tbuckley/cabot-search huggingface dataset:
Expression of the neutrophil elastase gene during human bone marrow cell differentiation.
Authors: P Fouret, R M du Bois, J F Bernaudin, H Takahashi, V J Ferrans, R G Crystal
Journal: The Journal of Experimental Medicine (1989)

Neutrophil elastase, a potent serine protease carried and released by activated neutrophils, is not synthesized by neutrophils, but by their bone marrow precursor cells. Using in situ hybridization with 35S-labeled antisense and sense neutrophil elastase cRNA probes, the present study demonstrates that expression of the neutrophil elastase gene is tightly controlled in bone marrow precursors and occurs during a very limited stage of differentiation of the neutrophil myeloid series, almost entirely at the promyelocyte stage. Neutrophil elastase mRNA transcript levels are detectable to a limited extent in blasts, increase markedly in the promyelocyte stage, and then disappear as promyelocytes further differentiate. Control probes specific for myeloperoxidase, lactoferrin, and beta-globin mRNA transcripts, respectively, demonstrated contrasting gene expression. Myeloperoxidase mRNA transcripts were also found almost exclusively at the promyelocyte stage, but myeloperoxidase mRNA levels disappeared earlier than do neutrophil elastase mRNA levels, suggesting that expression of these genes may be differently controlled. In comparison, lactoferrin mRNA transcripts were detected late in the neutrophil lineage, while beta-globin mRNA was detected only in cells of the erythroid lineage. Together these observations suggest that the expression of the neutrophil elastase gene is likely under very tight control, and is likely different than that for other constituents of the neutrophil granules.
Cutaneous Changes Associated With Marek's Disease of Chickens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lapen, R. F., Piper, R. C., Kenzy, S. G.
Journal: JNCI Journal of the National Cancer Institute (1970)

Intranuclear inclusion bodies were observed in the leather follicle epithelium of chickens with Marek's disease (MD). These inclusions and associated cellular degenerations were shown to be part of the MD process by correlation of their occurrence with that of MD and by determination of their distributional dependence on the presence of the immunofluorescent (IF) antigen of MD. Inclusions and IF antigen appeared in the epithelial layers of the feather follicle, superficial to, but never in, the basal layer. The distributional relationship between cutaneous IF antigen and lymphoid aggregates, typical of MD, was studied; there was an apparent interaction between the aggregates and IF antigen.
Dietary and Nutritional Factors and Pancreatic Cancer: a Case-Control Study Based on Direct Interviews
Authors: D. T. Silverman, C. A. Swanson, G. Gridley, S. Wacholder, L. M. Brown, R. B. Hayes, J. F. Fraumeni, R. N. Hoover, L. M. Pottern, R. S. Greenberg, G. M. Swanson, J. B. Schoenberg, A. G. Schwartz
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The relationship between diet and pancreatic cancer remains unclear. In this study, we assessed the role of diet and nutrition as risk factors for pancreatic cancer, using data obtained from direct interviews only, rather than data from less reliable interviews with next of kin. We evaluated whether dietary factors could explain the higher incidence of pancreatic cancer experienced by black Americans compared with white Americans. Methods: We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. Reliable dietary histories were obtained for 436 patients and 2003 general- population control subjects aged 30-79 years. Results: Obesity was associated with a statistically significant 50%- 60% increased risk of pancreatic cancer that was consistent by sex and race. Although the magnitude of risk associated with obesity was identical in blacks and whites, a higher percentage of blacks were obese than were whites (women: 38% versus 16%; men: 27% versus 22%). A statistically significant positive trend in risk was observed with increasing caloric intake, with subjects in the highest quartile of caloric intake experiencing a 70% higher risk than those in the lowest quartile. A statistically significant interaction between body mass index (weight in kg/height in m2 for men and weight in kg/height in m1.5 for women) and total caloric intake was observed that was consistent by sex and race. Subjects in the highest quartile of both body mass index and caloric intake had a statistically significant 180% higher risk than those in the lowest quartile. Conclusions: Obesity is a risk factor for pancreatic cancer and appears to contribute to the higher risk of this disease among blacks than among whites in the United States, particularly among women. Furthermore, the interaction between body mass index and caloric intake suggests the importance of energy balance in pancreatic carcinogenesis.
Relationship Styles and Mortality in Patients With Diabetes
Authors: Paul Ciechanowski, Joan Russo, Wayne J. Katon, Elizabeth H.B. Lin, Evette Ludman, Susan Heckbert, Michael Von Korff, Lisa H. Williams, Bessie A. Young
Journal: Diabetes Care (2009)

OBJECTIVE Prior research has shown that less social support is associated with increased mortality in individuals with chronic illnesses. We set out to determine whether lower propensity to seek support as indicated by relationship style, based on attachment theory, is associated with mortality in patients with diabetes. RESEARCH DESIGN AND METHODS A total of 3,535 nondepressed adult patients with type 1 and type 2 diabetes enrolled in a health maintenance organization in Washington State were surveyed at baseline and followed for 5 years. Relationship style was assessed at baseline. Patients with a greater propensity to seek support were classified as having an interactive relationship style and those less inclined to seek support as having an independent relationship style. We collected Washington State mortality data and used Cox proportional hazards models to estimate relative risk (RR) of death for relationship style groups. RESULTS The rate of death in the independent and interactive relationship style groups was 39 and 29 per 1,000 individuals, respectively. Unadjusted RR of death was 1.33 (95% CI 1.12–1.58), indicating an increased risk of death among individuals with an independent relationship style. After adjustment for demographic and clinical covariates, those with an independent relationship style still had a greater risk of death compared with those with an interactive relationship style (hazard ratio 1.20 [95% CI 1.01–1.43]). CONCLUSIONS In a large sample of adult patients with diabetes, a lower propensity to reach out to others is associated with higher mortality over 5 years. Further research is needed to examine possible mechanisms for this relationship and to develop appropriate interventions.
Mast cell IL-4 expression is regulated by Ikaros and influences encephalitogenic Th1 responses in EAE
Authors: G. D. Gregory
Journal: Journal of Clinical Investigation (2006)

When exposed to a pathogen, a naive CD4+ T cell is forced to make a cell fate decision that leads to a polarized population of Th1 IFN-γ– or Th2 IL-4– producing cells. Although IL-4 has traditionally been considered a factor that promotes Th2 cell differentiation, recent evidence has demonstrated that the site and timing of IL-4 expression in an immune response determines its ultimate effects on CD4+ T cell fate. Using a mast cell (MC) reconstitution model, we demonstrate that MC-derived IL-4 promoted Th1 responses in vivo. Furthermore, MCs from genetically disparate mouse strains varied in their potential for IL-4 expression. Independent of the activation mode, MCs from Th1-prone C57BL/6 mice exhibited a more robust Il4 response than did the Th2-prone strain Balb/c. The hierarchy of IL-4 expression potential was directly associated with the degree of basal chromatin accessibility at cis-regulatory elements conserved noncoding sequence–1 and VA enhancer within the Th2 locus. GATA1/2 and Ikaros, factors with opposing roles in chromatin remodeling, acted at these sites. We propose that GATA and Ikaros proteins coordinately fine-tune accessibility at the Il4 locus during development to variably regulate IL-4 expression. These events likely contribute to the genetically determined heterogeneity in Th1 responses that underlie susceptibility to many diseases.
<i>Ex vivo</i>Nicotine Stimulation Augments the Efficacy of Therapeutic Bone Marrow–Derived Dendritic Cell Vaccination
Authors: Feng Guang Gao, Da Fang Wan, Jian Ren Gu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To explore the preventive and therapeutic antitumor effects of nicotine-treated immature dendritic cells (imDC). Experimental Design: First, bone marrow–derived imDCs were stimulated with nicotine in vitro, and nicotinic acetylcholine receptor, costimulator molecules, chemokine receptor, and endocytosis ability of imDCs were detected by flow cytometry. Second, the DC-dependent antigen-specific T-cell proliferation, CTL priming, and interleukin-12 secretion were determined by flow cytometry, enzyme-linked immunospot assay, and ELISA, respectively. Finally, preventive and therapeutic antitumor effects of such imDCs were determined by i.p. transfer against tumor challenge or implantation in mice. Results: Nicotine could up-regulate expression of nicotinic acetylcholine receptor, costimulatory molecules, such as CD80, CD86, and CD40, adhesion molecule CD11b, and chemokine receptor CCR7 and enhance endocytosis ability of imDCs. In addition, nicotine could promote imDC-dependent CTL priming and interleukin-12 secretion in vitro. Most importantly, systemic transfer of ex vivo nicotine-stimulated imDCs could reveal preventive and therapeutic effect on tumor development. Conclusions: Ex vivo nicotine stimulation can significantly improve the efficacy of imDCs for adaptive therapy of cancer and nicotine-treated imDCs may be considered as a potential candidate for preventive and therapeutic tumor vaccination.
Relationship of daytime asthma symptom frequency to morning peak expiratory flow
Authors: HA Atherton, PT White, G Hewett, K Howells
Journal: European Respiratory Journal (1996)

Since management plans based on peak flow measurements are increasingly used, the relationship between peak flow rate and ensuing symptom frequency is of particular interest to the treatment of asthma. The objective of this study was to examine to what extent morning peak flow was related to symptom frequency during the day. In 168 out of 307 randomly selected adult asthmatics from a general practice population, adequate recordings of morning peak flow (amPF) and symptom frequency during the day (DSF) were obtained for 28 days. In each individual, the relationship between these two variables was studied and the mean values of these two variables over 28 days were calculated. The relationship between the means of the variables was also examined for the group as a whole. In individuals, the correlation between amPF and DSF varied widely; only 16% of patients had a good relationship (Pearson r = -1 to -0.5). For the whole group, the relationship between mean amPF and mean DSF best fitted a curvilinear model (r = -0.6). This was unaffected by age, sex or the use of inhaled steroids. For the majority of asthmatics, morning peak flow may be an unreliable predictor of expected symptoms during that day. Reliance on peak flow measurement as a tool enabling asthmatics to manage their asthma on a daily basis needs to be reconsidered.
Sleep apnoea and cancer: the new challenge
Authors: Patrick Lévy, Diane Godin-Ribuot, Jean-Louis Pepin
Journal: European Respiratory Journal (2014)

Obstructive sleep apnoea (OSA) is a well-known public health problem owing to its high prevalence and the numerous consequences of the disorder, including excessive daytime somnolence, cognitive impairment and consequently traffic accidents [1]. There is an excess in cardiovascular mortality that has been repeatedly reported in longitudinal cohorts, in both general and clinical populations. Despite many confounding factors, including age, sex and obesity, evidence has accumulated over the past 25 years regarding strong associations between OSA, cardiovascular diseases i.e. hypertension [2], coronary artery disease, cerebrovascular disease, heart rate and conduction disorders, and excess mortality. Through a complex interaction between obesity, metabolism, sleep and sleep apnoea, metabolism seems to be altered by OSA [3], although it remains uncertain whether treating OSA may improve blood glucose control, lipid metabolism [4] or adipose tissue distribution [5]. More recently, it has been suspected that the excess in mortality in OSA could not only be attributed to cardiometabolic consequences but also to cancer. Cancer has been found to be associated with sleep disordered breathing (SDB) in two large observational studies [6, 7]. This had been previously suspected through proof-of-concept animal studies that demonstrated an association between intermittent hypoxia, a major consequence of SDB, carcinogenesis and acceleration of tumour growth [8]. Intermittent hypoxia is a particular condition with relatively specific cellular effects [9], including changes in host immune responses that could favour cancer progression [10]. The relationship between SDB and cancer has been studied in animal [8, 11, 12] and clinical studies; they suggest that SDB, mainly through intermittent hypoxia, is likely to be associated with an increase in growth rate [8], incidence [6] and mortality [7] …
MicroRNA Regulation and Cardiac Calcium Signaling
Authors: Masahide Harada, Xiaobin Luo, Toyoaki Murohara, Baofeng Yang, Dobromir Dobrev, Stanley Nattel
Journal: Circulation Research (2014)

MicroRNAs (miRNAs) are emerging as key control molecules in the regulation of gene expression, and their role in heart disease is becoming increasingly evident. Given the critical role of Ca(2+) handling and signaling proteins in the maintenance of cardiac function, the targeting of such proteins by miRNAs would be expected to have important consequences. miRNAs have indeed been shown to control the expression of genes encoding important Ca(2+) handling and signaling proteins, and are themselves regulated by Ca(2+)-dependent processes. Ca(2+)-related miRNAs have been found to be significant pathophysiological contributors in conditions like myocardial ischemic injury, cardiac hypertrophy, heart failure, ventricular arrhythmogenesis, and atrial fibrillation. This review is a comprehensive analysis of the present knowledge concerning miRNA regulation of Ca(2+) handling processes, the participation of Ca(2+)-regulating miRNAs in the evolution of heart disease, the mutual relationship between Ca(2+) signaling and miRNAs in the control of cardiac function, and the potential value of miRNA-control of Ca(2+) handling as a therapeutic target.
Effects of Thyroid Hormone on A1C and Glycated Albumin Levels in Nondiabetic Subjects With Overt Hypothyroidism
Authors: Mee Kyoung Kim, Hyuk Sang Kwon, Ki-Hyun Baek, Je Hoon Lee, Woo Chan Park, Hyung Sun Sohn, Kwang-Woo Lee, Ki-Ho Song
Journal: Diabetes Care (2010)

OBJECTIVE We aimed to determine the effects of thyroid hormone on A1C and glycated albumin (GA) in nondiabetic patients with overt hypothyroidism. RESEARCH DESIGN AND METHODS A1C levels were measured in 45 nondiabetic patients with overt hypothyroidism and 180 euthyroid control subjects. A1C, GA, fasting blood glucose (FBG), 1,5-anhydroglucitol, and erythrocyte indexes were determined in 30 nondiabetic patients with overt hypothyroidism before and after thyroid hormone replacement. RESULTS A1C levels were higher in patients with hypothyroidism compared with control subjects. A1C levels were decreased by thyroid hormone replacement. Thyroid hormone replacement increased serum erythropoietin, reticulocyte count, and mean corpuscular hemoglobin (MCH). The change in A1C level was significantly correlated with the change in reticulocyte count or MCH. Thyroid hormone replacement decreased serum levels of albumin and GA. However, FBG and 1,5-anhydroglucitol levels were not altered. CONCLUSIONS Levels of A1C and GA are spuriously high in nondiabetic patients with overt hypothyroidism.
The Pharmacology of Renal Lithiasis
Authors: T H Steele
Journal: The Annual Review of Pharmacology and Toxicology (1977)

Although the history of pharmacologic intervention in patients afflicted with ne­ phrolithiasis is a long one, many of the remedies employed probably have had a more soothing effect upon the conscience of the physician than on the colic of the patient. Striking exceptions have been the efficacy of penicillamine in the treatment of cystinuria and of allopurinol in the treatment of uric acid calculi. In recent years, however, significant advances have occurred in our knowledge regarding the patho­ genesis of many (formerly) idiopathic cases of calcium stone formation. This, together with improved techniques for diagnosis, has led to several novel phar­ macologic approaches to the treatment and prevention of calcium-containi ng stones. This review is concerned primarily with these newer aspects pertaining to calcium stone disease.
Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants
Authors: Dontscho Kerjaschki, Nicole Huttary, Ingrid Raab, Heinz Regele, Katalin Bojarski-Nagy, Gregor Bartel, Stefan M Kröber, Hildegard Greinix, Agathe Rosenmaier, Franz Karlhofer, Nikolaus Wick, Peter R Mazal
Journal: Nature Medicine (2006)
Abstract 3393: Using protein microarray technology to screen anti-PD-1 monoclonal antibodies for specificity and applications in anatomic pathology
Authors: Caiwei Chen, Yanlin Tang, Haitao Wei, Kehu Yuan, Guiyin Wu, Jian Chen, Boyang Chu, Guangli Wang, Youmin Shu, Wei-Wu He, Donghui Ma
Journal: Cancer Research (2015)

Abstract Programmed death-1 (PD-1) expresses in many tumors in response to inflammation. It is up-regulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands PD-L1 and PDL2 and serves as a key checkpoint of the immune system. Pembrolizumab is the first anti-PD-1 therapy approved in the United States and received FDA's Breakthrough Therapy designation for advanced melanoma. Thus, to evaluate PD1 protein levels in formalin-fixed paraffin-embedded tissue samples, a high quality monoclonal antibody validated for immunohistochemistry (IHC) is needed. To develop the best monoclonal antibody for PD-1 IHC analysis, 41 monoclonal antibodies were generated. 8 of them work for IHC application on FFPE tissue sections. To identify clones that are mono-specific on target, only two clones passed our high density protein microarray chip tests. Other immunoassays and species cross-reactivity tests were also explored. In summary, two newly generated monoclonal antibodies demonstrated ultra-specificity against PD-1 protein and superior performance for IHC analyses. These two clones could be utilized as companion diagnostic reagents to stratify cancer patients before pembrolizumab prescription. Citation Format: Caiwei Chen, Yanlin Tang, Haitao Wei, Kehu Yuan, Guiyin Wu, Jian Chen, Boyang Chu, Guangli Wang, Youmin Shu, Wei-Wu He, Donghui Ma. Using protein microarray technology to screen anti-PD-1 monoclonal antibodies for specificity and applications in anatomic pathology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3393. doi:10.1158/1538-7445.AM2015-3393
The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget’s disease
Authors: T. Ohnishi, S. Watanabe
Journal: British Journal of Dermatology (2000)

Despite the similarity in clinical appearance, there is a significant difference in the prognosis between primary extramammary Paget's disease (EPD) and the pagetoid spread of underlying regional internal malignancy (secondary EPD, pagetoid phenomenon). Fifteen cases of primary EPD (11 carcinoma in situ and four invasive carcinoma), seven cases of secondary EPD (five colorectal adenocarcinoma and two urothelial carcinoma), and six cases of anal canal carcinoma were retrieved and analysed immunohistochemically using six kinds of monoclonal anticytokeratin antibodies. No expression of cytokeratins 1, 5, 10, 13 and 14 was observed in any cases examined in this study. All 15 cases of primary EPD had the immunophenotype cytokeratin (CK)7+/CK20-. CK20 expression was diffusely positive in six cases of secondary pagetoid spread (two urothelial carcinoma and four colorectal adenocarcinoma), and focally in one case (a colorectal adenocarcinoma). In anal canal carcinoma, three of six cases showed CK20 diffuse expression and the remaining three cases expressed CK20 focally. CK7 expression was observed in three of six cases of anal canal carcinoma and in two of five cases of secondary EPD associated with colorectal adenocarcinoma. The combination of CK7 and CK20 demonstrates these to be useful markers in distinguishing 'primary' EPD from a pagetoid spread of extracutaneous malignancies. Namely, immunophenotypes other than CK7+/CK20- in Paget cells suggest underlying regional internal malignancy.
The Clinical Potential of Pretreatment Serum Testosterone Level to Improve the Efficiency of Prostate Cancer Screening
Authors: Masashi Yano, Takashi Imamoto, Hiroyoshi Suzuki, Satoshi Fukasawa, Satoko Kojima, Akira Komiya, Yukio Naya, Tomohiko Ichikawa
Journal: European Urology (2006)
Is Cheyne-Stokes respiration friend or foe of heart failure?
Authors: Fumihiko Yasuma
Journal: Thorax (2012)

I agree with Dr MT Naughton's interesting opinion expressed in ‘Cheyne-Stokes respiration: friend or foe?’ in his recent opinion in Thorax. 1 Central sleep apnoea with Cheyne-Stokes respiration (CSA-CSR) indeed has multiple features more likely to be compensatory than injurious in heart failure (HF). His view, however, seems to lack insight into the heart–lung interaction in CSA-CSR, and reminds me of the fundamental question of ‘why does the heartbeat synchronise with respiratory rhythm?’.2

In polygraphic recording in a HF patient with CSA-CSR (figure 1A), heartbeats are clustered during the hyperventilation period and scattered during the apnoeic period of CSR-CSA with cycle-length of approximately 90 s. This phenomenon is known as …