Robarts Immunology and Transplantation Publications

Lymphocytes: Antigen-induced Gene Activation

Joaquin Madrenas — Sun, 24 Jan 2010 17:26:16 PST

Lymphocytes: Antigen-induced Gene Activation

Gabriel Criado et al. — Sun, 24 Jan 2010 17:11:12 PST

Lymphocytes are activated upon antigen recognition by their clone-specific surface antigen receptors. Lymphocyte activation includes multiple signalling cascades that converge in the cell nucleus to cause significant changes in the pattern of gene expression that determine the phenotype of activated lymphocytes and ultimately, the type of immune response.

Triggering of the T Cell Receptor: Implications for Transplantation

Joaquin Madrenas — Sun, 24 Jan 2010 16:54:32 PST

Isolation of a Murine Renal Cell Population which Expresses a Truncated T Cell Receptor-alpha mRNA

J. Madrenas et al. — Sun, 24 Jan 2010 16:43:16 PST

The Mediators of Inflammation (Interleukin-1, Interferon-tau and Tumor Necrosis Factor) and Their Relevance to Rejection

P. F. Halloran et al. — Sun, 24 Jan 2010 16:39:15 PST

The Molecular Immunology of Transplantation and Graft Rejection

P. F. Halloran et al. — Sun, 24 Jan 2010 16:35:05 PST

The Effect of Cyclosporine on One-Centre Long-Term Multivariate Analysis of Kidney Transplants

J. Madrenas et al. — Sun, 24 Jan 2010 16:27:04 PST

Non Immunological Analytic Data for the Differential Diagnosis between Miliary Tuberculosis (MTBC) and Bird Breeder's Disease (BBD)

J. Madrenas et al. — Sun, 24 Jan 2010 16:17:24 PST

A group of 86 patients diagnosed as having MTBC were compared to a group of 25 patients with BBD on the basis of various blood values included in routine analysis (hemogram, leukocyte count and differential, blood electrolyte values, urea, creatinine, total proteins and proteinogram). After statistical evaluation of the results, we concluded that the finding of low values for hemoglobin, and red blood cell (RBC) count and hematocrit, alterations of leukocyte count and differential, hypoalbuminemia, and hyponatremia, in a patient with fever and a miliary chest X-ray pattern, supports the diagnosis of MTBC. On the other hand, normal values for the above parameters, together with hypergammaglobulinemia favors the diagnosis of BBD. Our data also demonstrated a 79% mortality rate in patients with MTBC and plasma urea levels of more than 55 mg/100 ml (p less than 0.001).

Partial Recovery of Renal Function in an Oliguric Patient Affected with Goodpasture's Syndrome after Treatment with Steroids, Immunosuppressives, and Plasmapheresis

J. Fort et al. — Sun, 24 Jan 2010 15:57:16 PST

Hepatitis Toxica por Sales de Oro

Puig J. Madrenas et al. — Sun, 13 Dec 2009 06:34:50 PST

Polimiositis y Carcinoma Pulmonar

Puig J. Madrenas et al. — Sun, 13 Dec 2009 06:31:09 PST

Carcinoid Tumor, Atrophic Gastritis, and Iron Deficiency Anemia

Mercedes Biosca et al. — Sun, 13 Dec 2009 06:08:26 PST

Digoxin-like Immunoreacting Activity in the Serum of Patients on Regular Hemodialysis

J. Madrenas et al. — Sun, 13 Dec 2009 06:04:41 PST

Extra-Uterine Muumlllerian Carcinosarcoma

Magda Campins et al. — Sun, 13 Dec 2009 05:56:57 PST

Carcinosarcoma of the Müllerian system is an uncommon tumor. We report here a case of extra-uterine carcinosarcoma from pelvic wall, presenting 11 years after hysterectomy. Accidental surgical implantation of endometrioid cells is suggested as the pathogenic mechanism in this case.

An Alternative Approach for Statistical Analysis of Kidney Transplant Data: Multivariate Analysis of Single-center Experience

J. Madrenas et al. — Sat, 12 Dec 2009 14:12:16 PST

To avoid the center effect and the possible hidden interactions of multicenter studies, the validity of the Cox Proportional Hazards Model for the analysis of a single-center kidney transplant program was tested, considering 287 renal transplants performed in a 10-year period. The inclusion of type of donor and main immunosuppressive drug as covariates in the model did not violate the proportionality assumption of the Cox model. According to this method, the following covariates were significant in predicting graft survival: cyclosporine, type of donor, good human leukocyte antigen (HLA)-A and HLA-B match (DR data were not considered), highest percentage of reactive antibodies against panel cells, and nephroangiosclerosis as a primary renal disease. Cyclosporine did not significantly improve graft survival in living related donor transplants. Pretransplant blood transfusions, cold ischemia time, and donor ABO blood group were initially significant but dropped out in the step-down procedure. Recipient's age at transplant, cyclosporine, HLA-A and HLA-B match, and nephroangiosclerosis were significant in predicting patient survival. It was concluded that using long-term data of cadaveric and living related renal transplants either on azathioprine or cyclosporine is a valid way to perform multivariate analysis of single-center transplant programs that do not have large samples.

Regulation of MHC Transcription

Philip F. Halloran et al. — Sat, 12 Dec 2009 14:09:47 PST

The Mechanism of Action of Cyclosporine: A Perspective for the 90's

Philip F. Halloran et al. — Sat, 12 Dec 2009 14:07:17 PST

The introduction of cyclosporine (CyA) as a pharmacological agent has resulted not only in a dramatic improvement in the clinical management of transplant recipients but also in a better understanding of the molecular basis of the immune response, especially T cell function. Knowledge of the mechanism of action of CyA has led to exciting areas of study. Among these are the sequence of regulatory events leading to T cell activation, the potential relevance of isomerases in signal transduction pathways (as the receptor for CyA, cyclophilin has been shown to be an isomerase), the blocking effect of CyA on the development of multidrug resistance, and the striking parallelism between CyA and the newer immunosuppressive agent FK-506. These fields promise to be relevant in solving some of the crucial questions in transplantation immunology, and developing better strategies for immunosuppression.

Interferon Gamma-mediated Renal MHC Expression in Mercuric Chloride-induced Glomerulonephritis

Joaquín Madrenas et al. — Sat, 12 Dec 2009 14:05:42 PST

Interferon gamma-mediated renal MHC expression in mercuric chloride-induced glomerulonephritis. In rodents, mercuric chloride (HgCl2) causes an autoimmune disorder with glomerulonephritis (GN), and represents an animal model for the pathogenesis of GN. We have tested the hypothesis that HgCl2 induces major histocompatibility complex (MHC) expression in renal parenchymal cells, and studied the kinetics of this induction and its temporal relation to the development of immune complex deposition in the glomeruli. Mice treated with doses of HgCl2 between 2 and 3.2 mg/kg three times for one week had increased renal expression of MHC class I and class II (at the mRNA and the product levels). Class I induction was observed in proximal tubule cells, endothelial cells and glomerular cells. Class II induction was seen mainly in interstitial cells and, to a lesser extent, in tubule cells. Rénal MHC expression was maximal at one week, decreased progressively after the second week of HgCl2 administration, and reached basal levels by 23 weeks. In contrast, the amount of lymphocyte infiltration in the kidney increased from the first to the fifth week and was followed by the appearance of glomerular immune deposits from the third week on. Glomerular immune complex deposits were maximal at five weeks and, by 23 weeks, immune deposits in HgCl2-treated mice were only slightly increased over those observed in the sham group. Renal MHC induction by HgCl2 was significantly reduced by treatment with monoclonal antibody against interferon gamma. Our results indicate that, in the early phase of HgCl2-induced GN, there is induction of expression for MHC class I and II products, mediated by interferon-gamma (INF-gamma), and raise the possibility that the induction of MHC expression or other changes in gene expression induced by INF-gamma may be involved in the later development of autoimmune renal injury.

Thymus-independent Expression of a Truncated T Cell Receptor-alpha mRNA in Murine Kidney

J. Madrenas et al. — Sat, 12 Dec 2009 14:02:05 PST

During studies on gene expression in the kidney, we unexpectedly observed that murine kidney expresses a truncated form of TCR-alpha mRNA (1.3-1.4 kb). This transcript was not associated with the presence of complete TCR-alpha mRNA (1.7 kb) or detectable TCR-beta or -delta transcripts, thus indicating that the truncated TCR-alpha mRNA could not be attributed to blood contamination of the kidney RNA preparation. The truncated TCR-alpha message appeared to contain at least the C alpha region, as suggested by hybridization with an intra-C alpha 24 oligonucleotide probe, by amplification of the C alpha region with the polymerase chain reaction from total kidney mRNA, and by sequencing of, and hybridization with, the amplified products. In situ hybridization of kidney sections indicated that the transcript was expressed in interstitial cells. Northern blots of cortex and medulla RNA showed that the cells expressing the truncated TCR-alpha mRNA were predominantly located in the medulla. To investigate the possibility that the transcript was not produced by T cells or NK cells, fractionation of renal cell suspensions were performed. The truncated TCR-alpha mRNA was detected in a fraction containing large (low buoyant density) cells in which no expression of CD3, Thy 1, or NK-1.1 was detected, indicating that these cells are not mature T cells, do not express a functional TCR, and are not NK cells. The cells expressing the truncated TCR-alpha mRNA were radiosensitive, and were not thymus dependent, because this transcript was as abundant in nude mice as in normal mice. The transcript was not detected in bone marrow. Expression of the truncated TCR-alpha mRNA was not dependent on an intact recombinase activity as its expression was not affected by the severe combined immunodeficiency mutation. Our results show that murine kidney contains a population of radiosensitive thymus-independent large interstitial cells that express a truncated TCR-alpha mRNA that is not associated with surface expression of functional TCR. These cells may have attempted to rearrange TCR-alpha genes, suggesting that they may be related to the lymphoid lineage.

Complement-dependent Cytotoxicity for Negative Selection at the mRNA Level

N. S. Gill et al. — Sat, 12 Dec 2009 13:58:32 PST

Complement-Dependent Cytotoxicity (CDC) is a common technique used for isolating and characterizing cell populations. However, the molecular events resulting from CDC-mediated cell injury remain obscure. In order to use CDC as a selection procedure for studies at the RNA level, we examined if CDC is associated with rapid degradation of RNAs from target cells without affecting the stability and viability of RNAs of non-target cells. Using a model of anti-CD3-mediated CDC, we show that T cell-specific RNAs were absent immediately after CDC. However, ribosomal RNAs and mRNAs from non-targeted cells (non-T cells) were not affected by CDC. Our results indicate that CDC is associated with rapid degradation of only target cell RNAs, validating CDC as a method for cell isolation without interfering with further studies at the RNA level.