bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung cancer cell lines
Authors: Plummer Howard K , Dhar Madhu S , Cekanova Maria , Schuller Hildegard M 
Published: August 2005

Abstract

Background
Previous data from our laboratory has indicated that there is a functional link between the β-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer.

Methods
GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU) assay.

Results
GIRK1 mRNA was expressed in three of six small cell lung cancer (SCLC) cell lines, and either GIRK2, 3 or 4 mRNA expression was detected in all six SCLC cell lines. Treatment of NCI-H69 with β2-adrenergic antagonist ICI 118,551 (100 μM) daily for seven days led to slight decreases of GIRK1 mRNA expression levels. Treatment of NCI-H69 with the β-adrenergic agonist isoproterenol (10 μM) decreased growth rates in these cells. The GIRK inhibitor U50488H (2 μM) also inhibited proliferation, and this decrease was potentiated by isoproterenol. In the SCLC cell lines that demonstrated GIRK1 mRNA expression, we also saw GIRK1 protein expression. We feel these may be important regulatory pathways since no expression of mRNA of the GIRK channels (1 & 2) was found in hamster pulmonary neuroendocrine cells, a suggested cell of origin for SCLC, nor was GIRK1 or 2 expression found in human small airway epithelial cells. GIRK (1,2,3,4) mRNA expression was also seen in A549 adenocarcinoma and NCI-H727 carcinoid cell lines. GIRK1 mRNA expression was not found in tissue samples from adenocarcinoma or squamous cancer patients, nor was it found in NCI-H322 or NCI-H441 adenocarcinoma cell lines. GIRK (1,3,4) mRNA expression was seen in three squamous cell lines, GIRK2 was only expressed in one squamous cell line. However, GIRK1 protein expression was not seen in any non-SCLC cells.

Conclusion
We feel that this data may indicate that stimulation of GIRK1 or GIRK2 channels may be important in lung cancer. Stimulation of GIRK channels and β-adrenergic signaling may activate similar signaling pathways in both SCLC and breast cancer, but lead to different results.
Computational identification of residues that modulate voltage sensitivity of voltage-gated potassium channels
Authors: Li Bin , Gallin Warren J 
Published: August 2005

Abstract

Background
Studies of the structure-function relationship in proteins for which no 3D structure is available are often based on inspection of multiple sequence alignments. Many functionally important residues of proteins can be identified because they are conserved during evolution. However, residues that vary can also be critically important if their variation is responsible for diversity of protein function and improved phenotypes. If too few sequences are studied, the support for hypotheses on the role of a given residue will be weak, but analysis of large multiple alignments is too complex for simple inspection. When a large body of sequence and functional data are available for a protein family, mature data mining tools, such as machine learning, can be applied to extract information more easily, sensitively and reliably. We have undertaken such an analysis of voltage-gated potassium channels, a transmembrane protein family whose members play indispensable roles in electrically excitable cells.

Results
We applied different learning algorithms, combined in various implementations, to obtain a model that predicts the half activation voltage of a voltage-gated potassium channel based on its amino acid sequence. The best result was obtained with a k-nearest neighbor classifier combined with a wrapper algorithm for feature selection, producing a mean absolute error of prediction of 7.0 mV. The predictor was validated by permutation test and evaluation of independent experimental data. Feature selection identified a number of residues that are predicted to be involved in the voltage sensitive conformation changes; these residues are good target candidates for mutagenesis analysis.

Conclusion
Machine learning analysis can identify new testable hypotheses about the structure/function relationship in the voltage-gated potassium channel family. This approach should be applicable to any protein family if the number of training examples and the sequence diversity of the training set that are necessary for robust prediction are empirically validated. The predictor and datasets can be found at the VKCDB web site [1].
Handheld computers and the 21st century surgical team: a pilot study
Authors: Aziz Omer , Panesar Sukhmeet S , Netuveli Gopalakrishnan , Paraskeva Paraskevas , Sheikh Aziz , Darzi Ara 
Published: August 2005

Abstract
Background
The commercial development and expansion of mobile phone networks has led to the creation of devices combining mobile phones and personal digital assistants, which could prove invaluable in a clinical setting. This pilot study aimed to look at how one such device compared with the current pager system in facilitating inter-professional communication in a hospital clinical team.

Methods
The study looked at a heterogeneous team of doctors (n = 9) working in a busy surgical setting at St. Mary's Hospital in London and compared the use of a personal digital assistant with mobile phone and web-browsing facilities to the existing pager system. The primary feature of this device being compared to the conventional pager was its use as a mobile phone, but other features evaluated included the ability to access the internet, and reference data on the device. A crossover study was carried out for 6 weeks in 2004, with the team having access to the personal digital assistant every alternate week. The primary outcome measure for assessing efficiency of communication was the length of time it took for clinicians to respond to a call. We also sought to assess the ease of adoption of new technology by evaluating the perceptions of the team (n = 9) to personal digital assistants, by administering a questionnaire.

Results
Doctors equipped with a personal digital assistant rather than a pager, responded more quickly to a call and had a lower of failure to respond rate (RR: 0.44; 95%CI 0.20–0.93). Clinicians also found this technology easy to adopt as seen by a significant reduction in perceptions of nervousness to the technology over the six-week study period (mean (SD) week 1: 4.10 (SD 1.69) vs. mean (SD) week 6: 2.20 (1.99); p = 0.04).

Conclusion
The results of this pilot study show the possible effects of replacing the current hospital pager with a newer, more technologically advanced device, and suggest that a combined personal digital assistant and mobile phone device may improve communication between doctors. In the light of these encouraging preliminary findings, we propose a large-scale clinical trial of the use of these devices in facilitating inter-professional communication in a hospital setting.
Contemporary specificities of labour in the health care sector: introductory notes for discussion
Authors: Campos Francisco Eduardo , da Motta e Albuquerque Eduardo 
Published: August 2005

Abstract
Background
This paper combines the literature on public health, on economics of health and on economics of technological innovation to discuss the peculiarities of labour in the health care sector.

Method and framework
The starting point is the investigation of the economic peculiarities of medical care.

Results and discussions
This investigation leads to the identification of the prevalence of non-market forms of medical care in the countries of the Organisation for Economic Co-operation and Development (OECD). Furthermore, the health care system has a distinctive characteristic from other economic sectors: it is the intersection between social welfare and innovation systems. The relationship between technological innovation and cost in the health care sector is surveyed. Finally, the Brazilian case is discussed as an example of a developing country.

Conclusion
The peculiarities of labour in the health care sector suggest the need to recognize the worth of sectoral labour and to cease to treat it separately. This process should take into account the rapid development of the health innovation system and one important consequence: the obsolescence of the acquired knowledge. One way to dignify labour is to implement continued education and training of health professions personnel.
Evidence that spontaneous reactivation of herpes virus does not occur in mice
Authors: Gebhardt Bryan M , Halford William P 
Published: August 2005

AbstractBackgroundSome species, including humans and rabbits, exhibit periodic viral reactivation and shed infectious virus at the infected end organ. Mice may be an exception, because spontaneous shedding of infectious virus rarely, if ever, occurs. However, spontaneous molecular reactivation,i.e., the expression of a few viral genes and the synthesis of the viral glycoproteins coded for by these genes, has been reported. This finding has prompted the assumption that molecular reactivation is an indicator of reactivation and the production of infectious virus. The goal of this study was to differentiate between viral gene expression during latency and the episodic production of infectious virus in mice.ResultsViral reactivation and infection were not seen in herpes simplex virus type 1 (HSV-1) latent ganglion graft recipient BALB/c scid or immunocompetent BALB/c mice, which survived the 65-day observation period with no evidence of viral infection although the immunocompetent mice developed cellular and humoral immunity to HSV-1. In contrast, BALB/c scid recipients of ganglia containing reactivating virus invariably developed a local and, subsequently, systemic viral infection and died within 14 days. Immunocompetent BALB/c mice that received ganglion grafts containing reactivating virus survived the infection and became immune to the virus. Trigeminal ganglia removed from scid and immunocompetent recipient graft sites 5, 14, and 28 days after transplantation contained latent virus and viable neurons.ConclusionThe results suggest that, within the limits of detection of the experiments, spontaneous episodic production of immunogenic viral antigens but not of infectious virus occurs in mouse neural ganglia during latency.
Matrix attachment regions as targets for retroviral integration
Authors: Johnson Chassidy N , Levy Laura S 
Published: August 2005

Abstract

Background
The randomness of retroviral integration has been debated for many years. Recent evidence indicates that integration site selection is not random, and that it is influenced by both viral and cellular factors. To study the role of DNA structure in site selection, retroviral integration near matrix attachment regions (MARs) was analyzed for three different groups of retroviruses. The objective was to assess whether integration near MARs may be a factor for integration site selection.

Results
Results indicated that MLV, SL3-3 MuLV, HIV-1 and HTLV-1 integrate preferentially near MARs, specifically within 2-kilobases (kb). In addition, a preferential position and orientation relative to the adjacent MAR was observed for each virus. Further analysis of SL3-3 MuLV insertions in common integration sites (CISs) demonstrated a higher frequency of integration near MARs and an orientation preference that was not observed for integrations outside CISs.

Conclusion
These findings contribute to a growing body of evidence indicating that retroviral integration is not random, that MARs influence integration site selection for some retroviruses, and that integration near MARs may have a role in the insertional activation of oncogenes by gammaretroviruses.
Medication errors: a prospective cohort study of hand-written and computerised physician order entry in the intensive care unit
Authors: Shulman Rob , Singer Mervyn , Goldstone John , Bellingan Geoff 
Published: August 2005

Abstract
Introduction
The study aimed to compare the impact of computerised physician order entry (CPOE) without decision support with hand-written prescribing (HWP) on the frequency, type and outcome of medication errors (MEs) in the intensive care unit.

Methods
Details of MEs were collected before, and at several time points after, the change from HWP to CPOE. The study was conducted in a London teaching hospital's 22-bedded general ICU. The sampling periods were 28 weeks before and 2, 10, 25 and 37 weeks after introduction of CPOE. The unit pharmacist prospectively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods, during the course of his normal chart review.

Results
The total proportion of MEs was significantly lower with CPOE (117 errors from 2429 prescriptions, 4.8%) than with HWP (69 errors from 1036 prescriptions, 6.7%) (p < 0.04). The proportion of errors reduced with time following the introduction of CPOE (p < 0.001). Two errors with CPOE led to patient harm requiring an increase in length of stay and, if administered, three prescriptions with CPOE could potentially have led to permanent harm or death. Differences in the types of error between systems were noted. There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined (p = 0.01). The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods (19.4 versus 20.0, respectively, p = 0.71).

Conclusion
Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score (if intercepted errors were included). Moderate and major errors, however, remain a significant concern with CPOE.
Use of Molecular Tumor Characteristics to Prioritize Mismatch Repair Gene Testing in Early-Onset Colorectal Cancer
Authors: Southey Melissa C. , Jenkins Mark A. , Mead Leeanne , Whitty Jonathan , Trivett Melanie , Tesoriero Andrea A. , Smith Letitia D. , Jennings Kim , Grubb Garry , Royce Simon G. , Walsh Michael D. , Barker Melissa A. , Young Joanne P. , Jass Jeremy R. , St John D. James B. , Macrae Finlay A. , Giles Graham G. , Hopper John L. 
Published: August 2005

PurposeThe relationships between mismatch repair (MMR) protein expression, microsatellite instability (MSI), family history, and germline MMR gene mutation status have not been studied on a population basis.MethodsWe studied 131 unselected patients with colorectal cancer diagnosed younger than age 45 years. For the 105 available tumors, MLH1, MSH2, MSH6, and PMS2 protein expression using immunohistochemistry (IHC) and MSI were measured. Germline DNA was screened for hMLH1, hMSH2, hMSH6, and hPMS2 mutations for the following patients: all from families fulfilling the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer (HNPCC); all with tumors that were high MSI, low MSI, or that lacked expression of any MMR protein; and a random sample of 23 with MS-stable tumors expressing all MMR proteins.ResultsGermline mutations were found in 18 patients (nine hMLH1, four hMSH2, four hMSH6, and one hPMS2); all tumors exhibited loss of MMR protein expression, all but one were high MSI or low MSI, and nine were from a family fulfilling Amsterdam Criteria. Sensitivities of IHC testing, MSI (high or low), and Amsterdam Criteria for MMR gene mutation were 100%, 94%, and 50%, respectively. Corresponding positive predictive values were 69%, 50%, and 75%.ConclusionsTumor IHC analysis of four MMR proteins and MSI testing provide a highly sensitive strategy for identifying MMR gene mutation–carrying, early-onset colorectal cancer patients, half of whom would have been missed using Amsterdam Criteria alone. Tumor-based approaches for triaging early-onset colorectal cancer patients for MMR gene mutation testing, irrespective of family history, appear to be an efficient screening strategy for HNPCC.
Evidence for an Age Cutoff Greater Than 365 Days for Neuroblastoma Risk Group Stratification in the Children's Oncology Group
Authors: London W.B. , Castleberry R.P. , Matthay K.K. , Look A.T. , Seeger R.C. , Shimada H. , Thorner P. , Brodeur G. , Maris J.M. , Reynolds C.P. , Cohn S.L. 
Published: August 2005

Purpose In the Children's Oncology Group, risk group assignment for neuroblastoma is critical for therapeutic decisions, and patients are stratified by International Neuroblastoma Staging System stage, MYCN status, ploidy, Shimada histopathology, and diagnosis age. Age less than 365 days has been associated with favorable outcome, but recent studies suggest that older age cutoff may improve prognostic precision. Methods To identify the optimal age cutoff, we retrospectively analyzed data from the Pediatric Oncology Group biology study 9047 and Children's Cancer Group studies 321p1-p4, 3881, 3891, and B973 on 3,666 patients (1986 to 2001) with documented ages and follow-up data. Twenty-seven separate analyses, one for each different age cutoff (adjusting for MYCN and stage), tested age influence on outcome. The cutoff that maximized outcome difference between younger and older patients was selected. Results Thirty-seven percent of patients were younger than 365 days, and 64% were ≥ 365 days old (4-year event-free survival [EFS] rate ± SE: 83% ± 1% [n = 1,339] and 45% ± 1% [n = 2,327], respectively; P < .0001). Graphical analyses revealed the continuous nature of the prognostic contribution of age to outcome. The optimal 460-day cutoff we selected maximized the outcome difference between younger and older patients. Forty-three percent were younger than 460 days, and 57% were ≥ 460 days old (4-year EFS rate ± SE: 82% ± 1% [n = 1,589] and 42% ± 1% [n = 2,077], respectively; P < .0001). Using a 460-day cutoff (assuming stage 4, MYCN-amplified patients remain high-risk), 5% of patients (365 to 460 days: 4-year EFS 92% ± 3%; n = 135) fell into a lower risk group. Conclusion The prognostic contribution of age to outcome is continuous in nature. Within clinically relevant risk stratification, statistical support exists for an age cutoff of 460 days.
Patients' Perceptions of Quality of Care for Colorectal Cancer by Race, Ethnicity, and Language
Authors: Ayanian John Z. , Zaslavsky Alan M. , Guadagnoli Edward , Fuchs Charles S. , Yost Kathleen J. , Creech Cynthia M. , Cress Rosemary D. , O'Connor Lilia C. , West Dee W. , Wright William E. 
Published: August 2005

Purpose To identify opportunities for improving care, we evaluated patients' perceptions of the quality of their cancer care by race, ethnicity, and language. Patients and Methods We surveyed a population-based cohort of 1,067 patients with colorectal cancer in northern California approximately 9 months after diagnosis. Adjusting for clinical and demographic factors, mean problem scores were analyzed on a 100-point scale for six domains of care. Results Mean problem scores were highest for health information (47.8), followed by treatment information (32.3), psychosocial care (31.7), coordination of care (21.3), confidence in providers (13.1), and access to cancer care (12.7). In adjusted comparisons with white patients, African American patients reported more problems with coordination of care (difference, 9.8; P < .001), psychosocial care (difference, 7.2; P = .03), access to care (difference, 6.6; P = .03), and health information (difference, 12.5; P < .001). Asian/Pacific Islander patients reported more problems than did white patients with coordination of care (difference, 13.2; P < .001), access to care (difference, 15.5; P < .001), and health information (difference, 12.6; P = .004). Hispanic patients tended to report more problems with coordination of care (difference, 4.4; P = .06), access to care (difference, 5.8; P = .08), and treatment information (difference, 7.0; P = .06). Non–English-speaking white patients reported more problems than other white patients with coordination of care (difference, 21.9; P < .001), psychosocial care (difference, 16.1; P = .009), access to care (difference, 19.8; P = .003), and treatment information (difference, 17.8; P = .002). Non–English-speaking Hispanic patients reported more problems than other Hispanic patients with confidence in providers (difference, 16.9; P = .01). Conclusion Efforts to improve patients' experiences with cancer care should address disparities by race, ethnicity, and language, particularly in coordination of care, access to care, and the provision of relevant information.
Peer-Delivered Smoking Counseling for Childhood Cancer Survivors Increases Rate of Cessation: The Partnership for Health Study
Authors: Emmons Karen M. , Puleo Elaine , Park Elyse , Gritz Ellen R. , Butterfield Rita M. , Weeks Jane C. , Mertens Ann , Li Frederick P. 
Published: August 2005

PurposeCancer survivors smoke at rates that are only slightly lower than the general population. This article reports on the final outcomes of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study (CCSS).MethodsThis study is a randomized control trial with follow-up at 8 and 12 months that involved smokers (n = 796) enrolled onto the CCSS cohort. Participants were randomly assigned to either a self-help or a peer-counseling program that included up to six telephone calls from a trained childhood cancer survivor, tailored and targeted materials, and free nicotine replacement therapy. The intervention was delivered by telephone and postal service mail.ResultsThe quit rate was significantly higher in the counseling group compared with the self-help group at both the 8-month (16.8% v 8.5%; P < .01) and 12-month follow-ups (15% v 9%; P ≤ .01). Controlling for baseline self-efficacy and readiness to change, the intervention group was twice as likely to quit smoking, compared with the self-help group. Smoking cessation rate increased with an increase in the number of counseling calls. The cost of delivering the intervention was approximately $300 per participant. The incremental cost-effectiveness of the intervention compared with controls was $5,371 per additional quit.ConclusionInterventions to prevent future illnesses are of critical importance to childhood cancer survivors. The Partnership for Health intervention resulted in a doubling of smoking cessation quit rates. Because of the seriousness of smoking among childhood cancer survivors, this intervention model may be appropriate as a multicomponent treatment program for survivors who smoke.
Patientennahe Bestimmung natriuretischer Peptide Near-patient testing of natriuretic peptides
Authors: Peetz Dirk , Hafner Gerd , Lackner Karl J. 
Published: August 2005

Zusammenfassung
Die B-Typ natriuretischen Peptide (BNP und NT-proBNP) haben sich in den letzten Jahren als neue, zuverlässige Labormarker der chronischen Herzinsuffizienz etabliert. Weitere in jüngster Zeit untersuchte Indikationsgebiete für BNP/NT-proBNP sind: Differentialdiagnose der akuten Dyspnoe, linksventrikuläre Hypertrophie, linksventrikuläre diastolische Dysfunktion, Vorhofflimmern, Herzklappenerkrankungen, die Therapiesteuerung bei Behandlung herzinsuffizienter Patienten sowie die Prognoseabschätzung bei Herzinsuffizienz und nach einem akuten Myokardinfarkt. Es existieren jedoch keine Daten, welche die Bestimmung von BNP- oder NT-proBNP unter speziellen Fragestellungen der patientennahen Testung untersuchen. In der vorliegenden Arbeit soll daher ein Überblick über die physiologischen und pathophysiologischen Grundlagen der Bestimmung natriuretischer Peptide, die analytischen Aspekte und verfügbaren Testsysteme sowie über vorhandene ökonomische Daten gegeben werden; diese sollen jeweils in Hinblick auf eine patientennahe Diagnostik beleuchtet werden.