Cytokines in NZB CD5+ B clones.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
P Gascon
Publications and source records attributed to P Gascon.
Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2 production by substance p.
Substance P (SP), a tachykinin neuropeptide, has been previously reported to stimulate T cell proliferation, and SP receptors have been identified on subpopulations of T lymphocytes. The effect of SP on the interleukin-2 (IL-2) production has been investigated by using the murine EL-4.IL-2 and LBRM-T6G T cell lines. SP synergized with phorbol 12-myristate 13-acetate (PMA) in a dose-dependent manner to induce IL-2 production. The generated interleukin was identified as IL-2 by neutralization with a specific anti-murine IL-2 monoclonal antibody. The effect of SP was specific, since spantide and physalaemin which have affinity for SP receptors inhibited the generation of IL-2 by SP. These results provide additional evidence for the immunoregulatory role of neuropeptides, and suggest that the immunostimulatory action of SP could be mediated, at least in part, through the upregulation of IL-2 expression.
Animals↗
Idiopathic myelofibrosis in pregnancy: a case report and review of the literature.
Idiopathic myelofibrosis is a rare myeloproliferative disorder characterized by excessive accumulation of connective tissue in the bone marrow in association with anemia, splenomegaly, and extramedullary hematopoiesis. The cause of this disease is unknown, and the prognosis is generally poor. To our knowledge, this is the first case report of a patient with idiopathic myelofibrosis who carried a term pregnancy. In spite of the increased perinatal risks, a favorable outcome was possible with close antepartum surveillance.
Adult↗
The gelatinous bone marrow (serous atrophy) in patients with acquired immunodeficiency syndrome. Evidence of excess sulfated glycosaminoglycan.
Patients with the acquired immunodeficiency syndrome uniformly exhibit hematologic abnormalities characterized by anemia and/or pancytopenia. In a study of 75 consecutive bone marrow biopsy specimens from patients with acquired immunodeficiency syndrome, 29% exhibited serous atrophy, characterized by marrow hypoplasia, fat atrophy, and deposition of extracellular "gelatinous" material (gelatinous transformation). The latter material was composed exclusively of glycosaminoglycans (alcian blue positive at pHs of 2.5 and 1.0, and sensitive to testicular hyaluronidase digestion). Excess glycosaminoglycan, which significantly alters the bone marrow microenvironment, is detrimental to erythropoiesis. The present findings support the concept that the damaged hematopoietic inductive microenvironment in patients with acquired immunodeficiency syndrome leads to failure of hematopoiesis, and, hence, to peripheral hematologic abnormalities.
Acquired Immunodeficiency Syndrome↗
Erythroderma as the initial presentation of the acquired immunodeficiency syndrome.
A 32-year-old black homosexual man, seronegative for human immunodeficiency virus antibody, presented with erythroderma. His peripheral blood was significant for circulating Sézary-like cells bearing the CD8(+) phenotype. Eighty-eight percent of his lymphocytes were CD8(+) as well. He seroconverted 3 months after the initial presentation. We conclude that erythroderma was the presenting sign of the acquired immunodeficiency syndrome.
Acquired Immunodeficiency Syndrome↗
Sign of Leser-Trélat with a metastatic mucinous adenocarcinoma.
We describe a middle-aged woman with the sudden onset of multiple seborrheic keratoses in association with a metastatic mucinous adenocarcinoma to the liver from an unknown primary neoplasm. This case illustrates the significance of the sign of Leser-Trélat and its association with cancer.
Adenocarcinoma, Mucinous↗
Severe anemia is an important negative predictor for survival with disseminated Mycobacterium avium-intracellulare in acquired immunodeficiency syndrome.
Disseminated Mycobacterium avium-intracellulare (MAI) in patients with the acquired immunodeficiency syndrome (AIDS) is usually unresponsive to antimycobacterial therapy. We examined clinical and laboratory characteristics of MAI organisms and their relationship to the length of survival. We studied factors influencing survival and compared these in 76 patients with AIDS with and without MAI. Serum levels of p24 antigen and erythropoietin, and CD4-positive helper T-lymphocytes in blood were assessed in 36 additional patients with various clinical stages of HIV infection. In patients with MAI infection, survival was significantly related only to total lymphocyte count, hematocrit, platelet count, and sex. Of these, hematocrit and total lymphocyte count were the only linear predictors of survival. Anemia was significantly more profound in patients with AIDS and MAI than in the other patients. This anemia in patients with MAI could not be ascribed to increased peripheral destruction of red cells, deficient nutritional factors, or erythropoietin production, HIV viral or bacterial load, or a general effect on other blood elements such as neutrophils or platelets. The influence of MAI on survival in patients with AIDS did depend upon whether the MAI occurred as an index infection or was preceded by other opportunistic infections. Patients with other preceding opportunistic infection lived for a much shorter duration from the time of diagnosis of MAI.
Acquired Immunodeficiency Syndrome↗
Monoclonal antibody therapy of cancer.
Explore the source record for details and available documents.
Animals↗
Fine mapping of chromosome 22 breakpoints within the breakpoint cluster region (bcr) implies a role for bcr exon 3 in determining disease duration in chronic myeloid leukemia.
The chromosomal translocation that fuses the phl gene with the c-abl proto-oncogene appears to be a pivotal step in the pathogenesis of some leukemias. In chronic myeloid leukemia (CML) the breakage within the phl gene is largely confined to a 5.8-kb segment referred to as the breakpoint cluster region (bcr). To determine whether the presence of specific bcr exons on the Philadelphia chromosome has any clinical significance, we have analyzed the bcr breakpoints in 134 patients with CML. As many as five probes were used in this analysis, including a synthetic oligonucleotide probe homologous to the bcr exon 3 (phl exon 14) region. The distribution of breakpoints indicates that, in fact, breakage is largely confined to a 3.1-kb segment lying between bcr exon 2 and exon 4 (phl exons 13-15). In 61 CML patients analyzed within 1 year of diagnosis, the distribution of breakpoints appeared to be random within the 3.1-kb region. However, a significant excess of 5' breakpoints was observed in the total population studied, consistent with previous data showing that patients with 3' breakpoints have shorter disease durations. Analysis using the bcr exon 3 sequence probe indicated it was probably the presence or absence of bcr exon 3 on the Philadelphia chromosome that accounts for some of the variability in disease duration seen in CML. The data suggest that the phl/abl protein product may influence the timing of the onset of blast crisis and imply a continuing role for this protein during the evolution of the disease.
Blotting, Southern↗
Impaired bone marrow in AIDS.
Fifty bone marrows from patients with AIDS were studied to identify the abnormalities related to marrow failure. Prominent reticulin fibrosis and increased atypical megakaryocytes were the major changes associated with the aberrant hematopoietic microenvironment.
Acquired Immunodeficiency Syndrome↗
Decreased interleukin-1 production in aplastic anemia.
PURPOSE: Interleukin-1 (IL-1), a monocyte factor, plays a central role in the regulation of the immune response; recent data have suggested that IL-1 is the same molecule as hemopoietin-1, a growth factor acting on the multipotent hematopoietic stem cell. IL-1 affects hematopoiesis (1) in vitro, by inducing the release of colony-stimulating factors and regulating early hematopoietic progenitor cells, and (2) in vivo, by stimulating stem cell recovery in irradiated or chemotherapy-treated mice. Several lines of evidence suggest that aplastic anemia may be mediated by cells of the immune system. We address the issue of abnormal IL-1 production in severe aplastic anemia and attempt to correlate normalization of the levels with response to anti-thymocyte globulin (ATG) therapy. PATIENTS AND METHODS: We studied IL-1 production by monocytes from 21 patients with aplastic anemia using a bioassay for IL-1 activity. Fifteen patients were evaluated before ATG therapy. Eight patients were studied before and three months after ATG. In addition, five patients were evaluated only after ATG treatment. One patient did not respond to ATG but did respond to intravenous acyclovir, and was studied before and after acyclovir therapy. Twenty patients with other hematologic disorders requiring transfusions and 30 normal healthy volunteers were also assessed. RESULTS: IL-1 production was markedly decreased in 75 percent of patients with aplastic anemia when compared with that in normal control subjects (p less than 0.005). Hematologic recovery correlated with normalization of IL-1 production in all but two cases (p less than 0.04). CONCLUSION: These observations represent the first evidence of monocyte dysfunction and deficient hematopoietic growth factor production in aplastic anemia. Decreased IL-1 production may have a pathologic role in some cases of aplastic anemia.
Adult↗
B19 parvovirus replicates in circulating cells of acutely infected patients.
B19 parvovirus is the etiologic agent of fifth disease and transient aplastic crisis. In natural infections, B19 antigen and DNA have been detected in sera early in the course of aplastic crisis and only rarely in fifth disease. We have found B19 DNA in circulating cells of infected patients by DNA dot blot with a virus-specific probe: in four of four sickle cell patients with aplastic crisis, in one asymptomatic sibling, and in one normal adult with fifth disease. Only two of the sera showed B19 DNA. High-molecular weight intermediate forms were detected by Southern analysis of DNA extracted from cells, thus indicating active replication of virus in cells rather than passive adsorption to their surface membranes. Separation of cells into high- and low-density fractions resulted in a concentration of the virus DNA in the granulocytic fraction.
Acute Disease↗
A rare restriction enzyme site polymorphism in the breakpoint cluster region (bcr) of chromosome 22.
Detection of rearrangement of the breakpoint cluster region (bcr) of chromosome 22 by Southern blot analysis can be used for the routine diagnosis of CML. Restriction fragment length polymorphisms (RFLPs) in the bcr can potentially be confused with translocation since both alter the size of DNA fragments obtained. By digesting DNA with the restriction enzyme BamHl and analyzing with probes commonly used for identifying rearrangement of the bcr, we have observed a RFLP within the bcr. For one CML patient studied in detail, the presence of the polymorphism was confirmed by comparing the results of analyses of granulocytes and a T cell-enriched population. The same polymorphism was detected in three additional CML patients and a patient with thrombocytosis. For the diagnosis of CML, verification of rearrangement with multiple probes and/or restriction enzyme combinations is necessary to rule out false positives, as well as to reduce the chance of false negatives due to co-migration of DNA fragments.
Adult↗
Human serum sickness: a prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone marrow failure.
We have prospectively evaluated the clinical and immunological features of serum sickness in 35 patients treated for bone marrow failure with anti-thymocyte globulin (ATG 15 mg/kg/day) and methylprednisolone (1 to 1.5 mg/kg/day). Twenty-one patients were treated for 10 days and 14 were treated for 28 days. Clinical evidence of serum sickness developed in 30 patients (86%) and included fever and malaise (100%), cutaneous eruptions (93%), arthralgias (67%), gastrointestinal complaints (67%), cephalgia (57%), blurring of vision (37%), arthritis, (30%) and lymphadenopathy (13%). Clinical serum sickness began on day 7 +/- 1 (X +/- S.E.M.) and lasted for 10 +/- 2 days in the 18 affected patients receiving the shorter course of ATG. In the 12 affected patients receiving the longer course of ATG, serum sickness began on day 9 +/- 1. The earliest manifestations of serum sickness were fever, malaise, and cutaneous eruptions. Cutaneous findings consisted of morbilliform eruptions (n = 19) and urticaria (n = 1) or a combination (n = 8) that lasted 10 to 14 days. Twenty-one patients (75%) developed a highly characteristic serpiginous band of erythema and purpura along the sides of the fingers, toes, palms and soles 12 to 48 hours before other symptoms of serum sickness. Biopsies of lesional skin during the course of serum sickness revealed immune deposits (IgM, IgE, IgA and C3) in dermal vasculature in 7 of 9 patients. Immunological changes that occurred during the course of serum sickness included increased serum levels of IgG, IgM, IgA, and IgE. Circulating immune complexes, as measured by the C1q-binding assay, increased from a mean value of 12% to 45% on day 13 +/- 1. Complement levels (C3, C4, and CH50) decreased 50 to 80% from their baseline levels on day 10 +/- 2. Acute phase reactants increased: erythrocyte sedimentation rate, C-reactive protein and beta-2 microglobulin. Abnormal urinalysis developed in 17 patients (57%) over the course of serum sickness and included proteinuria, hematuria and hemoglobinuria on day 10 +/- 3. Hematopoietic response occurred in 43%. All 5 patients who did not develop serum sickness recovered from bone marrow failure. Our data document the clinical and immunopathological findings in human serum sickness and suggest that the principles of antigen-antibody interaction, complement activation, and resultant inflammatory response as seen in the previous animal studies are directly applicable to studies of patients with serum sickness.
Adolescent↗
Uveitis, cutaneous and neurosarcoid: treatment with low-dose cyclosporine A.
Explore the source record for details and available documents.
Adult↗
Lymphocyte phenotype and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anaemia.
Twenty-two patients with adult onset aplastic anaemia were analysed before and after therapy with anti-thymocyte globulin (ATG). Lymphocyte phenotype, lymphokine levels or production, and haematopoietic progenitor cell number were measured 3 months after therapy; clinical response was determined 1 year post-therapy. By flow cytometry there was a significant reduction in both the proportion and absolute number of peripheral blood lymphocytes expressing activation antigen Tac (IL-2 receptor) and in the proportion of HLA-DR+ lymphocytes. For T cells bearing HLA-DR, there were proportional decreases in both activated helper and suppressor cells. There was no statistically significant difference pre-ATG to post-ATG in the absolute numbers of total, helper and suppressor lymphocytes. In all 10 haematologic responders the number of Tac bearing lymphocytes after ATG therapy was in the normal range, but half of 12 non-responding patients continued to have abnormally elevated numbers of Tac+ T cells. The proportion of Tac+ cells were not related to transfusion history. Gamma-interferon levels in serum by radioimmunoassay were elevated in almost half the aplastic patients; post-ATG, gamma-interferon was detectable in only three patients. Haematologic response to ATG therapy was associated with increased numbers of haematopoietic progenitors post-treatment, but pre-treatment values were not predictive of a response. These results are consistent with a pathogenic role for activated T-cells and their lymphokine products and suggest that the target of ATG therapy may be a Tac+ lymphocyte.
Adolescent↗
Serum sickness and haematopoietic recovery with antithymocyte globulin in bone marrow failure patients.
We have evaluated 33 patients with various bone marrow dyscrasias treated with horse antithymocyte globulin (ATG) (Upjohn) to determine the relationship of haematopoietic response to the occurrence of serum sickness. Patients received ATG intravenously over 10 or 28 d at a dose of 15 mg/kg/d. Total or partial haematological responses were noted in 12 of 33 patients. Twenty-eight patients developed clinical signs of serum sickness 6-14 d after the first infusion of ATG, while five patients did not. Twenty-five of these patients were evaluated by immunochemical assays for circulating immune complexes (C1q-binding assay) and 21 patients for serum complement (C3, C4 and CH50 assay) levels. There was a direct correlation between increases in immune complex levels, decreases in serum complement levels, and the development of the clinical signs and symptoms and serum sickness. Twenty-one of 28 patients who developed serum sickness failed to show haematological improvement. However, haematopoietic recovery occurred in all five patients who did not manifest serum sickness (P less than 0.05) and in four patients who failed to develop immune complexes. These findings indicate that the development of serum sickness is not required for a haematopoietic response with ATG and may indeed impair recovery.
Adolescent↗
Biological and immunological characterization of ATG and ALG.
Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are effective therapies in aplastic anemia; their mechanism of action is undefined. We assayed multiple properties of ATG and ALG to address the biological and immunological bases for differences between ATG and ALG and lot variation. In addition, we studied a lot reported to be inactive in an American clinical trial; however in retrospect, this lot appeared to be active in patients treated in Europe. Immunoprecipitation of thymocyte and lymphocyte membrane proteins with ATG and ALG showed between 14 and 18 major bands on SDS-PAGE, but the patterns for ATG and ALG were not identical. The ability of ATG and ALG to block binding of labeled monoclonal antibodies was assessed using flow cytometry and a radioimmunoassay. In general, there was more lot variation among ALGs than ATGs; however, all ALG lots were more potent blockers of binding of anti-HLA-DR and anti-Leu 1 antibodies than was ATG. Both ALG and ATG effectively blocked binding of anti-Leu 2a, anti-Leu 3a, anti-Leu 4, anti-Leu 5b, and anti-IL 2 receptor abs; neither blocked binding of anti-Leu 7. All preparations were capable of inducing T-cell blastogenesis, although there was considerable lot variation. All lots lysed 60% to 75% T cells in a rabbit complement-mediated cytotoxicity assay, with most having a plateau of activity at 5 to 10 ug/mL. Two lots of ALG, including the lot reported to be clinically inactive, showed less toxicity at suboptimal concentrations and did not plateau even at 80 ug/mL. In total, these results indicate important differences between ATG and ALG in general, more lot variation among ALGs than ATGs and only differences in cytotoxicity between an "inactive" lot of ALG and most, but not all, other active ATG and ALG preparations.
Anemia, Aplastic↗