摘要:

AbstractPlasma proteins were studied in 84 patients with hemophilia A, who were receiving factor replacement therapy. Compared with age‐matched controls, 63 patients (75%) had subnormal haptoglobin and 58 (69%) had elevated alpha‐2‐macroglobulin.Causes for depressed haptoglobin were sought by correlating ABO blood types, liver function tests, factor VIII procoagulant levels, and intensity of yearly exposure to clotting factor products. Subnormal haptoglobin levels in chronically transfused patients may relate in part to hemolysis from AB incompatability. However, depressed haptoglobin levels were also found in group O hemophiliacs without other evidence of hemolysis. Most patients lacked evidence of active liver disease, making synthetic deficiency unlikely. There was close correlation between depressed haptoglobin and severity of clotting factor deficiency.The degree of alpha‐2‐macroglobulin elevation correlated with severity of procoagulant deficiency but not with intensity of clotting factor replacement therapy. Since alpha‐2‐macroglobulin plays a major role in the catabolism of fibrinogen, elevated levels may represent a compensatory increase in response to exogenous fibrinogen contained in the clotting factor concentrates. Alternatively, since alpha‐2‐macroglobulin has potent immunosuppressive properties, the elevation may represent a response to transfused alloantigens. Whatever the underlying cause, it is likely the elevations are due to endogenous production rather than to transfusions since clotting factor concentrates contain minimal amounts of alph

ISSN:0361-8609    

DOI:10.1002/ajh.2830180302

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

年代:1985

数据来源: WILEY

摘要:

AbstractThe occurrence of γ‐chain abnormal hemoglobins and of γ‐thalassemia in Chinese newborns was evaluated through analyses of the Hb F of over 1,100 babies and of the DNA from one baby and his parents. Gene mapping data identified this baby as a homozygote for ‐GγAγ‐thalassemia, which is caused by a deletion of about 5 kb due to an unequal crossing‐over between the ‐Gγ‐ and ‐Aγ‐ genes. This condition is the same as that observed in Indian and Japanese babies [2,3]. Its gene frequency among babies from the Shanghai area was 0.012. A previously unrecognizedGγ chain variant, Hb F‐Shanghai or α2Gγ266(E10)Lys→Arg, was observed in one newborn. This variant was not detected by conventional techniques but only by high performance liquid chromatography, as theGγ66 Lys andGγ66 Arg chains had slightly different chromatographic mobilities. Lys at position γ66 participates in contacts with the heme group, and its substitution by another amino acid residue might interfere with physiochemical and/or functional properties. No other γ‐chain variants have been detected except the well‐know

ISSN:0361-8609    

DOI:10.1002/ajh.2830180303

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

年代:1985

数据来源: WILEY

摘要:

AbstractSeven nonsplenectomized patients with blastic CGL have received high dose BCNU chemotherapy followed by cryopreserved peripheral blood stem cells (PBSC). The PBSC obtained at diagnosis were stored in the vapor phase of liquid nitrogen in 10% dimethyl sulfoxide for 11–46 months prior to use. Patients received 2.9 × 108(1.9–7.8) thawed washed mononuclear cells/kg over 30 minutes with minimal morbidity. One patient was not rendered pancytopenic and died with blastic leukemia at 4 months. One patient, previously treated with daily busulfan, died of progressive hepatic failure 2 months after high dose BCNU. Restoration of the chronic phase of CGL was observed in the remaining five patients. Peripheral blood counts returned to normal ranges after a median of 19 days. Median survival for all patients is 11 months. Cytogenetic studies revealed elimination of acquired aneuploid cell lines in four of seven patients with persistence of Ph1. We conclude that: 1) frozen PBSC retain their viability for up to 4 years after cryopreservation and 2) the use of autologous PBSC following ablative chemotherapy may be associated with both symptomatic and karyotypic improvement in patients with blastic

ISSN:0361-8609    

DOI:10.1002/ajh.2830180304

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

年代:1985

数据来源: WILEY

摘要:

AbstractTwo patients with aplastic anemia evolving from cellular bone marrows with severely diminished megakaryocytes are reported. During this evolution a plasma inhibitor of in vitro granulocyte‐macrophage colony formation was demonstrated associated with non‐A, non‐B hepatitis in one patient. The second patient had abnormal liver function that corrected after the delivery of a normal newborn but there was persistence of pancytopenia without evidence of a plasma inhi

ISSN:0361-8609    

DOI:10.1002/ajh.2830180305

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

年代:1985

数据来源: WILEY

摘要:

AbstractNeutrophils from a patient with lactoferrin deficiency were examined and the quantity and subcellular localization of protein markers were determined on Percoll density gradients. Distribution of azurophilic and specific granule markers was abnormal in that azurophilic granules were lighter than normal and appeared in the fraction of the gradient where normally the specific granules sediment. The specific granule membrane markers, cytochrome b‐235and its associated flavoprotein, were abnormally distributed in the γ fraction, the site of the plasma membrane marker alkaline phosphatase. Thus, the b‐cytochrome‐flavoprotein complex had either been incorporated into the plasma membrane or was still present in the membranes of granules that were abnormally light and cosedimented with the plasma membranes. This is of particular interest in regard to the patient's respiratory burst oxidase function, since the b‐cytochrome/flavoprotein complex normally translocates from the specific granules to the plasma membrane to constitute the active respiratory burst oxidase. The functional consequences of this abnormal distribution are discussed, as is the importance of characterizing both intragranular enzymatic markers and granule membrane proteins to define granular d

ISSN:0361-8609    

DOI:10.1002/ajh.2830180306

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

年代:1985

数据来源: WILEY

摘要:

AbstractSplenic atrophy or evidence of hyposplenism occurs in as many as one third of all patients with S‐C hemoglobinopathy. Yet there are few reports in the literature of clinically apparent splenic infarction in this disease. We describe four instances of acute splenic infarction in three patients with hemoglobin S‐C disease which illustrate a wide spectrum of clinical manifestations and severity. Of particular interest were the observations of coincident occurrences of splenic sequestration and functional hyposplenism with splenic infarction, suggesting a close pathophysiological relationship among these syndro

ISSN:0361-8609    

DOI:10.1002/ajh.2830180307

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

年代:1985

数据来源: WILEY

摘要:

AbstractLymphocytes incubated under high oxygen tensions have impaired lymphoblastic transformation to nonspecific mitogens. Since carbohydrate metabolism may be essential for an optimal proliferation of these cells following an antigenic stimulus, we have characterized the effect of hyperoxia on the glucose metabolism of human lymphocytes in vitro. The mean rates of glucose utilization, Krebs cycle activity, and hexose monophosphate shunt activity were determined for unstimulated and phyto‐hemagglutinin (PHA)‐stimulated cultures incubated for 3 days. In unstimulated cultures, hyperoxia stimulated glucose utilization and markedly impaired Krebs cycle activity but did not alter HMPS activity. These observations suggest that hyperoxia impairs the mitochrondrial activity of lymphocytes and that increased glycolysis compensates for the loss of cellular energy normally produced by this organelle. Under high oxygen tension PHA‐stimulated cultures failed to show the burst in HMPS activity and increased Krebs cycle activity characteristic of cultures incubated under physiological oxygen tensions and consumed less glucose. Our results indicate that hyperoxia alters the glucose metabolism of lymphocytes. This metabolic alteration may be related to the impaired function of the cells under hyperoxic condi

ISSN:0361-8609    

DOI:10.1002/ajh.2830180308

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

年代:1985

数据来源: WILEY

摘要:

Abstract111Indium—transferrin (111In) and99mTechnetium‐colloids (99mTc) bone marrow imaging of 55 myelofibrosis (MF) cases has been compared with clinical, histological, and iron‐kinetics data. The best correlations are seen between the splenic uptake of111In with the spleen/sacrum ratio of59Fe at the first hour (r = 0.69, P<0.001) and also with the splenic erythropoiesis histologically assessed in ten splenectomized patients ( r = 0.75, P<0.01). Moreover, sacrum uptake of111In, when compared with sacrum uptake of59Fe (r = 0.51, P<0.001) and with hematopoietic cellularity of the bone marrow (r = 0.57, P<0.001) reflects faithfully the hematopoietic cell content of the marrow.Thus,111In bone marrow imaging provides a noninvasive and useful tool for the diagnosis of myeloid metaplasia in MF. Ferrokinetic studies still appreciate with better insight the amount of ineffective erythropoiesis or hemolysis and remains therefore of great value when splenectomy is disc

ISSN:0361-8609    

DOI:10.1002/ajh.2830180309

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

年代:1985

数据来源: WILEY

摘要:

Abstract5‐Azacytidine (azaC) has previously been shown to raise Hb F levels in the repeatedly phlebotomized baboon (PCV: around 20%). The administration of tetrahydrouridine (THU), an inhibitor of the enzymatic conversion of azaC to 5‐azauridine, made it possible to reduce the amount of azaC and also of 2‐deoxy‐5‐azacytidine (d‐azaC) by more than 90% and still achieve maximal Hb F elevations. However, the granulocytopenia, usually occurring after 5‐azaC, was not altered by the lowering of the dosages in the presence of THU. Thus, the granulocytopenia is not due to 5‐azauridine or other catabolic products resulting from deamination. It is also unlikely that it is caused by a direct influence of azaC on RNA since d‐azaC also causes granulocytopenia. The persistence of reticulocytosis throughout the treatment with azaC or d‐azaC makes it appear likely that the observed increase in Hb F levels to more than 60% of total hemoglobin is not due to a cytotoxic effect on erythropoiesis resulting in a shift of cell populations toward greater immaturity, but to a direct influence of the drug on the regulation of γ glo

ISSN:0361-8609    

DOI:10.1002/ajh.2830180310

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

年代:1985

数据来源: WILEY

摘要:

AbstractRestriction enzyme analysis of the α and ζ globin genes was carried out in four cases of Hb Bart's hydrops fetalis, in three patients with Hb H disease without Hb CoSp, in three patients with Hb H disease with Hb CoSp, in 47 individuals with α thalassemia trait, and in 47 normal individuals. All four cases of Hb Bart's hydrops fetalis resulted from deletions of α1 and α2 globin genes which did not extend to the ψζ1 and ζ2 globin genes. The same type of deletion was observed in α thal1carriers, but two newborns (one Malay and one of Chinese extraction) had a nondeletion type of α thal1which was confirmed by quantitative αglobin gene analysis. In addition, two other newborns diagnosed as α thal1trait carriers (one Malay, one Chinese) were shown to have a deletion of both α globin genes by quantitative α globin gene analysis, but further testing with ζ globin gene probe failed to reveal an abnormal fragment length characteristic of an α globin gene deletion. We believe that this last condition is due to a large deletion which includes all α globin genes and all ζ globin genes on the same chromosome. On another front, Bgl II restriction analysis of all four Hb Bart's hydrops fetalis cases and the α thal1trait carriers showed a 10.5‐kb Bgl II restriction fragment, in the hydrops fetalis as a single band, while in the carriers this 10.5‐kb fragment was accompanied by the usual normal 12.5‐kb and 11.3‐kb fragments. We report that this 10.5‐kb fragment, previously thought to be specific for the Southeast Asian α thal1gene deletion, is also common in normal individuals. Nevertheless, digestion with other enzymes can clearly differentiate the α thal1and normal genotypes. We distinguish the findings in the α thalassemias from the extensive DNA polymorphism in the reg

ISSN:0361-8609    

DOI:10.1002/ajh.2830180311

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

年代:1985

数据来源: WILEY