Biomedical subjects

J A Lees

Publications and source records attributed to J A Lees.

44 records · Page 3Linked to original sources

PubMed1990

The effect of patterns of rumen fermentation on the response by dairy cows to dietary protein concentration.

Four groups of seven dairy cows were given hay plus high-fibre concentrates based on sugar-beet feed (hay-concentrate, 40:60 w/w) or high-starch concentrates based on flaked maize (hay-concentrate, 20:80 w/w), with a crude protein (nitrogen x 6.25) content of either 160 or 220 g/kg dry matter, over weeks 4-18 of lactation. Performance during week 3 of lactation, when all cows were fed on a standard ration, was used as a covariate. For diets with a high-fibre content, higher protein concentrations led to increases in yields of milk and milk fat, with no effect on live-weight loss. For diets with a high-starch content, higher protein concentrations did not affect milk yield or composition but resulted in an increase in live weight rather than a decrease. Diets with a high-starch content led to increased proportions of propionic acid in the rumen and increased concentrations of insulin in the blood. It is concluded that the source of carbohydrate needs to be taken into account when predicting the response to protein supply by dairy cows.

Animals↗

PubMed1990

A 22-amino-acid peptide restores DNA-binding activity to dimerization-defective mutants of the estrogen receptor.

We have identified residues within the estrogen receptor that are required for dimerization and high-affinity DNA binding. A 22-amino-acid peptide encompassing these residues was sufficient to restore DNA-binding activity to a mutant receptor lacking most of the hormone-binding domain. Point mutagenesis of the fusion protein confirmed that this sequence continued to mediate dimerization in a manner similar to that within the native receptor, although its position relative to the DNA-binding domain was appreciably altered.

Amino Acid Sequence↗

PubMed1989

Identification of two transactivation domains in the mouse oestrogen receptor.

We have identified two discrete transactivation domains within the mouse oestrogen receptor whose relative activities vary according to the target promoter. One domain lies within the N-terminal region and is active in the absence of oestradiol. The second domain is contained within the C-terminal portion of the protein and depends upon oestrogen binding for its activity. The location and oestrogen dependence of this domain has been confirmed using chimaeric receptors containing the Lex A DNA binding domain. Although transactivation by the C-terminal domain is dependent upon ligand binding the analysis of receptor deletion mutants has demonstrated that these two functions are not entirely coincident.

Animals↗

PubMed1989

Identification of constitutive and steroid-dependent transactivation domains in the mouse oestrogen receptor.

We have identified two transactivation domains in the mouse oestrogen receptor whose activities depend on the target promoter. The major domain is contained within the C-terminal portion of the protein and depends upon oestrogen binding for its activity. The location and oestrogen dependence of this domain has been confirmed using chimaeric receptors containing the Lex A DNA binding domain. Although transactivation by the C-terminal domain is dependent upon ligand binding the analysis of receptor deletion mutants has demonstrated that these two functions are not entirely coincident. The second transactivation domain lies within the N-terminal region and is active in the absence of oestradiol. The differences in oestrogen requirement for the activity of the two transactivation domains may account for the partial agonist activity of certain antihormones.

Animals↗

PubMed1989

A proposed consensus steroid-binding sequence--a reply.

A consensus sequence has been proposed as necessary for steroid binding on the basis of sequence homology in steroidogenic enzymes, steroid binding proteins and steroid receptors. We have mapped the limit of sequences important for steroid binding in the mouse estrogen receptor using Scatchard analysis of deletion mutants. Since a mutant lacking the entire proposed consensus is still able to bind estradiol with essentially wild type affinity, the functional significance of this motif is unclear.

Amino Acid Sequence↗

PubMed1987

Structural organization and expression of the mouse estrogen receptor.

Complementary DNA clones corresponding to the mouse uterus estrogen receptor mRNA have been isolated and characterized. Nucleotide sequence analysis predicts that full-length cDNA has the potential to code for a polypeptide of 599 amino acids, and comparison with the protein sequences of the rat, human, and chicken estrogen receptors reveals overall homologies of 97%, 88% and 77%, respectively. Genomic clones for the mouse estrogen receptor have been isolated from a cosmid library and used in conjunction with the cDNA clones to study the expression of the receptor in vivo by RNase mapping, primer extension, and Northern blotting. These analyses demonstrate that transcription initiates at multiple sites which span a region of at least 62 base pairs and that the estrogen receptor is encoded by mRNA of approximately 6.5 kilobases in size. There are 10 major starts in total, one of which is situated 31 nucleotides downstream from a TATA box-like motif and coincides with the start of the cDNA clone pMOR8. The ability of the cDNA clone to produce a functional protein was verified by transfection into COS-1 cells which lack endogenous estrogen receptor. The mouse estrogen receptor, in a SV40-based expression vector, was cotransfected with a chimeric marker plasmid consisting of an estrogen response element from the vitellogenin A2 gene linked to the thymidine kinase promoter and the chloramphenicol acetyl transferase gene. In the presence of estradiol chloramphenicol acetyl transferase activity is stimulated by up to 80-fold, while tamoxifen and 4-hydroxytamoxifen act primarily as antiestrogens in this in vitro assay.

Amino Acid Sequence↗

PubMed1986

Hypoglycemia in hospitalized patients. Causes and outcomes.

We analyzed 137 episodes of hypoglycemia (serum glucose less than or equal to 49 mg per deciliter) occurring in 94 adult patients hospitalized during a six-month period at a tertiary care hospital. Forty-five percent of the patients had diabetes mellitus, and administered insulin was implicated in 90 percent of episodes in diabetics. Hypoglycemia in diabetic patients occurred under a variety of circumstances, frequently because of decreased caloric intake related to illness or hospital routine. Insulin-induced hypoglycemia also occurred during treatment of hyperkalemia (eight patients) or during hyperglycemia related to total parenteral nutrition (six patients). Forty-six of the 94 patients had chronic renal insufficiency, and 20 of these 46 had underlying diabetes mellitus. Thus, renal insufficiency unrelated to diabetes mellitus was the second most frequent diagnosis associated with hypoglycemia. The majority of other cases of hypoglycemia were related to liver disease, infections, shock, pregnancy, neoplasia, or burns. Hypoglycemia was not the apparent cause of death in any patient, but the overall hospital mortality was 27 percent and was related to the degree of hypoglycemia and the number of risk factors for hypoglycemia. We conclude that hypoglycemia is a common problem in hospitalized patients, is common in renal insufficiency, is usually iatrogenic, and correlates with high mortality in severely ill patients.

Adult↗

PubMed1985

Pyocystis, pyonephrosis and perinephric abscess in end stage renal disease.

We report 8 patients with end stage renal disease on maintenance hemodialysis who had pyocystis, pyonephrosis or a perinephric abscess. Delay in diagnosis was frequent because the urine-deprived bladder and kidneys were dismissed as potential sites of infection. Treatment of pyocystis with bladder irrigations often was successful and obviated cystectomy. Pyonephrosis or perinephric abscess was a more serious problem and required unilateral nephrectomy.

Abscess↗