PubMed Health⌕ Search

Biomedical subjects

S Hoare

Publications and source records attributed to S Hoare.

35 records · Page 2Linked to original sources
PubMed1997

Abnormal technetium labelled white cell scan in the colitis of chronic granulomatous disease.

A child with colitis was treated for Crohn's disease, diagnosed on history, clinical and colonoscopic findings, radiolabelled white cell bowel scan, and colonic histology. After septicaemia caused by an unusual organism, further investigation lead to a diagnosis of chronic granulomatous disease (CGD). The granulomatous colitis of CGD is clinically, histologically, and on white cell scanning, indistinguishable from that in Crohn's disease and should be considered in atypical cases. Infection with unusual 'pseudomonads' should prompt the exclusion of this disorder.

Burkholderia Infections↗
PubMed1996

Dietary supplementation and rapid catch-up growth after acute diarrhoea in childhood.

Diarrhoea is a major cause of short-term growth faltering in children of the developing world. If catch-up weight gain is delayed by inadequate dietary intake, or by further bouts of diarrhoea, progressive growth failure occurs. To test the hypothesis that early refeeding is as effective as later feeding after acute diarrhoea with weight loss, we measured the effects of a timed dietary intervention on weight gain after acute diarrhoea in underweight Gambian children. Thirty-four children aged 4-22 months with weight loss following acute diarrhoea were given a high-energy-protein supplement for 14 d beginning either immediately after rehydration or a fortnight later. With a 50% increase in energy intake and a 100% increase in protein intake there was a rapid and highly significant (P < 0.001) gain in weight within a fortnight whether the supplement was given immediately or 2 weeks after presentation. Rates of weight increase were similar whether supplementation was provided early or late, but over the full 28 d (of intervention and non-intervention) children who received late supplementation had greater overall weight gain (P < 0.02) than those supplemented early. Vigorous and early feeding with a high-energy-protein supplement should be central to the management of malnourished children with acute diarrhoea in developing countries, and may be as important as control of diarrhoea in preventing malnutrition and growth failure. This may be achieved in the community using locally available foods, in the face of continuing diarrhoea.

Acute Disease↗
PubMed1995

Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.

A conserved region in the hormone-dependent activation domain AF2 of nuclear receptors plays an important role in transcriptional activation. We have characterized a novel nuclear protein, RIP140, that specifically interacts in vitro with this domain of the estrogen receptor. This interaction was increased by estrogen, but not by anti-estrogens and the in vitro binding capacity of mutant receptors correlates with their ability to stimulate transcription. RIP140 also interacts with estrogen receptor in intact cells and modulates its transcriptional activity in the presence of estrogen, but not the anti-estrogen 4-hydroxytamoxifen. In view of its widespread expression in mammalian cells, RIP140 may interact with other members of the superfamily of nuclear receptors and thereby act as a potential co-activator of hormone-regulated gene transcription.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Measurement of starch digestion of naturally 13C-enriched weaning foods, before and after partial digestion with amylase-rich flour, using a 13C breath test.

Malnutrition in infancy is a global problem which leads to retardation of childhood growth and development. There is a pressing need to improve weaning strategies for infants of the developing world. Traditional Gambian weaning foods are watery and of low energy density, but addition of energy in the form of fat and carbohydrate leads to thick, viscous gruels which are difficult to ingest. Partial digestion with amylase (EC 3.2.1.1)-rich flour reduces their viscosity while retaining their energy density. The aim of the present study was to measure the digestibility of a maize-based weaning food, before and after amylase digestion, in malnourished children using a 13C breath test. Ten children (aged 7-16 months; mean weight-for-age Z score -0.8) received isovolumetric and isoenergetic quantities of a maize-based weaning food naturally abundant with 13C. Breath samples were collected at intervals of 30 min for 5 h thereafter and 13CO2 enrichment was measured by isotope-ratio mass spectrometry. Percentage dose of 13C recovered increased from a mean 13.7 (SD 3.7)% before, to 18.3 (SD 5.6)% after ingestion of amylase-treated weaning foods (P < 0.1). There was a significant inverse relation between age and weight, and percentage dose of 13C recovered in children receiving amylase-treated feeds. There were no differences in concentrations of amylase in saliva of infants or breast milk of their mothers. Partial digestion of supplementary foods may improve the nutrition of undernourished weaning children, not only by reducing their viscosity, thereby increasing ingestion, but also by improving their digestion and thereby their absorption.

Age Factors↗
PubMed1995

Neutrophil elastase and cathepsin G protein and messenger RNA expression in bone marrow from a patient with Chediak-Higashi syndrome.

Aims-To determine whether neutrophil elastase and cathepsin G are expressed, at transcriptional or translational levels, in the bone marrow from a patient with Chediak-Higashi syndrome.Methods-Blood neutrophils were isolated from three patients with Chediak-Higashi disease and bone marrow was collected from one. Cell lysates were analysed for neutrophil elastase and cathepsin G activity by enzyme linked immunosorbent assay and western immunoblotting. Northern blotting was used to detect messenger RNA (mRNA) for cathepsin G, elastase and beta-actin in bone marrow extracts, and immunohistochemistry was used to localise the enzymes in marrow myeloid cells.Results-Elastase and cathepsin G were not detected in blood neutrophils from the patients with Chediak-Higashi disease, but were present in bone marrow cells, although immunohistochemistry showed they were not within cytoplasmic granules. The concentrations of elastase and cathepsin G in Chediak-Higashi bone marrow were about 25 and 15%, respectively, of those in normal marrow. Quantitative scanning of northern blots showed that elastase and cathepsin G mRNA, corrected for beta-actin mRNA, were expressed equally in normal marrow.Conclusions-Transcription of elastase and cathepsin G mRNA in promyelocytes of patients with Chediak-Higashi disease is normal, but the protein products are deficient in these cells and absent in mature neutrophils. This suggests that the translated proteins are not packaged into azurophil granules but are degaded or secreted from the cells.

Journal Article↗
PubMed1994

Biochemical indices and neuromuscular function tests in rural Gambian schoolchildren given a riboflavin, or multivitamin plus iron, supplement.

Ninety preselected children, aged between 8 and 14 years, living in two rural West African (Gambian) villages, were randomly divided into three groups, matched for age and sex. One group received a placebo (lactose) tablet, one received riboflavin (5 mg) on 5 d every week, which was sufficient to correct an endemic riboflavin deficiency, and one received a multivitamin supplement (Protovit; Hoffmann La Roche), on 5 d every week, together with FeSO4 (200 mg) once weekly, and the supplements were given for 1 year. Neuromuscular tests, including arm tremor and manipulative skills, were performed on three occasions: once just before the introduction of the supplements; again 6 weeks after commencing the supplements; and again 1 year later. Venous blood samples were collected at the same time as the first two sets of neuromuscular tests. These samples were used for haematology and nutrient status indices: plasma ferritin, ascorbic acid, cyanocobalamin and pyridoxal phosphate, and erythrocyte tests for folate status, for riboflavin status (erythrocyte glutathione reductase activation coefficient) and thiamine status (erythrocyte transketolase activation coefficient). The riboflavin in both supplements achieved a clear-cut response in biochemical status, which was dose-dependent. The pyridoxine, ascorbic acid and Fe components of the multivitamin also affected the associated biochemical indices. Although overall the arm tremor and related neuromuscular function tests did not respond significantly to the supplements, significant improvement was seen in the boys for the arm-tremor test in both the supplemented groups.

Adolescent↗
PubMed1994

Breakthrough infections and identification of a viral variant in Gambian children immunized with hepatitis B vaccine.

Hepatitis B (HB) breakthrough infections, identified by the presence of HB core (c) antibody, were found in 32 of 358 Gambian children vaccinated with plasma-derived HB vaccine. Over 2 years, 15 of these children lost their HBc antibodies. These children had significantly higher HB surface antibody levels before infection than those who retained HBc antibodies. One child, who responded well to the vaccine, had HB viral DNA detected in the presence of HBs antibodies. The S gene sequence of this DNA showed nucleotide changes that resulted in an amino acid substitution at residue 141 (lysine to glutamic acid) of the surface antigen. This finding suggests the child was infected with a variant virus that was not neutralized by antibodies resulting from HB vaccination.

Child↗
PubMed1993

A trial of zinc supplementation in young rural Gambian children.

The present study tested the hypothesis that inadequate Zn intake might be responsible for failure to thrive and impaired catch-up growth in young rural Gambian children, and that Zn supplements might be beneficial. Gambian children might be deprived of Zn because of its poor availability from their predominantly plant-based diet. Rural Gambian children (110; fifty boys, sixty girls) aged between 0.57 and 2.30 years were divided into two matched groups, one to receive 70 mg Zn twice weekly for 1.25 years, and the other a placebo. Growth and mid-upper-arm circumference were measured at weekly intervals throughout the study and illnesses were monitored. Capillary blood and urine samples were collected at 0, 2 and 8 weeks. Body weights and arm circumferences showed a linear increase, plus a seasonal effect (rainy season faltering). For body weight there was no significant overall effect of the supplement. For arm circumference, a very small (2%) but significant (P < 0.01) difference favoured the supplemented group. Plasma thymulin was much lower at the first clinic than at the second and third clinics, and in vitro Zn stimulation was greater at the first clinic. There was, however, no effect of Zn in vivo. Likewise, Zn did not significantly benefit T-cell numbers or ratios, secretory IgA in urine, circulating hormone levels or biochemical indices of Zn status. One index of intestinal permeability, i.e. lactulose: creatinine, was improved (P < 0.02) by the supplement, but the lactulose: mannitol value was not; this requires further investigation. Dietary Zn deficiency is, thus, unlikely to be of major overall importance for rural Gambian children's ability to thrive, and blanket Zn supplementation is not justified. There may, however, be vulnerable sub-groups who would benefit from Zn supplements.

Anthropometry↗
PubMed1992

Is cow's milk suitable for the dietary supplementation of rural Gambian children? 1. Prevalence of lactose maldigestion.

To define the age-related prevalence of lactose maldigestion (LM), 218 children aged 13-72 months from a rural Gambian village were studied using a lactose breath hydrogen test. There was a significant rise in LM from 21% to 76% between the 2nd and 3rd-5th years of life (p < 0.001). Only eight children had diarrhoea within 2 weeks before the test. Diarrhoea and abdominal discomfort followed in only seven children (3%). There was no difference in mean time of introduction of supplementary diet or cessation of breastfeeding between children aged 12-36 months with lactose digestion and LM. There was a greater proportion of children with normal lactose digestion than with LM in those still receiving breast milk (85% vs 15%), and a greater proportion of LM in the fully weaned group (63% vs 37%) (p < 0.001). There was no relation between weight-for-age or weight-for-height and the ability to digest lactose. The ability to digest lactose is lost in the majority of children during the 2nd year, coincident with the cessation of breastfeeding, but is not a major factor associated with growth failure thereafter.

Age Factors↗
PubMed1992

Is cow's milk suitable for the dietary supplementation of rural Gambian children? 2. Patterns of cow's milk intake.

Cow's milk has been advocated as a source of supplementary diet for children in many parts of the developing world. The frequency and forms of cow's milk intake and the factors regulating its availability and consumption by 507 children aged up to 6 years in three Gambian villages were measured. Nineteen per cent of mothers did not give cow's milk to their children. Of 413 children taking cow's milk, 41% consumed it only once a week, 32% two to four times a week, 19% once a day and 8% more than once a day. Eighty per cent of children took both fresh and sour milk. Forty-one per cent of infants up to 1 year old received cow's milk at some time. There was a decrease with age in the proportion of children taking fresh milk and a rise with age in the proportion taking sour milk alone (p < 0.001) and both forms of milk. Only 2% of children were reported to have an adverse reaction to fresh cow's milk. The main factors affecting intake were the availability of money and milk. The consumption of cow's milk in early life is common and free of adverse effects. When it is available, it should be used to supplement the diet of the weaned child.

Animals↗
PubMed1991

Vaccination against hepatitis B and protection against chronic viral carriage in The Gambia.

358 children in the Gambian villages of Keneba and Manduar, where hepatitis B virus (HBV) infection is endemic, were vaccinated with plasma-derived vaccine against HBV according to one of four regimens and followed for up to 4 years. Two regimens by which vaccine was injected intradermally into children between 0 and 4 years old led to peak geometric mean (95% CI) concentrations of antibody against HBV surface antigen of 270 (202-358) and 555 (418-748) mlU/ml. The third regimen--intramuscular vaccination of children aged between 0 and 4 years--gave geometric mean peak antibody concentrations of 926 (765-1122) mlU/ml. A fourth regimen was intramuscular vaccination of children between 1 and 9 months old, which gave geometric mean antibody concentrations of 5431 (3903-75,456) mlU/ml. Despite these widely divergent responses and a 89% decay in antibody over the first 2 years, vaccination against HBV was 97% effective in preventing chronic infection. Vaccination was less effective in preventing uncomplicated infection: 5.3% of 264 vaccinees in Keneba and 19.1% of 94 vaccinees in Manduar tested positive for antibody to HBV core antigen. These "breakthrough infections" did not differ in frequency between regimens, and were associated with low initial antibody responses and chronic maternal carriage of HBV.

Adolescent↗
PubMed1990

Inhibition of estrogen receptor-DNA binding by the "pure" antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization.

Many estrogen-antagonist and -agonist ligands have been synthesized, some of which have proved clinically important in the treatment of hormone-dependent breast tumors and endocrine disorders. Here we show that the "pure" antiestrogen ICI 164,384 inhibits mouse estrogen receptor-DNA binding in vitro. The effects of this steroid on DNA binding can be overcome by addition of anti-receptor antibody whose epitope lies N-terminal to the receptor DNA-binding domain. Since this antibody is also capable of restoring DNA-binding activity to receptor mutants that either lack the dimerization domain or bear deleterious mutations within it, we propose that ICI 164,384 reduces DNA binding by interfering with receptor dimerization. In contrast, when complexed with the antagonist/partial agonist tamoxifen, the estrogen receptor is capable of binding to DNA in vitro, but tamoxifen does not promote the agonist-induced conformational change obtained with estradiol. The implications of these data are discussed in relation to the in vivo properties of these drugs.

Amino Acid Sequence↗
PubMed1983

Post-operative serum sialyltransferase levels and prognosis in breast cancer.

Serum sialyltransferase (SST) activity was measured 10 days after mastectomy in 153 patients with operable breast cancer. Enzyme activity declined with time in storage (1-42 months). After correction for loss of activity in storage, patients with SST activity below the median value had a longer disease-free interval (DFI) than those with SST activity above the median, and this difference remained when patients were stratified by axillary nodal status, tumor size, and tumor grade. Survival was longer in patients with low SST activity. Post-operative elevation of SST indicates a poor prognosis in patients with operable breast cancer.

Breast Neoplasms↗
PubMed1982

Serum sialyl transferase levels in patients with metastatic breast cancer treated by chemotherapy.

Serum sialyl transferase (SST) was measured in 49 female patients with advanced breast cancer and 60 female controls. The mean SST level was significantly raised in patients with advanced breast cancer. There was no correlation between specific sites, or numbers of sites of metastatic disease and SST levels. The patients with advanced breast cancer were all treated with chemotherapy; in 13/21 responders there was a significant fall in SST and in 2 responders a significant rise in SST. The 6 patients who died after one course of chemotherapy had a significantly higher mean SST than those surviving longer. SST appears to lack sufficient specificity to be of practical value as a marker of response in patients with breast cancer treated by chemotherapy, though constant measurement of changes in SST may be of use in monitoring drug response. Raised SST at the commencement of chemotherapy may signify poor prognosis.

Antineoplastic Agents↗
PubMedDate not supplied

Differential interaction of steroid hormone receptors with LXXLL motifs in SRC-1a depends on residues flanking the motif.

Steroid hormones induce the transcriptional activity of their cognate receptors by recruiting a variety of cofactors. One of these, steroid receptor co-activator-1 (SRC-1) interacts with the ligand binding domains of a number of different receptors by means of LXXLL motifs. We have investigated the relative interaction of four such motifs in SRC-1a using a yeast two-hybrid assay. We demonstrate that ERalpha, ERbeta and ERbeta2 preferentially interact with motif 2 while GR, AR, PPARalpha and PPARgamma preferentially interact with motif 4. We show that the interactions depend not only on the LXXLL motif itself but also on residues flanking the motif.

Amino Acid Motifs↗