tbuckley/cabot-search huggingface dataset:
Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C
Authors: I J Hickman, A D Clouston, G A Macdonald, D M Purdie, J B Prins, S Ash, J R Jonsson, E E Powell
Journal: Gut (2002)

Steatosis occurs in more than 50% of patients with chronic hepatitis C and is associated with increased hepatic fibrosis. In many of these patients the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease-that is, related to visceral adiposity and obesity.The effect of a three month weight reduction programme on liver biochemistry and metabolic parameters was examined in 19 subjects with steatosis and chronic hepatitis C. Paired liver biopsies were performed in 10 subjects, prior to and 3-6 months following the intervention, to determine the effect of weight loss on liver histology.There was a mean weight loss of 5.9 (3.2) kg and a mean reduction in waist circumference of 9.0 (5.0) cm. In 16 of the 19 patients, serum alanine aminotransferase levels fell progressively with weight loss. Mean fasting insulin fell from 16 (7) to 11 (4) mmol/l (p<0.002). Nine of 10 patients with paired liver biopsies had a reduction in steatosis irrespective of viral genotype. In these subjects the median modified Knodell fibrosis score decreased from 3 to 1 (p=0.04) and activated stellate cells significantly decreased (p<0.004).Weight loss in patients with chronic hepatitis C may be associated with a reduction in steatosis and abnormal liver enzymes and an improvement in fibrosis, despite the persistence of the virus. Weight reduction may provide an important adjunct treatment strategy for patients with chronic hepatitis C.
Sport concussion knowledge base, clinical practises and needs for continuing medical education: a survey of family physicians and cross-border comparison
Authors: Constance M Lebrun, Martin Mrazik, Abhaya S Prasad, B Joel Tjarks, Jason C Dorman, Michael F Bergeron, Thayne A Munce, Verle D Valentine
Journal: British Journal of Sports Medicine (2012)

Evolving concussion diagnosis/management tools and guidelines make Knowledge Transfer and Exchange (KTE) to practitioners challenging.Identify sports concussion knowledge base and practise patterns in two family physician populations; explore current/preferred methods of KTE.A cross-sectional study.Family physicians in Alberta, Canada (CAN) and North/South Dakota, USA.CAN physicians were recruited by mail: 2.5% response rate (80/3154); US physicians through a database: 20% response rate (109/545). INTERVENTION/INSTRUMENT: Online survey. MAIN AND SECONDARY OUTCOME MEASURES: Diagnosis/management strategies for concussions, and current/preferred KTE.Main reported aetiologies: sports/recreation (52.5% CAN); organised sports (76.5% US). Most physicians used clinical examination (93.8% CAN, 88.1% US); far fewer used the Sport Concussion Assessment Tool (SCAT1/SCAT2) and balance testing. More US physicians initially used concussion-grading scales (26.7% vs 8.8% CAN, p=0.002); computerised neurocognitive testing (19.8% vs 1.3% CAN; p<0.001) and Standardised Assessment of Concussion (SAC) (21.8% vs 7.5% CAN; p=0.008). Most prescribed physical rest (83.8% CAN, 75.5% US), while fewer recommended cognitive rest (47.5% CAN, 28.4% US; p=0.008). Return-to-play decisions were based primarily on clinical examination (89.1% US, 73.8% CAN; p=0.007); US physicians relied more on neurocognitive testing (29.7% vs 5.0% CAN; p<0.001) and recognised guidelines (63.4% vs 23.8% CAN; p<0.001). One-third of Canadian physicians received KTE from colleagues, websites and medical school training. Leading KTE preferences included Continuing Medical Education (CME) courses and online CME.Existing published recommendations regarding diagnosis/management of concussion are not always translated into practise, particularly the recommendation for cognitive rest; predicating enhanced, innovative CME initiatives.
Why there are two cyclooxygenase isozymes
Authors: William L. Smith, Robert Langenbach
Journal: Journal of Clinical Investigation (2001)

Since the discovery in 1991 of a second isoform of prostaglandin endoperoxide H synthase (PGHS, or cyclooxygenase), there has been considerable interest in the question of why two isoforms of this enzyme are necessary and what roles they might play. PGHS-1–deficient (1) and PGHS-2–deficient (2, 3) mice and isoform-specific inhibitors have been developed and used to investigate the physiological functions of PGHS-1 and PGHS-2. These studies suggest that there are processes in which each isozyme is uniquely involved (e.g., platelet aggregation for PGHS-1, ovulation for PGHS-2) and others in which both isozymes function coordinately (e.g., carcinogenesis, inflammation). There are also physiological events in which one PGHS isozyme normally functions but for which the other can compensate when the first is lacking (e.g., parturition and remodeling of the ductus arteriosus). Biochemical studies indicate that each isoform can function independently; namely, that there are distinct PGHS-1 and PGHS-2 prostanoid biosynthetic pathways. Thus, the unique physiological roles for each isozyme can be rationalized by what is known about the biochemistry of the enzymes.

To facilitate discussion of the physiological functions of PGHS-1 and PGHS-2 and to point out those functions for which PGHS-1 and PGHS-2 can substitute for one another, we describe the following in sequence: (a) physiological processes that depend solely or primarily on PGHS-1, (b) physiological processes that depend solely or primarily on PGHS-2, and (c) processes in which both PGHS-1 and PGHS-2 are involved and act coordinately. We then summarize the biochemical evidence for distinct PGHS-1 and PGHS-2 biosynthetic pathways.
Microfabrication in Biology and Medicine
Authors: Joel Voldman, Martha L. Gray, Martin A. Schmidt
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Microfabrication uses integrated-circuit manufacturing technology supplemented by its own processes to create objects with dimensions in the range of micrometers to millimeters. These objects can have miniature moving parts, stationary structures, or both. Microfabrication has been used for many applications in biology and medicine. These applications fall into four domains: tools for molecular biology and biochemistry, tools for cell biology, medical devices, and biosensors. Microfabricated device structures may provide significantly enhanced function with respect to a conventional device. Sometimes microfabrication can enable devices with novel capabilities. These enhancing and enabling qualities are conferred when microfabrication is used appropriately to address the right types of problems. Herein, we describe microfabrication technology and its application to biology and medicine. We detail several classes of advantages conferred by microfabrication and how these advantages have been used to date.
Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide.
Authors: S J Collins, F W Ruscetti, R E Gallagher, R C Gallo
Journal: The Journal of Experimental Medicine (1979)

The HL-60 human promyelocytic leukemia cell line can be induced to terminally differentiate to mature myeloid cells sharing a number of functional characteristics with normal granulocytes including response to chemoattractants, development of complement receptors, phagocytosis, superoxide production, and nitroblue tetrazolium dye reduction. Hence the Me2SO-induced HL-60 cells provide a unique in vitro model for studying various important aspects of human myeloid cell differentiation.
Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
Authors: Paul A. Goepfert, Wendy Lumm, Paul Farmer, Philippa Matthews, Andrew Prendergast, Jonathan M. Carlson, Cynthia A. Derdeyn, Jianming Tang, Richard A. Kaslow, Anju Bansal, Karina Yusim, David Heckerman, Joseph Mulenga, Susan Allen, Philip J.R. Goulder, Eric Hunter
Journal: The Journal of Experimental Medicine (2008)

In a study of 114 epidemiologically linked Zambian transmission pairs, we evaluated the impact of human leukocyte antigen class I (HLA-I)–associated amino acid polymorphisms, presumed to reflect cytotoxic T lymphocyte (CTL) escape in Gag and Nef of the virus transmitted from the chronically infected donor, on the plasma viral load (VL) in matched recipients 6 mo after infection. CTL escape mutations in Gag and Nef were seen in the donors, which were subsequently transmitted to recipients, largely unchanged soon after infection. We observed a significant correlation between the number of Gag escape mutations targeted by specific HLA-B allele–restricted CTLs and reduced VLs in the recipients. This negative correlation was most evident in newly infected individuals, whose HLA alleles were unable to effectively target Gag and select for CTL escape mutations in this gene. Nef mutations in the donor had no impact on VL in the recipient. Thus, broad Gag-specific CTL responses capable of driving virus escape in the donor may be of clinical benefit to both the donor and recipient. In addition to their direct implications for HIV-1 vaccine design, these data suggest that CTL-induced viral polymorphisms and their associated in vivo viral fitness costs could have a significant impact on HIV-1 pathogenesis.
Mucosal Dendritic Cells
Authors: Akiko Iwasaki
Journal: Annual Review of Immunology (2007)

The internal surfaces of the human body are covered by distinct types of epithelial cells and mucus-secreting cells. The mucosal surfaces serve many vital functions, such as respiration (nasal passage and lung), absorption (gastrointestinal tract), excretion (lung, urinary tract, large intestine), and reproduction (reproductive tract). In performing these functions, the host is inevitably exposed to environmental antigens, food particles, commensal flora, and pathogens. Mucosal surfaces contain specialized dendritic cells (DCs) capable of sensing these external stimuli and mounting appropriate local responses depending on the nature of the elements they encounter. In the absence of pathogens, mucosal DCs either ignore the antigen or induce regulatory responses. Upon recognition of microorganisms that invade the mucosal barrier, mucosal DCs mount robust protective immunity. This review highlights progress in our understanding of how mucosal DCs process external information and direct appropriate responses by mobilizing various cells of the innate and adaptive immune systems to achieve homeostasis and protection.
Identification of a common gene signature for type II cytokine–associated myeloid cells elicited in vivo in different pathologic conditions
Authors: Gholamreza Hassanzadeh Ghassabeh, Patrick De Baetselier, Lea Brys, Wim Noël, Jo A. Van Ginderachter, Sofie Meerschaut, Alain Beschin, Frank Brombacher, Geert Raes
Journal: Blood (2006)
Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis
Authors: Thomas Yates, Steven M Haffner, Phillip J Schulte, Laine Thomas, Kim M Huffman, Connie W Bales, Robert M Califf, Rury R Holman, John J V McMurray, M Angelyn Bethel, Jaakko Tuomilehto, Melanie J Davies, William E Kraus
Journal: The Lancet (2013)
Rotator cuff degeneration and lateral epicondylitis: a comparative histological study.
Authors: M D Chard, T E Cawston, G P Riley, G A Gresham, B L Hazleman
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--Rotator cuff tendinitis and lateral epicondylitis are common in clinical practice but the underlying pathology is poorly understood. The study examined both normal and biopsy tendon specimens histologically, to determine the mechanisms involved in tendon degeneration. METHODS--Rotator cuff tendons from 83 cadavers aged 11-94 and tendon biopsy specimens from 20 patients with lateral epicondylitis aged 27-56 years were examined histologically. RESULTS--The microscopic changes found in the tendon biopsies from the elbow were similar to those found in the cadaveric rotator cuff tendons. Abnormalities ranged from minor blood vessel wall changes and loss of tenocytes to calcification. The most frequent abnormality was glycosaminoglycan infiltration and fibrocartilaginous transformation. There appeared to be some sequence in the changes observed which were milder in younger patients. Only 17% of cadaver tendons, below the age of 39 were abnormal but abnormalities increase in later life to around 40-50%. CONCLUSIONS--There was an increasing incidence of degenerative changes in tendons with age. The changes observed in biopsy samples of common extensor tendons were the same as those seen in aged supraspinatus tendons, but these changes were not seen in control common extensor tendons.
Circulating levels of frizzled-related protein (FRZB) are increased in patients with early rheumatoid arthritis and decrease in response to disease-modifying antirheumatic drugs
Authors: F. Corallini, P. Secchiero, G. Castellino, M. Montecucco, F. Trotta, G. Zauli
Journal: Annals of the Rheumatic Diseases (2010)

Products of the secreted frizzled-related protein (FRZB) families have crucial roles in the development and maintenance of bone, cartilage and joints, mainly by inhibiting the wnt and/β catenin pathway.1 In particular, while several important studies have associated FRZB (also known as sFRP3) with an increased susceptibility to the development of osteoarthritis,2,–,4 no information is available on the potential role of circulating FRZB in early rheumatoid arthritis (ERA).

We have measured the serum levels of FRZB by ELISA (R&D Systems, Minneapolis, Minnesota, USA) in a cohort of patients presenting with ERA, defined as previously described.5 Serological signs of inflammation (raised erythrocyte sedimentation rate or C reactive …
Psychosocial Telephone Counseling for Survivors of Cervical Cancer: Results of a Randomized Biobehavioral Trial
Authors: Lari Wenzel, Kathryn Osann, Susie Hsieh, Jo A. Tucker, Bradley J. Monk, Edward L. Nelson
Journal: Journal of Clinical Oncology (2015)

Purpose Survivors of cervical cancer experience quality-of-life (QOL) disruptions that persist years after treatment. This study examines the effect of a psychosocial telephone counseling (PTC) intervention on QOL domains and associations with biomarkers. Patients and Methods We conducted a randomized clinical trial in survivors of cervical cancer, who were ≥ 9 and less than 30 months from diagnosis (n = 204), to compare PTC to usual care (UC). PTC included five weekly sessions and a 1-month booster. Patient-reported outcomes (PROs) and biospecimens were collected at baseline and 4 and 9 months after enrollment. Changes in PROs over time and associations with longitudinal change in cytokines as categorical variables were analyzed using multivariable analysis of variance for repeated measures. Results Participant mean age was 43 years; 40% of women were Hispanic, and 51% were non-Hispanic white. Adjusting for age and baseline scores, participants receiving PTC had significantly improved depression and improved gynecologic and cancer-specific concerns at 4 months compared with UC participants (all P &lt; .05); significant differences in gynecologic and cancer-specific concerns (P &lt; .05) were sustained at 9 months. Longitudinal change in overall QOL and anxiety did not reach statistical significance. Participants with decreasing interleukin (IL) -4, IL-5, IL-10, and IL-13 had significantly greater improvement in QOL than those with increasing cytokine levels. Conclusion This trial confirms that PTC benefits mood and QOL cancer-specific and gynecologic concerns for a multiethnic underserved population of survivors of cancer. The improvement in PROs with decreases in T-helper type 2 and counter-regulatory cytokines supports a potential biobehavioral pathway relevant to cancer survivorship.
Rate of Healing of Neuropathic Ulcers of the Foot in Diabetes and Its Relationship to Ulcer Duration and Ulcer Area
Authors: Paul Ince, Fran L. Game, William J. Jeffcoate
Journal: Diabetes Care (2007)

To examine the outcome of neuropathic foot ulcers and to seek associations between healing and features of the ulcers at baseline.Data were collected prospectively during the course of routine management. All patients were selected who presented to a single unit between 1 January 2000 and 31 December 2004 with neuropathic foot ulcers and without evidence of either peripheral arterial disease or infection. Associations were sought between ulcer characteristics at baseline and clinical outcome.A total of 154 patients (66.9% male) presented with 410 ulcers. Age was 57.4 +/- 12.0 years (means +/- SD). A total of 178 (43.4%) ulcers were on the plantar aspect of the foot; 73.7% of ulcers had a cross-sectional area of <1 cm2. Median ulcer duration at referral was 15 days (range 1-1,046). Healing without amputation was observed in 91.7%. The percentage of ulcers healed at 12, 20, and 52 weeks were 59.3, 70.5, and 86.6%, respectively. Significant associations were observed between area at referral and outcome type (chi2 P < 0.0001), prior ulcer duration (Kruskal-Wallis P = 0.006), and time to healing (Kruskal-Wallis P = 0.014), as well as between ulcer duration and time to healing (Spearman rho, r = 0.104, P = 0.047). There was no difference between plantar and nonplantar ulcers.The rate of healing in this cohort provides a benchmark for comparison with other centers. While further work is needed to determine how outcomes can be improved in unselected series such as these, the confirmation of close relationships between ulcer duration at referral, ulcer area, and outcome emphasizes the importance of early expert assessment of newly occurring neuropathic ulcers.
Influenza vaccines in patients with IBD: ready for primetime?
Authors: K. M. Kunisaki
Journal: Gut (2011)

Influenza viruses have long been a major global public health problem. In particular, sudden shifts in influenza strains can result in global pandemics, as recently experienced with 2009 Influenza A (H1N1). When the WHO declared an end to the pandemic in August 2010, >18 000 deaths had been attributed to 2009 H1N1.1 This number was thankfully much lower than initially feared, but concern persists of a future recurrence of the 1918 ‘Spanish flu’ pandemic that resulted in an estimated 50 million global deaths.2

Influenza vaccination is considered the most effective method to lessen the public health impact of influenza. Among healthy adults, influenza vaccination has been shown to be safe, reduce influenza symptoms and reduce working days lost.3 However, influenza vaccination is poorly studied in those with immunocompromise.

In their paper published in Gut ( see page 456 ), Rahier and colleagues provide novel new data regarding influenza vaccination in an immunocompromised patient population—patients with inflammatory bowel disease …
In vivo estimation of cardiac transmembrane current.
Authors: F X Witkowski, K M Kavanagh, P A Penkoske, R Plonsey
Journal: Circulation Research (1993)

The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in vivo technique that incorporates an electrode array with cellular dimensions to continuously estimate the extracellular counterparts of cardiac Ims. Mathematical modeling was performed for uniform plane wave propagation to clarify the biophysical basis and underlying assumptions inherent in this approach. Five-element electrode arrays incorporating 75-microns-diameter silver electrodes with center-to-center distances of 210 microns were experimentally verified to provide spatially sufficient samples for voltage gradient determinations of myocardial activation. Similar results were obtained with 25-microns-diameter electrodes at a center-to-center spacing of 65 microns. An estimate of Im was obtained from the derivative of the magnitude of the voltage gradient of the measured interstitial potentials. The inward component of Im generated by normal Na+ channel activation at 37 degrees C was measured in vivo to be less than 1 msec in duration, consistent with previously known voltage-clamp and simulation results. Intravenous KCl bolus injection was used to demonstrate the voltage-dependent depression of Na(+)-mediated Im in vivo, culminating in either severely depressed Na(+)-mediated or Ca(2+)-mediated activations. Normal Na(+)-, depressed Na(+)-, and possibly Ca(2+)-mediated currents can be recorded in vivo using this technique.
Survival differences between European and US patients with colorectal cancer: role of stage at diagnosis and surgery
Authors: L Ciccolallo, R Capocaccia, M P Coleman, F Berrino, J W W Coebergh, R A M Damhuis, J Faivre, C Martinez-Garcia, H Møller, M Ponz de Leon, G Launoy, N Raverdy, E M I Williams, G Gatta
Journal: Gut (2005)

<b>Background:</b> Population based colorectal cancer survival among patients diagnosed in 1985–89 was lower in Europe than in the USA (45% <i>v</i> 59% five year relative survival). <b>Aims:</b> To explain this difference in survival using a new analytic approach for patients diagnosed between 1990 and 1991. <b>Subjects:</b> A total of 2492 European and 11 191 US colorectal adenocarcinoma patients registered by 10 European and nine US cancer registries. <b>Methods:</b> We obtained clinical information on disease stage, number of lymph nodes examined, and surgical treatment. We analysed three year relative survival, calculating relative excess risks of death (RERs, referent category US patients) adjusted for age, sex, site, surgery, stage, and number of nodes examined, using a new multivariable approach. <b>Results:</b> We found that 85% of European patients and 92% of US patients underwent surgical resection. Three year relative survival was 69% for US patients and 57% for European patients. After adjustment for age, sex, and site, the RER was significantly high in all 10 European populations, ranging from 1.07 (95% confidence interval 0.86–1.32) (Modena, Italy) to 2.22 (1.79–2.76) (Thames, UK). After further adjustment for stage, surgical resection, and number of nodes examined (a determinant of stage), RERs ranged from 0.77 (0.62–0.96) to 1.59 (1.28–1.97). For some European registries the excess risk was small and not statistically significant. <b>Conclusions:</b> US-Europe survival differences in colorectal cancer are large but seem to be mostly attributable to differences in stage at diagnosis. There are wide variations in diagnostic and surgical practice between Europe and the USA.
Erratum to “Human pluripotent stem cell-derived hepatocytes support complete replication of hepatitis C virus” [J Hepatol 2012;57:246–251]
Authors: Philip Roelandt, Susan Obeid, Jan Paeshuyse, Jolien Vanhove, Alfons Van Lommel, Yaakov Nahmias, Frederik Nevens, Johan Neyts, Catherine M. Verfaillie
Journal: Journal of Hepatology (2012)
Acute intralipid infusion reduces cardiac luminal lipoprotein lipase but recruits additional enzyme from cardiomyocytes
Authors: D QI, K KUO, A ABRAHANI, D AN, Y QI, J HEUNG, G KEWALRAMANI, T PULINILKUNNIL, S GHOSH, S INNIS
Journal: Cardiovascular Research (2006)

Objective: Lipoprotein lipase (LPL) metabolizes the triglyceride (TG) core of lipoproteins. We evaluated whether circulating lipids can regulate LPL by influencing the transfer of enzyme from the myocyte to the endothelial lumen.