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)

CD36 is an 88-kDa glycoprotein that has been identified on platelets, monocytes, and some endothelial cells. Experimental evidence suggests that CD36 mediates the binding of Plasmodium falciparum-infected RBC to a variety of cells, and therefore may play a role in the vascular complications associated with malaria. Additionally, CD36 may also bind the extracellular matrix proteins thrombospondin and collagen. Human umbilical vein endothelial cells have been used in in vitro models examining the binding of P. falciparum RBC to endothelial cells, but they do not consistently express cell surface CD36. Inasmuch as human dermal microvascular endothelial cells (HDMEC) differ in a variety of ways from large vessel endothelial cells, we have examined HDMEC for cell surface expression of CD36 in vivo and in vitro. Direct immunofluorescence of skin showed bright staining of HDMEC with antibody recognizing CD36 and flow cytometric analysis of cultured HDMEC revealed cell surface expression. In contrast, large vessel endothelial cells were not stained with antibody recognizing CD36 in vivo and cultured cells derived from umbilical vein failed to express cell surface CD36 in vitro. Western immunoblots of lysates of HDMEC but not human umbilical vein endothelial cells demonstrated an 88-kDa protein that comigrated with CD36 from platelets. Functional studies demonstrated that adherence of PRBC to HDMEC was inhibited up to 66% by mAb recognizing CD36. Furthermore, the expression of CD36 on HDMEC was increased in a dose- and time-dependent manner by IFN-gamma, and was decreased by protein kinase C agonists. These data demonstrate that HDMEC express functionally active CD36 and this expression can be positively and negatively regulated by soluble factors. This study demonstrates that HDMEC are useful in the study of CD36-mediated binding of PRBC to endothelial cells in vitro and provides further evidence of distinct phenotypic differences between HDMEC and large vessel endothelial cells.
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PMID:Human dermal microvascular endothelial but not human umbilical vein endothelial cells express CD36 in vivo and in vitro. 137 Jan 73

Mice infected with the rodent malaria parasite Plasmodium berghei exhibit ultrastructural changes of the blood-brain barrier during the course of infection. Firm adherence including cellular interdigitation of infected cells or leucocytes and even clusters of cells to the vascular-endothelial lining is repeatedly observed early during infection. Ghosts and membrane remnants can be found engulfed in the surface of the endothelial cells. Frequently leucocytes migrate between endothelial cells and even cause a lift off and degeneration of these cells. In addition, endothelial cells exhibit increased pinocytotic activity, many irregular cytoplasmic extensions and even phagocytic activity. These changes are associated with degenerative changes in the basement membrane. Swelling and deposition of collagen-like fibres and even loss of fragments of basement membrane is observed. In some places fingerlike extensions of pericytes passed through the basement membrane and contacted or even bulged into the cytoplasm of endothelial cells. Ballooning and even coalescence of perivascular astrocytes was observed and contributed to the appearance of a perivascular oedematous space. The observed changes indicate a progressive deterioration of the blood-brain barrier eventually leading to endothelial lesions and hemorrhage.
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PMID:Ultrastructural changes in the blood-brain barrier of mice infected with Plasmodium berghei. 148 95

A 45-year-old man was admitted to our hospital with chief complaint of fever. The chest X-ray examination showed 2-3 mm fine nodular shadows throughout the entire lung fields. Eosinophilia was present in the peripheral blood. Spike-like high fever (39 degrees C) appeared every 48 hours. All bacteriologic cultures from blood, bone marrow aspirate, sputum, gastric juice, and bronchoalveolar lavage fluid were negative. Furthermore, the antibody titer of malaria was negative. No antibiotics were effective in this case. Histological examination of the transbronchial lung biopsy showed non-specific inflammation, but the open lung biopsy specimen showed scattering of tiny granulomatous lesions. These granulomas were composed of histiocytes with indented nuclei, fibroblasts, varying amounts of collagen fibers, and eosinophils. The histiocytes were positive for S-100 protein staining and identified as Langerhans' cells. Therefore, this patient was diagnosed as having pulmonary eosinophilic granuloma. Two months later, the abnormal shadows on the chest X-ray and high fever spontaneously resolved without steroid therapy. This case was considered to be unique with respect to the peripheral blood eosinophilia, the three-day fever, and spontaneous improvement, compared with the former reported case.
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PMID:[A case of pulmonary eosinophilic granuloma with three-day fever]. 156 29

Glycoprotein (GP) IIIb (also termed GPIV or CD36) is an integral platelet membrane protein, and has been identified as a binding site for thrombospondin, collagen, and malaria-infected erythrocytes. PAS-IV is an integral membrane protein found in lactating mammary epithelial cells and capillary endothelial cells. The N-terminal sequence of PAS-IV is nearly identical to that of GPIIIb and monospecific anti-PAS-IV antibody reacts with GPIIIb, indicating that PAS-IV is structurally related to GPIIIb. In this study, human platelet GPIIIb and bovine epithelial PAS-IV were compared in terms of structural, immunologic, and functional characteristics. The two-dimensional tryptic peptide map of both intact and deglycosylated PAS-IV was highly similar but not identical to that of GPIIIb. PAS-IV and GPIIIb reacted to an equal extent with monoclonal antibodies OKM5 and OKM8 by enzyme-linked immunosorbent assay. GPIIIb bound to surface immobilized thrombospondin (TSP) in a concentration-dependent and saturable manner, with approximately 60% reduction in binding in the presence of EDTA. PAS-IV bound to TSP with similar characteristics except that maximum binding was consistently approximately 50% of that of GPIIIb and binding was not inhibited by EDTA. GPIIIb supported adhesion of Plasmodium falciparum-infected erythrocytes (PRBC) in a dose-dependent manner while no significant adhesion of PRBC to PAS-IV was observed. Our data demonstrate that while epithelial PAS-IV and platelet GPIIIb are structurally and immunologically related, there are significant differences in their functional properties. Whether this result is due to different posttranslational glycosylation modifications or that PAS-IV and GPIIIb represent a family of related cell adhesive protein receptors remains to be determined.
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PMID:Epithelial membrane glycoprotein PAS-IV is related to platelet glycoprotein IIIb binding to thrombospondin but not to malaria-infected erythrocytes. 171 May 15

Platelet aggregation responses were studied in platelet-rich plasma from six healthy volunteers before and 2 and 6 h after ingestion of 600 mg chloroquine sulphate. Apart from a mild reduction in height of aggregation response to 1 microgram ml-1 collagen 2 h post-drug ingestion (mean percentage of pre-drug values +/- s.e.m. = 87.8% +/- 4.0%; P = 0.04), no significant differences were observed in platelet responses to ADP (1 and 5 microM) or collagen (1 and 4 micrograms ml-1) at 2 or 6 h post-chloroquine compared to the pre-drug values. In vitro, drug concentrations approximately 1000 times greater than those used therapeutically were required for 50% inhibition of platelet aggregation and ATP release in response to 5 microM ADP, 1 microgram ml-1 collagen and 4 micrograms ml-1 collagen (IC50 concentrations +/- s.e.m. for inhibition of aggregation = 98.5 +/- 3.7, 53.5 +/- 56.4 and 113.0 +/- 6.2 mg l-1 respectively; IC50s +/- s.e.m. for inhibition of ATP release = 0.9 +/- 0.2, 14.7 +/- 4.0 and 23.0 +/- 5.3 mg l-1 respectively). These data provide no cause for concern in using chloroquine for malaria prophylaxis in patients with impaired haemostasis.
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PMID:The in-vitro and ex-vivo effects of chloroquine sulphate on platelet function: implications for malaria prophylaxis in patients with impaired haemostasis. 232 91

The authors have studied in vitro the platelet aggregability induced with ADP, collagen and ristocetin. Chloroquine was added at increasing concentration (3,2 mgr/l, 16 mgr/l, 32 mgr/l). The results have been highly significant. They showed that chloroquine has an anti aggregating effect with the three inducing agents. This effect was increasing with the chloroquine concentration. Some previous works have been indicative of the inhibiting effect of chloroquine on platelet aggregability. In the treatment of the malaria, this inhibiting effect could be complementary with the specific antiparasitic effect. On the other hand the inhibiting effect on platelet aggregability could be useful for the prevention of thrombosis.
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PMID:[Antiaggregation action of chloroquine]. 236 48

The splenic response in lethal 17XL Plasmodium yoelii murine malaria is vigorous, displaying marked phagocytosis, erythropoiesis, lymphopoiesis, plasmacytopoiesis, and, from day 3 of infection, increasing levels of parasitized erythrocytes. There is also a pronounced response of newly characterized fibroblastic stromal cells which branch and fuse with one another, forming extensive, complex, irregular, syncytial membranous sheets which provide a variety of barriers. Hence, I term these barrier cells (BC), and their fusion results in barrier-forming complexes (BFC). BC form adherent surfaces, trapping parasitized erythrocytes and monocytes-macrophages, facilitating phagocytosis. They envelop single plasma cells, erythrocytes, erythroblasts, lymphocytes, reticulocytes, monocytes-macrophages, or clusters of them. They surround blood vessels, forming blood-spleen barriers. They are insinuated into the circumferential reticulum at the periphery of white pulp, isolating white pulp. They form channels in red pulp, directing blood flow. They are associated with collagen. There appear to be several sources of BC. They may originate by activation of established reticular cells which form the filtration beds, by activation of reticular cells covering the pulp surface of capsule and trabeculae, and as a major source in this malaria, from circulating progenitors entering the splenic pulp from the vasculature. In non-lethal malaria, these barrier systems protect splenic reticulocytes from parasitization. In the lethal 17XL malaria they do not, and there follows a considerable increase in parasitization in the spleen with a corresponding increase in active macrophages. Large-scale parasitization and parasite recycling through the great stores of splenic reticulocytes in the lethal malaria, and the failure of parasitization of these splenic reticulocytes reserves on the non-lethal malaria, suggests that the actions of the spleen aggravate the lethal malaria and ameliorate the non-lethal. This is supported by the finding that non-lethal malaria is aggravated and lethal malaria ameliorated by splenectomy.
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PMID:Mechanisms of splenic control of murine malaria: cellular reactions of the spleen in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice, and the consequences of pre-infective splenectomy. 247 37

This paper describes changes in the circulating platelets of 25 patients with acute malaria within 2 to 6 days of onset of illness. Thrombocytopenia was observed in 10 out of 15 patients with Plasmodium falciparum infection, and in 4 out of 9 patients with P. vivax infection. One patient with a mixed infection of both species had a disseminated intravascular coagulation. Platelet antibody was detected in the sera of 8 out of 11 cases by the complement lysis inhibition technique and indirect immunofluorescence. The mean platelet antibody concentrations in the sera of 11 patients and 53 control subjects were 122.70 +/- 80.25 ng/10(7) platelets and 36.69 +/- 18.72 ng/10(7) platelets, respectively. An inverse relationship between the platelet count and platelet antibody levels in serum supported the view that thrombocytopenia in malaria may be partly immune-mediated. Platelet aggregation responses to agonists such as ADP, adrenaline, collagen and ristocetin revealed hyperactivity. Ultrastructural study of unstimulated platelets from patients revealed several changes such as centralization of dense granules, glycogen depletion, and formation of pseudopods and microaggregates, indicating in vivo activation of the platelets, which may also lead to thrombocytopenia.
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PMID:Functional and ultrastructural changes of platelets in malarial infection. 306 47

Pre- and post syndrome sera from five Burkitt's lymphoma patients who partook in the Ugandan prospective study (A. Geser et al., Int. J. Cancer 29 (1982) 397-400) were investigated with respect to autoantibodies. Neighbours and siblings of these patients served as controls and all of these groups were compared with sera from 50 Caucasian normal controls (CNC). Antibody levels significantly higher than those in CNC were found in all African groups for actin, desmin, vimentin, tubulin, keratin, laminin, and collagen type I. Polyclonal B-cell activation, as measured by antibodies to DNP, and high levels of antibodies to P. falciparum were also found. Anti-DNP and antibodies to malaria were also present in sera from our earlier study on Burkitt's lymphoma (E. Vainio et al., Clin. exp. Immunol. 54 (1983) 387-396). Whereas EBV infected B cells do produce autoantibodies, there is a potentiation of autoantibody formation as a result of infection with malaria, which seems to provide an independent trigger of polyclonal B cell activation. This latter event might be one of the factors which results in a correlation of Burkitt's lymphoma with malaria endemic regions.
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PMID:Autoantibodies in Burkitt's lymphoma patients from the Ugandan prospective study. 351 27

Elucidation of the complete amino acid sequence of TSP has suggested plausible explanations for all of the earlier observations on TSP structure and has already suggested new and interesting avenues of investigation aimed at determining the precise function and mechanism of TSP action as a matrix protein. The potential for Ca++-regulated exposure of the RGDA sequence could represent a new level of control for this important recognition system. We have already shown that the binding of TSP to collagen is modulated by the binding of Ca++ to this region of TSP. That is, high Ca++ results in a lower affinity of TSP for collagen, whereas lower Ca++ concentrations enhance the affinity of this interaction. The highly conserved, although short, 15-residue segment, which is nearly identical to region II of the sporozoite malaria protein, may indicate that TSP interacts with a receptor on liver cells, which the malaria parasite uses to gain its initial toehold in the body. If so, this would be another example of pathogenic organisms using a preexisting host recognition system to gain entry to cells where it can multiply. The collagen propeptide-like segment occurs in the collagen-binding domain of TSP and thus may represent the site at which TSP interacts with the collagens. These speculations form the starting point for many exciting lines of experimentation, which will provide us with a better understanding of the role of TSP in hemostasis, in the matrix of a variety of cells, and in development.
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PMID:Structure of human thrombospondin: complete amino acid sequence derived from cDNA. 368 18


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