Comparing Galaxy Morphology at Ultraviolet and Optical Wavelengths

We have undertaken an imaging survey of 34 nearby galaxies in far-ultraviolet (FUV, ~1500A) and optical (UBVRI) passbands to characterize galaxy morphology as a function of wavelength. This sample, which includes a range of classical Hubble types from elliptical to irregular with emphasis on spirals at low inclination angle, provides a valuable database for comparison with images of high-z galaxies whose FUV light is redshifted into the optical and near- infrared bands. Ultraviolet data are from the UIT Astro-2 mission. We present images and surface brightness profiles for each galaxy, and we discuss the wavelength-dependence of morphology for different Hubble types in the context of understanding high-z objects. In general, the dominance of young stars in the FUV produces the patchy appearance of a morphological type later than that inferred from optical images. Prominent rings and circumnuclear star formation regions are clearly evident in FUV images of spirals, while bulges, bars, and old, red stellar disks are faint to invisible at these short wavelengths. However, the magnitude of the change in apparent morphology ranges from dramatic in early--type spirals with prominent optical bulges to slight in late-type spirals and irregulars, in which young stars dominate both the UV and optical emission. Starburst galaxies with centrally concentrated, symmetric bursts display an apparent ``E/S0'' structure in the FUV, while starbursts associated with rings or mergers produce a peculiar morphology. We briefly discuss the inadequacy of the optically-defined Hubble sequence to describe FUV galaxy images and estimate morphological k-corrections, and we suggest some directions for future research with this dataset.Comment: Accepted for publication in the ApJS. 15 pages, 17 JPEG figures, 10 GIF figures. Paper and full resolution figures available at http://nedwww.ipac.caltech.edu/level5/Kuchinski/frames.htm

The diagnostic value of liver biopsy

BACKGROUND: Since the introduction of molecular diagnostic tools such as markers for hepatitis C and different autoimmune diseases, liver biopsy is thought to be useful mainly for staging but not for diagnostic purposes. The aim was to review the liver biopsies for 5 years after introduction of testing for hepatitis C, in order to evaluate what diagnostic insights – if any – remain after serologic testing. METHODS: Retrospective review of all liver biopsies performed between 1.1.1995 and 31.12.1999 at an academic outpatient hepatology department. The diagnoses suspected in the biopsy note were compared with the final diagnosis arrived at during a joint meeting with the responsible clinicians and a hepatopathologist. RESULTS: In 365 patients, 411 diagnoses were carried out before biopsy. 84.4 % were confirmed by biopsy but in 8.8 %, 6.8 % and 10.5 % the diagnosis was specified, changed or a diagnosis added, respectively. Additional diagnoses of clinical relevance were unrecognized biliary obstruction and additional alcoholic liver disease in patients with chronic hepatitis C. Liver biopsy led to change in management for 12.1 % of patients. CONCLUSION: Even in the era of advanced virological, immunological and molecular genetic testing, liver biopsy remains a useful diagnostic tool. The yield is particularly high in marker negative patients but also in patients with a clear-cut prebiopsy diagnosis, liver biopsy can lead to changes in patient management

Solvent isotope effect on bile formation in the rat.

2H2O affects many membrane transport processes by solvent and kinetic isotope effects. Since bile formation is a process of osmotic filtration where such effects could be important, we investigated the effects of 2H2O on bile formation in the in situ perfused rat liver. Dose finding experiments showed that at high concentrations, 2H2O increased vascular resistance and induced cholestasis; at 60% 2H2O however, a clear dissociation between the vascular and biliary effects was observed. Therefore, further experiments were carried out at this concentration. The main finding was a reduction in bile salt-independent bile flow from 0.99 +/- 0.04 to 0.66 +/- 0.04 microliters.min-1.g-1 (P < 0.001). This was associated with a 40% reduction in biliary bicarbonate concentration (P < 0.001). Choleretic response to neither taurocholate nor ursodeoxycholate was altered by 2H2O; in particular, there was a similar stimulation of bicarbonate secretion by ursodeoxycholate in the presence of 60% 2H2O. To further elucidate this phenomenon, the effect of 2H2O on three proteins potentially involved in biliary bicarbonate secretion was studied in vitro. 2H2O slightly inhibited cytosolic carboanhydrase and leukocyte Na+/H(+)-exchange, these effects reached statistical significance at 100% 2H2O only, however. In contrast, Cl-/HCO(3-)-exchange in canalicular membrane vesicles was already inhibited by 50% (P < 0.001) at 60% 2H2O. Finally, there was a slight reduction in biliary glutathione secretion while that of the disulphide was not affected. Our results are compatible with an inhibition of canalicular Cl-/HCO(3-)-exchange by 2H2O. Whether this is due to altered hydration of the exchanger and/or of the transported bicarbonate remains to be determined

Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial

BACKGROUND--There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS--To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS--One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS--Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS--A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS--Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses

Curvature of designed armadillo repeat proteins allows modular peptide binding

Designed armadillo repeat proteins (dArmRPs) were developed to create a modular peptide binding technology where each of the structural repeats binds two residues of the target peptide. An essential prerequisite for such a technology is a dArmRP geometry that matches the peptide bond length. To this end, we determined a large set (n=27) of dArmRP X-ray structures, of which 12 were previously unpublished, to calculate curvature parameters that define their geometry. Our analysis shows that consensus dArmRPs exhibit curvatures close to the optimal range for modular peptide recognition. Binding of peptide ligands can induce a curvature within the desired range, as confirmed by single-molecule FRET experiments in solution. On the other hand, computationally designed ArmRPs, where side chains have been chosen with the intention to optimally fit into a geometrically optimized backbone, turned out to be more divergent in reality, and thus not suitable for continuous peptide binding. Furthermore, we show that the formation of a crystal lattice can induce small but significant deviations from the curvature adopted in solution, which can interfere with the evaluation of repeat protein scaffolds when high accuracy is required. This study corroborates the suitability of consensus dArmRPs as a scaffold for the development of modular peptide binders

Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis

BACKGROUND: Clinical outcomes of chronic hepatitis C infection in patients with advanced fibrosis include liver failure, hepatocellular carcinoma, and death. OBJECTIVE: To investigate whether sustained virologic response to treatment for hepatitis C is associated with improved clinical outcomes. DESIGN: Retrospective cohort study. SETTING: 5 hepatology units of tertiary care centers in Europe and Canada caring for patients with chronic hepatitis C treated between 1990 and 2003. PATIENTS: Consecutively treated patients with chronic hepatitis C who had biopsy-proven advanced fibrosis or cirrhosis (Ishak score, 4 to 6). MEASUREMENTS: Sustained virologic response, defined as absence of detectable hepatitis C virus RNA at 24 weeks after the end of treatment, and clinical outcomes, defined as death (liver-related or non-liver-related), liver failure, and hepatocellular carcinoma. RESULTS: Of 479 patients, 29.6% had sustained virologic response and 70.3% did not. Median follow-up was 2.1 years (interquartile range, 0.8 to 4.9 years). Four patients with and 83 without sustained virologic response had at least 1 outcome event. Sustained virologic response was associated with a statistically significant reduction in the hazard of events (adjusted hazard ratio, 0.21 [95% CI, 0.07 to 0.58]; P = 0.003). The effect was largely attributable to a reduction in liver failure, which developed in no patients with and 42 patients without sustained virologic response (5-year occurrence, 0% vs. 13.3% [CI, 8.4% to 18.2%]; unadjusted hazard ratio, 0.03 [CI, 0.00 to 0.91]). LIMITATIONS: Because few events occurred in the sustained virologic response group, the study had limited ability to detect differences between groups in individual outcomes. In addition, the study was retrospective; selection and survival biases may therefore influence estimates of effect. CONCLUSION: Sustained virologic response to treatment is associated with improved clinical outcomes, mainly prevention of liver failure, in patients with chronic hepatitis C and advanced fibrosis

Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus

Recent studies suggest that diabetes mellitus increases the risk of developing hepatocellular carcinoma (HCC). The aim of this study is to quantify the risk of HCC among patients with both diabetes mellitus and hepatitis C in a large cohort of patients with chronic hepatitis C and advanced fibrosis. We included 541 patients of whom 85 (16%) had diabetes mellitus. The median age at inclusion was 50 years. The prevalence of diabetes mellitus was 10.5% for patients with Ishak fibrosis score 4, 12.5% for Ishak score 5, and 19.1% for Ishak score 6. Multiple logistic regression analysis showed an increased risk of diabetes mellitus for patients with an elevated body mass index (BMI) (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.00-1.11; P = 0.060) and a decreased risk of diabetes mellitus for patients with higher serum albumin levels (OR, 0.81; 95% CI, 0.63-1.04; P = 0.095). During a median follow-up of 4.0 years (interquartile range, 2.0-6.7), 11 patients (13%) with diabetes mellitus versus 27 patients (5.9%) without diabetes mellitus developed HCC, the 5-year occurrence of HCC being 11.4% (95% CI, 3.0-19.8) and 5.0% (95% CI, 2.2-7.8), respectively (P = 0.013). Multivariate Cox regression analysis of patients with Ishak 6 cirrhosis showed that diabetes mellitus was independently associated with the development of HCC (hazard ratio, 3.28; 95% CI, 1.35-7.97; P = 0.009). CONCLUSION: For patients with chronic hepatitis C and advanced cirrhosis, diabetes mellitus increases the risk of developing HCC