Two distinct cytolytic pathways have been characterized: one in which the interaction between the Fas antigen and its ligand results in apoptosis, and another in which the pore forming protein perforin and the serine protease granzyme B contribute to DNA fragmentation and cell death. We investigated intrarenal expression of these molecular executors of cell death in light of the potential participation of cytolytically active cellular elements in the antiallograft repertory. Reverse transcriptase-polymerase chain reaction was used to identify intrarenal expression of Fas antigen, Fas ligand, granzyme B and perforin in eighty human renal allograft biopsies; mRNA display was correlated with the Banff histological diagnosis of renal allografts. Our studies demonstrate that: (1) intrarenal expression of Fas ligand mRNA and of granzyme B mRNA are correlates of acute but not chronic rejection; (2) Fas ligand mRNA is not detectable in allografts in the absence of rejection; (3) intrarenal coexpression of members of each lytic pathway (Fas ligand and Fas, granzyme B, and perforin) and that of both pathways (e.g., Fas ligand and granzyme B) are correlates of acute rejection; and (4) a direct correlation exists between the histological severity of acute rejection and intrarenal coexpression of mRNA encoding Fas ligand, Fas, granzyme B, and perforin. Our studies identify, for the first time, the differential expression of the two major lytic pathways in acute and chronic allograft rejection and suggest that specific therapy directed at the cytotoxic attack molecules might be efficacious in the prevention and/or treatment of acute rejection.
Chronic diarrhea is a common bowel disorder; disturbance of intestinal microorganisms may play a role in its pathogenesis. This study assessed the clinical efficacy of lyophilized, heat-killed Lactobacillus acidophilus LB versus living lactobacilli in the treatment of chronic diarrhea. One hundred thirty-seven patients with chronic diarrhea were randomly allocated to receive either a 4-week course of 2 capsules of Lacteol Fort twice a day (Lacteol group, 69 patients) or a 4-week course of 5 chewable tablets of Lacidophilin three times a day (Lacidophilin group, 64 patients). The frequency of stools was recorded quantitatively, and semiquantitative parameters such as stool consistency, abdominal pain, distention, and feeling of incomplete evacuation were evaluated. At the second and fourth week of treatment, mean bowel frequency was significantly lower in the Lacteol group than in the Lacidophilin group (1.88 +/- 1.24 vs 2.64 +/- 1.12, 1.39 +/- 0.92 vs 2.19 +/- 1.05; P<.05). At the end of the treatment, the clinical symptoms were markedly improved in the Lacteol group, indicating that L. acidophilus LB is more effective than living lactobacilli in the treatment of chronic diarrhea.
As altered rectal perception is present in almost all patients with IBS, it might be a reliable biological characteristic of the disease. Alterations in the MC and SP of the intestinal mucosa may be important factors in visceral hypersensitivity.
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