tbuckley/cabot-search huggingface dataset:
A Prospective Cohort Study on Toenail Selenium Levels and Risk of Gastrointestinal Cancer
Authors: P. A. v. d. Brandt, R. A. Goldbohm, P. van 't Veer, P. Bode, E. Dorant, R. J. J. Hermus, F. Sturmans
Journal: JNCI Journal of the National Cancer Institute (1993)

Various animal studies and ecologic studies suggest an inverse association between low dietary selenium intake and risk of various types of cancer.The goal of this prospective cohort study was to investigate the association between toenail selenium levels and risks of stomach cancer and colorectal cancer.Our cohort study on diet and cancer started in The Netherlands in 1986 with enrollment of 120,852 subjects aged 55-69 years. Of this number, 58,279 were men and 62,573 were women. Following the case-cohort approach for analysis of the data, we randomly selected from the cohort a subcohort of 3500 subjects (1688 men and 1812 women). After 3.3 years of follow-up, 155 incident cases of microscopically confirmed stomach cancer, 313 cases of colon cancer, and 166 cases of rectal cancer had been detected in the cohort. Toenail selenium data were available for 104 patients with stomach cancer, 234 with colon cancer, and 113 with rectal cancer and for 2459 subjects from the subcohort.In a multivariate analysis, the relative rates (RRs) of stomach cancer for subjects in increasing quintiles of toenail selenium level were 1.00, 0.44, 0.59, 0.84, and 0.64 (trend, P = .491). For men, there was some evidence for an inverse association between toenail selenium levels and stomach cancer: The RR for those in the highest compared with the lowest quintile of toenail selenium was 0.40 (95% confidence interval = 0.17-0.96), but the trend was not statistically significant (P = .136). For stomach cancer in women, there was no negative association with toenail selenium levels. Toenail selenium level was not associated with the risk of colon or rectal cancer. After exclusion of cases diagnosed in the 1st year of follow-up, the RRs of colon cancer for increasing quintiles of toenail selenium were 1.00, 1.27, 1.17, 0.75, and 1.07 (trend, P = .544); for rectal cancer, RR estimates were 1.00, 1.73, 0.83, 1.58, and 1.12 (trend, P = .890).These data support a suggestive but inconsistent inverse association between selenium levels and risk of stomach cancer. Our findings, like those of other studies, do not suggest an inverse association with risk of colorectal cancer.
Functional coupling expression of COX-2 and cPLA2 induced by ATP in rat vascular smooth muscle cells: role of ERK1/2, p38 MAPK, and NF-κB
Authors: Chih-Chung Lin, Wei-Ning Lin, Wei-Jung Wang, Chi-Chin Sun, Wei-Hsuan Tung, Hui-Hsin Wang, Chuen-Mao Yang
Journal: Cardiovascular Research (2009)

AimsVascular smooth muscle cells (VSMCs) that function as synthetic units play important roles in inflammatory diseases such as atherosclerosis and angiogenesis. As extracellular nucleotides such as ATP have been shown to act via activation of P2 purinoceptors implicated in various inflammatory diseases, we hypothesized that extracellular nucleotides contribute to vascular diseases via upregulated expression of inflammatory proteins, such as cyclooxygenase (COX-2) and cytosolic phospholipase A2 (cPLA2) in VSMCs.
Adrenal Medullary Secretion of Epinephrine and Norepinephrine in Dogs Subjected to Hemorrhagic Hypotension
Authors: VINCENT V. GLAVIANO, NOEL BASS, FLORIAN NYKIEL
Journal: Circulation Research (1960)

The response of the adrenal medulla in anesthetized dogs to hemorrhagic hypotension of a varied level and duration was observed to be primarily accompanied by a highly significant increase in adrenal plasma epinephrine. On the other hand, the secretion of norepinephrine had an unpredictable occurrence in adrenal blood samples collected in periods of hypotension. The essential determinant of adrenal blood flow was observed to be the level of mean blood pressure. While this relationship was not in strict proportion, changes in mean blood pressure were invariably followed by changes in adrenal blood flow in the same direction. The adrenal medulla of dogs in hemorrhagic irreversible shock was observed to continue to secrete epinephrine at very low levels of mean blood pressure, characteristic of terminal shock. Reports by other groups of investigators on elevated peripheral blood levels of epinephrine in hemorrhagic shock have been found to result mainly from an actively secreting adrenal medulla.
Effects of locality based community hospital care on independence in older people needing rehabilitation: randomised controlled trial
Authors: John Green, John Young, Anne Forster, Karen Mallinder, Sue Bogle, Karin Lowson, Neil Small
Journal: BMJ (2005)

Objective To determine the effects on independence in older people needing rehabilitation in a locality based community hospital compared with care on a ward for elderly people in a district general hospital. Design Randomised controlled trial. Setting Care in a community hospital and district general hospital in Bradford, England. Participants 220 patients needing rehabilitation after an acute illness that required hospital admission. Interventions Patients were randomly allocated to a locality based community hospital or to remain within a department for the care of elderly people in a district general hospital. Main outcome measures Primary outcomes were Nottingham extended activities of daily living scale and general health questionnaire 28 (carer). Secondary outcomes were activities of daily living (Barthel index), Nottingham health profile, hospital anxiety and depression scale, mortality, destination after discharge, satisfaction with services, carer strain index, and carer's satisfaction with services. Results The median length of stay was 15 days for both the community hospital and the district general hospital groups (interquartile range: community hospital 9-25 days; district general hospital 9-24 days). Independence at six months was greater in the community hospital group (adjusted mean difference 5.30, 95% confidence interval 0.64 to 9.96). Results for the secondary outcome measures, including care satisfaction and measures of carer burden, were similar for both groups. Conclusions Care in a locality based community hospital is associated with greater independence for older people than care in wards for elderly people in a district general hospital.
Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells
Authors: Diego V. Bohórquez, Rafiq A. Shahid, Alan Erdmann, Alex M. Kreger, Yu Wang, Nicole Calakos, Fan Wang, Rodger A. Liddle
Journal: Journal of Clinical Investigation (2015)

Satiety and other core physiological functions are modulated by sensory signals arising from the surface of the gut. Luminal nutrients and bacteria stimulate epithelial biosensors called enteroendocrine cells. Despite being electrically excitable, enteroendocrine cells are generally thought to communicate indirectly with nerves through hormone secretion and not through direct cell-nerve contact. However, we recently uncovered in intestinal enteroendocrine cells a cytoplasmic process that we named neuropod. Here, we determined that neuropods provide a direct connection between enteroendocrine cells and neurons innervating the small intestine and colon. Using cell-specific transgenic mice to study neural circuits, we found that enteroendocrine cells have the necessary elements for neurotransmission, including expression of genes that encode pre-, post-, and transsynaptic proteins. This neuroepithelial circuit was reconstituted in vitro by coculturing single enteroendocrine cells with sensory neurons. We used a monosynaptic rabies virus to define the circuit’s functional connectivity in vivo and determined that delivery of this neurotropic virus into the colon lumen resulted in the infection of mucosal nerves through enteroendocrine cells. This neuroepithelial circuit can serve as both a sensory conduit for food and gut microbes to interact with the nervous system and a portal for viruses to enter the enteric and central nervous systems.
New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling
Authors: Willem A. Dik, Karin Pike-Overzet, Floor Weerkamp, Dick de Ridder, Edwin F.E. de Haas, Miranda R.M. Baert, Peter van der Spek, Esther E.L. Koster, Marcel J.T. Reinders, Jacques J.M. van Dongen, Anton W. Langerak, Frank J.T. Staal
Journal: The Journal of Experimental Medicine (2005)

To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human T cell development, we analyzed TCR gene rearrangements by quantitative PCR analysis in nine consecutive T cell developmental stages, including CD34+ lin− cord blood cells as a reference. The same stages were used for gene expression profiling using DNA microarrays. We show that TCR loci rearrange in a highly ordered way (TCRD-TCRG-TCRB-TCRA) and that the initiating Dδ2-Dδ3 rearrangement occurs at the most immature CD34+CD38−CD1a− stage. TCRB rearrangement starts at the CD34+CD38+CD1a− stage and complete in-frame TCRB rearrangements were first detected in the immature single positive stage. TCRB rearrangement data together with the PTCRA (pTα) expression pattern show that human TCRβ-selection occurs at the CD34+CD38+CD1a+ stage. By combining the TCR rearrangement data with gene expression data, we identified candidate factors for the initiation/regulation of TCR recombination. Our data demonstrate that a number of key events occur earlier than assumed previously; therefore, human T cell development is much more similar to murine T cell development than reported before.
Selective apoptosis of lung cancer cells with talc
Authors: P. Lee, L. Sun, C. K. Lim, S. E. Aw, H. G. Colt
Journal: European Respiratory Journal (2010)

To the Editors: 

Lung cancer is the leading cause of cancer deaths worldwide, with adenocarcinoma being the most common cell type. The majority of patients with lung cancer present at an advanced stage of disease with only 15% being amenable to surgery for cure; treatment is, therefore, palliative. For patients with malignant effusions due to pleural metastasis, chemical pleurodesis is one method by which to prevent recurrence. While there are many intrapleural sclerosing agents, most data pertaining to pleurodesis have been reported with tetracycline derivatives, bleomycin and talc 1.

A number of studies have demonstrated superior efficacy of talc over other sclerosing agents commonly used for the palliation of malignant pleural effusions 2, and talc is the preferred pleurodesis agent according to a survey of chest physicians 3. Despite talc's wide clinical use, the exact mechanisms for its efficacy as well as its apoptotic effects on lung cancer cells in vitro have not been studied. The objectives of our study were to determine if talc caused apoptosis of lung cancer cells, and to compare talc against other commonly administered intrapleural sclerosing agents by extending the experiments to include bleomycin and doxycyline.

The lung adenocarcinoma cell line (LAC, A549) was purchased from American Type Culture Collection (Rockville, MD, USA). Human pleural mesothelial cells (PMC) characterised by classic cobblestone morphology, cytokeratin and without factor VIII antigen were isolated from pleural fluid obtained via thoracentesis from patients with symptomatic transudative pleural effusions secondary to congestive heart failure, and …
Cimetidine and duodenal ulcer.
Authors: N R Peden, K G Wormsley
Journal: BMJ (1979)

the fact that death is usually due to acute arrhythmia rather than pump failure points to (fresh) ischaemia as the cause.Lowering of blood pressure may be the actual mechanism responsible for initiating this.However, in- creased blood viscosity and platelet adhesive- ness could well raise the threshold of blood pressure which is operative.
Modulation of phagosome-lysosome fusion in mouse macrophages.
Authors: M C Kielian, Z A Cohn
Journal: The Journal of Experimental Medicine (1981)

A previously described fluorescence assay has been used to characterize factors that modulate phagosome-lysosome (P-L) fusion in mouse macrophages. Fusion was not affected by enzymatic modification or by concanavalin A cross-linking of the plasma membrane or by coating the phagocytic particle with concanavalin A or immune serum. Pretreatment of cells with 10-5-10-4 M colchicine, or treatment immediately after ingestion with 1-10 microgram/ml cytochalasin did not alter P-L fusion; implying that the cytoskeleton does not control fusion in a rate-limiting way. Fusion was strikingly elevated in 5-h cultures of activated macrophages from immune-boosted mice. A lower enhancement was seen in cells activated by proteose-peptone, a nonspecific inflammatory agent.
Acute bacterial meningitis in young adults mistaken for substance abuse.
Authors: L N Baldwin, A Henderson, P Thomas, M Wright
Journal: BMJ (1993)

Ifmisuse ofdrugs is suspected, a plasma or urinary drug screen is indicated.Particular caution should be exercised when prescribing for' young and elderly patients, and for those with personality disorders and bipolar depressive illnesses.A simple sleep log with mood, alertness, and behavioural self rating scales during the first three months of treatment helps to monitor treatment.Changes in lifestyle and behaviour will also help.For patients who wish to drive it is sensible to assess response over a six month period before considering issuing a provisional licence.Central nervous system stimulants should not be prescribed to anybody with a history of psychosis, physical violence, or drug misuse, or to woxnen who are pregnant or breast feeding.Cardiovascular risks should be assessed with care.Sleep can kill.
Lowering of Microalbuminuria in Diabetic Patients by a Sympathicoplegic Agent
Authors: KRZYSZTOF STROJEK, WLADYSLAW GRZESZCZAK, JUTA GÓRSKA, MONIKA I. LESCHINGER, EBERHARD RITZ
Journal: Journal of the American Society of Nephrology (2001)

Abstract. There is convincing evidence for a specific BP-independent effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 ± 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 ± 5.1 yr) with baseline urinary albumin excretion rates (AER) &gt;20 μg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 ± 7.1 mmHg in the third week of placebo and 91.1 ± 8.7 mmHg on moxonidine). There was a significant ( P &lt; 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 μg/min (range, 15.9 to 117 μg/min) versus 29.0 (range, 9.03 to 85.8 μg/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for the finding.
Comment on: Luijf et al. Premeal Injection of Rapid-Acting Insulin Reduces Postprandial Glycemic Excursions in Type 1 Diabetes. Diabetes Care 2010;33:2152–2155
Authors: Andrea E. Scaramuzza, Dario Iafusco, Alessandra Bosetti, Alessandra De Palma, Gian Vincenzo Zuccotti
Journal: Diabetes Care (2011)

Referring to the article by Luijf et al. (1), administrating rapid-acting insulin analogs 15 min before mealtimes resulted in fewer episodes of postprandial hyperglycemia and more time spent in the 3.5–10.0 mmol/L range, without increased risk of hypoglycemia. No effect was noted when administered 30 min before meals. Authors speculate that if insulin administered 15 min before the meal is optimum, then both −30 and 0 min treatment periods had an equal 15 min mismatch, resulting in almost equal postprandial glycemic control.

In our opinion (2), it is a matter of mimicking the “cephalic phase,” which is lost in patients with type 1 diabetes. A recent study (3) shows the mechanisms and physiological relevance of the cephalic insulin response to meal ingestion in healthy …
Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet.
Authors: D E Greenwalt, S H Scheck, T Rhinehart-Jones
Journal: Journal of Clinical Investigation (1995)

High levels of CD36 expression are found in triglyceride storing and secreting cells such as differentiated adipocytes and mammary secretory epithelial cells and in some capillary endothelial cells. We have found high levels of CD36 in the capillary endothelium of murine adipose tissue and in cardiac and skeletal muscles. Muscle cells themselves were CD36 negative. No CD36 was found in brain endothelium. Cardiac and skeletal muscle tissues are highly oxidative and catabolize long-chain fatty acids as a source of energy while brain tissue does not use long-chain fatty acids for energy production. Since capillary endothelial cell CD36 expression appeared to correlate with parenchymal cell fatty acid utilization and since CD26 has been identified recently as a long-chain fatty acid-binding protein, we examined heart tissue CD36 expression in murine models of insulin-dependent (nonobese diabetic, NOD) and non-insulin-dependent diabetes mellitus (KKAY). Diabetic NOD and KKAY mice had serum triglyceride levels 2.6- and 4.2-fold higher, respectively, than normal mice and exhibited 7- and 3.5-fold higher levels of heart microsomal CD36, respectively, than control mice. Mice fed a 40% fat diet expressed heart tissue CD36 at a level 3.5-fold higher than those fed a 9% fat diet. These data suggest that endothelial cell CD36 expression is related to parenchymal cell lipid metabolism.
* Image cytometry DNA ploidy abnormalities are an independent risk factor for cancer progression in non-dysplastic barrett's oesophagus and low grade dysplasia: results of the NIBR study
Authors: J. M. Dunn, E. L. Bird-Lieberman, H. G. Coleman, D. Oukrif, K. Arthur, P. Lao-Sirieix, L. Murray, D. McManus, M. R. Novelli, R. Fitzgerald, L. B. Lovat
Journal: Gut (2011)

<h3>Introduction</h3> The risk of progression to oesophageal adenocarcinoma (OAC) from non-dysplastic Barrett9s Oesophagus (BO) is low and unpredictable. Low grade dysplasia (LGD) may increase risk but is associated with significant interobserver variability by pathologists. Biomarkers are needed to better stratify patient risk. DNA ploidy abnormalities (aneuploidy/tetraploidy) reflect genomic instability and confer an increased risk of cancer progression, when measured by flow cytometry (FC). Image cytometry DNA ploidy analysis (ICDA) is a technique with equivalent accuracy to FC and uses formalin fixed tissue, allowing archival analysis. <h3>Methods</h3> Multi centre nested case–control study conducted within the population-based Northern Ireland BO Register (NIBR), which includes all BO patients diagnosed between 1993 and 2005. Cases had histologically confirmed OAC or high grade dysplasia (HGD) diagnosed ≥6 months after BO diagnosis. Each case was matched to 3 BO controls, based on age (±5 years), sex and year of BO diagnosis. Conditional logistic regression analysis was applied to investigate risk of progression prior to and post adjustment for potential confounders. Standard protocols for ICDA followed. All ICDA analysis was blinded to outcomes. <h3>Results</h3> 89 cases of progression from BO to HGD/Cancer were matched to 291 BO controls. Of the 380 patients samples, 92% were successfully analysed by ICDA, including 78 cases. Mean (±SD) follow-up time for cases and controls was 4.06 ± 2.95 years (range 0.5–12.1 years) and 7.42 ± 2.91 years respectively. There was a significantly increased risk for progression to OAC and HGD when DNA ploidy abnormalities were present (OR = 4.17; 95% CI = 2.37–7.35). After multi-variate analysis DNA ploidy abnormalities remained a significant predictor of risk for HGD and cancer (OR = 3.14; 95% CI = 1.64 to 5.98). In a risk model, the presence of DNA ploidy abnormalities and IND/LGD conferred a high risk of progression to OAC/HGD (OR = 52.93; 95% CI = 6.71 to 417.35). The risk of progression in patients who were diploid with IND/LGD or in patients with DNA ploidy abnormalities in NDBO was similar (OR = 2.23; 95% CI = 1.15 to 4.32). <h3>Conclusion</h3> This multicentre blinded biomarker study demonstrates that DNA ploidy abnormalities measured by ICDA are independent risk factors for the development of OAC and HGD in BO. The presence of DNA ploidy abnormalities in patients with LGD confers a significantly increased risk of progression to OAC/HGD. This group may be suitable for endoscopic therapy.
Frzb, a Secreted Wnt Antagonist, Decreases Growth and Invasiveness of Fibrosarcoma Cells Associated with Inhibition of Met Signaling
Authors: Yi Guo, Jun Xie, Elyssa Rubin, Ya-Xiong Tang, Fritz Lin, Xiaolin Zi, Bang H. Hoang
Journal: Cancer Research (2008)

Abstract Soft tissue sarcomas (STS) have a strong propensity for aggressive growth and metastasis. We showed that the secreted Wnt antagonist Frzb exhibited potent antitumor activity against prostate cancer, an epithelial type of malignancy. In this study, we further showed the antitumor efficacy of Frzb in STS, a mesenchymal group of cancer. Frzb transfection of HT1080 (fibrosarcoma) and SW872 (liposarcoma) cell lines and their conditioned media resulted in a significant reduction in cellular invasion, motility, and colony formation in soft agar compared with vector control–transfected cells. In a xenograft mouse model, Frzb dramatically suppressed tumor growth of HT1080 cells in nude mice. In a tail-vein injection metastatic model, Frzb-transfected HT1080 cells formed fewer and smaller lung nodules than vector control cells. In addition, we identified new mechanisms for Frzb antitumor activities. Frzb reduced c-Met expression and inhibited Met-mediated signaling, associated with up-regulation of epithelial markers (i.e., keratins 8 and 18) and down-regulation of mesenchymal markers (i.e., vimentin, N-cadherin, fibronectin, Slug, and Twist). Similar to Frzb, silencing of c-Met by short hairpin RNA or using a dominant-negative LRP5 receptor also suppressed Met signaling, leading to reduced cellular motility, invasion, and in vivo tumor growth. Given recent studies indicating an important role of c-Met in sarcoma development and progression, our data showed that Frzb expression was significantly inversely correlated with Met expression in both STS cell lines and tissues. These results suggested the usefulness of Frzb in modulating Met signaling as a new treatment strategy for STS. [Cancer Res 2008;68(9):3350–60]