Prevention of graft-versus-host disease and bone marrow rejection: kinetics of induction of tolerance by UVB modulation of accessory cells and T cells in the bone marrow inoculum

UVB irradiation (700 J/m2) of bone marrow cells (UVB-BMC) before transplantation into lethally gamma-irradiated (10.5 Gy) allogeneic rats prevents graft-versus-host disease (GVHD) and induces a stable complete lymphohematopoietic chimerism. To better understand the underlying mechanism of the development of stable chimerism and induction of tolerance to donor organs in this model, we examined if the addition of T cells or dendritic cells (DC), as antigen presenting cells (APC), would restore the immunogenicity of UVB-BMC in in vitro mixed lymphocyte reaction (MLR) and induce in vivo bone marrow (BM) graft rejection. Whereas gamma-irradiated, unfractionated BMC induce allogeneic T cells to proliferate, UVB irradiation of BMC abolishes the stimulatory capacity of such cells in a primary MLR. Addition of purified T cells, CD4+ T cells, CD8+ T cells or B cells, respectively, failed to restore the capacity of UVB-BMC to stimulate allogeneic T- cell proliferation. In contrast, the addition of only a small number of splenic accessory cells or purified DC, which by themselves were relatively ineffective in stimulating T-cell proliferation, restored the accessory function and the allostimulatory capacity of UVB-BMC. To define the molecular defect induced by UVB irradiation, cytokines were added as costimulatory factors to primary MLRs and the results showed that the addition of interleukin (IL)-2 or IL-6 but not IL-1 or interferon gamma (IFN-gamma) restored the stimulatory capacity of UVB BMC. This finding suggests that UVB may alter the production, and/or utilization of IL-2 and IL-6 either at the membrane or cytoplasmic level. Parallel in vivo studies showed that addition of DC to UVB BM inoculum resulted in failure of BM engraftment, whereas addition of T cells led to development of fatal GVHD, thus suggesting that UVB modulation of accessory cells reduces graft immunogenicity and prevents BMT rejection, while modulation of T cells prevents GVHD. Our data provide evidence that UVB modulation of APC and mature T cells contained within BMC is potentially useful in preventing GVHD without endangering successful engraftment and may serve as a model for induction of adult chimerism and tolerance without the development of GVHD.     

The unmasking of <Emphasis Type="Italic">Pneumocystis jiroveci</Emphasis> pneumonia during reversal of immunosuppression: case reports and literature review

Background  

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.     

Immunologic heterogeneity of diffuse large cell lymphoma

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell- restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B- DLCLs.     

Pinealectomy affects the diurnal variations in 2－［~（125）I］ iodomelatonin binding sites in chicken bursa of Fabricius

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3H-1,2-二氢-1-吡里酮衍生物的合成

发现3 H-1,2-二氢-1-吡咯里嗪酮具有明显的抗炎镇痛作用。用Friedel-Crafts酰化和Dieckmann缩合等反应制备了该酮的一些衍生物,其中五个未见于文献报道。药理实验证明,这些化合物均有不同程度的抗炎镇痛作用。     

PREVALENCE OF MITRAL VALVE PROLAPSE IN HONG KONG CHINESE A CLINICAL AND AUTOPSY STUDY

The prevalence of mitral valve pro.lapse in Chinese was determined by screening 156 heal- thy subjects and by patholobic examination of 86 adult autopsies. Mitral valve prolapse was found in 7.7% in the clinical study and 5.8% in the autopsy study. A slight female preponderance was noted.     

Gallbladder and bile duct stones: percutaneous therapy with primary MTBE dissolution and mechanical methods

The authors describe percutaneous treatment of gallbladder or bile duct stones in 18 patients who were poor surgical candidates or in whom conventional therapy failed. Dissolution was performed in most cases with methyl tert-butyl ether (MTBE) because of its potent dissolution properties; other solvents used included monooctanoin or chelating solutions. Gallbladder stones were eliminated in 11 of 13 patients (six of seven with dissolution alone, four of four with dissolution and basket extraction, one with basket removal alone). In five patients with stones in the common bile duct (n = 3), cystic duct remnant (n = 1), and intrahepatic bile ducts (n = 1), stones were eliminated with dissolution alone in two and with dissolution plus basket extraction in one. In two patients percutaneous therapy failed due to complications (vagal hypotension with bile peritonitis and transient respiratory arrest) that occurred during catheter placement. Preliminary results suggest that MTBE is effective for dissolution of many gallbladder stones and some bile duct stones. Noncholesterol solvents and adjuvant mechanical maneuvers are valuable adjuncts to achieve complete stone elimination.