摘要:

AbstractThe‐117(G→A)Aγ hereditary persistence of fetal hemoglobin (Greek HPFH) and β039‐thal mutations are rather frequent in Sardinia so that their interaction is to be expected. Characterization of eight compound heterozygotes for these defects indicated that HPFH was linked to haplotype VII and β039‐thal to haplotype II. Haplotype II β039‐thal chromosome carries theAγTgene which is a useful marker of γ‐gene expression. Since the Hb F level in these compound heterozygotes was significantly higher than in 46 −117 HPFH carriers, theAγt, andGγ globin level was determined.AγTwas underexpressed whileGγ was significantly increased, which suggests that in −117Aγ HPFH/β039‐thal healthy subjects the increase in Hb F production is determined only by the −117 mutatedAγ gene and the adjacen

ISSN:0361-8609    

DOI:10.1002/ajh.2830490402

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

年代:1995

数据来源: WILEY

摘要:

AbstractGamma inferferon (γIFN), alpha tumor necrosis factor (αTNF), and interleukin 6 (IL‐60) are cytomines produced by a wide variety of cells, incuding T lymphocys and NK cells. These cytokines affect B‐cell proliferation and differentiation into immunoglobulin seceting cells. In addition, γIFN and αTNF also enhance the function of macrophagesm, upregulating the expresson of their igG receptors. Abonormalities in the production of these cytokines may be involved in the clinical course of autoimmune thrombocytopenic purpura (ATP). This paper describes the production of these cytokines in PHA‐stimulated peripheral blood CCD2+ cells from ATP patients.Both γIFN and αTNF were significantly increased in PHA‐stimulated CD2+ cells from therapy‐dependent ATP patients (platelet counts50,000/μl without need treatment) (P<0.05). No significant differences were found in γlFN production by PHA‐stimulated CD2+ cells between therapy‐dependent ATP patients and healthy controls (P<0.05). However, the production of αTNF by PHA‐stimulated CD2+ cells from therapy‐dependent ATP patients was significantly higher compared to that found in healthy controls (P<0.05). There were no significant differences in IL‐6 production by PHA‐stimulated CD2+ cells from ATP patients and healthy controls (P<0.05).These findings demonstrate abnormal γlFN and αTNF secretion in purified CD2 cells from ATP patients. The clinical severity of the disease is associated with the altered secretion of these lymphokines by

ISSN:0361-8609    

DOI:10.1002/ajh.2830490403

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe aim of this study was to investigate whether abnormalities in the fibrinolytic system and in the naturally occurring anticoagulant proteins could contribute to the thrombotic risk in essential thrombocythemia. Euglobulin lysis time, fibrin plate lysis area, tissue plasminogen activator antigen, and activity and plasminogen activator inhibitor antigen were measured before and after venous occlusion in a group of 16 patients with essential thrombocythemia and in 16 healthy age and sex matched controls. In addition, resting levels of antithrombin III, D‐dimer, prothrombin fragment 1 + 2, and protein C and S were assessed. The results were related to the presence or absence of a thrombotic history.The results demonstrated that the patients had a significantly elevated fibrin plate lysis area and significantly decreased plasminogen activator antigen, both at baseline and after venous occlusion. They also had significantly decreased levels of plasma protein C and total protein S. There was a modest, non‐significant elevation in the plasma concentration of D‐Dimer and F 1 + 2. Those patients with a history of thrombosis had significantly lower protein C levels compared with individuals without a thrombotic history.We conclude that patients with essential thrombocythemia have evidence of activated fibrinolysis in the resting state and after stimulation. This, and the decreased levels of protein C and total protein S, may be secondary to chronic clinically occult thrombosis occurring in myeloproliferative disorders. © 1995 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830490404

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

年代:1995

数据来源: WILEY

摘要:

AbstractAnabolic‐androgenic steroid abuse has recently been linked with acute vascular events in athletes. To date, the relationship between steroid abuse and the potential for cardiovascular disease has been considered almost exclusively in terms of lipid metabolism. However, recent reports of thrombosis in androgen abusing athletes with no evidence of atherosclerosis suggests the hypothesis that thrombosis risk in such athletes could be mediated through androgen induced abnormalities of coagulation.To determine if anabolic‐androgenic steroid abuse in weight lifters is associated with an activation of the hemostatic system we studied forty‐nine weight lifters recruited through advertisements. History of androgen use or abstinence was confirmed via urine assays. Plasma was assayed for clotting and fibrinolytic activity by measuring thrombin/ antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and D‐dimers (D‐di); markers of the endothelial based fibrinolytic components were assayed by measuring tissue plasminogen activator antigen (t‐PA Ag) and its inhibitor (PAI‐1); finally, the activity of antithrombin III, protein C, and protein S were measured.Abnormally high concentrations of TAT complexes were noted in 16% of our confirmed steroid using weight lifters compared to 6% of our confirmed nonusers (P= .01). Steroid users also demonstrated abnormally high concentrations of F1 + 2 and D‐dimers when compared to nonusers (44 vs. 24%,P<.001, and 9 vs. 0%, respectively). Non‐steriod users were more likely to have elevated levels of t‐PA Ag and PAI‐1 than our steroid using weight lifters (bothP<.001). The activities of antithrombin III and protein S were more likely to be higher in users compared to nonusers (22 vs. 6%,P= .005; 19 vs. 0%, respectively).Some anabolic‐androgenic steroid using weight lifters have an accelerated activation of their hemostatic system as evidenced by increased generation of both thrombin and plasmin. These changes could reflect a thrombotic diathesis that may contribute to vascular occlusion reported in young athletes using these drugs. The predictive value of these coagulation abnormalities in terms of risk of thrombosis to individual steroid using weight lifters or the population as a whole remains to be studied.

ISSN:0361-8609    

DOI:10.1002/ajh.2830490405

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

年代:1995

数据来源: WILEY

摘要:

AbstractPlasma and platelet von Willebrand factor (vWF) measurements, multimeric pattern and subunit composition of plasma vWF were obtained in 29 consecutive patients with chronic myeloproliferative syndromes. In the 8 patients with chronic myelogenous leukemia (CML), plasma vWF was significantly higher than in the 11 patients with essential thrombocythemia (ET) and in the 10 patients with polycythemia Vera (PV). The RiCof/ vWF:Ag ratio was low in all these groups of patients (mean 0.64 = 0.1, 0.66 = 0.2; and 0.61 = 0.2; normal 0.97 = 0.2). Bleeding time was prolonged (>7.5 min) in 1/8 CML patients, 1/10 with PV, and 3/11 with ET. Plasma vWF multimers showed a minor loss of the largest multimers in 3/8 patients with CML, 4/10 with PV, and a more severe reduction in 9/11 ET patients. The latter pattern correlated with an abnormal proteolysis of vWF, expressed by a major increase of the 140‐Kd fragment and decrease of the intact 225‐Kd subunit in ET patients, whereas the 176‐Kd fragment was significantly increased in all the subgroups of patients. Platelet vWF was significantly higher in CML patients in comparison to ET and normal controls. However, minor losses of the larger multimers were evident in all the subsets of patients. In ET patients also the intermediate forms were lacking in platelets, accompanied by a significant decrease of platelet RiCof. This abnormality was significantly correlated with the occurrence of bleeding symptoms in PV and ET patients (P = 0.007; Fisher's exact test). In conclusion, plasma and platelet vWF abnormalities are common findings in myeloproliferative syndromes and are more severe in ET. The more pronounced platelet vWF abnormalities in ET may reflect the more frequent bleeding symptoms observed in this disorder. © 1995 wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830490406

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

年代:1995

数据来源: WILEY

摘要:

AbstractA Spanish family with α‐thalassemia‐1 (α‐Thal‐1), deletion (—MA), is described. In addition to the loss of 22 kb of DNA with a deletion of the α1, α2, α1, α2, and Ψζ1genes, a triplication of the ζ gene cluster in “cis” is produced. The structure of this triplication is formed by the Ψα1, gene, the interzeta region, and, possibly, the insertion of the Ψα2fragme

ISSN:0361-8609    

DOI:10.1002/ajh.2830490407

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

年代:1995

数据来源: WILEY

摘要:

AbstractDiscordant morphology between lymph node or extra‐nodal site and bone marrow (BM) involvement by non‐Hodgkin's malignant lymphoma (NHL) is a common occurrence, causing diagnostic difficulties. Additional diagnostic problems are posed by lymphoid aggregates commonly found in the BM of elderly patients, the age group with the highest incidence of lymphoma. Morphologic features are used to distinguish between benign and malignant lesions but no feature is diagnostic and exceptions are numerous. Immu‐nophenotyping is helpful for detecting B cell monoclonality, but it cannot detect T cell monoclonality. Unique B and T cell gene rearrangement patterns, the molecular “signature” of the lymphoma, can be used to detect monoclonal lymphoid populations. Finding the same rearrangement pattern in the BM as in the primary mass is proof of BM involvement by the same clone of malignant cells. We used B/T and Bcl‐2 gene rearrangements to help diagnose cases with discordant morphology between primary site and BM. One hundred and seventy‐five specimens, obtained from patients undergoing staging or restaging for NHL, were analyzed for B/T cell and Bcl‐2 gene rearrangements by multiple restriction endonuclease digestion and Southern hybridization with 32P labeled JH, JK, CTα, and Bcl‐2 probes. Forty‐two specimens (24%) from 24 patients showed discordant morphology: of 13 specimens with atypical lymphoid aggregates, only one had B cell gene rearrangement; of 15 specimens with morphologically benign lymphoid aggregates, one demonstrated B cell gene rearrangement; and of 14 specimens positive for NHL with different morphology than the lymph node, 13 were positive for B cell gene rearrangements. Molecular analysis can aid in the diagnosis of NHL, can establish a “baseline” for detection of recurrence, and is useful in monitoring therapy. These data suggest that it is also a tool for the pathologist in cases of discordant morphology between the primary tumor and BM, and should be strongly considered for each site

ISSN:0361-8609    

DOI:10.1002/ajh.2830490408

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

年代:1995

数据来源: WILEY

摘要:

AbstractTo determine the difference in reactivity of factor Vlll (FVIII) inhibitor to FVlll/von Willebrand Factor (vWF) complex and FVlll free of vWF, an autoantibody to FVlll light chain was tested. A patient (1‐3) suffered from autoimmune hemolytic anemia with autoantibody to FVIII. Epitope specificity of the patient's IgG (1‐3 IgG) was shown to be the C2 domain of FVlll light chain (2170‐2332) by Western blotting using recombinant FVlll deletions expressed in Escherichia coli. The inhibitory effect on FVlll procoagulant activity (VIII :C) of 1‐3 lgG was tested against a conventional FVlll concentrate; Haemate P, a monoclonal antibody‐purified FVlll concentrate; Hemofil M, and a recombinant FVlll (rFVIII); Kogenate. 1‐3 lgG showed only 1.3 BU/mgIgG for Haemate P, in contrast to 20 BU/mglgG for both Hemofil M and Kogenate. The ratio of VIII:C/vWF:Ag in Haemate P and Hemofil M was 1/3.43 and 1/0.01, respectively, while Kogenate did not contain vWF. The inhibitory effect of the 1‐3 IgG was then compared with Kogenate and its complex with vWF. The inhibitory effect was decreased against the rFVlll by forming a complex with vWF. from 22 BU/mglgG to o.5 BU/mgIgG. Fab from the 1‐3 IgG had the same effect. In addition, vWF showed a protective effect on FVlll inactivation by the 1‐3 IgG in a dose dependent manner. Fifty‐nine percent of residual VIII:C was retained in the presence of 8 U/ml of vWF after 1 hr incubation with 1‐3 lgG. These results suggested that vWF could compete with the 1‐3 IgG for binding to FVIII.

ISSN:0361-8609    

DOI:10.1002/ajh.2830490409

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

年代:1995

数据来源: WILEY

摘要:

AbstractObjectives: To determine the prevalence and describe the clinical correlates of subnormal cobalamin levels in subjects infected with the human immunodeficiency virus (HIV), and to assess its relationship to virus‐mediated immunosuppression and/or anti‐viral therapy.Setting: Outpatient referral clinic in tertiary care hospital.Patient population: 200 HIV infected individuals.Study design: Descriptive cross sectional survey, with prospective follow‐up in a subgroup of patients before and after initiation of zidovudine therap.Measures: Routine complete blood count, serum B12 assay, CD4 counts. Serum homocysteine levels, and Schilling tests were performed on subgroups of study subjects.Results: Subnormal serum B12 levels were found in 61 subjects (30.5%). B12 deficient subjects were more likely to be taking zidovudine. (P = .007). Serum homocysteine levels were significantly higher in patients with subnormal cobalamin levels but were unrelated to CD4 counts or zidovudine use, and were rarely outside of the normal range. Malabsorption of vitamin B12 as evidenced by abnormal Schilling tests was more likely among patients with more advanced HIV disease, or gastrointestinal symptoms but was not necessarily associated with low B12 levels.Conclusions: Decreased cobalamin levels are found frequently in HIV disease, especially among those treated with zidovudine. Evidence of B12 malabsorption is found among those with more advanced disease and gastrointestinal sym

ISSN:0361-8609    

DOI:10.1002/ajh.2830490410

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

年代:1995

数据来源: WILEY

摘要:

AbstractP‐glycoprotein 170 (P‐gp), the multidrug transport pump, excludes drugs from the interior of cells and is inhibited by agents such as cyclosporin A (CsA), verapamil, and FK‐506, which are also substrates for the P‐gp pump. This work documents the age‐ and differentiation‐related changes in P‐gp on T and B lymphocytes from human blood or spleen, and its absence on most thymus and bone marrow cells. Analysis of rhodamine 123 (Rh123) dye efflux, and its inhibition by cyclosporin A, was used as a quantitative measure of functional P‐gp, and reactivity with MRK‐16 was used as a measure of P‐gp Surface expression. The dye efflux and phenotypic expression of P‐gp+ PBMC appeared equivalent to that of a moderately drug‐resistant cell line, although efflux is prolonged. The sensitivity to inhibition by CsA, cyclosporin G (CsG), and PSC833 of P‐gp on PBMC, thymocytes, or T‐cell lines varied with apparent cell‐type specificity. Normal blood and splenic T‐ or B‐cells included 50‐80% of cells with surface P‐gp (MRK‐16+), which mediated CsA‐sensitive dye export. The proportion of P‐gp+ T‐ and B‐cells was lowest among children under age 10 years, increased in adulthood, and decreased after age 60. Thymus included 30% of P‐gp+ cells mediating CsA‐sensitive dye export, including CD3−4‐8‐ progenitors and mature CD3hi CD4+8‐ or CD4−8+ thymocytes. Mature T‐cells in cord or adult blood, spleen, and bone marrow included a large proportion (50‐60%) with efficient CsA‐sensitive dye export, preferentially among the CD45RA+ subset. Monocytes from all tissue sources, and most bone marrow cells, expressed surface P‐gp but retained Rh123, suggesting the absence of a functional dye export mechanism. In vitro mitogen‐stimu‐lated PBMC T and B lymphocytes lost P‐gp function within 4‐24 hr, consistent with the observation that P‐gp was reduced on antigen‐xperienced CD45RO+ T‐cells in vivo. Drug export by P‐gp may protect lymphocytes from toxic effects of CsA, and may contribute to the immunosuppressive effects of such drugs. The developmentally regulated expression of P‐gp function on lymphocytes, and its modulation on activated T‐ o

ISSN:0361-8609    

DOI:10.1002/ajh.2830490411

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

年代:1995

数据来源: WILEY