tbuckley/cabot-search huggingface dataset:
Defining Disease in the Information Age
Authors: Olavo B Amaral
Journal: PLoS Medicine (2006)

I am a disease monger.I teach primary care doctors how to identify bipolar disorder.Worse yet, I take money from pharmaceutical companies for doing so.I use it to subsidize my practice so that I can treat patients with no insurance, or little money, who now account for over a third of my patients-in part because the pharmaceutical companies have drained so much money out of the health-care system.Ironic, isn't it?My Web site PsychEducation.org(http:⁄⁄www.psycheducation.org) is number one on Google for searches on "bipolar II."See if you think it looks like disease mongering.Hundreds of people have written thanking me for explaining bipolar II and the concept of a bipolar spectrum, indicating that this new perspective really helps them understand their long-standing symptoms.To my immediate recall, none have complained about being led astray by an overbroad interpretation of bipolarity.Notice that, just like Mr. Moynihan, one of the guest editors of your April 2006 series of articles on disease mongering [1], I could be mongering even now, as I too have a new book.At least I'm not trying to attract attendees to my conference.Tricky, isn't it.Has there been an oversimplifi cation in this analysis?(PsychEducation.org
Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period
Authors: J-P Raynauld, J Martel-Pelletier, M-J Berthiaume, F Abram, D Choquette, B Haraoui, J F Beary, G A Cline, J M Meyer, J-P Pelletier
Journal: Annals of the Rheumatic Diseases (2007)

To evaluate in patients with knee osteoarthritis (OA) the size changes in bone oedema and cysts over 24 months, and to contrast these changes with cartilage volume loss using quantitative magnetic resonance imaging.107 patients with knee OA, selected from a large trial evaluating the effect of a bisphosphonate, were analysed by magnetic resonance imaging at baseline and 24 months. Assessments of subchondral bone oedema and cysts, and cartilage volume were done.At baseline, 86 patients showed the presence of at least one type of bone lesion: 71 oedema, 61 cysts and 51 both. At 24 months, although not statistically significant, the oedema total size change increased by 2.09 (SD 15.03) mm, and the cyst by 1.09 (8.13) mm; mean size change for the oedema was +0.38 (2.18) mm and -0.10 (4.36) mm for the cyst. When analysed according to subregions, an increase was found for the cyst size in the trochlea (+0.67 (2.74) mm, p = 0.02) and in the lateral tibial plateau (+0.15 (0.83) mm, p = 0.09), and for the oedema size in the medial tibial plateau (+1.73 (8.11) mm, p = 0.05). At 24 months, significant correlations were seen between the loss of cartilage volume and oedema size change in the medial condyle (-0.40, p = 0.0001) and the medial tibial plateau (-0.23, p = 0.03), and the changes in cyst size in the medial condyle (-0.29, p = 0.01). A multivariate analysis showed that the oedema size change was strongly and independently associated with medial cartilage volume loss (-0.31, p = 0.0004).These data demonstrate that bone lesions are prevalent in knee OA. The correlation of the oedema and cyst size increase in the medial compartment over time with a greater loss of cartilage volume in this area underlines the importance of subchondral bone lesions in OA pathophysiology.
Chemokine Signaling and Functional Responses: The Role of Receptor Dimerization and TK Pathway Activation
Authors: Mario Mellado, José Miguel Rodríguez-Frade, Santos Mañes, Carlos Martínez-A
Journal: Annual Review of Immunology (2001)

A broad array of biological responses, including cell polarization, movement, immune and inflammatory responses, and prevention of HIV-1 infection, are triggered by the chemokines, a family of structurally related chemoattractant proteins that bind to specific seven-transmembrane receptors linked to G proteins. Here we discuss one of the early signaling pathways activated by chemokines, the JAK/STAT pathway. Through this pathway, and possibly in conjunction with other signaling pathways, the chemokines promote changes in cellular morphology, collectively known as polarization, required for chemotactic responses. The polarized cell expresses the chemokine receptors at the leading cell edge, to which they are conveyed by rafts, a cholesterol-enriched membrane fraction fundamental to the lateral organization of the plasma membrane. Finally, the mechanisms through which the chemokines promote their effect are discussed in the context of the prevention of HIV-1 infection.
Expression of the cystic fibrosis gene in adult human lung.
Authors: J F Engelhardt, M Zepeda, J A Cohn, J R Yankaskas, J M Wilson
Journal: Journal of Clinical Investigation (1994)

Critical to an understanding of the pulmonary disease in cystic fibrosis (CF) and the development of effective gene therapies is a definition of the distribution and regulation of CF gene expression in adult human lung. Previous studies have detected the product of the CF gene, the CF transmembrane conductance regulator (CFTR), in submucosal glands of human bronchi. In this report, we have characterized the distribution of CFTR RNA and protein in the distal airway and alveoli of human lungs. Samples from eight human lungs were analyzed for CFTR expression by in situ hybridization and immunocytochemistry. CFTR was detected in a subpopulation of epithelial cells at every level of the distal lung, including proximal, terminal, and respiratory bronchioles, and the alveoli. However, there was substantial variation in the level of CFTR expression between samples. In bronchioles, CFTR protein localized to the apical plasma membrane and was found primarily in a subpopulation of nonciliated cells. CFTR was expressed in the same distribution as the Clara cell marker CC10 in proximal bronchioles, however, expression was discordant in the more distal bronchioles and alveoli where CC10 was not detected. These studies suggest that epithelial cells of the distal lung may play a primary role in the pathogenesis of CF as well as expand the spectrum of target cells that should be considered in the development of gene therapies.
Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience
Authors: F. Mirici-Cappa, A. Gramenzi, V. Santi, A. Zambruni, A. Di Micoli, M. Frigerio, F. Maraldi, M. A. Di Nolfo, P. Del Poggio, L. Benvegnu, G. Rapaccini, F. Farinati, M. Zoli, F. Borzio, E. G. Giannini, E. Caturelli, M. Bernardi, F. Trevisani
Journal: Gut (2010)

<h3>Objectives</h3> The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. We compared the presenting features and outcome of HCC in elderly (≥70 years) and younger patients (&lt;70 years). <h3>Design</h3> Multicentre retrospective cohort study and nested case–control study. <h3>Patients</h3> 614 elderly and 1104 younger patients from the ITA.LI.CA database, including 1834 HCC cases consecutively diagnosed from January 1987 to December 2004. Both groups were stratified according to treatment: hepatic resection, percutaneous procedures, transarterial chemoembolisation (TACE). Survival was assessed in the whole population and in each treatment subgroup. Age, sex, aetiology, cirrhosis, comorbidities and cancer stage (CLIP score) were tested as predictors of survival. In each subgroup, differences in patient survival were also assessed after adjustment and matching by propensity score. <h3>Results</h3> Ageing was associated with a higher prevalence of comorbidities, better liver function and CLIP score. Regardless of age, two-thirds of patients underwent radical treatments or TACE. Elderly patients underwent more ablative procedures and fewer resections or TACE sessions. The survival of elderly and younger patients was comparable in each treatment subset, and was predicted by CLIP score. This result was confirmed by the propensity analysis. <h3>Conclusions</h3> The overall applicability of radical or effective HCC treatments was unaffected by old age. However, treatment distribution differed, elderly individuals being more frequently treated with percutaneous procedures and less frequently with resection or TACE. Survival was unaffected by age and primarily predicted by cancer stage, assessed by the CLIP system, both in the overall population and in treatment subgroups.
Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis.
Authors: I A Rooney, J P Atkinson, E S Krul, G Schonfeld, K Polakoski, J E Saffitz, B P Morgan
Journal: The Journal of Experimental Medicine (1993)

We demonstrate here that CD59, an inhibitor of the membrane attack complex (MAC) of the complement system, is present in cell-free seminal plasma (SP) at a concentration of at least 20 micrograms/ml. Analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and Edman degradation indicated that this protein, SP CD59, was similar, if not identical, to CD59 isolated from erythrocyte (E) membranes (E CD59). Like purified E CD59, SP CD59 also possesses a glycosyl phosphatidyl inositol (GPI) anchor and incorporates into the membranes of heterologous cells where it inhibits lysis by the human MAC. This phenomenon could be demonstrated not only if cells were incubated with purified SP CD59 but also if unfractionated SP were used. Further, CD59 in unfractionated SP bound to washed spermatozoa, increasing their membrane content of the protein. The mechanism by which this protein retains its GPI anchor while apparently present in the fluid phase is of interest and was further investigated. Using the techniques of high-speed centrifugation, fast performance liquid chromatography fractionation, and electron microscopy, we found that all detectable SP CD59 was associated with vesicular extracellular organelles. These organelles, named "prostasomes," were previously known to be present in SP and to interact with spermatozoa, although their function was uncertain. Interaction of heterologous E with prostasomes rendered the cells more resistant to lysis by human MACs. We propose that these organelles represent a pool of CD59 from which protein lost from spermatozoa, perhaps as a result of low level complement attack or of normal membrane turnover, can be replenished.
Circulating immunoblasts in polymyalgia rheumatica.
Authors: A A Eghtedari, W Esselinckx, P A Bacon
Journal: Annals of the Rheumatic Diseases (1976)

The percentage of immunoblasts circulating in the peripheral blood has been examined in a group of 29 patients with polymyalgia rheumatica (PMR). Less than 0.5% of immunoblasts were found in healthy young controls, but 18 of 29 unselected patients with PMR were positive when first tested, a similar proportion to that found in rheumatoid arthritis. Raised immunoblasts were found in only one of 12 elderly controls. The presence of circulating immunoblasts correlated with the activity of polymyalgia both as assessed by the erythrocyte sedimentation rate (ESR) and as assessed by an independent clinical observer. This was true in the group overall and in those patients where serial studies were made. Patients studied from the time of disease presentation showed a concurrent fall in ESR and in immunoblasts on starting steroid therapy. Detection of circulating immunoblasts can be a useful additional test in the assessment of disease activity in PMR, especially in cases with a low ESR. The presence of circulating immunoblasts supports the concept of an immunological aetiology for PMR. This is strengthened by the finding that raised immunoglobulins were more common in patients with circulating immunoblasts.
Facial Expression Recognition in Adolescents With Mood and Anxiety Disorders
Authors: Erin B. McClure, Kayla Pope, Andrea J. Hoberman, Daniel S. Pine, Ellen Leibenluft
Journal: American Journal of Psychiatry (2003)

The authors examined facial expression recognition in adolescents with mood and anxiety disorders.Standard facial emotion identification tests were given to youth with bipolar disorder (N=11) or DSM-IV anxiety disorders (N=10) and a group of healthy comparison subjects (N=25).Relative to the anxiety disorder and healthy comparison groups, the subjects with bipolar disorder made more emotion recognition errors when presented with faces of children. Unlike the anxious and comparison subjects, bipolar disorder youth were prone to misidentify faces as angry. No differences in emotion recognition errors were seen when the adolescents were presented with adult faces.A bias to misinterpret the facial expressions of peers as angry may characterize youth with bipolar disorder but not youth with anxiety disorders. This bias may relate to social impairment in youth with bipolar disorder.
Practice variation in treatment of primary biliary cirrhosis and effect on clinical outcomes
Authors: Jayant A. Talwalkar, Andrea A. Gossard
Journal: Hepatology (2008)

The article by Jackson et al.1 and accompanying editorial by Corpechot and Poupon2 have raised the interesting question of practice variation in the diagnosis and treatment of primary biliary cirrhosis (PBC). In general, the variable use of effective medical therapies continues to be linked with the notion of inconsistent clinical outcomes for chronic disease overall.3 Given the available data, it is difficult to ignore the likelihood that ursodeoxycholic acid (UDCA) therapy has influenced the natural history of PBC in various populations. In addition, there is empiric evidence supporting the existence of practice variation in UDCA prescribing patterns for PBC within the United States.4 Specifically, the timing of UDCA therapy may be quite varied with at least 10% of patients beginning UDCA greater than 1 year after initial diagnosis. Although specific details about provider adherence rates to weight-based dosing (13-15 mg/kg/day) remain unavailable, it is likely that significant variations exist in the United States, given the large dose range (from 1.5 to 23.1 mg/kg/day, median 11.5) reported by practicing gastroenterologists in the United Kingdom.5 Drug-related adverse event rates as high as 35% leading to UDCA discontinuation are also reported among U.S. residents with PBC.4 This far exceeds rates observed in published randomized controlled trials to date. Given the cohort used by Jackson et al., it would have been intriguing to know how often dose reduction and/or drug cessation occurred in their population. Finally, medical therapies with questionable or no benefit for PBC are prescribed by 10%-15% of providers based on published reports.5 Estimated rates of similar practices in the United States remain unknown. Despite the overall rarity of PBC, these observations underscore the need to recognize differences in treatment patterns which may influence long-term outcome in PBC. Similarly, ongoing educational efforts to decrease the use of ineffective therapies with unfavorable risk/benefit profiles in altering the natural history of PBC would be welcomed. Jayant A. Talwalkar M.D., MPH*, Andrea A. Gossard CNP*, * The Miles and Shirley Fiterman Center for Digestive Diseases, The Mayo Clinic, Rochester, MN.
Evidence for Independent Heritability of the Glycation Gap (Glycosylation Gap) Fraction of HbA1c in Nondiabetic Twins
Authors: Robert M. Cohen, Harold Snieder, Christopher J. Lindsell, Huriya Beyan, Mohammed I. Hawa, Stuart Blinko, Raymond Edwards, Timothy D. Spector, R. David G. Leslie
Journal: Diabetes Care (2006)

HbA(1c) (A1C) is substantially determined by genetic factors not shared in common with glucose. Fractions of the variance in A1C, the glycation gap (GG; previously called the glycosylation gap) and the hemoglobin glycosylation index, correlate with diabetes complications. We therefore tested whether GG (measured A1C - A1C predicted from glycated serum proteins [GSPs]) was genetically determined and whether it accounted for the heritability of A1C.We conducted a classic twin study on A1C and GSP collected in 40 and 46 pairs of monozygotic and dizygotic healthy female twins, respectively. The predicted A1C was based on the regression line between A1C and GSP in a separate population spanning the pathophysiologic range.GG was more strongly correlated between monozygotic (r = 0.65) than dizygotic (r = 0.48) twins, adjusted for age and BMI. The best-fitting quantitative genetic model adjusted for age and BMI showed that 69% of population variance in GG is heritable, while the remaining 31% is due to unique environmental influences. In contrast, GSP was similarly correlated between monozygotic (r = 0.55) and dizygotic (r = 0.49) twins, hence not genetically determined. GG was strongly correlated to A1C (r = 0.48), attributable mostly to genetic factors. About one-third of the heritability of A1C is shared with GG; the remainder is specific to A1C.Heritability of the GG accounts for about one-third of the heritability of A1C. By implication, there are gene(s) that preferentially affect erythrocyte lifespan or glucose and/or nonenzymatic glycation or deglycation in the intracellular, rather than extracellular, compartment.
The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade
Authors: Peter Blaha, Sinda Bigenzahn, Zvonimir Koporc, Maximilian Schmid, Felix Langer, Edgar Selzer, Helga Bergmeister, Friedrich Wrba, Josef Kurtz, Christopher Kiss, Erich Roth, Ferdinand Muehlbacher, Megan Sykes, Thomas Wekerle
Journal: Blood (2003)
Evolution of a Novel Carotenoid-Binding Protein Responsible for Crustacean Shell Color
Authors: N. M. Wade, A. Tollenaere, M. R. Hall, B. M. Degnan
Journal: Molecular Biology and Evolution (2009)

Carotenoids are commonly used by disparate metazoans to produce external coloration, often in direct association with specific proteins. In one such example, crustacyanin (CRCN) and the carotenoid astaxanthin combine to form a multimeric protein complex that is critical for the array of external shell colors in clawed lobsters. Through a combined biochemical, molecular genetic, and bioinformatic survey of the distribution of CRCN across the animal kingdom, we have found that CRCNs are restricted to, but widespread among, malacostracan crustaceans. These crustacean-specific genes separate into two distinct clades within the lipocalin protein superfamily. We show that CRCN differentially localizes to colored shell territories and the underlying epithelium in panulirid lobsters. Given the paramount importance of CRCN in crustacean shell colors and patterns and the critical role these play in survival, reproduction, and communication, we submit that the origin of the CRCN gene family early in the evolution of malacostracan crustaceans significantly contributed to the success of this group of arthropods.
Can Circulating Tumor Cells Predict Resistance in Metastatic Breast Cancer?
Authors: Aju Mathew, Adam M. Brufsky, Nancy E. Davidson
Journal: Clinical Cancer Research (2015)

Circulating tumor cell (CTC) enumeration provides prognostic but not predictive information for chemotherapy in metastatic breast cancer. Because CTC measurement is reproducible and allows molecular profiling, an assay to assess endocrine resistance was developed. Whether this CTC-based assay can be used to reliably select endocrine therapy must be tested.
Inherited Distal Renal Tubular Acidosis
Authors: Fiona E Karet
Journal: Journal of the American Society of Nephrology (2002)

Renal acid-base balance may become deranged in a number of ways, some of which are the consequence of inherited disorders. Two main groups of distal renal acidopathies result either from a direct inability to secrete acid in the distal nephron (giving rise to type 1 renal tubular acidosis [RTA]) or
Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial
Authors: G. Petrof, M. Martinez-Queipo, J.E. Mellerio, P. Kemp, J.A. McGrath
Journal: British Journal of Dermatology (2013)

Fibroblast cell therapy can modify disease biology in recessive dystrophic epidermolysis bullosa (RDEB) although whether it improves wound healing is not clear. To assess the effects of injecting of allogeneic fibroblasts into the margins of chronic erosions in individuals with RDEB in a prospective, double‐blind, randomized, vehicle‐controlled phase II trial. Erosions were randomized 1 : 1, to either a single treatment of 5 × 106 fibroblasts per linear cm of erosion margin or vehicle. All subjects continued standard wound care. The trial sponsor, participants and study outcome assessor were masked to treatment allocation. A hierarchy of endpoints germane to erosion closure was assessed. Twenty‐six erosions in 11 subjects with RDEB were injected; 14 erosions received fibroblasts and 12 vehicle alone. A single series of injections was given at day 0 and all follow‐up visits were completed. Treatment difference between fibroblasts and vehicle was −23·5% [95% confidence interval (CI) −3·5 to −43·5, P = 0·025] at day 7, −19·15% (95% CI 3·36 to −41·66, P = 0·089) at day 14 and –28·83% (95% CI 7·97 to −65·63, P = 0·11) at day 28. Beyond day 28, however, changes in mean erosion area did not differ significantly between the two groups. A single intradermal injection of allogeneic fibroblasts increases the initial rate of erosion healing in subjects with RDEB within the first 28 days but not thereafter. Further studies are needed to address the potential benefits of retreatment as well as optimal cell delivery.
Metastasis-Enhancing Effect of Heparin and Its Relationship to a Lipoprotein Factor&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: S Y Chan, M Pollard
Journal: JNCI Journal of the National Cancer Institute (1980)

The effect of low-dose heparin on spontaneous metastasis formation was studied with the PA-III rat prostate adenocarcinoma cell line model system. In LW rats given heparin iv at a dose of 1,000 U/kg body weight (three times/wk), the metastatic spread of implanted PA-III cells from the footpad through ipsilateral lymphatics to the lungs was enhanced. The weights of the draining lymph nodes (popliteal, inguinal, and axillary) and the number of lung tumor colonies were significantly increased compared with those in the saline-treated control tumor-bearing rats. The growth of the primary tumor was also enhanced. Heparin alone did not induce enlarged lymph nodes in rats nor did it change the growth pattern of PA-III cells in vitro. The accelerated metastatic spread of the PA-III cells was possibly related to the destruction of the oncolytic activity of the very low-density lipoprotein by the lipoprotein lipases induced by the iv administration of heparin. However, the possibility that other mechanisms could be operative in this phenomenon has not been ruled out.