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Biomedical subjects

H Williams

Publications and source records attributed to H Williams.

At least 73 records · Page 4Linked to original sources
PubMed2000

The inhibitory effect of interleukin-10 on mouse osteoclast formation involves novel tyrosine-phosphorylated proteins.

Interleukin-10 (IL-10) inhibits osteoclast (OC) formation in rat and mouse systems. However, little is known concerning the mechanism of this inhibitory effect. Using a coculture system of mouse bone marrow cells and primary osteoblastic cells (POB), we evaluated the potential target cells for IL-10 and components of the IL-10 activating pathway. In the coculture system, IL-10 treatment abolished OC differentiation in a dose-dependent manner. This inhibitory effect occurred regardless of the stage of cellular proliferation and differentiation, suggesting that IL-10 may act on a variety of genes participating in OC formation. IL-10 specifically abrogated the production of IL-6 by enriched bone marrow-derived mononuclear cells (BMM) but not by osteoblastic cells. IL-10 treatment also stimulated the binding of a protein in the BMM to an IL-10 response element, whereas no such activation was induced in osteoblastic cells. In contrast, interferon gamma (IFN-gamma), another inhibitory factor, stimulated tyrosine-phosphorylated proteins to bind to an IL-10 response element in both monocytes and osteoblastic cells. These data suggest that the BMM are the direct target of IL-10 action. Importantly, oligonucleotide-specific precipitation confirmed that IL-10 treatment strongly augmented 88, 85, and 70 kDa tyrosine-phosphorylated proteins in BMM. Taken together, these data show that IL-10 inhibits mouse OC formation by acting directly on hemopoietic OC precursor, through a novel signal transduction and activation pathway.

Animals↗
PubMed2000

Is paediatric day case tonsillectomy desirable? The parents' perspective.

Tonsillectomy is the most commonly performed otolaryngological procedure in most units. There is considerable financial pressure to perform paediatric tonsillectomy as a day case. Responding to concern that day case tonsillectomy might not be welcomed by parents or felt to be in the best interests of the patients, we carried out an audit of paediatric tonsillectomy, by means of a questionnaire for parents and nursing staff to complete while 32 consecutive patients underwent tonsillectomy as inpatients. Although eight parents (25%) felt that day surgery should be an option, none of those surveyed felt that on this occasion their child was well enough to be discharged home six hours postoperatively. Furthermore, no child in the audit fulfilled all the essential discharge criteria at six hours. In this area, at least, it appears parents do not uniformly welcome paediatric day case tonsillectomy.

Ambulatory Surgical Procedures↗
PubMed2000

Differences in the calcium-handling response of isolated rat and guinea-pig cardiomyocytes to metabolic inhibition: implications for cell damage.

Species differences in response to hypoxic damage have been observed in studies using whole hearts. The aims of this study were to determine whether (i) species differences in response to simulated hypoxia could be detected at the level of the single myocyte, and (ii) there were any interspecies differences in the Ca2+ handling properties of the cells. Ventricular myocytes were isolated from hearts of adult rats and guinea-pigs and electrically stimulated on the stage of a fluorescence microscope. Cell length was measured using an edge-tracking device, and total intracellular [Ca2+] ([Ca2+]i) determined using indo-1. Cells were exposed to metabolic inhibition (MI) (2.5 mM NaCN and no glucose) to simulate hypoxia followed by washout of CN and re-addition of glucose ('reperfusion'). Following exposure to MI, rat cells underwent rigor contracture in 18.8+/-0.8 min (n = 80 cells), whereas the time was longer for guinea-pig cells (32.9+/-1.2 min, n = 83) (P<0.001). If cells were reperfused after 1-5 min in rigor, then rat cells showed improved morphological recovery compared with guinea-pig cells (P< 0.05); thereafter recovery decreased with increasing time spent in rigor, and was similar in both groups. In indo-1 loaded cells, [Ca2+]i was significantly increased in cells from both species at the end of MI; however, the actual increase was much higher in guinea-pig cells. Upon reperfusion, [Ca2+]i recovered fully in rat cells, but in guinea-pig cells there was no significant decrease. The restoration of [Ca2+]i to normal levels in rat cells following MI was associated with improved contractile recovery compared with guinea-pig cells. We conclude that rat cells are more resistant to effects of MI than are guinea-pig cells; this may be related to species differences in Ca2+ handling during and following exposure to MI.

Animals↗
PubMed2000

Systematic review of treatments for atopic eczema.

BACKGROUND: Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all community cases. Moderate-to-severe atopic eczema can have a profound effect on the quality of life for both sufferers and their families. In addition to the effects of intractable itching, skin damage, soreness, sleep loss and the social stigma of a visible skin disease, other factors such as frequent visits to doctors, special clothing and¿the need to constantly apply messy topical applications all add to the burden of disease. The cause of atopic eczema is unknown, though a genetic pre-disposition and a combination of allergic and non-allergic factors appear to be important in determining disease expression. Treatment of atopic eczema in the UK is characterised by a profusion of treatments aimed at disease control. The evidential basis of these treatments is often unclear. Most people with atopic eczema are managed in primary care where the least research has been done. OBJECTIVES: The objectives of this scoping review are two-fold. To produce an up-to-date coverage 'map' of randomised controlled trials (RCTs) of treatments of atopic eczema. To assist in making treatment recommendations by summarising the available RCT evidence using qualitative and quantitative methods. METHODS DATA SOURCES: Data sources included electronic searching of MEDLINE, EMBASE, the Cochrane Controlled Clinical Trials Register, the Cochrane Skin Group specialised register of trials, hand-searching of atopic eczema conference proceedings, follow-up of references in retrieved articles, contact with leading researchers and requests to relevant pharmaceutical companies. INCLUSION/EXCLUSION CRITERIA: Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included. DATA EXTRACTION: Data extraction was conducted by two observers onto abstraction forms, with discrepancies resolved by discussion. QUALITY ASSESSMENT: The quality assessment of retrieved RCTs included an assessment of: a clear description of method and concealment of allocation of randomisation, the degree to which assessors and participants were blinded to the study interventions, and whether all those originally randomised were included in the final main analysis. DATA SYNTHESIS: Where possible, quantitative pooling of similar RCTs was conducted using the Cochrane Collaboration's methods. Where statistical heterogeneity was found, sources of heterogeneity in terms of study participants, formulation or posology of intervention, and use of co-treatments were explored. Where pooling was not deemed to be appropriate, detailed descriptions of the study characteristics and main reported results were presented along with comments on study quality. RESULTS: A total of 1165 possible RCTs were retrieved in hard copy form for further scrutiny. Of these, 893 were excluded from further analysis because of lack of appropriate data. The 272 remaining RCTs of atopic eczema covered at least 47 different interventions, which could be broadly categorised into ten main groups. Quality of reporting was generally poor, and limited statistical pooling was possible only for oral cyclosporin, and only then after considerable data transformation. There was reasonable RCT evidence to support the use of oral cyclosporin, topical corticosteroids, psychological approaches and ultraviolet light therapy. There was insufficient evidence to make recommendations on maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, topical coal tar and topical doxepin. (ABSTRACT TRUNCATED)

Administration, Cutaneous↗
PubMed1999

Worldwide variations in the prevalence of symptoms of atopic eczema in the International Study of Asthma and Allergies in Childhood.

BACKGROUND: Little is known about the prevalence of atopic eczema outside Northern Europe. OBJECTIVES: We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. METHODS: A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. RESULTS: Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. CONCLUSIONS: Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.

Adolescent↗
PubMed1999

Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.

Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270). We have previously narrowed the TRMA locus from a 16-cM to a 4-cM interval on chromosomal region 1q23.3 (refs 3,4) and this region has been further refined to a 1.4-cM interval. Previous studies have suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. Here we identify the TRMA gene by positional cloning. We assembled a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region. This clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers and narrowed the locus to an approximately 400-kb region. Mutations in a new gene, SLC19A2, encoding a putative transmembrane protein homologous to the reduced folate carrier proteins, were found in all affected individuals in six TRMA families, suggesting that a defective thiamine transporter protein (THTR-1) may underlie the TRMA syndrome.

Amino Acid Sequence↗
PubMed1999

A full genome scan for late onset Alzheimer's disease.

We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of >/=65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE)straightepsilon4 allele and 63 pairs where neither possessed anstraightepsilon4 allele. Sixteen peaks with a multipoint lod score (MLS) >1 either in the whole sample, the straightepsilon4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfilLander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to alpha2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.

Age of Onset↗
PubMed1999

Changes in adult zebra finch song require a forebrain nucleus that is not necessary for song production.

Male zebra finches normally crystallize song at approximately 90 days and do not show vocal plasticity as adults. However, changes to adult song do occur after unilateral tracheosyringeal (ts) nerve injury, which denervates one side of the vocal organ. We examined the effect of placing bilateral lesions in LMAN (a nucleus required for song development but not for song maintenance in adults) upon the song plasticity that is induced by ts nerve injury in adults. The songs of birds that received bilateral lesions within LMAN followed by right ts nerve injury silenced, on average, 0.25 syllables, and added 0.125 syllables (for an average turnover of 0.375 syllables), and changed neither the frequency with which individual syllables occurred within songs nor the motif types they used most often. In contrast, the songs of birds that received sham lesions followed by ts nerve injury lost, on average, 1.625 syllables, silenced 0.125 syllables, and added 0.75 syllables, turning over an average of 2.5 syllables. They also significantly changed both the frequency with which individual syllables were included in songs and the motif variants used. Thus, song plasticity induced in adult zebra finches with crystallized songs requires the presence of LMAN, a nucleus which had been thought to play a role in vocal production only during song learning. Although the changes to adult songs induced by nerve transection are more limited than those that arise during song development, the same circuitry appears to underlie both types of plasticity.

Aging↗
PubMed1999

Danger signals and the combined oral contraceptive pill.

The COCP is a safe form of contraception for the majority of women. The challenge is to identify the women who have risk factors that make the use of COCP less safe. This approach is summarised by a recent consensus statement from an international conference on evidence based prescribing of COCPs. This states that 'current evidence suggests only two prerequisites for the safe provision of COCPs: a careful personal and family medical history with particular attention to cardiovascular risk factors, and an accurate blood pressure measurement'.

Adult↗
PubMed1998

The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding.

The serine/threonine kinase p38 is a ubiquitous, highly conserved, stress responsive, signal-transducing enzyme. It regulates the production of proinflammatory mediators and is the target of the cytokine synthesis inhibitory pyridinylimidazoles. We have expressed human p38 in Drosophila S2 cells and characterized preparations of mixed unphosphorylated/monophosphorylated (inactive) and homogeneously diphosphorylated (active) forms of the enzyme. We observed that only the active preparation of the enzyme has significant kinase activity when assayed using an ATF2-GST fusion protein as the substrate. We determined that the value of KM[ATP] in this reaction is 25 microM and that the pyridinylimidazole inhibitor of p38 kinase activity, SB203580, competes with ATP. We have found that a tritiated pyridinylimidazole, SB202190, has an equal affinity for both the active and inactive forms of the enzyme and that SB203580 competes with it equally well for binding to either form of the enzyme. However, ATP can compete with the tritiated inhibitor for binding to only the active form of the enzyme. Further, we demonstrate in vivo that at concentrations consistent with its IC50 as a cytokine inhibitor, SB203580 can inhibit stimulus-induced phosphorylation of p38 at the Thr-Gly-Tyr activation motif. Our observations suggest that pyridinylimidazoles may block the biological activity of p38 kinase by binding to the inactive form of p38 and reducing its rate of activation. Under these conditions, ATP would not effectively compete with the inhibitors in vivo.

Adenosine Triphosphate↗
PubMed1998

The Cochrane Skin Group. Preparing, maintaining, and disseminating systematic reviews of clinical interventions in dermatology.

In 1979, Prof Archie Cochrane challenged the medical profession to produce a critical summary of randomized controlled clinical trials according to specialty, which should be updated periodically. The Cochrane Collaboration, an international voluntary group of reviewers and researchers from a range of professional backgrounds dedicated to producing systematic reviews, was established in 1992 in response to Cochrane's challenge. Systematic reviews produced by the Cochrane Collaboration start with individuals who formulate questions that are important to the care of patients. Every effort is then made to locate published and unpublished evidence to answer the question, and explicit criteria are used to select studies for inclusion in the review and to assess their quality. If appropriate, meta-analysis is used to combine results from several smaller studies to produce an overall result. Reviews are published in the Cochrane Library, an electronic publication (CD-ROM or diskette form), and the reviews are updated quarterly. In December 1997, a Cochrane Skin Group was registered with the Cochrane Collaboration to prepare, maintain, and disseminate reviews on the effects of health care for people with dermatological conditions. Currently, 25 titles and 9 review protocols have been registered with the Cochrane Skin Group, and the first set of dermatological reviews will be available before the end of 1999. The Cochrane Skin Group aims to become the best source of unbiased external evidence for summarizing the effects of dermatological care.

Dermatology↗
PubMed1998

Alternative splicing of human NrCAM in neural and nonneural tissues.

Neural cell adhesion molecule NrCAM exists in a variety of isoforms as a result of alternative splicing of individual exons during RNA processing. In this report we demonstrate that many of the alternative splicing events described for chick are conserved in man and describe a novel variant of NrCAM cDNA. Furthermore, we show that NrCAM is expressed at significant levels outside the nervous system; in particular in pancreas, adrenal glands, and placenta and that expression in both brain and other tissues is accompanied by a very variable pattern of exon utilization in fetal and adult cells.

Adrenal Glands↗
PubMed1998

Urinary complications of Miami pouch: trend of conservative management.

OBJECTIVE: Continent urinary diversions have become popular among gynecologic oncologists. Much information has been gained concerning the complications and current management of patients with continent ileocolonic reservoirs. The high mortality rate associated with reoperation has led clinicians to adopt a trend toward conservative means of management. The purpose of this study was to evaluate the applicability of conservative management of complications related to the creation of the continent ileocolonic reservoir Miami pouch. STUDY DESIGN: Patients who underwent creation of the Miami pouch at the Division of Gynecologic Oncology, University of Miami School of Medicine, since 1988 have been included in this study. Management of complications, with particular emphasis on the conservative treatment, has been reviewed in detail for each patient. Open surgery and conservative treatment have been compared. RESULTS: Seventy-seven patients underwent creation of the Miami pouch from February 1988 to September 1997. Sixty (77.9%) patients were affected by recurrent cervical cancer; 72 (93.5%) were previously radiated. The perioperative mortality rate was 11.7% (9 patients). Six of these patients died as a result of sepsis; all of them underwent reoperation at least once. The most common urinary complications were ureteral stricture or obstruction (22.1%), difficult catheterization (19.5%), and pyelonephritis (13%). Conservative management strategies used for these complications included percutaneous nephrostomy, stent placement, balloon dilatation, radiologically (ultrasonography, fluoroscopy, computed tomography) guided placement of catheters, and antibiotic treatment. Eighty percent of the complications associated with the ileocolonic reservoir were resolved with conservative treatment, whereas 16.9% required surgical revision. CONCLUSION: On the basis of these findings, conservative management of urinary reservoir complications should always be considered before surgical intervention is attempted. The exact time to engage in open revision should be individualized on the basis of the clinical condition of each patient. It is our belief that the conservative approach should be instituted whenever possible but surgical intervention not be delayed when absolutely indicated.

Adult↗