bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane electrical excitability is necessary for the free‐running larval Drosophila circadian clock
Authors: Nitabach Michael N. , Sheeba Vasu , Vera David A. , Blau Justin , Holmes Todd C. 
Published: August 2004

AbstractDrosophila larvae and adult pacemaker neurons both express free‐running oscillations of period (PER) and timeless (TIM) proteins that constitute the core of the cell‐autonomous circadian molecular clock. Despite similarities between the adult and larval molecular oscillators, adults and larvae differ substantially in the complexity and organization of their pacemaker neural circuits, as well as in behavioral manifestations of circadian rhythmicity. We have shown previously that electrical silencing of adult Drosophila circadian pacemaker neurons through targeted expression of either an open rectifier or inward rectifier K+ channel stops the free‐running oscillations of the circadian molecular clock. This indicates that neuronal electrical activity in the pacemaker neurons is essential to the normal function of the adult intracellular clock. In the current study, we show that in constant darkness the free‐running larval pacemaker clock—like that of the adult pacemaker neurons they give rise to—requires membrane electrical activity to oscillate. In contrast to the free‐running clock, the molecular clock of electrically silenced larval pacemaker neurons continues to oscillate in diurnal (light–dark) conditions. This specific disruption of the free‐running clock caused by targeted K+ channel expression likely reflects a specific cell‐autonomous clock‐membrane feedback loop that is common to both larval and adult neurons, and is not due to blocking pacemaker synaptic outputs or disruption of pacemaker neuronal morphology. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2005
Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000
Authors: Tonks A. , Wyldes M. , Somerset D. A. , Dent K. , Abhyankar A. , Bagchi I. , Lander A. , Roberts E. , Kilby M. D. 
Published: August 2004

AbstractObjectivesTo describe trends in incidence, associated anomalies, clinical outcomes and sensitivity of prenatal diagnosis for congenital malformations of the diaphragm in the West Midlands Region between 1995 and 2000.MethodsInformation was retrieved from a population‐based register of major congenital malformations in a health region of England, the West Midlands Congenital Anomaly Register (WMCAR), between 1995 and 2000.ResultsOne hundred and sixty‐one confirmed cases of congenital malformations of the diaphragm were notified from 396 577 births. This gives an incidence of 4.1 per 10 000 births. After natural losses and terminations, the incidence at birth was 2.9 per 10 000 registered births. For live‐born cases, the infant mortality rate was 317 per 1000 births. 47% of the cases had additional structural or chromosomal anomalies; the infant mortality rate for these complex cases was 533 per 1000, an increased relative risk of 2.37 compared with isolated lesions. 66% of the cases were diagnosed prenatally, 51% of isolated lesions and 84% of complex cases. Fourteen prenatally diagnosed cases (12%) were false‐positives; however, 11 of these cases had other significant pathology. These 14 cases were not included in the 161 confirmed cases.ConclusionCongenital malformations of the diaphragm remain associated with considerable infant mortality. Most cases are now diagnosed before birth and the prognosis is adversely affected by the presence of other structural or chromosomal anomalies. This presents significant challenges for those involved in counselling the parents of affected fetuses. Copyright © 2004 John Wiley & Sons, Ltd.
Randomised trial comparing an interactive multimedia decision aid with a leaflet and a video to give information about prenatal screening for Down syndrome
Authors: Leung K. Y. , Lee C. P. , Chan H. Y. , Tang M. H. Y. , Lam Y. H. , Lee A. 
Published: August 2004

AbstractObjectives(1)To compare an interactive multimedia decision aid (IMDA) with a leaflet and a video to give information about prenatal screening for Down syndrome and (2) to determine the women's acceptance of IMDA.MethodsTwo hundred and one women were recruited from the prenatal clinic of a university teaching hospital and randomised into the intervention group (IMDA, video, and information leaflet) or the control group (video and information leaflet).ResultsThere were no significant differences in the initial decision for and the final uptake of the prenatal screening test between the control and intervention groups. The proportion of women who were undecided was less than 10% in both groups. Of the women in the intervention group, 86.6% and 78.9% agreed that IMDA was user‐friendly and acceptable, respectively. Significantly more women aged <35 (88.1%) accepted IMDA than women aged >=35 (68.3%) (P = 0.030), but the logistic regression analysis did not confirm this finding after adjusting for other factors (computer knowledge and usage of computer).ConclusionThe use of IMDA did not affect the women's overall uptake rate of the prenatal screening test for Down syndrome. More women less than 35 years accepted IMDA probably because they used computer more frequently and had more computer knowledge. Copyright © 2004 John Wiley & Sons, Ltd.
Prenatal diagnosis of Pfeiffer syndrome type II
Authors: Blaumeiser Bettina , Loquet Philip , Wuyts Wim , Nöthen Markus M. 
Published: August 2004

AbstractPfeiffer syndrome is an autosomal dominant disorder characterized by coronal craniosynostosis, midface hypoplasia, broad thumbs and great toes. On the basis of clinical findings, three subtypes have been delineated. The clinical variability of Pfeiffer syndrome as well as other causes of craniosynostosis can make a prenatal diagnosis based on sonography alone difficult. We describe a fetus in whom sonographic findings (including 3D ultrasound) suggested a Pfeiffer syndrome type II and in which subsequent molecular analysis verified the diagnosis by identifying a de novo mutation in the FGFR2 gene. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis of Pfeiffer syndrome in a patient without family history. Copyright © 2004 John Wiley & Sons, Ltd.
The reporting odds ratio and its advantages over the proportional reporting ratio
Authors: Rothman Kenneth J. , Lanes Stephan , Sacks Susan T. 
Published: August 2004

AbstractPurposeThe proportional reporting ratio (PRR) is the proportion of spontaneous reports for a given drug that are linked to a specific adverse outcome, divided by the corresponding proportion for all or several other drugs. The PRR is similar to the proportional mortality ratio (PMR), an old epidemiologic measure calculated from death registries and constructed in similar fashion to the PRR. The PMR has important deficiencies, however, which the PRR shares. Miettinen and Wang demonstrated that the PMR could be improved by reformulating it as an odds ratio and applying the principles of a case‐control study to the measure. In this paper, we review the problem with the PRR and show how the corresponding odds ratio represents an improvement over the PRR.MethodsThe method used is discussion and illustration by way of a hypothetical example.ResultsThe PRR does not estimate relative risk. If, however, a spontaneous report database is viewed as source data for a case‐control study, the reporting odds ratio (ROR) can be used to estimate relative risk. Treating the data as source data for a case‐control study allows for further reduction of bias by the judicious choice of controls.ConclusionsCalculating the ROR in spontaneous report databases offers advantages over the PRR. It allows for estimation of the relative risk, and focuses attention on which people or reports should be included or excluded from the control series, permitting more deliberate elimination of biases. It also highlights the inherent weaknesses in spontaneous report data, which become more evident in light of the usual principles of control selection in case‐control studies.
A retrospective, study of prescribing for erectile dysfunction in a UK population during 1997–2000: demand was neither excessive nor continuing to rise
Authors: Sullivan Frank , Donnelly Louise , Donnan Peter 
Published: August 2004

AbstractPurposeThe UK NHS restricted the prescription of sildenafil to a range of clearly defined clinical situations. We describe the pattern of pharmaceutical management of erectile dysfunction (ED) during the period when the new drug was introduced and then regulated.MethodsWe studied the population of males aged over 16 (n = 121 783) who were continuously registered with 60 practices in Tayside between 1 October 1997 and 30 June 2000 using record linkage and case‐note verification. The patients' GPs allowed a research nurse to examine the records of these patients for demographic details, comorbidities and resource use.ResultsFive hundred and fifty five patients received 2493 prescriptions for alprostadil or sildenafil. The addition of an oral agent to the available therapies in 1998 did lead to a more rapid rise in prescribed treatments but this reached a plateau 3.47 per 1000 adult males per quarter after 12–15 months. Fifty eight per cent of the men had a comorbidity associated with ED. More comorbidities were found in men aged 50–69 and those living in areas of greater deprivation. Depression was a more common comorbidity in younger patients and more men from affluent areas were prescribed sildenafil following prostatectomy.ConclusionsIn the Tayside region of the UK, the introduction of an effective, acceptable oral therapy for erectile dysfunction led to a rise in prescriptions issued for ED. This rise appeared to stop after 12–15 months, perhaps partly because of the governmental restrictions imposed. Copyright © 2003 John Wiley & Sons, Ltd.
Breast cancer incidence and use of antihypertensive medication in women
Authors: González‐Pérez Antonio , Ronquist Gunnar , García Rodríguez Luis Alberto 
Published: August 2004

AbstractPurposeBreast cancer is the most common cancer in women worldwide. We attempted to investigate the association between the risk of breast cancer and use of captopril and other antihypertensive medication.MethodsWe performed a cohort study with a nested case‐control analysis using the General Practitioner Research Database (GPRD) from the UK. We obtained adjusted estimates by fitting logistic regression models.ResultsThe incidence rate of breast cancer in our cohort of women aged 30–79 years was 156 per 100 000 person‐years. Overall, incidence of breast cancer among users of antihypertensive drugs was no different from the one among non‐users (odds ratio (OR): 1.0; 95% confidence interval (CI): 0.9–1.1). Captopril was not associated with a reduced risk of breast cancer (OR: 0.9; 95%CI: 0.6–1.3).ConclusionsWe did not find any clear association between antihypertensive drugs and risk of breast cancer. Similarly, captopril was not associated with a reduced risk of breast cancer risk. Copyright © 2003 John Wiley & Sons, Ltd.
Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease
Authors: Gearry Richard B. , Barclay Murray L. , Burt Michael J. , Collett Judith A. , Chapman Bruce A. 
Published: August 2004

AbstractPurposeThe thiopurine drugs, azathioprine and 6‐mercaptopurine are effective in the treatment of inflammatory bowel disease (IBD). However, their use is limited by serious adverse effects that can lead to cessation of therapy. The incidence of these adverse effects has been reported to be approximately 9% but in Christchurch it was felt that the incidence was higher.MethodsWe searched our letter database to identify all patients with IBD who had received a thiopurine drug between 1996 and 2002. The case notes were then reviewed to identify those patients who had suffered an adverse effect that required cessation of the drug.ResultsFrom a total of 216 patients with IBD taking a thiopurine drug, 56 (25.9%) had an adverse reaction requiring cessation of the drug. Adverse effects included allergic‐type (25%), liver test abnormalities (34%), nausea/vomiting (6%), bone marrow suppression (7%), pancreatitis (7%) and other (9%). Males were significantly more likely than females to have an allergic‐type reaction (p=0.003). All adverse effects resolved with cessation of the drug, with a median of 7 days to resolution. Of the patients with liver test abnormalities on azathioprine, most were able to tolerate 6‐mercaptopurine, however challenge with 6‐mercaptopurine was not successful for most other patients.ConclusionsIn Canterbury, New Zealand, patients with IBD have a high rate of therapy‐limiting adverse effects to thiopurine drugs. There is a significant gender bias for allergic‐type adverse effects. Mechanisms for both these observations are not clear. Copyright © 2004 John Wiley & Sons, Ltd.
The use of non‐prescription medicines by general practitioner attendees
Authors: Urquhart Gordon , Sinclair Hazel K. , Hannaford Philip C. 
Published: August 2004

AbstractPurposeAgainst a background of increasing availability and use of non‐prescription medicines, this study set out to explore: use of such medicines by patients seeing their general practitioner (GP); frequency of GP enquiry about such use; and frequency of recommendations to use a non‐prescription medicine.MethodPatients attending four general practices in Aberdeen, Scotland, completed separate questionnaires (before and after seeing their GP).ResultsSome 461 individuals waiting to see their GP were invited to participate: 427 (93%) completed the pre‐consultation questionnaire and 305 (71% of questionnaires issued) completed the post‐consultation questionnaire. Almost half (45%) of all participants reported using non‐prescription medicines in the 7 days prior to visiting their doctor; with 20% of the medicines purchased from non‐pharmacy retail outlets. Thirteen per cent of participants were asked about their use of non‐prescribed medicines by their GP. Eight per cent of participants were recommended to use a non‐prescription medicine by their GP.ConclusionAlthough there was a high level of recent use of non‐prescribed medicines by the general practice attenders, relatively few reported being asked about such use, or were recommended to use such medicines by their GP. Copyright © 2004 John Wiley & Sons, Ltd.
A potential signal of Bell's palsy after parenteral inactivated influenza vaccines: reports to the Vaccine Adverse Event Reporting System (VAERS)—United States, 1991–2001,
Authors: Zhou Weigong , Pool Vitali , DeStefano Frank , Iskander John K. , Haber Penina , Chen Robert T. 
Published: August 2004

AbstractPurposePost‐licensure experience with a new intranasal inactivated influenza vaccine in Switzerland recently identified an increased risk for Bell's palsy. We reviewed reports in the Vaccine Adverse Event Reporting System (VAERS) to assess if parenteral inactivated influenza vaccines (influenza vaccines) may also increase the risk for Bell's palsy.MethodsReports of Bell's palsy after influenza vaccines in VAERS from 1/1/1991 to 12/31/2001 were identified by searching the Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) for ‘paralysis facial’ and by text string search in the automated database. The text descriptions on each report were reviewed to verify the diagnosis. The proportional reporting ratio (PRR) was calculated to aid signal detection.ResultsWe found a total of 197 reports of Bell's palsy after receipt of influenza vaccines. The diagnosis was verified for 154 (78.2%), of which 145 (94.2%) had received influenza vaccines alone. The verified reports were submitted from 35 states; 58% of the reports involved persons living in states where the risk of Lyme disease, which can also cause facial paralysis, was low, minimal or none. The PRRs in all age groups exceeded the criteria for a signal of possible association. The highest PRR was 3.91 in the ≥65 years age group.ConclusionsOur findings revealed a signal of possible association between influenza vaccines and an increased risk of Bell's palsy. A population‐based controlled study is needed to determine whether this association could be causal and to quantify the risk. Published in 2004 by John Wiley & Sons, Ltd.
Automated, on‐line two‐dimensional nano liquid chromatography tandem mass spectrometry for rapid analysis of complex protein digests
Authors: Mitulović Goran , Stingl Christoph , Smoluch Marek , Swart Remco , Chervet Jean‐Pierre , Steinmacher Ines , Gerner Christopher , Mechtler Karl 
Published: August 2004

AbstractEvaluation of cellular processes and their changes at the level of protein expression and post‐translational modifications may allow identification of novel proteins and the mechanisms involved in pathogenic processes. However, the number of proteins and, after tryptic digestion, of peptides from a single cell can be tremendously high. Separation and analysis of such complex peptide mixtures can be performed using multidimensional separation techniques such as two‐dimensional gel electrophoresis or two‐dimensional‐high‐performance liquid chromatography (2‐D‐HPLC). The aim of this work was to establish a fully automated on‐line 2‐D‐HPLC separation method with column switching for the separation of complex tryptic digests. A model mixture of five proteins as well as a nuclear matrix protein sample were digested with trypsin and separated using a strong cation exchange (SCX) column in the first dimension and nano reversed phase in the second dimension. Separated peptides were detected using an ion trap mass spectrometer. The advantages of this new fully automated method are rapid sample loading, the possibility of injecting large volumes and no introduction of salt into the mass spectrometer. Furthermore, column switching allows the independent control and optimization of the two dimensions independently.
A simple and inexpensive approach to interfacing high‐performance liquid chromatography and matrix‐assisted laser desorption/ionization‐time of flight‐mass spectrometry
Authors: Fung Kim Y. C. , Askovic Srdjan , Basile Franco , Duncan Mark W. 
Published: August 2004

AbstractThe ability to obtain the accurate mass of a protein in a complex sample mixture aids in determining its correct in vivo form. This is important when identifying post‐translationally modified proteins, protein variants or isoforms. The central technique used to separate proteins, 2‐dimensional gel electrophoresis offers excellent separation capabilities but does not provide adequate mass accuracy. In this study, an alternative method, liquid chromatography (LC) coupled with matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF)‐MS (LC‐MALDI) is described. LC‐MALDI‐MS was used to separate and determine the mass of proteins and peptides in a complex biological sample (i.e., human pituitary gland homogenate). Peptides and proteins were first separated by capillary chromatography and the eluent mixed post‐column with sinapinic acid matrix. The flow was then deposited directly onto a standard MALDI target via a capillary nebulizer. In addition to offering high mass accuracy, this method can be applied to peptide and protein quantification.
Proteomic and functional characterization of endogenous adiponectin purified from fetal bovine serum
Authors: Wang Yu , Lu Gang , Wong Winifred P. S. , Vliegenthart Johannes F. G. , Gerwig Gerrit J. , Lam Karen S. L. , Cooper Garth J. S. , Xu Aimin 
Published: August 2004

AbstractAdiponectin is a plasma protein exclusively secreted from fat tissue. Many recent pharmacological studies suggest that recombinant adiponectin has multiple therapeutic potentials for obesity‐related metabolic disorders, including type 2 diabetes, dyslipidemia, insulin resistance and atherosclerosis. However, the physiological relevance of these findings remains to be further established. In the present study, we have purified endogenous adiponectin from fetal bovine serum and characterized its post‐translational modifications and physiological functions in animal models. Endogenous bovine serum adiponectin consists predominantly of full‐length proteins that form multiple oligomeric complexes, including trimers, hexamers and higher molecular species. Two‐dimensional gel electrophoresis revealed that bovine serum adiponectin exists as multiple post‐translationally modified isoforms with distinct molecular weight and isolectric point. Further analysis using mass spectrometry and Edman degradation sequencing demonstrated that five conserved lysine residues (Lys 28, 60, 63, 72 and 96) within the collagenous domain of bovine adiponectin are hydroxylated and glycosylated by a glucosylα(1–2)galactosyl group. Injection of endogenous bovine adiponectin into C57 mice potently decreased circulating glucose levels and enhanced lipid clearance after a high fat meal. Chronic administration of this protein for a period of two weeks significantly increased insulin sensitivity and glucose tolerance, and depleted hepatic lipid accumulation in high‐fat fed mice. These results provide direct evidence that endogenous bovine adiponectin is a physiological hormone that can regulate lipid and glucose metabolism.
A proteomic approach to cisplatin resistance in the cervix squamous cell carcinoma cell line A431
Authors: Castagna Annalisa , Antonioli Paolo , Astner Hubert , Hamdan Mahmoud , Righetti Sabina Carla , Perego Paola , Zunino Franco , Righetti Pier Giorgio 
Published: August 2004

AbstractSince drug resistance is a complex and multifactorial event involving activation/repression of multiple biochemical pathways, we used a proteomic approach to study cisplatin resistance and drug response in human tumor cell lines. The cervix squamous cell carcinoma cell line A431 and its cisplatin‐resistant subline, A431/Pt, were used as a model system. The experimental set‐up involved not just a two‐way comparison of the control vs. the drug‐resistant cell line, but also an acute cisplatin treatment of both cell lines, leading to a four‐way comparison, as follows: 1) A431 vs. A431/Pt cells; 2) A431 vs. A431 cisplatin exposed cells; 3) A431/Pt vs. A431/Pt cisplatin exposed cells; 4) A431 cisplatin exposed cells vs. A431/Pt cisplatin exposed cells. We found modulation of proteins, which could be classified under various categories, such as molecular chaperones (e.g. heat‐shock proteins HSP60, HSP90, HSC71, heat‐shock cognate 71 kDa protein), Ca2plus;‐binding proteins (e.g. calmodulin, calumenin), proteins involved in drug detoxification (such as peroxiredoxins PRX 2 and PRX 6, and glutathione‐S‐transferase, GST), anti‐apoptotic proteins (such as 14‐3‐3 switched on in cisplatin‐exposed cells) and ion channels (such as VDAC‐1, voltage‐dependent anion‐selective channel). In particular, the basal levels of HSC71 and HSP60 were increased in A431/Pt cells as compared to A431 cells, and cisplatin exposure resulted in up‐regulation of HSP60 and HSP90 only in A431 cells. Moreover, cisplatin exposure up‐regulated the anti‐apoptotic 14‐3‐3 protein in both cell lines, GST in sensitive cells and PRX6 in A431/Pt cells. These findings are consistent with a constitutive expression of defence factors by resistant cells and with activation by cisplatin of mechanisms acting to protect cells from drug‐induced damage. This pattern of response, also observed in parental cells, could reflect an intrinsic resistance of this tumor type.