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Biomedical subjects

Mark Griffiths

Publications and source records attributed to Mark Griffiths.

At least 19 recordsLinked to original sources
PubMed2006

New flow cytometric technique for the evaluation of circulating endothelial progenitor cell levels in various disease groups.

Circulating endothelial progenitor cells (EPC) localise to sites of ischaemia and play a role in vascular repair and re-endothelialisation of injured blood vessels. Low levels of EPCs are associated with cardiovascular disease (CVD) in the general population. It is not clear at present whether and how the numbers of circulating EPCs vary in diseases other than CVD. We have enumerated EPCs by the flow cytometric analysis of whole blood by using a novel cocktail of monoclonal antibodies. This consisted of CD2FITC, CD13FITC and CD22FITC to eliminate non-progenitor cells and VEGFR2PE and CD133-streptavidin-PeCy7 to include only EPCs. We analysed 250 patients with varying stages of uraemia, 36 patients with inflammatory bowel disease (IBD) and 9 patients with acute respiratory distress syndrome and compared this to 74 healthy controls. Using flow cytometry we were able to measure the circulating levels of EPCs, with a result available within hours of the sample being obtained. Circulating EPC numbers vary in different patient groups and healthy controls. In uraemic patients, irrespective of disease severity, there are lower numbers of circulating EPC numbers compared to normal controls (46.6+/-3.7 vs. 66.1+/-4.7; p=0.03). This new technique provides a means of monitoring patients and shows a reduction in circulating EPCs in uraemic patients; this abnormality may be a target of novel therapies.

Adolescent↗
PubMed2006

Sonographic evaluation of inflammatory bowel disease: a prospective, blinded, comparative study.

BACKGROUND: Children with inflammatory bowel disease (IBD) undergo invasive and repeated investigations, including contrast radiology and endoscopy. OBJECTIVE: To assess transabdominal sonography of the colon and distal ileum compared to colonoscopy and barium radiology in known or suspected IBD. MATERIALS AND METHODS: A prospectively recruited cohort of 44 children (median age 12 years, range 3.5-16.5 years; 24 males) underwent transabdominal sonography prior to colonoscopy (n=33) or barium follow-through (n=25). Diagnoses were: Crohn disease (n=25), ulcerative colitis (n=12), indeterminate colitis (n=1), normal (n=6). RESULTS: Bowel wall thickness (BWT) and endoscopic severity were compared in 153 colonic segments. No difference was found between normal and mildly affected segments. BWT was less in normal bowel than moderate (P<0.001) or severe (P<0.001) lesions. Where BWT was >2.9 mm, sensitivity for moderate/severe disease was 48%, specificity 93%, positive predictive value 83% (likelihood ratio 7). Barium radiology showed terminal ileum abnormality in ten patients (40%). Where ileal BWT was >2.5 mm, comparative sensitivity was 75%, specificity 92%, positive predictive value 88% (likelihood ratio 9). Superior mesenteric artery Doppler did not correlate with disease severity. CONCLUSION: Increased BWT has good positive predictive value for moderate/severe disease in the colon proximal to the rectum (>3 mm), and terminal ileum (>2.5 mm). BWT below this cannot exclude moderate/severe mucosal lesions.

Adolescent↗
PubMed2006

Affect and the computer game player: the effect of gender, personality, and game reinforcement structure on affective responses to computer game-play.

Previous research on computer games has tended to concentrate on their more negative effects (e.g., addiction, increased aggression). This study departs from the traditional clinical and social learning explanations for these behavioral phenomena and examines the effect of personality, in-game reinforcement characteristics, gender, and skill on the emotional state of the game-player. Results demonstrated that in-game reinforcement characteristics and skill significantly effect a number of affective measures (most notably excitement and frustration). The implications of the impact of game-play on affect are discussed with reference to the concepts of "addiction" and "aggression."

Adolescent↗
PubMed2005

CD46 plays a key role in tailoring innate immune recognition of apoptotic and necrotic cells.

Complement is the canonical innate immune system involved in host defense and tissue repair with the clearance of cell debris. In contrast to the robust armory mounted against microbial nonself-pathogens, complement is selectively activated on altered self (i.e. apoptotic and necrotic cells) to instruct the safe demise by poorly characterized mechanisms. Our data shed new light on the role of complement C1q in sensing nucleic acids (NA) rapidly exposed on apoptotic Jurkat T cell membranes and in driving C3 opsonization but without the lytic membrane attack complex. DNA/RNase-treated apoptotic cells failed to activate complement. We found that several other apoptotic cell models, including senescent keratinocytes, ionophore-treated sperm cells, and CMK-derived platelets, stained for cleaved caspase 3 were rapidly losing the key complement regulator CD46. CD46 from nuclear and membrane stores was found to cluster into blebs and shed into microparticles together with NA, phosphatidylserine, C1q, and factor H. Classical and alternative pathways of complement were involved in the recognition of H2O2-treated necrotic cells. Membrane attack complex was detected on necrotic cells possibly as a result of CD46 and CD59 shedding into soluble forms. Our data highlight a novel and universal paradigm whereby the complement innate immune system is using two synergistic strategies with the recognition of altered self-NA and missing self-CD46 signals to instruct and tailor the efficient removal of apoptotic and necrotic cells in immunoprivileged sites.

Apoptosis↗
PubMed2005

CpG-island fragments from the HNRPA2B1/CBX3 genomic locus reduce silencing and enhance transgene expression from the hCMV promoter/enhancer in mammalian cells.

BACKGROUND: The hCMV promoter is very commonly used for high level expression of transgenes in mammalian cells, but its utility is hindered by transcriptional silencing. Large genomic fragments incorporating the CpG island region of the HNRPA2B1 locus are resistant to transcriptional silencing. RESULTS: In this report we describe studies on the use of a novel series of vectors combining the HNRPA2B1 CpG island with the hCMV promoter for expression of transgenes in CHO-K1 cells. We show that the CpG island gives at least twenty-fold increases in the levels of EGFP and EPO observed in pools of transfectants, and that transgene expression levels remain high in such pools for more than 100 generations. These novel vectors also allow facile isolation of clonal CHO-K1 cell lines showing stable, high-level transgene expression. CONCLUSION: Vectors incorporating the hnRPA2B1 CpG island give major benefits in transgene expression from the hCMV promoter, including substantial improvements in the level and stability of expression. The utility of these vectors for the improved production of recombinant proteins in CHO cells has been demonstrated.

Animals↗
PubMed2005

Pulmonary thrombosis in steroid-sensitive nephrotic syndrome.

Thrombo-embolic episodes are an uncommon but known complication of nephrotic syndrome. However, pulmonary thrombosis/thromboembolism is rare, especially in children. We describe the cases of two girls, aged 12 years, who presented with severe oedema in relapse. They had intermittent tachypnoea, and CT pulmonary angiography (CTPA) provided a less invasive and more definitive way of confirming pulmonary thrombosis/thromboembolism. They received heparin with resolution of the tachypnoea. Anticoagulation was continued for 6 months after the episode in one patient. They have been in remission for more than 1 year, and a thrombophilia screen does not indicate a predisposing tendency to the formation of clots. Pulmonary thrombosis/thromboembolism could present with subtle symptoms and needs prompt diagnosis and treatment to prevent a fatal outcome.

Anticoagulants↗
PubMed2005

A high-resolution linkage-disequilibrium map of the human major histocompatibility complex and first generation of tag single-nucleotide polymorphisms.

Autoimmune, inflammatory, and infectious diseases present a major burden to human health and are frequently associated with loci in the human major histocompatibility complex (MHC). Here, we report a high-resolution (1.9 kb) linkage-disequilibrium (LD) map of a 4.46-Mb fragment containing the MHC in U.S. pedigrees with northern and western European ancestry collected by the Centre d'Etude du Polymorphisme Humain (CEPH) and the first generation of haplotype tag single-nucleotide polymorphisms (tagSNPs) that provide up to a fivefold increase in genotyping efficiency for all future MHC-linked disease-association studies. The data confirm previously identified recombination hotspots in the class II region and allow the prediction of numerous novel hotspots in the class I and class III regions. The region of longest LD maps outside the classic MHC to the extended class I region spanning the MHC-linked olfactory-receptor gene cluster. The extended haplotype homozygosity analysis for recent positive selection shows that all 14 outlying haplotype variants map to a single extended haplotype, which most commonly bears HLA-DRB1*1501. The SNP data, haplotype blocks, and tagSNPs analysis reported here have been entered into a multidimensional Web-based database (GLOVAR), where they can be accessed and viewed in the context of relevant genome annotation. This LD map allowed us to give coordinates for the extremely variable LD structure underlying the MHC.

Haplotypes↗
PubMed2005

Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, "protective" glial stem cells and stromal ependymal cells.

In invertebrates and primitive vertebrates, the brain contains large numbers of "professional" macrophages associated with neurones, ependymal tanycytes and radial glia to promote robust regenerative capacity. In higher vertebrates, hematogenous cells are largely excluded from the brain, and innate immune molecules and receptors produced by the resident "amateur" macrophages (microglia, astrocytes and ependymal cells) control pathogen infiltration and clearance of toxic cell debris. However, there is minimal capacity for regeneration. The transfer of function from hematogenous cells to macroglia and microglia is associated with the sophistication of a yet poorly-characterized neurone-glia network. This evolutionary pattern may have been necessary to reduce the risk of autoimmune attack while preserving the neuronal web but the ability to repair central nervous system damage may have been sacrificed in the process. We herein argue that it may be possible to re-educate and stimulate the resident phagocytes to promote clearance of pathogens (e.g., Prion), toxic cell debris (e.g., amyloid fibrils and myelin) and apoptotic cells. Moreover, as part of this greater division of labour between cell types in vertebrate brains, it may be possible to harness the newly described properties of glial stem cells in neuronal protection (revitalization) rather than replacement, and to control brain inflammation. We will also highlight the emerging roles of stromal ependymal cells in controlling stem cell production and migration into areas of brain damage. Understanding the mechanisms involved in the nurturing of damaged neurons by protective glial stem cells with the safe clearance of cell debris could lead to remedial strategies for chronic brain diseases.

Animals↗
PubMed2005

Current controversies in oral lichen planus: report of an international consensus meeting. Part 2. Clinical management and malignant transformation.

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focused on (1) the relationship between oral LP and viral infection, with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.

Cell Transformation, Neoplastic↗
PubMed2005

Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis.

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focuses on (1) the relationship between oral LP and viral infection with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.

Apoptosis↗
PubMed2005

Online therapy for addictive behaviors.

Clinicians working in the field of addictive behaviors cannot afford to ignore the Internet. Psychological advice, help, and treatment for addicts are no exceptions, with both counseling and psychotherapy entering the computer age. This paper reviews the main issues in the area and approaches the discussion acknowledging that online therapy has to be incorporated within the overall framework of the need for clinical assistance. The paper also provides brief overviews of some websites as illustrative examples of what types of online therapy are available.

Behavior, Addictive↗
PubMed2005

Prevalence of pathological Internet use among university students and correlations with self-esteem, the General Health Questionnaire (GHQ), and disinhibition.

Over the last few years, there has been increased interest in the addictive potential of the Internet. The current study was an attempt to replicate common findings in the literature and provide more evidence for the existence of Internet addiction among students--a population considered to be especially vulnerable. A total of 371 British students responded to the questionnaire, which included the Pathological Internet Use (PIU) scale, the General Health Questionnaire (GHQ-12), a self-esteem scale, and two measures of disinhibition. Results showed that 18.3% of the sample were considered to be pathological Internet users, whose excessive use of the Internet was causing academic, social, and interpersonal problems. Other results showed that pathological Internet users had lower self-esteem and were more socially disinhibited. However, there was no significant difference in GHQ scores. These results are discussed in relation to the methodological shortcomings of research in the area as a whole.

Adult↗
PubMed2004

Internet gambling and social responsibility: an exploratory study.

Within the last few years, we have seen a substantial increase in the amount of gambling opportunities offered on the Internet. Many concerns have been raised about the activity, including the potential for excessive gambling, and the lack of safeguards for vulnerable populations such as adolescents and problem gamblers. Given these concerns, a representative selection of 30 U.K.-owned Internet gambling sites were studied to examine what safeguards were in place to encourage social responsibility of Internet gamblers. It was found that very few sites were engaged in socially responsible practice and that much more could be done to protect vulnerable groups. The findings from this study were then used to compile a list of recommendations for good practice among Internet gambling operators.

Gambling↗