bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human activated protein C variants in a rat model of arterial thrombosis
Authors: Malm Karl , Arnljots Björn , Dahlbäck Björn 
Published: October 2008

Abstract

Background
Activated protein C (APC) inhibits coagulation by degrading activated factor V (FVa) and factor VIII (FVIIIa), protein S (PS) functioning as a cofactor to APC.

Methods
By mutagenesis of the vitamin K-dependent Gla domain of APC, we have recently created an APC variant having enhanced anticoagulant activity due to increased affinity for negatively charged phospholipid membranes. In the present study, the potential antithrombotic effects of this APC variant, and of a variant APC that is additionally mutated in the serine protease domain, have been evaluated in a blind randomized study in a rat model of arterial thrombosis. In this model, we have previously found the combination of bovine APC and PS to be highly antithrombotic. Four treatment groups each containing 10 rats were, in a blind random fashion, given intravenous bolus injections of wild-type or mutant variants of APC (0.8 mg/kg) together with human PS (0.6 mg/kg) or human PS (0.6 mg/kg) alone. A control group with 20 animals where given vehicle only.

Results
A trend to increased patency rates was noted in a group receiving one of the APC variants, but it did not reach statistical significance.

Conclusion
In conclusion, administration of human APC variants having enhanced anticoagulant efficacy together with human PS in a rat model of arterial thrombosis did not give an efficient antithrombotic effect. The lack of effect may be due to species-specific differences between the human protein C system and the rat hemostatic system.
Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations
Authors: Shi Hong , Zhong Hua , Peng Yi , Dong Yong-Li , Qi Xue-Bin , Zhang Feng , Liu Lu-Fang , Tan Si-Jie , Ma Runlin Z , Xiao Chun-Jie , Wells R Spencer , Jin Li , Su Bing 
Published: October 2008

Abstract

Background

The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario.

Results

In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations.

Conclusion

We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.
The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study
Authors: Davis Allan P , Murphy Cynthia G , Rosenstein Michael C , Wiegers Thomas C , Mattingly Carolyn J 
Published: October 2008

Abstract

Background
The etiology of many chronic diseases involves interactions between environmental factors and genes that modulate physiological processes. Understanding interactions between environmental chemicals and genes/proteins may provide insights into the mechanisms of chemical actions, disease susceptibility, toxicity, and therapeutic drug interactions. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) provides these insights by curating and integrating data describing relationships between chemicals, genes/proteins, and human diseases. To illustrate the scope and application of CTD, we present an analysis of curated data for the chemical arsenic. Arsenic represents a major global environmental health threat and is associated with many diseases. The mechanisms by which arsenic modulates these diseases are not well understood.

Methods
Curated interactions between arsenic compounds and genes were downloaded using export and batch query tools at CTD. The list of genes was analyzed for molecular interactions, Gene Ontology (GO) terms, KEGG pathway annotations, and inferred disease relationships.

Results
CTD contains curated data from the published literature describing 2,738 molecular interactions between 21 different arsenic compounds and 1,456 genes and proteins. Analysis of these genes and proteins provide insight into the biological functions and molecular networks that are affected by exposure to arsenic, including stress response, apoptosis, cell cycle, and specific protein signaling pathways. Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association.

Conclusion
CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases. While many reports describe the molecular response to arsenic, CTD integrates these data with additional curated data sets that facilitate construction of chemical-gene-disease networks and provide the groundwork for investigating the molecular basis of arsenic-associated diseases or toxicity. The analysis reported here is extensible to any environmental chemical or therapeutic drug.
Computed Tomography Colonography in Acromegaly
Authors: Resmini Eugenia , Tagliafico Alberto , Bacigalupo Lorenzo , Giordano Giorgia , Melani Enrico , Rebora Alberto , Minuto Francesco , Rollandi Gian Andrea , Ferone Diego 
Published: October 2008

Abstract
Introduction and Aim: Acromegalic patients have an increased risk for the development of colorectal cancer. For this reason, since 1996, screening colonoscopy has been recommended in all patients with acromegaly. The aim of our study was to assess the feasibility and to evaluate the results of computed tomography (CT)-colonography in acromegaly.
Patients and Methods: We examined 23 acromegalic patients with no history of colorectal cancer (11 females and 12 males; age range 18–79 yr; disease duration range 1–15 yr) with CT-colonography. Twenty of them underwent traditional colonoscopy after the CT-colonography.
Results: CT-colonography examination results were adequate in 17 of 23 cases (73%). CT-colonography found 12 polyps in eight patients, 95% confirmed by traditional colonoscopy. One polyp was a sigmoid cancer, and the diagnosis was confirmed at surgery. There were no polyps found by traditional colonoscopy that CT-colonography was not able to identify. The lesions were located in right colon (two), transversum (three), left colon (five), and sigmoid colon (two). Patient acceptance of the technique was good in 65%, medium in 20%, and poor in 15%.
Conclusion: For the first time we have demonstrated that CT-colonography has the potential ability to replace traditional colonoscopy in acromegalic patients. CT-colonography could be used as a screening modality for colon cancer in acromegaly.
Effect of Glucagon-Like Peptide-1 on β- and α-Cell Function in Isolated Islet and Whole Pancreas Transplant Recipients
Authors: Rickels Michael R. , Mueller Rebecca , Markmann James F. , Naji Ali 
Published: October 2008

AbstractContext: Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced β-cell secretory capacity indicates a low functional β-cell mass.Objective: We sought to determine whether glucagon-like peptide-1 (GLP-1) enhanced glucose-dependent insulin secretion and glucagon suppression in islet recipients, and whether GLP-1 effects were dependent on functional β-cell mass by simultaneously studying recipients of whole pancreas transplants.Setting: The study was performed in a clinical and translational research center.Participants: Five intraportal islet and six portally drained pancreas transplant recipients participated in the study.Intervention: Subjects underwent glucose-potentiated arginine testing with GLP-1 (1.5 pmol · kg−1 · min−1) or placebo infused on alternate randomized occasions, with 5 g arginine injected under basal and hyperglycemic clamp conditions.Results: Basal glucose was lower with increases in insulin and decreases in glucagon during GLP-1 vs. placebo in both groups. During the hyperglycemic clamp, a significantly greater glucose infusion rate was required with GLP-1 vs. placebo in both groups (P &lt; 0.05), an effect more pronounced in the pancreas vs. islet group (P &lt; 0.01). The increased glucose infusion rate was associated with significant increases in second-phase insulin secretion in both groups (P &lt; 0.05) that also tended to be greater in the pancreas vs. islet group (P = 0.08), whereas glucagon was equivalently suppressed by the hyperglycemic clamp during GLP-1 and placebo infusions in both groups. The GLP-1-induced increase in second-phase insulin correlated with the β-cell secretory capacity (P &lt; 0.001). The proinsulin secretory ratio (PISR) during glucose-potentiated arginine was significantly greater with GLP-1 vs. placebo infusion in both groups (P &lt; 0.05).Conclusions: GLP-1 induced enhancement of glucose-dependent insulin secretion, but not glucagon suppression, in islet and pancreas transplant recipients, an effect dependent on the functional β-cell mass that may be associated with depletion of mature β-cell secretory granules.
Double Ordered Layers within Microphase-separated Lamellar Structure of Double Liquid Crystalline Side-chain Type Block Copolymer
Authors: Maeda Rina , Hayakawa Teruaki , Tokita Masatoshi , Kakimoto Masa-aki , Urushibata Hiroaki 
Published: October 2008

Abstract
A new hierarchical nanostructure was created by self-assembly of a double liquid crystalline side-chain type block copolymer. The block copolymer was successfully prepared via a nitroxide-mediated living free radical polymerization and formed double ordered layers within a phase-separated lamellar structure of the cast film.
Cancer and Evolution
Authors: Bodmer Walter. F. 
Published: October 2008

Cancer mostly is a disease of old age. Evolutionary pressures have pushed the somatic "error rate", especially the mutation rate, down to a level where for most organisms cancer is no longer of any selective significance. This appears to be a by-product of the selection that gives rise to senescence, following the arguments of Medawar, Holliday, and Kirkwood.
The development of a cancer is discussed from an evolutionary viewpoint, emphasising the role of selection versus mutation and the fact that each cancer is an independent evolutionary process. The nature of the selective advantages associated with the somatic genetic changes during a cancer's evolution can sometimes be inferred by reference to the known types of mutations found in cancers. Examples are given using colorectal cancer as a model. The major selective forces involve the balance between selection for increased growth rate and against apoptosis. There are strong arguments against the much discussed role of genomic instability as a requirement for cancer. Current evidence suggests that instability is a byproduct of selection against apoptosis. There is an important contrast between germ line and somatic changes, the former being the basis for inherited susceptibilities to cancer, while the latter are the fundamental changes that turn a normal cell into a cancer cell.
Tissue stem cells, as in the colonic crypt, provide the source, through division and differentiation, of the differentiated cells in a crypt. Mathematical models can provide an explanation for how the balance in a crypt between stem cells, intermediate proliferating cells, and non-proliferating differentiated cells is maintained. Perturbations of the renewal parameters in the model can explain the evolution of benign tumors, namely polyps or adenomas, and the eventually exponential growth of cells resulting in a fully developed carcinoma. It seems probable that the origin of most carcinomas is in the intermediate proliferating cells, and that these are therefore the likely source of cancer stem cells.
On Ribosome Conservation and Evolution
Authors: Agmon Ilana , Bashan Anat , Yonath Ada 
Published: October 2008

The ribosome is a ribozyme whose active site, the peptidyl transferase center (PTC), is situated within a highly conserved universal symmetrical region that connects all ribosomal functional centers involved in amino acid polymerization. The linkage between this elaborate architecture and A-site tRNA position revealed that the A-> P-site passage of the tRNA terminus in the peptidyl transferase center is performed by a rotatory motion, synchronized with the overall tRNA/mRNA sideways movement. Guided by the PTC, the rotatory motion leads to stereochemistry suitable for peptide bond formation, as well as for substrate-mediated catalysis, consistent with quantum mechanical calculations elucidating the transition state mechanism for peptide bond formation and indicating that the peptide bond is being formed during the rotatory motion.
Analysis of substrate binding modes to inactive and active ribosomes illuminated the significant PTC mobility and supported the hypothesis that the ancient ribosome produced single peptide bonds and non-coded chains, utilizing free amino acids. Genetic control of the reaction evolved after poly-peptides capable of enzymatic function were created, and an ancient stable RNA fold was converted into tRNA molecules. As the symmetry relates only the backbone fold and nucleotide orientations, but not nucleotide sequence, it emphasizes the superiority of functional requirement over sequence conservation, and indicates that the PTC has evolved by gene fusion, presumably by taking advantage of similar RNA fold structures.
Risk of Adverse Gastrointestinal Events from Inhaled Corticosteroids
Authors: Hansen Richard A. , Tu Wanzhu , Wang Jane , Ambuehl Roberta , McDonald Clement J. , Murray Michael D. 
Published: October 2008

Study Objective. To determine whether patients prescribed inhaled corticosteroids are at risk for adverse gastrointestinal effects.Design. Retrospective cohort studySetting. Urban health center with an academic affiliation.Patients. A total of 19,443 adults (mean age 31.8 yrs) with airways disease, defined as a diagnosis of asthma or chronic obstructive pulmonary disease, and who were prescribed both an inhaled corticosteroid and albuterol (7156 patients) or inhaled albuterol alone (12,287 patients) between 1977 and February 2002.Measurements and Main Results. The frequency of adverse gastrointestinal events in the patients who used inhaled corticosteroids and albuterol was compared with that in the patients who used albuterol alone. Adverse gastrointestinal outcomes included events such as gastritis, ulcers, and bleeding. Cox proportional hazards models were used to determine the risk of adverse events, controlling for possible confounders such as alcohol use or nonsteroidal antiinflammatory drug use. Adverse gastrointestinal events were observed in 461 (6.4%) patients using inhaled corticosteroids and albuterol and in 302 (2.5%) patients using only albuterol. After controlling for potential confounders, patients who used inhaled corticosteroids and albuterol had an increased risk for adverse gastrointestinal events compared with patients who used only inhaled albuterol (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02‐1.56). A prescription for a spacer device reduced this risk among patients using an inhaled corticosteroid (HR 0.26, 95% CI 0.20‐0.34).Conclusion. Patients using inhaled corticosteroids appear to have a slight risk for adverse gastrointestinal events that is mitigated in patients who used a spacer device.
Use of Recombinant Human Erythropoietin and Risk of Severe Retinopathy in Extremely Low‐Birth‐Weight Infants
Authors: Schneider Jacqueline K. , Gardner Debra K. , Cordero Leandro 
Published: October 2008

Study Objectives. To evaluate the frequency and severity of retinopathy of prematurity in extremely low‐birth‐weight (ELBW) infants who received recombinant human erythropoietin (rHuEPO), and to compare the frequency of blood cell transfusions these infants required with a matched control group who did not receive rHuEPO.Design. Retrospective cohort analysis.Setting. Level III neonatal intensive care unit in a large academic medical center.Patients. One hundred thirty‐eight ELBW infants who received rHuEPO and 138 ELBW infants who did not (control group) but who were matched by birth weight, gestational age, sex, and year of birth and who survived to the first ophthalmologic examination.Measurements and Main Results. The rHuEPO was started before the 8th day of life in 115 (83%) of the 138 infants. Stages III‐V retinopathy of prematurity occurred with similar frequency in both groups of infants (rHuEPO group 19% [26 infants] vs control group 20% [27 infants], p>0.05). Infants in the rHuEPO group received fewer transfusions on average during their hospitalization compared with those in the control group (4.2 vs 6.1 transfusions, p<0.01).Conclusion. Use of rHuEPO for prevention or treatment of anemia of prematurity in ELBW infants does not increase the frequency of severe retinopathy of prematurity and reduces the number of transfusions.
Antibiotic Allergies in the Medical Record: Effect on Drug Selection and Assessment of Validity
Authors: Lutomski Dave M. , LaFollette Jennifer A. , Biaglow Michael A. , Haglund Lisa A. 
Published: October 2008

Study Objectives. To determine the frequency with which reported antibiotic allergies alter drug selection and to assess the validity of these allergies.Design. Retrospective medical record review, with concurrent interviews conducted in a selected subgroup of patients.Setting. Tertiary care academic medical center.Patients. Three hundred patients with at least one documented antibiotic allergy and who received an antibiotic while hospitalized.Measurements and Main Results. Data were collected to determine the patients' allergies documented in the medical record. The first antibiotic regimen that each patient received while hospitalized was evaluated for deviation from the standard of care as determined from institutional protocols, recommendations in the literature, and expert opinion. A total of 416 allergies to antibiotics were reported. Penicillins were the agents most commonly reported (198 reports), followed by sulfonamides, cephalosporins, macrolides, and fluoroquinolones. The reported allergies altered antibiotic therapy in 91 (30.3%) patients. Report of a penicillin or cephalosporin allergy and use of antibiotics for prophylaxis were strong predictors of altered therapy. The subgroup consisted of 100 patients who were interviewed to determine the specific details of their reported allergic reactions. For 22 of the 100 patients, major discrepancies were found between their verbal reports and medical record documentation. The Naranjo adverse drug reaction probability scale was used to determine the validity of their reactions. Among these 100 patients, 109 (78.4%) of 139 reported reactions to antibiotics were deemed to be allergic in nature. For 55 (50.5%) of the 109 allergic reactions, the Naranjo score was 5 or greater, which correlates with probable to definite validity.Conclusion. Discrepancies between the medical record and in‐depth allergy histories are common, and the validity of reported allergic reactions is frequently questionable. Because documentation of an antibiotic allergy frequently alters therapy, increased effort to verify these reactions may be beneficial.
Plasma apelin levels in diabetic patients with and without neuropathy
Authors: Şenol Mehmet , Terekeci Hakan , İpçioğlu Osman , Çağıltay Eylem , Toğrol Erdem , Özdağ Fatih , Şahan Burak , Öktenli Çağatay , Saraçoğlu Mehmet 
Published: October 2008

Abstract
The aim of this study was to investigate the plasma apelin levels in diabetic patients with and without neuropathy. All consecutive diabetic patients who presented for routine follow-up at our outpatient clinic were invited to participate in this clinical study. Forty diabetic patients (20 female and 20 male) and twenty-two non-diabetic control subjects (9 female and 13 male) were included in the study. Neurological evaluations in diabetic subjects were done by nerve conduction studies and evaluated with the Neuropathy Symptom Score. Fasting plasma glucose, HbA1c, lipid and apelin levels were measured in each subject. The mean plasma apelin level was significantly higher in the diabetic patients than in the control subjects (p = 0.026). Apelin levels were statistically similar between diabetic patients with and without neuropathy (p = 0.43). Further, plasma apelin levels were found to be higher in diabetic patients with neuropathy when compared with those of healthy control subjects (p = 0.02). In diabetic patients with neuropathy, plasma apelin levels correlated significantly with diabetes duration (r = 0.5, p = 0.02). We propose that apelin levels in diabetic patients are higher in the presence of neuropathy and longer disease duration, although this might not solely suffice as an indicator for the presence of neuropathy in diabetic patients. Drawing attention to the possible association between the apelinergic system and diabetes mellitus, we believe that further studies with larger samples should be carried out also to investigate the presence of retinopathy and nephropathy.
Schooling and the Encouragement of Farming Amongst Pastoralists in Tanzania
Authors: Bishop Elizabeth 
Published: October 2008

Abstract
This article uses qualitative and quantitative data to document the nature of educational practices in a pastoralist area in Tanzania, and to provide evidence that the schooling process, amongst other influences, has encouraged and facilitated the uptake and expansion of farming by these pastoralists. The article argues that the schooling process has influenced pastoralists' livelihood choices, and thus the nature and viability of pastoralism.