Bruce R. MacPherson

Contractile cells of the kidney in primary glomerular disorders: an immunohistochemical study using an anti-alpha-smooth muscle actin monoclonal antibody.

Mesangial cells of the renal glomerulus are thought to have contractile properties, resembling those of smooth muscle cells. Since actin synthesis in mesangial cells is increased in selected animal models of glomerulonephritis, we evaluated the expression of alpha-smooth muscle actin (ASMA), the principal actin isoform found in smooth muscle cells, in biopsy specimens from patients with primary glomerular disorders and in control tissues. Normal glomeruli and glomeruli in acute tubulointerstitial disorders showed few or no ASMA-positive cells in the glomeruli. In contrast, ASMA expression in mesangial cells was increased in minimal change disease, focal segmental glomerulosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, and immunoglobulin A nephropathy. In membranoproliferative glomerulonephritis and cryoglobulinemic glomerulonephritis both mesangial and capillary loop ASMA-positive cells were observed with a segmental distribution. In addition, ASMA-positive interstitial cells were seen in many biopsy specimens and often were increased in number in biopsy specimens showing early interstitial fibrosis and tubular atrophy. We conclude that ASMA synthesis in mesangial cells is upregulated in a variety of glomerular disorders, frequently associated with increased cell proliferation and mesangial matrix production. This phenotypic change may be an indicator of mesangial cell activation after injury and may have important pathophysiologic consequences.

Focal segmental glomerulosclerosis in patients receiving lithium carbonate.

Lithium carbonate is a commonly used psychiatric medication with a number of toxic renal effects, which include nephrotic-range proteinuria. A review of the literature concerning lithium-induced proteinuria is presented and three cases of nephrotic-range proteinuria are described in association with lithium therapy. The pathology in these three cases was focal segmental glomerulosclerosis, a finding not previously described.

Validation of HLAMatchmaker algorithm in identifying acceptable HLA mismatches for thrombocytopenic patients refractory to platelet transfusions

BACKGROUND: HLAMatchmaker (HLAMM) is an algorithm that determines donor‐recipient histocompatibility based on HLA type. This study determines the effectiveness of HLAMM in identifying suitable platelet (PLT) donors for refractory patients.

Suramin inhibits the mixed lymphocyte reaction by suppressing lymphokine production

New compounds with a greater potency than cyclosporin A (CyA) for thwarting host rejection of organ transplantation are being sought. Suramin sodium may be a novel drug to prevent or delay graft rejection and graft-vs-host disease (GVHD), because of itsin vitro andin vivo immunosuppressive properties. Since the allogeneic mixed lymphocyte reaction (MLR) is considered to be thein vitro counterpart of the initial T-lymphocyte recognition and response to allogeneic histocompatibility antigens on grafted tissue or organ and to GVHD, we initially evaluated thein vitro suppressive effect of suramin in the allogeneic MLR. Suramin inhibited the H-2- and HLA-incompatible MLR in a dose-dependent manner. The suppressive effect was observed both in the primary and in the secondary MLR. The suppression of the MLR by suramin is due predominantly to the inhibition of interleukin-2 (IL-2) production by the responding T cells.

A 59-Year-Old Woman With Immunotactoid Glomerulopathy, Heavy-Chain Disease, and Non-Hodgkin Lymphoma

Immunotactoid glomerulopathy is one of several renal disorders characterized by the extracellular deposition of nonamyloid fibrillary deposits. There is considerable debate as to whether immunotactoid glomerulopathy should be distinguished from fibrillary glomerulonephritis, a closely related entity. Currently, the distinction is based on fibril size and arrangement. We report the case of a 59-year-old woman in whom a diagnosis of immunotactoid glomerulopathy was made after a 2-year history of proteinuria. Electron microscopy of her renal biopsy showed randomly arranged microtubular subepithelial and mesangial deposits, which measured 34 nm in average diameter. She was later discovered to have circulating immunoglobulin G heavy chains without associated light chains (gamma-heavy-chain disease) and, subsequently, non-Hodgkin lymphoma, follicular lymphoma, grade I (World Health Organization classification). Approximately 100 cases of gamma-heavy-chain disease have been reported in the literature since it was originally described by Franklin in 1964. However, while there are 10 reports in the literature of heavy-chain disease with fibrillary deposits in the kidney, none fit the criteria for immunotactoid glomerulopathy.