bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐interferon‐based therapy: an option for amelioration of necro‐inflammation in hepatitis C patients who cannot afford interferon therapy
Authors: El‐Zayadi Abdel‐Rahman , Attia Mohy , Badran Hanaa M. , El‐Tawil Ahmed , Zalata Khaled , Barakat Eman , Selim Osaima , El‐Nakeeb Adham , Saied Ahmed 
Published: July 2005

Abstract:Objectives: Interferon (IFN) therapy is not affordable by the majority of Egyptian patients. Our aim was to tailor an effective and inexpensive regimen that ameliorates hepatic necro‐inflammatory activity among chronic hepatitis C (CHC) patients.Methods: One hundred and seventy naïve CHC patients with elevated alanine aminotransferase (ALT) (>1.5‐fold) and detectable hepatitis C virus (HCV)‐RNA by polymerase chain reaction, who cannot afford IFN‐based therapy were randomly allocated either to non‐interferon‐based therapy (N‐IFN‐BT) (group I) or silymarin therapy (group II). Group I comprised 87 patients (biopsy proved chronic hepatitis in 62 patients) who were administered a daily combination of ribavirin (600–800 mg) plus amantadine (200 mg) and ursodeoxycholic acid (UDCA) (500 mg) for 24 weeks. Group II comprised 83 patients who were administered Silymarin 450 mg/day for 24 weeks.Results: Statistical evaluation was conducted on 82 patients from group I and 72 from group II because of the withdrawal of five and 11 patients from Groups I and II, respectively. Age, sex, social status and biochemical parameters were comparable in both groups. Normalization of ALT at the end of treatment was achieved in 58.5% and 15.3% (P<0.001), whereas end of treatment virologic response (ETVR) was achieved in 2.4% and 0% of Groups I and II, respectively. Twenty‐four weeks after cessation of therapy, sustained biochemical response (SBR) was achieved in 28% and 2.8% (P<0.001), while sustained virologic response (SVR) was maintained in 2.4% and 0% of the patients in Groups I and II, respectively. In Group I, histopathological examination revealed a decreased activity index by an average score of 1.5 points among 38/62 of the rebiopsied patients.Conclusion: Twenty‐four weeks N‐IFN‐BT achieved a fourfold‐higher ETBR and a tenfold‐higher SBR compared with silymarin therapy, which reflects an improvement of necroinflammatory activity as proven by repeat histopathology.
Hepatic gene expression in patients with obesity‐related non‐alcoholic steatohepatitis
Authors: Younossi Zobair M. , Gorreta Francesco , Ong Janus P. , Schlauch Karen , Del Giacco Luca , Elariny Hazem , Van Meter Amy , Younoszai Abraham , Goodman Zachary , Baranova Anna , Christensen Alan , Grant Geraldine , Chandhoke Vikas 
Published: July 2005

Abstract: Background: Non‐alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non‐alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized.Aim: This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics.Design: Consecutive patients undergoing bariatric surgery were prospectively recruited. Extensive clinical data and two liver biopsy specimens were obtained at the time of enrollment. A single hepatopathologist reviewed and classified the liver biopsies. Patients with excessive alcohol use and other causes of liver disease were excluded. A group of 29 NASH patients, 12 with steatosis alone, seven obese controls and six non‐obese controls were selected for further investigation. Customized cDNA microarrays containing 5220 relevant genes were designed specifically for this study. Microarray experiments were run in triplicate for each sample and a selected group of genes were confirmed using real‐time PCR.Outcome Measure: Differential hepatic gene expressions in patients with NASH as compared with controls.Results: Thirty‐four genes with significant differential expression were identified in patients with NASH when compared with non‐obese controls. Moreover, 19 of these genes showed no significant expression differences in obese vs. non‐obese controls, suggesting a stronger association of these genes to NASH.Conclusions: Several differentially expressed genes in patients with NASH are related to lipid metabolism and extracellular matrix remodeling. Additionally, genes related to liver regeneration, apoptosis, and the detoxification process were differentially expressed. These findings may help clarify the molecular pathogenesis of NASH and identify potential targets for therapeutic intervention.
Early treatment response predicts the need for liver transplantation in autoimmune hepatitis
Authors: Tan Patrick , Marotta Paul , Ghent Cameron , Adams Paul 
Published: July 2005

Abstract: Background: The need for immunosuppression in autoimmune hepatitis is established. Previous studies have investigated short‐term outcomes in patients who respond to treatment. This study assesses long‐term prognosis of patients who fail to respond to standard immunosuppression.Methods: 163 charts were reviewed, composed of 108 non‐transplant patients and 55 patients who required liver transplantation (LT). Clinical endpoints were based on aminotransaminases: Early treatment response (ER) was a 50% improvement at 6 months of therapy, Complete remission (CR) was an improvement to <2X normal, Relapse was worsening to >3X normal, Incomplete response (IR) was some response but no CR in 3 years, and No response (NR) was no improvement after 3 years.Results: 85% of non‐LT and 25% of LT patients achieved ER, 91% of non‐LT and 26% of LT patients achieved CR. 41% of non‐LT patients relapsed on maintenance treatment, and 41% of non‐LT patients relapsed when withdrawn from treatment. 9% of non‐LT and 58% of LT patients had IR. 16% in LT group showed NR, while all non‐LT patients showed some response. All paired comparisons were statistically different (P<0.05). Multiple regression analysis revealed that lack of ER predicts need for LT (P=0.0005). 87% of patients who achieved ER did not require LT, whereas 16% of patients who failed ER showed NR and all required LT. Odds ratio of a patient who failed ER proceeding to LT, compared to a patient who achieved ER, was 16.8 (7.5 to 37.7, 95% CI).Conclusion: Patients who fail to show a 50% improvement in transaminases at 6 months of standard immunosuppression should be considered for alternate treatment modalities or be referred earlier for LT.
Autoimmune hepatitis type 1: safety and efficacy of prolonged medical therapy
Authors: Seela Srinivas , Sheela Harinath , Boyer James L. 
Published: July 2005

Abstract: Studies on the long‐term outcome of immunosuppression in patients with autoimmune hepatitis (AIH) type 1 are limited.Aim: To assess the efficacy and safety of prolonged medical therapy for up to four decades in a cohort of patients with AIH.Methods: Forty‐two patients were followed long term in the Yale Liver Clinics who met the criteria of ‘definite autoimmune hepatitis’ as defined by the International Autoimmune Hepatitis Group. Records were reviewed for the dosage of immunosuppression, rate of relapse, steroid side effects, current status of liver function tests and evidence for cirrhosis and its complications.Results: Mean follow‐up was 16 years and ranged from 7 to 43 years. The median follow‐up was 13.5 years. Steroid withdrawal resulted in a mean of 1.78 relapses/patient (range, 0–8). All but six patients responded well to prednisone and azathioprine and alanine aminotransferases were completely normal in 29 (81%) at last exam. Five patients have discontinued medication. Steroid side effects have been minimal (weight gain in eight, osteoporosis in three) except for one patient who recovered successfully from cryptococcal meningitis and another with aseptic necrosis of the hip. Progression to cirrhosis occurred in 54% with evidence of esophageal varices in 37% but none developed hepatocellular carcinoma. Only one patient has received a liver transplant, while five others are currently listed because of symptoms of ascites, encephalopathy or bleeding from esophageal varices.Conclusions: AIH can be managed effectively over three to four decades with low‐dose immunosuppression resulting in essentially normal lifestyles and minimal side effects. Liver transplantation with an increased risk of rejection and graft failure in this group can be avoided for long periods in most of these patients.
Fasudil hydrochloride hydrate, a Rho‐kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity in hepatic stellate cells
Authors: Fukushima Marie , Nakamuta Makoto , Kohjima Motoyuki , Kotoh Kazuhiro , Enjoji Munechika , Kobayashi Naoya , Nawata Hajime 
Published: July 2005

Abstract: Background/Aims: The Rho–ROCK signaling pathways play an important role in the activation of hepatic stellate cells (HSCs). We investigated the effects of fasudil hydrochloride hydrate (fasudil), a Rho‐kinase (ROCK) inhibitor, on cell growth, collagen production, and collagenase activity in HSCs.Methods: Rat HSCs and human HSC‐derived TWNT‐4 cells were cultured for studies on stress fiber formation and α‐smooth muscle actin (α‐SMA) expression. Proliferation was measured by BrdU incorporation, and apoptosis by TUNEL assay. The phosphorylation states of the MAP kinases (MAPKs), extra cellular signal –regulated kinase 1/2 (ERK1/2), c‐jun kinase (JNK), and p38 were evaluated by western blot analysis. Type I collagen, matrix metalloproteinase‐1 (MMP‐1) and tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) production and gene expression were evaluated by ELISA and real‐time PCR, respectively. Collagenase activity (active MMP‐1) was also evaluated.Results: Fasudil (100 μM) inhibited cell spreading, the formation of stress fibers, and expression of α‐SMA with concomitant suppression of cell growth, although it did not induce apoptosis. Fasudil inhibited phosphorylation of ERK1/2, JNK, and p38. Treatment with fasudil suppressed the production and transcription of collagen and TIMP, stimulated the production and transcription of MMP‐1, and enhanced collagenase activity.Conclusion: These findings demonstrated that fasudil not only suppresses proliferation and collagen production but also increases collagenase activity.
Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors
Authors: Di Stefano Giuseppina , Fiume Luigi , Bolondi Luigi , Lanza Marcella , Pariali Milena , Chieco Pasquale 
Published: July 2005

Abstract:Background/Aims: The hepatocyte receptor for asialoglycoproteins (ASGP‐R) internalizes macromolecules exposing galactosyl residues (MEGRs) which can be used as liver‐addressed drug carriers. This receptor was also found on the cells of the large majority of well differentiated hepatocarcinomas (HCCs). The aim of the present experiments was to ascertain whether ASGP‐R of HCCs is functionally active and these tumors can internalize higher quantities of MEGRs than extra‐hepatic tissues.Methods: We injected radioactive lactosaminated human albumin (L‐HSA) in rats with HCCs produced by nitroso‐diethylamine and measured the radioactivity of tumors, surrounding liver, heart, intestine and kidney. L‐HSA is a MEGR successfully used in humans as a hepatotropic drug carrier.Results: The levels of radioactivity of HCCs were two to three times lower than those of surrounding liver, but several times higher than those of extra‐hepatic tissues. L‐HSA accumulation in the tumors mainly occurred via the ASGP‐R, as indicated by the 20 times lower penetration of non‐lactosaminated HSA. L‐HSA uptake by the well‐differentiated tumors were four times higher compared with that by the poorly differentiated forms.Conclusions: The present results suggest that in the chemotherapy of HCCs expressing the ASGP‐R the extra‐hepatic toxicity of anticancer agents can be reduced by conjugation to L‐HSA.
Enzymic and non‐enzymic cross‐linking mechanisms in relation to turnover of collagen: relevance to aging and exercise
Authors: Avery N. C. , Bailey A. J. 
Published: July 2005

The molecular mechanisms involved in the aging of collagen and consequent increase in mechanical strength and stiffness occur in a series of enzymic and non‐enzymic intermolecular cross‐links. The enzymic mechanism involves divalent aldimine intermolecular cross‐links derived from the reaction of aldehydes which then mature to trivalent cross‐links and further stabilize the collagen fiber and is now well known. Recent studies have demonstrated that the rate of turnover and level of telopeptide lysyl hydroxylation modifies the nature of the cross‐link and hence the mechanical strength of the fiber.The slow turnover of mature collagen subsequently allows accumulation of the products of the adventitious non‐enzymic reaction of glucose with the lysines in the triple helix to form glucosyl lysine and its Amadori product, that is, the Maillard reaction. These products are subsequently oxidized to a complex series of advanced glycation end‐products, some of which are intermolecular cross‐links between the triple helices rendering the fiber too stiff for optimal functioning of the collagen fibers, and consequently of the particular tissue involved. The glycation reactions following maturation are true aging processes, and attempts at their specific inhibition involve competitive inhibition of the Maillard reaction and chemical cleavage of the glycation cross‐links.It is clear that the nature of the age‐related cross‐links and hence tissue strength depends on the rate of turnover of the collagen. An examination of the particular effect of strenuous exercise on the rate of turnover of collagen and hence cross‐linking in different tissues could lead to a better understanding of optimal sports training regimes.
The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease
Authors: Pufe T. , Petersen W. J. , Mentlein R. , Tillmann B. N. 
Published: July 2005

More than 100 years ago Wilhelm Roux (1895) introduced the term “functional adaptation to anatomy and physiology”. Compared with other organ systems the functional adaptation processes are best identifiable in the locomotor system, like for example in the two types of tendons: traction and gliding tendons. Traction tendons are tendons where the direction of pull is in line with the direction of the muscle (e.g. Achilles tendon). Gliding tendons (e.g. tibialis posterior tendon) change direction by turning around a bony or fibrous hypomochlion. In this region the tendon is subjected to intermittent compressive and shear forces and the extracellular matrix consists of avascular fibrocartilage. Avascularity is considered to be a key factor for the etiology of degenerative tendon disease. The repair capability after repetitive microtrauma is strongly compromised in avascular tissue of gliding tendons. Reduced vascularity is not a specific feature of gliding tendons; several studies have shown that the number and size of blood vessels are largely shortened in the waist of the Achilles tendon. However, histological biopsies from degenerated Achilles tendons and Doppler flow examinations revealed a high blood vessel density in patients with degenerative tendon disease.Angiogenesis is mediated by angiogenic factors and recent studies have shown that the vascular endothelial growth factor (VEGF) is highly expressed in degenerative Achilles tendons, whereas VEGF expression is nearly completely downregulated in healthy tendons. Several factors are able to upregulate VEGF expression in tenocytes: hypoxia, inflammatory cytokines and mechanical load. Since VEGF has the potential to stimulate the expression of matrix metalloproteinases and inhibit the expression of tissue inhibitors of matrix metalloproteinases tissue inhibitor of metalloproteinases (TIMP) in various cell types (e.g. endothelial cells, fibroblasts, chondrocytes), this cytokine might play a significant role for the pathogenetic processes during degenerative tendon disease. An animal experiment in the rabbit has shown that local injection of VEGF reduced the material properties of the Achilles tendon. These experimental findings are in accordance with clinical results that a locally administered (in the area with neovascularization) sclerosing drug (Polidocanol) has a beneficial effect on chronic mid‐portion Achilles tendinosis.In conclusion, decreased and increased vascularity might be involved in the pathogenesis of degenerative Achilles tendon disease.
The correlation of metallicity gradient with galaxy mass
Authors: Forbes Duncan A. , Sánchez-Blázquez Patricia , Proctor Robert 
Published: July 2005

Abstract
A number of previous studies have searched for a correlation between radial metallicity gradients and early-type galaxy mass – no convincing trends have been found. Here we re-examine this issue with several key enhancements: using total metallicity from studies that have broken the age–metallicity degeneracy, excluding galaxies with young stellar ages (i.e. those that have experienced a recent central starburst) and using the K band to derive galaxy luminosities. We find that Coma cluster galaxies have metallicity gradients that correlate with galaxy mass. Furthermore, gradients have values similar to those of monolithic collapse models. The combination of dissipative formation and energy injection from supernovae provides a mechanism for the trends with galaxy mass; however, other explanations are possible. Additional high-quality observational data are needed to constrain further the gas physics involved in galaxy formation.
Radial velocity moments of dark matter haloes
Authors: Wojtak Radosław , Łokas Ewa L. , Gottlöber Stefan , Mamon Gary A. 
Published: July 2005

Abstract
Using cosmological N-body simulations, we study the radial velocity distribution in dark matter haloes, focusing on the lowest-order even moments, dispersion and kurtosis. We determine the properties of 10 massive haloes in the simulation box, approximating their density distribution by the Navarro, Frenk & White (NFW) formula characterized by the virial mass and concentration. We also calculate the velocity anisotropy parameter of the haloes, and find it mildly radial and increasing with distance from the halo centre. The radial velocity dispersion of the haloes shows a characteristic profile with a maximum, while the radial kurtosis profile decreases with distance starting from a value close to Gaussian near the centre. We therefore confirm that dark matter haloes possess intrinsically non-Gaussian, flat-topped velocity distributions. We find that the radial velocity moments of the simulated haloes are quite well reproduced by the solutions of the Jeans equations obtained for the halo parameters with the anisotropy measured in the simulations. We also study the radial velocity moments for a composite cluster made of 10 haloes out to 10 virial radii. In this region the velocity dispersion decreases systematically to reach the value of the background, while kurtosis increases from below to above the Gaussian value of 3, signifying a transition from a flat-topped to a strongly peaked velocity distribution with respect to the Gaussian, which can be interpreted as the dominance of ordered flow with a small dispersion. We illustrate the transition by showing explicitly the velocity distribution of the composite cluster in a few radial bins.
Gl 86B: a white dwarf orbits an exoplanet host star
Authors: Mugrauer M. , Neuhäuser R. 
Published: July 2005

Abstract
In this Letter we present our first high-contrast observations of the exoplanet host star Gl 86 using NAOS-CONICA (NACO) and its new Simultaneous Differential Imager (SDI) as well as results from NACO spectroscopy. Els et al. found a faint comoving companion located only ∼2 arcsec east of the exoplanet host star Gl 86A. Our high-contrast SDI observations rule out additional stellar companions from 1 au up to 23 au, and are sensitive for faint T-dwarf companions down to 35 MJup. We present evidence for orbital motion of Gl 86B around the exoplanet host star Gl 86A, which finally confirms that this is a bound binary system. With the given photometry from Els et al. and the NACO spectroscopy obtained, we prove that the companion Gl 86B is a cool white dwarf with an effective temperature of 5000 ± 500 K. This is the first confirmed white dwarf companion to an exoplanet host star and the first observational confirmation that planets survive the post-main-sequence evolution (giant phase and planetary nebula) of a star from which they are separated by only one to two dozen astronomical units, as expected from theory.
Evidence for dust reddening in damped Lyα absorbers identified through Ca ii (H&K) absorption
Authors: Wild Vivienne , Hewett Paul C. 
Published: July 2005

Abstract
We present a new sample of 31 Ca ii (H&K) λλ3935, 3970 absorption-line systems with 0.84 &lt; zabs &lt; 1.3 discovered in the spectra of Sloan Digital Sky Survey (SDSS) Data Release 3 quasars, together with an analysis of their dust content. The presence of calcium absorption together with measurements of the Mg iiλ2796, Fe iiλ2600 and Mg iλ2853 lines leads to the conclusion that the majority of our systems are damped Lyα (DLA) absorbers. The composite spectrum in the rest frame of the absorber shows clear evidence for reddening. Large and Small Magellanic Cloud extinction curves provide satisfactory fits, with a best-fitting E(B – V) of 0.06, while the Galactic dust extinction curve provides a poor fit due to the lack of a strong 2175-Å feature. A trend of increasing dust content with equivalent width of Ca ii is present. Monte Carlo techniques demonstrate that the detection of reddening is significant at &gt;99.99 per cent confidence. The discovery of significant amounts of dust in a subsample of DLAs has direct implications for studies of the metallicity evolution of the Universe and the nature of DLAs in relation to high-redshift galaxies. The gas:dust ratio is discussed. Our results suggest that at least ∼40 per cent of the Ca ii absorption systems are excluded from the magnitude-limited SDSS quasar sample as a result of the associated extinction, a fraction similar to the upper limit deduced at higher redshifts from radio-selected surveys.
Genitourinary medicine and surgery in Nelson’s navy
Authors: Goddard J C 
Published: July 2005

Abstract
Surgeons of the Royal Navy during the Napoleonic and revolutionary wars, between 1793 and 1815, were solely responsible for all health care of the officers, men, and boys of their ships. This paper examines the genitourinary medicine and surgery encountered by the naval surgeons at the time of Nelson. Primary sources are examined to explore the presentation, case mix, and management of genitourinary disease during this period. A general overview is given of the life and work of the Royal Naval surgeons at the end of the 18th century. The documents that were examined contained 39 surgeon’s journals, these were written by 26 surgeons on 13 different ships. The journals contained 446 presentations to the sick list of men with genitourinary symptoms. The presenting symptoms are grouped together under the following headings; venereal disease, penile pathology, scrotal pain and swelling, urinary symptoms and retention, stone disease and trauma. Examination of these journals permits a glimpse of medical life in the Royal Navy during the time of Nelson. The case load and management of genitourinary disease shows the diversity of presentation to these surgeons.