tbuckley/cabot-search huggingface dataset:
Chronic Arm Morbidity After Curative Breast Cancer Treatment: Prevalence and Impact on Quality of Life
Authors: Winkle Kwan, Jeremy Jackson, Lorna M. Weir, Carol Dingee, Greg McGregor, Ivo A. Olivotto
Journal: Journal of Clinical Oncology (2002)

To determine the prevalence of and contributing factors for chronic arm morbidity including lymphedema in breast cancer patients after treatment and to assess the impact of arm morbidity on quality of life (QOL).A four-question screening questionnaire was developed and mailed to a random sample of 744 breast cancer patients treated curatively in two cancer centers from 1993 to 1997. Patients were without recurrence and at least 2 years from diagnosis. Respondents were classified as with or without arm-related symptoms on the basis of the survey. Stratified random samples from each group were then invited for a detailed assessment of their symptoms and signs, including the presence of lymphedema. Their QOL was assessed by the European Organization for Research and Treatment of Cancer QOL Questionnaire C-30 and by a detailed arm problem questionnaire that assessed various aspects of daily arm functioning.Approximately half of all screened patients were symptomatic and 12.5% of all assessed patients had lymphedema. Axillary dissection (AD) and axillary radiotherapy (RT) after dissection were statistically significantly related to the occurrence of arm symptoms (odds ratio for AD = 3.3, P <.001; odds ratio for RT = 3.1, P <.001). Symptomatic patients and patients with lymphedema both had impaired QOL compared with asymptomatic patients.Treatment for breast cancer is associated with considerable arm morbidity, which has a negative impact on QOL. Arm morbidity should be carefully monitored in future studies involving local treatment modalities for breast cancer.
PET-CT in lung cancer: data discrepancies
Authors: J. M. Paredes, J. Mehta
Journal: Thorax (2011)

The Danish study of positron emission tomography (PET)–CT versus conventional staging (CS) in non-small cell lung cancer has been reported twice now1 2 and corrected once.3

However, there are discrepancies in numbers between the manuscripts,1 2 which is surprising given the …
L-arginine-dependent nitric oxide synthase: a new metabolic pathway in the lung and airways
Authors: PG Jorens, PA Vermeire, AG Herman
Journal: European Respiratory Journal (1993)

An L-arginine-dependent pathway, metabolising L-arginine to citrulline and nitrogen oxides, has been described in many cell types in different species, including man. Two subtypes of this nitric oxide synthase have been reported: a constitutive enzyme type, releasing nitric oxide after stimulation, is typically found in endothelial and neural cells; another subtype can be induced in macrophages after cytokine treatment. This review summarizes the literature on the known and proposed roles of this L-arginine-dependent nitric oxide production in different pulmonary processes. Nitric oxide has been reported to act as a neurotransmitter in the inhibitory nonadrenergic, noncholinergic nerves in the airways of guinea-pig and man. It is released in cytostatic processes by immune-stimulated alveolar macrophages. Recent data on the role of L-arginine-dependent processes in immune-complex-mediated lung injury, histamine-induced activation of guanylate cyclase or cytokine networks in the lung are also discussed. Finally, similarities and differences between tracheal epithelium-derived relaxing factor and nitric oxide are analysed. The details of the role and distribution of nitric oxide synthase in the (human) lung and airways are not yet completely understood. Nitric oxide is believed to play a role in various pulmonary physiological processes, such as bronchodilation and the cytotoxic action of certain cells. The modulation of nitric oxide release will therefore, most probably lead to application of novel therapies in diseases such as asthma and inflammatory pulmonary diseases.
Activated liver dendritic cells generate strong acquired immunity in α-galactosylceramide treatment
Authors: Akira Sasakawa, Tomohide Tatsumi, Tetsuo Takehara, Shinjiro Yamaguchi, Masashi Yamamoto, Kazuyoshi Ohkawa, Takuya Miyagi, Norio Hayashi
Journal: Journal of Hepatology (2009)
Emerging Antimicrobial Resistance in <i>Neisseria gonorrhoeae</i>: Urgent Need to Strengthen Prevention Strategies
Authors: Kimberly A. Workowski, Stuart M. Berman, John M. Douglas
Journal: Annals of Internal Medicine (2008)

Prevention and control of gonorrhea is an important public health concern due to the high burden of disease, the recent increase in reported infection rates, and the reproductive and economic consequences of infection. Effective antibiotic treatment is one essential component of an integrated approach to gonorrhea control. Over the past 60 years, however, development of resistance in Neisseria gonorrhoeae to multiple antimicrobial classes challenges this component of gonorrhea control. An integrated, comprehensive prevention strategy should include enhancement of national and international surveillance systems to monitor antimicrobial resistance and new strategies to maximize the benefit and prolong the utility of antimicrobials, including combination regimens, implementation of screening recommendations for individuals at high risk for infection, and the assurance of prompt and effective treatment for infected persons and their sexual partners. Progress in controlling the epidemic and avoiding a resurgence as treatment options wane will require careful attention to all components of a comprehensive prevention strategy.
Major Effect on Susceptibility to Urethan-lnduced Pulmonary Adenoma by a Single Gene in BALB/cBy Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A M Malkinson, D S Beer
Journal: JNCI Journal of the National Cancer Institute (1983)

Fewer lung adenomas were induced by urethan in BALB/cBy mice than in the A/J or SWR/J mouse strains. When BALB mice were crossed with either of these more sensitive strains the response of the progeny to urethan was most easily explained by a single gene which regulates susceptibility, with the more resistant phenotype behaving as a dominant trait. C56BL/6J mice were more resistant to adenoma induction than were BALB mice; progeny obtained when these two strains were crossed resembled the BALB susceptibility phenotype. As an approach to understanding the mechanism of action of this gene, agents that modulate adenoma initiation and tumor promotion were tested in BALB mice and other strains. The number of adenomas in BALB mice were increased severalfold by multiple urethan injections, which presumably affect initiation, and by the use of butylated o-hydroxytoulene as a promoting agent. Tumor incidence in A-mice was increased 50% by each treatment; neither procedure caused tumors to appear in the resistant DBA/2J, C3H/-21BG, or C57BL/6J strains. No relationship was observed between the strain dependency of the lethal effects of multiple injections of these agents and the relative susceptibilities of these strains to adenoma induction. The role of certain host factors in the regulation of tumor susceptibility was also tested. Homozygosity for the beige (bg) mutation had no effect on tumor numbers in C57 mice, suggesting that natural killer cells, deficient in bg/bg mice, played no major role in determining adenoma susceptibility in this strain. No correlation was found between the susceptibility of various sublines to urethan-induced lung adenoma and the reported relative tumoricidal capacities of the peritoneal macrophages from these sublines.
THE ULTRASTRUCTURE OF HUMAN THYROGLOBULIN
Authors: B. Bloth, R. Bergquist
Journal: The Journal of Experimental Medicine (1968)

Thyroglobulin molecules purified in a single step procedure by gel filtration were studied in the electron microscope using the negative staining technique. The molecule had the shape of a flexible helix with two turns. Its length was about 220 A and the maximal diameter of the coiled part of the molecule was estimated to be 110 A. The pitch varied between 40 and 50 A. Thyroglobulin molecules dried in sodium tungstosilicate on a carbon film as for electron microscopy retained their hemagglutination-inhibiting activity and 19S sedimentation constant when redissolved in physiological buffer.
Policy Dilemmas in Latino Health Care and Implementation of the Affordable Care Act
Authors: Alexander N. Ortega, Hector P. Rodriguez, Arturo Vargas Bustamante
Journal: Annual Review of Public Health (2015)

The changing Latino demographic in the United States presents a number of challenges to health care policy makers, clinicians, organizations, and other stakeholders. Studies have demonstrated that Latinos tend to have worse patterns of access to, and utilization of, health care than other ethnic and racial groups. The implementation of the Affordable Care Act (ACA) of 2010 may ameliorate some of these disparities. However, even with the ACA, it is expected that Latinos will continue to have problems accessing and using high-quality health care, especially in states that are not expanding Medicaid eligibility as provided by the ACA. We identify four current policy dilemmas relevant to Latinos' health and ACA implementation: (a) the need to extend coverage to the undocumented; (b) the growth of Latino populations in states with limited insurance expansion; (c) demands on public and private systems of care; and (d) the need to increase the number of Latino physicians while increasing the direct patient-care responsibilities of nonphysician Latino health care workers.
Within the fold: assessing differential expression measures and reproducibility in microarray assays
Authors: Ivana V Yang, Emily Chen, Jeremy P Hasseman, Wei Liang, Bryan C Frank, Shuibang Wang, Vasily Sharov, Alexander I Saeed, Joseph White, Jerry Li, Norman H Lee, Timothy J Yeatman, John Quackenbush
Journal: Genome biology (2002)

'Fold-change' cutoffs have been widely used in microarray assays to identify genes that are differentially expressed between query and reference samples. More accurate measures of differential expression and effective data-normalization strategies are required to identify high-confidence sets of genes with biologically meaningful changes in transcription. Further, the analysis of a large number of expression profiles is facilitated by a common reference sample, the construction of which must be carefully addressed. We carried out a series of 'self-self' hybridizations in which aliquots of the same RNA sample were labeled separately with Cy3 and Cy5 fluorescent dyes and co-hybridized to the same microarray. From this, we can analyze the intensity-dependent behavior of microarray data, define a statistically significant measure of differential expression that exploits the structure of the fluorescent signals, and measure the inherent reproducibility of the technique. We also devised a simple procedure for identifying and eliminating low-quality data for replicates within and between slides. We examine the properties required of a universal reference RNA sample and show how pooling a small number of samples with a diverse representation of expressed genes can outperform more complex mixtures as a reference sample. Analysis of cell-line samples can identify systematic structure in measured gene-expression levels. A general procedure for analyzing cDNA microarray data is proposed and validated. We show that pooled reference samples should be based not only on the expression of individual genes in each cell line but also on the expression levels of genes within cell lines.
Genome adaptation to chemical stress: clues from comparative transcriptomics in Saccharomyces cerevisiae and Candida glabrata
Authors: Gaëlle Lelandais, Véronique Tanty, Colette Geneix, Catherine Etchebest, Claude Jacq, Frédéric Devaux
Journal: Genome biology (2008)

Recent technical and methodological advances have placed microbial models at the forefront of evolutionary and environmental genomics. To better understand the logic of genetic network evolution, we combined comparative transcriptomics, a differential clustering algorithm and promoter analyses in a study of the evolution of transcriptional networks responding to an antifungal agent in two yeast species: the free-living model organism Saccharomyces cerevisiae and the human pathogen Candida glabrata.We found that although the gene expression patterns characterizing the response to drugs were remarkably conserved between the two species, part of the underlying regulatory networks differed. In particular, the roles of the oxidative stress response transcription factors ScYap1p (in S. cerevisiae) and Cgap1p (in C. glabrata) had diverged. The sets of genes whose benomyl response depends on these factors are significantly different. Also, the DNA motifs targeted by ScYap1p and Cgap1p are differently represented in the promoters of these genes, suggesting that the DNA binding properties of the two proteins are slightly different. Experimental assays of ScYap1p and Cgap1p activities in vivo were in accordance with this last observation.Based on these results and recently published data, we suggest that the robustness of environmental stress responses among related species contrasts with the rapid evolution of regulatory sequences, and depends on both the coevolution of transcription factor binding properties and the versatility of regulatory associations within transcriptional networks.
Prospective evaluation of hydrocortisone and suramin in patients with androgen-independent prostate cancer.
Authors: W K Kelly, T Curley, C Leibretz, A Dnistrian, M Schwartz, H I Scher
Journal: Journal of Clinical Oncology (1995)

To assess efficacy of intermittent infusion of suramin in patients with androgen-independent prostate cancer who have had disease progression on hydrocortisone.Chemotherapy-naive patients with progressive androgen-independent prostate cancer were given hydrocortisone 40 mg/d and monitored for treatment effect. At the time of disease progression, suramin was administered on a pharmacokinetically derived, 2-week dosing schedule.Thirty patients with a median Karnofsky performance status (KPS) of 90% were treated with hydrocortisone. No responses were seen in 12 patients with measurable disease or 29 patients with abnormal bone scans. Thirty patients had an increasing prostate-specific antigen (PSA) level before treatment and six (20%) had a more than 50% decline in PSA from the baseline value for a median of 16 weeks (range, 12 to 52+). Twenty-eight patients had disease progression after a median of 7 weeks (range, 3 to 23), and two patients have continued to receive hydrocortisone for 44 and 52 weeks. Twenty-eight patients received hydrocortisone and suramin, with median suramin concentrations of 97 to 170 micrograms/mL for 4 weeks. No responses in measurable disease and no improvements in bone scans were seen. Five patients (18%) showed a more than 50% decline in PSA levels from baseline, of whom three had previously responded to hydrocortisone. Only two of 24 patients who did not show a posttherapy decline in PSA levels after hydrocortisone had a reduction in PSA levels with the addition of suramin. Toxicity profiles were acceptable with each agent, although a higher proportion of subjects showed hematologic, cardiac, and neurologic events when suramin was added.Suramin has limited efficacy in patients with androgen-independent prostate cancer who have had disease progression after hydrocortisone.
CO<sub>2</sub>-Induced Panic Attacks: A Twin Study
Authors: Laura Bellodi, Giampaolo Perna, Daniela Caldirola, Cinzia Arancio, Angelo Bertani, Daniela Di Bella
Journal: American Journal of Psychiatry (1998)

Objective: The authors investigated the role of genetic factors in 35% CO2-induced panic attacks.Method: Ninety twins recruited from general population were challenged with one-vital capacity inhalations of 35% CO2–65% O2. Probandwise concordance rates were calculated and rates compared for monozygotic and for dizygotic twins.Results: A significantly higher concordance was found for 35% CO2-induced panic attacks among monozygotic than dizygotic twins (55.6% versus 12.5%).Conclusions: These results suggest a relevant role of genetic factors in 35% CO2-induced panic attacks. Am J Psychiatry 1998; 155: 1184-1188
The Synergistic Interactions of Allergic Lung Inflammation and Intratracheal Cationic Protein
Authors: Jason H. T. Bates, Ana Cojocaru, Hans C. Haverkamp, Lisa M. Rinaldi, Charles G. Irvin
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Airways hyperresponsiveness (AHR) is a hallmark feature of asthma, and can be caused by various disparate mechanisms. Mouse models of AHR have been useful for studying these mechanisms in isolation, but such models still typically do not exhibit the same degree of AHR as seen in severe human asthma. We hypothesized that more severe AHR in mice could be achieved by imbuing them with more than one mechanism of AHR.Objectives: We sought to determine if the airway wall thickening accompanying allergic inflammation and the exaggerated smooth muscle shortening induced by intratracheal cationic protein could act together to produce a severe form of AHR.Methods: We used the forced oscillation technique to measure methacholine responsiveness in BALB/c mice that had been sensitized and challenged with ovalbumin followed by an intratracheal instillation of poly-l-lysine.Measurements and Main Results: We found that both ovalbumin and poly-l-lysine treatment alone caused moderate levels of AHR. When the two treatments were combined, however, they synergized in terms of their effect on lung stiffness to an extent that could even be fatal, reflecting a significantly enhanced level of airway closure.Conclusions: Our results suggest that mechanistic synergy between airway wall thickening and exaggerated smooth muscle shortening produces a more germane mouse model of asthma that may have particular relevance to the pathophysiology of the acute severe asthma exacerbation.
A whole-genome assembly of the domestic cow, Bos taurus
Authors: Aleksey V Zimin, Arthur L Delcher, Liliana Florea, David R Kelley, Michael C Schatz, Daniela Puiu, Finnian Hanrahan, Geo Pertea, Curtis P Van Tassell, Tad S Sonstegard, Guillaume Marçais, Michael Roberts, Poorani Subramanian, James A Yorke, Steven L Salzberg
Journal: Genome biology (2009)

Abstract Background The genome of the domestic cow, Bos taurus , was sequenced using a mixture of hierarchical and whole-genome shotgun sequencing methods. Results We have assembled the 35 million sequence reads and applied a variety of assembly improvement techniques, creating an assembly of 2.86 billion base pairs that has multiple improvements over previous assemblies: it is more complete, covering more of the genome; thousands of gaps have been closed; many erroneous inversions, deletions, and translocations have been corrected; and thousands of single-nucleotide errors have been corrected. Our evaluation using independent metrics demonstrates that the resulting assembly is substantially more accurate and complete than alternative versions. Conclusions By using independent mapping data and conserved synteny between the cow and human genomes, we were able to construct an assembly with excellent large-scale contiguity in which a large majority (approximately 91%) of the genome has been placed onto the 30 B. taurus chromosomes. We constructed a new cow-human synteny map that expands upon previous maps. We also identified for the first time a portion of the B. taurus Y chromosome.
Truncated Estrogen Receptor α 46-kDa Isoform in Human Endothelial Cells
Authors: Gemma A. Figtree, Denise McDonald, Hugh Watkins, Keith M. Channon
Journal: Circulation (2003)

Background— Estrogen acutely activates endothelial nitric oxide synthase (eNOS). However, the identity of the receptors involved in this rapid response remains unclear. Methods and Results— We detected an estrogen receptor α (ERα) transcript in human endothelial cells that encodes a truncated 46-kDa ERα (Δ1a-hERα-46). A corresponding 46-kDa ERα protein was identified in endothelial cell lysates. Transfection of cDNAs encoding the full-length ERα (ERα-66) and Δ1a-hERα-46 resulted in appropriately sized recombinant proteins identified by anti-ERα antibodies. Confocal microscopy revealed that a proportion of both ERα-66 and hERα-46 was localized outside the nucleus and mediated specific cell-surface binding of estrogen as assessed by FITC-conjugated, BSA-estrogen binding studies. Both ERα isoforms colocalized with eNOS and mediated acute activation of eNOS in response to estrogen stimulation. However, estrogen-stimulated transcriptional activation mediated by Δ1a-hERα-46 was much less than with ERα-66. Furthermore, Δ1a-hERα-46 inhibited classical hERα-66–mediated transcriptional activation in a dominant-negative fashion. Conclusions— These findings suggest that expression of an alternatively spliced, truncated ERα isoform in human endothelial cells confers a unique ability to mediate acute but not transcriptional responses to estrogen.
Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase η for A/T
Authors: Michael S. Neuberger, Cristina Rada
Journal: The Journal of Experimental Medicine (2006)

Somatic hypermutation (SHM) introduces nucleotide substitutions into immunoglobulin variable (Ig V) region genes at all four bases, but the mutations at C/G and A/T pairs are achieved by distinct mechanisms. Mutations at C/G pairs are a direct consequence of the C→U deamination catalyzed by activation-induced deaminase (AID). Mutations at A/T pairs, however, require a second mutagenic process that occurs during patch repair of the AID-generated U/G mismatch. Several DNA polymerases have been proposed to play a role in SHM, but accumulating evidence indicates that the mutations at A/T are overwhelmingly achieved by recruitment of DNA polymerase η.
Industry-Sponsored Research: A More Comprehensive Alternative
Authors: Peter Mansfield
Journal: PLoS Medicine (2006)

Joal HillI read with interest the debate about for-profi t versus non-profi t institutional review boards (IRBs) [1], but was disappointed that no one addressed the ability (or inability) of for-profi t IRBs to review studies with the local context of research subjects in mind and then monitor what actually occurs during the consent process throughout the research trial.To my mind the "bigness" of for-profi t IRBs may be more of an impediment in protecting research subjects than their inherent confl ict of interest.Our IRB has reviewed consent forms approved by central/for-profi t IRBs that contained obvious errors such as schemas that did not match protocol narrative and use of eight point font in a study of geriatric subjects.Even when the initial review is outstanding, it seems a practical impossibility for a single IRB to provide meaningful monitoring of the actual consent process and implementation of the protocol at sites throughout the country.The greater "effi ciency" of for-profi t IRBs is only a meaningful benefi t if increased speed can be shown not to occur at the expense of careful review of consent forms, real understanding of the local research context, and a commitment to audit the informed consent process throughout the study for the protection of research subjects, including ongoing education and advice for researchers and their teams.This is not to say that all local IRBs perform this function as they should, but it does seem almost impossible for one IRB to perform local review and oversight for research sites around the nation in a way that really makes a difference for the men, women, and children who give of their time and their bodies so that society can benefi t.