Search PubMed⌕ Search

Biomedical subjects

A Hill

Publications and source records attributed to A Hill.

At least 109 records · Page 6Linked to original sources
PubMed1998

Body mass index: a comparison between self-reported and measured height and weight.

BACKGROUND: Body mass index is used to measure obesity in individuals and to monitor trends in population obesity. Some observers use self-reported height and weight to assess body mass index; others use measured parameters. This paper reports on a study to compare body mass index when calculated from self-reported and measured heights and weights. METHODS: A randomized postal questionnaire survey and follow-up clinical measurement study were carried out in a geographically defined population in the rural South West of England; subjects were 6000 residents of Somerset health district aged 16-64 years selected from the Family Health Services Authority register. RESULTS: The response rate for the postal questionnaire was 57.6 per cent. A total of 73.3 per cent of responders agreed to clinical measurements; 84 per cent of measured volunteers had over-reported their height and 74 per cent under-reported their weight. The difference between body mass indices based on self-reported and measured values of height and weight is highly statistically significant for the whole population and for most age-sex and body mass groups. CONCLUSIONS: Self-reported heights and weights are unreliable and if used for monitoring health targets should be treated with caution.

Adolescent↗
PubMed1998

14-3-3 proteins are part of an abscisic acid-VIVIPAROUS1 (VP1) response complex in the Em promoter and interact with VP1 and EmBP1.

Protein-DNA complexes were formed when nuclear extracts from embryogenic rice suspension cultures or maize embryos were incubated with an abscisic acid-VIVIPAROUS1 (VP1) response element (Em1a) from the Em promoter. Monoclonal antibodies generated to GF14, a 14-3-3 protein from plants, resulted in gel retardation of the Em1a-protein complexes. Antibodies generated to the C and N termini of GF14 detected protein isoforms in rice nuclear and cytoplasmic extracts, but no differences in distribution of the GF14 isoforms were recognized between the nucleus and cytoplasm or when abscisic acid-treated and untreated tissues were compared. When recombinant GF14 fusion proteins from rice were added to nuclear extracts, novel complexes were formed that required the dimerization domain of GF14. Chemical cross-linking showed that GF-14 interacted with the basic leucine zipper factor EmBP1, which binds specifically to Em1a, and with VP1, which transactivates Em through Em1a. GF14 proteins from rice were shown to interact with VP1 in yeast through the dimerization domain of GF14. Our results indicated that GF14 interacts with both site-specific DNA binding proteins (i.e., EmBP1) and tissue-specific regulatory factors (i.e., VP1) and may provide a structural link between VP1 and the Em1a transcriptional complex.

14-3-3 Proteins↗
PubMed1998

Survival of bioluminescent Listeria monocytogenes and Escherichia coli O157:H7 in soft cheeses.

Pasteurized and raw milks that had been inoculated at 10(4) cfu/ml with bioluminescent strains of Listeria monocytogenes and Escherichia coli O157:H7 were used in the manufacture of Camembert and Feta cheeses with or without nisin-producing starter culture. Survival of both organisms was determined during the manufacture and storage of Camembert and Feta cheeses at 2 +/- 1 degree C for 65 and 75 d, respectively. Bacterial bioluminescence was used as an indicator to enumerate the colonies plated on selective Listeria agar and on MacConkey agar. Escherichia coli O157:H7 survived the manufacturing process of both cheeses and was present at the end of the storage period in greater numbers than in the initial inoculum. At the end of 75 d of storage, E. coli O157:H7 was found in the brine of Feta cheese. The counts of L. monocytogenes increased as the pH of the Camembert cheese increased, and there were significant differences between the counts from samples taken from the inside and the counts from samples obtained near the surface of the cheese. The Feta cheese that contained nisin was the only cheese in which L. monocytogenes was at the level of the initial inoculum after 75 d of storage.

Cheese↗
PubMed1998

Prevalence of alcohol dependence and abuse in general practice.

The aim of this study is to deliver representative epidemiological data about the prevalence of alcohol abuse and dependence in general practices in an urban area. In 12 general practices at Luebeck, a Northern German city with 220,000 inhabitants, a total of 929 patients (aged between 14 and 75 years) were screened using the CAGE and the Short Michigan Alcoholism Screening Test. If one of these screening questionnaires or the General Practitioners' assessment of the patient indicated an alcohol problem, the patient underwent a standardized diagnostic interview using the alcohol section of the Schedules for Clinical Assessment in Neuropsychiatry. The prevalence rates according to ICD-10 or DSM-III-R were 3.5% for alcohol abuse and 7.2% for alcohol dependence, the sex ratio was 1:2.8 (female:male). These results are compared with previous findings, and general epidemiological implications of this study are discussed.

Adolescent↗
PubMed1998

The white blood cell and plasma fibrinogen in thrombotic stroke. A significant correlation.

OBJECTIVES: Thrombotic stroke is a common disorder with considerable mortality and morbidity. Risk factors for stroke include cigarette smoking, hypertension and hyperlipidaemia and these have been linked to abnormalities of haemorrheology and coagulation such as increased fibrinogen. Other haemorrheological abnormalities have also been documented. These include an elevation in the white blood cell (WBC) count. The aim of our study was to evaluate plasma fibrinogen, WBC aggregation and the release of free radicals in thrombotic stroke. EXPERIMENTAL DESIGN: Thirty-four patients with thrombotic stroke were enrolled in the study. The data were compared to 58 matched controls. SETTING: This study was carried out in Ninewells Hospital, Dundee on patients previously admitted to the medical wards with acute stroke. MEASURES: Plasma fibrinogen, WBC aggregation and plasma malondialdehyde (MDA) were measured in this study. RESULTS: As expected, the stroke patients have a significantly higher fibrinogen level (4.3+/-1.2 g/dl versus 3.1+/-0.6, p<0.001). WBC aggregation is also increased in the patient group (47.5+/-10.4% versus 42.7+/-10.6, p=0.036), as is plasma MDA (8.6+/-2.0 micromol/l versus 7.1+/-1.07, p<0.001). The factor VIII von Willebrand factor antigen measured as a marker as vascular damage was also significantly higher in the patient group (251+/-87% versus 182+/-64, p<0.001). There was also a statistically significant correlation between fibrinogen level and WBC aggregation, and fibrinogen and MDA. These are both statistically significant p=0.012 and p<0.001 respectively. CONCLUSIONS: We believe our study suggests that enhanced WBC aggregation/adhesion with release of free radicals may be another mechanism whereby fibrinogen exerts its known detrimental effect in stroke development. This may allow planning of therapeutic strategies as yet undeveloped.

Aged↗
PubMed1997

Cytomegaloviruses use multiple mechanisms to elude the host immune response.

The study of the effects of cytomegaloviruses on the MHC class I-restricted antigen presentation pathway has yielded an embarrassment of riches. The human cytomegalovirus (HCMV) encodes at least five to six different glycoproteins, each interfering in a different way with elimination of the virus by the host immune system. Most likely, it is the concerted action of these glycoproteins that allows HCMV to escape from elimination by the host immune system during acute and perhaps also persistent infection. Prime targets of these CMV glycoproteins are MHC class I glycoproteins: the very molecules that signal the presence of a virally infected cell to the immune system. Recently, several novel links in the multi-step process of immune evasion by HCMV have been discovered.

Animals↗
PubMed1997

The active site of ICP47, a herpes simplex virus-encoded inhibitor of the major histocompatibility complex (MHC)-encoded peptide transporter associated with antigen processing (TAP), maps to the NH2-terminal 35 residues.

The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the transporter associated with antigen processing (TAP)-dependent peptide translocation. As a consequence, empty major histocompatibility complex (MHC) class I molecules are retained in the endoplasmic reticulum and recognition of HSV-infected cells by cytotoxic T lymphocytes is abolished. We chemically synthesized full-length ICP47 (sICP47) and show that sICP47 inhibits TAP-dependent peptide translocation in human cells. Its biological activity is indistinguishable from that of recombinant ICP47 (rICP47). By using synthetic peptides, we mapped the core sequence of ICP47 minimally required for TAP inhibition to residues 2-35. This segment is located within the region of the molecule conserved between ICP47 from HSV-1 and HSV-2. Through alanine scanning substitution we identified three segments within this region that are critical for the ability to inhibit TAP function. The interaction of ICP47 with TAP is unlikely to mimic precisely that of the transported peptides, as deduced from differential labeling of the TAP1 and TAP2 subunits using sICP47 fragments with chemical cross-linkers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Genomic organization and promoter structure of the human EXT1 gene.

Hereditary predisposition to multiple exostoses is a genetically heterogeneous disease. Recently, we have reported the identification of the EXT1 gene on human chromosome 8. We have now isolated a cDNA clone from a human adult lung cDNA library and have determined the genomic organization and promoter structure of the EXT1 gene. The gene is composed of 11 exons, ranging from 90 to 1735 bp, and spans approximately 350 kb of genomic DNA. Sequence analysis of the promoter region revealed the presence of a CpG island containing GC and CAAT boxes, but no TATA box. Such a promoter is characteristic for housekeeping genes. This finding is in good agreement with the ubiquitous expression of the EXT1 gene.

Adult↗
PubMed1997

Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial.

Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.

Adolescent↗
PubMed1997

Identification of novel mutations in the human EXT1 tumor suppressor gene.

Hereditary multiple exostoses (EXT) is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3, respectively. Recently, the EXT1 gene has been isolated and partially characterized and appears to encode a tumor suppressor gene. We have identified six mutations in the human EXT1 gene from six unrelated multiple exostoses families segregating for the EXT gene on chromosome 8. One of the mutations we detected is the same 1-bp deletion in exon 6 that was previously reported in two independent EXT families. The other five mutations, in exons 1, 6, 9, and the splice junction at the 3' end of exon 2, are novel. In each case, the mutation is likely to result in a truncated or nonfunctional EXT1 protein. These results corroborate and extend the previous report of mutations in this gene in two EXT families, and provide additional support for the EXT1 gene as the cause of hereditary multiple exostoses in families showing linkage to chromosome 8.

Alternative Splicing↗
PubMed1997

Thrombotic thrombocytopenic purpura: a treatable cause of childhood encephalopathy.

We describe two patients less than 13 years of age with thrombotic thrombocytopenic purpura, a rare disorder in childhood. Both children were treated with plasma exchange therapy, which resulted in a rapid resolution of symptoms. This disorder is a cause of childhood encephalopathy, which can be treated effectively with plasma exchange.

Brain Diseases↗
PubMed1997

A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.

Carcinoma of unknown primary site (CUPS) accounts for 5-10% of all malignancies. Forty patients with metastatic CUPS or advanced oesophagogastric/pancreatic adenocarcinomas were recruited. Eligibility included ECOG performance status 0-2, minimum life expectancy of 3 months and measurable disease. The regimen consisted of bolus intravenous 5 fluorouracil (5-FU) and leucovorin (20 mg m-2) days 1-5 and carboplatin (AUC5) on day 3. The leucovorin/carboplatin/5-FU (LCF) was repeated every 4 weeks. The starting dose of 5-FU was 350 mg m-2 day-1 with escalation to 370 and then 400 mg m-2 day -1 after the toxicity at the previous level had been assessed. The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity. In addition, objective and symptomatic responses, quality of life and survival were assessed. The MTD of 5-FU in the LCF regimen was 370 mg m-2. The predominant toxicity was asymptomatic marrow toxicity. The 350 mg m-2 level was then expanded. There were two toxic deaths due to neutropenic sepsis, one at 370 mg m-2 after one course and one at 350 mg m-2 after four courses. The objective response rate was 25% with one complete response (CR) and nine partial responses (PRs). The median duration of response was 3.4 months (range 1-10). The CR and eight of the nine PRs were in CUPS patients. Twelve patients developed progressive disease on LCF. Median survival for all 40 patients was 7.8 months (10 months median survival for those treated at 350 mg m-2). The majority of patients described a symptomatic improvement with LCF chemotherapy. The recommended dose of 5-FU for future studies is 350 mg m-2 combined with leucovorin 20 mg m-2 and carboplatin (AUC5).

Adenocarcinoma↗
PubMed1997

Emergency admissions for upper gastrointestinal disease and their relation to NSAID use.

BACKGROUND: There are considerable variations in estimates of the number of emergency upper gastrointestinal admissions per annum which are attributable to nonsteroidal anti-inflammatory drug (NSAID) use. AIM: To obtain a more accurate estimate of the number of these emergency admissions per annum in UK. METHODS: A retrospective survey of the case notes of all emergency admissions for upper gastrointestinal disease ('Cases') to two English District General Hospitals with a combined catchment population of 550,000. Records of all community deaths attributed to upper gastrointestinal diagnoses (with the same ICD codes) were also surveyed. Matched controls were identified from emergency admissions not caused by upper gastrointestinal diagnoses. The proportions of patients taking NSAIDs on admission to hospital (or at the time of death at home) and the outcome following admission to hospital were analysed. RESULTS: 620 emergency upper gastrointestinal admissions were identified and matched with 460 controls. Cases were more likely to be NSAID users than Controls (31% vs. 16%, OR 2.4, 95% CI: 1.8, 3.3: P < 0.001). Case NSAID use was higher in females and with increasing age. As severity of mode of presentation worsened, the probability of NSAID use increased (e.g. OR relative to controls for peptic pain 1.9, for perforation 5.9). Blood transfusion requirements were significantly higher (P < 0.0001) in Cases taking NSAIDs, although NSAID use did not influence mortality. Extrapolation from these data indicate that there are 65,000 emergency upper gastrointestinal admissions per annum in UK; 12,000 of these admissions (including 2230 deaths) are attributable to NSAID use. A further 330 attributable deaths occur in the community. CONCLUSIONS: There is a strong association between NSAID use and propensity for upper gastrointestinal emergency admission; NSAID use is associated with significant morbidity and mortality each year in UK.

Adolescent↗
PubMed1997

Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2).

HLA-DQ8 (A1*0301, B1*0302) and -DQ2 (A1*0501, B1*0201) are both associated with diseases such as insulin-dependent diabetes mellitus and coeliac disease. We used the technique of pool sequencing to look at the requirements of peptides binding to HLA-DQ8, and combined these data with naturally sequenced ligands and in vitro binding assays to describe a novel motif for HLA-DQ8. The motif, which has the same basic format as many HLA-DR molecules, consists of four or five anchor regions, in the positions from the N-terminus of the binding core of n, n + 3, n + 5/6 and n + 8, i.e. P1, P4, P6/7 and P9. P1 and P9 require negative or polar residues, with mainly aliphatic residues at P4 and P6/7. The features of the HLA-DQ8 motif were then compared to a pool sequence of peptides eluted from HLA-DQ2. A consensus motif for the binding of a common peptide which may be involved in disease pathogenesis is described. Neither of the disease-associated alleles HLA-DQ2 and -DQ8 have Asp at position 57 of the beta-chain. This Asp, if present, may form a salt bridge with an Arg at position 79 of the alpha-chain and so alter the binding specificity of P9. HLA-DQ2 and -DQ8 both appear to prefer negatively charged amino acids at P9. In contrast, HLA-DQ7 (A1*0301, B1*0301), which is not associated with diabetes, has Asp at beta 57, allowing positively charged amino acids at P9. This analysis of the sequence features of DQ-binding peptides suggests molecular characteristics which may be useful to predict epitopes involved in disease pathogenesis.

Alleles↗
PubMed1997

Non-response bias in a lifestyle survey.

BACKGROUND: Monitoring health targets is often undertaken using questionnaire surveys of lifestyle risk factors. Non-response bias is recognized but rarely quantified. METHODS: Following a questionnaire survey on a random sample of 6009 residents of Somerset with a response rate of 57.6 per cent, a telephone survey was undertaken on a random sample of 400 non-responders. A small number of the more important questions from the questionnaire were put to the non-responders over the phone. RESULTS: Fifty-nine per cent of the sample were contacted and agreed to participate. Statistically significant differences between responders and non-responders to the original questionnaire were detected for current smoking, hazardous alcohol consumption and lack of moderate or vigorous activity. CONCLUSIONS: Lifestyle questionnaire surveys need to include an assessment of the non-response bias.

Adolescent↗