bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line
Authors: Sarmiento Rosa E , Tirado Rocio G , Valverde Laura E , Gómez-Garcia Beatriz 
Published: July 2007

Abstract

Background
The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV) antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2) were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs) and intracellular viral proteins were detected by indirect immunoflourescence.

Results
Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death.

Conclusion
The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell.
Molecular biology of cantharidin in cancer cells
Authors: Rauh Rolf , Kahl Stefan , Boechzelt Herbert , Bauer Rudolf , Kaina Bernd , Efferth Thomas 
Published: July 2007

AbstractHerbal medicine is one of the forms of traditional medical practice. Traditional Chinese medicine (TCM) and traditional Vietnamese medicine (TVM) are well-known for their long-standing tradition of herbal medicine.Secreted by many species of blister beetle, most notably by the 'Spanish fly' (Lytta vesicatoria), cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). Blister beetle has been used in Asian traditional medicine to treatMolluscum contagiosumvirus (MCV) infections and associated warts, and is now also used for cancer treatment. A combination of both genomic and postgenomic techniques was used in our studies to identify candidate genes affecting sensitivity or resistance to cantharidin. Cantharidin was not found to be related to multidrug resistance phenotype, suggesting its potential usefulness for the treatment of refractory tumors. Oxidative stress response genes diminish the activity of cantharidin by inducing DNA strand breaks which may be subject to base excision repair and induce apoptosis in a p53- and Bcl2-dependent manner.Cantharidin is one of many natural products used in traditional Chinese medicine and traditional Vietnamese medicine for cancer treatment. Combined methods of pharmaceutical biology and molecular biology can help elucidate modes of action of these natural products.
Rapid Maturation of Glycoprotein Hormone Free α-Subunit (GPHα) and GPHαα Homodimers
Authors: Krause Jean-Michel , Berger Peter , Roig Jordi , Singh Vinod , Merz Wolfgang E. 
Published: July 2007

AbstractThe dynamics of glycoprotein hormone α-subunit (GPHα) maturation and GPHαα homodimer formation were studied in presence (JEG-3 choriocarcinoma cells) and absence (HeLa cells) of hCGβ. In both cases, the major initially occurring GPHα variant in [35S]Met/Cys-labeled cells carried two N-glycans (Mr app = 22 kDa). Moreover, a mono-N-glycosylated in vivo association-incompetent GPHα variant (Mr app = 18 kDa) was observed. In JEG-3 cells the early 22-kDa GPHα either associated with hCGβ, or showed self-association to yield GPHαα homodimers, or was later converted into heavily glycosylated large free GPHα (Mr app = 24 kDa). Micro-preparative isolation of intracellular GPHαα homodimers of JEG-3 cells and their conversion by reduction revealed that they consisted of 22-kDa GPHα monomers and not of large free GPHα. In HeLa cells, the large free GPHα variant was not observed, whereas GPHαα homodimers were present. Intracellularly, early GPHαα homodimers (35 kDa) and late variants (JEG-3: 44 kDa, HeLa: 39 kDa) were found. Both cell types secreted 45 kDa GPHαα homodimers. Large free GPHα and GPHαα homodimers were more rapidly sialylated than hCG αβ-heterodimers indicating a sequestration mechanism in the secretory pathway. In GPHαα homo- as well as hCG αβ-heterodimers the subunit interaction site, located on loop 2 of GPHα (amino acids 33–42), became immunologically inaccessible indicating similar spatial orientation of GPHα in both types of dimers. The studies demonstrate the formation, in vivo dynamics of GPHαα homodimers, and the pathways of the cellular metabolism of variants of GPHα, monoglycosylated GPHα and large free GPHα.
Transcriptional Cross Talk between the Forkhead Transcription Factor Forkhead Box O1A and the Progesterone Receptor Coordinates Cell Cycle Regulation and Differentiation in Human Endometrial Stromal Cells
Authors: Takano Masashi , Lu Zhenxiao , Goto Tomoko , Fusi Luca , Higham Jenny , Francis Julia , Withey Anna , Hardt Jennifer , Cloke Brianna , Stavropoulou Alexandra V. , Ishihara Osamu , Lam Eric W.-F. , Unterman Terry G. , Brosens Jan J. , Kim J. Julie 
Published: July 2007

AbstractDifferentiation of human endometrial stromal cells (HESCs) into decidual cells is associated with induction of the forkhead transcription factor forkhead box O1A (FOXO1). We performed a genomic screen to identify decidua-specific genes under FOXO1 control. Primary HESCs were transfected with small interfering RNA targeting FOXO1 or with nontargeting control small interfering RNA before treatment with a cAMP analogue and the progestin, medroxyprogesterone acetate for 72 h. Total RNA was processed for whole genome analysis using high-density oligonucleotide arrays. We identified 3405 significantly regulated genes upon decidualization of HESCs, 507 (15.3%) of which were aberrantly expressed upon FOXO1 knockdown. Among the most up-regulated FOXO1-dependent transcriptional targets were WNT signaling-related genes (WNT4, WNT16 ), the insulin receptor (INSR), differentiation markers (PRL, IGFBP1, and LEFTY2), and the cyclin-dependent kinase inhibitor p57Kip2 (CDKN1C). Analysis of FOXO1-dependent down-regulated genes uncovered several factors involved in cell cycle regulation, including CCNB1, CCNB2, MCM5, CDC2 and NEK2. Cell viability assay and cell cycle analysis demonstrated that FOXO1 silencing promotes proliferation of differentiating HESCs. Using a glutathione-S-transferase pull-down assay, we confirmed that FOXO1 interacts with progesterone receptor, irrespectively of the presence of ligand. In agreement, knockdown of PR disrupted the regulation of FOXO1 target genes involved in differentiation (IGFBP1, PRL, and WNT4) and cell cycle regulation (CDKN1, CCNB2 and CDC2) in HESCs treated with either cAMP plus medroxyprogesterone acetate or with cAMP alone. Together, the data demonstrate that FOXO1 engages in transcriptional cross talk with progesterone receptor to coordinate cell cycle regulation and differentiation of HESCs.
Pharmacists’ Knowledge and Attitudes Toward Herbal Medicine
Authors: Chang Ziba Gorji , Kennedy Daniel T , Holdford David A , Small Ralph E 
Published: July 2007

Objective: The use and sales of herbal medications have increased dramatically over the past several years. Pharmacists are in an ideal position to educate patients about herbal medicines. This study was intended to determine the knowledge and attitudes of pharmacists regarding herbal medications. Methods: A survey was distributed to pharmacists at several state and regional meetings in Virginia and North Carolina between August and October 1998. The survey evaluated demographic data, attitudinal scales, and a 15-item herbal medicine knowledge test. Pharmacists immediately returned the surveys to the distributor on completion. Results: Of the 217 surveys distributed. 164 met the Inclusion criteria for further evaluation. Of the pharmacists surveyed, 68.0% practiced in a community pharmacy, 45.1% had previous continuing education on herbal medications, and 73.6% sold herbal medications in their practice settings. The average score on the herbal knowledge test was 6.3 (maximum score of 15). Pharmacists with previous continuing education scored significantly higher than those without prior continuing education (p < 0.001). Of the 15 questions, the five that pharmacists were most likely to answer correctly assessed the uses of herbal medications. Additionally, pharmacists with prior continuing education or with access to herbal medication information at their practice site were more likely to agree that providing information about herbal medication is a pharmacist's professional responsibility (p = 0.02 and p = 0.01, respectively). Conclusions: The findings from this study demonstrate that pharmacists were more likely to answer correctly about the uses of herbal medications than about drug interactions, adverse drug effects, and precautions of herbal medications. Additionally, pharmacists with previous continuing education on herbal medications were more knowledgeable about these products. With the increasing use of herbal medications, there is a greater need for pharmacy training programs in this area.
Nonselective Nonsteroidal Antiinflammatory Drugs and Cardiovascular Risk: Are They Safe?
Authors: Waksman Javier C , Brody Aaron , Phillips Scott D 
Published: July 2007

Objective: To assess possible cardiovascular risks associated with use of nonselective nonsteroidal antiinflammatory drugs (NSAIDs). Data Sources: Medline and Embase were searched from January 1985 through April 2007 and relevant studies were retrieved. Study Selection and Data Extraction: Peer-reviewed, prospective, double-blind, case–control, and cohort-design studies published in the English language literature were considered eligible for review. Previous meta-analyses and systematic reviews were also analyzed. In total, 17 case–control studies; 9 cohort studies; 1 prospective, double-blind study; 3 meta-analyses; and 1 systematic review of observational studies were identified. Data Synthesis: Three studies were prospective and the remainder consisted of observational, retrospective studies, with most reporting acute fatal or nonfatal myocardial infarction as the cardiovascular endpoint. Among the nonselective NSAIDs, diclofenac appears to pose the highest risk for cardiovascular toxicity; other agents trend toward a neutral effect with respect to cardiovascular risk. Although the data are suggestive, it remains unclear whether naproxen provides protective cardiovascular effects among patients on chronic therapy. Conclusions: Currently available data are insufficient for defining evidence-based clinical guidelines for the use of NSAIDs, and the need for additional research, specifically randomized controlled trials, is evident. Diclofenac demonstrates a significant risk while naproxen appears to pose the lowest, albeit nonsignificant, risk for cardiovascular morbidity. Although the current clinical evidence may not warrant recommending naproxen as the preferred NSAID treatment, it may be prudent to avoid diclofenac for patients with cardiovascular risk factors requiring NSAID treatment.
Management Options for Patients with Aspirin and Nonsteroidal Antiinflammatory Drug Sensitivity
Authors: Knowles Sandra R , Drucker Aaron M , Weber Elizabeth A , Shear Neil H 
Published: July 2007

Objective: To evaluate and provide management strategies for patients with aspirin or nonselective nonsteroidal antiinflammatory drug (NSAID) sensitivity. Data Sources: Literature retrieval was accessed through MEDLINE (1966–March 2007) using the terms acetaminophen, aspirin, antiinflammatory agents nonsteroidal, urticaria, angioedema, asthma, leukotriene antagonists, desensitization, and tacrolimus. Article references retrieved were hand-searched for other relevant articles. Study Selection and Data Extraction: All studies published in English were evaluated. Studies, review articles, and commentaries on aspirin-induced asthma and aspirin- or NSAID-induced urticaria/angioedema were included in the review. Data Synthesis: Aspirin sensitivity is most often manifested as respiratory reactions (eg, bronchospasm, profuse rhinorrhea, conjunctival injection) or urticaria/angioedema. The primary mechanism is believed to be inhibition of the cyclooxygenase 1 (COX-1) enzyme; as such, patients with aspirin sensitivity often display cross-reactions to nonselective NSAIDs that inhibit the COX-1 enzyme. Management strategies include avoidance of aspirin and cross-reacting nonselective NSAIDs. However, desensitization to aspirin is a viable option for patients with aspirin-induced respiratory reactions, especially for those who require aspirin for thromboembolic prophylaxis. Aspirin desensitization is maintained indefinitely with a daily aspirin dose. There is limited evidence of the use of leukotriene modifiers in preventing aspirin-induced asthma. COX-2 selective NSAIDs, especially in patients with aspirin-induced asthma, have not been found to cross-react. However, approximately 4% of patients with a history of aspirin-induced skin reactions may experience a cutaneous reaction following a challenge to a COX-2 selective NSAID. Since acetaminophen is a weak inhibitor of the COX-1 enzyme, patients with aspirin-induced asthma should not take more than 1000 mg of acetaminophen in a single dose. Conclusions: Management of patients with aspirin/NSAID sensitivity includes avoidance of aspirin/nonselective NSAIDs, use of COX-2 selective NSAIDs, acetaminophen in doses less than 1000 mg, and desensitization. The role of leukotriene modifiers requires further study before they can be recommended for patients.
Hypersensitivity Reaction to Amiodarone in a Patient with a Previous Reaction to an lodinated Radiocontrast Agent
Authors: Stafford Leanne 
Published: July 2007

Objective: To describe a case of a hypersensitivity reaction to oral amiodarone in a patient with a previous reaction to an iodinated radiocontrast agent. Case Summary: A 55-year-old man experienced facial urticaria after intraarterial injection of iohexol, an iodinated radiocontrast agent, during coronary angiography, which was successfully treated with intravenous hydrocortisone and promethazine. The procedure revealed significant triple vessel disease, and the patient subsequently underwent coronary artery bypass grafting in October 2006. Postoperatively, the patient experienced 2 episodes of fast atrial fibrillation, the first of which was treated successfully with intravenous amiodarone. The second episode resulted in the commencement of therapy with oral amiodarone 400 mg 3 times daily. Within one hour after the first dose, the patient experienced tip swelling and tingling, which was again treated with intravenous promethazine. Amiodarone was stopped; the patient remained in sinus rhythm and was discharged without further incident. Discussion: Amiodarone is a class III antiarrhythmic agent frequently used in the management of atrial fibrillation after cardiac surgery. The approved product information lists known hypersensitivity to iodine as a contraindication to its administration, but no other cases of amiodarone hypersensitivity in a patient with a previous reaction to an iodinated radiocontrast agent have been published, Conversely, it has been suggested that the drug may be safely used in such patients. The Naranjo probability scale supported a probable adverse reaction of hypersensitivity associated with amiodarone therapy in this patient. Conclusions: Prescribers should exercise caution in the administration of amiodarone to patients with a true, documented history of hypersensitivity to an iodinated compound.
Update on Abatacept: A Selective Costimulation Modulator for Rheumatoid Arthritis
Authors: Bruce Susan P , Boyce Eric G 
Published: July 2007

Objective: To review and update the pharmacology, pharmacokinetics, safety, precautions, efficacy, and use of abatacept for rheumatoid arthritis (RA). Data Sources: Studies and abstracts were identified through MEDLINE, International Pharmaceutical Abstracts, Cochrane databases, and Science Citation Index (1990–April 2007). Key search terms included abatacept, CTLA4–Ig, and BMS 1888667. Information available only in abstract form was retrieved from national and international rheumatology associations. Additional data were obtained from the manufacturer. Study Selection and Data Extraction: All available animal and human studies describing the pharmacology of abatacept and human studies describing the pharmacokinetics, pharmacodynamics, efficacy, safety, adverse events, and precautions of abatacept were included. Data Synthesis: Abatacept significantly improves the signs and symptoms of moderate-to-severe RA in patients who experienced an Inadequate response to methotrexate or antitumor necrosis factor-α inhibitors. By month 12, approximately 50% of patients achieved remission (defined as a disease activity score <2.6) that was maintained until at least 24 months of therapy. The most common adverse events include headache, upper respiratory tract infections, nausea, and nasopharyngitis. Rare but serious adverse events include serious infections and malignancy. Conclusions: Abatacept has documented efficacy and safety in patients with inadequate responses to methotrexate and antitumor necrosis factor agents in both short- and long-term studies. Additional clinical trial and postmarketing evidence is necessary to understand the long-term safety, efficacy, economics, and rote of abatacept in clinical practice.
Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges
Authors: Khan Arshad M. , Ponzio Todd A. , Sanchez-Watts Graciela , Stanley B. Glenn , Hatton Glenn I. , Watts Alan G. 
Published: July 2007

Paraventricular hypothalamic (PVH) corticotropin-releasing hormone (CRH) neuroendocrine neurons mount neurosecretory and transcriptional responses to glycemic challenges [intravenous 2-deoxyglucose (2-DG) or insulin]. Although these responses require signals from intact afferents originating from hindbrain CA (catecholaminergic) neurons, the identity of these signals and the mechanisms by which they are transduced by PVH neurons during glycemic challenge remain unclear. Here, we tested whether the prototypical catecholamine, norepinephrine (NE), can reproduce PVH neuroendocrine responses to glycemic challenge. Because these responses include phosphorylation of p44/42 mitogen-activated protein (MAP) kinases [extracellular signal-regulated kinases 1/2 (ERK1/2)], we also determined whether NE activates ERK1/2 in PVH neurons and, if so, by what mechanism.We show that systemic insulin and 2-DG, and PVH-targeted NE microinjections, rapidly elevated PVH phospho-ERK1/2 levels. NE increasedCrhand c-fosexpression, together with circulating ACTH/corticosterone. However, because injections also increased c-Fos mRNA in other brain regions, we used hypothalamic slices maintainedin vitroto clarify whether NE activates PVH neurons without contribution of inputs from distal regions. In slices, bath-applied NE triggered robust phospho-ERK1/2 immunoreactivity in PVH (including CRH) neurons, which attenuated markedly in the presence of the α1adrenoceptor antagonist, prazosin, or the MAP kinase kinase (MEK) inhibitor, U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene). Therefore, at a systems level, local PVH delivery of NE is sufficient to account for hindbrain activation of CRH neuroendocrine neurons during glycemic challenge. At a cellular level, these data provide the first demonstration that MAP kinase signaling cascades (MEK→ERK) are intracellular transducers of noradrenergic signals in CRH neurons, and implicate this transduction mechanism as an important component of central neuroendocrine responses during glycemic challenge.
Maternal Psychological Reaction to Newborn Genetic Screening for Type 1 Diabetes
Authors: Kerruish Nicola J. , Campbell-Stokes Priscilla L. , Gray Andrew , Merriman Tony R. , Robertson Stephen P. , Taylor Barry J. 
Published: July 2007

OBJECTIVE. The purpose of this work was to describe levels of maternal anxiety, depressive symptoms, and perceptions of infant vulnerability associated with newborn genetic screening for susceptibility to type 1 diabetes.PATIENTS AND METHODS. Mothers of infants tested at birth for genetic susceptibility to type 1 diabetes as part of a prospective study investigating potential environmental triggers of autoimmunity were recruited to this study. Three mother-infant cohorts were studied: 38 infants at increased genetic risk, 73 at low risk, and 76 who had not undergone testing. The Vulnerable Baby Scale, Edinburgh Postnatal Depression Scale, and state subscale of the State Trait Anxiety Inventory were administered at the 9-week, 4-month, and 1-year postnatal ages. Genetic-risk notification occurred at the 10-week postnatal age. Mothers whose infants had undergone genetic testing were also asked to subjectively rate how much they thought and worried about their child's genetic test result. Statistical analyses were conducted to test for differences in questionnaire scores among the 3 groups.RESULTS. No difference among the groups was detected in Vulnerable Baby Scale or Edinburgh Postnatal Depression Scale scores using linear mixed-effects model analysis. Maternal anxiety was paradoxically slightly lower in the increased-risk group shortly after notification of results, but there were no significant differences among the groups by 1 year. Mothers of infants in the high-risk group reported thinking and worrying about their child's test result significantly more than mothers of low-risk infants at both time points after notification of results.CONCLUSIONS. Newborn genetic screening to identify infants at risk for type 1 diabetes is not associated with elevated levels of maternal anxiety, depressive symptoms, or heightened perceptions of infant vulnerability. However, responses to subjective assessment questions suggest that it is possible that more subtle effects on mothers do occur, and this requires further investigation.