摘要:

AbstractWashed human platelets were found to enhance phytohemagglutinin (PHA)‐stimulated tissue factor (TF) synthesis when incubated with autologous mononuclear cell cultures. Furthermore, platelets increased TF synthesis even when no other stimulator was present during the incubation. Experiments utilizing similar cultures derived from blood of patients with Glanzmann's disease, von Willebrand's disease, and platelet storage pool disease indicated that platelets with each of these genetic defects possessed the capacity to enhance the synthesis of this initiator of coagulation by unstimulated cells as did normal platelets.The degree of platelet enhancement varied between individuals, but for any given donor, the extent of the effect depended on the concentration of platelets used. The effect was demonstrable at platelet/monocyte ratios ranging from a low of approximately 15 to the highest ratio used, about 300. For comparison the ratio of these two cellular elements in normal human blood is estimated to be approximately 1,000. These findings may reflect a relationship between these two cell types that can occur in viv

ISSN:0361-8609    

DOI:10.1002/ajh.2830190402

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

年代:1985

数据来源: WILEY

摘要:

AbstractWhether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1mice were studied at ages 3, 13, or 27‐28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43 % vs 49% (p<0.001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20‐25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with59Fe.59Fe was given following the second bleed, and 1 day later RBC59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal‐appearing hair; the latter was subdivided into those weighing less (25‐26 g) or more (30‐34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild “dilutional” anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine

ISSN:0361-8609    

DOI:10.1002/ajh.2830190403

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

年代:1985

数据来源: WILEY

摘要:

AbstractPrevious studies from our laboratory have demonstrated that the aggregation response of platelets inhibited by agents blocking cyclooxygenase activity could be restored to a normal state of sensitivity by prior stimulation of α‐adrenergic receptors. Since cyclooxygenase activity and thromboxane synthesis are not absolutely required for irreversible platelet aggregation, it is important to define precisely what role this pathway serves in platelet physiology. The present study has evaluated the influence of agents that selectively block arachidonic acid conversion at different steps of synthesis. Inhibition of peroxidase, cyclooxygenase, lipoxygenase, and thromboxane synthetase blocked the second wave response of platelets to several agonists, but did not cause dissociation of aggregates preformed by prior exposure to arachidonate (AA) or adenosine diphosphate. Phospholipase (A2/C) inhibitors, similar to prostaglandin inhibitors, blocked the second wave response of platelets to the action of agonists and, in addition, caused dissociation of aggregates induced by aggregating agents. Results of our study demonstrate that when single agonists are tested at threshold concentrations, products of arachidonate metabolism may play a role in the activation process. However, continued generation of these metabolites does not appear to be essential for the maintenance of irreversible aggregation. When a combination of agents or high concentration of physiological agonists are used, both activation and irreversible aggregation can be secured independent of prostaglandin synthesis or the release reacti

ISSN:0361-8609    

DOI:10.1002/ajh.2830190404

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

年代:1985

数据来源: WILEY

摘要:

AbstractHighGγ values (78% and higher) have been observed in about 3% of Chinese newborns from the Shanghai area. We describe here two arrangements different from the normal ‐Gγ‐Aγ‐δ‐β arrangement which have been characterized in the DNA from three of these babies. One baby was heterozygous for a chromosome with two linkedGγ globin genes (‐Gγ‐Gγ‐δ‐β), which has also been observed in Black newborns [Powers et al, Nucleic Acids Res 12: 7023, 1984], while the two other babies were heterozygous for a chromosome with triplicated γ globin genes, presumably of the ‐Gγ‐AγGγ‐Aγ‐δ‐β arrangement. A similar triplication has been observed in natives of the New Hebrides [Tre

ISSN:0361-8609    

DOI:10.1002/ajh.2830190405

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

年代:1985

数据来源: WILEY

摘要:

AbstractThe incidence, severity, and pathogenic mechanism of heparin‐associated thrombocytopenia with both bovine and porcine heparin administration were studied in forty normal males randomized to one of four treatment groups: beef lung heparin #1, beef lung heparin #2, porcine gut heparin, and saline control. All of the subjects receiving heparin developed a reversible increase in serum transaminases (SGOT, SGPT). However, other measurements of liver function were normal. Thirty‐three percent of these heparinized normals had decreased platelet counts. The incidence of platelet count decrease was similar for both bovine and porcine heparins, but 4 of the 20 normals receiving bovine heparin had platelet counts less than 150,000/μl. Immune pathogenesis was investigated by analyzing plasma from the volunteers for both platelet antibody and immune complexes. None of the men had increased plateletassociated IgG. Among the ten subjects with decreased platelet counts, IgG immune complexes were detected in three and C1qin seven. The heparin‐associated thrombo‐cytopenia appears not to be mediated by a platelet antibody. More probably it reflects a direct effect of the heparin on p

ISSN:0361-8609    

DOI:10.1002/ajh.2830190406

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

年代:1985

数据来源: WILEY

摘要:

AbstractUtilizing chromogenic synthetic substrate‐based methods, determination of the plasma concentration of plasminogen, α‐antiplasmin, α‐macroglobulin, and Bβ15‐42‐related peptides were made at the time of birth in both newborns and mothers. Plasminogen levels were increased in the maternal group (150 ± 26%), and markedly decreased in the newborn group (67 ± 14%). The major inhibitors of fibrinolysis, α2‐antiplasmin and α2‐macroglobulin, were within normal range in both groups. Determination of Bβ15‐42‐related peptide showed markedly increased levels in the maternal group above control values (115 ± 102, normal 29 ± 12); the newborn group showed values only mildly elevated above control values (39 ± 21). The results demonstrate increased fibrinolytic activity in both groups, though the degree of activation is significantly higher in the maternal group, as reflected by the higher levels of Bβ15‐42‐related peptides. Fibrinopeptide A levels confirm an activation of coagulation in both maternal and newborn groups (22 ± 4 ng/ml and 138 ± 22 ng/ml, respectively) with a significantly increased l

ISSN:0361-8609    

DOI:10.1002/ajh.2830190407

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

年代:1985

数据来源: WILEY

摘要:

AbstractDiscrepancies in correlations between fibrinolytic activity and metastatic potential of malignant cells has resulted in speculation on the putative role of plasminogen activators (PA) in cancer. In this report we have compared lymphocyte PA from 40 patients with chronic lymphocytic leukemia (CLL) to normal human B‐ and T‐ lymphocytes. Lymphocytes were isolated from peripheral blood by Ficoll‐Hypaque centrifugation. The B‐ and T‐cells were further separated on nylon wool columns. Cell PA activity and cell membrane PA were determined using3H‐fibrin‐coated plates with added human plasminogen. Lymphocytes did not lyse3H‐fibrin in the absence of plasminogen. Plasminogen‐dependent fibrinolytic activities of normal B‐ and T‐ lymphocytes were comparable. The addition of protease inhibitors with trypsin or plasmin specificity to lymphocytes significantly inhibited normal PA, thus substantiating the serine protease spectrum of lymphocyte PA. Examination of lymphocytes from>95% of patients with chronic lymphocytic leukemia revealed a marked decrease in lymphocyte and cell membrane PA as compared to normals. No correlation between Stage of CLL and lymphocyte PA was observed. Likewise, an inhibitor of PA in CLL lymphocytes was not detected. The function of PA in normal B‐ lymphocyte physiology and the potential pathogenetic role of diminished PA in CLL lymphocyte

ISSN:0361-8609    

DOI:10.1002/ajh.2830190408

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

年代:1985

数据来源: WILEY

摘要:

AbstractDespite markedly prolonged activated partial thromboplastin times (APTT) patients with Fletcher factor (prekallikrein) deficiency do not clinically bleed. However, there is one reported case of myocardial infarction associated with prekallikrein deficiency. These clinical observations suggest that the contact mechanism has a minor role in normal in vivo hemostatic function. We report a further two cases of prekallikrein deficiency in Caucasian siblings. The propositus presented with multipie cerebral thrombosis. Cautious anticoagulation resulted in massive cerebral hemorrhage and death of this patient. The sibling was investigated in an attempt to establish a possible defective fibrinolytic pathway in vivo. New sensitive tests for fibrinolysis were used. These included radioimmunoassay of fibrin degradation product “D,” Bβ 15‐42, and in vitro125I‐labelled fibrin lysis assays. The plasma half‐life of prekallikrein in this patient was calculated to be 58 hr. Family studies of heterozygotes were also performed. Prekallikrein deficiency is found not to be important in normal in vivo fibrinolysis, which possibly operates via tissue or vessel wall fibrinolytic activat

ISSN:0361-8609    

DOI:10.1002/ajh.2830190409

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

年代:1985

数据来源: WILEY

摘要:

AbstractA 57‐year‐old married Chinese male without a family history of bleeding disorder was presented with severe hemorrhagic tendency and was subsequently found to be suffering from an acquired inhibitor against coagulation factor V. The prolonged prothrombin time and activated partial thromboplastin time could not be corrected by the addition of normal plasma. Subnormal value of factor V level was noted accompanied with an abnormal platelet factor III availability test. With specific antisera and staphylococcal protein A, the inhibitor was characterized as an IgG(lambda) antibody. The hemorrhagic tendency and abnormal laboratory data were corrected after treating the patient with platelet concentrate transfusion and cyclophospham

ISSN:0361-8609    

DOI:10.1002/ajh.2830190410

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

年代:1985

数据来源: WILEY

摘要:

AbstractA severe and persistent pancytopenia occurred in a 42‐year‐old woman with a non Hodgkin's lymphoma following a 10‐day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU‐E, BFU‐E, CFU‐GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E‐rosette +, Tγ+, OKT8 + (suppressor/cytotoxic) T‐and/or Leu 7 + natural killer (NK) lymphocytes and 50% were IgM Kappa, B1 +, B‐lymphocytes. In vitro erythroid culture studies were consistent with T‐cell‐mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10‐day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T‐ and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating

ISSN:0361-8609    

DOI:10.1002/ajh.2830190411

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

年代:1985

数据来源: WILEY