bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferative Pituitary Lesions in Rats Treated with Salmon or Porcine Calcitonin
Authors: Brown W. Ray , Fetter Arthur D. , Van Ryzin Robert J. , Langloss John M. 
Published: September 2009

Calcitonin, the serum calcium-lowering hormone, has been used in the treatment of hypercalcemia of malignancy and postmenopausal osteoporosis in humans for several years without any adverse effects. Recent studies in rats have indicated that calcitonin may be associated with morphologic effects on the pituitary. A large study was performed on 2 strains of rats, Sprague-Dawley (SD) and Fischer-344 (F-344), with 2 types of calcitonin, salmon-derived (sCT) and porcine-derived (pCT) calcitonin to evaluate possible effects on the pituitary. Sixteen groups of 42 male and 42 female SD or F-344 rats were given 0 (vehicle control), 1.25, 5.0, or 80.0 IU/kg/day of sCT or pCT, once daily, subcutaneously, for 1 yr. An increased incidence of adenomas of the adenohypophysis was observed in male SD rats at all dose levels of sCT, female SD rats given 80 IU/kg/day of sCT, male SD rats at the high dose level of pCT, and male F-344 rats at the high dose level of sCT. Also, an increased incidence of total proliferative lesions, due mostly to an increased incidence of focal hyperplasia of the pars distalis, occurred in female F-344 rats given the high dose of sCT. These pituitary proliferations were histologically similar to those that occur spontaneously, and the incidences observed were comparable to those that could occur in rats on 2-yr or lifetime studies, indicating that the injection of calcitonin had decreased the latency period.
The Long-Term Outcome of Recurrent Defects after Rotator Cuff Repair
Authors: Dodson Christopher C. , Kitay Alison , Verma Nikhil N. , Adler Ronald S. , Nguyen Joseph , Cordasco Frank A. , Altchek David W. 
Published: September 2009

Background Retears of the rotator cuff are not uncommon after arthroscopic and mini-open rotator cuff repairs. In most studies, the clinical results in patients with persistent defects demonstrated significantly less pain and better function and strength compared with their preoperative state at an early follow-up. Hypothesis The clinical and structural outcomes of patients with known rotator cuff defects will remain unchanged after a longer period of follow-up. Study Design Case series; Level of evidence, 4. Methods This study was performed in 15 patients (18 shoulders) from a previous study who had recurrent rotator cuff defects 3.2 years after repair. Each patient completed the American Shoulder and Elbow Surgeons Scoring Survey, the Simple Shoulder Test, the L'Insalata Scoring Survey, and a visual analog scale for pain. Eleven patients (13 shoulders) were clinically reexamined at an average of 7.9 years for range of motion and strength, with targeted ultrasound. Results At the 7.9 year follow-up the average scores were 95 (American Shoulder and Elbow Surgeons), 95 (L'Insalata), 11 (Simple Shoulder Test), and 0 (visual analog for pain), which were not statistically significantly different from the scores at 3.2 years. There was no change in the average range of motion; however, there was a statistically significant reduction in forward flexion strength and external rotation strength, as measured by a dynamometer. The average external rotation strength decreased by a mean of 42% and the mean forward flexion strength decreased by a mean of 45% (P < .001). Furthermore, there was a statistically significant increase in the mean size of the defect, from 273 mm2 to 467 mm2 (P < .001). Finally, the size of the defect increased in all patients, and no defects healed structurally. Conclusion At an average of 7.9 years, patients with recurrent defects after rotator cuff repair still had an improvement in terms of pain, function, and satisfaction. However, the rotator cuff defect significantly increased in size, and there was a progression of strength deficits. These findings suggest that patients with recurrent defects can remain asymptomatic over the long term but will predictably lose strength in the involved extremity. Furthermore, the study demonstrated that defects after rotator cuff repair increase in size but often remain asymptomatic.
Dietary Management of Inborn Errors of Amino Acid Metabolism With Protein-Modified Diets
Authors: Thomas Enolia 
Published: September 2009

This paper presents experiences encountered with protein-modified diets (PMD) in the management of 67 patients, aged 1 day to 14 years, followed in the Pediatric Nutrition Clinic in the past 5 years. All had inborn errors of amino acid metabolism : maple syrup urine disease (MSUD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency, propionic acidemia (PPA), or methylmalonic aciduria (MMA). In early infancy, the diet prescription is frequently adjusted to search for the infant's tolerance level of restricted amino acids. The levels must be established when natural foods other than milk are added to the PMD. The amino acids restricted are leucine, isoleucine, and valine in MSUD; leucine in HMG-CoA lyase deficiency; and isoleucine, methionine, threonine, and valine in PPA and MMA. Efficacy of the PMD depends on accuracy in prediction of the restricted amino acid requirement and the willingness and ability of parents and patients to conform to its demands. (J Child Neurol 1992;7(Suppl):S92-S111.)
An evaluation of performance-arts based HIV-prevention events in London with 13—16 year olds
Authors: Campbell Tomás , Bath Michael , Bradbear Rachel , Cottle Justine , Parrett Neil 
Published: September 2009

Aim: The London borough of Newham is ethnically diverse and is one of the poorest regions in the UK. Rates of teenage pregnancy, sexually transmitted infections (STIs) and HIV are high compared to the rest of the country. One strand of the local school-based HIV-prevention programme for young people utilizes performance arts as a tool for HIV education and prevention. This study evaluated HIV knowledge, confidence and intention to use a condom in two groups of 13—16 year olds who had participated in performance-based events. Method: Group 1 ( n = 14) participated in a six-week programme of performance arts-based HIV education and prevention workshops, which culminated in a theatre-based performance. Group 2 ( n = 65) were audience members who attended the performance. Participants completed a short questionnaire containing both qualitative and quantitative items. Results: Qualitative data suggested that the participants had learned about condoms and their efficacy in preventing acquisition of HIV and sexually transmitted diseases. Quantitative results indicated that after participation in the events, respondents had more information about HIV and condom use; were more confident that they could insist on condom use with partners; and planned to use condoms in the future. There was a statistically significant difference between Groups 1 and 2 but because of the small numbers in Group 1 this result should be interpreted cautiously. Conclusions: Performance-based HIV-prevention activities may be a useful way to deliver HIV-prevention messages to young people. This evaluation will form the basis of a more systematic and robust evaluation of future events.
Undifferentiated hematopoietic cells are characterized by a genome-wide undermethylation dip around the transcription start site and a hierarchical epigenetic plasticity
Authors: Chung Yun Shin , Kim Hye Joung , Kim Tae-Min , Hong Sung-Hyun , Kwon Kyung-Rim , An Sungwhan , Park Jung-Hoon , Lee Suman , Oh Il-Hoan 
Published: September 2009

Abstract
Evidence for the epigenetic regulation of hematopoietic stem cells (HSCs) is growing, but the genome-wide epigenetic signature of HSCs and its functional significance remain unclear. In this study, from a genome-wide comparison of CpG methylation in human CD34+ and CD34− cells, we identified a characteristic undermethylation dip around the transcription start site of promoters and an overmethylation of flanking regions in undifferentiated CD34+ cells. This “bivalent-like” CpG methylation pattern around the transcription start site was more prominent in genes not associated with CpG islands (CGI−) than CGI+ genes. Undifferentiated hematopoietic cells also exhibited dynamic chromatin associated with active transcription and a higher turnover of histone acetylation than terminally differentiated cells. Interestingly, inhibition of chromatin condensation by chemical treatment (5-azacytidine, trichostatin A) enhanced the self-renewal of “stimulated” HSCs in reconstituting bone marrows but not “steady-state” HSCs in stationary phase bone marrows. In contrast, similar treatments on more mature cells caused partial phenotypic dedifferentiation and apoptosis at levels correlated with their hematopoietic differentiation. Taken together, our study reveals that the undifferentiated state of hematopoietic cells is characterized by a unique epigenetic signature, which includes dynamic chromatin structures and an epigenetic plasticity that correlates to level of undifferentiation.
Epitopia: a web-server for predicting B-cell epitopes
Authors: Rubinstein Nimrod D , Mayrose Itay , Martz Eric , Pupko Tal 
Published: September 2009

AbstractBackgroundDetecting candidate B-cell epitopes in a protein is a basic and fundamental step in many immunological applications. Due to the impracticality of experimental approaches to systematically scan the entire protein, a computational tool that predicts the most probable epitope regions is desirable.ResultsThe Epitopia server is a web-based tool that aims to predict immunogenic regions in either a protein three-dimensional structure or a linear sequence. Epitopia implements a machine-learning algorithm that was trained to discern antigenic features within a given protein. The Epitopia algorithm has been compared to other available epitope prediction tools and was found to have higher predictive power. A special emphasis was put on the development of a user-friendly graphical interface for displaying the results.ConclusionEpitopia is a user-friendly web-server that predicts immunogenic regions for both a protein structure and a protein sequence. Its accuracy and functionality make it a highly useful tool. Epitopia is available athttp://epitopia.tau.ac.iland includes extensive explanations and example predictions.
Transcriptome analysis of the responses of Staphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance
Authors: Pietiäinen Milla , François Patrice , Hyyryläinen Hanne-Leena , Tangomo Manuela , Sass Vera , Sahl Hans-Georg , Schrenzel Jacques , Kontinen Vesa P 
Published: September 2009

Abstract

Background
Understanding how pathogens respond to antimicrobial peptides, and how this compares to currently available antibiotics, is crucial for optimizing antimicrobial therapy. Staphylococcus aureus has several known resistance mechanisms against human cationic antimicrobial peptides (CAMPs). Gene expression changes in S. aureus strain Newman exposed to linear CAMPs were analyzed by DNA microarray. Three antimicrobial peptides were used in the analysis, two are derived from frog, temporin L and dermaseptin K4-S4(1-16), and the ovispirin-1 is obtained from sheep.

Results
The peptides induced the VraSR cell-wall regulon and several other genes that are also up-regulated in cells treated with vancomycin and other cell wall-active antibiotics. In addition to this similarity, three genes/operons were particularly strongly induced by the peptides: vraDE, SA0205 and SAS016, encoding an ABC transporter, a putative membrane-bound lysostaphin-like peptidase and a small functionally unknown protein, respectively. Ovispirin-1 and dermaseptin K4-S4(1-16), which disrupt lipid bilayers by the carpet mechanism, appeared to be strong inducers of the vraDE operon. We show that high level induction by ovispirin-1 is dependent on the amide modification of the peptide C-terminus. This suggests that the amide group has a crucial role in the activation of the Aps (GraRS) sensory system, the regulator of vraDE. In contrast, temporin L, which disrupts lipid bilayers by forming pores, revealed a weaker inducer of vraDE despite the C-terminal amide modification. Sensitivity testing with CAMPs and other antimicrobials suggested that VraDE is a transporter dedicated to resist bacitracin. We also showed that SA0205 belongs to the VraSR regulon. Furthermore, VraSR was shown to be important for resistance against a wide range of cell wall-active antibiotics and other antimicrobial agents including the amide-modified ovispirin-1, bacitracin, teicoplanin, cefotaxime and 10 other β-lactam antibiotics, chlorpromazine, thioridazine and EGTA.

Conclusion
Defense against different CAMPs involves not only general signaling pathways but also CAMP-specific ones. These results suggest that CAMPs or a mixture of CAMPs could constitute a potential additive to standard antibiotic treatment.
New insights into molecular pathways associated with flatfish ovarian development and atresia revealed by transcriptional analysis
Authors: Tingaud-Sequeira Angèle , Chauvigné François , Lozano Juanjo , Agulleiro María J , Asensio Esther , Cerdà Joan 
Published: September 2009

Abstract

Background
The Senegalese sole (Solea senegalensis) is a marine flatfish of increasing commercial interest. However, the reproduction of this species in captivity is not yet controlled mainly because of the poor knowledge on its reproductive physiology, as it occurs for other non-salmonid marine teleosts that exhibit group-synchronous ovarian follicle development. In order to investigate intra-ovarian molecular mechanisms in Senegalese sole, the aim of the present study was to identify differentially expressed genes in the ovary during oocyte growth (vitellogenesis), maturation and ovarian follicle atresia using a recently developed oligonucleotide microarray.

Results
Microarray analysis led to the identification of 118 differentially expressed transcripts, of which 20 and 8 were monitored by real-time PCR and in situ hybridization, respectively. During vitellogenesis, many up-regulated ovarian transcripts had putative mitochondrial function/location suggesting high energy production (NADH dehydrogenase subunits, cytochromes) and increased antioxidant protection (selenoprotein W2a), whereas other regulated transcripts were related to cytoskeleton and zona radiata organization (zona glycoprotein 3, alpha and beta actin, keratin 8), intracellular signalling pathways (heat shock protein 90, Ras homolog member G), cell-to-cell and cell-to-matrix interactions (beta 1 integrin, thrombospondin 4b), and the maternal RNA pool (transducer of ERBB2 1a, neurexin 1a). Transcripts up-regulated in the ovary during oocyte maturation included ion transporters (Na+-K+-ATPase subunits), probably required for oocyte hydration, as well as a proteinase inhibitor (alpha-2-macroglobulin) and a vesicle calcium sensor protein (extended synaptotagmin-2-A). During follicular atresia, few transcripts were found to be up-regulated, but remarkably most of them were localized in follicular cells of atretic follicles, and they had inferred roles in lipid transport (apolipoprotein C-I), chemotaxis (leukocyte cell-derived chemotaxin 2,), angiogenesis (thrombospondin), and prevention of apoptosis (S100a10 calcium binding protein).

Conclusion
This study has identified a number of differentially expressed genes in the ovary that were not previously found to be regulated during ovarian development in marine fish. Specifically, we found evidence, for the first time in teleosts, of the activation of chemoattractant, angiogenic and antiapoptotic pathways in hypertrophied follicular cells at the onset of ovarian atresia.
Interaction of ZEB and Histone Deacetylase with the PLDLS-binding cleft region of monomeric C-terminal Binding Protein 2
Authors: Zhao Ling-Jun , Kuppuswamy M , Vijayalingam S , Chinnadurai G 
Published: September 2009

AbstractBackgroundProteins of the C-terminal binding protein (CtBP) family, CtBP1 and CtBP2 are closely related transcriptional regulators that are coded by two different gene loci in the vertebrate genomes. They perform redundant and unique functions during animal development. CtBP proteins mediate their transcriptional function through interaction with various DNA-binding repressors that contain PLDLS-like motifs and chromatin modifying enzymes, such as class I histone deacetylases (HDAC) that do not contain such motifs. The N-terminal region of CtBP1/2 forms a hydrophobic cleft and is involved in interaction with both PLDLS-containing factors and non-PLDLS factors. CtBP proteins function as dimers to mediate transcriptional repression and dimerization is modulated by specific binding to NAD/NADH.ResultsIn this study, we have investigated the role of dimerization of CtBP2 in recruitment of PLDLS-motif cofactors and non-PLDLS cofactors. Our results indicate that mutations in CtBP2 that interfere with dimerization abolish CtBP2 interaction with most cellular factors, except the PLDLS-motif factor zinc-finger E-box binding homeobox (ZEB) and the non-PLDLS factor HDAC2. Unlike most PLDLS-containing CtBP-binding proteins, ZEB contains three PLDLS-like motifs and all three contribute to the interaction with the CtBP2 monomer. Despite the ability to interact with ZEB and HDAC, the CtBP2 monomer fails to mediate ZEB-dependent transcriptional repression. The lack of repression activity of the CtBP2 monomer is correlated with the competition between ZEB and HDAC for interaction with the CtBP2 monomer.ConclusionThese results suggest a competition between the canonical PLDLS-motif factors such as E1A and non-PLDLS factor HDAC for interaction with CtBP. They also indicate that the affinity for the CtBP monomer may be determined by the number as well as amino acid sequence compositions of the PLDLS-like motifs. Our results are consistent with a model that the CtBP2 dimer may interact with a PLDLS-containing repressor through one monomer and recruit HDAC and other chromatin modifying enzymes through the second monomer in the CtBP2 dimer.
Atherosclerosis profile and incidence of cardiovascular events: a population-based survey
Authors: Robinson Jennifer G , Fox Kathleen M , Bullano Michael F , Grandy Susan ,   the SHIELD Study Group
Published: September 2009

Abstract

Background
Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD) events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals.

Methods
Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization). Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events.

Results
Of 17,640 respondents, 488 (2.8%) reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2) [all p < 0.05]. Incident CVD was twice as high in respondents with subclinical atherosclerosis (25.8%) as in those without atherosclerosis or clinical CVD (12.2%). In individuals with subclinical atherosclerosis, men (RR = 1.77, p = 0.050) and individuals with circulation problems (RR = 2.36, p = 0.003) were at greatest risk of experiencing CVD events in the next 2 years.

Conclusion
Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.
Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure
Authors: Hsieh Szu-Min , Chang Sui-Yuan , Hung Chien-Ching , Sheng Wang-Huei , Chen Mao-Yuan , Chang Shan-Chwen 
Published: September 2009

Abstract

Background
Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.

Methods
To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.

Results
Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.

Conclusion
Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.
Complete absence of M2-pyruvate kinase expression in benign pancreatic ductal epithelium and pancreaticobiliary and duodenal neoplasia
Authors: Aloysius Mark M , Zaitoun Abed M , Bates Timothy E , Albasri Abdulkader , Ilyas Mohammad , Rowlands Brian J , Lobo Dileep N 
Published: September 2009

Abstract

Background
Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas.

Methods
Immunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12).

Results
Benign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis) showed complete lack of expression (IHS = 0).

Conclusion
Complete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.