Biomedical subjects

J Howson

Publications and source records attributed to J Howson.

4 recordsLinked to original sources

PubMed2005

Evidence for association of OCTN genes and IBD5 with ulcerative colitis.

BACKGROUND AND AIMS: Genetic association between Crohn's disease (CD) and OCTN1 (SLC22A4) C1672T/OCTN2 (SLC22A5) G-207C variants in IBD5 has recently been reported. These genes encode solute carriers and the association was suggested to be distinct from the background IBD5 risk haplotype. There have been conflicting reports of the association between markers in the IBD5 region and ulcerative colitis (UC) and interaction (epistasis) between this locus and CARD15. Our aim was to ascertain the contribution of OCTN variants to UC and CD in a large independent UK dataset, to seek genetic evidence that the OCTN association is distinct from the IBD5 risk haplotype and to identify interactions between the IBD5 and CARD15 loci. METHODS: A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN2-207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096. Data were analysed by logistic regression methods within STATA. RESULTS: OCTN variants were as strongly associated with UC and IBD overall as they were with CD (p = 0.0001; OR 1.3 (95% confidence interval 1.1-1.5)). OCTN variants were in tight linkage disequilibrium with the extended IBD5 risk haplotype D' 0.79 and 0.88, and r2 = 0.62 and 0.72 for IGR2096 and 3096, respectively. There was no deviation from a multiplicative model of interaction between CARD15 and IBD5 on the penetrance scale. CONCLUSIONS: The OCTN variants were associated with susceptibility to IBD overall. The effect was equally strong in UC and CD. Although OCTN variants may account for the increased risk of IBD associated with IBD5, a role for other candidate genes within this extended haplotype was not excluded. There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD.

Adult↗

PubMed2001

Identification of a novel lipopolysaccharide-inducible gene with key features of both A kinase anchor proteins and chs1/beige proteins.

Mutations in chs1/beige result in a deficiency in intracellular transport of vesicles that leads to a generalized immunodeficiency in mice and humans. The function of NK cells, CTL, and granulocytes is impaired by these mutations, indicating that polarized trafficking of vesicles is controlled by CHS1/beige proteins. However, a molecular explanation for this defect has not been identified. Here we describe a novel gene with orthologues in mice, humans, and flies that contains key features of both chs1/beige and A kinase anchor genes. We designate this novel gene lba for LPS-responsive, beige-like anchor gene. Expression of lba is induced after LPS stimulation of B cells and macrophages. In addition, lba is expressed in many other tissues in the body and has three distinct mRNA isoforms that are differentially expressed in various tissues. Strikingly, LBA-green-fluorescent protein (GFP) fusion proteins are localized to vesicles after LPS stimulation. Confocal microscopy indicates this protein is colocalized with the trans-Golgi complex and some lysosomes. Further analysis by immunoelectron microscopy demonstrates that LBA-GFP fusion protein can localize to endoplasmic reticulum, plasma membrane, and endocytosis vesicles in addition to the trans-Golgi complex and lysosomes. We hypothesize that LBA/CHS1/BG proteins function in polarized vesicle trafficking by guiding intracellular vesicles to activated receptor complexes and thus facilitate polarized secretion and/or membrane deposition of immune effector molecules.

Adaptor Proteins, Signal Transducing↗

PubMed1998

An evaluation of partner notification for HIV infection in genitourinary medicine clinics in England.

OBJECTIVE: To evaluate the feasibility and effectiveness of a standardized HIV partner notification programme within genitourinary medicine clinics in England. DESIGN: A prospective survey of HIV partner notification activity over a 12-month period. SETTING: Nineteen genitourinary medicine clinics in England. PATIENTS AND PARTICIPANTS: A total of 501 eligible HIV-positive patients (either newly diagnosed or with whom partner notification had not been undertaken previously) seen during the study period. MAIN OUTCOME MEASURES: The numbers of partners named by patients, and the number of contacts notified, counselled and HIV-tested. RESULTS: Information on overall partner notification activity was obtained by reviewing available medical records of 471 patients; 353 (75%) had discussed partner notification with a health-care worker during the study period and 197 (42%) had undertaken partner notification. Detailed information on outcomes was obtained for only 70 patients who named 158 contacts as being at risk of acquiring HIV. Although 71 (45%) contacts were eventually notified, only 28 were subsequently seen in participating clinics. Almost all contacts (n = 27) requested HIV counselling and testing, and five were diagnosed HIV-positive. Patient referral was the most popular notification method chosen. CONCLUSIONS: This study illustrates some of the practical difficulties that limit HIV partner notification within genitourinary medicine clinics. These include health-care workers' misgivings about undertaking partner notification, insufficient locating information to identify contacts, and migration of newly diagnosed patients, which prevents continuity and completion of notification. Nevertheless, HIV partner notification uncovered previously undiagnosed HIV infections. Further work needs to be undertaken in staff training and policy implementation if higher rates of partner notification and outcome measurements are to be achieved.

Adolescent↗

PubMed1994

Photosystem I: Structural and functional studies.

In this article we describe the current knowledge of the structure of photosystem I, in particular the cyanobacterial form of this photosynthetic complex. We also describe recent experiments on the stability of the complex in detergents and denaturants and discuss the results in relation to the functional properties of the complex in electron transport across the thylakoid membrane.

Absorption↗