Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glucose-6-phosphate dehydrogenase (G6PD) stain was adapted to skeletal muscle by using homogenate assays and quantitative cytochemical stains to determine the "correct" localization. For both feline and human skeletal muscles, the appropriate level of phenazine methosulfate eliminated fiber typing, which was falsely localizing the rate-limiting, bound reduced form of NADPH rather than the soluble G6PD. Use of a viscous solution of polyvinyl alcohol was necessary to prevent enzyme diffusion. Under these conditions, G6PD produced a mild myoplasmic stain with even sarcoplasmic reticulum granularity in human biopsy specimens. Fibers that were degenerating or regenerating by hematoxylin-eosin or alkaline phosphatase stains yielded an intense myoplasmic G6PD stain. Additional degenerating fibers were also often detectable with G6PD staining. No increased staining was found in denervated or atrophic fibers. Absence of staining (after 2 hours) was not a reliable indicator of G6PD deficiency, although it could be used for preliminary screening of muscle biopsy specimens.
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PMID:A glucose-6-phosphate dehydrogenase stain for frozen human skeletal muscle biopsy specimens. A sensitive indicator of fiber degeneration. 169 37

A 52 yr old Caucasian female (F. E.) had hemolytic anemia, a leukemoid reaction, and fatal sepsis due to Escherichia coli. Her leukocytes ingested bacteria normally but did not kill catalase positive Staphylococcus aureus, Escherichia coli, and Serratia marcescens. An H(2)O(2)-producing bacterium, Streptococcus faecalis, was killed normally. Granule myeloperoxidase, acid and alkaline phosphatase, and beta glucuronidase activities were normal, and these enzymes shifted normally to the phagocyte vacuole (light and electron microscopy). Intravacuolar reduction of nitroblue tetrazolium did not occur. Moreover, only minimal quantities of H(2)O(2) were generated, and the hexose monophosphate shunt (HMPS) was not stimulated during phagocytosis. These observations suggested the diagnosis of chronic granulomatous disease. However, in contrast to control and chronic granulomatous disease leukocytes, glucose-6-phosphate dehydrogenase activity was completely absent in F. E. leukocytes whereas NADH oxidase and NADPH oxidase activities were both normal. Unlike chronic granulomatous disease, methylene blue did not stimulate the hexose monophosphate shunt in F. E. cells. Thus, F. E. and chronic granulomatous disease leukocytes appear to share certain metabolic and bactericidal defects, but the metabolic basis of the abnormality differs. Chronic granulomatous disease cells lack oxidase activity which produces H(2)O(2); F. E. cells had normal levels of oxidase activity but failed to produce NADPH due to complete glucose-6-phosphate dehydrogenase deficiency. These data indicate that a complete absence of leukocyte glucose-6-phosphate dehydrogenase with defective hexose monophosphate shunt activity is associated with low H(2)O(2) production and inadequate bactericidal activity, and further suggest an important role for NADPH in the production of H(2)O(2) in human granulocytes.
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PMID:Complete deficiency of leukocyte glucose-6-phosphate dehydrogenase with defective bactericidal activity. 440 Dec 71

This review has concentrated on clinical syndromes for which a congenital basis of polymorphonuclear neutrophil dysfunction has been identified. The first clinical syndrome found to be associated with dysfunctional polymorphs was chronic granulomatous disease of childhood. Identification of a cellular defect in oxidative metabolism and microbicidal activity of polymorphonuclear neutrophils from patients with CGD stimulated intense investigation of the function of phagocytes in several clinical entities characterized by increased susceptibility to infection. Other diseases with a probable congenital basis for polymorph dysfunction include Chediak-Higashi syndrome, myeloperoxidase deficiency, severe glucose-6-phosphate dehydrogenase deficiency, and Down's syndrome. Functional defects have also been identified in neutrophils with morphologic abnormalities, such as the Pelger-Huet anomaly and the May-Hegglin anomaly, and in neutrophils without alkaline phosphatase or with a disorder of the glutathione system. The evidence for a relation between these cellular disorders and susceptibility to infection is tentative. Patients with congenital disorders of polymorphonuclear neutrophil microbicidal function frequently suffer prolonged infections in spite of appropriate antimicrobial therapy, and severe lesions recur with discouraging frequency. These lesions are usually soft tissue or bone abscesses, and the etiologic agents are typically staphylococci, gram-negative enteric species, or fungi. The infectious disease problems of patients with phagocytic cell disorders are usually quite distinct from the problems of patients without immunoglobulins or with complement deficiency. Patients with agammaglobulinemia, for example, suffer recurrent septicemia or meningitis due to Streptococcus pneumonia or H. influenzae. Septicemia, especially with the pyogenic bacterial species, is unusual in patients with polymorphoinuclear dysfunction. A major contribution of the currently intense investigation of cells from patients with congenital disorders of phagocyte function has been the greatly increased understanding of the molecular events necessary for the normal function of these cells. The role of the oxidative metabolic burst during phagocytosis has been clearly identified as essential to the microbicidal function of polymorphs and monocytes, and the glutathione system has been identified as essential to the regulation of these oxidative reactions. It is anticipated that these studies may lead to practical methods for "stimulating the phagocytes" in patients with increased susceptibility to infection.
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PMID:Congenital disorders of the function of polymorphonuclear neutrophils. 625 30

Molecular, kinetic, and functional studies were carried out on erythrocytes and leukocytes in a Spanish male with G6PD deficiency, congenital nonspherocytic hemolytic anemia (CNSHA), and increased susceptibility to infections. G6PD activity was absent in patient's red cells and was about 2% of normal in leukocytes. Molecular studies using standard methods (WHO, 1967) showed G6PD in the patient to have a slightly fast electrophoretic mobility at pH 8.0 with otherwise normal properties (heat stability at 46 degrees C, apparent affinity for substrates, optimum pH, and utilization of substrate analogues). Other tests showed the patient's granulocytes to engulf latex particles normally, but to have impaired reduction of nitroblue tetrazolium and ferricytochrome-c as well as reduced iodination. Chemotaxis and random migration of the patient's granulocytes were normal as were myeloperoxidase, leukocyte alkaline phosphatase (LAP), and ultrastructural features. The molecular characteristics of G6PD in the patient differed from those of all previously reported variants associated with CNSHA, so the present variant was provisionally called G6PD Barcelona to distinguish it from other G6PD variants previously described. Possible mechanisms for the severe deficiency of G6PD in erythrocytes and granulocytes was investigated by studies on the immunologic specific activity of the mutant enzyme.
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PMID:Severe-glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with chronic hemolytic anemia, granulocyte dysfunction, and increased susceptibility to infections: description of a new molecular variant (G6PD Barcelona). 705 48