bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNAs modulate the chemosensitivity of tumor cells
Authors: Blower Paul E. , Chung Ji-Hyun , Verducci Joseph S. , Lin Shili , Park Jong-Kook , Dai Zunyan , Liu Chang-Gong , Schmittgen Thomas D. , Reinhold William C. , Croce Carlo M. , Weinstein John N. , Sadee Wolfgang 
Published: January 2008

AbstractMicroRNAs are strongly implicated in such processes as development, carcinogenesis, cell survival, and apoptosis. It is likely, therefore, that they can also modulate sensitivity and resistance to anticancer drugs in substantial ways. To test this hypothesis, we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly. In the experimental system, we increased the expression of individual microRNAs by transfecting their precursors (which are active) or suppressed the expression by transfection of antisense oligomers. In three NCI-60 human cancer cell lines, a panel of 60 lines used for anticancer drug discovery, we assessed the growth-inhibitory potencies of 14 structurally diverse compounds with known anticancer activities. Changing the cellular levels of let-7i, mir-16, and mir-21 affected the potencies of a number of the anticancer agents by up to 4-fold. The effect was most prominent with mir-21, with 10 of 28 cell-compound pairs showing significant shifts in growth-inhibitory activity. Varying mir-21 levels changed potencies in opposite directions depending on compound class; indicating that different mechanisms determine toxic and protective effects. In silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that ∼30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents. Ten of those microRNAs have already been implicated in cancer biology. Our results support a substantial role for microRNAs in anticancer drug response, suggesting novel potential approaches to the improvement of chemotherapy. [Mol Cancer Ther 2008;7(1):1–9]
Visible Light Modulates the Expression of Cancer-Retina Antigens
Authors: Bazhin Alexandr V. , Schadendorf Dirk , Owen Robert W. , Zernii Evgeni Yu , Philippov Pavel P. , Eichmüller Stefan B. 
Published: January 2008

Abstract
Proteins involved in the visual signaling cascade show light-dependent expression levels in photoreceptor cells. Recently, these proteins have been described to be expressed in neuroectodermal tumors and to function as cancer-retina antigens. Here, we show that light can down-regulate gene expression of rhodopsin, transducin, and cyclic guanosine 3′,5′-monophosphate phosphodiesterase 6 (PDE6) and up-regulate guanylyl cyclase 1, recoverin, and arrestin in human melanoma cells in vitro, comparable to physiologic changes earlier observed in photoreceptor cells. Similar modulation can be detected at the protein level in melanoma cells except for no changes in PDE6 protein levels. Two regulatory pathways have been identified: Sp1/Sp3/Sp4 proteins for rhodopsin and PDE6, and mitogen-activated protein kinases for recoverin and arrestin. The visual cascade and retinoic acid as its derivate do not play any role in this process. Putative explanations for light-dependent modulation of cancer-retina antigen expression in melanoma cells are discussed. (Mol Cancer Res 2008;6(1):110–8)
Genomic Changes and Gene Expression Profiles Reveal That Established Glioma Cell Lines Are Poorly Representative of Primary Human Gliomas
Authors: Li Aiguo , Walling Jennifer , Kotliarov Yuri , Center Angela , Steed Mary Ellen , Ahn Susie J. , Rosenblum Mark , Mikkelsen Tom , Zenklusen Jean Claude , Fine Howard A. 
Published: January 2008

AbstractGenetic aberrations, such as gene amplification, deletions, and loss of heterozygosity, are hallmarks of cancer and are thought to be major contributors to the neoplastic process. Established cancer cell lines have been the primary in vitro and in vivo models for cancer for more than 2 decades; however, few such cell lines have been extensively characterized at the genomic level. Here, we present a high-resolution genome-wide chromosomal alteration and gene expression analyses of five of the most commonly used glioma cell lines and compare the findings with those observed in 83 primary human gliomas. Although genomic alterations known to occur in primary tumors were identified in the cell lines, we also observed several novel recurrent aberrations in the glioma cell lines that are not frequently represented in primary tumors. Additionally, a global gene expression cluster distinct from primary tumors was identified in the glioma cell lines. Our results indicate that established cell lines are generally a poor representation of primary tumor biology, presenting a host of genomic and gene expression changes not observed in primary tissues, although some discrete features of glioma biology were conserved in the established cell lines. Refined maps of genetic alterations and transcriptional divergence from the original tumor type, such as the one presented here, may help serve as a guideline for a more biologically rational and clinically relevant selection of the most appropriate glioma model for a given experiment. (Mol Cancer Res 2008;6(1):21–30)
MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia
Authors: Garzon Ramiro , Volinia Stefano , Liu Chang-Gong , Fernandez-Cymering Cecilia , Palumbo Tiziana , Pichiorri Flavia , Fabbri Muller , Coombes Kevin , Alder Hansjuerg , Nakamura Tatsuya , Flomenberg Neal , Marcucci Guido , Calin George A. , Kornblau Steven M. , Kantarjian Hagop , Bloomfield Clara D. , Andreeff Michael , Croce Carlo M. 
Published: January 2008

Abstract
MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.
Obstructive sleep apnoea is associated with decreased insulin sensitivity in females
Authors: Theorell-Haglöw J. , Berne C. , Janson C. , Lindberg E. 
Published: January 2008

The aim of the present study was to assess associations between obstructive sleep apnoea and insulin sensitivity in a population-based sample of females.In total, 400 females aged 20–70 yrs underwent a full-night polysomnography, fasting blood sampling, measurement of anthropometric variables and oral glucose tolerance test with measurement of the insulin response (n = 358). The apnoea/hypopnoea index (AHI) was calculated from the results of the polysomnography. From the results of the oral glucose tolerance test, an insulin sensitivity index (ISI) was calculated.Females with an AHI <5 (n = 119) had a mean±sdISI of 8.3±3.8, whereas females with an AHI ≥30 (n = 34) had an ISI of 6.2±4.0. Nocturnal minimal saturation was independently associated with decreased insulin sensitivity when controlling for age, waist/hip ratio, level of physical activity, smoking and alcohol consumption (95% confidence interval (CI) 0.004–0.14). When adjusting for confounders, the AHI was associated with increased fasting and 2-h insulin levels (95% CI 0.14–0.99 and 95% CI 0.28–6.47, respectively).Obstructive sleep apnoea was found to be independently associated with decreased insulin sensitivity in the present population-based sample of females.
Differential regulation ofMoraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms
Authors: Slevogt H. , Maqami L. , Vardarowa K. , Beermann W. , Hocke A. C. , Eitel J. , Schmeck B. , Weimann A. , Opitz B. , Hippenstiel S. , Suttorp N. , N'Guessan P. D. 
Published: January 2008

Moraxella catarrhalisis a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells,M. catarrhalisinduces release of the pro-inflammatory cytokine interleukin (IL)-8, which plays a pivotal role in orchestrating airway inflammation.The present study demonstrated that protein kinase (PK)C was activated by Moraxella infection and positively regulatedM. catarrhalis-triggered nuclear factor (NF)-κB activation and subsequent IL-8 release. Activation of the PKC/NF-κB signalling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein A2. In addition, it was shown that specific isoforms of PKC play differential roles in the fine-tuning of theM. catarrhalis-induced NF-κB-dependent gene expression through controllingil8promoter activity. Inhibition of PKCα and ϵ with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCθincreased, theM. catarrhalis-induced IL-8 transcription and cytokine release.In conclusion, it was shown thatMoraxella catarrhalisinfection activates protein kinase C and its isoforms α, ϵ andθ, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.
The role of Drosophila Merlin in spermatogenesis
Authors: Dorogova Natalia V , Akhmametyeva Elena M , Kopyl Sergei A , Gubanova Natalia V , Yudina Olga S , Omelyanchuk Leonid V , Chang Long-Sheng 
Published: January 2008

Abstract

Background

Drosophila Merlin, the homolog of the human Neurofibromatosis 2 (NF2) gene, is important for the regulation of cell proliferation and receptor endocytosis. Male flies carrying a Mer
3 allele, a missense mutation (Met177→Ile) in the Merlin gene, are viable but sterile; however, the cause of sterility is unknown.

Results
Testis examination reveals that hemizygous Mer
3 mutant males have small seminal vesicles that contain only a few immotile sperm. By cytological and electron microscopy analyses of the Mer
3, Mer
4 (Gln170→stop), and control testes at various stages of spermatogenesis, we show that Merlin mutations affect meiotic cytokinesis of spermatocytes, cyst polarization and nuclear shaping during spermatid elongation, and spermatid individualization. We also demonstrate that the lethality and sterility phenotype of the Mer
4 mutant is rescued by the introduction of a wild-type Merlin gene. Immunostaining demonstrates that the Merlin protein is redistributed to the area associated with the microtubules of the central spindle in telophase and its staining is less in the region of the contractile ring during meiotic cytokinesis. At the onion stage, Merlin is concentrated in the Nebenkern of spermatids, and this mitochondrial localization is maintained throughout sperm formation. Also, Merlin exhibits punctate staining in the acrosomal region of mature sperm.

Conclusion

Merlin mutations affect spermatogenesis at multiple stages. The Merlin protein is dynamically redistributed during meiosis of spermatocytes and is concentrated in the Nebenkern of spermatids. Our results demonstrated for the first time the mitochondrial localization of Merlin and suggest that Merlin may play a role in mitochondria formation and function during spermatogenesis.
Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses
Authors: Yan Yuhe , Jung Yong T , Wu Tiyun , Kozak Christine A 
Published: January 2008

Abstract

Background
We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni. Cytopathicity was attributed to different amino acid substitutions at the same critical env residue involved in receptor interaction: S82F in the Moloney variant Spl574, and S84A in the Friend mouse leukemia virus F-S MLV. Because M. dunni cells carry a variant CAT-1 cell surface virus receptor (dCAT-1), we examined the role of this receptor variant in cytopathicity and host range.

Results
We expressed dCAT-1 or mCAT-1 of NIH 3T3 origin in cells that are not normally infectible with ecotropic MLVs and evaluated the transfectants for susceptibility to virus infection and to virus-induced syncytium formation. The dCAT-1 transfectants, but not the mCAT-1 transfectants, were susceptible to virus-induced cytopathicity, and this cytopathic response was accompanied by the accumulation of unintegrated viral DNA. The dCAT-1 transfectants, however, did not also reproduce the relative resistance of M. dunni cells to Moloney MLV, and the mCAT-1 transfectants did not show the relative resistance of NIH 3T3 cells to Spl574. Western analysis, use of glycosylation inhibitors and mutagenesis to remove receptor glycosylation sites identified a possible role for cell-specific glycosylation in the modulation of virus entry.

Conclusion
Virus entry and virus-induced syncytium formation using the CAT-1 receptor are mediated by a small number of critical amino acid residues in receptor and virus Env. Virus entry is modulated by glycosylation of cellular proteins, and this effect is cell and virus-specific.
Fetus in fetu: a case report
Authors: Khalifa Nisreen M , Maximous Doaa W , Abd-Elsayed Alaa A 
Published: January 2008

Abstract

Introduction
Fetus in fetu is a rare abnormality secondary to the abnormal embryogenesis in a diamniotic, monochorionic pregnancy. It is a rare pathological condition and fewer than 100 cases have been reported in the literature.

Case presentation
A 2 month old girl with an abdominal mass since birth, was referred to the Cancer Institute with a suspected diagnosis of a Wilms' tumor. Conventional radiograph of the abdomen revealed a mass containing numerous calcifications. CT scan showed a heterogeneous retroperitoneal mass containing well-defined calcified structures. The decision was made to recommend surgical exploration and the mass was successfully excised. Physical examination of the mass with review of literature confirmed the diagnosis of fetus in fetu.

Conclusion
Although it is a rare condition imaging may play an important role in the correct prospective diagnosis of fetus in fetu. Surgical excision is the recommended treatment.
Implementing Change: Lessons for Medicaid Reformers
Authors: Bachman Sara S. , Beatrice Dennis F. , Altman Stuart H. 
Published: January 2008

Major Medicaid reforms initiated in Arizona, California, and New York in the 1980s form the foundation of this study, which explores issues to consider when implementing change in state Medicaid programs. We prepared case studies of these reforms, describing the innovations and assessing the implementation process in each state. These case studies are used to illustrate broad issues and processes of Medicaid reform. Six lessons emerge from our analysis: (1) Expect reform models to change over time; (2) strive for predictability and continuity in the reform; (3) encourage behavior changes through the use of incentives; (4) use special administrative or political channels to simplify the reform; (5) expect reform models to converge over time; and (6) implementation difficulties can be predicted. These lessons should educate decision makers about how to implement possible future solutions to problems like those seen in Medicaid programs at the start of this decade.
It must be remembered that there is nothing more difficult to plan, more doubtful of success, nor more dangerous to manage than the creation of a new system. For the initiator has the enmity of all who would profit by the preservation of the old institutions and merely lukewarm defenders in those who would gain by new ones.
Machiavelli, The Prince
Implementing a Competitive Medical Care System Through Public Policy
Authors: McClure Walter 
Published: January 2008

This paper seeks to clarify so-called competition strategies for medical care, and to present a more flexible approach for public policy to encourage competition. In so doing, it appears useful to divide a competition strategy into two parts: (1) a structurally sound market model for the future medical delivery and financing system, and (2) a strategy to implement the chosen model. Policymakers may choose any model that satisfies the structural conditions of a sound market. After listing these principal conditions, this paper presents two distinct market models that satisfy them in entirely different ways and a third model that combines the first two.
Once a specific market model is chosen, policymakers may choose among a variety of ways to implement it. Some implementation strategies require coercive legislation, others rely more on persuasive leadership, pressures, and incentives. The paper points out that all of these strategies must address certain common action areas; it then proposes one implementation strategy in some detail and uses it to illustrate a way to address each of these areas. Although it certainly is not the only possible strategy, the proposal would appear to be a practical approach for implementing effective competition.
The Embattled Hospital: Cost Control Measures versus Imperatives for Expansion
Authors: Reilly Bernard J. , Legge Jerome S. 
Published: January 2008

As the costs of the American health care system escalate, there is a tendency to identify the biggest cost item and attempt to reduce it to a manageable size. However, since that biggest cost item, the hospital, is a creation of uncontrolled forces within the system as a whole, attempts to manage costs will be limited in effectiveness. The hospital is the end product of an uncontrolled system, a product that displays little understanding of the economic principles of trade-off, efficiency, and productivity.
To limit spending in the hospital care system, controls must be rooted in an analysis of the forces that have shaped the hospital's present form and structure. Factors to be considered are those that have defined what a “good” hospital is, who its real consumers are, and what economic and quality control factors must be part of the entire health system.
This article suggests modification of public policies relative to medical manpower and insurance, and recommends adoption of reimbursement by Diagnostic Related Groups.
The Triumph of Accommodation: The Rise of Private Health Plans in America, 1929–1959
Authors: Starr Paul 
Published: January 2008

[The following is a chapter from Book Two of The Social Transformation of American Medicine and should be seen as a piece of a larger puzzle. Throughout the entire work I am concerned with the origins of the social and economic structure of medical institutions. One of the problems is the historical selection of organizational forms: why hospitals, clinics, public health agencies, medical schools, or, in this case, private health insurance and prepayment plans assumed distinctive organizational forms in the United States.
These issues come up in the context of a more general argument about the development of the medical profession and its relation to the broader society. Book One deals with the initial loss and later recovery of professional authority, status, and control of the medical market between the late colonial period and the early twentieth century. The final chapters of Book One analyze the rise of organizations impinging upon private physicians (hospitals; public health institutions; corporations, fraternal societies, and private clinics) and try to account for the professions success in escaping both corporate and governmental control.
Book Two then turns to the struggles over the politics and business of medicine in the twentieth century, from the debate about compulsory health insurance through the growth of corporate health care today. The first chapter, “The Mirage of Reform,” tries to explain the failure to pass a government health insurance program first during the Progressive era, again during the New Deal, and once again under President Truman. In the process of discussing these developments between 1915 and 1950, I try to delineate the changing political and economic forces that shaped the debate. Then, in the chapter below, I turn to the system that appeared in place of a public program and try to account for its organization.]
Effectiveness of State Mandates to Maintain Local Government Health Services for the Poor
Authors: Brown E. Richard , Cousineau Michael R. 
Published: January 2008

State governments have used several types of mandates to assure that local governments fulfill state-defined responsibilities, including public health care for the poor. This article reports the findings of a study of procedural public-participation mandates and financial sanctions imposed by California to hold counties to their obligations to provide indigent health care.
An inventory of the laws' implementation in all California counties found noncompliance by some counties, although all counties complied after a state Health Services Department unit was established to monitor the counties and provide them with state aid. Case studies in eight counties identified factors that influenced the effectiveness of the laws in modifying or reversing county proposals to close county hospitals or reduce other health services. Policy guidelines are suggested for states that want to develop mandates to enforce indigent-care responsibilities of local governments.
Highly Selective Synthetic Reactions by the Combined Use of Organometallic Reagents and Radical Species
Authors: Oshima Koichiro 
Published: January 2008

Abstract
During these thirty years, we have pursued new methodologies in organic synthesis and developed many synthetically useful reactions. Among them, four topics are described in this article. (1) Regio- and stereoselective silylmetalation of acetylenes has been examined. Whereas platinum- or copper-catalyzed silylmagnesation of terminal acetylenes afforded (E)-1-silyl-1-alkene exclusively, palladium-catalyzed silylalumination with PhMe2Si-AlEt2 provided 2-silyl-1-alkenes with high regioselectivity. (2) Triethylborane induced radical addition of Ph3SnH to acetylenes gave 1-triphenylstannyl-1-alkenes in the presence of small amount of oxygen. The reaction has two distinguishing characteristics. One feature is that Et3B can initiate the radical reaction at low temperature, such as −78 °C. (3) The other distinctive feature of Et3B-induced radical reaction is that many solvents could be used for the reaction. Thus, water was chosen as a solvent, and Et3B-induced atom-transfer radical cyclization of iodo acetals and iodoacetates in water was examined. (4) Three types of organometallic ate complexes, R3MnMgBr, R3MgLi, and R3Co(L2)MgBr, were prepared and used for organic synthesis. Treatment of gem-dibromocyclopropane with trialkylmanganate provided alkylated cyclopropane after aqueous workup. Aryl and alkenyl halides could be converted into the corresponding magnesium reagents by the action of trialkylmagnesate via halogen–magnesium exchange. Finally, synthetic reactions catalyzed by cobalt complexes are described. Without suffering from β-elimination, cobalt complexes allow cross-coupling reactions of alkyl halides with Grignard reagents.