bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway
Authors: Bendre Manali S. , Margulies Aaron G. , Walser Brandon , Akel Nisreen S. , Bhattacharrya Sudeepa , Skinner Robert A. , Swain Frances , Ramani Vishnu , Mohammad Khalid S. , Wessner Lisa L. , Martinez Alfredo , Guise Theresa A. , Chirgwin John M. , Gaddy Dana , Suva Larry J. 
Published: December 2005

Abstract
Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show a predilection to metastasize to bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation and bone resorption. IL-8 mRNA expression was surveyed in a panel of human breast cancer lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, and ZR-75, and the human lung adenocarcinoma cell line A549. IL-8 mRNA expression was higher in cell lines with higher osteolytic potential in vivo. Human osteoclast formation was increased by MDA-MET or A549 cell-conditioned medium, but not by MDA-MB-231. Pharmacologic doses of receptor activator of nuclear factor-κB (RANK)-Fc or osteoprotogerin had no effect on the pro-osteoclastogenic activity of the conditioned medium; however, osteoclast formation stimulated by conditioned medium was inhibited 60% by an IL-8-specific neutralizing antibody. The data support a model in which tumor cells cause osteolytic bone destruction independently of the RANK ligand (RANKL) pathway. Tumor-produced IL-8 is a major contributor to this process. The role of secreted IL-8 isoforms was examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, which detected distinct IL-8 isoforms secreted by MDA-MET and MDA-231 cells, suggesting different pro-osteoclastogenic activities of the two IL-8-derived peptides. These data indicate that (a) osteoclast formation induced by MDA-MET breast cancer cells and A549 adenocarcinoma cells is primarily mediated by IL-8, (b) cell-specific isoforms of IL-8 with distinct osteoclastogenic activities are produced by tumor cells, and (c) tumor cells that support osteoclast formation independent of RANKL secrete other pro-osteoclastogenic factors in addition to IL-8.
A Selective Tumor Microvasculature Thrombogen that Targets a Novel Receptor Complex in the Tumor Angiogenic Microenvironment
Authors: El-Sheikh Amr , Borgstrom Per , Bhattacharjee Gourab , Belting Mattias , Edgington Thomas S. 
Published: December 2005

Abstract
We have previously shown that part of the heparin-binding domain of the vascular endothelial growth factor (VEGF), designated HBDt, localizes very selectively to surfaces of the endothelial cells of i.t blood vessels. Here, we have coupled the HBDt to the extracellular domain of tissue factor (TFt), to locally initiate the thrombogenic cascade. In tumor-bearing mice, infusion of this HBDt.TFt results in rapid occlusive thrombosis selective only for tumor microvasculature with resultant infarctive destruction of tumors. We now show that infusion of an optimal combination of this HBDt.TFt and its requisite cofactor (factor VIIa) in tumor models results in significant tumor eradication. Binding studies and confocal microscopy indicate that the target for the HBDt.TFt seems to be a trimolecular complex of chondroitin C sulfate proteoglycan, neuropilin-1, and VEGF receptor-2, overexpressed together only in highly angiogenic sites of the tumor microenvironment. The HBDt.TFt was also colocalized with the trimolecular receptor complex in endothelial sprouts from tumor tissues, and its binding inhibited the growth of such sprouts. In vitro, we show that the HBDt structure has its highest affinity for chondroitin 6 sulfate. We show the potential of this HBDt.TFt as a candidate therapeutic and elucidate its target in vivo.
Tumor Inflammatory Angiogenesis and Its Chemoprevention
Authors: Albini Adriana , Tosetti Francesca , Benelli Roberto , Noonan Douglas M. 
Published: December 2005

Abstract
The importance of angiogenesis for the growth of tumors is widely recognized. Drugs that successfully target the endothelium, such as antivascular endothelial growth factor antibodies, are beginning to have an effect on the life expectancy of cancer patients. However, the endothelial cell is not the only possible target for antiangiogenic therapy or prevention of vascularization (angioprevention). It is evident from the literature that native immune cells recruited into tumors in turn stimulate the endothelium and are responsible for an indirect pathway of tumor vascularization. Inflammation-dependent angiogenesis seems to be a central force in tumor growth and expansion, a concept supported by the observation that the use of “classic” anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs, leads to angiogenesis inhibition. The mechanisms of inflammatory angiogenesis provide new approaches to target, cure, or even better, prevent tumor angiogenesis by treatment with synthetic or natural agents with anti-inflammatory properties. We propose chemoprevention of inflammatory angiogenesis as a way of checking the cancer before it progresses.
Business Growth and Development Trajectories in Lagging and Remote Areas of Southern Europe
Authors: Skuras Dimitris , Meccheri Nicolas , Moreira Manuel Belo , Rosell Jordi , Stathopoulou Sophia 
Published: December 2005

The resurgence of many lagging, mountainous or peripheral areas of the European Union may be attributed to the significant regional exports by firms located there. A survey in four mountainous areas of Southern Europe revealed that nearly one-third of surveyed businesses spanning the whole range of economic activities and industries sell more than 50 percent of their value of production outside the geographical boundaries of the local area. Strategic entrepreneurship creates two broad sets of ‘windows of entrepreneurial-locational opportunity’ and firms from different industries of the manufacturing sector together with firms from the services or the hospitality industries may utilize the same common stock of resources and develop the same conventions irrespective of the industry they operate in. As such, local clusters should not be defined in terms of industries and/or sectors but in terms of common strategic entrepreneurial actions that can mix industries under common opportunities (entrepreneurship) and advantages (strategies). These firms are the mountain gazelles as they present very high growth rates and serve as paradigms and a source for innovative thought by other local entrepreneurs.
High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis
Authors: De Tommaso Adriana MA , Andrade Paula D , Costa Sandra CB , Escanhoela Cecília AF , Hessel Gabriel 
Published: December 2005

AbstractBackgroundBiliary atresia (BA) is the most severe hepatic disorder in newborns and its etiopathogenesis remains unknown. Viral involvement has been proposed, including the human cytomegalovirus (HCMV). The aims of the study were to use the polymerase chain reaction (PCR) to screen the liver tissue of infants with extrahepatic cholestasis for HCMV and to correlate the results with serological antibodies against HCMV and histological findings.MethodsA retrospective study in a tertiary care setting included 35 patients (31 BA, 1 BA associated with a choledochal cyst, 2 congenital stenosis of the distal common bile duct and 1 hepatic cyst). HCMV serology was determined by ELISA. Liver and porta hepatis were examined histologically. Liver samples from infants and a control group were screened for HCMV DNA.ResultsTwelve patients had HCMV negative serology, 9 were positive for IgG antibodies and 14 were positive for IgG and IgM. Nine liver and seven porta hepatis samples were positive for HCMV DNA but none of the control group were positive (general frequency of positivity was 34.3% – 12/35). There was no correlation between HCMV positivity by PCR and the histological findings. The accuracy of serology for detecting HCMV antibodies was low.ConclusionThese results indicate an elevated frequency of HCMV in pediatric patients with extrahepatic neonatal cholestasis. They also show the low accuracy of serological tests for detecting active HCMV infection and the lack of correlation between HCMV positivity by PCR and the histopathological changes.
Correlates of health and healthcare performance: applying the Canadian health indicators framework at the provincial-territorial level
Authors: Arah OA , Westert GP 
Published: December 2005

Abstract

Background
Since, at the health system level, there is little research into the possible interrelationships among the various indicators of health, healthcare performance, non-medical determinants of health, and community and health system characteristics, we conducted this study to explore such interrelationships using the Canadian Health Indicators Framework.

Methods
We conducted univariate correlational analyses with health and healthcare performance as outcomes using recent Canadian data and the ten Canadian provinces and three territories as units of the analyses. For health, 6 indicators were included. Sixteen healthcare performance indicators, 12 non-medical determinants of health and 16 indicators of community and health system characteristics were also included as independent variables for the analysis. A set of decision rules was applied to guide the choice of what was considered actual and preferred performance associations.

Results
Health (28%) correlates more frequently with non-medical determinants than healthcare does (12%), in the preferred direction. Better health is only correlated with better healthcare performance in 13% of the cases in the preferred direction. Better health (24%) is also more frequently correlated with community and health system characteristics than healthcare is (13%), in the preferred direction.

Conclusion
Canadian health performance is a function of multiple factors, the most frequent of which may be the non-medical determinants of health and the community characteristics as against healthcare performance. The contribution of healthcare to health may be limited only to relatively small groups which stand to benefit from effective healthcare, but its overall effect may be diluted in summary measures of population health. Interpreting multidimensional, multi-indicator performance data in their proper context may be more complex than hitherto believed.
Cell biology as the basis of a better understanding of cancer
Authors: Wheatley Denys N 
Published: December 2005

Abstract
Clinicians will argue that cancer can only really receive the treatment that is needed through thorough understanding of medicine. However, even empirical approaches to therapy result in experimental analysis of the agencies involved on test cells, usually in culture. From the obverse perspective, cell biologists will argue that until we fully understand cell cycle regulation, tumour management will be too imprecise to make the best advances. A forum is needed whereby the fundamental studies on cells prior to, during and after transformation in vitro can be freely reported (open access) and discussed. The action of anticancer agents and cancer preventative substances can more easily be studied in vitro before the often excessive complexity of making similar studies in experimental and human cancers is tackled. Cancer Cell International is committed to providing such a forum. Ironically within a few months of launching this open access journal, Elsevier had much the same idea, and there one has to pay for the privilege of downloading vital papers in this biomedical field.
A low-carbohydrate, ketogenic diet to treat type 2 diabetes
Authors: Yancy William S , Foy Marjorie , Chalecki Allison M , Vernon Mary C , Westman Eric C 
Published: December 2005

Abstract

Background
The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes.

Methods
From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A1c.

Results
Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0 ± 7.9 years and BMI was 42.2 ± 5.8 kg/m2. Hemoglobin A1c decreased by 16% from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A1c. Fasting serum triglyceride decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly.

Conclusion
The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.
Auditory processing in individuals with auditory neuropathy
Authors: Kumar Ajith U , Jayaram M 
Published: December 2005

Abstract

Background
Auditory neuropathy is a disorder characterized by no or severely impaired auditory brainstem responses in presence of normal otoacoustic emissions and/or cochlear microphonics. Speech perception abilities in these individuals are disproportionate to their hearing sensitivity and reported to be dependent on cortical evoked potentials and temporal processing abilities. The disproportionate loss of auditory percept in presence of normal cochlear function is suggestive of impairment of auditory neural synchrony.

Methods
We studied the auditory evoked potentials and psychophysical abilities in 14 adults with auditory neuropathy to characterize their perceptual capabilities. Psychophysical tests included measurement of open set speech identification scores, just noticeable difference for transition duration of syllable /da/ and temporal modulation transfer function. Auditory evoked potentials measures were, recording of P1/N1, P2/N2 complex and mismatch negativity (MMN).

Results
Results revealed a significant correlation between temporal processing deficits and speech perception abilities. In majority of individuals with auditory neuropathy P1/N1, P2/N2 complex and mismatch negativity could be elicited with normal amplitude and latency. None of the measured evoked potential parameters correlated with the speech perception scores. Many of the subjects with auditory neuropathy showed normal MMN even though they could not discriminate the stimulus contrast behaviorally.

Conclusion
Conclusions drawn from the study are
1. Individuals with auditory neuropathy have severely affected temporal processing.
2. The presence of MMN may not be directly linked to presence of behavioral discrimination and to speech perception capabilities at least in adults with auditory neuropathy.
Polarized subsets of human T-helper cells induce distinct patterns of chemokine production by normal and systemic sclerosis dermal fibroblasts
Authors: Chizzolini Carlo , Parel Yann , Scheja Agneta , Dayer Jean-Michel 
Published: December 2005

AbstractThe role of fibroblasts in inflammatory processes and their cross-talk with T cells is increasingly being recognized. Our aim was to explore the capacity of dermal fibroblasts to produce inflammatory chemokines potentially involved in fibrosis occurring in response to contact with polarized human T cells. Our findings indicate that the program of chemokine production by fibroblasts is differentially regulated depending on the T-helper (Th) cell subset used to activate them. Thus, Th1 and Th2 cells preferentially induced production of IFN-γ inducible protein (IP)-10 and IL-8, respectively, whereas monocyte chemoattractant protein (MCP)-1 was equally induced by both subsets at mRNA and protein levels. Neutralization experiments indicated that membrane-associated tumour necrosis factor-α and IL-1 played a major role in the induction of IL-8 and MCP-1 by Th1 and Th2 cells, whereas membrane-associated IFN-γ (present only in Th1 cells) was responsible, at least in part, for the lower IL-8 and higher IP-10 production induced by Th1 cells. The contributions of tumour necrosis factor-α, IL-1 and IFN-α were confirmed when fibroblasts were cultured separated in a semipermeable membrane from living T cells activated by CD3 cross-linking. We observed further differences when we explored signal transduction pathway usage in fibroblasts. Pharmacological inhibition of c-Jun N-terminal kinase and nuclear factor-κB resulted in inhibition of IL-8 mRNA transcription induced by Th1 cells but not that by Th2 cells, whereas inhibition of MEK/ERK (mitogen-activated protein kinase of extracellular signal-regulated kinase/extracellular signal-regulated kinase) and nuclear factor-κB resulted in inhibition of MCP-1 mRNA induced by Th2 but not by Th1 cells. Finally, no distinct differences in chemokine production were observed when the responses to T cell contact or to prototypic Th1 and Th2 cytokines were examined in systemic sclerosis versus normal fibroblasts. These findings indicate that fibroblasts have the potential to participate in shaping the inflammatory response through the activation of flexible programs of chemokine production that depend on the Th subset eliciting their response.
Uncovering the Richness of the Stimulus: Structure Dependence and Indirect Statistical Evidence
Authors: Reali Florencia , Christiansen Morten H. 
Published: December 2005

AbstractThe poverty of stimulus argument is one of the most controversial arguments in the study of language acquisition. Here we follow previous approaches challenging the assumption of impoverished primary linguistic data, focusing on the specific problem of auxiliary (AUX) fronting in complex polar interrogatives. We develop a series of corpus analyses of child‐directed speech showing that there is indirect statistical information useful for correct auxiliary fronting in polar interrogatives and that such information is sufficient for distinguishing between grammatical and ungrammatical generalizations, even in the absence of direct evidence. We further show that there are simple learning devices, such as neural networks, capable of exploiting such statistical cues, producing a bias toward correct AUX questions when compared to their ungrammatical counterparts. The results suggest that the basic assumptions of the poverty of stimulus argument may need to be reappraised.
Distinguishing Between Causes and Enabling Conditions—Through Mental Models or Linguistic Cues?
Authors: Kuhnmünch Gregory , Beller Sieghard 
Published: December 2005

AbstractThe mental model theory of naive causal understanding and reasoning (Goldvarg & Johnson‐Laird, 2001, Cognitive Science, 25, 565–610) claims that people distinguish between causes and enabling conditions on the basis of sets of models that represent possible causal situations. In the tasks used to test this hypothesis, however, the proposed set of models was confounded with linguistic cues that frame which event to assume as given (the enabling condition) and which to consider as responsible for the effect under this assumption (the cause). By disentangling these two factors, we were able to show that when identifying causes and enabling conditions in these tasks, people rely strongly on the linguistic cues but not on the proposed set of models and that this set of models does not even reflect people's typical interpretation of the tasks. We propose an alternative explanation that integrates syntactic and causal considerations.
Cervical dyskaryosis among women with and without HIV: prevalence and risk factors
Authors: Mbizvo E M , Msuya S E , Stray-Pedersen B , Chirenje M Z , Hussain A 
Published: December 2005

Women in developing countries often present for medical care with advanced cervical cancer, although this condition is preventable through regular screening and early treatment. This study sought to identify the prevalence and risk factors for cervical dyskaryosis among women in Zimbabwe with and without HIV. In a cross-sectional study, 200 consenting women were screened for cervical dyskaryosis and sexually transmitted infections (STI). The relationship between various risk factors for cervical dyskaryosis was examined. The overall prevalence of cervical dyskaryosis was high (19%), and significantly higher among HIV-infected women at 30% compared with 13% among seronegative women, with a peak at a younger age among seropositive women. Use of intravaginal herbs, practising intravaginal cleansing, being single, a history of three or more lifetime sexual partners and a history of previous STI were associated with cervical dysplasia. The high frequency of cervical abnormality lends weight to the demand for implementation of regular screening programmes and health education.