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Biomedical subjects

I Hughes

Publications and source records attributed to I Hughes.

At least 19 recordsLinked to original sources
PubMed2001

Techniques for analysis and purification in high-throughput chemistry.

The success of combinatorial chemistry, and the increased emphasis on single well-characterised compounds of high purity, has had a significant impact on analytical and purification technologies. The requirement for ever-increasing throughput has led to the automation and parallelisation of these techniques. Advances have also been made in developing faster methods to augment throughput further.

Chromatography, High Pressure Liquid↗
PubMed2001

An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.

A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.

Adolescent↗
PubMed2000

Biological consequences of global warming: is the signal already apparent?

Increasing greenhouse gas concentrations are expected to have significant impacts on the world's climate on a timescale of decades to centuries. Evidence from long-term monitoring studies is now accumulating and suggests that the climate of the past few decades is anomalous compared with past climate variation, and that recent climatic and atmospheric trends are already affecting species physiology, distribution and phenology.

Journal Article↗
PubMed2000

Minicore myopathy in children: a clinical and histopathological study of 19 cases.

Minicore myopathy is a congenital myopathy characterized by multifocal areas of degeneration in muscle fibres. Genetic heterogeneity expected on the basis of clinical variability awaits further resolution. We reviewed 19 cases in order to further delineate the phenotype. Marked hypotonia was the predominant presenting feature, with evidence of antenatal onset in 30% of cases. Weakness was most pronounced axially and proximally, often more severely affecting the shoulder girdle. Mild facial involvement was frequent. Varying degrees of scoliosis were obvious in all patients older than 10 years. In addition, two patients who were also the most severely affected had complete external ophthalmoplegia. One patient showed marked distal involvement. Respiratory failure developed in half of all patients after 10 years of age and correlated strongly with the degree of scoliosis. Cardiac involvement occurred mainly secondary to respiratory impairment. The course appeared static in most cases. Loss of independent walking was observed only in one case at the age of 10 years. On ultrasound scan, differential involvement within the quadriceps was documented in several patients. Variability in fibre size, type 1 predominance and atrophy with occasional type 2 hypertrophy were prominent but nonspecific histological changes. Apart from typical minicores, a marked increase in internal nuclei was the most prominent histological feature. With the exception of one family in which two generations were affected, inheritance appeared autosomal-recessive or sporadic in all cases.

Adolescent↗
PubMed1999

Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.

Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.

Actins↗
PubMed1999

Androgen receptors in bone-forming tissue.

Androgen receptors (AR) were stained in sections of normal human growth plate of the costo sternal junction obtained at postmortem from one 4-day-old and two 5-day-old male infants, and in osteoblasts, grown in culture obtained from the femora of 3 male patients undergoing orthopaedic surgery for osteoarthritis. In the growth plate AR were found mostly in a narrow band of chondrocytes occupying an area about midway between the proximal and distal end of the epiphysis. Nearly all AR were in the cytoplasm and appeared in a granular form; there was no diffuse staining and the nuclei were either completely devoid of AR or only contained a few. Less-differentiated chondroblasts, perichondrial cells and hypertrophic chondrocytes contained few or no AR. Osteoblasts (and osteocytes) contained numerous AR and almost all were in the cytoplasm. Normal human osteoblasts, in their second or third passage, were grown on coverslips either in a medium with no added androgen or in the presence of 5alpha-dihydrotestosterone or methyltrienolone for a period of 24 h or longer. In control cultures, with vehicle and no added androgen, nearly all AR were found in the cytoplasm, with hardly any in the nucleus. In the presence of added androgen some osteoblasts from two of the specimens demonstrated a clear translocation of AR into the nucleus, whilst osteoblasts from a third specimen failed to translocate. These preliminary results indicate that AR translocation to the nucleus occurs in osteoblastic cells derived from osteoarthritic subjects. However, the ability to translocate may depend on the state of differentiation of the osteoblast and on culture conditions.

Aged↗
PubMed1999

Coping with anxiety and panic: a factor analytic study.

OBJECTIVES: This study aimed to explore the coping styles that agoraphobia sufferers adopt when attempting to cope with symptoms of anxiety and panic. It aimed to extend Watts's (1989) Coping with Anxiety Questionnaire (CAQ) by including items to assess self-vigilance. It was hypothesized that agoraphobia sufferers would adopt consistent coping styles that would be related to symptom severity. DESIGN: A factor analysis was performed on questionnaire data. METHOD: A postal questionnaire was completed by members (N = 112) of a self-help group for agoraphobia and panic sufferers. All participants completed the Beck Anxiety Inventory, an Agoraphobia Severity Scale and a slightly modified version of the CAQ. Coping styles were identified via factor analysis of the CAQ items. RESULTS: Three coping styles were identified, which were labelled Effective Coping, Avoidant Coping and Self-vigilance. The latter two coping styles were found to be correlated with increased levels of agoraphobic symptomatology and with higher levels of anxiety. CONCLUSIONS: The present results support the previous research on coping tactics in anxiety and are compatible with cognitive therapy accounts of the role of self-vigilance in anxiety disorders.

Adaptation, Psychological↗
PubMed1998

Design of self-coded combinatorial libraries to facilitate direct analysis of ligands by mass spectrometry.

The direct analysis of selected components from combinatorial libraries by sensitive methods such as mass spectrometry is potentially more efficient than deconvolution and tagging strategies since additional steps of resynthesis or introduction of molecular tags are avoided. A substituent selection procedure is described that eliminates the mass degeneracy commonly observed in libraries prepared by "split-and-mix" methods, without recourse to high-resolution mass measurements. A set of simple rules guides the choice of substituents such that all components of the library have unique nominal masses. Additional rules extend the scope by ensuring that characteristic isotopic mass patterns distinguish isobaric components. The method is applicable to libraries having from two to four varying substituent groups and can encode from a few hundred to several thousand components. No restrictions are imposed on the manner in which the "self-coded" library is synthesized or screened.

Drug Design↗
PubMed1998

Survey of methods of teaching and learning in undergraduate pharmacology within UK higher education.

Many of the pharmacology teachers surveyed in a questionnaire on pharmacology teaching and learning are aware of nontraditional teaching and learning methods and believe they are both appropriate to the discipline and effective in producing learning gain in the students. The reasons that nontraditional teaching methods are not used extensively include a shortage of staff time together with a perception that nontraditional teaching methods are staff-time intensive, a lack of effective motivation and reward of staff by their institutions for implementing nontraditional teaching methods and a shortage of the appropriate facilities and resources required. The questionnaire and its results are discussed in this article.

Adult↗
PubMed1998

Changes in the male voice at puberty: vocal fold length and its relationship to the fundamental frequency of the voice.

Ultrasound measurements of the vocal folds were taken for a number of boys passing through puberty. The boys were grouped according to their pubertal stage as defined by Tanner and there was a gradual increase in the length of the vocal folds as puberty progressed. The fundamental frequency of the boys' speaking voice was recorded via laryngography and a good correlation between the length of the vocal folds and the frequency of the voice was seen. The sudden drop in frequency seen between Tanner stages 3 and 4 did not correlate with similar changes in the length of the vocal folds at this time but stroboscopic findings suggest a change in the structure and mass of the vocal folds at this time of maximum frequency change.

Adolescent↗
PubMed1996

Mutation analysis of the 2 kb 5' to SRY in XY females and XY intersex subjects.

Mutations in the Y linked testis determining gene SRY cause 46,XY sex reversal. However, only about 15% of cases of 46,XY sex reversal are accounted for by mutations in SRY. In this study we have investigated the possibility that mutations affecting the expression of SRY might cause some of the cases of sex reversal in which the coding sequence of SRY is normal. We have screened 2 kb of DNA immediately 5' to the SRY coding sequence in 49 subjects with varying degrees of 46,XY sex reversal. Two variant bases were identified, one of which was determined to be a polymorphism and the other is unique, but familial.

DNA Mutational Analysis↗
PubMed1995

Localisation of androgen receptors in dermal fibroblasts, grown in vitro, from normal subjects and from patients with androgen insensitivity syndrome.

Human genital skin fibroblasts show the androgen receptor (AR) as bright red granules (0.5 micron in diameter) after treatment with one (of 3) primary polyclonal antibody and a secondary antibody linked to alkaline phosphatase. Almost all AR were cytoplasmic in 12 normal strains and in 8 strains from patients with partial (PAIS) and 6 with complete androgen insensitivity syndrome (CAIS). When 25.8 nM 5-alpha-dihydrotestosterone (DHT) or methyltrienolone was added to the medium, some AR were translocated into the nucleus in 13 experiments with 8 strains of normal fibroblasts; of 8 strains of patients with PAIS 3 failed to translocate to a detectable extent in the presence of androgen in the medium and none of the 6 strains from patients with CAIS translocated.

Androgens↗
PubMed1993

Synthesis of novel modified dipeptide inhibitors of human collagenase: beta-mercapto carboxylic acid derivatives.

The synthesis of a series of thiol-containing, modified dipeptide inhibitors (8) of human collagenase, which incorporate various carboxylic acid derivatives at the presumed P1 position, beta to the thiol group, is described. The compounds were evaluated, in vitro, for their ability to inhibit the degradation of rat skin type 1 collagen by purified human lung fibroblast collagenase, and structure-activity relationship studies are described. Optimum potency (IC50 values in the nanomolar range) was achieved by incorporating methyl (compounds 43a, 56a, and 57ab) or benzyl esters (44a) at the P1 position. Small amides were also accommodated (e.g. primary amide 47a), but in general, increasing the size of the P1 amide substituent lowered potency. PheNHMe, TrpNHMe, and Tyr(Me)NHMe substituents were found to be approximately equipotent P2'-residues. The results of testing all four diastereoisomers 56a-d of the compound with (S)-TrpNHMe at the P2' position indicated that the S,S,S diastereoisomer 56a possessed highest potency (IC50 2.5 nM) and that the second most potent diastereoisomer was 56d (IC50 12 nM) with the R,R,S configuration. It appeared that the orientation of the P1' and the thiol-bearing centers to each other is a more critical influence on potency than any absolute stereochemical requirements. It is suggested that the high potency of the beta-mercapto carboxylic acid derivatives may be a consequence of bidentate coordination of the thiol and carbonyl groups to the active-site zinc ion in the collagenase enzyme.

Animals↗
PubMed1993

Measles encephalitis during immunosuppressive treatment for acute lymphoblastic leukaemia.

Between 1971 and 1989 measles encephalitis was identified in five children receiving chemotherapy for acute lymphoblastic leukaemia. Review of these and previously reported cases of measles encephalitis in immunosuppressed patients failed to identify any pathognomonic features in the history, the clinical presentation, or the results of electroencephalography or computed tomography. Detection of measles virus antigen in nasopharyngeal secretions or intrathecal synthesis of specific antibody was not possible in all instances. Early diagnosis by direct detection of viral antigen in the brain was confounded by difficulties in identifying areas of the brain suitable for biopsy. Increasing herd immunity to measles in the general population by vaccination is the only effective intervention against measles encephalitis in immunosuppressed children. Measles encephalitis must be remembered as a possible explanation of encephalopathy in the immunocompromised child: the benefits of early use of antiviral agents need to be evaluated.

Brain↗