Search PubMed⌕ Search

Biomedical subjects

M S Newman

Publications and source records attributed to M S Newman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Isolation and regional localization of the murine homeobox-containing gene Hox-3.3 to mouse chromosome region 15E.

A murine homeobox-containing cDNA clone has been isolated from an adult spinal cord library. Using in situ hybridization and somatic cell genetics techniques, the newly isolated homeobox gene has been mapped to mouse chromosome region 15E. Because of its chromosomal location, we called this gene locus Hox-3.3. Nucleotide sequence analysis revealed that the Hox-3.3 gene represents the murine cognate of the human homeobox gene c8. The presumptive organization of the murine Hox-3 homeobox gene cluster is discussed.

Amino Acid Sequence↗
PubMed1988

Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21.

The human interferon-beta 2 gene (IFNB2) is identical to the genes encoding the B-cell stimulatory factor (BSF-2), the hybridoma growth factor (HGF), and the hepatocyte stimulating factor (HSF). This protein mediates major alterations in the secretion of a wide spectrum of plasma proteins by the liver in response to tissue injury (the acute-phase response). We have used a cDNA probe specific to the human IFNB2 gene in DNA hybridization experiments and report the regional localization of this gene to human chromosome 7p15-p21. Southern blot analyses of DNA extracted from a panel of mouse X human somatic cell hybrids localized this gene to human chromosome 7p. In situ hybridization of the IFNB2 cDNA probe to prebanded human metaphase chromosome spreads allowed the further localization of this gene to 7p15-p21.

Animals↗
PubMed1987

Concerning steric effects in antimalarial agents.

Acridine, the parent nucleus of atabrine, is much more toxic than its 4,5-dimethyl derivative. The 4,5-dimethyl derivative of atabrine was therefore synthesized in the hope of producing a better-tolerated drug. The analogue was considerably more toxic than atabrine.

Acridines↗
PubMed1986

The cytosolic receptor binding affinities and AHH induction potencies of 29 polynuclear aromatic hydrocarbons.

The dose-response rat hepatic cytosolic receptor-binding avidities, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction potencies in rat hepatoma H-4-II E cells in culture were determined for 29 polynuclear aromatic hydrocarbons. It was apparent that the magnitude of the EC50 values for these in vitro responses were strongly dependent on structure. Dibenz[a,h]anthracene (1.6 X 10(-8) M), 7-methylbenz[a]anthracene (1.6 X 10(-8) M), 3-methylcholanthrene (2.8 X 10(-8) M) and picene (4.5 X 10(-8) m) exhibited the highest affinity for the receptor protein and these compounds were only 5-fold less active the 2,3,7,8-tetrachlorodibenzo-p-dioxin (1 X 10(-8) M). All of the compounds which were active in the receptor-binding and monooxygenase enzyme-induction assays possessed one common structural feature, namely the presence of a phenanthrene structure fused with at least 1 benzo ring. The results also demonstrated that there was not any apparent correlation between the receptor-binding avidities and in vitro monooxygenase enzyme-induction potencies for the most active polynuclear aromatic hydrocarbons.

Animals↗
PubMed1983

The effect of steric strain in the bay-region of polycyclic aromatic hydrocarbons: tumorigenicity of alkyl-substituted benz[a]anthracenes.

3,6-Dimethylcholanthrene (3,6-DMC) and 7,11,12-trimethylbenz[a]anthrene (7,11,12-TMBA) were tested for tumor-initiating activity on mouse skin as an approach to evaluate the potential role of steric strain in the bay-region on tumorigenic potency. Methyl-substitution at the 6-position of 3-methylcholanthrene (3-MC) increases steric strain in the bay-region of the hydrocarbon as it does at the 12-position of benz[a]anthracene (BA) causing both hydrocarbons to become non-planar. 3,6-DMC had at least 2- to 3-fold higher tumor-initiating activity than did 3-MC. Introduction of an 11-methyl group in 7,12-dimethylbenz[a]anthracene (7,12-DMBA) results in the formation of a more highly hindered (buttressing effect) hydrocarbon. 7,11,12-TMBA had 5% or less of the tumor-initiating activity of 7,12-DMBA, although the hydrocarbon still had relatively high tumorigenic activity on mouse skin. The results obtained with 3,6-DMC and studies reported previously with other methyl-substituted hydrocarbons, show that hydrocarbons possessing steric strain in the bay-region of the molecule can have enhanced tumorigenic activity. The basis of this steric effect remains unclear, however, as a result of the decreased tumorigenic activity of the 11-methyl-substituted derivative of 7,12-DMBA. The weak tumor-initiating activity of BA was enhanced at least 4- to 8-fold as a result of methyl-substitution at the 6- and 8-positions (6,8-dimethylbenz[a]anthracene). The higher tumorigenic activity of 6,8-dimethylbenz[a]anthracene compared to BA is consistent with a presumed decrease in metabolic detoxification of the dimethyl-substituted derivative at the 5,6- and 8,9-double bonds.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Metabolism and tumorigenicity of 7-, 8-, 9-, and 10-fluorobenzo(a)pyrenes.

The skin tumor-initiating activities of 7-, 8-, 9-, and 10-fluorobenzo(a)pyrenes have been compared to that of benzo(a)pyrene in female Sencar mice after 16 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Single initiating doses of 200 or 400 nmol of each hydrocarbon were tested, and the mice were treated twice weekly with 3.2 nmol of the promoter. Under these conditions, benzo(a)pyrene caused an average of 2.9 and 5.7 papillomas/mouse, respectively, whereas none of the four fluorinated hydrocarbons had significant tumor-initiating activity. Examination of the hepatic metabolism of 7- and 8-fluorobenzo(a)pyrene revealed that a 7,8-dihydrodiol was not detected as a metabolite; thus, the bay-region diol-epoxide pathway known to be responsible for the tumorigenic activity of benzo(a)pyrene is blocked. Although 7,8-dihydrodiols are formed from 9- and 10-fluorobenzo(a)pyrene, these dihydrodiols with fluorine substituted on the 9,10-double bond may not be converted to diol-epoxides by the cytochrome P-450 system, or such fluorinated 7,8-diol-9,10-epoxides may not be tumorigenic.

Animals↗
PubMed1982

Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz[a]anthracenes.

As an approach for elucidation of structure activity relationships that underlie the exceptionally large difference in carcinogenic activity between benz[a]anthracene and 7,12-dimethylbenz[a]anthracene (7,12-DMBA), 11 methyl- and/or fluorine-substituted benz[a]anthracenes were evaluated for tumor-initiating activity on mouse skin. Outbred CD-1 and outbred Sencar mice received a single topical application of the hydrocarbons followed by twice weekly applications of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate for 16-26 weeks. 7,12-DMBA was almost two orders of magnitude more active as a tumor-initiator than 7- and 12-methylbenz[a]anthracene. Methyl substitution at the 7- and 7,12-positions of benz[a]anthracene was significantly more effective in the enhancement of tumorigenic activity than fluorine substitution at these positions. Although 7-fluorobenz[a]anthracene, 12-fluorobenz[a]anthracene, and 7,12-difluorobenz[a]anthracene had only 0.15, 0.26, and less than 0.005 times the tumor-initiating activity of their respective methyl-substituted derivatives, they were severalfold more active than benz[a]anthracene. 7-Fluorobenz[a]anthracene was slightly less active than 12-fluorobenz[a]anthracene, whereas 7-methylbenz[a]anthracene was about twofold more than 12-methylbenz[a]anthracene. For 7,12-di-substituted benz[a]anthracenes, 7-methyl-12-fluorobenz[a]anthracene was more than twice as tumorigenic as 7-fluoro-12-methylbenz[a]anthracene, but each was individually more active than 7-methylbenz[a]anthracene and 12-methylbenz[a]anthracene, respectively. Both fluorinated compounds were much less active than 7,12-DMBA. Substitution of fluorine or methyl at the 5-position of 7-methylbenz[a]anthracene and substitution of fluorine at the 5-position of 12-methylbenz[a]anthracene dramatically reduced their tumorigenic activity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Synthesis and carcinogenic activity of 5-fluoro-7-(oxygenated methyl)-12-methylvenz[a]anthracenes.

Treatment of 7,12-benz[a]anthraquinone (2) with methylmagnesium iodide or methyllithium yields mixtures of cis- and trans-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (3a,b), in which the ratio of cis to trans lies in the 3--4:1 region. Each isomer afforded high yields of 7-chloromethyl-12-methylbenz[a]anthracene (5) on treatment with hydrogen chloride in ethyl acetate. Similarly, 5-fluoro-7,12-benz[a]anthraquinone (8) afforded a mixture of cis- and trans-5-fluoro-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (9) which yielded 7-chloromethyl-5-fluoro-12-methylbenz[a]anthracene (10) on treatment with HCl. The chloromethyl compounds, 5 and 10, yielded 7-acetoxymethyl-12-methylbenz[a]anthracene (6) and 7-acetoxymethyl-5-fluoro-12-methylbenz[a]anthracene (11) on treatment with acetate ion. Hydrolysis of 6 and 11 yielded 7-hydroxymethyl-12-methylbenz[a]anthracene (7) and 5-fluoro-7-hydroxymethyl-12-methylbenz[a]anthracene (12), respectively. Since neither 11 nor 12 is appreciably carcinogenic, the carcinogenic metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) probably does not involve attack at the 7-methyl group.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Dermatophilosis in two polar bears.

Dermatophilosis was diagnosed in 2 of 13 captive polar bears (Thalarctos maritimus), causing generalized dermatitis of 3 years' and 6 months' duration, respectively. Progressive clinical signs included yellowing and darkening of the hair, pruritus, encrustation of skin, and reluctance to bathe. Dramatic resolution of lesions occurred during 8 weeks of twice-weekly intramuscular treatment with long-acting penicillin.

Actinomycetales↗