tbuckley/cabot-search huggingface dataset:
Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix.
Authors: U Saxena, M G Klein, T M Vanni, I J Goldberg
Journal: Journal of Clinical Investigation (1992)

Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of 125I-labeled LDL, LDL transport across the monolayers was unchanged; but, at all concentrations of LDL tested (1-100 micrograms), LDL retention by the monolayers increased more than fourfold. 125I-labeled LDL binding to extracellular matrix increased when LPL was added directly to the matrix or was added to the basolateral side of the endothelial cell monolayers. Increased LDL binding required the presence of LPL and was not associated with LDL aggregation. LPL also increased VLDL, but not HDL, retention. Monoclonal anti-LPL IgG decreased both VLDL and LDL retention in the presence of LPL. Lipoprotein transport across the monolayers increased during hydrolysis of VLDL triglyceride (TG). In the presence of LPL and VLDL, VLDL transport across the monolayers increased 18% and LDL transport increased 37%. High molar concentrations of oleic acid to bovine serum albumin (3:1) in the medium increased VLDL transport approximately 30%. LDL transport increased 42% when oleic acid was added to the media. Therefore, LPL primarily increased retention of LDL and VLDL. A less remarkable increase in lipoprotein transport was found during hydrolysis of TG-containing lipoproteins. We hypothesize that LPL-mediated VLDL and LDL retention within the arterial wall potentiates conversion of these lipoproteins to more atherogenic forms.
An Animal Model of MYC-Driven Medulloblastoma
Authors: Yanxin Pei, Colin E. Moore, Jun Wang, Alok K. Tewari, Alexey Eroshkin, Yoon-Jae Cho, Hendrik Witt, Andrey Korshunov, Tracy-Ann Read, Julia L. Sun, Earlene M. Schmitt, C. Ryan Miller, Anne F. Buckley, Roger E. McLendon, Thomas F. Westbrook, Paul A. Northcott, Michael D. Taylor, Stefan M. Pfister, Phillip G. Febbo, Robert J. Wechsler-Reya
Journal: Cancer Cell (2012)
Evidence for a Structural Requirement for the Aggregation of Platelets by Collagen
Authors: Russell Jaffe, Daniel Deykin
Journal: Journal of Clinical Investigation (1974)

This study investigates whether soluble collagen can initiate platelet aggregation or whether a higher degree of polymerization is required. Purified rat skin collagen was prepared in four states. Soluble monomeric collagen, containing 2 muM calcium chloride, was maintained at 4 degrees C until use. A previously uncharacterized form of collagen, soluble microfibrillar collagen, was prepared from monomeric collagen containing calcium chloride by allowing it to polymerize at 23 degrees C. Viscometric and electron microscopic characterization of microfibrillar collagen indicated polymerization to ordered native filaments. Particulate native macrofibrillar collagen was prepared from monomeric collagen by allowing it to polymerize at 37 degrees C in the absence of calcium. Particulate collagen, in which the fibers were randomly associated, was prepared by salt precipitation of calcium-free monomeric collagen. Microfibrillar and native macrofibrillar collagen initiated platelet aggregation, with a lag phase of approximately 60 s. Monomeric collagen initiated aggregation with a lag phase of approximately 180 s. The duration of the lag phase for platelet aggregation initiated by monomeric collagen was independent of the dose. Salt-precipitated particulate collagen did not initiate platelet aggregation. Agents which prolong the transition from monomeric collagen to fibrillar collagen (urea, arginine) retarded or prevented the aggregation of platelets by monomeric collagen. Sodium borohydride, which stabilizes the intraand intermolecular cross-links of collagen did not affect platelet aggregation. Penicillamine, which displaces the intermolecular cross-links and binds the intramolecular cross-links of collagen, did not prevent platelet aggregation. The data suggest that an architectural requirement exists for the initiation of self-perpetuating platelet aggregation; that tropocollagen units do not fulfill this requirement; that a soluble collagen preparation, microfibrillar collagen, contains the minimal structural unit; and that cross-linkages within collagen do not play a critical role in platelet aggregation.
Inactivation of the<i>APC</i>Gene Is Constant in Adrenocortical Tumors from Patients with Familial Adenomatous Polyposis but Not Frequent in Sporadic Adrenocortical Cancers
Authors: Sébastien Gaujoux, Stéphane Pinson, Anne-Paule Gimenez-Roqueplo, Laurence Amar, Bruno Ragazzon, Pierre Launay, Tchao Meatchi, Rossella Libé, Xavier Bertagna, Anne Audebourg, Jessica Zucman-Rossi, Frédérique Tissier, Jérôme Bertherat
Journal: Clinical Cancer Research (2010)

In adrenocortical tumors (ACT), Wnt/β-catenin pathway activation can be explained by β-catenin somatic mutations only in a subset of tumors. ACT is observed in patients with familial adenomatous polyposis (FAP) with germline APC mutations, as well as in patients with Beckwith-Wiedemann syndrome with Wilms' tumors reported to have WTX somatic mutations. Both APC and WTX are involved in Wnt/β-catenin pathway regulation and may play a role in ACT tumorigenesis. The aim of this study was to report if APC and WTX may be associated with FAP-associated and sporadic ACT.ACTs from patients with FAP and sporadic adrenocortical carcinomas (ACC) with abnormal β-catenin localization on immunohistochemistry but no somatic β-catenin mutations were studied. APC was analyzed by denaturing high-performance liquid chromatography followed by direct sequencing and by multiplex ligation-dependent probe amplification when allelic loss was suspected. WTX was studied by direct sequencing.Four ACTs were observed in three patients with FAP and were ACC, adrenocortical adenoma, and bilateral macronodular adrenocortical hyperplasia, all with abnormal β-catenin localization. Biallelic inactivation of APC was strongly suggested by the simultaneous existence of somatic and germline alterations in all ACTs. In the 20 sporadic ACCs, a silent heterozygous somatic mutation as well as a rare heterozygous polymorphism in APC was found. No WTX mutations were observed.ACT should be considered a FAP tumor. Biallelic APC inactivation mediates activation of the Wnt/β-catenin pathway in the ACTs of patients with FAP. In contrast, APC and WTX genetic alterations do not play a significant role in sporadic ACC.
Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual nonfusion pattern and observations on bacterial survival.
Authors: J A Armstrong, P D Hart
Journal: The Journal of Experimental Medicine (1975)

Tubercle bacilli of the pathogenic human strain H37Rv had previously been shown to multiply, after ingestion by cultured mouse peritoneal macrophages, within phagosomes that tended to remain unfused with secondary lysosomes. Means were sought therefore for promoting experimentally a modification of the host response so as to attain a high level of phagolysosome formation, enabling tests to be made of any effects on the course and outcome of the intracellular infection. This was achieved by exposing viable bacilli to specific rabbit antiserum before their ingestion. Quantitative assessments, using electron microscopy, now showed that a majority of the phagosomes containing intact bacilli had fused with ferritin-labeled lysosomes, and frequently the fusion was massive. Bacterial viability studies established that the serum pretreatment was not itsel bactericidal. In the course of progressive infections with strain H37Rv, monitored by counts both of viable bacterial units and of intracellular acid-fast organisms, no appreciable difference was found between the intracellular growth rates of control and antiserum-treated bacilli. Concurrent electron microscopy showed that bacilli could remain intact and multiply both in phaagolysosomes and in unfused phagosomes, ruling out the possibility of selective growth of antiserum-pretreated bacilli within the minority of phagosomes that remained unfused. It was concluded that "turning on" phagosome-lysosome fusion in normal macrophages did not influence the outcome of infection with virulent M. tuberculosis; lysosome contents manifestly failed to exercise an antibacterial effect on this organism. Nevertheless, the possibility remains that the lysosomes of specific immune macrophages have antituberculous potentiality. In that case the experimental "turning on or off" of fusion could be a decisive factor in the outcome of a virulent challenge. Should it not be, the antibacterial capabilities of immune cells would need to be ascribed to factors other than lysosomal attack, the latter being essentially for disposal of the dead organisms.
Eating Attitudes and Behaviors in 1,435 South African Caucasian and Non-Caucasian College Students
Authors: Daniel le Grange, Christy F. Telch, Jason Tibbs
Journal: American Journal of Psychiatry (1998)

The purpose of this study was to examine the presence and severity of eating disorder pathology in students representing South Africa's ethnically and culturally diverse population.A questionnaire survey, which involved the Eating Attitude Test and the Bulimic Investigatory Test, was administered to 1,435 South African college students (739 Caucasian and 696 non-Caucasian) from six universities in two urban centers.Black students scored significantly higher than the other ethnic groups on these measures. In addition, a comparable percentage of black and Caucasian female students had scores within the clinical range on these scales. Male students scored consistently lower than female students.This study's findings challenge the notion that eating disorders are primarily a Western, Caucasian phenomenon and raise the possibility that the risk of eating disorders may increase in developing societies.
Multiple keratoacanthomas: association with deficient cell mediateted immunity
Authors: A. CLAUDY, J. THIVOLET
Journal: British Journal of Dermatology (1975)

A case of multiple keratoacanthomas associated with deficient cell mediated immunity in a 44-year-old male Caucasian is presented. Many attempts to restore the lymphocyte function (transfer factor, levamisole) have failed but the treatments may have had a curative effect on the development of new lesions. The significance of impaired cellular immune defense mechanisms is discussed.
Survival in Recipients of Marginal Cadaveric Donor Kidneys Compared with Other Recipients and Wait-Listed Transplant Candidates
Authors: AKINLOLU O. OJO, JULIE A. HANSON, HERWIG-ULF MEIER-KRIESCHE, CHIKE N. OKECHUKWU, ROBERT A. WOLFE, ALAN B. LEICHTMAN, LAWRENCE Y. AGODOA, BRUCE KAPLAN, FRIEDRICH K. PORT
Journal: Journal of the American Society of Nephrology (2001)

Abstract. An increasing number of cadaveric kidney transplants are now performed with organs from donors who would have been deemed unsuitable in earlier times. Although good allograft outcomes have been obtained with these marginal donor transplants, it is unclear whether recipients of marginal kidney transplants achieve a reduction in long-term mortality as do recipients of “ideal” kidneys. Patients with end-stage renal disease registered on the cadaveric renal transplant waiting list between January 1, 1992, and June 30, 1997, were studied for mortality risks according to three outcomes: wait-listed on dialysis treatment with no transplant (WLD); transplantation with marginal donor kidney (MDK); and “ideal” or optimal donor kidney transplantation (IDK). Thirty-four percent of wait-list registrants had received a cadaveric kidney transplant by June 30, 1998. Of these, 18% received a marginal kidney that had one or more of the following pretransplant factors: donor age &gt;55 yr, non-heartbeating donor, cold ischemia time &gt;36 h, and donor hypertension or diabetes mellitus of &gt; 10 yr duration. Five-year graft and patient survival was 53% and 74% for MDK recipients compared with 67% ( P &lt; 0.001) and 80% ( P &lt; 0.001) for IDK recipients. Adjusted annual death rate and estimated remaining life time was 6.3%, 4.7%, and 3.3% and 15.3 yr, 20.4 yr, and 28.7 yr for WLD, MDK, and IDK groups, respectively. The average increase in life expectancy for MDK recipients compared with the WLD cohort was 5 yr, although this benefit varied from 3 to 10 yr depending on the recipient's characteristics. It is concluded that transplantation of a marginal kidney is associated with a significant survival benefit when compared with maintenance dialysis.
Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts
Authors: T. S. S. Genders, E. W. Steyerberg, M. G. M. Hunink, K. Nieman, T. W. Galema, N. R. Mollet, P. J. d. Feyter, G. P. Krestin, H. Alkadhi, S. Leschka, L. Desbiolles, M. F. L. Meijs, M. J. Cramer, J. Knuuti, S. Kajander, J. Bogaert, K. Goetschalckx, F. Cademartiri, E. Maffei, C. Martini, S. Seitun, A. Aldrovandi, S. Wildermuth, B. Stinn, J. Fornaro, G. Feuchtner, T. De Zordo, T. Auer, F. Plank, G. Friedrich, F. Pugliese, S. E. Petersen, L. C. Davies, U. J. Schoepf, G. W. Rowe, C. A. G. van Mieghem, L. van Driessche, V. Sinitsyn, D. Gopalan, K. Nikolaou, F. Bamberg, R. C. Cury, J. Battle, P. Maurovich-Horvat, A. Bartykowszki, B. Merkely, D. Becker, M. Hadamitzky, J. Hausleiter, M. Dewey, E. Zimmermann, M. Laule
Journal: BMJ (2012)

<b>Objectives</b> To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. <b>Design </b>Retrospective pooled analysis of individual patient data. <b>Setting </b>18 hospitals in Europe and the United States. <b>Participants</b> Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). <b>Main outcome measures</b> Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. <b>Results</b> We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. <b>Conclusions</b> Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.
The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension: a comparative study
Authors: A Maetzel
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To compare the economic burden to society incurred by patients with RA, OA, or high blood pressure (HBP) in Ontario, Canada. <b>Methods:</b> Consecutive subjects recruited by 52 rheumatologists (RA) and 76 family physicians (OA and HBP) were interviewed at baseline and 3 months. Information was collected on demographics, health status, and any comorbidities. A detailed, open ended resource utilisation questionnaire inquired about the use of medical and non-medical resources and patient and care giver losses of time and related expenses. Annual costs were derived as recommended by national costing guidelines and converted to American dollars (year 2000). Statistical comparisons were made using ordinary least squares regression on raw and log transformed costs, and generalised linear modelling with adjustment for age, sex, educational attainment, and presence of comorbidities. <b>Results:</b> Baseline and 3 month interviews were completed by 253/292 (86.6%) patients with RA and 473/585 (80.9%) patients with OA and/or HBP. Baseline and total annual disease costs for RA (n = 253), OA and HBP (n = 191), OA (n = 140), and HBP (n = 142), respectively, were $9300, $4900, $5700, and US$3900. Indirect costs related to RA were up to five times higher than indirect costs incurred by patients with OA or HBP, or both. The presence of comorbidities was associated with disease costs for all diagnoses, cancelling out potential effects of age or sex. <b>Conclusion:</b> The economic burden incurred by RA significantly exceeds that related to OA and HBP, while differences between patients with a diagnosis of OA without HBP or a diagnosis of HBP alone were non-significant, largely owing to the influence of comorbidities.
Correction of vitamin E deficiency in children with chronic cholestasis. II. Effect on gastrointestinal and hepatic function
Authors: Ronald J. Sokol, James E. Heubi, Catherine McGraw, William F. Balistreri
Journal: Hepatology (1986)

Although secondary vitamin E deficiency causes a reversible neurologic disorder in children with chronic cholestasis, the effect of this deficiency state on other organ systems is unknown. We studied the effects of vitamin E therapy on selected gastrointestinal and hepatic functions in five children with chronic cholestasis and well-documented biochemical and neurologic evidence of vitamin E deficiency. After 2 to 3 years of oral or parenteral vitamin E therapy, there was no improvement in fecal fat losses, severity of vitamin E malabsorption (as measured by an oral vitamin E tolerance test) or total serum fatty acid concentrations. Serial analyses of liver function blood tests demonstrated a marked decline in fasting serum cholylglycine concentrations during 18 to 31 months of vitamin E therapy, while other liver function tests showed no consistent changes. We conclude that vitamin E deficiency does not appear to alter intestinal absorption of fat or vitamin E; however, vitamin E deficiency may further impair already compromised hepatic function during pathologic conditions such as cholestasis.
Management and Outcomes of Care of Fever in Early Infancy
Authors: Robert H. Pantell
Journal: JAMA (2004)

Fever in infants challenges clinicians in distinguishing between serious conditions, such as bacteremia or bacterial meningitis, and minor illnesses. To date, the practice patterns of office-based pediatricians in treating febrile infants and the clinical outcomes resulting from their care have not been systematically studied.To characterize the management and clinical outcomes of fever in infants, develop a clinical prediction model for the identification of bacteremia/bacterial meningitis, and compare the accuracy of various strategies.Prospective cohort study.Offices of 573 practitioners from the Pediatric Research in Office Settings (PROS) network of the American Academy of Pediatrics in 44 states, the District of Columbia, and Puerto Rico.Consecutive sample of 3066 infants aged 3 months or younger with temperatures of at least 38 degrees C seen by PROS practitioners from February 28, 1995, through April 25, 1998.Management strategies, illness frequency, and rates and accuracy of treating bacteremia/bacterial meningitis.The PROS clinicians hospitalized 36% of the infants, performed laboratory testing in 75%, and initially treated 57% with antibiotics. The majority (64%) were treated exclusively outside of the hospital. Bacteremia was detected in 1.8% of infants (2.4% of those tested) and bacterial meningitis in 0.5%. Well-appearing infants aged 25 days or older with fever of less than 38.6 degrees C had a rate of 0.4% for bacteremia/bacterial meningitis. Frequency of other illnesses included urinary tract infection, 5.4%; otitis media, 12.2%; upper respiratory tract infection, 25.6%; bronchiolitis, 7.8%; and gastroenteritis, 7.2%. Practitioners followed current guidelines in 42% of episodes. However, in the initial visit, they treated 61 of the 63 cases of bacteremia/bacterial meningitis with antibiotics. Neither current guidelines nor the model developed in this study performed with greater accuracy than observed practitioner management.Pediatric clinicians in the United States use individualized clinical judgment in treating febrile infants. In this study, relying on current clinical guidelines would not have improved care but would have resulted in more hospitalizations and laboratory testing.
Narrative Review: The Pathophysiology of Fibromyalgia
Authors: Aryeh M. Abeles, Michael H. Pillinger, Bruce M. Solitar, Micha Abeles
Journal: Annals of Internal Medicine (2007)

Primary fibromyalgia is a common yet poorly understood syndrome characterized by diffuse chronic pain accompanied by other somatic symptoms, including poor sleep, fatigue, and stiffness, in the absence of disease. Fibromyalgia does not have a distinct cause or pathology. Nevertheless, in the past decade, the study of chronic pain has yielded new insights into the pathophysiology of fibromyalgia and related chronic pain disorders. Accruing evidence shows that patients with fibromyalgia experience pain differently from the general population because of dysfunctional pain processing in the central nervous system. Aberrant pain processing, which can result in chronic pain and associated symptoms, may be the result of several interplaying mechanisms, including central sensitization, blunting of inhibitory pain pathways, alterations in neurotransmitters, and psychiatric comorbid conditions. This review provides an overview of the mechanisms currently thought to be partly responsible for the chronic diffuse pain typical of fibromyalgia.