bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythropoietin enhancement of rat pancreatic tumor cell proliferation requires the activation of ERK and JNK signals
Authors: Bose Chhanda , Udupa Kodetthoor B.
Published: June 2008

Erythropoietin (EPO) regulates the proliferation and differentiation of erythroid cells by binding to its specific transmembrane receptor EPOR. Recent studies, however, have shown that the EPOR is additionally present in various cancer cells and EPO induces the proliferation of these cells, suggesting a different function for EPO other than erythropoiesis. Therefore, the purpose of the present study was to examine EPOR expression and the role of EPO in the proliferation and signaling cascades involved in this process, using the rat pancreatic tumor cell line AR42J. Our results showed that AR42J cells expressed EPOR, and EPO significantly enhanced their proliferation. Cell cycle analysis of EPO-treated cells indicated an increased percentage of cells in the S phase, whereas cell numbers in G0/G1 phase were significantly reduced. Phosphorylation of extracellular regulatory kinase 1/2 (ERK1/2) and c-Jun NH2 terminal kinase 1/2 (JNK1/2) was rapidly stimulated and sustained after EPO addition. Treatment of cells with mitogen-activated protein/ERK kinase (MEK) inhibitor PD98059 or JNK inhibitor SP600125 significantly inhibited EPO-enhanced proliferation and also increased the fraction of cells in G0/G1 phase. Furthermore, the inhibition of JNK using small interference RNA (siRNA) suppressed EPO-enhanced proliferation of AR42J cells. Taken together, our results indicate that AR42J cells express EPOR and that the activation of both ERK1/2 and JNK1/2 by EPO is essential in regulating proliferation and the cell cycle. Thus both appear to play a key role in EPO-enhanced proliferation and suggest that the presence of both is required for EPO-mediated proliferation of AR42J cells.
Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants
Authors: Kidd Mark , Modlin Irvin M. , Gustafsson Bjorn I. , Drozdov Ignat , Hauso Oyvind , Pfragner Roswitha
Published: June 2008

Mechanisms by which gut luminal content regulates secretion and motility are ill understood. We evaluated whether neuroendocrine enterochromaffin (EC) cells act as luminal sensors for a wide variety of nutrients and defined the secretory mechanisms of this process. Pure (98–99%) FACS-sorted human EC cells and neoplastic EC cells (KRJ-I) were studied. RT-PCR identified transcripts for T2R1 (bitter), OR1G1 (class II olfactory) and trace amine (TAR1) G protein-coupled receptors (GPCRs) and transporters for glutamine (SNAT1/2), glucose (GLUT1/3/SGLT1), and bile salts (ABST). Glutamine and sodium deoxycholate stimulated 5-HT release (EC50= 0.002–0.2 μM; 2-fold release) but were 10–100 times more potent in neoplastic EC cells, which also secreted 6–13 times more 5-HT. Tastants (caffeine, tyramine, octopamine) and olfactants (thymol and eugenol) also stimulated normal and neoplastic EC cell 5-HT secretion (EC50= 1.2 nM to 2.1 μM and 0.05 nM to 0.1 μM release, respectively); 2-deoxyglucose and the artificial sweetener sucralose also stimulated (EC50= 9.2 and 0.38 nM). 5-HT release was associated with ERK phosphorylation (1.5-fold, P < 0.02) and could be inhibited by a somatostatin analog (IC50= 1 pM). Eleven secretory associated genes including the vesicle docking inhibitor STXBP3 were upregulated in response to glutamine and bile salt stimulation in neoplastic EC cells. Targeting STXBP3 expression by use of antisense knockdown significantly ( P < 0.05) reduced 5-HT secretion. In conclusion, EC cells express GPCRs and transporters for luminal tastants, olfactants, glutamine, glucose, and bile salts. Activation includes a panel of secretory genes, ERK phosphorylation, and 5-HT secretion. Luminal EC cell regulation is likely to be as important as G cell regulation in gastric acid secretion; development of agents to target EC cell function is therefore a critical therapeutic goal.
Differentiation of a murine intestinal epithelial cell line (MIE) toward the M cell lineage
Authors: Kanaya Takashi , Miyazawa Kohtaro , Takakura Ikuro , Itani Wataru , Watanabe Kouichi , Ohwada Shyuichi , Kitazawa Haruki , Rose Michael T. , McConochie Huw R. , Okano Hideyuki , Yamaguchi Takahiro , Aso Hisashi
Published: June 2008

M cells are a kind of intestinal epithelial cell in the follicle-associated epithelium of Peyer's patches. These cells can transport antigens and microorganisms into underlying lymphoid tissues. Despite the important role of M cells in mucosal immune responses, the origin and mechanisms of differentiation as well as cell death of M cells remain unclear. To clarify the mechanism of M cell differentiation, we established a novel murine intestinal epithelial cell line (MIE) from the C57BL/6 mouse. MIE cells grow rapidly and have a cobblestone morphology, which is a typical feature of intestinal epithelial cells. Additionally, they express cytokeratin, villin, cell-cell junctional proteins, and alkaline phosphatase activity and can form microvilli. Their expression of Musashi-1 antigen indicates that they may be close to intestinal stem cells or transit-amplifying cells. MIE cells are able to differentiate into the M cell lineage following coculture with intestinal lymphocytes, but not with Peyer's patch lymphocytes (PPL). However, PPL costimulated with anti-CD3/CD28 MAbs caused MIE cells to display typical features of M cells, such as transcytosis activity, the disorganization of microvilli, and the expression of M cell markers. This transcytosis activity of MIE cells was not induced by T cells isolated from PPL costimulated with the same MAbs and was reduced by the depletion of the T cell population from PPL. A mixture of T cells treated with MAbs and B cells both from PPL led MIE cells to differentiate into M cells. We report here that MIE cells have the potential ability to differentiate into M cells and that this differentiation required activated T cells and B cells.
Hepatic Mrp4 induction following acetaminophen exposure is dependent on Kupffer cell function
Authors: Campion Sarah N. , Johnson Rachel , Aleksunes Lauren M. , Goedken Michael J. , van Rooijen Nico , Scheffer George L. , Cherrington Nathan J. , Manautou José E.
Published: June 2008

During acetaminophen (APAP) hepatotoxicity, increased expression of multidrug resistance-associated proteins 2, 3, and 4 (Mrp2-4) occurs. Mrp4 is the most significantly upregulated transporter in mouse liver following APAP treatment. Although the expression profiles of liver transporters following APAP hepatotoxicity are well characterized, the regulatory mechanisms contributing to these changes remain unknown. We hypothesized that Kupffer cell-derived mediators participate in the regulation of hepatic transporters during APAP toxicity. To investigate this, C57BL/6J mice were pretreated with clodronate liposomes (0.1 ml iv) to deplete Kupffer cells and then challenged with APAP (500 mg/kg ip). Liver injury was assessed by plasma alanine aminotransferase and hepatic transporter protein expression was determined by Western blot and immunohistochemistry. Depletion of Kupffer cells by liposomal clodronate increased susceptibility to APAP hepatotoxicity. Although increased expression of several efflux transporters was observed after APAP exposure, only Mrp4 was found to be differentially regulated following Kupffer cell depletion. At 48 and 72 h after APAP dosing, Mrp4 levels were increased by 10- and 33-fold, respectively, in mice receiving empty liposomes. Immunohistochemistry revealed Mrp4 staining confined to centrilobular hepatocytes. Remarkably, Kupffer cell depletion completely prevented Mrp4 induction by APAP. Elevated plasma levels of TNF-α and IL-1β were also prevented by Kupffer cell depletion. These findings show that Kupffer cells protect the liver from APAP toxicity and that Kupffer cell mediators released in response to APAP are likely responsible for the induction of Mrp4.
Biventricular pacing in chronic heart failure acutely facilitates the arterial baroreflex
Authors: Gademan Maaike G. J. , van Bommel Rutger J. , Ypenburg Claudia , Haest Joris C. W. , Schalij Martin J. , van der Wall Ernst E. , Bax Jeroen J. , Swenne Cees A.
Published: June 2008

Metabolic and mechanical stress in the failing heart activates the cardiac sympathetic afferent reflex (CSAR). It has been demonstrated that cardiac resynchronization therapy (CRT) acutely reduces MSNA in clinical responders. Mechanistically, this beneficial effect might be explained by acute deactivation of the CSAR. In addition to sympathoexcitation, CSAR inhibits the arterial baroreflex at the level of the nucleus tractus solitarii. Hence, in responders, CRT is likely to remove/reduce this inhibition. Therefore, we hypothesized that CRT acutely facilitates the arterial baroreflex. One day after implantation of a CRT device in 32 patients with chronic heart failure (LVEF; 27 ± 6%), we measured noninvasive baroreflex sensitivity (BRS) and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). BRS changes were correlated with the difference in unpaced/paced LVEF, a measure of acute mechanical response to CRT. CRT increased BRS by 35% from 2.96 to 3.79 ms/mmHg ( P < 0.02) and increased HRV (standard deviation of the intervals between normal beats) from 18.5 to 24.0 ms ( P < 0.01). The CRT-induced relative change in BRS correlated with the change in LVEF ( r = 0.44; P < 0.01). In conclusion, CRT acutely increases BRS and HRV. This favorable response of the autonomic nervous system might be caused by CRT-induced CSAR deactivation. Follow-up studies should verify the mechanism of the acute response and the possible predictive value of an acute positive BRS response.
Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury
Authors: Lai Zhong-Fang , Chen Yu-Zhen , Feng Li-Ping , Meng Xian-Min , Ding Jin-Feng , Wang Lai-Yuan , Ye Jue , Li Ping , Cheng Xiao-Shu , Kitamoto Yasunori , Monzen Koshiro , Komuro Issei , Sakaguchi Nobuo , Kim-Mitsuyama Shokei
Published: June 2008

TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome. In the present study we investigated the role of TNNI3K in the cardiac myogenesis process and in the repair of ischemic injury. Pluripotent P19CL6 cells with or without transfection by pcDNA6-TNNI3K plasmid were used to induce differentiation into beating cardiomyocytes. TNNI3K promoted the differentiation process, judging from the increasing beating mass and increased number of α-actinin-positive cells. TNNI3K improved cardiac function by enhancing beating frequency and increasing the contractile force and epinephrine response of spontaneous action potentials without an increase of the single-cell size. TNNI3K suppressed phosphorylation of cardiac troponin I, annexin-V+ cells, Bax protein, and p38/JNK-mediated apoptosis. Intramyocardial administration of TNNI3K-overexpressing P19CL6 cells in mice with myocardial infarction improved cardiac performance and attenuated ventricular remodeling compared with injection of wild-type P19CL6 cells. In conclusion, our study clearly indicates that TNNI3K promotes cardiomyogenesis, enhances cardiac performance, and protects the myocardium from ischemic injury by suppressing p38/JNK-mediated apoptosis. Therefore, modulation of TNNI3K activity would be a useful therapeutic approach for ischemic cardiac disease.
Factors released from embryonic stem cells inhibit apoptosis in H9c2 cells through PI3K/Akt but not ERK pathway
Authors: Singla Dinender K. , Singla Reetu D. , McDonald Debbie E.
Published: June 2008

We recently reported that embryonic stem cells-conditioned medium (ES-CM) contains antiapoptotic factors that inhibit apoptosis in the cardiac myoblast H9c2 cells. However, the mechanisms of inhibited apoptosis remain elusive. In this report, we provide evidence for the novel mechanisms involved in the inhibition of apoptosis provided by ES-CM. ES-CM from mouse ES cells was generated. Apoptosis was induced after exposure with H2O2 (400 μm) in H9c2 cells followed by the replacement with ES-CM or culture medium. H9c2 cells treated with H2O2 were exposed to ES-CM, and ES-CM plus cell survival protein phosphatidylinositol 3-kinase/Akt inhibitor, LY-294002, or extracellular signal-regulated kinase (ERK1/2) inhibitor, PD-98050. After 24 h, H9c2 cells treated with ES-CM demonstrated a significant increase in cell survival. ES-CM significantly inhibited ( P < 0.05) apoptosis determined by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining, apoptotic ELISA, and caspase-3 activity. Importantly, enhanced cell survival and inhibited apoptosis with ES-CM was abolished with LY-294002. In contrast, PD-98050 shows no effect on ES-CM-increased cell survival. Furthermore, H2O2-induced apoptosis is associated with decreased levels of phosphorylated (p)Akt activity. Following treatment with ES-CM, we observed a decrease in apoptosis with an increase in pAkt, and the increased activity was attenuated with the Akt inhibitor, suggesting that the Akt pathway is involved in the decreased apoptosis and cell survival provided by ES-CM. In contrast, we observed no change in ES-CM-decreased apoptosis or pERK with PD-98050. In conclusion, we suggest that ES-CM inhibited apoptosis and is mediated by Akt but not the ERK pathway.
Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow
Authors: Metaxa Eleni , Meng Hui , Kaluvala Shashikanth R. , Szymanski Michael P. , Paluch Rocco A. , Kolega John
Published: June 2008

Little is understood about endothelial cell (EC) responses to high flow, which mediate adaptive outward remodeling as well as cerebral aneurysm development. Opposite EC behaviors have been reported in vivo including cell loss during aneurysm initiation and cell proliferation during adaptive outward remodeling. This study aims at elucidating the EC growth response to elevated wall shear stress (WSS) and determining if nitric oxide (NO) is involved. A confluent EC monolayer was subjected to steady-state, laminar flow with WSS ranging from 15 to 100 dyn/cm2 for 24 and 48 h. Cells oriented to the direction of the flow with a time course that varied with WSS. At 48 h, all cells were aligned with the flow. EC proliferation was examined using bromodeoxyuridine (BrdU) incorporation. The percentage of proliferating ECs rose linearly from 15 to 50 dyn/cm2 to more than sixfold at 50–100 dyn/cm2 compared with the accepted physiological baseline of 15–20 dyn/cm2. In addition, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) staining revealed that apoptosis decreased with increasing WSS. These results demonstrate that high WSS stimulates EC proliferation and suppresses apoptosis. Furthermore, immunostaining revealed increased endothelial nitric oxide synthase (eNOS) production with increasing WSS. NOS inhibition with Nω-nitro-l-arginine methyl ester (l-NAME) drastically reduced the WSS-stimulated proliferation, indicating a critical role of NO production in the stimulation of EC proliferation by high WSS.
Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice
Authors: Bem R. A. , Farnand A. W. , Wong V. , Koski A. , Rosenfeld M. E. , van Rooijen N. , Frevert C. W. , Martin T. R. , Matute-Bello G.
Published: June 2008

Activation of the Fas/Fas ligand (FasL) system in the lungs results in a form of injury characterized by alveolar epithelial apoptosis and neutrophilic inflammation. Studies in vitro show that Fas activation induces apoptosis in alveolar epithelial cells and cytokine production in alveolar macrophages. The main goal of this study was to determine the contribution of alveolar macrophages to Fas-induced lung inflammation in mice, by depleting alveolar macrophages using clodronate-containing liposomes. Liposomes containing clodronate or PBS were instilled by intratracheal instillation. After 24 h, the mice received intratracheal instillations of the Fas-activating monoclonal antibody Jo2 or an isotype control antibody and were studied 18 h later. The Jo2 MAb induced increases in bronchoalveolar lavage fluid (BALF) total neutrophils, lung caspase-3 activity, and BALF total protein and worsened histological lung injury in the macrophage-depleted mice. Studies in vitro showed that Fas activation induced the release of the cytokine KC in a mouse lung epithelial cell line, MLE-12. These results suggest that the lung inflammatory response to Fas activation is not primarily dependent on resident alveolar macrophages and may instead depend on cytokine release by alveolar epithelial cells.
Effect of small intestinal glucose load on plasma ghrelin in healthy men
Authors: Cukier Kimberly , Pilichiewicz Amelia N. , Chaikomin Reawika , Brennan Ixchel M. , Wishart Judith M. , Rayner Christopher K. , Jones Karen L. , Horowitz Michael , Feinle-Bisset Christine
Published: June 2008

Postprandial ghrelin suppression arises from the interaction of meal contents with the small intestine and may relate to elevations in blood glucose and/or plasma insulin. We sought to determine whether the suppression of ghrelin by small intestinal glucose is dependent on the glucose load and can be accounted for by changes in blood glucose and/or plasma insulin. Blood glucose, plasma insulin, and plasma ghrelin levels were measured in 10 healthy males (aged 32 ± 4 yr; body mass index: 25.1 ± 0.4 kg/m2) during intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2), and 4 kcal/min (G4), as well as intraduodenal hypertonic saline (control) for 120 min. There was a progressive decrease in ghrelin with all treatments, control at 45 min and between 90 and 120 min ( P < 0.05) and G1 ( P < 0.05), G2 ( P < 0.0001), and G4 ( P < 0.0001) between 30 and 120 min to reach a plateau at ∼90 min. There was no difference in plasma ghrelin between G1, G2, or G4. Control suppressed ghrelin to a lesser extent than intraduodenal glucose ( P < 0.05). The suppression of ghrelin was not related to rises in blood glucose or plasma insulin. Suppression of ghrelin by intraduodenal glucose in healthy males is apparently independent of the glucose load and unrelated to blood glucose or insulin levels.
Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence
Authors: Song C. Kay , Vaughan Cheryl H. , Keen-Rhinehart Erin , Harris Ruth B. S. , Richard Denis , Bartness Timothy J.
Published: June 2008

A precise understanding of neural circuits controlling lipid mobilization and thermogenesis remains to be determined. We have been studying the sympathetic nervous system (SNS) contributions to white adipose tissue (WAT) lipolysis largely in Siberian hamsters. Central melanocortins are implicated in the control of the sympathetic outflow to WAT, and, moreover, the melanocortin 4 receptors (MC4-R) appear to be principally involved. We previously found that acute third ventricular melanotan II (MTII; an MC3/4-R agonist) injections increase sympathetic drive (norepinephrine turnover) to interscapular brown adipose tissue (IBAT) and IBAT temperature. Here we tested whether MC4-R mRNA is expressed in IBAT SNS outflow neurons using in situ hybridization for the former and injections of the transneuronal viral retrograde tract tracer, pseudorabies virus (PRV) into IBAT, for the latter. Significant numbers of double-labeled cells for PRV and MC4-R mRNA were found across the neuroaxis (mean of all brain sites ∼60%), including the hypothalamic paraventricular nucleus (PVH; ∼80%). Acute parenchymal MTII microinjections into the PVH of awake, freely-moving hamsters, using doses below those able to increase IBAT temperature when injected into the third ventricle, increased IBAT temperature for as long as 4 h, as measured by temperature transponders implanted below the tissue. Collectively, these data add significant support to the view that central melanocortins are important in controlling IBAT thermogenesis via the SNS innervation of this tissue, likely through the MC4-Rs.
Urotheliogenic modulation of intrinsic activity in spinal cord-transected rat bladders: role of mucosal muscarinic receptors
Authors: Ikeda Y. , Kanai A.
Published: June 2008

We examined the modulation of intrinsic (i.e., spontaneous) detrusor contractions by the urothelium and the lamina propria through optical mapping approaches. Normal adult and spinal cord-transected (SCT) rat bladders were stained with Ca2+- and voltage-sensitive dyes, and optical activity generated from intrinsic contractions was mapped from the mucosal surface of whole bladder sheets. Both normal adult and SCT rat bladders displayed intrinsic contractions, where normal bladders showed low-amplitude, high-frequency contractions with disorganized patterns of activity. In contrast, in the SCT animals there were high-amplitude, low-frequency contractions that displayed an organized spread of membrane potential and intracellular Ca2+. The difference in contractile activity was mirrored in the Ca2+ and membrane potential maps of bladder sheets. Normal bladders showed multiple initiation sites across the mucosal surface, whereas SCT bladders showed only one or two fixed initiation sites localized to the dome. The magnitude of intrinsic contractions could be enhanced by stretch or low-dose arecaidine (50 nM), a muscarinic-specific agonist. Partial removal of the mucosa decreased the amplitude of the intrinsic contractions and decreased the response to stretch or arecaidine. Optical mapping of mucosa-denuded sheets, where enhanced spontaneous activity was abolished, or application of 1 μM nifedipine to remove smooth muscle signals, but not the mucosal signals, shows that intrinsic activity in pathological bladders is driven by the mucosal layer. In summary, we suggest an urotheliogenic origin for intrinsic activity, where structures within the mucosal layer organize and thereby enhance intrinsic detrusor contractions.
Maintenance of airway caliber in isolated airways by deep inspiration and tidal strains
Authors: LaPrad Adam S. , West Adrian R. , Noble Peter B. , Lutchen Kenneth R. , Mitchell Howard W.
Published: June 2008

Deep inspirations (DIs) are large periodic breathing maneuvers that regulate airway caliber and prevent airway obstruction in vivo. This study characterized the intrinsic response of the intact airway to DI, isolated from parenchymal attachments and other in vivo interactions. Porcine isolated bronchial segments were constricted with carbachol and subjected to transmural pressures of 5–10 cmH2O at 0.25 Hz (tidal breathing) interspersed with single DIs of amplitude 5–20 cmH2O, 5–30 cmH2O, or 5–40 cmH2O (6-s duration) or DI of amplitude 5–30 cmH2O (30-s duration). Tidal breathing was ceased after DI in a subset of airways and in control airways in which no DI was performed. Luminal cross-sectional area was measured using a fiber-optic endoscope. Bronchodilation by DI was amplitude dependent; 5–20 cmH2O DIs produced less dilation than 5–30 cmH2O and 5–40 cmH2O DIs ( P = 0.003 and 0.012, respectively). Effects of DI duration were not significant ( P = 0.182). Renarrowing after DI followed a monoexponential decay function to pre-DI airway caliber with time constants between 27.4 ± 4.3 and 36.3 ± 6.9 s. However, when tidal breathing was ceased after DI, further bronchoconstriction occurred within 30s. This response was identical in both the presence and absence of DI ( P = 0.919). We conclude that the normal bronchodilatory response to DI occurs as a result of the direct mechanical effects of DI on activated ASM in the airway wall. Further bronchoconstriction occurs by altering the airway wall stress following DI, demonstrating the importance of continual transient strains in maintaining airway caliber.
The bimodal quasi-static and dynamic elastance of the murine lung
Authors: Zosky Graeme R. , Janosi Tibor Z. , Adamicza Ágnes , Bozanich Elizabeth M. , Cannizzaro Vincenzo , Larcombe Alexander N. , Turner Debra J. , Sly Peter D. , Hantos Zoltán
Published: June 2008

The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H2O transrespiratory pressure (Prs) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated. Thoracic gas volume was calculated using plethysmography and electrical stimulation of the intercostal muscles. Lung mechanics were tracked during inflation-deflation maneuvers using a modification of the forced oscillation technique. Inflation beyond 20 cm H2O caused a shift in subsequent PV curves with an increase in slope of the inflation limb and an increase in lung volume at 20 cm H2O. There was an overall decrease in tissue elastance and a fundamental change in its volume dependence. This apparent “softening” of the lung could be recovered by partial degassing of the lung or applying a negative transrespiratory pressure such that lung volume decreased below functional residual capacity. Allowing the lung to spontaneously recover revealed that the lung required ∼1 h of mechanical ventilation to return to the original state. We propose a number of possible mechanisms for these observations and suggest that they are most likely explained by the unfolding of alveolar septa and the subsequent redistribution of the fluid lining the alveoli at high transrespiratory pressure.
Habitual loading results in tendon hypertrophy and increased stiffness of the human patellar tendon
Authors: Couppé C. , Kongsgaard M. , Aagaard P. , Hansen P. , Bojsen-Moller J. , Kjaer M. , Magnusson S. P.
Published: June 2008

The purpose of this study was to examine patellar tendon (PT) size and mechanical properties in subjects with a side-to-side strength difference of ≥15% due to sport-induced loading. Seven elite fencers and badminton players were included. Cross-sectional area (CSA) of the PT obtained from MRI and ultrasonography-based measurement of tibial and patellar movement together with PT force during isometric contractions were used to estimate mechanical properties of the PT bilaterally. We found that distal tendon and PT, but not mid-tendon, CSA were greater on the lead extremity compared with the nonlead extremity (distal: 139 ± 11 vs. 116 ± 7 mm2; mid-tendon: 85 ± 5 vs. 77 ± 3 mm2; proximal: 106 ± 7 vs. 83 ± 4 mm2; P < 0.05). Distal tendon CSA was greater than proximal and mid-tendon CSA on both the lead and nonlead extremity ( P < 0.05). For a given common force, stress was lower on the lead extremity (52.9 ± 4.8 MPa) compared with the nonlead extremity (66.0 ± 8.0 MPa; P < 0.05). PT stiffness was also higher in the lead extremity (4,766 ± 716 N/mm) compared with the nonlead extremity (3,494 ± 446 N/mm) ( P < 0.05), whereas the modulus did not differ (lead 2.27 ± 0.27 GPa vs. nonlead 2.16 ± 0.28 GPa) at a common force. These data show that a habitual loading is associated with a significant increase in PT size and mechanical properties.
Independent effects of weight and mass on plantar flexor activity during walking: implications for their contributions to body support and forward propulsion
Authors: McGowan C. P. , Neptune R. R. , Kram R.
Published: June 2008

The ankle plantar flexor muscles, gastrocnemius (Gas) and soleus (Sol), have been shown to play important roles in providing body support and forward propulsion during human walking. However, there has been disagreement about the relative contributions of Gas and Sol to these functional tasks. In this study, using independent manipulations of body weight and body mass, we examined the relative contribution of the individual plantar flexors to support and propulsion. We hypothesized that Gas and Sol contribute to body support, whereas Sol is the primary contributor to forward trunk propulsion. We tested this hypothesis by measuring muscle activity while experimentally manipulating body weight and mass by 1) decreasing body weight using a weight support system, 2) increasing body mass alone using a combination of equal added trunk load and weight support, and 3) increasing trunk loads (increasing body weight and mass). The rationale for this study was that muscles that provide body support would be sensitive to changes in body weight, whereas muscles that provide forward propulsion would be sensitive to changes in body mass. Gas activity increased with added loads and decreased with weight support but showed only a small increase relative to control trials when mass alone was increased. Sol activity showed a similar increase with added loads and with added mass alone and decreased in early stance with weight support. Therefore, we accepted the hypothesis that Sol and Gas contribute to body support, whereas Sol is the primary contributor to forward trunk propulsion.
Physical activity in aging: Comparison among young, aged, and nonagenarian individuals
Authors: Johannsen Darcy L. , DeLany James P. , Frisard Madlyn I. , Welsch Michael A. , Rowley Christina K. , Fang Xiaobing , Jazwinski S. Michal , Ravussin Eric
Published: June 2008

Physical activity (PA) is known to decline with age; however, there is a paucity of data on activity in persons who are in their nineties and beyond. We used objective and reliable methods to measure PA in nonagenarians (≥90 yr; n = 98) and hypothesized that activity would be similar to that of aged (60–74 yr; n = 58) subjects but less than in young (20–34 yr; n = 53) volunteers. Total energy expenditure (TEE) was measured by doubly labeled water over 14 days and resting metabolic rate (RMR) by indirect calorimetry. Measures of PA included activity energy expenditure adjusted for body composition, TEE adjusted for RMR, physical activity level (PAL), and activity over 14 days by accelerometry expressed as average daily durations of light and moderate activity. RMR and TEE were lower with increasing age group ( P < 0.01); however, RMR was not different between aged and nonagenarian subjects after adjusting for fat-free mass, fat mass, and sex. Nonagenarians had a lower PAL and were more sedentary than the aged and young groups ( P < 0.01); however, the nonagenarians who were more active on a daily basis walked further during a timed test, indicating higher physical functionality. For all measures of activity, no differences were found between young and aged volunteers. PA was markedly lower in nonagenarians compared with young and aged adults. Interestingly, PA was similar between young volunteers and those who were in their 60s and 70s, likely due to the sedentary nature of our society, particularly in young adults.
Correspondence between food consistency and suprahyoid muscle activity, tongue pressure, and bolus transit times during the oropharyngeal phase of swallowing
Authors: Taniguchi Hiroshige , Tsukada Tetsu , Ootaki Sachiko , Yamada Yoshiaki , Inoue Makoto
Published: June 2008

This study aimed to evaluate the effects of food texture and viscosity on the swallowing function by measuring tongue pressure and performing a videofluorographic (VF) examination. Eleven normal adults were recruited for this study. Test foods with different consistencies and liquid contents, i.e., a half-solid nutrient made of 0.8 and 1.5% agar powder, syrup, and a liquid containing 40 wt/vol% barium sulfate, were swallowed, and the anterior (AT) and posterior tongue pressures (PT) and electromyographic (EMG) activity of the suprahyoid muscles were recorded, together with VF images. The timing of each event obtained from EMG, tongue pressure, and VF recordings was measured and then compared. We found that the AT and PT activity patterns were similar and showed a single peak. The peak, area, and time duration of all of the variables for AT and PT and EMG burst increased with increasing hardness of the bolus. The onset of the EMG burst always preceded those of the AT and PT activities, while there were no significant differences in peak and offset times among EMG burst, AT, and PT. Total swallowing time and oral ejection time were significantly longer during the swallowing of 1.5% agar than any other boluses, while pharyngeal transit time and clearance time were significantly longer during the swallowing of syrup, which was as hard as the liquid, but showed a higher viscosity than the liquid. The results suggested that the major effects of food hardness were to delay oral ejection time, which strongly delays total swallowing time. In addition, pharyngeal bolus transit is not dependent on the hardness of food but on its viscosity.
Pre- and Postsynaptic Serotoninergic Excitation of Globus Pallidus Neurons
Authors: Rav-Acha Moshe , Bergman Hagai , Yarom Yosef
Published: June 2008

The basal ganglia (BG) play a critical role in the pathogenesis and pathophysiology of Parkinson's disease (PD). Recent studies indicate that serotoninergic systems modulate BG activity and may be implicated in the pathophysiology and treatment of PD. The globus pallidus (GP), the rodent homologue of the primate GPe, is the main central nucleus of the basal ganglia, affecting the striatum, the subthalamic nucleus (STN), and BG output structures. We therefore studied the effect of serotonin (5-HT) and specific 5-HT agonists and antagonists on GP neurons from rat brain slices. Using intra- and extracellular recordings of GP neurons we found that serotonin increases the firing rate of GP neurons. Analyzing the effects of specific 5-HT agonists and antagonists on the firing rate of GP neurons showed that the increase in firing rate is due to the activation of 5-HT1B and 5-HT1A receptors. Intracellular recordings in both voltage- and current-clamp modes revealed that serotonin mediates its effect via pre- and postsynaptic mechanisms. The presynaptic effect is mediated by attenuation of γ-aminobutyric acid release, probably through activation of 5-HT1B receptors. Postsynaptically, serotonin activates a hyperpolarization-activated cation channel, probably via 5-HT1A receptors. Furthermore, serotonin decreases the fast synaptic depression characteristic of the striatal afferent input. The decreased serotonin concentrations in the BG nuclei in PD may contribute to depressed GP activity and enhance the emergence of BG pathological synchronous oscillations. We therefore suggest that future therapeutics of PD should be directed toward restoration of normal serotonin levels in BG nuclei.
Monoaminergic Modulation of the Na+-Activated K+Channel in Kenyon Cells Isolated From the Mushroom Body of the Cricket (Gryllus bimaculatus) Brain
Authors: Aoki Kozue , Kosakai Kumiko , Yoshino Masami
Published: June 2008

Recent studies have suggested that octopamine (OA) and dopamine (DA) play important roles in mediating the reward and punishment signals, respectively, in olfactory learning in insect. However, their target molecules and the signaling mechanisms are not fully understood. In this study, we showed for the first time that OA and DA modulate the Na+-activated K+(KNa) channels in an opposite way in Kenyon cells isolated from the mushroom body of the cricket, Gryllus bimaculatus. Patch-clamp recordings showed that the single-channel conductance of the KNachannel was about 122 pS with high K+in the patch pipettes. The channel was found to be activated by intracellular Na+but less activated by Li+. K+channel blockers TEA and quinidine reduced the open probability (Po) of this channel. Bath application of OA and DA respectively increased and decreased the Po of KNachannel currents. An increase and a decrease in Po of KNachannels were also observed by applying the membrane-permeable analogs 8-Br-cyclic-AMP and 8-Br-cGMP, respectively. Furthermore, it was revealed that cAMP-induced increase and cGMP-induced decrease in Po were attenuated by the specific protein kinase A (PKA) inhibitor H-89 and protein kinase G (PKG) inhibitor KT5823, respectively. These results indicate that the KNachannel is a target molecule for OA and DA and that cAMP/PKA and cGMP/PKG signaling pathways are also involved in the modulation of KNachannels.
Multiuser Scheduling on the Downlink of an LTE Cellular System
Authors: Kwan Raymond , Leung Cyril , Zhang Jie
Published: June 2008

The challenge of scheduling user transmissions on the downlink of a long‐term evolution (LTE) cellular communication system is addressed. In particular, a novel optimalmultiuser scheduler is proposed. Numerical results show that the system performance improves with increasing correlation among OFDMA subcarriers. It is found that only a limited amount of feedback information is needed to achieve relatively good performance. A suboptimal reduced‐complexity scheduler is also proposed and shown to provide good performance. The suboptimal scheme is especially attractive when the number of users is large, in which case the complexity of the optimal scheme is high.
Ultrasoft and High Magnetic Moment CoFe Films Directly Electrodeposited from a B-Reducer Contained Solution
Authors: Zong Baoyu , Han Guchang , Qiu Jinjun , Guo Zaibing , Wang Li , Yeo Wee-Kay , Liu Bo
Published: June 2008

A methodology to fabricate ultrasoft CoFe nano-/microfilms directly via electrodeposition from a semineutral iron sulfate solution is demonstrated. Using boron-reducer as the additive, the CoFe films become very soft with high magnetic moment. Typically, the film coercivity in the easy and hard axes is 6.5 and 2.5 Oersted, respectively, with a saturation polarization up to an average of 2.45 Tesla. Despite the softness, these shining and smooth films still display a high-anisotropic field of
~45 Oersted with permeability up to 104. This kind of films can potentially be used in current and future magnetic recording systems as well as microelectronic and biotechnological devices.
On the Periodicity of a Difference Equation with Maximum
Authors: Gelisken Ali , Cinar Cengiz , Yalcinkaya Ibrahim
Published: June 2008

We investigate the periodic nature of solutions of the max difference equation xn+1 = max⁡{xn, A}/(xnxn−1), n = 0, 1, …, where A is a positive real parameter, and the initial conditions and such that r−1 and r0 are positive rational numbers. The results in this paper answer the Open Problem 6.2 posed by Grove and Ladas (2005).
Training Sequence Length Optimization for a Turbo‐Detector Using Decision‐Directed Channel Estimation
Authors: Hadj Kacem Imed , Sellami Noura , Fijalkow Inbar , Roumy Aline
Published: June 2008

We consider the problem of optimization of the training sequence length when
a turbo‐detector composed of a maximum a posteriori (MAP) equalizer and a
MAP decoder is used. At each iteration of the receiver, the channel is estimated using the hard
decisions on the transmitted symbols at the output of the decoder. The optimal length of the
training sequence is found by maximizing an effective signal‐to‐noise ratio (SNR) taking into
account the data throughput loss due to the use of pilot symbols.
Adiponectin Serum Levels and Their Relationships to Androgen Concentrations and Ovarian Volume during Puberty in Girls with Type 1 Diabetes Mellitus
Authors: Iñiguez Germán , Torrealba Isabel M. , Avila Alejandra , Cassorla Fernando , Codner Ethel
Published: June 2008

Aim: To study the adiponectin levels during puberty in girls with type 1 diabetes mellitus (DM1) and their relationship to body mass index (BMI), Tanner stage, ovarian volume (OV), and androgen levels. Methods: We studied adiponectin and testosterone levels and OV in 56 pubertal girls with DM1 and in 59 healthy girls serving as controls. The effects of DM1, BMI standard deviation scores (BMI SDS), testosterone, and OV over adiponectin levels were assessed. Results: The adiponectin levels were higher in the DM1 girls as compared with the controls. There was a significant decrease in adiponectin concentrations during puberty in DM1 girls only. The adiponectin levels in the girls with DM1, but not in the controls, exhibited a negative correlation with OV (r = –0.427, p = 0.002) and testosterone (r = –0.262, p = 0.049). Regression analysis showed DM1, BMI SDS, testosterone levels, and OV to be significant factors over adiponectin levels. The effect of Tanner stage was due to differences in BMI SDS. Conclusions: Decreasing adiponectin levels observed during puberty in adolescents with DM1 correlate with increasing testosterone levels and OV. We observed higher adiponectin levels in DM1 patients only at the beginning of puberty. The lack of elevated adiponectin levels observed during the late stages of puberty in girls with DM1 may be involved in the metabolic abnormalities observed during this stage.
Pulmonary Hypertension in an Infant with Achondroplasia
Authors: Schiller Ofer , Schwartz Michael , Bruckheimer Elchanan , Michowitz Shalom , Garty Ben Zion
Published: June 2008

An 18-month-old achondroplastic child presented with respiratory distress and severe pulmonary hypertension which was considered to be due to an atrial septal defect. The septal defect was closed via catheterization with Amplatzer occluder device, but the patient showed only mild to moderate clinical improvement. In addition, sleep monitoring study revealed apneas, oxygen desaturation and CO2 retention; therefore, magnetic resonance imaging of the brain was performed, showing medullary compression by a stenotic foramen magnum. Surgical craniocervical decompression led to an improvement in sleep disturbances and pulmonary hypertension. In conclusion, several factors, among which medullary compression, may be a cause of pulmonary hypertension in achondroplasia patients.
Subthalamic Stimulation for Essential Tremor
Authors: Lind Göran , Schechtmann Gaston , Lind Charlotta , Winter Jaleh , Meyerson Björn A. , Linderoth Bengt
Published: June 2008

Background/Aims/Methods: In order to explore the usefulness and long-term result of subthalamic nucleus (STN) stimulation for the treatment of essential tremor (ET), we evaluated 3 groups of patients undergoing deep brain stimulation (DBS) for ET. Results: Group 1 consisted of 3 patients who 9 years ago at intra-operative testing had good tremor reduction from STN stimulation. The second group consisted of 10 patients treated with DBS in the ventral intermediate (Vim) nucleus of the thalamus. The third group comprised 9 patients subjected to STN stimulation for ET with 1–3 years of follow-up. The 3 ET patients with STN stimulation in group 1 have continued to have excellent tremor reduction for up to 9 years. The second group, with Vim stimulation, showed less favourable long-term results. All of the recent STN stimulation group experienced good tremor reduction, but some of the patients above 70 years of age reported troublesome side effects. Conclusion: Provided that intra-operative test stimulation produces satisfactory tremor control, STN is a good target for long-term treatment of ET. For patients above the age of 70 years, however, the Vim is a preferable target.
Percutaneous Balloon Compression for the Treatment of Recurrent Trigeminal Neuralgia: Long-Term Outcome in 29 Patients
Authors: Omeis Ibrahim , Smith David , Kim Susan , Murali Raj
Published: June 2008

Objective: To analyze the long-term clinical outcomes and complication rates associated with percutaneous balloon compression (PBC) of the trigeminal ganglion in patients with recurrent trigeminal neuralgia (TN) who were treated surgically with procedures other than PBC. Methods: In this retrospective study, the authors reviewed the results of 29 patients who underwent 41 PBC procedures for recurrent TN between 1998 and 2006. Results: The overall mean length of follow-up was 49 months (range 1–101). Pain relief was immediate in 24 (83%) patients. There was no pain relief in 5 patients (17%). 2 patients were lost to follow-up. 12 (54.5%) of 22 patients remained pain-free during a mean follow-up period of 65 months (range 40–101). The other 10 patients (45.5%) who had immediate pain relief experienced recurrent pain, with a mean time to recurrence of 7.3 months (17 days to 38 months). PBC was repeated in 11 patients, and was performed a third time in 2 patients. Morbidities included minor dysesthesia (2 patients), masseter weakness (2 patients), corneal anesthesia (1 patient), anesthesia dolorosa (1 patient), and subarachnoid hemorrhage (1 patient with history of multiple myeloma). Conclusion: PBC is a useful treatment for patients with recurrent TN who have already been treated surgically. Long-term relief of pain in this subset of TN patients is achieved nearly half of the time with side-effect profiles similar to those reported in published data.
Increased S100β Is Associated with Reduced Cognitive Function in Healthy Older Adults
Authors: Yadavalli Suhrida , Gunstad John , Glickman Ellen , Alexander Thomas , Spitznagel Mary Beth , Juvancic-Heltzel Judi , Murray Leigh , Collinsworth Tiffany
Published: June 2008

Objectives: Vascular pathology is associated with reduced performance on neuropsychological tests, particularly in older adults. A likely explanation involves a disruption in the blood brain barrier (BBB). Work from clinical samples show alterations in BBB function is associated with cognitive dysfunction on testing, though no study has examined this possibility in healthy older adults. Materials and Methods: 35 older adults, without significant neurological or psychiatric history, underwent fasting blood draw and neuropsychological testing. Serum levels of S100β were quantified to provide a measure of BBB function. Results: Partial correlations showed S100β levels were inversely related to performance in multiple cognitive domains, including memory (r = 0.43, p = 0.02), psychomotor speed and visual attention (r = 0.37, p = 0.05), and working memory (r = –0.48, p = 0.008). Conclusions: Findings indicate that increased S100β levels are associated with poorer cognitive function in neurologically healthy older adults, implicating BBB function in age-related cognitive decline. Further work is needed to clarify possible mechanisms, particularly longitudinal studies that involve neuroimaging.
Polo-Like Kinase 1 as a New Target for Non-Hodgkin’s Lymphoma Treatment
Authors: Liu Lin , Zhang Min , Zou Ping
Published: June 2008

Objectives: The study was devised to detect expression of polo-like kinase 1 (PLK1) in non-Hodgkin’s lymphoma (NHL) and assess its value as a new target for NHL treatment. Methods: The expression of PLK1 in NHL was detected by immunohistochemical techniques. Lymphoma cells were transfected with RNA interference plasmid targeted against PLK1 gene. Western blot was used to examine PLK1 expression in transfected cells. Proliferation, cell cycle and apoptosis were monitored by MTT and flow cytometry. Results: The expression rate of PLK1 in NHL was 63.6% (56/88). In B cell NHL and T cell NHL, PLK1 expression had relationships with systemic symptom, lactate dehydrogenase level and International Prognostic Index scores. PLK1 overexpression was associated with shortened event-free survival and was an independent prognostic factor for NHL. PLK1 depletion by RNA interference plasmid in lymphoma cell lines could lead to cell growth suppression, cell cycle arrest and apoptosis induction. Conclusions: PLK1 overexpression is an adverse predictive factor in NHL and PLK1 could be a new therapeutic target for NHL.