tbuckley/cabot-search huggingface dataset:
Distinction of Normal, Preneoplastic, and Neoplastic Mouse Mammary Primary Cell Cultures by Water Nuclear Magnetic Resonance Relaxation Times23
Authors: Paula T. Beall, Bonnie B. Asch, Donald C. Chang, Daniel Medina, Carlton F. Hazlewood
Journal: JNCI Journal of the National Cancer Institute (1980)

Normal, preneoplastic, and neoplastic primary cultures of mouse mammary epithelial cells were distinguishable on the basis of water proton nuclear magnetic resonance (NMR) relaxation times--i.e., spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). T1 values were 916 +/- 24 msec for normal cells, 1,029 +/- 24 msec for preneoplastic cells, and 1,155 +/- 42 msec for neoplastic cells. This method of distinction between normal and neoplastic cells (P less than 0.001) and normal and preneoplastic cells (P less than 0.005) supported previous findings in whole tissues. NMR relaxation times resulted in better distinction between these cell populations than any other technique except direct histology. The T1 and T2 values of water protons in cells grown in primary culture were higher than those of established mouse mammary cancer cell lines. The differences in T1 and T2 did not correlate with cellular hydration. The data suggested a basic difference in water-macromolecular surface interactions among normal, preneoplastic, and neoplastic cells.
Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene
Authors: W. Janssens, R. Bouillon, B. Claes, C. Carremans, A. Lehouck, I. Buysschaert, J. Coolen, C. Mathieu, M. Decramer, D. Lambrechts
Journal: Thorax (2009)

<h3>Introduction</h3> Vitamin D deficiency has been associated with many chronic illnesses, but little is known about its relationship with chronic obstructive pulmonary disease (COPD). <h3>Objectives</h3> Serum 25-hydroxyvitamin D (25-OHD) levels were measured in 414 (ex)-smokers older than 50 years and the link between vitamin D status and presence of COPD was assessed. The rs7041 and rs4588 variants in the vitamin D-binding gene (<i>GC</i>) were genotyped and their effects on 25-OHD levels were tested. <h3>Results</h3> In patients with COPD, 25-OHD levels correlated significantly with forced expiratory volume in 1 s (FEV<sub>1</sub>) (r=0.28, p&lt;0.0001). Compared with 31% of the smokers with normal lung function, as many as 60% and 77% of patients with GOLD (Global Initiative for Obstructive Lung Disease) stage 3 and 4 exhibited deficient 25-OHD levels &lt;20 ng/ml (p&lt;0.0001). Additionally, 25-OHD levels were reduced by 25% in homozygous carriers of the rs7041 at-risk T allele (p&lt;0.0001). This correlation was found to be independent of COPD severity, smoking history, age, gender, body mass index, corticosteroid intake, seasonal variation and rs4588 (p&lt;0.0001). Notably, 76% and 100% of patients with GOLD stage 3 and 4 homozygous for the rs7041 T allele exhibited 25-OHD levels &lt;20 ng/ml. Logistic regression corrected for age, gender and smoking history further revealed that homozygous carriers of the rs7041 T allele exhibited an increased risk for COPD (OR 2.11; 95% CI 1.20 to 3.71; p=0.009). <h3>Conclusion</h3> Vitamin D deficiency occurs frequently in COPD and correlates with severity of COPD. The data warrant vitamin D supplementation in patients with severe COPD, especially in those carrying at-risk rs7041 variants.
Sexuality and obesity, a gender perspective: results from French national random probability survey of sexual behaviours
Authors: N. Bajos, K. Wellings, C. Laborde, C. Moreau
Journal: BMJ (2010)

<b>Objectives</b> To analyse the association between body mass index (BMI) and sexual activity, sexual satisfaction, unintended pregnancies, and abortions in obese people and to discuss the implications for public health practices, taking into account the respondents’ and their partners’ BMI. <b>Design</b> Random probability survey of sexual behaviours. <b>Setting</b> National population based survey of 12 364 men and women aged 18-69 living in France in 2006. <b>Participants</b> Random selection of 5535 women and 4635 men, of whom 3651 women and 2725 men were normal weight (BMI 18.5-&lt;25), 1010 women and 1488 men were overweight (BMI 25-&lt;30), and 411 women and 350 men were obese (BMI &gt;30). <b>Results</b> Obese women were less likely than normal weight women to report having a sexual partner in the past 12 months (odds ratio 0.71, 95% confidence interval 0.51 to 0.97). Obese men were less likely than normal weight men to report more than one sexual partner in the same period (0.31, 0.17 to 0.57, P&lt;0.001) and more likely to report erectile dysfunction (2.58, 1.09 to 6.11, P&lt;0.05). Sexual dysfunction was not associated with BMI among women. Obese women aged under 30 were less likely to seek healthcare services for contraception (0.37, 0.18 to 0.76) or to use oral contraceptives (0.34, 0.15 to 0.78). They were also more likely to report an unintended pregnancy (4.26, 2.21 to 8.23). <b>Conclusion</b> There is a link between BMI and sexual behaviour and adverse sexual health outcomes, with obese women less likely to access contraceptive healthcare services and having more unplanned pregnancies. Prevention of unintended pregnancies among these women is a major reproductive health challenge. Healthcare professionals need to be aware of sensitivities related to weight and gender in the provision of sexual health services.
Melanoma incidence has risen in Europe
Authors: Esther de Vries, Jan-Willem W Coebergh
Journal: BMJ (2005)

EDITOR—Welch et al say that the increased incidence of cutaneous melanoma is a result of overdiagnosis because of increased diagnostic scrutiny, rather than an increase in the true occurrence.1 They observed that incidence rates of melanoma among American citizens aged 65 and older were strongly correlated with biopsy rates and that mortality from melanoma remained stable.

We wish to comment on this from …
A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon antibody, in patients with moderate to severe Crohn's disease
Authors: W Reinisch
Journal: Gut (2005)

<b>Introduction:</b> This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon γ antibody, in patients with moderate to severe Crohn's disease (CD). <b>Patients and methods:</b> Forty five patients with a CD activity index (CDAI) of 250–450 were randomised in a double blind, placebo controlled, dose escalating fashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo. By day 29, patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals. Primary objectives were safety and tolerability. Secondary outcomes included assessments of immunogenicity, clinical activity, and potential pharmacodynamic surrogates. <b>Results:</b> Treatment was generally well tolerated. There were slightly more reports of chills, flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab cohorts. Two serious adverse events rated as worsening of CD occurred under fontolizumab. Antibodies to fontolizumab were confirmed in one patient. No differences in clinical activity parameters were noted between any of the active treatment groups and placebo, with the placebo group having a particularly favourable outcome (60% response and 40% remission). By day 29, a more enhanced decrease in median Crohn's disease endoscopic index of severity (p = 0.02) and serum C reactive protein (p&lt;0.001) was observed in the 4.0 mg/kg (n = 14) fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effects were observed by immunohistochemistry. <b>Conclusions:</b> Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD. A biological activity of fontolizumab is suggested.
The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region
Authors: M Rinaudo-Gaujous, X Roblin, H Marotte, S Paul
Journal: Annals of the Rheumatic Diseases (2015)

We read with a great interest the report by Van Schie et al 1 which highlighted that the antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region. The results described in this report confirm very clearly the results that we obtained recently.

This study adds to the one we performed, which shows the neutralising capacity of antidrug antibodies (ADAs) against infliximab (IFX) in patients with inflammatory bowel disease (IBD) treated by IFX. We assessed ADAs’ biological activity by a functional assay using a reporter HEK-Dual TNF cell line developed for TNF detection (InvivoGen). Briefly, sera of patients with IBD were first incubated …
The impact of patients' preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis Commentary: patients, preferences, and evidence
Authors: J. Protheroe
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To investigate the impact of patients9 preferences for the treatment of atrial fibrillation, by using individualised decision analysis combining probability and utility assessments into a decision tree. <b>Design:</b> Observational study based on interviews with patients. <b>Setting:</b> Eight general practices in Avon. <b>Participants:</b> 260 randomly selected patients aged 70–85 years with atrial fibrillation. <b>Main outcome measures:</b> Patients9 treatment preferences regarding anticoagulation treatment (warfarin) after individualised decision analysis; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription. <b>Results:</b> Of 195 eligible patients, 97 participated in decision making using decision analysis. Among these 97, the decision analysis indicated that 59 (61%; 95% confidence interval 50% to 71%) would prefer anticoagulation treatment—considerably fewer than those who would be recommended treatment according to guidelines. There was marked disagreement between the decision analysis and guideline recommendations (kappa =0.25 or less). Of 38 patients whose decision analysis indicated a preference for anticoagulation, 17 (45%) were being prescribed warfarin; on the other hand, 28 (47%) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be. <b>Conclusions:</b> In the context of shared decision making, individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation. Taking account of patients9 preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations. Decision analysis as a shared decision making tool should be evaluated in a randomised controlled trial.
Predictive Role of the <i>UGT1A1</i>, <i>UGT1A7</i>, and <i>UGT1A9</i> Genetic Variants and Their Haplotypes on the Outcome of Metastatic Colorectal Cancer Patients Treated With Fluorouracil, Leucovorin, and Irinotecan
Authors: Erika Cecchin, Federico Innocenti, Mario D'Andrea, Giuseppe Corona, Elena De Mattia, Paola Biason, Angela Buonadonna, Giuseppe Toffoli
Journal: Journal of Clinical Oncology (2009)

Purpose UGT1A1 ★ 28 is considered the main pharmacogenetic predictor of the toxicity outcome of irinotecan-treated patients. We evaluated the effect of other UGT1A variants and haplotypes involved in 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation on severe toxicity and efficacy of fluorouracil, leucovorin, and irinotecan (FOLFIRI). Patients and Methods In addition to UGT1A1 ★ 28, UGT1A1 ★ 60, UGT1A1 ★ 93, UGT1A7 ★ 3, and UGT1A9 ★ 22 were genotyped in 250 metastatic colorectal cancer patients, and associations with severe hematologic and nonhematologic toxicity, objective response, time to progression (TTP), and overall survival were evaluated. In a subset of 71 patients, pharmacokinetic data were also available. Results UGT1A7 ★ 3 was the only marker of severe hematologic toxicity after the first cycle (odds ratio [OR], 3.94; 95% CI, 1.05 to 14.82; P = .04) in a multivariate analysis. It was also associated with glucuronidation ratio (SN-38G area under the curve [AUC]/SN-38 AUC) and biliary index (irinotecan AUC) × (SN-38 AUC/SN-38G AUC). Haplotype I (all the reference sequence alleles but UGT1A9 ★ 22) was a predictor of severe hematologic toxicity during the entire course of therapy (OR, 0.39; 95% CI, 0.19 to 0.82; P = .01), together with sex (OR, 2.08; 95% CI, 1.01 to 4.28; P = .05). In addition to UGT1A1 ★ 28, haplotype II (all the variant alleles but UGT1A9 ★ 22) was associated with a response rate (OR, 8.61; 95% CI, 1.75 to 42.38; P = .01). UGT1A1 ★ 28 was the only marker associated with TTP. Conclusion We propose that UGT1A variants additional to UGT1A1 ★ 28 might improve the prediction of the outcome of colorectal cancer patients treated with FOLFIRI. A UGT1A haplotype-based approach might be an efficacious strategy to achieve treatment individualization of FOLFIRI.
Mixed gonadal dysgenesis. Association with unilateral testis and XY chromosome complement
Authors: L. Yoon
Journal: JAMA (1976)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
DTS-108, A Novel Peptidic Prodrug of SN38: <i>In vivo</i> Efficacy and Toxicokinetic Studies
Authors: Florence Meyer-Losic, Céline Nicolazzi, Jérôme Quinonero, Fabien Ribes, Matthieu Michel, Vincent Dubois, Catherine de Coupade, Matthieu Boukaissi, Anne-Sophie Chéné, Isabelle Tranchant, Valérie Arranz, Imane Zoubaa, Jean-Sébastien Fruchart, Denis Ravel, Jonathan Kearsey
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Irinotecan is a prodrug converted to the active cytotoxic molecule SN38 predominantly by the action of liver carboxylesterases. The efficacy of irinotecan is limited by this hepatic activation that results in a low conversion rate, high interpatient variability, and dose-limiting gastrointestinal toxicity. The purpose of this study was to evaluate a novel peptidic prodrug of SN38 (DTS-108) developed to bypass this hepatic activation and thus reduce the gastrointestinal toxicity and interpatient variability compared with irinotecan. Experimental Design: SN38 was conjugated to a cationic peptide (Vectocell) via an esterase cleavable linker. The preclinical development plan consisted of toxicity and efficacy evaluation in a number of different models and species. Results: The conjugate (DTS-108) is highly soluble, with a human plasma half-life of 400 minutes in vitro. Studies in the dog showed that DTS-108 liberates significantly higher levels of free SN38 than irinotecan without causing gastrointestinal toxicity. In addition, the ratio of the inactive SN38-glucuronide metabolite compared with the active SN38 metabolite is significantly lower following DTS-108 administration, compared with irinotecan, which is consistent with reduced hepatic metabolism. In vivo efficacy studies showed that DTS-108 has improved activity compared with irinotecan. A significant dose-dependent antitumoral efficacy was observed in all models tested and DTS-108 showed synergistic effects in combination with other clinically relevant therapeutic agents. Conclusions: DTS-108 is able to deliver significantly higher levels of SN38 than irinotecan, without the associated toxicity of irinotecan, resulting in an increased therapeutic window for DTS-108 in preclinical models. These encouraging data merit further preclinical and clinical investigation.
Influence of inflammatory phenotype in severe refractory asthma on metabolomic profile of oxidative stress in exhaled breath condensate (EBC)
Authors: Vratislav Sedlák, Petr Cáp, Petr Kacer, Marek Kuzma, Daniela Pelclova
Journal: European Respiratory Journal (2013)

Severe refractory asthma (SRA) is still a disputable medical condition. It is supposed that intensity of inflammation and oxidative stress (ROS) exceeds the level in controlled asthma. Aims:  Our hypothesis was that oxidative stress metabolomics in exhaled breath condensate (EBC) differs in SRA in distinct phenotypes. We harvested EBC of 40 SRA patients from center for SRA and markers of ROS were compared between subgroups of eosinophilic (EA, n=13) and non-eosinophilic (NEA, n=26) phenotype defined by peripheral blood eosinophilia (PBE) >4%, results were compared to 21 healthy controls.  Methods:  Metabolomic analysis of EBC using liquid chromatography and mass spectrometry was used to detect concentrations of 22 markers of ROS (malondialdehyde, leukotriens, 4-hydroxy-2-noneal (4-HNE). EBC was collected by standardized protocol (EcoScreen). Measured results were analyzed together with FEV1, FeNO50, PBE and subgroups statistically evaluated.  Results:  EA and NEA did not differ in gender, age (48.2 vs 51.2), presence of atopy, asthma control test score (13.0 vs 14.5), FEV1 (1.5 vs 1.6 L/s) (all p>0.05). In EA were higher FeNO levels (18 vs 46 ppb, p=0.01), hyperinflation (RV 3.84 vs 3.02 l, p=0.049), asthma exacerbations (6.3 vs 2.9 per year, p Conclusion:  Our data shows increased lipoperoxidation of ω-3 and 6 fatty acids by ROS only in NEA. We conclude that NEA phenotype of SRA would benefit from antioxidative therapy.
Autoamplification of NFATc1 expression determines its essential role in bone homeostasis
Authors: Masataka Asagiri, Kojiro Sato, Takako Usami, Sae Ochi, Hiroshi Nishina, Hiroki Yoshida, Ikuo Morita, Erwin F. Wagner, Tak W. Mak, Edgar Serfling, Hiroshi Takayanagi
Journal: The Journal of Experimental Medicine (2005)

NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1(-/-) hematopoietic stem cells to osteoclast-deficient Fos(-/-) mice, and by Fos(-/-) blastocyst complementation, thus avoiding the embryonic lethality of NFATc1(-/-) mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis.
RASSF1A and the BH3-only mimetic ABT-737 promote apoptosis in pediatric medulloblastoma cell lines
Authors: Jane Levesley, Meryl E. Lusher, Janet C. Lindsey, Steven C. Clifford, Richard Grundy, Beth Coyle
Journal: Neuro-Oncology (2011)

The RASSF1A tumor suppressor is potentially the most important candidate gene identified in medulloblastoma to date, being epigenetically silenced in >79% of primary tumors. However, its functional role has not been previously addressed in this tumor type. Here, we demonstrate that expression of RASSF1A promotes the induction of cell death after activation of both the extrinsic and intrinsic apoptotic pathways in medulloblastoma cells. Treatment of UW228-3 cells stably expressing RASSF1A with an anti-CD95 antibody to induce extrinsic apoptosis and etoposide or cisplatin to activate intrinsic apoptosis augmented tumor cell killing in a caspase-dependent manner. This led to increased activation of the pro-apoptotic BCL-2 family member BAX. On the basis of this knowledge, we demonstrate how the loss of RASSF1A function in medulloblastoma cells might be overcome using the novel BH3-only mimetic ABT-737 in combination with chemotherapeutic agents to target the BCL-2 anti-apoptotic members. We show that ABT-737 increased susceptibility to apoptosis induced by DNA damage regardless of RASSF1A expression status through increased activation of BAX. Our findings identify the RASSF1A tumor suppressor as a promoter of apoptotic signaling pathways. Investigation of its mechanism of action has revealed that these pathways can still be promoted in its absence and how these potentially represent novel therapeutic targets for medulloblastoma.
Blood Pressure Control and Cognitive Impairment—Why Low Is Not Always Better
Authors: Behnam Sabayan, Rudi G. J. Westendorp
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal