Multiple allogeneic progenitors in combination function as a unit to support early transient hematopoiesis in transplantation.

Cord blood (CB) is a valuable donor source in hematopoietic cell transplantation. However, the initial time to engraftment in CB transplantation (CBT) is often delayed because of low graft cell numbers. This limits the use of CB.

Inhibitory function of NKT cells during early induction phase of nickel allergy.

Until now, metal allergies have been regarded as a Th1-type immune response.　However, because the contribution of a Th2-type immune response has been suggested by clinical findings, we previously examined the Th2-type immune response during the development of metal allergies using a GATA-3 transgenic (GATA-3 Tg) mouse model. As a result, a Th2-type immunization reaction was suggested to be involved in the early phase of metal allergies.

A possible clue for the production of anti-glomerular basement membrane antibody associated with ureteral obstruction and hydronephrosis.

Background: Anti-glomerular basement membrane (anti-GBM) antibody-mediated glomerulonephritis (anti-GBM GN) is an autoimmune disease with rapidly progressive glomerulonephritis. Based on a case report of anti-GBM GN following hydronephrosis, we hypothesized that hydronephrosis may act as a trigger for the development of anti-GBM antibodies.

Patients And Methods: We evaluated 11 patients who were diagnosed with hydronephrosis.

Curative haploidentical BMT in a murine model of X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by defective microbial killing in phagocytes. Long-term prognosis for CGD patients is generally poor, highlighting the need to develop minimally toxic, curative therapeutic approaches. We here describe the establishment of a mouse model in which X-linked CGD can be cured by allogeneic bone marrow transplantation.

Cognate interaction plays a key role in the surveillance of autoreactive B cells in induced mixed bone marrow chimerism in BXSB lupus mice.

The effects of bone marrow transplantation (BMT) as a treatment for and/or preventive measure against autoimmune diseases in mice were investigated extensively. The reconstitution of the hematopoietic system with a mixture of autologous and heterologous bone marrow cells was reported to suppress the development of autoimmune diseases. However, the pathological mechanism through which mixed chimerism results in the suppression of disease development is still unknown.

Allogenic mixed chimerism induced by nonlymphoablative regimen including donor BMT with low-dose TBI and anti-CD40L cured proliferative glomerulonephritis in lupus mice.

Allogeneic mixed chimerism achieved by low-dose total body irradiation (TBI) and anti-CD40L monoclonal antibody (mAb) with donor bone marrow transplantation (BMT) and host T cell depletion overcomes both allo- and autoimmunity. We investigated whether a similar regimen without T cell depletion cured diffuse proliferative glomerulonephritis. Male BXSB mice (H-2b) were injected with 20 x 10(6) BALB/c (H-2d) BM cells.

Prominent dominant negative effect of a mutant Fas molecule lacking death domain on cell-mediated induction of apoptosis.

Using a panel of transfectant B lymphoma cells expressing varying amounts of the mutant Fas together with the endogenous wild type Fas, semi-quantitative studies on the dominant negative effect of a murine mutant Fas molecule lacking death domain were carried out. In anti-Fas antibody-mediated induction of apoptosis, the mutant molecules exerted significant dominant-negative effect only when their expression level was comparable to or higher than that of wild type molecules, or when exposed to low amounts of the antibody. The inhibitory effect was accompanied by the failure in DISC formation in spite of Fas aggregation.

Complement mediates nephrin redistribution and actin dissociation in experimental membranous nephropathy.

Background: The onset of proteinuria in passive Heymann nephritis, (PHN), a rat model of human membranous nephropathy (MN), is complement-dependent and is associated with altered podocyte slit diaphragm integrity and dissociation of nephrin from the actin cytoskeleton. These studies examined if complement is responsible for these podocyte changes.

Methods: PHN was induced with sheep anti-Fx1A.

Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy.

These studies examined the expression of the podocyte slit diaphragm protein nephrin and its association with actin at the onset of proteinuria in passive Heymann nephritis (PHN), a rat model of human membranous nephropathy. Four days after immunization, 58% of PHN rats had mild proteinuria. At that time, most slit diaphragms were still visible on electron microscopy; however, in those locations where the deposits encroached on the filtration slits, the slit diaphragms were either displaced or absent.

Podocyte slit-diaphragm protein nephrin is linked to the actin cytoskeleton.

Nephrin is an Ig-like transmembrane protein. It is a major component of the podocyte slit diaphragm and is essential for maintaining normal glomerular permeability. CD2-associated protein (CD2AP) is also necessary for normal glomerular permeability and is a putative nephrin adapter molecule.