (7%), phthisis bulbi (5%), and erosion of the silicone tube (1%).
Black People↗
Suppressed natural killer cell activity in patients with chronic autoimmune thrombocytopenic purpura.
Natural killer (NK) cell activity was studied in 17 patients with primary chronic idiopathic autoimmune thrombocytopenic purpura (ATP). Fifteen of 17 patients had a significantly reduced NK cytotoxicity against 51chromium labeled K562 target cells (mean LU20% = 18 +/- 20 in patients versus 65 +/- 25 in controls, P less than 0.001). NK activity was also significantly reduced in all of six patients with secondary ATP as compared with normal controls (LU20% 28 +/- 15, respectively, P less than 0.005). The NK activity in both patient groups correlated with the duration of therapy being received (r = 0.60, P less than 0.001). Immunophenotypic analysis of peripheral blood mononuclear cells from patients with ATP revealed that CD8- cells bearing CD57 (HNK-1, Leu 7) and CD3- cells bearing CD56 (Leu 19) were quantitatively within the normal range. These findings indicate that patients with ATP have a functional defect in NK cytolytic activity.
Adolescent↗
Simple method for differentiating between HLA and platelet-specific antibodies by flow cytometry.
Since platelets express both platelet-specific and class I HLA antigens, serum antiplatelet reactivity assessed by most platelet antibody techniques could be due to antibodies with either or both specificities. Flow cytometric analysis of sera for detection of antiplatelet antibody commonly employs a purified platelet preparation as target cells. A method is described for investigating sera for platelet antibodies by flow cytometry using a mixture of platelets and lymphocytes. The mixture of lymphocytes and platelets as target cells has the advantage of confirming the presence of the HLA antibodies in reactive sera. The concomitant use of platelets and lymphocytes treated with citric acid, pH3, or with chloroquine (to remove or alter surface HLA antigens without affecting platelet specific antigens) may further assist in identifying antiplatelet antibodies in alloimmunized patients. These techniques may also be useful in platelet crossmatching procedures.
Antigens, Human Platelet↗
White cell depletion of red cell and pooled random-donor platelet concentrates by filtration and residual lymphocyte subset analysis.
This study comparing the relative white cell (WBC)-depleting efficiency of single and double filtration used two filters and new, sensitive, and reliable methods for performing WBC counts on WBC-depleted blood products. A single filtration of red cell (RBC) concentrates with a cotton-wool filter reduced WBC content by 98.64 percent, but the range of residual WBCs was wide, and many filtered units still contained more than the theoretical immunizing dose of 5 to 10 x 10(6) WBCs. A second filtration, however, always produced RBC units that had less than 5 x 10(6) WBCs. Although the degree of WBC depletion observed after a single filtration of a 6-unit pool of random-donor platelet concentrates was greater with a polyester filter than with the cotton-wool filter (98.92 vs. 98.14% reduction, respectively, when mean prefiltration WBC count was less than 600 x 10(6], in both cases, 25 percent of filtered products still contained greater than 5 x 10(6) WBCs; a second filtration (with the cotton-wool filter), however, produced units that were always below the immunizing dose. All double-filtered platelet concentrates had less than 10(6), and one-half had less than 10(4) residual WBCs. Platelet loss was similar with both filters (+/- 16% loss with one filtration). The effectiveness of the filters in producing products that were WBC-depleted below the immunizing dose was dependent on the prefiltration WBC content (but not on the age of the units), and it may be worthwhile to employ methods to ensure that total prefiltration WBC count of the product is less than 400 x 10(6).(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD↗
Peripheral tolerance in transgenic mice: tolerance to class II MHC and non-MHC transgene antigens.
Explore the source record for details and available documents.
Animals↗