PubMed Health⌕ Search

Biomedical subjects

M W Flye

Publications and source records attributed to M W Flye.

At least 181 records · Page 10Linked to original sources
PubMed1988

Characterization of kidney cell-specific, non-major histocompatibility complex alloantigen using antibodies eluted from rejected human renal allografts.

Previous studies from our laboratories (1) have indicated that eluates prepared from rejected kidneys have antibodies not only reactive to MHC class I and class II antigens but also to antigens unique for monocytes, endothelial cells, and kidney cells. To further define the serological and biochemical nature of antigens detected by the antibodies eluted from rejected kidneys, 13 eluates prepared from rejected renal allografts and two eluates from normal kidneys were absorbed with pooled platelets, normal splenic leukocytes and/or B cells from chronic lymphocytic leukemia patients. All of the eluates failed to react with normal T and B lymphocytes by microcytotoxicity and immunofluorescence assays. However, the eluates from rejected kidneys, but not normal kidneys, reacted with peripheral blood monocytes, endothelial cells cultured from umbilical cord as well as primary kidney cells. Detailed immunohistochemical analysis of frozen kidney sections showed that the eluates from rejected kidneys reacted with structures of the cortex while sparing the structures in the medullary region. All eluates bound to the glomerulus with intense fluorescence, but not to the mesangium and Bowman's capsule, while binding to interstitial capillaries, venous endothelium, and tubular epithelium varied. More significantly, none of the eluates reacted with frozen sections of the liver, spleen, or lymph node including the endothelial lining of blood vessels in these organs. Thus, the data indicate that the eluates prepared from rejected kidneys are recognizing organ-specific antigens expressed on the kidney cells. To identify the alloantigen(s) recognized by the eluted antibodies, an immunoblot analysis was performed against phase separated membrane proteins isolated from cortical kidney cells solubilized in 2X precondensed Triton X-114. A protein of Mr. 90,000-100,000 was identified as the target non-MHC antigen to which the eluates prepared from rejected allografts were reactive. Furthermore, our results suggest a possible polymorphism among these antigens.

Endothelium, Vascular↗
PubMed1988

Renal allograft recipient immunomodulation by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 151 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate and 21 were two-haplotype disparate. Presensitization was present in ten patients and attempts at desensitization were uniformly unsuccessful. Of the 151 nonpresensitized patients, transient sensitization occurred in 3% and permanent sensitization in 7%. One hundred thirty-five of 140 nonsensitized patients underwent renal transplantation from the specific blood donor and 56% have never experienced a rejection episode. The allograft survival rate at 2 years (93%) and 7 years (87%) is significantly better (P less than .01) than our historical experience with one-haplotype living-related transplants at 2 years (68%) and 7 years (59%). The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (2%) argue for a modification of the immunologic response, perhaps by clonal deletion, rather than a selecting-out process as the mechanism for improved allograft survival.

Azathioprine↗
PubMed1987

Arteriovenous shunt construction for vascular access in the rat.

A method is described that allows high-frequency venous and arterial blood sampling in the laboratory rat. After distal ligation and division of the external jugular vein and carotid artery, sections of Teflon intravenous catheters are inserted and secured with circumferential ligatures. Between these Teflon segments, a vascular circuit is maintained with the interposition of silicone tubing. The silicone tube segment has been filled with heparinized saline, divided in half, and joined at its center by another segment of the catheter. This in situ arteriovenous (AV) shunt system is secured in the neck of the host animal by creating a subcutaneous tunnel and externalization of a portion of the shunt loop. The shunt facilitates repetitive blood sampling from the conscious rat. The procedure time is approximately 45 minutes, and patency can be assured over several days. Additional uses of the system include pretreatment injection protocols and postoperative drug therapy.

Animals↗
PubMed1987

Reversal of ischemic liver failure by intrasplenic liver cell transplantation.

A model of ischemic hepatic failure in Sprague-Dawley rats (SD) with 100% mortality has been developed by one-hour occlusion of the right portal vein and hepatic artery followed by left 70% hepatectomy. The intrasplenic injection of 40 x 10(6) syngeneic adult or three-day neonatal single liver cell suspensions decreased the mortality from 100% to 50% and 36%, respectively. Mortality decreased with increasing time from the intrasplenic injection of neonatal liver cells to the time of acute hepatic ischemia. Mortality also decreased with increasing interval between hepatic ischemia and removal of the transplanted liver cells by splenectomy. Intrasplenic injection of graded doses of neonatal liver cells decreased mortality from 75% at a dose of 10 x 10(6) cells, to 36% at 160 x 10(6) cells. Treatment of neonatal liver cells with metabolic inhibitors did not significantly affect their ability to reverse acute hepatic ischemia.

Animals↗
PubMed1987

T-lymphocyte subsets in renal allograft recipients treated with cyclosporine and azathioprine.

Thirty-nine renal allograft recipients were prospectively studied to determine the quantitative effects of different immunosuppression protocols on T-cell subsets (total lymphocytes [T3], helper/inducer [T4] and suppressor/cytotoxic [T8]). Eighteen patients were initially immunosuppressed with only azathioprine and prednisone but required subsequent treatment for rejection by the addition of antithymocyte globulin (ATG) (Upjohn, Kalamazoo, MI) or conversion to cyclosporine. Three of these patients had ATG-resistant rejections and were treated with the monoclonal antibody ORTHO OKT3 (ORTHO Pharmaceuticals, Raritan, NJ). Twenty-one patients were treated only with cyclosporine and prednisone. Plasma levels of cyclosporine, as determined by high-performance liquid chromatography, were kept in the range of 50-100 ng/mL (mean: 78.1 +/- 52.1). One patient had a lymphoma, two patients had failed grafts, and three patients converted their cytomegalovirus titers. The results demonstrate that the immunosuppressive agents, azathioprine, prednisone, and cyclosporine, have an additive effect in depressing the T-lymphocytes and their subsets. In addition, ATG and cyclosporine had a more selective ablation of the T4 subset, resulting in a reversal of the T4/T8 ratios. This depression was independent of the plasma level of cyclosporine. Finally, the pan T-cell monoclonal antibody OKT3 led to severe depletion of all T-cell subsets but resulted in a normal T4/T8 ratio. In conclusion, immunosuppressive agents have a variable effect on T-lymphocytes and their subsets that cannot be adequately characterized by the T4/T8 ratio alone, but which should be quantitatively assessed by examining all subsets.

Antibodies, Monoclonal↗
PubMed1987

Antiidiotypic antibodies to human major histocompatibility complex class I and II antibodies in hepatic transplantation and their role in allograft survival.

In order to evaluate the role of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, serial serum samples obtained from 10 liver recipients both pre- and posttransplantation were analyzed for the development of HLA alloantisera inhibitory activity by a microcytotoxicity inhibition assay. Seven of the 10 recipients developed strong anti-anti-HLA activity during the immediate posttransplant period, which was able to block killing of a specific alloantiserum to class I MHC antigens (44-100%). Recipients' sera were also able to block class II alloantisera (HLA-DR8) cytotoxicity of B-lymphocytes. The inhibitory activity developed 10-15 days posttransplantation, was cyclical, and was present in the immunoglobulin fraction of the serum. One patient developed specific antibodies to anti-HLA-B7 and had no inhibition for alloantisera to HLA-B8,B17,B49 and B13. Another developed antibodies capable of blocking anti-HLA B44 (mismatched donor antigen) and also cytotoxicity of HLA-B17,B49 (crossreactive group), but showed no significant inhibition of HLA-B13,B8 and B7. One recipient, transplanted across strong (1:500 titer) antilymphocyte crossmatch, rejected the graft within 1 month and failed to develop any inhibitory antibodies to anti-HLA. Two other patients who lost their grafts within 2 months posttransplantation developed only minimal (11% and 16%) and transient inhibition. Immunoprecipitation of surface-labeled, mixed lymphocyte culture stimulated lymphocytes, with sera containing inhibitory antibodies, identified membrane components of approximate molecular weights of 54,43 and 17,000, suggesting T cell clonotypic structures. Thus, these studies provide support for the development of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, which may play a regulatory role in the tolerance of allograft.

Antibodies, Anti-Idiotypic↗
PubMed1987

Hepatoblastoma presenting as isosexual precocity. The clinical importance of histologic and serologic parameters.

A 2-year-old boy presented with sexual precocity secondary to a hormone-producing hepatoblastoma. The tumor demonstrated an aggressive histologic pattern and stained immunohistochemically for alpha-fetoprotein and beta-subunit human chorionic gonadotrophin. After a successful liver transplant these tumor markers were closely followed. We conclude that histologic subclassification of hepatoblastoma is most useful for predicting likelihood of resectability. Tumors with predominantly fetal-type histology tend to be better circumscribed and are more likely to be resectable with improved survival relative to tumors with predominantly embryonal histology. The presence or absence of mesenchymal elements does not seem to have prognostic importance. Anaplastic features predict a poor outcome, but it remains for these to be uniformly defined and applied. Small uniform cellular histology with neuroblastoma-like differentiation appears to be particularly ominous. Serologic tumor markers, especially alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) are useful as monitors of potential tumor recurrence, but their efficacy is compromised by the unpredictable variation of tumor cell metabolism, undoubtedly a result of the genetic instability and heterogeneity of proliferating malignant cells.

Carcinoma, Hepatocellular↗
PubMed1987

Preoperative immunomodulation of renal allograft recipients by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 113 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor/recipient combinations were at least 1-haplotype disparate and 17 were 2-haplotype disparate. Presensitization, defined as a positive Amos or antiglobulin T cell CM or a positive high-titer (greater than or equal to 1:8) B cell CM was present in 10 patients and not present in 103 patients. Attempts at desensitization of the already sensitized group were uniformly unsuccessful. Treatment of the 103 nonpresensitized patients resulted in transient sensitization in 3 patients, permanent sensitization in 8, and no evidence of sensitization in 92. Ninety-one nonsensitized patients underwent renal transplantation from the specific blood donor, and only 5 have experienced renal allograft rejection loss during a mean follow-up period of 26 months (6 to 70 months). Fifty-four percent have never experienced a rejection episode. The allograft survival rate at 2 years (91%) and 5 years (89%) is significantly better (P less than .01) than our historical experience with 1-haplotype living-related transplants at 2 years (66%) and 5 years (64%). The low rate of sensitization (8%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of rejection (5%) argues for a modification of the immunologic response rather than a selecting out process as the mechanism for improved allograft survival.

Azathioprine↗
PubMed1986

Dysphagia aortica. Clinical, radiological, and manometric findings.

Three patients with dysphagia caused by compression of the distal esophagus by a tortuous nonaneurysmal atherosclerotic aorta are described. All three patients were elderly women; systemic hypertension and cardiomegaly were present in two patients. Barium studies of the esophagus showed displacement and compression of the distal esophagus by the thoracic aorta. Debilitating dysphagia was treated surgically in one patient. The other two patients had milder symptoms and were managed conservatively. Esophageal manometry in these three patients showed superimposed pulsations and elevated intraluminal pressure just proximal to the lower esophageal sphincter. To evaluate the significance of these manometric findings and their correlation with clinical symptoms, we reviewed manometric tracings in 47 normal subjects. Ten of these subjects had an elevation of baseline intraluminal esophageal pressure as a result of superimposed vascular pulsations. We conclude that compression of the distal esophagus by a tortuous atherosclerotic aorta in the appropriate setting can lead to clinically significant dysphagia and a manometric finding of vascular compression of the esophagus does not necessarily correlate symptomatic dysphagia.

Adult↗
PubMed1986

Liver transplant rejection arteritis: serial hepatic arteriography.

Two liver transplant recipients underwent serial hepatic arteriography, demonstrating a severe, rapidly progressive arteritis involving the hilar hepatic arteries. Liver biopsies in these patients demonstrated ischemic necrosis as a prominent feature. The angiographic appearance and therapeutic implications of liver transplant rejection arteritis are presented.

Arteritis↗
PubMed1986

Renal allografts in acute rejection: evaluation using duplex sonography.

Sixty-nine duplex sonographic studies were performed in 24 patients who had received renal allografts. After a prospective qualitative analysis of the Doppler waveforms, results were correlated with biopsy material and each patient's clinical course. Increased pulsatility of the Doppler waveform of intrarenal arterial flow constituted an abnormal study, indicating acute rejection. Overall sensitivity varied with the histologic form of rejection, with a 60% sensitivity for acute interstitial rejection with or without vascular rejection and an 82% sensitivity for acute vascular rejection. Overall specificity was 95% and 96%, respectively. Early rejection was also accurately detected in three patients less than 48 hours following kidney transplantation. Duplex sonography has a useful role in evaluating posttransplantation renal failure. Abnormal study results may obviate the need for biopsy and help in guiding clinical management.

Adolescent↗
PubMed1986

Liver transplant recipients: portable duplex US with correlative angiography.

Twenty patients, aged 4 months to 58 years, were evaluated for liver transplantation by duplex sonography, and 15 transplantations were completed; 42 postoperative examinations were performed. Sonographic findings were correlated with seven preoperative and five postoperative angiographic evaluations. Preoperative duplex US findings included tumors, portal vein occlusion, varices, biliary obstruction, and variant vascular anatomy. Postoperative findings included hepatic artery occlusion, portal vein occlusions (one with cavernous transformation), portal vein stenosis, biliary obstruction, intrahepatic and extrahepatic fluid collections, and air in the portal vein due to ischemic bowel. Use of angiography allowed confirmation of the vascular abnormalities and demonstrated evidence of rejection in patients with normal Doppler waveforms. Duplex sonography is a valuable portable technique for evaluating these patients and can be used in triage of patients requiring angiography.

Adolescent↗
PubMed1986

Relationships of cyclosporine concentrations in serum, whole blood, and bile after renal and hepatic transplantation.

"Trough" (minimum inter-dose) cyclosporine concentrations were measured by liquid chromatography in samples of serum and whole blood or bile obtained from renal- and hepatic-transplant patients. Overall, concentrations in whole blood correlated poorly with concentrations in concurrently obtained serum. The poor correlation also held for individual patients over time. The degree of variability observed for individuals is especially disconcerting. Although cyclosporine measurements in whole blood may mitigate time- and temperature-dependent changes in the drug's distribution after collection, concentrations in serum separated after distribution are less dependent on the cellular mass in blood, and may better reflect the amount of drug available to receptor sites. This consideration may be particularly important in the postoperative period, when fluctuations in the cellular mass of blood are frequent. Concentrations of cyclosporine were also determined in concurrently collected bile and serum samples after liver transplantation. Concentrations of unchanged drug in bile were variably higher than those in serum. Bile/serum concentration ratios ranged from 65/1 to 4.6/1. It is postulated that bile/blood concentration ratios may reflect liver function.

Bile↗
PubMed1985

Hamster vein xenografts for arterial replacements in rats.

Experimental studies of vein homografts in rats have shown prolonged patency resulting from an attenuated immune response. This study examined the response to Golden Syrian hamster vein xenografts. While one group of Sprague-Dawley rats served as a control, a second group was sensitized with 5 X 10(6) viable hamster splenic lymphocytes given i.m. ten days and two days prior to microvascular replacement of a 2-cm. segment of infrarenal abdominal aorta with hamster vena cava. Graft patency was assessed daily by palpation and Doppler examination of femoral pulses. A technical error resulted in graft thrombosis in one sensitized rat at two days, but the remaining 19 grafts remained patent up to four months. The assay of lymphocytotoxicity by trypan blue excision revealed significant antibody response in all sensitized animals (average 64% cytotoxicity at 1/20 serum dilution) at the time of and subsequent to graft placement. There was no significant antibody response in the nonsensitized group (10% cytotoxicity for undiluted serum). The minimal degree of intimal thickening and medial degeneration on histological examination of grafts did not differ between the two groups. The patency of hamster venous xenografts may be well maintained in the rat despite a vigorous antibody response to lymphocyte antigens.

Animals↗