Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our results demonstrate that expression of neuropeptide tyrosine, one of the most abundant and widespread peptides in the mammalian nervous system, occurs in non-neuronal cells, in keeping with the emerging view that neuropeptide synthesis is not restricted to cells of the nervous system. RNA blot analyses and radioimmunoassays detected both NPY mRNA and NPY peptide in rat and mouse spleen, bone marrow, and peripheral blood cells. Immunohistochemical staining of sections from rat bone marrow with an NPY-specific antiserum revealed NPY-like immunoreactivity in megakaryocytes. In situ hybridization confirmed that the NPY-like peptide detected in megakaryocytes was synthesized de novo from NPY mRNA present in these cells. Megakaryocytes, the platelet-forming cells, originate from pluripotent hematopoietic stem cells present in the bone marrow as well as in the spleen of rodents. During microvascular damage, platelets aggregate at the damaged site and release bioactive substances. NPY is known to be a potent vasoconstrictor. Therefore, we propose that megakaryocyte-derived NPY is stored in platelets and released during platelet aggregation, resulting in a long-lasting vasoconstriction. Greatly elevated levels of megakaryocyte-derived NPY, as compared to the level found in BALB/C mice, were found in several mouse strains (NZB, NZB x W, and BXSB) which develop an autoimmune disease resembling systemic lupus erythematosus. Whether the elevation of megakaryocyte-derived NPY plays a role in the autoimmune disease progression in these mice or whether it merely reflects a related hematopoietic abnormality remains to be determined. Subtractive hybridization was used to isolate two cDNA clones that are predominantly expressed in the brain and the immune system. These and similarly derived cDNA clones will be used as molecular probes to study the mechanisms governing tissue-specific expression in the nervous and immune systems. Discovering the function of the proteins encoded by such cDNA clones may reveal evolutionary mechanisms shared by the nervous and immune systems, as well as a molecular basis for the interaction between these systems.
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PMID:A molecular genetic approach to the identification of genes expressed predominantly in the neuroendocrine and immune systems. 332 23

We studied a patient with a rare complication of amegakaryocytic thrombocytopenia (AMT) associated with systemic lupus erythematosus (SLE). To investigate the underlying pathogenesis of AMT, the effects of peripheral blood T cells and serum on human megakaryocyte progenitor cells were studied using in vitro coculture techniques. Mononuclear bone marrow cells (2 X 10(5) from normal donors produced 33.6 +/- 8.8 (n = 10) colony-forming unit-megakaryocytes (CFU-M) in our plasma clot system. When 2 X 10(5) of the patient's T cells were added to the culture system, the number of CFU-M decreased to only 3.5 +/- 0.6/2 X 10(5) bone marrow cells. No evidence of inhibitory effects was found by the addition of the patient's serum and complement to the culture system. The T cells stored at -80 degrees C on admission were also capable of suppressing autologous CFU-M after recovery from AMT. These results indicate that in vitro suppression of CFU-M from allogenic and autologous bone marrow cells by this patient's T cells provides an explanation for the pathogenesis of AMT associated with SLE.
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PMID:Cell-mediated amegakaryocytic thrombocytopenia associated with systemic lupus erythematosus. 348 42

The megakaryocyte number and mean megakaryocyte area were determined in histological sections of sternal bone marrow from 26 patients with systemic lupus erythematosus (SLE). Also 20 platelet survival studies were carried out in these patients. The results were analyzed with respect to corticosteroid (CS) and CS + azathioprine (AT) therapy. The mean bone marrow megakaryocyte number as highest in untreated SLE patients, slightly lower in patients receiving CSs and lowest in those receiving CSs + AT. The difference was, however, not significant. The mean megakaryocyte areas were smallest in untreated SLE patients, slightly larger in those treated with CSs and significantly (p less than 0.05) larger in patients who received CSs + AT than in untreated patients. Platelet production rate was normal in all 3 groups of SLE patients. The results suggest that CS and AT therapy in SLE intervenes with the bone marrow megakaryopoiesis without affecting the production rate of platelets.
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PMID:Bone marrow megakaryocytes and platelet kinetics in systemic lupus erythematosus. With special reference to corticosteroid and azathioprine therapy. 710 69

An indirect platelet immunofluorescence assay (PIFA) was developed for detection of circulating antiplatelet antibody in dogs with suspected immune-mediated thrombocytopenia (ITP). The PIFA was performed on 10 healthy dogs with normal platelet counts; 76 thrombocytopenic dogs, 20 of which were suspected of having ITP; and 18 dogs with other diseases and normal platelet counts. All normal dogs and negative test results. Fourteen (70%) of 20 dogs suspected of having ITP had positive test results. Fifteen of the remaining 56 thrombocytopenic dogs had positive test results, 9 had cancer and 6 had other immune-mediated diseases including systemic lupus erythematosus (SLE). In this study, the PIFA assay seemed to be more sensitive (70%) than the megakaryocyte immunofluorescence assay (41%) in the diagnosis of ITP. Of the 9 PIFA-positive dogs with neoplasia, 6 had lymphoproliferative disorders. The PIFA was positive in 5 of 18 diseased dogs with normal platelet counts. There was an inverse relationship between the platelet count and the intensity of fluorescence in the PIFA-positive dogs. We conclude that the PIFA is a sensitive screening method for detecting circulating antiplatelet antibody.
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PMID:Detection of antiplatelet antibody with a platelet immunofluorescence assay. 817 61

A case of full blown systemic lupus erythematosus (SLE) was treated with steroid. The patient was in remission with low dose of prednisolone for a year. When she became pregnant, there was no relapse of SLE activities in any organ. However, she developed gum bleeding and petechiae due to thrombocytopenia in the second half of the pregnancy. With a normal amount of megakaryocyte in the bone marrow, it was supposed to be due to SLE which no longer responded to even a full dose of steroid. Therefore, danazol 600 mg/day was given orally and she made a complete recovery within one week. She delivered vaginally a normal female newborn without fetal thrombocytopenia or bleeding.
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PMID:Danazol for thrombocytopenia in pregnancy with underlying systemic lupus erythematosus. 870 26

A 52-year-old female was admitted to our hospital in August 1988, for evaluation of purpura and gingival bleeding. Hematologic examination showed mild leukocytosis (12,400/microliter) and severe thrombocytopenia (1,000/microliter). On bone marrow examination, megakaryocyte count was normal and the number of myeloblasts was increased (7.2%). Serological examination was positive for anti-nuclear antibody and anti-DNA antibody. She was diagnosed as having idiopathic or autoimmune thrombocytopenia, and received thrombocyte transfusion and gamma-globulin administration. Hematologic values improved temporarily, but leukocytosis and thrombocytopenia recurred. On the 22nd hospital day, leukocytes increased to 49,300/microliter and thrombocytes decreased to 10,000/microliter. Bone marrow myeloblasts were also increased to 18.8%, and she was suspected of having myelodysplastic syndrome. Then, hematologic values improved simultaneously, and she was discharged in November 1988. After the discharge, leukocyte count ranged from 6,000 to 16,500/microliter, but the number of bone marrow myeloblasts was normal. However, transient thrombocytopenia appeared in association with decrease or absence of bone marrow megakaryocytes and rise of platelet associated-IgG, (PA-IgG) to 99.6 ng/10(7) cells. From September to December 1989, she complained of fever, morning stiffness, multiple arthralgia, and oral ulcer. On serological findings, she was positive for LE cell. Therefore, she was diagnosed as having systemic lupus erythematosus (SLE). In January 1990, she had a high grade fever and dyspnea. Bilateral pleuritis and interstitial pneumonitis were shown on the chest roentgenogram. She received gamma-globulin administration, methylprednisolone pulse therapy, and mechanical ventilation. However, hypoxia developed rapidly, and she died of respiratory failure. Autopsy revealed severe interstitial pneumonitis, fibrinous pleuritis, fibrinous pericarditis, and vasculitis in the arcuate artery of the kidney. This is the first report of SLE complicating thrombocytopenia associated with decrease of megakaryocytes and rise of the PA-IgG, and severe leukocytosis associated with increased bone marrow myeloblasts.
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PMID:[An autopsy case of systemic lupus erythematosus complicating leukocytosis, amegakaryocytic thrombocytopenia, interstitial pneumonitis, and pleulitis]. 881 May 48

Autoimmune thrombocytopenia can be a serious manifestation of systemic lupus erythematosus (SLE) which necessitates treatment with immunosuppressive agents and platelet transfusions. Interleukin-11 (IL-11) is a unique thrombopoietic growth factor which causes proliferation of megakaryocyte progenitors as well as induces megakaryocytic maturation. To our knowledge, this agent has not been used in the treatment of autoimmune thrombocytopenia, since theoretically there is a danger of IL-11 stimulating the immune system by up-regulating the lymphoid stem cells. We describe a 36-year-old splenectomized woman with known SLE who presented with pulmonary hemorrhage, acute renal failure, change in mental status, and severe thrombocytopenia (platelet count 2,000/mm3). Her pulmonary, renal, and central nervous system complications responded to intensive therapy with intravenous (IV) pulse methylprednisone and cyclophosphamide along with hemodialysis. The thrombocytopenia remained refractory to the above treatment plus daily multiple platelet transfusions and IV immunoglobulin. Treatment with recombinant human IL-11 (25 microg/kg/day subcutaneously) was initiated and continued for 5 days. Her platelet count improved to 25,000/mm3 within 48 hours, and she experienced no adverse effects.
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PMID:Treatment of lupus-induced thrombocytopenia with recombinant human interleukin-11. 1121 56

Thrombocytopenia due to immune mechanisms is rare and difficult to manage in elderly patients. We describe a case of an 89-year-old female with severe immune thrombocytopenia (ITP) who rapidly improved by pulse therapy with cyclophosphamide. She was admitted to our hospital because she had arthralgia in both sides of her femoral region since January 1999, aphthous stomatitis and ecchymosis of the leg since April 1999, and bloody phlegm in July 1999. On admission, her peripheral blood count revealed severe thrombocytopenia (0.1 x 10(4)/microl). Her megakaryocyte count from bone marrow was increased to 512/microl without abnormal cells. Systemic lupus erythematosus was suspected because of strong positive protein in the urine in addition to the clinical and hematological findings described above, but she was negative for all the autoantibodies examined. Finally, she was diagnosed as having ITP on the basis of high platelet associated immunoglobulin G in addition to hematological and physical findings and she was treated with prednisolone. It was difficult to maintain her platelet count with only prednisolone, but 600 mg of cyclophosphamide rapidly increased her platelet count in spite of tapering the prednisolone. In September 2000, her platelet count was kept within normal limits by administration of 15 mg/day of prednisolon. It is suggested that immunosuppressive therapy for ITP using high-dose cyclophosphamide is useful in elderly patients as well as in juvenile adult patients.
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PMID:Immune thrombocytopenia in an elderly patient treated successfully by pulse therapy with cyclophosphamide. 1176 16

In order to investigate the clinical characteristics of hematological abnormality in patients with systemic lupus erythematosus (SLE) and inquire into the basis for differential diagnosis, the hematological data of 92 cases with lupus erythematosus-related hematological disorder (SLERHD) were retrospectively analyzed by use of SPSS/PC software. The results showed that these patients were short of specificity in clinical manifestation and hemogram, however, all cases possessed multiple SLE-related autoantibodies, increase of serum globulin level and varying extent dermal and arthral signs. The incidence of primary or initial symptom in the 92 cases was as follow: 65 anemia (72.8%), 39 purpura (42.4%), 17 hemolytic anemia (18.5%), 56 leukopenia (60.9%), 54 thrombocytopenia (58.7%), and 41 pancytopenia (44.6%). The bone marrow examinations showed that the cellularity of nucleated cells was mostly normal, and active proliferation in 57 cases (61.9%) and hypercellularity in 35 cases (38.1%); the G/E ratio was normal in majority, and G/E ratio > 3 in 59 cases (64.1%) and < 3 in 33 cases (35.9%) and G/E < 1 in 17 cases with hemolytic anemia Coombs' test positive; megakaryocyte counts were normal in 11 cases (11.9%), increase in 80 cases (86.9%) and lower than 7/marrow smear in 1 case (1.1%). Neutrophil alkaline phosphatase staining was negative in all of the cases. From above data it is concluded that patients with SLERHD are varied in clinical and blood pictures, but all patients are provided with multiple SLE-related autoantibodies, globulinemia and dermal and arthral signs. It is easy to identify SLERHD from aplastic anemia, myelodysplastic syndrome, idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia and Evans' syndrome by comprehensive and detailed clinical and laboratory examinations.
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PMID:[Clinical features of hematological abnormality in systemic lupus erythematosus-related hematological disorders]. 1251 74

Platelets are an abundant source of CD40 ligand (CD154), an immunomodulatory and proinflammatory molecule implicated in the onset and progression of several inflammatory diseases, including systemic lupus erythematosus (SLE), diabetes, and cardiovascular disease. Heretofore considered largely restricted to activated T cells, we initiated studies to investigate the source and regulation of platelet-associated CD154. We found that CD154 is abundantly expressed in platelet precursor cells, megakaryocytes. We show that CD154 is expressed in primary human CD34+ and murine hematopoietic precursor cells only after cytokine-driven megakaryocyte differentiation. Furthermore, using several established megakaryocyte-like cells lines, we performed promoter analysis of the CD154 gene and found that NFAT, a calcium-dependent transcriptional regulator associated with activated T cells, mediated both differentiation-dependent and inducible megakaryocyte-specific CD154 expression. Overall, these data represent the first investigation of the regulation of a novel source of CD154 and suggests that platelet-associated CD154 can be biochemically modulated.
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PMID:Nuclear factor of activated T cells (NFAT) mediates CD154 expression in megakaryocytes. 1818 Mar 80


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