bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profound retinal ischaemia after ranibizumab administration in an eye with ocular ischaemic syndrome
Authors: Kofoed Peter Kristian , Munch Inger Christine , Larsen Michael 
Published: October 2009

Acta Ophthalmol. 2010: 88: 808–810Abstract.Purpose:  To report the result of ranibizumab administration in an eye with ocular ischaemic syndrome.Methods:  Fluorescein angiography, ocular pneumoplethysmography and retinal vessel calibre measurement.Results:  An 85‐year‐old man with ocular ischaemic syndrome demonstrated vision loss, retinal vessel calibre constriction and profound retinal ischaemia after intravitreal ranibizumab.Conclusion:  We advise against the use of intravitreal vascular endothelial growth factor inhibitors in eyes with ocular ischaemic syndrome.
Bacteriophage Cocktail for the Prevention of Biofilm Formation by
Pseudomonas aeruginosa
on Catheters in an
In Vitro
Model System
Authors: Fu Weiling , Forster Terri , Mayer Oren , Curtin John J. , Lehman Susan M. , Donlan Rodney M. 
Published: October 2009

ABSTRACT

Microorganisms develop biofilms on indwelling medical devices and are associated with device-related infections, resulting in substantial morbidity and mortality. This study investigated the effect of pretreating hydrogel-coated catheters with
Pseudomonas aeruginosa
bacteriophages on biofilm formation by
P. aeruginosa
in an
in vitro
model. Hydrogel-coated catheters were exposed to a 10 log
10
PFU ml
−1
lysate of
P. aeruginosa
phage M4 for 2 h at 37°C prior to bacterial inoculation. The mean viable biofilm count on untreated catheters was 6.87 log
10
CFU cm
−2
after 24 h. The pretreatment of catheters with phage reduced this value to 4.03 log
10
CFU cm
−2
(
P
< 0.001). Phage treatment immediately following bacterial inoculation also reduced biofilm viable counts (4.37 log
10
CFU cm
−2
reduction;
P
< 0.001). The regrowth of biofilms on phage-treated catheters occurred between 24 and 48 h, but supplemental treatment with phage at 24 h significantly reduced biofilm regrowth (
P
< 0.001). Biofilm isolates resistant to phage M4 were recovered from catheters pretreated with phage. The phage susceptibility profiles of these isolates were used to guide the development of a five-phage cocktail from a larger library of
P. aeruginosa
phages. The pretreatment of catheters with this cocktail reduced the 48-h mean biofilm cell density by 99.9% (from 7.13 to 4.13 log
10
CFU cm
−2
;
P
< 0.001), but fewer biofilm isolates were resistant to these phages. These results suggest the potential of applying phages, especially phage cocktails, to the surfaces of indwelling medical devices for mitigating biofilm formation by clinically relevant bacteria.
Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms
Authors: Price Patricia , Murdoch David M. , Agarwal Upasna , Lewin Sharon R. , Elliott Julian H. , French Martyn A. 
Published: October 2009

SUMMARYUp to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.
Modern Uses of Electron Microscopy for Detection of Viruses
Authors: Goldsmith Cynthia S. , Miller Sara E. 
Published: October 2009

SUMMARYElectron microscopy, considered by some to be an old technique, is still on the forefront of both clinical viral diagnoses and viral ultrastructure and pathogenesis studies. In the diagnostic setting, it is particularly valuable in the surveillance of emerging diseases and potential bioterrorism viruses. In the research arena, modalities such as immunoelectron microscopy, cryo-electron microscopy, and electron tomography have demonstrated how viral structural components fit together, attach to cells, assimilate during replication, and associate with the cellular machinery during replication and egression. These studies provide information for treatment and vaccine strategies.
Towards evidence-based classification in Paralympic athletics: evaluating the validity of activity limitation tests for use in classification of Paralympic running events
Authors: Beckman E M , Tweedy S M 
Published: October 2009

Objective:To classify Paralympic athletes, classifiers use test batteries to obtain an objective, pre-competition estimate of an athlete’s training level. Five tests were evaluated to determine which combination explained the maximum variance in running performance in a non-disabled population. A non-disabled sample was required to permit psychometric evaluation of the tests without the confounding influence of impairment, and to provide an indication of normative performance.Design:Sixty-seven non-disabled participants (male and female; mean (SD) age 24.78 (6.53) years) completed a six-test battery comprising a 30 m sprint (criterion activity limitation test) and five supplementary activity limitation tests: standing broad jump, four bounds, 10 m skip, running in place and split jumps.Results:Test reliability was high for all tests (intraclass correlations  =  0.80–0.99). Pearson correlations with the 30 m sprint were moderate to strong for standing broad jump (−0.82), four bounds (−0.80) and 10 m skip (0.67), but weaker for split jumps (0.35) and running in place (0.19). Multiple regression indicated that standing broad jump, four bounds and 10 m skip explained 75% of the variance in running performance.Conclusions:The test battery is reliable and valid in the non-disabled population and therefore has potential utility in Paralympic classification. Test results were normally distributed, a necessary prerequisite for meaningful interpretation of future studies in athletes with impairments. Further studies evaluating the battery in populations of athletes with impairments of coordination, strength and range of movement are now warranted.
Spawning time variation in Icelandic summer-spawning herring (Clupea harengus)
Authors: Óskarsson Guðmundur J. , Taggart Christopher T. 
Published: October 2009

Different fish stocks of the same species are defined by spatial and temporal differences in spawning, though spawning time can vary within and among stocks. Here we address spawning time variation in Icelandic summer-spawning (ISS) Atlantic herring ( Clupea harengus ). We do so by examining influencing factors that include variation in stock size structure, spawning experience (recruit vs. repeat spawners), spawning stock biomass (SSB), sea temperature, and combinations thereof. Our results, based on temporal variation in ovary weight (OW), relative ovary weight (RG), and maturation stage, across a time series of nearly 50 years and eight length classes of ISS herring, show that spawning occurs over a relatively invariant 30-day period defined by day-of-the-year. Logistic regression analyses and temporal development in OW and RG show that maximum spawning invariably occurs on day-of-the-year 200 ± 15 days, and seasonal variation in mesenteric fat content is physiologically consistent with the timing. We show that the smaller recruit spawners tend to spawn ~17 days later, on average, than the larger repeat spawners. Spawning occurs ~7 days later when SSB is greater than the long-term average, and spawning may be delayed by as much as 10 days during periods of colder than average ocean temperature.
Evaluating the demographic significance of genetic homogeneity using a coalescent-based simulation: a case study with gag (Mycteroperca microlepis)
Authors: Cushman Elizabeth L. , Jue Nathaniel K. , Strand Allan E. , Sotka Erik E. 
Published: October 2009

Gag ( Mycteroperca microlepis ) from the eastern Gulf of Mexico and northwestern Atlantic are managed as separate stocks, although evidence for their demographic isolation remains equivocal. Several hundred individuals were genotyped at 11 microsatellite loci and it was found that gag across these regions were genetically indistinguishable (FST < 0.001). A coalescent-based computer simulation was employed to quantitatively assess the relative importance of dispersal rate, population size, and time since divergence on gag genetic homogeneity. Using empirical estimates of long-term effective population size (16 500), a range of dispersal rates and divergence times (500 to 500 000 generations) was modeled, and it was concluded that present-day genetic homogeneity must be maintained by dispersal rates of at least 20–30 migrants per generation and up to hundreds or thousands per generation. This study also documents the absence of significant temporal genetic structure and inbreeding in the Atlantic when comparing cohorts separated in time from weeks to 20 years. This suggests that the long-standing practice of overfishing gag has yet to manifest as an inbreeding effect. Overall, gag dispersal rates remain uncertain, and consequently, this study can neither support nor refute management schemes that independently regulate gag in the eastern Gulf of Mexico and northwestern Atlantic.
Cretaceous felsic volcanism in New Zealand and Lord Howe Rise (Zealandia) as a precursor to final Gondwana break-up
Authors: Tulloch A. J. , Ramezani J. , Mortimer N. , Mortensen J. , van den Bogaard P. , Maas R. 
Published: October 2009

Abstract

We report new, highly precise, U–Pb and Ar/Ar ages for seven Cretaceous rhyolites, tuffs and granites from across Zealandia spanning a 30 Ma period from arc magmatism to continental break-up. Combined with previously published data, these reveal a strong episodicity in Cretaceous silicic magmatism outside the Median Batholith. 112 Ma tuffs are known only from the Eastern Province in association with a Cretaceous normal fault system. Both 101 and 97 Ma groups of rhyolites and tuffs occur across the entire width and half the length of Zealandia from near the palaeotrench to the continental interior, indicating widespread and effectively instantaneous extension. We attribute an increase in A-type character with time (112–101–97–88–82 Ma) to the progressive thinning of the Zealandia continental crust whereby, with time, there is less opportunity for crustal contamination. Extension directions associated with 101, 97 and 82 Ma magmatism and associated core complex exhumation across Zealandia are all oriented
c.
30° oblique to the margin. These observations suggest Zealandia rifting was controlled by either >83 Ma capture of Zealandia by the Pacific Plate and/or <83 Ma Zealandia–West Antarctica spreading, rather than by laterally migrating triple junctions, slab windows or plume heads.
Anticancer Chemotherapy Inhibits MHC Class I–Related Chain A Ectodomain Shedding by Downregulating ADAM10 Expression in Hepatocellular Carcinoma
Authors: Kohga Keisuke , Takehara Tetsuo , Tatsumi Tomohide , Miyagi Takuya , Ishida Hisashi , Ohkawa Kazuyoshi , Kanto Tatsuya , Hiramatsu Naoki , Hayashi Norio 
Published: October 2009

Abstract
MHC class I–related chain A (MICA) is a ligand for the NKG2D-activating immunoreceptor that mediates activation of natural killer (NK) cells. The ectodomain of MICA is shed from tumor cells, which may be an important means of evading antitumor immunity. We previously reported that patients with hepatocellular carcinoma (HCC) display high levels of soluble MICA in circulation, which could be downregulated by chemotherapy. The present study shows that anti-HCC drugs suppress MICA ectodomain shedding by inhibiting expression of a disintegrin and metalloproteinase 10 (ADAM10). Both ADAM10 and CD44, a typical substrate of the ADAM10 protease, were expressed in human HCC tissues and HCC cells but not in normal liver tissues or cultured hepatocytes. Small interfering RNA–mediated knockdown experiments revealed that ADAM10 is a critical sheddase for both MICA and CD44 in HCC cells. Of interest is the finding that epirubicin clearly downregulated ADAM10 expression and MICA shedding in HCC cells; its suppressive effect on MICA shedding was abolished in ADAM10-depleted cells. Epirubicin treatment also enhanced the NKG2D-mediated NK sensitivity of HCC cells. Patients with HCC had significantly higher levels of serum-soluble CD44, which correlated well with serum-soluble MICA levels, thus suggesting a close link between ADAM10 activity and MICA shedding in these patients. Soluble MICA and CD44 levels were downregulated with a significant correlation in patients treated by transarterial chemoembolization using epirubicin. In conclusion, anticancer drugs can modulate expression of ADAM10, which is critically involved in MICA ectodomain shedding. Epirubicin therapy may have a previously unrecognized effect on antitumor immunity in HCC patients. [Cancer Res 2009;69(20):8050–7]
A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients with Solid Malignancies
Authors: Burris Howard A. , Taylor Charles W. , Jones Suzanne F. , Koch Kevin M. , Versola Melissa J. , Arya Niki , Fleming Ronald A. , Smith Deborah A. , Pandite Lini , Spector Neil , Wilding George 
Published: October 2009

Abstract
Purpose: This study determined the range of tolerable doses, clinical safety, pharmacokinetics, and preliminary evidence of clinical activity following once or twice daily administration of lapatinib in patients with solid malignancies.
Experimental Design: Cancer patients (n = 81) received oral doses of lapatinib ranging from 175 to 1,800 mg once daily or 500 to 900 mg twice daily. Clinical assessments of safety and antitumor activity were recorded and blood was sampled for pharmacokinetic assessments. The effect of a low-fat meal on lapatinib pharmacokinetics was assessed in a subset of patients.
Results: Lapatinib was well tolerated, such that dose escalation was limited at 1,800 mg once daily only by pill burden. Twice-daily dosing was implemented to further explore tolerability, and was limited by diarrhea to 500 mg twice daily. The most commonly reported adverse events with once-daily dosing were diarrhea (48%), nausea (40%), rash (40%), and fatigue (38%) and with twice-daily dosing were diarrhea (85%), rash (54%), and nausea (34%). Lapatinib serum concentrations accumulated upon repeated dosing, increasing nearly in proportion with dose, and were significantly increased when dosed with food or administered twice daily. One patient with head and neck cancer achieved a confirmed complete response and 22 patients had stable disease of ≥8 weeks including three patients with stable disease of &gt;10 months (renal, lung, and salivary gland cancers).
Conclusion: Lapatinib was well tolerated following once and twice daily administration. Systemic exposure to lapatinib was dependent on the dose, duration and frequency of dosing, and prandial state. Clinical activity was observed. (Clin Cancer Res 2009;15(21):6702–8)
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Reverses Mesenchymal to Epithelial Phenotype and Inhibits Metastasis in Inflammatory Breast Cancer
Authors: Zhang Dongwei , LaFortune Tiffany A. , Krishnamurthy Savitri , Esteva Francisco J. , Cristofanilli Massimo , Liu Ping , Lucci Anthony , Singh Balraj , Hung Mien-Chie , Hortobagyi Gabriel N. , Ueno Naoto T. 
Published: October 2009

Abstract
Purpose: Inflammatory breast cancer (IBC) is a rare but aggressive type of advanced breast cancer. Epidermal growth factor receptor (EGFR) expression is an independent poor prognostic factor in IBC. The purpose of this study was to determine the effect on IBC tumorigenicity and metastasis of blocking the EGFR pathway.
Experimental Design: IBC cell lines, which express high level of EGFR, were treated with EGFR small interfering RNA and with the EGFR tyrosine kinase inhibitor erlotinib. The role of EGFR in IBC cell proliferation, motility, invasiveness, and change of the expression levels of epithelial-mesenchymal transition markers was examined. The role of extracellular signal–regulated kinase (ERK)-1/2 in erlotinib activity was also studied. The activity of erlotinib in tumor growth and metastasis was examined in an orthotopic xenograft model of IBC.
Results: Erlotinib inhibited proliferation and anchorage-independent growth of IBC cells, and this inhibition was ERK dependent. Erlotinib inhibited cell motility and invasiveness and reversed the mesenchymal phenotype of IBC cells to epithelial phenotype in three-dimensional culture. Erlotinib dramatically inhibited IBC tumor growth in a xenograft model. Interestingly, erlotinib inhibited spontaneous lung metastasis, even at a low dose that had no significant effect on primary tumor growth. These erlotinib-treated tumors were converted to epithelial phenotype from mesenchymal phenotype.
Conclusions: The EGFR pathway is involved in tumor growth and metastasis of IBC. Targeting EGFR through the ERK pathway may represent an effective therapeutic approach to suppress tumorigenicity and prevent metastasis in EGFR-expressing IBC. (Clin Cancer Res 2009;15(21):6639–48)
Lymphocytic Reaction to Colorectal Cancer Is Associated with Longer Survival, Independent of Lymph Node Count, Microsatellite Instability, and CpG Island Methylator Phenotype
Authors: Ogino Shuji , Nosho Katsuhiko , Irahara Natsumi , Meyerhardt Jeffrey A. , Baba Yoshifumi , Shima Kaori , Glickman Jonathan N. , Ferrone Cristina R. , Mino-Kenudson Mari , Tanaka Noriko , Dranoff Glenn , Giovannucci Edward L. , Fuchs Charles S. 
Published: October 2009

Abstract
Purpose: Host immune response to tumor may be an important prognostic factor for colon cancer patients. However, little is known on prognostic significance of histopathologic lymphoid reaction to tumor, independent of the number of lymph nodes examined and tumoral molecular alterations, including microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), both of which are associated with lymphocytic reaction and clinical outcome.
Experimental Design: Using 843 colorectal cancer patients in two independent prospective cohorts, we examined patient prognosis in relation to four components of lymphocytic reaction (i.e., Crohn's-like reaction, peritumoral reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes) and overall lymphocytic score (0-12). CIMP was determined using eight markers including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1. Cox proportional hazard models computed hazard ratio for mortality, adjusted for covariates including tumor stage, body mass index, lymph node count, KRAS, BRAF, p53, cyclooxygenase-2 (PTGS2), MSI, CIMP, and LINE-1 methylation.
Results: Increasing overall lymphocytic reaction score including tumor-infiltrating lymphocytes was associated with a significant improvement in colorectal cancer–specific and overall survival (log-rank P &lt; 0.003). These findings remained significant (adjusted hazard ratio estimates, 0.49-0.71; Ptrend &lt; 0.009) in multivariate models that adjusted for covariates, including body mass index, MSI, CIMP, LINE-1 hypomethylation, and cyclooxygenase-2. The beneficial effect of tumoral lymphocytic reaction was consistent across strata of clinical, pathologic, and molecular characteristics.
Conclusions: Lymphocytic reactions to tumor were associated with improved prognosis among colorectal cancer patients, independent of lymph node count and other clinical, pathologic, and molecular characteristics. (Clin Cancer Res 2009;15(20):6412–20)
GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers
Authors: Sabbatini Peter , Korenchuk Susan , Rowand Jason L. , Groy Arthur , Liu Qi , Leperi Dominic , Atkins Charity , Dumble Melissa , Yang Jingsong , Anderson Kelly , Kruger Ryan G. , Gontarek Richard R. , Maksimchuk Kenneth R. , Suravajjala Sapna , Lapierre Russell R. , Shotwell J. Brad , Wilson Joseph W. , Chamberlain Stanley D. , Rabindran Sridhar K. , Kumar Rakesh 
Published: October 2009

Abstract
The insulin-like growth factor-I receptor (IGF-IR) signaling pathway is activated in various tumors, and inhibition of IGF-IR kinase provides a therapeutic opportunity in these patients. GSK1838705A is a small-molecule kinase inhibitor that inhibits IGF-IR and the insulin receptor with IC50s of 2.0 and 1.6 nmol/L, respectively. GSK1838705A blocks the in vitro proliferation of cell lines derived from solid and hematologic malignancies, including multiple myeloma and Ewing's sarcoma, and retards the growth of human tumor xenografts in vivo. Despite the inhibitory effect of GSK1838705A on insulin receptor, minimal effects on glucose homeostasis were observed at efficacious doses. GSK1838705A also inhibits the anaplastic lymphoma kinase (ALK), which drives the aberrant growth of anaplastic large-cell lymphomas, some neuroblastomas, and a subset of non–small cell lung cancers. GSK1838705A inhibits ALK, with an IC50 of 0.5 nmol/L, and causes complete regression of ALK-dependent tumors in vivo at well-tolerated doses. GSK1838705A is therefore a promising antitumor agent for therapeutic use in human cancers. [Mol Cancer Ther 2009;8(10):2811–20]