tbuckley/cabot-search huggingface dataset:
Decrease of hepatic triglyceride lipase levels and increase of cholesteryl ester transfer protein levels in patients with primary biliary cirrhosis: Relationship to abnormalities in high-density lipoprotein
Authors: Hisatoyo Hiraoka, Shizuya Yamashita, Yuji Matsuzawa, Masaharu Kubo, Shuichi Nozaki, Naohiko Sakai, Ken-Ichi Hirano, Sumio Kawata, Seiichiro Tarui
Journal: Hepatology (1993)

Serum levels of high-density lipoprotein cholesterol are often increased in patients with primary biliary cirrhosis. To elucidate the mechanism of the elevation of high-density lipoprotein cholesterol levels in this disease, lipoprotein abnormalities were analyzed in 10 patients subdivided into two groups according to concentration of high-density lipoprotein cholesterol. Activities and protein masses of lipoprotein lipase, hepatic triglyceride lipase and cholesteryl ester transfer protein were also determined. Serum highdensity lipoprotein cholesterol concentration exceeded 90 mg/dl in 5 of 10 patients. Lipoprotein particles in the high-density lipoprotein2 fraction (with density between 1.063 and 1.125 gm/ml) were enriched with apolipoprotein E and larger in size than those of normal controls. In patients with and without hyperalphalipoproteinemia, hepatic triglyceride lipase activity was significantly decreased (p < 0.05); this was due to the reduction of its protein mass. Lipoprotein lipase activity and protein mass were normal. It is noteworthy that increases in cholesteryl ester transfer protein activity and mass were observed. The enhancement of cholesteryl ester transfer protein activity was more remarkable in the patients with hyperalphalipoproteinemia than in those without hyperalphalipoproteinemia. Because a significant postive correlation was demonstrated between activity and protein mass (r = 0.90, p <0.001), the increase of cholesteryl ester transfer protein activity may be attributed to the increase of its protein mass. These data suggest that the decrease of hepatic triglyceride lipase levels at least partly explains the appearance of apolipoprotein E–rich large high-density lipoprotein particles in patients with primary biliary cirrhosis. Considering that the deficiency of cholesteryl ester transfer protein has been shown to cause marked hyperalphalipoproteinemia with similar abnormalities of high-density-lipoprotein particles, the increase of cholesteryl ester transfer protein activity in primary biliary cirrhosis with hyperalphalipoproteinemia is peculiar and interesting, although its mechanism remains unknown. (HEPATOLOGY 1993;18:103–110).
Coronary Angiographic Changes with Lovastatin Therapy: The Monitored Atherosclerosis Regression Study (MARS)
Authors: David H. Blankenhorn
Journal: Annals of Internal Medicine (1993)

Objective: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. Design: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. Setting: Community- and university-based cardiac catheterization laboratories. Participants: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. Intervention: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. Outcome: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). Results: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). Conclusion: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall. * For current author affiliations and addresses, see end of text. See the appendix for a listing of the members of the MARS Research Group. Dr. Blankenhorn died on 9 May 1993.
Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis
Authors: Maria J H Boumans, Rogier M Thurlings, Lorraine Yeo, Dagmar Scheel-Toellner, Koen Vos, Danielle M Gerlag, Paul P Tak
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients. Methods Twenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp–van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor κB ligand (RANKL), osteocalcin and cross-linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment. Results After 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor κB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p&lt;0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change. Conclusions Rituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA.
Nonsyndromatic paucity of interlobular bile ducts: Light and electron microscopic evaluation of sequential liver biopsies in early childhood
Authors: Ellen Kahn, Fredric Daum, James Markowitz, Saul Teichberg, Lynn Duffy, Rita Harper, Harvey Aiges
Journal: Hepatology (1986)

Liver biopsies and/or autopsy specimens from 17 children (ages 1 week to 5 years) with nonsyndromatic paucity of the interlobular bile ducts were studied by light and electron microscopy. Initial biopsies were obtained before 90 days of age from all patients, and two or more specimens were available from nine. No specific underlying condition was found in nine infants. The remaining cases were associated with Down's syndrome (n = 2), hypopituitarism (n = 2), cystic fibrosis (n = 1), α 1 -antitrypsin deficiency (n = 1), cytomegalovirus (n = 1) and Ivemark syndrome (n = 1). Before 90 days of age, portal changes included duct paucity and fibrosis. Lobular changes were nonspecific, consisting of cholestasis, giant cell transformation, extramedullary hematopoiesis and perisinusoidal fibrosis. Duct paucity, portal fibrosis and perisinusoidal fibrosis persisted after 90 days. Cholestasis was mild or no longer apparent. Portal changes before 90 days of age appear to be sufficiently distinctive to microscopically distinguish nonsyndromatic from syndromatic paucity. Electron microscopic findings suggest that paucity in nonsyndromatic patients may result from a primary ductal insult: ultrastructural studies revealed bile duct destruction characterized by undulation and breaks in the basal lamina and infiltration of the epithelium by lymphocytes. Bile canalicular dilatation with blunting of microvilli and electron-dense material in the lumen, predominantly seen before 90 days, also reinforces the hypothesis of a primary ductal defect.
Mutational Analysis of Circulating Dna and Cells in Patients with Metastatic Colorectal Cancer
Authors: J.L. García, I. Matos, R. Lozano Mejorada, E. Fonseca, R. Benito, A. Santos-Briz, A. Brownrigg-Gleeson, J.M. Hernandez-Rivas, J.J. Cruz Hernandez
Journal: Annals of Oncology (2014)
THE POLICY OF THE OSTRICH
Authors: J. G. Adami
Journal: BMJ (1919)

after thirty-six moutls' service than it is after tlhree iontls, indicates that in tihese cases as well this increase is tranisitory; on restinig, the albuminuria soon returns to its old level.Resultts of Investi,qatiion itto the Possible Relationship of Previoussly EKxisting Abitunziiria to TWar Nephriti.4.Out of the 50,000 men examined only 161 cases were returned up to Marck, 191&, as possibly suffering from nephritis.In 29 of these the diagnosis was doubtful, as they were returned as suffering from "albuminuria."In the remaining 132 a diagnosis of nephritis was ultimately obtained in all cases, though in
Longitudinal Association of Glucose Metabolism With Retinopathy
Authors: Robyn J. Tapp, Gabriella Tikellis, Tien Y. Wong, C. Alex Harper, Paul Z. Zimmet, Jonathan E. Shaw
Journal: Diabetes Care (2008)

OBJECTIVE—We determined the longitudinal association of glucose metabolism with retinopathy in a sample of the Australian population. RESEARCH DESIGN AND METHODS—The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged ≥25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999–2000 and 5 years later in 2004–2005 in participants identified as having diabetes (based on self-report and oral glucose tolerance test) and impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1,192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system. RESULTS—The 5-year incidences of retinopathy were 13.9 and 3.0% among those with known and newly diagnosed diabetes at baseline, respectively. Of those who developed incident newly diagnosed diabetes at follow-up, 11.9% had retinopathy at baseline compared with 5.6% of those who did not progress to incident newly diagnosed diabetes (P = 0.037). After adjustment for factors identified as risk factors for diabetes, individuals with retinopathy signs at baseline were twice as likely to develop incident newly diagnosed diabetes compared with those who did not have retinopathy signs at baseline. CONCLUSIONS—The 5-year incidence of retinopathy was 13.9% among individuals with known diabetes. Nondiabetic individuals with retinopathy signs at baseline had a twofold higher risk of developing incident newly diagnosed diabetes 5 years later. This result provides further evidence that mild retinopathy signs may be a preclinical marker of underlying microvascular disease and future diabetes risk.
Phenolic glycolipid-I of Mycobacterium leprae induces general suppression of in vitro concanavalin A responses unrelated to leprosy type.
Authors: H K Prasad, R S Mishra, I Nath
Journal: The Journal of Experimental Medicine (1987)

Using a costimulant assay, in vitro Con A responses of patients across the leprosy spectrum were found to be markedly suppressed by phenolic glycolipid-I (PGL-I), a unique antigen of M. leprae. The degree of inducible suppression as well as the number of leprosy patients showing suppression of mitogenic responses was higher with PGL-I as compared with integral M. leprae (p less than 0.05 to less than 0.01). Both untreated lepromatous (60%) as well as tuberculoid leprosy (67%) patients showed significant suppression ranging from 13 to 64% and 12 to 79%, respectively. Thus, PGL-I appears to have a universal suppressive effect on Con A responses and is unlikely to play a central role in determining the leprosy spectrum.
General practice registrar responses to the use of different risk communication tools in simulated consultations: a focus group study
Authors: A. Edwards, G. Elwyn, R. Gwyn
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To pilot the use of a range of complementary risk communication tools in simulated general practice consultations; to gauge the responses of general practitioners in training to these new consultation aids. <b>Design:</b> Qualitative study based on focus group discussions. <b>Setting:</b> General practice vocational training schemes in South Wales. <b>Participants:</b> 39 general practice registrars and eight course organisers attended four sessions; three simulated patients attended each time. <b>Method:</b> Registrars consulting with simulated patients used verbal or "qualitative" descriptions of risks, then numerical data, and finally graphical presentations of the same data. Responses of doctors and patients were explored by semistructured discussions that had been audiotaped for transcription and analysis. <b>Results:</b> The process of using risk communication tools in simulated consultations was acceptable to general practitioner registrars. Providing doctors with information about risks and benefits of treatment options was generally well received. Both doctors and patients found it helped communication There were concerns about the lack of available, unbiased, and applicable evidence and a shortage of time in the consultation to discuss treatment options adequately. Graphical presentation of information was often favoured—an approach that also has the potential to save consultation time. <b>Conclusions:</b> A range of risk communication "tools" with which to discuss treatment options is likely to be more applicable than a single new strategy. These tools should include both absolute and relative risk information formats, presented in an unbiased way. Using risk communication tools in simulated consultations provides a model for training in risk communication for professional groups. <h3>Key messages</h3> Involving patients in decisions about their treatment or care improves health outcomes Successful involvement of patients requires effective communication of risks Having a range of risk communication tools from which to choose when discussing treatment options is likely to be more appropriate and flexible for clinical practice than single new strategies Different presentation formats include verbal descriptions of risks, numerical data, and graphical depiction of the information Graphical presentation of data on risk can be effective and save time in general practice consultations
Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data
Authors: N. Derichs, J. Sanz, T. Von Kanel, C. Stolpe, A. Zapf, B. Tummler, S. Gallati, M. Ballmann
Journal: Thorax (2010)

The value of the signs and symptoms of pregnancy and of the pregnancy diagnostic test as predictors of pregnancy was estimated for 1,592 women seen in general practice. The presence of a sign or symptom alone is a poor pointer to a diagnosis of pregnancy. The combination of pairs of features improves the value, the best being breast signs combined with either the presence of signs of pregnancy on vaginal examination or a palpable fundus, both giving predictive values of 0·89. The pregnancy diagnostic test alone, however, had a predictive value of 0·91, a value of 1·00 indicating 100 per cent reliability.
The value of an interview
Authors: J R Pilley
Journal: Journal of the Royal Society of Medicine (2007)

In the letter we call on Reed to cease all involvement in arms fairs.In particular we state that Reed's involvement in the arms trade 'is entirely at odds with the ethical and social obligations we have to promote the beneficial applications of our work and prevent its misuse, to anticipate and evaluate the possible unintended consequences of scientific and technological developments, and to consider at all times the moral responsibility we carry for our work.'
Expression and function of a variant T cell receptor complex lacking CD3-gamma.
Authors: P Pérez-Aciego, B Alarcón, A Arnaiz-Villena, C Terhorst, M Timón, O G Segurado, J R Regueiro
Journal: The Journal of Experimental Medicine (1991)

A T cell line termed DIL2 has been derived from an infant with a polyclonal T cell receptor (TCR)/CD3 cell surface expression defect. Indirect immunofluorescence showed that the expression of certain TCR/CD3 epitopes (like those detected by WT31 and BMA031 monoclonals) was strongly reduced (around five-fold) on DIL2, whereas other epitopes (like those detected by SP34 and Leu4) were only around two-fold lower than in normal T cell lines. Specific immunoprecipitates of surface-radioiodinated DIL2 cells contained TCR-alpha, TCR-beta, CD3-delta, CD3-epsilon and TCR-zeta chains, but lacked CD3-gamma. This structural TCR/CD3 variant was, however, capable of transducing certain activation signals, since normal proliferation and a low but significant calcium flux was observed in DIL2 cells after engagement with specific antibodies. Our data suggest that a functional TCR/CD3 complex can be expressed on the surface of T cells in the absence of CD3-gamma.
Type I IFN enhances follicular B cell contribution to the T cell–independent antibody response
Authors: Cristina L. Swanson, Timothy J. Wilson, Pamela Strauch, Marco Colonna, Roberta Pelanda, Raul M. Torres
Journal: The Journal of Experimental Medicine (2010)

Humoral immunity to viruses and encapsulated bacteria is comprised of T cell–independent type 2 (TI-2) antibody responses that are characterized by rapid antibody production by marginal zone and B1 B cells. We demonstrate that toll-like receptor (TLR) ligands influence the TI-2 antibody response not only by enhancing the overall magnitude but also by skewing this response to one that is dominated by IgG isotypes. Importantly, TLR ligands facilitate this response by inducing type I interferon (IFN), which in turn elicits rapid and significant amounts of antigen-specific IgG2c predominantly from FO (follicular) B cells. Furthermore, we show that although the IgG2c antibody response requires B cell–autonomous IFN-α receptor signaling, it is independent of B cell–intrinsic TLR signaling. Thus, innate signals have the capacity to enhance TI-2 antibody responses by promoting participation of FO B cells, which then elaborate effective IgG anti-pathogen antibodies.
Cardiac Output in Pregnancy: Correlation Between Evans Blue Dye and Blood Pressure Methods
Authors: CHARLES H. HENDRICKS, EDWARD J. QUILLIGAN
Journal: Circulation Research (1955)

Cardiac output estimations done by the pulse pressure method were compared to those done simultaneously by the dye method in pregnancy, labor, and in the early puerperium. The subjects selected were young, healthy and without edema or clinical evidence of heart disease. A total of 30 determinations was carried out on 23 subjects. Agreement within 25 per cent of the dye method was attained in 90 per cent of the blood pressure method tests.
Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability
Authors: Georg Hennemann, Roelof Docter, Edith C. H. Friesema, Marion de Jong, Eric P. Krenning, Theo J. Visser
Journal: Endocrine Reviews (2001)

Although it was originally believed that thyroid hormones enter target cells by passive diffusion, it is now clear that cellular uptake is effected by carrier-mediated processes. Two stereospecific binding sites for each T4 and T3 have been detected in cell membranes and on intact cells from humans and other species. The apparent Michaelis-Menten values of the high-affinity, low-capacity binding sites for T4 and T3 are in the nanomolar range, whereas the apparent Michaelis- Menten values of the low-affinity, high-capacity binding sites are usually in the lower micromolar range. Cellular uptake of T4 and T3 by the high-affinity sites is energy, temperature, and often Na+ dependent and represents the translocation of thyroid hormone over the plasma membrane. Uptake by the low-affinity sites is not dependent on energy, temperature, and Na+ and represents binding of thyroid hormone to proteins associated with the plasma membrane. In rat erythrocytes and hepatocytes, T3 plasma membrane carriers have been tentatively identified as proteins with apparent molecular masses of 52 and 55 kDa. In different cells, such as rat erythrocytes, pituitary cells, astrocytes, and mouse neuroblastoma cells, uptake of T4 and T3 appears to be mediated largely by system L or T amino acid transporters. Efflux of T3 from different cell types is saturable, but saturable efflux of T4 has not yet been demonstrated. Saturable uptake of T4 and T3 in the brain occurs both via the blood-brain barrier and the choroid plexus-cerebrospinal fluid barrier. Thyroid hormone uptake in the intact rat and human liver is ATP dependent and rate limiting for subsequent iodothyronine metabolism. In starvation and nonthyroidal illness in man, T4 uptake in the liver is decreased, resulting in lowered plasma T3 production. Inhibition of liver T4 uptake in these conditions is explained by liver ATP depletion and increased concentrations of circulating inhibitors, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indoxyl sulfate, nonesterified fatty acids, and bilirubin. Recently, several organic anion transporters and L type amino acid transporters have been shown to facilitate plasma membrane transport of thyroid hormone. Future research should be directed to elucidate which of these and possible other transporters are of physiological significance, and how they are regulated at the molecular level.
Influence of Muscle Afferents on Cutaneous and Muscle Vessels in the Dog
Authors: DENIS L. CLEMENT, JOHN T. SHEPHERD
Journal: Circulation Research (1974)

In 13 anesthetized dogs with their vagi cut and their carotid sinuses kept at constant pressure, the gracilis artery, cranial tibial artery, and lateral saphenous vein of the left hind limb were isolated and perfused at constant flow. In the right hind limb, muscle afferents were stimulated by electrodes in the thigh muscles. At 5 Hz, aortic blood pressure decreased 45 ± 8 mm Hg; perfusion pressure decreased in the gracilis muscle and the paw (26 ± 6 mm Hg and 26 ± 5 mm Hg, respectively) and increased in the saphenous vein (13 ± 3 mm Hg). These effects were not prevented by paralysis of the stimulated muscles, beta-receptor blockade, or administration of atropine or antihistaminic drugs. At 40 Hz, aortic blood pressure increased 29 ± 8 mm Hg; perfusion pressure increased in the gracilis muscle and the paw (33 ± 5 mm Hg and 33 ± 3 mm Hg, respectively) and decreased in the saphenous vein (20 ± 2 mm Hg). These effects were prevented or reversed by paralysis of the stimulated muscles. Similar effects were obtained by central stimulation of the femoral nerve. Left sympathectomy or alpha-receptor blockade abolished the responses in the isolated vascular beds. Thus, muscle contraction is necessary only to activate the muscle afferents which cause constriction of resistance vessels in muscle and paw and dilation of cutaneous veins.