ISSN:0361-8609    

DOI:10.1002/ajh.2830420112

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

年代:1993

数据来源: WILEY

摘要:

AbstractA series of morbidly obese patients was treated surgically with a gastric bypass, and a subsequent series received a vertical banded gastroplasty.To compare some of the nutritional effects of these two procedures we measured serum vitamin B12levels, absorption of food vitamin B12, frequency of microcytosis of erythrocytes, and frequency of anemia at one or more years after surgery.Patients with a gastric bypass showed greater weight loss, a greater frequency of microcytosis and anemia, more frequent subnormal serum levels of vitamin B12, and impressive failure to absorb food vitamin B12. Boiling the food containing vitamin B12led to increased absorption. © 1993 Wiley‐Liss, I

ISSN:0361-8609    

DOI:10.1002/ajh.2830420113

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

年代:1993

数据来源: WILEY

摘要:

AbstractNewly identified iron binding proteins isolated from rat duodenal homogenates permit better understanding of iron absorption. Mucins bind iron at acid pH to keep iron soluble and available for absorption at the more alkaline pH of the duodenum; this explains iron deficiency following prolonged achlorhydria. Integrin (90/150 kD) was identified on the absorptive surface of enterocytes in association with radioiron and is believed to facilitate transit of iron through the microvillous membrane. Mobilferrin, a 56 kD iron binding protein, was isolated from enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrins in the apical cytoplasm. We postulate it accepts dietary iron from integrin and acts as the shuttle protein for iron in the cytoplasm. Since iron in enterocytes remains in equilibrium with body stores, we postulate mucosal iron uptake is regulated by the number of iron binding sites either occupied or unoccupied by iron on mobilferrin. Iron repletion of enterocytes from body stores is accomplished via transferrin receptors on the posterolateral membranes of enterocytes. Increased transfer of iron from blood into absorptive enterocytes occurs in iron replete animals to inhibit mucosal uptake of dietary iron. Little transfer of iron from plasma to enterocytes occurs in iron deficiency. Enhanced mucosal transfer of iron into the body occurs with increased body need for iron. The exact mechanism for mucosal transfer of iron into the plasma has not been defined but may also be mediated by an integrin. © 1993 Wiley‐Liss, I

ISSN:0361-8609    

DOI:10.1002/ajh.2830420114

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

年代:1993

数据来源: WILEY

摘要:

AbstractA recombinant plasmid carrying human transferrin receptor cDNA in reverse orientation downstream from the human cytomegalovirus immediate early promoter/enhancer element was introduced into the HuH‐7 human hepatoma cell line by lipofection. Cell surface transferrin binding and iron uptake from transferrin each decreased by about 50% in stable transfectants bearing integrated antisense DNA expression vector. Northern blot analysis indicated that the abundance of target transferrin receptor message was not altered by antisense RNA. These results suggest that the antisense transcript interferes with expression of the endogenous transferrin receptor gene at the level of translation. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830420115

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

年代:1993

数据来源: WILEY

摘要:

AbstractTo examine the relationship between hepatic iron stores and plasma ferritin concentration in individuals treated with red cell transfusion and iron chelation therapy, 37 patients with sickle cell anemia and 74 patients with thalassemia major were studied. In each patient, hepatic iron stores were measured by an independently validated noninvasive magnetic method, and plasma ferritin was determined by immunoassay. The correlation between hepatic iron and plasma ferritin was significant both in patients with sickle cell anemia (R = 0.75,P<0.0001) and in those with thalassemia major (R = 0.76,P<0.0001). Regression analysis showed no significant difference between the two groups in the linear relationships between hepatic iron stores and plasma ferritin. Considering all 111 transfused patients as a group, the coefficient of correlation between hepatic iron stores and plasma ferritin was highly significant (R = 0.76,P<0.0001). Regression analysis found that variation in body iron stores, as assessed by magnetic determinations of hepatic iron, accounted for only ∼57% of the variation in plasma ferritin, suggesting that the remainder was the result of other factors, such as hemolysis, ineffective erythropoiesis, ascorbate deficiency, inflammation, and liver disease. The 95% prediction intervals for hepatic iron concentration, given the plasma ferritin, were so broad as to make a single determination of plasma ferritin an unreliable predictor of body iron stores. Variability resulting from factors other than iron status limits the clinical usefulness of the plasma ferritin concentration as a predictor of body iron stores. © 1993 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830420116

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe have studied two babies with Hb H disease from birth to about six months of age and analyzed the changes in the relative quantities of the five globin chains (α, β,Gγ,Aγ) and the four hemoglobins (Hb F, Hb A, Hb Bart's, Hb H) using different high performance liquid chromatography procedures. The types of Hb H disease were —(SEA)/‐α (3.7 kb) and —(Fil)/‐α (3.7 kb); the larger—(Fil) deletion includes the functional 2‐globin gene, explaining the higher chain level in the baby with the —(SEA)/‐α (3.7 kb) type. The functional hemoglobin level at birth (Hb A + Hb F) was 11 to 12 g/dl with 3 to 4 g/dl Hb Bart's (γ4). Only 5% of the “fast‐moving” hemoglobin was Hb H (β4). The level of Hb F at birth was low (less than 50% of the total Hb A + Hb F). After birth, the α and γ chain production decreases rapidly resulting in a severe anemia (total functional hemoglobin ∼7 g/dl) at 30 to 60 days postnatally, improving gradually to 8.5–9.5 g/dl at age of three months. The preferential formation of Hb A over Hb F at birth, and presumably prenatally, has the advantage that the level of the highly unstable Hb H is kept low; it also results in low levels of Hb F impairing the oxygen transfer capability of the

ISSN:0361-8609    

DOI:10.1002/ajh.2830420117

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

年代:1993

数据来源: WILEY

摘要:

AbstractPresent concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5‐azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating γ‐chain synthesis. © 1993 Wiley‐Li

ISSN:0361-8609    

DOI:10.1002/ajh.2830420118

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.2830420119

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe have previously obtained evidence that N‐terminal band 3 peptides inhibited deoxyhemoglobin S (deoxy S) polymerization as determined by equilibrium solubility assays. An N:1‐15AA fragment binds to the 2,3‐diphosphoglycerate (2,3‐DPG) receptor locus of deoxy S with five to seven amino acids (AA) extending internally, while ten to eight AA remained external to deoxy S and inhibited polymerization by steric hindrance. A true mirror‐image peptide, corresponding to two N:1‐8AA + lysine (K) linked by coupler, binds to the 2,3‐DPG loci of two deoxy S molecules, tethering them together to form “binary complexes” incapable of entering the polymer chains. The reduction in the concentration of deoxy S available for extended chain formation decreased polymerization. We now report time:viscosity profiles of the sol‐gel transformation of purified solutions of deoxy S with and without peptides and studies of the gel solidity at equilibrium. Samples with peptides had longer lag times than controls of similar deoxy S concentrations. The mirror‐image peptide was a more effective inhibitor than the N:1‐15AA peptide. When the mirror‐image peptide was present in peptide:hemoglobin molar ratios of 0.25‐1:1, the increases in lag time were equivalent to decreasing the deoxy S concentrations by 15–25%, comparable to projected major therapeutic effects. Gel solidity, determined by yield temperature, was less in the sample with mirror‐image peptide compared to control. These results support the proposed mechanisms of inhibition of deoxy S polymerization by band 3 p

ISSN:0361-8609    

DOI:10.1002/ajh.2830420120

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

年代:1993

数据来源: WILEY

摘要:

AbstractWhile no significant physiologic function of hemoglobin A2(Hb A2), the minor basic component of human hemoglobin, has been recognized, only its oxygen equilibria have been studied in detail. Since hemoglobin A2and its oxidative denaturation product, hemichrome A2, bind to the red cell membrane, particularly to band 3, to a greater extent than do Hb A or hemichrome A, some of the properties of Hb A2that might influence hemoglobin‐membrane association were examined. Hemoglobin A2exhibited slightly increased susceptibility to autoxidation to methemoglobin. No differences were noted between methemoglobins A and A2, including the rates of enzymatic reduction and stability of the heme‐globin linkage. Oxyhemoglobin A2had a slightly lower solubility in phosphate buffer than did hemoglobin A. While the hemichromes (prepared with phenylhydrazine) of hemoglobins A2and A had the same optical spectra, the A2hemichrome exhibited greater stability. It is suggested that the differences in products of oxidative denaturation may provide the basis for functional differences between hemoglobins A2and A. © 1993 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830420121

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

年代:1993

数据来源: WILEY