Search PubMed⌕ Search

Biomedical subjects

J Davies

Publications and source records attributed to J Davies.

At least 73 records · Page 4Linked to original sources
PubMed2001

Cryptic duplication of 21q in an individual with a clinical diagnosis of Down syndrome.

We describe an adult male who was diagnosed with Down syndrome (DS) at 9 months of age, but had repeatedly normal karyotypes until recent mid-resolution chromosome studies showed a possible duplication of 21q22.13 to 21q22.3. The abnormality was investigated using fluorescent in situ hybridization (FISH) studies. These showed hybridization of a whole chromosome paint probe (wcp21, Oncor Coatasome 21) to the entire length of both chromosome 21 homologues and one very large hybridization signal of a cosmid contig probe localized within bands 21q22.13-21q22.2(LSI-21, Vysis) on the ?dup(21q) homologue. CGH analysis identified a ratio of 1.5 for the segment of chromosome 21 involving band 21q22, indicating a gain of part, or all, of the terminal band of chromosome 21. The karyotype was thus defined as 46,XY,?dup(21) (q22.13q22.2).ish dup(21)(LSI-21++,wcp21+). Common DS characteristics in our case and 12 previously reported cases with duplications involving chromosome 21 included mental retardation, fifth finger clinodactyly, open mouth and oblique eye fissures. Transverse palmar creases and congenital heart defects, seen in DS less than 40% of the time, were infrequent. Presence of these features did not appear to depend on the specific portion of chromosome 21 that was duplicated. A review of 18 additional clinical features showed no consistent phenotype-genotype correlations.

Adult↗
PubMed2001

Rapid identification and characterization of hammerhead-ribozyme inhibitors using fluorescence-based technology.

The ability to rapidly identify small molecules that interact with RNA would have significant clinical and research applications. Low-molecular-weight molecules that bind to RNA have the potential to be used as drugs. Therefore, technologies facilitating the rapid and reliable identification of such activities become increasingly important. We have applied a fluorescence-based assay to screen for modulators of hammerhead ribozyme (HHR) catalysis from a small library of antibiotic compounds. Several unknown potent inhibitors of the hammerhead cleavage reaction were identified and further characterized. Tuberactinomycin A, for which positive cooperativity of inhibition in vitro was found, also reduced ribozyme cleavage in vivo. The assay is applicable to the screening of mixtures of compounds, as inhibitory activities were detected within a collection of 2,000 extracts from different actinomycete strains. This approach allows the rapid, reliable, and convenient identification and characterization of ribozyme modulators leading to insights difficult to obtain by classical methodology.

Anti-Bacterial Agents↗
PubMed2001

Chromosome localization and gene-copy-number quantification of three random integrations in Chinese-hamster ovary cells and their amplified cell lines using fluorescence in situ hybridization.

We have used fluorescence in situ hybridization (FISH) to localize three random Chinese-hamster ovary (CHO) cell chromosomal integration sites and determine gene copy number in their amplified cell lines. Metaphase FISH showed all three to have integrated into different chromosome positions on different chromosomes. All three Geneticin parent cell lines were found to have single integration sites by Southern-blot analysis, and these data were confirmed using both metaphase and interphase FISH. Following amplification, metaphase FISH showed that amplification in two of the cell lines occurred by duplication in the chromosome arm where the integration occurred. However, for one cell line, amplification resulted in the translocation of amplified genes from one marker chromosome to another. Interphase FISH showed an expected increase in gene copy number upon amplification with methotrexate.

Animals↗
PubMed2001

Ways of coping and the health of relatives facing drug and alcohol problems in Mexico and England.

AIMS: To compare two contrasting socio-cultural groups in terms of parameters relating to the stress - coping - health model of alcohol, drugs and the family, and to test hypotheses derived from the model in each of the two groups separately. DESIGN: Cross-sectional, comparative and correlational, using standard questionnaire data, supplemented by qualitative interview data to illuminate the findings. PARTICIPANTS: One hundred close relatives, mainly partners or parents, from separate families in Mexico City, and 100 from South West England. Data sources. Coping Questionnaire (CQ), Family Environment Scale (FES), Symptom Rating Test (SRT), Semi-structured interview. FINDINGS: Mean symptom scores were high in both groups, and not significantly different. The hypothesis that relatives in Mexico City, a more collectivist culture, would show more tolerant - inactive coping was not supported, but there was support for the prediction that relatives in South West England would show more withdrawal coping. This result may be as much due to differences in poverty and social conditions as to differences in individualism - collectivism. As predicted by the stress - coping - health model, tolerant - inactive coping was correlated with symptoms, in both groups, after controlling for family conflict, but there was only limited support for a moderating role of coping. Wives of men with alcohol problems in Mexico City, and wives of men with other drug problems in South West England, reported particularly high levels of both engaged and tolerant - inactive coping. CONCLUSIONS: Tolerant - inactive coping may be bad for relatives' health: causality may be inferred but is not yet proved. Certain groups are more at risk of coping in this way. Qualitative data help understand the nature of tolerant - inactive coping and why it occurs despite the view of relatives themselves that it is counter-productive.

Adaptation, Psychological↗
PubMed2001

Intracellular and extracellular regulation of ureteric bud morphogenesis.

The urinary collecting duct system of the permanent kidney develops by growth and branching of an initially unbranched epithelial tubule, the ureteric bud. Formation of the ureteric bud as an outgrowth of the wolffian duct is induced by signalling molecules (such as GDNF) that emanate from the adjacent metanephrogenic mesenchyme. Once it has invaded the mesenchyme, growth and branching of the bud is controlled by a variety of molecules, such as the growth factors GDNF, HGF, TGFbeta, activin, BMP-2, BMP-7, and matrix molecules such as heparan sulphate proteoglycans and laminins. These various influences are integrated by signal transduction systems inside ureteric bud cells, with the MAP kinase, protein kinase A and protein kinase C pathways appearing to play major roles. The mechanisms of morphogenetic change that produce branching remain largely obscure, but matrix metalloproteinases are known to be necessary for the process, and there is preliminary evidence for the involvement of the actin/myosin contractile cytoskeleton in creating branch points.

Actins↗
PubMed2001

Gluteus minimus: observations on its insertion.

In 17 adult and 3 full term fetuses the hip joints were dissected to expose the insertion of gluteus minimus. An attachment of the deep surface of the tendon as it passes over the hip joint capsule was found in every case. Histological examination of this insertion confirmed the presence of short intramuscular tendons firmly anchoring the tendon to the capsule. It is suggested that this attachment retracts the capsule during hip joint motion, thereby preventing capsular entrapment.

Adult↗
PubMed2001

The role of the collectin system in pulmonary defence.

The human collectin system comprises the serum protein, mannose- binding lectin and the hydrophilic surfactant proteins A and D. The three proteins possess structural and functional similarities and are important components of innate immunity. Through a variety of mechanisms, including direct opsonisation and complement activation, they assist in host defence against a wide array of micro-organisms. Investigation of the roles of the surfactant proteins in pulmonary disease has been assisted recently by the development of transgenic knockout mice. Animals deficient in these proteins display susceptibility to certain bacterial and viral pathogens, stimulating research into the role of polymorphisms in these genes in human respiratory disease. The role of MBL in human pulmonary disease is less well established, although accumulating evidence suggests that it is a modifier for lung disease in tuberculosis and cystic fibrosis.

Adult↗
PubMed2001

The effect of pulsed irrigation on the incidence of heterotopic ossification after total hip arthroplasty.

Heterotopic ossification (HO) is a common complication of total hip arthroplasty (THA). Pulsed lavage is being used with increasing frequency for THA. A prospective randomized, double-blind trial was initiated to determine if pulsed lavage affected the incidence of HO. A total of 94 THAs in 91 patients were analyzed. No significant difference in the incidence of HO was found between the 2 groups. Hypertrophic osteoarthritis was found to be a significant risk factor for HO. The findings suggest that the osteogenic precursor cells thought to be involved in the pathogenesis of HO possibly are derived from within the local soft tissues in the proximity of the hip joint.

Arthroplasty, Replacement, Hip↗
PubMed2001

A survey of patient dose and image quality for computed tomography scanners in Wales.

The main aim of the study was to assess the current level of radiation dose from computed tomography scanning in the NHS in Wales and to compare these results with previous studies in Wales and the UK. In addition, the relationship between patient dose and image quality was investigated by comparing mean patient dose calculations with image noise using two quality assurance (QA) phantoms. The results show that although the introduction of spiral scanners has reduced the dose per examination, the collective dose per scanner has actually increased. The results also highlight the potential for relating dose and objective measures of image quality to assist in the selection of scanning parameters to optimise dose without compromising image quality.

Adult↗
PubMed2001

Involvement of the amino-terminal beta-hairpin of the Aspergillus ribotoxins on the interaction with membranes and nonspecific ribonuclease activity.

Ribotoxins are a family of potent cytotoxic proteins from Aspergillus whose members display a high sequence identity (85% for about 150 amino acid residues). The three-dimensional structures of two of these proteins, alpha-sarcin and restrictocin, are known. They interact with phospholipid bilayers, according to their ability to enter cells, and cleave a specific phosphodiester bond in the large subunit of ribosome thus inhibiting protein biosynthesis. Two nonconservative sequence changes between these proteins are located at the amino-terminal beta-hairpin of alpha-sarcin, a characteristic structure that is absent in other nontoxic structurally related microbial RNases. These two residues of alpha-sarcin, Lys 11 and Thr 20, have been substituted with the equivalent amino acids in restrictocin. The single mutants (K11L and T20D) and the corresponding K11L/T20D double mutant have been produced in Escherichia coli and purified to homogeneity. The spectroscopic characterization of the purified proteins reveals that the overall native structure is preserved. The ribonuclease and lipid-perturbing activities of the three mutants and restrictocin have been evaluated and compared with those of alpha-sarcin. These proteins exhibit the same ability to specifically inactivate ribosomes, although they show different activity against nonspecific substrate analogs such as poly(A). The mutant variant K11L and restrictocin display a lower phospholipid-interacting ability correlated with a decreased cytotoxicity. The results obtained are interpreted in terms of the involvement of the amino-terminal beta-hairpin in the interaction with both membranes and polyadenylic acid.

Allergens↗
PubMed2001

Use of cough swabs in a cystic fibrosis clinic.

We audited prospectively 322 cough swabs taken from cystic fibrosis children and compared cough swabs with concomitant sputum samples in 30 expectorating patients. A positive cough swab is a strong predictor of sputum culture. However, a negative cough swab does not rule out infection. Persistent symptoms should be further investigated.

Adolescent↗
PubMed2001

Etiology of severe pneumonia in the very elderly.

The etiology of severe pneumonia requiring mechanical ventilation in the very elderly has been imprecise because of lack of comprehensive studies and low yield of diagnostic approach. Overall, 104 patients 75 yr of age and older with severe pneumonia were studied prospectively at two university-affiliated hospitals. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar secretions. Streptococcus pneumoniae (14%), gram-negative enteric bacilli (14%), Legionella sp. (9%), Hemophilus influenzae (7%), and Staphylococcus aureus (7%) were the predominant pathogens in community-acquired pneumonia (CAP). Staphylococcus aureus (29%), gram-negative enteric bacilli (15%), Streptococcus pneumoniae (9%), and Pseudomonas aeruginosa (4%) accounted for most isolates of nursing home-acquired pneumonia (NHAP). The case fatality rate was 55% (53% for CAP and 57% for NHAP; p > 0.5). Activity of Daily Living (ADL) Index, pulmonary, endocrine and central nervous system (CNS) comorbidities were associated with distinct microbial etiology. By multivariate analysis, hospital mortality was associated independently with 24-h urine output (odds ratio [OR], 5.6; 95% confidence interval [CI], 2.5 to 7.9; p < 0.001), septic shock (OR, 4.3; 95% CI, 1.9 to 8.9; p = 0.0059), radiographic multilobar involvement (OR, 3.7; 95% CI, 1.8 to 15.6; p = 0.02), and inadequate antimicrobial therapy (OR, 2.6; 95% CI, 1.4 to 23.9; p = 0.034). Further studies should focus on identifying effective antimicrobial regimens in randomized trials.

Age Factors↗
PubMed2001

Morbid obesity in the medical ICU.

STUDY OBJECTIVE: To describe the clinical course, complications, and prognostic factors of morbidly obese patients admitted to the ICU compared to a control group of nonobese patients. DESIGN: A retrospective study. SETTING: Two university-affiliated hospitals. METHODS: We reviewed the medical records of 117 morbidly obese patients (body mass index >/= 40 kg/m(2)) admitted to the medical ICU between January 1994 and June 2000. Data collected included demographic information, comorbid condition, APACHE (acute physiology and chronic health evaluation) II score, invasive procedures, organ failure, and in-hospital mortality. RESULTS: Obstructive airway disease, pneumonia, and sepsis were the main reasons for admission to the ICU in the morbidly obese group. Sixty-one percent of the morbidly obese patients and 46% of the nonobese group required mechanical ventilation (p = 0.02). The mean lengths of mechanical ventilation and ICU stay were significantly longer for the morbidly obese group (7.7 +/- 9.6 days and 9.3 +/- 10.5 days vs 4.6 +/- 7.1 days and 5.8 +/- 8.2 days, respectively; p < 0.001). APACHE II scores were not significantly different in the two groups (19.1 +/- 7.6 and 20.6 +/- 12.2; p = 0.6). Overall mortality was 30% for the morbidly obese patients and 17% for the nonobese group (p = 0.019). By multivariate analysis, multiorgan failure (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.1 to 16.6), PaO(2)/fraction of inspired oxygen < 200 for > 48 h (OR, 2.3; 95% CI, 1.2 to 7.8), and depressed left ventricular ejection fraction < 40% (OR, 1.4; 95% CI, 1.03 to 13.8) were independently associated with ICU mortality in the morbidly obese group. CONCLUSION: We conclude that critically ill morbidly obese patients are at increased risk of morbidity and mortality compared to the nonobese patients.

APACHE↗
PubMed2000

An SNP map of human chromosome 22.

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.

Cell Line↗