bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Janus Kinase 2 Is Required for Expression and Nuclear Accumulation of Cyclin D1 in Proliferating Mammary Epithelial Cells
Authors: Sakamoto Kazuhito , Creamer Bradley A. , Triplett Aleata A. , Wagner Kay-Uwe 
Published: May 2007

AbstractUsing a conditional knockout approach, we previously demonstrated that the Janus kinase 2 (Jak2) is crucial for prolactin (PRL) signaling and normal mammary gland development. PRL is suggested to synchronously activate multiple signaling cascades that emerge on the PRL receptor (PRLR). This study demonstrates that Jak2 is essential for the activation of the signal transducer and activator of transcription 5 (Stat5) and expression of Cish (cytokine-inducible SH2-containing protein), a Stat5-responsive negative regulator of Jak/Stat signaling. However, Jak2 is dispensable for the PRL-induced activation of c-Src, focal adhesion kinase, and the MAPK pathway. Despite activation of these kinases that are commonly associated with proliferative responses, the ablation of Jak2 reduces the multiplication of immortalized mammary epithelial cells (MECs). Our studies show that signaling through Jak2 controls not only the transcriptional activation of the Cyclin D1 gene, but, more importantly, it regulates the accumulation of the Cyclin D1 protein in the nucleus by altering the activity of signal transducers that mediate the phosphorylation and subsequent nuclear export of Cyclin D1. In particular, the levels of activated Akt (protein kinase B) and inactive glycogen synthase kinase-3β (i.e. a kinase that regulates the nuclear export and degradation of Cyclin D1) are reduced in MECs lacking Jak2. The proliferation of Jak2-deficient MECs can be rescued by expressing of a mutant form of Cyclin D1 that cannot be phosphorylated by glycogen synthase kinase-3β and therefore constitutively resides in the nucleus. Besides discriminating Jak2-dependent and Jak2-independent signaling events emerging from the PRLR, our observations provide a possible mechanism for phenotypic similarities between Cyclin D1 knockouts and females lacking individual members of the PRLR signaling cascade, in particular the PRLR, Jak2, and Stat5.
A Common Polymorphism in the Bile Acid Receptor Farnesoid X Receptor Is Associated with Decreased Hepatic Target Gene Expression
Authors: Marzolini Catia , Tirona Rommel G. , Gervasini Guillermo , Poonkuzhali Balasubramanian , Assem Mahfoud , Lee Wooin , Leake Brenda F. , Schuetz John D. , Schuetz Erin G. , Kim Richard B. 
Published: May 2007

AbstractThe farnesoid X receptor (FXR or NR1H4) is an important bile-acid-activated, transcriptional regulator of genes involved in bile acid, lipid, and glucose homeostasis. Accordingly, interindividual variations in FXR expression and function could manifest as variable susceptibility to conditions such as cholesterol gallstone disease, atherosclerosis, and diabetes. We performed an FXR polymorphism discovery analysis of European-, African-, Chinese-, and Hispanic-Americans and identified two rare gain-of-function variants and a common single nucleotide polymorphism resulting in a G-1T substitution in the nucleotide adjacent to the translation initiation site (FXR*1B) with population allelic frequencies ranging from 2.5 to 12%. In cell-based transactivation assays, FXR*1B (-1T) activity was reduced compared with FXR*1A (-1G). This reduced activity for FXR*1B resulted from neither decreased translational efficiency nor the potential formation of a truncated translational variant. To further define the relevance of this polymorphism, gene expression was examined in a human liver bank to reveal that levels of the FXR target genes small heterodimer partner and organic anion transporting polypeptide 1B3 were significantly reduced in livers harboring an FXR*1B allele. These findings are the first to identify the presence of a common genetic variant in FXR with functional consequences that could contribute to disease risk or therapeutic outcomes.
Response of SMRT (Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor) and N-CoR (Nuclear Receptor Corepressor) Corepressors to Mitogen-Activated Protein Kinase Kinase Kinase Cascades Is Determined by Alternative mRNA Splicing
Authors: Jonas Brian A. , Varlakhanova Natalia , Hayakawa Fumihiko , Goodson Michael , Privalsky Martin L. 
Published: May 2007

AbstractThe SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) corepressors are important mediators of transcriptional repression by nuclear hormone receptors. SMRT is regulated by MAPK kinase kinase (MAPKKK) cascades that induce its release from its receptor partners, its export from nucleus to cytoplasm, and derepression of target gene expression. Intriguingly, the otherwise closely related N-CoR is refractory to MAPKKK signaling under the same conditions. However, both SMRT and N-CoR are expressed as a series of alternatively spliced protein variants differing in structure and function. We have now characterized the impact of this alternative mRNA splicing on the corepressor response to MAPKKK signaling. Whereas the SMRTα, SMRTτ, and SMRTsp2 splice variants are released from their nuclear receptor partners in response to MAPKKK activation, the SMRTsp18 variant, which resembles N-CoR in its overall molecular architecture, is relatively refractory to this kinase-induced release. Alternative splicing of N-CoR, in contrast, had only minimal effects on the resistance of this corepressor to MAPKKK inhibition. Notably, all of the SMRT splice variants examined redistributed from nucleus to cytoplasm in response to MAPKKK cascade signaling, but none of the N-CoR splice variants did so. Different tiers of the MAPKKK cascade hierarchy contributed to these different aspects of corepressor regulation, with MAP/ERK kinase kinase 1 and MAP/ERK kinase 1 regulating subcellular redistribution and ERK2 regulating nuclear receptor-corepressor interaction. We conclude that cells can customize their transcriptional response to MAPKKK cascade signaling by selective expression of the SMRT or N-CoR locus, by selective utilization of a specific corepressor splice variant, and by selective exploitation of specific tiers of the MAPK cascade.
Evaluation of Consultation in Community Pharmacies with Mystery Shoppers
Authors: Alte Dietrich , Weitschies Werner , Ritter Christoph A 
Published: May 2007

BACKGROUND: Consultation of patients in community pharmacies (CPs) must meet standards, especially in selling over-the-counter drugs; however, there has been no information as to whether northeastern German CPs meet these standards. OBJECTIVE: To estimate aspects of consultation quality in CPs in Mecklenburg-Vorpommern, located in northeastern Germany, study factors related to consultation quality, and check compliance with Pharmacy Practice Law, because not all pharmaceutical professions may legally sell drugs. METHODS: In 2005, 6 mystery shoppers (pharmacy students) presented with a headache to 146 of 398 CPs; they requested a sleeping pill plus an antihistaminic drug and completed data collection forms. Consultation scores were calculated and effects of pharmacy/staff characteristics on consultation were modeled with linear (consultation score) and logistic regression (failure to detect a drug—drug interaction). Variables used in models were staff profession, pharmacy size (number of staff), city/town size (number of pharmacies), and day of the week in which shoppers visited the pharmacy. RESULTS: Despite a high willingness of pharmacy staff to provide consultation (83% spontaneously offered advice), northeastern German CPs did not achieve their professional mission. Extreme variation was evident in their questioning of the mystery shoppers regarding use of important single items (from 1% for pregnancy/breast-feeding considerations to 56% for dosing instructions). In all cases, drugs were sold to the shoppers; most (91%) were single agents. Drug—drug interaction detection was low: 43 (30%) counselors informed mystery shoppers about the interaction. The profession of the consulting staff and the size of the pharmacy were associated with consultation quality (highest for pharmacists; lowest for small pharmacies [2–4 staff]). For interaction detection, consulting staff profession was relevant: pharmacists had OR of 3.2 for the detection compared with pharmacy engineers/assistants. In 7 pharmacies, staff illegally sold drugs to customers. CONCLUSIONS: Northeastern German CPs have much need and potential for improvement in consultation quality and drug—drug interaction detection. In-depth elicitation of symptoms and details of patients' situations must be improved. Relevant training should be provided, including use of software to identify drug interactions. Mystery shopper studies give valuable information for tailoring training schemes.
Acetaminophen and Ibuprofen for Prevention of Adverse Reactions Associated with Childhood Immunization
Authors: Manley Jennifer , Taddio Anna 
Published: May 2007

Objective: To evaluate the literature examining prophylactic use of acetaminophen and ibuprofen for prevention of adverse reactions associated with childhood immunization. Data Sources: Articles were identified via MEDLINE/PubMed/EMBASE (1966–March 2007) using the following key terms: vaccination, immunization, diphtheria–tetanus toxoids–whole pertussis (DTwP), diphtheria tetan us–toxoid. whole pertussis, diphtheria-tetanus toxoids–acellular pertussis (DTaP), acellular pertussis, Haemophilus influenzae type B, inactivated poliovirus, pneumococcal 7-valent conjugate, measles, mumps, rubella, meningococcal C-conjugate, varicella zoster, hepatitis B, influenza, pneumococcal polysaccharide, adverse reactions, analgesics, antipyretics, acetaminophen, ibuprofen, infant, and child. Study Selection and Data Extraction: No limitations were placed on article selection. Data Synthesis: Five articles examining the effects of prophylactic acetaminophen or ibuprofen for adverse effects associated with either DTaP or DTwP vaccine were retrieved. In one randomized controlled trial of children aged 4–6 years given DTaP, no effect of prophylactic acetaminophen 15 mg/kg/dose, up to 450 mg, or ibuprofen 10 mg/kg/dose, up to 300 mg, was found on the incidence of fever, redness, pain, swelling, or itching. In 3 randomized studies of DTwP, either acetaminophen 10–15 mg/kg/dose or ibuprofen 20 mg/kg/24 hours, given in 3 equal doses before or at the time of immunization and every 4–8 hours thereafter for 12 or more hours, reduced fever, pain, fussiness, and local redness in infants 2–7 months of age compared with placebo. Results were not duplicated in older infants/children. No studies investigated use of prophylactic acetaminophen or ibuprofen for any other vaccine. Conclusions: Use of prophylactic acetaminophen and ibuprofen may reduce the incidence of adverse reactions in young infants receiving DTwP vaccine; however, DTwP has been replaced with DTaP, and no benefits have been demonstrated for this vaccine when evaluated in children aged 4–6 years, or with any other vaccine currently in use. Thus, neither drug can be recommended prophylactically to prevent vaccine-associated adverse reactions. Individuals at high risk for seizures may, however, warrant special consideration.
Evolution of Peroxisome Proliferator-Activated Receptor Agonists
Authors: Chang Feng , Jaber Linda A , Berlie Helen D , O'Connell Mary Beth 
Published: May 2007

OBJECTIVE: To discuss the evolution of peroxisome proliferator-activated receptor (PPAR) agonists from single site to multiple subtype or partial agonists for the treatment of type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome. DATA SOURCES: Information was obtained from MEDLINE (1966-March 2007) using search terms peroxisome proliferator-activated receptor agonist, PPAR dual agonist, PPAR α/γ agonist, PPAR pan agonist, partial PPAR, and the specific compound names. Other sources included pharmaceutical companies, the Internet, and the American Diabetes Association 64th-66th Scientific Sessions abstract books. STUDY SELECTION AND DATA EXTRACTION: Animal data, abstracts, clinical trials, and review articles were reviewed and summarized. DATA SYNTHESIS: PPAR α, γ, and δ receptors play an important role in lipid metabolism, regulation of adipocyte proliferation and differentiation, and insulin sensitivity. The PPAR dual agonists were developed to combine the triglyceride lowering and high-density lipoprotein cholesterol elevation from the PPAR-α agonists (fibrates) with the insulin sensitivity improvement from the PPAR-γ agonists (thiazolidinediones). Although the dual agonists reduced hemoglobin A1C(A1C) and improved the lipid profile, adverse effects led to discontinued development. Currently, PPAR-γ agonists (GW501516 in Phase I trials), partial PPAR-γ agonists (metaglidasen in Phase II and III trials), and pan agonists (α, γ, δ netoglitazone in Phase II and III trials) with improved cell and tissue selectivity are undergoing investigation to address multiple aspects of the metabolic syndrome with a single medication. By decreasing both A1C and triglycerides, metaglidasen did improve multiple aspects of the metabolic syndrome with fewer adverse effects than compared with placebo. Metaglidasen is now being compared with pioglitazone. CONCLUSIONS: Influencing the various PPARs results in improved glucose, lipid, and weight management, with effects dependent on full or partial agonist activity at single or multiple receptors. Although the dual PPAR compounds have been associated with unacceptable toxicities, new PPAR agonist medications continue to be developed and investigated to discover a safe drug with benefits in multiple disease states.
Assessing the Validity of Self-Reported Medication Adherence in Hepatitis C Treatment
Authors: Smith Scott R , Wahed Abdus S , Kelley Stephanie S , Conjeevaram Hari S , Robuck Patricia R , Fried Michael W 
Published: May 2007

Objective: To assess the validity of self-reported medication adherence provided by individuals in treatment for hepatitis C virus (HCV) infection with a regimen of peginterferon and ribavirin. Methods: Adherence was evaluated prospectively among 196 African American and 205 white subjects enrolled in Virahep-C (Viral Resistance to Antiviral Therapy of Chronic Hepatitis C), a treatment study for genotype 1 HCV infection. Adherence to the prescribed dose was measured by 2 methods: self-report questions administered during multiple clinic visits, using a touch screen computer; and recordings of bottle openings, using an electronic monitor placed inside the cap of prescription containers. Self-reported responses were compared with the electronic monitor data. Nonparametric tests were used to test the association between adherence measures at 4, 12, 24, 36, and 48 weeks of treatment. Results: The estimated proportion of participants who were adherent prior to a given visit ranged from 85% to 97% (ribavirin) and 97% to 100% (peginterferon) by self report and from 69% to 90% (ribavirin) and 64% to 100% (peginterferon) by electronic monitors. For ribavirin, the percentage of cases in which the 2 measurement methods agreed varied from 68% to 90%; peginterferon agreement was from 84% to 100%. Overall, adherence was higher for peginterferon than for ribavirin but decreased over time for both medications. Self-reported adherence was usually higher than that assessed by electronic measures, and the level of discrepancy increased during the course of treatment. Conclusions: Adherence to peginterferon and ribavirin decreased gradually during therapy but remained relatively high. Simple self-reported measures can be used to screen for nonadherence to HCV drug therapy, but should be considered as overestimation of the actual amounts taken.
Lubiprostone: A Chloride Channel Activator for Treatment of Chronic Constipation
Authors: Ambizas Emily M , Ginzburg Regina 
Published: May 2007

OBJECTIVE: To review lubiprostone's pharmacology, pharmacokinetics, efficacy, and safety in the treatment of chronic constipation. DATA SOURCES: A literature search was conducted using PubMed/MEDLINE (1966–January 2007), IngentaConnect, and International Pharmaceutical Abstracts (1977–January 2007). Key words used included lubiprostone, Amitiza, and chronic constipation. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources that were published in English were evaluated. DATA SYNTHESIS: Lubiprostone is a chloride channel activator approved by the Food and Drug Administration for the treatment of chronic constipation. A randomized, double-blind, parallel-group, placebo-controlled study evaluating the effect of lubiprostone on gastric function showed slowed gastric emptying and increased small bowel and colonic transit time. Peak plasma concentration was shown to be around 1.14 hours, with a majority of the drug excreted in the urine within 48 hours. Phase III trials have noted that most patients with chronic constipation have a spontaneous bowel movement within 24 hours after taking lubiprostone. The most common adverse events in these trials were nausea, diarrhea, abdominal pain, and headache. Lubiprostone use has not been studied in the pediatric population. CONCLUSIONS: Lubiprostone may be a reasonable alternative for use in patients who either fail or are intolerant of standard therapy for chronic constipation. Head-to-head comparison studies with conventional therapy are needed to contrast clinical efficacy and safety of this medication.
Zhan Wang: Urban Landscape
Authors: stomberg john 
Published: May 2007

The artist Zhan Wang replicates the city of Beijing using a variety of mass-produced cookware and his own, hand-molded, stainless steel rock formations. The installation, called Urban Landscape: Beijing, simultaneously extends and significantly alters both the tradition of Marcel Duchamp and the general precepts of minimalist sculpture. His work also addresses current social concerns such as urbanization and globalization.
Urban Landscape: Beijing embodies Zhan's expansive worldview. In the context of his work, the artist discusses concerns that range from economics, theology, sociology, urban planning, and architecture to formal art issues, such as the use of found objects and the role of the grid. He encourages our contemplation of rapid modernization in China--and the negative effect it can have on life there--and shares our pleasure in the gleaming surfaces of his materials. Urban Landscape: Beijing evokes both the allure of modern urban culture and the consequences of urban renewal--it offers the sensuous pleasure of modernity and the sting of the price paid.
Divine Wisdom and Dolorous Mysteries: Habsburg Marian Devotion in Two Motets from Monteverdi's Selva morale et spirituale
Authors: WEAVER ANDREW H. 
Published: May 2007

Despite recent scholarly interest in Monteverdi's Selva morale et spirituale (1641), many aspects of this large, complex print remain enigmatic, and the intended context for much of the music in the collection has long been a matter of pure conjecture. Yet two of the most anomalous features of the Selva morale, the solo motets Ab aeterno ordinata sum and Pianto della Madonna, can now be placed into the context of the Habsburg court in Vienna during the reign of Ferdinand III (1637–57).
Both of these works play directly into the most important aspects of Habsburg Marian devotion. Ab aeterno is a setting of Proverbs 8:23–31, a text that although very rare for seventeenth-century motets would nonetheless have been widely understood as a celebration of the Immaculate Conception of the Blessed Virgin. The Pianto, a Latin contrafactum of Monteverdi's celebrated Lamento d'Arianna, would have been perfectly suited for the Habsburgs' Fifteen Mysteries Celebration, a Lenten devotion in praise of the Most Holy Rosary. Various types of evidence, including liturgical and other religious writings, Habsburg sermons, and additional musical works, support these interpretations of Monteverdi's motets and reveal their importance to the imperial court. That the composer did indeed include the motets in his print with the Habsburg court in mind is further indicated by similarities between the Selva morale and an earlier publication stemming directly from Ferdinand III's court: Giovanni Felice Sances's Motetti a voce sola of 1638.
Sentinel Lymph Node Biopsy in Male Patients with Early Breast Cancer
Authors: Gentilini Oreste , Chagas Eduardo , Zurrida Stefano , Intra Mattia , De Cicco Concetta , Gatti Giovanna , Silva Luzemira , Renne Giuseppe , Cassano Enrico , Veronesi Umberto 
Published: May 2007

Learning Objectives
After completing this course, the reader will be able to: Evaluate the feasibility of sentinel lymph node biopsy in male breast cancer patients.Determine which male breast cancer patients can be candidates for sentinel lymph node biopsy.Identify the main biological features of male breast cancer and evaluate differences with respect to female breast cancer.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Anal Cancer: An Overview
Authors: Uronis Hope E. , Bendell Johanna C. 
Published: May 2007

Learning Objectives
After completing this course, the reader will be able to: Discuss the epidemiology of and the risk factors for anal cancer.Outline standard treatment for anal cancer and describe its complications.Understand the issues related to treating HIV-positive patients with anal cancer.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Tumor Suppressor Role of Notch-1 Signaling in Neuroendocrine Tumors
Authors: Kunnimalaiyaan Muthusamy , Chen Herbert 
Published: May 2007

Abstract
A growing body of literature is demonstrating that Notch signaling is a more complex process than originally thought. Contradictory findings of notch-1 acting as an oncogene or a tumor suppressor revealed that its role is very specific to the cellular context. In this review we focus on the tumor suppressor role of Notch-1 signaling in neuroendocrine tumors (NETs) such as carcinoid and medullary thyroid cancers. NETs secrete various bioactive hormones that can cause debilitating symptoms. Surgery is the only potential curative treatment for the patients with NETs. Notch-1 signaling is absent in these tumors and activation of Notch-1 significantly reduces tumor growth in vitro. Therefore, identification of compound(s) that activate the Notch-1 pathway in NETs could be a potential strategy to treat patients with NETs.
FDA Drug Approval Summary: Panitumumab (Vectibix™)
Authors: Giusti Ruthann M. , Shastri Kaushikkumar A. , Cohen Martin H. , Keegan Patricia , Pazdur Richard 
Published: May 2007

Learning Objectives
After completing this course, the reader will be able to: Add panitumumab (Vectibix™) to the armamentarium of drugs for colorectal cancer.Identify the patient group that is eligible for panitumumab therapy.Identify biologic agents that have activity in colorectal cancer.List the FDA criteria for the analysis of progression-free survival and for accelerated approval.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com