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

The membrane protein CD36 has been reported to carry out a wide range of potential functions, including serving as a receptor for thrombospondin, collagen, oxidized low density lipoprotein, fatty acids, anionic phospholipids, and Plasmodium falciparum malaria parasitized erythrocytes. This implicates CD36 in cellular adhesion, human atherosclerotic lesion formation, lipid metabolism, and malaria. A presumed rat homolog of CD36 was previously reported to be palmitoylated. We confirmed that human CD36 is palmitoylated and identified cysteines 3, 7, 464, and 466 as the palmitoylation sites using a mutagenesis approach. This result suggests that both the N- and C-terminal tails of CD36 are cytoplasmic. Published models for the topology of CD36 have the C terminus located in the cytoplasm but differ as to whether the N terminus is cytoplasmic or extracellular. To address this question, a C-terminal truncation mutant of CD36 was made by introducing a stop codon just upstream of the C-terminal transmembrane domain. This mutant was found membrane-bound when expressed in human embryonic kidney 293 cells, indicating that the N-terminal hydrophobic domain serves as a transmembrane anchor, and thus supporting a CD36 topology with two transmembrane domains.
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PMID:CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails. 879 90

During a four-year period, 86 children with fever lasting for at least 6 days without diagnosis at admission after initial physical examination and preliminary laboratory tests were included in a retrospective analysis. Their ages ranged from 2 months to 16 years, and there were 55 males and 31 females. Bacterial infections occurred in 19 patients (22%), viral infections in 17 (20%), mycoplasmal infections in 3 and malaria in 1. Collagen vascular diseases were diagnosed in 13 children (15%), including 7 juvenile rheumatoid arthritis and 5 systemic lupus erythematosus. Thirteen children (15%) had neoplastic or hematological diseases, including leukemia, lymphoma, myelodysplastic syndrome, and neuroblastoma. The fevers of the other 14 patients (16%) were attributed to central fever. The overall diagnostic rate was 98%. Twenty-two children had a poor outcome, including 6 children with collagen vascular diseases and 12 with neoplasms. Diagnoses were made mainly through a complete medical history, meticulous physical examination, regular laboratory tests, and an observation of clinical course. Invasive tissue studies can be fruitful when used appropriately and should be considered for specific indication only.
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PMID:Prolonged fever in children. 893 8

The Cinchona bark contains alkaloids like quinine, quinidine, cinchonine and cinchonidine. These agents are effective antimalarial drugs and have been used clinically in malaria caused by Plasmodium falciparum. Previous studies show that quinine and quinidine exert effects on cardiovascular system. This study was conducted to examine the effect of cinchonine on human platelet aggregation. The results show that cinchonine inhibited platelet aggregation mediated by platelet agonists, epinephrine (200 microM), ADP (4.3 microM), platelet activating factor (PAF; 800 nM) and collagen (638 nM) but had no effect on arachidonic acid (AA; 0.75 mM). Cinchonine was most effective in inhibiting aggregation induced by platelet activating factor and epinephrine with IC50 values of 125 and 180 microM respectively, however, higher concentrations of cinchonine were required to inhibit aggregation mediated by ADP or collagen (IC50; 300 microM). Pretreatment of platelets with cinchonine inhibited aggregation caused by Ca2+ ionophore, A-23187 (6 microM), in a dose-dependent manner (IC50; 300 microM) indicating an inhibitory effect on Ca2+-signaling cascade. This was supported by measuring [Ca2+]i in platelets loaded with Fura-2AM where cinchonine inhibited the rise in cytosolic Ca2+ mediated by A-23187 (6 microM) or collagen (638 nM). Results show that cinchonine (20 microM) also inhibited aggregation when platelets were pretreated with protein kinase C (PKC) activator, phorbol myristate acetate (PMA; 0.1 microM) in combination with low doses of platelet activating factor (80 nM). Cinchonine, however, had no effect on AA-induced platelet aggregation and thromboxane A2 (TXA2) synthesis in platelets. These results suggest that antiplatelet effects of cinchonine are mediated mainly through inhibition of Ca2+-influx and protein kinase C pathways in platelets.
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PMID:The inhibitory effect of cinchonine on human platelet aggregation due to blockade of calcium influx. 977 5

CD36 is one of the major glycoproteins of platelets and known as GPIV. Besides platelets, CD36 is distributed in megakaryocytes, monocytes, capillary endothelium and mammary epithelial cells. In vitro analyses, CD36 is reported to act as receptors to a variety of ligands including collagen, thrombospondin, malaria-infected erythrocytes and oxidized LDL. However, it remains unclear to which of these functions CD36 is critical in vivo. CD36-deficient individuals can be the key to answer this question. In calcium-deficient state, CD36-deficient platelets exhibited a delay and decline of irreversible aggregation on agonist stimulation. Irreversible aggregation of platelets depends on intake of arachidonic acid once-secreted from platelets and production of its metabolite Eps/TxA2. The calcium influx in response to U46619 (TxA2 analogue) of CD36-deficient platelets was not different from normal platelets in the presence of indomethacin and ETYA. Defective aggregation of CD36-deficient platelets in calcium-deficient state seemed to be derived from defective intake of arachidonic acid. This assumption was verified by our results that inhibitory effect of arachidonic acid in aggregation depended on the presence of platelet CD36. Intake of arachidonic acid through CD36 may have an effect in low concentration state of arachidonic acid. The CD36 deficiency is present in several % in Japanese and approximately 0.3% in Caucasians and is divided in type I (deficient in platelets and monocytes) and type II (deficient only in platelets). Analyses of CD36 cDNA revealed that codon 90 (proline/serine) was critical as to the surface expression of CD36 protein. By analyses of CD36 genomic DNA, the CD36 gene could be classified; 1) serine90 type that was not translated as CD36 protein, 2) proline90 type that was not transcribed to mRNA, 3) proline90 type that was transcribed only in monocytes and not in platelets, 4) proline90 type that was transcribed in platelets but in very small amounts and 5) wild type proline 90. The results of family studies were consistent with the assumption described above.
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PMID:Platelet membrane protein CD36. 1038 59

This is Part II of a 2-part paper on fever of unknown origin (FUO) in children. It examines the aetiology and management of prolonged FUO in children and the difficulties in the management of FUO in children in developing countries. Part I of this paper discussed acute FUO in children and was published in the March 2001 issue of Paediatric Drugs. Prolonged FUO is documented fever of more than 7 to 10 days which has no apparent source and no apparent diagnosis after 1 week of clinical investigations. About 34% of cases of prolonged FUO are caused by infections, with bacterial meningitis and urinary tract infection accounting for about 6.5 and 11.4%, respectively, of cases attributable to infections. Chronic infections, particularly tuberculosis and 'old' disorders such as Kawasaki disease, cat-scratch disease and Epstein-Barr virus infection presenting with 'new' manifestations, collagen-vascular diseases and neoplastic disorders are the other issues of major concern in prolonged FUO. Overall, however, there is a trend towards an increased number of undiagnosed cases. This is due to advancements in diagnostic techniques, such that illnesses which were previously common among the causes of prolonged FUO are now diagnosed earlier, before the presentation becomes that of prolonged FUO. Clinical examination supplemented with laboratory tests to screen for serious bacterial infections should be the mainstay of initial evaluation of children with prolonged FUO. Use of scanning techniques (such as computerised tomography and ultrasound) as additional supplements to this clinical examination may allow for the earlier diagnosis of causes of prolonged FUO in children such as 'occult' abdominal tumours. A common error in management of children with prolonged FUO is the failure to perform a complete history and physical examination; repeated clinical examination and continued observation are of paramount importance in the diagnosis of difficult cases. Major difficulties in the management of FUO in children in developing countries include constraints in the availability and reliability of laboratory tests, cost, misuse of antibiotics and difficulties encountered in the diagnosis of malaria and typhoid fever. Malaria and typhoid fever are major aetiological considerations in both acute and prolonged FUO in children in developing countries. The newer quinolones may hold great promise for the treatment of serious bacterial infections, including meningitis, which are associated with prolonged FUO in developing countries.
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PMID:Management of children with prolonged fever of unknown origin and difficulties in the management of fever of unknown origin in children in developing countries. 1135 97

An estimated 1049 million persons harbour T. trichiura, including 114 million preschool-age children and 233 million school-age children. The prevalence of T. trichiura is high and may reach 95% in children in many parts of the world where protein energy malnutrition and anaemias are also prevalent and access to medical care and educational opportunities is often limited. The Trichuris dysentery syndrome (TDS) associated with heavy T. trichiura, which includes chronic dysentery, rectal prolapse, anaemia, poor growth, and clubbing of the fingers constitutes an important public health problem, as do lighter but still heavy infections, even if not strictly TDS, especially in children. The profound growth stunting in TDS can be reversed by repeated treatment for the infection and, initially, oral iron. However findings from Jamaica strongly suggest that the significant developmental and cognitive deficits seen are unlikely to disappear without increasing the positive psychological stimulation in the child's environment. The severe stunting in TDS now appears likely to be a reaction at least in part to a chronic inflammatory response and concomitant decreases in plasma insulin-like growth factor-1 (IGF-1), increases in tumor necrosis factor-alpha (TNF-alpha) in the lamina propria of the colonic mucosa and peripheral blood (which likely decrease appetite and intake of all nutrients) and a decrease in collagen synthesis. Improvements in cognitive performance have been found after treatment for relatively heavy infections (without chronic dysentery) in school-going children; it is unclear precisely how much T. trichiura interferes with children's ability to access educational opportunities, but treatment of infections whenever possible is obviously sensible. The blood loss that can occur in T. trichiura infection is likely to contribute to anaemia, particularly if the child also harbours hookworm, malaria and/or has a low intake of dietary iron. Community control is important, particularly for the individuals within a population who harbour heavy worm burdens; this means children, with special attention to girls who will experience increased iron requirements and blood loss due to menstruation, pregnancies, and lactation. Mebendazole and albendazole, both of which are on the WHO Essential Drugs List, are very effective against T. trichiura; multiple doses are needed to attain complete parasitological cure in all cases. However the goal of control programmes in endemic areas is morbidity reduction, which follows when intensity of infection is significantly reduced.
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PMID:The public health significance of Trichuris trichiura. 1138 93

The ookinete is a motile form of the malaria parasite that travels from the midgut lumen of the mosquito, invades the epithelial cells and settles beneath the basal lamina. The events surrounding cessation of ookinete motility and its transformation into an oocyst are poorly understood, but interaction between components of the basal lamina and the parasite surface has been implicated. Here we report that interactions occur between basal lamina constituents and ookinete proteins and that these interactions inhibit motility and are likely to be involved in transformation to an oocyst. Plasmodium berghei ookinetes bound weakly to microtitre plate wells coated with fibronectin and much more strongly to wells coated with laminin and collagen IV. A 1:1 mixture of collagen and laminin significantly enhanced binding. Binding increased with time of incubation up to 10 h and different components showed different binding profiles with time. Two parasite molecules were shown to act as ligands for basal lamina components. Western blots demonstrated that the surface molecule Pbs21 bound strongly to laminin but not to collagen IV whereas a 215 kDa molecule (possibly PbCTRP) bound to both laminin and collagen IV. Furthermore up to 90% inhibition of binding of ookinetes to collagen IV/laminin combination occurred if parasites were pre-incubated with anti-Pbs21 monoclonal antibody 13.1. Some transformation of ookinetes to oocysts occurred in wells coated with laminin or laminin/collagen IV combinations but collagen IV alone did not trigger transformation. No binding or transformation occurred in uncoated wells. Our data support the suggestion that ookinete proteins Pbs21 and a 215 kDa protein may have multiple roles including interactions with midgut basal lamina components that cause binding, inhibit motility and trigger transformation.
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PMID:The role of Plasmodium berghei ookinete proteins in binding to basal lamina components and transformation into oocysts. 1179 26

A prerequisite for understanding the role that mosquito midgut extracellular matrix molecules play in malaria parasite development is proper isolation and characterisation of the genes coding for components of the basal lamina. Here we have identified genes coding for alpha1 and alpha2 chains of collagen IV from the major malaria vector, Anopheles gambiae. Conserved sequences in the terminal NC1 domain were used to obtain partial gene sequences of this functional region, and full sequence was isolated from a pupal cDNA library. In a DNA-derived phylogeny, the alpha1 and alpha2 chains cluster with dipteran orthologs, and the alpha2 is ancestral. The expression of collagen alpha1(IV) peaked during the pupal stage of mosquito development, and was expressed continuously in the adult female following a blood meal with a further rise detected in older mosquitoes. Collagen alpha1(IV) is also upregulated when the early oocyst of Plasmodium yoelii was developing within the mosquito midgut and may contribute to a larger wound healing response. A model describing the expression of basal lamina proteins during oocyst development is presented, and we hypothesise that the development of new basal lamina between the oocyst and midgut epithelium is akin to a wound healing process.
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PMID:Anopheles gambiae collagen IV genes: cloning, phylogeny and midgut expression associated with blood feeding and Plasmodium infection. 1281 48

Although antimalarial drugs have been developed primarily to treat malaria, they are also beneficial for many dermatological, immunological, and rheumatological diseases, for which they are mostly used today in the Western world. The aim of the present study was to investigate the effect of quinine sulfate (QS) on the multiplication and adsorption of herpes virus type I (HSV-1). When Vero cells (African green monkey kidney) are infected with HSV-1 in the presence of QS, the viral adsorption is reduced, as demonstrated by a decrease of the number of microscopic plaques of the virus. When the virus-infected Vero cells are incubated in the presence of QS, the multiplication of HSV-1 is also reduced, and the diameter of the plaque are visibly smaller. The practical implications of the antiviral action of antimalarial drugs might be especially important to immunosuppressed patients who receive these drugs for autoimmune collagen-vascular diseases or as additional therapy for AIDS.
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PMID:Quinine sulfate and HSV replication. 1295 50

Halothane as a cause of hepatitis is rare and may be overlooked when evaluating a patient with sudden onset jaundice. A 34-year-old lady, a nurse, presented to the liver clinic with sudden onset non-pruritic jaundice. Viral and collagen serological tests were all normal, malaria and sickling tests were negative, but transaminases were elevated. She reported inadvertent exposure to halothane in surgical theatre where she works. She improved on conservative management, then had a re-exposure to halothane after three weeks and developed a similar clinical picture, which improved on conservative management. In an area endemic of malaria, hepatitis and haemolysing conditions like sickle cell anaemia, the diagnosis of halothane hepatitis requires high index of suspicion. The mechanism of halothane-induced hepatic damage in this patient is very likely idiosyncratic. This is because of the modest dose at first exposure and more severe clinical picture at re-exposure.
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PMID:Halothane induced hepatitis: case report. 1571 33


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