Cytomegalovirus (CMV) glycoprotein B genotypes and response to antiviral therapy, in solid-organ-transplant recipients with CMV disease.
(57/498)
Cytomegalovirus (CMV) can be classified into 4 glycoprotein B (gB) genotypes, on the basis of sequence variation in the UL55 gene. We assessed the effect that CMV gB genotype has on virologic and clinical response to therapy, in 50 solid-organ-transplant recipients with CMV disease. CMV loads were determined at regular intervals after the start of therapy. Genotype results were correlated with CMV-load kinetics in response to therapy with ganciclovir. At the onset of treatment, the distribution of CMV gB genotypes was as follows: gB1, 19/50 (38%); gB2, 9/50 (18%); gB3, 12/50 (24%); gB4, 2/50 (4%); and mixed-genotype infection, 8/50 (16%). Between viral genotype groups, time to clearance of CMV, failure to clear CMV, and calculated CMV-load half-life after the start of therapy were not significantly different. The CMV gB genotype did not affect the rate of disease recurrence or occurrence of tissue-invasive disease. It appears that the gB genotype, which causes CMV disease, does not significantly influence CMV-load kinetics or clinical response to therapy. (+info)
Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas.
(58/498)
EBV-infected B-cell lymphomas are a potentially life-threatening complication in bone marrow and solid organ transplant recipients. Immunosuppressive drugs required to prevent allograft rejection also impair anti-EBV T-cell immunity, thereby increasing the risk of EBV-associated disease. Here we demonstrate that the immunosuppressant rapamycin (RAPA) has a strong antiproliferative effect in vitro on B-cell lines derived from organ transplant recipients with EBV-associated posttransplant lymphoproliferative disorder (PTLD). Furthermore, RAPA significantly inhibits or delays the growth of solid tumors established from EBV-infected B-cell lines in a xenogeneic mouse model of PTLD. RAPA acts via cell cycle arrest, induction of apoptosis, and, most importantly, inhibition of interleukin 10 secretion, a necessary autocrine growth factor. The reduced interleukin 10 production is accompanied by corresponding decreases in the constitutive activation of the growth-promoting transcription factors signal transducer and activator of transcription 1 and 3. Thus, RAPA can limit B-cell lymphoma growth while simultaneously providing immunosuppression to prevent graft rejection in patients who are otherwise at risk for EBV-associated PTLD. Moreover, these findings may have application to other EBV-associated malignancies. (+info)
Human tissue preservation: development of regulations and removal of some legal barriers.
(59/498)
Human tissue must be obtained promptly postmortem if it is to be successfully preserved. Legal assistance toward this goal has been established by the California Legislature. To implement this legislation the State Board of Public Health has established regulations relating to human tissue preservation. These are the first such regulations in the nation. Tissue preservation is not yet fully developed. Much research is in progress to overcome many problems. The future may hold interesting developments. Present laws and regulations will implement them. (+info)
Passive transfer of contact sensitivity by tritiated thymidine-labeled lymphoid cells.
(60/498)
Passive transfer of tritiated thymidine-labeled lymphoid cells sensitized to the simple chemical DNFB into homologous guinea pigs resulted in positive contact skin reactions 24 hours after skin testing with DNFB. Labeled sensitized cells were found to accumulate at these sites, whereas, labeled nonsensitized lymphoid cells did not appear non-specifically in contact skin reaction sites. The labeled cells were small and large lymphocytes and immature cells of the lymphoid series. The maximum reactions were obtained at 24 hours, with an average of 3.4 per cent of the infiltrating mononuclear cells showing a label. At 48 hours, the macro- and microscopic reactions were similar to the 24 hour reactions but diminished in intensity, and the number of labeled cells in the infiltrates had decreased to 1 per cent of the total infiltrating mononuclear cells. (1/4) to (1/3) of the labeled cells were found within the epidermis in the test skin sites. These data have indicated that contact sensitivity, like tuberculin sensitivity, required the sensitized cell to initiate the skin reaction and that the majority of the cellular infiltrate was the result of non-specific host response to injury. (+info)
The role of the cheek pouch in effecting transplantation immunity in the hamster.
(61/498)
The cheek pouch of the hamster is alymphatic. Molecules, too large to penetrate the vascular endothelium, reach general circulation by slowly diffusing through the cheek pouch membrane to vessels found in the connective tissues in the neck and these vessels drain primarily into the superficial cervical node. The tissues of the cheek pouch membrane limit the diffusion of large particles and it is this "barrier" which explains, in part, the "privilege" conferred by the cheek pouch. (+info)
Antibody response to homografts. VIII. Relation of mouse hemagglutinins and cytotoxins.
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Antigenic differences between certain inbred strains of mice which could not be revealed by hemagglutination techniques were readily disclosed by lymphocyte cytotoxicity. With an improved cytotoxicity test lymphotoxic titers were as high as 1:512 with non-hemagglutinating A anti CBA antisera. In other mouse strain combinations, a close parallel of both types of antibody activity was obtained. Though both activities were absorbed from antisera proportionally by erythrocytes and lymph node cells, 100 to 1000 times as many erythrocytes as lymphocytes were necessary to produce an equivalent reduction in antibody activity. These findings suggest that erythrocytes may possess only subthreshold quantities of certain antigens which are present in readily detectable levels on lymphocytes. Lymphocyte cytotoxicity therefore may assay a wider range of allogenic antigens than hemagglutination. (+info)
Apparent reversion to trophism of a free omental graft: a preliminary report.
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In a previous paper we reported evidence which suggested that a free omental graft has trophic characteristics similar to those of the chorionic epithelium of the early embryo, through which it establishes arteriolar or larger connections with aorta, heart and pericardium within 10 days after it has been placed in contact with the denuded surfaces of each structure. The theory of omental trophism was tested by dropping pieces of omentum completely detached into the pleural and peritoneal cavities of white rats. When examined 25 or more days later a percentage of omental grafts appeared healthy and were attached to pleura, lung, heart and to various structures in the peritoneal cavity. In the pleural grafts, histological sections revealed a continuity between the omental grafts and the sub-pleural tissues. A blood-hungry free omental graft appears to seek out its own blood supply. Neither pleura nor serosa was able to repel its primitive probing for a new blood supply. (+info)
SPECIFICITY OF PASSIVELY TRANSFERRED DELAYED HYPERSENSITIVITY.
(64/498)
Guinea pigs were injected intravenously with lymphoid cells sensitized to tubercle bacilli (TBC cells) and with lymphoid cells sensitized by contact to a simple chemical, dinitrofluorobenzene (DNFB cells). In each transfer, either the TBC cells or the DNFB cells were labeled with H(3)-thymidine. Immediately after transfusion, each recipient was skin tested with PPD and DNFB. 24 hours later these lesions were removed for determination of total radioactivity and for autoradiographic analysis. When TBC cells labeled with H(3)-thymidine were transferred with DNFB cells without an isotopic marker, the total radioactivity and the concentration per gram of skin lesion were greater in the PPD test sites. In the reciprocal arrangement, when DNFB cells labeled with H(3)-thymidine were transfused with TBC cells without an isotopic tag, the total radioactivity and the concentration per gram of skin lesion were greater in the DNFB test site. Similar results were obtained in guinea pigs which were actively immunized by tubercle bacilli and passively by transfer of DNFB cells. Autoradiographic analysis of test sites from guinea pigs passively transferred with both types of sensitized cells confirmed these findings. By calculation, only a very small number of transferred sensitized cells reached the specific test lesion. Most of the cellular infiltrate was derived from the responding host. The specificity of the reaction of delayed hypersensitivity was apparently achieved by retention of the sensitized cells after they had arrived by chance at the specific antigen depot and was not due to a non-specific stickiness of sensitized or inflamed lymphoid cells. (+info)