Advances in the discovery of drugs that treat pulmonary arterial hypertension.

Introduction: Distal pulmonary arterial remodeling and elevated pulmonary vascular resistance are characteristic of pulmonary arterial hypertension (PAH). Current approved vasodilator-specific PAH therapy that includes phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids has demonstrated dramatic enhancement in functional capacity, quality of life, and invasive hemodynamics. However, none of these treatments are curative, underscoring the need to identify new pathophysiologic signaling pathways.

Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease characterized by pulmonary artery vasoconstriction and vascular remodeling leading to vascular rarefaction with elevation of pulmonary arterial pressures and pulmonary vascular resistance. Often PAH will cause death from right heart failure. Current PAH-targeted therapies improve functional capacity, pulmonary hemodynamics and reduce hospitalization.

Induction of regulatory T cells from mature T cells by allogeneic thymic epithelial cells in vitro.

The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro.

Altered allogeneic immune responses in middle-aged mice.

It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for transplantation immunology.

Diagnosis and treatment of central nervous system involvement in non-Hodgkin's lymphoma.

The diagnosis of lymphoma of the central nervous system (CNS) has been facilitated by advances in neuroimaging and laboratory analysis of cerebrospinal fluid. The most common form of central nervous system CNS involvement in non-Hodgkin's lymphoma (NHL) is leptomeningeal disease. After a diagnosis is established, the use of intrathecal or systemic chemotherapy and radiotherapy can improve survival and palliate symptoms.

Cellular and molecular characterization of early and late retinal stem cells/progenitors: differential regulation of proliferation and context dependent role of Notch signaling.

Retinal stem cells/progenitors that define the evolutionarily conserved early and late stages of retinal histogenesis are known to have distinct competence to give rise to stage-specific retinal cell types. However, the information regarding their innate proliferative behavior and phenotypic potential in terms of generating neurons and glia is lacking. Here we demonstrate that, like their counterparts in other central nervous system (CNS) regions during early and late stages of embryonic development, the early and late retinal stem cells/progenitors display different proliferative response to fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) and bias towards generating neurons or glia.

Identification of c-Kit receptor as a regulator of adult neural stem cells in the mammalian eye: interactions with Notch signaling.

Neural stem cells are present in specific regions of the adult central nervous system (CNS). Recent evidence suggests that the ciliary epithelium (CE), a CNS derivative, in the adult mammalian eye, harbors a quiescent population of neural stem cells. Here, we report the identification of c-Kit signaling as one of the regulators of adult CE neural stem cells in vitro.

The interaction defect of accessory molecules is responsible for the poor ex vivo response to human antigens of mouse T helper cells.

Mouse T cells fail to respond to xenogeneic pig and human antigens using the direct antigen-presenting pathway. The poor response by mouse CD8 cells is because of multiple defects in the molecular interactions between mouse CD8 cells and xenogeneic antigen-presenting cells (APCs). Using human CD4/DR3+, mouse CD4-/major histocompatibility complex (MHC) class II - mice, we investigated the defects in molecular interaction responsible for the poor response to xenogeneic antigens by naïve mouse CD4+ cells.

Xenogeneic skin graft rejection in M-CSF/macrophage deficient osteopetrotic mice.

Background: The cellular infiltrate in xenografts suggests that macrophages may be involved in xenograft rejection. However, the precise role of macrophages in xenograft rejection has not yet been fully addressed.

Methods: Xenogeneic rat skin grafts were transplanted to macrophage colony stimulating factor (M-CSF)/macrophage-deficient osteopetrotic ([OP]-/-) and wild-type control mice.

Prolongation of allogeneic skin graft survival by injection of anti-Ly49A monoclonal antibody YE1/48.

Ly49A receptors expressed on NK, NKT, and T cells play inhibitory roles in regulating the immune responses in vivo and in vitro. Whether or not injection of anti-Ly49A monoclonal antibody (mAb) YE1/48 can block allograft rejection has not been evaluated. Balb/c mouse recipients received intraperitoneal injections of YE1/48 mAb (0.

Antibody-based therapy of non-Hodgkin's lymphoma.

Monoclonal antibodies (mAb) have dramatically advanced our ability to treat non-Hodgkin's lymphoma (NHL), and there has been a virtual explosion of clinical data regarding their use. Rituximab is a humanized anti-CD20 mAb and has significant single agent activity in follicular lymphoma, and to a lesser extent in mantle-cell and diffuse large B-cell lymphoma (DLCL). Rituximab appears to have synergistic activity with cytotoxic chemotherapy and the combination has recently demonstrated improved rates of complete remission (CR) and overall survival in older patients with DLCL.

Immunotherapy: a novel treatment for Non-Hodgkin's lymphoma.

Objectives: To provide an overview of the principles of immunology, including immunotherapy, and information about monoclonal antibody therapy in the treatment of non-Hodgkin's lymphoma.

Data Sources: Published literature.

Conclusions: Immunotherapy is a form of disease treatment that enhances the immune system with the use of biologic agents.