bluuebunny/crossref_metadata_2025 huggingface dataset:
Distributional Ratings of Performance: More Evidence for a New Rating Format
Authors: Woehr David J. , Miller Michael J.
Published: December 2005

We examined the extent to which performance ratings obtained using a distributional rating format differ from ratings obtained using a more typical global rating scale format. We sought to determine whether a distributional format actually elicits different information than a global format and the extent to which measures of within performance variability derived from distributional ratings are related to levels of interrater agreement on global rating scales. Confirmatory factor analyses of three models of measurement equivalence indicated that a model of tau-equivalence in which the two rating formats provided similar measurements but with differing levels of measurement error provided the best fit to the data. Further, we found a large, significant relationship between measures of within dimension performance variabili5 and interrater agreement. Our results suggest that a distributional rating format is a viable alternative rating format that may provide a richer source of information than do more typical global rating scales.
Quality of the Health Delivery System
Authors: Rameshan P. , Singh Shailendra
Published: December 2005

This case study examines the customer orientation of primary health centres (PHCs) of a district in Uttar Pradesh. Ten PHCs have been studied for this purpose. The study explores input level facilities and human resources available for providing services. Attitude and behviour of doctors and other staff towards customers (patients and attendants of patients) were studied from the perspective of the customers. Similarly, we tried to understand the viewpoints of health officials at district and PHC levels. Customers wanted to improve services of PHCs through panchayat pressure, persuasion and leaders’ intervention. Agitation was the relatively less preferred strategy. They also did not want to passively tolerate poor services at PHCs. Doctors and staff had their own grievances that affected their morale and performance.
Nurses’ Perceptions of their Role in Caring for Diabetic Patients at the Primary Care Level
Authors: Kassean H.K.
Published: December 2005

Despite considerable investment and sustained efforts from the Ministry of Health and Quality of Life (MOHQL) and the National Non-communicable Disease Prevention and Control Programme, the incidence of diabetes in Mauritius remains one of the highest in the world. This study explores the views of nurses on how well they were able to fulfil their role in caring for patients with diabetes at the primary health care level. A phenomenological approach was used for the research and data were collected through a semi-structured interview from 10 participants at five community health care centres. Colaizzi's framework was adopted for data analysis. The findings revealed that the majority of nurses did not feel knowledgeable enough to give effective care to diabetic patients. The following four main themes emerged: management of care, barriers to caring, communication skills, and training and educational needs in diabetes care. Due to the deficit in their level of knowledge in diabetes care and management, nurses admitted not being able to effectively fulfil their role as ‘teacher, coach, manager and supporter’. This study has implications for clinical practice in that appropriate training must be provided to these nurses if significant improvements are to be made in the outcomes.
Integrating Traditional Services within Primary Health Care
Authors: Dalal Ajit K.
Published: December 2005

This article critically reviews the current status of primary health care services in India. It was observed that medical services have primarily relied on Western medicine, and are incompatible with prevailing health beliefs and practices. The failure of Western medicine and, as a consequence, that of primary health care, calls for developing some culturally compatible health care models for India. The traditional health services that have existed for thousands of years and have wide acceptance and application throughout India need to be rejuvenated and integrated within the existing health care programmes. The possibilities of such hybrid services are explored in this article to improve the quality of health and well-being of the masses.
Social and Behavioural Consequences of the Orissa Supercyclone
Authors: Suar Damodar , Kar Suryatapa
Published: December 2005

This article examines the social and behavioural consequences of the Orissa supercyclone. Theory-driven secondary data were analysed at the macro level, covering the period from 1997 to 2001, of the cyclone-affected districts and of the state. The transient consequences were sudden upsurge in infant deaths and admission of psychiatric patients to the state hospital immediately following the disaster. The non-transient consequences were decreasing paddy productivity, fish production, enrolment in primary schools, and increasing loans, consumption of fertilisers, greater numbers of general patients in the state hospital, and increased paan and tobacco consumption that persisted for more than a year.
Medicinal Plants and Primary Health Care
Authors: Singhal Rekha
Published: December 2005

This article aims to uncover gender roles in utilisation and management of medicinal plants for primary health care and community well-being. Men (n = 237) and women (n = 242) from 27 villages with a high concentration of indigenous peoples from central India were included in the study. Methods of mental mapping, process documentation, participatory rural appraisal and focused group discussion were employed to collect data. The results demonstrate that both rural men and women have a wealth of traditional knowledge relating to medicinal uses of plants. They are also aware of interconnections between their well-being and the sustainable use of medicinal plants. Gender role analysis in relation to medicinal plants revealed that the collection, processing, storage and utilisation of medicinal plants are largely assigned to women. Similarly, responsibility of transfer of this knowledge to the future generation is women's domain. However, due to increased recognition of ayurvedic medicine, development of organised markets for medicinal plants, and acute poverty and illiteracy among rural people, sustainable utilisation of medicinal plants are threatened. The findings indicate need to recognise gender roles and incorporate indigenous knowledge, for sustainable medicinal plants management through their involvement in decision-making institutions.
A transforming growth factor–β–induced protein stimulates endocytosis and is up-regulated in immature dendritic cells
Authors: Cao Weiping , Tan Patrick , Lee Chee How , Zhang Haifeng , Lu Jinhua
Published: December 2005

Dendritic cells (DCs) exhibit distinct functional properties at immature and mature states. To identify genes preferentially regulated in monocyte-derived immature DCs (imDCs), 13 000-element microarrays were hybridized with RNA isolated from imDCs, mature DCs (mDCs), monocytes, and macrophages and a TGF-β–induced protein (βig-h3) was identified as being most prominently up-regulated in imDCs. By polymerase chain reaction (PCR), little βig-h3 mRNA was detected in monocytes and macrophages, but it was abundant in imDCs. On DC activation with LPS, βig-h3 mRNA became diminished, and in tissues, βig-h3 mRNA was abundantly expressed in lymphoid-rich tissues such as the spleen, bone marrow, small intestines, and colon. βig-h3 was expressed in 293T cells and purified as a 70-kDa protein and, by Western blotting, βig-h3 was predominantly detected in the medium of imDCs. We demonstrate that βig-h3 binds to macrophages and imDCs but not to mDCs and activates the Rac GTPase in macrophages, stimulating macrophage membrane ruffling and enhancing macrophage endocytosis. imDC endocytosis was also inhibited by purified anti–βig-h3 antibodies. Therefore, βig-h3 appears to be selectively up-regulated in imDCs to regulate antigen uptake through endocytosis.
Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura
Authors: Banno Fumiaki , Kokame Koichi , Okuda Tomohiko , Honda Shigenori , Miyata Shigeki , Kato Hisashi , Tomiyama Yoshiaki , Miyata Toshiyuki
Published: December 2005

ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation through cleavage of von Willebrand factor (VWF) multimers. In humans, genetic or acquired deficiency in ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi. In this study, we report characterization of mice bearing a targeted disruption of the Adamts13 gene. ADAMTS13-deficient mice were born in the expected mendelian distribution; homozygous mice were viable and fertile. Hematologic and histologic analyses failed to detect any evidence of thrombocytopenia, hemolytic anemia, or microvascular thrombosis. However, unusually large VWF multimers were observed in plasma of homozygotes. Thrombus formation on immobilized collagen under flow was significantly elevated in homozygotes in comparison with wild-type mice. Thrombocytopenia was more severely induced in homozygotes than in wild-type mice after intravenous injection of a mixture of collagen and epinephrine. Thus, a complete lack of ADAMTS13 in mice was a prothrombotic state, but it alone was not sufficient to cause TTP-like symptoms. The phenotypic differences of ADAMTS13 deficiencies between humans and mice may reflect differences in hemostatic system functioning in these species. Alternatively, factors in addition to ADAMTS13 deficiency may be necessary for development of TTP.
Thrombopoietin regulates IEX-1 gene expression through ERK-induced AML1 phosphorylation
Authors: Hamelin Virginie , Letourneux Claire , Romeo Paul-Henri , Porteu Françoise , Gaudry Murielle
Published: December 2005

The extracellular signal-regulated kinases (ERKs) are required for thrombopoietin (TPO) functions on hematopoietic cells, but the ERKs targets involved remain unknown. Here we show that the regulation of the immediate early gene X-1 (IEX-1), identified as an ERK substrate in response to TPO, was mediated by an ERK-dependent phosphorylation of AML1. The addition of TPO to UT7-Mpl cells and primary megakaryocytes induced gene expression of IEX-1. Neither erythropoietin (EPO) nor granulocyte macrophage-colony stimulating factor (GM-CSF) was able to activate IEX-1 gene expression in UT7-Mpl cells. The induced expression was mediated by a transcriptional activation of the IEX-1 promoter and required an AML1-binding site located at –1068. The direct involvement of AML1 in the regulation of IEX-1 gene expression was shown by both the use of AML1 mutants and by shRNA experiments targeting endogenous AML1. Finally, the ability of TPO to induce the IEX-1 gene expression was inhibited by U0126, a specific inhibitor of the ERKs activator MEK and AML1 transcriptional activity was shown to be modulated by TPO through ERK-dependent phosphorylation. Taken together, these data suggest that AML1 plays a role in modulating the IEX-1 expression and that the ERK-dependent AML1 phosphorylation regulates the TPO-mediated activation of IEX-1.
Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia
Authors: Stirewalt Derek L. , Kopecky Kenneth J. , Meshinchi Soheil , Engel Julia H. , Pogosova-Agadjanyan Era L. , Linsley Jeremy , Slovak Marilyn L. , Willman Cheryl L. , Radich Jerald P.
Published: December 2005

FLT3 internal tandem duplications (FLT3/ITDs) in the juxtamembrane domain are found in approximately 25% of acute myeloid leukemia (AML) patients, ranging in size from 3 to hundreds of nucleotides. We examined whether the sizes of FLT3/ITDs were associated with clinical outcomes in 151 AML patients enrolled in Southwest Oncology Group studies: S9333 and S9500. FLT3/ITDs were identified in 32% of patients (median ITD size = 39 nucleotides; range, 15-153 nucleotides). The CR rates were 35%, 67%, and 52% for patients with large (≥ 40), small (< 40), and no ITDs, respectively (P = .19). Increasing ITD size was associated with decreasing OS (estimated 5-year OS: large = 13%, small = 26%, and no ITD = 21%, P = .072) and RFS (estimated 5-year RFS: large = 13%, small = 27%, and no ITD = 34%, P = .017). These studies suggest that ITD size may have prognostic significance.
Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD
Authors: Couriel Daniel R. , Hosing Chitra , Saliba Rima , Shpall Elizabeth J. , Anderlini Paolo , Rhodes Beverly , Smith Veronica , Khouri Issa , Giralt Sergio , de Lima Marcos , Hsu Yvonne , Ghosh Shubhra , Neumann Joyce , Andersson Borje , Qazilbash Muzzafar , Hymes Sharon , Kim Stella , Champlin Richard , Donato Michele
Published: December 2005

Chronic graft-versus-host disease (GVHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photochemotherapy (ECP) has been tested extensively in small cohorts of patients with chronic GVHD. In this study, we retrospectively evaluated 71 patients with severe chronic GVHD treated with ECP. Response rate was 61% (n = 43), and 14 patients had complete responses (CRs). The best responses were observed in skin, liver, oral mucosa, and eye. Factors affecting outcomes were assessed in the less heavily pretreated subgroup (n = 63). Thrombocytopenia was associated with a lower response rate (P = .04), and there was a trend toward a higher response rate in de novo chronic GVHD. At 6 months, a total of 27 (69%) of 39 patients who were alive continued to have a sustained response (CR 4 [10%] of 39, and partial response [PR] 23 [59%] of 39). The cumulative incidence of steroid discontinuation at 1 year was 22%. The overall survival since initiation of therapy was 53% at 1 year. Response to ECP and platelet count at initiation of therapy were the strongest predictors of nonrelapse mortality (NRM) on univariate analysis. Objective responses were observed in a substantial number of patients with both skin and visceral chronic GVHD failing corticosteroids and other immunosuppression.
Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: transcriptional silencing, inactivating mutations, and allele loss
Authors: Kaufman Yotam , Ifergan Ilan , Rothem Lilah , Jansen Gerrit , Assaraf Yehuda G.
Published: December 2005

The reduced folate carrier (RFC) is the dominant route for the uptake of various antifolates including PT523, a potent dihydrofolate reductase inhibitor (Ki = 0.35 pM) and an excellent transport substrate of the RFC (Kt = 0.7 μM). Here, we describe the multiple mechanisms of RFC inactivation in human leukemia PT523-resistant cells originally harboring 3 RFC alleles. Cellular exposure to gradually increasing PT523 concentrations resulted in sublines displaying up to 3500-fold resistance to various hydrophilic antifolates that rely on RFC for their cellular uptake. Antifolate-resistant cells lost RFC gene expression (65%-99% loss) due to impaired promoter binding of various transcription factors that regulate RFC gene expression. Additionally, DNA sequencing revealed that PT523-resistant cells contained a cluster of 4 nearly consecutive mutations residing on a single RFC allele including L143P, A147V, R148G, and Q150Stop. Southern blot analysis established the loss of an RFC allele in PT523-resistant cells. These alterations resulted in markedly decreased RFC protein levels (∼80%-99% loss) and consequently impaired [3H]methotrexate transport (87%-99% loss). This study provides the first evidence that acquisition of PT523 resistance in human leukemia cells harboring 3 RFC alleles is due to multiple coexisting alterations including transcriptional silencing, inactivating mutations, and RFC allele loss.
Relevance of human metapneumovirus in exacerbations of COPD
Authors: Rohde G , Borg I , Arinir U , Kronsbein J , Rausse R , Bauer TT , Bufe A , Schultze-Werninghaus G
Published: December 2005

Background and methods

Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.

Results

We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.

Conclusion

HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.
WebArray: an online platform for microarray data analysis
Authors: Xia Xiaoqin , McClelland Michael , Wang Yipeng
Published: December 2005

Background

Many cutting-edge microarray analysis tools and algorithms, including commonly used limma and affy packages in Bioconductor, need sophisticated knowledge of mathematics, statistics and computer skills for implementation. Commercially available software can provide a user-friendly interface at considerable cost. To facilitate the use of these tools for microarray data analysis on an open platform we developed an online microarray data analysis platform, WebArray, for bench biologists to utilize these tools to explore data from single/dual color microarray experiments.

Results

The currently implemented functions were based on limma and affy package from Bioconductor, the spacings LOESS histogram (SPLOSH) method, PCA-assisted normalization method and genome mapping method. WebArray incorporates these packages and provides a user-friendly interface for accessing a wide range of key functions of limma and others, such as spot quality weight, background correction, graphical plotting, normalization, linear modeling, empirical bayes statistical analysis, false discovery rate (FDR) estimation, chromosomal mapping for genome comparison.

Conclusion

WebArray offers a convenient platform for bench biologists to access several cutting-edge microarray data analysis tools. The website is freely available at http://bioinformatics.skcc.org/webarray/. It runs on a Linux server with Apache and MySQL.
Kinetics of cancer: a method to test hypotheses of genetic causation
Authors: Frank Steven A , Chen Peng-Chieh , Lipkin Steven M
Published: December 2005

Background

Mouse studies have recently compared the age-onset patterns of cancer between different genotypes. Genes associated with earlier onset are tentatively assigned a causal role in carcinogenesis. These standard analyses ignore the great amount of information about kinetics contained in age-onset curves. We present a method for analyzing kinetics that measures quantitatively the causal role of candidate genes in cancer progression. We use our method to demonstrate a clear association between somatic mutation rates of different DNA mismatch repair (MMR) genotypes and the kinetics of cancer progression.

Methods

Most experimental studies report age-onset curves as the fraction diagnosed with tumors at each age for each group. We use such data to estimate smoothed survival curves, then measure incidence rates at each age by the slope of the fitted curve divided by the fraction of mice that remain undiagnosed for tumors at that age. With the estimated incidence curves, we compare between different genotypes the median age of cancer onset and the acceleration of cancer, which is the rate of increase in incidence with age.

Results

The direction of change in somatic mutation rate between MMR genotypes predicts the direction of change in the acceleration of cancer onset in all 7 cases (p ˜ 0.008), with the same result for the association between mutation rate and the median age of onset.

Conclusion

Many animal experiments compare qualitatively the onset curves for different genotypes. If such experiments were designed to analyze kinetics, the research could move to the next stage in which the mechanistic consequences of particular genetic pathways are related to the dynamics of carcinogenesis. The data we analyzed here were not collected to test mechanistic and quantitative hypotheses about kinetics. Even so, a simple reanalysis revealed significant insights about how DNA repair genotypes affect separately the age of onset and the acceleration of cancer. Our method of comparing genotypes provides good statistical tests even with small samples for each genotype.
Integrating complementary and alternative medicine into academic medical centers: Experience and perceptions of nine leading centers in North America
Authors: Vohra Sunita , Feldman Kymm , Johnston Brad , Waters Kellie , Boon Heather
Published: December 2005

Background

Patients across North America are using complementary and alternative medicine (CAM) with increasing frequency as part of their management of many different health conditions. The objective of this study was to develop a guide for academic health sciences centers that may wish to consider starting an integrative medicine program.

Methods

We queried North American leaders in the field of integrative medicine to identify initial sites. Key stakeholders at each of the initial sites visited were then asked to identify additional potential study sites (snowball sampling), until no new sites were identified. We conducted structured interviews to identify critical factors associated with success and failure in each of four domains: research, education, clinical care, and administration. During the interviews, field notes were recorded independently by at least two investigators. Team meetings were held after each visit to reach consensus on the information recorded and to ensure that it was as complete as possible. Content analysis techniques were used to identify key themes that emerged from the field notes.

Results

We identified ten leading North American integrative medical centers, and visited nine during 2002–2003. The centers visited suggested that the initiation of an integrative medicine program requires a significant initial outlay of funding and a motivated "champion". The centers had important information to share regarding credentialing, medico-legal issues and billing for clinical programs; identifying researchers and research projects for a successful research program; and strategies for implementing flexible educational initiatives and establishing a functional administrative structure.

Conclusion

Important lessons can be learned from academic integrative programs already in existence. Such initiatives are timely and feasible in a variety of different ways and in a variety of settings.
Hydrogen production by Cyanobacteria
Authors: Dutta Debajyoti , De Debojyoti , Chaudhuri Surabhi , Bhattacharya Sanjoy K
Published: December 2005

The limited fossil fuel prompts the prospecting of various unconventional energy sources to take over the traditional fossil fuel energy source. In this respect the use of hydrogen gas is an attractive alternate source. Attributed by its numerous advantages including those of environmentally clean, efficiency and renew ability, hydrogen gas is considered to be one of the most desired alternate. Cyanobacteria are highly promising microorganism for hydrogen production. In comparison to the traditional ways of hydrogen production (chemical, photoelectrical), Cyanobacterial hydrogen production is commercially viable. This review highlights the basic biology of cynobacterial hydrogen production, strains involved, large-scale hydrogen production and its future prospects. While integrating the existing knowledge and technology, much future improvement and progress is to be done before hydrogen is accepted as a commercial primary energy source.
Intestinal invasion and disseminated disease associated with Penicillium chrysogenum
Authors: Barcus Adrian L , Burdette Steven D , Herchline Thomas E
Published: December 2005

Background

Penicillium sp., other than P. marneffei, is an unusual cause of invasive disease. These organisms are often identified in immunosuppressed patients, either due to human immunodeficiency virus or from immunosuppressant medications post-transplantation. They are a rarely identified cause of infection in immunocompetent hosts.

Case presentation

A 51 year old African-American female presented with an acute abdomen and underwent an exploratory laparotomy which revealed an incarcerated peristomal hernia. Her postoperative course was complicated by severe sepsis syndrome with respiratory failure, hypotension, leukocytosis, and DIC. On postoperative day 9 she was found to have an anastamotic breakdown. Pathology from the second surgery showed transmural ischemic necrosis with angioinvasion of a fungal organism. Fungal blood cultures were positive for Penicillium chrysogenum and the patient completed a 6 week course of amphotericin B lipid complex, followed by an extended course oral intraconazole. She was discharged to a nursing home without evidence of recurrent infection.

Discussion

Penicillium chrysogenum is a rare cause of infection in immunocompetent patients. Diagnosis can be difficult, but Penicillium sp. grows rapidly on routine fungal cultures. Prognosis remains very poor, but aggressive treatment is essential, including surgical debridement and the removal of foci of infection along with the use of amphotericin B. The clinical utility of newer antifungal agents remains to be determined.
Kinetics of hepatitis C virus RNA load during pegylated interferon alpha-2a and ribavirin treatment in naïve genotype 1 patients
Authors: Ouzan Denis , Khiri Hacène , Pénaranda Guillaume , Joly Hélène , Halfon Philippe
Published: December 2005

Background

Pegylated interferon given for 24 or 48 weeks constitutes the most effective initial therapy for the treatment of chronic hepatitis C. It has been shown that viral load at week 2 appears the best time for predicting response to treatment. The objectives of this study were to assess whether the hepatitis C virus (HCV) RNA viral decline is predictive of sustained virological response (SVR) and to determine the best time for predicting complete response in our cohort of naïve patients treated with pegylated interferon alpha-2a (Peg-IFN alpha-2a) and ribavirin.

Results

Twenty patients treated with Peg-IFN alpha-2a and ribavirin for 48 weeks were studied. Six months after the end of treatment, a SVR (negative HCV RNA measured by PCR six months after the end of therapy) was obtained in 9 patients. Samples were obtained before and at week 2, 4, 8, and 12. At the end of week 2, viral load decreased more than 1.39 log in 8 out of the 9 patients with SVR and in 1 out of the 11 other patients. When we considered the viral load reduction from baseline to each week of treatment, week 2 appeared to be the best point time for predicting SVR, with a sensitivity of 91% (95%CI: 59;99), a specificity of 89% (52;98), a positive predictive value of 91% (59;99) and a negative predictive value of 89% (57;98).

Conclusion

During treatment with Peg-IFN alpha-2a plus ribavirin in genotype 1 patients, when the main objective of the treatment is viral eradication, viral kinetics showed that week 2 appeared to be the best time point for predicting SVR. Our results must be further confirmed on a larger cohort.
Targeted infection of HIV-1 Env expressing cells by HIV(CD4/CXCR4) vectors reveals a potential new rationale for HIV-1 mediated down-modulation of CD4
Authors: Ye Zhiping , Harmison George G , Ragheb Jack A , Schubert Manfred
Published: December 2005

Background

Efficient targeted gene transfer and cell type specific transgene expression are important for the safe and effective expression of transgenesin vivo. Enveloped viral vectors allow insertion of exogenous membrane proteins into their envelopes, which could potentially aid in the targeted transduction of specific cell types. Our goal was to specifically target cells that express the T cell tropic HIV-1 envelope protein (Env) using the highly specific interaction of Env with its cellular receptor (CD4) inserted into the envelope of an HIV-1-based viral vector.

Results

To generate HIV-1-based vectors carrying the CD4 molecule in their envelope, the CD4 ectodomain was fused to diverse membrane anchors and inserted together with the HIV-1 coreceptor CXCR4 into the envelopes of HIV-1 vector particles. Independent of the type of CD4 anchor, all chimeric CD4 proteins inserted into HIV-1 vector envelopes and the resultant HIV(CD4/CXCR4) particles were able to selectively confer neomycin resistance to cells expressing the fusogenic T cell tropic HIV-1 Env protein. Unexpectedly, in the absence of Env on the target cells, all vector particles carrying the CD4 ectodomain anchored in their envelope adhered to various cell types without infecting these cells. This cell adhesion was very avid. It was independent of the presence of Env on the target cell, the type of CD4 anchor or the presence of CXCR4 on the particle. In mixed cell populations with defined ratios of Env+/Env-cells, the targeted transduction of Env+cells by HIV(CD4/CXCR4) particles was diminished in proportion to the number of Env-cells.

Conclusion

Vector diversion caused by a strong, non-selective cell binding of CD4+-vector particles effectively prevents the targeted transduction of HIV-1 Env expressing cells in mixed cell populations. This Env-independent cell adhesion severely limits the effective use of targeted HIV(CD4/CXCR4) vectors designed to interfere with HIV-1 replicationin vivo. Importantly, the existence of this newly described and remarkably strong CD4-dependent cell adhesion suggests that the multiple viral efforts to reduce CD4 cell surface expression may, in part, be to prevent cell adhesion to non-target cells and thereby to increase the infectivity of viral progeny. Preventing CD4 down-modulation by HIV-1 might be an effective component of a multi-faceted antiviral strategy.
Transient expression vectors for functional genomics, quantification of promoter activity and RNA silencing in plants
Authors: Hellens Roger P , Allan Andrew C , Friel Ellen N , Bolitho Karen , Grafton Karryn , Templeton Matthew D , Karunairetnam Sakuntala , Gleave Andrew P , Laing William A
Published: December 2005

Background

We describe novel plasmid vectors for transient gene expression using Agrobacterium, infiltrated into Nicotiana benthamiana leaves. We have generated a series of pGreenII cloning vectors that are ideally suited to transient gene expression, by removing elements of conventional binary vectors necessary for stable transformation such as transformation selection genes.

Results

We give an example of expression of heme-thiolate P450 to demonstrate effectiveness of this system. We have also designed vectors that take advantage of a dual luciferase assay system to analyse promoter sequences or post-transcriptional regulation of gene expression. We have demonstrated their utility by co-expression of putative transcription factors and the promoter sequence of potential target genes and show how orthologous promoter sequences respond to these genes. Finally, we have constructed a vector that has allowed us to investigate design features of hairpin constructs related to their ability to initiate RNA silencing, and have used these tools to study cis-regulatory effect of intron-containing gene constructs.

Conclusion

In developing a series of vectors ideally suited to transient expression analysis we have provided a resource that further advances the application of this technology. These minimal vectors are ideally suited to conventional cloning methods and we have used them to demonstrate their flexibility to investigate enzyme activity, transcription regulation and post-transcriptional regulatory processes in transient assays.
Molecular processes during fat cell development revealed by gene expression profiling and functional annotation
Authors: Hackl Hubert , Burkard Thomas Rainer , Sturn Alexander , Rubio Renee , Schleiffer Alexander , Tian Sun , Quackenbush John , Eisenhaber Frank , Trajanoski Zlatko
Published: December 2005

Background

Large-scale transcription profiling of cell models and model organisms can identify novel molecular components involved in fat cell development. Detailed characterization of the sequences of identified gene products has not been done and global mechanisms have not been investigated. We evaluated the extent to which molecular processes can be revealed by expression profiling and functional annotation of genes that are differentially expressed during fat cell development.

Results

Mouse microarrays with more than 27,000 elements were developed, and transcriptional profiles of 3T3-L1 cells (pre-adipocyte cells) were monitored during differentiation. In total, 780 differentially expressed expressed sequence tags (ESTs) were subjected to in-depth bioinformatics analyses. The analysis of 3'-untranslated region sequences from 395 ESTs showed that 71% of the differentially expressed genes could be regulated by microRNAs. A molecular atlas of fat cell development was then constructed by de novo functional annotation on a sequence segment/domain-wise basis of 659 protein sequences, and subsequent mapping onto known pathways, possible cellular roles, and subcellular localizations. Key enzymes in 27 out of 36 investigated metabolic pathways were regulated at the transcriptional level, typically at the rate-limiting steps in these pathways. Also, coexpressed genes rarely shared consensus transcription-factor binding sites, and were typically not clustered in adjacent chromosomal regions, but were instead widely dispersed throughout the genome.

Conclusions

Large-scale transcription profiling in conjunction with sophisticated bioinformatics analyses can provide not only a list of novel players in a particular setting but also a global view on biological processes and molecular networks.
Functional expression of the CD163 scavenger receptor on acute myeloid leukemia cells of monocytic lineage
Authors: Bächli Esther B , Schaer Dominik J , Walter Roland B , Fehr Jörg , Schoedon Gabriele
Published: December 2005

The hemoglobin–haptoglobin (Hb–Hp) scavenger receptor CD163 is a monocyte/macrophage-restricted surface antigen, whose expression is strongly up-regulated by glucocorticoids. We have previously shown that CD163 is expressed by acute myeloid leukemia (AML) cells of monocytic lineage. Herein, we expand this finding by demonstrating constitutive and glucocorticoid-enhanced CD163 expression on French-American-British M4/M5 AML cells, and leukemic blasts of other AML subtypes and normal hematopoietic progenitor cells do not express CD163. We provide evidence that the functional characteristics of CD163 are preserved on malignant cells by showing the capability of types M4/M5 blast cells to internalize Hb–Hp by a CD163-mediated mechanism. Together, our results identify CD163 as a potential target for therapeutic intervention. It is important that CD163 does not appear to be released from leukemic blasts under noninflammatory conditions, thus reducing the probability of off-target side-effects as a result of competitive binding of potential therapeutic ligands to nonmembrane-bound CD163.
Gene expression changes by amyloid β peptide-stimulated human postmortem brain microglia identify activation of multiple inflammatory processes
Authors: Walker Douglas G , Link John , Lue Lih-Fen , Dalsing-Hernandez Jessica E , Boyes Barry E
Published: December 2005

A central feature of the inflammatory pathology in Alzheimer’s disease is activated microglia clustered around aggregated amyloid β (Aβ) peptide-containing plaques. In vitro-cultured microglia can be activated to an inflammatory state by aggregated Aβ with the induction of a range of different neurotoxic factors and provide a model system for studying microglia Aβ interactions. Gene expression responses of human postmortem brain-derived microglia to aggregated Aβ were measured using whole genome microarrays to address the hypothesis that Aβ interactions with human microglia primarily induce proinflammatory genes and not activation of genes involved in Aβ phagocytosis and removal. The results demonstrated that Aβ activation of microglia induced a large alteration in gene transcription including activation of many proinflammatory cytokines and chemokines, most notably, interleukin (IL)-1β, IL-8, and matrix metalloproteinases (MMP), including MMP1, MMP3, MMP9, MMP10, and MMP12. All of these genes could amplify ongoing inflammation, resulting in further neuronal loss. Changes in expression of receptors associated with Aβ phagocytosis did not match the changes in proinflammatory gene expression. Time-course gene expression profiling, along with real-time polymerase chain reaction validation of expression changes, demonstrated an acute phase of gene induction for many proinflammatory genes but also chronic activation for many other potentially toxic products. These chronically activated genes included indoleamine 2,3-dioxygenase and kynureninase, which are involved in formation of the neurotoxin quinolinic acid, and S100A8, a potential proinflammatory chemokine. These studies show that activation of microglia by Aβ induces multiple genes that could be involved in inflammatory responses contributing to neurodegenerative processes.
Dendritic cells during polymicrobial sepsis rapidly mature but fail to initiate a protective Th1-type immune response
Authors: Flohé Stefanie B , Agrawal Hemant , Schmitz Daniel , Gertz Michaela , Flohé Sascha , Schade F Ulrich
Published: December 2005

Polymicrobial sepsis is associated with immunosuppression caused by the predominance of anti-inflammatory mediators and profound loss of lymphocytes through apoptosis. Dendritic cells (DC) are potent antigen-presenting cells and play a key role in T cell activation. We tested the hypothesis that DC are involved in sepsis-mediated immunosuppression in a mouse cecal ligation and puncture (CLP) model, which resembles human polymicrobial sepsis. At different time-points after CLP, DC from the spleen and peripheral lymph nodes were characterized in terms of expression of costimulatory molecules, cytokine synthesis, and subset composition. Splenic DC strongly up-regulated CD86 and CD40 but not CD80 as soon as 8 h after CLP. In contrast, lymph node DC equally increased the expression of CD86, CD40, and CD80. However, this process of maturation occurred later in the lymph nodes than in the spleen. Splenic DC from septic mice were unable to secrete interleukin (IL)-12, even upon stimulation with CpG or lipopolysaccharide + CD40 ligand, but released high levels of IL-10 in comparison to DC from control mice. Neutralization of endogenous IL-10 could not restore IL-12 secretion by DC of septic mice. In addition, the splenic CD4+CD8– and CD4–CD8+ subpopulations were lost during sepsis, and the remaining DC showed a reduced capacity for allogeneic T cell activation associated with decreased IL-2 synthesis. Thus, during sepsis, splenic DC acquire a state of aberrant responsiveness to bacterial stimuli, and two DC subtypes are selectively lost. These changes in DC behavior might contribute to impaired host response against bacteria during sepsis.
Validation of Probabilistic Linkage to Match De‐identified Ambulance Records to a State Trauma Registry
Authors: Newgard Craig D.
Published: December 2005

Objectives:
To validate the accuracy of using probabilistic linkage for matching de‐identified ambulance records to a state trauma registry.

Methods:
This was a retrospective cohort analysis. Three thousand nine hundred nineteen true matches between ambulance and state trauma registry data from 1998 to 2003 were identified by deterministic matching on trauma identification number and verified by human review. Two thousand thirty‐eight ambulance records from trauma patients not meeting criteria for a true match, and an identical number of trauma registry records randomly selected from the one local county served by a different EMS provider, were included as nonmatches. There were 17 variables considered for linkage, which included the following: age, gender, race, county, hospital, date, rural setting, call and arrival times, mechanism, penetrating injury, vital signs, intubation, and intoxication. Probabilistic linkage was used to link the two data sets, using seven different combinations of common variables (maximum, 17; minimum, 4). The sensitivity and specificity of identifying true matches and nonmatches (95% confidence intervals [95% CI]) were calculated for each combination of variables.

Results:
Using all 17 available variables, 3,766 of 3,919 true matches were appropriately linked (sensitivity, 96.1%; 95% CI = 95.4% to 96.7%), with eight mismatches (specificity, 99.6%; 95% CI = 99.2% to 99.8%). Sensitivity fell below 95% with < 15 variables; however, sensitivity was very dependent on the inclusion of variables with high discriminatory power. Specificity remained >98% regardless of the number of variables included.

Conclusions:
Probabilistic linkage is a valid method for matching ambulance records to a trauma registry without the use of patient identifiers; however, the sensitivity of identifying true matches is critically dependent on the number and type of common variables included in the analysis.
Student Evaluations of Twenty-eight Social Psychology Texts
Authors: Stang David J.
Published: December 2005

Text authors write for teachers, it is said, but this study shows a way to obtain consumer assessment while providing a learning experience.
Model for a Non-Credit Lecture Series in Human Sexuality
Authors: Coplin Haskell R.
Published: December 2005

The combination of professional expertise and student-led discussions in a short course leads to a high enrollment, credit course.
Sexual Awareness Training for Counselors
Authors: Landis C. E. , Miller H. R. , Wettstone R. P.
Published: December 2005

An intensive weekend experience focuses on participants' sexual feelings, attitudes, and behavior in preparation for effective counseling.
Predicting Student Ratings of College Teaching from Peer Ratings of Personality Types
Authors: Murray Harry G.
Published: December 2005

Students respond best to a teacher who is friendly, fair, and flexible, if he has definite goals and can take the initiative in class.
The Psychologist's Role in Women's Studies
Authors: Brodsky Annette M.
Published: December 2005

Participation of women psychologists on an interdisciplinary teaching team offers an opportunity to serve psychology as well as the women's movement.
A New Method for Teaching Multiple Regression to Behavioral Science Students
Authors: Williams Richard H.
Published: December 2005

Describing a computing algorithm which promotes intuitive understanding rather than memorization for students in statistics.
Increasing Originality on Essay Examinations in Psychology
Authors: Johnson Donald M.
Published: December 2005

Most teachers would agree that education for original thinking is worthwhile. Two experiments reported here show how it may be accomplished within the class setting.
Inner-City Field Work in Learning Disabilities
Authors: Moffett Patrick S.
Published: December 2005

A program involving college psychology majors in the diagnosis and remediation of specific learning disabilities of children in an East Harlem school.
The Educational Laboratory: Output or Input?
Authors: Graf Eric , Williams David V.
Published: December 2005

A departmental staff has integrated research participation for its majors in a plan based upon a well developed, active-service-system conceptual model.
Systematic Manipulation of Student Pacing, the Perfection Requirement, and Contact with a Teaching Assistant in an Introductory Psychology Course
Authors: Fernald Peter S. , Chiseri Michael J. , Lawson David W. , Scroggs Gayle F. , Riddell Jeanne C.
Published: December 2005

Which of these three major features of PSI is most responsible for its effectiveness? The answer depends in part upon the criterion of effectiveness employed.
Introduction to the Fields of Psychology: A Course Proposal
Authors: Gottlieb Michael C.
Published: December 2005

Describing a course designed to assist in the better preparation of undergraduates for graduate school.
Teaching a Research Methods Course in Developmental Psychology: Some Principles, Methods, and Problems
Authors: Harris Lauren Jay
Published: December 2005

Experimental Child Psychology taught by a teacher who believes that research is fun only if the problems are not too easily solved.
A Survey of the Introductory Course in Psychology
Authors: Irion Arthur L.
Published: December 2005

Forty-three site visits and 193 questionnaires kept this psychologist busy for a sabbatical year and yielded numerous valuable insights.
Bring a Real World Example of Emotional Behavior into the Classroom
Authors: Ware James P.
Published: December 2005

Case History of a Rumor. CBS Reports. 16 mm, 52 minutes, black and white, rental only, $11.05. University of Illinois Visual Aids Service.
A Rare Learning Experience
Authors: Carroll J. Gregory
Published: December 2005

Learning. 30 minutes, color, sound. Sale: $425. Rental: $38. Produced by CRM Educational Films, 1971. Distributed by McGraw-Hill Film Rental Library, Princeton Road, Hightstown, NJ 08520
Teaching Psychology/Religion in the Seventies: Monopoly or Cooperation?
Authors: Vande Kemp Hendrika
Published: December 2005

Does “giving psychology away” also apply to the psychology of religion? This study shows where the courses are taught, who teaches them, and the nature of those courses.
Personality Variables and Beliefs about Psychological Issues
Authors: Steininger Marion , Voegtlin Kathleen
Published: December 2005

Correlation data suggest some interesting implications about students' acceptance or rejection of attitudes toward human nature.
Design and Evaluation of a Personalized Instruction Course in Behavioral Self-Control
Authors: Barrera Manuel , Glasgow Russell E.
Published: December 2005

Self-improvement via a PSI course is not only painless, but is evaluated with high marks by the students.
ESP in the Psychology Curriculum
Authors: McBurney Donald H.
Published: December 2005

The Psychology Staff at Pittsburgh wanted to increase its credibility with the students and achieve the objectives of a liberal arts course.
Some Longitudinal Data on Grading Practices at One University
Authors: Longstreth Langdon E. , Jones Donald
Published: December 2005

Grade inflation appears to be related to two different faculty characteristics on this particular campus, at least.
Incentive Preferences of Introductory Psychology Students
Authors: Bebeau Muriel J. , Eubanks James L. , Sullivan Howard J.
Published: December 2005

Students' expressed evaluations of incentives used to promote learning may not agree with teachers' choices.
Fifteen Years of Teaching General Psychology by Television
Authors: McKinney Fred , Miller David J.
Published: December 2005

A veteran of TV instruction describes how the course was initiated, evaluated, and modified, in order to maintain its success.
Introductory Psychology: Should it be Taught as a General Survey Course?
Authors: Senn David J.
Published: December 2005

A rating study from two institutions indicates that students assess the survey course less favorably than they do the alternative proposed.
An Interdisciplinary Approach to the Introductory Psychology Course
Authors: Levine Robert V.
Published: December 2005

Professors from four departments developed a model for an interdisciplinary student experience where the whole was greater than the sum of its parts.
Assessing the Effectiveness of a Training Program for the University Teaching Assistants
Authors: Carroll J. Gregory
Published: December 2005

An experimental study indicates that trained TAs make more use of objectives and engage in more student-centered teaching than do the non-trained.