In vitro propagation and homing of liver-derived dendritic cell progenitors to lymphoid tissues of allogeneic recipients: Implications for the establishment and maintenance of donor cell chimerism following liver transplantation

Dendritic cell (DC) progenitors were propagated in liquid culture from nonparenchymal cells resident in normal mouse (B10.BR; H-2k, I-E+) liver in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The liver-derived DC progenitors were MHC class II-/dim and did not express counter receptors for CTLA-4, a structural homologue of the Т cell activation molecule CD28. Following subcutaneous or intravenous injection, these liver-derived cells migrated to Т cell-dependent areas of lymph nodes and spleen of unmodified, allogeneic (BIO; H-2b; I-E_) recipients, where they were identified 1-5 days, and 1 and 2 months after injection by their strong surface expression of donor MHC class II (I-Ek) and their dendritic morphology. Maximal numbers of liver-derived DC in the spleen were recorded 5 days after injection. Both clusters of strongly donor MHC class II+ cells— and (more rarely) dividing cells—could also be identified, suggesting cell replication in situ. Using the same techniques employed to generate DC progenitors from normal liver, GM-CSF-stimulated cells were propagated for 10 days from the bone marrow and spleen of nonimmunosuppressed mice sacrificed 14 days after orthotopic liver transplantation (B10;H-2b → C3H;H-2k). Immunocytochemical staining for recipient and donor MHC class II phenotype revealed the growth both of host cells with DC characteristics, and of cells expressing donor alloantigens (I-Ab). These results are consistent with the growth, in response to GM-CSF, of donor-derived DC from progenitors seeded from the liver allograft to recipient lymphoid tissue. The functional activity of the progenitors of chimeric DC and the possible role of these cells in the establishment and maintenance of donor-specific tolerance following liver transplantation remain to be determined. © 1995 by Williams and Wilkins

Comparison of various lazaroid compounds for protection against ischemic liver injury

Lazaroids are a group of 21-aminosteroids that lack steroid action but have a potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation. However, there have been conflicting reports on the effectiveness and potency of the various lazaroid compounds. In this study, we compared the effectiveness of three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic vascular exclusion model. The agents were given to the animals intravenously for 30 min before ischemia. The animals were divided into 5 groups: Control (n=10), no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10 mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg). The effect of treatment was evaluated by two-week animal survival, hepatic tissue blood flow, liver function tests, blood and tissue biochemistry, and histological analyses. Animal survival in all treated groups was significantly improved compared with the control (83-100% versus 30%). Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups, except for an early significant increase in Group G. Postreperfusion hepatic tissue blood flow was much higher in all treated animals (50% of the preischemic level vs. 25% in the control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed adenine nucleotide degradation during ischemia and enhanced the resynthesis of high-energy phosphates after reperfusion. Although structural abnormalities in postreperfusion liver tissues were markedly ameliorated in all treated groups, Group A2 showed significantly less neutrophil infiltration. Liver injury from warm ischemia and reperfusion was attenuated with all lazaroid compounds, of which U-74500A at 5 mg/kg exhibited the most significant protective activity

Embolic stroke complicating Staphylococcus aureus endocarditis circumstantially linked to rectal trauma from foreign body: a first case report

BACKGROUND: Diagnostic and therapeutic instrumentation of the lower gastrointestinal tract has been reported to result in bacteremia and endocarditis. No such case has been reported in persons with a history of rectal foreign body insertion despite its potential for greater trauma. CASE PRESENTATION: A 58-year-old male was admitted with confusion and inability to speak. His past history was notable for hospitalization to extract a retained plastic soda bottle from the rectosigmoid two years prior. On examination, he was febrile, tachycardic and hypotensive. There was an apical pansystolic murmur on cardiac examination. He had a mixed receptive and expressive aphasia, and a right hemiparesis. On rectal examination he had perianal erythema and diminished sphincter tone. Magnetic resonance imaging of the brain showed infarction of the occipital and frontal lobes. Transesophageal Echocardiography of the heart revealed vegetations on the mitral valve. All of his blood culture bottles grew methicillin sensitive Staphylococcus aureus. He was successfully treated for bacterial endocarditis with intravenous nafcillin and gentamicin. The rectum is frequently colonized by Staphylococcus aureus and trauma to its mucosa can lead to bacteremia and endocarditis with this organism. In the absence of corroborative evidence such as presented here, it is difficult to make a correlation between staphylococcal endocarditis and anorectal foreign body insertion due to patients being less than forthcoming CONCLUSION: There is a potential risk of staphylococcal bacteremia and endocarditis with rectal foreign body insertion. Further studies are needed to explore this finding. Detailed sexual history and patient counseling should be made a part of routine primary care

Analysis of arterial intimal hyperplasia: review and hypothesis

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it "benign intimal hyperplasia". However, normal or "benign " intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl