Publications

Hepatic tissue engineering using primary hepatocytes has been considered a valuable new therapeutic modality for several classes of liver diseases. Recent progress in the development of clinically feasible liver tissue engineering approaches, however, has been hampered mainly by insufficient cell-to-cell contact of the engrafted hepatocytes. We developed a method to engineer a uniformly continuous sheet of hepatic tissue using isolated primary hepatocytes cultured on temperature-responsive surfaces. Sheets of hepatic tissue transplanted into the subcutaneous space resulted in efficient engraftment to the surrounding cells, with the formation of two-dimensional hepatic tissues that stably persisted for longer than 200 d. The engineered hepatic tissues also showed several characteristics of liver-specific functionality. Additionally, when the hepatic tissue sheets were layered in vivo, three-dimensional miniature liver systems having persistent survivability could be also engineered. This technology for liver tissue engineering is simple, minimally invasive and free of potentially immunogenic biodegradable scaffolds.

Ciguatoxins (CTX) are a suite of cyclic polyether toxins produced by the marine dinoflagellate Gambierdiscus sp., are potent activators of voltage-gated sodium channels and a leading cause of human poisoning from food fish. This report characterizes the genomic and proteomic response in whole blood of adult male mice exposed i.p. to 264 ng/kg of the Pacific congener of CTX (P-CTX-1) at 1, 4 and 24h. Whole genome microarray expression data were filtered by tightness of fit between replicates, fold change (1.8) and p-value (10(-5)), resulting in 183 annotated genes used for trending analysis, K-means clustering and ontology classification. Genes involved with cytokine signaling, proteasome complex and ribosomal function were dominant. qPCR performed on 19 genes of interest had a correlation of 0.95 to array results by Pearson's correlation coefficient. Serum protein analysis showed small but significant changes in 6 of 60 proteins assayed: Ccl2, Ccl12, CD40, IL-10, leptin and M-CSF. In large part, the gene expression was consistent with a Th2 immune response with interesting similarities to expression seen in asthmatic models.

OBJECTIVES

The purpose of this study was to identify genetic variants associated with severe coronary artery disease (CAD).

METHODS AND RESULTS

We used 3 case-control studies of white subjects whose severity of CAD was assessed by angiography. The first 2 studies were used to generate hypotheses that were then tested in the third study. We tested 12,077 putative functional single nucleotide polymorphisms (SNPs) in Study 1 (781 cases, 603 controls) and identified 302 SNPs nominally associated with severe CAD. Testing these 302 SNPs in Study 2 (471 cases, 298 controls), we found 5 (in LPA, CALM1, HAP1, AP3B1, and ABCG2) were nominally associated with severe CAD and had the same risk alleles in both studies. We then tested these 5 SNPs in Study 3 (554 cases, 373 controls). We found 1 SNP that was associated with severe CAD: LPA I4399M (rs3798220). LPA encodes apolipoprotein(a), a component of lipoprotein(a). I4399M is located in the protease-like domain of apolipoprotein(a). Compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (confidence interval 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (P=0.003).

CONCLUSIONS

The LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.

Valvular heart disease (VHD) associated with rheumatoid arthritis (RA) has not been well characterized and its clinical predictors are undefined. Therefore, 34 volunteers with RA with a mean age of 50 +/- 10 years underwent clinical evaluation and transesophageal echocardiography. Findings on transesophageal echocardiography were compared with those of 34 gender-matched healthy volunteers with a mean age of 42 +/- 6 years. Twenty patients (59%) had mainly (97%) left-sided VHD (valve nodules in 11, 32%; valve thickening in 18, 53%; valve regurgitation in 7, 21%; and valve stenosis in 1, 3%) compared with 5 controls (15%; [nodules in 1, 3%; thickening in 4, 12%; and regurgitation in 1, 3%; p < or =0.05 for all vs patients). Valve nodules were generally single and small (4 to 12 mm); were oval with regular borders and had homogenous echocardiographic reflectance; were typically located at the leaflets' basal or mid portions; and equally affected the aortic and mitral valves. Valve thickening was equally diffuse or localized; when localized affected any leaflet portion; was usually mild (89%); involved similarly the mitral and aortic valves (47% and 32%, respectively); and rarely (6%) involved the annulus and subvalvular apparatus. Valve regurgitation manifested as mild aortic regurgitation in 4 patients, moderate mitral regurgitation in 4 patients, and moderate tricuspid regurgitation in 1 patient. Mitral and aortic valve stenoses occurred in 1 patient (3%). No correlation was found between VHD and duration, activity, severity, pattern of onset and course, extra-articular disease, serology, or therapy of RA. In conclusion, RA-associated VHD is common, valve nodules and thickening are its distinctive features, and it is not associated with clinical variables of RA.

OBJECTIVES

Sexually transmitted infection (STI) screening in correctional facilities provides access to people at high risk for STIs who might not be screened elsewhere. These screening programmes are becoming more widespread, but with decreasing funding for STI control, maximising screening impact has become increasingly important. We aimed to make recommendations about the impact of age and sex targeted screening in correctional facilities.

METHODS

We compared the prevalence of chlamydia and gonorrhoea for January 2003-July 2005 among different age groups of females and males screened in San Francisco correctional facilities -- youth detention (12-17 years) and adult jail (18-35 years).

RESULTS

16 975 chlamydia tests and 13,443 gonorrhoea tests were performed. The age specific chlamydia test positivity among females aged 12-17 years, 18-25 years, and 26-30 years, respectively, was 9.6% (105/1092), 9.4% (196/2088), and 6.3% (40/639), compared with 3.3% (100/3065), 6.2% (400/6470), and 3.9% (118/3046) among males. The age specific gonorrhoea test positivity among females in these same age groups was 3.2% (34/1062), 2.7% (57/2082), and 2.4% (15/635), compared with 0.7% (7/1026), 1.2% (67/5507), and 1.0% (25/2555) among males. Of the 1198 STIs identified, 1,020 (85.1%) were treated.

CONCLUSIONS

On the basis of this report and national data, STI control programmes with limited funds should prioritise screening females in youth detention first, women aged < or = 30 years in adult jail second, and men aged < or = 25 years in adult jail third. Males in youth detention should have a lower priority than young adults in jails.