tbuckley/cabot-search huggingface dataset:
Soluble interleukin-2 receptor in lichen planus
Authors: R. Valsecchi, M. Bontempelli, A.Di Landro, G. Imberti, T. Cainelli
Journal: British Journal of Dermatology (1991)

Journal Article Soluble interleukin‐2 receptor in lichen planus Get access R. Valsecchi, R. Valsecchi Department of Dermatology, Ospedali Riuniti of Bergamo Bergamo, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Bontempelli, M. Bontempelli Department of Immunohaematology, Ospedali Riuniti of Bergamo Bergamo, Italy Search for other works by this author on: Oxford Academic Google Scholar A.Di Landro, A.Di Landro Department of Dermatology, Ospedali Riuniti of Bergamo Bergamo, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Imberti, G. Imberti Department of Dermatology, Ospedali Riuniti of Bergamo Bergamo, Italy Search for other works by this author on: Oxford Academic Google Scholar T. Cainelli T. Cainelli Department of Dermatology, Ospedali Riuniti of Bergamo Bergamo, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 4, 1 October 1991, Pages 403–404, https://doi.org/10.1111/j.1365-2133.1991.tb14186.x Published: 01 October 1991
Resveratrol: Challenges in Translation to the Clinic — A Critical Discussion
Authors: Lalita Subramanian, Sherry Youssef, Saswati Bhattacharya, Jason Kenealey, Arthur S. Polans, Paul R. van Ginkel
Journal: Clinical Cancer Research (2010)

Low cancer survival rates and the serious side effects often associated with current chemotherapeutics highlight the need for new and effective nontoxic anticancer agents. Since 1997 when Jang and colleagues first described resveratrol's ability to inhibit carcinogenesis, it has consistently proven effective at tumor inhibition in diverse human cancer models. This finding has raised the hope that resveratrol would pioneer a novel class of nontoxic chemotherapeutics. As a consequence of initial basic and preclinical studies, resveratrol is now being extensively promoted in the unregulated nutraceutical sector. However, some fundamental aspects of resveratrol's action need to be understood before it can be developed into a clinically viable anticancer drug. These areas pertain to the key mechanism(s) by which resveratrol potentiates its antitumor effects. Current research suggests that these mechanisms might be through novel pathways, requiring an understanding of cellular uptake, sentinel targets, and in vivo biological networks. The metabolism of resveratrol and its bioavailability also warrant further consideration in light of recent in vitro and in vivo studies. Finally, we need to appreciate the sorts of information about resveratrol that may translate between different disease entities. We present a critical discussion of these issues and suggest important experiments that could pave the way to the successful translation of resveratrol to the clinic.
The relation of sensation in the anal canal to the functional anal sphincter: a possible factor in anal continence
Authors: H. L. Duthie, R. C. Bennett
Journal: Gut (1963)

In normal subjects the length of the functional anal sphincter has been compared with the extent of sensation to light touch in the anal canal. At rest, the sphincteric zone was the longer. On distension of the rectum, a decrease in pressure in the anal canal so shortened the functional sphincter that intrarectal pressure extended down to contact the sensory zone. This mechanism may allow the sensation in the anal canal to play a part in the fine adjustment of anal continence.
R J Reynolds fined $20m for advertising to young people
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

The leading US tobacco companies have had a losing streak of lawsuits on the west coast in the past month. On 6 June a Supreme Court judge in San Diego, California, Ronald Prager fined R J Reynolds $20m (£14m; €21m) for violating the $246bn multistate master settlement agreement of 1998 by advertising to young people.

In the settlement, tobacco companies agreed not to target advertising at young people, not to use cartoons in their advertising—such as Joe Camel ( BMJ 1996;313:1349 and BMJ 1994;308:677)—and not to advertise on outdoor billboards.

“Other companies scaled back …
Impact of Diabetes on Work Cessation
Authors: Eléonore Herquelot, Alice Guéguen, Sébastien Bonenfant, Rosemary Dray-Spira
Journal: Diabetes Care (2011)

To measure the impact of diabetes on work cessation, i.e., on the risks of work disability, early retirement, and death while in the labor force.We used data from the GAZEL prospective cohort of 20,625 employees of the French national gas and electricity company "EDF-GDF." We identified 506 employees with diabetes and randomly selected 2,530 nondiabetic employed control subjects matched for major sociodemographic and occupational characteristics. Using a multistate Cox model, we estimated hazard ratios (HRs) comparing the risks of transition from employment to disability, retirement, and death over time between participants with versus without diabetes.Employment rate decreased more rapidly in participants with diabetes (51.9 and 10.1% at 55 and 60 years, respectively) compared with nondiabetic participants (66.5 and 13.4%, respectively). Participants with diabetes had significantly increased risks of transition from employment to disability (HR 1.7 [95% CI 1.0-2.9]), retirement (HR 1.6 [1.5-1.8]), and death (HR 7.3 [3.6-14.6]) compared with participants without diabetes. Between 35 and 60 years, each participant with diabetes lost an estimated mean time of 1.1 year in the workforce (95% CI 0.99-1.14) compared with a nondiabetic participant.Our results provide evidence for a profound negative impact of diabetes on workforce participation in France. Social and economic consequences are major for patients, employers, and society-a burden that is likely to increase as diabetes becomes more and more common in the working-aged population.
The role of oxidative stress in the genesis of heart disease
Authors: P Singal
Journal: Cardiovascular Research (1998)

Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical — a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.
Variation and control of specific antigen-binding cell populations in individual fetal mice.
Authors: P D'Eustachio, J E Cohen, G M Edelman
Journal: The Journal of Experimental Medicine (1976)

To determine the extent and nature of individual variation in the development of specific antigen-binding cells, the numbers of cells specific for each of two antigens in the spleens of individual random-bred Swiss-L and inbred CBA/J and BALB/c fetal mice were measured as a function of spleen size. For Swiss-L fetuses, the ratio of antigen-binding cells to nucleateated cells varied more than would arise from sampling fluctuation. For each inbred strain, however, the number of cells specific for a given antigen was a constant proportion of the total number of nucleated cells within sampling error. These proportions varied from antigen to antigen, and from strain to strain. The ratio of the proportions of cells specific for the two antigens, however, differed no more from CBA/J to BALB/c mice than would be expected in repeated samples of cells from the spleen of a single fetus. These results confirm at the level of the individual fetus the uniform pattern of development seen for populations of fetuses. They reveal a surprising precision in the proliferation of specific antigen-binding cell populations and suggest that the development of these cells may be subject to strong genetic controls.
Restoring balance to B cells in ADA deficiency
Authors: Eline T. Luning Prak
Journal: Journal of Clinical Investigation (2012)

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.
Associations of overall sitting time and TV viewing time with fibrinogen and C reactive protein: the AusDiab study
Authors: Bethany J Howard, Beverley Balkau, Alicia A Thorp, Dianna J Magliano, Jonathan E Shaw, Neville Owen, David W Dunstan
Journal: British Journal of Sports Medicine (2014)

Background/aim Sedentary behaviour is associated with increased risk for all-cause and cardiovascular mortality. Plasma fibrinogen and C reactive protein (CRP)—key inflammatory and/or haemostatic markers—may contribute to this association; however, few studies have examined their relationships with sedentary behaviours. We examined associations of overall sitting and TV viewing time with fibrinogen and high-sensitivity CRP (hsCRP). Methods Plasma fibrinogen and hsCRP were measured in 3086 Australian adults (mean age: 55±12 years) who participated in the 2004–2005 AusDiab (Australian Diabetes, Obesity and Lifestyle) study. Multiple linear regression analyses examined cross-sectional associations of self-reported overall sitting and TV viewing time (h/day) with plasma fibrinogen and hsCRP, adjusting for sociodemographic, behavioural and medical treatments and conditions as potential covariates. Results Overall sitting time and TV viewing time were positively associated with plasma fibrinogen (sitting: β: 0.02 g/L, 95% CI (0.01 to 0.02); TV time: 0.03 g/L (0.02 to 0.05)) and hsCRP (sitting: 2.4% (1.2% to 3.6%); TV time: 4.5% (1.7% to 7.4%)). Associations were independent of leisure-time physical activity, but after adjusting for waist circumference, they remained for fibrinogen, but for hsCRP were attenuated to the null. Interactions were observed for gender×TV (p=0.011) with fibrinogen (associations in women only) and for waist circumference×TV (p=0.084) with hsCRP (associations in low-risk only). Conclusions Overall sitting time was positively associated with plasma fibrinogen and hsCRP in men and women; associations of TV viewing time with fibrinogen were observed in women only. Abdominal adiposity-mediated associations for hsCRP but not for fibrinogen. Prospective and intervention studies are needed to establish likely causality and elucidate potential mechanisms.
Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis
Authors: E. Yusuf, A. Ioan-Facsinay, J. Bijsterbosch, I. Klein-Wieringa, J. Kwekkeboom, P. E. Slagboom, T. W. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2011)

To investigate the association between baseline serum adipokines levels-leptin, adiponectin and resistin-and long-term progression of hand osteoarthritis (HOA).Baseline and 6-year radiographs of 164 patients (mean age 60 years, 81% women) with HOA (defined as a Kellgren and Lawrence score ≥2 in at least two hand joints) were assessed for joint space narrowing (JSN) in 32 hand joints using the Osteoarthritis Research Society International atlas. Progression was defined as a change in the sum of the JSN score above the smallest detectable change of 2, reflecting change above measurement error. Serum adipokines were measured at baseline and patients were categorised by adipokine tertiles. RRs (and 95% CI) of HOA progression for patients in the second and third tertiles were calculated relative to the first tertile, using generalised estimating equations. Adjustments were made for age, sex and body mass index.Patients in the two highest tertiles of adiponectin had a decreased risk of 70% (RR=0.3 (0.2 to 0.7)) for HOA progression in comparison with patients in the lowest tertile. Leptin and resistin levels were not associated with progression.Adiponectin levels are associated with progression of HOA, suggesting that adiponectin may be involved in the pathophysiology of OA.
Amelioration of Diabetic Nephropathy in SPARC-Null Mice
Authors: Sekiko Taneda, Jeffrey W. Pippin, E. Helene Sage, Kelly L. Hudkins, Yasuo Takeuchi, William G. Couser, Charles E. Alpers
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. SPARC (Secreted Protein, Acidic and Rich in Cysteine) is a matricellular protein that inhibits mesangial cell proliferation and also affects production of extracellular matrix (ECM) by regulating transforming growth factor-β1 (TGF-β1) and type I collagen in mesangial cells. This study is an investigation of the role of SPARC in streptozotocin (STZ)–induced diabetic nephropathy (DN) of 6-mo duration in wild type (WT) and SPARC-null mice. SPARC expression was evaluated by immunohistochemistry (IHC) and by in situ hybridization (ISH). Deposition of type I and IV collagen and laminin was evaluated by IHC, and TGF-β 1 mRNA was assessed by ISH. Renal function studies revealed no significant difference in BUN between diabetic SPARC-null mice and diabetic WT mice, whereas a significant increase in albumin excretion was detected in diabetic WT relative to diabetic SPARC-null mice. Diabetic WT animals exhibited increased levels of SPARC mRNA and protein in glomerular epithelial cells and in interstitial cells, in comparison with nondiabetic WT mice. Neither SPARC mRNA nor protein was detected in SPARC-null mice. Morphometry revealed a significant increase in the percentage of the glomerular tufts occupied by ECM in diabetic WT compared with nondiabetic WT mice, although there was no difference in the mean glomerular tuft area among groups. In contrast, diabetic SPARC-null mice did not show a significant difference in the percentage of the glomerular tufts occupied by ECM relative to nondiabetic null mice. Tubulointerstitial fibrosis was ameliorated in diabetic SPARC-null mice compared with diabetic WT animals. Further characterization of diabetic SPARC-null mice revealed diminished glomerular deposition of type IV collagen and laminin, and diminished interstitial deposition of type I and type IV collagen correlated with decreases in TGF-β 1 mRNA compared with WT diabetic mice. These observations suggest that SPARC contributes to glomerulosclerosis and tubulointerstitial damage in response to hyperglycemia through increasing TGF-β 1 expression in this model of chronic DN. E-mail: [email protected]
Key roles of Src family tyrosine kinases in the integrity of the pulmonary vascular bed
Authors: Christophe Guignabert, David Montani
Journal: European Respiratory Journal (2012)

The pulmonary blood vessels have unique structural and functional properties. The pulmonary circulation is a high-flow, low-resistance, low-pressure system, which is mainly explained by two important characteristics of the pulmonary vascular bed: a high compliance of the pulmonary pre-capillary arterioles characterised by thin media and a high capacity to recruit vessels available to cope with an increase in blood flow. Local variations in response to various vasoactive molecules, such as hypoxia and nitric oxide, are well known, but the molecular mechanisms underlying the sensing of those stimuli remain obscure. In contrast to the systemic arteries, the hypoxic stimulus induces vasoconstriction of the pulmonary arteries, an effect that is more pronounced as the vessel diameter decreases [1, 2]. Different potassium channels are expressed and distributed in several types of pulmonary arterial smooth muscle cells (PA-SMCs) and contribute to this large functional diversity. Although voltage-gated potassium channel (KV)1.2, KV1.5, KV2.1, KV3.1b and KV9.3 play important roles in the hypoxia-inhibited potassium current found in PA-SMCs, much attention has been attracted by KV1.5 [3]. …
Targeting DNA-PKcs and telomerase in brain tumour cells
Authors: Resham Lal Gurung, Hui Kheng Lim, Shriram Venkatesan, Phoebe Su Wen Lee, M Prakash Hande
Journal: Molecular Cancer (2014)

Patients suffering from brain tumours such as glioblastoma and medulloblastoma have poor prognosis with a median survival of less than a year. Identifying alternative molecular targets would enable us to develop different therapeutic strategies for better management of these tumours. Glioblastoma (MO59K and KNS60) and medulloblastoma cells (ONS76) were used in this study. Telomerase inhibitory effects of MST-312, a chemically modified-derivative of epigallocatechin gallate, in the cells were assessed using telomere repeat amplification protocol. Gene expression analysis following MST-312 treatment was done by microarray. Telomere length was measured by telomere restriction fragments analysis. Effects of MST-312 on DNA integrity were evaluated by single cell gel electrophoresis, immunofluorescence assay and cytogenetic analysis. Phosphorylation status of DNA-PKcs was measured with immunoblotting and effects on cell proliferation were monitored with cell titre glow and trypan blue exclusion following dual inhibition. MST-312 showed strong binding affinity to DNA and displayed reversible telomerase inhibitory effects in brain tumour cells. In addition to the disruption of telomere length maintenance, MST-312 treatment decreased brain tumour cell viability, induced cell cycle arrest and double strand breaks (DSBs). DNA-PKcs activation was observed in telomerase-inhibited cells presumably as a response to DNA damage. Impaired DNA-PKcs in MO59J cells or in MO59K cells treated with DNA-PKcs inhibitor, NU7026, caused a delay in the repair of DSBs. In contrast, MST-312 did not induce DSBs in telomerase negative osteosarcoma cells (U2OS). Combined inhibition of DNA-PKcs and telomerase resulted in an increase in telomere signal-free chromosomal ends in brain tumour cells as well. Interestingly, continual exposure of brain tumour cells to telomerase inhibitor led to population of cells, which displayed resistance to telomerase inhibition-mediated cell arrest. DNA-PKcs ablation in these cells, however, confers higher cell sensitivity to telomerase inhibition, inducing cell death. Efficient telomerase inhibition was achieved with acute exposure to MST-312 and this resulted in subtle but significant increase in DSBs. Activation of DNA-PKcs might indicate the requirement of NHEJ pathway in the repair telomerase inhibitor induced DNA damage. Therefore, our results suggest a potential strategy in combating brain tumour cells with dual inhibition of telomerase and NHEJ pathway.
GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity
Authors: Michael A. Spinner, Lauren A. Sanchez, Amy P. Hsu, Pamela A. Shaw, Christa S. Zerbe, Katherine R. Calvo, Diane C. Arthur, Wenjuan Gu, Christine M. Gould, Carmen C. Brewer, Edward W. Cowen, Alexandra F. Freeman, Kenneth N. Olivier, Gulbu Uzel, Adrian M. Zelazny, Janine R. Daub, Christine D. Spalding, Reginald J. Claypool, Neelam K. Giri, Blanche P. Alter, Emily M. Mace, Jordan S. Orange, Jennifer Cuellar-Rodriguez, Dennis D. Hickstein, Steven M. Holland
Journal: Blood (2013)
Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction
Authors: Qizhi Tang, Jason Y. Adams, Cristina Penaranda, Kristin Melli, Eliane Piaggio, Evridiki Sgouroudis, Ciriaco A. Piccirillo, Benoit L. Salomon, Jeffrey A. Bluestone
Journal: Immunity (2008)
New approaches to the assessment and treatment of the idiopathic inflammatory myopathies
Authors: Frederick W Miller
Journal: Annals of the Rheumatic Diseases (2012)

The rarity and heterogeneity of the idiopathic inflammatory myopathies (IIM), and the few validated assessment tools available, have limited information to guide the management of patients with polymyositis, dermatomyositis or inclusion body myositis. In light of the need for such tools, the International Myositis Assessment and Clinical Studies Group (IMACS) was formed as a multidisciplinary consortium of rheumatologists, neurologists, dermatologists, physiatrists and other myositis experts to develop consensus and standards for the conduct and reporting of myositis studies, and to facilitate myositis research. IMACS has developed consensus core set measures of disease activity, disease damage and patient-reported outcomes, and compiled a preliminary definition of improvement. The IMACS tools assist in the evaluation of the extent of disease activity and damage, although other approaches—including key clinical features, laboratory tests, muscle T1 and short τ inversion recovery MRI and immunological markers—are also helpful. Clinical remission is a realistic objective for most patients and should be pursued aggressively to optimise outcomes. Physical therapy and rehabilitation should be applied early and consistently to achieve optimal strength and function. Treatments that have been developed for other immune-mediated diseases are also being used and tested in the IIM, and some have shown anecdotal evidence of benefit. Recent advances in understanding the pathogenesis of myositis, development of assessments and treatments for other diseases that can be applied to myositis, and international collaborations and consensus standards for evaluating the IIM, all promise improvements in the assessment and treatment of myositis in the future.