Biomedical subjects

J A Straw

Publications and source records attributed to J A Straw.

At least 37 records · Page 2Linked to original sources

PubMed1982

Glial DNA synthesis and cell proliferation in the lesioned frontal cortex of the rat.

Proliferation of rat neurological cells was quantified following a lesion of the frontal cortex, with the rate of incorporation of intraventricularly administered [3H]thymidine ([3H]TdR) into cortical DNA serving as an index of glial proliferation. Incorporation of [3H]uridine into the corresponding RNA fractions did not serve this purpose. The intraventricular route of administration of thymidine greatly reduced the amount of [3H]TdR needed to label DNA relative to systemic injection. The rate of incorporation of [3H]TdR into DNA was linear for 75 min post-injection. Significantly more [3H]TdR was incorporated into DNA of the lesioned frontal cortex than that of the contralateral control cortex, during the first 4 days post-trauma. The majority of the acid-insoluble radioactivity (from [3H]TdR) was localized in the nuclear subcellular fraction of the cortex. Experiments indicated that the enhanced incorporation of [3H]TdR was not the result of altered metabolism or pool sizes of TdR in the lesioned cortex. Histological analysis indicated that there was a significant increase in the number of glial cells in the lesioned cortex by day 4 post-lesion, which corresponded to the increase in DNA synthetic activity. It was concluded that mechanical trauma to the frontal cortex of the rat results in an increase in the number of glial cells at and near the lesion which is accompanied by an increase in incorporation of [3H]TdR into cortical DNA. This method of measuring posttraumatic DNA synthesis has several advantages over autoradiography.

Animals↗

PubMed1981

Differences in the pharmacokinetics of the diastereoisomers of citrovorum factor in dogs.

The pharmacokinetics of d- and l-citrovorum factor (CF) are quite different with respect to the postdistributional plasma decay rates. The natural (l) isomer had a half-life (beta) of 47 +/- 4 (S.E.) min compared to 143 +/- 15 min for the unnatural (d) isomer. Renal clearance was the same for both isomers and was proportional to glomerular filtration rate. Urinary excretion appeared to be the only route of elimination of the d isomer, while l-CF was extensively metabolized. Consequently, the unnatural isomer accumulated in great excess over the natural isomer and its active metabolite, 5-methyltetrahydrofolate. The apparent volume of distribution was about 58% of body weight for both isomers, which indicates that they have equal access to tissue compartments. The data suggest that d-CF can compete with l-CF and 5-methyltetrahydrofolate for entry into cells. Under certain conditions, accumulation of d-CF may interfere with rescue from methotrexate toxicity.

Animals↗

PubMed1977

Some observations on the reversibility of methotrexate toxicity in normal proliferating tissues.

Thymidine, in the absence of hypoxanthine, failed to protect normal mice from the acute toxicity of methotrexate, though tumor-bearing animals could be protected with thymidine alone, probably as a result of the availability of DNA degradation products released from drug-sensitive tumor cells. Although metrotrexate induced an early purine deficiency in gut cells, this effect was not detected in bone marrow. Later, purine deficiency became apparent in the gut and bone marrow of methotrexate-treated animals.

Animals↗

PubMed1976

Treatment with o,p'-DDD (mitotane) decreased cytochrome P-450, heme, and microsomal protein content in the dog adrenal cortex in vivo.

Treatment with o,p'-DDD, at a does which markedly inhibits steroidogenesis (60 mg/kg, intravenously), significantly decreased adrenal mitochondrial and microsomal "P-450" and microsomal protein contnet 34%, 55%, and 35% respectively, within 3 hours. The reduction of cytochrome P-450 content was accompanied by decrease in heme content, which explains the apparent loss of cytochrome P-450. This action provides a possible explanation for the inhibition of steroidogenesis caused by o,p'-DDD, and indicates that o,p'-DDD initiates a very destructive process in the dog adrenal cortex.

Adrenal Cortex↗

PubMed1975

The kinetics of methotrexate distribution in spontaneous canine lymphosarcoma.

A mathematical model is presented to simulate the time-dependent uptake of methotrexate in spontaneous canine lymphosarcomas in vivo. Blood flow ratew in these tumors are high so that transport to the tumor is limited by cell membrane resistance. A significant amount of rapidly exchangeable methotrexate appears to exist in extracellular space loosely bound to proteins or cell membranes. Transmembrane drug transport follows Michaelis-Menten kinetics, wigh the maximum facilitated transport ranging from 0.002 to 0.007 mug/min/ml for the separate tumors studied and a Michaelis constant for transport equal to 0.2 mug/ml. This is in the range of Michaelis constants reported for normal tissues in rats in vivo and in several cell linnes in vitro.

Animals↗

PubMed1975

Distribution of anticancer agents in spontaneous animal tumors. II. Distribution of gallium in canine lymphosarcoma.

The physiologic disposition of pharmacologic doses of gallium was studied in control dogs and dogs with spontaneous lymphosarcoma. Gallium 67 (67Ga) was administered iv with carrier gallium added at a dose of 8 mg/kg. About 50% of the injected dose was excreted in the urine by 48 hours (mostly in the first 12 hr), whereas negligible amounts were excreted in bile. The distribution of 67Ga in normal tissues was similar in control and tumor-bearing dogs. The tissue-to-plasma concentrations of gallium were considerably greater than 1 in the kidney cortex, bone marrow, bone, small intestine, and liver 6-72 hours after administration of the drug. At comparable time periods, tissue-to-plasma ratios of gallium were less than 1 in skeletal muscle and brain. In dogs with lymphosarcoma there was neither selective uptake nor selective retention of gallium in comparison to most normal tissues. In fact, several normal tissues, particularly kidney cortex and bone marrow, concentrated gallium greatly in excess of tumors. Qualitatively similar findings were obtained in a dog with malignant melanoma. These findings were contrary to what one would predict from reports showing that carrier-free 67Ga is selectively concentrated in various human and animal tumors. This indicates the need for more extensive studies of the physiologic disposition of pharmacologic (antitumor) doses of gallium in humans and appropriate animal models.

Animals↗

PubMed1974