tbuckley/cabot-search huggingface dataset:
Inhibitor of differentiation-1 (Id1) characterization in poor-prognosis (PP) human bladder cancer (BCa) primary tumors and matched metastases (MTS) using a new monoclonal antibody (MoAb)
Authors: M. Ponz-Sarvisé, A. Calvo, M. Redrado, P. A. Nguewa, L. Abella, R. Catena, J. García-Foncillas, A. Panizo, I. Gil- Bazo
Journal: Journal of Clinical Oncology (2009)

e16119 Background: Id1, involved in cell differentiation, proliferation, tumor angiogenesis and metastasis, has recently showed to mediate lung MTS from breast cancer (PNAS 2007). The expression of Id1 in human cancer has been related to poor prognosis breast, prostate (Gil-Bazo, Amer Soc Clin Oncol GU. 2009) and other non-adenocarcinoma tumors. To date one study showed remarkable Id1 expression (exp.) in 28% of unselected human BCa using a new MoAb (195–14) for immunohistochemistry (IHC) analysis. Our aim is to study Id1 exp. in a group of PP BCa and their matched MTS using this MoAb (195–14). Methods: We selected 22 patients (pts) treated in our institution. Formalin-fixed and paraffin- embedded bladder biopsy samples of each patient and matched MTS samples of 9 of them were stained and scored for tumor and endothelial Id1 exp. Anti-human Id1 rabbit MoAb 195–14 (1:500), (Biocheck), was used for IHC. Results: 90% of pts were males; median age was 61. Most pts had PP advanced (22,7 % stage III; 68,2% stage IV) BCa. Primary tumor samples and additional 9 matched MTS biopsy samples were analyzed. In contrast with the previous data 80% of primary invasive BCa and more than 75% of MTS showed tumor cell Id1 exp. As previously reported Id1 exp. in tumor samples endothelial cells reached 70%. We also observed Id1 exp. in tumor in situ areas near the invasive carcinoma in 16 out of 20 pts expressing Id1 in the primary tumor. Conclusions: For the first time using a MoAb against Id1 and in accord with our previous observations in prostate cancer the selection of PP pts increases tumor cell Id1 exp. from 28 up to 80%. Interestingly we show BCa MTS to express Id1 with a similar exp. pattern than primary tumors. Id1 exp. profile in PP and metastatic initiation of BCa needs further research. Id1 exp. in tumor in situ areas suggests Id1 as an initial factor in the BCa carcinogenic process and in the case of being confirmed Id1 could represent a target in BCa prophylaxis. No significant financial relationships to disclose.
Immediate Allergic Response in Small Airways
Authors: A. WOHLSEN, S. UHLIG, C. MARTIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The role of small airways in the immediate allergic response is largely unknown. We therefore used the model of precision-cut lung slices (PCLS) in combination with quantitative videomicroscopy to study the early allergic response to allergen in airways ranging from 50 to 900 μ m. After PCLS from untreated Wistar rats had been passively sensitized for 16 h with serum from sensitized Brown Norway rats, exposure to 0.1% ovalbumin resulted in an immediate allergic response. Both extent (r = 0.74, p < 0.0001) and velocity (r = 0.49, p < 0.0001) of the allergen-induced bronchoconstriction increased with decreasing airway size. In addition, we observed that smaller airways not only contracted stronger and quicker, but that they also relaxed faster, suggesting that smaller airways are more reactive in principle. The allergen-induced bronchoconstriction in PCLS was prevented by the serotonin receptor antagonist ketanserin (IC50 6 nM), but not by antagonists directed against histamine, acetylcholine, PAF, or endothelin receptors, or by cyclooxygenase or lipoxygenase inhibitors. Like allergen, serotonin provoked responses that were stronger in smaller airways. These findings suggest that the immediate allergic response in rat PCLS depends largely on serotonin and that this response can occur in nearly all airway generations, but is most pronounced in the smallest airways, that is, the terminal bronchioles.
Loss of NKX3.1 Favors Vascular Endothelial Growth Factor-C Expression in Prostate Cancer
Authors: Heyu Zhang, Michael H. Muders, Jinping Li, Francesca Rinaldo, Donald J. Tindall, Kaustubh Datta
Journal: Cancer Research (2008)

Decreased levels of the prostate-specific homeobox protein NKX3.1 are correlated with hormone-refractory and metastatic prostate cancer. Thus, it is compelling to define the NKX3.1-regulated genes that may be important for the progression of the advanced stage of the disease. In this study, we showed that vascular endothelial growth factor-C (VEGF-C) is one such target gene of NKX3.1. NKX3.1 inhibited VEGF-C expression in prostate cancer, and the loss of NKX3.1 led to increased VEGF-C expression. Histone deacetylase 1 acted as a corepressor of VEGF-C expression along with NKX3.1. Activated RalA acted in synergy with the loss of NKX3.1 for VEGF-C transcription. Patients with deletions at chromosome 8p21.1-p21.2 as a sole deletion developed lymph node metastasis. Interestingly, the higher expression of VEGF-C in prostate cancer is also correlated with lymph node metastasis. Therefore, regulation of VEGF-C expression by NKX3.1 provides a possible mechanism by which the loss of NKX3.1 protein level leads to lymphangiogenesis in the late stages of advanced prostate cancer.
HbA1c in Nondiabetic Dutch Infants Aged 8–12 Months
Authors: Hanneke Jansen, Haika G. Huiting, Salome Scholtens, Pieter J.J. Sauer, Ronald P. Stolk
Journal: Diabetes Care (2011)

OBJECTIVE An international committee of experts recommended using HbA1c for diagnostic testing for diabetes. Little is known about normal values of HbA1c in infants. The aim of this study is to describe the distribution of HbA1c in 8- to 12-month-old nondiabetic infants. RESEARCH DESIGN AND METHODS HbA1c was measured in 86 infants participating in the Groningen Expert Center for Kids with Obesity (GECKO)-Drenthe birth cohort study. Anthropometric measurements were performed at Well Baby Clinics. Data on parents and children were collected prospectively using questionnaires. RESULTS HbA1c was normally distributed with a mean (SD) HbA1c level of 5.38% (0.24), range 4.8–6.0% or 35.29 mmol/mol (2.65), range 29.1–42.1 mmol/mol. Age, sex, birth weight, duration of breastfeeding, anthropometric measurements, and maternal BMI were not associated with HbA1c. CONCLUSIONS We found a normal distribution of HbA1c with a relatively high mean HbA1c of 5.38%. No significant association between risk factors for type 2 diabetes and HbA1c levels was found.
Diabetes in Older Adults
Authors: M. Sue Kirkman, Vanessa Jones Briscoe, Nathaniel Clark, Hermes Florez, Linda B. Haas, Jeffrey B. Halter, Elbert S. Huang, Mary T. Korytkowski, Medha N. Munshi, Peggy Soule Odegard, Richard E. Pratley, Carrie S. Swift
Journal: Diabetes Care (2012)

More than 25% of the U.S. population aged ≥65 years has diabetes (1), and the aging of the overall population is a significant driver of the diabetes epidemic. Although the burden of diabetes is often described in terms of its impact on working-age adults, diabetes in older adults is linked to higher mortality, reduced functional status, and increased risk of institutionalization (2). Older adults with diabetes are at substantial risk for both acute and chronic microvascular and cardiovascular complications of the disease.

Despite having the highest prevalence of diabetes of any age-group, older persons and/or those with multiple comorbidities have often been excluded from randomized controlled trials of treatments—and treatment targets—for diabetes and its associated conditions. Heterogeneity of health status of older adults (even within an age range) and the dearth of evidence from clinical trials present challenges to determining standard intervention strategies that fit all older adults. To address these issues, the American Diabetes Association (ADA) convened a Consensus Development Conference on Diabetes and Older Adults (defined as those aged ≥65 years) in February 2012. Following a series of scientific presentations by experts in the field, the writing group independently developed this consensus report to address the following questions:

1.  What is the epidemiology and pathogenesis of diabetes in older adults?

2.  What is the evidence for preventing and treating diabetes and its common comorbidities in older adults?

3.  What current guidelines exist for treating diabetes in older adults?

4.  What issues need to be considered in individualizing treatment recommendations for older adults?

5.  What are consensus recommendations for treating older adults with or at risk for diabetes?

6.  How can gaps in the evidence best be filled?

According to the most recent surveillance data, the prevalence of diabetes among U.S. adults aged ≥65 years varies from 22 to 33%, depending on the diagnostic criteria …
Passive Smoking Exposure and Female Breast Cancer Mortality
Authors: D. Wartenberg
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Several studies have reported positive associations between environmental tobacco smoke (ETS) and increased risk of breast cancer. However, studies of active smoking and risk of breast cancer are equivocal and in general do not support a positive association. To try to resolve this paradox, we examined the association between breast cancer mortality and potential ETS exposure from spousal smoking in an American Cancer Society prospective study of U.S. adult women. Methods: We assessed breast cancer death rates in a cohort of 146 488 never-smoking, single-marriage women who were cancer free at enrollment in 1982. Breast cancer death rates among women whose husbands smoked were compared with those among women married to men who had never smoked. Cox proportional hazards modeling was used to control for potential risk factors other than ETS exposure. Results: After 12 years of follow-up, 669 cases of fatal breast cancer were observed in the cohort. Overall, we saw no association between exposure to ETS and death from breast cancer (rate ratio [RR] = 1.0; 95% confidence interval [CI] = 0.8–1.2). We did, however, find a small, not statistically significant increased risk of breast cancer mortality among women who were married before age 20 years to smokers (RR = 1.2; 95% CI = 0.8–1.8). Conclusions: In contrast to the results of previous studies, this study found no association between exposure to ETS and female breast cancer mortality. The results of our study are particularly compelling because of its prospective design as compared with most earlier studies, the relatively large number of exposed women with breast cancer deaths, and the reporting of exposure by the spouse rather than by proxy.
Association of BclI polymorphism of the glucocorticoid receptor gene locus with response to glucocorticoids in inflammatory bowel disease
Authors: S. De Iudicibus, G. Stocco, S. Martelossi, I. Drigo, S. Norbedo, P. Lionetti, E. Pozzi, A. Barabino, G. Decorti, F. Bartoli, A. Ventura
Journal: Gut (2007)

Glucocorticoids (GCs) are immunosuppressive drugs used for the acute treatment of patients with moderate to severe inflammatory bowel disease (IBD),1 but interindividual variability in the response to these agents is frequently observed.2 GCs diffuse freely into cells and bind to an intracellular receptor (hGR/NR3C1), so the sensitivity to these drugs may depend on the receptor number and affinity or on their availability to the receptors, and transport proteins (including P-glycoprotein (Pgp) encoded by the MDR1/ABCB1 gene) can modify their intracellular concentration.3,4 Polymorphisms in the hGR and MDR1 genes have been described in different populations and may contribute to the variability in sensitivity to GCs observed in the clinical setting.3,4

A study was conducted to estimate the impact of genetic variations in hGR and MDR1 genes on the efficacy and individual response to GCs in young patients with IBD. Polymorphisms of the hGR gene ( Bcl I and N363S which are related to GC hypersensitivity and ER22/23EK which is associated with relative resistance to GCs5) and the MDR1 gene (C3435T and G2677T which are associated with changes in Pgp expression and activity6) were studied in 119 young patients …
Use of inhaled corticosteroids in patients with mild asthma.
Authors: S Lorentzson, J Boe, G Eriksson, G Persson
Journal: Thorax (1990)

A double blind, parallel group study was carried out to investigate the effect of inhaled budesonide in a moderate (200 micrograms) and a low (100 micrograms) twice daily dosage compared with the effect of placebo in 103 adults with mild symptomatic asthma. Subjects recorded peak expiratory flow (PEF), asthma symptoms, and beta 2 agonist consumption at home for a period of seven weeks (a one week run in and six weeks9 treatment). Morning baseline PEF (around 80% of predicted normal) increased non-significantly to 88% with 200 micrograms budesonide daily and to 90% (p less than 0.05) with 400 micrograms, compared with 81% with placebo. Evening PEF (around 94% of predicted normal) did not change significantly with active or placebo treatment. By comparison with placebo, there was a significant decrease in nocturnal asthma symptoms and beta 2 agonist consumption. The changes during the day were less pronounced and significant only for 400 micrograms budesonide daily. No significant differences between the two active treatments were detected. It is concluded that low doses of inhaled budesonide are effective in patients with mild symptomatic asthma, particularly for night time symptoms and early morning lung function. The early introduction of inhaled corticosteroids for patients with mild asthma and night time symptoms may improve their quality of life during the night and early morning.
Disinfection of upper gastrointestinal fibreoptic endoscopy equipment: an evaluation of a cetrimide chlorhexidine solution and glutaraldehyde.
Authors: D L Carr-Locke, P Clayton
Journal: Gut (1978)

There is little information available on the bacteriological contamination of upper gastrointestinal fibreoptic endoscopes during routine use and the effects of 9disinfecting solutions9. A bacteriological evaluation was therefore made of cleaning an endoscope and its ancillary equipment with (1) water, (2) an aqueous solution of 1% cetrimide with 0.1% chlorhexidine, and (3) activated aqueous 2% glutaraldehyde. All equipment, but particularly the endoscope itself, was found to be heavily contaminated after use with a wide variety of organisms of which 53% were Gram positive. Cleaning the endoscope and ancillary equipment with water and the cetrimide/chlorhexidine solution alone or in combination was inadequate to produce disinfection but immersion in glutaraldehyde for two minutes consistently produced sterile cultures with our sampling technique. A rapid and simple method for disinfection of endoscopic equipment is therefore recommended and we think this is especially suitable for busy endoscopy units.
Abnormal Calcium Signaling and Sudden Cardiac Death Associated With Mutation of Calsequestrin
Authors: Serge Viatchenko-Karpinski, Dmitry Terentyev, Inna Györke, Radmila Terentyeva, Pompeo Volpe, Silvia G. Priori, Carlo Napolitano, Alessandra Nori, Simon C. Williams, Sandor Györke
Journal: Circulation Research (2004)

Mutations in human cardiac calsequestrin (CASQ2), a high-capacity calcium-binding protein located in the sarcoplasmic reticulum (SR), have recently been linked to effort-induced ventricular arrhythmia and sudden death (catecholaminergic polymorphic ventricular tachycardia). However, the precise mechanisms through which these mutations affect SR function and lead to arrhythmia are presently unknown. In this study, we explored the effect of adenoviral-directed expression of a canine CASQ2 protein carrying the catecholaminergic polymorphic ventricular tachycardia-linked mutation D307H (CASQ2(D307H)) on Ca2+ signaling in adult rat myocytes. Total CASQ2 protein levels were consistently elevated approximately 4-fold in cells infected with adenoviruses expressing either wild-type CASQ2 (CASQ2(WT)) or CASQ2(D307H). Expression of CASQ2(D307H) reduced the Ca2+ storing capacity of the SR. In addition, the amplitude, duration, and rise time of macroscopic I(Ca)-induced Ca2+ transients and of spontaneous Ca2+ sparks were reduced significantly in myocytes expressing CASQ2(D307H). Myocytes expressing CASQ2(D307H) also displayed drastic disturbances of rhythmic oscillations in [Ca2+]i and membrane potential, with signs of delayed afterdepolarizations when undergoing periodic pacing and exposed to isoproterenol. Importantly, normal rhythmic activity was restored by loading the SR with the low-affinity Ca2+ buffer, citrate. Our data suggest that the arrhythmogenic CASQ2(D307H) mutation impairs SR Ca2+ storing and release functions and destabilizes the Ca2+-induced Ca2+ release mechanism by reducing the effective Ca2+ buffering inside the SR and/or by altering the responsiveness of the Ca2+ release channel complex to luminal Ca2+. These results establish at the cellular level the pathological link between CASQ2 mutations and the predisposition to adrenergically mediated arrhythmias observed in patients carrying CASQ2 defects.
Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study
Authors: Evanthia Galanis, Jan C. Buckner, Matthew J. Maurer, Jeffrey I. Kreisberg, Karla Ballman, J. Boni, Josep M. Peralba, Robert B. Jenkins, Shaker R. Dakhil, Roscoe F. Morton, Kurt A. Jaeckle, Bernd W. Scheithauer, Janet Dancey, Manuel Hidalgo, Daniel J. Walsh
Journal: Journal of Clinical Oncology (2005)

Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM).Recurrent GBM patients with < or = 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly.Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme-inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/- decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 months and was significantly longer for responders (5.4 months) versus nonresponders (1.9 months). Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response (71% v 31%; P = .04). Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor samples (P = .04).Temsirolimus is well tolerated in recurrent GBM patients. Despite the effect of EIACs on temsirolimus metabolism, therapeutic levels were achieved. Radiographic improvement was observed in 36% of temsirolimus-treated patients, and was associated with significantly longer TTP. High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors.
High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions
Authors: Ashraf Badros, Bart Barlogie, Christopher Morris, Raman Desikan, Sara R. Martin, Nikhil Munshi, Maurizio Zangari, Jayesh Mehta, Amir Toor, Michele Cottler-Fox, Athanasios Fassas, Elias Anaissie, Steven Schichman, Guido Tricot
Journal: Blood (2001)
Contact allergy to allergens of the TRUE-test (panels 1 and 2) has decreased modestly in the general population
Authors: J.P. Thyssen, A. Linneberg, T. Menné, N.H. Nielsen, J.D. Johansen
Journal: British Journal of Dermatology (2009)

The prevalence of contact allergy in the general population is nearly 20%.This study aimed to monitor the development of contact allergy to allergens from the TRUE-test (panels 1 and 2) between 1990 and 2006.Two random samples of adults from the general population in Copenhagen, Denmark, were invited to participate in a general health examination including patch testing. In 1990 and 2006, we patch tested and questioned 543 and 3460 adult Danes. Patch test readings were performed on day 2 only.The overall prevalence decreased significantly from 15.5% in 1990 to 10.0% in 2006, mainly as a result of a decrease in thimerosal allergy from 3.4% to 0.8%. Furthermore, the prevalence of cobalt allergy and rubber-related allergens decreased from 1.1% to 0.2% and from 1.5% to 0.2%, respectively. Stratification by sex and age group revealed decreasing prevalences of contact allergy in all male age groups and in young and middle-aged female age groups (18-55 years) whereas increasing prevalences were observed among older women (56-69 years). The diverging trend observed in women was probably explained by a cohort effect due to a change in the prevalence of nickel allergy following the Danish regulation on nickel exposure.Although the overall prevalence of contact allergy decreased in the general population, frequent contact allergens such as fragrance mix II and methyldibromo glutaronitrile were not tested. Thus, contact allergy remains prevalent in the general population.
Smooth Muscle Cell–Specific Runx2 Deficiency Inhibits Vascular Calcification
Authors: Yong Sun, Chang Hyun Byon, Kaiyu Yuan, Jianfeng Chen, Xia Mao, Jack M. Heath, Amjad Javed, Kui Zhang, Peter G. Anderson, Yabing Chen
Journal: Circulation Research (2012)

Rationale: Vascular calcification is a hallmark of atherosclerosis, a major cause of morbidity and mortality in the United States. We have previously reported that the osteogenic transcription factor Runx2 is an essential and sufficient regulator of calcification of vascular smooth muscle cells (VSMC) in vitro. Objective: To determine the contribution of osteogenic differentiation of VSMC to the pathogenesis of vascular calcification and the function of VSMC-derived Runx2 in regulating calcification in vivo. Methods and Results: SMC-specific Runx2-deficient mice, generated by breeding SM22α-Cre mice with the Runx2 exon 8 floxed mice, exhibited normal aortic gross anatomy and expression levels of SMC-specific marker genes. Runx2 deficiency did not affect basal SMC markers, but inhibited oxidative stress-reduced expression of SMC markers. High-fat-diet-induced vascular calcification in vivo was markedly inhibited in the Runx2-deficient mice in comparison with their control littermates. Runx2 deficiency inhibited the expression of receptor activator of nuclear factor κB ligand, which was accompanied by decreased macrophage infiltration and formation of osteoclast-like cells in the calcified lesions. Coculture of VSMC with bone marrow–derived macrophages demonstrated that the Runx2-deficient VSMC failed to promote differentiation of macrophages into osteoclast-like cells. Conclusions: These data have determined the importance of osteogenic differentiation of VSMC in the pathogenesis of vascular calcification in mice and defined the functional role of SMC-derived Runx2 in regulating vascular calcification and promoting infiltration of macrophages into the calcified lesion to form osteoclast-like cells. Our studies suggest that the development of vascular calcification is coupled with the formation of osteoclast-like cells, paralleling the bone remodeling process.