tbuckley/cabot-search huggingface dataset:
Periodontal disease is significantly higher in non-smoking treatment-naive rheumatoid arthritis patients: results from a case-control study
Authors: Damodaram Potikuri, Kalyan Chakravarthy Dannana, Suresh Kanchinadam, Sumeet Agrawal, Anuradha Kancharla, Liza Rajasekhar, Shantakumari Pothuraju, Narsimulu Gumdal
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To find the strength of association between periodontal disease (PD) and rheumatoid arthritis (RA) in non-smoking, disease modifying antirheumatic drug (DMARD)-naive RA patients in a case-control design. <h3>Methods</h3> Patients of RA (DMARD-naive, non-smokers) satisfying the American college of Rheumatology 1987 criteria and healthy controls were included. PD was defined as present if the mean pocket depth (MPD) is ≥3 mm. Demographic data and disease specific variables were recorded for RA patients and healthy controls. Titres of immunoglobulin M-rheumatoid factor (IgM-RF) and anticitrullinated peptide antibodies (ACPAs) were measured using ELISA. <h3>Results</h3> Patients with RA (n=91) had a 4.28 (CI 2.35 to 7.38) higher odds of PD (64.8% vs 28%, p&lt;0.001) compared with healthy controls (n=93). The MPD was 3.61±1.22 mm in cases and 2.46±0.74 mm in controls (p&lt;0.001). IgM-RF titres (110.56±95.81 vs 66.53±70.29; p=0.02) and ACPA titres (753.05±1088.27 vs 145.15±613.16, p=0.001) were significantly higher in RA patients with PD than those without PD. The MPD positively correlated with titres of ACPAs in RA patients (r=0.24; p=0.02). <h3>Conclusions</h3> PD is more frequent and severe in non-smoking DMARD-naive RA patients compared with healthy controls. PD in RA is associated with high titres of ACPAs.
Selective Killing of Cancer Cells by Leaf Extract of Ashwagandha: Identification of a Tumor-Inhibitory Factor and the First Molecular Insights to Its Effect
Authors: Nashi Widodo, Kamaljit Kaur, Bhupal G. Shrestha, Yasuomi Takagi, Tetsuro Ishii, Renu Wadhwa, Sunil C. Kaul
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha. Experimental Design: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract. Results: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as withanone. Conclusion: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.
Clinicopathological Validation Study of Four Sets of Clinical Criteria for Vascular Dementia
Authors: Gabriel Gold, Constantin Bouras, Alessandra Canuto, Maria Fernanda Bergallo, François R. Herrmann, Patrick R. Hof, Pierre-André Mayor, Jean-Pierre Michel, Panteleimon Giannakopoulos
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors' goal was to validate the clinical criteria for vascular dementia of the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC), the National Institute for Neurological Disorders and Stroke–Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), DSM-IV, and ICD-10. METHOD: Sensitivity and specificity were assessed by comparing the clinical with the neuropathological diagnosis of 89 autopsied patients with dementia from a geriatric and psychiatric hospital. All cases were reviewed by a clinician and a neuropathologist who were blind to each other's findings. RESULTS: Neuropathologically there were 20 cases of vascular dementia, 23 cases of mixed dementia, and 46 cases of Alzheimer's disease among the autopsied patients. The sensitivity was 0.50 for DSM-IV criteria for vascular dementia, 0.70 for ADDTC criteria for possible vascular dementia, 0.55 for NINDS-AIREN criteria for possible vascular dementia, 0.20 for ICD-10 criteria for vascular dementia, 0.25 for ADDTC criteria for probable vascular dementia, and 0.20 for NINDS-AIREN criteria for probable vascular dementia. Specificity was 0.84, 0.78, 0.84, 0.94, 0.91, and 0.93, respectively. The proportion of cases clinically classified as vascular dementia ranged from 0% to 13% for neuropathologically confirmed cases of Alzheimer's disease and 9% to 39% for neuropathologically confirmed cases of mixed dementia. There was no statistically significant relationship between the neuropathological diagnosis and three of the clinical criteria sets studied (ICD-10 criteria for vascular dementia and ADDTC and NINDS-AIREN criteria for probable vascular dementia). CONCLUSIONS: Clinical criteria for vascular dementia are not interchangeable. The ADDTC criteria for possible vascular dementia are the most sensitive for the detection of vascular dementia; however, the DSM-IV criteria for vascular dementia and the NINDS-AIREN criteria for possible vascular dementia may be more effective in excluding mixed dementia. Given their inability to detect the vast majority of cases of vascular dementia, the ICD-10 criteria for vascular dementia and the ADDTC and NINDS-AIREN criteria for probable vascular dementia should be revised.
What are ventilation defects in asthma?
Authors: Sarah Svenningsen, Miranda Kirby, Danielle Starr, Harvey O Coxson, Nigel A M Paterson, David G McCormack, Grace Parraga
Journal: Thorax (2013)

<h3>Background</h3> Hyperpolarised <sup>3</sup>He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood. <h3>Objective</h3> To better understand the determinants of ventilation defects in asthma, we evaluated well-established clinical as well as <sup>3</sup>He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma. <h3>Methods</h3> Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3<sup>rd</sup> to 5th generation airway wall area and wall thickness per cent and lumen area. <h3>Results</h3> Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of <sup>3</sup>He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV<sub>1</sub>)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV<sub>1</sub> by 20% (p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04). <h3>Conclusions</h3> Subjects with asthma with <sup>3</sup>He ventilation defects were older with significantly worse airway hyper-responsiveness, inflammation and airway remodelling but similar FEV<sub>1</sub> as subjects with asthma without defects; hyperpolarised <sup>3</sup>He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways.
Removal of intracellular Mg2+ activates cardiac Na+/Ca2+ exchanger
Authors: T Kiyosue
Journal: Cardiovascular Research (2002)

See article by Wei et al. [1] (pages 334–340) in this issue. 

The Na+/Ca2+ exchanger (NCX) expels Ca2+ from myocytes in exchange for extracellular Na+ and balances Ca2+ influx through L-type Ca2+ channels during cardiac excitation. In this issue of Cardiovascular Research, Wei et al. [1] report that cardiac NCX is regulated by intracellular Mg2+ (Mg2+ i ). Their results suggest some similarities of mammalian cardiac NCX to that of squid nerves (NCX-SQ) [2]. In squid nerve, rapid removal of Mg2+ i  produced marked activation of the exchanger. Further removal of ATP did not suppress the activated NCX-SQ, but readmission of Mg2+ i  abolished this NCX-SQ stimulation. Phosphatidylinositols, which are known to modulate the activity of cardiac NCX [3], were not involved in the stimulation of NCX-SQ by Mg2+ i  removal [2]. In pig ventricular myocytes [1], when Mg2+ i  was reduced by cell dialysis with a low Mg2+ internal solution (0.18 mM), whole cell NCX current was augmented regardless of the levels of free Ca2+, ATP and MgATP. These findings are quite comparable to those in squid nerves: removal of ATP in the absence of Mg2+ i  kept the NCX-SQ in a highly stimulated state.

Among the results by Wei et al. [1], the absence of the effect of ATP on stimulated NCX by … 

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Are obese children at risk of sleep disordered breathing
Authors: D Shaw
Journal: Thorax (2004)

▴ Wing YK, Hui SH, Pak WM, et al . A controlled study of sleep related disordered breathing in obese children. Arch Dis Child2003;88:1043–7

[OpenUrl][1][Abstract/FREE Full Text][2]



This study tested the hypothesis that obese children are at greater risk of sleep disordered breathing (SDB) than children of normal weight, and that the risk is potentiated by pharyngeal tissue enlargement. 46 obese children (mean (SD) age 10.8 (2.3) years; BMI 27.4 (5.1) kg/m2) and 44 sex and age matched …

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Effect of hyperbaric oxygen on oxygen uptake and measurements in the blood and tissues in a normobaric environment
Authors: A N H Hodges, J S Delaney, J M Lecomte, V J Lacroix, D L Montgomery
Journal: British Journal of Sports Medicine (2003)

Objective: To examine venous partial pressure of oxygen (Pv o 2 ), transcutaneous oxygen tension (tcP o 2 ), and V o 2 max in a normobaric environment after a single hyperbaric oxygen (HB o 2 ) treatment. Methods: This was a prospective study of conditions after the intervention compared with baseline. The participants were 10 moderately trained (V o 2 max = 57.6 ml/kg/min) men. Two HB o 2 treatments consisting of breathing 95% oxygen at 2.5 atmospheres absolute (ATA) for 90 minutes were administered on non-consecutive days. Baseline testing included measures of V o 2 max , tcP o 2 , and anthropometry. At 6.0 (1.0) minutes after the first HB o 2 treatment, a V o 2 max test was performed. After the second HB o 2 treatment, leg and chest tcP o 2 and Pv o 2 were monitored for 60 minutes. Results: V o 2 max , running time, and peak blood lactate were not altered after the HB o 2 treatment. Leg tcP o 2 was lower (p = 0.003) and chest tcP o 2 was unchanged after the HB o 2 treatment compared with baseline values. Pv o 2 was significantly (p&lt;0.001) lower in the first three minutes after treatment than subsequent values, but no other differences were found. Conclusions: A single HB o 2 treatment at 2.5 ATA for 90 minutes does not raise Pv o 2 , tcP o 2 , or V o 2 max in a normobaric, normoxic environment.
Reduced Phospholamban Phosphorylation Is Associated With Impaired Relaxation in Left Ventricular Myocytes From Neuronal NO Synthase–Deficient Mice
Authors: Yin Hua Zhang, Mei Hua Zhang, Claire E. Sears, Krzysztof Emanuel, Charles Redwood, Ali El-Armouche, Evangelia G. Kranias, Barbara Casadei
Journal: Circulation Research (2007)

Stimulation of nitric oxide (NO) release from the coronary endothelium facilitates myocardial relaxation via a cGMP-dependent reduction in myofilament Ca2+ sensitivity. Recent evidence suggests that NO released by a neuronal NO synthase (nNOS) in the myocardium can also hasten left ventricular relaxation; however, the mechanism underlying these findings is uncertain. Here we show that both relaxation (TR50) and the rate of [Ca2+]i transient decay (tau) are significantly prolonged in field-stimulated or voltage-clamped left ventricular myocytes from nNOS-/- mice and in wild-type myocytes (nNOS+/+) after acute nNOS inhibition. Disabling the sarcoplasmic reticulum abolished the differences in TR50 and tau, suggesting that impaired sarcoplasmic reticulum Ca2+ reuptake may account for the slower relaxation in nNOS-/- mice. In line with these findings, disruption of nNOS (but not of endothelial NOS) decreased phospholamban phosphorylation (P-Ser16 PLN), whereas nNOS inhibition had no effect on TR50 or tau in PLN-/- myocytes. Inhibition of cGMP signaling had no effect on relaxation in either group whereas protein kinase A inhibition abolished the difference in relaxation and PLN phosphorylation by decreasing P-Ser16 PLN and prolonging TR50 in nNOS+/+ myocytes. Conversely, inhibition of type 1 or 2A protein phosphatases shortened TR50 and increased P-Ser16 PLN in nNOS-/- but not in nNOS+/+ myocytes, in agreement with data showing increased protein phosphatase activity in nNOS-/- hearts. Taken together, our findings identify a novel mechanism by which myocardial nNOS promotes left ventricular relaxation by regulating the protein kinase A-mediated phosphorylation of PLN and the rate of sarcoplasmic reticulum Ca2+ reuptake via a cGMP-independent effect on protein phosphatase activity.
Novel Therapeutic Inhibitors of the c-Met Signaling Pathway in Cancer
Authors: Joseph Paul Eder, George F. Vande Woude, Scott A. Boerner, Patricia M. LoRusso
Journal: Clinical Cancer Research (2009)

A wide variety of human malignancies exhibit sustained c-Met stimulation, overexpression, or mutation, including carcinomas of the breast, liver, lung, ovary, kidney, and thyroid. Notably, activating mutations in c-Met have been positively identified in patients with a particular hereditary form of papillary renal cancer, directly implicating c-Met in human tumorigenesis. Aberrant signaling of the c-Met signaling pathway due to dysregulation of the c-Met receptor or overexpression of its ligand, hepatocyte growth factor (HGF), has been associated with an aggressive phenotype. Extensive evidence that c-Met signaling is involved in the progression and spread of several cancers and an enhanced understanding of its role in disease have generated considerable interest in c-Met and HGF as major targets in cancer drug development. This has led to the development of a variety of c-Met pathway antagonists with potential clinical applications. The three main approaches of pathway-selective anticancer drug development have included antagonism of ligand/receptor interaction, inhibition of the tyrosine kinase catalytic activity, and blockade of the receptor/effector interaction. Several c-Met antagonists are now under clinical investigation. Preliminary clinical results of several of these agents, including both monoclonal antibodies and small-molecule tyrosine kinase inhibitors, have been encouraging. Several multitargeted therapies have also been under investigation in the clinic and have demonstrated promise, particularly with regard to tyrosine kinase inhibition.
The role of leptin in pulmonary neutrophilia during murine acute lung injury
Authors: N.D. Ubags, J.H. Vernooy, E. Burg, C. Lenox, L.L. Kordonowy, J. Petty, K. DiPalma, E.F. Wouters, B.T. Suratt
Journal: European Respiratory Journal (2011)

Rationale:  One of the hallmarks of Acute Lung Injury (ALI) is the extensive recruitment of neutrophils to the lung. Recent evidence shows that leptin expression is increased in the injured human lung, and is known to have diverse effects on leucocytes. We hypothesized that leptin contributes directly to neutrophil recruitment in the lung during ALI.   Methods:  C57/Bl6 wild type (WT) mice were examined in a lipopolysaccharide (LPS) model of lung injury with or without oropharyngeal aspiration of recombinant leptin. We measured bronchoalveolar lavage (BAL) neutrophilia, leptin concentrations and inflammatory cytokine levels at 24 hours after injury. In addition, the effects of LPS induced lung injury were examined in leptin resistant ( db/db ) obese and Diet Induced Obese (DIO) mice and their lean controls. Lastly, we examined chemotaxis to leptin in neutrophils isolated from lean and obese uninjured mice.   Results:  BAL leptin levels were significantly increased in injured WT mice (1324 pg/ml ± 320) relative to their saline-treated controls (96 pg/ml ± 74) 24 hours after LPS exposure. Recombinant leptin augmented airspace neutrophilia after LPS exposure in WT mice, yet inflammatory cytokine levels in BAL remained unchanged. In addition, we observed attenuation in BAL neutrophilia in both  db/db  and DIO obese mice compared to their lean controls. Lastly, neutrophils were found to migrate to leptin  in vitro , and obesity blunted this response.   Conclusion:  Our findings indicate that leptin plays a role in neutrophil recruitment to the lung during ALI. This appears to occur in part via leptin-induced neutrophil chemotaxis, which is diminished in obesity.
Elevated serum antibodies against insulin-like growth factor-binding protein-2 allow detecting early-stage cancers: evidences from glioma and colorectal carcinoma studies
Authors: Y. Li, T. Jiang, J. Zhang, B. Zhang, W. Yang, G. You, K. Xu, J. Wu, C. Luo, S.W. Song
Journal: Annals of Oncology (2012)
Exercise Capacity and All-Cause Mortality in African American and Caucasian Men With Type 2 Diabetes
Authors: Peter Kokkinos, Jonathan Myers, Eric Nylen, Demosthenes B. Panagiotakos, Athanasios Manolis, Andreas Pittaras, Marc R. Blackman, Roshney Jacob-Issac, Charles Faselis, Joshua Abella, Steven Singh
Journal: Diabetes Care (2009)

OBJECTIVE The purpose of this study was to assess the association between exercise capacity and mortality in African Americans and Caucasians with type 2 diabetes and to explore racial differences regarding this relationship. RESEARCH DESIGN AND METHODS African American (n = 1,703; aged 60 ± 10 years) and Caucasian (n = 1,445; aged 62 ± 10 years) men with type 2 diabetes completed a maximal exercise test between 1986 and 2007 at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Three fitness categories were established (low-, moderate-, and high-fit) based on peak METs achieved. Subjects were followed for all-cause mortality for 7.3 ± 4.7 years. RESULTS The adjusted mortality risk was 23% higher in African Americans than in Caucasians (hazard ratio 1.23 [95% CI 1.1–1.4]). A graded reduction in mortality risk was noted with increased exercise capacity for both races. There was a significant interaction between race and METs (P &amp;lt; 0.001) and among race and fitness categories (P &amp;lt; 0.001). The association was stronger for Caucasians. Each 1-MET increase in exercise capacity yielded a 19% lower risk for Caucasians and 14% for African Americans (P &amp;lt; 0.001). Similarly, the risk was 43% lower (0.57 [0.44–0.73]) for moderate-fit and 67% lower (0.33 [0.22–0.48]) for high-fit Caucasians. The comparable reductions in African Americans were 34% (0.66 [0.55–0.80]) and 46% (0.54 [0.39–0.73]), respectively. CONCLUSIONS Exercise capacity is a strong predictor of all-cause mortality in African American and Caucasian men with type 2 diabetes. The exercise capacity-related reduction in mortality appears to be stronger and more graded for Caucasians than for African Americans.
Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children: validation study
Authors: Matthias Kappler, Susanne Krauss-Etschmann, Veronika Diehl, Hannelore Zeilhofer, Sibylle Koletzko
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate two commercial stool tests for detection of secretory IgA antibodies against gliadin and human tissue transglutaminase for diagnosis of coeliac disease in children with symptoms. <b>Setting</b> Tertiary care children9s hospital. <b>Participants</b> Coded stool samples from 20 children with newly diagnosed coeliac disease and 64 controls. Six children with coeliac disease had stool tests every two weeks for three months after starting a gluten-free diet. <b>Main outcome measures</b> Secretory IgA antibodies against gliadin and human tissue transglutaminase in stool samples, determined in duplicate by using recommended cut-off limits. <b>Results</b> Sensitivity of faecal antibodies against human tissue transglutaminase was 10% (95% confidence interval 1% to 32%), and specificity was 98% (91% to 100%). For antibodies against gliadin, sensitivity was 6% (0% to 29%) and specificity was 97% (89% to 100%). Optimisation of cut-off limits by receiver operating characteristic analysis and use of results of both tests increased sensitivity to 82%, but specificity decreased to 58%. All follow-up stool tests remained negative, except for two positive anti-gliadin results in one patient, six and 10 weeks after the gluten-free diet was started. <b>Conclusions</b> Neither stool test was suitable for screening for coeliac disease in children with symptoms.