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J A Kimball

Publications and source records attributed to J A Kimball.

10 recordsLinked to original sources
PubMed1995

Reduced human IgG anti-ATGAM antibody formation in renal transplant recipients receiving mycophenolate mofetil.

Exposure to the equine-derived polyclonal antithymocyte preparation, ATGAM, frequently elicits human anti-ATGAM antibody formation. The influence of concomitant immunosuppressants on this antiantibody response has not been established. We therefore evaluated IgG antibody formation to ATGAM in 47 patients receiving ATGAM as part of a prospective, randomized, double-blinded study of mycophenolate mofetil versus azathioprine for maintenance immunosuppression after primary cadaveric renal transplantation. All patients received ATGAM for induction of immunosuppression plus methylprednisolone, prednisone, and cyclosporine. In addition, patients were randomized to receive maintenance immunosuppression consisting of either azathioprine (AZA) 1-2 mg/kg/day, mycophenolate mofetil 2 gm/day (MMF2), or mycophenolate mofetil 3 gm/day (MMF3). Patient sequential sera were independently tested for IgG anti-ATGAM antibody by 2 laboratories, which were blinded to treatment arm assignments, using enzyme-linked immunosorbent assays. Both laboratories found significantly greater anti-ATGAM antibody formation in group AZA compared with groups MMF2 and MMF3: laboratory 1 reported sensitization rates in the 3 groups of 94% (AZA), 50% (MMF2) (P < 0.02 vs. AZA), and 60% (MMF3) (P < 0.05 vs. AZA); and laboratory 2 reported rates of 67% (AZA), 17% (MMF2) (P < 0.02 vs. AZA), and 10% (MMF3) (P < 0.02 vs. AZA). In addition, fewer patients formed high titer antibody in the MMF arms compared to the AZA arm: 56% (AZA), 0% (MMF2) (P < 0.02 vs. AZA), and 20% (MMF3) (P < 0.02 vs. AZA) of patients for laboratory 1; and 20% (AZA), 0% (MMF2) (P < 0.05 vs. AZA), and 0% (MMF3) (P < 0.05 vs. AZA) of patients for laboratory 2. Differences in test results between the 2 laboratories were explained by differences in the sensitivity of their respective immunoassays and in the criteria used for assigning a positive result to test specimens. In this protocol, MMF at 2-3 gm/day was associated with a reduced incidence and titer of IgG anti-ATGAM antibody formation compared with standard azathioprine dosing. Although MMF previously has been reported to inhibit T cell responses that mediate acute cellular rejection, this is the first demonstration that MMF significantly inhibits human B cell responses to antigen in vivo.

Adult↗
PubMed1995

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation.

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.

Adult↗
PubMed1994

A prospective, double-blind, randomized study of high-versus low-dose OKT3 induction immunosuppression in cadaveric renal transplantation.

We undertook a prospective, double-blind study of high-(5-mg) versus low-(2-mg) dose OKT3 for induction immunosuppression (12 days) in cadaveric renal allograft transplantation. Maintenance immunosuppression was identical in both groups and consisted of azathioprine and prednisone initially, with cyclosporine beginning on the 5th postoperative day. Twenty-six patients were randomized. The groups were similar in terms of age, kidney ischemia time, peak PRA, and latest PRA. There were more diabetics and women in the high-dose group. Patient survival at 12 months was 100% in both groups. Graft survival at 12 months was 92% and 100% in the high- and low-dose groups, respectively. Infections were mostly minor and equal in frequency in the two groups. All patients receiving high- or low-dose OKT3 had manifestations of the cytokine release syndrome; these were delayed in onset in the low-dose group. Eleven patients (85%) in each group produced anti-OKT3 antibodies. Lymphocyte depletion after 1 day was major (> 98%) and identical in both groups. CD3 antigens were removed more slowly in the low-dose group but eventually at equal rates in both groups. Cost was significantly lower in the low-dose group. We conclude that while both doses of OKT3 were effective and safe for induction immunosuppression, it may be prudent to use a lower dose of OKT3 for induction immunosuppression because of its potential to reduce cytokine-mediated effects and to avoid the complications of overimmunosuppression and because of the lower costs associated with it.

Adolescent↗
PubMed1993

Cervical carotid MR angiography with multiple overlapping thin-slab acquisition: comparison with conventional angiography.

OBJECTIVE: Multiple overlapping thin-slab acquisition (MOTSA) is a hybrid time-of-flight MR angiography technique that combines the advantages of two- and three-dimensional methods. A venetian blind-like artifact, resulting from variations in signal intensity at slab boundaries, is a potentially significant disadvantage. The objective of this study was to determine the accuracy of MOTSA MR angiography for the measurement of stenosis and to evaluate the effectiveness of modifications to reduce the venetian blind artifact. SUBJECTS AND METHODS: Fifty-one consecutive patients undergoing conventional and MR angiography of the carotid arteries for suspected atherosclerotic disease were studied. Methods established in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) were used to measure stenosis. Measurements from the conventional angiograms were compared with those from the MR angiograms. Modifications of the MR angiographic technique that were instituted after the initial 26 patients to reduce the venetian blind artifact included new acquisition parameters and the use of a postprocessing algorithm. RESULTS: After modification, highly significant improvements in Spearman ranked correlation coefficients were observed for MR angiography interobserver comparison (.573 to .974, p < .001) and comparison of conventional and MR angiography (.774 to .949, p < .001). A corresponding reduction was observed in the standard deviation of the difference measurement for percent stenosis for both interobserver (34.5% to 11.7%, p < .001) and intertechnique (22.6% to 12.6%, p < .001) comparisons. In the postmodification group, the interobserver correlation coefficients for conventional and MR angiography were not significantly different (.969 vs .974). The areas under the receiver-operating-characteristic curves used to predict surgically significant disease for the premodification and postmodification groups were 0.79 and 0.98, respectively, for observer A and 0.85 and 0.95, respectively, for observer B. CONCLUSION: Improved acquisition parameters and postprocessing significantly reduce the severity of the venetian blind artifact and increase the accuracy of MOTSA MR angiography in the measurement of percent stenosis. With these improvements, MOTSA MR angiography shows promise for noninvasive evaluation of stenosis of the carotid arteries.

Artifacts↗
PubMed1991

Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium.

To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

5'-Nucleotidase↗