Isolated gastric sarcoidosis. Unique remnant of disseminated disease

Isolated granulomatous disease was identified in a gastrectomy specimen after a gastrointestinal hemorrhage in a 61-year-old white woman. She died postoperatively. No other areas of granulomatous tissue were identified at autopsy. Ten years previously, pulmonary sarcoidosis was proven on lung biopsy. Conceivable, other reported cases of unexplained "idiopathic" granulomatous disease of the stomach may represent residua of prior disseminated sarcoidosis.     

Use of antidepressants in the frail elderly. When, why, and how

Sir Martin Roth has stated, "where there is depression, there is hope," to emphasize the fact that depression can be a treatable source of excess disability, even when it is superimposed upon irreversible chronic medical illness. Both the potential benefits and the risks of antidepressant medications are increased in the frail elderly. This article presents an approach toward defining who should be treated and for ensuring that elderly patients receive adequate treatment.     

Bone marrow transplantation in miniature swine. III. Graft-versus-host disease and the effect of T cell depletion of marrow

Graft-versus-host disease (GVHD) has been evaluated in partially inbred miniature swine in order to study this complication of allogeneic bone marrow transplantation (BMT) in a major histocompatibility complex (MHC) genetically defined large animal model. Bone marrow from MHC homozygous ("parental") swine was injected into irradiated (900 rads total-body irradiation) MHC heterozygous ("F1") swine that shared one haplotype with the donor. All 18 animals successfully engrafted with donor bone marrow, and 17 of these developed skin rash of varying intensity depending on the extent of T cell depletion of infused marrow. Of 18 animals, 8 received undepleted bone marrow from exsanguinated donors and 2 also received additional peripheral blood lymphocytes (PBL) as a source of mature T cells. All 8 showed a moderate-to-severe rash, and the 2 pigs that received additional donor PBL developed the most severe rash. The cutaneous eruption seen in this model clinically, histologically, and immunologically resembled human GVHD. Two protocols of T cell depletion of donor bone marrow by antiporcine T cell monoclonal antibodies plus complement were tested for their effect on development of GVHD. The combination of two monoclonal antibodies, 74-12-4 (PT4) and 76-2-11 (PT8), had a marginal effect on the subsequent development of cutaneous manifestations of GVHD. However, treatment of the donor marrow by a combination of three monoclonal antibodies--PT4, PT8, and MSA4 (PT11)--effectively decreased the severity of the GVHD skin rash. These results indicate that (1) the GVHD associated with allogeneic bone marrow transplantation in swine is dependent on T cells in the marrow; (2) effective T cell depletion of donor marrow by monoclonal antibodies and complement does not prevent engraftment; and (3) this swine GVHD model, which allows study with F1 and homozygous parental combinations in an MHC genetically defined large animal, is particularly useful for the understanding of GVHD pathogenesis, prevention, and treatment.     

Recombinant interleukin 2 and anti-Tac influence the growth of enriched multipotent hemopoietic progenitors: proposed hypotheses for different responses in early and late progenitors

Experiments were designed to evaluate the effect of recombinant IL-2 on growth of hemopoietic precursors from different sources (normal cord blood and bone marrow, and PB from CGL patients). For this purpose, combined cell sorting techniques and multipotent colony forming cell assays were used. A monoclonal antibody BI-3C5, which recognizes an antigen present on early lympho-myeloid cells as well as on all colony forming cells (CFU-GEMM assay), was used to enrich the studied populations. Double colour immunofluorescence techniques were performed to analyse the expression of Tac antigen on early progenitors. The results showed that rIL-2 had a stimulatory effect on growth of enriched progenitors from the three sources and surprisingly that addition of anti-Tac did not abolish this effect. On the contrary, anti-Tac enhanced even more growth of these sorted BI-3C5 precursors, suggesting a ligand action of the antibody. More interestingly, a low percentage of cord cells (1 in 1000) expressed both BI-3C5 and Tac antigens. The vast majority of cells did not concomitantly express both markers. The double labelled cells had a lymphoid-like morphology, high nucleus/cytoplasmic ratio and 2-3 nucleoli. The results will be discussed focusing on early and late "stem" cell growth.     

The myocardium in congestive heart failure

It is now apparent that the myocardium in patients with congestive heart failure (CHF) is not normal, because important structural and molecular changes modify function in these hearts. It appears likely that the myocardium in these patients with CHF becomes unable to provide enough chemical energy to meet its mechanical requirements. If this interpretation is correct, the resulting condition of "energy starvation" would have several important implications for therapy. For example, inotropic stimulation, by increasing energy expenditure, could contribute to the progressive myocardial cell death that characterizes end-stage cardiac hypertrophy. Conversely, the reduction in myocardial contractility that develops in the chronically over-loaded heart reduces myocardial energy expenditure, and changes in the expression of myosin isoforms improve cardiac efficiency. Therefore, an important goal of therapy in the patient with CHF is to reduce energy expenditure by unloading the failing heart and, in some cases, by administration of negative inotropic drugs.     

Local circuits and ocular dominance columns in monkey striate cortex

The relationships between ocular dominance columns and intrinsic cortical circuitry were examined in brain slices prepared from the striate cortex of macaques. Ocular dominance columns in layer 4C beta were visualized in vitro following anterograde transport of rhodamine injected into the lateral geniculate nucleus in vivo. The axonal and dendritic arborizations of individual layer 4C beta cells were revealed by intracellular fluorescent dye injections. Both qualitative observations and quantitative analysis showed that the dendrites of cells close to borders remained preferentially, although not absolutely, in the "home" column (the column containing the cell body). Thus, the segregated pattern of afferent input appears to have considerable influence on the pattern of dendritic arbors. Similarly, while axon collaterals within layer 4C beta could cross into the adjacent column, their limited lateral spread produced arbors that remained primarily within the home column. The terminal arbors of collaterals that travelled from layer 4C beta to layer 3 had a larger lateral spread, and the termination pattern appeared to be independent of column borders. Thus, our observations indicate that, while the course of many layer 4C beta dendrites appears to be guided by columnar boundaries as defined by geniculate afferents, there exist morphological substrates for intercolumnar interactions even between 4C beta cells. Intercolumnar interactions are seen more commonly in layer 3, however, where larger, denser axon arbors originating from 4C beta cells can freely cross ocular dominance column boundaries.     

Nodular glomerulopathy associated with nonamyloidotic kappa light chain deposits and excess immunoglobulin light chain synthesis

A nodular glomerulopathy characterized by mesangial deposits of monoclonal kappa light chains was detected by immunofluorescence in a renal biopsy from a patient with proteinuria and hypertension. These nodules lacked the tinctorial and morphologic features of amyloid. Ultrastructurally, the nodules contained electron-dense granular deposits as well as fibrils in parallel arrangement. The fibrils measured 110-140 A in diameter. They were consistent in size with amyloid fibrils. However, they differed in lacking the randomly oriented network of typical amyloid fibrils and more closely resembled fibrils intrinsic to mesangial matrix. The patient had no bone marrow or X-ray evidence of myeloma and no evidence of free monoclonal light chains in serum or concentrated urines. Biosynthetic studies of the patient's bone marrow cells demonstrated unbalanced immunoglobulin synthesis with excess production of monoclonal kappa light chains. These observations suggest that the observed glomerulopathy results from direct deposition of monoclonal light chains. Deposits with kappa light chain determinants have been found in 7 other patients with similar nodular glomerulopathies, 4 of whom had diagnosed clinical myeloma. The lesion of nonamyloidotic nodular glomerulopathy previously described in 19 patients, nor examined by immunopathologic techniques or not shown to contain light chain determinants, may have a similar pathogenesis.     

Chromosome mapping of cell membrane antigens expressed on activated B cells

Hybrids formed by fusion of either human acute lymphoblastic or chronic lymphocytic leukemia cells and the mouse myeloma P3.X63.Ag8/653 have been used to show that the expression of two cell surface antigens, Bp37 and p76, associated with B cell activation and detected by the monoclonal antibodies BB1 and BB2, respectively, segregate with human chromosomes 12 and 19, respectively. Another antigen expressed on activated B cells (p24) also maps to chromosome 12 (Katz et al., Eur. J. Immunol. 1984. 13: 1008) which is of interest in the light of the frequent involvement of this chromosome in certain B cell leukemias and lymphomas.     

Immunization of rabbits with a modified vaccinia Ankara recombinant virus bearing the HIV envelope antigen on its outer membrane

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia virus, which propagates efficiently in chicken embryo fibroblasts but fails to complete its growth cycle in many types of mammalian cells. We constructed a recombinant virus MVA/EK5, which has a chimeric gene encoding for the extracellular domain of the HIV envelope protein fused to the cytoplasmic and transmembrane domain of the B5R protein of vaccinia virus. The fused HIV envelope antigen was expressed in the African green monkey kidney BS-C-1 cells infected with the recombinant virus. This virus, which had been grown in chicken embryo fibroblasts, induced in rabbits antibodies against the HIV envelope antigen, in addition to those against poxvirus.