tbuckley/cabot-search huggingface dataset:
Mouse bone marrow-derived mast cells (mBMMC) obtained in vitro from mice that are mast cell-deficient in vivo express the same panel of granule proteases as mBMMC and serosal mast cells from their normal littermates.
Authors: K K Eklund, N Ghildyal, K F Austen, D S Friend, V Schiller, R L Stevens
Journal: The Journal of Experimental Medicine (1994)

The ear, skin, and purified serosal mast cells of WBB6F1/J-(+/+) (WB-(+/+)) and WCB6F1/J-(+/+) (WC-(+/+)) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA). In contrast, no mast cell protease transcripts are present in abundance in the ear and skin of WBB6F1/J-W/Wv (W/Wv) and WCB6F1/J-Sl/Sld (Sl/Sld) mice which are mast cell-deficient in vivo due to defects in their c-kit and c-kit ligand genes, respectively. We now report that the immature bone marrow-derived mast cells (mBMMC) obtained in vitro with recombinant interleukin 3 (rIL-3) or WEHI-3 cell conditioned medium from WB-(+/+), WC-(+/+), W/Wv, and Sl/Sld mice all contain high steady-state levels of the mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMC-CPA transcripts. As assessed immunohistochemically, mMCP-2 protein and mMCP-5 protein are also present in the granules of mBMMC from WB-(+/+), WC-(+/+), and W/Wv mice. That Sl/Sld and W/Wv mBMMC contain high steady-state levels of five granule protease transcripts expressed by the mature serosal, ear, and skin mast cells of their normal +/+ littermates suggests that c-kit-mediated signal transduction is not essential for inducing transcription of these protease genes. Because rIL-4 inhibits the rIL-10-induced expression of mMCP-1 and mMCP-2 in BALB/cJ mBMMC, the ability of rIL-4 to influence protease mRNA levels in WC-(+/+) mBMMC and W/Wv mBMMC was investigated. Although rIL-10 induced expression of the mMCP-1 transcript in WC-(+/+) and W/Wv mBMMC, rIL-4 was not able to suppress the steady-state levels of the mMCP-1 transcript or any other protease transcript in these cultured mast cells. Thus, not only do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mast cell-deficient strains and their normal littermates but the subsequent induction of late-expressed proteases in BALB/cJ mBMMC is more tightly regulated by IL-3 and IL-4.
G protein–coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth
Authors: Sandra M Pasternack, Ivar von Kügelgen, Khalid Al Aboud, Young-Ae Lee, Franz Rüschendorf, Katrin Voss, Axel M Hillmer, Gerhard J Molderings, Thomas Franz, Alfredo Ramirez, Peter Nürnberg, Markus M Nöthen, Regina C Betz
Journal: Nature Genetics (2008)
Day Napping and Short Night Sleeping Are Associated With Higher Risk of Diabetes in Older Adults
Authors: Qun Xu, Yiqing Song, Albert Hollenbeck, Aaron Blair, Arthur Schatzkin, Honglei Chen
Journal: Diabetes Care (2009)

OBJECTIVE To examine whether day napping or short night sleeping is associated with higher risk of diabetes. RESEARCH DESIGN AND METHODS This was a prospective study of hours of day napping and night sleeping assessed in 1996–1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants in the National Institutes of Health (NIH)-AARP Diet and Health Study. Odds ratios (ORs) and 95% CI were derived from multivariate logistic regression models. RESULTS Longer day napping was associated with a higher risk of diabetes. After adjustment for potential confounders, ORs were 1.23 (95% CI 1.18–1.29) for those reporting &amp;lt;1 h and 1.55 (95% CI 1.45–1.66) for those reporting ≥1 h of napping compared with individuals who did not nap (Ptrend &amp;lt; 0.0001). For night sleeping, with 7–8 h as the referent, the OR was 1.46 (95% CI 1.31–1.63) for &amp;lt;5 h, 1.11 (1.06–1.16) for 5–6 h, and 1.11 (0.99–1.24) for ≥9 h. In both analyses, additional adjustment for BMI only modestly attenuated the associations. Further analysis showed a statistically significant interaction between hours of napping and sleeping on diabetes (Pinteraction &amp;lt; 0.0001). Among participants with no napping, only short night sleeping was associated with higher occurrence of diabetes, whereas among those with ≥1 h of napping, both long and short sleeping was associated with higher risk. CONCLUSIONS Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit.
Bleeding from oesophageal ulceration induced by endoscopic variceal ligation for primary prophylaxis
Authors: R. S. Kumarasena, M. A. Niriella, U. Kalubowila, A. P. de Silva, A. S. Dassanayake, H. J. de Silva
Journal: Gut (2010)

<i>185/333</i> genes and transcripts from the purple sea urchin, <i>Strongylocentrotus purpuratus</i>, predict high levels of amino acid diversity within the encoded proteins. Based on their expression patterns, 185/333 proteins appear to be involved in immune responses. In the present study, one- and two-dimensional Western blots show that 185/333 proteins exhibit high levels of molecular diversity within and between individual sea urchins. The molecular masses of 185/333-positive bands or spots range from 30 to 250 kDa with a broad array of isoelectric points. The observed molecular masses are higher than those predicted from mRNAs, suggesting that 185/333 proteins form strong associations with other molecules or with each other. Some sea urchins expressed &gt;200 distinct 185/333 proteins, and each animal had a unique suite of the proteins that differed from all other individuals. When sea urchins were challenged in vivo with pathogen-associated molecular patterns (PAMPs; bacterial LPS and peptidoglycan), the expression of 185/333 proteins increased. More importantly, different suites of 185/333 proteins were expressed in response to different PAMPs. This suggests that the expression of 185/333 proteins can be tailored toward different PAMPs in a form of pathogen-specific immune response.
STUDIES ON ORGAN TRANSPLANTATION
Authors: K. Kawamura
Journal: The Journal of Experimental Medicine (1919)

Our experiments on dogs showed that the thyroid gland which was autoplastically transplanted, by means of various methods of blood vessel anastomosis, could live in good condition and functionate favorably several months after the operation, even after the interruption of the circulation for 1(1/2) hours. They further showed that the circulation through the transplanted blood vessels as well as glands was as good as normal, and that permanent successful results of the homoplastic transplantation of the gland are as yet not possible.
Prognostic Utility of Novel Biomarkers of Cardiovascular Stress
Authors: Thomas J. Wang, Kai C. Wollert, Martin G. Larson, Erin Coglianese, Elizabeth L. McCabe, Susan Cheng, Jennifer E. Ho, Michael G. Fradley, Anahita Ghorbani, Vanessa Xanthakis, Tibor Kempf, Emelia J. Benjamin, Daniel Levy, Ramachandran S. Vasan, James L. Januzzi
Journal: Circulation (2012)

Background— Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. Methods and Results— To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a “multimarker” score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point ( P &lt;0.001) except coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2; 95% confidence interval, 2.2–4.7; P &lt;0.001), 6-fold risk of heart failure (6.2; 95% confidence interval, 2.6–14.8; P &lt;0.001), and 2-fold risk of cardiovascular events (1.9; 95% confidence interval, 1.3–2.7; P =0.001). Addition of the multimarker score to clinical variables led to significant increases in the c statistic ( P =0.005 or lower) and net reclassification improvement ( P =0.001 or lower). Conclusion— Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.
Creating the American Junkie--Addiction Research in the Classic Era of Narcotic Control
Authors: R. L. DuPont
Journal: JAMA (2003)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Magnetic resonance evidence of hypoxia in a homozygous alpha-knockout of a transgenic mouse model for sickle cell disease.
Authors: M E Fabry, R P Kennan, C Paszty, F Costantini, E M Rubin, J C Gore, R L Nagel
Journal: Journal of Clinical Investigation (1996)

All transgenic mouse models for sickle cell disease express residual levels of mouse globins which complicate the interpretation of experimental results. We now report on a mouse expressing high levels of human betaS and 100% human alpha-globin. These mice were created by breeding the alpha-knockout and the mouse beta(major)-deletion to homozygosity in mice expressing human alpha- and betaS-transgenes. These betaS-alpha-knockout mice have accelerated red cell destruction, altered hematological indices, ongoing organ damage, and pathology under ambient conditions which are comparable with those found in alphaH betaS-Ant[betaMDD] mice without introduction of additional mutations which convert betaS into a "super-betaS" such as the doubly mutated betaS-Antilles. This is of particular importance for testing strategies for gene therapy of sickle cell disease. Spin echo magnetic resonance imaging at room air and 100% oxygen demonstrated the presence of blood hypoxia (high levels of deoxygenated hemoglobin) in the liver and kidneys that was absent in control mice. We demonstrate here that transgenic mice can be useful to test new noninvasive diagnostic procedures, since the magnetic resonance imaging technique described here potentially can be applied to patients with sickle cell disease.
Phase II Study of Sunitinib in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: GORTEC 2006-01
Authors: Jean-Pascal H. Machiels, Stéphanie Henry, Sylvie Zanetta, Marie-Christine Kaminsky, Nicolas Michoux, Denis Rommel, Sandra Schmitz, Emmanuelle Bompas, Anne-Françoise Dillies, Sandrine Faivre, Anne Moxhon, Thierry Duprez, Joel Guigay
Journal: Journal of Clinical Oncology (2009)

PURPOSE To assess the efficacy and toxicity of sunitinib monotherapy in palliative squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Thirty-eight patients with SCCHN having evidence of progressive disease (PD) were treated with sunitinib 37.5 mg/d given continuously until PD or unacceptable toxicity. The primary end point was the rate of disease control, defined as stable disease (SD) or partial response (PR) at 6 to 8 weeks after treatment initiation (two-stage design, Simon). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed in a subset of patients before and 6 to 8 weeks after treatment. The volume transfer constant of the contrast agent (K(trans)) was used to measure changes in the microcirculation blood flow and endothelial permeability of the tumor. Results A PR was observed in one patient, SD in 18, and PD in 19 (Response Evaluation Criteria in Solid Tumors [RECIST]), resulting in a disease control rate of 50%. Among the 18 patients with SD, there were five unconfirmed PRs and six additional minor responses. A significant decrease in K(trans) was seen in three of the four patients who received DCE-MRI monitoring. Grade 5 head and neck bleeds occurred in four patients. Local complications, including the appearance or worsening of tumor skin ulceration or tumor fistula, were recorded in 15 patients. CONCLUSION Sunitinib demonstrated modest activity in palliative SSCHN. The severity of some of the complications highlights the importance of improved patient selection for future studies with sunitinib in head and neck cancer. Sunitinib should not be used outside clinical trials in SSCHN.
Relationship of body mass index and current asthma status among adult asthmatics presenting in the outpatient department
Authors: Shane Boiser, Joel Santiaguel, Adele Espaldon
Journal: European Respiratory Journal (2012)

PURPOSE: To determine whether a relationship between body mass index (BMI) and current asthma status among adult asthmatics seen in the outpatient department exists and the impact of asthma control upon enrollment to the asthma comprehensive care unit for proper education.

METHODS: All adult patients who fulfilled the inclusion criteria seen in the outpatient department (OPD) of the Philippine General Hospital from November 2010 to December 2011 referred by consultants, fellows in training and residents will be gathered and ask to complete a questionnaire after informed consent was obtained. If subject has no pulmonary function test, a free pulmonary function test will be done. Levels of control will be determined as well as medications and computation of BMI.

RESULTS: BMI status was significantly associated with outcome measures. Majority of the obese patients have uncontrolled asthma. Results showed that patients, regardless of their body mass index, who were enrolled at the Philippine General Hospital Asthma Comprehensive Care Unit, have better asthma control, decrease asthma severity, higher FEV1, and good response to bronchodilator.

CONCLUSIONS: Obese asthmatic patients have more severe asthma, poorer asthma control, with more recent asthma attacks, more frequent usage of relievers, and less responsive to bronchodilators. Those asthmatics with proper education of their disease have better levels of control.

CLINICAL IMPLICATIONS: Proper weight management improves asthma control; prevent asthma attacks and better response to bronchodilators. Thus prevent hospitalization. Enrollment to asthma education program enhanced asthma management.
Short term variability in FEV1: relation to pretest activity, level of FEV1, and smoking habits.
Authors: P M Tweeddale, S Merchant, M Leslie, F Alexander, G J McHardy
Journal: Thorax (1984)

The natural variability in forced expiratory volume in one second (FEV1) over 20 minutes was determined in 54 fit hospital employees and 13 patients with restrictive lung disorders. Initial FEV1 ranged from 1.1 to 6.3 1 BTPS. Variability when expressed as absolute change was similar at all levels of FEV1, so that, when expressed as percentage change, variability decreased with increasing FEV1. Smoking habits did not appear to affect variability but activity before the test did. On the basis of these results an absolute change in FEV1 of 190 ml would be necessary for 95% confidence that the change in FEV1 occurred other than by chance in any one individual. This suggests that the absolute change in FEV1 might be a more reliable criterion than percentage change when distinguishing between natural variability and a response to inhalation of bronchodilators.
Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure
Authors: Hans Bisgaard, Angela Simpson, Colin N.A Palmer, Klaus Bønnelykke, Irwin Mclean, Somnath Mukhopadhyay, Christian B Pipper, Liselotte B Halkjaer, Brian Lipworth, Jenny Hankinson, Ashley Woodcock, Adnan Custovic
Journal: PLoS Medicine (2008)

Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
Apolipoprotein E in Creutzfeldt-Jakob disease
Authors: Yasushi Nakagawa, Tetsuyuki Kitamoto, Hisako Furukawa, Koji Ogomori, Jun Tateishi, Inga Zerr, Marion Helmhold, Thomas Weber, AllenD. Roses, AnnMarie Saunders, WarrenJ. Strittmatter, DonaldE. Schmechel, MargaretA. Pericak-Vance, Bradley Hyman
Journal: The Lancet (1995)
Mutational Status of the <i>TP53</i> Gene As a Predictor of Response and Survival in Patients With Chronic Lymphocytic Leukemia: Results From the LRF CLL4 Trial
Authors: David Gonzalez, Pilar Martinez, Rachel Wade, Sarah Hockley, David Oscier, Estella Matutes, Claire E. Dearden, Sue M. Richards, Daniel Catovsky, Gareth J. Morgan
Journal: Journal of Clinical Oncology (2011)

TP53 mutations have been described in chronic lymphocytic leukemia (CLL) and have been associated with poor prognosis in retrospective studies. We aimed to address the frequency and prognostic value of TP53 abnormalities in patients with CLL in the context of a prospective randomized trial.We analyzed 529 CLL samples from the LRF CLL4 (Leukaemia Research Foundation Chronic Lymphocytic Leukemia 4) trial (chlorambucil v fludarabine with or without cyclophosphamide) at the time of random assignment for mutations in the TP53 gene. TP53 mutation status was correlated with response and survival data.Mutations of TP53 were found in 40 patients (7.6%), including 25 (76%) of 33 with 17p deletion and 13 (3%) of 487 without that deletion. There was no significant correlation between TP53 mutations and age, stage, IGHV gene mutations, CD38 and ZAP-70 expression, or any other chromosomal abnormality other than 17p deletion, in which concordance was high (96%). TP53 mutations were significantly associated with poorer overall response rates (27% v 83%; P < .001) and shorter progression-free survival (PFS) and overall survival (OS; 5-year PFS: 5% v 17%; 5-year OS: 20% v 59%; P < .001 for both). Multivariate analysis that included baseline clinical variables, treatment, and known adverse genetic factors confirmed that TP53 mutations have added prognostic value.TP53 mutations are associated with impaired response and shorter survival in patients with CLL. Analysis of TP53 mutations should be performed in patients with CLL who have progressive disease before starting first-line treatment, and those with mutations should be selected for novel experimental therapies.
Aspirin and Breast Cancer: No Surprises Yet
Authors: L. Rosenberg
Journal: JNCI Journal of the National Cancer Institute (1996)

In this issue of the Journal, a report by Egan et al. (/) from the Nurses' Health Study suggests that the use of aspirin does not reduce the incidence of breast cancer. Was there any reason to think that it would? In 1991, my colleagues and I reported in this Journal on the relation of nonsteroidal anti-inflammatory drug (NSAID) use to the risk of large-bowel cancer (2). Our analysis was stimulated by the results of experiments in rodents, in which a variety of NSAIDs reduced the incidence of chemically induced colon cancer, possibly through reducing prostaglandin synthesis (5-9). It had also been reported that sulindac, a nonaspirin NSAID, caused regression of adenomatous colon polyps in humans (10). Our hospital-based, case-control study of large-bowel cancer yielded a statistically significant relative risk estimate of 0.5 for continuing regular NSAID use, mostly aspirin, and we proposed that NSAID use might reduce colon cancer incidence in humans. Subsequent results from case-control and follow-up studies and from a randomized trial of aspirin as a prophylaxis against myocardial infarction have, for the most part, supported a reduction in the incidence of large-bowel cancer in NSAID users, with most of the information referring to aspirin (11-18). The