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Biomedical subjects

A J Pesce

Publications and source records attributed to A J Pesce.

At least 55 records · Page 3Linked to original sources
PubMed1987

The effect of oral metoclopramide on the absorption of cyclosporine.

This study was performed to determine the effect of coadministered oral metoclopramide on the absorption of oral cyclosporine in 14 kidney transplant patients. The study was conducted on two consecutive days. Ten patients were studied twice, and 4 patients once, giving 24 studies. The total dosage of metoclopramide was 20 mg. The day on which metoclopramide was administered was chosen randomly. Whole-blood cyclosporine levels were analyzed by high-performance liquid chromatography. Coadministration of cyclosporine with metoclopramide resulted in a significant increase in mean maximum blood concentration (567 ng/ml versus 388 ng/ml) and mean area under the blood-concentration-versus-time curve (4120 ng X hr/ml versus 3370 ng X hr/ml); and a significant decrease in mean time to reach maximum concentration. The mean increase in area under the blood-concentration-versus-time curve was 29%. No significant changes were observed in the elimination of cyclosporine when it was coadministered with metoclopramide. These observations suggest that coadministered metoclopramide increased the total absorption of cyclosporine. Metoclopramide has been shown to hasten gastric emptying; since cyclosporine is absorbed predominantly in the small intestine, coadministration of metoclopramide resulted in increased bioavailability of cyclosporine.

Adult↗
PubMed1987

An immune complex glomerulopathy associated with glomerular capillary thrombosis in the laboratory mouse. A highly reproducible accelerated model utilizing cationized antigen.

An accelerated, highly reproducible model of an immune complex glomerulopathy in the laboratory mouse was developed by using cationized bovine gamma-globulin (cat-BGG) as the nephritogenic agent. Preimmunized Balb/c mice given three 250-micrograms doses of cat-BGG consistently develop a nonproliferative glomerular lesion which becomes manifested clinically by the nephrotic syndrome and results in death within 14 days. Significant proteinuria is evident by day 4 (24 hours after the third dose of cat-BGG) at which time extensive deposits of cat-BGG, IgG, and C3 are localized along the glomerular capillary walls. At the ultrastructural level, subepithelial deposits and foot process effacement are evident. By day 6, subendothelial and mesangial deposits are also present, and by day 10, extensive glomerular capillary thrombosis and early crescent formation develop. The reproducibility and rapidity of the induction of disease, and the spectrum of pathological changes occurring in the glomeruli make this murine model of an immune complex glomerulopathy potentially useful for the study of the mechanisms underlying the induction and progression of glomerular injury and the evaluation of potential therapy.

Animals↗
PubMed1987

The effect of oral metoclopramide on the absorption of cyclosporine.

This study was performed to determine the effect of coadministered oral metoclopramide on the absorption of oral cyclosporine in 14 kidney transplant patients with stable renal function. The study was conducted on two consecutive days. Ten patients were studied twice and four patients once, giving 24 studies. The total dosage of metoclopramide was 20 mg. The day on which metoclopramide was administered was chosen randomly. Whole blood cyclosporine levels were analyzed by high performance liquid chromatography. Coadministration of cyclosporine with metoclopramide resulted in a significant increase in mean maximum blood concentration (567 ng/mL nu 388 ng/mL) and mean area under the blood concentration nu time curve (4120 ng X h/mL nu 3370 ng X h/mL), and a significant decrease in mean time to reach maximum concentration: The mean increase in area under the blood concentration versus time curve was 29%. No significant changes were observed in the elimination of cyclosporine when it was coadministered with metoclopramide. These observations suggest that coadministered metoclopramide increased the total absorption of cyclosporine. Metoclopramide has been shown to hasten gastric emptying; since cyclosporine is absorbed predominantly in the small intestine, coadministration of metoclopramide resulted in increased bioavailability of cyclosporine.

Administration, Oral↗
PubMed1986

Cationic antigens. Problems associated with measurement by ELISA.

The measurement of the mouse antibody response to cationized bovine serum albumin (cat BSA) and bovine gammaglobulin (cat BGG) was complicated because of the unique properties of these antigens. Cat BGG non-specifically bound rabbit anti-mouse gammaglobulin conjugated to alkaline phosphatase. This was minimized by adding the polyanion, heparin. Cat BSA also reacted non-specifically with some conjugates, but the reaction with specific antibody was enhanced by the addition of the polyanions heparin or dextran sulfate. The non-specific reaction did not appear to be related to the concentration of antigen used to coat the plastic plates. In addition, in ELISA inhibition experiments high concentration of antigens (greater than 100 micrograms/ml) seemed to result in non-specific inhibition of the antibody antigen reaction. A proposed model to explain the problems is based on the polycationic surface formed by coating the plates with the cationized proteins. This cationic surface can be neutralized by polyanions, reducing the non-specific and enhancing the specific reactions. It appears that other polycationic molecules might share these unique properties and these factors must be considered when they are measured.

Alkaline Phosphatase↗
PubMed1986

Enzyme-linked immunoabsorbant assay of apolipoprotein AII in plasma, with use of a monoclonal antibody.

We produced a monoclonal antibody (C2-22) to human apolipoprotein (Apo) AII and describe its use in an enzyme-linked immunoabsorbant assay (ELISA) for Apo AII in human plasma and lipoprotein subfractions. No cross reactivity of the antibody with Apo CI, CII, CIII, E, or ablumin was detected. Apo AI and low- and very-low-density lipoprotein cross reacted by 0.25%, less than 0.2%, and less than 0.3%, respectively. Whole plasma high-density lipoprotein (HDL) and HDL subfractions (HDL2 and HDL3) produced parallel displacement curves. This quantitative ELISA is based on competition between solid-phase-bound Apo AII and free Apo AII. Bound C2-22 is detected by alkaline-phosphatase-labeled second antibody. The standard curve for the assay is linear for plasma diluted 500-fold originally containing 140 to 1140 mg of Apo AII per liter. Delipidation of plasma samples exposed no additional antigenic sites. Within- and between-run CVs were respectively 8.4% and 8.7% at 327 mg/L of Apo AII, and 6.8% and 7.4% at 587 mg/L. Results correlated well with those by a polyvalent-antisera-based RIA procedure: r = 0.916, p less than 0.01, RIA = 0.896 ELISA -19.1 mg/L.

Animals↗
PubMed1985

Evaluation of amitriptyline pharmacokinetics during peritoneal dialysis.

The pharmacokinetics of a single oral dose of amitriptyline were examined in five functionally anephric patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The concentration of the parent drug and its major metabolite nortriptyline in plasma were measured by high performance liquid chromatography. Patients on CAPD did not have a significantly extended elimination half-life (t 1/2) as compared to literature controls. However, the variation in t 1/2 was extremely large in both the CAPD and normal renal function groups (range 15-34 h and 24-70 h, respectively). No statistically significant change was observed (p less than 0.05). Although a major route of elimination was removed and there was no change in t 1/2, the drug levels in these patients should be closely monitored because of the large variability in patient metabolism.

Adult↗
PubMed1985

Animal model for theophylline--cimetidine drug interaction.

Cimetidine (300 mg I.V.) and theophylline (15 mg/kg I.V.) were studied in Beagle dogs for possible drug interaction. The drugs were administered alone and in combination using a crossover design. Although none of the determined pharmacokinetic parameters for theophylline changed significantly in the presence of cimetidine, a trend towards significance was found for the terminal half-life, area under the curve, and mean residence time. The magnitude in changes found in Beagles is representative of the changes reported in man.

Animals↗
PubMed1984

Analysis of humoral and cellular factors that contribute to impaired immune responsiveness in experimental uremia.

An experimental model in rats was developed to define the nature of humoral and cellular factors that contribute to impaired immune responsiveness in chronic renal failure. Addition of uremic rat serum to both normal and uremic lymphocytes significantly suppressed cellular responses, the suppression being more pronounced with uremic lymphocytes. Lymphocytes from uremic rats were only marginally less responsive than normal lymphocytes to concanavalin A stimulation when normal rat serum was added to the cultures, indicating that the cellular factors in impairment were less important than humoral ones. Antibody formation in rat splenocyte cultures to bovine serum albumin was suppressed by addition of uremic serum, but the response to sheep erythrocytes was unaffected. Thus the effect on antibody response in uremic animals is dependent upon the antigen tested.

Animals↗
PubMed1984

Kinetics of oral tolerance: study of variables affecting tolerance induced by oral administration of antigen.

The induction of antigen-specific tolerance by oral administration of hen egg albumin (OVA) was shown to be time- and dose-dependent. The IgE response was the most effectively suppressed by antigen feeding prior to or after parenteral immunization. The effect on IgG response paralleled that observed on the IgE response, but the magnitude of suppression was less pronounced. The IgA response was enhanced rather than suppressed if the interval between feeding and parenteral immunization was short or if the animals were antigen-fed after the intraperitoneal priming.

Administration, Oral↗
PubMed1984

Expression of normal and tumor-associated antigens in human breast carcinoma.

The expression of six cytoplasmic/membrane antigens (beta 2-microglobulin, HLA, HLA-DR, carcinoembryonic antigen, and two breast tumor-associated antigens (TAAs), B6.2 and B72.3) was investigated in serial sections of 28 human breast carcinomas using monoclonal antibodies and the avidin-biotin complex immunoperoxidase technique. The frequency of expression and linkage between these antigens was determined, and antigenic expression was related to patient age, morphologic differentiation, cytologic grade, and estrogen receptor/progesterone receptor content of the tumor. The expression of beta 2-microglobulin and HLA correlated with morphologic differentiation, well-differentiated and moderately well-differentiated tumors expressing these antigens more often than poorly differentiated tumors. Expression of the TAAs, however, was not related to differentiation. There was no linkage between beta 2-microglobulin/HLA and the TAAs. Carcinoembryonic antigen was found to be linked to the TAA, B6.2. Expression of the TAA, B72.3, correlated with patient age. Eighty percent (23 of 28) of the tumors were positive for carcinoembryonic antigen or at least one of the TAAs. The estrogen receptor/progesterone receptor status of the tumor was not statistically related to the expression of any of the antigens studied. Analysis of tumor antigen profiles may provide important information relevant to prognosis, therapy, and early detection of cancer, as well as insights into the nature of the neoplastic process.

Adult↗
PubMed1983

Immunoregulatory properties of antigenic fragments from bovine serum albumin.

Regulation of the immune response to bovine serum albumin (BSA) by defined substructures of the protein was investigated. The fragments consisted of 41 to 307 amino acids each bearing unique serologic determinants. When administered intravenously the fragments were capable of suppressing the immune response to the entire BSA molecule. The suppression was T-cell mediated and affected the determinants that were linked. The fragments also primed for a secondary anti-BSA response when given in adjuvant; however, the ability to prime was restricted to determinants on the immunizing fragment. The data demonstrate that immune responses to a large protein molecule can be regulated by a relatively small component of its structure and that the ability of a fragment to induce help is more restricted than is its suppressive potential.

Amino Acids↗
PubMed1983

Induction of oral tolerance in mice unresponsive to bacterial lipopolysaccharide.

C3H/HeJ lipopolysaccharide (LPS)-unresponsive and closely related C3H/HeSn LPS-responsive mice were rendered tolerant to hen albumin by antigen feeding before parenteral immunization. Both single and multiple feedings of antigen were effective in inducing tolerance to hen albumin in LPS-responsive and -unresponsive strains of mice. Our data demonstrate that ability to respond to LPS is not a prerequisite for induction of oral tolerance to a soluble protein antigen.

Albumins↗
PubMed1983

Pitfalls and errors in drug monitoring: analytical aspects.

Drug analyses, whether for purposes of evaluating new drug products or as part of clinical monitoring programs, have become frequently requested tests in both clinical and industrial laboratories. From the time of phlebotomy, throughout the transportation, processing and storage of the specimen, during the actual analytical procedure and throughout the clerical reporting of the data, certain potential errors and limitations in the system exist which should be fully recognized for proper evaluation of the laboratory data.

Humans↗
PubMed1982

Immunochemical cross-reactivity between cyanogen bromide fragments of human serum albumin.

The antigenic structure of human albumin was investigated in order to establish whether or not there was any similarity between its antigenic sites. Using immunoadsorbent columns prepared with cyanogen bromide fragments of human serum albumin, antibodies directed against different portions of the albumin molecules were isolated. Measurement of the amount of the antibodies isolated and study of their specificity by inhibition techniques show that these subpopulations of antibodies reacted not only with the fragment used for their isolation (homologous) but also with the other fragments (heterologous). Heterologous fragments were inhibiting only at a very high concentration with regard to the homologous ones. These results show that there is a weak cross-reactivity between different portions of the albumin molecule. This reaction is most probably due to the homology existing in the sequence of the human albumin molecule which has arisen by gene duplication. The same type of behavior can be predicted to extent to other molecules which have evolved by similar mechanisms.

Cross Reactions↗
PubMed1982

Evaluation of the peroxidase-antiperoxidase method for demonstrating cell membrane B2-microglobulin.

The peroxidase-antiperoxidase (PAP) immunohistochemical technic was evaluated for its usefulness in studying B2-microglobulin (B2m) expression in the cell membrane of human tumor lines grown in athymic mice. Eleven human tumor xenograft lines expressing various amounts of B2m were used. B2m was assessed by three methods: PAP technic on formalin-fixed, paraffin-embedded tissue; indirect immunofluorescence on frozen sections; and radioimmunoassay on soluble tumor extracts. The three technics gave comparable results, and the PAP technic proved to be useful in evaluating B2m.

Animals↗