tbuckley/cabot-search huggingface dataset:
IL-12 unmasks latent autoimmune disease in resistant mice.
Authors: B M Segal, E M Shevach
Journal: The Journal of Experimental Medicine (1996)

Inbred mice exhibit a spectrum of susceptibility to induction of experimental allergic encephalomyelitis (EAE). We have compared the immune responses of the susceptible SJL (H-2s) and resistant B10.S (H-2s) strains to determine factors other than the MHC background which control resistance/susceptibility to EAE. The resistance of the B10.S strain was found to be secondary to an antigen-specific defect in the generation of Th 1 cells that produce IFN gamma. This defect in IFN gamma production could be restored by exposure of the myelin basic protein (MBP)-reactive T cells to IL-12 with the subsequent induction of the ability to transfer EAE to naive recipients. These findings have important implications for the therapeutic use of IL-12 and IL-12 antagonists and may explain the association between relapses/exacerbation of autoimmune disease and infectious diseases.
Skin Autofluorescence
Authors: Esther G. Gerrits, Helen L. Lutgers, Nanne Kleefstra, Reindert Graaff, Klaas H. Groenier, Andries J. Smit, Rijk O. Gans, Henk J. Bilo
Journal: Diabetes Care (2008)

OBJECTIVE—Skin autofluorescence is a noninvasive measure of the level of tissue accumulation of advanced glycation end products, representing cumulative glycemic and oxidative stress. Recent studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as the predictive value of skin autofluorescence for total and cardiovascular mortality in type 2 diabetes. Our aim was to investigate the predictive value of skin autofluorescence for the development of microvascular complications in type 2 diabetes. RESEARCH DESIGN AND METHODS—At baseline, skin autofluorescence of 973 type 2 diabetic patients with well-controlled diabetes was noninvasively measured with an autofluorescence reader. The aggregate clinical outcome was defined as the development of any diabetes-associated microvascular complication of 881 surviving patients, which was assessed at baseline and at the end of follow-up. Single end points were the development of diabetes-associated retinopathy, neuropathy, and (micro)albuminuria. RESULTS—After a mean follow-up period of 3.1 years, baseline skin autofluorescence was significantly higher in patients who developed any microvascular complication, neuropathy, or (micro)albuminuria but not in those who developed retinopathy. Multivariate analyses showed skin autofluorescence as a predictor for development of any microvascular complication along with A1C, for development of neuropathy along with smoking, and for development of (micro)albuminuria together with sex, A1C, and diabetes duration. Skin autofluorescence did not have predictive value for the development of retinopathy, albeit diabetes duration did. CONCLUSIONS—Our study is the first observation of skin autofluorescence measurement as an independent predictor of development of microvascular complications in type 2 diabetes.
Ancient Gene Paralogy May Mislead Inference of Plastid Phylogeny
Authors: Huan Qiu, Eun Chan Yang, Debashish Bhattacharya, Hwan Su Yoon
Journal: Molecular Biology and Evolution (2012)

Because of its ancient origin more than 1 billion years ago, the highly reduced plastid genomes of Plantae (e.g., plant chloroplasts) provide limited insights into the initial stages of endosymbiont genome reduction. The photosynthetic amoeba Paulinella provides a more useful model to study this process because its alpha-cyanobacterium-derived plastid originated ∼60 Ma and the genome still contains ∼1,000 genes. Here, we compared and contrasted features associated with genome reduction due to primary endosymbiosis in Paulinella plastids and in marine, free-living strains of the picocyanobacterium, Prochlorococcus. Both types of genomes show gene inactivation, concerted evolution, and contraction of gene families that impact highly conserved single-copy phylogenetic markers in the plastid such as psbA, psbC, and psbD. Our data suggest that these photosystem II genes may provide misleading phylogenetic signal because each of the constituent Plantae lineages has likely undergone a different, independent series of events that led to their reduction to a single copy. This issue is most problematic for resolving basal Plantae relationships when differential plastid gene loss was presumably ongoing, as we observe in Paulinella species. Our work uncovers a key, previously unappreciated aspect of organelle genome reduction and demonstrates "work-in-progress" models such as Paulinella to be critical to gain a fuller understanding of algal and plant genome evolution.
Rates of Change Differ among Measures of Visual Function in Patients with Retinitis Pigmentosa
Authors: Karen Holopigian, Vivienne Greenstein, William Seiple, Ronald E. Carr
Journal: Ophthalmology (1996)

Purpose: To assess changes in measures of visual function in patients with retinitis pigmentosa (RP) over time.Methods: Patients with RP and visual acuity of 20/40 or better and central visual fields of 10 0 or larger were enrolled in a 9-year prospective study.The following measures of visual function were obtained annually over the follow-up period: visual acuity, Goldmann visual fields (V4e target), focal electroretinograms, and hue discrimination.Results: Over the follow-up period, the averaged group data showed changes in all measures of visual function.The smallest amount of change occurred for visual acuity and hue discrimination, and the greatest amount of change occurred for visual field area.Examination of individual patient data over the follow-up period indicated that the rates of change varied among patients and that losses in function for one measure did not correlate well with losses on other measures.Conclusions: These results stress that although visual function deteriorated over time for this group of patients with RP, there were differences among our measures of visual function.Measures that primarily assess central retinal function change relatively slowly compared with measures that assess more peripheral retinal function.
International Union of Pharmacology. XLI. Compendium of Voltage-Gated Ion Channels: Potassium Channels
Authors: George A. Gutman, K. George Chandy, John P. Adelman, Jayashree Aiyar, Douglas A. Bayliss, David E. Clapham, Manuel Covarriubias, Gary V. Desir, Kiyoshi Furuichi, Barry Ganetzky, Maria L. Garcia, Stephan Grissmer, Lily Y. Jan, Andreas Karschin, Donghee Kim, Sabina Kuperschmidt, Yoshihisa Kurachi, Michel Lazdunski, Florian Lesage, Henry A. Lester, David McKinnon, Colin G. Nichols, Ita O'Kelly, Jonathan Robbins, Gail A. Robertson, Bernardo Rudy, Michael Sanguinetti, Susumu Seino, Walter Stuehmer, Michael M. Tamkun, Carol A. Vandenberg, Aguan Wei, Heike Wulff, Randy S. Wymore
Journal: Pharmacological Reviews (2003)

This summary article presents an overview of the molecular relationships among the voltage-gated potassium channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels. The complete Compendium, including data tables for each member of the potassium channel family can be found at http://www.iuphar-db.org/iuphar-ic/.
Stress Signaling from Human Mammary Epithelial Cells Contributes to Phenotypes of Mammographic Density
Authors: Rosa Anna DeFilippis, Colleen Fordyce, Kelley Patten, Hang Chang, Jianxin Zhao, Gerald V. Fontenay, Karla Kerlikowske, Bahram Parvin, Thea D. Tlsty
Journal: Cancer Research (2014)

Abstract Telomere malfunction and other types of DNA damage induce an activin A–dependent stress response in mortal nontumorigenic human mammary epithelial cells that subsequently induces desmoplastic-like phenotypes in neighboring fibroblasts. Some characteristics of this fibroblast/stromal response, such as reduced adipocytes and increased extracellular matrix content, are observed not only in tumor tissues but also in disease-free breast tissues at high risk for developing cancer, especially high mammographic density tissues. We found that these phenotypes are induced by repression of the fatty acid translocase CD36, which is seen in desmoplastic and disease-free high mammographic density tissues. In this study, we show that epithelial cells from high mammographic density tissues have more DNA damage signaling, shorter telomeres, increased activin A secretion and an altered DNA damage response compared with epithelial cells from low mammographic density tissues. Strikingly, both telomere malfunction and activin A expression in epithelial cells can repress CD36 expression in adjacent fibroblasts. These results provide new insights into how high mammographic density arises and why it is associated with breast cancer risk, with implications for the definition of novel invention targets (e.g., activin A and CD36) to prevent breast cancer. Cancer Res; 74(18); 5032–44. ©2014 AACR.
HMG CoA reductase inhibition reduces sarcolemmal Na+–K+ pump density
Authors: D Gray
Journal: Cardiovascular Research (2000)

Objectives: HMG CoA reductase inhibitors reduce cellular availability of mevalonate, a precursor in cholesterol synthesis. Since the cholesterol content of cell membranes is an important determinant of Na+–K+ pump function we speculated that treatment with HMG CoA reductase inhibitors affects Na+–K+ pump activity. Methods: We treated rabbits and rats for 2 weeks with the HMG CoA reductase inhibitor lovastatin and measured Na+–K+ pump current (Ip) in isolated rabbit cardiac myocytes using the whole cell patch-clamp technique, K-dependent p-nitrophenyl phosphatase (p-NPPase) activity in crude myocardial and skeletal muscle homogenates, and vanadate-facilitated 3H-ouabain binding in intact skeletal muscle samples from rats. Results: Treatment with lovastatin caused statistically significant reductions in Ip, myocardial and skeletal muscle K-dependent p-NPPase activity and 3H-ouabain binding in the myocardium and skeletal muscle. The lovastatin-induced decrease in Ip was eliminated by parenteral co-administration of mevalonate. However, this was not related to cardiac cholesterol content. Conclusions: Treatment with lovastatin reduces Na+–K+ pump activity and abundance in rabbit and rat sarcolemma.
Pulmonary dendritic cells: thinking globally, acting locally
Authors: Troy D. Randall
Journal: The Journal of Experimental Medicine (2010)

The phrase "think globally, act locally" was coined in the early 1970s and directed individuals to clean up their local environment with the ultimate goal of improving the health of the entire planet. Several recent studies indicate that similar considerations apply to the immune system, in which small numbers of leukocytes, such as pulmonary dendritic cells, can modify the local immune environment in the lung and promote a positive outcome for the organism.
Significance of delta agent infection in chronic hepatitis B virus infection: a study in British carriers.
Authors: I V Weller, P Karayiannis, A S Lok, L Montano, M Bamber, H C Thomas, S Sherlock
Journal: Gut (1983)

Delta antigen (delta) is a transmissible agent requiring hepatitis B virus (HBV) for its replication. Antibody to delta (anti-delta) was present in nine of 71 (13%) British HBV carriers: six were intravenous drug abusers and two were haemophiliacs. Anti-delta was negative in 30 HBsAg positive homosexuals. Cirrhosis was common in patients with anti-delta and those with anti-delta positive cirrhosis were significantly younger than those with anti-delta negative cirrhosis. In British HBV carriers delta infection is associated with intravenous drug abuse and haemophilia and perhaps a more rapid progression of chronic liver disease.
Protective Effect of Natural Rotavirus Infection in an Indian Birth Cohort
Authors: Beryl P. Gladstone, Sasirekha Ramani, Indrani Mukhopadhya, Jayaprakash Muliyil, Rajiv Sarkar, Andrea M. Rehman, Shabbar Jaffar, Miren Iturriza Gomara, James J. Gray, David W.G. Brown, Ulrich Desselberger, Sue E. Crawford, Jacob John, Sudhir Babji, Mary K. Estes, Gagandeep Kang
Journal: New England Journal of Medicine (2011)

More than 500,000 deaths are attributed to rotavirus gastroenteritis annually worldwide, with the highest mortality in India. Two successive, naturally occurring rotavirus infections have been shown to confer complete protection against moderate or severe gastroenteritis during subsequent infections in a birth cohort in Mexico. We studied the protective effect of rotavirus infection on subsequent infection and disease in a birth cohort in India (where the efficacy of oral vaccines in general has been lower than expected).
THE REACTIVITY OF THE CAPILLARY BED OF THE NAILFOLD TO CIRCULATING EPINEPHRINE AND NOR-EPINEPHRINE IN PATIENTS WITH NORMAL BLOOD PRESSURE AND WITH ESSENTIAL HYPERTENSION
Authors: Sheldon E. Greisman
Journal: Journal of Clinical Investigation (1952)

Several studies have attempted to determine whether the vascular system of patients with essential hypertension is hyper-reactive to epinephrine. In these studies vascular reactivity was judged solely by the increase in arterial blood pressure following the parenteral administration of this pressor substance. Some investigators believed that this method indicated vascular hyperreactivity to epinephrine in patients with essential hypertension; others concluded that the vascular reactivity remained within the normal range (17). Epinephrine does not alter blood pressure by a single mechanism. Some vascular beds (skin and splanchnic area) are constricted, others (muscular) are dilated by the drug. The resultant change in the overall peripheral resistance depends upon which effect predominates. Epinephrine also acts directly upon the heart, and increases the cardiac output. Alteration of blood pressure following epinephrine administration is therefore a resultant of the changes of three separate mechanisms-vasoconstriction, vasodilatation, and car
Artificial and bioartificial liver devices: present and future
Authors: B. Carpentier, A. Gautier, C. Legallais
Journal: Gut (2009)

Liver failure is associated with high morbidity and mortality without transplantation. There are two types of device for temporary support: artificial and bioartificial livers. Artificial livers essentially use non-living components to remove the toxins accumulated during liver failure. Bioartificial livers have bioreactors containing hepatocytes to provide both biotransformation and synthetic liver functions. We review here the operating principles, chemical effects, clinical effects and complications of both types, with specific attention paid to bioartificial systems. Several artificial support systems have FDA marketing authorisation or are CE labelled, but the improvement they provide in terms of patient clinical outcome has not yet been fully demonstrated. At present, different bioartifical systems are being investigated clinically on the basis of their promises and capacity to provide and replace most liver functions. However, important issues such as cost, cell availability, maintenance of cell viability and functionality throughout treatment, and regulatory issues, as well as difficult challenges, including implementing cell-housing devices at the patient's bedside on an emergency basis, have delayed their appearance in intensive care units and on the market. Bioreactors are, nevertheless, when combined with artificial components, a pragmatic approach for future treatment of liver failure.
Comparison of the Atkins, Zone, Ornish, and LEARN Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women
Authors: Christopher D. Gardner, Alexandre Kiazand, Sofiya Alhassan, Soowon Kim, Randall S. Stafford, Raymond R. Balise, Helena C. Kraemer, Abby C. King
Journal: JAMA (2007)

Popular diets, particularly those low in carbohydrates, have challenged current recommendations advising a low-fat, high-carbohydrate diet for weight loss. Potential benefits and risks have not been tested adequately.To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables.Twelve-month randomized trial conducted in the United States from February 2003 to October 2005 among 311 free-living, overweight/obese (body mass index, 27-40) nondiabetic, premenopausal women.Participants were randomly assigned to follow the Atkins (n = 77), Zone (n = 79), LEARN (n = 79), or Ornish (n = 76) diets and received weekly instruction for 2 months, then an additional 10-month follow-up.Weight loss at 12 months was the primary outcome. Secondary outcomes included lipid profile (low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol, and triglyceride levels), percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure. Outcomes were assessed at months 0, 2, 6, and 12. The Tukey studentized range test was used to adjust for multiple testing.Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months, and mean 12-month weight loss was significantly different between the Atkins and Zone diets (P<.05). Mean 12-month weight loss was as follows: Atkins, -4.7 kg (95% confidence interval [CI], -6.3 to -3.1 kg), Zone, -1.6 kg (95% CI, -2.8 to -0.4 kg), LEARN, -2.6 kg (-3.8 to -1.3 kg), and Ornish, -2.2 kg (-3.6 to -0.8 kg). Weight loss was not statistically different among the Zone, LEARN, and Ornish groups. At 12 months, secondary outcomes for the Atkins group were comparable with or more favorable than the other diet groups.In this study, premenopausal overweight and obese women assigned to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight at 12 months than women assigned to follow the Zone diet, and had experienced comparable or more favorable metabolic effects than those assigned to the Zone, Ornish, or LEARN diets [corrected] While questions remain about long-term effects and mechanisms, a low-carbohydrate, high-protein, high-fat diet may be considered a feasible alternative recommendation for weight loss.clinicaltrials.gov Identifier: NCT00079573.
Glomerular Plasmin-Like Activity in Relation to Nephritis-Associated Plasmin Receptor in Acute Poststreptococcal Glomerulonephritis
Authors: Takashi Oda, Kazuo Yamakami, Fumihiro Omasu, Shigenobu Suzuki, Soichiro Miura, Tetsuzo Sugisaki, Nobuyuki Yoshizawa
Journal: Journal of the American Society of Nephrology (2004)

A nephritogenic antigen for acute poststreptococcal glomerulonephritis (APSGN) was isolated recently from group A streptococcus and termed nephritis-associated plasmin receptor (NAPlr). In vitro experimental data indicate that the pathogenic role of NAPlr occurs through its ability to bind to plasmin and maintain its proteolytic activity. However, the mechanism whereby this antigen induces glomerular damage in vivo has not been fully elucidated. Renal biopsy tissues from 17 patients with APSGN, 8 patients with rapidly progressive glomerulonephritis, and 10 normal kidneys were analyzed in this study. Plasmin-like activity was assessed on cryostat sections by in situ zymography with a plasmin-sensitive synthetic substrate. Serial sections were simultaneously assessed for NAPlr deposition by immunofluorescence staining. Glomerular plasmin-like activity was absent or weak in normal controls and in patients with rapidly progressive glomerulonephritis, although tubulointerstitial activity was occasionally detected. Prominent glomerular plasmin-like activity was found in patients who had APSGN and in whom glomerular NAPlr was positive, whereas it was absent or weak in patients who had APSGN and in whom glomerular NAPlr was negative. The distribution of glomerular plasmin-like activity was identical to that of NAPlr deposition but was generally different from that of fibrin(ogen) deposition as assessed by double staining. The activity was abolished by the addition of aprotinin to the reaction mixture but was not altered by the addition of a matrix metalloprotease inhibitor, a cysteine protease inhibitor, or inhibitors of plasminogen activators. Thus, upregulated glomerular plasmin-like activity in relation to NAPlr deposition in APSGN was identified. This result supports the nephritogenic character of NAPlr and offers insight into the mechanism whereby this antigen induces nephritis.
Costs and Cost Effectiveness of a Health Care Provider–Directed Intervention to Promote Colorectal Cancer Screening Among Veterans
Authors: Michael S. Wolf, Karen A. Fitzner, Eowyn F. Powell, Kathryn R. McCaffrey, A. Simon Pickard, June M. McKoy, Julia Lindenberg, Glen T. Schumock, Kenneth R. Carson, M. Rosario Ferreira, Nancy C. Dolan, Charles L. Bennett
Journal: Journal of Clinical Oncology (2005)

Colorectal cancer screening is underused, particularly in the Veterans Affairs (VA) population. In a randomized controlled trial, a health care provider-directed intervention that offered quarterly feedback to physicians on their patients' colorectal cancer screening rates led to a 9% increase in colorectal cancer screening rates among veterans. The objective of this secondary analysis was to assess the cost effectiveness of the colorectal cancer screening promotion intervention.Providers in the intervention arm attended an educational workshop on colorectal cancer screening and received confidential feedback on individual and group-specific colorectal cancer screening rates. The primary end point was completion of colorectal cancer screening tests. Sensitivity analyses investigated cost-effectiveness estimates varying the data collection methods, costs of labor and technology, and the effectiveness of the intervention.Rates of colorectal cancer screening for the intervention versus control arms were 41.3% v 32.4%, respectively (P < .05). The incremental cost-effectiveness ratio was dollar 978 per additional veteran screened based on feedback reports generated from manual review of records. However, if feedback reports could be generated from information technology systems, sensitivity analyses indicate that the cost-effectiveness estimate would decrease to dollar 196 per additional veteran screened.An intervention based on quarterly feedback reports to physicians improved colorectal cancer screening rates at a VA medical center. This intervention would be cost effective if relevant data could be generated by existing information technology systems. Our findings may have broad applicability because a 2005 Medicare initiative will provide the VA electronic medical record system as a free benefit to all US physicians.