tbuckley/cabot-search huggingface dataset:
A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells.
Authors: R Kain, K Matsui, M Exner, S Binder, G Schaffner, E M Sommer, D Kerjaschki
Journal: The Journal of Experimental Medicine (1995)

Necrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. Gp130 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in approximately 90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PR3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a different, structurally related 130-kD membrane protein on the cell surface of renal microvascular endothelial cells are autoantigenic targets for ANCA in patients with active NCGN.
The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification
Authors: Francis Coffey, Sang-Yun Lee, Terkild B. Buus, Jens-Peter Holst Lauritsen, Gladys W. Wong, Michelle L. Joachims, Linda F. Thompson, Juan Carlos Zúñiga-Pflücker, Dietmar J. Kappes, David L. Wiest
Journal: The Journal of Experimental Medicine (2014)

Numerous studies indicate that γδ T cell receptor (γδTCR) expression alone does not reliably mark commitment of early thymic progenitors to the γδ fate. This raises the possibility that the γδTCR is unable to intrinsically specify fate and instead requires additional environmental factors, including TCR–ligand engagement. We use single cell progenitor assays to reveal that ligand acts instructionally to direct adoption of the γδ fate. Moreover, we identify CD73 as a TCR ligand-induced cell surface protein that distinguishes γδTCR-expressing CD4−CD8− progenitors that have committed to the γδ fate from those that have not yet done so. Indeed, unlike CD73− γδTCR+ progenitors, which largely adopt the αβ fate upon separation from the intrathymic selecting environment, those that express CD73 remain CD4−CD8− and committed to the γδ fate. CD73 is expressed by &amp;gt;90% of peripheral γδ cells, suggesting this is a common occurrence during development. Moreover, CD73 induction appears to mark a metastable intermediate stage before acquisition of effector function, suggesting that γδ lineage and effector fate are specified sequentially. These findings have important implications for the role of ligand in γδ lineage commitment and its relationship to the specification of effector fate.
Periodontal disease adversely affects the survival of patients with end-stage renal disease
Authors: Abhijit V. Kshirsagar, Ronald G. Craig, Kevin L. Moss, James D. Beck, Steven Offenbacher, Peter Kotanko, Philip J. Klemmer, Maki Yoshino, Nathan W. Levin, Julie K. Yip, Khalid Almas, Eva M. Lupovici, Len A. Usvyat, Ronald J. Falk
Journal: Kidney International (2009)
In Vivo Multiphoton Microscopy of Basal Cell Carcinoma
Authors: Mihaela Balu, Christopher B. Zachary, Ronald M. Harris, Tatiana B. Krasieva, Karsten König, Bruce J. Tromberg, Kristen M. Kelly
Journal: JAMA Dermatology (2015)

Basal cell carcinomas (BCCs) are diagnosed by clinical evaluation, which can include dermoscopic evaluation, biopsy, and histopathologic examination. Recent translation of multiphoton microscopy (MPM) to clinical practice raises the possibility of noninvasive, label-free in vivo imaging of BCCs that could reduce the time from consultation to treatment.To demonstrate the capability of MPM to image in vivo BCC lesions in human skin, and to evaluate if histopathologic criteria can be identified in MPM images.Imaging in patients with BCC was performed at the University of California-Irvine Health Beckman Laser Institute & Medical Clinic, Irvine, between September 2012 and April 2014, with a clinical MPM-based tomograph. Ten BCC lesions were imaged in vivo in 9 patients prior to biopsy. The MPM images were compared with histopathologic findings.MPM imaging identified in vivo and noninvasively the main histopathologic feature of BCC lesions: nests of basaloid cells showing palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis.The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors.This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions. Future studies are needed to validate the technique and correlate MPM performance with histopathologic examination.
Submissions, impact factor, reviewer's recommendations and geographical bias within the peer review system (1997–2002) Focus on Germany
Authors: T Opthof
Journal: Cardiovascular Research (2002)

At the occasion of the Congress of the European Society of Cardiology in Berlin in 2002 we provide our readership with data on the impact factor of Cardiovascular Research and on the submission of manuscripts from different parts of the world.

Fig. 1 shows the increase in submissions over the last years. The average of monthly submissions is well above 90 since the year 2000. In previous editorials we commented on the steady increase of submissions from Europe during the last decade [1–4]. Although there were slightly less submissions from Europe in 2000 compared with 1999, the year 2001 showed an all time high of 651 manuscripts (Fig. 2). From North America we received more manuscripts in 2001 than in the two preceding years. European submissions keep track with the general increase in submissions, leading to percentage of 55.3% in 2001. From North America (USA and Canada) we received 22.3% of the total number of manuscripts in 2001 and 10.9% came from Japan with the remaining 11.5% from the rest of the world. There is a trend to an increase of submissions from the rest of the world since 1997. With respect to individual countries most manuscripts in 2001 still were sent from the USA (16.7%), with Germany (13.2%) and the UK (11.2%), taking the second and third positions.



Fig. 1 
Total number of submissions per month during the years 1997–2001 and over the first 4 months of 2002 (2002/4).





Fig. 2 
Total number of submissions from Europe and North America from 1997 till 2001.



Fig. 3 shows the official impact factor for Cardiovascular Research as communicated by the Institute for Scientific Information (solid line) and our own estimates (dashed line) since 1997. The last official impact factor was 3.783 (2000). We predict an impact factor of 4.60 … 

* Corresponding author. Tel.: +31-30-253-8923; fax: +31-30-2539-036
Down-regulation of Type I Insulin-like Growth Factor Receptor Increases Sensitivity of Breast Cancer Cells to Insulin
Authors: Hua Zhang, Alissa M. Pelzer, David T. Kiang, Douglas Yee
Journal: Cancer Research (2007)

Abstract The type I insulin-like growth factor receptor (IGF1R) and insulin receptor (IR) are structurally and functionally related heterotetrameric receptors. Activation of IGF1R has been shown to regulate breast cancer cell biology, and it has become an attractive therapeutic target. Most strategies have focused on targeting IGF1R alone without affecting IR levels given the known physiologic functions of IR. Human breast cancer cell lines and tissues revealed mRNA expression of both IGF1R and IR. Because αβ chains of IGF1R and IR form hybrid receptors, we hypothesized that agents solely targeting IGF1R may affect tumor biology mediated by IGF1R/IR hybrids and IR. We used small interfering RNA (siRNA) technology to specifically down-regulate IGF1R by 60% to 80% in the MDA-435/LCC6 cell line, which was sufficient to diminish activation of IGF1R by IGF-I. IGF1R down-regulation by siRNA did not affect IR levels but, interestingly, sensitized cells to insulin activation of downstream signaling pathways in several breast cancer cell lines. IGF1R siRNA treatment diminished hybrid receptor formation, suggesting that specific down-regulation of IGF1R resulted in enhanced holo-IR formation. In addition, IGF1R down-regulation increased insulin binding consistent with the formation of an increased number of holo-IR on the cell surface. Accordingly, insulin-stimulated glucose uptake was enhanced on IGF1R down-regulation. In conclusion, our data suggest that specific siRNA targeting of IGF1R alone in breast cancer increases insulin sensitivity. Because IR also activates signaling pathways similar to IGF1R in breast cancer cells, agents targeting both receptors may be necessary to disrupt the malignant phenotype regulated by this growth factor system. [Cancer Res 2007;67(1):391–7]
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 36
Authors: A J Zemski, R M Quinlivan, M Gibala, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2012)

What do a much loved but potentially over-consumed sweetener, an algae and a citric acid cycle intermediary have in common? It is not often that they might be found on the same menu, other than our alphabet soup of supplements. This issue deals with the use of sucrose in sports product, an interest in spirulina beyond its general health claims and a product which might enhance the function of a key pathway in exercise metabolism. It should be noted that we have not overlooked sodium bicarbonate; this topic was dealt with under ‘Buffers’, which appeared in a previous issue of the journal.1

### AJ Zemski

Spirulina constitutes microalgae belonging to the cyanobacteria class, with nutritional supplements (tablets, flakes and powders) typically being produced from the cultivation of two species Arthrospira platensis and Arthrospira maxima . It is also used as a feed supplement in the aquaculture, aquarium and poultry industries. Spirulina was primarily recognised as being rich in proteins and essential fatty acids, but recently has attracted attention due to its content of phytochemicals with antioxidant and hypolipidemic properties.2 Claims for general health benefits from spirulina intake are centuries old.2 Claimed ergogenic benefits relate to antioxidant defence and favourable changes in substrate utilisation during exercise. Indeed, moderately trained runners who received spirulina supplementation for 4 weeks (6 g/day) showed increased fat utilisation, reductions in markers of antioxidant stress and increased endurance at high intensity exercise (95% VO2 …
Pathways of Low-Income Minority Patients to Outpatient Psychiatric Treatment
Authors: Heidi Boerstler, John M. de Figueiredo
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Low-income outpatients with scheduled appointments (“scheduled patients”) were compared with those who sought treatment without appointments (“walk-ins”). METHOD: The charts of scheduled patients and walk-ins at an outpatient mental health clinic serving a low-income group were reviewed to determine sociodemographic and clinical characteristics and patients’ pathways to treatment. RESULTS: Walk-ins (N=241) outnumbered scheduled patients (N=141). The two groups differed significantly in type of presenting complaint and source of referral. A higher proportion of walk-ins sought help with social relationships, while more scheduled patients had complaints involving social performance. Self-referrals were more common among the scheduled patients, and family members were more likely to have motivated the walk-ins. CONCLUSIONS: The two groups have more in common than might be expected. Scheduled patients are probably more motivated to seek treatment and therefore more likely to initiate appointments. Walk-ins appear to postpone asking for help until their families urge them to do so.
The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally.
Authors: J D Wene, W E Connor, L DenBesten
Journal: Journal of Clinical Investigation (1975)

The hypothesis that clinical and biochemical essential fatty acid deficiency (EFA) might occur from the feeding of eucaloric, fat-free diets was tested in two experiments in healthy men. In Study I, eight men were given fat-free, eucaloric diets containing 80% of calories as glucose and 20% as amino acid hydrolysates by a constant drip over a 24-h period. The diets were fed in succession for periods of 2 wk each, either through a superior vena cava catheter or via a nasogastric tube. EFA deficiency was detected by decreases in linoleic acid and by the appearance of 5, 8, 11-eicosatrienoic acid in lipid fractions of plasma. Linoleic acid decreased significantly during 2 wk of the fat-free diet given intravenously from 48.8 to 9.8% (percent of total fatty acids) in cholesterol esters, from 21.2 to 3.2% in phospholipids, from 9.6 to 2.0% in free fatty acids, and from 14.1 to 2.6% in triglycerides. Eicosatrienoic acid, normally undetectable, appeared 0.6% in cholesterol esters, 2.5% in phospholipids, 0.2% in free fatty acids, and 2.3% in triglycerides. EFA deficiency occurred similarly during the nasogastric feeding. In Study II a subject received the same diet continuously by the nasogastric route for 10 days followed by a 24-h fast. He was then given the fat-free diet intermittently in three meals per day for 3 days. Finally, he was repleted with a diet containing 2.6% linoleic acid. By the 3rd day of the continuous nasogastric feeding, linoleic acid had fallen significantly and eicosatrienoic acid had appeared in plasma lipid fractions as in Study I. These findings were accentuated by day 10. Adipose tissue fatty acid composition did not change. Free fatty acid outflow from adipose tissue was presumably suppressed during the 10 days of continuous feeding. With increased free fatty acid outflow during fasting and intermittent feeding, linoleic acid rose and eicosatrienoic acid decreased. After 13 days of repletion with dietary linoleic acid, the EFA deficiency readily develops when fat-free diets containing glucose are given intravenously or orally as constant 24-h infusions. These diets are similar to the hyperalimentation formulas now being used clinically.
Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis
Authors: G Wells, T Li, L Maxwell, R Maclean, P Tugwell
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To evaluate the responsiveness of patient reported outcomes (PROs), including fatigue, sleep, activity limitation, and quality of life, in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> Data were considered from a randomised controlled trial comparing abatacept (n = 258) with placebo (n = 133) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy (ATTAIN study). PROs assessed included SF-36, activity limitation, fatigue, and sleep. For each outcome the treatment difference, relative per cent improvement, standardised response mean (SRM), and relative efficiency for assessing an outcome's ability to detect a treatment effect relative to tender joint count (TJC) were calculated. A relative efficiency &gt;1 suggests a measure that is more efficient than TJC in detecting treatment effect. <h3>Results:</h3> Moderate to large SRMs (⩾0.6) were observed for the PRO measures. In particular, SRMs (95% confidence interval) were: physician global, 0.72 (0.51 to 0.94); HAQ, 0.63 (0.42 to 0.85); SF-36 physical component score, 0.62 (0.40 to 0.83); SF-36 bodily pain, 0.68 (0.46 to 0.90); and fatigue, 0.59 (0.38 to 0.81). Relative efficiencies for physician global (1.6), SF-36 bodily pain domain (1.4), pain intensity (1.4), HAQ (1.2), SF-36 physical component score (1.2), fatigue (1.1), and patient global assessment (1.04) were all more responsive than TJC. The SF-36 mental component score (0.3), swollen joint count (0.6), activity limitation (0.8), sleep (0.7), and C reactive protein (0.9) were less responsive. <h3>Conclusions:</h3> Using PROs for evaluating treatments for RA can detect improvements and will identify changes that are important to patients. In general, physical assessments are more responsive to an effective treatment than mental assessments.
Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes
Authors: G BASTA
Journal: Cardiovascular Research (2004)

The formation of advanced glycation end products (AGEs) is an important biochemical abnormality that accompanies diabetes mellitus and, likely, inflammation in general. Here we summarize and discuss recent studies indicating that the effects of AGEs on vessel wall homeostasis may account for the rapidly progressive atherosclerosis associated with diabetes mellitus. Driven by hyperglycemia and oxidant stress, AGEs form to a greatly accelerated degree in diabetes. Within the vessel wall, collagen-linked AGEs may "trap" plasma proteins, quench nitric oxide (NO) activity and interact with specific receptors to modulate a large number of cellular properties. On plasma low density lipoproteins (LDL), AGEs initiate oxidative reactions that promote the formation of oxidized LDL. Interaction of AGEs with endothelial cells as well as with other cells accumulating within the atherosclerotic plaque, such as mononuclear phagocytes and smooth muscle cells (SMCs), provides a mechanism to augment vascular dysfunction. Specifically, the interaction of AGEs with vessel wall components increases vascular permeability, the expression of procoagulant activity and the generation of reactive oxygen species (ROS), resulting in increased endothelial expression of endothelial leukocyte adhesion molecules. AGEs potently modulate initiating steps in atherogenesis involving blood-vessel wall interactions, triggering an inflammatory-proliferative process and, furthermore, critically contribute to propagation of inflammation and vascular perturbation in established disease. Thus, a better understanding of the biochemical mechanisms by which AGEs contribute to such processes in the vessel wall could be relevant to devise preventive and therapeutic strategies for diabetic atherosclerosis.
Interactions of Hormone Replacement Therapy, Body Weight, and Bilateral Oophorectomy in Breast Cancer Risk
Authors: Yong Cui, Sandra L. Deming-Halverson, Alicia Beeghly-Fadiel, Loren Lipworth, Martha J. Shrubsole, Alecia M. Fair, Xiao-Ou Shu, Wei Zheng
Journal: Clinical Cancer Research (2014)

To examine potential modifying effects of body weight and bilateral oophorectomy on the association of hormone replacement therapy (HRT) with risk of breast cancer, overall and by subtypes according to status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) among postmenopausal women.This analysis included 2,510 postmenopausal white women recruited in the Nashville Breast Health Study, a population-based case-control study of breast cancer. Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI) for associations between HRT use and risk of breast cancer overall and by subtypes, adjusted for age and education.Among women with natural menopause and body mass index (BMI) < 25 kg/m(2), ever-use of HRT was associated with increased breast cancer risk (OR, 1.95; 95% CI, 1.32-2.88). Risk was elevated with duration of HRT use (P for trend = 0.002). Similar association patterns were found for ER(+), ER(+)PR(+), and luminal A cancer subtypes but not ER(-), ER(-)PR(-), and triple-negative cancer. In contrast, ever-HRT use in overweight women (BMI ≥ 25 kg/m(2)) showed no association with risk of breast cancer overall or by subtypes; interaction tests for modifying effect of BMI were statistically significant. Ever-HRT use was associated with decreased breast cancer risk (OR, 0.70; 95% CI, 0.38-1.31) among women with prior bilateral oophorectomy but elevated risk (OR, 1.45; 95% CI, 0.92-2.29) among those with hysterectomy without bilateral oophorectomy (P for interaction = 0.057). Similar associations were seen for virtually all breast cancer subtypes, although interaction tests were statistically significant for ER(+) and luminal A only.Body weight and bilateral oophorectomy modify associations between HRT use and breast cancer risk, especially the risk of hormone receptor-positive tumors.
IL-17A Production by Renal γδ T Cells Promotes Kidney Injury in Crescentic GN
Authors: Jan-Eric Turner, Christian Krebs, Andre P. Tittel, Hans-Joachim Paust, Catherine Meyer-Schwesinger, Sabrina B. Bennstein, Oliver M. Steinmetz, Immo Prinz, Tim Magnus, Thomas Korn, Rolf A.K. Stahl, Christian Kurts, Ulf Panzer
Journal: Journal of the American Society of Nephrology (2012)

The Th17 immune response appears to contribute to the pathogenesis of human and experimental crescentic GN, but the cell types that produce IL-17A in the kidney, the mechanisms involved in its induction, and the IL-17A-mediated effector functions that promote renal tissue injury are incompletely understood. Here, using a murine model of crescentic GN, we found that CD4(+) T cells, γδ T cells, and a population of CD3(+)CD4(-)CD8(-)γδT cell receptor(-)NK1.1(-) T cells all produce IL-17A in the kidney. A time course analysis identified γδ T cells as a major source of IL-17A in the early phase of disease, before the first CD4(+) Th17 cells arrived. The production of IL-17A by renal γδ T cells depended on IL-23p19 signaling and retinoic acid-related orphan receptor-γt but not on IL-1β or IL-6. In addition, depletion of dendritic cells, which produce IL-23 in the kidney, reduced IL-17A production by renal γδ T cells. Furthermore, the lack of IL-17A production in γδ T cells, as well as the absence of all γδ T cells, reduced neutrophil recruitment into the kidney and ameliorated renal injury. Taken together, these data suggest that γδ T cells produce IL-17A in the kidney, induced by IL-23, promoting neutrophil recruitment, and contributing to the immunopathogenesis of crescentic GN.