bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatic point mutations in RUNX1/CBFA2/AML1 are common in high‐risk myelodysplastic syndrome, but not in myelofibrosis with myeloid metaplasia
Authors: Steensma David P. , Gibbons Richard J. , Mesa Ruben A. , Tefferi Ayalew , Higgs Douglas R.
Published: December 2004

Objective: Acquired somatic point mutations in RUNX1/CBFA2/AML1 have recently been described in a subset of patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Given the importance of core‐binding factor in megakaryocytic differentiation and platelet production, as well as the central role of megakaryocytes in the pathophysiology of myelofibrosis with myeloid metaplasia (MMM), we hypothesised that RUNX1 gene mutations might be common in MMM. In addition, it is unclear whether patients with MDS‐associated acquired alpha thalassaemia (ATMDS), a special subgroup with a very high incidence of point mutations in the ATRX gene, have an especially high incidence of RUNX1 mutations.

Methods: We analysed samples from 78 patients for RUNX1 point mutations by denaturing high‐performance liquid chromatography (DHPLC): 26 with MMM and 52 with MDS, including 18 with ATMDS.

Results:  We found five RUNX1 mutations in MDS patients (9.6%), all of whom had RAEB‐2 or a history of treated AML, but none in MMM patients. ATMDS patients did not have an increased risk of RUNX1 point mutations (2/18, 11.1%) when compared with MDS without thalassaemia (3/34, 8.8%; P = 0.58).

Conclusion:  RUNX1 point mutations are common in high‐risk MDS, but not in MMM. DHPLC is a useful technique for high‐throughput analysis of RUNX1 mutation status in myeloid disorders, and may be complementary to screening via other methods.
Chronic treatment with the glutamate receptor antagonist MK‐801 alters periodontal disease susceptibility
Authors: Breivik Torbjørn , Gundersen Yngvar , Osmundsen Harald , Opstad Per Kristian , Fonnum Frode
Published: December 2004

Objective:  Previous experiments in rats suggest that hypothalamic–pituitary–adrenal (HPA) axis over‐responsiveness, which leads to increased secretion of immunoregulatory glucocorticoid hormones, increases periodontal disease susceptibility, whereas HPA axis under‐responsiveness is associated with increased resistance to the disease. The present study was designed to investigate whether MK‐801 (dizocilipine malate), an antagonist of the glutamate receptor N‐methyl‐d‐aspartate (NMDA) in the brain, which has been found to play an important role in the regulation of the HPA axis, would influence the outcome of experimental ligature‐induced periodontal disease in a rat model.

Methods:  Experimental periodontal disease was induced in periodontal disease susceptible and HPA axis high‐responding Fischer 344 rats 2 days before chronic treatment with MK‐801(1 mg/kg intraperitoneally). The periodontal breakdown was assessed after the ligatures had been in place for 23 days. Following intraperitoneal Gram‐negative bacterial lipopolysaccharide stimulation (Escherichia coli, 250 µg/kg), concentrations of glucocorticoid receptors (GRs) in the hippocampus, and levels of the cytokine tumour necrosis factor α (TNF‐α), as well as the HPA axis‐derived hormone corticosterone, were measured in serum.

Results:  Compared to vehicle‐treated controls, MK‐801‐treated rats had significantly increased periodontal tissue destruction (p < 0.01). MK‐801‐treated rats also showed significantly increased expression of GRs in the hippocampus (p < 0.05), elevated levels of corticosterone (p < 0.001) and reduced levels of TNF‐α (p < 0.01) in serum 2 h after lipopolysaccharide stimulation.

Conclusion:  These findings may implicate glutamate receptor‐dependent mechanisms in periodontal disease, and support the concept of a bidirectional immune–brain–immune regulatory network with importance for periodontal health and disease.
Reactive changes of interstitial glia and pinealocytes in the rat pineal gland challenged with cell wall components from gram‐positive and ‐negative bacteria
Authors: Jiang‐Shieh Ya Fen , Wu Ching Hsiang , Chien Hsiung Fei , Wei I. Hua , Chang Min Lin , Shieh Jeng Yung , Wen Chen Yuan
Published: December 2004

Abstract:  Lipopolysaccharide (LPS), the major proinflammatory component of gram‐negative bacteria, is well known to induce sepsis and microglial activation in the CNS. On the contrary, the effect of products from gram‐positive bacteria especially in areas devoid of blood–brain barrier remains to be explored. In the present study, a panel of antibodies, namely, OX‐6, OX‐42 and ED‐1 was used to study the response of microglia/macrophages in the pineal gland of rats given an intravenous LPS or lipoteichoic acid (LTA). These antibodies recognize MHC class II antigens, complement type 3 receptors and unknown lysosomal proteins in macrophages, respectively. In rats given LPS (50 μg/kg) injection and killed 48 h later, the cell density and immunoexpression of OX‐6, OX‐42 and ED‐1 in pineal microglia/macrophages were markedly increased. In rats receiving a high dose (20 mg/kg) of LTA, OX‐42 and OX‐6, immunoreactivities in pineal microglia/macrophages were also enhanced, but that of ED‐1 was not. In addition, both bacterial toxins induced an increase in astrocytic profiles labelled by glial fibrillary acid protein. An interesting feature following LPS or LTA treatment was the lowering effect on serum melatonin, enhanced serotonin immunolabelling and cellular vacuolation as studied by electron microscopy in pinealocytes. The LPS‐ or LTA‐induced vacuoles appeared to originate from the granular endoplasmic reticulum as well as the Golgi saccules. The present results suggest that LPS and LTA could induce immune responses of microglia/macrophages and astroglial activation in the pineal gland. Furthermore, the metabolic and secretory activity of pinealocytes was modified by products from both gram‐positive and ‐negative bacteria.
Melatonin attenuates gray and white matter damage in a mouse model of transient focal cerebral ischemia
Authors: Lee E‐Jian , Lee Ming‐Yang , Chen Hung‐Yi , Hsu Yun‐Shang , Wu Tian‐Shung , Chen Shur‐Tzu , Chang Guan‐Liang
Published: December 2004

Abstract:  We have previously shown that melatonin reduces infarct volumes and enhances neurobehavioral and electrophysiological recoveries following transient middle cerebral artery (MCA) occlusion in rats. In the study, we examined whether melatonin would display neuroprotection against neuronal, axonal and oligodendrocyte pathology after 24 hr of reperfusion following 1 hr of MCA occlusion in mice. Melatonin (5 mg/kg) or vehicle was given intraperitoneally at the commencement of reperfusion. Neurological deficits were assessed 24 hr after ischemia. Gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein and microtubule‐associated protein tau‐1 immunohistochemistry to identify postischemic disrupted axonal flow and oligodendrocyte pathology, respectively. Oxidative damage was assessed by 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and 4‐hydroxynonenal (4‐HNE) immunohistochemistry. Relative to controls, melatonin‐treated animals not only had a significantly reduced volume of gray matter infarction by 42% (P < 0.001), but also exhibited a decreased score of axonal damage by 42% (P < 0.001) and a reduction in the volume of oligodendrocyte pathology by 58% (P < 0.005). Melatonin‐treated animals also had significantly reduced immunopositive reactions for 8‐OHdG and 4‐HNE by 53% (P < 0.001) and 49% (P < 0.001), respectively. In addition, melatonin improved sensory and motor neurobehavioral outcomes by 47 and 30%, respectively (P < 0.01). Thus, delayed (1 hr) treatment with melatonin reduced both gray and white matter damage and improved neurobehavioral outcomes following transient focal cerebral ischemia in mice. The finding of reduced oxidative damage observed with melatonin suggests that its major mechanisms of action are mediated through its antioxidant and radical scavenging activity.
5‐Hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C
Authors: Keithahn Christian , Lerchl Alexander
Published: December 2004

Abstract:  Hydroxyl radicals are involved in direct damage of important biomolecules. Potent radical scavengers such as vitamin C and indoles of the tryptophan family can avert the potential damage. Melatonin and its precursor 5‐hydroxytryptophan (5‐HTP) were compared with water‐soluble vitamin C. Different scavenger concentrations were measured in a steady‐state luminol chemiluminescence system (SLCL‐system) with combined Fe(II) chloride (0.1 mm) and hydrogen peroxide (1.0 mm) as hydroxyl radical generators. 5‐HTP showed highest hydroxyl radical scavenging effects with a 50% inhibition concentration (IC50) of 1.8 μm. For vitamin C an IC50 of 12.7 μm was measured, whereas melatonin in pure demineralized water was much less efficient (IC50 = 724 μm). A comparison between melatonin in aqueous solution and melatonin in ethanol solution revealed that melatonin was significantly more effective in pure demineralized water.
Regulation of Intracellular Phosphatidylinositol‐4‐Phosphate by the Sac1 Lipid Phosphatase
Authors: Tahirovic Sabina , Schorr Markus , Mayinger Peter
Published: December 2004

Phosphatidylinositol 4‐phosphate (PtdIns(4)P) regulates diverse cellular processes, such as actin cytoskeletal organization, Golgi trafficking and vacuolar biogenesis. Synthesis and turnover of PtdIns(4)P is mediated by a set of specific lipid kinases and phosphatases. Here we show that the polyphosphoinositide phosphatase Sac1p has a central role in compartment‐specific regulation of PtdIns(4)P. We have found that sac1Δ mutants show pleiotropic, synthetically lethal interactions with mutations in genes required for vacuolar protein sorting (Vps). Disruption of the SAC1 gene also caused a defect in the late endocytic pathway. These trafficking phenotypes correlated with a dramatic accumulation of PtdIns(4)P at vacuolar membranes. In addition, sac1 mutants displayed elevated endoplasmic reticulum PtdIns(4)P. The accumulation of PtdIns(4)P at the endoplasmic reticulum and vacuole and the endocytic defect could be compensated by mutations in the PtdIns 4‐kinase Stt4p. Our results indicate that elimination of Sac1p causes accumulation of a Stt4p‐specific PtdIns(4)P pool at internal membranes which impairs late endocytic and vacuolar trafficking. We conclude that Sac1p functions in confining PtdIns(4)P‐dependent processes to specific intracellular membranes.
Golgi Vesiculation Induced by Cholesterol Occurs by a Dynamin‐ and cPLA2‐Dependent Mechanism
Authors: Grimmer Stine , Ying Ming , Wälchli Sébastien , van Deurs Bo , Sandvig Kirsten
Published: December 2004

It was recently demonstrated that an increase in the cellular cholesterol level leads to vesiculation of the Golgi apparatus. This vesiculation affects the entire Golgi apparatus and is a reversible process. We have now started to elucidate the mechanism behind this cholesterol‐induced vesiculation of the Golgi apparatus. Transient transfection of cells with dominant negative mutant constructs of dynamin 1 and 2 inhibited the vesiculation; expression of dynK44A in HeLa cells stably transfected with this construct had the same effect. However, the vesiculation seems to be independent of clathrin, as cholesterol‐induced vesiculation still occurred following knock down of clathrin heavy chain in HeLa cells using RNA interference as well as in BHK cells where expression of antisense to clathrin heavy chain had been induced. Importantly, the cPLA2 inhibitor MAFP and the chelator BAPTA‐AM that binds cytosolic Ca2+ inhibited the cholesterol‐induced vesiculation, suggesting involvement of a cPLA2 that requires cytosolic Ca2+ for translocation to membranes. Furthermore, in response to an increased cellular cholesterol level, an EGFP‐cPLA2 fusion protein translocated to the Golgi apparatus. Thus, our results demonstrate that the cholesterol‐induced vesiculation of the Golgi apparatus is mediated by a cPLA2‐ and dynamin‐dependent mechanism.
Constitutive and Protein Kinase C‐Induced Internalization of the Dopamine Transporter is Mediated by a Clathrin‐Dependent Mechanism
Authors: Sorkina Tatiana , Hoover Brian R. , Zahniser Nancy R. , Sorkin Alexander
Published: December 2004

The amount of dopamine transporter (DAT) present at the cell surface is rapidly regulated by the rates of DAT internalization to endosomes and DAT recycling back to the plasma membrane. The re‐distribution of the transporter from the cell surface to endosomes was induced by phorbol ester activation of protein kinase C in porcine aortic endothelial cells stably expressing the human DAT. Inhibition of DAT recycling with the carboxylic ionophore monensin also caused significant accumulation of DAT in early endosomes and a concomitant loss of DAT from the cell surface, due to protein kinase C‐independent constitutive internalization of DAT in the absence of recycling. Such monensin‐induced relocation of DAT to endosomes was therefore utilized as a measure of the constitutive internalization of DAT. Knock‐down of clathrin heavy chain or dynamin II by small interfering RNAs dramatically inhibited both constitutive and protein kinase C‐mediated internalization of DAT. In contrast, neither monensin‐dependent nor phorbol ester‐induced re‐distribution of DAT were affected by inhibitors of endocytosis through cholesterol‐rich membrane microdomains. Mutational analysis revealed the potential importance of amino acid residues 587–597 in DAT internalization. Altogether, the data suggest that both constitutive and protein kinase C‐mediated internalization of DAT utilize the clathrin‐dependent endocytic pathway, but likely involve unconventional mechanisms.
The influence of impact object characteristics on impact force and force absorption by mouthguard material
Authors: Takeda Tomotaka , Ishigami Keiichi , Shintaro Kawamura , Nakajima Kazunori , Shimada Atsushi , Regner Connell Wayne
Published: December 2004

Abstract –  Most impact force and impact energy absorption tests for mouthguards have used a steel ball in a drop‐ball or the pendulum device. However, in reality most sports‐related trauma is caused by objects other than the steel ball, e.g. various sized balls, hockey puck, or bat or stick. Also, the elasticity, the velocity and the mass of the object could change the degree and the extent of injuries. In this study, we attempted to measure the impact force from actual sports equipment in order to clarify the exact mechanism of dental‐related sports injuries and the protective effects of mouthguards. The present study was conducted using the pendulum impact device and load cell. Impact objects were removable. Seven mobile impact objects were selected for testing: a steel ball, baseball, softball, field hockey ball, ice hockey puck, cricket ball, and wooden baseball bat. The mouthguard material used in this study was a 3‐mm‐thick Drufosoft (Dreve‐Dentamid GmbH, Unna, Germany), and test samples were made of the one‐layer type. The peak transmitted forces without mouthguard ranged from the smallest (ice hockey stick, 46.9 kgf) to the biggest (steel ball, 481.6 kgf). The peak transmitted forces were smaller when the mouthguard was attached than without it for all impact materials but the effect was significantly influenced by the object type. The steel ball showed the biggest (62.1%) absorption ability while the wooden bat showed the second biggest (38.3%). The other balls or the puck showed from 0.6 to 6.0% absorbency. These results show that it is important to test the effectiveness of mouthguards on specific types of sports equipment. In future, we may select different materials and mouthguard designs suitable for specific sports.
Incidence of dental trauma associated with facial trauma in Brazil: a 1‐year evaluation
Authors: Da Silva Alessandro Costa , Passeri Luis Augusto , Mazzonetto Renato , De Moraes Márcio , Moreira Roger William Fernandes
Published: December 2004

Abstract –  Dental trauma occurs frequently in young people, and mostly occurs in conjunction with facial trauma. In the literature, there are still few reports relating dental trauma, facial trauma, and soft‐tissue injuries. This research aimed to evaluate: (i) the overall incidence of dental trauma in 340 patients who presented with facial trauma over a 1‐year‐period, (ii) the epidemiology of these related diseases, and (iii) the most common dental trauma when a facial trauma was present. Of all facial trauma, 15.29% presented dental trauma, of which luxations and avulsions were the most frequent injuries (40.30% each), occurring mainly on weekends (38.46%) and in October (15.38%), followed by March and June (13.46% each). The sex ratio presented the proportion of 3.3:1 (M:F). Trauma occurred mainly in the second decade (44.23%). These results highlight the high incidence of dental and facial trauma, and suggest the importance of the adoption of appropriate prevention protocols and effective therapeutic methods.
Feed‐forward inhibition shapes the spike output of cerebellar Purkinje cells
Authors: Mittmann Wolfgang , Koch Ursula , Häusser Michael
Published: December 2004

Although the cerebellum is thought to play a key role in timing of movements on the time scale of milliseconds, it is unclear how such temporal fidelity is ensured at the cellular level. We have investigated the timing of feed‐forward inhibition onto interneurons and Purkinje cells activated by parallel fibre stimulation in slices of cerebellar cortex from P18–25 rats. Feed‐forward inhibition was activated within ∼1 ms after the onset of excitation in both cell types. The rapid onset of feed‐forward inhibition sharply curtailed EPSPs and increased the precision of the resulting action potentials. The time window for summation of EPSPs was reduced to 1–2 ms in the presence of feed‐forward inhibition, which could inhibit the efficacy of asynchronous EPSPs for up to 30 ms. Our findings demonstrate how the inhibitory microcircuitry of the cerebellar cortex orchestrates synaptic integration and precise timing of spikes in Purkinje cells, enabling them to act as coincidence detectors of parallel fibre input.
Ageing and gonadectomy have similar effects on hypoglossal long‐term facilitation in male Fischer rats
Authors: Zabka A. G. , Mitchell G. S. , Behan M.
Published: December 2004

Long‐term facilitation (LTF), a form of serotonin‐dependent respiratory plasticity induced by intermittent hypoxia, decreases with increasing age or following gonadectomy in male Sprague‐Dawley (SD) rats. Ageing is accompanied by decreasing levels of testosterone, which in turn influences serotonergic function. In addition, LTF in young male rats differs among strains. Thus, we tested the hypothesis that LTF is similar in middle‐aged and gonadectomized young male rats of an inbred rat strain commonly used in studies on ageing (F344) by comparison with SD rats. We further tested whether the magnitude of LTF correlates with circulating serum levels of testosterone and/or progesterone. Young and middle‐aged intact and young gonadectomized (GDX) male Fischer 344 rats were anaesthetized, neuromuscularly blocked and ventilated. Integrated phrenic and hypoglossal (XII) nerve activities were measured before, during and 60 min following three 5‐min episodes of isocapnic hypoxia. LTF was observed in phrenic motor output in young and middle‐aged intact and young GDX rats. In contrast, XII LTF was observed only in young intact rats. In middle‐aged and young GDX rats, XII LTF was significantly lower than in young intact rats (P < 0.05). Furthermore, XII LTF was positively correlated with the testosterone/progesterone ratio. These data show that serotonin‐dependent plasticity in upper airway respiratory output is similar in F344 and SD rat strains. Furthermore, LTF is similarly impaired in middle‐aged and gonadectomized male rats, suggesting that gonadal hormones play an important role in modulating the capacity for neuroplasticity in upper airway motor control.
Elasticity theory, fracture mechanics, and some relevant thermal properties of quasi-crystalline materials
Authors: Fan Tian-You , Mai Yiu-Wing
Published: December 2004

A review is given on the basic concepts and fundamental framework of the theory of elasticity for quasi-crystalline materials, including some 1D, 2D, and 3D quasi-crystals. The elasticity of quasi-crystals embodies some new concepts, field variables, and equations. It is much more complicated and beyond the scope of classical elasticity which holds only for conventional structural materials, including crystalline materials. Hence, some well-developed methods in classical elasticity cannot be directly applied to solve the problems of elasticity of quasi-crystalline materials. But the ideas of the classical theory of elasticity provide beneficial insight to treat this new subject. A decomposition and superposition procedure is suggested to simplify the elasticity problems of 1D and 2D quasi-crystals. Application of displacement and stress potentials further simplifies the problems. The large number of complicated equations involving elasticity is reduced to a single or a few partial differential equations of higher order by this technique. Also, efforts have been made to simplify the equations for 3D cubic quasi-crystals to a single partial differential equation of higher order. Simplification of the basic equations provides the possibility to solve boundary value or initial-boundary value problems of elasticity. For this purpose, some direct and systematic methods of mathematical physics and function theory are developed, and a series of analytic (classical) solutions, mainly for dislocations and cracks in materials, are derived. In addition, attention is drawn to those variational problems and generalized solutions (weak solutions) of boundary value problems and numerical implementation by the finite element method. The above may be seen as a development of the theory and methodology akin to those of classical elasticity. Based on the exact solutions of crack problems with different configurations under different motion states for different quasi-crystal systems, we put forward a framework of fracture mechanics of quasi-crystalline materials. This may be seen as an extension of the development of fracture mechanics for conventional structural materials. Also, some elastodynamic problems for some 1D and 2D quasi-crystals are studied, related results for dislocation and crack dynamics are found, and possible connections with certain thermal properties of quasi-crystalline materials, eg, specific heat and other thermo-dynamic functions, are discussed. There are 75 references cited in this review article.
Investigations of Particle Velocities in a Slurry Pump Using PIV: Part 1, The Tongue and Adjacent Channel Flow
Authors: Kadambi Jaikrishnan R. , Charoenngam Pathom , Subramanian Amirthaganesh , Wernet Mark P. , Sankovic John M. , Addie Graeme , Courtwright Robert
Published: December 2004

Transport of solid-liquid slurries in pipeline transport over short and medium distances is very important in many industries, including mining related processes. The particle image velocimetry technique was successfully utilized to investigate the velocities and kinetic energy fluctuations of slurry particles at the tongue region of an optically-clear centrifugal pump. The experiments were conducted using 500 micron glass beads at volumetric concentrations of 2.5% and 5% and at pump speeds of 725 rpm and 1000 rpm. The fluctuation kinetic energy increased approximately 200% to 500% as the pump speed was increased from 725 rpm to 1000 rpm. The directional impingement mechanism is more significant at the pressure side of the blade, tongue and the casing. This mechanism becomes more important as the speed increases. This suggests that the impeller, tongue and the casing of the slurry pump can wear out quickly, especially with an increase in speed. In this paper the emphasis is on the tongue region. The random impingement mechanism caused by the fluctuation kinetic energy of the solids can play an important role on the erosion of the tongue area.
Methods for Calculating Bending Moment and Shear Force in the Moving Mass Problem
Authors: Biondi Bruno , Muscolino Giuseppe , Sidoti Anna
Published: December 2004

Two methods able to capture with different levels of accuracy the discontinuities in the bending moment and shear force laws in the dynamic analysis of continuous structures subject to a moving system modeled as a series of unsprung masses are presented. The two methods are based on the dynamic-correction method, which improves the conventional series expansion by means of a pseudostatic term, and on an eigenfunction series expansion of the continuous system response, which takes into account the effect of the moving masses on the structure, respectively.
On the Autonomous Gain and Phase Tailoring Transfer Functions of Symmetrically Distributed Piezoelectric Sensors
Authors: Hsu Yu-Hsiang , Lee Chih-Kung
Published: December 2004

A new design concept for a distributed sensor, which was developed based on the principle that the strain distribution of an arbitrary finite plate structure can be expressed as the superposition of even and odd strain functions, is presented. The distributed sensors adopt a symmetric weighting electrode to match the symmetric distribution of the even parts of the strain in order to introduce a no-phase delay low-pass filter to tailor the sensor transfer function. Both the design concept and the experimental results are detailed herein.
Thermo-Mechanical Exergy Analysis of Balcova Geothermal District Heating System in Izmir, Turkey
Authors: Ozgener Leyla , Hepbasli Arif , Dincer Ibrahim
Published: December 2004

This paper deals with a thermo-mechanical exergy analysis of Balcova Geothermal District Heating System (BGDHS) in Izmir, Turkey using actual system data and an assessment of the district heating system performance, energy and exergy efficiencies, and exergy destructions. The exergy destructions in the overall BGDHS are quantified and illustrated using an exergy flow diagram. Also, both energy and exergy flow diagrams are compared. The exergy destructions in the system particularly occurs in terms of the exergy of the fluid lost in the pumps, the heat exchanger losses, the exergy of the thermal water (geothermal fluid) reinjected and the natural direct discharge of the system, accounting for 3.06%, 7.24%, 22.66% and 24.1%, respectively of the total exergy input to the BGDHS. Both energy and exergy efficiencies of the overall BGDHS are investigated for system performance analysis and improvement and are determined to be 37.60% and 42.94%, respectively.
Visible light exposure induces VEGF gene expression through activation of retinoic acid receptor-α in retinoblastoma Y79 cells
Authors: Akiyama Hideo , Tanaka Toru , Doi Hiroshi , Kanai Hiroyoshi , Maeno Toshitaka , Itakura Hirotaka , Iida Tomohiro , Kimura Yasutaka , Kishi Shoji , Kurabayashi Masahiko
Published: December 2004

Neovascularization of the retina and choroids is the pathological hallmark of many retinopathies, but its molecular mechanisms remain unclear. Vascular endothelial growth factor (VEGF), which is induced by hypoxia or cytokines, plays a critical role in the abnormal growth of blood vessels. In this study, we report that visible light exposure induces VEGF gene expression in retinoblastoma Y79 cells. Fluorescent light exposure (700 lux, wavelength 400∼740 nm) caused a significant increase in VEGF transcripts and protein levels. Such an induction seemed to be specific to certain cells, including photoreceptor cells, because light-induced VEGF expression was not observed in either nontransformed cells, such as retinal pigment epithelium cells, and bovine aortic endothelial cells or transformed cells, such as CV-1 and HepG2 cells. Pertussis toxin and guanosine 5′-[β-thio]diphosphate, specific inhibitors for rhodopsin-associated G protein, blunted this induction. Progressive deletion and site-specific mutation analyses indicate that light stimulation increases VEGF promoter activity through G+C-rich sequence, which is proven by Sp1 binding sites by supershift assays. Electrophoretic mobility shift assays show that light stimulation increases Sp1 binding. Synthetic retinoic acid receptor-α (RARα) antagonist completely abrogated light-mediated increase in VEGF expression. Transfection of Y79 cells with dominant negative mutant of RARα significantly attenuated the light-mediated induction of VEGF promoter activity. In conclusion, our data indicate that light exposure increases VEGF expression through the mechanisms involving activation of Sp1 and RARα signaling in Y79 cells. This study provides new insight into the role of visible light in the transcription and induction of VEGF gene expression.
Iron alters glutamate secretion by regulating cytosolic aconitase activity
Authors: McGahan M. Christine , Harned Jill , Mukunnemkeril Marilyn , Goralska Malgorzata , Fleisher Lloyd , Ferrell Jenny B.
Published: December 2004

Glutamate has many important physiological functions, including its role as a neurotransmitter in the retina and the central nervous system. We have made the novel observations that retinal pigment epithelial cells underlying and intimately interacting with the retina secrete glutamate and that this secretion is significantly affected by iron. In addition, iron increased secretion of glutamate in cultured lens and neuronal cells, indicating that this may be a common mechanism for the regulation of glutamate production in many cell types. The activity of the iron-dependent enzyme cytosolic aconitase (c-aconitase) is increased by iron. The conversion of citrate to isocitrate by c-aconitase is the first step in a three-step process leading to glutamate formation. In the present study, iron increased c-aconitase activity, and this increase was associated with an increase in glutamate secretion. Inhibition of c-aconitase by oxalomalate decreased glutamate secretion and completely inhibited the iron-induced increase in glutamate secretion. Derangements in both glutamate secretion and iron metabolism have been noted in neurological diseases and retinal degeneration. Our results are the first to provide a functional link between these two physiologically important substances by demonstrating a significant role for iron in the regulation of glutamate production and secretion in mammalian cells resulting from iron regulation of aconitase activity. Glutamatergic systems are found in many nonneuronal tissues. We provide the first evidence that, in addition to secreting glutamate, retinal pigment epithelial cells express the vesicular glutamate transporter VGLUT1 and that regulated vesicular release of glutamate from these cells can be inhibited by riluzole.
Roles of degree of fat deposition and its localization on VEGF expression in adipocytes
Authors: Miyazawa-Hoshimoto Saori , Takahashi Kazuo , Bujo Hideaki , Hashimoto Naotake , Yagui Kazuo , Saito Yasushi
Published: December 2004

Vascular endothelial growth factor (VEGF) is an important angiogenic factor and is expressed in wide variety of cell types. In this study, we investigated the mechanism of VEGF production in adipocytes in three sets of experiments. First, to clarify the relation between plasma VEGF concentrations and their expressions in adipose tissues, we investigated the genetically obese db/db and KK-Aymice. Plasma VEGF concentrations in obese mice were significantly higher than in control and were related to adiposity. VEGF expressions in visceral fat were enhanced during growth and were related to fat deposition. Next, to demonstrate the relation between VEGF production and lipid accumulation in adipocytes, we analyzed VEGF mRNA expression and its protein secretion in 3T3-L1 cells. VEGF production was enhanced during lipid accumulation in 3T3-L1 cells after adipocyte conversion. Next, to clarify the role of anatomic localization on VEGF expression in adipocytes, we implanted 3T3-L1 cells into visceral or subcutaneous fat in athymic mice. 3T3-L1 cells implanted into the mesenteric area expressed more VEGF mRNA than that into the subcutaneous area. Plasma VEGF concentration in the mice implanted in visceral fat was higher than in controls. These results suggest that both the anatomic localization and the lipid accumulation are important for the VEGF production in adipocytes.
Effects of caloric restriction on cell proliferation in several tissues in mice: role of intermittent feeding
Authors: Hsieh Elaine A. , Chai Christine M. , Hellerstein Marc K.
Published: December 2004

Reduced cell proliferation may mediate anticarcinogenic effects of caloric restriction (CR). Using heavy water (2H2O) labeling, we investigated the cell proliferation response to CR in detail, including time course, effect of refeeding, and role of intermittent feeding with 5% CR. In the time-course study, 8-wk-old female C57BL/6J mice were placed on a 33% CR regimen (fed 3 times/wk) for varying durations. Compared with responses in controls fed ad libitum (AL), proliferation rates of keratinocytes, mammary epithelial cells, and T cells were markedly reduced within 2 wk of CR. In mice fed 95% ad libitum (C95, fed 3 times/wk), cell proliferation was also reduced in all tissues so that differences from 33% CR were only significant at 1 mo. In the refeeding study, mice were refed a C95 diet for varying durations after 1 mo of 33% CR. Cell proliferation rebounded to a suprabasal rate in all tissues after 2 wk of refeeding and then normalized after 2 mo, although the C95 group again exhibited lower cell proliferation than the AL group. The role of intermittent feeding was studied by comparing 33% CR and C95 animals (both fed intermittently) with animals fed isocalorically either daily or continuously by pellet dispenser. Intermittent feeding had no additive effect on 33% CR but reduced cell proliferation in all tissues at the 95% caloric intake level. In summary, the CR effect on cell proliferation is potent, rapid, and reversible in several tissues, and an intermittent feeding pattern reproduces much of the effect in the absence of substantial CR.
Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver
Authors: Yu Hong-Jeng , Lin Bor-Ru , Lee Hsuan-Su , Shun Chia-Tung , Yang Chih-Ching , Lai Ting-Yu , Chien Chiang-Ting , Hsu Su-Ming
Published: December 2004

Increased hepatic sympathetic activity affects hepatic metabolism and hemodynamics and subsequently causes acute hepatic injury. We examined whether the vesicovascular reflex evoked by bladder overdistension could affect hepatic function, specifically reactive oxygen species (ROS)-induced inflammation and apoptosis, through activation of the hepatic sympathetic nerve. We evaluated the hepatic hemodynamics, hepatic sympathetic nervous activities, and cystometrograms in anesthetized rats subjected to acute urinary retention. We used a chemiluminescence method, an in situ nitro blue tetrazolium perfusion technique, and a DNA fragmentation/apoptosis-related protein assay to demonstrate de novo and colocalize superoxide production and apoptosis formation in rat liver. Acute urinary retention increased the hepatic sympathetic-dependent vesicovascular reflex, which caused hepatic vasoconstriction/hypoxia and increased superoxide anion production from the periportal Kupffer cells and hepatocytes, which were aggravated by the increase in volume and duration of urinary retention. The ROS-enhanced proinflammatory NF-κB, activator protein-1, and ICAM-1 expression also promoted proapoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, poly-(ADP-ribose)-polymerase cleavages, and DNA fragmentation and apoptotic cells in the liver. The proinflammatory and proapoptotic mechanisms were significantly attenuated in rats treated with hepatic sympathetic nerve denervation or catechin (antioxidant) supplement. In conclusion, our results suggest that acute urine retention enhances hepatic sympathetic activity, which causes hepatic vasoconstriction and evokes proinflammatory and proapoptotic oxidative injury in the rat liver. Reduction of the hepatic sympathetic tone or antioxidant supplement significantly attenuates these injuries.
BK-β1 subunit: immunolocalization in the mammalian connecting tubule and its role in the kaliuretic response to volume expansion
Authors: Pluznick Jennifer L. , Wei Peilin , Grimm P. Richard , Sansom Steven C.
Published: December 2004

Large, Ca2+-activated K+channels (BK), comprised of α- and β-subunits, mediate K+secretion during high flow rates in distal nephron segments. Because the BK-β1 subunit enhances Ca2+sensitivity of BK in a variety of cells, we determined its role in flow-induced K+secretion and its localization in the mammalian nephron. To determine the role of BK-β1 in the kaliuretic response to volume expansion, the rate of K+excretion (UKV) vs. varied urinary flow rates were determined in wild-type and BK-β1 knockout mice (BK-β1−/−). When flow rate was varied by volume expansion (2 ml·h−1·25 g body wt−1) for 30 to 60 min in wild-type mice, we found that the UKV increased significantly with increasing urine flow rates ( r2= 0.50, P < 0.00001, n = 31), as demonstrated previously in distal nephron of rats and rabbits. However, in BK-β1−/−mice, UKV did not vary with changing flow rates ( r2= 0.15, P = 0.08, n = 20). Using immunohistochemical techniques, we found that BK-β1 was strongly expressed in the apical membrane of the murine distal nephron and that 98% of BK-β1 protein detected by histochemistry colocalized with NCX, a marker of connecting tubules (CNT). Both BK-β1 and NCX colocalized with BK-α in separate experiments. Furthermore, we confirmed BK-β1 protein expression in the apical membrane of connecting tubules in rabbits. BK-β1 RNA from rabbit CNT was sequenced and was identical to previously published rabbit muscle sequences. These data show that the BK-β1 accessory subunit is present in the CNT segment of the mammalian distal nephron and has a significant role in the kaliuretic response to increased urinary flow induced by volume expansion.
Screen conformal half‐lightlike submanifolds
Authors: Duggal K. L. , Sahin B.
Published: December 2004

We study some properties of a half‐lightlike submanifold M, of
a semi‐Riemannian manifold, whose shape operator is conformal
to the shape operator of its screen distribution. We show that
any screen distribution S(TM) of M is integrable and the
geometry of M has a close relation with the nondegenerate
geometry of a leaf of S(TM). We prove some results on symmetric
induced Ricci tensor and null sectional curvature of this class.
Effect of randomly fluctuating environment on autotroph‐herbivore model system
Authors: Saha Tapan , Bandyopadhyay Malay
Published: December 2004

First we deal with a brief introduction of the
autotroph‐herbivore model system along with deterministic analysis
of local stability, bifurcation behavior, and persistence of the
populations. The second part consists of the stochastic formulation of
the model system to incorporate the effect of environmental
fluctuation and then analysis of nonequilibrium fluctuation.
Stochastic stability criteria of the model system under the
influence of random environmental fluctuation are obtained through
the convergence conditions of second‐order moments.
Evaluation of Serum β-Carboxy-Terminal Cross-Linking Telopeptide of Type I Collagen as Marker of Bone Resorption in Chronic Hemodialysis Patients
Authors: Reichel Helmut , Roth Heinz-Jürgen , Schmidt-Gayk Heinrich
Published: December 2004

Background: The carboxy-terminal cross-linking telopeptide of type I collagen (β-CrossLaps, β-CTX) is released into the circulation during degradation of type I collagen and serves as a marker of bone resorption. β-CTX is known to undergo a diurnal rhythm in normal individuals and to accumulate in chronic renal failure. β-CTX has a potential role in noninvasive diagnosis of renal bone disease. Methods: Serum β-CTX was compared to parathyroid hormone (PTH) and other biochemical bone markers in 90 unselected hemodialysis patients. Results: Mean β-CTX was elevated above the normal range (1.72 ± 0.93 µg/l); there were large individual variations. Serum β-CTX was significantly correlated with various PTH assays (r >0.56) and with tartrate-resistant acid phosphatase 5b (TRACP 5b, r = 0.629), bone-specific alkaline phosphatase (r = 0.404) and osteocalcin (r = 0.534, all correlations p < 0.001). The correlation between β-CTX and PTH was significantly higher than the correlation between TRACP 5b and PTH. Several factors which could confound interpretation of serum β-CTX were assessed in further studies: (i) There was no recognizable influence of the time of blood sampling (morning dialysis shift versus afternoon dialysis shift) on serum β-CTX. (ii) Serum β-CTX was not significantly related to residual diuresis of patients. Conclusions: We found a high association between β-CTX and other established markers of bone and calcium metabolism demonstrating the potential utility of β-CTX as marker of bone resorption in renal bone disease. However, further studies employing bone histology are still warranted to exactly define the influence of glomerular retention on serum β-CTX in end-stage renal disease.
Airway Wall Thickness in Patients with COPD and Healthy Current Smokers and Healthy Non-Smokers: Assessment with High Resolution Computed Tomographic Scanning
Authors: Deveci Figen , Murat Ayşe , Turgut Teyfik , Altuntaş Elif , Muz M. Hamdi
Published: December 2004

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction caused by emphysema or airway narrowing, or both. Recently airway dimensions have been measured using high-resolution computed tomography (HRCT). To evaluate large and small airway dimensions by HRCT and compare them with pulmonary function tests in patients with COPD and in smokers with or without airflow obstruction. Methods: We used HRCT scanning to measure airway wall thickness at the segmental and sub-segmental levels in COPD patients (group II, stage II, n = 17, and group III, stage III, n = 5), healthy current smokers (group I, n = 10) and healthy non-smokers (group 0, n = 10). Results: FEV1 was lower in patients with severe or moderate COPD than in healthy current smokers and non-smokers. FEV1 was lower in group I than group 0 (p < 0.005). There was no statistically significant difference between patients with moderate COPD and severe COPD in the ratio of airway wall thickness to outer diameter (T/D ratio) or the percentage wall area (WA%). Both groups II and III had higher T/D ratios than group I (p < 0.01), and group I had a higher T/D ratio than group 0 (p < 0.001). Both groups II and III had higher WA% than group I (p < 0.01 and p < 0.05, respectively), and group I had a higher WA% than group 0 (p < 0.001). A negative correlation was found between airway wall thickness and FEV1. Conclusions: Computed tomography measurements of large and small airway dimensions are useful for evaluating lung function in patients with COPD and healthy current smokers. Airway wall thickening is inversely related to the degree of airflow obstruction and positively related to cumulative smoking history.
BALF Nitrite as an Indicator of Inflammation in Children with Cystic Fibrosis
Authors: Çetin İlker , Özçelik Uğur , Göçmen Ayhan , Kiper Nural , Doğru Deniz , Yalçın Ebru
Published: December 2004

Background: A unique substance reflecting the degree of inflammation localized to the lower respiratory tract in patients with cystic fibrosis (CF) has been the concern of several investigators and nitric oxide has gained interest for this purpose in the last decades. Objectives: The aim of this study was to evaluate the cytokine and nitrite levels by showing the relationship between them in serum and bronchoalveolar lavage fluid (BALF) of patients with CF and patients in which flexible fiberoptic bronchoscopy (FFB) was applied because of indications other than infection. Methods: 20 children with CF with mean age 8.2 years and 10 children as control group with mean age 4.2 years were included in the study. Cultures for aerobes, anaerobes, fungi and mycobacteria, cell differentials, cytokine and nitrite measurements were made from BALF specimens. White blood cell (WBC) count, erythrocyte sedimentation rate (ESR), quantitative C-reactive protein (QCRP), cytokine and nitrite levels were measured from serum samples. Results: BALF neutrophil, TNF-α, IL-8 and nitrite levels were significantly higher in patients with CF than control patients. There was no correlation between serum and BALF cytokine and nitrite levels. However, there was a significantly positive correlation between BALF IL-8 and nitrite levels in patients with CF (r = 0.5) and also in control patients (r = 0.6). Conclusions: The results suggest that BALF nitrite levels reflect the degree of inflammation localized to lower respiratory tract and may be a useful indicator of airway inflammation for patients with CF.
Can We Still Miss Tetrachloroethylene-Induced Lung Disease? The Emperor Returns in New Clothes
Authors: Tanios Maged A. , El Gamal Hesham , Rosenberg Beth J. , Hassoun Paul M.
Published: December 2004

Hypersensitivity pneumonitis (HP) is a complex syndrome of varying intensity and clinical presentation, and has been described in association with numerous exposures. Early diagnosis is essential to limit irreversible lung damage. We describe a case of HP in a 42-year-old dry cleaner following occupational exposure to tetrachloroethylene (TCE). The diagnosis was suspected based on clinical presentation and radiographic studies, and confirmed by lung biopsy. A review of the literature reveals that HP has not been reported previously as an occupational lung disease in dry cleaners. We conclude that HP should be suspected in dry cleaners presenting with pulmonary complaints, and TCE should be considered as a potential trigger of disease. The spectrum of TCE-related occupational diseases and the diagnosis of HP are reviewed.
A Case of Drug-Induced Pneumonitis Caused by Carvedilol
Authors: Markou Nikolaos , Antzoulatos Nikolaos , Haniotou Aekaterini , Kanakaki Maria , Parissis John , Damianos Anastasios
Published: December 2004

We present a case of drug- induced pneumonitis caused by carvedilol. Forty days after drug cessation, there was almost complete resolution of pulmonary infiltrates. This is the first report of pneumonitis caused by carvedilol.
Stress-Induced Sensitization of the Hypothalamic-Pituitary Adrenal Axis Is Associated with Alterations of Hypothalamic and Pituitary Gene Expression
Authors: O’Connor Kevin A. , Ginsberg Abigail B. , Maksimova Elena , Wieseler Frank Julie L. , Johnson John D. , Spencer Robert L. , Campeau Serge , Watkins Linda R. , Maier Steven F.
Published: December 2004

We have previously reported that inescapable tail shock (IS) produces persistent changes in hypothalamic-pituitary-adrenal (HPA) axis function. These changes are manifest as an elevation in basal corticosterone (CORT) levels, a sensitization of adrenocorticotropin hormone (ACTH) and CORT responses to subsequent challenge, and a failure of dexamethasone to suppress both the ACTH and CORT responses to a subsequent challenge. The experiments presented here examine IS-induced alterations in the responsiveness of the HPA axis, particularly at the level of the anterior pituitary. The data presented show that adrenalectomy does not abolish the IS-induced sensitization of the HPA axis, suggesting that the sensitization is not solely caused by a defect in glucocorticoid negative feedback. Analysis of gene expression in the anterior pituitary revealed that IS exposure persistently elevated basal levels of proopiomelanocortin (POMC; the precursor to ACTH) mRNA and sensitized the POMC hnRNA and c-fos mRNA response to a subsequent challenge. Analysis of gene expression in the parvocellular division of the paraventricular nucleus of the hypothalamus (pPVN) after IS exposure revealed that basal levels of corticotropin-releasing hormone (CRH) mature mRNA are elevated and the c-fos mRNA response to a subsequent challenge is enhanced. Finally, a blunted in vitro ACTH response to CRH challenge is observed after IS exposure. These data suggest that the ultimate source of the IS-induced sensitization is not the anterior pituitary and implicate an increased drive on the anterior pituitary from the pPVN.