bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamma Knife surgery for glossopharyngeal neuralgia
Authors: Yomo Shoji , Arkha Yasser , Donnet Anne , Régis Jean
Published: November 2008

Gamma Knife surgery (GKS) is widely recognized as an effective, minimally invasive treatment for intractable trigeminal neuralgia, but the role of GKS in glossopharyngeal neuralgia (GPN) remains unclear. This study involved 2 patients with medically intractable GPN who were treated using GKS. One patient required 2 treatments because of a recurrence of symptoms (at maximum doses of 60 and 70 Gy), and the other patient had a single intervention (at a maximum dose of 75 Gy). The GKS target was the distal part of the glossopharyngeal nerve. Patients were investigated prospectively, treated, and then assessed periodically with respect to pain relief and neurological function. Complete pain relief was achieved initially after all 3 interventions. The first patient was pain free without medication for 2 months after the first treatment (60 Gy) and for 4 months after the second treatment (70 Gy). The second patient (treated with 75 Gy) was still pain free without medication at the last follow-up (12 months). Neither patient had any neurological complications. The initial response of GPN to low-dose GKS was favorable, but symptoms may recur. No adverse neurological effects were observed in any of the lower cranial nerves. It will be necessary to investigate the optimal radiation dose and target of GKS for achieving long-term pain relief in GPN.
Traumatic clival subdural hematoma in an adult
Authors: Casey David , Chaudhary Bedansh Roy , Leach Paul A. , Herwadkar Amit , Karabatsou Konstantina
Published: November 2008

Retroclival hematomas are a rare entity. They are usually associated with significant trauma, and patients frequently have focal neurological deficits, especially cranial nerve palsies. Previous case reports of epidural clival hematomas have been described almost exclusively in the pediatric population. The authors report a unique case of traumatic clival subdural hematoma, which has never been described in an adult except in the context of hemophilia.

An 18-year-old man presented with continuing nausea and headaches following a seemingly trivial head injury. He was found to have a posterior fossa retroclival hematoma extending into the spinal subdural space but without any neurological deficits. He was treated conservatively, with a good outcome. The authors discuss the possible mechanisms of injury, management, and complications related to this rare condition, and they review the pertinent literature.
Adult Spinal Cord Stem/Progenitor Cells Transplanted as Neurospheres Preferentially Differentiate into Oligodendrocytes in the Adult Rat Spinal Cord
Authors: Mothe Andrea J. , Kulbatski Iris , Parr Ann , Mohareb Michael , Tator Charles H.
Published: November 2008

Neural stem/progenitor cells (NSPCs) capable of generating new neurons and glia reside in the adult mammalian spinal cord. Transplantation of NSPCs has therapeutic potential for spinal cord injury, although there is limited information on the ability of these cells to survive and differentiate in vivo. Neurospheres cultured from the periventricular region of the adult spinal cord contain NSPCs that are self-renewing and multipotent. We examined the survival, proliferation, migration, and differentiation of adult spinal cord NSPCs generated from green fluorescent protein (GFP) transgenic rats and transplanted into the intact spinal cord. The grafted GFP-expressing cells survived for at least 6 weeks in vivo and migrated from the injection site along the rostro-caudal axis of the spinal cord. Transplanted cells transiently proliferated following transplantation and approximately 17% of the GFP-positive cells were apoptotic at 1 day. Also, better survival was seen with NSPCs transplanted as neurospheres in comparison to NSPCs transplanted as dissociated cells. By 1 week posttransplantation, grafted cells primarily expressed an oligodendrocytic phenotype and only 2% differentiated into astrocytes. Approximately 75% versus 38% of the grafted cells differentiated into oligodendrocytes after transplantation into spinal white versus gray matter, respectively. This is the first report to examine the time course of cell survival, proliferation, apoptosis, and phenotypic differentiation of transplanted NSPSs in the spinal cord. This is also the first report to examine the differences between transplanted NSPCs grafted as neurospheres or dissociated cells, and to compare the differentiation potential after transplantation into spinal cord white versus gray matter.
Determination of Viability of Human Cartilage Allografts by a Rapid and Quantitative Method Not Requiring Cartilage Digestion
Authors: López Carmen , Ajenjo Nuria , Muñoz-Alonso Maria J. , Farde Pilar , León J. , Gómez-Cimiano J.
Published: November 2008

Fresh osteochondral allograft transplantation is increasingly used for the treatment of cartilage pathologies of the knee. It is believed that transplantation success depends on the presence of viable chondrocytes in the graft, but methods to evaluate graft viability require the isolation of chondrocytes by enzymatic digestion of the cartilage and/or the use of radioactive precursors. We have adapted the well-known cell viability assay based on the reduction of tetrazolium derivatives to evaluate cartilage viability. We took advantage from the histological properties of cartilage tissue and the fact that some tetrazolium derivatives (e.g., WST-1, XTT) give soluble reduction products that can permeate the hyaline cartilage matrix. We have validated this assay in human cartilage explants from arthrotomy interventions and deceased donors, measuring the reduced product in the explant supernatant. Using this method we have compared the performance of several culture media in cartilage viability. From those tested, DMEM supplemented with fetal bovine serum results in higher viability of the cartilage and the explants remain viable at least 15 days in culture at 37°C. Cartilage cells continued expressing chondrocyte-specific genes, suggesting the maintenance of chondrogenic phenotype. The described method offers a quantitative and convenient method to measure the viability of human cartilage grafts.
Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF
Authors: Behrstock Soshana , Ebert Allison D. , Klein Sandra , Schmitt Melanie , Moore Jeannette M. , Svendsen Clive N.
Published: November 2008

The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson's and Huntington's disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line-derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration, or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington's model) with indirect lesions of the dopamine system (Parkinson's model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC, which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases.
Grooming, rank, and agonistic support in tufted capuchin monkeys
Authors: Schino Gabriele , Di Giuseppe Francesca , Visalberghi Elisabetta
Published: November 2008

Studies investigating the relation between allogrooming and social rank in capuchin monkeys (genusCebus) have yielded inconsistent results. In this study, we investigated the relation between grooming, agonistic support, aggression and social rank in a captive group of tufted capuchin monkeys (C. apella). Differently from most previous studies, we based our analyses on a relatively large database and studied a group with known genealogical relationships. Tufted capuchin females did not exchange grooming for rank‐related benefits such as agonistic support or reduced aggression. Coherently with this picture, they did not groom up the hierarchy and did not compete for accessing high‐ranking grooming partners. It is suggested that a small group size, coupled with a strong kin bias, may make the exchange of grooming for rank‐related benefits impossible or unprofitable, thus eliminating the advantages of grooming up the hierarchy. We provide several possible explanations for the heterogeneity of results across capuchin studies that have addressed similar questions. Am. J. Primatol. 71:101–105, 2009. © 2008 Wiley‐Liss, Inc.
Tribological behavior of Kevlar fabric composites filled with nanoparticles
Authors: Guo Fang , Zhang Zhaozhu , Zhang Huijuan , Liu Weimin
Published: November 2008

The friction and wear characteristics of ZnO‐ or montmorillonite‐nanoparticle‐filled Kevlar fabric composites with different filler proportions when sliding against stainless steel pins under dry friction conditions were studied, with unfilled Kevlar fabric composites used as references. The worn surface and transfer film of Kevlar fabric composites were then examined with a scanning electron microscope. It was found that ZnO and montmorillonite as fillers could improve the tribological behavior of the Kevlar fabric composites with various applied loads, and the best antiwear property was obtained with the composites containing 5 wt % ZnO or montmorillonite. This indicated that these nanoparticles could prevent the destruction of Kevlar fabric composites during the friction process. The transfer film established by these nanoparticles during the sliding wear of the composites against their metallic counterpart made contributions to reducing the friction coefficient and wear rate of the Kevlar fabric composites measured in the test. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Children's health risk assessment: incorporating a lifestage approach into the risk assessment process
Authors: Brown Rebecca C. , Barone Stanley , Kimmel Carole A.
Published: November 2008

This overview paper provides the historical context for the incorporation of lifestage‐specific concerns in human health risk assessment, briefly explains the process employed in a lifestage framework for risk assessment, and discusses the scientific rationale for how utilizing lifestage data will strengthen the overall risk assessment process. This risk assessment approach will add value by: (1) providing a more complete evaluation of the potential for vulnerability at different lifestages, including a focus on the underlying biological events and incorporation of mode of action information related to different critical developmental periods; (2) evaluating the potential for toxicity during all lifestages after early lifestage exposure; (3) reviewing the importance of integrating exposure information and adverse health effects across lifestages; and (4) serving as a basis to extend some aspects of the children's health risk assessment framework to all lifestages. Birth Defects Res (Part B), 2008. © 2008 Wiley‐Liss, Inc.
Applying innovative educational principles when classes grow and resources are limited
Authors: Omer Selma , Hickson Gilles , Taché Stephanie , Blind Raymond , Masters Susan , Loeser Helen , Souza Kevin , Mkony Charles , Debas Haile , O'Sullivan Patricia
Published: November 2008

Teaching to large classes is often challenging particularly when the faculty and teaching resources are limited. Innovative, less staff intensive ways need to be explored to enhance teaching and to engage students. We describe our experience teaching biochemistry to 350 students at Muhimbili University of Health and Allied Sciences (MUHAS) under severe resource limitations and highlight our efforts to enhance the teaching effectiveness. We focus on peer assisted learning and present three pilot initiatives that we developed to supplement teaching and facilitate student interaction within the classroom. These included; instructor‐facilitated small group activities within large group settings, peer‐led tutorials to provide supplemental teaching and peer‐assisted instruction in IT skills to enable access to online biochemistry learning resources. All our efforts were practical, low cost and well received by our learners. They may be applied in many different settings where faculties face similar challenges.
XX Through‐Cage Bonding in Cu, Ni, and Cr Complexes with M3X2 Cores (X=S, As)
Authors: Carrasco Rosa , Aullón Gabriel , Alvarez Santiago
Published: November 2008

Density functional calculations on trinuclear complexes bridged by two sulfur atoms, [(tmeda)3Cu3(μ‐S)2]3+, [(tmeda)3Ni3(μ‐S)2]2+, and [(tmeda)3Ni3(μ‐S2)]4+, as well as on the formation of [(tmeda)3Cu3(μ‐S)2]3+ from a dinuclear [(tmeda)2Cu2(μ‐S2)]2+ complex and a mononuclear [(tmeda)Cu(η2‐S2)]+ fragment, are reported. A qualitative orbital analysis of the M3X2 framework bonding is presented for the case in which each metal atom M has a square planar coordination sphere completed by one bidentate or two monodentate ligands (that is, [(L2M)3X2] compounds). It is concluded that a framework electron count (FEC) of 12 corresponds to systems with six MX bonds but no XX bond through the cage, while an FEC of 10 favors the formation of an XX bond. Framework electron counting rules are also presented for related M3X2 cores in [(L5M)3X2] complexes, based on a qualitative molecular orbital (MO) analysis supported by DFT calculations on [(OC)15Cr3(μ‐As2)].
Norcantharidin Analogues: Synthesis, Anticancer Activity and Protein Phosphatase 1 and 2A Inhibition
Authors: Hill Timothy A. , Stewart Scott G. , Gordon Christopher P. , Ackland Stephen P. , Gilbert Jayne , Sauer Benjamin , Sakoff Jennette A. , McCluskey Adam
Published: November 2008

Cantharidin (1) and its derivatives are of significant interest as serine/threonine protein phosphatase 1 and 2A inhibitors. Additionally, compounds of this type have displayed growth inhibition of various tumour cell lines. To further explore both of these inhibition pathways, a number of amide–acid norcantharidin analogues (15–26) were prepared. Compounds23and24, containing two carboxylic acid residues, showed good PP1 and PP2A activity, with IC50values of ∼15 and ∼3 μm,respectively. Substituted aromatic amide analogues45,48,49,52,53, and54also displayed good PP1 and PP2A inhibition, with IC50values in the range of 15–10 μM(PP1) and 11–5 μM(PP2A). However, bulkyorthosubstituents on the aromatic ring caused the aromatic ring to be skewed from the NCO planarity, leading to a decrease in PP1 and PP2A inhibition. A number of analogues,20,22, 25and46, showed excellent tumour growth inhibition, with46in particular being more potent than the lead, norcantharidin2.
Reactions of Hydrazines with AlH3·NMe2Et – Formation of Aluminum‐Nitrogen Heterocycles
Authors: Uhl Werner , Vogelpohl Andreas
Published: November 2008

Treatment of the alane–amine adduct AlH3·NMe2Et with 1,2‐diphenylhydrazine, H5C6–N(H)–N(H)–C6H5, afforded a five‐membered Al2N3 heterocycle (1) by the elimination of hydrogen and partial cleavage of N–N bonds. The structure of 1 comprises two aluminum atoms bridged by a dianionic diphenylhydrazinediido (–H5C6–N–N–C6H5–) and an imido ligand (H5C6–N2–). Each aluminum atom is further attached to a terminal hydrogen atom and a (ethyl)dimethylamino group. 1‐Aminopyrrole, H2N–NC4H4 gave a singular tricyclic cage compound (2) under similar conditions. The amino groups were completely deprotonated. N–N bond cleavage was not observed. Compound 2 possesses a central Al2N2 ring. Its nitrogen atoms are bridged by an Al2N group, whereas an N2Al group bridges both aluminum atoms. All nitrogen atoms are part of N–N bonds, and all metal atoms are further bonded to terminal hydrogen atoms. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
The Chemistry of Technetium–Water Complexes within the Manganese Triad: Challenges and Perspectives
Authors: Alberto Roger
Published: November 2008

The chemistry of technetium is essentially driven by radiopharmaceutical applications. These comprise the syntheses of novel complexes but, moreover, the combination of targeting biomolecules with metal complexes. Aqua ions are especially convenient for facilitatating the introduction of metal cations into biomolecules, but are nonexistent for Tc and Re in the Mn triad. This microreview will discuss the chemistry of those Tc complexes that contain H2O as ligands. Special attention will be payed to organometallic aqua ions, i.e. complexes that are typically organometallic with water as ligand. Of particular interest is the coordination chemistry of [M(OH2)3(CO)3]+ (M = Mn, Tc, Re) complexes in water since it is the origin of the widely applied radiopharmaceutical research with 99mTc and 188Re. The chemistry of organometallic aqua ions is not confined to Werner‐type ligands, hence, a further emphasis will be placed on pure organometallic chemistry in water.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
An Overview of Syntheses of Apogalanthamine Analogues and 7‐Aza Derivatives of Steganacin and Steganone (Eur. J. Org. Chem. 35/2008)
Authors: Appukkuttan Prasad , Van der Eycken Erik
Published: November 2008

The cover picture shows flowers belonging to the crinum family, a member of the well‐known amaryllidaceae family, in the background. A number of naturally occurring alkaloids with very intriguing biological potential have been isolated from the amaryllidaceae family of flowers. The structures shown in the foreground of the cover picture are some representative examples of amaryllidaceae alkaloids, such as narciclassine, hippadine, lycorine etc., as well as a few unnatural analogues bearing close structural similarity to some of the amaryllidaceae alkaloids. Details of some of the structures and the recent advances in the synthesis of some of the unnatural and yet structurally similar alkaloid analogues are presented in the Microreview by P. Appukkuttan and E. Van der Eycken on p. 5867ff.
How potent are news reversals?: Evidence from the futures markets
Authors: Chatrath Arjun , Christie‐David Rohan A. , Lee Kiseop
Published: November 2008

A theoretical model is presented, which predicts a heightening in return volatility following a news reversal. A reversal occurs when a value of an economic indicator that is larger than the forecasted value is followed in the following month by a value smaller than the forecasted value, or vice versa. The model also suggests that the effects of a news reversal will be more pronounced early in the monthly macroeconomic news cycle. The predictions of the model for trading activity are less clear. The main predictions of the model were tested employing intraday data for the nearby Treasury bond futures contract. Consistent with the model, the data show significantly greater responses in volatility per standard‐deviation surprise when there is a news reversal, than otherwise. Further, the increased sensitivity in volatility is especially perceptible early in the announcement cycle. © 2008 Wiley Periodicals, Inc. Jrl Fut Mark 29:42–73, 2009
A likelihood ratio test of population Hardy‐Weinberg equilibrium for case‐control studies
Authors: Yu Chang , Zhang Sanguo , Zhou Chuan , Sile Saba
Published: November 2008

Testing Hardy‐Weinberg equilibrium (HWE) in the control group is commonly used to detect genotyping errors in genetic association studies. We propose a likelihood ratio test for testing HWE in the study population using both case and control samples. This test incorporates underlying association models. Another feature is that, when we infer the disease‐genotype association, we explicitly incorporate HWE or a possible departure from Hardy‐Weinberg equilibrium (DHWE) into the model. Our unified framework enables us to infer the disease‐genotype association when a detected DHWE needs to be part of the model after causes for the DHWE are explored. Real data sets are used to illustrate the application of the methodology and its implication in genetic association studies. Our analysis and interpretation touch on issues such as genotyping errors, population selection, population stratification, or the study sampling plan, that all could be the cause of DHWE. Genet. Epidemiol. 2009. Published 2008 Wiley‐Liss, Inc.
Ecogeographic genetic epidemiology
Authors: Sloan Chantel D. , Duell Eric J. , Shi Xun , Irwin Rebecca , Andrew Angeline S. , Williams Scott M. , Moore Jason H.
Published: November 2008

Complex diseases such as cancer and heart disease result from interactions between an individual's genetics and environment, i.e. their human ecology. Rates of complex diseases have consistently demonstrated geographic patterns of incidence, or spatial “clusters” of increased incidence relative to the general population. Likewise, genetic subpopulations and environmental influences are not evenly distributed across space. Merging appropriate methods from genetic epidemiology, ecology and geography will provide a more complete understanding of the spatial interactions between genetics and environment that result in spatial patterning of disease rates. Geographic information systems (GIS), which are tools designed specifically for dealing with geographic data and performing spatial analyses to determine their relationship, are key to this kind of data integration. Here the authors introduce a new interdisciplinary paradigm, ecogeographic genetic epidemiology, which uses GIS and spatial statistical analyses to layer genetic subpopulation and environmental data with disease rates and thereby discern the complex gene‐environment interactions which result in spatial patterns of incidence.Genet. Epidemiol. 2009. © 2008 Wiley‐Liss, Inc.
Factors related to perceived quality of life in patients with Alzheimer's disease: the patient's perception compared with that of caregivers
Authors: Conde‐Sala Josep Lluís , Garre‐Olmo Josep , Turró‐Garriga Oriol , López‐Pousa Secundino , Vilalta‐Franch Joan
Published: November 2008

Aims

To compare care recipient and caregiver perceptions of quality of life in patients (QoL‐p) with Alzheimer's disease (AD). To identify associated factors, and the concordances‐discrepancies.

Method

Cross‐sectional analytic study of 236 patients and their carers using the Quality of Life in Alzheimer's Disease (QoL‐AD) scale, socio‐demographic data and clinical examination.

Results

Patients scored the QoL‐AD more favourably than did caregivers (34.4vs31.3,p < 0.001). Cognitive deterioration did not affect the perception of QoL‐AD (rho = −0.05,p = 0.394). The neuropsychiatric symptoms was associated with a negative perception of the QOL‐AD in both patients (rho = −0.22,p < 0.01) and caregivers (rho = −0.47,p < 0.001). Greater functional autonomy was associated with a better perception of the QOL‐AD in patients (rho = 0.17,p < 0.01) and even more so in caregivers (rho = 0.56,p < 0.001). In carers, burden (rho = −0.56,p < 0.001) and mental health (rho = 0.31,p < 0.001) were inversely associated with the QoL‐AD. QoL‐AD scores of both patients and caregivers were higher for men, married subjects, those who lived with their spouse and those living in their own home. When the carer was a spouse both patients and caregivers scored the QoL‐AD higher than when the carer was a son or daughter (35.5vs33.4 and 33.7; 32.9vs30.5 and 27.7,p < 0.001).

Conclusions

Patients have a better perception of QoL‐p. Caregivers give a more negative evaluation of neuropsychiatric symptoms, but have a more positive view of functional autonomy. Carers who are spouses have a better perception of QoL‐p than do carers who are sons or daughters. Copyright © 2008 John Wiley & Sons, Ltd.
TNM‐based stage groupings in head and neck cancer: Application in cancer of the hypopharynx
Authors: Hall Stephen F. , Groome Patti A. , Irish Jonathan , O'Sullivan Brian
Published: November 2008

Background.

The purpose of this study was to test the Union Internationale Contre le Cancer (UICC)/TNM category–based head and neck cancer stage grouping systems proposed in the literature for their ability to create clinically relevant prognostic groups of like‐patients with cancer of the hypopharynx.

Methods.

Population‐based retrospective survival study of 595 patients with squamous cell carcinoma of the hypopharynx across Ontario, Canada, from January 1990 to January 2000. The grouping systems of UICC/TNM, T and N Integer Score (TANIS), Hart, Berg, Snyderman, Kiricuta, and Hall were tested and compared for prognostic ability using hazard consistency, hazard discrimination, percent variance explained, outcome prediction, and balance.

Results.

All 8 systems predicted disease‐specific survival. The system proposed by Snyderman performed the best, and UICC/TNM sixth edition did not perform as well as most.

Conclusion.

The UICC/TNM stage group classification, although successful in creating statistically distinct groups, did not perform as well as other stage grouping systems, continuing a theme that has been reported previously. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
An application of thermal microscopes to the measurement of thermal effusivity of films
Authors: Hatori Kimihito , Suzuki Kei , Fukuyama Hiroyuki , Ohta Hiromichi
Published: November 2008

The application of thermal microscopes to the measurement of local thermal properties has drawn considerable scientific interest. We report on the application of a thermal microscope to the measurement of thermal effusivity for films comprising alumina deposited on a substrate, which were fabricated by an electrophoretic deposition method. The measured data was analyzed to consider the undulations on the sample surface The thermal effusivity of these samples was approximately 1×103 Js−0.5m−2K−1; this value is smaller than that for dense alumina because the alumina grain makes contact with a point. © 2008 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20227
Taking stem cells to the clinic: Major challenges
Authors: Bongso Ariff , Fong Chui‐Yee , Gauthaman Kalamegam
Published: November 2008

Stem cell therapy offers tremendous promise in the treatment of many incurable diseases. A variety of stem cell types are being studied but human embryonic stem cells (hESCs) appear to be the most versatile as they are pluripotent and can theoretically differentiate into all the tissues of the human body via the three primordial germ layers and the male and female germ lines. Currently, hESCs have been successfully converted in vitro into functional insulin secreting islets, cardiomyocytes, and neuronal cells and transfer of such cells into diabetic, ischaemic, and parkinsonian animal models respectively have shown successful engraftment. However, hESC‐derived tissue application in the human is fraught with the problems of ethics, immunorejection, tumorigenesis from rogue undifferentiated hESCs, and inadequate cell numbers because of long population doubling times in hESCs. Human mesenchymal stem cells (hMSC) though not tumorigenic, also have their limitations of multipotency, immunorejection, and are currently confined to autologous transplantation with the genuine benefits in allogeneic settings not conclusively shown in large controlled human trials. Human Wharton's jelly stem cells (WJSC) from the umbilical cord matrix which are of epiblast origin and containing both hESC and hMSC markers appear to be less troublesome in not being an ethically controversial source, widely multipotent, not tumorigenic, maintain “stemness” for several serial passages and because of short population doubling time can be scaled up in large numbers. This report describes in detail the hurdles all these stem cell types have to overcome before stem cell‐based therapy becomes a genuine reality. J. Cell. Biochem. 105: 1352–1360, 2008. © 2008 Wiley‐Liss, Inc.
Matrix metalloproteinase (MMP)‐12 regulates MMP‐9 expression in interleukin‐1β‐treated articular chondrocytes
Authors: Oh Hwanhee , Yang Siyoung , Park Meeyoung , Chun Jang‐Soo
Published: November 2008

Limited information is available on the expression and role of matrix metalloproteinase (MMP)‐12 in chondrocytes. We characterized the expression mechanism of MMP‐12 and possible function in chondrocytes. Interleukin (IL)‐1β induced the expression and activation of MMP‐12 in primary culture chondrocytes and cartilage explants via mitogen‐activated protein (MAP) kinase signaling pathways. Among MAP kinases, extracellular signal‐regulated kinase and p38 kinase are necessary for MMP‐12 expression, whereas c‐jun N‐terminal kinase is required for the activation of MMP‐12. The possibility that MMP‐12 acts as a modulator of other MMP was examined. MMP‐12 alone did not affect other MMP expressions. However, MMP‐12 enhanced expression and activation of MMP‐9 in the presence of IL‐1β. Our results indicate that IL‐1β in chondrocytes induces the expression and activation of MMP‐12, which, in turn, augments MMP‐9 expression and activation. J. Cell. Biochem. 105: 1443–1450, 2008. © 2008 Wiley‐Liss, Inc.
Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients
Authors: Krautkrämer Ellen , Klein Theresa M. , Sommerer C. , Schnitzler Paul , Zeier Martin
Published: November 2008

The reactivation and replication of the BK polyomavirus (BKV) leading to BKV‐associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I‐IV) based on genotype variations within the VP1‐coding region. The type‐specific amino acid differences cluster within the BC‐loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC‐loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC‐loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC‐loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC‐loops. J. Med. Virol. 81:75–81, 2009. © 2008 Wiley‐Liss, Inc.
Diverse IgG subclass responses to adeno‐associated virus infection and vector administration
Authors: Murphy Samuel L. , Li Hojun , Mingozzi Federico , Sabatino Denise E. , Hui Daniel J. , Edmonson Shyrie A. , High Katherine A.
Published: November 2008

Humoral immune responses occur following exposure to Adeno‐associated virus (AAV) or AAV vectors. Many studies characterized antibody responses to AAV, but human IgG subclass responses to AAV have not been previously described. In this study, IgG subclass responses were examined in serum samples of normal human subjects exposed to wild‐type AAV, subjects injected intramuscularly with AAV vectors and subjects injected intravascularly with AAV vectors. A diversity of IgG subclass responses to AAV capsid were found in different subjects. IgG1 was found to be the dominant response. IgG2, IgG3, and IgG4 responses were also observed in most normal human subjects; IgG2 and IgG3 each represented the major fraction of total anti‐AAV capsid IgG in a subset of normal donors. Subjects exposed to AAV vectors showed IgG responses to AAV capsid of all four IgG subclasses. IgG responses to AAV capsid in clinical trial subjects were inversely proportional to the level of pre‐existing anti‐AAV antibody and independent of the vector dose. The high levels of anti‐AAV capsid IgG1 can mask differences in IgG2, IgG3, and IgG4 responses that were observed in this study. Analysis of IgG subclass distribution of anti‐AAV capsid antibodies indicates a complex, non‐uniform pattern of responses to this viral antigen. J. Med. Virol. 81:65–74, 2009. © 2008 Wiley‐Liss, Inc.
The incidence of human bocavirus infection among children admitted to hospital in Singapore
Authors: Tan Boon‐Huan , Lim Elizabeth Ai‐Sim , Seah Shirley Gek‐Kheng , Loo Liat‐Hui , Tee Nancy W.S. , Lin Raymond T.P. , Sugrue Richard Joseph
Published: November 2008

Human bocavirus (HBoV) is a parvovirus, belonging to the genus Bocavirus. The virus was identified recently in Sweden, and has now been detected in several different countries. Although it is associated with lower respiratory tract infections in pediatric patients, the incidence of HBoV infection in a developed country in South East Asia, has not been examined. The objective of this study was to determine the importance of HBoV as a cause of lower respiratory tract infections among children admitted to hospital in Singapore. Five hundred nasopharyngeal swabs were collected from anonymized pediatric patients admitted to the Kandang Kerbau Women's and Children's Hospital for acute respiratory infections. The specimens were tested for the presence of HBoV using polymerase chain reactions. HBoV was detected in 8.0% of the patients tested, and a majority of these HBoV patients exhibited lower respiratory tract infections. A significant level of coinfection with respiratory syncytial viruses and rhinoviruses was also observed in these HBoV patients. The data suggest that HBoV is an important cause of lower respiratory tract infections among children admitted to hospital in Singapore, and is the first study examining the incidence of HBoV infection in a developed country in South East Asia. J. Med. Virol. 81:82–89, 2009. © 2008 Wiley‐Liss, Inc.
Selection of drug‐resistant HIV‐1 during the early phase of viral decay is uncommon in treatment‐naïve patients initiated on a three‐ or four‐drug antiretroviral regimen including lamivudine
Authors: Bergroth Tobias , Ekici Halime , Gisslén Magnus , Loes Sabine Kinloch‐de , Goh Li‐Ean , Freedman Andrew , Lampe Fiona , Johnson Margaret A. , Sönnerborg Anders
Published: November 2008

Therapy failure due to drug resistance development is a common phenomenon in HIV‐infected patients. However, when the drug pressure leads to the earliest selection of drug‐resistant HIV‐1 populations is still unclear. In this study, the extent to which selection of the HIV‐1 reverse transcriptase M184I/V mutations occur during the initial phase of viral decay in treatment‐naïve HIV‐1 infected patients receiving antiretroviral therapy (ART) was examined. Plasma virus from three cohorts of treatment‐naïve patients initiating quadruple (n = 43), triple (n = 14) or dual (n = 15) lamivudine‐containing ART were analyzed for M184I/V during the first 6 months of therapy using direct sequencing and a sensitive selective real‐time PCR method. Among quadruple ART patients, who all were treated at primary HIV‐1 infection, only one patient developed M184V after 6 weeks of therapy, having had wild‐type virus at baseline. No mutations were found in chronically infected patients on triple ART. In patients on dual therapy, M184I/V mutants were found frequently. Selection of M184I/V mutants was found to be rare during the initial phase of viral decay after initiation of ART in adherent patients given a three or four‐drug combination, in contrast to those receiving a less potent regimen. The results suggest that triple and quadruple lamivudine + PI or PI/r containing ART given to treatment‐naïve adherent patients is potent enough to prevent development of resistance during the first months of therapy. J. Med. Virol. 81:1–8, 2009. © 2008 Wiley‐Liss, Inc.
Identification of genetic mutations associated with attenuation and changes in tropism of Urabe mumps virus
Authors: Shah Dion , Vidal Silvia , Link Malen A. , Rubin Steven A. , Wright Kathryn E.
Published: November 2008

Although several effective mumps virus vaccines have been developed, almost nothing is known about the genetic changes responsible for loss of virulence. One vaccine, Urabe AM9, was withdrawn from the market because of insufficient attenuation. The vaccine was found to contain a mixture of viruses that could be distinguished based on the sequence of the hemagglutinin‐neuraminidase gene (HN). Viruses containing lysine at HN amino acid position 335 were isolated from cases of post‐vaccination parotitis or meningitis whereas viruses containing glutamic acid at this position were not associated with post‐vaccination disease. Using a rat based model of mumps neurovirulence, we demonstrate that this latter virus is significantly attenuated compared to a virus isolated from a patient with post‐vaccination meningitis. Complete sequence analysis of the genomes of the two viruses identified sixteen genetic differences, some or all of which must be responsible for differences in virulence. These same genetic differences also account for changes in tropism in cell culture. J. Med. Virol. 81:130–138, 2009. © 2008 Wiley‐Liss, Inc.
Leucine‐rich repeat kinase 2 (LRRK2): A key player in the pathogenesis of Parkinson's disease
Authors: Gandhi Payal N. , Chen Shu G. , Wilson‐Delfosse Amy L.
Published: November 2008

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine‐rich repeat kinase‐2 (LRRK2) have recently been linked to autosomal dominant, late‐onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multidomain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease‐associated mutations are found throughout the multidomain structure of the protein. LRRK2, however, is unique among the PD‐causing genes, because a missense mutation, G2019S, is a frequent determinant of not only familial but also sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. In this Mini‐Review, we look at the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2. © 2008 Wiley‐Liss, Inc.
Prevention of epilepsy by taurine treatments in mice experimental model
Authors: Junyent F. , Utrera J. , Romero R. , Pallàs M. , Camins A. , Duque D. , Auladell C.
Published: November 2008

An experimental model based on kainic acid (KA) injections replicates many phenomenological features of human temporal lobe epilepsy, the most common type of epilepsy in adults. Taurine, 2‐aminoethanesulfonic acid, present in high concentrations in many invertebrate and vertebrate systems, is believed to serve several important biological functions. In addition, it is believed to have a neuroprotective role against several diseases. In the present study, an experimental mouse model based on taurine pretreatment prior to KA administration has been improved to study whether taurine has a neuroprotective effect against KA‐induced behavior and cell damage. Under different treatments tested, taurine's most neuroprotective effects were observed with intraperitoneal taurine injection (150 mg/kg dosage) 12 hr before KA administration. Thus, a reduction in or total absence of seizures, together with a reduction in or even disappearance of cellular and molecular KA‐derived effects, was detected in mice pretreated with taurine compared with those treated only with KA. Moreover, the use of tritiated taurine revealed taurine entry into the brain, suggesting possible changes in intracellular:extracellular taurine ratios and the triggering of pathways related to neuroprotective effects. © 2008 Wiley‐Liss, Inc.
Influence of patellar ligament insertion angle on quadriceps usage during walking in anterior cruciate ligament reconstructed subjects
Authors: Shin Choongsoo S. , Chaudhari Ajit M. , Dyrby Chris O. , Andriacchi Thomas P.
Published: November 2008

Reduced quadriceps contraction has been suggested as an adaptation to prevent anterior tibial translation in anterior cruciate ligament (ACL)‐deficient knees. This theory has been supported by a recent study that peak knee flexion moment (thought to be created by a decrease of quadriceps contraction) during walking was negatively correlated with patellar ligament insertion angle (PLIA) in ACL‐deficient knees, but not in contralateral, uninjured knees. In addition, the PLIA was significantly smaller in ACL‐deficient knees than in contralateral, uninjured knees. However, it is unknown whether ACL reconstruction restores the PLIA or whether the relationship between the PLIA and knee flexion moments previously observed in ACL‐deficient knees disappears. This study tested the following hypotheses: (1) The PLIA of ACL‐reconstructed knees is significantly smaller than the PLIA of uninjured contralateral knees; (2) Peak knee flexion moment (balanced by net quadriceps moment) during walking is negatively correlated with the PLIA in ACL‐reconstructed knees. The PLIA of 24 ACL‐reconstructed and contralateral knees were measured using MRI, and peak knee flexion moments during walking were measured. Results showed that the PLIA of ACL‐reconstructed (22.9 ± 4.4°) knees was not significantly smaller (p = 0.09, power = 0.99) than the PLIA of contralateral (24.1 ± 4.8°) knees. Peak knee flexion moment was not correlated with the PLIA following ACL reconstruction (R2 = 0.016, power = 0.99). However, the magnitude of the knee flexion moment remained significantly lower in ACL‐reconstructed knees. In summary, this study has shown that the PLIA of ACL‐reconstructed knees returned to normal and that patients no longer adapt their gait in response to the PLIA, though quadriceps function did not return to normal levels. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 730–735, 2009
Raman and FTIR imaging of lung tissue: bronchopulmonary sequestration
Authors: Krafft Christoph , Codrich Daniela , Pelizzo Gloria , Sergo Valter
Published: November 2008

Bronchopulmonary sequestration (BPS) involves abnormal pulmonary tissue lacking trancheobronchial connection and having a separate vascular supply that arises from the thoracic or abdominal aorta. For the first time, BPS is studied by Raman and Fourier‐transform infrared (FTIR) imaging. Cryosections were mounted on calcium fluoride substrates from tissue samples of two BPS patients. Raman images were collected at a step size of 66–100 µm to assess the whole tissue section, and at a lower step size of 10 µm to resolve details in selected areas. FTIR images were collected at resolutions of 63 and 4 µm per pixel. Data sets were segmented by cluster analyses, and the spectra of each cluster were compared. The spectra revealed higher red blood cell content and lower collagen and lipid content in BPS than in an additional tissue section from the BPS margin. Comparison with previous Raman and FTIR images of congenital cystic adenomatoid malformations (CCAM) and normal lung tissue suggested that the marginal tissue sample of the BPS patient contains CCAM. We conclude that CCAM and BPS are biochemically distinct, which enable the differential diagnosis of lung malformations by specific vibrational spectroscopic fingerprints. Copyright © 2008 John Wiley & Sons, Ltd.
Milling and physicochemical properties of chickpea (Cicer arietinum L.) varieties
Authors: Ravi Ramasamy , Harte Janice B.
Published: November 2008

BACKGROUND: Physical characteristics of chickpea (Cicer arietinum L.) seeds such as grain size, weight and hull content are important from a milling and marketing point of view. Chemical characteristics provide the information on nutritional status of grains. Chickpea of Desi (cv. A1) and Kabuli (cv. L550) cultivars were analyzed for their physicochemical, milling and milled flour quality characteristics.

RESULTS: Between dry and wet milling, higher yield of dhal was obtained from wet milling, which was found to be true in both cultivars. An extra yield of 2–4% was obtained in wet milling. Between the cultivars, Desi was found to be the higher dhal‐yielding cultivar in both dry and wet milling methods. Fat, ash and protein contents were found to be higher in Kabuli than in Desi and the values were respectively 5.3%, 3.5% and 24.9% for Kabuli and 4.3%, 2.2% and 22.6% for Desi.

CONCLUSION: The chickpea cultivars Desi and Kabuli vary significantly in their physical properties such as seed color, size, 100‐seed weight and 100‐seed volume. Between the dry and wet milling, a higher yield (2–4%) of dhal was obtained from wet milling. Between the cultivars, electronic nose analysis of chickpea flour indicated the possibility of differentiating the variations associated with varietal difference and milling. The gel electrophoresis pattern of chickpea showed as many as 15 protein bands in flours from both the cultivars, either in phosphate or SDS buffer. The Rapid Visco Analyzer profile did not show a significant difference between the two cultivars. Copyright © 2008 Society of Chemical Industry
A Novel Double‐Network Hydrogel Induces Spontaneous Articular Cartilage Regeneration in vivo in a Large Osteochondral Defect
Authors: Yasuda Kazunori , Kitamura Nobuto , Gong Jian Ping , Arakaki Kazunobu , Kwon Hyuck Joon , Onodera Shin , Chen Yong Mei , Kurokawa Takayuki , Kanaya Fuminori , Ohmiya Yoshihiro , Osada Yoshihito
Published: November 2008

We have developed a novel method to induce spontaneous hyaline cartilage regeneration in vivo for a large osteochondral defect by implanting a plug made from a double‐network hydrogel composed of poly(2‐acrylamido‐2‐methylpropanesulfonic acid) and poly(N,N′‐dimethylacrylamide) at the bottom of the defect, leaving the cavity vacant. In cells regenerated in the treated defect, type‐2 collagen, Aggrican, and SOX9 mRNAs were highly expressed and the regenerated matrix was rich in proteoglycan and type‐2 collagen at 4 weeks. This fact gave a significant modification to the commonly established concept that hyaline cartilage tissue cannot regenerate in vivo. This study prompted an innovative strategy in the field of joint surgery to repair an osteochondral defect using an advanced, high‐function hydrogel.

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Methods to Investigate the Adhesion of Soft Nano‐Coatings on Metal Substrates – Application to Polymer‐Coated Stents
Authors: Lewis François , Mantovani Diego
Published: November 2008

Soft coatings are widely used to tailor the surface chemistry of materials without altering their bulk properties. However, the strength of adhesion between the coating and the substrate must be high enough for long‐term applications. This has become a major challenge in the medical field, especially for polymer‐coated stents, mainly due to several coating failures reported after mechanical expansion during clinical implantation. In this work, the applicability of current polymer‐metal adhesion tests to polymer‐coated stents is discussed. The small punch test was proposed as an adhesion test that allows fundamental studies on the adhesion and coating properties. This adhesion test was applied to thin fluorocarbon coatings deposited by plasma on 316L stainless steel.

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