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Biomedical subjects

M Drew

Publications and source records attributed to M Drew.

14 recordsLinked to original sources

Where do young adult renal transplant recipients fit in?

Young adult renal transplant recipients often have unique concerns and interests. To give them an opportunity to share these concerns with peers, a support group was established at Boston Children's Hospital. Despite a less than enthusiastic beginning, this group is now well attended, meets four times a year, and has continued for over 4 years. The group has become a comfortable setting where the participants discuss their unique perspectives on schooling, family, and relationships.

Adaptation, Psychological

Very late antigen (VLA) expression by normal and neoplastic human plasma cells; including an assessment of antibodies submitted to the Vth International Workshop on Leucocyte Differentiation Antigens using human myeloma cell lines.

The biology of normal plasma cells and the pathophysiology of human multiple myeloma remain poorly understood. Functional assays are scarce and at present cell phenotyping is providing the most information about how human plasma cells may behave. Three different types of human plasma cells: normal, fresh neoplastic myeloma cells and plasma cell lines, have been studied for their reactivity with antibodies to the beta-1 integrins (Very Late Antigens; VLAs), including a panel obtained from the Vth International Workshop on Leucocyte Differentiation Antigens. Most plasma cell targets express VLA-4 (CD49d positive) and the common beta chain recognized by CD29. CD49e (VLA-5) was occasionally positive. Other VLAs were not usually expressed. These data suggest the wide use by plasma cells of VLA-4, possibly as a ligand with fibronectin and high endothelial venules (HEV). Of other adhesion structures expressed by plasma cells, only CD44 is seen as frequently, and this is also a HEV ligand.

Antibodies

Centrocytes rapidly adopt a memory B cell phenotype on co-culture with autologous germinal centre T cell-enriched preparations.

B cells, after mutating their Ig B-region genes in germinal centres (GC), undergo apoptosis, unless they receive antigen-dependent selection signals. The signals appear to be delivered by GC T cells, require CD40 ligand expression and may induce differentiation to memory cells. Cultured GC B cells are prevented from entering apoptosis by ligating their surface CD40, but the resulting phenotype is not associated with B cells found in vivo. Conversely, GC B cells rapidly adopt a memory B cell phenotype on culture with autologous memory CD4(+) T cells that have been induced to express CD40 ligand transiently. This effect is prevented by blocking CD40 ligand. Naive CD4(+) T cells, induced to express CD40 ligand, do not prevent GC B cells undergoing apoptosis.

Adolescent

Multiple myeloma: the biology of malignant plasma cells.

Multiple myeloma remains a difficult disorder to treat and cures are virtually unknown. Most modalities of treatment have been tried on an empirical basis, and a greater understanding of the nature of myeloma progenitors may lead to more specific therapies. In the past few years interest in the biology of myeloma plasma cells has increased and the current state of knowledge is summarised in this review. Myeloma clonogenic, or colony, assays have been attempted by many groups. Despite this, no direct equivalent is available of the CFU-GM assay for granulocyte-macrophage progenitors in normal marrow. No published methods have been exported widely to other laboratories. Recently, myeloma plasma cells were found to express a wide range of adhesion molecules permitting cell to cell and cell to stroma interactions. This finding may explain the difficulty of myeloma colony assays, since adhesive clumping must be prevented. The observation that interleukin (IL)-6 can stimulate myeloma plasma cells led to further work with other cytokines such as IL-3 and GM-CSF. The precise role of IL-6 in the usual case of bone marrow myeloma remains unclear however.

Aged

Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells.

Normal and malignant plasma cells were investigated for the expression of seven cellular adhesion molecules by immunofluorescence microscopy. The antigens investigated were CD2 and its ligand, LFA-3 (CD58). LFA-1 alpha (CD11a) and LFA-1 beta (CD18) and their ligand ICAM-1 (CD54), H-CAM (lymphocyte homing receptor; CD44) and N-CAM (CD56). Marrow from 18 patients with myeloma, two with plasma cell leukaemia (PCL), four with monoclonal gammopathy of uncertain significance (MGUS) and 10 normal allogeneic bone marrow donors was studied. All plasma cells from normals and multiple myeloma patients were negative for CD2, CD11a and CD18. All normal and myeloma marrow plasma cells were positive for ICAM-1. 16/18 myeloma cases tested, and all other samples (normal, MGUS and PCL), contained plasma cells positive for H-CAM. Only one normal, but 12/16 myelomas tested were positive for N-CAM (P less than 0.02). One of four MGUS cases was moderately positive and one other weakly positive for N-CAM. Both PCLs were N-CAM negative. 12/18 myelomas were positive for LFA-3, but only two normals (P less than 0.05). All MGUS cases were negative for LFA-3, as was one PCL, the other being weakly positive. Three cases were negative for both adhesion molecules, three cases expressed only N-CAM or LFA-3 and 10 cases expressed both. LFA-3 and N-CAM are expressed significantly in myeloma rather than normal plasma cells. Cases of MGUS may express N-CAM but not, in this small series, LFA-3. Plasma cells in the peripheral blood (PCL) and plasma cell lines express little or no LFA-3 or N-CAM.

Antigens, CD

The role of adhesion molecules in multiple myeloma.

Human myeloma plasma cells had been considered to express few surface antigens until recently. The past two International Workshops on Leucocyte Differentiation Antigens have shown that myeloma cells can express a range of surface molecules, and it has become clear that many of these have adhesive functions. The identification of ICAM-1 (CD54) and H-CAM (CD44) on human plasma cells was the initial observation, and other antigens such as N-CAM (CD56) and LFA-3 (CD58) have been confirmed as features of malignant plasma cells in particular. The degree of expression of LFA-1 (CD11a) remains to be characterised fully. It seems probable that the loss of some adhesion structures may be associated with increased malignancy and plasma cell leukaemia. At the present time there are few studies relating to the function of these molecules, although homotypic adhesion appears to occur, and it is likely that such studies will shed light on the pathogenesis of myeloma.

Antigens, CD

Normal and neoplastic human plasma cells express bcl-2 antigen.

The bcl-2 (B-cell leukaemia/lymphoma 2) proto-oncogene is associated with the 14;18 translocation in follicular lymphoma juxtaposing bcl-2 with the immunoglobulin heavy chain region. bcl-2 has been cloned and sequenced and a monoclonal antibody to amino acids 41 to 54 of the bcl-2 protein has been raised. The expression of bcl-2 in follicular lymphoma has been demonstrated by immunohistological staining and also in normal lymphocytes. The presence of the bcl-2 onco-protein has been demonstrated by immunofluorescence using conventional and confocal microscopy in normal and malignant plasma cells from myeloma patients and myeloma cell lines. Plasma cells from 8/8 normal donors were positive, although the proportion of positive cells and the intensity of staining varied. Eight of 10 patients with myeloma or plasma cell leukaemia had positive plasma cells, and 6/11 plasma cell lines and one lymphoma cell line also expressed the onco-protein. bcl-2 expression is a feature of normal plasma cells and data from the cell lines confirm that expression is not dependent on the presence of the 14;18 translocation.

Chromosomes, Human, Pair 14

Complications of intertrochanteric rotational osteotomy.

Intertrochanteric anterior rotational osteotomy is a recently developed surgical procedure to treat osteonecrosis of the femoral head. We reviewed the radiographic findings in four cases to acquaint radiologists with the usual appearance of the procedure and to assess surgical complications. In all cases, immediate postoperative radiographs showed rotation of the necrotic portion of the femoral head anteriorly so that it was no longer weight-bearing. Clinical and radiologic follow-up ranged from 12 to 30 months. In this time, three patients developed complications, including non-union of the osteotomy, further osteonecrosis with collapse of the femoral head, and worsening pain in the absence of progressive radiologic change. Radiology provides an important means of assessing rotational osteotomy, particularly in demonstrating sufficient rotation of the femoral head to assure nonweight-bearing by diseased bone. Also, surgical complications such as nonunion and hardware loosening may be identified. Nevertheless, the patient may deteriorate clinically even in the absence of radiologic demonstration of disease progression, and the absence of radiographic change does not assure a successful surgical outcome.

Adult