bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular Safety in Patients Using Sildenafil Citrate Therapy for Erectile Dysfunction
Authors: Laties Alan , Sharlip Ira 
Published: January 2006

ABSTRACT
Sildenafil citrate improves erectile function in men with erectile dysfunction (ED) by selectively inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), which is present in all vascular tissue. Sildenafil also has a weaker inhibitory action on PDE6, located in the rod and cone photoreceptors. Modest, transient visual symptoms, typically blue tinge to vision, increased brightness of lights, and blurry vision, have been reported with sildenafil use and occur more frequently at higher doses. Visual function studies in healthy subjects and in patients with eye disease suggest that sildenafil does not affect visual acuity, visual fields, and contrast sensitivity. Transient, mild impairment of color discrimination can occur around the time of peak plasma levels. Spontaneous postmarketing reports of visual adverse events, including nonarteritic anterior ischemic optic neuropathy (NAION), have been reported during the 7 years that sildenafil has been prescribed to more than 27 million men worldwide. However, because men with ED frequently have vascular risk factors that may also put them at increased risk for NAION, a causal relationship is difficult to establish. No consistent pattern has emerged to suggest any long-term effect of sildenafil on the retina or other structures of the eye or on the ocular circulation.
Diabetes nurse case management: An effective tool
Authors: Mullen Barbara Ann , Watts Kelley Patricia Ann 
Published: January 2006

AbstractPurpose: In March 2000, a large tertiary military medical treatment facility on the east coast implemented a diabetes nurse case management program to coordinate care for patients with diabetes mellitus type 1 or type 2 and a hemoglobin A1c value of 8.0% or greater. Although proven successful for patients while enrolled in the program, there was a lack of research that evaluated how successful patients were at continuing diabetes self‐management once discharged. This study evaluated glycosylated hemoglobin A1c (A1c), total cholesterol (TC), triglyceride, and low‐density lipoprotein (LDL) levels in patients at admission, discharge, and 6 months following discharge from the program.Data sources: A retrospective medical record review of laboratory data was evaluated using descriptive statistics and paired t‐test.Conclusions: Significant reductions in A1c and TC values from admission to discharge were achieved, which the patients maintained 6 months following discharge. There was also a significant reduction in LDL value from admission to 6 months following discharge.Implications for practice: This study supports the value of nurse case management for patients with diabetes.
Sensitivity of Multiple Damage Parameters to Compressive Overload in
Cortical Bone
Authors: Morgan Elise F. , Lee John J. , Keaveny Tony M. 
Published: January 2006

Abstract
Damage accumulation plays a key role in weakening bones prior to complete fracture and in stimulating bone remodeling. The goal of this study was to characterize the degradation in the mechanical properties of cortical bone following a compressive overload. Longitudinally oriented, low-aspect ratio specimens (n=24) of bovine cortical bone were mechanically tested using an overload-hold-reload protocol. No modulus reductions greater than 5% were observed following overload magnitudes less than 0.73% strain. For each specimen, changes in strength and Poisson’s ratio were greater (p=0.02) than that in modulus by 10.8- and 26.6-fold, respectively, indicating that, for the specimen configuration used in this study, longitudinal elastic modulus is one of the least sensitive properties to a compressive overload. Residual strains were also proportionately greater by 6.4-fold (p=0.01) in the transverse than axial direction. These results suggest that efforts to relate microcrack density and morphology to changes in compressive mechanical properties of cortical bone may benefit from considering alternative parameters to modulus reductions.
Ethnic variations in the management of patients with acute stroke
Authors: Bourke J , Sylvester R , Sharma P 
Published: January 2006

Abstract

Background
There is increasing interest in the management of stroke in ethnic minorities but few studies have considered this issue. This study investigated if differences in acute stroke management exist between a white European and Bangladeshi populations living in London, England.

Methods
All stroke surviving patients discharged over a five year period in a major London teaching hospital based in an ethnically diverse area of inner city London were recruited. Cerebrovascular risk factors, their management, and investigation for acute stroke syndromes were recorded and comparison between white and Bangladeshi cohorts was made. Categorical data were analysed using Fisher's exact test.

Results
Measurement of cholesterol concentrations are undertaken less often in those from a Bangladeshi background (25%) compared with white Europeans (76%) (p&lt;0.0001). Statin therapy tends to be given less often to Bangladeshis. However, neuroimaging (p&lt;0.05) and echocardiography (p&lt;0.0001) is performed more often in Bangladeshis compared with white Europeans.

Conclusion
There are variations in the management of acute stroke because of ethnicity and these variations could have substantial consequences on secondary rates of cerebrovascular and cardiovascular disease. Whether the reasons for this disparity are attributable to inequity or iniquity of care need to be further investigated perhaps along with the development of ethnicity specific protocols. Overall the management of stroke and its risk factors in either racial group remains lamentable.
Acquired haemophilia heralded by bleeding into the oral mucosa in a patient with bullous pemphigoid, rheumatoid arthritis, and vitiligo
Authors: Patel R S , Harman K E , Nichols C , Burd R M , Pavord S 
Published: January 2006

Abstract
Acquired haemophilia is rare and potentially fatal, with a mortality of 20% if left untreated. There is a strong association with other autoimmune diseases. This report describes a patient with rheumatoid arthritis, vitiligo, and bullous pemphigoid where the diagnosis of acquired haemophilia was made after an extensive bleed into a bullous lesion in the buccal mucosa. This case highlights some of the potential complications of acquired haemophilia and its treatment.
Application of Gleason analogous grading system and flow cytometry DNA analysis in a novel knock-in mouse prostate cancer model
Authors: Wu G , Yu Lei , Wang L , Wang H , Xuan J W 
Published: January 2006

Abstract

Objective
A new knock-in mouse adenocarcinoma prostate model (KIMAP) was established, which showed a close to human kinetics of tumour development. This study used a new mouse histological grading system similar to the human Gleason grading system and flow cytometry DNA analysis to measure and compare the new KIMAP model with human CaP and transgenic mouse adenocarcinoma prostate (TGMAP) model.

Methods
According to heterogeneity of the clinical standard for prostate cancer diagnosis, a close to human mouse standard for histological grading and scoring system, Gleason analogous grading system, was established in this study. Sixty KIMAP and 48 TGMAP prostate cancer samples were measured and compared with human CaP. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from both TGMAP and KIMAP models.

Results
Mice with CaP from KIMAP (n = 60) and TGMAP (n = 48) models showed a different distribution of histological scores (p = 0.000). KIMAP mice showed higher percentage (53.3%) of compound histological score rate than TGMAP (25%), but closer to the human clinical average (50%), which showed significant correlation with age (p = 0.001), while TGMAP mice showed unbalanced and random score distribution in all age groups. Flow cytometry analyses showed that most tumour tissues in KIMAP were diploid, analogous to the human condition, while all the TGMAP mice showed aneuploid tumours.

Conclusions
Results of this study further show that KIMAP, a new generation of murine prostate cancer model, could be used as a supplementary model in addition to the currently widely used transgenic models.
Amiodarone toxicity presenting as pulmonary mass and peripheral neuropathy: the continuing diagnostic challenge
Authors: Azzam I , Tov N , Elias N , Naschitz J E 
Published: January 2006

Abstract
A 64 year old man receiving long term amiodarone treatment presented with dyspnea, cough, and weight loss. Radiographs and computed tomography showed a lung mass with associated multiple pulmonary nodules. Biopsies of the pulmonary mass showed foamy histiocytes without malignant cells. However, findings on FDG-PET scan were consistent with a malignant tumour. These findings on computed tomography and PET scan and the unusually late resolution of the pulmonary lesions after withdrawal of amiodarone treatment posed a challenging diagnostic problem.
FUZZY RULE EXTRACTION FROM A FEED FORWARD NEURAL NETWORK BY TRAINING A REPRESENTATIVE FUZZY NEURAL NETWORK USING GRADIENT DESCENT
Authors: BROUWER ROELOF K. 
Published: January 2006

Neural networks are good at representing functions or data transformations. However just as in the case of the biological brain the mathematical description of the data transformation is hidden. In the case of the human brain the transformation, in terms of rules, may be extracted by interviewing the person, In the case of the artificial neural network other approaches have to be utilized. In the case described here a second neural network that represents the transformation in terms of fuzzy rules is trained using gradient descent. The parameters that are learned are the parameters of the fuzzy sets and also the connection weights in [0,1] between the outputs of the membership function units and the final output units. There is an output unit for each rule and consequent membership function. The fuzzy output set with the highest membership value is taken to be the output fuzzy set. The extracted rules are of the form if x 0 is Small or x 0 is Medium and x 1 is Large or x 1 is Medium then y is Large. x 0 and x 1 are inputs and y is the output. The cost measure consists of several terms indicating how close the actual output is to a target output, how close the weights are to 0 and 1, and how close the output of membership values is to a 1 of n vector. The cost measure is a linear combination of these individual terms. By changing the constant multipliers the relative importance of the cost measures can be changed and studied. The method has been tried on randomly generated feedforward neural networks and also on data produced by functions with specific properties. The fizzy network is trained using data produced by the feedforward neural network or the known function. This method can also be used in extracting rules such as control rules implicitly used by a human if input and output data is gathered from the human.
Distinct Transcription Profiles of Primary and Secondary Glioblastoma Subgroups
Authors: Tso Cho-Lea , Freije William A. , Day Allen , Chen Zugen , Merriman Barry , Perlina Ally , Lee Yohan , Dia Ederlyn Q. , Yoshimoto Koji , Mischel Paul S. , Liau Linda M. , Cloughesy Timothy F. , Nelson Stanley F. 
Published: January 2006

Abstract
Glioblastomas are invasive and aggressive tumors of the brain, generally considered to arise from glial cells. A subset of these cancers develops from lower-grade gliomas and can thus be clinically classified as “secondary,” whereas some glioblastomas occur with no prior evidence of a lower-grade tumor and can be clinically classified as “primary.” Substantial genetic differences between these groups of glioblastomas have been identified previously. We used large-scale expression analyses to identify glioblastoma-associated genes (GAG) that are associated with a more malignant phenotype via comparison with lower-grade astrocytomas. We have further defined gene expression differences that distinguish primary and secondary glioblastomas. GAGs distinct to primary or secondary tumors provided information on the heterogeneous properties and apparently distinct oncogenic mechanisms of these tumors. Secondary GAGs primarily include mitotic cell cycle components, suggesting the loss of function in prominent cell cycle regulators, whereas primary GAGs highlight genes typical of a stromal response, suggesting the importance of extracellular signaling. Immunohistochemical staining of glioblastoma tissue arrays confirmed expression differences. These data highlight that the development of gene pathway-targeted therapies may need to be specifically tailored to each subtype of glioblastoma. (Cancer Res 2006; 66(1): 159-67)
Expression of the Steroid and Xenobiotic Receptor and Its Possible Target Gene, Organic Anion Transporting Polypeptide-A, in Human Breast Carcinoma
Authors: Miki Yasuhiro , Suzuki Takashi , Kitada Kunio , Yabuki Nami , Shibuya Rie , Moriya Takuya , Ishida Takanori , Ohuchi Noriaki , Blumberg Bruce , Sasano Hironobu 
Published: January 2006

Abstract
Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas. Therefore, we first examined SXR/hPXR expression in 60 breast carcinomas using immunohistochemistry and quantitative reverse transcription-PCR. We then searched for possible SXR/hPXR target genes using microarray analysis of carcinoma cells captured by laser microscissors. SXR/hPXR was detected in carcinoma tissues but not in nonneoplastic and stromal cells of breast tumors. A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases. Furthermore, in estrogen receptor–positive cases, SXR/hPXR expression was also positively correlated with expression of the cell proliferation marker, Ki-67. Microarray analysis showed that organic anion transporting polypeptide-A (OATP-A) was most closely correlated with SXR/hPXR gene expression, and both OATP-A mRNA and protein were significantly associated with SXR/hPXR in both breast carcinoma tissues and its cell lines. These results suggest that SXR/hPXR and its target gene, such as OATP-A, may play important roles in the biology of human breast cancers. (Cancer Res 2006; 66(1): 535-42)
In vitro and In vivo Antitumor Effects of the Dual Insulin-Like Growth Factor-I/Insulin Receptor Inhibitor, BMS-554417
Authors: Haluska Paul , Carboni Joan M. , Loegering David A. , Lee Francis Y. , Wittman Mark , Saulnier Mark G. , Frennesson David B. , Kalli Kimberly R. , Conover Cheryl A. , Attar Ricardo M. , Kaufmann Scott H. , Gottardis Marco , Erlichman Charles 
Published: January 2006

Abstract
The insulin-like growth factor receptor (IGF-IR) and insulin receptor are either overactivated and/or overexpressed in a wide range of tumor types and contribute to tumorigenicity, proliferation, metastasis, and drug resistance. Here, we show that BMS-554417, a novel small molecule developed as an inhibitor of IGF-IR, inhibits IGF-IR and insulin receptor kinase activity and proliferation in vitro, and reduces tumor xenograft size in vivo. In a series of carcinoma cell lines, the IC50 for proliferation ranged from 120 nmol/L (Colo205) to &gt;8.5 μmol/L (OV202). The addition of stimulatory ligands was unnecessary for the antiproliferative effect in MCF-7 and OV202 cells. BMS-554417 treatment inhibited IGF-IR and insulin receptor signaling through extracellular signal-related kinase as well as the phosphoinositide 3-kinase/Akt pathway, as evidenced by decreased Akt phosphorylation at Ser473. At doses that inhibited proliferation, the compound also caused a G0-G1 arrest and prevented nuclear accumulation of cyclin D1 in response to LR3 IGF-I. In Jurkat T-cell leukemia cells, this agent triggered apoptotic cell death via the mitochondrial pathway. BMS-554417 was orally bioavailable and significantly inhibited the growth of IGF1R-Sal tumor xenografts in vivo. BMS-554417 is a member of a novel class of IGF-IR/insulin receptor inhibitors that have potential clinical applications because of their antiproliferative and proapoptotic activity in vitro and in vivo. (Cancer Res 2006; 66(1): 362-71)
Thioredoxin-1 Modulates Transcription of Cyclooxygenase-2 via Hypoxia-Inducible Factor-1α in Non–Small Cell Lung Cancer
Authors: Csiki Ildiko , Yanagisawa Kiyoshi , Haruki Nobuhiro , Nadaf Sorena , Morrow Jason D. , Johnson David H. , Carbone David P. 
Published: January 2006

Abstract
Hypoxic induction of gene expression occurs mainly via the hypoxia-inducible factor-1 (HIF-1) transcription factor and is a critical step in tumor growth. Cyclooxygenase-2 (COX-2) is commonly overexpressed in non–small cell lung cancer (NSCLC). In this study, we sought to determine the role of HIF-1 in the induction of COX-2 expression during hypoxia. Through sequence comparison of hypoxia-responsive genes, COX-2 promoter deletion analysis, and site-directed mutagenesis, we identified a hypoxia-responsive element within the COX-2 promoter that interacts with HIF-1α and underlies the mechanism of hypoxic activation of COX-2 in lung cancer cells. Proteomic analysis of NSCLC identified thioredoxin-1 as a redox protein overexpressed in NSCLC correlated with poor prognosis. We also show that thioredoxin-1 stabilizes HIF-1α to induce hypoxia-responsive genes under normoxic conditions. Our results identify two new mechanisms for regulation of COX-2 expression in NSCLC. (Cancer Res 2006; 66(1): 143-50)
Tumor-Derived Interleukin-4 Reduces Tumor Clearance and Deviates the Cytokine and Granzyme Profile of Tumor-Induced CD8+ T Cells
Authors: Olver Stuart , Groves Penny , Buttigieg Kathy , Morris Edward S. , Janas Michelle L. , Kelso Anne , Kienzle Norbert 
Published: January 2006

AbstractAn interleukin (IL)-4-containing tumor environment is reported to be beneficial for immune clearance of tumor cells in vivo; however, the effect of IL-4 on the effector CD8+ T cells contributing to tumor clearance is not well defined. We have used the immunogenic HLA-CW3-expressing P815 (P.CW3) mastocytoma and investigated whether IL-4 expression by the tumor affects tumor clearance and, if so, whether it alters the tumor-induced Vβ10+ CD8+ T-cell response. P.CW3 were stably transfected with IL-4 or the empty control vector, and independent cell lines were injected i.p. into syngeneic DBA/2 mice. After apparent clearance of primary tumors over 12 to 15 days, secondary tumors arose that lacked surface expression and H-2-restricted antigen presentation of CW3 in part due to the loss of the HLA-CW3 expression cassette. Surprisingly, mice that received IL-4-producing tumor cells showed delayed primary tumor clearance and were significantly more prone to develop secondary tumors compared with mice receiving control tumor cells. Tumor clearance was dependent on CD8+ T cells. The IL-4-secreting P.CW3 tumor cells led to markedly higher mRNA expression of IL-4 and granzyme A and B but no differences in IFN-γ and IL-2 production, cell proliferation, or ex vivo CTL activity in primary Vβ10+ CD8+ T cells when compared with the control tumor cells. We concluded that tumor-derived IL-4 selectively changed the quality of the tumor-induced CD8+ T-cell response and resulted in unexpected negative effects on tumor clearance. These data bring into question the delivery of IL-4 to the tumor environment for improving tumor immunotherapy. (Cancer Res 2006; 66(1): 571-80)
In vivo Imaging of Adenovirus Transduction and Enhanced Therapeutic Efficacy of Combination Therapy with Conditionally Replicating Adenovirus and Adenovirus-p27
Authors: Lee Choon-Taek , Lee Yoon-Jin , Kwon Sung-Youn , Lee Jaeho , Kim Kwang Il , Park Kyung-Ho , Kang Joo Hyun , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Chung June-Key , Shim Young-Soo , Curiel David T. , Carbone David P. 
Published: January 2006

Abstract
Gene therapy is hampered by poor gene transfer to the tumor mass. We previously proposed a combination adenoviral gene therapy containing a conditionally replicating adenovirus (CRAD) expressing mutant E1 (Δ24RGD) and a replication-defective E1-deleted adenovirus to enhance the efficiency of gene transfer. Mutant E1 expressed by Δ24RGD enables the replication of replication-defective adenoviruses in tumors when cancer cells are co-infected with both viruses. In this study, gene transfer rates in xenografts tumors were monitored by bioluminescence in cells infected with the replication-defective adenovirus-luciferase (ad-luc). Tumor masses treated with CRAD + ad-luc showed dramatically stronger and more prolonged luciferase expression than ad-luc-treated tumors and this expression spread through the entire tumor mass without significant systemic spread. Transduction with CRAD + replication-defective adenovirus-p27 increased the expression of p27 by 24-fold versus transduction with ad-p27 alone. Treatment of a lung cancer cell line and of established lung cancer xenografts with CRAD + adenovirus-p27 also induced stronger growth suppression than treatment with either virus alone. These findings confirm the selective replication of E1-deleted adenovirus containing a therapeutic gene due to the presence of mutant E1 produced by Δ24RGD in tumors. Moreover, this replication increased the therapeutic gene transfer rate and enhanced its antitumor effects. (Cancer Res 2006; 66(1): 372-7)
Endostatin-Cytosine Deaminase Fusion Protein Suppresses Tumor Growth by Targeting Neovascular Endothelial Cells
Authors: Ou-Yang Fu , Lan Keng-Li , Chen Chun-Te , Liu Jaw-Ching , Weng Chu-Li , Chou Chao-Kai , Xie Xiaoming , Hung Jen-Yu , Wei Yongkun , Hortobagyi Gabriel N. , Hung Mien-Chie 
Published: January 2006

Abstract
Endostatin, an angiogenesis inhibitor tested in multiple clinical trials, selectively targets neovascular endothelial cells, suppressing tumor growth. To enhance the therapeutic efficacy of endostatin, we fused endostatin with cytosine deaminase, which converts a prodrug 5-flucytosine into a cytotoxic 5-fluorouracil. This therapeutic strategy was developed based on the observation that the endostatin-green fluorescence protein gene and endostatin-luciferase gene selectively target to endothelial cells in vitro and to the tumor site in vivo, respectively. When we used the endostatin-cytosine deaminase fusion protein to treat s.c. grafted tumors or experimental metastasis tumors, our results showed that endostatin-cytosine deaminase treatment provided stronger tumor growth suppression and increased mean survival time of the mice compared with the treatments of endostatin alone, cytosine deaminase alone, or endostatin plus cytosine deaminase. The endostatin-cytosine deaminase protein significantly inhibited the growth of endothelial cells and preferentially induced tumor cell apoptosis. This endostatin-cytosine deaminase fusion approach opens an avenue for cancer-targeting therapy. (Cancer Res 2006; 66(1): 378-84)