bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ECOLOGY AND DISTRIBUTION IN SINGAPORE OF BIDENS PILOSA L. (ASTERACEAE)
Authors: LOK A. F. S. L. , TAN K.-X. , TAN H. T. W.
Published: August 2010

Bidens pilosa is less widespread than the other composites commonly found in Singapore as it is animal-dispersed, as opposed to wind-dispersed like most of the Asteraceae. However, this species has been observed to spread over a large area within a year in suitable habitats of sandy or rocky moist substrate with adequate sunlight, such as Jalan Chichau and Jalan Lam Sam. Judging by its invasive success in other tropical and subtropical countries, it should do well in Singapore. More studies can be done on this species, and the populations in the abovementioned localities should be closely monitored to determine the success, and the spread of the species.
AN ANNOTATED CHECKLIST OF THE NON-NATIVE FRESHWATER FISH SPECIES IN THE RESERVOIRS OF SINGAPORE
Authors: NG HEOK HEE , TAN HEOK HUI
Published: August 2010

We have recorded 54 species of non-native or alien freshwater fishes from 14 of the 15 reservoirs in Singapore. 31 of these species are established and breeding in the reservoirs. Three species (Mystus wolffii, Amphilophus citrinellum, and Satanoperca jurupari) represent new alien records for Singapore.
Vasoconstriction resulting from dynamic membrane trafficking of TRPM4 in vascular smooth muscle cells
Authors: Crnich Rachael , Amberg Gregory C. , Leo M. Dennis , Gonzales Albert L. , Tamkun Michael M. , Jaggar Jonathan H. , Earley Scott
Published: August 2010

The melastatin (M) transient receptor potential (TRP) channel TRPM4 mediates pressure and protein kinase C (PKC)-induced smooth muscle cell depolarization and vasoconstriction of cerebral arteries. We hypothesized that PKC causes vasoconstriction by stimulating translocation of TRPM4 to the plasma membrane. Live-cell confocal imaging and fluorescence recovery after photobleaching (FRAP) analysis was performed using a green fluorescent protein (GFP)-tagged TRPM4 (TRPM4-GFP) construct expressed in A7r5 cells. The surface channel was mobile, demonstrating a FRAP time constant of 168 ± 19 s. In addition, mobile intracellular trafficking vesicles were readily detected. Using a cell surface biotinylation assay, we showed that PKC activation with phorbol 12-myristate 13-acetate (PMA) increased (∼3-fold) cell surface levels of TRPM4-GFP protein in <10 min. Similarly, total internal reflection fluorescence microscopy demonstrated that stimulation of PKC activity increased (∼3-fold) the surface fluorescence of TRPM4-GFP in A7r5 cells and primary cerebral artery smooth muscle cells. PMA also caused an elevation of cell surface TRPM4 protein levels in intact arteries. PMA-induced translocation of TRPM4 to the plasma membrane was independent of PKCα and PKCβ activity but was inhibited by blockade of PKCδ with rottlerin. Pressure-myograph studies of intact, small interfering RNA (siRNA)-treated cerebral arteries demonstrate that PKC-induced constriction of cerebral arteries requires expression of both TRPM4 and PKCδ. In addition, pressure-induced arterial myocyte depolarization and vasoconstriction was attenuated in arteries treated with siRNA against PKCδ. We conclude that PKCδ activity causes smooth muscle depolarization and vasoconstriction by increasing the number of TRPM4 channels in the sarcolemma.
Epinephrine-mediated regulation of PDK4 mRNA in rat adipose tissue
Authors: Wan Zhongxiao , Thrush A. Brianne , Legare Melanie , Frier Bruce C. , Sutherland Lindsey N. , Williams Deon B. , Wright David C.
Published: August 2010

Fatty acid reesterification in adipose tissue is dependent on the generation of glycerol 3-phosphate, and, at least in rodent adipose tissue, this appears to occur primarily through glyceroneogenesis. A key enzyme in this process is pyruvate dehydrogenase kinase 4 (PDK4). PDK4 is induced in white adipose tissue by thiazolidinediones (TZDs) and the inhibition or knockdown of PDK4 inhibits TZD-induced increases in glyceroneogenesis. Since TZDs have many unwanted side effects, we were interested in identifying alternative mechanisms that could regulate PDK4 mRNA expression in white adipose tissue. In this regard we hypothesized that exercise, fasting, and epinephrine would increase PDK4 mRNA levels in rat epididymal adipose tissue. We further postulated that the p38 mitogen-activated protein kinase (MAPK) and 5′-AMP-activated protein kinase (AMPK) signaling pathways would control PDK4 mRNA expression in cultured adipose tissue. Exercise, fasting, and in or ex vivo epinephrine treatment increased PDK4 mRNA levels. These perturbations did not increase the expression of PDK1, -2, or -3. Pyruvate dehydrogenase phosphorylation was increased after an overnight fast and 4 h after the cessation of exercise. In cultured adipose tissue, epinephrine increased p38 and AMPK signaling; however, the direct activation of AMPK by AICAR or metformin led to reductions in PDK4 mRNA levels. The p38 inhibitor SB202190 reduced epinephrine-mediated increases in p38 MAPK activation without altering hormone-sensitive lipase or AMPK phosphorylation or attenuating epinephrine-induced increases in lipolysis. Reductions in p38 MAPK signaling were associated with decreases in PDK4 mRNA expression. The inhibition of peroxisome proliferator-activated receptor-γ (PPARγ) also attenuated the induction of PDK4. Our results are the very first to demonstrate an epinephrine-mediated regulation of PDK4 mRNA levels in white adipose tissue and suggest that p38 MAPK and PPARγ could be involved in this pathway.
Functional NMDA receptors with atypical properties are expressed in podocytes
Authors: Anderson Marc , Suh Jae Mi , Kim Eun Young , Dryer Stuart E.
Published: August 2010

N-methyl-d-aspartate (NMDA) receptors are essential for normal nervous system function, but their excessive activation can lead to neuronal degeneration. NMDA receptors are also expressed in peripheral tissues, where their properties and significance are not well understood. Here we show that functional NMDA receptors are expressed in podocytes, polarized cells that form an essential component of the glomerular filtration apparatus. Application of NMDA to podocyte cell lines or primary cultures of mouse podocytes evoked macroscopic currents mediated by cation channels, with significant permeability to Ca2+. Podocyte NMDA receptors do not desensitize with prolonged exposure to NMDA. They are blocked by supraphysiological concentrations of external or internal Mg2+and, also, by the prototype antagonists MK-801 and d-2-aminophosphonovaleric acid. NMDA responses in podocytes were strongly potentiated by d-serine, but not by glycine, even at high concentrations. d-Aspartate and l-homocysteate are effective agonists of podocyte NMDA receptors. Surprisingly, l-glutamate and l-aspartate did not evoke robust ionic currents in podocytes, regardless of the concentration or membrane potential at which these amino acids were tested. NMDA application for 2 h caused activation of secondary signals through Erk and Akt pathways and, at higher concentrations, caused activation of RhoA. Exposure to NMDA for 6 h did not cause loss of cultured podocytes but did lead to a reduction in nephrin expression. NMDA receptors that respond to circulating ligands may play a role in regulation of glomerular function or dysfunction, but they are unlikely to be components of a local glutamate signaling system in glomeruli.
Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern
Authors: Ramalingam Arivudainambi , Wang Xuexuan , Gabello Melissa , Valenzano M. Carmen , Soler Alejandro P. , Ko Akihiro , Morin Patrice J. , Mullin James M.
Published: August 2010

The beneficial effects of caloric restriction in increasing longevity and forestalling age-related diseases are well known. Dietary restriction of methionine also renders similar benefits. We recently showed in a renal epithelial cell culture system that reduction of culture medium methionine by 80% resulted in altered tight junctional (TJ) claudin composition and also improved epithelial barrier function ( 51 ). In the current study, we examined the effect of dietary restriction of methionine on TJ barrier function in rat gastrointestinal tissue to see whether this phenomenon also holds true in a tissue model and for a different epithelial cell type. After 28 days on methionine-restricted (MR) diet, rats showed small but significant reductions in the plasma and (intracellular) colonocyte levels of methionine. Colon mucosal sheets from rats on the MR diet showed increased transepithelial electrical resistance with concomitant decrease in paracellular diffusion of14C-d-mannitol, suggesting improved barrier function relative to rats on control diet. This improved barrier function could not be explained by changes in colon crypt length or frequency. Neither was the colonocyte mitotic index nor the apoptotic frequency altered significantly. However, TJ composition/structure was being altered by the MR diet. RT-PCR and Western blot analysis showed an increase in the abundance of claudin-3 and an apparent change in the posttranslational modification of occludin, data reinforcing a paracellular barrier alteration. Overall, our data suggest that reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition.
Insulin resistance syndrome blunts the mitochondrial anabolic response following resistance exercise
Authors: Nilsson Mats I. , Greene Nicholas P. , Dobson Justin P. , Wiggs Michael P. , Gasier Heath G. , Macias Brandon R. , Shimkus Kevin L. , Fluckey James D.
Published: August 2010

Metabolic risk factors associated with insulin resistance syndrome may attenuate augmentations in skeletal muscle protein anabolism following contractile activity. The purpose of this study was to investigate whether or not the anabolic response, as defined by an increase in cumulative fractional protein synthesis rates (24-h FSR) following resistance exercise (RE), is blunted in skeletal muscle of a well-established rodent model of insulin resistance syndrome. Four-month-old lean ( Fa/?) and obese ( fa/fa) Zucker rats engaged in four lower body RE sessions over 8 days, with the last bout occurring 16 h prior to muscle harvest. A priming dose of deuterium oxide (2H2O) and 2H2O-enriched drinking water were administered 24 h prior to euthanization for assessment of cumulative FSR. Fractional synthesis rates of mixed (−5%), mitochondrial (−1%), and cytosolic (+15%), but not myofibrillar, proteins (−16%, P = 0.012) were normal or elevated in gastrocnemius muscle of unexercised obese rats. No statistical differences were found in the anabolic response of cytosolic and myofibrillar subfractions between phenotypes, but obese rats were not able to augment 24-h FSR of mitochondria to the same extent as lean rats following RE (+14% vs. +28%, respectively). We conclude that the mature obese Zucker rat exhibits a mild, myofibrillar-specific suppression in basal FSR and a blunted mitochondrial response to contractile activity in mixed gastrocnemius muscle. These findings underscore the importance of assessing synthesis rates of specific myocellular subfractions to fully elucidate perturbations in basal protein turnover rates and differential adaptations to exercise stimuli in metabolic disease.
Methods to quantify sex steroid hormones in bone: applications to the study of androgen ablation and administration
Authors: Yarrow Joshua F. , Conover Christine F. , Lipinska Judyta A. , Santillana Cesar A. , Wronski Thomas J. , Borst Stephen E.
Published: August 2010

Bone may contain an intraskeletal reservoir of sex steroids that is capable of producing biological effects. The purposes of these experiments were to 1) establish and validate methods to extract and measure intraskeletal sex hormones, 2) compare serum and intraskeletal sex hormone abundance, and 3) determine the impact of testosterone-enanthate administration and orchiectomy on intraskeletal sex hormone concentrations. Tibiae from male F344 rats were crushed, suspended in an aqueous buffer, disrupted mechanically and sonically, extracted with organic solvents, dried, and reconstituted in assay buffer appropriate for measurement of testosterone, dihydrotestosterone, and estradiol by immunoassay. Prior to extraction, bone homogenate was spiked with [3H]testosterone, [3H]dihydrotestosterone, or [3H]estradiol, and >80% of each 3H-labeled sex hormone was recovered. Extracted bone samples were also assayed with and without known amounts of unlabeled sex hormones, and >97% of the expected hormone concentrations were measured. Administration of testosterone-enanthate increased intraskeletal testosterone 11-fold and intraskeletal dihydrotestosterone by 82% without altering intraskeletal estradiol ( P < 0.01). Conversely, orchiectomy did not alter intraskeletal testosterone or estradiol but increased intraskeletal dihydrotestosterone by 39% ( P < 0.05). In intact rats, intraskeletal testosterone and dihydrotestosterone were directionally higher than in serum, whereas intraskeletal estradiol was directionally lower than serum. Serum androgens were positively correlated with intraskeletal androgens ( r = 0.74–0.96, P < 0.001); however, neither serum nor intraskeletal androgens nor serum estradiol were correlated with intraskeletal estradiol. We report the validation of a novel method for measuring intraskeletal sex hormones. Our findings demonstrate that the intraskeletal sex steroid reservoirs are modifiable and only partially influenced by circulating sex hormones.
Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men
Authors: Alibegovic A. C. , Sonne M. P. , Højbjerre L. , Bork-Jensen J. , Jacobsen S. , Nilsson E. , Færch K. , Hiscock N. , Mortensen B. , Friedrichsen M. , Stallknecht B. , Dela F. , Vaag A.
Published: August 2010

Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-γ coactivator-1α ( PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity.
p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway
Authors: Sun Lin , Xiao Li , Nie Jing , Liu Fu-you , Ling Guang-hui , Zhu Xue-jing , Tang Wen-bin , Chen Wen-cui , Xia Yun-cheng , Zhan Ming , Ma Ming-ming , Peng You-ming , Liu Hong , Liu Ying-hong , Kanwar Yashpal S.
Published: August 2010

p66Shc, a promoter of apoptosis, modulates oxidative stress response and cellular survival, but its role in the progression of diabetic nephropathy is relatively unknown. In this study, mechanisms by which p66Shc modulates high-glucose (HG)- or angiotensin (ANG) II-induced mitochondrial dysfunction were investigated in renal proximal tubular cells (HK-2 cells). Expression of p66Shc and its phosphorylated form (p-p66Shc, serine residue 36) and apoptosis were notably increased in renal tubules of diabetic mice, suggesting an increased reactive oxygen species production. In vitro, HG and ANG II led to an increased expression of total and p-p66Shc in HK-2 cells. These changes were accompanied with increased production of mitochondrial H2O2, reduced mitochondrial membrane potential, increased translocation of mitochondrial cytochrome c from mitochondria into cytosol, upregulation of the expression of caspase-9, and ultimately reduced cell survival. Overexpression of a dominant-negative Ser36 mutant p66Shc (p66ShcS36A) or treatment of p66Shc- or PKC-β-short interfering RNAs partially reversed these changes. Treatment of HK-2 cells with HG and ANG II also increased the protein-protein association between p-p66Shc and Pin1, an isomerase, in the cytosol, and with cytochrome c in the mitochondria. These interactions were partially disrupted with the treatment of PKC-β inhibitor or Pin1-short interfering RNA. These data suggest that p66Shc mediates HG- and ANG II-induced mitochondrial dysfunctions via PKC-β and Pin1-dependent pathways in renal tubular cells.
Temporal Shift From Velocity to Position Proprioceptive Feedback Control During Reaching Movements
Authors: Niu C. Minos , Corcos Daniel M. , Shapiro Mark B.
Published: August 2010

Reaching movements to a target usually have stereotypical kinematics. Although this suggests that the desired kinematics of a movement might be planned, does it also mean that deviations from the planned kinematics are corrected by proprioceptive feedback control? To answer this question, we designed a task in which the subjects made center-forward movements to a target while holding the handle of a robot. Subjects were instructed to make movements at a peak velocity of 1 m/s. No further instructions were given with respect to the movement trajectory or the velocity time profile. In randomly chosen trials the robot imposed servo-controlled deviations from the previously computed unperturbed velocity and position time profiles. The duration of the velocity deviations and the magnitude of accumulated position deviations were manipulated. The subjects were instructed to either “Attempt to correct” or “Do not correct” the movement. The responses to the imposed deviations in the surface electromyograms in the elbow and shoulder agonist muscles consisted of an initial burst followed by a sharp decrease in the “Do not correct” condition or by sustained activity in the “Attempt to correct” condition. The timing and magnitude of the initial response burst reflected those of the velocity deviations and were not affected by the instruction. The timing and magnitude of the late response activity reflected position feedback control and were strongly affected by the instruction. We suggest that proprioceptive feedback control is suppressed in the beginning of the movement, then velocity feedback control is activated in the middle of the movement to control a desired velocity, whereas position feedback control is facilitated late in the movement to acquire the final position.
Facial Injections of Pruritogens and Algogens Excite Partly Overlapping Populations of Primary and Second-Order Trigeminal Neurons in Mice
Authors: Akiyama T. , Carstens M. Iodi , Carstens E.
Published: August 2010

Intradermal cheek injection of pruitogens or algogens differentially elicits hindlimb scratching or forelimb wiping, suggesting that these behaviors distinguish between itch and pain. We studied whether pruritogens and algogens excite separate or overlapping populations of primary afferent and second-order trigeminal neurons in mice. Calcium imaging of primary sensory trigeminal ganglion (TG) cells showed that 15.4% responded to histamine, 5.8% to the protease-activated receptor (PAR)-2 agonist, 13.4% to allyl isothiocyanate (AITC), and 36.7% to capsaicin. AITC and/or capsaicin activated the vast majority of histamine- and PAR-2 agonist–sensitive TG cells. A chemical search strategy identified second-order neurons in trigeminal subnucleus caudalis (Vc) responsive to histamine, the PAR-2 agonist, or AITC. A minority of histamine or PAR-2 agonist–responsive Vc neurons responded to the other pruritogen, whereas a large majority of puritogen-responsive Vc neurons responded to capsaicin and/or AITC. A minority of AITC-responsive Vc neurons responded to pruritogens, whereas most responded to capsaicin. These data indicate that most primary and higher-order trigeminal sensory neurons are activated by both pruritic and algesic stimuli, although a minority exhibit selectivity. The results are discussed in terms of population codes for itch and pain that result in distinct behavioral responses of hindlimb scratching and forelimb wiping that are mediated at lumbar and cervical segmental levels, respectively.
Differential Contributions of Thalamic Nuclei in the Generation of Antisaccades
Authors: Cameron Ian G. M. , Watanabe Masayuki
Published: August 2010

Our knowledge of thalamus function comes largely from anatomical studies showing, for example, that the ventroanterior (VA) and ventrolateral (VL) nuclei are connected to “motor” regions, whereas the mediodorsal (MD) nucleus is connected to prefrontal “executive” regions. Interestingly, Kunimatsu and Tanaka recently showed that preparatory signals for antisaccades (a motor response requiring executive control) were enhanced compared with prosaccades in the VA/VL but not in the MD, which is surprising given MD's connection to executive regions.
The Effect of Imatinib Mesylate for Newly Diagnosed Philadelphia Chromosome-Positive, Chronic-Phase Myeloid Leukemia in Sub-Saharan African Patients: The Experience of Côte d'Ivoire
Authors: Koffi K. G. , Nanho D. C. , N'dathz E. , Kouehion P. , Dissieka R. , Attia A. , Mozard K. , Tolo A. , Boidy K. , Meité N. , Ayemou R. , Sekongo M. , Tea N. , Sanogo I.
Published: August 2010

Imatinib mesylate, showed encouraging activity in chronic myelogenous leukemia. However, there are few data regarding his efficacy and response monitoring in Sub-Saharan African patients. Our objective was to assess response to imatinib mesylate (Glivec) in Côte d’Ivoire patients with newly diagnosed Chronic Myeloid Leukemia (CML). From May 2005 to September 2009, we treated 42 patients (40 years; range 16–69) with Philadelphia chromosome (Ph+) positive in chronic phase CML with oral imatinib mesylate at daily doses of 400 mg. Overall survival (OS) and frequency of complete or major cytogenetic remission (CCR/MCR) were evaluated. At a median follow up of 32 (range 7.6–113) months, the CHR rate in our study group was 76%. A major CR was found in 19 patients (45%) with 17% and 29% complete and partial CR respectively. There were no significant differences in the incidence of major cytogenetic response by known prognostics factors. Median time to CHR was 8 months (range 0.4–25), and 16 months (range: 0.1–36) for CR. Projected 5-year OS rate was 72% (95%CI 42–88). We conclude that imatinib therapy sub-Saharan African CML patients is very promising and has favorably changed the prognosis for black African patients with CML.
Combined Reversed Phase HPLC, Mass Spectrometry, and NMR Spectroscopy for a Fast Separation and Efficient Identification of Phosphatidylcholines
Authors: Willmann Jan , Thiele Herbert , Leibfritz Dieter
Published: August 2010

In respect of the manifold involvement of lipids in biochemical processes, the analysis of intact and underivatised lipids of body fluids as well as cell and tissue extracts is still a challenging task, if detailed molecular information is required. Therefore, the advantage of combined use of high‐pressure liquid chromatography (HPLC), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy will be shown analyzing three different types of extracts of the ubiquitous membrane component phosphatidylcholine. At first, different reversed phase modifications were tested on phosphatidylcholines (PC) with the same effective carbon number (ECN) for their applicability in lipid analysis. The results were taken to improve the separation of three natural PC extract types and a new reversed phase (RP)‐HPLC method was developed. The individual species were characterized by one‐ and two‐dimensional NMR and positive or negative ion mode quadrupole time of flight (q‐TOF)‐MS as well as MS/MS techniques. Furthermore, ion suppression effects during electrospray ionisation (ESI), difficulties, limits, and advantages of the individual analytical techniques are addressed.
Aberrant Silencing of Cancer-Related Genes by CpG Hypermethylation Occurs Independently of Their Spatial Organization in the Nucleus
Authors: Easwaran Hariharan P. , Van Neste Leander , Cope Leslie , Sen Subhojit , Mohammad Helai P. , Pageau Gayle J. , Lawrence Jeanne B. , Herman James G. , Schuebel Kornel E. , Baylin Stephen B.
Published: August 2010

Aberrant promoter DNA-hypermethylation and repressive chromatin constitutes a frequent mechanism of gene inactivation in cancer. There is great interest in dissecting the mechanisms underlying this abnormal silencing. Studies have shown changes in the nuclear organization of chromatin in tumor cells as well as the association of aberrant methylation with long-range silencing of neighboring genes. Furthermore, certain tumors show a high incidence of promoter methylation termed as the CpG island methylator phenotype. Here, we have analyzed the role of nuclear chromatin architecture for genes in hypermethylated inactive versus nonmethylated active states and its relation with long-range silencing and CpG island methylator phenotype. Using combined immunostaining for active/repressive chromatin marks and fluorescence in situ hybridization in colorectal cancer cell lines, we show that aberrant silencing of these genes occurs without requirement for their being positioned at heterochromatic domains. Importantly, hypermethylation, even when associated with long-range epigenetic silencing of neighboring genes, occurs independent of their euchromatic or heterochromatic location. Together, these results indicate that, in cancer, extensive changes around promoter chromatin of individual genes or gene clusters could potentially occur locally without preference for nuclear position and/or causing repositioning. These findings have important implications for understanding relationships between nuclear organization and gene expression patterns in cancer. Cancer Res; 70(20); 8015–24. ©2010 AACR.
Folotyn (Pralatrexate Injection) for the Treatment of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma: U.S. Food and Drug Administration Drug Approval Summary
Authors: Malik Shakun M. , Liu Ke , Qiang Xu , Sridhara Rajeshwari , Tang Shenghui , McGuinn W. David , Verbois S. Leigh , Marathe Anshu , Williams Gene M. , Bullock Julie , Tornoe Christoffer , Lin Sue Ching , Ocheltree Terrance , Vialpando Milinda , Kacuba Alice , Justice Robert , Pazdur Richard
Published: August 2010

Purpose: On September 24, 2009, the U.S. Food and Drug Administration granted accelerated approval for Folotyn (pralatrexate injection, Allos Therapeutics, Inc.) as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL); it is the first drug approved for this indication.

Experimental Design: This review was based on study PDX-008, a phase II, single-arm, nonrandomized, open-label, international, multicenter trial, designed to evaluate the safety and efficacy of pralatrexate when administered concurrently with vitamin B12 and folic acid supplementation in patients with relapsed or refractory PTCL.

Results: The overall response rate was 27% in 109 evaluable patients [95% confidence interval (CI), 19–36%]. Twelve percent of 109 evaluable patients (95% CI, 7–20%)] had a response duration of ≥14 weeks. Six of these 13 patients achieved a complete response, and one patient had complete response unconfirmed. The most common grade 3 and 4 toxicities were thrombocytopenia, mucositis, and neutropenia.

Conclusion: This accelerated approval was based on a response rate that is reasonably likely to predict clinical benefit in this heavily pretreated patient population with this rare disease. The applicant has committed to conducting postmarketing clinical trials to assess clinical benefit. The recommended starting dose of pralatrexate in patients with relapsed or refractory PTCL is 30 mg/m2 via intravenous push over 3 to 5 min weekly for 6 weeks followed by a one-week rest (one cycle). Intramuscular injection of 1 mg vitamin B12 should be administered every 8 to 10 weeks along with 1.0 mg folic acid given orally once a day. Clin Cancer Res; 16(20); 4921–7. ©2010 AACR.
Disruption of Androgen and Estrogen Receptor Activity in Prostate Cancer by a Novel Dietary Diterpene Carnosol: Implications for Chemoprevention
Authors: Johnson Jeremy J. , Syed Deeba N. , Suh Yewseok , Heren Chenelle R. , Saleem Mohammad , Siddiqui Imtiaz A. , Mukhtar Hasan
Published: August 2010

Emerging data are suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion, agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of nontoxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through molecular modeling, we found that carnosol, a dietary diterpene, fits within the ligand-binding domain of both AR and ER-α. Using a time-resolved fluorescence resonance energy transfer assay, we found that carnosol interacts with both AR and ER-α and additional experiments confirmed that it functions as a receptor antagonist with no agonist effects. LNCaP, 22Rv1, and MCF7 cells treated with carnosol (20-40 μmol/L) showed decreased protein expression of AR and ER-α. Oral administration of carnosol at 30 mg/kg 5 days weekly for 28 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 36% (P = 0.028) and was associated with a decrease in serum prostate-specific antigen by 26% (P = 0.0042). These properties make carnosol unique to any known antiandrogen or antiestrogen investigated thus far for the simultaneous disruption of AR and ER-α. We suggest that carnosol may be developed or chemically modified through more rigorous structure-activity relationship studies for a new class of investigational agents—a dual AR/ER modulator. Cancer Prev Res; 3(9); 1112–23. ©2010 AACR.
Coronary Artery Bypass Grafting After Recent or Remote Percutaneous Coronary Intervention in the Commonwealth of Massachusetts
Authors: Stevens Louis-Mathieu , Khairy Paul , Agnihotri Arvind K.
Published: August 2010

Background—

In this study, we sought to characterize the outcomes after isolated coronary artery bypass grafting (CABG) in patients with a history of remote (≥14 days), and recent (<14 days), percutaneous coronary intervention (PCI).

Methods and Results—

Patients with PCI within 5 years of CABG were identified among 12 591 primary isolated CABG reported in the mandatory Massachusetts Adult Cardiac Surgery Database. Patients were excluded if they were out-of-state (n=1043, 8%), had undergone primary PCI for acute myocardial infarction (n=401, 3%), had a PCI-CABG interval >5 years or unknown (n=136 and n=673, 1% and 5%). Patients with a history of remote and recent PCI were analyzed separately. Each CABG patient with PCI was matched to 3 patients without PCI using a propensity score. Outcomes were analyzed using generalized estimating equations and stratified proportional hazards models, with a mean follow-up of 4.1±1.2 years. There were 1117 CABG patients (9%) with prior PCI (n
remote
=823; n
recent
=294). In matched CABG patients with remote prior PCI, no differences were found in 30-day mortality (1.1% versus 1.5%;
P
=0.432), hospital morbidity (41% versus 40%;
P
=0.385) and overall survival (hazard ratio, [95% confidence interval] for death for prior PCI, 0.93 [0.74 to 1.18];
P
=0.555). In matched CABG patients with recent prior PCI, hospital morbidity was higher (59% versus 45%;
P
<0.001), but no differences were found in 30-day mortality (3.5% versus 3.1%;
P
=0.754) and overall survival (HR, 1.18 [0.83 to 1.69];
P
=0.353).

Conclusions—

In patients undergoing CABG, remote prior PCI (≥14 days) was not associated with adverse outcomes at 30 days or during long-term follow-up.
Glocalization of social work practice: Global and local responses to globalization
Authors: Hong Philip Young P. , In Han Song
Published: August 2010

Globalization has become a catchword for the integration of local markets into world capitalism. This article raises social justice concerns in governments shirking their social responsibilities for caring for those who are most vulnerable to the risk of globalization. By structuring the world as a global society where both local and global responses can interact to ameliorate the conditions of global citizens, the article proposes a glocalization approach to social work practice: thinking globally and acting locally (Lyons, 2006). It argues for the formation and growth of global civil society, accompanied by the establishment of a global social policy system and sub-systems.
Post-colonialist practice: An Australian social worker in rural Zambia
Authors: Fox Mim
Published: August 2010

Globalization has seen an increase in social workers engaging in post-colonialist practice around the world. A working example is provided of an Australian social worker travelling to rural Zambia with the aim of the development and implementation of grief and loss workshops for local community leaders. Principles of community development, adult education and community education theories inform such practice, allowing the external social worker to contribute positively to the life of another community. In this environment the internal and external resources of the social worker are tested and utilized in the aim of joint partnership.
Polymorphisms in the Matrilin-1 Gene and Risk of Mandibular Prognathism in Koreans
Authors: Jang J.Y. , Park E.K. , Ryoo H.M. , Shin H.I. , Kim T.H. , Jang J.S. , Park H.S. , Choi J.Y. , Kwon T.G.
Published: August 2010

Previous linkage analysis of an Asian population proposed possible candidate genes for mandibular prognathism, such as Matrilin-1 (cartilage matrix protein). To investigate the association between the single-nucleotide polymorphisms (SNPs) in Matrilin-1 and mandibular prognathism, we investigated three sequence variants (-158 T>C, 7987 G>A, 8572 C>T) in 164 mandibular prognathism patients and 132 control individuals with a normal occlusion. The results showed that the 8572 TT genotypes in Matrilin-1 showed increased risk of mandibular prognathism (OR = 9.28, 95% Cl = 1.19~197.57, P < 0.05), whereas the 7987 AA genotype showed a protective effect for mandibular prognathism (OR = 0.16, 95% Cl = 0.05~0.47, P < 0.05). Genotyping results showed that the Matrilin-1 polymorphism haplotype TGC (ht4; 158T, 7987G, and 8572C alleles) had a pronounced risk effect for mandibular prognathism compared with controls (OR = 5.16, 95% Cl = 2.03~13.93, P < 0.01). The results suggest that polymorphisms in Matrilin-1 could be used as a marker for genetic susceptibility to mandibular prognathism.
Towards an ontology of Bob Dylan
Authors: Richardson William J.
Published: August 2010

This lecture was first delivered at Tulane University, New Orleans, Louisiana, in 1966. What relevance it may have to the Dylan of 2010 only the reader can say.
The illusion of purity: Chantal Mouffe’s realist critique of cosmopolitanism
Authors: Thaler Mathias
Published: August 2010

Over the last 20 years, cosmopolitan theories have been benefiting greatly from the dialogue between defenders and critics of world citizenship. Yet, the decidedly polemic aspect of this debate, while allowing for intellectual progress, is also responsible for overdrawn generalizations. Instead of entering into the debate directly, this article attempts to refute a specific anti-cosmopolitan claim raised by Chantal Mouffe. Her realist objection to cosmopolitanism, derived from the conceptual framework of agonistic pluralism, is mistaken at a crucial point: a firm dichotomy between politics and morality cannot provide an alternative to theories of world citizenship, because Mouffe’s embrace of multipolarity as a principle of global politics must equally appeal to a set of universal norms governing international relations. This article argues that even the realist model of multipolarity needs to conceive of a minimal morality to create the symbolic ground on which various power centres can be held accountable.
The Effect of Age on the Outcomes of Arthroscopic Repair of Type II Superior Labral Anterior and Posterior Lesions
Authors: Alpert Joshua M. , Wuerz Thomas H. , O'Donnell Thomas F. X. , Carroll Kaitlin M. , Brucker Nathan N. , Gill Thomas J.
Published: August 2010

Background

The majority of clinical outcome studies of type II superior labral anterior and posterior (SLAP) repair assess patients younger than age 40. Biceps tenotomy or tenodesis is often recommended for patients older than age 40 with superior labrum-biceps complex injury.

Hypothesis

There is no difference in patient clinical outcomes comparing arthroscopic type II SLAP repair in patients younger or older than age 40.

Study Design

Cohort study; Level of evidence, 3.

Methods

Fifty-two patients stratified to groups younger than age 40 (21 patients; average age, 32.9 years) and older than age 40 (31 patients; average age, 55.1 years) were identified at a minimum 2-year follow-up (average, 28 months) after type II SLAP repair by a single surgeon using suture anchors. Outcome scores included American Shoulder and Elbow Society scores (ASES), Short Form-12 scores, Simple Shoulder Test scores, and visual analog pain scale.

Results

At follow-up, there was no statistical difference in visual analog pain scale (P = .16), ASES scores (P = .07), Simple Shoulder Test scores (P =.41), Short Form-12 testing, or range of motion testing. Patients older than age 40 noted their shoulder to be 87% of normal; 26 of 31 (84%) were satisfied to completely satisfied, and 28 of 31 (90%) would have the surgery again. Patients younger than 40 noted their shoulder to be approximately 89% of normal; 20 of 21 (95%) were satisfied to completely satisfied, and 18 of 21 (86%) would have the same procedure performed again.

Conclusion

Our findings support that arthroscopic treatment of isolated type II SLAP repair using suture anchors can yield good to excellent results in patients older and younger than age 40. We found no statistically significant difference in patient outcome scores, satisfaction levels, or willingness to have the same procedure again when comparing arthroscopic SLAP repair in patients younger or older than age 40.
The Evolution of Nursing Home Report Cards
Authors: Castle Nicholas , Diesel Jill , Ferguson-Rome Jamie C.
Published: August 2010

Nursing home report cards can be potentially key tools for disseminating information to consumers. However, few accounts of state-based nursing home report cards are available. In the research presented here, the scale, scope, utility, and changes over time in these nursing home report cards are described. This article finds that the number of report cards has increased from 24 in 2003 to 29 in 2009. The quality information presented varies considerably; however, deficiency citations are still the most frequently reported quality indicators. The utility of report cards varies considerably. The authors present their opinions of features that seem most conducive for consumer use of these report cards.
Distrusting Democrats and Political Participation in New Democracies
Authors: Carlin Ryan E.
Published: August 2010

Distrusting democrats seek accountability and advocate reform in established democracies. Do they behave similarly in new democracies? Using AmericasBarometer survey data, cluster analysis identifies five profiles of democratic support in Chile: democrat, delegative, fair-weather, illiberal, and autocrat. Chilean distrusting democrats are more active in protest politics but less active in electoral politics than other Chileans, especially fair-weather democrats. The support profiles better predict these behaviors than the classic Linzian and Churchillian measures of democratic support. Thus, distrusting democrats in Chile only partially emulate their counterparts in established democracies, suggesting citizen-led democratic reforms in new democracies could be far more challenging.
Intersectionality and Public Policy: Some Lessons from Existing Models
Authors: Hankivsky Olena , Cormier Renee
Published: August 2010

In comparison to research practices, intersectionality is an underdeveloped concept within policy discourse and application. Because of the complexity and relative newness of this approach, policy analysis grounded within an intersectionality framework remains largely undertheorized, and methods for integrating intersectionality into policy processes are in the nascent stages. This article (1) defines intersectionality and demonstrates the need for this approach in public policy, (2) outlines challenges in applying intersectionality to policy making, and (3) describes and evaluates three innovative approaches to applying intersectionality to policy development and analysis.
Anti-Inflammatory Effect of Maraviroc in an HIV-Infected Patient With Concomitant Myositis: A Case Report
Authors: Capetti Amedeo F. , Pocaterra Daria , Zucchi Patrizia , Carenzi Laura , Rizzardini Giuliano
Published: August 2010

We report the surprising yet sought impact that an antiretroviral (ARV) regimen containing maraviroc had on an HIV-infected and heavily highly active antiretroviral therapy (HAART)-experienced patient with chronic polymyositis. The patient had elevated creatine kinase (CK) levels in serum for 6 years, reaching peaks over 900 U/L and showing only partial response to high-dose steroids, not responding to HAART withdrawal. The disease started while on second-line HAART and gradually impaired his muscular function, leading to the absolute loss of the ability to stand on his legs. Atherosclerosis and hypertension contributed to the development of myocardial infarction. The association of unboosted atazanavir (ATV) plus maraviroc was designed hoping in a protective role on the cardiovascular system and in an anti-inflammatory effect that some authors have hypothesized. After only 3 months the patient’s CK levels had normalized and with the help of rehabilitation he recovered the ability to walk, which he still maintains at the one year of observation.
Occurrence of Stavudine-Induced Lactic Acidosis in 3 Members of an African Family
Authors: Fielder Jon , Rambiki Kelvin
Published: August 2010

Fixed-dose combinations containing stavudine have played a critical role in the worldwide scale-up of antiretroviral therapy, but increasing concern exists regarding adverse events due to mitochondrial toxicity. We describe the first reported occurrence of lactic acidosis within a family of 3 HIV-infected individuals. This report is only the second of lactic acidosis affecting an African child. Further research is indicated to identify possible genetic and other risk factors underlying mitochondrial toxicity in African populations, especially among pediatric cohorts.
Influence of primary annealing on Goss development in grain oriented silicon steels
Authors: Jia J L , Liu L H , Shi W , Wu X L , Li L J , Zhai Q J
Published: August 2010

Two different primary annealing conditions (continuous heating and discontinuous heating) on conventional oriented silicon steel were employed, and the evolution of microstructure and Goss frequency, as well as orientations of Goss neighbourhood from recovery to secondary recrystallisation, was investigated by means of optical microscopy and advanced electron backscatter diffraction (EBSD) technique. It could be concluded that high Goss frequency before secondary recrystallisation possibly did not contribute to sharp Goss orientation, even excellent magnetic property and that no grains with less deviation from ideal Goss first began to grow. As for coincidence site lattice (CSL) grain boundary and high energy grain boundary theories, the latter can explain the development of Goss due to its high frequency compared with CSL boundary of low frequency.
Ultrasonic spot welding of aluminium to steel for automotive applications—microstructure and optimisation
Authors: Prangnell P. , Haddadi F. , Chen Y. C.
Published: August 2010

Energy efficient methods for joining aluminium to steel have potential for major applications in the automobile industry. Results are reported where 1 mm gauge 6111 aluminium and DC04 steel automotive sheet have been successfully joined using the novel process of high power ultrasonic spot welding. The microstructure and performance of the joints were examined, as a function of the welding conditions. A maximum failure load of 2·8 kN was obtained in lap shear tests, compared with 2·9 kN for comparable AI-AI joints. The failure mode changed from interfacial debonding to nugget pullout and back to interfacial failure as the weld energy increased. A thin <2 μm reaction layer of FeAI3 and Fe2Al5 formed at the interface with increasing weld energy. The factors determining the joint characteristics, interface reaction, and the microstructure evolution in the welds are discussed.
Effects of liquid–liquid transition on solidification of Sb–10 wt-%Cu alloy
Authors: Zu F. Q. , Mao L. N. , Hu C. M. , Chen J. , Huang Z. Y. , Liu Y. C. , Liu M. Q.
Published: August 2010

The electrical resistivity of the liquid Sb–10 wt-%Cu alloy as a function of temperature was measured using direct current four probe technique. In a relatively high temperature zone above the liquidus, the resistivity–temperature ( ρ – T ) curves of the melt change abnormally; moreover, the changing pattern in the first heating process is completely different from the ones in the subsequent heating and cooling cycles. Since resistivity is a structural sensitive parameter, these abnormal changes of ρ – T curves indicate that the temperature-induced liquid–liquid structure transitions (L-LSTs) probably occur in Sb–10 wt-%Cu melt, with some reversible characters. To explore the effects of the L-LST on the solidification behaviours and solidified microstructures of this alloy, solidification experiments were further carried out according to the temperature ranges with anomalous changes on ρ – T curves. Results show that after the melt experienced the L-LST, larger undercooling, shorter solidified time and much finer microstructures with differently microscopic patterns could be obtained.