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Biomedical subjects

M J Ryan

Publications and source records attributed to M J Ryan.

At least 127 records · Page 7Linked to original sources
PubMed1983

Survey of new antihypertensive drugs: 1982.

Over 500 compounds reported to have antihypertensive activity have been cataloged from the world literature (1979-1982). The agents were classified according to mechanism: 1) drugs interacting at alpha-adrenoceptor sites; 2) beta-adrenoceptor antagonists; 3) drugs interacting with the autonomic nervous system by mechanisms other than 1 and 2; 4) inhibitors of the renin-angiotensin system; 5) diuretics; 6) vasodilator antihypertensives; and 7) drugs with miscellaneous mechanisms and/or sites of action. Within each class the drugs were subclassified and compounds that best fit the prototypes identified. The scheme is subjective, largely because of conflicting information cited in the literature. It is clear that many new drugs are at various stages of development. Whether or not these drugs will survive the scrutiny of rigorous and lengthy preclinical and clinical development, and in fact prove to be better antihypertensive agents than the currently marketed agents, remains to be established.

Antihypertensive Agents↗
PubMed1982

A Hammondia-like coccidian with a mink-muskrat life cycle.

A tissue cyst-forming coccidian morphologically resembling the known species Hammondia has a mink-muskrat life cycle. Cysts are found in skeletal muscle of muskrats (Ondatra zibetheca). Mink (Mustela vison) fed infected muskrat carcasses shed oocysts for 4 to 6 days after a prepatent period of 6 to 8 days. The oocysts, 99% of which are unsporulated in mink feces, measure 11.5 to 12 microns X 10 to 11 microns. Sporulated oocysts have 2 sporocysts, each with 4 sporozoites. The present work was insufficient to establish whether this Hammondia-like parasite is identical to the known Hammondia spp. or is a new parasite, although the evidence gathered supports the hypothesis that this parasite is a new member of the genus Hammondia.

Animals↗
PubMed1981

Acute fatal toxoplasmosis in squirrels.

Two dead gray squirrels submitted to the Northeastern Research Center for Wildlife Diseases ahd nonsuppurative encephalitis and interstitial pneumonitis, with Toxoplasma gondii cysts and tachyzoites in many tissues. These infections have rarely been reported from gray squirrels but could mimic clinical rabies.

Animals↗
PubMed1981

Synthesis and angiotensin-converting enzyme inhibitory activity of 3-(Mercaptomethyl)-2-oxo-1-pyrrolidineacetic acids and 3-(Mercaptomethyl)-2-oxo-1-piperidineacetic acids.

A number of gamma- and delta-lactam derivatives were synthesized and their in vitro angiotensin-converting enzyme (ACE) inhibitory activities were compared. The structures of these compounds were designed to include many of the important features of captopril. The synthesis involved the preparation of a variety of novel 3-methylene-2-pyrrolidinones (3-5 and 16) and 3-methylene-2-piperidinones (3a-5a, 10-12, and 17). The key intermediate 3-methylenelactams 3 and 3a were obtained from 3-(hydroxymethyl)lactams 2 and 2a by a direct dehydration with dicyclohexylcarbodiimide using cuprous iodide as a catalyst. Introduction of the sulfhydryl group was accomplished by a Michael addition of these alpha, beta-unsaturated lactams. The compound with the highest in vitro activity was 3-(mercaptomethyl)-2-oxo-1-piperidineacetic acid (7a). The activity of the 7a both in vitro and in vivo (dog) was shown to be less than that of captopril by a factor of about 100.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1979

A synthetic tyrosine suppressor tRNA gene with an altered promoter sequence. Its cloning and relative expression in vivo.

The total synthesis of a tyrosine suppressor tRNA gene with a modified promoter is described. The alteration involves the replacement of the four G:C base pairs immediately preceding the start point of transcription by A:T base pairs. The new sequence contains the recognition sequence for the HindIII restriction endonuclease at the transcriptional start point, thus permitting fusion of the structural gene with promoters containing independent sequence modifications. The construction, cloning, and biological activity of several recombinant DNAs containing the tRNA gene with the modified promoter are described. The expression of this gene in vivo is compared with that of both the unmodified synthetic suppressor gene and a naturally occurring tyr su3+ gene cloned onto a multicopy plasmid.

Base Sequence↗
PubMed1979

Total synthesis of a tyrosine suppressor transfer RNA gene. XVI. Enzymatic joinings to form the total 207-base pair-long DNA.

The total synthesis of a 207-base pair-long DNA, which is biologically functional as a tyrosine suppressor transfer RNA gene, has been completed. The synthesis involved the enzymatic joining of the previously synthesized duplexes. Thus, the duplex corresponding to the promoter region [P] (Sekiya, T., Brown, E.L., Ramamoorthy, B., Fritz, H.-J., Gait, M.J., Lees, R.G., Ryan, M.J., Khorana, H.G., and Norris, K.E. (1979) J. Biol. Chem. 254, 5781-5786) was jointed to Duplex [I] (Caruthers, M.H., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol Chem. 251, 658-666) to form [P + I]. Separatively, Duplex [III + IV + Vb] was prepared from the previously described Duplexes [III], [IV], and [Vb]. (Loewen, P.C., Miller, R.C., Panet, A., Sekiya, T., and Khorana, H.G. (1976) J. Biol. Chem. 251, 642-650; Sekiya, T., Besmer, P., Takeya, T., and Khorana, H.G. 1976) J. Biol. Chem. 251, 634-641; Ramamoorthy, B., Lees, R.G., Kleid, D., and Khorana, H.G., (1976) J. Biol Chem. 251, 676-694). The product [P + I], was joined to Duplex [II] (Panet, A., Kleppe, R., Kleppe, K., and Khorana, H.G. (1976) J. Biol. Chem. 251, 651-657) and then to [III + IV + Vb] without isolation of the intermediates. In all the above joinings, the duplexes carried 32P-labeled phosphate groups at the appropriate 5'-ends. The total DNA and the intermediate duplexes were all characterized by their relative mobilities in electrophoresis on polyacrylamide gel slabs, by nearest neighbor analysis, and by degradation to 5'-nucleotides of radioactively labeled joined products. Two succeeding papers describe the transcription in vitro and the suppressor activity in vivo, of the synthetic gene now described.

Base Sequence↗
PubMed1979

Total synthesis of a tyrosine suppressor tRNA gene. XV. Synthesis of the promoter region.

By use of polynucleotide kinase and polynucleotide ligase, the 10 deoxyoligonucleotide segments, whose syntheses have been described in accompanying papers, have been joined to form the 62-nucleotide-long DNA corresponding to the promoter region of an Escherichia coli suppressor tRNA gene. The following sequence in the joining reactions was used to obtain error-free and optimal yields of the products: 1) joining of Segment P-1 to P-3 in the presence of Segment P-2; 2) joining of Segments P-4 to P-7 to form Duplex [P4-7]; 3) joining of Segments P-8 to P-10 to Duplex [P4-7] to form Duplex [P4-10]; and finally, 4) joining of P-(1 + 3) and P-2 to Duplex [P4-10] to form the total promoter Duplex [P].

Base Sequence↗
PubMed1979

Total synthesis of a tyrosine suppressor tRNA gene. XVIII. Biological activity and transcription, in vitro, of the cloned gene.

The chemically synthesized gene for Escherichia coli tyrosine suppressor tRNA has been joined to both plasmid (ColE1 ampr) and bacteriophage (Charon 3A) vector chromosomes after the latter had been digested with the restriction endonuclease EcoRI. Suppression of both bacterial (trpA, his, lacZ) and bacteriophage lambda amber mutations (Aam32, Bam1) has been demonstrated after transformation of E. coli with the recombinant DNA molecules carrying the synthetic suppressor tRNA gene. The cloned synthetic gene has been reisolated from the vector chromosomes after digestion of the latter with EcoRI restriction endonuclease and characterized in regard to its size and its ability to serve as a source of suppressor activity in further transformation experiments. This synthetic gene has also been shown to suppress bacterial amber mutations after it had been incorporated into the E. coli chromosome as part of a lambda prophage. Transcription, in vitro, of the cloned synthetic suppressor gene gave a product which, on treatment with a crude E. coli extract, afforded the tyrosine suppressor tRNA precursor. The latter was characterized by two-dimensional fingerprinting after digestion with T1-RNase. Exposure of the in vitro transcript to RNase P Selectively released the 41-nucleotide-long fragment characteristic of the 5'-end of the tRNA precursor. Thus, the nucleotide sequence of the cloned gene is accurate and its expression is controlled by its promoter.

Base Sequence↗