bluuebunny/crossref_metadata_2025_split huggingface dataset:
PqsA is required for the biosynthesis of 2,4-dihydroxyquinoline (DHQ), a newly identified metabolite produced by Pseudomonas aeruginosa and Burkholderia thailandensis
Authors: Lépine François , Dekimpe Valérie , Lesic Biliana , Milot Sylvain , Lesimple Alain , Mamer Orval A. , Rahme Laurence G. , Déziel Eric 
Published: July 2007

Abstract
A new metabolite, 2,4-dihydroxyquinoline (DHQ), was identified in cultures of the bacteria Pseudomonas aeruginosa and Burkholderia thailandensis. We found that the biosynthesis of DHQ correlates with the presence of a functional PqsA, which is a product of the pqsABCDE operon responsible for the synthesis of 4-hydroxy-2-alkylquinolines (HAQs) in P. aeruginosa. However, DHQ is not a degradation product or precursor of HAQs. This finding sheds some light on the poorly understood biosynthesis pathway of HAQs, which includes important communication signals regulating the expression of virulence factors.
Loss of Glycemic Control in Patients with Type 2 Diabetes Mellitus Who Were Receiving Initial Metformin, Sulfonylurea, or Thiazolidinedione Monotherapy
Authors: Riedel Aylin A. , Heien Herbert , Wogen Jenifer , Plauschinat Craig A. 
Published: July 2007

Study Objectives. To examine glycosylated hemoglobin (A1C) values longitudinally in patients who newly started metformin, sulfonylurea, or thiazolidinedione monotherapy; in a subset of patients whose A1C values were 7% or greater before starting therapy (baseline) and who achieved A1C goal (A1C < 7%) during therapy, rates of secondary failure (i.e., A1C value returned to ≥ 7% during therapy) were compared for each drug.Design. Four‐year retrospective analysis.Data Source. Administrative database from a large health care plan.Patients. Patients who filled at least one prescription for metformin (5453 patients), sulfonylurea (2373), and thiazolidinedione (1590) therapy, respectively, between January 1, 2001, and March 31, 2004, were enrolled.Measurements and Main Results. Patients' demographic and clinical characteristics, baseline A1C values, changes in A1C values (last available result during follow‐up minus baseline value), and A1C values before and after the addition of an antidiabetic drug other than the index drug (therapy intensification) were documented. Mean age was 50.7 years; 5027 (53.4%) were men. Mean baseline A1C value was 8.4%, and about 70% of patients had an AIC value of 7% or greater before starting therapy. Mean follow‐up was 1.9 years, and mean decrease in A1C values was 1.47% (to 6.91%). The probabilities of attaining A1C goals were similar for patients receiving metformin, sulfonylurea, or thiazolidinedione therapy. The rate of therapy intensification among patients taking metformin (24.7%) was lower than that of patients taking a sulfonylurea (30.1%, p<0.001) but similar to that of those taking a thiazolidinedione (24.6%). Secondary failure occurred in 36.3% of patients; mean time from the start of therapy to its failure was about 1.51 years. Patients receiving a sulfonylurea were 1.25 (95% confidence interval [CI] 1.05–1.50) times more likely than patients receiving metformin to experience secondary failure, whereas failure rates were similar for thiazolidinediones and metformin (odds ratio 0.78, 95% CI 0.62–0.99).Conclusion. In the subset of patients assessed for secondary failure, although treatment initially reduced A1C values, more than one third experienced failure. Real‐world studies of A1C goal attainment must follow patients on a long‐term basis to assess the maintenance of glycemic control over time.
Hemodynamic and Cognitive Effects of Lofexidine and Methadone Coadministration: A Pilot Study
Authors: Schroeder Jennifer R. , Schmittner John , Bleiberg Joseph , Epstein David H. , Krantz Mori J. , Preston Kenzie L. 
Published: July 2007

Study Objective. To determine the hemodynamic and cognitive effects of lofexidine and methadone coadministration.Design. Prospective, double‐blind study.Setting. Outpatient drug treatment research clinic.Subjects. Fourteen participants (aged 18–45 yrs) with physical dependence on opioids.Intervention. Subjects were stabilized on methadone maintenance therapy, starting with 30 mg/day and increasing by 10‐mg/day increments, based on each subject's tolerability to achieve a target dose of 80 mg/day. After 3 weeks of methadone stabilization, lofexidine 0.4 mg/day or matching placebo were coadministered with methadone, in doses escalating by 0.2‐mg/week increments, to achieve a target dose of 1.6 mg/day over the next 8 weeks.Measurements and Main Results. Acute orthostatic vital signs and neuropsychological effects of lofexidine and methadone coadministration were monitored for 5 hours after the dose on the first day of each new lofexidine dose. Orthostatic vital signs and adverse events were assessed daily thereafter to determine the effects of repeated doses. Lofexidine significantly decreased sitting systolic and diastolic blood pressure (p=0.045 and p=0.033, respectively) compared with placebo (i.e., methadone alone). With lofexidine 0.4 mg/day, mean decreases in systolic and diastolic blood pressure were 27 ± 17 and 15 ± 16 mm Hg, respectively. No significant association was noted between changes in orthostatic vital signs and lofexidine dose. Decreased cognitive efficiency was associated with lofexidine administration, and higher lofexidine doses adversely affected performance on a mathematical task compared with placebo (p=0.0035). The rate of adverse events was no higher with lofexidine than with placebo; the majority (54.3%) were common adverse effects of lofexidine.Conclusion. Significant changes in hemodynamic and cognitive efficiency were observed with coadministration of lofexidine and methadone compared with methadone alone. When patients receiving methadone are prescribed lofexidine, they should be closely monitored for cardiovascular and cognitive changes.
The Role of the Donor in the Repair of the Marrow Vascular Niche Following Hematopoietic Stem Cell Transplant
Authors: Slayton William B. , Li Xiao-Miao , Butler Jason , Guthrie Steven M. , Jorgensen Marda L. , Wingard John R. , Scott Edward W. 
Published: July 2007

Abstract
Bone marrow sinusoids maintain homeostasis between developing hematopoietic cells and the circulation, and they provide niches for hematopoietic progenitors. Sinusoids are damaged by chemotherapy and radiation. Hematopoietic stem cells (HSCs) have been shown to produce endothelial progenitor cells that contribute to the repair of damaged blood vessels. Because HSCs home to the marrow during bone marrow transplant, these cells may play a role in repair of marrow sinusoids. Here, we explore the role of donor HSCs in the repair of damaged sinusoids following hematopoietic stem cell transplant. We used three methods to test this role: (a) expression of platelet endothelial cell adhesion molecule to identify endothelial progenitors and the presence of the Y chromosome to identify male donor cells in female recipients; (b) presence of the Y chromosome to identify male donor cells in female recipients, and expression of the panendothelial marker mouse endothelial cell antigen-32 to identify sinusoidal endothelium; and (c) use of Tie-2/green fluorescent protein mice as donors or recipients and presence of Dil-Ac-LDL to identify sinusoids. We found that sinusoids were predominantly host-derived posttransplant. Donor cells spread along the marrow vasculature early post-transplant in a pattern that matched stromal-derived factor-1 expression. Furthermore, these engrafting progenitors were positioned to provide physical support, as well as growth and survival signals in the form of vascular-endothelial growth factor-A. Occasionally, donor cells provide cellular “patches” in the damaged sinusoids, although this occurred at a low level compared with hematopoietic engraftment. Donor support for the repair of the marrow vascular niche may be a critical first step of hematopoietic engraftment.
Disclosure of potential conflicts of interest is found at the end of this article.
CD45-Positive Blood Cells Give Rise to Uterine Epithelial Cells in Mice
Authors: Bratincsák András , Brownstein Michael J. , Cassiani-Ingoni Riccardo , Pastorino Sandra , Szalayova Ildikó , Tóth Zsuzsanna E. , Key Sharon , Németh Krisztián , Pickel James , Mezey Éva 
Published: July 2007

Abstract
The uterine endometrium is composed of epithelial and stromal cells, which undergo extensive degeneration and regeneration in every estrous cycle, and dramatic changes occur during pregnancy. The high turnover of cells requires a correspondingly high level of cell division by progenitor cells in the uterus, but the character and source of these cells remain obscure. In the present study, using a novel transgenic mouse, we showed that CD45-positive hematopoietic progenitor cells colonize the uterine epithelium and that in pregnancy more than 80% of the epithelium can derive from these cells. Since we also found green fluorescent protein (GFP)-positive uterine endothelial cells in long-term GFP bone marrow-transplanted mice, we conclude that circulating CD45+ cells play an important role in regenerating the uterine epithelium.
Disclosure of potential conflicts of interest is found at the end of this article.
Chondrogenic Differentiation of Human Bone Marrow Stem Cells in Transwell Cultures: Generation of Scaffold-Free Cartilage
Authors: Murdoch Alan D. , Grady Lisa M. , Ablett Matthew P. , Katopodi Theoni , Meadows Roger S. , Hardingham Tim E. 
Published: July 2007

Abstract
Human bone marrow stem cells (hMSCs) have been shown to differentiate in vitro into a number of cell lineages and are a potential autologous cell source for the repair and replacement of damaged and diseased musculoskeletal tissues. hMSC differentiation into chondrocytes has been described in high-density cell pellets cultured with specific growth and differentiation factors. We now describe how culture of hMSCs as a shallow multicellular layer on a permeable membrane over 2–4 weeks resulted in a much more efficient formation of cartilaginous tissue than in established chondrogenic assays. In this format, the hMSCs differentiated in 14 days to produce translucent, flexible discs, 6 mm in diameter by 0.8–1 mm in thickness from 0.5 × 106 cells. The discs contained an extensive cartilage-like extracellular matrix (ECM), with more than 50% greater proteoglycan content per cell than control hMSCs differentiated in standard cell pellet cultures. The disc constructs were also enriched in the cartilage-specific collagen II, and this was more homogeneously distributed than in cell pellet cultures. The expression of cartilage matrix genes for collagen type II and aggrecan was enhanced in disc cultures, but improved matrix production was not accompanied by increased expression of the transcription factors SOX9, L-SOX5, and SOX6. The fast continuous growth of cartilage ECM in these cultures up to 4 weeks appeared to result from the geometry of the construct and the efficient delivery of nutrients to the cells. Scaffold-free growth of cartilage in this format will provide a valuable experimental system for both experimental and potential clinical studies.
Disclosure of potential conflicts of interest is found at the end of this article.
SAVANNA RESPONSES TO FERAL BUFFALO IN KAKADU NATIONAL PARK, AUSTRALIA
Authors: Petty Aaron M. , Werner Patricia A. , Lehmann Caroline E. R. , Riley Jan E. , Banfai Daniel S. , Elliott Louis P. 
Published: July 2007

Savannas are the major biome of tropical regions, spanning 30% of the Earth's land surface. Tree : grass ratios of savannas are inherently unstable and can be shifted easily by changes in fire, grazing, or climate. We synthesize the history and ecological impacts of the rapid expansion and eradication of an exotic large herbivore, the Asian water buffalo (Bubalus bubalus), on the mesic savannas of Kakadu National Park (KNP), a World Heritage Park located within the Alligator Rivers Region (ARR) of monsoonal north Australia. The study inverts the experience of the Serengeti savannas where grazing herds rapidly declined due to a rinderpest epidemic and then recovered upon disease control.Buffalo entered the ARR by the 1880s, but densities were low until the late 1950s when populations rapidly grew to carrying capacity within a decade. In the 1980s, numbers declined precipitously due to an eradication program. We show evidence that the rapid population expansion and sudden removal of this exotic herbivore created two ecological cascades by altering ground cover abundance and composition, which in turn affected competitive regimes and fuel loads with possible further, long‐term effects due to changes in fire regimes. Overall, ecological impacts varied across a north–south gradient in KNP that corresponded to the interacting factors of precipitation, landform, and vegetation type but was also contingent upon the history of buffalo harvest. Floodplains showed the greatest degree of impact during the period of rapid buffalo expansion, but after buffalo removal, they largely reverted to their prior state. Conversely, the woodlands experienced less visible impact during the first cascade. However, in areas of low buffalo harvest and severe impact, there was little recruitment of juvenile trees into the canopy due to the indirect effects of grazing and high frequency of prescribed fires once buffalo were removed. Rain forests were clearly heavily impacted during the first cascade, but the long term consequences of buffalo increase and removal remain unclear. Due to hysteresis effects, the simple removal of an exotic herbivore was not sufficient to return savanna systems to their previous state.
Association of the Estrogen Receptor-α Gene With the Metabolic Syndrome and Its Component Traits in African-American Families
Authors: Gallagher Carla J. , Langefeld Carl D. , Gordon Candace J. , Campbell Joel K. , Mychalecky Josyf C. , Bryer-Ash Michael , Rich Stephen S. , Bowden Donald W. , Sale Michèle M. 
Published: July 2007

OBJECTIVE— We previously detected an association between a region of the estrogen receptor-α (ESR1) gene and type 2 diabetes in an African-American case-control study; thus, we investigated this region for associations with the metabolic syndrome and its component traits in African-American families from the Insulin Resistance Atherosclerosis Family Study.
RESEARCH DESIGN AND METHODS— A total of 17 single nucleotide polymorphisms (SNPs) from a contiguous 41-kb intron 1–intron 2 region of the ESR1 gene were genotyped in 548 individuals from 42 African-American pedigrees. Generalized estimating equations were computed using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation.
RESULTS— Significant associations were detected between ESR1 SNPs and the metabolic syndrome (P = 0.005 to P = 0.029), type 2 diabetes (P = 0.001), insulin sensitivity (P = 0.0005 to P = 0.023), fasting insulin (P = 0.022 to P = 0.033), triglycerides (P = 0.021), LDL (P = 0.016 to P = 0.034), cholesterol (P = 0.046), BMI (P = 0.016 to P = 0.035), waist circumference (P = 0.012 to P = 0.023), and subcutaneous adipose tissue area (P = 0.016).
CONCLUSIONS— It appears likely that ESR1 contributes to type 2 diabetes and CVD risk via pleiotropic effects, leading to insulin resistance, a poor lipid profile, and obesity.
Progression to Type 2 Diabetes Characterized by Moderate Then Rapid Glucose Increases
Authors: Mason Clinton C. , Hanson Robert L. , Knowler William C. 
Published: July 2007

OBJECTIVE—The transition of an individual from normoglycemia to diabetes has generally been thought to involve either moderate or rapid changes in glucose over time, although few studies have analyzed these changes. We sought to determine whether a general pattern of glucose change exists in most individuals who become diabetic.
RESEARCH DESIGN AND METHODS—We examined longitudinal data from Pima Indians who developed diabetes after several biennial examinations to characterize changes in 2-h plasma glucose. A distinct pattern of glucose change was apparent in the time course of most individuals, an initial linear trend followed by a steeper rise in glucose values. A model consisting of additive linear and exponential functions was hypothesized to account for this pattern and was tested for goodness of fit on 55 individuals who became diabetic after at least 10 previous examinations.
RESULTS—The combined linear and exponential model provided a significantly better fit than linear or exponential models alone in 40 of the 55 cases (P &lt; 10−38). Using this model, the timeframe over which glucose values rose suddenly was estimated, having a median time to onset of &lt;4.5 years from the time at which the exponential effect had contributed a modest increase of 10 mg/dl to the initial linear trend.
CONCLUSIONS—We conclude that there are two distinct processes affecting glucose levels in most individuals who progress to type 2 diabetes and that the rapid glucose rise identified in these people may be an important period for physiologic and preventive research.
Selective Downregulation of the High–Molecular Weight Form of Adiponectin in Hyperinsulinemia and in Type 2 Diabetes
Authors: Basu Rita , Pajvani Utpal B. , Rizza Robert A. , Scherer Philipp E. 
Published: July 2007

OBJECTIVE—Adiponectin is an adipocyte-specific secretory protein found in circulation in several different forms and is present at significantly lower levels in the plasma of diabetic patients compared with that of insulin-sensitive individuals. We wanted to test whether insulin per se is a contributing factor toward lower plasma adiponectin concentrations and, if so, whether the splanchnic bed contributes to this phenomenon.
RESEARCH DESIGN AND METHODS—We sampled femoral artery and hepatic venous samples and measured the high–molecular weight (HMW) and low–molecular weight (LMW) fractions of adiponectin in 11 type 2 diabetic and 7 nondiabetic subjects matched for age, sex, and BMI during basal conditions and during a hyperglycemic (∼9.5 mmol/l) hyperinsulinemic (∼700 pmol/l) clamp.
RESULTS—Under these conditions, total arterial adiponectin, HMW, and the ratio of HMW to total adiponectin all were lower (P &lt; 0.01) in the diabetic versus nondiabetic subjects, whereas the LMW form did not significantly differ. Under hyperinsulinemic conditions, total adiponectin levels dropped, primarily due to a reduction of the HMW form, whereas LMW forms were not significantly affected.
CONCLUSIONS—HMW adiponectin and the ratio of HMW to total adiponectin are lower in individuals with diabetes than in nondiabetic subjects. We conclude that HMW adiponectin is downregulated in hyperinsulinemia and type 2 diabetes.
High Expression Rates of Human Islet Amyloid Polypeptide Induce Endoplasmic Reticulum Stress–Mediated β-Cell Apoptosis, a Characteristic of Humans With Type 2 but Not Type 1 Diabetes
Authors: Huang Chang-jiang , Lin Chia-yu , Haataja Leena , Gurlo Tatyana , Butler Alexandra E. , Rizza Robert A. , Butler Peter C. 
Published: July 2007

OBJECTIVE—Endoplasmic reticulum (ER) stress–induced apoptosis may be a common cause of cell attrition in diseases characterized by misfolding and oligomerisation of amyloidogenic proteins. The islet in type 2 diabetes is characterized by islet amyloid derived from islet amyloid polypeptide (IAPP) and increased β-cell apoptosis. We questioned the following: 1) whether IAPP-induced β-cell apoptosis is mediated by ER stress and 2) whether β-cells in type 2 diabetes are characterized by ER stress.
RESEARCH DESIGN AND METHODS—The mechanism of IAPP-induced apoptosis was investigated in INS-1 cells and human IAPP (HIP) transgenic rats. ER stress in humans was investigated by β-cell C/EBP homologous protein (CHOP) expression in 7 lean nondiabetic, 12 obese nondiabetic, and 14 obese type 2 diabetic human pancreata obtained at autopsy. To assure specificity for type 2 diabetes, we also examined pancreata from eight cases of type 1 diabetes.
RESULTS—IAPP induces β-cell apoptosis by ER stress in INS-1 cells and HIP rats. Perinuclear CHOP was rare in lean nondiabetic (2.6 ± 2.0%) and more frequent in obese nondiabetic (14.6 ± 3.0%) and obese diabetic (18.5 ± 3.6%) pancreata. Nuclear CHOP was not detected in lean nondiabetic and rare in obese nondiabetic (0.08 ± 0.04%) but six times higher (P &lt; 0.01) in obese diabetic (0.49 ± 0.17%) pancreata. In type 1 diabetic pancreata, perinuclear CHOP was rare (2.5 ± 2.3%) and nuclear CHOP not detected.
CONCLUSIONS—ER stress is a mechanism by which IAPP induces β-cell apoptosis and is characteristic of β-cells in humans with type 2 diabetes but not type 1 diabetes. These findings are consistent with a role of protein misfolding in β-cell apoptosis in type 2 diabetes.
Islet Surface Heparinization Prevents the Instant Blood-Mediated Inflammatory Reaction in Islet Transplantation
Authors: Cabric Sanja , Sanchez Javier , Lundgren Torbjörn , Foss Aksel , Felldin Marie , Källen Ragnar , Salmela Kaija , Tibell Annika , Tufveson Gunnar , Larsson Rolf , Korsgren Olle , Nilsson Bo 
Published: July 2007

OBJECTIVE—In clinical islet transplantation, the instant blood-mediated inflammatory reaction (IBMIR) is a major factor contributing to the poor initial engraftment of the islets. This reaction is triggered by tissue factor and monocyte chemoattractant protein (MCP)-1, expressed by the transplanted pancreatic islets when the islets come in contact with blood in the portal vein. All currently identified systemic inhibitors of the IBMIR are associated with a significantly increased risk of bleeding or other side effects. To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface.
RESEARCH DESIGN AND METHODS—A biotin/avidin technique was used to conjugate preformed heparin complexes to the surface of pancreatic islets. This endothelial-like coating was achieved by conjugating barely 40 IU heparin per full-size clinical islet transplant.
RESULTS—Both in an in vitro loop model and in an allogeneic porcine model of clinical islet transplantation, this heparin coating provided protection against the IBMIR. Culturing heparinized islets for 24 h did not affect insulin release after glucose challenge, and heparin-coated islets cured diabetic mice in a manner similar to untreated islets.
CONCLUSIONS—This novel pretreatment procedure prevents intraportal thrombosis and efficiently inhibits the IBMIR without increasing the bleeding risk and, unlike other pretreatment procedures (e.g., gene therapy), without inducing acute or chronic toxicity in the islets.