Alpha 4 beta 1 and alpha 5 beta 1 are differentially expressed during myelopoiesis and mediate the adherence of human CD34+ cells to fibronectin in an activation-dependent way

To study the receptors involved in the interaction between extracellular matrix proteins and hematopoietic progenitor cells, we analyzed the expression of beta 1 integrins on CD34+ bone marrow cells by means of immunoflowcytometry. Alpha 4 beta 1 and alpha 5 beta 1 were expressed, whereas alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, and alpha v beta 1 were virtually absent. Furthermore, we assessed the alpha 4 and alpha 5 expression on committed myeloid progenitor cells. These colony-forming cells were detected in the alpha 4 dull fraction and the alpha 5 dull fraction. During myeloid differentiation, both in vivo and in vitro, a differential expression of alpha 4 beta 1 and alpha 5 beta 1 was observed. alpha 5 beta 1 was found to be lost at the myelocytic-metamyelocytic stage, before the loss of alpha 4 beta 1, at the band stage. Functional studies showed no binding of erythroid progenitor-depleted, CD34+ bone marrow cells to fibronectin. However, protein kinase C activation strongly induced fibronectin binding (68% of the cells). Inhibition experiments with specific antibodies and peptides showed the binding to be mediated by both alpha 4 beta 1 and alpha 5 beta 1. Also, colony-forming cells of granulocytes and macrophages were demonstrated to adhere to fibronectin in an activation-dependent way. During granulocyte colony-stimulating factor-induced in vitro maturation, the activation-dependent fibronectin binding capacity is gradually lost. We conclude that: (1) CD34+ bone marrow cells express alpha 4 beta 1 and alpha 5 beta 1; (2) the expression of alpha 4 beta 1 and alpha 5 beta 1 is differentially expressed during myeloid differentiation; and (3) binding of CD34+ bone marrow cells to fibronectin is activation dependent.     

Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase [see comments]

We analyzed the outcome of 450 HLA-identical sibling bone marrow transplants for chronic myelogenous leukemia (CML) in chronic phase performed between 1985 and 1990 and reported to the International Bone Marrow Transplant Registry (IBMTR). All patients received either hydroxyurea (n = 292) or busulfan (n = 158) to treat their CML before transplant. The median interval between diagnosis and transplant was 10 months (range, 1 to 191). Patients treated with hydroxyurea had a higher probability (95% confidence interval) of leukemia-free survival (LFS) at 3 years than those treated with busulfan (61% [51% to 70%] v 45% [36% to 55%], P < .0003). Probability of LFS was also higher in patients transplanted within 1 year of diagnosis (61% [53 to 68%] v 47% [38% to 57%], P < .001). After adjustment for patient and transplant covariables in a multivariate analysis, prior chemotherapy and duration of disease pretransplant were independently associated with LFS. These data support the use of hydroxyurea rather than busulfan and transplant within 1 year of diagnosis for patients with CML and an HLA-identical sibling.     

Artificial urinary sphincters: plain radiography of malfunction and complications

Inflatable artificial urinary sphincters provide excellent voluntary continence. Eighty-four consecutive patients underwent implantation of artificial urinary sphincters for intractable urinary incontinence; 33 patients had 58 episodes of sphincter malfunction, and eight patients had eight complications involving a functional prosthetic sphincter. Retrospective analysis was performed to determine the value of plain radiography of the pelvis in patients with sphincter malfunction or complication. The cause of malfunction in the majority of patients was a system leak and subsequent loss of hydraulic fluid (31 occurrences; 53%). Plain radiography permitted correct identification of all instances of fluid leakage in patients with opacified prostheses. Plain radiographs were of no value in examining patients with nonopacified prostheses or the complications of cuff erosion or wound infection. Due to the low cost and noninvasive nature of plain radiography of the pelvis, we conclude that it should be used as the initial diagnostic modality in patients with previously opacified but currently dysfunctional artificial urinary sphincters.     

Shoulder instability: evaluation with MR imaging

Instability of the glenohumeral joint is a common cause of chronic shoulder pain and disability. One or more episodes of subluxation or dislocation may result in a tear, detachment, or attenuation of the glenoid labrum, stripping of the joint capsule from the scapula, or trauma to the tendons or muscles of the rotator cuff. A series of 27 shoulders examined with magnetic resonance (MR) imaging showed changes of glenohumeral instability, which were confirmed with open or arthroscopic surgery. MR imaging was capable of displaying common types of pathologic conditions resulting from instability, including labral trauma, capsular detachment, and retraction of the subscapularis muscle. MR imaging is a valuable diagnostic tool for the evaluation of glenohumeral instability.