tbuckley/cabot-search huggingface dataset:
Clinical Significance of Circulating Tumor Cells, Including Cancer Stem-Like Cells, in Peripheral Blood for Recurrence and Prognosis in Patients With Dukes' Stage B and C Colorectal Cancer
Authors: Hisae Iinuma, Toshiaki Watanabe, Koshi Mimori, Miki Adachi, Naoko Hayashi, Junko Tamura, Keiji Matsuda, Ryoji Fukushima, Kota Okinaga, Mitsuru Sasako, Masaki Mori
Journal: Journal of Clinical Oncology (2011)

Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery.In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n = 420) or prospective validation set (n = 315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay.In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer.In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.
Acanthocytes in the Urine
Authors: Gunnar H. Heine, Urban Sester, Matthias Girndt, Hans Köhler
Journal: Diabetes Care (2004)

The presence of hematuria has been suggested to indicate nondiabetic nephropathy in diabetic patients with proteinuria. However, hematuria is frequently found in patients with biopsy-proven diabetic glomerulosclerosis without nondiabetic nephropathy. Urine microscopy allows discrimination of glomerular hematuria, which is defined as acanthocyturia (urinary excretion of acanthocytes, which are dysmorphic erythrocytes with vesicle-like protrusions), from nonglomerular hematuria. We hypothesized that acanthocyturia is an uncommon finding in diabetic nephropathy, which suggests the presence of a nondiabetic nephropathy in diabetic patients with proteinuria.Urine samples of patients with the clinical diagnosis of diabetic nephropathy (n = 68), of patients with biopsy-proven glomerulonephritis (n = 43), and of age-matched healthy control subjects (n = 20) were examined by phase-contrast microscopy for the presence of hematuria (>/=8 erythrocytes/ micro l) and acanthocyturia. Acanthocyturia of >/=5% (5 acanthocytes among 100 excreted erythrocytes) was classified as glomerular hematuria; acanthocyturia of 2-4% was classified as suspected glomerular hematuria.Hematuria was found in 62% of patients with the clinical diagnosis of diabetic nephropathy, in 84% of patients with glomerulonephritis, and in 20% of the healthy control subjects upon a single urine examination. In contrast, glomerular hematuria occurred in 4% of patients with diabetic nephropathy and in 40% of patients with glomerulonephritis (P < 0.001).In contrast to hematuria, acanthocyturia is uncommon in patients with the clinical diagnosis of diabetic nephropathy. In diabetic patients with proteinuria, the finding of acanthocyturia points to nondiabetic glomerulopathies, and renal biopsy should be considered.
Acrodermatitis enteropathica with normal serum zinc levels: diagnostic value of small bowel biopsy and essential fatty acid determination.
Authors: D Mack, B Koletzko, S Cunnane, E Cutz, A Griffiths
Journal: Gut (1989)

We report a patient with acrodermatitis enteropathica and a normal serum zinc level in whom the diagnosis was confirmed by plasma phospholipid fatty acid and a small bowel biopsy response to oral zinc therapy. Acrodermatitis enteropathica is a rare autosomal recessive condition of zinc deficiency characterised by chronic diarrhoea associated with failure to thrive, periorificial dermatitis and alopecia, susceptibility to infections and behavioural changes. Diagnosis is usually established by reduced serum zinc levels (classical acrodermatitis enteropathica). Paneth cell abnormalities on electron microscope of a small bowel biopsy can be supportive. A few cases with the typical picture of acrodermatitis enteropathica without hypozincaemia (variant acrodermatitis enteropathica) have been described. The diagnosis of variant acrodermatitis enteropathica to date has been based on an entirely empiric, but nonetheless convincing clinical response to oral zinc therapy. Laboratory aids to diagnosis have been lacking.
Dietary Fat and Protein in Relation to Risk of Non-Hodgkin's Lymphoma Among Women
Authors: S. Zhang, D. J. Hunter, B. A. Rosner, G. A. Colditz, C. S. Fuchs, F. E. Speizer, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Non-Hodgkin's lymphoma occurs more frequently in individuals with suppressed immune status, and some types of dietary fat and protein have been associated with decreased immune responses. In this study, we examined the intake of specific types of dietary fat and protein in relation to the risk of non-Hodgkin's lymphoma. METHODS: We documented 199 incident cases of non-Hodgkin's lymphoma in a cohort of 88 410 women, who were enrolled in the Nurses' Health Study and were aged 34-60 years in 1980, during 14 years of follow-up. Relative risks of the disease and 95% confidence intervals (95% CIs) were calculated. All P values are two-sided and were considered to be statistically significant for P <.05. RESULTS: Intake of saturated fat was associated with an increase in risk that was not statistically significant; the multivariate relative risk for the highest versus the lowest quintiles of intake was 1.4 (95% CI = 0.7-3.0; P for trend = .42). Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of non-Hodgkin's lymphoma; the multivariate relative risk for consumption of these meats at least once per day as compared with less than once per week was 2.2 (95% CI = 1.1-4.4; P for trend = .002). Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease; the multivariate relative risk for the highest versus the lowest quintiles was 2.4 (95% CI = 1.3-4.6; P for trend = .01). Higher intake of red meat cooked by broiling or barbecuing—but not by roasting, pan-frying, or boiling or stewing—was associated with an increase in risk that was not statistically significant. CONCLUSIONS: Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's lymphoma. These relationships and their potential mechanisms deserve further examination.
Prolonged fever, dyspnoea and diffuse pleural thickening in a 20-year-old man
Authors: C Cai, D R Li, Q S Zeng, S Q Zhong, N S Zhong
Journal: Thorax (2007)

A 20-year-old man was referred for intermittent high fever, night sweat and loss of body weight for 6 months associated with progressive exertional dyspnoea which developed 4 weeks before admission. The patient was unresponsive to antibiotics and 14 day pre-emptive antituberculous chemotherapy with rifampicin, isoniazid, ethambutol and pyrazinamide. His temperature was 39.8°C, …
Deciphering intratumor heterogeneity and temporal acquisition of driver events to refine precision medicine
Authors: Crispin Hiley, Elza C de Bruin, Nicholas McGranahan, Charles Swanton
Journal: Genome biology (2014)

Abstract The presence of multiple subclones within tumors mandates understanding of longitudinal and spatial subclonal dynamics. Resolving the spatial and temporal heterogeneity of subclones with cancer driver events may offer insight into therapy response, tumor evolutionary histories and clinical trial design.
Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy
Authors: Uzma F. Mehdi, Beverley Adams-Huet, Philip Raskin, Gloria L. Vega, Robert D. Toto
Journal: Journal of the American Society of Nephrology (2009)

Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio > or =300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, -51.0%, -11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, -37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial.
Graduate Medical Education: The Policy Debate
Authors: Gerard F Anderson, George D Greenberg, Barbara O Wynn
Journal: Annual Review of Public Health (2001)

▪ Abstract The cost of providing graduate medical education to the approximately 100,000 medical residents in the United States is approximately $18 billion. The government, primarily through the Medicare program, funds almost two thirds of the cost. Unfortunately, the federal government lacks a coherent policy with respect to what objectives it wants to achieve for this expenditure. This article traces (a) the evolution of graduate medical education funding; (b) current proposals to reform the funding mechanism; (c) how the Medicare program currently funds graduate medical education; (d) how funds are allocated to specific institutions; and (e) specific policy objectives that academic medical centers should be held accountable for achieving in return for receiving public funds.
S42 Airway epithelial toll receptor expression in asthma and its relationship to disease severity
Authors: L. Cottey, N. Jayasekera, H.-M. Haitchi, B. Green, C. Grainge, P. Howarth
Journal: Thorax (2010)

<h3>Introduction</h3> Asthma is classically considered a Th2 mediated disease. However, severe and treatment-resistant disease is more heterogeneous and often associated with airway neutrophil recruitment. This may be related to an altered airway bacterial colonisation. Bacteria express pathogen associated molecular patterns (PAMP9s) that are recognised as non-self by pattern recognition receptors (PRRs). These PRRs represent an essential component of the innate immunity and an important family of PPRs are the Toll-like receptors (TLR). These are expressed on a range of innate immune cells including epithelial cells. TLR-1, -2, -4, -5 and -6 are located on the cell surface membrane and respond to bacterial cell wall components. This study has investigated the expression of mRNA for TLR-2, -4 and -5 in airway epithelial cells in asthmatics and healthy volunteers. <h3>Methods</h3> Epithelial brushings were obtained from the large central airways at fibre-optic bronchoscopy from 18 healthy non-asthmatic volunteers (8 female and mean age 26 years) and 34 asthmatic volunteers (25 female, mean age 43 years). The asthmatic group comprised 7 non-steroid treated and 27 steroid treated asthmatics. The brushings were placed in Trizol and the RNA subsequently extracted and converted to cDNA, prior to real time TaqMan RT-qPCR analysis for the Toll receptors, TLR2, TLR4 and TLR5, as well as IL-8. <h3>Results</h3> Gene expression for TLR-2 (p=0.008) and TLR-4 (p=0.012) was significantly increased within the epithelial brushing sample from the asthmatics compared to the healthy control subjects whilst that for TLR-5 did not differ significantly. Interleukin 8 mRNA was also increased within the epithelial brushing sample in the asthmatics (p=0.007) compared to that in the healthy control subjects. These significant differences from the healthy population were also individually present in both the mild and severe asthmatic groups, with no significant difference being evident between mild and severe asthma. <h3>Conclusions</h3> These findings reveal up regulation of epithelial gene expression for members of the Toll receptor family relevant to bacterial responses within the airways. Additionally there is enhanced IL-8 gene expression. These features are indicative of on-going innate immune airway responses in asthma. The relevance of this to clinical disease expression requires understanding.
Overexpression of Human Catalase Inhibits Proliferation and Promotes Apoptosis in Vascular Smooth Muscle Cells
Authors: Michael R. Brown, Francis J. Miller, Wei-Gen Li, Andy N. Ellingson, Jonathan D. Mozena, Papri Chatterjee, John F. Engelhardt, Ralf M. Zwacka, Larry W. Oberley, Xiang Fang, Arthur A. Spector, Neal L. Weintraub
Journal: Circulation Research (1999)

Abstract —The role of reactive oxygen species, such as superoxide anions (O 2 · − ) and hydrogen peroxide (H 2 O 2 ), in modulating vascular smooth muscle cell proliferation and viability is controversial. To investigate the role of endogenously produced H 2 O 2 , rat aortic smooth muscle cells were infected with adenoviral vectors containing cDNA for human catalase (Ad Cat ) or a control gene, β-galactosidase (Ad LacZ ). Infection with Ad Cat resulted in dose-dependent increases in intracellular catalase protein, which was predominantly localized to peroxisomes. After infection with 100 multiplicity of infection (MOI) of Ad Cat , cellular catalase activity was increased by 50- to 100-fold, and intracellular H 2 O 2 concentration was reduced, as compared with control. Infection with Ad Cat reduced [ 3 H]thymidine uptake, an index of DNA synthesis, in cells maintained in medium supplemented with 2% serum (0.37±0.09 disintegrations per minute per cell [Ad LacZ ] versus 0.22±0.08 disintegrations per minute per cell [Ad Cat ], P &lt;0.05). Five days after infection with 100 MOI of Ad Cat , cell numbers were reduced as compared with noninfected or Ad LacZ -infected cells (157 780±8413 [Ad Cat ], P &lt;0.05 versus 233 700±3032 [noninfected] or 222 410±5332 [Ad LacZ ]). Furthermore, the number of apoptotic cells was increased 5-fold after infection with 100 MOI of Ad Cat as compared with control. Infection with Ad Cat resulted in induction of cyclooxygenase (COX)–2, and treatment with a COX-2 inhibitor overcame the Ad Cat -induced reduction in cell numbers. These findings indicate that overexpression of catalase inhibited smooth muscle proliferation while increasing the rate of apoptosis, possibly through a COX-2–dependent mechanism. Our results suggest that endogenously produced H 2 O 2 importantly modulates survival and proliferation of vascular smooth muscle cells.
Cholesterol synthesis is required for cutaneous barrier function in mice.
Authors: K R Feingold, M Q Man, G K Menon, S S Cho, B E Brown, P M Elias
Journal: Journal of Clinical Investigation (1990)

Previous studies have shown that topical acetone treatment results in the removal of stratum corneum lipids and disruption of the permeability barrier. This disruption stimulates epidermal lipid synthesis which is associated with the rapid restoration of stratum corneum lipids and barrier function. The aim of this study was to determine the role of cutaneous cholesterol synthesis in the barrier recovery. Here we show that topical lovastatin, a competitive inhibitor of HMG CoA reductase, inhibits cholesterol synthesis. After acetone disruption of the barrier, the normal rapid return of cholesterol to the stratum corneum and recovery of barrier function is impaired in animals treated topically with lovastatin. When lovastatin animals are simultaneously treated topically with either mevalonate, the immediate product of HMG CoA reductase, or cholesterol, the final end product of the pathway, the recovery of the barrier is normalized. Lovastatin resulted in the delayed secretion and abnormal appearance of lamellar bodies. These results provide the first evidence demonstrating that cholesterol synthesis is required for the maintenance of barrier structure and function and suggests a crucial role for cholesterol synthesis in allowing for terrestrial existence.
A dose escalation trial of adjuvant cyclophosphamide and epirubicin in combination with 5-fluorouracil using G-CSF support for premenopausal women with breast cancer involving four or more positive nodes
Authors: B. Findlay, K. Tonkin, M. Crump, B. Norris, M. Trudeau, M. Blackstein, M. Burnell, J. Skillings, D. Bowman, D. Walde, M. Levine, K.I. Pritchard, M.J. Palmer, D. Tu, L. Shepherd
Journal: Annals of Oncology (2007)
Health Impact Assessment of Global Climate Change: Expanding on Comparative Risk Assessment Approaches for Policy Making
Authors: Jonathan Patz, Diarmid Campbell-Lendrum, Holly Gibbs, Rosalie Woodruff
Journal: Annual Review of Public Health (2008)

Climate change is projected to have adverse impacts on public health. Cobenefits may be possible from more upstream mitigation of greenhouse gases causing climate change. To help measure such cobenefits alongside averted disease-specific risks, a health impact assessment (HIA) framework can more comprehensively serve as a decision support tool. HIA also considers health equity, clearly part of the climate change problem. New choices for energy must be made carefully considering such effects as additional pressure on the world's forests through large-scale expansion of soybean and oil palm plantations, leading to forest clearing, biodiversity loss and disease emergence, expulsion of subsistence farmers, and potential increases in food prices and emissions of carbon dioxide to the atmosphere. Investigators must consider the full range of policy options, supported by more comprehensive, flexible, and transparent assessment methods.
RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells
Authors: M. T. Zdrenghea, A. G. Telcian, V. Laza-Stanca, C. M. Bellettato, M. R. Edwards, A. Nikonova, M. R. Khaitov, N. Azimi, V. Groh, P. Mallia, S. L. Johnston, L. A. Stanciu
Journal: European Respiratory Journal (2011)

The cytokine interleukin (IL)-15, major histocompatibility complex (MHC) class I molecules and MHC class I chain-related proteins (MIC) A and B are involved in cellular immune responses to virus infections but their role in respiratory syncytial virus (RSV) infection has not been studied. We aimed to determine how RSV infection modulates IL-15 production, MHC class I and MICA expression in respiratory epithelial cells, the molecular pathways implicated in virus-induced IL-15 production and how interferon (IFN)-γ alters RSV-induced IL-15 production and MHC class I and MICA expression. We infected respiratory epithelial cell lines (A549 and BEAS-2B cells) and primary bronchial epithelial cells with RSV and measured production of IL-15, expression of MHC I and MICA and the role of the transcription factor nuclear factor (NF)-κB. We report here that RSV increases IL-15 in respiratory epithelial cells <i>via</i> virus replication and NF-κB-dependent mechanisms. Furthermore, RSV infection of epithelial cells upregulated cell surface expression of MICA and levels of soluble MICA. IFN-γ upregulated RSV induction of soluble IL-15 but inhibited induction of MICA. Upregulation of IL-15, MHC I and MICA are likely to be important mechanisms in activating immune responses to RSV by epithelial cells.
The role of chemo-attractant lipoxygenase products in the pathogenesis of psoriasis
Authors: R. D. R. CAMP, A. I. MALLET, F. M. CUNNINGHAM, E. WONG, P. M. WOOLLARD, P. DOWD, A. KOBZA BLACK, M. W. GREAVES
Journal: British Journal of Dermatology (1985)

Journal Article The role of chemo‐attractant lipoxygenase products in the pathogenesis of psoriasis Get access R. D. R. CAMP, R. D. R. CAMP Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Dr R. D. R. Camp, Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar A. I. MALLET, A. I. MALLET Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar F. M. CUNNINGHAM, F. M. CUNNINGHAM Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar E. WONG, E. WONG Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar P. M. WOOLLARD, P. M. WOOLLARD Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar P. DOWD, P. DOWD Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar A. KOBZA BLACK, A. KOBZA BLACK Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar M. W. GREAVES M. W. GREAVES Institute of Dermatology, Homerton Grove, London E9 6BX, U. K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s28, 1 July 1985, Pages 98–103, https://doi.org/10.1111/j.1365-2133.1985.tb15634.x Published: 01 July 1985