Search PubMed⌕ Search

Biomedical subjects

M L Rose

Publications and source records attributed to M L Rose.

At least 91 records · Page 5Linked to original sources
PubMed1993

Effect of tirilazad mesylate (U74006F) on eicosanoid and tumor necrosis factor generation in healthy and endotoxemic neonatal calves.

The effects of a 21-aminosteroid, tirilazad mesylate (U74006F; The Upjohn Co., Kalamazoo, MI), developed for treatment of central nervous system trauma in human beings, on eicosanoid and tumor necrosis factor (TNF) generation were evaluated in both healthy and endotoxin-challenged neonatal calves. Endotoxemia was induced in 24 neonatal calves by intravenous infusion of Escherichia coli lipopolysaccharide (3.25 micrograms/kg) over 3 hr. Group I calves received the endotoxin infusion alone; group II calves received an infusion of 0.9% saline and were treated with tirilazad mesylate (1.5 mg/kg) 1 hr after the infusion was started, group III and IV calves were treated with tirilazad mesylate 1 hr after or before endotoxin infusion was started. Tirilazad mesylate effectively suppressed production of plasma prostacyclin (6-keto-PGF1 alpha) and TNF in endotoxin-challenged neonatal calves. In addition, production of thromboxane B2 was mitigated by treatment with tirilazad mesylate both 1 hr before and 1 hr after initiation of endotoxin infusion. It appears that tirilazad mesylate effectively suppresses eicosanoid and TNF generation induced by endotoxin, and thus may be beneficial in the treatment of endotoxemia and septicemia in neonatal calves.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Anti-endothelial antibodies and coronary artery disease after cardiac transplantation.

Accelerated coronary artery disease is the most serious complication after cardiac transplantation. The disease has a multifactorial aetiology, with little agreement about the relative importance of the various risk factors. We have investigated the frequency of anti-endothelial antibodies against human umbilical vein endothelial cells by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis and western blotting. Peptide-specific anti-endothelial antibodies were found in 15/21 heart transplant recipients with accelerated coronary artery disease, and 1/20 transplant patients who had not developed the disease. Positive immunofluorescence of patients' serum on frozen sections of coronary vessels confirmed the endothelial specificity of antibodies. These results provide evidence of an immune aetiology for transplant-associated coronary artery disease and could have important implications for its diagnosis and therapy.

Adolescent↗
PubMed1992

Antiheart antibodies following open heart surgery: incidence and correlation with postpericardiotomy syndrome.

One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis of myocardial proteins followed by Western blotting is a sensitive method for the detection of antiheart antibodies after cardiac transplantation. In a previous study we found that the majority of patients made antiheart antibodies after cardiac transplantation. It is possible that these antibodies were formed in response to cardiac damage caused during the surgical procedure rather than being specific to the transplantation situation. In this study we have evaluated the role of open cardiac surgery in the formation of antiheart antibodies for the first 9 months of the postoperative period using the Western blotting technique and correlated that with the development of post-pericardiotomy syndrome. Only 25% (9/36) of patients showed any increase in the pre-existing level of antiheart antibodies or developed antiheart antibodies with new reactivities. None of the patients in the study developed manifestations specific for post-pericardiotomy syndrome during the period of follow-up. The results support the contention that the high incidence of antiheart antibodies formed after cardiac transplantation is due to a humoral immune response to the presence of alloantigens on the grafted heart rather than as a result of the surgical procedure itself.

Adult↗
PubMed1992

Specificity of lymphocytotoxic antibodies formed after cardiac transplantation and correlation with rejection episodes.

Eighty-two patients have been studied to determine the class and specificity of lymphocytotoxic antibodies produced during the 6 months following cardiac transplantation. Weekly serum samples were monitored for panel-reactive lymphocytotoxic antibodies (PRA) and donor reactive lymphocytotoxic antibodies using dithiothreitol to determine immunoglobulin class. Sera containing donor-reactive antibodies were further analyzed in a cytotoxic inhibition assay to determine whether the antibodies were directed against HLA or non-HLA determinants. A total of 67 (82%) of the patients produced detectable PRA following transplantation, no correlation was found between PRA and the incidence and severity of rejection. In 33 cases where an HLA specificity was defined, the antibody was not directed against the donor HLA phenotype. In contrast, the 32 (53%) recipients who had formed donor-reactive antibodies within 6 months of operation had required significantly more antirejection therapy (methylprednisolone) than the crossmatch-negative recipients (P less than 0.01). This was the case for both IgG and IgM responses. Of 24 positive donor responses, 18 were found to be specific for HLA antigens. These were both IgM (6 cases) and IgG (12 cases) HLA-specific antibodies, and their occurrence was strongly correlated with rejection (P less than 0.001).

Adult↗
PubMed1992

Induction of vascular adhesion molecules during rejection of human cardiac allografts.

Adhesion of leukocytes to vascular endothelium is a necessary step leading to the migration of cells into underlying tissues. Vascular adhesion molecules regulate this process and may play an important role in graft rejection. Immunocytochemical studies have been used to investigate the expression of vascular adhesion molecules (ICAM-1, PECAM, VCAM-1, and ELAM-1) in normal donor heart (n = 15) and myocardial biopsies from heart transplant patients with acute rejection (n = 15). Sections were also stained with antibodies against endothelium, leukocytes, MHC antigens, and markers of cell activation. In donor heart EN4, vWF, ICAM-1, PECAM, MHC class I--and, to a lesser extent, VCAM-1 and DR antigen--are expressed on arterioles and venules, whereas ELAM-1 and Pal-E are restricted to venules. Expression of Pal-E, VCAM-1, ICAM-1, and DR antigen was increased during rejection. Capillary endothelium normally expresses EN4, ICAM-1, PECAM, MHC class I, and DR antigen but little, if any, VCAM-1 or ELAM-1. During rejection, however, there is an increased expression of all adhesion molecules. This is paralleled by an increased expression of vWF by capillary endothelium. In addition, ICAM-1 like MHC class I antigen is induced on the myocardial membrane and intercalating discs. Endocardium from donor heart expresses EN4, vWF, PECAM, MHC class I, and sometimes Pal-E and ICAM-1, but very little VCAM-1, ELAM-1 or DR antigen. There is an increased expression of Pal-E, ICAM-1, VCAM-1, and DR antigen on endocardium from rejecting heart biopsies. Proliferating Ki-67+ cells and activated T cells expressing the receptor for IL-2 were also found in biopsies during rejection episodes.

Adolescent↗
PubMed1992

Clinical efficacy of tirilazad mesylate for treatment of endotoxemia in neonatal calves.

The clinical efficacy of the lazaroid, tirilazad mesylate, a new therapeutic agent for prophylaxis and treatment of endotoxemia, was evaluated in 24 neonatal Holstein calves. Endotoxemia was induced by IV infusion of commercial Escherichia coli lipopolysaccharide (3.25 micrograms/kg of body weight) over 3 hours. Group-1 calves were given endotoxin alone; group-2 calves were given an infusion of 0.9% sterile saline solution, then were treated with tirilazad mesylate (1.5 mg/kg) 1 hour after the infusion was started. Group-3 calves were treated with tirilazad mesylate 1 hour after the start of the endotoxin infusion, and group-4 calves were given tirilazad mesylate 1 hour before the start of the endotoxin infusion. Clinical signs of endotoxemia were mitigated by tirilazad mesylate. In addition, tirilazad mesylate protected calves from endotoxin-induced hyperglycemia; treatment after endotoxin infusion decreased the severity of hypoglycemia and prevented lactic acidosis. Treatment with tirilazad mesylate after initiation of endotoxin infusion was as protective as was pretreatment.

Animals↗
PubMed1991

Renal haemodynamics of cyclosporin A nephrotoxicity in children with juvenile dermatomyositis.

1. Renal haemodynamics were monitored over an average period of 19 months in 17 children being treated with cyclosporin A. Sixteen had juvenile dermatomyositis and one had chronic polyneuropathy. The dose of cyclosporin A ranged from 2.3 to 8.3 mg day-1 kg-1 (median 4.1 mg day-1 kg-1). 2. Glomerular filtration rate (expressed in terms of extracellular fluid volume), renal blood flow (expressed as a fraction of cardiac output) and filtration fraction were measured by using 99mTc-labelled diethylenetriamine-penta-acetate. They were compared with the dosage and trough blood levels of cyclosporin A, and, in 15 patients receiving prednisolone in addition to cyclosporin A, with steroid dosage. 3. All 17 children had a renogram performed 6 months after starting cyclosporin A treatment. Nine of them also had a renogram before starting cyclosporin A treatment (baseline study), while 13, in addition to their renogram 6 months after starting cyclosporin A treatment, also had at least one further renogram. 4. Glomerular filtration rate/extracellular fluid volume fell slightly but significantly from 0.009 (SD 0.0013) before starting cyclosporin A treatment to 0.0085 (0.002) min-1 (P less than 0.01) 6 months after cyclosporin A treatment in the nine children who underwent a baseline study. This was accompanied by a significant (P less than 0.001) fall in filtration fraction from 0.108 (0.015) to 0.088 (0.014). However, renal blood flow/cardiac output showed no change. 5. In the 13 children studied beyond 6 months after starting cyclosporin A treatment, there was no further significant overall change in any renal haemodynamic variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Immune response to the endothelium in myocarditis, dilated cardiomyopathy and rejection after heart transplantation.

The role of endothelial cells in inflammatory heart disease and rejection after heart transplantation is only partly understood. To determine whether an immune reaction against endothelial cells occurs we examined endomyocardial biopsies from patients with myocarditis (n = 13), dilated cardiomyopathy (n = 23), no clinical rejection (n = 10) and moderate to severe rejection after heart transplantation (n = 10). These were compared to 'normal' donor hearts with monoclonal endothelial-specific antibodies EN4, Pal-E and F VIII-related antigen. Nearly all endothelial cells were stained positively with EN4. There were no significant changes in the binding of the antibodies except in rejection when Pal-E and F VIII-related antigen were significantly increased. It is concluded that apart from their possible role as antigen-presenting cells, endothelial cells are important targets in rejection after heart transplantation. Damage or cytolysis of endothelial cells may cause both altered transendothelial permeability and functional decrease in antigen presentation.

Antibodies, Monoclonal↗
PubMed1991

Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value.

Enteroviruses are well recognized in the aetiology of myocarditis. Molecular hybridization using enterovirus group-specific probes shows that virus can be detected in endomyocardial biopsies and persists in myocardium after the inflammation heals. Virus persistence is associated with the subsequent development of dilated cardiomyopathy, progressing to end-stage disease requiring cardiac transplantation. Infectious virus cannot usually be isolated from myocardium nor can virus-specific antigens be detected after the initial inflammatory stage. Patients with healed myocarditis or dilated cardiomyopathy may have no histological evidence of inflammation despite detection of virus-specific RNA sequences by molecular hybridization. Persisting enterovirus RNA in dilated cardiomyopathy is the strongest known predictor of poor prognosis. The molecular mechanism of virus persistence is the selection of defective virus mutants during the initial phase of disease.

Cardiomyopathy, Dilated↗
PubMed1991

Demonstration by western blotting of antiheart antibodies before and after cardiac transplantation.

Western blotting has been used to detect antiheart antibodies in two groups of patients: two who required retransplantation for hyperacute rejection, and 22 consecutive patients, whose serum was tested at monthly intervals for three months following transplantation. Pretransplant and posttransplant serum samples were tested for IgM and IgG reactivity against the patients own heart and donor heart. In all patients the pretransplant lymphocytic crossmatch had been negative. In the two patients requiring retransplantation, both had multiple bands of strong IgM and IgG against their own heart prior to transplantation as well as antibodies against the donor heart. The study of 22 consecutive patients revealed that (1) the presence of strong antibody prior to transplantation is associated with unusually severe or frequent rejection episodes, (2) 20/22 patients made antiheart antibody following transplantation, but in 12 patients it was IgM only, and (3) most of the antiheart antibodies made posttransplant were not specific for the donor heart. Comparison of Western blotting with immunofluorescent detection of antibodies on frozen sections revealed that the Western blotting procedure is more sensitive and results are easier to interpret.

Adolescent↗
PubMed1990

Mediastinal squamous cell carcinoma and thyroid carcinoma in an aged horse.

A mediastinal squamous cell carcinoma and thyroid carcinoma were found in an aged horse. Clinical signs consisted of bilateral thyroid gland enlargement, chronic cough, and mild respiratory distress. The neoplasms were not treated. Squamous cell carcinoma is a common neoplasm in horses, but not in the cranial portion of the mediastinum. Thyroid carcinomas in horses are uncommon. This combination of neoplasms is rare and may have been associated with a defect in the immune system.

Animals↗
PubMed1990

Improved high-performance liquid chromatographic method for analysis of cyclosporin A using an automated sample processor.

Transplant patients receiving the immunosuppressive drug cyclosporin A require regular monitoring to maintain levels within a narrow therapeutic range. A stable, accurate and reproducible high-performance liquid chromatographic method for analysis of cyclosporin A in whole blood has been developed using the Varian Advanced Automated Sample Processor. Starting with 200 microliters of blood, absolute recovery of both cyclosporin A and the internal standard was 81% with a detection limit of 12.5 ng/ml. The assay is perfectly linear over the range 0-1000 ng/ml (r2 = 1.0). At a concentration of 250 ng/ml, the coefficient of variation, both between samples and between assays, is 1.87%. Chromatographic cycle time is 10.2 min per sample. Up to eighty samples can be processed by one person in a working day, with final results within 16 h.

Automation↗
PubMed1990

Identification of antigen presenting cells in normal and transplanted human heart: importance of endothelial cells.

The nature of class II-positive cells in normal and transplanted human heart has been investigated using immunoperoxidase and dual-immunofluorescent techniques. In normal heart approximately 83% of DR expression can be accounted for by EN4+ endothelial cells, most of which express intercellular adhesion molecule 1 constitutively. Few cells bearing the leukocyte common antigen are found in normal heart; most of them are RFD7+ macrophages or T cells. There is a paucity of RFD1+ dendritic cells. In transplanted heart showing signs of rejection, the infiltrate consists of RFD7+, RFD1+, RFD7+, RFD1+ cells and T lymphocytes. The increased class II expression within these biopsies is confined to the infiltrating cells. Dual-immunofluorescence demonstrates that nearly all the RFD1+ cells are from the recipient. In conclusion, in normal heart presentation of allogeneic class II is by the intercellular adhesion molecule-1-positive endothelial cells. After transplantation, there is an influx of recipient cells of the macrophage/dendritic series which are probably able to process allogeneic class II.

Antigen-Presenting Cells↗
PubMed1990

Immunocytochemical changes suggestive of damage to endothelial cells during rejection of human cardiac allografts.

Interest in the endothelium as a possible initiator or target of the antiallograft response prompted the following study. Immunocytochemical techniques have been used to investigate the expression of the endothelial markers EN4, Pal-E, and FVIII-RA in normal human heart, cardiac biopsies from patients with various cardiac diseases (dilated cardiomyopathy [DCM] and myocarditis [MCO]), and cardiac biopsies from heart-transplant recipients undergoing acute rejection or free of rejection. Quantitative data demonstrated greater preponderance of EN4 cells in normal heart than the other markers. In biopsies showing histologic signs of rejection, there was no difference in the number of EN4 positive cells compared to normal. In contrast, there was found a striking increase in the proportion of cells that are Pal-E positive and a significant increase in the proportion of FVIII-RA positive cells in these biopsies. The patient details provided suggest these results do not reflect vascular damage due to cyclosporine but may well reflect damage caused by the rejection process.

Adolescent↗
PubMed1990

Selection for donor-specific cytotoxic T lymphocytes within the allografted human heart.

Lymphocytes were cultured from cardiac biopsies following heart transplantation using interleukin-2-conditioned medium. Using the technique of limiting dilution analysis the frequency of donor specific cytotoxic T lymphocytes was measured in cells cultured from biopsies and compared with that in peripheral blood lymphocytes taken at the same time as the biopsy. The graft cell population showed a considerably higher frequency of donor-specific CTL when compared with the PBL. CTL frequencies in the graft cells were always higher against the donor than against third-party cells. These data demonstrate that there was either selective sequestration or selective expansion of donor-reactive T cells in the heart following cardiac transplantation. These results emphasize the need to investigate more closely the events occurring in the heart, and may explain the lack of specificity and sensitivity in immune monitoring (IM) or cytoimmune monitoring (CIM) seen in many centers.

Antigens, CD↗