Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A brain biopsy obtained from a twenty-eight month old boy with ceroidlipofuscinosis was studied by light and electron microscopy. There were widespread intracellular deposits of autofluorescent material taking the fat stains. Cytoplasmic inclusions were plentiful in neurons, astrocytes, oligocytes, M cells and vascular elements. Their substructure ranged from that of variably dense aggregates of essentially homogeneous or granular appearance to that of miscellaneous collections of lamellar pairs and/or tubular structures of variable length. Stacks of 2 to 4 linear profiles with a curved outline were rarely seen and then almost exclusively inside cytosomes of endothelial cells. Similar observations were made in peripheral nerve, skin and liver biopsies. The granules of peripheral blood neutrophilic leukocytes were unremarkable. A small percentage of lymphocytes contained granular cytoplasmic bodies not unlike those known to be an ordinary feature of some lymphocytes of the average blood sample. However, a certain resemblance between these bodies and some of the cytosomes seen in the patient's tissues was also apparent. Myeloperoxidase activity was tested with paraphenylenediamine and was found to be normal on two occasions. The patient's age, cytosome morphology and distribution and results of peroxidase assay add special interest to this case of generalized ceroidlipofuscinosis. However, none of these features, either singly or in combination, warrants creation of a distinct subtype within this group of disorders. Myeloperoxidase deficiency is probably just another phenotypical marker of some patients with generalized ceroidlipofuscinosis rather than the genetic defect of Batten disease.
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PMID:Cytosome morphology and distribution of generalized ceroidlipofuscinosis in a twenty-eight month old boy with normal myeloperoxidase activity. 17 May 59

One of the most important mechanisms of phagocytic killing of ingested microorganisms by leukocytes is the generation of toxic oxygen products. During phagocytosis, neutrophils, as well as monocytes and macrophages, display a strongly increased cell respiration. Quantitatively the most important product of this reaction is hydrogen peroxide. Superoxide is also generated in large amounts, probably as an intermediate in the formation of hydrogen peroxide. Indications exist that singlet oxygen and hydroxyl radicals are also formed in this process. Some of these oxygen products have microbicidal properties by themselves. The effect of hydrogen peroxide is greatly enhanced by the enzyme myeloperoxidase. Several dysfunctions of this sytem are known. In chronic granulomatous disease the enzyme system that produces superoxide is not operative. Thus, no superoxide or hydrogen peroxide is generated, leading to a severely decreased bacterial killing capacity. The exact molecular defects in the X-linked and the autosomal form are as yet undefined. Two variants are also known: lipochrome histiocytosis, with different clinical and histological manifestations, and a 'triggering defect' where only strongly opsonized particles trigger the respiratory burst. Myeloperoxidase deficiency leads to slightly decreased killing capacity, especially for yeasts. In glucose-6-phosphate dehydrogenase deficiency no oxygen radicals or hydrogen peroxide are produced because no equivalents for oxygen reduction can be generated in the hexose-monophosphate shunt. Deficiencies in the glutathione redox system also result in impaired phagocyte function, probably because the cells have to be protected against their own toxic oxygen products.
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PMID:Defects in the oxidative killing of microorganisms by phagocytic leukocytes. 22 41

Advances in molecular genetic understanding of disease processes has been extended to a number of phagocytic disorders. Most of these disorders were extensively characterized at the functional and protein level prior to cloning of the relevant genes. Nucleotide sequence data has been essential for establishing the mechanism and mode of inheritance of genetically transmitted phagocyte disorders. Such data provides insights into the functionally important regions of affected proteins and information regarding regulation of these genes and homologies to other known proteins. From such data it is also possible to determine the evolutionary history of these genes. Chronic granulomatous disease, a phenotypic classification of a heterogeneous group of defects in oxidative metabolism, has now been defined in terms of specific molecular defects. Cloning of the two subunits of cytochrome b558 has led the way to characterization of the X-linked form and one of the autosomal recessive forms of this disease and confirmed the importance of this protein in the phagocyte oxidative burst. The absence of lactoferrin associated with hereditary specific granule deficiency is a result of decreased transcription of the lactoferrin gene in myeloid cells. Myeloperoxidase deficiency is likely a result of a mutation of the gene coding for myeloperoxidase. More precise understanding of expression of the lactoferrin and myeloperoxidase genes may be important in elucidating some of the underlying mechanisms in the pathogenesis of myeloid malignancies. A rare disorder, leukocyte adhesion deficiency, has provided a model for establishing the relationship between the several distinct alpha subunits and the shared common beta subunit of leukocyte adhesion proteins. These proteins have been shown to be genetically related to the superfamily of extracellular matrix receptors termed 'integrins'. Because these proteins have been highly conserved at the genetic level across a variety of species, comparison of nucleotide sequence data has illuminated some of the evolutionary history of these genes as they arose from ancestral genes. Studies of these adhesion protein genes may contribute new information in the broader context of how the functions of these genes evolved.
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PMID:The molecular biology of selected phagocyte defects. 267 50

Myeloperoxidase deficiency is the most common neutrophilic lysosomal enzyme deficiency. Case studies indicate that individuals with myeloperoxidase deficiency are not susceptible to serious infection in the absence of coexisting conditions such as diabetes mellitus. We present a case of myeloperoxidase deficiency manifesting as disseminated pustular candidal dermatitis in a nondiabetic male. Ceftriaxone therapy was administered to the patient for 8 days after he received a closed head injury and before the development of fever and pustular dermatitis. Candida albicans was isolated from the skin lesion. His neutrophils demonstrated a qualitative lack of myeloperoxidase. Patients who develop rapidly disseminated fungal dermatitis while they are receiving antimicrobial therapy that is relatively limited in coverage should be evaluated for myeloperoxidase deficiency.
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PMID:Myeloperoxidase deficiency manifesting as pustular candidal dermatitis. 911 58

Myeloperoxidase deficiency is the most common inherited phagocyte disorder (1:2000) and causes an abnormal dihydrorhodamine oxidation test, which also is seen in chronic granulomatous disease. A patient with Candida meningitis and low dihydrorhodamine oxidation signal was diagnosed with chronic granulomatous disease but actually had compound heterozygous myeloperoxidase deficiency.
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PMID:Complete Myeloperoxidase Deficiency: Beware the "False-Positive" Dihydrorhodamine Oxidation. 2730 73