Search PubMed⌕ Search

Biomedical subjects

S Hughes

Publications and source records attributed to S Hughes.

At least 217 records · Page 12Linked to original sources
PubMed1985

Hepatic delta 6-desaturase activity in lean and genetically obese ob/ob mice.

Hepatic delta 6-desaturase activity is primarily located in the mitochondrial fraction in mice. Both delta 6- and delta 5-desaturase activities are increased in the liver of young (6-week-old) obese mice. The increase in hepatic delta 6-desaturase activity in obese mice does not occur until weaning. Neither restriction of food intake nor hyperinsulinaemia normalize hepatic delta 6-desaturase activity of obese mice. Both cold acclimation and tri-iodothyronine (30 micrograms/day per kg) decreased hepatic delta 6-desaturase activity of obese mice to levels observed in lean mice, whereas the increase in activity in obese mice was still maintained after the induction of hypothyroidism.

Animals↗
PubMed1984

Mutagenesis of the region between env and src of the SR-A strain of Rous sarcoma virus for the purpose of constructing helper-independent vectors.

The major goal of these experiments is to derive stable, helper independent, retroviral vectors using the SR-A strain of Rous sarcoma virus. Because src is flanked by direct repeats of 110 bases, both src, and sequences that replace src in vector constructions, are lost at high frequency. We have sought to eliminate this homology in order to stabilize the vectors. One copy of the direct repeat must be retained for the virus to replicate properly. Because the downstream direct repeat is linked to the polypurine tract the entire downstream direct repeat cannot easily be eliminated. We therefore sought to eliminate the upstream direct repeat. Using linkers a series of defined deletions and duplications has been created within the region between env and src. The region is relatively large, 379 bases, and has a complex history (it is derived from three different nucleic acid segments each with a distinct and separate origin). We show here that this region provides no functions essential for growth and, for src expression, provides only a functional splice acceptor. We were able to successfully replace the splice acceptor found in the wild type virus with an unrelated splice acceptor partially derived from a synthetic DNA segment. The final product is a replication competent virus that expresses src, and that lacks the entire upstream repeat. Since src is flanked by ClaI sites in these constructions, src can easily be replaced by other genes. Substituting the Tn5 neo gene for src in this construction yields a virus that expresses the neo gene nonselectively.

Animals↗
PubMed1984

An unusual 5' splice sequence is efficiently utilized in vivo.

The minor adult chicken alpha-globin gene (alpha D) has an intron splicing sequence at the 5' end of the second intron that begins with the dinucleotide G-C rather than the usual G-T. To understand what role this splice sequence plays in the processing and maturation of nuclear RNA to cytoplasmic RNA, we have analyzed the intron processing of the alpha D-globin transcript in both heterologous (monkey) and homologous (chicken) cells using simian virus 40 and retrovirus vectors, respectively. In both cell types, both introns of the alpha D-globin gene are efficiently and precisely removed.

Animals↗
PubMed1984

Mutation of a termination codon affects src initiation.

The four Rous sarcoma virus messages gag, gag-pol, env, and src all derive from a full-length RNA precursor. All four messages contain the same 5' leader segment. Three of the messages, gag, gag-pol, and env, use an AUG present in this leader to initiate translation. The src AUG initiation codon lies 3' of the leader segment, 90 bases downstream of the gag initiation codon in the spliced src message. However, in the spliced src message a UGA termination codon lies between the gag AUG and the src AUG. All three codons are in the same reading frame. By using oligonucleotide-directed mutagenesis, the UGA termination codon has been converted to CGA. Cells infected with the mutant (called 1057 CGA) were spindle shaped, distinct from the rounded shape of cells infected with the parental Rous sarcoma virus. The mutant virus initiates src translation at the gag AUG, producing a 63,000-dalton src protein. We suggest that the wild-type src message produces two polypeptides, a very small (nine-amino acid) peptide that is initiated at the gag AUG and the 60,000-dalton src protein that is initiated at the src AUG.

Amino Acid Sequence↗
PubMed1984

Controlled trial of rifampicin and ethambutol in Crohn's disease.

We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn's disease by carrying out a trial of treatment with antimycobacterial drugs. Twenty seven patients with Crohn's disease took part in a two year randomised double blind, crossover, controlled trial of rifampicin plus ethambutol against placebo. Fourteen patients completed the trial; four required an operation; five were withdrawn as poor compliers, and four because of adverse effects. There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn's disease activity index or any clinical indicator of disease activity. There was no suggestion that any subgroup of patients - for example, different regions of bowel affected or previous operation - were favourably affected by the drugs. There was no consistent pattern of change in prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period. A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy. The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn's disease.

Adult↗
PubMed1984

Loperamide has antisecretory activity in the human jejunum in vivo.

We investigated the possibility that loperamide might influence absorption and secretion in the human jejunum in vivo. Using a triple lumen tube perfusion technique in healthy normal volunteers we showed that loperamide did not affect net absorption of water or electrolytes under basal condition. When secretion was induced by prostaglandin E2, however, loperamide significantly reduced that secretion and in three out of six subjects secretion was abolished. Loperamide was effective when it was given either before or after secretion had been initiated. The results lend support to the suggestion that the antidiarrhoeal activities of loperamide may include an antisecretory effect.

Dinoprostone↗
PubMed1983

Isolation of Yersinia enterocolitica from pigs in the United Kingdom.

A survey of the incidence of Yersinia enterocolitica from pigs in the United Kingdom was carried out by two laboratories using pre-enrichment culture methods on colon/caecal contents, faeces and tonsil tissue. Altogether 1931 specimens were cultured and 112 strains of Y enterocolitica were isolated. Only two strains were related to biotype 4, human serotype O:3 and none to biotype 2, human serotype O:9. All other isolates belonged to biotype 1. Many serotypes were identified, the predominant ones being O:6 (30) and O:5 (15) but 41 strains could not be serotyped. Possible reasons for the low incidence of serotype O:3 are discussed.

Animals↗
PubMed1983

[Na+ + K+] ATP-ase in liver and brain of obese mice.

The activity of hepatic [Na+ + K+]ATP-ase showed a gene-dosage relationship in 6 week old mice. Before weaning hepatic [Na+ + K+]ATP-ase activity was normal in preobese mice but fell within 7 days of weaning to the low levels observed in older ob/ob mice. Brain [Na+ + K+]ATP-ase activity was unchanged in ob/ob mice although [3H]-ouabain binding was reduced. Arrhenius plots of [Na+ + K+]ATP-ase activity in liver and brain and of [3H]-ouabain binding to brain preparations showed breakpoints at lower temperatures in ob/ob than lean mice. These breakpoints were altered by pretreatment of tissue with deoxycholate. It is suggested that changes in membrane lipid composition might be an important factor regulating [Na+ + K+]ATP-ase in ob/ob mice.

Age Factors↗
PubMed1983

Clostridium difficile toxin-induced intestinal secretion in rabbit ileum in vitro.

In rabbit ileum in vitro Clostridium difficile toxin (200 microliter crude extract) almost abolished net Na absorption, by decreasing mucosa to serosa flux, and induced net Cl secretion by increasing the serosa to mucosa flux. These flux changes were induced when there was no visible histological damage to the mucosa. The toxin did not influence adenylate or guanylate cyclase activity in a plasma membrane fraction of isolated rabbit enterocytes nor did it affect cAMP concentrations in intact rabbit ileum pre-incubated with toxin. The flux responses to the toxin were prevented by removing calcium from the serosal medium, suggesting that the secretory process may be calcium dependent. These results indicate a possible mechanism by which this toxin could induce diarrhoea.

Animals↗