tbuckley/cabot-search huggingface dataset:
S40 Improving The Patient Journey: Thoracic Ultrasonography As An Adjunct To Decision Making And Diagnostic Pathways In Pleural Disease
Authors: J. Corcoran, R. Hallifax, I. Psallidas, A. Talwar, A. Sykes, N. Rahman
Journal: Thorax (2014)

<h3>Background and method</h3> Pleural disease represents a growing source of referrals to respiratory services. Physicians increasingly provide many of the diagnostic and therapeutic interventions these patients require independent of colleagues in radiology or thoracic surgery. This changing practice can streamline diagnostic pathways within individual centres, and is reflected in BTS guidelines and the need for respiratory physicians to train in thoracic ultrasonography (TUS). Patients referred to our tertiary-level service undergo in-depth TUS to help determine their diagnostic pathway; assessing factors including the nature of any pleural fluid, positioning of intercostal vessels, and movement of the underlying lung. We reviewed our procedural database (January 2010 to June 2014) and clinical records to identify cases where TUS influenced clinical decision making or subsequent investigations. <h3>Results</h3> Procedural triage: 359 patients underwent assessment for diagnostic procedures to obtain pleural tissue during the study period. 64 patients were directed to have TUS-guided cutting needle pleural biopsies due to co-morbidity or after TUS identified heavily septated fluid and/or absent lung sliding (representative of adherent lung) that would prevent local anaesthetic thoracoscopy (LAT). One patient was referred for surgical biopsies after TUS identified septated fluid and an at-risk intercostal vessel that would prevent safe intervention by the physician team. Advanced LAT: 294 LATs were scheduled during the study period. Four LATs were converted “on the table” to TUS-guided cutting needle biopsies after TUS identified increasing septation within the pleural space; a secure diagnosis was obtained in all cases. 95 LATs (32.3%) required Boutin needle pneumothorax induction under TUS guidance. This was successful in 77 cases (81.1%); in those LATs (n = 18) where pneumothorax formation failed an attempt to obtain pleural tissue was made in 10 cases using TUS-guided cutting needle biopsies, making a secure diagnosis in 6 patients. <h3>Conclusion</h3> TUS can greatly improve the patient’s journey from presentation with pleural disease to diagnosis and should be utilised in all cases. TUS allows selection of the most appropriate means of obtaining diagnostic pleural tissue and facilitates more complex procedures. As interventional respiratory physicians become familiar with the capabilities of TUS this type of advanced practice may become increasingly widespread.
MBP-1 Inhibits Breast Cancer Growth and Metastasis in Immunocompetent Mice
Authors: Tatsuo Kanda, Amit Raychoudhuri, Robert Steele, John E. Sagartz, Cheri West, Ratna B. Ray
Journal: Cancer Research (2009)

Abstract Breast cancer is the leading cause of cancer death among women. We have shown previously an antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of breast cancer growth and metastasis in an immunocompetent mouse model. For this, we have used a mouse breast cancer cell line (EO771) and syngeneic C57BL/6 mice. EO771 cells were implanted into the mammary fat pad of C57BL/6 mice. Replication-deficient recombinant adenovirus expressing MBP-1 was administered intratumorally to determine gene therapeutic potential. The results showed a significant regression of primary and distant (lung) tumor growth. Animals exhibited prolonged survival on treatment with MBP-1 compared with the control group (dl312). Subsequent studies suggested that MBP-1 inhibits matrix metalloproteinase expression in human breast cancer cells. Cells transduced with MBP-1 displayed inhibition of migration in a wound-healing assay. The conditioned medium from MBP-1–transduced cells blocked in vitro tube formation assay and inhibited expression of several angiogenic molecules. Taken together, our study shows that MBP-1 acts as a double-edged sword by inhibiting primary and metastatic tumor growth and modulating matrix metalloproteinase expression with a therapeutic potential against breast cancer progression. [Cancer Res 2009;69(24):9354–9]
Pathogenesis of Hyperthyroidism
Authors: I J Chopra, D H Solomon
Journal: Annual Review of Medicine (1983)

Graves' disease is the most frequent cause of hyperthyroidism in the United States. It occurs predominantly in a genetically predisposed population. Autoimmune abnormalities constitute a major component of the disease. Immunoglobulins of patients with Graves' disease manifest a number of thyroid-targeted activities, including a thyroid-stimulating activity that is related to interaction of immunoglobulin G (IgG) with the TSH receptor. That hyperthyroidism in Graves' disease is caused by thyroid-stimulating IgGs is an attractive hypothesis but the evidence in favor of the hypothesis is still insufficient. A better alternative hypothesis is not available, however.
Sickness certification system in the United Kingdom: qualitative study of views of general practitioners in Scotland
Authors: S. Hussey
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To explore how general practitioners operate the sickness certification system, their views on the system, and suggestions for change. <b>Design</b> Qualitative focus group study consisting of 11 focus groups with 67 participants. <b>Setting</b> General practitioners in practices in Glasgow, Tayside, and Highland regions, Scotland. <b>Sample</b> Purposive sample of general practitioners, with further theoretical sampling of key informant general practitioners to examine emerging themes. <b>Results</b> General practitioners believed that the sickness certification system failed to address complex, chronic, or doubtful cases. They seemed to develop various operational strategies for its implementation. There appeared to be important deliberate misuse of the system by general practitioners, possibly related to conflicts about roles and incongruities in the system. The doctor-patient relationship was perceived to conflict with the current role of general practitioners in sickness certification. When making decisions about certification, the general practitioners considered a wide variety of factors. They experienced contradictory demands from other system stakeholders and felt blamed for failing to make impossible reconciliations. They clearly identified the difficulties of operating the system when there was no continuity of patient care. Many wished either to relinquish their gatekeeper role or to continue only with major changes. <b>Conclusions</b> Policy makers need to recognise and accommodate the range and complexity of factors that influence the behaviour of general practitioners operating as gatekeepers to the sickness certification system, before making changes. Such changes are otherwise unlikely to result in improvement. Models other than the primary care gatekeeper model should be considered.
Pretransplant clinicopathological correlation in end-stage primary pulmonary hypertension
Authors: BP Madden, J Gosney, JG Coghlan, K Kamalvand, AW Caslin, P Smith, M Yacoub, D Heath
Journal: European Respiratory Journal (1994)

The aim of the study was to see if there was any correlation between the histopathology, ultrastructure, pulmonary endocrinology and clinical manifestations of end-stage primary pulmonary hypertension. Twenty patients undergoing heart-lung transplantation for the disease were studied. The nature and duration of symptoms and signs, results of haematological, electrocardiographic, radiographic, echocardiographic and haemodynamic studies, and the response of patients to vasodilators were compared with data from histopathological and ultrastructural study of lungs removed at transplantation. Length of clinical history and clinical evidence of severe disease were not necessarily associated with advanced histopathology, nor did the presence of small, contracted muscular pulmonary arteries imply responsiveness to vasodilators. Numbers of gastrin-releasing peptide-containing pulmonary endocrine cells were greater in lungs in which there was activity of myofibroblasts in pulmonary arterial vessels, and correlated negatively with mean pulmonary artery pressure and pulmonary artery systolic pressure. Whereas the prognosis of primary pulmonary hypertension cannot as yet be defined by other than its clinical manifestations, intimal proliferation as well as vasoconstriction may be important in its pathogenesis. The release of gastrin-releasing peptide from pulmonary endocrine cells may possibly be involved in this process.
The Role of HIV-Related Stigma in Utilization of Skilled Childbirth Services in Rural Kenya: A Prospective Mixed-Methods Study
Authors: Janet M. Turan, Abigail H. Hatcher, José Medema-Wijnveen, Maricianah Onono, Suellen Miller, Elizabeth A. Bukusi, Bulent Turan, Craig R. Cohen
Journal: PLoS Medicine (2012)

Background Childbirth with a skilled attendant is crucial for preventing maternal mortality and is an important opportunity for prevention of mother-to-child transmission of HIV. The Maternity in Migori and AIDS Stigma Study (MAMAS Study) is a prospective mixed-methods investigation conducted in a high HIV prevalence area in rural Kenya, in which we examined the role of women's perceptions of HIV-related stigma during pregnancy in their subsequent utilization of maternity services. Methods and Findings From 2007–2009, 1,777 pregnant women with unknown HIV status completed an interviewer-administered questionnaire assessing their perceptions of HIV-related stigma before being offered HIV testing during their first antenatal care visit. After the visit, a sub-sample of women was selected for follow-up (all women who tested HIV-positive or were not tested for HIV, and a random sample of HIV-negative women, n = 598); 411 (69%) were located and completed another questionnaire postpartum. Additional qualitative in-depth interviews with community health workers, childbearing women, and family members (n = 48) aided our interpretation of the quantitative findings and highlighted ways in which HIV-related stigma may influence birth decisions. Qualitative data revealed that health facility birth is commonly viewed as most appropriate for women with pregnancy complications, such as HIV. Thus, women delivering at health facilities face the risk of being labeled as HIV-positive in the community. Our quantitative data revealed that women with higher perceptions of HIV-related stigma (specifically those who held negative attitudes about persons living with HIV) at baseline were subsequently less likely to deliver in a health facility with a skilled attendant, even after adjusting for other known predictors of health facility delivery (adjusted odds ratio = 0.44, 95% CI 0.22–0.88). Conclusions Our findings point to the urgent need for interventions to reduce HIV-related stigma, not only for improving quality of life among persons living with HIV, but also for better health outcomes among all childbearing women and their families. Please see later in the article for the Editors' Summary.
Natural Selection on the Erythrocyte Surface
Authors: Jake Baum, Ryk H. Ward, David J. Conway
Journal: Molecular Biology and Evolution (2002)

Surface glycoproteins are principal receptors used by pathogens to invade target cells. It has been suggested that mammalian erythrocyte surface glycoproteins function as decoy receptors attracting pathogens to the anucleated erythrocyte and away from their target tissues. Glycophorin A (GYPA) is solely expressed on the erythrocyte surface where it is the most abundant sialoglycoprotein, although its function is unknown. The pathogen decoy hypothesis may be relevant here, as GYPA has been shown in vitro to bind numerous viruses and bacteria, which do not infect erythrocytes. However, it is also a receptor for erythrocyte invasion by the malarial parasite Plasmodium falciparum. Analyses of gypa sequence variation among six higher primates and within a human population show that there is a large excess of replacement (nonsynonymous) substitutions along each primate lineage (particularly on exons 2–4 encoding the extracellular glycosylated domain of GYPA) and a significant excess of polymorphisms in exon 2 (encoding the terminal portion of the extracellular domain) within humans. These two signatures suggest that there has been exceptionally strong positive selection on this receptor driving GYPA divergence during primate evolution and balancing selection maintaining allelic variation within human populations. The pathogen decoy hypothesis alone is adequate to explain both these signatures of between-species and within-species diversifying selection. This has implications for understanding the functions of erythrocyte surface components and their roles in health and disease.
Expression of CDX2 in normal and neoplastic human colon tissue and during differentiation of an in vitro model system
Authors: D Qualtrough, T Hinoi, E Fearon, C Paraskeva
Journal: Gut (2002)

The Cdx genes are expressed in the colorectal epithelium and are frequently downregulated during tumorigenesis. Overexpression of Cdx genes has been shown previously to result in cellular differentiation.To study expression of CDX2 in normal and neoplastic human colon using a newly isolated monoclonal antibody. To define expression of CDX1 and CDX2 in an in vitro model system of colorectal tumour progression and to ascertain whether these are subject to regulation during differentiation.Normal and neoplastic human colon was immunostained for CDX2. CDX1 and CDX2 expression was assayed in cell lines derived from premalignant colonic adenomas by western blotting. Differentiation was induced by sodium butyrate treatment or post confluent growth, and changes in CDX expression compared with carcinoma cell lines with low levels of CDX expression.CDX2 protein displayed no gradient of expression within the colonic crypt. Cell lines derived from adenomas, with high levels of CDX1 and CDX2, showed no regulation of these proteins when induced to differentiate by butyrate or confluency. CDX expression in these cell lines was independent of their APC or Ras status. CDX1 and CDX2 were expressed at very low levels in some carcinoma cell lines and were modestly upregulated on differentiation but were not restored to levels seen in adenoma cells.The lack of significant regulation on cellular differentiation and the absence of a detectable gradient in the crypt implies that CDX2 may confer tissue specificity but may not play the previously suggested role in crypt patterning.
Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1.
Authors: W F Davidson, J H Pierce, S Rudikoff, H C Morse
Journal: The Journal of Experimental Medicine (1988)

A cell line, HAFTL-1, derived by in vitro transformation of fetal liver cells with v-Ha-ras, was found to have molecular and phenotypic characteristics of pro-B cells recently committed to the Ly-1+ B cell differentiation pathway. Stimulation of these cells with LPS resulted in their differentiation within either the B or myelomonocytic lineages. Thus, lines derived from LPS-stimulated HAFTL-1 cells were shown to be clonally related, as evidenced by common v-ras integrations, but to exhibit characteristics of pre-B cells (ThB expression, continuing DJ heavy chain rearrangements) or mature macrophages (expression of Mac-1 and Mac-2, lysozyme and nonspecific esterase production, phagocytosis) while maintaining their Ly-1+ phenotype. These results suggest that events resulting in the irrevocable commitment to a single lineage occur late in differentiation, at least within the pathway yielding Ly-1+ B cells and a proposed subpopulation of Ly-1+ monocytes and macrophages. Final commitment to these lineages is carefully orchestrated, as evidenced by restricted expression of Ly-5 isoforms and production of IgH transcripts.
Characterization of New Estrogen Receptor Destabilizing Compounds: Effects on Estrogen-Sensitive and Tamoxifen-Resistant Breast Cancer
Authors: J. Hoffmann, R. Bohlmann, N. Heinrich, H. Hofmeister, J. Kroll, H. Kunzer, R. B. Lichtner, Y. Nishino, K. Parczyk, G. Sauer, H. Gieschen, H.-F. Ulbrich, M. R. Schneider
Journal: JNCI Journal of the National Cancer Institute (2004)

Antiestrogens of the selective estrogen receptor modulator (SERM) type, such as tamoxifen, have two major limitations: their mixed agonist and antagonist profile and the development of tumor resistance. We characterized two new pure antiestrogens-ZK-703 and ZK-253-that belong to the class of specific estrogen receptor destabilizers (SERDs), which includes fulvestrant, and compared their activity with that of fulvestrant and tamoxifen.Effects of antiestrogens on the growth of estrogen-dependent breast tumors in vivo were determined using several mouse xenograft models (including the tamoxifen-sensitive tumors MCF7, T47D, and MV3366 and the tamoxifen-resistant tumors ZR75-1 and MCF7/TAM) and chemically induced (nitrosomethyl urea [NMU] and dimethylbenzanthracene [DMBA]) rat breast cancer models (groups of 10 animals). We determined the initial response and effects on hormone receptor levels and the time to relapse after treatment (i.e., time to reach a predetermined tumor size threshold). Estrogen receptor (ER) levels were determined by immunoassay.ZK-703 (administered subcutaneously) and ZK-253 (administered orally) were more effective than tamoxifen or fulvestrant at inhibiting the growth of ER-positive breast cancer in all xenograft models. For example, MCF7 tumors relapsed (i.e., reached the size threshold) in 10 weeks in mice treated with tamoxifen but in 30 weeks in mice treated with ZK-703. ZK-703 and ZK-253 also prevented further tumor progression in tamoxifen-resistant breast cancer models to a similar extent (more than 30 weeks in mice with ZR75-1 and MCF7/TAM tumors). In the chemically induced rat breast cancer models, orally administered ZK-703 and ZK-253 caused a nearly complete (>80%) inhibition of tumor growth. ER levels were dramatically reduced in MCF7 tumors after 5 weeks of ZK-703 treatment compared with ER levels in vehicle-treated tumors; by contrast, ER levels in tamoxifen-treated tumors were higher than those in control tumors.ZK-703 and ZK-253 are potent, long-term inhibitors of growth in both tamoxifen-sensitive and tamoxifen-resistant breast cancer models.
Destruction of Vitamin B12 by Ascorbic Acid
Authors: Victor Herbert
Journal: JAMA (1974)

High doses of vitamin C, popularly used as a home remedy against the common cold, destroy substantial amounts of vitamin B when ingested with food. Because this undesirable effect is unequivocal when measured in vitro, while the value of ascorbic acid in preventing the common cold is highly equivocal, daily ingestion of 0.5 gm or more of ascorbic acid without regular evaluation of vitamin B<sub>12</sub>status is probably unwise. (<i>JAMA</i>230:241-242, 1974)
Is It Better to Transfer Long-Term Cancer Survivors to General Practitioners or Develop Clinics for Long-Term Survivors Within the Cancer Centers?
Authors: Umberto Tirelli, Michele Spina, Accursio F. Augello, Massimiliano Berretta, Maria Antonietta Annunziata, Marilena Bongiovanni
Journal: Journal of Clinical Oncology (2013)

We and others 9,10 have shown that breast cancer during pregnancy can be treated successfully and the pregnancy maintained for successful delivery of a healthy neonate.There seem to be three cohorts of concern-those diagnosed with cancer during pregnancy, those diagnosed in the postpartum period up to 1 year after delivery (pregnancy-associated breast cancer), and those successfully treated for primary breast cancer who have a subsequent pregnancy.For those in the first category, successful cancer treatment with viable neonates and healthy mothers is possible. 9For the third group, pregnancy after breast cancer treatment does not seem to impact recurrence or mortality risks irrespective of the primary tumor hormone receptor status. 7,8For the pregnancyassociated breast cancer group, an increased risk of breast cancer mortality is reported. 11,12Unfortunately, clinicians have no tools to assess this risk or methods to reduce the risk.For this group, additional assessment is needed of the risk associated with poorer outcome.
Localization of sites through which C-reactive protein binds and activates complement to residues 14-26 and 76-92 of the human C1q A chain.
Authors: H Jiang, F A Robey, H Gewurz
Journal: The Journal of Experimental Medicine (1992)

Studies were initiated to localize the C-reactive protein (CRP) binding site on the collagen-like region (CLR) of C1q. CRP bound preferentially to the A chain of reduced C1q, in contrast to aggregated immunoglobulin G (Agg-IgG), which reacted preferentially with the C chain. A group of C1q A chain peptides, including peptides identical to residues 81-97, 76-92, and 14-26, respectively, were synthesized from predicted binding regions. Peptide 76-92 contained two proximal lysine groups, and peptide 14-26 contained four proximal arginine groups. CRP-trimers and CRP-ligand complexes did not bind to immobilized peptide 81-97, but bound avidly to immobilized peptides 76-92 and 14-26. Agg-IgG did not bind to any of the peptides. Peptide 76-92 partially, and peptide 14-26 completely, inhibited binding of CRP to intact C1q. Peptide 14-26 also blocked C consumption initiated by CRP, but not by IgG. Replacement of the two prolines with alanines, or scrambling the order of the amino acids, resulted in loss of ability of peptide 14-26 to inhibit C1q binding and C activation by CRP, indicating a sequence specificity, and not a charge specificity alone, as the basis for the inhibitory activity of the peptide. Similar investigations with scrambled peptides showed a sequence specificity for the effects of peptide 76-92 as well. DNA and heparin inhibited binding of CRP trimers to intact C1q, as well as to each peptide 14-26 and 76-92, suggesting involvement of these regions in C1q-CLR binding reactions generally. Collectively, these data identify two cationic regions within residues 14-26 and 76-92 of the C1q A chain CLR as sites through which CRP binds and activates the classical C pathway, and suggest that these residues represent significant regions for C1q CLR binding reactions generally. To our knowledge, this represents the first delineation of sites on C1q through which binding and activation of the classical C pathway can occur.