bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B virus x protein in the pathogenesis of hepatitis B virus‐induced hepatocellular carcinoma
Authors: Kew Michael C 
Published: January 2011

AbstractCurrently available evidence supports a role for the hepatitis B virus (HBV) x gene and protein in the pathogenesis of HBV‐induced hepatocellular carcinoma (HCC). HBx gene is often included, and remains functionally active, in the HBV DNA that is frequently integrated into cellular DNA during hepatocellular carcinogenesis. HBx protein promotes cell cycle progression, inactivates negative growth regulators, and binds to and inhibits the expression of p53 tumour suppressor gene and other tumour suppressor genes and senescence‐related factors. However, the molecular mechanisms responsible for HBx protein‐induced HCC remain uncertain. Only some of the more fully documented or more recently recognised mechanisms are reviewed. During recent years evidence has accumulated that HBx protein modulates transcription of methyl transferases, causing regional hypermethylation of DNA that results in silencing of tumour suppressor genes, or global hypomethylation that results in chromosomal instability, thereby playing a role in hepatocarcinogenesis. HBx protein has both anti‐apoptotic and pro‐apoptotic actions, apparently contradictory effects that have yet to be explained. Particularly important among the anti‐apoptotic properties is inhibition of p53. Recent experimental observations suggest that HBx protein may increase the expression of TERT and telomerase activity, prolonging the life‐span of hepatocytes and contributing to malignant transformation. The protein also interferes with nucleotide excision repair through both p53‐dependent and p53‐ independent mechanisms. Carboxy‐terminal truncated HBx protein loses its inhibitory effects on cell proliferation and pro‐apoptotic properties, and it may enhance the protein's ability to transform oncogenes. Dysregulation of IGF‐II enhances proliferation and anti‐apoptotic effects of oncogenes, resulting in uncontrolled cell growth.
Hepatocyte growth factor twenty years on: Much more than a growth factor
Authors: Nakamura Takahiro , Sakai Katsuya , Nakamura Toshikazu , Matsumoto Kunio 
Published: January 2011

AbstractLiver regeneration depends on the proliferation of mature hepatocytes. In the 1980s, the method for the cultivation of mature hepatocytes provided an opportunity for the discovery of hepatocyte growth factor (HGF) as a protein that is structurally and functionally different from other growth factors. In 1991, the scatter factor, tumor cytotoxic factor, and 3‐D epithelial morphogen were identified as HGF, and Met tyrosine kinase was identified as the receptor for HGF. Thus, the connection of apparently unrelated research projects rapidly enriched the research on HGF in different fields. The HGF‐Met pathway plays important roles in the embryonic development of the liver and the placenta, in the migration of myogenic precursor cells, and in epithelial morphogenesis. The use of tissue‐specific knockout mice demonstrated that in mature tissues the HGF‐Met pathway plays a critical role in tissue protection and regeneration, and in providing less susceptibility to chronic inflammation and fibrosis. In various injury and disease models, HGF promotes cell survival, regeneration of tissues, and suppresses and improves chronic inflammation and fibrosis. Drug development using HGF has been challenging, but extensive preclinical studies to address its therapeutic effects have provided significant results sufficient for the development of HGF as a biological drug in the regeneration‐based therapy of diseases. Clinical trials using recombinant human HGF protein, or HGF genes, are in progress for the treatment of diseases.
Hepatitis C virus: How genetic variability affects pathobiology of disease
Authors: Chayama Kazuaki , Hayes C Nelson 
Published: January 2011

AbstractAs an RNA virus, hepatitis C virus (HCV) shows a characteristically high level of nucleotide diversity. Accumulation of nucleotide substitutions in the virus has resulted in diversification into quasispecies, subtypes and distinct genotypes. Pathobiological studies linking nucleotide and amino acid sequences with clinical findings have identified relationships between certain genotypes and characteristic biological properties. Genotype 3 HCV infection was found to be associated with a high level of liver steatosis. Genotypes 1 and 4 were found to be more resistant to interferon (IFN) based therapies than genotypes 2 and 3. Studies of genotype 1 sequences obtained from patients treated with IFN have identified a relationship between favorable response to interferon therapy and amino acid substitutions in the NS5A region (interferon response determining region; ISDR). Further studies have identified a relationship between the effect of IFN therapy and other regions of the NS5A protein. More recently, a relationship has been found between poor response to peg‐IFN plus ribavirin combination therapy and substitutions at amino acid 70 and 91 in the core protein. Furthermore, a correlation between human genetic variation in the IL28B (IFN‐lamda 3) locus and core amino acid substitutions has been characterized.In this review we briefly summarize the discovery, classification and nomenclature of HCV genotypes and subtypes. We also discuss amino acid substitutions within specific regions that have been reported to be associated with outcome of IFN and peg‐IFN plus ribavirin combination therapy.
Management of gastric varices
Authors: Hashizume Makoto , Akahoshi Tomohiko , Tomikawa Morimasa 
Published: January 2011

AbstractAlthough the incidence of bleeding from gastric varices is relatively low (10%–36%), the bleeding is massive once it has occurred and it increases the patient's mortality. The management of esophageal variceal bleeding is highly differentiated with several effective treatments available. In contrast, bleeding from gastric varices continues to be a therapeutic challenge. In the last decade, there have been increasing reports regarding the management of gastric varices. In this article we review recent progress in the management of gastric varices and discuss further expected studies.
Cell death and hepatocarcinogenesis: Dysregulation of apoptosis signaling pathways
Authors: Schattenberg Jorn Markus , Schuchmann Marcus , Galle Peter Robert 
Published: January 2011

AbstractHepatocellular carcinoma (HCC) remains a disease with a poor prognosis despite recent advances in the pathophysiology and treatment. Although the disease is biologically heterogeneous, dysregulation of cellular proliferation and apoptosis both occur frequently and contribute to the malignant phenotype. Chronic liver disease is associated with intrahepatic inflammation which promotes dysregulation of cellular signaling pathways; this triggers proliferation and thus lays the ground for expansion of premalignant cells. Cancer emerges when immunological control fails and transformed cells develop resistance against cell death signaling pathways. The same mechanisms underlie the poor responsiveness of HCC towards chemotherapy. Only recently advances in understanding the signaling pathways involved has led to the development of an effective pharmacological therapy for advanced disease. The current review will discuss apoptosis signaling pathways and focus on apoptosis resistance of HCC involving derangements in cell death receptors (e.g. tumor necrosis factor‐alpha [TNF], CD95/Apo‐1, TNF‐related apoptosis‐inducing ligand [TRAIL]) and associated adapter molecules (e.g. FADD and FLIP) of apoptotic signaling pathways. In addition, the role of the transcription factor nuclear factor‐kappaB (NFκB) and members of the B cell leukemia‐2 (Bcl‐2) family that contribute to the regulation of apoptosis in hepatocytes are discussed. Eventually, the delineation of cell death signaling pathways could contribute to the implementation of new therapeutic strategies to treat HCC.
Hepatic ischemia reperfusion injury: Contemporary perspectives on pathogenic mechanisms and basis for hepatoprotection—the good, bad and deadly
Authors: Teoh Narci C 
Published: January 2011

AbstractHepatic ischemia reperfusion (IR) injury is an important clinical problem complicating liver surgery and transplantation. The pathogenesis underlying reperfusion injury after warm ischemia is complex, encompassing a multitude of different cell types and signalling mechanisms innate and/or mobilized to the liver. Since the author's 2003 review in the Journal, considerable progress has been achieved in enhancing our understanding of some of the pathogenic pathways and crucial mediators of hepatic inflammation such as the heme oxygenase system, CXC chemokines, Toll‐like receptors as well as the mode of parenchymal cell death in IR injury. A better appreciation of these mechanisms will accelerate efforts in designing optimal interventions to prevent hepatic IR injury and improve outcomes after liver transplantation.
Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts
Authors: Jaeschke Hartmut 
Published: January 2011

AbstractLiver cell death induced by stresses such as ischemia‐reperfusion, cholestasis and drug toxicity can trigger a sterile inflammatory response with activation of innate immune cells through release of damage‐associated molecular patterns (DAMPs). A similar inflammatory response can be induced by pathogen‐associated molecular patterns (PAMPs) such as endotoxin. Both DAMPs and PAMPs activate through toll‐like receptors the resident macrophages (Kupffer cells) and recruit activated neutrophils and monocytes into the liver. Central to this inflammatory response is promotion of reactive oxygen species (ROS) formation by these phagocytes. ROS are the principal toxic mediators by which inflammatory cells kill their targets, e.g. bacteria during host defense but also hepatocytes and other liver cells. The mechanism of ROS‐induced cell killing during inflammation involves the promotion of mitochondrial dysfunction through an intracellular oxidant stress in hepatocytes leading mainly to oncotic necrosis and less apoptosis. The additional release of cell contents amplifies the inflammatory injury. However, an inflammatory oxidant stress insufficient to directly cause cell damage can induce transcription of stress defence genes including antioxidant genes. This preconditioning effect of ROS enhances the resistance against future inflammatory oxidant stress and promotes the initiation of tissue repair processes. Despite the substantial progress in our understanding of mechanisms of inflammatory liver injury during the last decade, more research is necessary to better understand the role of ROS in acute liver inflammation and to develop clinically applicable therapeutic strategies that selectively target the detrimental effects of oxidant stress without compromising the vital function of ROS in host defense.
A field study of seed germination in the endangered Trillium reliquum Freeman (Trilliaceae)
Authors: THOMPSON JACOB S. , LEEGE LISSA M. 
Published: January 2011

AbstractPrevious studies examining the seeds of most Trillium species have reported double dormancy, a type of seed dormancy where two cold periods and one warm period are needed for complete germination. In the present paper, we describe a field study examining the federally endangered Trillium reliquum Freeman (Trilliaceae) in which moderate to high numbers of seeds germinated after one winter following seed production. Sixteen baskets with seeds were placed in four T. reliquum populations (four baskets in each population) in Georgia, USA, in June 2005. In spring 2006, all seed baskets contained seedlings. Germination percentages ranged from 33.3 to 83.3% across sites with a mean of 56.9 ± 3.9%. Trillium reliquum had higher germination percentages compared with other field‐based germination studies with other Trillium species. Our findings will inform future demographic studies of T. reliquum and suggest that double dormancy in seeds may not be as widespread as previously reported within the genus Trillium.
Consequences of forest fragmentation in an understory plant community: extensive range expansion of native dwarf bamboo
Authors: TOMIMATSU HIROSHI , YAMAGISHI HIROKI , TANAKA IPPEI , SATO MASATOSHI , KONDO RENZO , KONNO YASUO 
Published: January 2011

AbstractUnderstory bamboo species are important and influential components of temperate forests in at least several parts of the world. Here we report a study testing the effect of forest fragmentation on the dynamics of the dwarf bamboo Sasa chartacea and on forest herb communities in the Tokachi plain of Hokkaido, Japan. We studied 16 forest fragments of different sizes and small plots established in these fragments to examine the relationship between the abundance of S. chartacea, landscape and environmental conditions, and forest herb communities. Sasa chartacea was more abundant near forest edges and in smaller fragments, suggesting that the species has expanded its local range and increased its abundance in response to forest fragmentation. Edge‐related changes in light and soil moisture might have facilitated this range expansion. The species richness of forest herbs was strongly negatively related to the density of S. chartacea. Because much larger variation in species richness was explained by S. chartacea density than distance to the nearest forest edge, the expansion of S. chartacea has likely excluded other understory species by competition. In addition, the density of S. chartacea significantly explained variation in the species composition of forest herbs across plots. Taken together, our results emphasize the key roles of dwarf bamboos in changing plant communities following forest fragmentation.
Association of lower hemoglobin level with depressive mood in elderly women at high risk of requiring care
Authors: Umegaki Hiroyuki , Yanagawa Madoka , Endo Hidetoshi 
Published: January 2011

Aim:  Despite the high prevalence of anemia and depression in the elderly, there have been few studies exploring the association between these two conditions. In the current study, we analyzed the association of hemoglobin level and depressive mood in a group of community‐dwelling elderly at high risk of requiring care.Methods:  All participants at a health check in a group of community‐dwelling elderly (1163 men and 2651 women) filled out a basic yes/no questionnaire consisting of simple assessments of their instrumental activities of daily living (7 items), memory problems (3 items), walking status (5 items), dysphagia (3 items), nutritional status (2 items) and depressive mood (5 items). Other examinations, including blood testing, were also performed. Multiple regression analysis with the score of depressive mood in the basic checklist was performed. The hemoglobin level was set for an explanatory value after adjustment for age, blood pressure, electrocardiogram abnormality, instrumental activities of daily living, walking status, nutritional status, dysphagia and memory problems.Results:  It was found that 30.5% of women and 31.8% of men had anemia. When the subjects were divided with depressive score of 2 points or more (the highest possible score was 5) and less, those with a higher depressive score had significantly lower hemoglobin levels than those with a lower score. Multiple regression analysis showed that lower hemoglobin level was significantly associated with depressive mood only in women (P = 0.046) but not in men (P = 0.579).Conclusion:  Lower hemoglobin level was significantly associated with depressive mood in elderly women at high risk for care, but not in elderly men at high risk for care. Geriatr Gerontol Int 2011; 11: 262–266.
Galantamine (Reminyl) once daily outcome and satisfaction survey (RODOS) in mild to moderate Alzheimer's disease: A study in a real life population
Authors: Van Puyvelde Katrien , Mets Tony ,   for the RODOS Study Group
Published: January 2011

Aim:  To record in real life the appreciation of elderly patients, their caregivers and physicians of a once daily formulation of prolonged release of galantamine in the treatment of mild to moderate Alzheimer's disease.Methods:  A prospective, multicenter, observational study was conducted in 128 elderly patients, treated for 6 months with galantamine, donepezil or rivastigmine.Results:  Of the patients treated with galantamine, 82 of the 97 (84.5%) were continuing their treatment after 6 months. These patients reported their condition as improved in 49%, unchanged in 47% and worsened in 4%. Caregivers rated global evaluation as 37% better, 41% unchanged and 22% worse. Physicians rated global clinical impression of change as 46% better, 34% unchanged and 20% worse. Measurements of cognition and behavior remained stable. The appreciation of physicians and caregivers corresponded well (P < 0.001). The incidence of serious side‐effects possibly related to galantamine was 9.3%, which was not different from that in patients treated with other cholinesterase inhibitors.Conclusion:  In a real life setting, galantamine once daily is safe and is favorably appreciated by patients, their caregivers and physicians. Geriatr Gerontol Int 2011; 11: 256–261.
Spiroplasma found in the eyes of scrapie affected sheep
Authors: Bastian Frank O. , Boudreaux Charles M. , Hagius Sue D. , Bulgin Marie S. , Sorensen‐Melson Sharon J. , Enright Frederick M. , Elzer Philip H. 
Published: January 2011

AbstractObjective  Scrapie, a transmissible spongiform encephalopathy (TSE) occurring naturally in sheep, characteristically shows a severe retinopathy that is well developed in the terminal phases of the disease. In this study, we set out to demonstrate similar retinal changes in our ruminant spiroplasmosis TSE model.Procedure  The eyes from deer, sheep, and goats that were inoculated intracranially with the laboratory strain of spiroplasma (suckling mouse cataract [SMCA] strain of Spiroplasma mirum) or with Spiroplasma sp. isolated from the brains affected with scrapie or with chronic wasting disease were examined by light microscopy for pathologic changes and by immunocytochemistry for distribution of spiroplasma antigen. The eyes were also obtained from a research flock of sheep with terminal scrapie, from which the intraocular tissues were submitted aseptically for culture assay in M1D broth or as explants on bovine corneal endothelia (BCE).Results  The eyes from the spiroplasmosis ruminant models showed retinopathy remarkably similar to eye lesions seen in sheep with scrapie. The spiroplasma antigen accrued in the ruminant model eye tissues, particularly in the retina, the vitreous humor, and the corneal endothelia. A Spiroplasma sp. grew out of the scrapie‐affected eyes both in the M1D broth and in the BCE cultures but did not expand. These new spiroplasma isolates differed immunologically from SMCA.Conclusion  These data showed a clear association of spiroplasma with scrapie suggesting that these bacteria have a role in the pathogenesis of TSE and that the eye should be a research focus for future studies of TSE.
Efficacy of topically applied liposome‐bound tetracycline in the treatment of dry eye model
Authors: Shafaa Medhat W. , El shazly Laila H. , El shazly Amany H. , El gohary Amal A. , El hossary Ghada G. 
Published: January 2011

AbstractObjective  To evaluate the effects of liposome‐bound tetracycline eye drops in a rabbit dry eye model evaluating their advantage of being less allergic, preservative free and prolonged action compared with other tear substitutes.Procedures  New Zealand albino rabbits were equally divided into control group and dry eye induced groups. Dryness was induced in 24 eyes of 12 healthy adult male albino rabbits by instilling atropine sulfate eye drops 1% three times daily for 1 week, then animals were subdivided into four groups; group 1 (rabbits with dry eye model), groups 2, 3, and 4: rabbits with dry eye model treated for 7 days starting on 7th day of dryness induction with either tetracycline, empty liposome, or combined tetracycline with liposome as topical eye drops respectively. Schirmer (STT) test and tear break up time (TBUT) were assessed on days 0, 2, 4, 7, 9, 11, and 14. Animals were sacrificed on day 14 and histopathological examination of the cornea and conjunctiva was performed.Results  Tear break up time and STT test values were significantly improved in groups 2, 3, 4 as compared with group 1. The histopathological examination showed normal cytoarchitecture of corneas and conjunctivae in groups 2, 3, 4 against the dryness effect that continued to affect the cornea and conjunctival epithelium in group 1. There was a significant improvement in the group treated with liposome‐bound tetracycline eye drops (group 4) as compared with tetracycline alone (group 2) and empty liposome (group 3).Conclusion  The use of liposome encapsulated tetracycline significantly improved STT and TBUT values as well as reverse surface ocular pathology.
Unilateral orbital lacrimal gland abscess in a horse
Authors: Greenberg Shari M. , Plummer Caryn E. , Brooks Dennis E. , Porter Michael , Farina Lisa L. , Winter Matthew D. 
Published: January 2011

AbstractA 20‐year‐old Thoroughbred gelding presented for evaluation of a periorbital dorsal swelling of the left eye that had been intermittently present for 3 months. Upon ocular examination, a firm, non‐painful swelling was identified under the upper eyelid in the region of the orbital lacrimal gland, and was noted to extend anteriorly from underneath the dorsal orbital rim. Ultrasonographic examination revealed a mixed echogenic mass along the dorsal orbital rim that followed the contour of the globe. CT scan showed a moderately contrast enhancing mass that was contiguous with the eyelid. Differential diagnoses included neoplasia, inflammatory lesions such as a granuloma, foreign body or abscess. Surgical exploration and excision of the mass revealed a lobular structure with a purulent center. Histopathology identified the mass as the orbital lacrimal gland with concurrent severe dacryoadenitis. Culture of the purulent center of the mass revealedbeta‐hemolytic Staphylococcus aureus. The patient was maintained on supportive care and antibiotic treatment based on sensitivity postoperatively. No recurrence was reported 40 months later. This paper aims to identify bacterial dacryoadenitis as a cause for unilateral periorbital swelling in the horse. Differential diagnoses for this presentation, as well as successful surgical management are discussed. To the author’s knowledge, this is the first case of bacterial dacryoadenitis and subsequent abscessation of the orbital lacrimal gland in the horse.
Internet user behaviour in France and Britain: exploring socio‐spatial disparity among adolescents
Authors: Lichy Jessica 
Published: January 2011

AbstractThe Internet has radically transformed society – although its diffusion has been uneven. Various studies of digital inequality have been undertaken in Anglo‐Saxon communities. Few studies have investigated digital inequality from a socio‐spatial perspective (urban vs. suburban, rather than urban vs. rural) in a French setting. This absence underscores a gap in knowledge and methodology. It highlights the complexities of gathering comparable data on Internet user behaviour beyond national borders. This paper takes a multidisciplinary approach to investigate emerging trends in Internet use across different territories (inner‐city and suburban, as opposed to urban vs. rural) by means of in‐depth interviews with Internet users aged 13–15 years old in France and Britain. The aim is to provide a broad understanding of the way in which teenage Internet users behave online in different territories. The investigation reveals a number of converging trends that are common to both France and Britain and some unexpected disparity.