bluuebunny/crossref_metadata_2025 huggingface dataset:
Ground motions during the 1994 Northridge earthquake
Authors: Finn W. D. Liam , Ventura Carlos E. , Schuster Norman D.
Published: August 2008

The seismological background of the Northridge earthquake on a blind thrust fault is presented. The extensive data base of recorded ground motion provided the opportunity to review the effectiveness of some widely used attenuation relations for peak horizontal acceleration and pseudo-spectral velocity. Large pulses of velocity and displacement were noted in some records and the potential implications of these for tall buildings are noted. Some major damage centres coincided with alluvial basins. Generation of surface waves within the basins during the main shock contributed to increased amplification and duration. Surface waves were detected at the site of the collapse of the I-10 interchange and in the damaged area of Sherman Oaks using aftershock data. Cedar Hill seismographic station in Tarzana recorded the highest accelerations of the earthquake, much higher than motions at nearby stations. These are currently attributed to topographic effects of the hill on which the station is located. Aftershock data from two major arrays found that the low amplitude motions were magnified significantly at the crest of the hill compared to motions at the base. Key words: earthquake, thrust fault, ground motion attenuation, fault fling, surface waves, basin effects, topographic effects.
Damage to concrete structures due to the 1994 Northridge earthquake
Authors: Mitchell Denis , DeVall Ronald H. , Saatcioglu Murat , Simpson Robert , Tinawi René , Tremblay Robert
Published: August 2008

Observations on damage to concrete structures, due to the 1994 Northridge earthquake, are reported from a Canadian code perspective. Most of the damaged structures were older, nonductile, structures that do not conform to current design and detailing requirements. Concern is expressed about the seismic hazard of older Canadian structures having similar deficiencies. A significant number of parking structures suffered extensive damage and a number of precast concrete parking structures collapsed. Deficiencies in these structures include lack of proper diaphragm connections, a mix of gravity load columns with ductile framing, inappropriate number and distribution of shear walls, torsional effects caused by ramps, and the creation of short columns due to geometric features. This earthquake also demonstrated the deficiencies in connections of pre-1973 tilt-up structures. Key words: seismic design, earthquake, Northridge, structures, codes, concrete, precast concrete.
Performance of masonry structures during the 1994 Northridge (Los Angeles) earthquake
Authors: Bruneau Michel
Published: August 2008

The surface magnitude 6.8 Northridge earthquake which struck the Los Angeles area on January 17, 1994, damaged a large number of engineered buildings, of nearly all construction types. As earthquakes of at least similar strength are expected to occur in most of eastern and western Canada, the study of the effects of this earthquake is of particular significance to Canada. This paper, as part of a concerted multi-paper reporting effort, concentrates on the damage suffered by masonry buildings during this earthquake, and explains why the various types of observed failures occurred. The seismic performance of all masonry construction similar to that commonly found in Canada is reviewed, but a particular emphasis is placed on providing an overview of damage to unreinforced masonry structures which had been rehabilitated before this earthquake. To provide a better appreciation of the impact of this earthquake on masonry buildings, and a better assessment of the engineering significance of their damage in a Canadian perspective, this paper first reviews the evolution of building code requirements for unreinforced masonry buildings up to the seismic retrofit ordinances enacted prior to this earthquake. Examples of various damage types, as observed by the author during his reconnaissance visit to the stricken area, are then presented, along with technically substantiated descriptions of the causes for this damage, and cross-references to relevant clauses from Canadian standards and codes, as well as the recently published Canadian Guidelines for the Seismic Evaluation of Existing Buildings, whenever appropriate. Key words: earthquake, unreinforced masonry, seismic rehabilitation, retrofit, retrofitted masonry building, reinforced masonry, buildings, failure, collapse, heritage buildings.
Performance of bridges in the 1994 Northridge earthquake
Authors: Mitchell Denis , Bruneau Michel , Saatcioglu Murat , Williams Martin , Anderson Donald , Sexsmith Robert
Published: August 2008

This paper describes damage to bridges caused by the 1994 earthquake at Northridge, California. A description of the damage and the probable causes are presented for the seven bridges that suffered some form of collapse. The majority of damage was due to column shear or combined shear and flexure failures, but restrainer failure was the cause of collapse in one bridge. The lack of damage to other bridges and to foundations is discussed. Key words: Northridge, earthquake, seismic, bridges, damage, performance.
Performance of lifelines during the 1994 Northridge earthquake
Authors: Lau David L. , Tang Alex , Pierre Jean-Robert
Published: August 2008

Lifelines are essential infrastructures and facilities that are considered vital to the rescue effort and recovery of the affected community in the event of a natural disaster or emergency. The lifeline systems in a densely populated area, such as the Los Angeles basin, are very complex. The Northridge earthquake, which occurred in southern California on January 17, 1994, caused extensive damage to many of these lifeline facilities in the epicentral area. Effects of the damages were felt not only in the vicinity area of the earthquake but also in areas far from the earthquake site. This paper describes the earthquake damage to and performance of gas and water distribution and electric power and telecommunication systems. The impact of these failures on the overall system performance are presented. The significance and effect of the interdependency of life systems in an integrated urban environment are discussed. Lessons learned on system performance, seismic risk, and reliability of lifeline systems from the Canadian perspective are presented. Key words: earthquake damages, electric power, gas, lifelines, performance, risk, telecommunication, water.
BOUNDARY EFFECTS IN STRING THEORY AND THE EFFECTIVE STRING COUPLING
Authors: DAVIS SIMON
Published: August 2008

The effect of the ideal boundaries of infinite-genus surfaces and Dirichlet boundaries on the value of the string coupling is evaluated. It is demonstrated that the value coincides with the unified gauge coupling and it is not altered by the inclusion of curved four-dimensional spacetimes in the path integral for quantum gravity or boundaries with fractional dimension and nonzero harmonic measure.
LIMITS ON THE TIME VARIATION OF FUNDAMENTAL CONSTANTS
Authors: FRITZSCH H.
Published: August 2008

We discuss possible time changes of the 28 fundamental constants of the Standard Model of Particle Physics. In particular, we concentrate on those constants, which are not known very precisely. Time variations of those constants might have been overlooked thus far. Future experiments should provide better limits, or might discover a time variation.
Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors
Authors: Masyuk Anatoliy I. , Gradilone Sergio A. , Banales Jesus M. , Huang Bing Q. , Masyuk Tatyana V. , Lee Seung-Ok , Splinter Patrick L. , Stroope Angela J. , LaRusso Nicholas F.
Published: August 2008

Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, contain primary cilia, which are mechano- and osmosensory organelles detecting changes in bile flow and osmolality and transducing them into intracellular signals. Here, we asked whether cholangiocyte cilia are chemosensory organelles by testing the expression of P2Y purinergic receptors and components of the cAMP signaling cascade in cilia and their involvement in nucleotide-induced cAMP signaling in the cells. We found that P2Y12 purinergic receptor, adenylyl cyclases (i.e., AC4, AC6, and AC8), and protein kinase A (i.e., PKA RI-β and PKA RII-α regulatory subunits), exchange protein directly activated by cAMP (EPAC) isoform 2, and A-kinase anchoring proteins (i.e., AKAP150) are expressed in cholangiocyte cilia. ADP, an endogenous agonist of P2Y12 receptors, perfused through the lumen of isolated rat intrahepatic bile ducts or applied to the ciliated apical surface of normal rat cholangiocytes (NRCs) in culture induced a 1.9- and 1.5-fold decrease of forskolin-induced cAMP levels, respectively. In NRCs, the forskolin-induced cAMP increase was also lowered by 1.3-fold in response to ATP-γS, a nonhydrolyzed analog of ATP but was not affected by UTP. The ADP-induced changes in cAMP levels in cholangiocytes were abolished by chloral hydrate (a reagent that removes cilia) and by P2Y12 siRNAs, suggesting that cilia and ciliary P2Y12 are involved in nucleotide-induced cAMP signaling. In conclusion, cholangiocyte cilia are chemosensory organelles that detect biliary nucleotides through ciliary P2Y12 receptors and transduce corresponding signals into a cAMP response.
Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat
Authors: Badejo Adeleke M. , Dhaliwal Jasdeep S. , Casey David B. , Gallen Thomas B. , Greco Anthony J. , Kadowitz Philip J.
Published: August 2008

The small GTP-binding protein Rho and its downstream effector, Rho-kinase, are important regulators of vasoconstrictor tone. Rho-kinase is upregulated in experimental models of pulmonary hypertension, and Rho-kinase inhibitors decrease pulmonary arterial pressure in rodents with monocrotaline and chronic hypoxia-induced pulmonary hypertension. However, less is known about responses to fasudil when pulmonary vascular resistance is elevated on an acute basis by vasoconstrictor agents and ventilatory hypoxia. In the present study, intravenous injections of fasudil reversed pulmonary hypertensive responses to intravenous infusion of the thromboxane receptor agonist, U-46619 and ventilation with a 10% O2 gas mixture and inhibited pulmonary vasoconstrictor responses to intravenous injections of angiotensin II, BAY K 8644, and U-46619 without prior exposure to agonists, which can upregulate Rho-kinase activity. The calcium channel blocker isradipine and fasudil had similar effects and in small doses had additive effects in blunting vasoconstrictor responses, suggesting parallel and series mechanisms in the lung. When pulmonary vascular resistance was increased with U-46619, fasudil produced similar decreases in pulmonary and systemic arterial pressure, whereas isradipine produced greater decreases in systemic arterial pressure. The hypoxic pressor response was enhanced by 5–10 mg/kg iv nitro-l-arginine methyl ester (l-NAME), and fasudil or isradipine reversed the pulmonary hypertensive response to hypoxia in control and in l-NAME-treated animals, suggesting that the response is mediated by Rho-kinase and L-type Ca2+ channels. These results suggest that Rho-kinase is constitutively active in regulating baseline tone and vasoconstrictor responses in the lung under physiological conditions and that Rho-kinase inhibition attenuates pulmonary vasoconstrictor responses to agents that act by different mechanisms without prior exposure to the agonist.
Menstrual cycle and oral contraceptive use do not modify postexercise heat loss responses
Authors: Kenny Glen P. , Leclair Emily , Sigal Ronald J. , Journeay W. Shane , Kilby Donald , Nettlefold Lindsay , Reardon Francis D. , Jay Ollie
Published: August 2008

It is unknown whether menstrual cycle or oral contraceptive (OC) use influences nonthermal control of postexercise heat loss responses. We evaluated the effect of menstrual cycle and OC use on the activation of heat loss responses during a passive heating protocol performed pre- and postexercise. Women without OC ( n = 8) underwent pre- and postexercise passive heating during the early follicular phase (FP) and midluteal phase (LP). Women with OC ( n = 8) underwent testing during the active pill consumption (high exogenous hormone phase, HH) and placebo (low exogenous hormone phase, LH) weeks. After a 60-min habituation at 26°C, subjects donned a liquid conditioned suit. Mean skin temperature was clamped at ∼32.5°C for ∼15 min and then gradually increased, and the absolute esophageal temperature at which the onset of forearm vasodilation (Thvd) and upper back sweating (Thsw) were noted. Subjects then cycled for 30 min at 75% V̇o2 peak followed by a 15-min seated recovery. A second passive heating was then performed to establish postexercise values for Thvd and Thsw. Between 2 and 15 min postexercise, mean arterial pressure (MAP) remained significantly below baseline ( P < 0.05) by 10 ± 1 and 11 ± 1 mmHg for the FP/LH and LP/HH, respectively. MAP was not different between cycle phases. During LP/HH, Thvd was 0.16 ± 0.24°C greater than FP/LH preexercise ( P = 0.020) and 0.15 ± 0.23°C greater than FP/LH postexercise ( P = 0.017). During LP/HH, Thsw was 0.17 ± 0.23°C greater than FP/LH preexercise ( P = 0.016) and 0.18 ± 0.16°C greater than FP/LH postexercise ( P = 0.001). Postexercise thresholds were significantly greater ( P ≤ 0.001) than preexercise during both FP/LH (Thvd, 0.22 ± 0.03°C; Thsw, 0.13 ± 0.03°C) and LP/HH (Thvd, 0.21 ± 0.03°C; Thsw, 0.14 ± 0.03°C); however, the effect of exercise was similar between LP/HH and FP/LH. No effect of OC use was observed. We conclude that neither menstrual cycle nor OC use modifies the magnitude of the postexercise elevation in Thvd and Thsw.
Recovery from supraspinal fatigue is slowed in old adults after fatiguing maximal isometric contractions
Authors: Hunter Sandra K. , Todd Gabrielle , Butler Jane E. , Gandevia Simon C. , Taylor Janet L.
Published: August 2008

This study compared the contribution of supraspinal fatigue to muscle fatigue in old and young adults. Transcranial magnetic stimulation (TMS) of motor cortex was used to assess voluntary activation during maximal voluntary contractions (MVCs) of elbow flexor muscles in 17 young adults (25.5 ± 3.6 yr; mean ± SD) and 7 old adults (73.0 ± 3.3 yr). Subjects performed a fatigue task involving six sustained MVCs (22-s duration, separated by 10 s). Young adults exhibited greater reductions in maximal voluntary torque (67 ± 15% of baseline) than the old (37 ± 6%; P < 0.001). Increments in torque (superimposed twitch) generated by TMS during sustained MVCs increased for the young and old ( P < 0.001) but were larger for the old adults at the start of the sustained contractions and during recovery ( P < 0.05). Voluntary activation was less for the old adults at the start of some sustained contractions and during recovery ( P = 0.02). Motor-evoked potential area increased similarly with age during the fatiguing task but was greater for the old adults than young during recovery. Silent period duration lengthened less for the old adults during the fatigue task. At the end of the fatiguing task, peak relaxation rate of muscle fibers had declined more in the young than the old adults. The greater endurance with age is largely due to a difference in mechanisms located within the muscle. However, recovery from the fatiguing exercise is impaired for old adults because of greater supraspinal fatigue than in the young.
Spontaneous and influenza virus-induced sleep are altered in TNF-α double-receptor deficient mice
Authors: Kapás Levente , Bohnet Stewart G. , Traynor Tim R. , Majde Jeannine A. , Szentirmai Éva , Magrath Paul , Taishi Ping , Krueger James M.
Published: August 2008

Tumor necrosis factor-α (TNF-α) is associated with sleep regulation in health and disease. Previous studies assessed sleep in mice genetically deficient in the TNF-α 55-kDa receptor. In this study, spontaneous and influenza virus-induced sleep profiles were assessed in mice deficient in both the 55-kDa and 75-kDa TNF-α receptors [TNF-2R knockouts (KO)] and wild-type (WT) strain controls. Under baseline conditions the TNF-2R KO mice had less non-rapid eye movement sleep (NREMS) than WTs during the nighttime and more rapid eye movement sleep (REMS) than controls during the daytime. The differences between nighttime maximum and daytime minimum values of electroencephalogram (EEG) delta power during NREMS were greater in the TNF-2R KO mice than in WTs. Viral challenge (mouse-adapted influenza X-31) enhanced NREMS and decreased REMS in both strains roughly to the same extent. EEG delta power responses to viral challenge differed substantially between strains; the WT animals increased, whereas the TNF-2R KO mice decreased their EEG delta wave power during NREMS. There were no differences between strains in body temperatures or locomotor activity in uninfected mice or after viral challenge. Analyses of cortical mRNAs confirmed that the TNF-2R KO mice lacked both TNF-α receptors; these mice also had higher levels of orexin mRNA and reduced levels of the purine P2X7 receptor compared with WTs. Results reinforce the hypothesis that TNF-α is involved in physiological sleep regulation but plays a limited role in the acute-phase response induced by influenza virus.
Effect of chronic unloading and rehabilitation on human Achilles tendon properties: a velocity-encoded phase-contrast MRI study
Authors: Shin Dongsuk , Finni Taija , Ahn Sinyeob , Hodgson John A. , Lee Hae-Dong , Edgerton V. Reggie , Sinha Shantanu
Published: August 2008

The objective of this study was to measure and monitor changes in Achilles tendon mechanical properties and force production capability of triceps surae muscles after 4 wk of limb suspension and 6 wk of physical rehabilitation. Five healthy volunteers underwent unilateral lower limb suspension followed by weekly physiotherapy. A velocity-encoded, phase-contrast magnetic resonance imaging (VE-PC-MRI) technique was used to estimate the tendon strain as a function of force produced during the submaximal isometric contractions. After limb suspension, triceps surae muscle strength decreased to 53.2 ± 15.6% (mean ± SD) of the presuspension level ( P < 0.05). Young's modulus, estimated from the slope of the tendon stress-strain relationship, decreased by 17.1% (from 140.50 ± 29.33 to 119.95 ± 36.07 MPa, P < 0.05), while the tendon transition point, reflecting the “toe region,” increased by 55.7% (from 2.2 ± 1.0% to 3.4 ± 1.24%). Muscle strength, tendon stiffness, and transition point recovered to presuspension levels by the end of 6 wk of rehabilitation. Calcaneus movement was significant during the “isometric” contraction, accounting for 52.13 ± 7.63% of the tendon displacement. Tendon cross-sectional area determined from anatomic magnetic resonance axial images remained unchanged, suggesting that the altered tendon elastic modulus and transition point were largely due to material deterioration. The increase in the transition point following chronic unloading as measured by the VE-PC-MRI technique has not been previously reported and offers new insights into the biomechanical changes that may occur in the tendon crimp structure.
Activated PPARγ Targets Surface and Intracellular Signals That Inhibit the Proliferation of Lung Carcinoma Cells
Authors: Han Shou Wei , Roman Jesse
Published: August 2008

Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights into the cellular mechanisms involved in the control of energy homeostasis, the regulation of cell differentiation, proliferation, and apoptosis, and the modulation of important biological and pathological processes related to inflammation and cancer biology, among others. Since then, PPARs have become an exciting target for the development of therapies directed at many disorders including cancer. PPARs are expressed in many tumors including lung cancer, and their function has been linked to the process of carcinogenesis. Consequently, intense research is being conducted in this area with the hope of discovering new PPAR‐related therapeutic targets for the treatment of lung cancer. This review summarizes the research being conducted in this area, and focuses on the mechanisms by which a member of this family (PPARγ) is believed to affect lung tumor cell biology.
S6K1 Plays a Key Role in Glial Transformation
Authors: Nakamura Jean L. , Garcia Edna , Pieper Russell O.
Published: August 2008

The mammalian target of rapamycin (mTOR) is a nutrient and ATP sensor suggested to play an important role in tumorigenesis, particularly in the setting of PTEN loss or activated Akt/PKB. Of mTOR's two known effectors, eIF4E has been implicated in tumorigenesis, whereas the role of S6 kinase (S6K1) in transformation is less understood. To assess the contribution of S6K1 to the transformed phenotype, we pharmacologically and genetically manipulated the mTOR-S6K pathway in glioma cells and monitored its effects on growth in soft agar, a hallmark of cellular transformation, and also assessed in vivo intracranial growth. Anchorage-independent growth by HRasV12-transformed human astrocytes as well as by U251 and U373 human glioma cells was inhibited by pharmacologic mTOR inhibition. Similarly, short hairpin RNA–mediated suppression of mTOR also reduced anchorage-independent growth of glioma cell lines. Expression of wild-type eIF4E in rapamycin-treated E6/E7/hTert/HRasV12 and U373 cells failed to rescue colony formation, although expression of wild-type S6K1 or rapamycin-resistant S6K1 in rapamycin-treated U373 and U251 provided partial rescue. Consistent with the latter observation, small interfering RNA–mediated suppression of S6K1 in HRasV12-transformed human astrocytes, U251, and U373 cells resulted in a significant loss of anchorage-independent growth. Furthermore, we found that in vivo short hairpin RNA–mediated suppression of S6K1 in HRasV12-transformed human astrocytes reduced intracranial tumor size, in association with reduced tumor levels of phosphorylated ribosomal protein S6. These findings implicate the mTOR-S6K pathway as a critical mediator of glial cell transformation. [Cancer Res 2008;68(16):6516–23]
R-Cadherin Expression Inhibits Myogenesis and Induces Myoblast Transformation via Rac1 GTPase
Authors: Kucharczak Jérôme , Charrasse Sophie , Comunale Franck , Zappulla Jacques , Robert Bruno , Teulon-Navarro Isabelle , Pèlegrin André , Gauthier-Rouvière Cécile
Published: August 2008

Cadherins are transmembrane glycoproteins that mediate Ca2+-dependent homophilic cell-cell adhesion and play a crucial role in proliferation, differentiation, and cell transformation. The goal of this study was to understand why R-cadherin is found in rhabdomyosarcomas (RMS), tumors of skeletal muscle origin, whereas it is absent in normal myoblasts. We show that R-cadherin expression in C2C12 myoblasts causes inhibition of myogenesis induction and impairment of cell cycle exit when cells are cultured in differentiation medium. Furthermore, R-cadherin expression elicits myoblast transformation, as shown by anchorage-independent growth in soft agar in vivo tumor formation assays and increased cell motility. In contrast, inhibition of R-cadherin expression using RNA interference hinders growth of RD cell line in soft agar and its tumorigenicity in mice. The analysis of the nature of R-cadherin–mediated signals shows that R-cadherin–dependent adhesion increases Rac1 activity. Dominant-negative forms of Rac1 inhibit R-cadherin–mediated signaling and transformation. In addition, expression of R-cadherin results in perturbed function of endogenous N-cadherin and M-cadherin. Together, these data suggest that R-cadherin expression inhibits myogenesis and induces myoblast transformation through Rac1 activation. Therefore, the properties of R-cadherin make it an attractive target for therapeutic intervention in RMS. [Cancer Res 2008;68(16):6559–68]
Cervical Cancer: Screening and Therapeutic Perspectives
Authors: Sankaranarayanan Rengaswamy , Thara Somanathan , Esmy Pulikottil Okkuru , Basu Partha
Published: August 2008

Cervical cancer is a major cause of mortality and premature death among women in their most productive years in low- and medium-resourced countries in Asia, Africa and Latin America, despite the fact that it is an eminently preventable cancer. While cytology screening programmes have resulted in a substantial reduction of cervical cancer mortality in developed countries, they have been shown to have a wide range of sensitivity in most routine settings including in developing countries. Although liquid-based cytology improves sample adequacy, claims on improved sensitivity remain controversial. Human papillomavirus testing is more sensitive than cytology, but whether this gain represents protection against future cervical cancer is not clear. Recently, in a randomized trial, the use of visual inspection with 4% acetic acid was shown to reduce cervical cancer incidence and mortality. Cryotherapy and large loop excision of the transformation zone are effective and safe treatment methods for cervical intraepithelial neoplasia. The clinical stage of cancer is the single most important prognostic factor and should be carefully evaluated in choosing optimal treatment between surgery and radiotherapy, with or without chemotherapy. At the public health level, health care infrastructure, affordability and capacity for initiating and sustaining vaccination and screening programmes are critical factors in cervical cancer control. On the other hand, an informed practitioner can utilize the multiple opportunities in routine primary care interactions for prevention, screening, early detection and prompt referral for treatment.
Norepinephrine and E139 Interactions on Epileptiform Activity in the Rat Hippocampus in vitro
Authors: Kombian Samuel B. , Ananthalakshmi Kethireddy V.V. , Edafiogho Ivan O.
Published: August 2008

Objectives: We tested if E139, an anticonvulsant enaminone, interacts with norepinephrine (NE) to suppress population responses and chemically induced in vitro seizures in the rat hippocampus. Materials and Methods: Evoked field population spikes (PS) were recorded in the hippocampal CA1 area, and in vitro seizures were generated chemically using the zero Mg2+ model. Results: Low concentrations of E139 (≤10 µM) reversibly inhibited PS amplitude while high concentrations (≧100 µM) enhanced them. For example, E139 (10 µM) depressed the PS amplitude by –23.9 ± 2.3%, while 1 mM caused an enhancement. NE also depressed the PS by –34.5 ± 6.0% and prevented E139 from subsequently depressing the PS amplitude. UK 14304, a selective α2-adrenoceptor agonist, also depressed the PS amplitude by –32.6 ± 9.4% and occluded E139 suppression. NE suppression of PS was blocked by phentolamine and yohimbine which also blocked the effect of E139. Prazosin, a selective α1-adrenoceptor antagonist, did not block NE (–24.8 ± 6.9%) or E139 (–29.7 ± 6.1%) effects. Zero Mg2+ buffer transformed a single PS to multiple spikes (MS; 3–8 spikes) and also induced spontaneous bursts (SB; 5–20/min). NE suppressed the number of MS from 5.6 ± 0.3 to 3.8 ± 0.2. At its peak effect, E139 was able to further suppress the number of MS to 3.0 ± 0.3. Yohimbine did not change the number of MS but blocked the NE- and E139-induced suppression of MS. SB frequency was suppressed by NE (–60.8 ± 11.7%) which occluded E139 effects. Finally, SB were reversibly abolished by yohimbine (–94.5 ± 11.7%). Conclusion: E139 suppressed population responses and in vitro epileptiform activity by both adrenergic and non-adrenergic mechanisms.
Amplification of Six Putative RD1 Genes of Mycobacterium tuberculosis for Cloning and Expression in Escherichia coli and Purification of Expressed Proteins
Authors: Amoudy Hanady A. , Mustafa Abu S.
Published: August 2008

Objectives: To amplify, clone and express in Escherichia coli six open reading frames (ORFs) predicted in the RD1 DNA segment of Mycobacterium tuberculosis and purify the expressed proteins to homogeneity. Materials and Methods: DNA corresponding to the coding regions of six RD1 ORFs, i.e. ORF10 to ORF15, was amplified from genomic DNA of M. tuberculosis, cloned in the plasmid vector pPCR-Script and subcloned in expression plasmid vectors pET29a and/or pGEX-4T for expression in E. coli as fusion proteins. The recombinant fusion proteins were identified by sodium dodecyl polyacrylamide gel electrophoresis and Western immunoblotting. Attempts were made to obtain purified proteins, free of the fusion partner, using affinity and fast protein liquid chromatography. Results: DNA corresponding to all six targeted RD1 ORFs was amplified from the genomic DNA of M. tuberculosis and five of the six ORFs, with the exception of ORF13, were cloned in the plasmid vectors and expressed in E. coli. Because of extensive degradation of ORF10 and ORF12 fusion proteins or nonbinding to the affinity columns of ORF15 fusion proteins, only ORF11 and ORF14 proteins were purified, free of the fusion partner, to homogeneity. Conclusion: All of the six targeted RD1 genes were amplified and five expressed using E. coli hosts, but only two of the expressed proteins were purified to homogeneity. Alternative expression systems are required to obtain all RD1 proteins for functional characterization.
Subclinical Hypothyroidism Is Characterized by Increased QT Interval Dispersion among Women
Authors: Bakiner O. , Ertorer M.E. , Haydardedeoglu F.E. , Bozkirli E. , Tutuncu N.B. , Demirag N.G.
Published: August 2008

Objective: Increased QT interval dispersion (QTd) is an electrocardiographic parameter shown to be associated with malignant ventricular arrhythmias and sudden death, and QT dispersion corrected for heart rate (QTc) has emerged as a potentially important predictor of cardiac death. Increased QTd has been detected to be directly related to thyroid-stimulating hormone (TSH) levels in overt hypothyroidism, however not much is known about subclinical hypothyroidism (SH). This study was conducted to investigate the QTc in SH and determine the changes following normalization of TSH levels with L-thyroxine. Subjects and Methods: Fifty-eight women with naive SH due to Hashimoto’s thyroiditis, mean age 39.37 ± 10.43 years, and 54 age-, sex- and weight-matched controls with normal TSH were included after exclusion of any factor that might interfere with cardiac conductibility. Electrocardiographic measurements were performed with a magnifier and Bazett’s formula was used to calculate QTc. The patients were separated into two groups regarding basal TSH levels (subgroup A: 5 > TSH > 10 mIU/l, n = 36; subgroup B: TSH > 10 mIU/l, n = 22). L-Thyroxine 1–2 µg/kg/day was administered to subgroup B. Results: Mean QTc interval of the study group was significantly longer than that of the control group (100 ± 30 vs. 76 ± 30 ms, p = 0.000). It was also longer in subgroup A (5 > TSH > 10 mIU/l, n = 36) and subgroup B (p = 0.001, p = 0.000, respectively). In subgroup B, following normalization of serum TSH, mean post-treatment QTc measurement was similar to that of the control group (75 ± 40 vs. 76 ± 30 ms, p > 0.05). Conclusion: We detected prolonged QTc among SH cases. Prolongation remained significant for the whole group as well as the two subgroups. The differences in QTc were corrected when TSH levels of >10 mIU/l returned to normal.
Germline Mutation in the von Hippel-Lindau Gene in Kuwait
Authors: AlFadhli Suad M. , Mohammed Bader , Yassin Ahmid
Published: August 2008

Objectives: We aimed to investigate germline mutation in another extended von Hippel-Lindau (VHL) family in Kuwait with Arabian and Persian genetic admixture. Materials andMethod: Polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) and direct sequencing of the PCR amplicons, that showed clear band shift, were used to screen the VHL gene in the index patient, 20 members of her family and 55 healthy controls of matching ethnicity. Result: The clinical history of all patients revealed multiple hemangioblastomas in various organs without pheochromocytomas. SSCP showed a clear band shift in 2 PCR amplicons, which were then sequenced. One was in the promoter region revealing a polymorphic site (A–123G) found as heterozygous in 40% of the healthy control subjects of the same ethnicity. The second band shift was in exon 2 seen in all clinically diagnosed VHL cases but not in the healthy members of the family or the screened healthy population. Direct sequencing revealed it was a heterozygous missense mutation G564T (Trp117Cys). Tracking the mutation in the family pedigree showed its origin from the Persian side. Conclusion: This is a second missense G564T mutation in another VHL patient from Kuwait that will help expand our knowledge of the VHL gene mutation spectrum in this region of the world.
Internal Herniation as a Major Cause of Intestinal Obstruction
Authors: Tekin Ahmet , Küçükkartallar Tevfik , Aksoy Faruk , Vatansev Celalettin , Belviranlı Metin , Tekin Sakir , Yol Serdar , Sahin Mustafa , Tavlı Sakir , Kartal Adil
Published: August 2008

Objectives: To evaluate internal herniation as a rare cause of intestinal obstruction.Materials and Methods: Files of 18 cases, operated due to internal herniation between 2000 and 2006 at Selcuk University, Meram School of Medicine, General Surgery Department, were reviewed retrospectively. Sixteen patients (88.8%) were male (mean age: 58.2 years; range: 42–67) and 2 were female (mean age: 56.5 years; range: 52–61).Cases were grouped according to the location of internal herniation, and the clinical findings and applied treatment strategies were evaluated. Results: All patients were taken into surgical operation after preoperative preparations were completed. Findings were as follows: 6 cases of paraduodenal internal herniation, 4 of internal herniation through a defect in the terminal mesoileum, 2 of herniation through a defect in the falciform ligament, 2 of herniation through a defect in the omentum majus, 1 of herniation to the recessus over the bladder, 2 of herniation through a defect in the transverse mesocolon and 1 iatrogenically caused internal herniation through a defect in the mesojejunum. Conclusion: In an adult patient with findings of intestinal obstruction, diagnosis is difficult. Most cases presented to date are incidental findings during laparotomy, and surgical treatment is necessary.
Incidence of Contrast-Induced Nephropathy with Volume Supplementation – Insights from a Large Cohort
Authors: Mueller-Lenke Nicole , Buerkle Gerd , Klima Theresia , Breidthardt Tobias , Buettner Heinz J. , Mueller Christian
Published: August 2008

Objective: The present study was performed to determine the effect of combined intravenous and oral volume supplementation on the incidence of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). Subjects and Methods: Consecutive patients (n = 958) receiving iomeprol 350 during PCI were evaluated prospectively for the development of CIN. All patients received protocol-defined intravenous and oral volume supplementation. CIN was defined as an increase in serum creatinine of at least 44 µmol/l within 48 h. Results: Of the 958 patients enrolled in the study, 147 (15%) were diabetic and 107 (11%) had stage III renal disease. The average baseline glomerular filtration rate was 88 ± 25 ml/min/1.73 m2. During the intervention an average of 238 ± 86 ml of contrast medium was administered. CIN developed in 13 of 958 (1.4%; 95% confidence interval 0.6–2.1%) patients. The incidence of CIN was low even in predefined risk subgroups (women: 2.4%, diabetics: 2.7%, patients with stage III kidney disease: 6.5%). Conclusions: The incidence of CIN is low when preprocedural fluid volume supplementation is used.
A Giant Hemorrhagic Adrenal Pseudocyst
Authors: Stimac Goran , Katusic Josip , Sucic Mario , Ledinsky Mario , Kruslin Bozo , Trnski Davor
Published: August 2008

Objective: To report a rare case of a giant hemorrhagic adrenal pseudocyst and highlight the importance of this entity to clinicians. Case Presentation: A 57-year-old woman presented with a 1-year history of abdominal pain and distension. Ultrasonography and multislice computed tomography revealed a giant cystic (partially solid) mass over the left suprarenal region measuring 20 × 17 × 15 cm. A complete endocrine workup failed to detect any hormonal hypersecretion. Intervention: The patient was treated with tumor excision through transabdominal pararectal approach. Histopathological examination revealed a hemorrhagic adrenal pseudocyst. Conclusion: To our knowledge the case presented here appears to be one of the largest hemorrhagic adrenal pseudocysts reported so far. Radiological and clinical features of the tumor are nonspecific and histopathological examination is essential to establish definitive diagnosis. An open, laparotomic adrenalectomy is the preferred surgical technique for better control of such a large mass with active bleeding inside.
Osteomalacic Myopathy Associated with Coexisting Coeliac Disease and Primary Biliary Cirrhosis
Authors: Demirag Mehmet D. , Goker Berna , Haznedaroglu Seminur , Ozturk Mehmet A. , Karakan Tarkan , Kuruoglu Reha
Published: August 2008

Objective: To report a patient with coeliac disease (CD) associated with primary biliary cirrhosis (PBC) who presented with myopathy without classical symptoms of CD. Clinical Presentation and Intervention: A 42-year-old woman presented with inability to walk and marked loss of motor function. She had elevated liver enzymes with a cholestatic pattern. Antimitochondrial antibody M2 band, anti-endomysial antibody, antigliadin IgA and IgM were positive. Histopathologic findings of the liver revealed PBC and duodenal biopsy was consistent with CD. She was also found to have osteomalacia. She showed slow response to gluten-free diet, but accelerated full recovery with vitamin D replacement. Conclusion: In PBC patients with subclinical CD and myopathy, vitamin D status can provide a basis for treatment.
Two Cardiovascular Risk Factors in One? Homocysteine and Its Relation to Glomerular Filtration Rate
Authors: Kielstein Jan T. , Salpeter Shelley R. , Buckley Nicholas S. , Cooke John P. , Fliser Danilo
Published: August 2008

Background: Hyperhomocysteinemia is thought to be an independent risk factor for cardiovascular disease, but the association between renal dysfunction and homocysteine may not have been fully taken into account. We performed a meta-analysis of studies that report correlations between glomerular filtration rate (GFR) and homocysteine plasma levels. Methods: Using a prespecified research strategy, we identified 41 studies involving 26,617 participants that reported Pearson or Spearman correlation coefficients for the association between 1/GFR and homocysteine. The summary correlation coefficients with 95% CI were obtained by pooling the logarithmic Z values derived from the individual trial correlation coefficients. Subgroup analysis was performed to compare results for measured GFR using clearance methods and various estimates of GFR. Results: The pooled correlation coefficient between homocysteine and 1/GFR was 0.37 (CI 0.32–0.40, p < 0.0001). The correlation coefficient based on various estimates of GFR was 0.33 (CI 0.29–0.38, p < 0.0001), and for measured GFR it was 0.45 (CI 0.39–0.51, p < 0.0001). The correlation coefficient was higher when GFR was measured using clearance methods compared with various estimates GFR (1.36 [CI 1.13–1.65], p = 0.0014). Conclusions: Homocysteine plasma levels significantly depend on renal function. This correlation is even more robust when GFR is measured using clearance methods. Therefore, in order to assess whether homocysteine is an independent cardiovascular risk factor, accurate adjustments for renal dysfunction are essential.
Cognitive Impairment after Tick-Borne Encephalitis
Authors: Gustaw-Rothenberg Katarzyna
Published: August 2008

Background/Aims: Tick-borne encephalitis (TBE) is a potentially debilitating disease caused by the TBE virus. Natural foci of TBE were localized in the Lublin region (Poland). We observed the growing tendency of the incidence of TBE in the Lublin region at the beginning of the 1990s. Farmers and forestry workers were most often infected due to the occupational risk. Methods: Forty farmers with TBE since the beginning of the year 2001 were included in the study. Serological measurements as well as medical and neuropsychological examination confirmed the infection. Dementia and mild cognitive impairment were diagnosed on the basis of DSM-IV-R, ICD-10 and Petersen criteria, respectively. Results: Long-term consequences of the illness have been reported in 22 subjects. In this group, cognitive impairment of the amnestic type was diagnosed. No decline in cognitive status was observed in the examined patients for 6 months. Conclusions: The diagnosis of human TBE is usually based on serology, which has a number of pitfalls. The outcome of the disease can mimic many neurological diseases. For that reason, the history of farmers with cognitive decline should be carefully examined. There is reasonable likelihood of cognitive decline in patients with TBE.
Prolongation of Corneal Allograft Survival by Topical Application of Everolimus in Experimental Keratoplasty
Authors: Li X.Q. , Büch G. , Otasevic L. , Schlickeiser S. , Bertelmann E. , Pleyer U.
Published: August 2008

Background: Everolimus is a novel proliferation signal inhibitor that has potent immunosuppressive activity. As previously shown, systemic administration of the drug could effectively enhance the mean survival time (MST) of corneal allografts. Commonly, the topical application of immunomodulatory agents is preferred over systemic use, in order to reduce the side effects. Purpose: To investigate the efficacy of topically applied everolimus to prevent corneal graft rejection in an experimental model. Methods: A total of 45 female Lewis rats received 3.5-mm grafts of MHCI/II incompatible Dark Agouti donors. Recipients were randomly assigned to receive either: (1) 0.05% everolimus microemulsion, (2) 0.025% everolimus microemulsion or (3) a vehicle as the control. Treatment was started on the day of surgery and applied 5 times daily. Grafts were graded every day and a rejection score was generated based on cornea clarity and oedema. Results: Local administration of 0.05 or 0.025% everolimus was effective in prolonging the mean survival time of corneal grafts (MST = 21 ± 6.57 days and 16.4 ± 2.3 days, respectively) as compared to vehicle control group (MST = 13.3 ± 1.7 days; p < 0.001 and p < 0.001). Real-time PCR demonstrated that topical administration of everolimus increased the mRNA levels of CD25, IL-10 and IFN-γ, but this was significant only for IL-10 (p = 0.015). Conclusions: These data indicate that topically applied everolimus is effective in prolonging corneal allograft survival in an experimental keratoplasty model.
Adrenergic Regulation of cAMP/Protein Kinase A Pathway in Corneal Epithelium and Endothelium
Authors: Grueb Matthias , Bartz-Schmidt Karl Ulrich , Rohrbach Jens Martin
Published: August 2008

Purpose: The G-protein-coupled receptor/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells. The aim of this study was to characterize subtypes of adrenergic G-protein-coupled receptors and their influence on cAMP concentration and PKA activity in bovine corneal epithelial and endothelial cells. Procedures: Adrenergic receptors and PKA were studied using polyclonal antibodies. cAMP concentration was determined with an enzyme immunoassay, and PKA activity was estimated by the kinases consumption of adenosine triphosphate. Results: In bovine corneal epithelial and endothelial cells, immunocytochemistry and Western blot were positive for α1-, α2A-, β1- and β2-adrenergic receptors. Stimulation of corneal epithelial and endothelial β-adrenoceptors with isoprenaline led to a dose-dependent increase in cAMP concentration and activation of PKA. Stimulation of corneal α2A-adrenoceptors with brimonidine resulted in a dose-dependent decrease in cAMP concentration and the inhibition of PKA activity. Conclusions: In corneal epithelial and endothelial cells, β-adrenergic stimulation leads to activation of PKA via stimulation of adenylyl cyclase, and α2A-adrenoceptor stimulation inhibits PKA activity via inhibition of adenylyl cyclase. Stimulation and inhibition of the corneal cAMP-PKA pathway may play a role in important corneal functions such as wound healing or homeostasis. Long-term therapy with α2A-agonists or β-antagonists may influence these functions in a currently unknown way.
Combined Effects of Cigarette Smoking and Alcohol Consumption on Perinatal Outcome
Authors: Odendaal Hein J. , Steyn D. Wilhelm , Elliott Amy , Burd Larry
Published: August 2008

Background: An increase in various congenital abnormalities associated with cigarette smoking and the use of alcohol during pregnancy has been reported in many studies. These exposures also increase the risk of pregnancy complications such as abruptio placentae, unexplained stillbirth, preterm labor and intrauterine growth restriction. However, very few studies have addressed the combined effect of smoking and drinking on pregnancy outcomes. Methods: In this review, the adverse effects of smoking or drinking on pregnancy were obtained from publications in which both substances were addressed in the same study population. A special effort was made to find studies in which the combined effect of these substances was investigated. Results: Preterm labor occurred more frequently in women who drank and smoked during pregnancy. This increased odds ratio was more than the sum of the effects of either smoking or drinking, indicating that the use of both substances by the same woman has a synergistic effect that increases the risk of preterm labor. This synergistic effect was also found for low birth weight and growth restriction. Conclusions: As most of the women who drink during pregnancy also smoke cigarettes, attention should be given to the prevention or reduced use of both substances during pregnancy.
Depression, Symptoms and the Quality of Life in Patients on Hemodialysis for End-Stage Renal Disease
Authors: Son Youn-Jung , Choi Kyung-Sook , Park Young-Rye , Bae Jun-Sang , Lee Jeong-Beom
Published: August 2008

Background: End-stage renal disease (ESRD) is a progressive, debilitating, chronic illness requiring nursing and medical interventions. The goal of this study was to explore the level of depression experienced by patients receiving hemodialysis (n = 146), and to compare the symptoms with the quality of life (QoL) between patients that were depressed and those that were not depressed. Methods: For this descriptive, cross-sectional survey, participants aged 18 and above were recruited from three different regions in the Republic of Korea. The level of depression, symptoms and QoL of the participants were measured by questionnaires from October to December 2006. The data was analyzed with descriptive statistics, the χ2 and t test using the SPSS WIN 14.0 program. Results: The prevalence of depression (PHQ-9) among the participants was 25.34%. There were more symptoms reported in the depressed group of patients than in those that were not depressed. In addition, the QoL was not as good in the depressed group when compared to patients that were not depressed. Conclusion: Therefore, the evaluation for depression may be an important part of the management of patients with ESRD. Further research is needed to understand the causal relationship between depression and health outcomes.