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J G Wilson

Publications and source records attributed to J G Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Physiological modeling of disposition of potential tumor-imaging radiopharmaceuticals in tumor-bearing mice.

Radiopharmaceuticals have great potential in the early detection of human tumors. Three potential 99mTc-labeled platinum compounds based on cisplatin have been synthesized and tested in tumored mice. This report presents the analysis of the disposition data obtained after a single intravenous injection with an empirical, physiologically based pharmacokinetic model. The radioactivity of each radiopharmaceutical after administration was measured in blood, urine, and 15 tissues, including tumor. Parameters included in the model were tissue volumes (experimentally determined), tissue blood flows (determined from literature values), tissue:blood extraction ratios (determined by nonlinear least-squares regression with MULTI-FORTE), and clearance terms (also determined by nonlinear least-squares regression). Data were weighted by the reciprocal of the square of the observed values. Good fits to the experimental data were obtained. As expected, the compound producing the best tumor:blood profile (3) also had the highest tumor extraction ratio (6.2 versus 2.0 and 1.3 for 1 and 2, respectively). Total body clearance values for the radioactivity associated with the three compounds 1-3 were calculated to be 0.09, 0.04, and 0.016 mL/min, respectively. Analysis of data with such an empirical, physiologically based model may assist future development of suitable tumor-imaging agents.

Animals↗
PubMed1979

The evolution of teratological testing.

The beginnings of mammalian experimental teratology in this century are briefly reviewed and it is noted that prior to 1960 a degree of sophistication in concept and technology had already been achieved. Thus, contrary to claims that teratology had its beginning with the thalidomide catastrophe, a modest but expanding activity and body of knowledge already existed before this unfortunate event. This activity and this knowledge, however, were largely confined to academic and research institute laboratories and made little impact on the agencies in medicine, government and industry which oversaw public health and safety and set policies intended to preserve them. No individual, group, or agency can rightly be blamed for not having sooner brought together the concepts and methodology needed for meaningful animal testing and the regulatory insignt and experience needed intelligently to apply test data to human safety evaluation and experience needed intelligently to apply test data to human safety evaluation. To accomplish this liaison seems to have required the largest toxicological catastrophe yet recorded in human history. The major events leading to formulation of the first standardized guidelines are reviewed, but it is emphasized that even today the best animal testing can only provide a limited statement of probability regarding human risk vis-à-vis safety.

Abnormalities, Drug-Induced↗
PubMed1979

Chronic mucocutaneous candidiasis. Immunologic studies of three generations of a single family.

A family consisting of eight members in three generations (age 10 months to 53 years) affected with chronic mucocutaneous candidiasis was studied along with three unaffected relatives. Dermatophytosis, loss of teeth and recurrent viral infections were present in some members. Results of tests for endocrinologic, muscle or liver disease, thymoma, iron deficiency, antitissue antibodies and malabsorption were normal in all patients. Antibody function and levels, B cell counts, serum complement, leukocyte enzymes, chemotaxis, phagocytosis and adherence were normal in all members. Plasma inhibitors to lymphocyte transformation and leukocyte inhibitory factor were not found. No unique HLA haplotype or antigen segregated in this family. Evaluation of cell-mediated immunity revealed total cutaneous anergy in three of eight whereas four of the other five had negative lymphocyte transformation and skin tests to Candida but responded normally to other antigens. Leukocyte inhibitory factor was not produced to Candida antigen in all four patients tested. T cell counts were within normal limits in all. Extensive evaluation of all limbs of the immune system in this family revealed a defect in cell-mediated immunity to Candida that appeared to be inherited as a dominant characteristic.

Adolescent↗
PubMed1978

Ethanol and heat-treated plasma fractionation methods in South Africa.

Modifications of the Cohn techniques are the methods of choice for the preparation fo dilute albumin (PPS) and gamma-globulin solutions on an industrial scale. For the manufacture of refined albumin solutions, however, considerable labour and material is saved if crude, ethanol-precipitated fractions are heated in the presence of stabilisers in order to purify the albumin. The technique is simple and cheap, and yields a safe product of high quality. Bacterially contaminated and highly haemoglobinized plasma can be successfully heat-treated.

Animals↗
PubMed1977

Embryotoxicity of the folate antagonist methotrexate in rats and rabbits.

The prenatal effects of methotrexate (MTX) in rats and rabbits were assessed. It was found highly embryotoxic in postimplantation rat embryos; 0.3 mg/kg ip or less caused nearly total embryolethality with slight teratogenicity. Rabbit embryos were far more resistant to small doses of MTX than rats, but 19.2 mg/kg iv, when given during days 10 to 15 of gestation, produced little death and a constant spectrum of malformation in a high percentage of offspring. Cleft palate, skull defects, and severe fore- and hindlimb dysplasias, occurred with a high degree of regularity and were strongly dose and developmental-stage specific.

Abnormalities, Drug-Induced↗
PubMed1977

Non-confirmation of thalidomide induced teratogenesis in rats and mice.

It has been reported that thalidomide, dissolved in a 1:3 mixture of Tween 20 and physiological saline and administered intraperitoneally to pregnant mice and rats induces a variety of malformations, including limb deformaties, characteristic of the primate syndrome. The studies reported herein attempted to confirm these findings without success although the rodent strains used were not the same. A low level of non-specific malformations was observed in the fetuses of both species at dose levels reported to cause a 47 percent and 92 percent rate of malformation in mice and rats respectively. One possible source of difference was Tween 20 which was toxic to the point of lethality in these studies at dose levels reported to be non-toxic in the earlier studies.

Abnormalities, Drug-Induced↗
PubMed1977

Teratogenic effects of environmental chemicals.

Despite the widespread distribution of a great many chemical substances in the environment, very few have been implicated in human teratogenicity, and most of these are drugs used at relatively high biological effect levels. Although several other types of environmental chemicals such as pesticides, solvents, and metals can be shown under laboratory conditions to have some teratogenic potential, there is little evidence that these, at present ambient concentrations and conditions of exposure, represent significant hazards to human intrauterine development. An exception to the latter generalization is methylmercury which, because of peculiarities in distribution, can reach high concentration in the human diet.

Animals↗
PubMed1977

The effects of thalidomide and two analogues on the regenerating forelimb of the newt.

Oral administration (3 mg/day) of thalidomide during the dedifferentiation and early limb-bud stages of newt forelimb regeneration produced a variety of specific limb deformities. Proximal and preaxial skeletal elements were the most severely malformed, e.g. preaxial hemimelia, severe proximal deformities, and preaxial polydactyly. Likewise, oral, daily doses (3 mg) of the teratogenic analogue, EM12, on days 7 and 8 following bilateral amputation caused the same incidence and type of forelimb abnormalities as did thalidomide. Conversely, the non-teratogenic analogue, EM87, when orally administered (3 mg/day) on days 7 and 8 post-amputation resulted in a low rate of limb deformities, similar in type to those seen in control regenerates. The type of limb deformities observed in the regenerating newt forelimb following thalidomide treatment nearly mimic those seen in the human and monkey syndromes. Therefore, the newt represents a possible model for investigating some of the problems associated with thalidomide teratogenesis.

Amputation, Surgical↗
PubMed1976

Reduced interlitter variability in rats resulting from a restricted mating period, and reassessment of the ""litter effect''.

Rats were mated for two or 15 hours and variability of day-12-embryos in weight, protein content, and [3H]thymidine incorporation was compared in the long mating period (LMP) and short mating period (SMP) groups by a 2-level nested analysis of variance. Variability in day-20 fetal weight was similarly compared. In both groups day-12 embryonic weight was relatively more variable than day-20 fetal weight, and variability was less in SMP than LMP animals for each comparison made, although statistical significance was attained only for thymidine incorporation. ""Litter effects'' were noted but not of the magnitude reported by other investigators. It was concluded that inappropriate statistical methods have encouraged the belief that among-litter variability usually exceeds within-litter fetal weight variability. The teratological implications of reduced development variability and the ""litter effect'' are discussed.

Abnormalities, Drug-Induced↗
PubMed1975

Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys.

Hydroxyurea was given to pregnant rhesus monkeys and pregnant rats in regimens adjusted to produce similar degrees of teratogenicity, for the purpose of comparing the distribution of the drug in the females and their embryos. According, in rats 137 mg/kg/day ip on days 9-12 resulted in a drug half-life in maternal plasma of about 15 min and in embryos about 85 min, after the last injection; and in monkeys 100 mg/kg/days iv on days 23-32 resulted in drug half-life in maternal plasma estimated to be 120 min and in embryos 265 min, after the last injection. Using as a baseline of biological effects the minimal concentration known to inhibit DNA synthesis in rat embryos and cancer cells, namely 10(-4) M, it was calculated that the rat embryos in the present study were exposed to this level or more for approximately 12 h whereas the monkey embryos were exposed for approximately 100 h. Although the teratogenic effects were not identical in the two species, these data are interpreted to mean that rat embryos are teratogenically much more sensitive to hydroxyurea than monkey embryos. These observations have important implications in the selection of appropriate species for tests to estimate human teratogenic risks. The rat, which is currently the most widely used animal for such tests, displays sizeable differences from rhesue monkeys, which is one of the animals thought to be most like man in teratogenic susceptibility.

Amniotic Fluid↗
PubMed1975

Inhibition of ATP synthesis associated with 6-aminonicotinamide (6-AN) teratogenesis in rat embryos.

Pregnant rats were injected ip with 6 mg/kg 6-aminonicotinamide (6-AN) at day 12 of gestation. Embryos removed between 1 and 48 h later had reduced adenosine triphosphate (ATP) concentrations, of about 50% of control values. All fetuses examined near term were malformed. Nicotinamide (NAM, 100 mg/kg) given ip 1 h after 6-AN afforded protection: malformations occurred in only 15% of the survivors; and there was minimal ATP reduction, 15% below control values. NAM given 2 and 4 h after 6-AN produced intermediate ATP concentrations and malformation frequencies. Thus, there was a relation between the embryotoxic and ATP-depressant actions of 6-AN in day 12 rat embryos.

6-Aminonicotinamide↗