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Biomedical subjects

M Douglas

Publications and source records attributed to M Douglas.

At least 73 records · Page 4Linked to original sources

Independent mutations at the amino terminus of a protein act as surrogate signals for mitochondrial import.

Intracellular delivery of the mitochondrial F1-ATPase beta-subunit precursor from the cytoplasm into the matrix of mitochondria is prevented by deletion of its mitochondrial import signal, a basic amphipathic alpha-helix at its amino terminus. Using a complementation assay, we have selected spontaneous mutations which restore the correct in vivo localization of the protein containing the import signal deletion. Analysis of these mutations revealed that different functional surrogate mitochondrial targeting signals formed within a narrow region of the extreme amino terminus of the import signal deleted beta-subunit. These modifications specifically replace different acidic residues with neutral or basic residues to generate a less acidic amphipathic helix within a region of the protein which is accessible for interaction with the membrane surface. The observations of this study confirm the requirement for amphipathicity as part of the mitochondrial import signal and suggest how mitochondrial targeting signals may have evolved within the extreme amino terminus of mitochondrial proteins.

Amino Acid Sequence↗

Pox-like lesions in a colony of carp (Cyprinus carpio).

Twelve carp (Cyprinus carpio) out of a total of 100 were affected with skin nodules, mainly located on the dorsal and lateral surface. Post mortem examination of six of the worst affected fish showed the nodules consisting of white gel-like outgrowths. No abnormality was apparent in any other tissue examined. Microscopically, the nodules were formed by proliferating hyperplastic epidermal cells. The other six fish were left for recovery and their nodules regressed spontaneously. The possible aetiological factors are listed.

Animals↗

Isolation of the structural genes for the alpha and beta subunits of the mitochondrial ATPase from the fission yeast Schizosaccharomyces pombe.

The structural genes for the two major subunits of the mitochondrial ATPase were isolated among genomic clones from the yeast Schizosaccharomyces pombe by transformation and complementation of mutants unable to grow on glycerol and lacking either the alpha or the beta subunits. The plasmid pMa1 containing a 2.3-kilobase genomic insert transformed the mutant A23-13 lacking a detectable alpha subunit. The transformant grew on glycerol and contained an alpha subunit of normal electrophoretic mobility. The plasmid pMa2 containing a 5.4-kilobase genomic insert transformed the mutant B59-1 lacking the beta subunit. The transformant grew on glycerol and contained a beta subunit of normal mobility. The structural gene for the beta ATPase subunit for the fission yeast S. pombe was localized within the pMa2 insert by hybridization to a probe containing the beta ATPase gene from the budding yeast Saccharomyces cerevisiae (Saltzgaber, J., Kunapuli, S., and Douglas, M. G. (1983) J. Biol. Chem. 258, 11465-11470). The mRNAs which hybridized to pMa1 and pMa2 were translated by a reticulocyte lysate into polypeptides of Mr = 59,000 and 54,000, respectively. These genes products reacted with an anti-F1-ATPase serum and therefore correspond most probably to precursors of the alpha and beta subunits.

Animals↗

SEM study of Strongylus vulgaris larva-induced arteritis in the pony.

This paper describes the histological and scanning electron microscopical examinations of the right colic artery of eight ponies. Lesions all had large thrombi surrounding a larva or larvae, with arterial wall thickening. Endothelial shape change, degeneration and loss were present. Fibrin-platelet red blood cell aggregates were present on endothelial surfaces as well as on the surface of thrombi. Damage to the intima appeared to produce the conditions for progressive thrombus formation.

Animals↗

The independence of insulin release and ambient insulin in vitro.

The effect of insulin on its own secretion was tested in three independent experimental models using insulin concentrations that approached physiologic values. The collected secretions from glucose-stimulated islet tissue had no effect on insulin release from other islets. Perifused insulin had no effect on the release of endogenous insulin even when the assay was completely controlled for dilutional effects. Perifused insulin had no effect on the release of prelabeled insulin from glucose-stimulated islets. Similarly, proinsulin did not affect insulin release. Porcine insulin did not affect the function of porcine or canine islets. These studies strongly support the independence of glucose-stimulated insulin secretion and ambient insulin.

Animals↗

Adenocarcinoma of the colon presenting as anaemia.

All patients with adenocarcinoma of the colon treated surgically at the Austin Hospital over a five-year period were reviewed to determine the relevance of anaemia in diagnosis. It was found that one-fifth of the patients presented with symptoms of anaemia to the doctor of first contact, and of these, one-third had an unwarranted delay in diagnosis (mean delay 13 months).

Adenocarcinoma↗