Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine and its derivative, hydroxychloroquine sulfate, have been used in treating malaria, dermatitides of systemic lupus erythematosus and rheumatoid arthritis. Hydroxychloroquine retinopathy is uncommon in Taiwan. Here we report a patient with hydroxychloroquine retinopathy which progressed even after discontinuation of hydroxychloroquine. A 42-year-old woman had systemic lupus erythematosus for twenty years. She had been treated with 200 to 400 mg of hydroxychloroquine per day (4 to 8 mg/kg of body weight/day) with a cumulative dose of 657 g. After bull's-eye maculopathy was found, hydroxychloroquine was discontinued. Her medical history revealed no chloroquine administration and no other systemic disease. Five years after cessation of the therapy, her visual acuity and visual fields continued to deteriorate. Ophthalmoscopic examination revealed the hydroxychloroquine retinopathy had advanced. To the best of our knowledge, the progression of hydroxychloroquine retinopathy after discontinuation of medications is a rare phenomenon. Regular ophthalmologic examinations should be performed for patients on hydroxychloroquine regimens because there is no satisfactory treatment for hydroxychloroquine retinal toxicity. Ophthalmologists, dermatologists and rheumatologists should monitor for ocular toxicity of hydroxychloroquine carefully.
 ...
PMID:Progression of hydroxychloroquine retinopathy after discontinuation of therapy: case report. 1148 Mar 31

A large number of malaria immune persons from Eastern India were found to possess antibodies to the ribosomal phosphoprotein P0 (PfP0) of the human malarial parasite Plasmodium falciparum. The characterization of PfP0 has been reported recently, and it has been shown that antibodies against PfP0 inhibit P. falciparum in vitro. About 10-15% of the patients suffering from the autoimmune disorder Systemic Lupus Erythematosus (SLE) possess autoantibodies to the human ribosomal P proteins. In order to test the cross-reactivity of the human and Plasmodium falciparum P0 proteins and to compare the SLE patients' and malaria immune persons' response, sera from 41 Indian SLE patients were tested against the P. falciparum PfP0 by Western blot analysis. Four of these samples (9.75%) were found to be cross-reactive to the carboxy-terminal domain of PfP0, but not to the amino-terminal domain of PfP0. The PfP0 reactive SLE sera inhibited the growth of Plasmodiumfalciparum in vitro. IgG purified from one such cross-reactive serum sample inhibited the growth of P. falciparum. Depletion of anti-P0 antibodies from this IgG preparation resulted in the removal of growth inhibition. Sera samples were collected from one of the PfP0 positive SLE patient from Mumbai, India, at different stages of the disease progression, and screened for the presence of anti-PfP0 antibodies. This patient's serum inhibited the parasite growth in vitro only during the phase in which anti-PfP0 antibodies were detected.
 ...
PMID:Sera from lupus patients inhibit growth of P. falciparum in culture. 1168

Anticardiolipin antibodies (aCL) were investigated in 137 individuals chronically exposed to malaria and living in Africa and Asia. They belonged to several groups according to parasite (Plasmodium falciparum or vivax) and clinical manifestations (i.e. asymptomatic parasite carriers, acute uncomplicated attack or severe malaria episodes). aCL were measured in an enzyme immunoassay (ELISA) performed in the presence of either goat serum (aCLs) or gelatin (aCLg). In a group of 53 patients with autoimmune manifestations (i.e. antiphospholipid syndrome and/or lupus), detection of IgG but not IgM aCL was markedly reduced in the presence of gelatin. In malaria donors, high prevalence of serum co-factor-independent IgG and IgM were detected, and the presence of goat serum in the assay consistently decreased their detection. aCLg levels were found to be related to the clinical/endemic status of donors. IgG aCLg were found to be higher in asymptomatic P. falciparum carriers than in patients with uncomplicated acute or cerebral malaria. IgM aCLg were higher in the cerebral malaria group than in groups with uncomplicated acute malaria patients or asymptomatic individuals. Data suggest that using a serum co-factor independent, sensitive ELISA, aCL are commonly detected during malarial infections and related to malarial infection status.
 ...
PMID:High prevalence of co-factor independent anticardiolipin antibodies in malaria exposed individuals. 1188 47

Chloroquine is a drug with over 60 years of safe clinical use in the treatment of malaria. The multiple mechanisms of chloroquine action have appeared to be useful in the therapy of many miscellaneous disorders well beyond its original antimalarial purposes. This paper is focused on the application of chloroquine for the treatment of malaria, porphyria cutanea tarda, rheumatoid arthritis, palindromic rheumatism and lupus. The possibility of the use of chloroquine in the therapy of other disorders such as diabetes mellitus, AIDS, hyperlipidemia, sarcoidosis, hypercalcemia, and melanoma is reviewed. Mechanisms of action of the drug as well as side effects on metabolism are discussed in view of recent discoveries.
 ...
PMID:[Chloroquine--miscellaneous properties of the antimalarial drug]. 1210 61

Alfa-Galactosyl Ceramide was isolated from Ocean sponge which has antitumor effect against several tumors in in vivo animal model with no cytotoxicity. KRN7000(KRN) is the most potent alpha-Galactosyl Ceramide modified from the one isolated from Ocean sponge. KRN is also active against metastatic tumors through the activation ofanimal immune system. Research efforts in learning the mechanism of action, we found the important role of dendritic cells(DC) and NKT cells. NKT cells was first characterized in 1988 which is overlap some part with NK cells and T-Cells and majority is different from NK and T. KRN is active through the activation of DC and NKT in giving antigen specific immune stimulation in animal. This antigen specific stimulation is memorized by immune system and can reject second tumor challenge. KRN is not active in nude mice and NKT deficient animal. NKT cells level in blood is lower in patients with autoimmune disease, cancer, HIV positive or aplastic anemia. NKT rapidly releases IL-4 and IFN-gamma at high level when activated. NKT is CD1d and TCR restricted. NKT plays important role in autoimmune disease such as Type 1 Diabetes, Scleroderma and Systemic Lupus Erythematosus, infections such as Mycobacteria, Listeria and Malaria, GVHD control and tumor rejection. NKT acts as double edge sword, aggressive and suppressive ways. KRN can prevent the onset of Type 1 Diabetes, inhibit replication of hepatitis virus B in liver and suppress malaria replication in activating NKT cells. KRN can activate NKT through DC and activated NKT activates NK, T and macrophage. KRN also expands NKT cells and expanded NKT has full function. Although the exact role of DC and NKT is not clear, KRN clinical study results in conjunction with DC and NKT cell activation are expected.
 ...
PMID:Role of NKT cells and alpha-galactosyl ceramide. 1243 Aug 64

Cytokine unbalance is responsible for the pathogenesis of diverse inflammatory, autoimmune and infectious diseases, and Tumor Necrosis Factor Alpha (TNF alpha), among other cytokines, plays a central role. TNF alpha production can be regulated at the transcriptional, post-transcriptional, and translational levels. Variability in the promoter and coding regions of the TNF alpha gene may modulate the magnitude of its secretory response. Up to date, several single nucleotide polymorphisms (SNPs) have been identified in the human TNF alpha gene promoter. One of these, is a guanine to adenine transition at position -308, that generates the TNF1 and TNF2 alleles, respectively. The TNF2 allele is associated to a high in vitro TNF expression, and it has also been linked to an increased susceptibility and severity, for a variety of illnesses, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer disease and cerebral malaria among others. It is also associated with a higher septic shock susceptibility and mortality. The investigation of polymorphisms within the TNF alpha cluster will be important in understanding the role of TNF alpha regulation in specific diseases.
 ...
PMID:[Tumor necrosis factor alpha genetic polymorphism as a risk factor in disease]. 1243 54

The quinolines have been used in the treatment of malaria, arthritis, and lupus for many years, yet the precise mechanism of their action remains unclear. In this study, we used a functional proteomics approach that exploited the structural similarities between the quinoline compounds and the purine ring of ATP to identify quinoline-binding proteins. Several quinoline drugs were screened by displacement affinity chromatography against the purine binding proteome captured with gamma-phosphate-linked ATP-Sepharose. Screening of the human red blood cell purine binding proteome identified two human proteins, aldehyde dehydrogenase 1 (ALDH1) and quinone reductase 2 (QR2). In contrast, no proteins were detected upon screening of the Plasmodium falciparum purine binding proteome with the quinolines. In a complementary approach, we passed cell lysates from mice, red blood cells, or P. falciparum over hydroxychloroquine- or primaquine-Sepharose. Consistent with the displacement affinity chromatography screen, ALDH and QR2 were the only proteins recovered from mice and human red blood cell lysate and no proteins were recovered from P. falciparum. Furthermore, the activity of QR2 was potently inhibited by several of the quinolines in vitro. Our results show that ALDH1 and QR2 are selective targets of the quinolines and may provide new insights into the mechanism of action of these drugs.
 ...
PMID:Discovery of novel targets of quinoline drugs in the human purine binding proteome. 1243 4

The mean number of complement receptor 1 (CR1) molecules on erythrocytes differs between normal individuals within the range of 100-1000 molecules per cell. In some disease states such as systemic lupus erythematosus (SLE), acquired immune deficiency syndrome (AIDS), insulin-dependent diabetes mellitus and malaria, erythrocyte CR1 levels are reduced and CR1 function may be impaired. Current methods for determining erythrocyte CR1 levels by flow cytometry require the use of freshly drawn blood samples because CR1 is lost from erythrocytes during storage. In order to facilitate field studies of associations between erythrocyte CR1 levels and disease, we have developed and validated an assay to quantify CR1 on both healthy and diseased erythrocytes that have been fixed in 5% formaldehyde or frozen in glycerol. These methods enable blood samples to be collected in areas lacking the facilities for flow cytometry and stored for later accurate quantification of CR1. Such procedures will be of particular benefit for future investigations of erythrocyte CR1 expression level and malaria susceptibility.
 ...
PMID:A simple method for accurate quantification of complement receptor 1 on erythrocytes preserved by fixing or freezing. 1244 29

Several observations suggest that bacteria induce autoimmunity in primary biliary cirrhosis (PBC). Since no PBC-specific bacterial species could be identified, it can be speculated that the triggers are non-species-specific bacterial proteins. This hypothesis would imply that several or even all bacterial species can trigger PBC. Therefore, we investigated whether PBC exhibits immune reactions to non-species-specific bacterial antigens. Yersinia enterocolitica O3 was screened for the presence of proteins that were labeled by immunoblotting using PBC sera. We focused our investigations on a 160-kDa protein, which was further enriched and characterized by partial N-terminal amino acid sequencing. The prevalence of antibodies to this protein was determined by immunoblotting in a variety of diseases. The 160-kDa protein was identified as the beta-subunit of bacterial RNA-polymerase, a highly conserved bacterial protein with a very high degree of sequence identity among all bacterial species. Antibodies to the beta-subunit of bacterial RNA polymerase were specific for this protein. Until now no mammalian protein could be found that cross-reacts with these antibodies. The prevalence of antibodies to the beta-subunit of bacterial RNA polymerase (ARPA) using the protein from Yersinia enterocolitica O3 (serum dilution 1:1000) was: healthy controls (HC, N = 101) 7.9%, primary biliary cirrhosis (PBC, N = 61) 32.8%, autoimmune hepatitis type 1 (AIH, N = 46) 26.1%, alcoholic liver cirrhosis (ALC, N = 44) 9.1%, Crohn's disease (CD, N = 38) 7.9%, ulcerative colitis (UC, N = 24) 8.3%, primary sclerosing cholangitis + UC (PSC/UC, N = 11) 0%, acute yersiniosis (Yers, N = 36) 19.4%, acute infection with Campylobacter jejuni (Camp, N = 10) 0%, acute Q-fever (QF, N = 16) 6.25%, chronic hepatitis C (HCV, N = 39) 7.7%, c-ANCA-positive vasculitis (Vasc, N = 40) 15%, systemic lupus erythematosus (SLE, N = 28) 10.7%, and malaria tropica (MT, N = 24) 16.7%. There was no significant difference between PBC and AIH. The group of autoimmune liver diseases (PBC + AIH, N = 107, 29.9%) differed highly significantly from HC, chronic inflammatory bowel diseases (CD + UC + PSC/UC, N = 73, 6.8%), ALC, and HCV and also differed significantly (P = 0.01) from the group with bacterial and parasitic diseases (Yers + Camp + QF + MT, N = 86,13.95%) and from the group with Vasc + SLE (N = 68,13.2%). Testing of ARPA using the protein from E. coli yielded nearly identical results. In conclusion, an increased prevalence of antibodies to the beta-subunit of bacterial RNA polymerase, a highly conserved non-species-specific bacterial protein, can be found in primary biliary cirrhosis, but also in autoimmune hepatitis type I. These findings do not add an argument for a bacterial trigger of PBC. Rather, they suggest that ARPA belong to the pool of natural antibodies that are up-regulated in autoimmune liver diseases.
 ...
PMID:Identification of beta-subunit of bacterial RNA-polymerase--a non-species-specific bacterial protein--as target of antibodies in primary biliary cirrhosis. 1275 71

We report on the characteristics of 21 patients with hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL), an entity recognized since 1994 in the Revised European American Lymphoma (REAL) classification. Median age was 34 years. Patients had splenomegaly (n = 21), hepatomegaly (n = 15), and thrombocytopenia (n = 20). Histopathologic findings were homogeneous and showed the presence of medium-sized lymphoma cells within the sinusoids of splenic red pulp, liver, and bone marrow. Marrow involvement was usually mild but could be demonstrated by phenotyping in all patients. Cells were CD3+CD5-, expressed the gammadelta T-cell receptor, and had a nonactivated cytotoxic cell phenotype (TIA-1+, granzyme B-). Most patients were CD4-/CD8- (16 of 18); CD56+ (15 of 18), expressed the Vdelta1epitope (Vd1+/Vd2-/Vd3-) (9 of 12); and were negative for Epstein-Barr virus (EBV) (18 of 20). Isochromosome arm 7q was documented in 9 of 13 patients. Eight patients had previously undergone kidney transplantation or had a history of systemic lupus, Hodgkin disease, or malaria. Prognosis was poor; median survival time was 16 months, and all but 2 patients ultimately died despite consolidative or salvage high-dose therapy. In conclusion, HSgammadeltaTCL is a disease with distinctive clinical, histopathologic, and phenotypic characteristics. Bone marrow biopsy with combined phenotyping is sufficient for diagnosis, and splenectomy is therefore unwarranted. Current treatment modalities appear to be ineffective in most patients.
 ...
PMID:Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. 1290 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>