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R A Muggia

Publications and source records attributed to R A Muggia.

5 recordsLinked to original sources
PubMed1993

Unmodified pancreatic islet allograft rejection results in the preferential expression of certain T cell activation transcripts.

Polymerase chain reaction-assisted reverse transcription was used to study the temporal course of rejection in unmodified recipients of murine pancreatic islet cell allografts (DBA/2-->B6AF1) by using syngeneic tissues as controls. The histologic appearance of the grafts was analyzed in parallel. Preproinsulin and constant region of the TCR-beta chain transcripts were studied as markers of graft integrity and infiltrating T cell mass, respectively. The participation of certain cytokines and CTL were analyzed by the detection of IL-2, IFN-gamma, IL-4, and CTL-specific serine protease (granzyme B) transcripts. The time-related disappearance of intragraft preproinsulin transcripts correlated with graft destruction, whereas the intensity of intragraft TCR-beta chain transcript levels correlated with the magnitude of mononuclear leukocyte infiltration in allografts. In unmodified allografts, the magnitude of IL-2 and IFN-gamma intragraft mRNA levels correlated with the intense mononuclear leukocyte infiltrate found on histologic examination at day 8. Only after stable IL-2 gene transcription on day 8 does evidence of graft destruction become apparent, indicating that IL-2 gene activation is closely related to and probably required for expression of alloimmune cytopathic processes. In contrast, IL-4 transcripts were absent or detected in low copy number throughout this time course. Intragraft expression of granzyme B mRNA, a CTL-specific transcript, peaked from day 8 to day 12 in allografts compared with syngeneic grafts or normal tissue. In syngeneic grafts IL-2 and/or IL-4 mRNA was essentially not detected. Although IFN-gamma and granzyme B transcripts were detected in syngeneic grafts, after 4 days the levels of detected transcripts were far less than those noted in allografts. In vivo detection of intragraft IL-2 transcripts in the relative absence of detectable IL-4 transcripts strongly suggests IL-2-dependent immune effector mechanisms are associated with, and perhaps responsible, for allograft rejection. Apparently IL-4-dependent effector mechanisms are not necessary for allograft rejection.

Animals↗
PubMed1992

Interleukin 2 receptor targeted fusion toxin (DAB486-IL-2) treatment blocks diabetogenic autoimmunity in non-obese diabetic mice.

Insulin-dependent diabetes mellitus (IDDM) is strikingly similar in the non-obese diabetic (NOD) mouse and humans. In IDDM, the systematic autoimmune destruction of insulin-producing beta cells within the pancreas is dependent on autoreactive T cells. This autoimmune process can be accelerated by transferring spleen cells from diabetic donors into irradiated syngeneic NOD mice. In a previous study we established that interleukin 2 receptor (IL 2R)-bearing cells propagated from pre-diabetic NOD mice promote IDDM. Therefore, we reasoned that specific elimination of IL 2R+ T cells should abort the diabetogenic process. T cell expressing IL 2R can be selectively destroyed with a diphtheria toxin-related IL 2 fusion protein (DAB486-IL-2). We set DAB486-IL-2 the challenging task of preventing fulminant IDDM accelerated by the adoptive transfer of diabetic spleen cells. Eight weeks after the adoptive transfer only 10% and 20% of NOD mice treated with 10 and 5 micrograms/day of DAB486-IL-2, respectively, became diabetic while 100% control mice (vehicle buffer) became diabetic within 5 weeks. A dose of 1 microgram/day of DAB486-IL-2 had no protective effect. Although the protection conferred by DAB486-IL-2 is not permanent, it is maintained for at least 4 weeks following cessation of treatment. Furthermore, even though these NOD mice do eventually become diabetic, the tempo of expression and severity of diabetes, as assessed by the level of hyperglycemia, is dramatically reduced. Although histologic examination of pancreas revealed minimal degree of mononuclear infiltrate within the islets in both groups, the vehicle control mice had fewer islets per section indicating many islets had already been destroyed. In addition, spleen cells from diabetic NOD mice which were pre-treated with DAB486-IL-2 (10 micrograms/day) for 1 week lost their ability to transfer disease. Taken together, these studies strongly support the concept that IL 2R-bearing T cells are essential for the induction of IDDM and suggest that DAB486-IL-2 would be a promising therapeutic approach in the treatment of human IDDM.

Animals↗
PubMed1992

Urinary ascites in the immediate postpartum period.

New onset ascites in the immediate postpartum period is a rare occurrence most often associated with the Budd-Chiari syndrome. We report a patient who developed postpartum ascites secondary to an intraperitoneal bladder perforation.

Adult↗