bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and Experiential Antecedents of Alcoholism: A Prospective Study
Authors: Goodwin Donald W. 
Published: February 2008

SUMMARYThe present work builds on an extensively studied obstetrical cohort that includes a group of individuals, now in their midteens, who had a parent treated for alcoholism. To generate a comparable sample today would not only require a very large effort (many years and considerable expense), but might not be possible in most countries because of lack of records or restricted access to them, as well as difficulty in, locating people after long periods. Such a study is still possible in Denmark, which has a long tradition of cooperation between public officials and scientific investigators and invaluable centralized population and psychiatric registers.Since such an opportunity may not present itself again, and since it is difficult to anticipate which avenues of investigation will be more profitable, the study is designed as a collaborative effort by investigators from a number of disciplines: psychiatric, psychological, neurologic, sociologic, biochemical, and electrophysiologic. From the enormous amount of data collected, genetic and experiential antecedents of alcoholism and associated psychopathology can be identified.
Clearance of dengue virus in the plasma‐derived therapeutic proteins
Authors: Xie Yi‐Wu , Chan Paul K.S. , Szeto Chi Kit , Kwok Sui Yi , Chu Ida M.T. , Chu Shirley S.L. , Cheung Jo L.K. , Wong Sai Wah , Ali Mahommed B. , Wong Bing‐Lou 
Published: February 2008

BACKGROUND: Viral safety is of paramount importance for human plasma–derived therapeutic proteins. Recent reports of blood‐associated transmission and continuous regional outbreaks of dengue fever have prompted a validation of clearance of dengue virus in the manufacture processes of the plasma‐derived products.STUDY DESIGN AND METHODS: A high titer of cultured dengue virus serotype 2 was spiked into process samples before individual steps of albumin and immunoglobulin manufacture processes, including cold ethanol precipitation, cation‐exchange chromatography, pasteurization, solvent/detergent treatment, and virus filtration. Clearance of dengue virus was quantified with TCID50 assays in the culture of Vero E6 cells and, when appropriate, real‐time polymerase chain reaction (RT‐PCR) assays.RESULTS: The individual process steps were all effective in the inactivation and/or removal of dengue virus, and the data obtained clearly demonstrate that the risk of dengue virus transmission was reduced cumulatively by at least 10.12 and at least 14.24 log in the albumin and immunoglobulin manufacture processes, respectively.CONCLUSION: The dedicated viral inactivation and/or removal approaches currently implemented in the manufacture of plasma‐derived products provide a good safety margin with regard to the transmission of dengue virus.
Interspecific competition between the ichneumonid Campoletis chlorideae and the braconid Microplitis mediator in their host Helicoverpa armigera
Authors: Tian Shen‐Peng , Zhang Ji‐Hong , Yan Yun‐Hua , Wang Chen‐Zhu 
Published: February 2008

AbstractWe investigated interspecific competition between Campoletis chlorideae Uchida (Hymenoptera: Ichneumonidae) and Microplitis mediator (Haliday) (Hymenoptera: Braconidae) in their host, the cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) under laboratory conditions. Cotton bollworm larvae were allowed to be parasitized by both wasp species simultaneously or sequentially at different time intervals. When host larvae were parasitized simultaneously by both parasitoids, the majority of the cocoons produced were of M. mediator. When host larvae were parasitized initially by M. mediator followed by C. chlorideae at 12 or 24 h, parasitoids emerging from the multiparasitized hosts were mainly M. mediator. In contrast, when host larvae were parasitized initially by C. chlorideae, followed by M. mediator 12 or 24 h later, parasitoids emerging from the multiparasitized hosts were mainly C. chlorideae. Dissections of host larvae at various time intervals after parasitization by the two parasitoids showed that first instars of M. mediator could physically attack the larvae of C. chlorideae, but not the eggs of C. chlorideae. When a host was parasitized by both wasp species sequentially, more host larvae died and the number of wasp offspring was significantly reduced compared to a host parasitized by only one wasp. Conversely, in simultaneous multiparasitism, the host mortality and wasp offspring production were not significantly different from those parasitized by single wasp species.
Gene expression profiling demonstrates a novel role for foetal fibrocytes and the umbilical vessels in human fetoplacental development
Authors: Kim Jung‐Sun , Romero Roberto , Tarca Adi Laurentiu , LaJeunesse Christopher , Han Yu Mi , Kim Mi Jeong , Suh Yeon Lim , Draghici Sorin , Mittal Pooja , Gotsch Francesca , Kusanovic Juan Pedro , Hassan Sonia , Kim Chong Jai 
Published: February 2008

AbstractThere is a difference in the susceptibility to inflammation between the umbilical vein (UV) and the umbilical arteries (UAs). This led us to hypothesize that there is an intrinsic difference in the pro‐inflammatory response between UA and UV. Real‐time quantitative RT‐PCR and microarray analysis revealed higher expression of interleukin (IL)‐1β and IL‐8 mRNA in the UV and differential expression of 567 genes between the UA and UV associated with distinct biological processes, including the immune response. Differential expression of human leukocyte antigen (HLA)‐DRA mRNA between the UA and UV was due to unexpected HLA‐DR+ cells migrating via the umbilical vessels into Wharton's jelly, more frequently in the UV. A significant proportion of these cells co‐expressed CD45 and type I pro‐collagen, and acquired CD163 or α‐smooth muscle actin immunoreactivity in Wharton's jelly. Migrating cells were also found in the chorionic and stem villous vessels. Furthermore, the extent of migration increased with progression of gestation, but diminished in intrauterine growth restriction (IUGR). The observations herein strongly suggest that circulating foetal fibrocytes, routing via umbilical and placental vessels, are a reservoir for key cellular subsets in the placenta. This study reports fibrocytes in the human umbilical cord and placenta for the first time, and a novel role for both circulating foetal cells and the umbilical vessels in placental development, which is deranged in IUGR.
Pro‐atherogenic lung and oral pathogens induce an inflammatory response in human and mouse mast cells
Authors: Oksaharju Anna , Lappalainen Jani , Tuomainen Anita M. , Pussinen Pirkko J. , Puolakkainen Mirja , Kovanen Petri T. , Lindstedt Ken A. 
Published: February 2008

AbstractA broad variety of microbes are present in atherosclerotic plaques and chronic bacterial infection increases the risk of atherosclerosis by mechanisms that have remained vague. One possible mechanism is that bacteria or bacterial products activate plaque mast cells that are known to participate in the pathogenesis of atherosclerosis. Here, we show by real‐time PCR analysis and ELISA that Chlamydia pneumoniae (Cpn) and a periodontal pathogen, Aggregatibacter actinomycetemcomitans (Aa), both induce a time and concentration‐dependent expression and secretion of interleukin 8 (IL‐8), tumour necrosis factor‐α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1) by cultured human peripheral blood‐derived mast cells, but not anti‐inflammatory molecules, such as IL‐10 or transforming growth factor β1 (TGF‐β1). The IL‐8 and MCP‐1 responses were immediate, whereas the onset of TNF‐α secretion was delayed. The Cpn‐mediated pro‐inflammatory effect was attenuated when the bacteria were inactivated by UV‐treatment. Human monocyte‐derived macrophages that were pre‐infected with Cpn also induced a significant pro‐inflammatory response in human mast cells, both in cocultures and when preconditioned media from Cpn‐infected macrophages were used. Intranasal and intravenous administration of live Cpn and Aa, respectively induced an accumulation of activated mast cells in the aortic sinus of apolipoprotein E‐deficient mice, however, with varying responses in the systemic levels of lipopolysaccharide (LPS) and TNF‐α. Pro‐atherogenic Cpn and Aa induce a pro‐inflammatory response in cultured human connective tissue‐type mast cells and activation of mouse aortic mast cells in vivo.
The glycosyltransferase activities of lysyl hydroxylase 3 (LH3) in the extracellular space are important for cell growth and viability
Authors: Wang Chunguang , Kovanen Vuokko , Raudasoja Päivi , Eskelinen Sinikka , Pospiech Helmut , Myllylä Raili 
Published: February 2008

AbstractLysyl hydroxylase (LH) isoform 3 is a post‐translational enzyme possessing LH, collagen galactosyltransferase (GT) and glucosyltransferase (GGT) activities. We have demonstrated that LH3 is found not only intracellularly, but also on the cell surface and in the extracellular space, suggesting additional functions for LH3. Here we show that the targeted disruption of LH3 by siRNA causes a marked reduction of both glycosyltransferase activities, and the overexpression of LH3 in HT‐1080 cells increases hydroxylation of lysyl residues and the subsequent galactosylation and glucosylation of hydroxylysyl residues. These data confirm the multi‐functionality of LH3 in cells. Furthermore, treatment of cells in culture medium with a LH3 N‐terminal fragment affects the cell behaviour, rapidly leading to arrest of growth and further to lethality if the fragment is glycosyltransferase‐deficient, and leading to stimulation of proliferation if the fragment contains LH3 glycosyltransferase activities. The effect is reversible, the cells recovering after removal of the glycosyltransferase‐deficient fragment. The findings were confirmed by overexpressing the full‐length LH3 in native or mutated forms in the cells. The data indicate that the increase in proliferation depends on the glycosyltransferase activity of LH3. The overexpression of a glycosyltransferase‐deficient mutant or targeted disruption of LH3 by siRNA in cells results in abnormal cell morphology followed by cell death. Our data clearly indicate that the deficiency of LH3 glycosyltransferase activities, especially in the extracellular space, causes growth arrest revealing the importance of the glycosyltransferase activities of LH3 for cell growth and viability, and identifying LH3 as a potential target for medical applications, such as cancer therapy.
Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling
Authors: Pilarsky Christian , Ammerpohl Ole , Sipos Bence , Dahl Edgar , Hartmann Arndt , Wellmann Axel , Braunschweig Till , Löhr Matthias , Jesnowski Ralf , Friess Helmut , Wente Moritz Nicolas , Kristiansen Glen , Jahnke Beatrix , Denz Axel , Rückert Felix , Schackert Hans K. , Klöppel Günter , Kalthoff Holger , Saeger Hans Detlev , Grützmann Robert 
Published: February 2008

AbstractPancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic stroma. Interactions between cancer and stromal cells play a critical role in tumour invasion, metastasis and chemoresistance. Therefore, we hypothesized that gene expression profile of the stromal components of pancreatic carcinoma is different from chronic pancreatitis and reflects the interaction with the tumour. We investigated the gene expression of eleven stromal tissues from PDAC, nine from chronic pancreatitis and cell lines of stromal origin using the Affymetrix U133 GeneChip set. The tissue samples were microdissected, the RNA was extracted, amplified and labelled using a repetitive in vitro transcription protocol. Differentially expressed genes were identified and validated using quantitative RT‐PCR and immuno‐histochemistry. We found 255 genes to be overexpressed and 61 genes to be underexpressed within the stroma of pancreatic carcinoma compared to the stroma of chronic pancreatitis. Analysis of the involved signal transduction pathways revealed a number of genes associated with the Wnt pathway of which the differential expression of SFRP1 and WNT5a was confirmed using immunohistochemistry. Moreover, we could demonstrate that WNT5a expression was induced in fibroblasts during cocultivation with a pancreatic carcinoma cell line. The identified differences in the expression profile of stroma cells derived from tumour compared to cells of inflammatory origin suggest a specific response of the tissue surrounding malignant cells. The overexpression of WNT5a, a gene involved in the non canonical Wnt signalling and chondrocyte development might contribute to the strong desmoplastic reaction seen in pancreatic cancer.
Localization of the low‐affinity nerve growth factor receptor p75 in human limbal epithelial cells
Authors: Girolamo Nick Di , Sarris Maria , Chui Jeanie , Cheema Haroon , Coroneo Minas T. , Wakefield Denis 
Published: February 2008

AbstractBiological effects of nerve growth factor (NGF) are mediated through receptors known as nerve growth factor receptors (NGFR), which include p75 and TrkA. This study was initiated after identifying NGFR as an up‐regulated gene in the limbus by cDNA microarray analysis and we postulate that its expression may be indicative of a stem/progenitor cell phenotype. Immunohistochemistry was performed on normal human adult (n= 5) and foetal (n= 3) corneal tissue using antibodies directed against p75, TrkA, NGF, p63, ABCG2 and CK3/12. Limbal, conjunctival and pterygium tissue was obtained from patients (n= 10) undergoing pterygium resection and used for immunohistochemical assessment. Paraffin‐embedded archival human skin specimens (n= 4) were also evaluated. In vitro expression of NGFR was determined in limbal, conjunctival and pterygium‐derived epithelial cells. p75 was selectively expressed by basal epithelial cells in pterygia, conjunctiva and limbus, but was absent in the central cornea. These results were confirmed with two additional p75 specific antibodies. In contrast, TrkA was found in full‐thickness pterygium, conjunctival, limbal and corneal epithelium in both adult and foetal eyes. p75 expression was identified in a small percentage, while TrkA was found on the entire population of cultured conjunctival, limbal and pterygium‐derived epithelial cells. This receptor was also observed in selective regions of the human epidermis and hair follicle bulge. Our results illustrate the selective expression of p75 in basal pterygium, conjunctival and limbal epithelium, while staining was absent in adult and foetal central cornea. p75 may represent an additional ocular surface epithelial stem/progenitor cell signature gene.
Proteasome inhibitor‐induced apoptosis is mediated by positive feedback amplification of PKCδ proteolytic activation and mitochondrial translocation
Authors: Sun Faneng , Kanthasamy Arthi , Song Chunjuan , Yang Yongjie , Anantharam Vellareddy , Kanthasamy Anumantha G. 
Published: February 2008

AbstractEmerging evidence implicates impaired protein degradation by the ubiquitin proteasome system (UPS) in Parkinson's disease; however cellular mechanisms underlying dopaminergic degeneration during proteasomal dysfunction are yet to be characterized. In the present study, we identified that the novel PKC isoform PKCδ plays a central role in mediating apoptotic cell death following UPS dysfunction in dopaminergic neuronal cells. Inhibition of proteasome function by MG‐132 in dopaminergic neuronal cell model (N27 cells) rapidly depolarized mitochondria independent of ROS generation to activate the apoptotic cascade involving cytochrome c release, and caspase‐9 and caspase‐3 activation. PKCδ was a key downstream effector of caspase‐3 because the kinase was proteolytically cleaved by caspase‐3 following exposure to proteasome inhibitors MG‐132 or lactacystin, resulting in a persistent increase in the kinase activity. Notably MG‐132 treatment resulted in translocation of proteolytically cleaved PKCδ fragments to mitochondria in a time‐dependent fashion, and the PKCδ inhibition effectively blocked the activation of caspase‐9 and caspase‐3, indicating that the accumulation of the PKCδ catalytic fragment in the mitochondrial fraction possibly amplifies mitochondria‐mediated apoptosis. Overexpression of the kinase active catalytic fragment of PKCδ (PKCδ‐CF) but not the regulatory fragment (RF), or mitochondria‐targeted expression of PKCδ‐CF triggers caspase‐3 activation and apoptosis. Furthermore, inhibition of PKCδ proteolytic cleavage by a caspase‐3 cleavage‐resistant mutant (PKCδ‐CRM) or suppression of PKCδ expression by siRNA significantly attenuated MG‐132‐induced caspase‐9 and ‐3 activation and DNA fragmentation. Collectively, these results demonstrate that proteolytically activated PKCδ has a significant feedback regulatory role in amplification of the mitochondria‐mediated apoptotic cascade during proteasome dysfunction in dopaminergic neuronal cells.
Depression and mortality in the visually‐impaired, community‐dwelling, elderly population of Quebec
Authors: Tournier Marie , Moride Yola , Ducruet Thierry , Moshyk Andriy , Rochon Sophie 
Published: February 2008

Abstract.Purpose:  To assess the effect of visual impairment (VI) on the risk of depression or death in the community‐dwelling elderly population.Methods:  A population‐based, retrospective fixed cohort study was conducted in the community‐dwelling elderly (age ≥ 65 years) outpatient population of Quebec. The cohort was assembled through the Quebec medical services database and consisted of the 5063 patients aged ≥ 65 years who received a diagnosis of VI during the years 2000–2004. The reference cohort consisted of 16 932 elderly subjects who were randomly selected among members of the public drug programme. The outcome variables were depression and death. The main independent variable was VI and covariates included age, gender, chronic disease score, fracture and diabetes.Results:  Controlling for covariates, VI was associated with an increased risk of depression although the effect was not modified by severity (hazard ratio [HR] = 1.35, 95% confidence interval [CI] 1.10–1.66 for severe VI; HR = 1.35, 95% CI 1.09–1.69 for moderate VI). Visual impairment was associated with an increased risk of mortality; patients with moderate vision loss had a higher risk of death (HR = 1.70, 95% CI 1.55–1.87) than those with severe vision loss (HR = 1.34, 95% CI 1.21–1.48).Conclusions:  Given the ageing of the population, VI in elderly subjects is becoming a public health concern. These findings enhance the need to detect and treat VI in order to improve the quality of life and to prevent premature mortality in the elderly population.
Intracameral triamcinolone acetonide to control postoperative inflammation following cataract surgery with phacoemulsification
Authors: Karalezli Aylin , Borazan Mehmet , Akova Yonca A. 
Published: February 2008

Abstract.Purpose:  To explore the efficacy, safety and tolerability of 1 mg intracameral triamcinolone acetonide (TA) in controlling ocular inflammation in patients undergoing cataract surgery.Methods:  Sixty eyes of 60 patients undergoing cataract extraction with phacoemulsification at the Department of Ophthalmology, Baskent University School of Medicine were randomized into two groups. After surgery, eyes in group A were injected with 1 mg/0.1 ml TA into the anterior chamber, but eyes in group B were not. Postoperatively; in group B, topical prednisolone acetate 1% eyedrops were administered six times per day for 7 days, then four times per day for 15 days, to control postoperative inflammation. In group A, topical corticosteroids were not used. To evaluate the efficacy of intracameral TA, anterior chamber cells, anterior chamber flare and conjunctival hyperaemia were measured on postoperative days 1, 7 and 30 by slit‐lamp biomicroscopy. The safety of intracameral TA was evaluated by visual acuity measurements, intraocular pressure values and fundus examination. Tolerance variables were assessed by the degree of burning, stinging and blurred vision.Results:  Both treatments were equally effective in controlling postoperative inflammation following phacoemulsification. No statistically significant differences between groups were observed for the efficacy, safety and tolerance variables, and no serious adverse events were observed.Conclusions:  Intracameral TA of 1 mg can effectively be used to control postoperative inflammation after uncomplicated cataract surgery with phacoemulsification. This makes it possible to decrease the dosage and duration of topical prednisolone acetate.
Erectile Dysfunction in Men Receiving Methadone and Buprenorphine Maintenance Treatment
Authors: Hallinan Richard , Byrne Andrew , Agho Kingsley , McMahon Chris , Tynan Philip , Attia John 
Published: February 2008

ABSTRACT

Introduction
Use of opiates/opioids is associated with hypoactive sexual desire, erectile and orgasmic dysfunction.

Aim
To determine prevalence and investigate etiology of sexual dysfunction in men on methadone or buprenorphine maintenance treatment (MMT, BMT).

Main Outcome Measures
International Index of Erectile Function (IIEF), hormone assays, Beck Depression Inventory.

Methods
A total of 103 men (mean age 37.6 ± 7.9) on MMT (N=84) or BMT (N=19) were evaluated using the IIEF, hormone assays, Beck Depression Inventory, body mass index (BMI), demographic, and other substance use measures.

Results
Mean total IIEF scores for partnered men were lower for MMT (50.4 ± 18.2; N=53) than reference groups (61.4 ± 16.8; N=415; P &lt;0.0001) or BMT (61.4 ± 7.0; N=14; P =0.048). Among partnered men on MMT, 53% had erectile dysfunction (ED) compared with 24% of reference groups; 26% had moderate to severe ED, 12.1% in under 40s and 40.0% among those 40+ years. On multiple regression, depression, older age, and lower total testosterone were associated with lower IIEF and EF domain; on multivariate analysis, there were no significant associations between IIEF or EF and free testosterone, opioid dose, cannabis or other substance use, viral hepatitis, or BMI. Total testosterone accounted for 16% of IIEF and 15% of EF variance. Men without sexual partners had lower Desire and Erection Confidence scores and less recent sexual activity, suggesting potentially higher prevalence of sexual dysfunction in this group.

Conclusion
Men on MMT, but not BMT, have high prevalence of ED, related to hypogonadism and depression. Practitioners should screen for sexual dysfunction in men receiving opioid replacement treatment. Future studies of sexual dysfunction in opioid-treated men should examine the potential benefits of dose reduction, androgen replacement, treatment of depression, and choice of opioid.