Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

At least 91 records · Page 5Linked to original sources

PubMed1997

Effect of interferon-alpha treatment of chronic hepatitis C on health-related quality of life.

Studies of interferon-alpha (IFN-alpha) therapy for chronic hepatitis C have focused on viral clearance; however, few have evaluated patient's health-related quality of life during therapy. This study evaluates health-related quality of life and the prevalence of anxiety and depression in patients with chronic hepatitis C before, during, and following IFN-alpha therapy. Patients undergoing IFN-alpha therapy for chronic hepatitis C were asked to complete health status measures as well as anxiety and depression inventories before, during, and following IFN-alpha therapy. These measures were compared to the results of healthy adults in the general US population. Thirty-eight of forty-eight eligible patients (79%) with chronic hepatitis C completed the questionnaires. Respondents demonstrated a significant increase in depression during the sixth month of interferon therapy in comparison to pretreatment results. Anxiety scores improved significantly after one month of IFN-alpha in comparison to pretreatment results. Scores on the health status measures did not vary with IFN-alpha therapy. Patient responses were analyzed with respect to biochemical response (normalized transaminases) to IFN-alpha. IFN-alpha responders, who were aware of their transaminase results, exhibited lower scores on anxiety subscales during and after therapy (P = 0.02-0.04). Scores on the health status subscale, role emotional, improved in IFN-alpha responders compared to nonresponders during the sixth month of therapy (P = 0.02). Response to IFN-alpha therapy was not associated with any other differences on subscale analysis. Patients with chronic hepatitis C exhibited health perceptions similar to the general US population, and these were unchanged during IFN-alpha therapy. However, the incidence of depression significantly increased during the sixth month of IFN-alpha therapy. IFN-alpha responders exhibited fewer emotional problems as well as a lower incidence of anxiety during and following therapy.

Adult↗

PubMed1997

Bone mineralization and turnover in children with congenital neutropenia, and its relationship to treatment with recombinant human granulocyte-colony stimulating factor.

Bone mineral content (BMC) of the radius was measured using single photon absorptiometry (SPA) in nine children with congenital neutropenia. Five had normal values. Two children with severe congenital neutropenia (SCN) had low BMC, and two boys with Schwachman syndrome had biochemistry suggestive of rickets.

Absorptiometry, Photon↗

PubMed1997

The antigen receptors on mature and immature T lymphocytes are coupled to phosphatidylcholine-specific phospholipase D activation.

Phosphatidylcholine-phospholipase D has been proposed to play a key role in the transduction of the proliferative responses of a wide range of mitogens and growth factors. We now report that the antigen receptors on T lymphocytes derived from human tonsillar or murine splenic preparations are coupled to phosphatidylcholine (PtdCho)-phospholipase D (PLD) activation following stimulation of these T cells with anti-CD3 antibodies. However, since we also demonstrate that the antigen receptors on murine thymocytes are coupled to PtdCho-PLD activation, we propose that it is unlikely that this PLD pathway plays a central role in the transduction of T-cell proliferative responses, but rather, may be involved in either driving cells into cycle or maintaining cell cycle progression, processes required both for proliferation and activation-induced cell death. Whilst the molecular mechanisms underlying T-cell receptor (TCR)-coupling to PtdCho-PLD activation in these cells have not been fully defined, kinetics studies and experiments using pharmacological inhibitors of protein tyrosine phosphatases (PTPases) and reconstituting CD3-coupled PtdCho-PLD activity in streptolysin-O permeabilized cells, suggest that the TCR/CD3 complex, under optimal conditions of activation, may be predominantly coupled to PtdCho-PLD activation downstream of tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma), phosphatidylinositol (PtdIns)P2 hydrolysis, calcium mobilization and protein kinase C (PKC) activation.

Animals↗

PubMed1997

Vulnerable families: a study of health visitors' prioritization of their work.

Changes in the NHS have supported the idea of targeting health services to those in greatest need. This has meant that health visitors are increasingly having to identify 'vulnerable' families in need of increased health visiting intervention. This paper reports on a qualitative study undertaken in order to explore the ways in which health visitors plan and organize their work in relation to the concept of vulnerability. Focus groups and semi-structured interviews were carried out with health visitors from two separate geographical areas, one an inner city area and the other suburban, in order to explore the criteria by which health visitors define vulnerability and decide to increase their levels of intervention to particular families. It was found that vulnerability was extremely difficult to define but that the health visitors used criteria which were appropriate to the particular localities in which they worked to identify vulnerable families and to increase their levels of intervention to those families. Health visitors were targeting their services within a framework of a basic minimum service to all and were assessing the health needs of individuals or families rather than planning their work on the basis of community or practice profiles.

Community Health Nursing↗

PubMed1997

An investigation of polymorphism in the interleukin-10 gene promoter.

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and B-cell proliferation factor and has been implicated in autoimmunity, tumorigenesis and transplantation tolerance. We have identified three single base pair substitutions in the IL-10 gene promoter and have investigated whether this polymorphism correlates with IL-10 protein production in vitro.

Cells, Cultured↗

PubMed1997

Oral granular cell tumours: a histological and immunocytochemical study.

In a series of nine cases of intra-oral granular cell tumors (GCTs) an attempt was made, using both histochemical and immunocytochemical methods, to determine whether these tumours show Schwann-cell or neuroendocrine differentiation. Positive immunostaining with protein gene product 9.5 (PGP 9.5), neurone-specific enolase (NSE) and S-100, in contrast to predominantly negative immunostaining in 12 cases of neurilemmoma of the head and neck, and a similar pattern of staining with luxol fast blue to five known neuroendocrine tumours, strongly suggests that granular cell tumors may be neuroendocrine in nature.

Adolescent↗

PubMed1997

Epstein-Barr virus: biology and disease.

Epstein-Barr virus is a human herpes virus which, whilst found as a widespread asymptomatic infection, is also associated with certain tumours of lymphoid and epithelial origin including Burkitt's lymphoma (BL), immunoblastic lymphoma (IBL), Hodgkin's Disease (HD) and nasopharyngeal carcinoma (NPC). A unique characteristic of EBV is its ability to infect and transform primary resting B lymphocytes in vitro into permanently growing lymphoblastoid cell lines (LCLs); this effect is associated with constitutive expression of a limited set of viral genes. Interestingly, the pattern of EBV gene expression observed in LCLs in vitro is also a feature of IBLs, a tumour associated with immunosuppression. The other EBV associated tumours display a more restricted pattern of EBV latent protein expression. B cell lines can be activated in vitro into the virus replicative cycle, where a large number of viral genes associated with EBV DNA replication and virus assembly are synthesised. Whilst EBV can be detected in throat washings from seropositive individuals, the only in vivo situation where full virus replication can be reliably observed in hairy leukoplakia (HL), a benign lesion of lingual epithelium frequently found in AIDS patients. Thus, the relative contribution of lymphoid cells and epithelial cells to latent EBV infection/persistence vs replication in vivo remains controversial. Recent studies suggest that HL represents a focus of EBV replication in the absence of a truly latent infection and this supports the contention that EBV persistence resides in the lymphoid compartment. These aspects together with the role of EBV in oral diseases and the effect of certain EBV genes on the control of epithelial cell growth and differentiation will be discussed.

Carcinoma↗

PubMed1997

The expression of the Epstein-Barr virus nuclear antigen (EBNA-I) in oral hairy leukoplakia.

OBJECTIVE: Oral hairy leukoplakia (OHL) is characterised by the presence of a replicative Epstein-Barr virus (EBV) in the superficial layers of the epithelium. There is some doubt, however, whether this reflects activation of a latent infection of the basal epithelial cells. EBV latency is associated with the expression of the viral gene product EBNA-I and the aim of this study was to investigate EBNA-I expression in OHL. METHODS: 22 biopsies of clinically suspicious OHL and three cases of normal mucosa were available as fresh frozen or paraffin embedded material. EBNA-I was detected immunocytochemically using a rat monoclonal antibody (IH4-I) following microwave irradiation. Lytic EBV infection was confirmed by the identification of the BZLF-I protein. RESULTS: 16 of the 22 cases displayed focal replicative EBV meeting the criteria for OHL, and in 13 of these, EBNA-I expression was restricted to the nuclei of epithelial cells in the upper layers of the epithelium. EBNA-I expression was absent from the basal cells in all cases and in the nine BZLF-I negative mucosal biopsies. CONCLUSION: These findings suggest that lytic EBV infection in OHL is not the result of activation of a latent infection of basal cells and suggests a role for EBNA-I, not only in latent EBV infection, but also in virus replication.

AIDS-Related Opportunistic Infections↗

PubMed1997

Humoral and cellular immunity in secondary infection due to murine Chlamydia trachomatis.

A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4+ T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8+ T-cell function (beta2-microglobulin deficient, MHC class I deficient [Beta2m-/-]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh-/-]), and gamma interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg-/-]) or interleukin-4 (C57BL/6J(tm1Cgn29) [IL4-/-]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development. Resistance to reinfection with MoPn was heavily dependent on CD4+ T cells. CD4 T-cell-deficient MHC class II-/- mice were very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance. These mice lacked antibody production but did produce IFN-gamma, apparently by mechanisms involving NK and CD8+ T cells. Neutralization of IFN-gamma in these mice led to a borderline increase in susceptibility, showing a possible role (albeit small) of this cytokine in this setting. Tumor necrosis factor alpha (TNF-alpha) was also present at increased levels in these mice. Igh-/- B-cell-deficient mice which produce no antibody to MoPn were only modestly more susceptible to reinfection than immunized B-cell-intact controls, showing that antibody, including lung immunoglobulin A, is not an absolute requirement for relatively successful host defense in this setting. Levels of lung IFN-gamma and TNF-alpha were elevated in Igh-/- mice compared to those in controls. IL-4-/- mice (deficient in Th2 function) could develop normal resistance to reinfection with MoPn. Conversely, normal mice rendered partially IFN-gamma deficient by antibody depletion were somewhat impaired in their ability to develop acquired immunity to MoPn, again indicating a role for this cytokine in host defense against rechallenge. Of most importance, however, congenitally IFN-gamma-deficient Ifg-/- mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating factor) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma is not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s). In vivo depletion of TNF-alpha significantly increased MoPn levels in the lungs in these mice. Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4+ T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody. Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study.

Animals↗

PubMed1997

Androgen insensitivity syndrome: a survey of diagnostic procedures and management in the UK.

OBJECTIVE: A two year survey of androgen insensitivity syndrome (AIS) to assess current diagnostic and management strategies. METHODS: Cases were ascertained by inclusion on the British Paediatric Surveillance Unit monthly report card for 24 months. RESULTS: Fifty one of 139 notifications were confirmed as AIS; 29 cases were complete AIS and 22 cases partial AIS. Seventy six per cent of complete AIS presented with an inguinal hernia, and half the complete AIS patients had an established family history of the disorder. Presentation in the partial AIS group was through ambiguous or undermasculinised genitalia; 59% of partial AIS were raised as male. CONCLUSIONS: The importance of karyotyping girls with inguinal hernias is confirmed, and further attention should be given to genetic counselling for families of complete AIS patients. A large number of cases were misreported as partial AIS, emphasising the importance of undertaking a comprehensive diagnostic evaluation in intersex states. A large percentage of children with partial AIS were raised as boys despite severe genital undermasculinisation, indicating the current lack of validated measures that predict genital response to androgen treatment. The management of AIS is discussed and diagnostic guidelines provided to improve the diagnostic yield in AIS.

Adolescent↗

PubMed1997

Changes in the male voice at puberty.

The changes in the male voice in relation to the biological characteristics of puberty were assessed longitudinally in 26 boys. Speaking and singing fundamental frequencies were analysed in relation to the Tanner staging of puberty, saliva testosterone levels, and the Cooksey classification of voice analysis. There were abrupt changes in voice characteristics between Tanner stages G3 and G4 and more gradually from stages C3 to C5 of Cooksey. Although testosterone concentrations were not predictive of the changes, there was a correlation with testis volume. Voice fundamental frequencies were seen to change abruptly in late puberty, in contrast with previous studies. There is a good correlation between the Tanner and Cooksey methods of classification during male puberty.

Adolescent↗

PubMed1997

The dissected aorta: part I. Early anatomic changes in an in vitro model.

PURPOSE: To define early anatomic changes in the aorta in an in vitro hydrostatic model of acute aortic dissection. MATERIALS AND METHODS: Aortic dissections were created in explanted aortas. A small portion of the dissection flap was resected to allow free communication between the true and false lumina. The aortas were suspended in a saline bath and distended by means of a saline fluid column. By using intravascular ultrasonography, the arc lengths of the outer walls of the true and false lumina and of the dissection flap were measured at increasing hydrostatic pressures and at increasing fractions of dissected wall circumference. RESULTS: The dissected aorta immediately became ectatic. At a given fraction of wall circumference involved in dissection, total aortic cross-sectional area increased with increased hydrostatic pressure. At a given hydrostatic pressure, this area increased with increased fraction of wall circumference dissected. Most of the increase was due to dilatation of the false lumen. There were minimal changes in true-lumen size. Dissection flap length, after initial contraction at the time of dissection, changed minimally with increasing pressure. CONCLUSION: Anatomic changes in the dissected aorta depend on hydrostatic pressure and on the percentage of aortic wall involved in the dissection.

Acute Disease↗

PubMed1997

The dissected aorta: part II. Differentiation of the true from the false lumen with intravascular US.

PURPOSE: To determine the intravascular ultrasound (US) features of aortic dissection that can be used to differentiate the true from the false lumen. MATERIALS AND METHODS: Intravascular US and aortography were performed in 34 patients with aortic dissection. Aortic necropsy specimens were available in five patients. True and false lumina in each patient were identified on the basis of surgical, necropsy, and radiologic findings. Intravascular US studies were reviewed with attention to several local imaging features, which were evaluated for sensitivity and specificity in the differentiation of true from false lumina. RESULTS: An acute angle between the dissection flap and the outer wall of the false lumen was found in 32 patients (sensitivity, 94%; specificity, 100%). The three-layered appearance of the intact wall of true lumen and single-layered appearance of the outer wall of false lumen were seen in 33 patients (sensitivity, 97%; specificity, 100%). Cobwebs were present in the false lumen in eight patients but were not seen in the true lumen (sensitivity, 24%; specificity, 100%). Aortic thrombus was seen in the false lumen in 10 patients but was not seen in the true lumen (sensitivity, 29%; specificity, 100%). CONCLUSION: Intravascular US findings can be used to differentiate the true from the false lumen in aortic dissection.

Adult↗

PubMed1997

The dissected aorta: part III. Anatomy and radiologic diagnosis of branch-vessel compromise.

PURPOSE: To determine the anatomic, hemodynamic, and radiologic characteristics of branch-vessel compromise in patients with aortic dissection. MATERIALS AND METHODS: Sixty-two patients with aortic dissection were evaluated with aortography (n = 62), intravascular ultrasound (US) (n = 35), and manometry (n = 56). Branch-vessel compromise with ischemia was suspected in 40 of these patients. Radiologic and manometric findings were correlated with clinical findings of ischemia. Femoral artery pulse strength was correlated with access from the respective femoral artery to the true and false lumina of the dissected aorta. RESULTS: Twenty-six of 40 patients suspected of having ischemia had angiographic evidence of branch-vessel compromise, and intravascular US helped identify two types of branch-vessel compromise in them: static (dissection intersected and narrowed the vessel origin) and dynamic (dissection spared the vessel origin, but the dissection flap appeared to compress the true lumen at or above the origin and covered the origin). False-lumen pressure in classic dissections exceeded (n = 16) or equaled (n = 30) true-lumen pressure. Branch vessels that arose exclusively from the false lumen were well perfused. Findings of a dissection flap oriented concave toward the false lumen were 91% sensitive and 72% specific for a true-lumen pressure deficit. CONCLUSION: Intravascular US and manometric findings clarify the mechanisms of branch-vessel compromise after aortic dissection and provide a rational guide for percutaneous treatment.

Adolescent↗

PubMed1997

Suprahepatic caval anastomotic stenosis complicating orthotopic liver transplantation: treatment with percutaneous transluminal angioplasty, Wallstent placement, or both.

OBJECTIVE: Our objective was to evaluate, over a 5-year period, the nonsurgical treatment of three patients with suprahepatic caval anastomotic stenosis who had undergone orthotopic liver transplantation. CONCLUSION: Balloon angioplasty is a safe and effective method for treating chronic caval stenosis occurring in patients who have undergone orthotopic liver transplantation. Caval stenosis identified in the early postoperative period, especially when such stenosis is associated with caval torsion or kinking, may be effectively treated by stent placement.

Adult↗

PubMed1996

Characteristics predicting incorrect metered-dose inhaler technique in older subjects.

OBJECTIVE: To determine whether cognitive status, hand strength, and demographic variables are predictive of correct use of metered-dose inhalers by older subjects. METHODS: Clinic patients (n = 29) and healthy volunteers (n = 42) older than 50 years with no previous or limited metered-dose inhaler use were enrolled. After cognitive (Mini-Mental State Examination) and hand strength assessments, subjects received extensive instruction in proper metered-dose inhaler technique. Technique was independently assessed by two evaluators immediately after instruction and 1 week later. Correct technique was defined as (1) activating the canister in the first half of inhalation, (2) continuing to inhale slowly and deeply, and (3) holding breath at full inspiration (5 seconds). Data for the two subject groups were pooled for analyses. RESULTS: The mean age of the subjects was 69.7 years. Forty subjects (56%) demonstrated correct metered-dose inhaler technique at 1 week. Logistic regression showed that hand strength measurement (odds ratio, 0.68; 95% confidence interval, 0.55 to 0.84), Mini-Mental State Examination score less than 24 (odds ratio, 3.66; 95% confidence interval, 1.07 to 12.4), and male gender (odds ratio, 5.01; 95% confidence interval, 1.07 to 23.5) were significant predictors of incorrect inhaler use. Correct use of the metered-dose inhaler was unrelated to age, education, or subject status. CONCLUSIONS: Clinicians should consider cognitive status and hand strength when metered-dose inhaler therapy is initiated for an older adult. Patients with cognitive impairment and hand strength deficits may require more extensive training, frequent follow-up, or alternative dosage forms.

Administration, Intranasal↗

PubMed1996

An approach to random mutagenesis of DNA using mixtures of triphosphate derivatives of nucleoside analogues.

We describe a new method for random mutagenesis of DNA based on the use of a mixture of triphosphates of nucleoside analogues. The method relies on DNA amplification in vitro with Taq polymerase and in the presence of the 5'-triphosphates of 6-(2-deoxy-beta-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido-[4,5-C] [1,2]oxazin-7-one(dP) and of 8-oxo-2' deoxyguanosine (8-oxodG). The newly synthesised triphosphate derivative of dP (dPTP) is an excellent substrate for Taq polymerase (Km = 22 microM versus Km = 9.5 microM for TTP); it is incorporated in place of TTP and, with a approximately fourfold lower efficiency, in place of dCTP. After 30 cycles of DNA amplification, equimolar mixtures of the four normal dNTPs and dPTP yield the following frequencies of the four transition mutations: A-->G (4.4 x 10(-2), T-->C (4.3 x 10(-2), G-->A (1.1 x 10(-2) and C-->T (1.0 x 10(-2). The triphosphate derivative of 8-oxodG (8-oxodGTP) is incorporated opposite template adenine and yields two transition mutations (A-->C and T-->G) at frequencies of 0.8 x 10(-2) and 1.2 x 10(-2) respectively. Reaction mixtures containing dPTP and 8-oxodGTP results in both dP and 8-oxodG-induced mutations and an extensive array of codon changes in the absence of insertions and deletions. The method described differs from previous mutagenesis procedures in three respects: (1) it enables very high frequencies of base substitutions (up to 1.9 x 10(-1) (2) it allows control of the mutational load via the number of DNA amplification cycles and (3) it yields both transition and transversion mutations. The procedure may find application in the generation of libraries of DNA and protein mutants from which species with improved or novel activities may be selected.

Amino Acid Sequence↗

PubMed1996

In situ detection of the Epstein-Barr virus-encoded nuclear antigen 1 in oral hairy leukoplakia and virus-associated carcinomas.

A new monoclonal antibody has been used to examine immunohistochemically the expression of the Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA) 1 in virus-associated epithelial lesions. EBNA1 was detected in the tumour cell nuclei of 10/13 undifferentiated nasopharyngeal carcinomas and of 10/10 EBV-associated gastric carcinomas. EBNA1 was also detected in 13 of 16 oral hairy leukoplakia (HL) samples, where its expression was confined to nuclei in the upper epithelial cell layers whilst basal epithelial cells were negative. This observation is in agreement with previous studies demonstrating the absence of latent EBV infection in the basal cell compartment of HL and suggests an essential role for EBNA1, not only in latent EBV infection but also in virus replication.

Antibodies, Monoclonal↗