ISSN:0361-8609    

DOI:10.1002/ajh.2830420102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0361-8609    

DOI:10.1002/ajh.2830420103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe ferrous iron of hemoglobin is exposed continuously to high concentrations of oxygen and, thereby, is oxidized slowly to methemoglobin, a protein unable to carry oxygen. To restore hemoglobin function, methemoglobin (ferrihemoglobin) must be reduced to hemoglobin (ferrohemoglobin). Under physiological conditions, methemoglobin reduction is accomplished mainly by red cell NADH‐cytochrome b5reductase (NADH‐methemoglobin reductase) so efficiently that there is insignificant amounts of methemoglobin in the circulating blood. However, should methemoglobin formation be increased—e.g., due to the presence of oxidant drugs, or an abnormal methemoglobin not amenable to reduction (hemoglobin M), or a deficiency in red cell cytochrome b5reductase—methemoglobinemia will result. Most methemoglobinemias have no adverse clinical consequences and need not be treated. Under certain conditions, such as exposure to large amounts of oxidant or in young infants, rapid treatment is necessary. In hereditary cytochrome b5deficiency, treatment is often directed at improving the poor cosmetic effect of persistent cyanosis with the minimum amount of drugs to give satisfactory clinical results. © 1993 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830420104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractNADPH‐dependent methemoglobin reductase, first detected in erythrocytes sixty years ago, has subsequently been purified and characterized as a methylene blue reductase and a flavin reductase. The reductase plays no role in methemoglobin reduction under normal conditions, but its activity serves as the basis for the treatment of methemoglobinemia with methylene blue or flavin. On‐going studies demonstrate that this cytosolic protein is also present in liver and that its primary structure distinguishes it from other known proteins. The bovine erythrocyte reductase tightly binds hemes, porphyrins, and fatty acids with resulting loss of activity. Pyrroloquinoline quinone serves as a high‐affinity substrate of the reductase, suggesting that this naturally‐occurring compound may be a physiological substrate. The ability of the reductase to catalyze the intracellular reduction of administered riboflavin to dihydroriboflavin suggested that this system might be exploited to protect tissues from oxidative damage. This hypothesis was supported by our finding that dihydroriboflavin reacts rapidly with Fe(IV)O and Fe(V)O oxidation states of hemeproteins, states that have been implicated in tissue damage associated with ischemia and reperfusion. Preliminary studies demonstrate that, as predicted, administration of low concentrations of riboflavin protects isolated rabbit heart from reoxygenation injury, rat lung from injury resulting from systemic activation of complement, and rat brain from damage caused by four hours of ischemia. Data from these animal studies suggest that flavin therapy holds promise in protecting tissue from the oxidative injuries of myocardial infarction, acute lung injury, stroke, and a number of other clinical conditions. © 1993 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830420105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractFor many years the red cell membrane has served as an extraordinarily valuable model for membrane structure and function. During the past 2 decades, the biochemical concept of the membrane skeleton was established, and, with the help of electron microscopy, a partial depiction of this structure evolved. Newer biophysical approaches designed to measure distances between various components of membrane skeleton as well as distances between the membrane skeleton and the overlying bilayer should now help to define this structure more realistically. Fluorescence resonance energy transfer, single photon radioluminescence, and total internal reflectance are three biophysical techniques that will enable us to measure such distances over a substantial range, which extends from a few Angstroms to ∼2 μm. The ability to make such measurements in intact cells and in fully hydrated, undenatured membrane preparations should add a new dimension to our understanding of the structure of the red cell membrane. © 1993 Wiley‐Liss

ISSN:0361-8609    

DOI:10.1002/ajh.2830420106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have compared characteristics of red cells from patients who were originally diagnosed as having two different disorders, high phosphatidyl choline hemolytic anemia (HPCHA) and hereditary xerocytosis (HX). Both types of cells had reduced intracellular potassium, with attendant cell dehydration and an increase in the relative amount of membrane phosphatidyl choline. Neither these observations nor a review of previous studies of HX and HPCHA revealed any means of distinguishing between the two disorders. Measurements of chloride‐dependent potassium transport revealed flux characteristics in both HX and HPCHA red cells that were different from those in simultaneously run control samples. HX and HPCHA red cells did not show the same kinds of deviations from the normal pattern. However, extensive characterization of transport behavior under a variety of controlled conditions will be required to determine whether these differences represent intrinsic differences in chloride‐dependent transport properties. It appears likely that HX and HPCHA both represent a spectrum of disorders resulting from a variety of defects that produce the same general pattern of abnormalities in cation content and membrane phospholipid composition © 1993 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830420107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0361-8609    

DOI:10.1002/ajh.2830420108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractSudden episodes of massive hemolysis have become the most common cause of death among captive black rhinoceroses, and there is evidence that they occur in the wild as well. We have observed radically unique enzyme and metabolite profiles in normal rhinoceros erythrocytes compared to humans and other mammals, including marked deficiencies of intracellular adenosine triphosphate (ATP), catalase, adenosine deaminase, and other enzymes involved in glycolysis, glutathione cycling, and nucleotide metabolism. Minimal concentrations of ATP appear to impair effective acceleration of hexosemono‐phosphate shunt activity in response to oxidants by restricting substrate generation at the hexokinase step. Antioxidant defenses are further compromised by catalase deficiency, which may be a general characteristic of rhinoceros erythrocytes, perhaps related to the common occurrence of severe mucocutaneous ulcerative disease. It is proposed that erythrocyte ATP deficiency in rhinoceroses may be an evolutionary adaptation conferring selective advantage against common hemic parasites, comparable to the role of human glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency in falciparum malaria. © 1993 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830420109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe human red cell has a life span of 120 days. The mechanism that determines cell removal from the circulation with such precision remains unknown. Most studies of red cell aging have been based on analysis of cells of progressively increasing age separated by density. The relationship between red cell age and density has been recently challenged, and the hypothesis has been put forward that cell death is not the result of a progressive deterioration of essential cell constituents. This theory was based on preliminary observations in transient erythroblastopenia of childhood, which could not later be confirmed. When the relationship between cell aging and increasing density is critically reviewed, it appears to be based on firm experimental evidence, confirmed by in vivo demonstration of decreasing survival of cells of increasing age. Analysis of studies using buoyant density gradients reveals that this technique can easily distinguish the single exponential slope of decline for those cell components that change progressively throughout the red cell life span from the biphasic decline of those that decrease drastically at the reticulocyte‐mature red cell transition. The view that the aging of the red cell and its removal from the circulation result from a progressive series of events during the 120 days of its life span appears to be the most consistent with the available data. Density separation, validated by much experimental evidence, remains a most useful technique for the study of the mechanism of aging of the red cell. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830420110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractGlucose‐6‐phosphate dehydrogenase (G6PD) deficiency was discovered in the 1950s. The history of the development of knowledge about G6PD deficiency is reviewed here. In the first decade after its discovery, the clinical manifestations of G6PD deficiency began to be understood. In the second decade, attention was focused on the degree of variability of this enzyme and the distinction of the various biochemical variants from one another. In the last decade, it has been possible to understand the mutations that effect this enzyme at the DNA level. Some 40 different mutations have now been characterized. Analysis of these mutations indicates that, while diversity sometimes exists within a mutation considered biochemical homogeneous, more often variants thought to be distinct prove to be identical. The study of G6PD mutations is beginning to provide insight into structurefunction relationships. © 1993 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830420111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY