bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGFR4 Prevents Hyperlipidemia and Insulin Resistance but Underlies High-Fat Diet–Induced Fatty Liver
Authors: Huang Xinqiang , Yang Chaofeng , Luo Yongde , Jin Chengliu , Wang Fen , McKeehan Wallace L. 
Published: September 2007

OBJECTIVE—Fibroblast growth factor (FGF) family signaling largely controls cellular homeostasis through short-range intercell paracrine communication. Recently FGF15/19, 21, and 23 have been implicated in endocrine control of metabolic homeostasis. The identity and location of the FGF receptor isotypes that mediate these effects are unclear. The objective was to determine the role of FGFR4, an isotype that has been proposed to mediate an ileal FGF15/19 to hepatocyte FGFR4 axis in cholesterol homeostasis, in metabolic homeostasis in vivo.
RESEARCH DESIGN AND METHODS—FGFR4−/− mice—mice overexpressing constitutively active hepatic FGFR4—and FGFR4−/− with constitutively active hepatic FGFR4 restored in the liver were subjected to a normal and a chronic high-fat diet sufficient to result in obesity. Systemic and liver-specific metabolic phenotypes were then characterized.
RESULTS—FGFR4-deficient mice on a normal diet exhibited features of metabolic syndrome that include increased mass of white adipose tissue, hyperlipidemia, glucose intolerance, and insulin resistance, in addition to hypercholesterolemia. Surprisingly, the FGFR4 deficiency alleviated high-fat diet–induced fatty liver in obese mice, which is also a correlate of metabolic syndrome. Restoration of FGFR4, specifically in hepatocytes of FGFR4-deficient mice, decreased plasma lipid levels and restored the high-fat diet–induced fatty liver but failed to restore glucose tolerance and sensitivity to insulin.
CONCLUSIONS—FGFR4 plays essential roles in systemic lipid and glucose homeostasis. FGFR4 activity in hepatocytes that normally serves to prevent systemic hyperlipidemia paradoxically underlies the fatty liver disease associated with chronic high-fat intake and obesity.
Association of the Vitamin D Metabolism Gene CYP27B1 With Type 1 Diabetes
Authors: Bailey Rebecca , Cooper Jason D. , Zeitels Lauren , Smyth Deborah J. , Yang Jennie H.M. , Walker Neil M. , Hyppönen Elina , Dunger David B. , Ramos-Lopez Elizabeth , Badenhoop Klaus , Nejentsev Sergey , Todd John A. 
Published: September 2007

OBJECTIVE—Epidemiological studies have linked vitamin D deficiency with the susceptibility to type 1 diabetes. Higher levels of the active metabolite 1α,25-dihydroxyvitamin D (1α,25(OH)2D) could protect from immune destruction of the pancreatic β-cells. 1α,25(OH)2D is derived from its precursor 25-hydroxyvitamin D by the enzyme 1α-hydroxylase encoded by the CYP27B1 gene and is inactivated by 24-hydroxylase encoded by the CYP24A1 gene. Our aim was to study the association between the CYP27B1 and CYP24A1 gene polymorphisms and type 1 diabetes.
RESEARCH DESIGN AND METHODS—We studied 7,854 patients with type 1 diabetes, 8,758 control subjects from the U.K., and 2,774 affected families. We studied four CYP27B1 variants, including common polymorphisms −1260C&gt;A (rs10877012) and +2838T&gt;C (rs4646536) and 16 tag polymorphisms in the CYP24A1 gene.
RESULTS—We found evidence of association with type 1 diabetes for CYP27B1 −1260 and +2838 polymorphisms, which are in perfect linkage disequilibrium. The common C allele of CYP27B1 −1260 was associated with an increased disease risk in the case-control analysis (odds ratio for the C/C genotype 1.22, P = 9.6 × 10−4) and in the fully independent collection of families (relative risk for the C/C genotype 1.33, P = 3.9 × 10−3). The combined P value for an association with type 1 diabetes was 3.8 × 10−6. For the CYP24A1 gene, we found no evidence of association with type 1 diabetes (multilocus test, P = 0.23).
CONCLUSIONS—The present data provide evidence that common inherited variation in the vitamin D metabolism affects susceptibility to type 1 diabetes.
Glucagon, in Concert With Insulin, Supports the Postabsorptive Plasma Glucose Concentration in Humans
Authors: Breckenridge Suzanne M. , Cooperberg Benjamin A. , Arbelaez Ana Maria , Patterson Bruce W. , Cryer Philip E. 
Published: September 2007

OBJECTIVE—Given the interest in glucagon antagonism as a potential treatment of diabetes, we tested the hypothesis that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.
RESEARCH DESIGN AND METHODS—Following preliminary studies that indicated that a peripheral intravenous insulin dose of 0.1 mU · kg−1 · min−1 (lower than those used previously) provides basal insulin replacement and that a glucagon dose of 1.0 ng · kg−1 · min−1 underreplaces basal glucagon, we infused the somatostatin analog octreotide (30 ng · kg−1 · min−1) (with growth hormone replacement) over 4 h in 14 healthy adults on four separate occasions to produce endogenous insulin and glucagon deficiency with 1) saline (combined insulin and glucagon deficiency), 2) insulin replacement (isolated glucagon deficiency), 3) partial glucagon replacement (insulin and partial glucagon deficiency), and 4) insulin and partial glucagon replacement (partial glucagon deficiency).
RESULTS—During combined insulin and glucagon deficiency, glucose production decreased and then increased, and mean (±SE) plasma glucose decreased from 83 ± 1 to 63 ± 2 mg/dl at 60 min and then increased to 89 ± 3 mg/dl at 240 min. During isolated glucagon deficiency, plasma glucose decreased to hypoglycemic levels and was 55 ± 2 mg/dl at 240 min (P &lt; 0.0001 vs. combined insulin and glucagon deficiency). Partial glucagon replacement raised plasma glucose to higher levels (P = 0.0469) during insulin deficiency and to higher levels (P = 0.0090) during insulin replacement.
CONCLUSIONS—These three findings provide direct evidence that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.
Noninvasive Magnetic Resonance Imaging of Microvascular Changes in Type 1 Diabetes
Authors: Medarova Zdravka , Castillo Gerardo , Dai Guangping , Bolotin Elijah , Bogdanov Alexei , Moore Anna 
Published: September 2007

OBJECTIVE— The pathogenesis of type 1 diabetes involves autoimmune lymphocytic destruction of insulin-producing β-cells and metabolic dysregulation. An early biomarker of pancreatic islet damage is islet microvascular dysfunction, and alterations in vascular volume, flow, and permeability have been reported in numerous models of type 1 diabetes. Consequently, the ability to noninvasively monitor the dynamics of the pancreatic microvasculature would aid in early diagnosis and permit the assessment, design, and optimization of individualized therapeutic intervention strategies.
RESEARCH DESIGN AND METHODS— Here, we used the long circulating paramagnetic contrast agent, protected graft copolymer (PGC) covalently linked to gadolinium-diethylenetriaminepentaacetic acid residues (GdDTPAs) labeled with fluorescein isothiocyanate (PGC-GdDTPA-F), for the noninvasive semiquantitative evaluation of vascular changes in a streptozotocin (STZ)-induced mouse model of type 1 diabetes. Diabetic animals and nondiabetic controls were monitored by magnetic resonance imaging (MRI) after injection of PGC-GdDTPA-F.
RESULTS— Our findings demonstrated a significantly greater accumulation of PGC-GdDTPA-F in the pancreata of diabetic animals compared with controls. MRI permitted the in vivo semiquantitative assessment and direct visualization of the differential distribution of PGC-GdDTPA-F in diabetic and control pancreata. Ex vivo histology revealed extensive distribution of PGC-GdDTPA-F within the vascular compartment of the pancreas, as well as considerable leakage of the probe into the islet interstitium. By contrast, in nondiabetic controls, PGC-GdDTPA-F was largely restricted to the pancreatic vasculature at the islet periphery.
CONCLUSIONS— Based on these observations, we conclude that in the STZ model of type 1 diabetes, changes in vascular volume and permeability associated with early stages of the disease can be monitored noninvasively and semiquantitatively by MRI.
Age-Related Changes in Strength, Joint Laxity, and Walking Patterns: Are They Related to Knee Osteoarthritis?
Authors: Rudolph Katherine S , Schmitt Laura C , Lewek Michael D 
Published: September 2007

Background and PurposeAging is associated with musculoskeletal changes and altered walking patterns. These changes are common in people with knee osteoarthritis (OA) and may precipitate the development of OA. We examined age-related changes in musculoskeletal structures and walking patterns to better understand the relationship between aging and knee OA.MethodsForty-four individuals without OA (15 younger, 15 middle-aged, 14 older adults) and 15 individuals with medial knee OA participated. Knee laxity, quadriceps femoris muscle strength (force-generating capacity), and gait were assessed.ResultsMedial laxity was greater in the OA group, but there were no differences between the middle-aged and older control groups. Quadriceps femoris strength was less in the older control group and in the OA group. During the stance phase of walking, the OA group demonstrated less knee flexion and greater knee adduction, but there were no differences in knee motion among the control groups. During walking, the older control group exhibited greater quadriceps femoris muscle activity and the OA group used greater muscle co-contraction.Discussion and ConclusionAlthough weaker, the older control group did not use truncated motion or higher co-contraction. The maintenance of movement patterns that were similar to the subjects in the young control group may have helped to prevent development of knee OA. Further investigation is warranted regarding age-related musculoskeletal changes and their influence on the development of knee OA.
Reference Group Data for the Functional Gait Assessment
Authors: Walker Martha L , Austin Alvis G , Banke Gina M , Foxx Suzanne R , Gaetano Lynn , Gardner Laurie A , McElhiney Jill , Morris Kisiah , Penn Liz 
Published: September 2007

Background and PurposeThe Functional Gait Assessment (FGA) is a clinical tool for evaluating performance in walking. The purpose of this study was to determine age-referenced norms for performance on the FGA in community-living older adults.SubjectsSubjects were 200 adults, ages 40 to 89 years, living independently.MethodsEach subject completed the FGA one time and was scored simultaneously by 2 testers.ResultsThe intraclass correlation coefficient for interrater reliability was .93. Mean scores for the FGA ranged from 29/30 for adults in their 40s to 21/30 for adults in their 80s.Discussion and ConclusionPatient performance on the FGA can be compared with age-referenced norms for expected performance. Further research is needed to determine the FGA’s usefulness in tracking clinical changes or predicting falls. The FGA is a reliable test for people without disease, and it is able to detect decreases in gait performance among typical older adults.
Automated live cell imaging of green fluorescent protein degradation in individual fibroblasts
Authors: Halter Michael , Tona Alex , Bhadriraju Kiran , Plant Anne L. , Elliott John T. 
Published: September 2007

AbstractTo accurately interpret the data from fluorescent proteins as reporters of gene activation within living cells, it is important to understand the kinetics of the degradation of the reporter proteins. We examined the degradation kinetics over a large number (>1,000) of single, living cells from a clonal population of NIH3T3 fibroblasts that were stably transfected with a destabilized, enhanced green fluorescent protein (eGFP) reporter driven by the tenascin‐C promoter. Data collection and quantification of the fluorescence protein within a statistically significant number of individual cells over long times (14 h) by automated microscopy was facilitated by culturing cells on micropatterned arrays that confined their migration and allowed them to be segmented using phase contrast images. To measure GFP degradation rates unambiguously, protein synthesis was inhibited with cycloheximide. Results from automated live cell microscopy and image analysis indicated a wide range of cell‐to‐cell variability in the GFP fluorescence within individual cells. Degradation for this reporter was analyzed as a first order rate process with a degradation half‐life of 2.8 h. We found that GFP degradation rates were independent of the initial intensity of GFP fluorescence within cells. This result indicates that higher GFP abundance in some cells is likely due to higher rates of gene expression, because it is not due to systematically lower rates of protein degradation. The approach described in this study will assist the quantification and understanding of gene activity within live cells using fluorescent protein reporters. Published 2007 Wiley‐Liss, Inc.
The stigma of public programs: Does a separate S‐CHIP program reduce it?
Authors: Ketsche Patricia , Adams E. Kathleen , Minyard Karen , Kellenberg Rebecca 
Published: September 2007

AbstractPrevious studies suggest access to and satisfaction with care may be different for enrollees in S‐CHIP and Medicaid, but it is unclear whether those differences are fully explained by socioeconomic characteristics of the enrollees. We analyze access and satisfaction of three groups of children: Medicaid enrolled, S‐CHIP enrolled, and children who are income eligible for Medicaid but carry a card similar to the state's S‐CHIP children's card. Both enrollees and providers may believe that these children are enrolled in S‐CHIP despite the fact that reimbursement is through the state's Medicaid system. Results indicate that the same network of providers treat, or are perceived by families to treat, the three groups differently. They support the notion that some of the differences in satisfaction between S‐CHIP and Medicaid enrollees are related to unmeasured characteristics (for example, income) of the families in the different programs, but that programmatic identity contributes substantially to differential care experience. © 2007 by the Association for Public Policy Analysis and Management
Bak Foong protects dopaminergic neurons against MPTP‐induced neurotoxicity by its anti‐apoptotic activity
Authors: Liu Bin , Xie Jun Xia , Tsang Lai Ling , Rowlands Dewi Kenneth , Ho Lok Sze , Gou Yu Lin , Chung Yiu Wa , Chan Hsiao Chang 
Published: September 2007

AbstractBak Foong pill (BFP) is a well‐known traditional Chinese medicine used for treatment of various gynaecological disorders. In addition, it exerts beneficial effects on other functional systems including the central nervous system. In the present study, we have investigated the possible neuroprotective action of BFP upon the nigrostriatal dopaminergic system by examining its effect on the expression patterns of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahyrdropyridine (MPTP)‐induced Parkinson's disease (PD) mouse model. MPTP significantly decreased TH and DAT mRNA levels in the striatum and midbrain of both female and male C57BL/6 mice. However, with BFP pre‐treatment mice showed a reduced neurotoxicity, with TH and DAT mRNA levels either not affected by MPTP or affected to a lesser extent in the midbrain and striatum when compared to vehicle treated animals. Possible anti‐apoptotic activity of BFP was further studied in a dopamine‐secreting neuroendocrine cell line, PC12. In this assay, MPTP elevated the expression of a pro‐apoptotic gene, Bax, while this expression was reduced by BFP pre‐treatment. Flow cytometry results also revealed that the effect of MPTP‐induced apoptosis in PC12 cell lines was significantly reduced by BFP. The present results suggest that BFP is able to protect dopaminergic neurons from neurotoxin‐induced neuronal injury with anti‐apoptotic activity being one of the possible mechanisms.
Immunological aspects of human amniotic fluid cells: Implication for normal pregnancy
Authors: Yan Wei‐Hua , Lin Aifen , Chen Xue‐Jiao , Dai Mei‐Zhen , Xu Hui‐Hui , Chen Bao‐Guo , Gan Lin‐Hong , Shi Wei‐Wu 
Published: September 2007

AbstractAmniotic fluid cells (AFCs) are routinely obtained and expanded in vitro for prenatal diagnosis; nevertheless current knowledge about their properties is limited. The detailed mechanisms underlying normal pregnancies are yet to be discovered. The goal of this study was to identify the immunological aspects of AFCs including cytokine production and human leukocyte antigen (HLA) expression, and to discuss its implication for pregnancy. Eighty‐six samples of AFCs were determined for HLA expression before and after culture. Cytokine production was measured with flow cytometry in AFC culture supernatants. Treatment of interferon (IFN)‐γ on induction of HLA‐DR expression in cultured AFCs was also investigated. Data indicated that both fresh and cultured AFCs express HLA‐I, HLA‐G, but not HLA‐DR, and the cultured AFCs predominately produce the cytokine interleukin (IL)‐6. Importantly, we observed that IFN‐γ could induce HLA‐DR expression on cultured AFCs in a dose‐dependent manner. Taken together, our results indicated that AFCs are functionally active cells and are significant in pregnancy.
Vitamin A treatment induces apoptosis through an oxidant‐dependent activation of the mitochondrial pathway
Authors: Klamt Fábio , Dal‐Pizzol Felipe , Gelain Daniel Pens , Dalmolin Rodrigo Siqueira , de Oliveira Birnfeld Ramatis , Bastiani Michele , Horn Fabiana , Moreira José Cláudio Fonseca 
Published: September 2007

AbstractEven though retinoids are widely used as adjuvant in chemotherapeutic interventions to improve cancer cell death, their mechanism(s) of action involves multiple overlapping pathways that remain unclear. We have previously shown that vitamin A, the natural precursor of the retinoids, induces oxidative‐dependent cytochrome c release from isolated mitochondria, suggesting a putative mechanism for apoptosis activation. Using Sertoli cells in culture, we show that retinol causes mitochondrial‐dependent apoptosis, involving oxidative stress. Apoptosis was evaluated by nuclear morphology, DNA fragmentation, and caspase‐3/7 activity. Retinol induced oxidant‐ and time‐dependent imbalance of several mitochondrial parameters, cytochrome c release and caspase‐3/7 activation, leading cells to commit apoptosis. All parameters tested were attenuated or blocked by trolox co‐administration, suggesting that retinol induces apoptosis through oxidative damage, which mitochondria plays a pivotal role.
Early‐stage apoptosis is associated with DNA‐damage‐independent ATM phosphorylation and chromatin decondensation in NIH3T3 fibroblasts
Authors: Schou Kenneth Bødtker , Schneider Linda , Christensen Søren Tvorup , Hoffmann Else Kay 
Published: September 2007

AbstractChromatin condensation and degradation of DNA into internucleosomal DNA fragments are key hallmarks of apoptosis. The phosphorylation of protein kinase ataxia telangiectasia mutated (ATM) and histone H2A.X was recently shown to occur concurrently with apoptotic DNA fragmentation. We have used immunofluorescence microscopy, Western blot analysis and alkali comet assays to show that phosphorylation of ATM in NIH3T3 fibroblasts occurs prior to apoptotic DNA fragmentation, nuclease degradation and phosphorylation of histone H2A.X in cells treated with low levels of either staurosporine (STS) or tumor necrosis factor‐α mixed with cycloheximide (TNF‐α/CHX). In extension to previous findings, ATM phosphorylation was associated with chromatin decondensation, i.e., by loss of dense foci of constitutive heterochromatin. These results suggest that chromatin is decondensed and that ATM is activated independently of DNA damage signaling pathways during the very early stages of apoptosis.
Post‐conditioning exacerbates the MnSOD immune‐reactivity after experimental cerebral global ischemia and reperfusion in the rat brain hippocampus
Authors: Nemethova Miroslava , Danielisova Viera , Gottlieb Miroslav , Burda Jozef 
Published: September 2007

AbstractThis study monitored the effects of sub‐lethal ischemia (post‐conditioning) applied after a previous ischemic attack by way of the MnSOD immune‐reactivity examined in CA1 and dentate gyrus of the rat hippocampus. The experimental 10 min transient cerebral ischemia was followed by 2 days of reperfusion, the rats then underwent a second ischemia (4 or 6 min post‐conditioning). MnSOD immune‐reactivity was evaluated after 5 h, 1 and 2 days. Results obtained by computer microdensitometric image analysis indicated that 4 min of ischemic post‐conditioning caused higher MnSOD immune‐reactivity than 6 min. However, higher viability of CA1 neurons after stronger (6 min) post‐conditioning when production of MnSOD is lower, as well as differences between MnSOD in CA1 and dentate gyrus indicates another mechanism switching pro‐apoptotic destination of CA1 neurons to anti‐apoptotic.
Effect of nicotine and polyaromtic hydrocarbons on cerebral endothelial cells
Authors: Hutamekalin Pilaiwanwadee , Farkas Attila E. , Orbók Anna , Wilhelm Imola , Nagyőszi Péter , Veszelka Szilvia , Deli Mária A. , Buzás Krisztina , Hunyadi‐Gulyás Éva , Medzihradszky Katalin F. , Meksuriyen Duangdeun , Krizbai István A. 
Published: September 2007

AbstractThe present study was designed to investigate the effect of nicotine and polyaromatic hydrocarbon compounds on cerebral endothelial cells (CECs). Nicotine treatments from 15 min to 5 h did not cause any changes in the expression and localization of principal junctional proteins. One day of treatment with a relatively high concentration of nicotine induced a decrease in the expression of the tight junction protein ZO‐1, occludin, and the adherens junction protein, cadherin. Treatment with 3 × 10−5 M phenanthrene for 24 h caused a redistribution of occludin from the Triton X‐100 insoluble to the Triton X‐100 soluble fraction. Transendothelial electrical resistance was not significantly affected by 24 h treatments with nicotine, methylanthracene or phenanthrene. However, 24 h nicotine treatment increased transendothelial permeability in CECs exposed to oxidative stress. Both nicotine and phenanthrene were able to regulate the expression of a large number of proteins as revealed by 2D electrophoresis. Our experiments suggest that tobacco smoking may affect the junctional complex of CECs, and that this effect is enhanced by oxidative stress.
Rice P1B-Type Heavy-Metal ATPase, OsHMA9, Is a Metal Efflux Protein
Authors: Lee Sichul , Kim Yu-Young , Lee Youngsook , An Gynheung 
Published: September 2007

Abstract
P1B-type heavy-metal ATPases (HMAs) are transmembrane metal-transporting proteins that play a key role in metal homeostasis. Despite their importance, very little is known about their functions in monocot species. We report the characterization of rice (Oryza sativa) OsHMA9, a member of the P1B-type ATPase family. Semiquantitative reverse transcription-polymerase chain reaction analyses of seedlings showed that OsHMA9 expression was induced by a high concentration of copper (Cu), zinc (Zn), and cadmium. We also determined, through promoter∷β-glucuronidase analysis, that the main expression was in the vascular bundles and anthers. The OsHMA9:green fluorescence protein fusion was localized to the plasma membrane. Heterologous expression of OsHMA9 partially rescued the Cu sensitivity of the Escherichia coli copA mutant, which is defective in Cu-transporting ATPases. It did not rescue the Zn sensitivity of the zntA mutant, which is defective in Zn-transporting ATPase. To further elucidate the functional roles of OsHMA9, we isolated two independent null alleles, oshma9-1 and oshma9-2, from the T-DNA insertion population. Mutant plants exhibited the phenotype of increased sensitivity to elevated levels of Cu, Zn, and lead. These results support a role for OsHMA9 in Cu, Zn, and lead efflux from the cells. This article is the first report on the functional characterization of a P1B-type metal efflux transporter in monocots.