摘要:

AbstractThe arachidonic acid metabolites produced by human peripheral blood monocytes were studied to determine which metabolites could have a role in thrombogenesis. Monocytes were found to be free of platelets by scanning electron microscopy and by measurement of 12‐HETE. Human peripheral blood monocytes produce thromboxane as their major metabolite. Thromboxane levels reached a plateau at 12–16 hours of culture. Monocytes produced relatively little prostaglandin E2 or F2. In contrast to our control platelet preparation, neither A23187 (1–10 μM) nor exogenous arachidonic acid (0–40 μM) caused an increase in monocyte thromboxane B2. On the other hand, lipopolysaccharide (20 μg per ml), collagen (2.5 mg per 107cells), and thrombin (5–10 units per ml) caused a two‐ to fivefold increase in monocyte thromboxane B2 in most donors but had no effect on prostaglandin F1α levels. Blockage of thromboxane synthase by 1‐benzylimidazole abolished thromboxane B2 production but did not increase prostaglandin F1α. Finally, aspirin‐treated platelets from a volunteer donor, which were refractory to 30 μM arachidonate, could be aggregated by isolated blood monocytes.Our data indicate that monocytes are capable of producing thromboxane in large amounts. The regulation of this increase, however, appears to be quite different from platelets. We postulate that monocytes may have a role in hemostasis by virtue of their ability to adhere at sites of vascular injury and release thromboxane, which may enhance platelet aggregation a

ISSN:0361-8609    

DOI:10.1002/ajh.2830310302

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

年代:1989

数据来源: WILEY

摘要:

AbstractTwelve infusions of plasma concentrates of von Willebrand factor (vWF) were given to four patients with severe (type III) von Willebrand disease (vWD). Their prolonged bleeding times were either completely or partially corrected after five infusions and had not changed after the remaining seven. In contrast, the low platelet coverage of the subendothelial surface of rabbit aorta perfused with normal washed platelets and red cells resuspended in preinfusion patient plasma was completely or partially corrected in ten instances by replacing preinfusion plasma with postinfusion plasma and remained unchanged in two. Postinfusion improvement in surface coverage was greater than that in bleeding time, suggesting that vWF from normal platelets is needed to support optimal platelet‐vessel wall interactions in vWD. This possibility was further explored through other perfusion experiments. The subendothelial surface covered by platelets from an untreated patient with type III vWD (containing no measurable vWF) or from a type IIA vWD patient (containing dysfunctional vWF) resuspended in normal plasma was much smaller than that covered by normal platelets resuspended in normal plasma. These results establish that platelet vWF is important in supporting platelet‐vessel wall interactions in vWD and also provide experimental support in favour of the therapeutic transfusion of normal platelets in addition to vWF concentrates to correct the bleeding time in vWD patie

ISSN:0361-8609    

DOI:10.1002/ajh.2830310303

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

年代:1989

数据来源: WILEY

摘要:

AbstractIn rats with subcutaneously transplanted mammary carcinoma 5A (MC) and 2 to 10‐fold elevations in the blood content of mature neutrophils, 30–50% of the neutrophils showed pronounced hypersegmentation. This phenomenon could be reproduced in liquid culture of bone marrow cells from normal (tumor‐free) animals by 48 hr incubation with the MC host's serum, or with MC‐conditioned medium whose activity was attributable to an over 50,000 MW protein. The effects in vitro, occurring without change in total cell number and accompanied by increases in γ‐glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) activity, included decreases in the percents of progenitors (myeloblasts, promyelocytes, myelocytes, metamyelocytes and bands) and an increase in mature neutrophils 50% of which exhibited obvious hypersegmentation. Much less if any neutrophil hypersegmentation, and no statistically significant decrease in immature cells, occurred in response to the several colony stimulating factors (CSFs) tested, although (in addition to inducing GGT and AP) some CSFs did cause an increase in mature neutrophils.These investigations demonstrate the efficacy of a MC‐elaborated blood‐borne protein to promote myeloid cell maturation, and describe a system for the first time in which neutrophil hypersegmentation can be st

ISSN:0361-8609    

DOI:10.1002/ajh.2830310304

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

年代:1989

数据来源: WILEY

摘要:

AbstractLarge granular lymphocytes (LGL) may exert regulatory influences on B cell immuno‐globulin synthesis. We, therefore, investigated the influence of LGL from controls and B cell chronic lymphocytic leukemia patients (B‐CLL) on control B cell proliferation to costimulation with the F(ab′)2fragment of goat antihuman μ and B cell growth factor (BCGF). Purified LGL (>90% by morphology) from control and B‐CLL peripheral blood were added in various concentrations to purified control B cells and incubated with anti‐μ, and BCGF for 3 days. [3H]‐thymidine uptake of B cells was then measured. There was no proliferation of control or CLL LGL alone to the costimulatory signals of the F(ab′)2fragments of goat antihuman μ chain and BCGF. Addition of control LGL to equal numbers of control B cells did not blunt control B cell responsiveness to BCGF (with control LGL 8,649±298 cpm vs. control B cells alone 8,336 ± 556 cpm, mean ± SEM). When control LGL were increased to 10:1 LGL:B cell ratio, the maximal inhibition by control LGL of control B cell proliferative response to BCGF was 23%. In contrast, addition of CLL LGL at a 1:1 LGL:B cell ratio resulted in marked impairment of the control B cell proliferative response to BCGF (with CLL LGL 3,586 ± 954 cpm vs. control B cells alone 8,649 ± 298 cpm). Inhibition by CLL LGL occurred in a cell‐concentration‐dependent manner. No difference in CLL LGL's inhibitory effect on either resting or activated control B cell responsiveness to BCGF was noted. Inhibition of de novo protein synthesis (by cycloheximide inhibition) of CLL LGL did impair CLL LGL's inhibitory capacity for BCGF‐induced B cell proliferation. A possible explanation for these findings includes the possibility that a subgroup of LGL with B cell suppressive activity may have expanded as a host response to the B cell leukemia or as part of the disorder

ISSN:0361-8609    

DOI:10.1002/ajh.2830310305

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe nature of the blast cells in 163 cases of acute leukemia was investigated by immunophenotyping, with particular emphasis on the expression of “ectopic” surface membrane structures. Although no antigen included in our panel except CD3 revealed absolute lineage restriction, immunological typing allowed a definite characterization of blast cells in more than 90% of cases. Four groups of patients were identified (A, B, C, D) with different degrees of antigen ectopic expression. We classified as group A leukemias (74%) those expressing conventional antigenic patterns, in absence of cross‐lineage markers. Samples classified as group B (18%) showed a single ectopic membrane specificity, apparently discordant with the overall composite phenotype; such a “low‐grade deviation” did not prevent a definite immunodiagnosis. Pattern C specimens (5%) revealed a promiscuous coexpression of markers related to different lineages (biphenotypic leukemias), whereas group D included unclassifiable phenotypes, characterized by no antigen or DR‐only expression. Our findings suggest the possibility of interpreting complex phenotypic constellations of membrane markers in a consistent and l

ISSN:0361-8609    

DOI:10.1002/ajh.2830310306

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe present two patients with human immunodeficiency virus‐1 (HIV‐1) infection in whom T‐cell non‐Hodgkin lymphoma developed, based on pathologic diagnosis, immunophenotyping, and T‐cell receptor gene rearrangement. Both cases were positive for human immunodeficiency virus‐1 by enzyme‐linked immunosorbent assay and immunoblot methods. Histologic sections from each patient showed a high‐grade pleomorphic T‐cell non‐Hodgkin lymphoma, and immunophenotyping demonstrated a prevalence of reactivity for CD4 (helper) over CD8 (suppressor) antigens. T‐cell receptor β‐chain gene rearrangement studies revealed a rearranged pattern with either theHindlll orBamHI enzymes, whereas immunoglobulin heavy chain genes retained a germ‐line configuration. Viral sequences specific for human T‐cell leukemia virus‐1, human T‐cell leukemia virus‐II, or HIV‐1 were not detected. Thus, although rare, T‐cell non‐Hodgkin lymphoma may b

ISSN:0361-8609    

DOI:10.1002/ajh.2830310307

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

年代:1989

数据来源: WILEY

摘要:

AbstractTo determine the diagnostic importance of platelet aggregation studies, we evaluated the clinical utility of these assays by a retrospective review of 188 adult patients initially studied for bleeding abnormalities with platelet aggregation tests at a tertiary care hospital from 1984 to 1987. The primary indications for requesting the tests in our patient population were for the evaluation of a positive bleeding history or abnormal bleeding time (68%), hypercoagulability (17%), thrombocytosis (9%), or a family history of a bleeding disorder (6%). There was a statistically higher incidence of platelet aggregation test abnormalities in patients with highly abnormal bleeding times (40%), in patients with thrombocytosis from myeloproliferative disorders (65%), and in patients with a family history of a bleeding disorder (58%), compared to the other groups studied (16–29%). Of the 64 platelet aggregation tests performed that were abnormal, the following abnormalities were identified: 19 aspirin‐like defects (poor response to arachidonate and decreased second wave responses to weak agonists), which were presumably drug‐induced, ten myeloproliferative‐type disorder defects (abnormal response to epinephrine predominantly) in patients known to have myeloproliferative disease, 34 abnormal patterns not characterized as aspirin or myeloproliferative disorder related, four of which ultimately led to a diagnosis of storage pool disease, and one spontaneous aggregation defect. Our results suggest that platelet aggregation tests rarely lead to the diagnosis of a specific, previously undiagnosed platelet function disorder. Specific recommendations are given for efficient utilization of platelet aggregatio

ISSN:0361-8609    

DOI:10.1002/ajh.2830310308

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe reported incidence of low serum vitamin B12levels in patients ranges from 4% to 8%. In only a small percentage can this be ascribed to readily diagnosed pernicious anemia, malabsorption syndrome, or to gastrointestinal surgery. This leaves a number of patients in whom the meaning of the low serum B12is not immediately apparent. In 71 patients with intact gastrointestinal tracts, hematological indices did not adequately separate patients with decreased absorption of unbound B12from those with normal absorption. A low absorption of B12, either unbound or food‐bound, was found, however, when the level of serum gastrin was elevated. In contrast, a normal absorption of unbound B12was likely (95% of 44 patients) when the serum gastrin was norma

ISSN:0361-8609    

DOI:10.1002/ajh.2830310309

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

年代:1989

数据来源: WILEY

摘要:

AbstractDesmopressin (DDAVP), a synthetic vasopressin, temporarily corrects bleeding abnormalities associated with mild hemophilia A, von Willebrand disease, and disorders of platelet function. The side effects of DDAVP are considered benign although most of its use has been in adults and older children. We report four children under the age of 2 years who became hyponatremic after intravenous DDAVP administration (0.3 μg/kg). Three of them developed grand mal seizures. A review of the literature and these cases indicate that associated risk factors for hyponatremia after DDAVP administration include stress, surgery, anesthesia and narcotics (endogenous release of antidiuretic hormone), vomiting (loss of Na+), liver disease (hindered metabolism of DDAVP), renal tubular acidosis (chronically low serum Na+), multiple doses of DDAVP, and overhydration with hyponatremic fluids. DDAVP is not a benign drug in this age group and shows a serious potential for hyponatremia and seizures. Fluid restriction, avoidance of hyponatremic solutions, and close monitoring of serum electrolytes and urine output for at least 15–20 hr after the administration of DDAVP, when used in children under the age of 2 years, is warrant

ISSN:0361-8609    

DOI:10.1002/ajh.2830310310

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

年代:1989

数据来源: WILEY

摘要:

AbstractTransferrin donates iron to reticulocytes as follows: it binds to a receptor on the reticulocyte surface; the complex is endocytosed; both irons are released and the transferrin is recycled to the cell exterior. It has been proposed that the trigger for iron release after transferrin endocytosis is acidification of the endocytic vesicle. But this could account for removal of only one of transferrin's two irons, since only one of the irons is labile at acid pH. Moreover, iron continues to be removed from transferrin when acidification of the vesicle is blocked by a chloride‐transport inhibitor. Thus a detailed explanation of iron removal from transferrin remains elusive. In earlier work we showed that iron can be removed from transferrin by whole hemolysates and also by the combined action of hemoglobin and ATP at pH 7. We now show that the iron released from transferrin by hemolysates, and by hemoglobin and ATP, is in the Fe(II) oxidation state. We also show that ADP and DPG can substitute for ATP and that NADH and NADPH can substitute for the hemoglobin, although with these substitutions Fe(II) is generated less efficiently. The reductive release of iron from transferrin is rapid enough to account for all the iron processed by a young reticulocyte. We speculate that transferrin iron may be reduced to Fe(II) before reaching the mitochondri

ISSN:0361-8609    

DOI:10.1002/ajh.2830310311

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

年代:1989

数据来源: WILEY