bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects
Authors: Wu Dong-Feng , Yin Rui-Xing , Aung Lynn Htet Htet , Li Qing , Yan Ting-Ting , Zeng Xiao-Na , Huang Ke-Ke , Huang Ping , Wu Jin-Zhen , Pan Shang-Ling 
Published: January 2012

Abstract

Background
Acyl-CoA:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C) concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP) and serum lipid levels in the hyperlipidemic subjects.

Methods
A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345) aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

Results
There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC), HDL-C and apolipoprotein (Apo) AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P < 0.05-0.01), the C allele carriers had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. The association of genotypes and serum HDL-C and ApoAI levels in hyperlipidemia was found mainly in the male subjects with hypercholesterolemia but not in those with hypertriglyceridemia. There were no significant differences in serum lipid levels between the AA and AC/CC genotypes in the normolipidemic subjects.

Conclusions
The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male)-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.
NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration
Authors: Qin Liya , Crews Fulton T 
Published: January 2012

Abstract

Background
Activation of microglia causes the production of proinflammatory factors and upregulation of NADPH oxidase (NOX) that form reactive oxygen species (ROS) that lead to neurodegeneration. Previously, we reported that 10 daily doses of ethanol treatment induced innate immune genes in brain. In the present study, we investigate the effects of chronic ethanol on activation of NOX and release of ROS, and their contribution to ethanol neurotoxicity.

Methods
Male C57BL/6 and NF-κB enhanced GFP mice were treated intragastrically with water or ethanol (5 g/kg, i.g., 25% ethanol w/v) daily for 10 days. The effects of chronic ethanol on cell death markers (activated caspase-3 and Fluoro-Jade B), microglial morphology, NOX, ROS and NF-κB were examined using real-time PCR, immunohistochemistry and hydroethidine histochemistry. Also, Fluoro-Jade B staining and NOX gp91phox immunohistochemistry were performed in the orbitofrontal cortex (OFC) of human postmortem alcoholic brain and human moderate drinking control brain.

Results
Ethanol treatment of C57BL/6 mice showed increased markers of neuronal death: activated caspase-3 and Fluoro-Jade B positive staining with Neu-N (a neuronal marker) labeling in cortex and dentate gyrus. The OFC of human post-mortem alcoholic brain also showed significantly more Fluoro-Jade B positive cells colocalized with Neu-N, a neuronal marker, compared to the OFC of human moderate drinking control brain, suggesting increased neuronal death in the OFC of human alcoholic brain. Iba1 and GFAP immunohistochemistry showed activated morphology of microglia and astrocytes in ethanol-treated mouse brain. Ethanol treatment increased NF-κB transcription and increased NOX gp91phox at 24 hr after the last ethanol treatment that remained elevated at 1 week. The OFC of human postmortem alcoholic brain also had significant increases in the number of gp91phox + immunoreactive (IR) cells that are colocalized with neuronal, microglial and astrocyte markers. In mouse brain ethanol increased gp91phox expression coincided with increased production of O2
- and O2
- - derived oxidants. Diphenyleneiodonium (DPI), a NOX inhibitor, reduced markers of neurodegeneration, ROS and microglial activation.

Conclusions
Ethanol activation of microglia and astrocytes, induction of NOX and production of ROS contribute to chronic ethanol-induced neurotoxicity. NOX-ROS and NF-κB signaling pathways play important roles in chronic ethanol-induced neuroinflammation and neurodegeneration.
High hepatitis B virus load is associated with hepatocellular carcinomas development in Chinese chronic hepatitis B patients: a case control study
Authors: Zhou Jin-Yong , Zhang Le , Li Lei , Gu Guang-Yu , Zhou Yi-Hua , Chen Jun-Hao 
Published: January 2012

Abstract

Background
Persistent hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) development. This study aimed to clarify whether the high HBV DNA level is associated with HCC development by comparing HBV DNA levels between HBV infected patients with and without HCC.

Results
There were 78 male and 12 female patients in each group and there was no statistical difference between these two group patients' average ages. The HBV DNA level in the HCC patients was 4.73 ± 1.71 Log10 IU/ml while 3.90 ± 2.01 Log10 IU/ml in non-HCC patients (P < 0.01). The HBeAg positive rate was 42.2% (38/90) in the HCC group while 13.3% (12/90) in the non-HCC group (P < 0.001). Compared with patients with HBV DNA level of < 3 Log10 IU/ml, the patients with level of 3 to < 4, 4 to < 5, 5 to < 6, or ≥ 6 Log10 IU/ml had the odds ratio for HCC of 1.380 (95% CI, 0.544-3.499), 3.671 (95% CI, 1.363-9.886), 5.303 (95% CI, 1.847-15.277) or 3.030 (95% CI, 1.143-8.036), respectively.

Conclusions
HBV-related HCC patients had higher HBV DNA level than non-HCC counterparts. Our findings imply that active HBV replication is associated with the HCC development.
Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction
Authors: Yan Qiang , Wang Baoyao , Sui Weiguo , Zou Guimian , Chen Huaizhou , Xie Shenping , Zou Hequn 
Published: January 2012

Abstract

Objective
To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction.

Methods
Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls.

Results
The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue.

Conclusion
There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue.

Virtual slides
The virtual slide(s) for this article can be found here:

http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.
The genetic control of growth rate: a systems biology study in yeast
Authors: Pir Pınar , Gutteridge Alex , Wu Jian , Rash Bharat , Kell Douglas B , Zhang Nianshu , Oliver Stephen G 
Published: January 2012

Abstract

Background
Control of growth rate is mediated by tight regulation mechanisms in all free-living organisms since long-term survival depends on adaptation to diverse environmental conditions. The yeast, Saccharomyces cerevisiae, when growing under nutrient-limited conditions, controls its growth rate via both nutrient-specific and nutrient-independent gene sets. At slow growth rates, at least, it has been found that the expression of the genes that exert significant control over growth rate (high flux control or HFC genes) is not necessarily regulated by growth rate itself. It has not been determined whether the set of HFC genes is the same at all growth rates or whether it is the same in conditions of nutrient limitation or excess.

Results
HFC genes were identified in competition experiments in which a population of hemizygous diploid yeast deletants were grown at, or close to, the maximum specific growth rate in either nutrient-limiting or nutrient-sufficient conditions. A hemizygous mutant is one in which one of any pair of homologous genes is deleted in a diploid, These HFC genes divided into two classes: a haploinsufficient (HI) set, where the hemizygous mutants grow slower than the wild type, and a haploproficient (HP) set, which comprises hemizygotes that grow faster than the wild type. The HI set was found to be enriched for genes involved in the processes of gene expression, while the HP set was enriched for genes concerned with the cell cycle and genome integrity.

Conclusion
A subset of growth-regulated genes have HFC characteristics when grown in conditions where there are few, or no, external constraints on the rate of growth that cells may attain. This subset is enriched for genes that participate in the processes of gene expression, itself (i.e. transcription and translation). The fact that haploproficiency is exhibited by mutants grown at the previously determined maximum rate implies that the control of growth rate in this simple eukaryote represents a trade-off between the selective advantages of rapid growth and the need to maintain the integrity of the genome.
Human papillomavirus 18 E6 inhibits phosphorylation of p53 expressed in HeLa cells
Authors: Ajay Amrendra K , Meena Avtar S , Bhat Manoj K 
Published: January 2012

Abstract

Background
In HPV infected cells p53 function is abrogated by E6 and even ectopically expressed p53 is unable to perform tumor suppressor functions. In addition to facilitating its degradation, E6 may also inhibit p53 transactivity, though the mechanisms are still poorly understood. It has been reported that inhibition of p300, an acetyltransferase responsible for p53 acetylation is inactivated by E6. Activation of overexpressed p53 to cause cell growth inhibition is facilitated by its phosphorylation. Previously, we reported that non-genotoxically overexpressed p53 in HeLa cells needs to be phosphorylated to perform its cell growth inhibitory functions. Since over expressed p53 by itself was not activated, we hypothesized an inhibitory role for E6.

Results
Majority of reports proposes E6 mediated degradation of p53 as a possible reason for its inactivation. However, results presented here for the first time demonstrate that overexpressed p53 is not directly associated with E6 and therefore free, yet it is not functionally active in HPV positive cells. Also, the stability of overexpressed p53 does not seem to be an issue because inhibition of proteasomal degradation did not increase the half-life of overexpressed p53, which is more than endogenous p53. However, inhibition of proteasomal degradation prevents the degradation of endogenous p53. These findings suggest that overexpressed p53 and endogenous p53 are differentially subjected to proteasomal degradation and the reasons for this discrepancy remain unclear. Our studies demonstrate that p53 over expression has no effect on anchorage independent cell-growth and E6 nullifies its cell growth inhibitory effect. E6 overexpression abrogates OA induced p53 occupancy on the p21 promoter and cell death as well. E6 did not decrease p53 protein but phospho-p53 level was significantly reduced.

Conclusion
We report for the first time that E6 de-activates p53 by inhibiting its phosphorylation. This prevents p53 binding to p21 promoter and thereby restraining its cell-growth inhibitory functions. Our study provides new evidence indicating that viral protein E6 inhibits p53 transactivity by mechanism independent of degradation pathway.
Multiple sclerosis: a chronic infective cerebrospinal venulitis?
Authors: Thibault P K 
Published: January 2012

The aetiology proposed for the development of chronic cerebrospinal venous insufficiency (CCSVI) associated with multiple sclerosis (MS) has been the presence of congenital truncular venous malformations. However, this hypothesis is not consistent with the epidemiology or geographical incidence of MS and is not consistent with many of the ultrasonographic or radiographical findings of the venous disturbances found in MS patients. However, the probability of a venous aetiology of MS remains strong based on evidence accumulated from the time the disorder was first described. The method used in this review was to search PubMed for all past medical publications related to vascular, venous, haematological, epidemiological, biochemical, and genetic investigations and treatments of MS. Epidemiological and geographical findings of prevalence of MS indicate the involvement of an infective agent. This review of the venous pathology associated with MS describes a hypothesis that the pathogenesis of the venous disease could be initiated by a respiratory infective agent such as Chlamydophila pneumonia, which causes a specific chronic persistent venulitis affecting the cerebrospinal venous system. Secondary spread of the agent would initially be via the lymphatic system to specifically involve the azygos, internal jugular and vertebral veins. The hypothesis proposes mechanisms by which an infective venous vasculitis could result in the specific neural damage, metabolic, immunological and vascular effects observed in MS. The hypothesis described is consistent with many of the known facts of MS pathogenesis and therefore provides a framework for further research into a venous aetiology for the disease. If MS does result from a chronic infective venulitis rather than a syndrome involving congenital truncular venous malformations, then additional therapies to the currently used angioplasties will be required to optimize results.
Enzyklopädisten und Lexika im Dienst der Diktatur?
Authors: Keiderling Thomas 
Published: January 2012

Vorspann
Sie sind Teil jeder Hochkultur: Enzyklopädien, Lexika, Nachschlagewerke oder nun auch eine Internetenzyklopädie wie Wikipedia. Aber wie „objektiv“ sind eigentlich diese Kompendien unseres Wissens? Wie weit haben etwa die Ideologien und die politischen Verwerfungen des 20. Jahrhunderts dort ihre Spuren hinterlassen? Thomas Keiderling untersucht dies an einem besonders prononcierten Fall und stellt dabei die Frage, wie weit eine so hochentwickelte Lexikon-Kultur wie die deutsche durch die Herrschaft des Nationalsozialismus beeinflusst und beschädigt wurde.
The Rosamond Plots
Authors: Mitchell Rebecca N. 
Published: January 2012

Abstract
In both Charlotte Brontë’s Jane Eyre (1847) and George Eliot’s Middlemarch (1871–72) an earnest and ambitious man falls in love with a superficial and beautiful woman named Rosamond. This essay explores the “Rosamond plots” to argue that Middlemarch stages a radical revision of the version of subjectivity vaunted in Jane Eyre. Via its invocation of Jane Eyre’s Rosamond plot, Middlemarch challenges the very nature of self-knowledge, questions the status of identification in intersubjective relationships, and insists upon the unknowability of the other. In Eliot’s retelling, the self-awareness promoted in Jane Eyre is not only insufficient, but also verges on self-absorption and even solipsism. One way in which Eliot enacts this revision is by shifting the focus of positive affective relationships away from models of identification. The change marks an evolution in our understanding of the way in which character and communal life is conceived by each author. More specifically, Eliot’s revisions situate empathic response as being dependent upon the recognition of the radical alterity of the other.
“Dirty Air”
Authors: Yeats George 
Published: January 2012

Abstract
This essay argues that the literary atmosphere of Charles Dickens’s Little Dorrit (1855–57) reciprocates the condition of the mid-century London air, as Dickens understood it. Through exploring the novel’s connections with contemporary medical-political debates about air purity, I hope to show that the novel can be read as a study of atmospheric influence, in both material and moral terms. In particular, I examine the metaphorical and phenomenal roles of airborne pollutants in the narrative. Dickens repeatedly correlates socioeconomic with meteorological climates: toxic investment spreads like an epidemic miasma; shady business dealings leave murky deposits; debtors are trapped in conditions of bodily and psychological stagnancy. Eventually these clouds lift from the imprisoned Clennam: as forms of atmospheric contamination the Marshalsea’s imprisoned air, the tainted ambience of the Clennam house are purified or dispersed. In Little Dorrit air becomes a medium of interchange between the body and its environment, between individuals and their society, and between the literal and the figurative.
“It Proves that Aestheticism Ought to Be Discarded”
Authors: Fischler Alan 
Published: January 2012

Abstract
Since the 1881 premiere of Patience, the sixth Gilbert and Sullivan opera, there has been abundant speculation about the real-life models on whom Gilbert based his rival poets, the “Fleshy” Reginald Bunthorne and the “Idyllic” Archibald Grosvenor. But all conjectures have failed to take account of the fact that, in Bunthorne, Gilbert conflates the beliefs and practices of Pre-Raphaelitism with those of Aestheticism—two artistic movements that were diametric opposites. Gilbert himself certainly knew the difference between them, but the reasons for his conflation may lie in his and his public’s perception that both movements were rooted in rebelliousness against prevailing bourgeois norms. Inasmuch as Bunthorne represents both, Dante Gabriel Rossetti would be his most likely antecedent, but Gilbert’s poet is probably an amalgamation of many of the major figures associated with each of these movements. Grosvenor, meanwhile, becomes the conqueror of Bunthorne by throwing off aestheticism and adopting bourgeois norms himself—and therefore he ought ultimately to be identified with another writer whose poetic practices and championship of middle-class values much resemble Grosvenor’s. That writer is W. S. Gilbert himself, who made a very lucrative career out of flattering the prejudices of respectable Victorian society.
The natural history of macroprolactinaemia
Authors: Hattori Naoki , Adachi Takashi , Ishihara Takashi , Shimatsu Akira 
Published: January 2012

ObjectiveMacroprolactinaemia is a condition in which serum prolactin (PRL) consists mainly of large molecular weight PRL (macroPRL). The aim of this study was to examine the natural history of macroprolactinaemia.Design and participantsSix hundred and fifty-four hospital workers participated in this study, including 27 subjects with macroprolactinaemia and 627 controls. MacroPRL and serum PRL concentrations were evaluated over a 4-year period. The ratio of macroPRL was examined by the polyethylene glycol (PEG) method and gel filtration chromatography. IgG-bound PRL and anti-PRL autoantibodies were examined by protein G and 125I-PRL binding studies respectively.ResultsOver the 4 years of the study, all 27 macroprolactinaemic subjects had persistent macroprolactinaemia without the development of raised free PRL, while none of the 627 controls developed macroprolactinaemia. The ratios of PEG–precipitable PRL and IgG-bound PRL did not significantly change, but 125I-PRL binding ratios significantly increased. As a whole, total and free serum PRL concentrations did not significantly change in subjects with macroprolactinaemia over the 4-year period. However, hyperprolactinaemia developed in five of the 18 macroprolactinaemic subjects who were initially normoprolactinaemic along with an increase in anti-PRL autoantibody titres. One of the remaining nine macroprolactinaemic subjects who were initially hyperprolactinaemic showed a decrease in serum PRL concentrations, which occurred concomitantly with a decrease in the anti-PRL autoantibody titre.ConclusionsMacroprolactinaemia may develop before middle age and is likely a chronic condition leading to hyperprolactinaemia.
A history of cranial radiotherapy is associated with a higher visceral to subcutaneous fat ratio in men with pituitary insufficiency
Authors: Borgers Anke J , Alkemade Anneke , Venema Henk W , Fliers Eric , Bisschop Peter H 
Published: January 2012

ObjectiveEndocrine deficiencies, like GH and estrogen deficiencies, are likely candidates to explain increased visceral to subcutaneous fat ratio in patients with pituitary insufficiency. However, recent reports pointed to cranial radiotherapy (CRT) as an additional determinant of an unfavorable fat distribution. Therefore, we determined the effect of CRT on abdominal fat distribution in men with treated pituitary insufficiency.DesignCross-sectional study.MethodsThirty-five consecutive male subjects (16 men with and 19 men without CRT aged 62±12 and 56±14 years respectively,P=0.175) visiting our Endocrine Outpatient Clinic for pituitary insufficiency were invited to participate in this study. A standardized single-slice abdominal CT scan at the level of fourth lumbar vertebra was performed to determine visceral fat area, subcutaneous fat area, and visceral to subcutaneous fat ratio. In addition, we assessed body mass index, total fat percentage with bioelectrical impedance analysis, resting energy expenditure with indirect calorimetry, calorie intake using a diary, and serum hormone concentrations.ResultsSubjects with CRT had a smaller subcutaneous fat area (225.1 (71.1–480.7) vs 269.0 (133.2–59.9) cm2,P=0.022) and a higher visceral to subcutaneous fat ratio (0.79 (0.39–1.55) vs 0.63 (0.23–0.88),P=0.001) than subjects without CRT. Both the groups were comparable for body mass index, waist–hip ratio, resting energy expenditure, and calorie intake. Importantly, serum hormone concentrations were similar.ConclusionIn men treated for pituitary insufficiency, previous CRT is associated with a higher visceral to subcutaneous fat ratio.