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Biomedical subjects

P C Walker

Publications and source records attributed to P C Walker.

26 records · Page 2Linked to original sources
PubMed1980

Localization of radiolabeled mouse alloantibody in a sarcoma induced by 3-methylcholanthrene.

The distribution of twice-purified I-125-labeled alloantibody, prepared from the serum of strain DBA/2J mice obtained after immunization with strain C3H/HeJ spleen cells, was studied in immunosuppressed DBA/2J mice bearing either an allogeneic C3H/HeJ MCA sarcoma (i.e., one induced by 3-methylcholanthrene) or a syngeneic MCA sarcoma. Radiolabeled antibody was isolated from labeled immune gamma globulin by adsorption onto C3H/HeJ red blood cells and elution from stroma prepared from these cells, followed by Sephadex G-200 gel filtration chromatography. This purified antibody bound specifically in vitro to C3H/HeJ red blood cells. In vivo this antibody localized preferentially in C3H/HeJ MCA sarcomas. An enrichment procedure was developed to increase the yield of radiolabeled alloantibody. The localization of I-131-labeled alloantibody in allogeneic tumor was visualized by external scintigraphy. Control I-131-labeled normal DBA/2J gamma globulin did not show such tumor localization.

Animals↗
PubMed1979

Distribution of radiolabeled alloantibodies in mice bearing 3-methylcholanthrene-induced sarcoma.

The distribution of purified 125I-labeled alloantibodies, prepared from the serum of DBA/2J mice obtained after immunization with C3H/HeJ spleen cells, was studied in immunosuppressed DBA/2J mice bearing either allogeneic C3H/HeJ 3-methylcholanthrene sarcomas growing s.c. or syngeneic SaD2 3-methylcholanthrene sarcomas. Once purified radiolabeled antibody was isolated from 125I-labeled immune gamma-globulin by a single adsorption onto C3H/HeJ RBC and elution from stroma prepared from these cells, by using 0.1 M glycine buffer (pH 3.0). Twice-purified alloantibody was then produced by Bio-Gel P-200 or Sephadex G-200 gel filtration chromatography or DEAE A-50 ion-exchange chromatography. In vitro, such purified antibodies bound specifically to C3H/HeJ RBC. In vivo, they localized to a significant extent following i.p. injection, preferentially in C3H/HeJ 3-methylcholanthrene sarcomas (4.4 to 8.9% of the injected dose per g of tumor equal to 1% of mouse weight), with mean tumor/blood ratios of 4.0 to 7.8, at 24 or 48 hr after injection. The percentage of injected dose localized in tumor and the tumor/blood ratio did not show significant differences with respect to time or method of antibody purification. Normal tissue/blood ratios in C3H/HeJ or SaD2 sarcoma-bearing mice were less than 0.9. The tumor/blood ratios in SaD2 sarcomas were approximately 0.6. Injection of 131I-labeled normal DBA/2J gamma-globulin resulted in normal tissue/blood and tumor/blood ratios of less than 0.9 in C3H/HeJ tumor-bearing mice.

Animals↗
PubMedDate not supplied

Evaluation of an empirical dosing schedule for gentamicin in neonates.

The standard gentamicin dosing recommendations for neonates appear to be inappropriate because they fail to consider the influence of neonatal development on gentamicin pharmacokinetics. Recent reports have emphasized that the standard regimens of 2.5 mg/kg q8-12h produce steady-state trough serum concentrations greater than 2 micrograms/ml in up to 91 percent of preterm infants of less than 35 weeks' gestation. A new dosing schedule based on postconceptional age (PCA) was developed to provide a better guideline for initiating and maintaining gentamicin therapy in neonates: PCA greater than 34 weeks, 2.5 mg/kg iv q12h; PCA 28-34 weeks, 2.5 mg/kg iv q16h; PCA less than 28 weeks, 2.5 mg/kg iv q24h. The new dosing schedule reduced the number of neonates with elevated trough concentrations (greater than 2 micrograms/ml) from 68.4 percent to 33-40 percent. Pharmacokinetic parameters for gentamicin in the various PCA groups were determined. Volume of distribution was constant across age groups (0.5 +/- 0.09 L/kg). Elimination rate constants (kel), half-lives, and clearance rates (Cl) ranged from 0.069 +/- 0.02 to 0.14 +/- 0.04 h-1, 10.71 +/- 2.92 to 6.04 +/- 1.24 h, and 0.58 +/- 0.25 to 0.93 +/- 0.24 ml/kg/min, respectively. Significant relationships were found between kel and Cl and patient age and weight; significant correlations were found between actual and estimated (based on PCA and weight) kel and Cl. Variability in kel and Cl estimated was considerable in spite of the correlations. The observed variability stresses again the need for pharmacokinetic monitoring of gentamicin therapy in neonates.

Aging↗