Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These experiments examined the effects of genes outside of the H-2 region on disease susceptibility and pathogenesis. Four strains of mice with the susceptible H-2 type, H-2d, but different non-H-2 genes were studied. B10, D2, Balb/c, NZB, and DBA/2J mice were injected with 4 mg of apoferritin i.p. q.d. for 28 days. B10, D2 and Balb/c mice developed proliferative and crescentic glomerulonephritis. NZB mice developed proliferative and crescentic glomerulonephritis with wire loop lesions suggestive of lupus. DBA/2J mice developed only minimal mesangial proliferation without crescents or necrosis. Electron microscopy showed subepithelial and mesangial deposits in B10, D2, moderate subepithelial and mesangial deposits in Balb/c, and marked mesangial, subendothelial and subepithelial deposits in NZB. Immunofluorescence demonstrated the presence of IgG, IgM, C3 and apoferritin in these deposits. The DBA/2J mice had only minimal mesangial deposits by immunofluorescence and electron microscopy. These experiments demonstrate that non-H-2 genes alter the H-2d determined disease susceptibility seen in H-2 congenic mice. NZB genes can alter the disease so that lupus-like lesions develop and DBA/2J genes can substantially ameliorate the disease.
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PMID:Non-H-2 genes alter the H-2 determined susceptibilities in immune complex nephritis. 253 Mar 82

A 52-year-old woman was admitted to our hospital because of a skin rash, high fever and myalgia. She had been diagnosed ten years ago by a dermatologist as having MCTD (mixed connective tissue disease). At the time of admission a diagnosis of active SLE was made by fulfilling four of the 1982 ARA criteria together with increasing levels of anti-DNA antibody and low levels of complements. Prednisolone (PSL) given orally in an initial dosage of 60 mg/day was effective during the first 6 weeks. Then a high fever, skin rash and pancytopenia appeared without active findings of SLE. Infection caused by bacteria, fungus or virus was suspected, but no infectious agent was present in cultures derived from blood or other sources. Antimicrobic drugs used were not effective at all. The clinical picture was suggestive of a drug allergy, but no causative drug was found. A diagnosis of hemophagocytic syndrome (HPS) was made because of the increased number of unusual hemophagocytic cells in the bone marrow. High levels of serum ferritin and neopterin, which are known to reflect macrophage activation, supported the diagnosis of HPS. HPS is characterized by activated phagocytosis presumably induced by hypersecretion of cytokines. Malignant lymphoma and infection are the two representative diseases which may cause HPS. Recently, an acute lupus HPS was reported in patients with active SLE. Here we reported a case of reactive HPS observed in a patient with SLE who had been receiving high dose PSL. Symptoms and findings of the patient gradually disappeared in several weeks after rapid reduction of the PSL dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemophagocytic syndrome observed in a patient with systemic lupus erythematosus]. 797 30

A patient with systemic lupus erythematosus developed unexplained fever, nonregenerative anemia, leukopenia, and elevations in serum triglyceride and ferritin levels. Bone marrow studies established the diagnosis of macrophage activation syndrome with active hemophagocytosis. No infectious cause was found but pulmonary nocardiosis developed during the course of the disease. Intravenous gammaglobulin therapy was followed by a transient remission. Cyclophosphamide was given subsequently. In lupus patients, macrophage activation syndrome is exceedingly rare and has the same clinical, laboratory, and histologic features as those seen in patients with hemopathies, infections, or immune deficiencies. Investigations for an underlying infection are often negative, suggesting that the macrophage activation syndrome is due to lupus-related immune changes. Treatment is not standardized and relapses are common. This diagnosis should be considered in lupus patients with febrile pancytopenia.
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PMID:[Macrophage activation syndrome in lupus]. 805 32

The case of a 75-year-old Japanese woman with adult-onset Still's disease who presented with cerebral haemorrhage is described. She had been in clinical remission for 2 years, after induction therapy including non-steroidal anti-inflammatory drugs, prednisolone, cyclophosphamide and mizoribine followed by auranofin, until her cerebral haemorrhage occurred, although her serum level of ferritin had gradually increased. After the onset of cerebral haemorrhage, the patient's serum level of thrombomodulin was elevated although c-reactive protein and lactate dehydrogenase were not increased. Anti-cardiolipin antibody and lupus anti-coagulant were not detected. Patients with adult-onset Still's disease are rarely reported to develop cerebral vascular disease, possibly because the disease is most frequent in young adults. The cerebral haemorrhage may have been caused by the vasculitis due to Still's disease.
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PMID:Cerebral haemorrhage complicating adult-onset Still's disease: a case report. 895 35

A potentially fatal hemophagocytic syndrome (HPS) has been noted in patients with reactive HPS. We describe 2 patients with reactive HPS treated with a regimen of therapeutic plasmapheresis and evaluate the efficacy of plasmapheresis for fatal HPS. Case 1 was a 31 year-old woman who had been treated for systemic lupus erythematosus (SLE) with corticosteroid hormones and immunosuppressants. She presented with persistent leukopenia and thrombocytopenia with spiking fever. She had an elevated level of serum ferritin, liver dysfunction, coagulopathy, and plasma inflammatory cytokines. Her bone marrow smear disclosed numerous hemophagocytosis of histiocytes. She was administered therapeutic plasmapheresis with total plasma exchange by fresh frozen plasma. There was an immediate and prominent decrease of cytokines, and she completely recovered. Case 2 was a 34 year-old woman who had been receiving high doses of corticosteroids and plasmapheresis for severe Stevens-Johnson's syndrome. After 18 months, she presented with physical and laboratory findings resembling lupus-like conditions and was administered high doses of corticosteroids and immunosuppressants. Human parvovirus B19 infection was detected by IgM and IgG antibodies and viral DNA from a bone marrow sample; moreover, a bone marrow smear disclosed findings of HPS. Repeated therapeutic plasmapheresis was effective for improving her symptoms and laboratory abnormalities; however, she suffered from septic methicilline resistant staphylococcus aureus infection and finally died of a brain hemorrhage resulting from disseminated intravascular coagulation (DIC).
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PMID:The efficacy of therapeutic plasmapheresis for the treatment of fatal hemophagocytic syndrome: two case reports. 1022 60

TALL-1 is a member of the tumor necrosis factor family that binds to BCMA, TACI, and BAFF-R, three receptors mostly expressed by mature B lymphocytes. Previous studies have shown that the TALL-1 signaling is critically involved in B cell proliferation, maturation, and progression of lupus-like, autoimmune diseases. In this report, we performed cDNA subtractive hybridization experiments to identify downstream genes up-regulated by TALL-1. These experiments indicated that 10 genes, including interleukin (IL)-10, lymphocyte activation gene-1 (LAG-1), GCP-2, PBEF, ferritin, PIM-2, TFG, CD27 ligand, DUSP5, and archain, were up-regulated at the mRNA level by TALL-1 stimulation in B lymphoma RPMI-8226 cells and/or primary B lymphocytes. We also demonstrated that TALL-1 activated transcription of IL-10 and LAG-1 in a nuclear factor-kappaB-dependent manner in reporter gene assays. Moreover, our findings indicated BAFF-R, but not TACI, could dramatically up-regulate IL-10 secretion by RPMI-8226 cells. The identification of TALL-1-up-regulated genes will help explain the mechanisms of TALL-1-triggered biological and pathological effects and to identify molecular targets for intervention of lupus-like autoimmune diseases.
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PMID:Identification of downstream genes up-regulated by the tumor necrosis factor family member TALL-1. 1214 33

Neonatal hemochromatosis is an enigmatic disease. Little is known about iron metabolism in this disease, including the tissue concentration of ferritin or its H and L subunit ratio. The authors report the tissue iron, ferritin, and ferritin subunit content of a child who died at 5 weeks of neonatal hemochromatosis. The child was born at 29 weeks gestation to a mother with lupus, sickle cell trait, and gestational diabetes. The child's severe liver dysfunction led to the clinical diagnosis of neonatal hemochromatosis at 1 week of age. Despite aggressive support, including red cell transfusions and chelation, the child died of an intracranial hemorrhage. Autopsy showed liver fibrosis and iron staining characteristic of neonatal hemochromatosis. Autopsy liver tissue was compared to age-matched control tissue. Soluble protein was analyzed by the Bradford method. Soluble iron (over 90% of total iron) was analyzed by the o-phenanthroline complex. Tissue ferritin and human ferritin controls (Calzyme) were analyzed by Western blotting after SDS-PAGE, identified with sheep anti-human ferritin antibodies (The BindingSite) secondary antibody-fluorescence for detection, and quantified using the Molecular Dynamics Storm 840 phosphorimager and ImageQuant software. Protein, iron, and total ferritin were similar in the normal and neonatal hemochromatosis liver tissues. Ferritin subunits, however, showed an increased H/L-subunit ratio compared to an age-matched control. This first report of a marked increase in the ferritin H/L-subunit ratio may point to an underlying mechanism of disease in this enigmatic disorder.
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PMID:Liver ferritin subunit ratios in neonatal hemochromatosis. 1263 19

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive <1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive >8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men >0.6 ng/mL]), and percent bioavailable test (8.1% [normal value >20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (Johnson & Johnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.
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PMID:Klinefelter's syndrome presenting with leg ulcers. 1536 65

We report the case of a 28-year-old woman with systemic lupus erythematosus who, during a flare, suddenly developed febrile pancytopenia, hyperferritinemia, and abnormal liver function tests. Bone marrow aspiration confirmed hemophagocytic syndrome (HPS). Lupus-related HPS was diagnosed and the patient was treated with intravenous immunoglobulin, high-dose steroids, and cyclophosphamide with an excellent outcome. In febrile patients with lupus, pancytopenia together with very high ferritin levels should raise the suspicion of HPS and because this may be fatal, early bone marrow aspiration is mandatory for the diagnosis. The exclusion of concurrent infection as the cause of HPS is very important for the establishment of the right therapeutic strategy.
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PMID:Lupus erythematosus complicated by hemophagocytic syndrome. 1714 63

We report three infants and one teenager with fatal virus-associated haemophagocytic syndrome (VAHS). Two infants were admitted to our hospital because of cardio-pulmonary arrest (CPA). The third infant was admitted to our department because of fever and liver dysfunction, and he was diagnosed as combined immunodeficiency with predominant T cell defect. The teenager was diagnosed as systemic lupus erythema (SLE) when she was 10 years old and admitted to our department because of fever and thrombocytopenia . The histological findings for the four patients' organs revealed many haemophagocytic cells . The patients were infected by Parainfluenza virus type 2 (PIV2), Enterovirus (EV), Cytomegalovirus (CMV), and Epstein-Barr virus (EBV), respectively. Their laboratory data revealed elevated levels of ferritin and IL-6, which also suggested virus-associated haemophagocytic syndrome (VAHS). Although aggressive therapies were performed in all cases, the outcome was fatal. Further investigation would be needed to clarify the mechanism of VAHS and an effective therapeutic regimen is needed.
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PMID:Virological and immunological characteristics of fatal virus-associated haemophagocytic syndrome (VAHS). 1723 99


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