摘要:

AbstractThe serum concentration of hyaluronan (HYA) was determined in 59 patients with various myeloproliferative disorders, including 33 patients with idiopathic myelofibrosis. In 18 patients the serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly. Raised serum HYA levels were seen in patients with active disease compared with age‐matched healthy subjects, whereas no significant difference in serum HYA was seen between patients with stable disease and age‐matched controls. Serum HYA concentrations correlated significantly with the leukocyte count (rho = 0.38; P<0.02) and with the serum concentration of PIIINP (rho = 0.50; P<0.001). During cytotoxic treatment, the serum HYA and PIIINP concentrations decreased in concert with declining leukocyte counts. These findings suggest that clonal expansion is accompanied by a bone marrow stromal reaction similar to the repair processes following injury to soft connective tissues. The relatively modest changes in serum HYA with frequent overlaps between patient categories and healthy subjects imply that the clinical utility of single determinations of serum HYA in the present disease groups is restrained. On the other hand, sequential measurements of HYA may provide a reflection of the myeloproliferative process in individual patie

ISSN:0361-8609    

DOI:10.1002/ajh.2830360102

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P<0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units × 3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU‐E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patien

ISSN:0361-8609    

DOI:10.1002/ajh.2830360103

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

年代:1991

数据来源: WILEY

摘要:

AbstractProtein C, a potent vitamin K‐dependent protein activated by an endothelial cell cofactor, thrombomodulin, has anticoagulant and profibrinolytic activity. Free protein S, a cofactor for protein C, potentiates protein C activity at the endothelial cell surface. Pulmonary thromboemboli are a consistent finding in adult respiratory distress syndrome (ARDS). To determine if protein S or protein C were affected by widespread endothelial cell damage in ARDS, we measured bound and free protein S levels and protein C antigenic and functional levels in 18 patients with acute lung injury, 6 critically ill patients without lung history, and 22 normal subjects. Free (PS:F) and bound (PS:Ag) protein S and protein C antigen (PC:Ag) levels were measured using an enzyme‐linked immunoassay and protein C function (PC:Fn) by measuring its anticoagulant activity. We found a significant decrease in bound and free protein S levels of both patient groups in comparison to normal and a shift toward the inactive, bound protein S form. In addition, a significant decrease in free protein S compared to bound protein S in both patient groups was observed. While both PC:Ag and PC:Fn were significantly reduced compared to normal, the PC:Fn was significantly and severely decreased out of proportion to the PC:Ag in both patient groups. There was no difference between those with and without lung injury for both protein S and protein C. Analyzed according to etiology of lung injury, there was no difference in the bound and free protein S, nor in PC:Ag and PC:Fn levels between patients with sepsis and trauma. However, there were significant decreases in both protein S and protein C levels compared with normal subjects. Levels of both PS and PC levels in patients who survived did not differ from those who died. In summary, our data show that both protein S and C are markedly deranged in acutely ill patients who suffered from either sepsis or trauma, and these changes are independent of lung injury. The marked reductions in functional activity of PS and PC may be contributing factors to the thromboembolic complications often observed in these patie

ISSN:0361-8609    

DOI:10.1002/ajh.2830360104

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

年代:1991

数据来源: WILEY

摘要:

AbstractEmbryonic globin chains were found to be synthesized in vitro by the BFU‐E colonies derived from adult sickle cell anemia (SS) patients, their heterozygous relatives as well as a few normal controls. In the absence of sufficient material for conducting direct structural analyses of these peptides, they were confirmed by evaluating the co‐migration of the ϵ‐ and ζ‐chains with the corresponding structurally characterized globin chains obtained from K562 cell lysates on a reversed phase high performance liquid chromatogram. The presence of ζ‐chain was also confirmed using an immunologic procedure. Furthermore, significant35S‐methionine incorporation peak was observed corresponding to the ζ‐chain synthesized by the BFU‐E‐derived colonies implying an active synthesis of this embryonic globin chain in BFU‐E cells obtained from hemopo

ISSN:0361-8609    

DOI:10.1002/ajh.2830360105

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

年代:1991

数据来源: WILEY

摘要:

AbstractA family with an antithrombin III variant (AT‐III‐Amiens) demonstrating abnormal heparin cofactor activity is described. Amplification and direct sequencing of genomic DNA by the polymerase chain reaction procedure permitted the identification of an Arg47Cys mutation in exon 2 of the variant antithrombin III g

ISSN:0361-8609    

DOI:10.1002/ajh.2830360106

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

年代:1991

数据来源: WILEY

摘要:

AbstractLimited data are available about the pharmacokinetics of placenta‐derived factor XIII (FXIII) concentrate in patients with FXIII deficiency. This concentrate contains only the active subunit A but not the carrier subunit B of the factor, and perplexities have been raised about its clinical use. Moreover, no data are available on its use in the rare patients completely lacking both subunit A and subunit B. Therefore, we evaluated the pharmacokinetics of a commercial placenta concentrate in three patients with FXIII deficiency: two lacking subunit A (type II) and one lacking both subunits (type I).The elimination half‐life of the infused placenta subunit A in the three patients was very similar (280, 283, and 272 hr) and was also consistent with the previously reported data for plasma‐derived FXIII. No thrombin‐independent activity was observed in our concentrate batches. The recovery was significantly lower in the type I patient, in whom infusion of subunit A was not able to elicit a monthly increment of subunit B, as usually observed in type II patients. Monthly infusions of placenta concentrate (at higher dosage in type I patient) have been administered to our patients for two to three years and no evidence of inhibitor against factor XIII activity has been observed.We conclude that placenta concentrates may be as effective as plasma derivatives in replacement therapy of factor XIII deficiency, even in patients who lack su

ISSN:0361-8609    

DOI:10.1002/ajh.2830360107

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

年代:1991

数据来源: WILEY

摘要:

AbstractSolid‐phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic patients were studied. A cross‐sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P1.5. These patient groups were followed for comparable periods of time (67.1‐71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV‐1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progressio

ISSN:0361-8609    

DOI:10.1002/ajh.2830360108

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

年代:1991

数据来源: WILEY

摘要:

AbstractAlthough some cases of the syndrome of hereditary persistence of fetal hemoglobin (HPFH) have been correlated with mutations causing a change in the binding of trans‐acting factors to DNA sequences flanking the γ‐globin gene, this mechanism has not been described in β‐thalassemias upstream of the canonical promoter of the β‐globin gene. In this report we describe such a change in binding of a protein that may explain a silent carrier phenotype of β‐thalassemia. We have previously demonstrated the binding of a protein (BP1) derived from a nuclear extract of human K562 cells to DNA 5′ to the human β‐globin gene in a region having a negative regulatory function. The binding of BP1 in this region can be detected by DNAse I footprinting and by gel mobility shift analysis. We have now compared binding of BP1 to the normal sequence and a mutated sequence (+ATA/‐T at −530 bp from the cap site) from the silent carrier of β‐thalassemia. Using mobility shift assays we show that BP1 binds about nine times more strongly to the mutated sequence than the normal sequence. These results suggest the possibility that the decreased expression of the β‐globin gene exhibited by the carrier may be due, at least in part, to tighter binding of a protein which functions as a negative

ISSN:0361-8609    

DOI:10.1002/ajh.2830360109

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe findings in the cord blood sample of an infant from a treated hemochromatotic mother of a raised transferrin saturation (88%) and a raised ferritin concentration (250.2 μg/L) together with elevated maternal values (66% and 91.6 μg/L, respectively) yet a normal total placental iron content (26.9 mg) suggested that in common with gastrointestinal mucosal cells and reticuloendothelial cells in hemochromatosis, the placental cell may exhibit an abnormality of iron storage and transpor

ISSN:0361-8609    

DOI:10.1002/ajh.2830360110

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

年代:1991

数据来源: WILEY

摘要:

AbstractBecause of the emergence of warfarin resistance, new potent long‐acting anticoagulants are now readily available in several over‐the‐counter rodenticide products. The availability of these “superwarfarin” compounds has led to accidental and purposeful human ingestions, one of which has resulted in a death. We summarize the prior case reports and report a second death. In addition, we report the availability of an assay to detect the presence of brodifacoum (a superwarfarin compound) in human plasma an

ISSN:0361-8609    

DOI:10.1002/ajh.2830360111

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

年代:1991

数据来源: WILEY