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Biomedical subjects

M K Patterson

Publications and source records attributed to M K Patterson.

At least 37 records · Page 2Linked to original sources
PubMed1983

Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration.

The comparative central nervous system (CNS) toxicity of serially administered intravenous doses of lidocaine, bupivacaine, etidocaine, and tetracaine was investigated in awake dogs. The mean cumulative dose required for convulsive activity was 4.0 mg/kg tetracaine, 5.0 mg/kg bupivacaine, 8.0 mg/kg etidocaine, and 22.0 mg/kg lidocaine. The cumulative convulsive dose of lidocaine was significantly greater than that of the other three agents (P less than 0.01). A comparison of the in vivo anesthetic potency and the acute CNS toxicity of these various agents suggests little difference in the therapeutic ratio between less potent anesthetics such as lidocaine and more potent drugs, i.e., tetracaine, bupivacaine, and etidocaine. The relative CNS toxicity of the different agents as determined in awake dogs in this study was compared with their relative cardiovascular toxicity previously evaluated in a series of ventilated dogs anesthetized with pentobarbital. The dose of lidocaine, etidocaine, tetracaine, and bupivacaine required to produce irreversible cardiovascular depression was 3.5-6.7 times greater than that which produced convulsions. These results suggest that the CNS is the primary target organ for the toxic effects of both highly lipid-soluble and highly protein-bound local anesthetics (i.e., bupivacaine, etidocaine, and tetracaine) and less lipid-soluble and less protein-bound drugs (i.e., lidocaine) following rapid intravenous administration.

Acetanilides↗
PubMed1981

Increase in proliferative markers after inhibition of transglutaminase.

Cystamine inhibited transglutaminase activity (R-glutaminyl-peptide:amine gamma-glutamyltransferase, EC 2.3.2.13) of proliferating WI-38 cells in a dose-dependent manner over the concentration range 0.005-0.25 mM when added to the culture medium. The epsilon-(gamma-glutamyl)lysine content in the cells was decreased and several proliferation markers were enhanced. "Non-mitotic" cells were stimulated by cystamine (about 25% of that observed with 10% fetal bovine serum) to undergo DNA synthesis with subsequent increases in nuclei number. Numerous other disulfides, thiols, and amines were ineffective when added to culture medium. The findings are supportive of the concept that growth control involves a relationship between isopeptide crosslinks and proliferation.

Cell Division↗
PubMed1980

Microwave fixation of cells in tissue culture.

Use of microwave irradiation has been evaluated for the in situ fixation of cells grown in tissue culture prior to fluorescent antibody staining. The results show total retention of cell protein in the matrix with microwave fixation, whereas 40-50% of the protein is lost during conventional formaldehyde fixation. Fluorescent antibody staining of cells shows that this protein loss reflects cell loss. A further advantage of microwave fixation is that photometric quantitation of fluorescence appears possible by random scanning of fluorescent antibody stained populations.

Cell Adhesion↗
PubMed1980

Transglutaminase and epsilon-(gamma-glutamyl) lysine isopeptide bonds in eukaryotic cells.

Transglutaminase activity was reduced in malignant hepatoma, virus-transformed human and hamster cells, and chemically transformed mouse cells when compared to normal counterparts. The reduction in enzyme activity reflected the presence of fewer transglutaminase molecules in transformed cells. Greater amounts of the enzyme activity were particulate-associated in confluent and arrested normal human cells. Indirect immunofluorescence studies with antibody to cellular transglutaminase demonstrated the presence of transglutaminase in Triton X-100-insoluble material. A parallel between pericellular fibronectin and transglutaminase (TGase) was demonstrated. Normal human and mouse cells that elicited contact inhibition of growth and had the high TGase activity also had more epsilon-(gamma-glutamyl) lysine isopeptide bonds than transformed counterparts. Similarly nonproliferating human cells had higher transglutaminase activity and isopeptide levels than did proliferating populations. These results suggest that isopeptide bond formation stabilizes the cell membrane and contributes to a nonproliferating state. Inhibition of isopeptide formation should therefore lead to a mitogenic response. Preliminary results support such a relationship. A model depicting control of isopeptide formation at either enzyme or substrate level is presented.

Animals↗
PubMed1977

Transglutaminase activity in normal and transformed cells.

Transglutaminase activity was determined in normal and transformed paired cell systems. Reduced enzyme activity was found in virus-transformed human and hamster cells and in chemically transformed mouse cells relative to normal counterparts. Most of the enzyme activity was localized in the particulate fraction sedimenting at 105,000 X g. Enzyme activity was highest when normal cell populations were in an essentially nonmitotic state. Protein capable of incorporating putrescine was present in normal and transformed human cells, although the rate of incorporation was lower in the latter. The putrescine acceptor in the normal cell paralleled enzyme activity and enzyme distribution. Trypsin (5 microng/ml) treatment of the normal cell resulted in a 3-fold increase in enzyme activity, which occurred independently of protein synthesis.

Cell Division↗
PubMed1976

Amino acid and hexose transport of normal and simian virus 40-transformed human cells.

Studies on amino acid and hexose transport were performed on human WI-38 cells and WI-38 SV40-transformed cells (VA13A and VA13-2RA). Depending upon cell line or conditions, either no difference or a relative decrease in initial uptake by transformed cells was found. Under similar growth conditions, transformed hamster cells (PyBHK-21/C13) had increased uptake, compared with the normal hamster cells (BHK-21/C13). The normal and transformed human cells were also similar in sialic acid content and agglutinated when treated with concanavalin A.

Agglutination Tests↗
PubMed1976

Differential transglutaminase distribution in normal rat liver and rat hepatoma.

Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma. Over 90% of the total enzyme activity was found in the 105,000 X g supernatant of normal liver, whereas only 30% was found in this fraction of the hepatomas, the remainder being found in the particulate fraction. The is distribution pattern did not correlate with protein distribution nor did it change during cellular proliferation, since regenerating liver and embryonic tissue had the same pattern as normal liver. Cell protein was a suitable acceptor substrate for the enzyme. Kinetic analyses showed that liver and hepatoma enzymes had a similar Km and Vmax for putrescine incorporation into cell protein. Hepatoma particulate enzyme was more stable than either liver or hepatoma supernatant enzyme. The enzyme may also act as the acceptor molecule.

Animals↗
PubMed1973

Asparagine-requiring tumor cell lines and their non-requiring variants: cytogenetics, biochemistry and population dynamics.

Asparagine-requiring Jensen and Walker rat tumor cells and their asparagine-independent variants have been analyzed. The following results were obtained: (1) Both cell lines have very low levels of asparagine synthetase, and non-requiring revertants isolated from these lines have elevated levels of the enzyme. (2) No differences in chromosome number were detected between the parent Jensen line and five Jensen non-requiring revertants isolated from it. (3) Both Jensen and Walker cells undergo asparagineless death when deprived of this amino acid, although the Jensen cells do so at a more rapid rate. (4) Jensen requiring lines are at a selective advantage when grown in competition with non-requiring variants in complete medium, and their growth rate is more rapid when grown separately. The selective coefficients for the variant with respect to the asparagine-requiring parent ASN(-) line were 0.94 for the competition experiments and 0.83 for growth rate estimates. (5) A somatic cell hybrid between Chinese hamster cells (which require asparagine at low densities, and posses measurable synthetase activity) and the Walker line was found to be asparagine-independent, and it possessed enzyme levels equivalent to the hamster parent. The results of these investigations suggest a parallel with microbial auxotrophic mutants and can be understood in terms of alterations within nuclear structural genes.

Ammonia↗