ISSN:0361-8609    

DOI:10.1002/ajh.2830010102

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

年代:1976

数据来源: WILEY

摘要:

AbstractNormal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes. When the percent of type III was low the net amount was increased as compared with normal. Hemolysates of non‐porphyric, reticulocyte‐rich red cells (hemolytic or posthemorrhagic anemia) formed only minute amounts of type I porphyrin but at the same time no more, or even less type III than the porphyric hemolysates, although representing red cells of greater reticulocyte content. No evidence of deficient heme synthesis was observed in porphyric hemolysates incubated with [14C] ‐porphobilinogen or59Fe. Other studies of porphyric hemolysates incubated with and without added mouse spleen synthetase failed to reveal evidence of an absolute UPG‐III cosynthetase (Co‐S) deficiency. The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA‐S or UPG‐S activity rather than a decrease of Co‐S. Possible mutations which might be responsible for this increase

ISSN:0361-8609    

DOI:10.1002/ajh.2830010103

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

年代:1976

数据来源: WILEY

摘要:

Abstract25‐yr old female identical twins of Italian‐American origin concordant for sickle β‐thalassemia were studied to explain their clinical differences. One of them has been severely affected from childhood with one aplastic crisis, an earlier onset of vaso‐occlusive crises, and recent cardiac decompensation; the other twin shows no cardiac decompensation.Similar are their degree of anemia, RBC indices, blood volumes, absence of splenic sequestration, depression of pO2, elevation of p50 and 2,3‐DPG, hemoglobin composition, and peripheral blood globin‐synthetic rates.Regarding differences, the more severely affected has a shorter51Cr RBC life span, a greater menstrual blood loss, and is more overweight, whereas the less severely affected has functional asplenia by99mTc scanning and a larger proportion of RBC with decreased cellular deformability.We conclude that in sickle β‐thalassemia: (1) genotype alone does not determine the clinical course; (2) significant differences in clinical course can occur with almost identical hemoglobin composition and globin synthetic rates; (3) cellular deformability changes do not correlate exactly with clinical course; and (4) functional asplenia and leanness may

ISSN:0361-8609    

DOI:10.1002/ajh.2830010104

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

年代:1976

数据来源: WILEY

摘要:

AbstractThe diseases commonly confused with sickle cell anemia include sickle cellβ‐thalassemia in which synthesis of βA‐chains are completely suppressed (HbS‐βO‐thalassemia). We obtained hematologic measurements and studied globin biosynthesis in five patients with this disorder and compared the results with those obtained in five patients with “mild” sickle cell anemia and seven individuals with sickle cell‐β‐thalassemia having hemoglobin A levels of 20–30% (HbS‐β+‐thalassemia). A distinction between HbS‐βO‐thalassemia and sickle cell anemia was not always possible on clinical, hematologic, or electrophoretic grounds. Thalassemia heterozygotes had hypochromia and microcytosis, not generally a feature of sickle cell anemia, although overlap of values did exist. The ratio of β to non‐β, or β to βS‐chains in sickle cell anemia approximated unity, whereas patients with HbS‐βO‐thalassemia had a deficit of β‐chain production relative to that of the β‐chain. The differentiation of HbS‐βO‐thalassemia and sickle cell anemia can be best made on the basis of family or biosynthetic study. We estimated the regional prevalence of Hb

ISSN:0361-8609    

DOI:10.1002/ajh.2830010105

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

年代:1976

数据来源: WILEY

摘要:

AbstractWe have studied the effects of zinc on the51Cr survival of red blood cells (RBC) from patients with homozygous sickle cell anemia (SCA) using an animal model in which the RBC were transfused into specially prepared rats. The slope (λs) of a standard51Cr RBC survival curve was used as a measure of the rate of RBC sequestration.The effects of intravenous zinc were of considerable therapeutic interest from the standpoint of setting guidelines for effective blood levels of zinc in patients. SCA RBC were transfused into rats whose plasma zinc levels had been raised 3–6 times above normal (300–600 μg/100 ml) by prior iv injection of zinc acetate; in three experiments the mean λss in zinc‐treated animals breathing 15–16% oxygen was significantly lower (meaning lessened sequestration and greater survival) than saline‐treated controls. A possible explanation for the requirement to lower ambient oxygen tension in order to see this zinc effect is discussed.We have further observed an increased mean λsfor RBC from 10 SCA patients compared to 4 normal controls (0.134 vs 0.030; t = 2.8, p<0.01). The λsvalues are quite patient specific (4 patients studied; F = 18.2, p = 0.002). In vitro pretransfusion treatment of SCA RBC with 1.5 mM zinc resulted in a significant increase in hemoglobin oxygen affinity and a marked reduction in λs(0.073 vs 0.120; t = 4.5, p<0.01). The mean λswas not affected by in vitro 0.3 mM zinc treatment; this level did not change hemoglobin oxygen affinity.We conclude that systemic zinc therapy in the animal model described, at plasma levels only slightly higher than those presently obtained in patients, prolongs SCA RBC survival. This animal model is a sensitive measure of the sicklability of SCA RBC and is useful in the testing of in vitro and in vivo ant

ISSN:0361-8609    

DOI:10.1002/ajh.2830010106

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

年代:1976

数据来源: WILEY

摘要:

AbstractWashed human platelets take up arachidonic acid from plasma and incorporate the fatty acid into the major classes of complex lipids. Thrombin impairs net incorporation. It activates endogenous phospholipases which liberate arachidonic acid from phospholipids. As a consequence of thrombin induced aggregation platelets release arachidonic acid intermediates formed by the action of platelet fatty acid cyclooxygenase and by platelet fatty acid lipoxygenase. Cyclooxygenase, but not lipoxygenase, is inhibited by aspirin and indomethicin. Analysis of the pathways of arachidonic acid metabolism may furnish new insight into platelet function and into disorders of primary hemostasis.

ISSN:0361-8609    

DOI:10.1002/ajh.2830010107

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

年代:1976

数据来源: WILEY

摘要:

AbstractUsing monospecific rabbit antihuman factor VIII antiserum, we have examined the amounts of factor VIII‐related antigen and compared these to the levels of factor VIII procoagulant activity in normal subjects and patients with von Willebrand's disease. We have observed that even without transfusion all nine probands with von Willebrand's disease and 20 of their 34 relatives possessed a significantly elevated factor VIII activity/factor VIII‐related antigen ratio when compared to that of 55 normal subjects. It is suggested that an elevated factor VIII activity/factor VIII‐related antigen ratio may be used for detection of the carriers of von Willebrand's di

ISSN:0361-8609    

DOI:10.1002/ajh.2830010108

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

年代:1976

数据来源: WILEY

摘要:

AbstractBone marrow cell responses to injections of nitrogen mustard, oncovin, procarbazine, hydrocortisone, and a regimen of all four drugs (MOPH) were evaluated in CRF1 and C57B 1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFU) after treatment. The study was done to determine whether the combined regimen, which is widely used clinically in treatment of disseminated Hodgkin's disease, is more or less detrimental to the hemopoietic system than the same drugs used as single agents. Nitrogen mustard and procarbazine used clinically as single drugs are given in three and two times, respectively, greater doses than in the combined regimen. Hydrocortisone, given singly, was least toxic of the drugs, reducing the CFU/femur to 63% and 71% of control values. MOPH appeared slightly more toxic than hydrocortisone, resulting in 41% and 52% of the CFU/femur surviving, and was about equally as toxic as oncovin alone. Nitrogen mustard and procarbazine, administered as single drugs in high doses, were highly suppressive, resulting in only 10–19% survival of CFU/femur, whereas, reduced doses of the two drugs as used in the MOPH regimen spared 30–45% of the CFU/femur. Survival of CFU after MOPH treatment was three to four times greater than after high doses of nitrogen mustard or procarbazine alone. The component drugs of the combined regimen did not act on separate populations of stem cells to produce an additive effect but appeared to inactivate the same population of ce

ISSN:0361-8609    

DOI:10.1002/ajh.2830010109

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

年代:1976

数据来源: WILEY

摘要:

AbstractPhototherapy with blue fluorescent light is widely employed for treatment of neonatal hyperbilirubinemia. Functional, biochemical, and morphologic changes produced by blue fluorescent light in human platelets were identified and characterized. Platelet‐rich plasma was exposed for up to 170 min to amounts of light equivalent to that used in phototherapy of neonatal hyperbilirubinemia. Within 110 min of light exposure, platelets were essentially no longer aggregable by ADP and connective tissue suspension and were depleted of ADP, ATP, and glycogen. Electron photomicrographs revealed these platelets to be swollen, depleted of glycogen granules and organelles, and to have ill‐defined membranes. Platelet injury could be accelerated by adding a photosensitizing agent, hematoporphyrin, to platelet samples before exposure. In contrast, control platelets kept in the dark for 170 min or nonirradiated platelets resuspended in irradiated plasma maintained their integrity. The results indicate that platelets are damaged in vitro when exposed to amounts of blue light used in photother

ISSN:0361-8609    

DOI:10.1002/ajh.2830010110

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

年代:1976

数据来源: WILEY

摘要:

AbstractCyclophosphamide, an immunosuppressive agent, was administered as an additional mode of therapy to 30 patients with idiopathic thrombocytopenic purpura (ITP) refractory to conventional management. Of 22 previously tested by splenectomy an excellent response was achieved in 12, who remained in complete hematologic remission for 14–96 months after therapy was discontinued; a fair response in 3, with definite increase in platelets, but not to normal levels; and a poor response in 7 who failed to improve. Of 8 nonsplenectomized patients who failed to respond to steroids or maintain a response after steroids were discontinued, 4 were considered excellent, 1 required continued therapy to remain in remission (good response), 2 were fair, and 1 was poor. Remission was observed in 2–10 weeks in both groups and appeared to be related to duration of disease; presence of disease for less than 1 year was associated with a much better response to treatment (11 of 15) when compared with disorders lasting over 2 years (6 of 15). Cyclophosphamide therapy offers additional means of treating patients with ITP who fail to respond to conventional therapy and may serve as an alternative to splenectomy when surgery is contraindica

ISSN:0361-8609    

DOI:10.1002/ajh.2830010111

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

年代:1976

数据来源: WILEY