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Biomedical subjects

S Wright

Publications and source records attributed to S Wright.

At least 289 records · Page 16Linked to original sources

DNA sequences required for regulated expression of beta-globin genes in murine erythroleukaemia cells.

We have introduced into murine erythroleukaemia (MEL) cells a series of human globin gene cosmids and two sets of hybrid genes constructed from the human beta-globin gene and the human gamma-globin or murine H-2Kbm1 genes. S1-nuclease analysis of the mRNA products from these genes before and after MEL cell differentiation showed that the human beta-globin gene, but not the human epsilon- or gamma-globin or H-2Kbm1 genes, is induced specifically. Hybrid genes containing human beta-globin DNA sequences from either 5' or 3' side of the translation initiation site were both inducible. Measurement of the relative rate of transcription showed this induction to be the result of transcriptional activation. We therefore suggest that DNA sequences which regulate beta-globin gene expression during MEL differentiation are located both 5' and 3' to the translation initiation site.

Animals↗

The first Meckel oration: on the causes of morphological differences in a population of guinea pigs.

The first morphological abnormality considered here was of a very superficial sort: deviations from the smooth coat of wild cavies and most guinea pigs. The deviations of "rough-furred" individuals range from a single irregularity or a single pair of rosettes to the "full rough" pattern. Roughness may be restricted to the hind toes, forehead, or hair around the eyes or belly, or (very rarely) to a small area on one side of the back. There is no indication of gene control in the last, and no analysis of the only strain (in Professor Castle's laboratory) that I have seen, of roughness restricted to the belly. A dominant gene, R, in combination with a semidominant modifier, M, account for the fancier roughs (R-MM toes only, R-mm full rough). A gene, st, that is completely dominant in the absence of R, semidominant in its presence, was descended from 3 animals from outside the colony. It accounts for a large forehead rosette, usually with a small white spot in front of its center. A statistically semidominant gene, Re, with extremely irregular, often asymmetric penetrance tends to cause rosettes about the eyes. This arose by mutation late in the history of the Whitman colony. It is strengthened by presence of R MM. Considerable variation occurs in the numbers of dorsal rosettes of R Mm and R mm. These have not been analyzed satisfactorily because the genetic differences are confounded by nongenetic ones. It is not practicable to summarize briefly all of the complex interaction effects of these factors, but it may be noted that the most surprising one had to do with genes St and R. The forehead rosette due to rr St closely resembles that of R mm (except for the absence of the pleiotropic white spot). The combination, R mm St St, shows none of the expected enhancement but instead shows nearly complete cancellation of the rosette. Moreover, the anterior dorsal rosettes of R mm st st are much reduced and seemingly shoved backward and laterally to give a large smooth shield back of the ears. St St also reduces the usual dorsal pair of rosettes of R Mm. With St st, all of these antagonistic effects are weaker and less regular. Another morphological deviation to be considered was the fairly common restoration of an atavistic little toe.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Severe Teratoid↗

DNA sequences required for regulated expression of beta-globin genes in murine erythroleukemia cells.

We introduced into MEL cells rabbit beta-globin gene deletion mutants and two sets of hybrid genes constructed from the inducible human beta-globin gene and noninducible human gamma-globin gene or the murine H-2Kbm1 class I MHC gene. S1 nuclease analysis of gene transcripts before and after MEL differentiation showed that induction of the rabbit beta-globin gene did not require more than 58 bp of DNA 5' to the transcription initiation site. Hybrid genes were constructed with human beta-globin DNA sequences from either 5' or 3' of the translation initiation site linked to the complementary parts of the gamma or H2Kbm1 genes. Both types of constructs were inducible during MEL differentiation. The relative rates of transcription of the 5' gamma-3' beta and 5'H2-3' beta hybrid genes show that induction of the hybrid gene transcripts results at least in part from transcriptional activation of the genes. We suggest that DNA sequences that regulate beta-globin gene transcription during MEL differentiation are located both 5' and 3' to the translation initiation site.

Animals↗

A cooperative organizational form for hospitals.

Hospitals face severe financial pressures at the same time that patients and physicians are demanding quality medical care and the latest technology, which is becoming increasingly costly. Hospitals must consider adopting and experimenting with a cooperative organization system, which groups physicians, nurses and administrators together in teams to plan jointly and allocate resources.

Budgets↗

Essential fatty acids in the plasma phospholipids of patients with atopic eczema.

We have measured all the essential fatty acids (EFA) in plasma phospholipids in forty-one adults with atopic eczema and fifty normal controls. The major dietary n-6 EFA, linoleic acid, was significantly elevated, but all its metabolites, 18:3n-6, 20:3n-6, 20:4n-6, 22:4n-6, and 22:5n-6 were significantly reduced. The major dietary n-3 EFA, alpha-linolenic acid, was also elevated, though not significantly, while all its metabolites were also significantly reduced. These observations suggest that atopic eczema is associated not with any defect of EFA intake, but with abnormal metabolism, possibly involving the enzyme delta-6-desaturase. Treatment with oral evening primrose oil produced partial correction of the n-6 EFA abnormality, but had no effect on the n-3 EFAs.

Adult↗

Effect of anthelmintic treatment on the productivity of lambs infected with the intestinal nematode, Trichostrongylus colubriformis.

Liveweight gain, food intake, wool growth and concentration of serum constituents were measured in four groups of three-month-old lambs. Groups 1 and 2 were infected on five days each week with 2500 Trichostrongylus colubriformis larvae for 18 weeks. Group 2 lambs were treated with fenbendazole (5 mg kg-1) at week 10 and week 15. Group 3 lambs were similarly infected for 10 weeks, treated with fenbendazole, but given no further larvae. A fourth control group remained uninfected throughout the trial. All lambs were killed at week 20. Mean worm populations were 16,130, 430 and zero for groups 1, 2 and 3 respectively. Over the first 10 weeks of infection, liveweight gain was reduced by 52, 43 and 51 per cent and wool growth by 33, 28 and 27 per cent respectively, in groups 1, 2 and 3. Serum hypophosphataemia and hypoalbuminaemia occurred in all three infected groups. Between weeks 10 and 20 overall weight gain and wool growth in group 1 lambs were 44 and 46 per cent lower than the controls, whereas weight gains of group 2 and group 3 lambs were similar to or slightly higher than in the controls. However, wool growth in these two groups after treatment was only 73 to 74 per cent of control values. Serum phosphorus concentrations increased to control levels within one week of anthelmintic treatment and serum albumin concentrations by two to four weeks. The ability of group 2 lambs to improve their performance after anthelmintic treatment, in the face of continued challenge, was attributed to development of resistance to reinfection.

Animals↗

The sequence GGCmCGG is resistant to MspI cleavage.

MspI essentially fails to cut the sequence GGCmCGG at enzyme concentrations which give total digestion of CCGG, CmCGG and GGCCGG sites. This result explains why certain sites in mammalian DNA are resistant to both MspI and HpaII and shows that this results from an idiosynchracy of MspI rather than a novel form of DNA methylation at this site in mammalian cells.

Animals↗

The response of articular cartilage to the in vivo replacement of synovial fluid with saline.

Experiments on rabbits were performed to determine whether continuous irrigation of a synovial joint produced irreversible degenerative changes in the articular cartilage. Continuous irrigation of a synovial joint permits observations of the effect on articular cartilage of altering the intra-articular environment. The right knee joints were irrigated with normal saline for varying periods, up to 14 days, and the left knees served as nonirrigated controls. One group of animals (short-term) was killed immediately following irrigation, while another group (long-term) was assessed after six months of cage activity following the irrigation period. Within each group, half were skeletally immature and half were mature. No differences in cell density, nuclei-to-lacunae ratio, or the ratio of calcified layer to total cartilage thickness were found in any group. Irrigation did produce a significant reduction in matrix staining with safranin-O. This was first detectable following three days of irrigation and was severe by seven to 14 days. Staining properties returned to normal after six months of cage activity. No obvious difference was found between immature and mature animals.

Age Factors↗