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Biomedical subjects

J Freedman

Publications and source records attributed to J Freedman.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Histopathologic study of the Molteno glaucoma implant in three patients.

Three eyes with the Molteno glaucoma implant (one eye with epithelial downgrowth, one eye with iridocorneal endothelial syndrome, and one eye with aphakia and glaucoma) were enucleated two to six years after implantation. Histopathologic examinations disclosed no evidence of erosion of sclera or conjunctiva of the eye by the glaucoma implant device. In the outer layers of the bleb wall, few and mostly degenerated inflammatory cells were present, which represented a minimal inflammatory reaction. Scanning electron microscopy of the tubes in these three patients showed that the tube was intact, patent, and without signs of degradation. The tube entering into the anterior chamber caused no appreciable inflammation and maintained its patency even when downgrowth epithelial cells lined the anterior chamber. The Molteno plate induced little or no inflammatory reaction. Therefore, the Molteno glaucoma implant is a useful device for patients with high risk for failure after surgery for glaucoma.

Aged↗
PubMed1990

Acute leukemia evolving from multiple myeloma and co-expressing myeloid and plasma cell antigens.

This report describes the development of acute myeloblastic leukemia in a patient after long-term alkylator therapy for multiple myeloma. Despite chromosome deletions -5, -7, the patient lacked the histochemistry and clinical findings characteristic of therapy-induced leukemia. In double-labeled surface marker studies by flow cytometry, the leukemic blast cells co-expressed myeloid and plasma cell surface markers. The findings may support the hypothesis of a single stem cell abnormality's being responsible for both the malignant plasma cells and the myeloid leukemic cells.

Acute Disease↗
PubMed1989

Immunohistochemical and behavioral analysis of spinal lesions induced by a substance P antagonist and protection by thyrotropin releasing hormone.

Using behavioural, morphological and immunohistochemical analysis, the effect of intrathecal administration of a substance P antagonist, Spantide [D-Arg1, D-Trp7,9, Leu11)-SP), was studied. Antisera raised against markers for motoneurons, local spinal neurons, descending bulbospinal systems and primary afferents were used. The effect of some drugs, including thyrotropin releasing hormone (TRH), on Spantide-induced effects were also analyzed. After injection of 2 micrograms of Spantide at the lumbar level, a marked necrosis of the spinal cord was observed extending for about 5-6 segments, affecting mostly the ventral horns. Thus, calcitonin gene related peptide (CGRP)-like immunoreactivity (LI) in motoneurons completely disappeared and no motoneurons could be seen in cresyl violet-stained sections. The first changes were observed 6 h after Spantide injection and at 24 h a complete necrosis was seen. Marked reductions in the number of 5-hydroxytryptamine (5-HT)- and substance P-positive fibers were also observed. The effects were less dramatic in the dorsal horns, but at the site of maximal effects there was a disturbance also of CGRP-, substance P-, and neuropeptide tyrosine (NPY)-positive fibers in the superficial layers of the dorsal horn. These effects could be completely counteracted by multiple intravenous injections of TRH as well as with 5-methoxy-N, N-dimethyltryptamine (5-MeDMT), a 5-HT agonist. The behavioural analysis showed parallel changes, with permanent motor impairment after Spantide-treatment and complete absence of these symptoms when TRH or 5-MeDMT was given in addition. Finally, the effect of Spantide on 5-HT, noradrenaline, substance P and CGRP levels was measured biochemically. The present results are discussed in the light of recent findings that Spantide can cause a dramatic reduction in spinal blood flow.

Animals↗
PubMed1989

Distribution of TRH-like immunoreactivity with special reference to coexistence with other neuroactive compounds.

During the last years, several important advancements have been made that are of importance for our understanding of the distribution and localization of neurons and cells producing TRH-LI. As detailed in other chapters in this volume, the precursor for TRH has been characterized that has allowed production of antibodies raised against specific sequences of this precursor. This, in turn, has provided new tools for the immunohistochemical elucidation of TRH systems in the CNS. The TRH precursor has also been cloned, leading to possibilities for studying the localization of TRH mRNA with in situ hybridization. Finally, as shown in this paper, improvement of the fixation technique has made it possible to visualize extensive TRH-immunoreactive cell body and fiber systems with antiserum raised against the TRH tripeptide. The results from the latter studies and those with antisera directed to the TRH precursor and in situ hybridization are in good agreement, with some minor exceptions. It should be pointed out that some of the systems described here, for example TRH positive-cell bodies in cortical areas and the hippocampal formation, contain only a very weak immunoreactivity. As always with immunohistochemical techniques, the possibility of crossreactivity with TRH-like peptides or TRH-like sequences within larger proteins must be considered. The present results confirm the presence of TRH-LI in the insulin-producing beta cells of the pancreas, which with the improved technique can be demonstrated also in early adulthood in rats and guinea pigs. Moreover, it could be established that TRH-LI is present in neurons in the gastrointestinal tract as well as in a population of endocrine cells in the antrum of the stomach of the guinea pig. These cells seem at least partly to be identical to the well-known gastrin-producing cells. TRH-LI has been observed to occur in neurons already containing a classical transmitter and/or other peptides. Of particular importance here seems to be a descending bulbospinal system that in addition to TRH co-contains 5-HT, substance P-LI, galanin-LI, human growth hormone immunoreactive material, and proctolin-like material. The significance of this coexistence is not well understood, but interesting interactions have been observed. Attempts to manipulate the TRH phenotype in these medullary neurons by transplantation to other sites in the brain has so far shown that the expression of this peptide seems fairly stable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Prevention of tumor growth and enhancement of cell-mediated immunity by an antigen-specific contrasuppressor factor from a T cell hybridoma.

We have produced a contrasuppressor T cell hybridoma which has positive effects on multiple forms of cell-mediated immunity. First of all, it protects the adoptive transfer of contact sensitivity from suppressor cells and factors. In addition, TcsF modifies the response to normally tolerogenic administrations of hapten, leading mice to develop contact sensitivity and CTL activity instead of tolerance. Most relevant to this conference, mice which have been both treated with AF5.C6 TcsF and painted with TNCB resist challenge with highly malignant TNP-modified tumors. These experiments suggest a decisive role for contrasuppression in tumor rejection.

Animals↗
PubMed1988

Intraarticular methylprednisolone therapy in hemophilic arthropathy.

This small pilot study examined the use of intraarticular methylprednisolone in hemophilic synovitis. Nineteen joints in ten adult hemophiliacs were studied. There was subjective improvement at 24 hr following injection in 79% of joints injected, and the improvement persisted up to 8 wk in 58%. The number of hemarthroses decreased following intraarticular steroids (mean of 7.7 bleeds in the 8 wk prior to injection versus a mean of 1.9 bleeds in the 8 wk following injection). Similarly the amount of clotting factor used for the injected target joint decreased from a mean of 7,616 units to 2,315 units postinjection (p less than .001). Improvement correlated with presence of synovitis but not with radiologic stage of the joint. Aspirated synovial fluids were analyzed and showed characteristics consistent with low-grade inflammation. These preliminary observations suggest that intraarticular corticosteroid injection may be a useful therapeutic tool in the medical management of hemophilic arthropathy.

Adult↗