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Biomedical subjects

K A Leonard

Publications and source records attributed to K A Leonard.

8 recordsLinked to original sources
PubMed1999

2,4,6-triarylchalcogenopyrylium dyes related in structure to the antitumor agent AA1 as in vitro sensitizers for the photodynamic therapy of cancer.

Cationic chalcogenopyrylium dyes 2-4 were synthesized in six steps from 4-(dimethylamino)phenylethyne (7), have absorption maxima in methanol of 594, 631, and 672 nm, respectively, and generate singlet oxygen with quantum yields [Phi((1)O(2))] of 0.020, 0.064, and 0.037, respectively. Dyes 2-4 are hydrolytically more stable than other chalcogenopyrylium dyes evaluated previously as sensitizers for photodynamic therapy. At 10 microM final concentration, all dyes 2-4 inhibited cytochrome c oxidase during irradiation of tumor mitochondrial suspensions treated with 10 microM dye. The degree of enzyme inhibition was abated in a reduced oxygen environment and in the presence of imidazole, a singlet oxygen trap. Superoxide dismutase, at a final concentration of 30 U, did not alter the photosensitized inhibition of mitochondrial cytochrome c oxidase by dyes 2-4. These data suggest that singlet oxygen may play a major role in the photosensitized inhibition of mitochondrial cytochrome c oxidase. Irradiation of R3230AC rat mammary adenocarcinoma cells in the presence of dyes 2-4 caused a significant loss in cell viability with thiopyrylium dye 2 displaying the greatest phototoxicity. Initial acute toxicity studies in vivo demonstrate that, at 10 mg/kg, none of the three dyes displayed overt toxicity.

Adenocarcinoma↗
PubMed1999

Synthesis and evaluation of chalcogenopyrylium dyes as potential sensitizers for the photodynamic therapy of cancer.

A series of thiopyrylium (2), selenopyrylium (3), and telluropyrylium dyes (4) was prepared via the addition of Grignard reagents to either 2, 6-di(4-dimethylamino)phenylchalcogenopyran-4-ones (5a) or 2-[4-(dimethylamino)phenyl]-6-phenylchalcogenopyran-4-ones (5b) followed by elimination and ion exchange to give the chloride salts. The absorption spectra and quantum yields for singlet oxygen generation of these dyes suggested that the dyes would have utility as sensitizers for PDT. Selenopyrylium dyes 3a and 3d with quantum yields for singlet oxygen generation of 0.040 and 0.045, respectively, were phototoxic to Colo-26 cells in culture. The toxicity of the dyes 2-4 was evaluated in clonogenic assays of human carcinoma cell lines. Importantly, the presence of a sulfur, selenium, or tellurium heteroatom in the molecules had no predictable impact on the toxicity of any particular dye set. Substituents at the 2-, 4-, and 6-positions of the dye had a much greater impact on cytotoxicity. The IC(50) values determined in the clonogenic assays did not correlate with chemical properties in the dye molecules such as reduction potential or lipophilicity. Initial in vivo toxicity studies showed no toxicity for these dyes at dosages between 7.2 and 38 micromol/kg in BALB/c mice.

Aniline Compounds↗
PubMed1995

Gun control.

Explore the source record for details and available documents.

Canada↗
PubMed1992

Immunohistologic demonstration of myocardial proteins with applications.

The authors used antibodies specific for creatine kinase MB isoenzyme (CK-MB) and myosin light chain-1 (MLC-1) for immunohistologic staining. At appropriate dilutions of antibody, frozen sections of human heart muscle were positive for both CK-MB and MLC-1, whereas sections of human skeletal muscle were negative for both proteins. Staining for both CK-MB and MLC-1 also was demonstrated in an immature teratoma. Furthermore, staining was localized to the rhabdomyosarcomatous elements within the teratoma; other components of the tumor did not stain for CK-MB or MLC-1. Biopsies of skeletal muscle revealed that regenerative, but not intact normal or degenerating, fibers also contained CK-MB and MLC-1. Immunohistologic stains for CK-MB and MLC-1 may be useful as tumor markers and as markers for regenerative muscle fibers.

Biopsy↗
PubMed1988

Secretion of creatine kinase MB isoenzyme by an immature teratoma with predominant rhabdomyosarcomatous elements.

A 37-year-old man with metastatic immature (malignant) teratoma with prominent rhabdomyosarcomatous elements had markedly increased activity of creatine kinase (EC 2.7.3.2) MB in serum. There was no electrocardiographic evidence of infarction or ischemia, and autopsy revealed no myocardial infarction, significant coronary atherosclerosis, myocarditis, or invasion of the heart by tumor. A high proportion of the creatine kinase activity in a homogenate of the tumor was attributable to the MB isoenzyme. Persistent increases of creatine kinase-MB and an unusually high MB isoenzyme activity, out of proportion to total creatine kinase activity, may indicate a nonmyocardial origin of this isoenzyme.

Adult↗
PubMedDate not supplied

Firearm deaths in Canadian adolescents and young adults.

This article describes the problem of firearm deaths among Canadians aged 15-24 years. It is based on data obtained from Statistics Canada, the Metropolitan Toronto Police Department, and the Canadian Department of Justice. Firearms are the third leading cause of death in this age group, accounting for 276 deaths in 1990, after motor vehicle accidents (997) and non-firearm suicides (358). Some 23% of Canadian homes contain a firearm; the average number of firearms per home is 2.67. Medical and public health professionals are urged to work toward prevention by educating patients and families about the risks of a firearm in the home and by supporting legislation to decrease the availability of firearms to young people.

Adolescent↗