bluuebunny/crossref_metadata_2025 huggingface dataset:
The expulsion of the Moriscos from Spain in 1609–1614: the destruction of an Islamic periphery
Authors: Jónsson Már
Published: July 2007

The Moriscos were nominally Christian after enforced conversions at the beginning of the sixteenth century, but they mainly clung to their Islamic ancestral faith, and they were expelled from Spain in 1609–14. This was a huge operation, as 300,000 Moriscos were expelled, most of them in the space of a few months. For it to succeed, the Spanish authorities deemed it necessary to resort to lies and subterfuges. Not many Moriscos resisted expulsion, even though few of them wanted to leave. The majority settled in North Africa, adapted quickly to new circumstances, and did not attempt to avenge their expulsion, for instance by resorting to corsair activities. Despite its scale, the event did not have major immediate political consequences, but it can now be seen as a tragic tale of mistaken assumptions and enmity on the Spanish side, an unexpected socio-economic opportunity for North Africa, and an enduring element in Christian-Muslim perceptions of each other’s faiths.
The Ferghana Valley at the crossroads of world history: the rise of Khoqand, 1709–1822
Authors: Levi Scott C.
Published: July 2007

The Khanate of Khoqand emerged, flourished and collapsed during the era of Chinese and Russian imperial expansion into Central Asia. While eighteenth-century Central Asia has long been considered to have been an unimportant backwater ‘on the margins of world history’, this essay juxtaposes focused research in local primary sources with a world historical perspective in an effort to illuminate some of the ways in which the region remained interactively engaged with its neighbours and, through them, with historical processes unfolding across the globe. The essay argues that these interactions were substantial, and that they contributed to Khoqand’s emergence as a significant regional power and centre of Islamic cultural activity in pre-colonial Central Asia.
The bounds of identity: the Goldsmid mission and the delineation of the Perso–Afghan border in the nineteenth century
Authors: Hopkins B. D.
Published: July 2007

This article examines boundary disputes between Qajar Persia and the emerging state of Afghanistan in the nineteenth century. It argues that disputes between these two Islamic polities were central to the creation of modern states through the territorialization of political identity, in the form of border delineation. The demarcation of territorial boundaries represented the ‘indigenization’ of Western norms of statehood. Indigenous political actors increasingly understood and envisaged their political communities in terms of territorial states, reinterpreting and redeploying European political concepts in indigenous spaces. The Perso-Afghan case exemplifies the assimilation of ideas of political territoriality, central to the construction of a modern state-based international order, in Muslim regions outside direct colonial control.
B-type Natriuretic Peptide (BNP) in der ambulanten Medizin – Nutzen und Tücken
Authors: Maeder  , Keller
Published: July 2007

B-type Natriuretic Peptide (BNP) ist ein etablierter Biomarker zur Differenzierung der akuten Atemnot auf der Notfallstation. Für die Verwendung von BNP in der ambulanten Medizin liegen bedeutend weniger Daten vor. BNP ist kein Universaltest zur Detektion einer kardialen Pathologie, sondern kann nur klar formulierte Fragen in wenigen definierten Situationen beantworten. Als diagnostischer Marker ist BNP auch im ambulanten Setting bei der Abklärung der Atemnot nützlich, indem es hilft, die Wahrscheinlichkeit einer ursächlichen Herzinsuffizienz einzuschätzen. BNP kann aber keine zuverlässige Information über die zugrunde liegende Herzkrankheit liefern, sodass praktisch immer Zusatzuntersuchungen (primär Echokardiographie) nötig sind. Andere diagnostische Anwendungen sind nicht etabliert. BNP ist zusätzlich hilfreich bei der Risikostratifizierung von Patienten mit bekannter Herzinsuffizienz, koronarer Herzkrankheit und pulmonaler Hypertonie.
Akutes Abdomen in der Schwangerschaft – Ultraschall als Mittel zur raschen Entscheidungsfindung
Authors: Müller  , Kurmanavicius
Published: July 2007

Schwangere Frauen mit abdominalen Schmerzen profitieren durch einen sofortigen Einsatz der Ultraschalldiagnostik. Zusammen mit der klinischen Untersuchung führt die Ultraschalluntersuchung vor Ort bei der Aufnahmeuntersuchung zu einer beschleunigten Diagnosestellung. Durch ein systematisches Vorgehen und der Einteilung in schwangerschaftsbedingte und schwangerschaftsunabhängige Ursachen können die Risiken für Mutter und Kind rasch erkannt und die weiteren diagnostischen und therapeutischen Schritte eingeleitet werden. Die Ultraschalluntersucher müssen die notwendige Erfahrung besitzen und es muss eine gute apparative Ausrüstung vor Ort zur Verfügung stehen.
Regulation of H2O and CO in tropical tropopause layer by the Madden‐Julian oscillation
Authors: Wong Sun , Dessler Andrew E.
Published: July 2007

Impacts of the Madden‐Julian oscillation (MJO) on the water vapor (H2O) and carbon monoxide (CO) abundances in the tropical tropopause layer (TTL) are investigated using Aura Microwave Limb Sounder (MLS) data for November 2004 to May 2005. The effects of the eastward propagation of MJO on H2O and CO abundances in the TTL are evident. Deep convection transports H2O into the upper troposphere up to about the 355‐ to 365‐K level. Around the 365‐ to 375‐K level, a dry anomaly is collocated with a cold anomaly, which is above a warm anomaly located near the region of convection enhancement. Tropical mean H2O at 375 K is regulated by the MJO through convection enhancement and is coherent with the local MJO‐related temperature variation. The locations of dehydration follow the eastward propagation of convection enhancement, and its area extent depends on the phase of the MJO. Enhancement of deep convection associated with the MJO also injects CO from the lower troposphere to the TTL up to 375 K. However, tropical mean CO at 375 K responds instantaneously to the large injection event occurring over the African continent.
How was the Triassic Songpan‐Ganzi basin filled? A provenance study
Authors: Enkelmann Eva , Weislogel Amy , Ratschbacher Lothar , Eide Elizabeth , Renno Axel , Wooden Joseph
Published: July 2007

The Triassic Songpan‐Ganzi complex comprises >200,000 km2of 5–15 km thick turbiditic sediments. Although surrounded by several magmatic and orogenic belts, the Triassic high‐ and ultrahigh‐pressure Qinling‐Tongbai‐Hong'an‐Dabie (QTHD) orogen, located several hundred kilometers to the east, was proposed as its major source. Middle to Late Triassic samples from the northern and southern Songpan‐Ganzi complex, studied using detrital white mica40Ar/39Ar ages, Si‐in‐white mica content, and detrital zircon U/Pb ages, suggest that the northern Songpan‐Ganzi deposystem obtained detritus from the north: the north China block, east Kunlun, northern Qaidam, Qilian, and western Qinling; the southern Songpan‐Ganzi deposystem was supplied from the northeasterly located Paleozoic QTHD area throughout the Ladinian and received detritus from the Triassic Hong'an‐Dabie orogen during the Carnian, indicative of exhumation of the orogen at that time. The QTHD orogen fed the Norian samples in the southeastern southern Songpan‐Ganzi deposystem, signifying long drainage channels along the western margin of the south China block. An additional supply from the Emeishan magmatic province and/or the Yidun arc is suggested by the paucity of white mica in the southern Songpan‐Ganzi deposystem. Mica ages of Rhaetian sediments from the northwestern Sichuan basin best correlate with those of the Triassic QTHD orogen. Our Si‐in‐white mica data demonstrate that the high‐ and ultrahigh‐pressure rocks of the Hong'an–Dabie Shan were not exposed in the Middle to Late Triassic.
Nearest‐neighbor classification for facies delineation
Authors: Tartakovsky Daniel M. , Wohlberg Brendt , Guadagnini Alberto
Published: July 2007

Geostatistics has become the dominant tool for probabilistic estimation of properties of heterogeneous formations at points where data are not available. Ordinary kriging, the starting point in the development of other geostatistical techniques, has a number of serious limitations, chief among which is the intrinsic hypothesis of the (second‐order) stationarity of the underlying random field. Attempts to overcome this limitation have led to the development of ever more complex flavors of kriging. We pursue an opposite strategy that consists of finding the simplest possible technique that is adequate for the task of facies delineation. Guided by the principle of parsimony, we identify nearest‐neighbor classification (NNC) as a viable alternative to geostatistics among deterministic techniques. We demonstrate that when used for the purpose of facies delineation, NNC, which has no fitting parameters and operational assumptions, outperforms indicator kriging, which has several parameters.
High diversity of bacterial mercuric reductase genes from surface and sub-surface floodplain soil (Oak Ridge, USA)
Authors: Oregaard Gunnar , Sørensen Søren J
Published: July 2007

DNA was extracted from different depth soils (0–5, 45–55 and 90–100 cm below surface) sampled at Lower East Fork Poplar Creek floodplain (LEFPCF), Oak Ridge (TN, USA). The presence of merA genes, encoding the mercuric reductase, the key enzyme in detoxification of mercury in bacteria, was examined by PCR targeting Actinobacteria, Firmicutes or β/γ-Proteobacteria. β/γ-Proteobacteria merA genes were successfully amplified from all soils, whereas Actinobacteria were amplified only from surface soil. merA clone libraries were constructed and sequenced. β/γ-Proteobacteria sequences revealed high diversity in all soils, but limited vertical similarity. Less than 20% of the operational taxonomic units (OTU) (DNA sequences ⩾95% identical) were shared between the different soils. Only one of the 62 OTU was ⩾95% identical to a GenBank sequence, highlighting that cultivated bacteria are not representative of what is found in nature. Fewer merA sequences were obtained from the Actinobacteria, but these were also diverse, and all were different from GenBank sequences. A single clone was most closely related to merA of α-Proteobacteria. An alignment of putative merA genes of genome sequenced mainly marine α-Proteobacteria was used for design of merA primers. PCR amplification of soil α-Proteobacteria isolates and sequencing revealed that they were very different from the genome-sequenced bacteria (only 62%–66% identical at the amino-acid level), although internally similar. In light of the high functional diversity of mercury resistance genes and the limited vertical distribution of shared OTU, we discuss the role of horizontal gene transfer as a mechanism of bacterial adaptation to mercury.
Association of parameter, software, and hardware variation with large-scale behavior across 57,000 climate models
Authors: Knight Christopher G. , Knight Sylvia H. E. , Massey Neil , Aina Tolu , Christensen Carl , Frame Dave J. , Kettleborough Jamie A. , Martin Andrew , Pascoe Stephen , Sanderson Ben , Stainforth David A. , Allen Myles R.
Published: July 2007

In complex spatial models, as used to predict the climate response to greenhouse gas emissions, parameter variation within plausible bounds has major effects on model behavior of interest. Here, we present an unprecedentedly large ensemble of >57,000 climate model runs in which 10 parameters, initial conditions, hardware, and software used to run the model all have been varied. We relate information about the model runs to large-scale model behavior (equilibrium sensitivity of global mean temperature to a doubling of carbon dioxide). We demonstrate that effects of parameter, hardware, and software variation are detectable, complex, and interacting. However, we find most of the effects of parameter variation are caused by a small subset of parameters. Notably, the entrainment coefficient in clouds is associated with 30% of the variation seen in climate sensitivity, although both low and high values can give high climate sensitivity. We demonstrate that the effect of hardware and software is small relative to the effect of parameter variation and, over the wide range of systems tested, may be treated as equivalent to that caused by changes in initial conditions. We discuss the significance of these results in relation to the design and interpretation of climate modeling experiments and large-scale modeling more generally.
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
Authors: Petersen Kitt Falk , Dufour Sylvie , Savage David B. , Bilz Stefan , Solomon Gina , Yonemitsu Shin , Cline Gary W. , Befroy Douglas , Zemany Laura , Kahn Barbara B. , Papademetris Xenophon , Rothman Douglas L. , Shulman Gerald I.
Published: July 2007

We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis was reduced by ≈60% in young, lean, insulin-resistant subjects compared with a similar cohort of age–weight–body mass index–activity-matched, insulin-sensitive, control subjects. In contrast, hepatic
de novo
lipogenesis and hepatic triglyceride synthesis were both increased by >2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an ≈20% reduction in plasma high-density lipoprotein concentrations but no differences in plasma concentrations of TNF-α, IL-6, adiponectin, resistin, retinol binding protein-4, or intraabdominal fat volume. These data demonstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic
de novo
lipogenesis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations. Furthermore, insulin resistance in these subjects was independent of changes in the plasma concentrations of TNF-α, IL-6, high-molecular-weight adiponectin, resistin, retinol binding protein-4, or intraabdominal obesity, suggesting that these factors do not play a primary role in causing insulin resistance in the early stages of the metabolic syndrome.
Human Th2 cells selectively express the orexigenic peptide, pro-melanin-concentrating hormone
Authors: Sandig Hilary , McDonald Joanne , Gilmour Jane , Arno Matthew , Lee Tak H. , Cousins David J.
Published: July 2007

Th1 and Th2 cells represent the two main functional subsets of CD4+T helper cell, and are defined by their cytokine expression. Human Th1 cells express IFNγ, whilst Th2 cells express IL-4, IL-5, and IL-13. Th1 and Th2 cells have distinct immunological functions, and can drive different immunopathologies. Here, we show thatin vitro-differentiated human Th2 cells highly selectively express the gene for pro-melanin-concentrating hormone (PMCH), using real-time RT-PCR, enzyme immunoassay, and Western blot analysis.PMCHencodes the prohormone, promelanin-concentrating hormone (PMCH), which is proteolytically processed to produce several peptides, including the orexigenic hormone melanin-concentrating hormone (MCH).PMCHexpression by Th2 cells was activation responsive and increased throughout the 28-day differentiation in parallel with the expression of the Th2 cytokine genes. MCH immunoreactivity was detected in the differentiated Th2 but not Th1 cell culture supernatants after activation, and contained the entire PMCH protein, in addition to several smaller peptides. Human Th1 and Th2 cells were isolated by their expression of IFNγ and CRTH2, respectively, and theex vivoTh2 cells expressedPMCHupon activation, in contrast to the Th1 cells. Because Th2 cells are central to the pathogenesis of allergic diseases including asthma, expression ofPMCHby activated Th2 cellsin vivomay directly link allergic inflammation to energy homeostasis and may contribute to the association between asthma and obesity.
ChlamydomonasOuter Arm Dynein Alters Conformation in Response to Ca2+
Authors: Sakato Miho , Sakakibara Hitoshi , King Stephen M.
Published: July 2007

We have previously shown that Ca2+directly activates ATP-sensitive microtubule binding by a Chlamydomonas outer arm dynein subparticle containing the β and γ heavy chains (HCs). The γ HC–associated LC4 light chain is a member of the calmodulin family and binds 1-2 Ca2+with KCa= 3 × 10−5M in vitro, suggesting it may act as a Ca2+sensor for outer arm dynein. Here we investigate interactions between the LC4 light chain and γ HC. Two IQ consensus motifs for binding calmodulin-like proteins are located within the stem domain of the γ heavy chain. In vitro experiments indicate that LC4 undergoes a Ca2+-dependent interaction with the IQ motif domain while remaining tethered to the HC. LC4 also moves into close proximity of the intermediate chain IC1 in the presence of Ca2+. The sedimentation profile of the γ HC subunit changed subtly upon Ca2+addition, suggesting that the entire complex had become more compact, and electron microscopy of the isolated γ subunit revealed a distinct alteration in conformation of the N-terminal stem in response to Ca2+addition. We propose that Ca2+-dependent conformational change of LC4 has a direct effect on the stem domain of the γ HC, which eventually leads to alterations in mechanochemical interactions between microtubules and the motor domain(s) of the outer dynein arm.
putzigIs Required for Cell Proliferation and Regulates Notch Activity inDrosophila
Authors: Kugler Sabrina J. , Nagel Anja C.
Published: July 2007

We have identified the gene putzig (pzg) as a key regulator of cell proliferation and of Notch signaling in Drosophila. pzg encodes a Zn-finger protein that was found earlier within a macromolecular complex, including TATA-binding protein-related factor 2 (TRF2)/DNA replication-related element factor (DREF). This complex is involved in core promoter selection, where DREF functions as a transcriptional activator of replication-related genes. Here, we provide the first in vivo evidence that pzg is required for the expression of cell cycle and replication-related genes, and hence for normal developmental growth. Independent of its role in the TRF2/DREF complex, pzg acts as a positive regulator of Notch signaling that may occur by chromatin activation. Down-regulation of pzg activity inhibits Notch target gene activation, whereas Hedgehog (Hh) signal transduction and growth regulation are unaffected. Our findings uncover different modes of operation of pzg during imaginal development of Drosophila, and they provide a novel mechanism of Notch regulation.
Inactivation of Rho GTPases withClostridium difficileToxin B Impairs Centrosomal Activation of Aurora-A in G2/M Transition of HeLa Cells
Authors: Ando Yoshikazu , Yasuda Shingo , Oceguera-Yanez Fabian , Narumiya Shuh
Published: July 2007

During G2 phase of cell cycle, centrosomes function as a scaffold for activation of mitotic kinases. Aurora-A is first activated at late G2 phase at the centrosome, facilitates centrosome maturation, and induces activation of cyclin B-Cdk1 at the centrosome for mitotic entry. Although several molecules including HEF1 and PAK are implicated in centrosomal activation of Aurora-A, signaling pathways leading to Aurora-A activation at the centrosome, and hence mitotic commitment in vertebrate cells remains largely unknown. Here, we have used Clostridium difficile toxin B and examined the role of Rho GTPases in G2/M transition of HeLa cells. Inactivation of Rho GTPases by the toxin B treatment delayed by 2 h histone H3 phosphorylation, Cdk1/cyclin B activation, and Aurora-A activation. Furthermore, PAK activation at the centrosome that was already present before the toxin addition was significantly attenuated for 2 h by the addition of toxin B, and HEF1 accumulation at the centrosome that occurred in late G2 phase was also delayed. These results suggest that Rho GTPases function in G2/M transition of mammalian cells by mediating multiple signaling pathways converging to centrosomal activation of Aurora-A.
Helicoverpa zea Trends from the Northeast: Suggestions Towards Collaborative Mapping of Migration and Pyrethroid Susceptibility
Authors: Fleischer Shelby , Payne Greg , Kuhar Thomas , Herbert Ames , Malone Sean , Whalen Joanne , Dively Galen , Johnson David , Hebberger Jo Anna , Ingerson-Mahar Joe , Holmstrom Kristian , Miller Doug
Published: July 2007

In the northeastern US, sweet corn is attacked by three lepidopterans, two of which are primarily migrants from the south. Knowledge about when and where these immigrants arrive can dramatically reduce insecticide inputs. We discuss progress on monitoring for pyrethroid resistance in one of the migrants, Helicoverpa zea, and in developing interactive cartography for regional monitoring of migratory lepidopterans in the northeastern US.

Accepted for publication 14 November 2006. Published 19 July 2007.
Mucin Gene Expression in Human Middle Ear Epithelium
Authors: Kerschner Joseph Edward
Published: July 2007

Objectives: To investigate the expression of recently identified human mucin genes in human middle ear epithelial (MEE) specimens from in vivo middle ear (ME) tissue and to compare this mucin gene expression with mucin gene expression in an immortalized cell culture in vitro source of human MEE.

Methods: Human MEE was harvested as in vivo specimens, and human MEE cell cultures were established for in vitro experimentation. RNA was extracted from MEE and primers designed for reverse‐transcription polymerase chain reaction to assess for mucin gene MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC8, MUC9, MUC11, MUC12, MUC13, MUC15, MUC16, MUC18, MUC19, and MUC20 expression. Mucin gene expression in the in vivo and in vitro ME tissue was compared against tissues with known expression of the mucin genes in question.

Results: Mucin genes MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, MUC8, MUC9, MUC11, MUC13, MUC15, MUC16, MUC18, MUC19, and MUC20 were identified and expressed in both the in vivo and in vitro samples of MEE. Mucin genes MUC6, MUC12, and MUC17 were not identified in either tissue samples.

Conclusion: Many of the mucin genes that have been recently identified are expressed in human MEE. These genes are expressed in a similar manner in both in vivo and in vitro models. Understanding the mechanisms in which these genes regulate the physiology and pathophysiology of MEE will provide a more thorough understanding of the molecular mechanics of the MEE and disease conditions such as otitis media.
Bilateral Neck Node Metastasis: A Predictor of Isolated Distant Metastasis in Patients With Oral and Oropharyngeal Squamous Cell Carcinoma After Primary Curative Surgery
Authors: Lim Young Chang , Koo Bon Seok , Choi Eun Chang
Published: July 2007

Objectives/Hypothesis: The presence of distant metastasis after the initial treatment of oral and oropharyngeal squamous cell carcinoma (OOSCC) is often associated with a poor prognosis. The purpose of our study was to evaluate the frequency of isolated distant metastasis (IDM) that occurred without any local or regional failure, and to identify its predictive factors in patients who were surgically treated.

Study Design: Retrospective chart review.

Methods: We performed a retrospective analysis of 230 OOSCC patients who underwent surgical treatment of the primary lesion along with a simultaneous neck dissection between May 1992 and August 2004. We evaluated the frequency of IDMs without local or regional recurrences and the influence of different variables in their appearance.

Results: The frequency of IDMs was 6%. Patients with oropharyngeal carcinoma had higher isolated distant failure compared with patients with oral cavity carcinoma (P < .05). In univariate analysis, the following conditions were significant predictors of IDM in patients with OOSCC: advanced local stage; clinical or pathologic positive neck node; the presence of more than two pathologic neck nodes; more than two bilateral pathologic nodal metastases; use of adjuvant radiotherapy; and advanced American Joint Committee on Cancer (AJCC) stage. However, in multivariate analysis, only the presence of pathologic positive lymph node, especially bilateral neck metastases, was an independent risk factor for the appearance of IDMs.

Conclusions: The incidence of IDMs in patients with OOSCC is relatively low. These events were significantly associated with bilateral neck node metastases.
Sentinel Node Biopsy for Oral and Oropharyngeal Squamous Cell Carcinoma of the Head and Neck
Authors: Stoeckli Sandro J.
Published: July 2007

Objectives: The aims were to assess the technical feasibility of sentinel node biopsy (SNB), to validate SNB against elective neck dissection, and to report the results of the clinical application of the SNB concept for early oral and oropharyngeal squamous cell carcinoma.

Study Design: Prospective consecutive cohort analysis.

Methods: Between 2000 and 2006, a total of 79 patients were included. Lymphatic mapping consisted of preoperative lymphoscintigraphy and intraoperative use of a hand‐held gammaprobe. Twenty‐eight patients were assessed for feasibility and validation; the SNB was done in context with an elective neck dissection. Fifty‐one patients were evaluated in an observational trial; elective neck dissection was performed only in case of positive SNB.

Results: Validation revealed a sentinel node detection rate by lymphoscintigraphy of 93%, with the gammaprobe of 100%. The negative predictive value of a negative SNB was 100%. During the observational trial 40% of the patients were upstaged as a result of a positive SNB. Intraoperative frozen section analysis showed a negative predictive value of 83%. Two patients (6%) with negative SNB experienced a neck recurrence, the negative predictive value of SNB was therefore 94%. Patients with positive SNB were treated successfully with elective neck dissection.

Conclusions: SNB is technically feasible and reproducible with a high sentinel node detection rate. Validation against elective neck dissection revealed a negative predictive value of 100%. Application of the SNB concept in clinical practice was very successful. The recurrence rate within the neck was very low and the morbidity and cost of an elective neck dissection could be spared to 60% of the patients.
Quality of Life Instruments in Ménière's Disease
Authors: Green J Douglas , Verrall Aimee , Gates George A.
Published: July 2007

Objective: Evaluate the sensitivity of quality of life (QoL) instruments over time in patients with Ménière's disease using general, symptom‐specific, and disease‐specific QoL instruments.

Study Design: Prospective study using QoL instruments administered serially over 4 months in patients undergoing treatment for Ménière's disease.

Methods: Sixty‐one people aged 33 to 71 years with active, unilateral, cochleovestibular Ménière's disease refractory to medical management completed two general QoL instruments, Sense of Coherence (SOC) and World Health Organization Quality of Life–Abbreviated Version (WHOQOL‐BREF), one symptom‐specific QoL instrument, Vertigo Symptom Scale (VSS), and one disease‐specific QoL instrument, Ménière's Disease Patient Oriented Severity Index (MDPOSI). All measures were administered at baseline and again 2 and 4 months later.

Results: Disease‐ and symptom‐specific instruments including the MDPOSI and VSS were positively correlated with vertigo control category (Pearson's R = 0.345, MDPOSI; 0.279, VSS), indicating sensitivity to the frequency of vertigo spells. These instruments were also sensitive to changes in vertigo over time. Standardized response means showed greatest responsiveness to change on the MDPOSI (0.80) and the VSS (0.79). Standardized response means for SOC and WHOQOL‐BREF were 0.03, and 0.32, respectively, suggesting poor responsiveness to change of symptoms. The VSS and MDPOSI were highly correlated (Pearson's r coefficient 0.744; P < .001).

Conclusions: A disease‐specific QoL instrument such as the MDPOSI and a symptom‐specific instrument such as the VSS more accurately reflect changes in control of vertigo in people with Ménière's disease over time than do general QoL instruments. These instruments can be used to determine the life impact of Ménière's disease and how aggressive therapy should be for the patient.
Spatial Hearing Disability After Acoustic Neuroma Removal
Authors: Douglas Susan A. , Yeung Phil , Daudia Anurag , Gatehouse Stuart , O'Donoghue Gerard M.
Published: July 2007

Objectives/Hypothesis: Previous studies on hearing loss (HL) after acoustic neuroma removal concentrate mainly on pure‐tone hearing results rather than hearing disability. Our objectives were to use the Speech, Spatial and Qualities of Hearing scale (SSQ), a comprehensively validated questionnaire, to characterize and quantify the auditory disabilities that patients experience with a profound unilateral HL after acoustic neuroma removal.

Study Design: Forty‐four patients with profound unilateral HL after acoustic neuroma surgery completed the SSQ. Their findings were compared with those of a control population sample matched for age, sex, and hearing level in the better hearing ear.

Results: In comparison with controls, with use of analysis of variance, acoustic neuroma patients scored poorly on all items except for the identification of sounds and objects (P = .123). The greatest difficulties involved speech in the presence of noise, situations of multiple speech‐streams and switching (such as listening to someone speaking and the television at the same time), the location of unseen objects, and increased listening effort (P < .05).

Conclusion: This study demonstrates that, compared with a control population, these patients experience a significant range of auditory disabilities. It is important that clinicians be aware of the impact of such a profound unilateral HL and its potential to affect daily life. Patient counseling prior to surgery is essential, especially in patients whose loss of binaural hearing could constitute a major disability.
Activation of both nuclear factor of activated T cells and inhibitor of nuclear factor‐κB kinase β‐subunit‐/nuclear factor‐κB is critical for cyclooxygenase‐2 induction by benzo[a]pyrene in human bronchial epithelial cells
Authors: Ding Jin , Wu Kangjian , Zhang Dongyun , Luo Wenjing , Li Jingxia , Ouyang Weiming , Song Lun , Huang Chuanshu
Published: July 2007

The carcinogenic effect of benzo[a]pyrene (B[a]P), presenting mainly in cigarette smoke and air pollution, has been well demonstrated both in vitro and in vivo. However, it is still not well understood how B[a]P facilitates pulmonary carcinogenesis. To explore this, we investigated the effect of B[a]P on the induction of cyclooxygenase‐2 (COX‐2), a critical enzyme implicated in inflammation and cancer development, as well as upstream signaling pathways leading to its expression in human bronchial epithelial cells (Beas‐2B). We found that exposure of Beas‐2B to B[a]P caused significant COX‐2 induction at both the transcriptional and protein levels. B[a]P also switched on the nuclear factor of activated T cells (NFAT) and nuclear factor κB (NF‐κB) signaling pathways. B[a]P‐induced COX‐2 expression was significantly blocked by inhibition of the NFAT pathway, and impairment of the NF‐κB signaling pathway by ectopic expression of an inhibitor of nuclear factor‐κB kinase β‐subunit (IKKβ) kinase inactive mutant (IKKβ‐KM) also dramatically inhibited COX‐2 induction. The IKKβ/NF‐κB‐dependent COX‐2 induction was further confirmed in mouse embryonic fibroblasts with IKKβ deficiency (IKKβ−/–) and in those that expressed reconstituted IKKβ. However, activation of the NFAT and NF‐κB signaling pathways by B[a]P were independent of each other, as blocking one signaling pathway didn't interrupt the activation of the other one. Mutation of either NFAT or NF‐κB binding sites significantly blocked COX‐2 promoter induction by B[a]P. Taken together, these data indicate that exposure of Beas‐2B to B[a]P can upregulate COX‐2 expression by increasing its transcription, which requires activation of both the NFAT and NF‐κB signaling pathways. (Cancer Sci 2007; 98: 1323–1329)
Inhibition of GSK‐3β activity attenuates proliferation of human colon cancer cells in rodents
Authors: Shakoori Abbas , Mai Wei , Miyashita Katsuyoshi , Yasumoto Kazuo , Takahashi Yutaka , Ooi Akishi , Kawakami Kazuyuki , Minamoto Toshinari
Published: July 2007

The authors’ recent discovery that glycogen synthase kinase‐3β (GSK‐3β) participates in colon cancer cells’ survival and proliferation prompted us to investigate whether GSK‐3β inhibition alters proliferation of colon cancer cells in vivo. Groups of four or five athymic mice (Balb/c, nu/nu) with subcutaneous xenografts of SW480 human colon cancer cells were treated with dimethyl sulfoxide (DMSO) or different doses (1, 2 and 5 mg/kg body weight) of either small‐molecule GSK‐3β inhibitor (SB‐216763 and AR‐A014418) by intraperitoneal injection three times per week for 5 weeks. Compared with DMSO (a diluent of the GSK‐3β inhibitors) as a control, either GSK‐3β inhibitor significantly inhibited proliferation of cancer cell xenografts in the rodents in a dose‐dependent manner. Histochemical and immunohistochemical analysis of tumor xenografts demonstrated a significant, dose‐dependent decrease in fractions of proliferating cells and an increase in the incidence of apoptosis of cancer cells in mice treated with either GSK‐3β inhibitor. No adverse events or effects were observed in the rodents during the course of treatment, except for rare lethal accidents due to intraperitoneal injection. Morphological examination showed no apparent pathologic changes in major organs including the lungs, liver, pancreas, kidneys, spleen and large bowel of rodents treated with DMSO and the GSK‐3β inhibitors. The results indicate that the GSK‐3β inhibitors would be a novel class of therapeutic agent for colon cancer. (Cancer Sci 2007; 98: 1388–1393)
Cleavage of growth differentiation factor 15 (GDF15) by membrane type 1‐matrix metalloproteinase abrogates GDF15‐mediated suppression of tumor cell growth
Authors: Abd El‐Aziz Shaban H. , Endo Yoshio , Miyamaori Hisashi , Takino Takahisa , Sato Hiroshi
Published: July 2007

Growth differentiation factor 15 (GDF15), a transforming growth factor (TGF)‐β superfamily member, has been cloned from a placenta cDNA library as a gene product that has promoted activation of pro‐matrix metalloproteinase (MMP)2 mediated by membrane type (MT)1‐MMP. Expression of MT1‐MMP in HEK293T cells caused cleavage of the GDF15 mature form at N252–M253 to produce a 6‐kDa C‐terminal fragment. Treatment of MCF7 cells with GDF15 induced activation of p53 and enhanced expression of p21, which was abrogated by MT1‐MMP expression. GDF15 mRNA synthesis was also shown to be induced by treatment of cells with GDF15. Treatment of MCF7 cells with GDF15 caused suppression of cell proliferation. However, proliferation of MCF7 cells transfected with the MT1‐MMP gene was not affected by GDF15 treatment, but was suppressed in the presence of the MMP inhibitor BB94. HT1080 cells transfected with the GDF15 gene, which endogenously express MT1‐MMP, synthesize a high‐level GDF15 precursor form and a low‐level mature form, and treatment of cells with BB94 enhanced production of the GDF15 mature form. Consistent with GDF15 production, HT1080 cells transfected with the GDF15 gene proliferated almost equally with control cells, and addition of BB94 effectively suppressed growth of HT1080 cells transfected with the GDF15 gene concomitant with the accumulation of the GDF15 mature form, but not control cells. These results suggest that MT1‐MMP contributes to tumor cell proliferation through the cleavage of GDF15, which down‐regulates cell proliferation by inducing activation of p53 and p21 synthesis. (Cancer Sci 2007; 98: 1330–1335)
Sipholenol A, a marine‐derived sipholane triterpene, potently reverses P‐glycoprotein (ABCB1)‐mediated multidrug resistance in cancer cells
Authors: Shi Zhi , Jain Sandeep , Kim In‐Wha , Peng Xing‐Xiang , Abraham Ioana , Youssef Diaa T.A. , Fu Li‐Wu , El Sayed Khalid , Ambudkar Suresh V. , Chen Zhe‐Sheng
Published: July 2007

Through extensive screening of marine sponge compounds, the authors have found that sipholenol A, a sipholane triterpene isolated from the Red Sea sponge, Callyspongia siphonella, potently reversed multidrug resistance (MDR) in cancer cells that overexpressed P‐glycoprotein (P‐gp). In experiments, sipholenol A potentiated the cytotoxicity of several P‐gp substrate anticancer drugs, including colchicine, vinblastine, and paclitaxel, but not the non‐P‐gp substrate cisplatin, and significantly reversed the MDR of cancer cells KB‐C2 and KB‐V1 in a concentration‐dependent manner. Furthermore, sipholenol A had no effect on the response to cytotoxic agents in cells lacking P‐gp expression or expressing MDR protein 1 or breast cancer resistance protein. Sipholenol A (IC50 > 50 µM) is not toxic to all the cell lines that were used, regardless of their membrane transporter status. Accumulation and efflux studies with the P‐gp substrate [3H]‐paclitaxel demonstrated that sipholenol A time‐dependently increased the intracellular accumulation of [3H]‐paclitaxel by directly inhibiting P‐gp‐mediated drug efflux. In addition, sipholenol A did not alter the expression of P‐gp after treating KB‐C2 and KB‐V1 cells for 36 h and 72 h. However, it efficaciously stimulated the activity of ATPase of P‐gp and inhibited the photolabeling of this transporter with its transport substrate [125I]‐iodoarylazidoprazosin. Overall, the present results indicate that sipholenol A efficiently inhibits the function of P‐gp through direct interactions, and sipholane triterpenes are a new class of potential reversing agents for treatment of MDR in P‐gp‐overexpressing tumors. (Cancer Sci 2007; 98: 1373–1380)
γ‐Herpesviruses and cellular signaling in AIDS‐associated malignancies
Authors: Noguchi Kohji , Fukazawa Hidesuke , Murakami Yuko , Takahashi Naoko , Yamagoe Satoshi , Uehara Yoshimasa
Published: July 2007

γ‐Herpesviruses, Epstein–Barr virus (EBV/HHV‐4) and Kaposi's sarcoma‐associated herpesvirus (KSHV/HHV‐8), are involved in human carcinogenesis, particularly in immunocompromised patients. Virus‐associated malignancies are becoming of significant concern for the mortality of long‐lived immunocompromised patients, and therefore, research of advanced strategies for AIDS‐related malignancies is an important field in cancer chemotherapy. Detailed understanding of the EBV and KSHV lifecycle and related cancers at the molecular level is required for novel strategies of molecular‐targeted cancer chemotherapy. The present review gives a simple outline of the functional interactions between KSHV‐ and EBV‐viral gene products and host cell deregulated signaling pathways as possible targets of chemotherapy against AIDS‐related malignancies. (Cancer Sci 2007; 98: 1288–1296)
Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group study 9004
Authors: Tobinai Kensei , Takeyama Kunihiko , Arima Fumito , Aikawa Keiko , Kobayashi Tohru , Hanada Shuichi , Kasai Masaharu , Ogura Michinori , Sueoka Eisaburo , Mukai Kiyoshi , Tajima Kinuko , Fukuda Haruhiko , Shirakawa Shigeru , Hotta Tomomitsu , Masanori Shimoyama ,   members of the Lymphoma Study Group of the Japan Clinical Oncology Group
Published: July 2007

Granulocyte colony‐stimulating factor (G‐CSF)‐supported, post‐remission chemotherapy (Cx) for adult acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) was evaluated. One hundred and forty‐three eligible patients (median age, 41 years) including 126 ALL and 17 LBL receiving induction Cx (vincristine, cyclophosphamide, prednisolone [PSL], doxorubicin, L‐asparaginase, intrathecal‐methotrexate [IT‐MTX]) were analyzed. For patients achieving complete response (CR), two courses of post‐remission Cx (course A of daunorubicin, cytosine arabinoside, vindesine, PSL plus IT‐MTX; course B of mitoxantrone, etoposide, vincristine, PSL plus IT‐MTX) with the use of G‐CSF were repeated alternately; thereafter, maintenance Cx including MTX and 6‐mercaptopurine was given for 2 years. One hundred and nineteen (83%) patients achieved CR, while 14 (10%) died during induction. Among the 119 patients achieving CR, five died in remission, 76 relapsed, and the remaining 38 were alive without disease. The median survival time of the 143 eligible patients was 26 months (95% confidence interval, 19–34). At a median follow‐up time of 9 years, the 5‐year survival rate was 32% and the 5‐year progression‐free survival (PFS) rate was 26%. The 5‐year survival rate of 36 patients who underwent autologous (n = 20) or allogeneic stem cell transplantation (SCT; n = 16) in the first CR group was 58%. Compared with the authors’ previous trials, survival and PFS were markedly improved. In conclusion, G‐CSF‐supported, intensive post‐remission Cx and subsequent SCT are worthy of further investigation for the treatment of adult ALL and LBL. (Cancer Sci 2007; 98: 1350–1357)
Immunophenotypic identification of possible therapeutic targets in paediatric non‐Hodgkin lymphomas: a children's oncology group report
Authors: Miles Rodney R. , Cairo Mitchell S. , Satwani Prakash , Zwick David L. , Lones Mark A. , Sposto Richard , Abromovitch Minnie , Tripp Sheryl , Angiolillo Anne L. , Roman Elizabeth , Davenport Virginia , Perkins Sherrie L.
Published: July 2007

Immunophenotypic analysis can identify protein epitopes in non‐Hodgkin lymphomas (NHL) that may respond to targeted immunotherapies, such as anti‐CD20 and anti‐CD52. Recent studies suggest additional targets may provide therapeutic benefits in NHL. This study evaluated protein expression of CD25, CD52, CD74 and CD80 in paediatric NHL to determine possible targets for immune‐based therapeutic approaches. Patient samples were derived from paediatric NHL clinical trials sponsored by the Children's Cancer Group (CCG, now the Children's Oncology Group, COG) and included Burkitt lymphoma (BL), diffuse large B‐cell lymphoma (DLBCL), disseminated T‐ and B‐cell lymphoblastic lymphoma (T‐LBL and B‐LBL) and anaplastic large cell (ALCL). Immunophenotypic studies were performed on formalin‐fixed, paraffin‐embedded diagnostic tissues. CD25 was expressed in 8% of T‐LBL and 75% of ALCL cases, but not in BL, DLBCL, or B‐LBL. CD52 was expressed in 99% of cases of paediatric NHL of all subtypes. CD74 was expressed in 100% of B‐LBL, BL and DLBCL, but was absent in ALCL and T‐LBL. CD80 was expressed in 12% of B‐LBL, 6% of BL and 10% of DLBCL cases studied, but was not detected in T‐cell NHL. These expression patterns suggest that CD25, CD52 and CD74 may represent potential new therapeutic targets in paediatric NHL.
Larval Pacific herring, Clupea pallasii (Valenciennes), are highly susceptible to viral haemorrhagic septicaemia and survivors are partially protected after their metamorphosis to juveniles
Authors: Hershberger P K , Gregg J , Pacheco C , Winton J , Richard J , Traxler G
Published: July 2007

Pacific herring were susceptible to waterborne challenge with viral haemorrhagic septicaemia virus (VHSV) throughout their early life history stages, with significantly greater cumulative mortalities occurring among VHSV‐exposed groups of 9‐, 44‐, 54‐ and 76‐day‐old larvae than among respective control groups. Similarly, among 89‐day–1‐year‐old and 1+year old post‐metamorphosed juveniles, cumulative mortality was significantly greater in VHSV‐challenged groups than in respective control groups. Larval exposure to VHSV conferred partial protection to the survivors after their metamorphosis to juveniles as shown by significantly less cumulative mortalities among juvenile groups that survived a VHS epidemic as larvae than among groups that were previously naïve to VHSV. Magnitude of the protection, measured as relative per cent survival, was a direct function of larval age at first exposure and was probably a reflection of gradual developmental onset of immunocompetence. These results indicate the potential for easily overlooked VHS epizootics among wild larvae in regions where the virus is endemic and emphasize the importance of early life history stages of marine fish in influencing the ecological disease processes.
Selected pathological, immunohistochemical and ultrastructural changes associated with an infection by Diphyllobothrium dendriticum (Nitzsch, 1824) (Cestoda) plerocercoids in Coregonus lavaretus (L.) (Coregonidae)
Authors: Dezfuli B S , Pironi F , Simoni E , Shinn A P , Giari L
Published: July 2007

The pathological changes induced by an infection of Diphyllobothrium dendriticum (Nitzsch, 1824) plerocercoids in powan, Coregonus lavaretus (L.), from Loch Lomond, Scotland, were assessed using immunohistochemical and ultrastructural techniques. In a sample of 26 powan, the occurrence of encysted plerocercoids of D. dendriticum on the outer surface of the stomach was 38.5% (n = 10) with the number of cysts ranging from 4 to 15 and measuring 4.2 ± 1.0 mm × 3.4 ± 0.9 mm (mean ± SD). Histological examination of intestinal samples also revealed plerocercoids (2–21) encapsulated within a proliferation of mesenteric fibrous tissues of the gastric wall and, occasionally, by the gut lamina propria‐submucosa and lamina muscularis. In section, cysts were tri‐layered and were formed from a series of concentric whorls of fibroblast and collagen fibre‐based connective elements. The extent of necrosis within each muscle layer and the serosa of the stomach differed, notably within the latter that was marked by a chronic inflammatory reaction and fibrosis. Within the cyst and around it, a large number of degranulating mast cell/eosinophilic granule cells were seen, in addition to melano‐macrophage centres. Immunohistochemical staining of sections of infected stomach revealed a high density of elements, in close proximity to plerocercoids, staining positive for serotonin, bombesin, substance P and galanin. Uninfected material did not present the same levels of activity. Sections through both infected and uninfected tissue were also tested for elements containing vasoactive intestinal peptide, met‐enkephalin, calcitonin gene‐related peptide, neuropeptide Y and nitric oxide synthase, but these were absent.
Metabolic control of the Escherichia coli universal stress protein response through fructose‐6‐phosphate
Authors: Persson Örjan , Valadi Åsa , Nyström Thomas , Farewell Anne
Published: July 2007

The universal stress protein (Usp) superfamily encompasses a conserved group of proteins involved in stress resistance, adaptation to energy deficiency, cell motility and adhesion, and is found in all kingdoms of life. The paradigm usp gene, uspA, of Escherichia coli is transcriptionally activated by a large variety of stresses, and the alarmone ppGpp is required for this activation. Here, we show that the uspA gene is also regulated by an intermediate of the glycolytic/gluconeogenic pathways. Specifically, mutations and conditions resulting in fructose‐6‐phosphate (F‐6‐P) accumulation elicit superinduction of uspA upon carbon starvation, whereas genetic manipulations reducing the pool size of F‐6‐P have the opposite effect. This metabolic control of uspA does not act via ppGpp. Other, but not all, usp genes of the usp superfamily are similarly affected by alterations in F‐6‐P levels. We suggest that alterations in the pool size of phosphorylated sugars of the upper glycolytic pathway may ensure accumulation of required survival proteins preceding the complete depletion of the external carbon source. Indeed, we show that uspA is, in fact, induced before the carbon source is depleted from the medium.