bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Expression of A3 Adenosine Receptors in Human Colorectal Cancer Is Reflected in Peripheral Blood Cells
Authors: Gessi Stefania , Cattabriga Elena , Avitabile Arianna , Gafa’ Roberta , Lanza Giovanni , Cavazzini Luigi , Bianchi Nicoletta , Gambari Roberto , Feo Carlo , Liboni Alberto , Gullini Sergio , Leung Edward , Mac-Lennan Stephen , Borea Pier Andrea 
Published: September 2005

AbstractPurpose: Adenosine is a ubiquitous nucleoside that accumulates at high levels in hypoxic regions of solid tumors, and A3 adenosine receptors have been recently demonstrated to play a pivotal role in the adenosine-mediated inhibition of tumor cell proliferation. In the present work, we addressed the question of the putative relevance of A3 subtypes in colorectal adenocarcinomas.Experimental Design: Seventy-three paired samples of tumor and surrounding peritumoral normal mucosa at a distance of 2 and 10 cm from the tumor and blood samples obtained from a cohort of 30 patients with colorectal cancer were investigated to determine the presence of A3 receptors by means of binding, immunocytochemistry, and real-time reverse transcription-polymerase chain reaction studies.Results: As measured by receptor binding assays, the density of A3 receptor was higher in colon carcinomas as compared with normal mucosa originating from the same individuals (P &lt; 0.05). Overexpression of A3 receptors at the protein level was confirmed by immunohistochemical studies, whereas no changes in A3 mRNA accumulation in tumors as compared with the corresponding normal tissue were revealed. The overexpression of A3 receptors in tumors was reflected in peripheral blood cells, where the density was approximately 3-fold higher compared with healthy subjects (P &lt; 0.01). In a cohort of 10 patients studied longitudinally, expression of A3 receptors in circulating blood cells returned to normal after surgical resection for colorectal cancer.Conclusions: This study provides the first evidence that A3 receptor plays a role in colon tumorigenesis and, more importantly, can potentially be used as a diagnostic marker or a therapeutic target for colon cancer.
Incidence of
BRAF
Oncogene Mutation and Clinical Relevance for Primary Cutaneous Melanomas
Authors: Shinozaki Masaru , Fujimoto Akihide , Morton Donald L. , Hoon Dave S. B. 
Published: September 2005

Abstract
Purpose: The purpose of the study was to clarify the incidence of B-raf oncogene (BRAF) mutations in primary cutaneous melanomas, their relation to tumor progression, and effect on disease outcome. Somatic mutations of BRAF kinase, a component of the Ras-mitogen-activated protein/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase pathway, are frequently reported (&gt;65%) in nevi and malignant melanomas.
Experimental Design: We assessed BRAF mutation frequency in exons 11 and 15 in primary (n = 59) and metastatic (n = 68) melanomas. Direct sequencing of PCR products was performed on DNA isolated and purified from microdissected tumors.
Results: Eighteen mutations (31%) at exon 15 were detected in primary melanoma with a significantly (P = 0.001) higher frequency in patients &lt; 60 years old. Incidence of BRAF mutation did not correlate with Breslow thickness. Presence of BRAF mutation of primary tumors did not effect overall disease-free survival. BRAF mutation frequency in metastatic lesions was 57% and significantly (P = 0.0024) higher than primary melanomas.
Conclusions: The study suggests that BRAF mutation may be acquired during development of metastasis but is not a significant factor for primary tumor development and disease outcome.
Interleukin-12 Enhances the Sensitivity of Human Osteosarcoma Cells to 4-Hydroperoxycyclophosphamide by a Mechanism Involving the Fas/Fas-Ligand Pathway
Authors: Duan Xiaoping , Zhou Zhichao , Jia Shu-Fang , Colvin Michael , Lafleur Elizabeth A. , Kleinerman Eugenie S. 
Published: September 2005

Abstract
Cyclophosphamide (CY) and its derivative ifosfamide are alkylating agents used to treat osteosarcoma (OS). The purpose of these studies was to determine whether alkylating agents affect the expression of Fas ligand (FasL) and whether interleukin 12 enhances the sensitivity of human OS cells to alkylating agents. 4-Hydroperoxycyclophosphamide (4-HC), the preactivated CY compound, and 4-hydroperoxydidechlorocloclophosphamide (4-HDC), its nonalkylating analogue, human OS LM6 cells, and a clone of cells derived by transfection with the interleukin 12 gene (LM6-#6) were used for these studies. Incubation of LM6 and LM6-#6 with 10 μm 4-HC increased the expression of FasL mRNA (2.5- and 3.0-fold, respectively). By contrast, 4-HDC, Adriamycin (ADR), cisplatin (CDP), and methotrexate (MTX) had no effect on FasL mRNA expression. Increased FasL expression after treatment with 4-HC was also demonstrated by immunohistochemistry and flow cytometry. Drug-induced FasL was functional and mediated cell death. We examined the effect of FasL up-regulation by 4-HC on LM6 and LM6-#6 cells. Flow cytometry showed that LM6-#6 cells expressed 2.2-fold more Fas than LM6 cells. Cytotoxicity of 4-HC, 4-HDC, ADR, CDP, and MTX on LM6, LM6-neo, and LM6-#6 were quantified. Colony-forming assay revealed an IC50 of 2.10 μm for 4-HC in LM6-neo cells compared with 0.41 μm in LM6-#6 cells. The IC50 for 4-HDC, ADR, CDP, and MTX were not significantly different between the two cell lines. We concluded that the increased expression of Fas enhanced LM6-#6 sensitivity to 4-HC. These data indicate that Fas/FasL may be involved in the cytotoxic pathway of CY. Combining biological agents with chemotherapeutic agents that have complementary Fas/FasL pathway actions may offer new therapeutic alternatives.
Detection of Isolated Tumor Cells by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism for K-ras Mutations in Tissue Samples of 199 Colorectal Cancer Patients
Authors: Dieterle Christoph P. , Conzelmann Michael , Linnemann Ulrich , Berger Martin R. 
Published: September 2005

AbstractThe aim of this study was to identify K-ras mutations as marker for isolated tumor cells in liver, lymph node, and bone marrow specimens of colorectal cancer patients. To detect these, a PCR-RFLP assay was used with a sensitivity exceeding that of routine histopathology by at least 1 order of magnitude. In addition, the ratio of mutated versus wild-type alleles was determined by an internal standard. Of 199 patients, 74 (37.5%) were found to bear a K-ras-positive tumor. Of these, 60 (81%) were mutated in codon 12 and 14 (19%) in codon 13 (P &lt; 0.001). In addition, 14 organs were found K-ras positive, 13 of which were from 12 patients with a K-ras-positive tumor (16%) and 1 from a patient with a K-ras-negative tumor (0.8%). Eight patients exhibited liver involvement and 6 showed lymph node involvement. Remarkably, no bone marrow specimen was found K-ras positive (P &lt; 0.017 versus liver involvement). Sequence analysis of tumor DNA revealed that GGT (Gly) was replaced by GAT (Asp; 35%), GTT (Val; 32%), AGT (Ser; 13%), GCT (Ala; 10%), TGT (Cys; 8%), and CGT (Arg; 2%) for codon 12, and by GAC (Asp) as the only type of mutation for codon 13. In colorectal carcinomas the ratio of K-ras mutated versus wild-type alleles ranged over 4 orders of magnitude (100-10−4, median: 10−2) and was correlated with both, residual tumor load (R1/2; P = 0.028) and distant metastasis (M1; P = 0.057). These results show that detection of K-ras mutated alleles by PCR-RFLP in patients with colorectal carcinoma may aid in the identification of isolated tumor cells. High ratios of K-ras alleles were correlated with certain negative prognostic parameters (R,M). In accord with its function as a primary filter for colorectal carcinoma cells, the liver was more often contaminated with K-ras-positive cells than bone marrow.
Clinical Significance of the Loss of
KiSS-1
and Orphan G-Protein–Coupled Receptor (
hOT7T175
) Gene Expression in Esophageal Squamous Cell Carcinoma
Authors: Ikeguchi Masahide , Yamaguchi Ken-ichi , Kaibara Nobuaki 
Published: September 2005

Abstract
Purpose: Lymph node metastasis is the most important predictor of prognosis in esophageal squamous cell carcinoma (ESCC). Recently, KiSS-1 was cloned as a human metastasis suppressor gene, and an orphan G-protein-coupled receptor (hOT7T175) was identified as the endogenous receptor of the KiSS-1 product. However, the clinical importance of KiSS-1 and hOT7T175 gene expression in ESCC remains unclear.
Experimental Design: In this study, total RNA was extracted from tumors and noncancerous epithelia of 71 patients with ESCC who underwent surgical esophageal resection. The expression levels of KiSS-1, hOT7T175, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were analyzed quantitatively by real-time reverse transcription-PCR and compared with the clinical findings.
Results: The mean KiSS-1:GAPDH and hOT7T175:GAPDH ratios of the tumors were 1.2 and 0.3 and were at the same levels as those in the noncancerous epithelia. The loss of KiSS-1 and hOT7T175 gene expression was detected in 38% and 61% of tumors. Loss of KiSS-1 and/or hOT7T175 gene expression was not correlated with tumor size or degree of tumor invasion but was found to be a significant predictor of lymph node metastasis.
Conclusions: Loss of KiSS-1 or hOT7T175 gene expression may be an important biomarker for detection of lymph node metastasis in ESCC.
Combination of an Src Kinase Inhibitor with a Novel Pharmacological Antagonist of the Urokinase Receptor Diminishes
in Vitro
Colon Cancer Invasiveness
Authors: Boyd Douglas D. , Wang Heng , Avila Hector , Parikh Nila U. , Kessler Horst , Magdolen Victor , Gallick Gary E. 
Published: September 2005

Abstract
Purpose: The urokinase-type plasminogen activator receptor (u-PAR) contributes to colon cancer invasion and metastases. We have shown previously that u-PAR expression in colon cancer is driven by the Src tyrosine kinase. In the current study, we determined the ability of PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a Src kinase inhibitor, to reduce u-PAR expression and colon cancer invasion.
Experimental Design: Western blotting, Northern blotting, and u-PAR promoter-reporter assays were performed to determine whether PP2 represses u-PAR expression. In vitro invasion assays were used to determine whether this kinase inhibitor, with or without a novel u-PAR antagonist, diminished cultured colon cancer invasiveness.
Results: A constitutively active c-Src increased in vitro invasiveness of SW480 cells, whereas HT-29 cells expressing antisense c-Src showed diminished invasiveness, validating c-Src as a target for low molecular weight compound(s). The Src inhibitor PP2 reduced u-PAR transcription in HT-29 cells over the concentration range that blocked Src kinase activity. PP2 also reduced u-PAR protein amounts in three other colon cancer cell lines with modest to high constitutive Src activity. Treatment of HT-29 cells and 2C8 cells (a SW480 clone expressing a constitutively active Src) with PP2 diminished their in vitro invasiveness. Furthermore, combination of the Src inhibitor with a novel u-PAR peptide antagonist (NI-5.12) proved superior to the individual agents in suppressing invasiveness.
Conclusions: A c-Src kinase inhibitor represses u-PAR expression and, alone or in combination with a u-PAR antagonist, diminishes colon cancer invasiveness. Thus, concurrent targeting of c-Src expression and pharmacological blockade of the u-PAR may represent a novel means of controlling colon cancer spread.
The Congress Party Model: South Africa's African National Congress (ANC) and India's Indian National Congress (INC) as Dominant Parties
Authors: Reddy Thiven 
Published: September 2005

AbstractThe paper argues that the model developed to analyze the dominance of the Indian National Congress of the political party system during the first two decades of independence helps in our understanding of the unfolding party system in South Africa. A comparison of the Congress Party and the African National Congress suggests many similarities. The paper is divided into three broad sections. The first part focuses on the dominant party system in India. In the second part, I apply the model of the Congress System to South Africa. I argue that the three features of the Congress System – a dominant party with mass based legitimacy, constituted by many factions and operating on the idiom of consensus-seeking internal politics, and sources of opposition who cooperate with factions in the dominant party to influence the political agenda – prevails in South Africa. In the third part, I draw on the comparison between the ANC and Congress Party to account for why certain nationalist movements become dominant parties. I emphasize that broad nationalist movements displaying high degrees of legitimacy and embracing democratic practices are adaptive to changing contexts and develop organizational mechanisms to manage internal party conflict. They contribute to the consolidation of democracy rather than undermine it.
The Bias in Moment Estimators for Parameters of Drop Size Distribution Functions: Sampling from Exponential Distributions
Authors: Smith Paul L. , Kliche Donna V. 
Published: September 2005

Abstract
The moment estimators frequently used to estimate parameters for drop size distribution (DSD) functions being “fitted” to observed raindrop size distributions are biased. Consequently, the fitted functions often do not represent well either the raindrop samples or the underlying populations from which the samples were taken. Monte Carlo simulations of the process of sampling from a known exponential DSD, followed by the application of a variety of moment estimators, demonstrate this bias. Skewness in the sampling distributions of the DSD moments is the root cause of this bias, and this skewness increases with the order of the moment. As a result, the bias is stronger when higher-order moments are used in the procedures. Correlations of the sample moments with the size of the largest drop in a sample (Dmax) lead to correlations of the estimated parameters with Dmax, and, in turn, to spurious correlations between the parameters. These things can lead to erroneous inferences about characteristics of the raindrop populations that are being sampled. The bias, and the correlations, diminish as the sample size increases, so that with large samples the moment estimators may become sufficiently accurate for many purposes.
Measuring Canopy Structure and the Kinematics of Subcanopy Flows in Two Forests
Authors: Staebler Ralf M. , Fitzjarrald David R. 
Published: September 2005

AbstractA better understanding of forest subcanopy flows is needed to evaluate their role in the horizontal movement of scalars, particularly in complex terrain. This paper describes detailed measurements of the canopy structure and its variability in both the horizontal and vertical directions at a deciduous forest in complex terrain (the Harvard Forest, Petersham, Massachusetts). The effects of the trunks and subcanopy shrubs on the flow field at each of six subcanopy array locations are quantified. The dynamics of the subcanopy flow are examined with pragmatic methods that can be implemented on a small scale with limited resources to estimate the stress divergence, buoyancy, and pressure gradient forces that drive the flow. The subcanopy flow at the Harvard Forest was driven by mechanisms other than vertical stress divergence 75% of the time. Nocturnal flows were driven predominantly by the negative buoyancy of a relatively cool layer near the forest floor. The direction of the resulting drainage flows followed the azimuth of the longest forest-floor slope. Similar results were found at a much flatter site at Borden, Ontario, Canada. There was no clear evidence of flow reversals in the subcanopy in the lee of ridges or hills at the Harvard Forest even in high wind conditions, contrary to some model predictions.
The Stigma of Mental Illness in Germany: A Trend Analysis
Authors: Angermeyer Matthias C. , Matschinger Herbert 
Published: September 2005

Background: While there are some indications that the mental health literacy of the public has improved within recent years, the findings concerning its attitudes towards the mentally ill are quite inconsistent. Aims: The aim of this study is to examine whether any changes have taken place inGermany over the last decade regarding the stigmatisation ofmentally ill people. Method: In 2001, a representative population survey was carried out among the German adult population, using the same sampling procedure and the same measure for the assessment of perceived stigma as in a previous survey that had been conducted in 1990. Results: Our findings suggest that in 2001, the German public was somewhat less inclined to believe that former mental patients are exposed to stigmatisation than a decade ago. While this holds especially true for the devaluation of patients, the picture is more mixed for discrimination. The trend towards less perceived stigmatisation is particularly pronounced among people who are familiar with psychiatric treatment. Conclusions: Since a substantial amount of perceived stigma still persists, further efforts to reduce the stigma attached to mental illness are needed.
Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia
Authors: Zhang Ji , Randall Mindy S. , Loyd Melanie R. , Li Weimin , Schweers Rachel L. , Persons Derek A. , Rehg Jerold E. , Noguchi Constance T. , Ihle James N. , Ney Paul A. 
Published: September 2005

AbstractFriend virus is an acutely oncogenic retrovirus that causes erythroblastosis and polycythemia in mice. Previous studies suggested that the Friend virus oncoprotein, gp55, constitutively activates the erythropoietin receptor (EPOR), causing uncontrolled erythroid proliferation. Those studies showed that gp55 confers growth factor independence on an interleukin-3 (IL-3)-dependent cell line (Ba/F3) when the EPOR is coexpressed. Subsequently, we showed that a truncated form of the stem-cell kinase receptor (sf-STK) is required for susceptibility to Friend disease. Given the requirement for sf-STK, we sought to establish the in vivo significance of gp55-mediated activation of the EPOR. We found that the cytoplasmic tyrosine residues of the EPOR, and signal transducer and activator of transcription-5 (STAT5), which acts through these sites, are not required for Friend virus-induced erythroblastosis. The EPOR itself was required for the development of erythroblastosis but not for gp55-mediated erythroid proliferation. Interestingly, the murine EPOR, which is required for gp55-mediated Ba/F3-cell proliferation, was dispensable for erythroblastosis in vivo. Finally, gp55-mediated activation of the EPOR and STAT5 are required for Friend virus-induced polycythemia. These results suggest that Friend virus activates both sf-STK and the EPOR to cause deregulated erythroid proliferation and differentiation.
Cerebrospinal fluid may mediate CNS ischemic injury
Authors: Wang Yanming F , Gwathmey Judith K , Zhang Guorong , Soriano Sulpicio G , He Shunli , Wang Yanguang 
Published: September 2005

Abstract

Background
The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult.

Methods
Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC) albumin.

Results
The severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion.
Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg.

Conclusion
We conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective.
Otitis Media: Review of the 2004 Treatment Guidelines
Authors: Cober Mary Petrea , Johnson Cary E 
Published: September 2005

OBJECTIVE To review the 2004 treatment guidelines provided by the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) regarding the treatment of otitis media in pediatric patients. DATA SOURCES A MEDLINE search, restricted to English-language articles about pediatric patients, was conducted (1966–May 2005) using the key words acute otitis media (AOM), guideline, observation therapy, and vaccination. Additional references were located through review of the bibliographies of cited articles. STUDY SELECTION AND DATA EXTRACTION Studies related to the fundamental basis of the updated guidelines and articles addressing current issues related to otitis media infection were included. DATA SYNTHESIS Otitis media affects many children in the US. Concerns have been raised about the proper treatment of AOM in the face of increasing drug resistance among primary pathogens responsible for infection. Some countries have chosen to observe patients for a designated period of time prior to initiation of antibiotic therapy. The AAP and AAFP have updated the treatment guidelines for otitis media to include the option of observation therapy, recommendations for dosing of various antibiotic regimens and their place in therapy, and the importance of initial pain management. CONCLUSIONS Updated treatment guidelines for otitis media have been developed in an effort to properly treat children while decreasing current resistance rates for common organisms that cause AOM. In the future, the therapeutic outcomes of observation therapy related to both the incidence of drug resistance and the possibility of increased complications related to otitis media will need to be evaluated in the US.