tbuckley/cabot-search huggingface dataset:
Multiple HNPCC tumours: ask the family!
Authors: H T LYNCH, P WATSON
Journal: Gut (1998)

See article on page 664 

Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common conditions predisposing to colorectal cancer (CRC). Affecting less than 1% of the general population, HNPCC confers a lifetime risk of CRC estimated at over 80%; the risk to age 40 may exceed 30%.1 It can be caused by inherited mutations in one of the several DNA mismatch repair (MMR) genes. The resulting DNA MMR deficiency in neoplastic tissue gives rise to microsatellite alterations, a reflection of genomic instability.2Patients with HNPCC are at increased risk of cancers other than CRC, including cancers of the endometrium, ovary, stomach, small bowel, and the upper urinary tract (renal pelvis and ureter).3 

Despite recent advances in the understanding of the molecular genetic basis of HNPCC, we are still far from the clinical ideal of being able to identify patients with this disorder among the population we serve. Tests for mutations in MMR genes are problematic. There are classic HNPCC families with clear linkage to one of the MMR genes which have been exhaustively but fruitlessly searched for mutations, indicating some types of HNPCC associated mutations are not identifiable by current technologies. Even when an inherited alteration of an MMR gene is discovered, its causal role …
Wind turbine noise
Authors: C. D. Hanning, A. Evans
Journal: BMJ (2012)

<h3>Background</h3> An autologous arteriovenous fistula (AVF) is the preferred hemodialysis vascular access, but successful creation is hampered by high rates of AVF failure. This study aimed to evaluate patient and surgical factors associated with AVF failure to improve vascular access selection and outcomes. <h3>Methods</h3> This is a <i>post hoc</i> analysis of all participants of FAVOURED, a multicenter, double-blind, multinational, randomized, placebo-controlled trial evaluating the effect of fish oil and/or aspirin in preventing AVF failure in patients receiving hemodialysis. The primary outcome of AVF failure was a composite of fistula thrombosis and/or abandonment and/or cannulation failure at 12 months post-AVF creation, and secondary outcomes included individual outcome components. Patient data (demographics, comorbidities, medications, and laboratory data) and surgical factors (surgical expertise, anesthetic, intraoperative heparin use) were examined using multivariable logistic regression analyses to evaluate associations with AVF failure. <h3>Results</h3> Of 536 participants, 253 patients (47%) experienced AVF failure during the study period. The mean age was 55±14.4 years, 64% were male, 45% were diabetic, and 4% had peripheral vascular disease. Factors associated with AVF failure included female sex (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.20 to 2.68), lower diastolic BP (OR for higher DBP, 0.85; 95% CI, 0.74 to 0.99), presence of central venous catheter (OR, 1.49; 95% CI, 1.02 to 2.20; <i>P</i>=0.04), and aspirin requirement (OR, 1.60; 95% CI, 1.00 to 2.56). <h3>Conclusions</h3> Female sex, requirement for aspirin therapy, requiring hemodialysis <i>via</i> a central venous catheter, and lower diastolic BP were factors associated with higher odds of AVF failure. These associations have potential implications for vascular access planning and warrant further studies.
Role of the Autonomic Nervous System in Modulating Cardiac Arrhythmias
Authors: Mark J. Shen, Douglas P. Zipes
Journal: Circulation Research (2014)

The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.
Production of epithelial cell growth factors by lamina propria mononuclear cells.
Authors: J R Lowes, J D Priddle, D P Jewell
Journal: Gut (1992)

The effects of lamina propria mononuclear cell culture supernatant on epithelial cell DNA synthesis were studied using cells isolated from patients with inflammatory bowel disease and normal controls. Supernatants from resting and phytohaemagglutinin stimulated cells were studied and supernatants that strongly promoted DNA synthesis were pooled, and growth factor activity partially characterised. The effects of recombinant interleukins-1 beta,2,3,interferon-gamma, and granulocyte macrophage colony stimulating factor were tested in the same system. Resting lamina propria mononuclear cells produce factors that increase DNA synthesis. Production of these factors is increased by phytohaemagglutinin stimulation. No significant differences were found in production of these factors between patients with inflammatory bowel disease and normal controls. The molecular weight of the active factor(s) lies in the region 31-48 kD. Chromatofocusing produced two peaks of activity, one in the region pk 5.5 and one around pk 6.4. The activity was heat and acid pH labile. Activity was not destroyed, however, by 0.05% trypsin. Recombinant granulocyte macrophage colony stimulating factor was a weak stimulus to epithelial DNA synthesis, interleukin-1 beta was weakly inhibitory but other cytokines tested did not have any effect. Granulocyte macrophage colony stimulating factor is probably important in controlling epithelial cell growth.
A New Disease: a Nasal Form of Pigeon Breeder's Disease
Authors: Z. PELIKAN, M. PELIKAN‐FILIPEK
Journal: Allergy (1983)

In 47 allergic rhinitis patients regularly exposed to pigeons, nasal provocation tests with pigeon dropping extracts, in combination with other parameters, were performed. Twenty‐five of the 47 patients developed a late nasal response (LNR) to pigeon droppings (53%), six of them an isolated response and 19 a dual response (immediate + late). The precipitating antibodies to pigeon droppings were positive in 20 (80%) and to pigeon serum in nine LNR patients (36%). Late skin responses to pigeon droppings occurred in 15 (60%) and to pigeon serum in seven LNR patients (28%). In 13 patients (52%) general malaise, in seven (28%) increased blood eosinophilia, in nine (36%) increased body temperature and in 11 (44%) haemorrhages in the nasal mucosa were observed during the LNR. The results of this study provide evidence for the existence of a new disease, a nasal form of pigeon breeder's disease.
Prostate Cancer Detection in the “Grey Area” of Prostate-Specific Antigen Below 10 ng/ml: Head-to-Head Comparison of the Updated PCPT Calculator and Chun’s Nomogram, Two Risk Estimators Incorporating Prostate Cancer Antigen 3
Authors: Sisto Perdonà, Vitor Cavadas, Giuseppe Di Lorenzo, Rocco Damiano, Gennaro Chiappetta, Paola Del Prete, Renato Franco, Giuseppina Azzarito, Stefania Scala, Claudio Arra, Marco De Sio, Riccardo Autorino
Journal: European Urology (2010)
Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells
Authors: S. Meindl, A. Rot, W. Hoetzenecker, S. Kato, H.S. Cross, A. Elbe-Burger
Journal: British Journal of Dermatology (2005)

1alpha,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)], the active metabolite of vitamin D, exerts its activities by binding to the vitamin D receptor (VDR) with subsequent function as a transcription factor. Targeted ablation of the VDR in mice results in rickets and alopecia.To study the consequences of VDR deficiency for skin physiology, and to investigate the mechanisms of the immunosuppressive effect of 1,25(OH)(2)D(3) on LC.We studied the structural, phenotypic and functional properties of skin and individual skin leucocyte populations in VDR(-/-) mice.The lack of VDR induced a wide spectrum of pathologies including dermal deposition of collagen, enlargement of sebaceous glands, dilation of the hair follicles, development of epidermal cysts, increased numbers of dendritic epidermal T cells (DETC) and hyperkeratosis. Ageing aggravated these changes. Intriguingly, Langerhans cells (LC) were indistinguishable in distribution, morphology and number compared with controls. In vitro, LC underwent a maturation/migration process similar to LC from control mice. Pretreatment of epidermal cells or LC-enriched epidermal cell suspensions with 1,25(OH)(2)D(3) impaired LC maturation and T-cell stimulatory capacity from VDR(+/+) but not VDR(-/-) mice, demonstrating that LC are targets of vitamin D(3) and that interaction between vitamin D(3) and LC results in a suppression of LC activity.Our data imply that VDR expression controls dermal collagen production, hair development and growth, proliferation of sebaceous glands and the homeostasis of DETC. Surprisingly, VDR deficiency does not influence LC phenotype and function.
Endothelial Dysfunction and Increased Arterial Intima-Media Thickness in Children With Type 1 Diabetes
Authors: Mikko J. Järvisalo, Maria Raitakari, Jyri O. Toikka, Anne Putto-Laurila, Riikka Rontu, Seppo Laine, Terho Lehtimäki, Tapani Rönnemaa, Jorma Viikari, Olli T. Raitakari
Journal: Circulation (2004)

Endothelial dysfunction may play a pathophysiological role in the development of atherosclerosis in subjects with type 1 diabetes. We examined whether alterations in vascular endothelial function exist in children with type 1 diabetes and tested the hypothesis that endothelial dysfunction is associated with early structural atherosclerotic vascular changes in these children.Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid artery intima-media thickness (IMT) in 75 children (mean age 11+/-2 years), 45 with type 1 diabetes (diabetes duration 4.4+/-2.9 years) and 30 healthy control children. Children with diabetes had lower peak FMD response (4.4+/-3.4% versus 8.7+/-3.6%, P<0.001) and increased IMT (P<0.001) compared with controls. Sixteen children with diabetes (36%) had endothelial dysfunction defined as total FMD response in the lowest decile for normal children. These children had increased carotid IMT (0.58+/-0.05 versus 0.54+/-0.04 mm, P=0.01) and higher LDL cholesterol concentration (2.63+/-0.76 versus 2.16+/-0.60 mmol/L, P=0.03) compared with diabetic children without endothelial dysfunction. Multivariate correlates of increased IMT included diabetes group (P=0.03), low FMD (P=0.03), and high LDL cholesterol (P=0.08).Impaired FMD response is a common manifestation in children with type 1 diabetes and is associated with increased carotid artery IMT. These data suggest that endothelial dysfunction in children with type 1 diabetes may predispose them to the development of early atherosclerosis.
Association of Arsenic with Adverse Pregnancy Outcomes/Infant Mortality: A Systematic Review and Meta-Analysis
Authors: Reginald Quansah, Frederick Ato Armah, David Kofi Essumang, Isaac Luginaah, Edith Clarke, Kissinger Marfoh, Samuel Jerry Cobbina, Edward Nketiah-Amponsah, Proscovia Bazanya Namujju, Samuel Obiri, Mawuli Dzodzomenyo
Journal: Environmental Health Perspectives (2015)

Exposure to arsenic is one of the major global health problems, affecting > 300 million people worldwide, but arsenic's effects on human reproduction are uncertain. We conducted a systematic review and meta-analysis to examine the association between arsenic and adverse pregnancy outcomes/infant mortality. We searched PubMed and Ovid MEDLINE (from 1946 through July 2013) and EMBASE (from 1988 through July 2013) databases and the reference lists of reviews and relevant articles. Studies satisfying our a priori eligibility criteria were evaluated independently by two authors. Our systematic search yielded 888 articles; of these, 23 were included in the systematic review. Sixteen provided sufficient data for our quantitative analysis. Arsenic in groundwater (≥ 50 μg/L) was associated with increased risk of spontaneous abortion (6 studies: OR = 1.98; 95% CI: 1.27, 3.10), stillbirth (9 studies: OR = 1.77; 95% CI: 1.32, 2.36), moderate risk of neonatal mortality (5 studies: OR = 1.51; 95% CI: 1.28, 1.78), and infant mortality (7 studies: OR = 1.35; 95% CI: 1.12, 1.62). Exposure to environmental arsenic was associated with a significant reduction in birth weight (4 studies: β = -53.2 g; 95% CI: -94.9, -11.4). There was paucity of evidence for low-to-moderate arsenic dose. Arsenic is associated with adverse pregnancy outcomes and infant mortality. The interpretation of the causal association is hampered by methodological challenges and limited number of studies on dose response. Exposure to arsenic continues to be a major global health issue, and we therefore advocate for high-quality prospective studies that include individual-level data to quantify the impact of arsenic on adverse pregnancy outcomes/infant mortality.
Abstract 914: Ciclopirox olamine (CPX) inhibits breast cancer cell proliferation by blocking the formation of a PEAK1-Src-eIF5a protein complex
Authors: Jessica M. Weems, Theresa A. Reno, Richard L. Klemke
Journal: Cancer Research (2012)

Abstract The antimycotic drug ciclopirox olamine (CPX) is being evaluated in clinical trials as a re-positioned anti-cancer agent. Although low micromolar concentrations of CPX have been shown to inhibit cell proliferation and solid tumor growth in preclinical models, the mechanism of action remains poorly characterized. In the present study, we demonstrated that CPX treatment potently inhibits cell proliferation and protein expression of the novel tyrosine kinase pseudopodium-enriched atypical kinase 1 (PEAK1) in several breast cancer cell lines, whereas forced overexpression of PEAK1 results in decreased sensitivity to CPX treatment and increased proliferation. PEAK1 protein expression modulates Src kinase activity in proliferating cancer cells and is upregulated in a number of human malignancies, but the mechanisms that regulate its expression have not been characterized (PNAS, 107(24), 10920-5). Here we demonstrate that CPX treatment inhibits the hypusination of eukaryotic translation initiation factor 5a (eIF5a), leading to decreased PEAK1 protein expression and Src kinase activity. siRNA knockdown of eIF5a inhibited PEAK1 expression and Src activity. Likewise, inhibition of Src kinase in cancer cells prevented eIF5a and PEAK1 protein expression, indicating that these proteins tightly regulate one another. Further investigation revealed that in breast cancer cells PEAK1, Src, and eIF5a form a complex which is disassociated by CPX treatment. These findings support a model in which PEAK1 amplification in malignant cells promotes increased Src kinase activity thereby leading to increased eIF5a-mediated PEAK1 protein expression levels. Taken together, these data indicate that CPX has significant potential as a repositioned therapeutic to combat PEAK1 and Src driven human cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 914. doi:1538-7445.AM2012-914
A neutrophil lysozyme leak in patients with familial mediterranean fever
Authors: Menashe Bar‐Eli, Mary C. Territo, Robert S. Peters, Arthur D. Schwabe
Journal: American Journal of Hematology (1981)

Abstract Polymorphonuclear cells derived from the peripheral blood of patients with Familial Mediterranean Fever release more lysozyme in response to high temperatures (42°, 46°C) than do control cells. No differences between the FMF and control cells were observed in the release of acid phosphatase, β‐glucuronidase, or lactoferrin. Colchicine treatment had no effect on the measurable release of the enzyme from PMNs derived from FMF patients. The increased release of lysozyme in response to high temperatures appears to be specific to FMF neutrophils, and was not found in PMNs from non‐FMF patients with febrile or inflammatory diseases, nor was it seen in monocytes derived from the FMF patients. It is suggested that the increased release of lysozyme from the neutrophils may be of importance in the pathogenesis of FMF.
Trauma Centers and Trauma Systems
Authors: Donald D. Trunkey
Journal: JAMA (2003)

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A dynamic electrical record of the pathway of human His bundle activation from surface mapping.
Authors: L G Horan, N C Flowers, G S Sohi
Journal: Circulation Research (1982)

Body surface potential maps of human His bundle activity have been difficult to product for two reasons: (1) The peak surface potentials are often less than 5 muv, and (2) the simultaneous atrial repolarization potentials frequently exceed 100 muv. We have therefore amplified surface signals 25 times the standard gain of 1000, and then removed by cross-correlation the static pattern of atrial repolarization for serial 1-msec maps of the P-R segment in five normal men. A consistent finding emerged: a positive anterior chest peak appeared 40 msec before QRS onset, and then-within 10 msec-spread out into a long, low transverse mound before disappearing in 5 more msec. The map data were analytically converted to serial electrical sources: the center of electrical activity moved first slightly down, then directly forward, before retracing its path and disappearing. The retrace and accompanying surface spread-out strongly suggests diverging dipolar sources. Thus the data fit a simple heart source which moves anteriorly and then breaks into two (right and left)-as expected from activation of the bundle of His and its bifurcation into left and right bundle branches.
Mortality in British military participants in human experimental research into chemical warfare agents at Porton Down: cohort study
Authors: K M Venables, C Brooks, L Linsell, T J Keegan, T Langdon, T Fletcher, M J Nieuwenhuijsen, N E S Maconochie, P Doyle, V Beral, L M Carpenter
Journal: BMJ (2009)

<b>Objective</b> To investigate any long term effects on mortality in participants in experimental research related to chemical warfare agents from 1941 to 1989. <b>Design</b> Historical cohort study. <b>Data sources </b>Archive of UK government research facility at Porton Down, UK military personnel records, and national death and cancer records. <b>Participants </b>18 276 male members of the UK armed forces who had spent one or more short periods (median 4 days between first and last test) at Porton Down and a comparison group of 17 600 non-Porton Down veterans followed to 31 December 2004. <b>Main outcome measures</b> Mortality rate ratio of Porton Down compared with non-Porton Down veterans and standardised mortality ratio of each veteran group compared with the general population. Both ratios adjusted for age group and calendar period. <b>Results</b> Porton Down veterans were similar to non-Porton Down veterans in year of enlistment (median 1951) but had longer military service (median 6.2 <i>v</i> 5.0 years). After a median follow-up of 43 years, 40% (7306) of Porton Down and 39% (6900) of non-Porton Down veterans had died. All cause mortality was slightly greater in Porton Down veterans (rate ratio 1.06, 95% confidence interval 1.03 to 1.10, P&lt;0.001), more so for deaths outside the UK (1.26, 1.09 to 1.46). Of 12 cause specific groups examined, rate ratios in Porton Down veterans were increased for deaths attributed to infectious and parasitic (1.57, 1.07 to 2.29), genitourinary (1.46, 1.04 to 2.04), circulatory (1.07, 1.01 to 1.12), and external (non-medical) (1.17, 1.00 to 1.37) causes and decreased for deaths attributed to in situ, benign, and unspecified neoplasms (0.60, 0.37 to 0.99). There was no clear relation between type of chemical exposure and cause specific mortality. The mortality in both groups of veterans was lower than that in the general population (standardised mortality ratio 0.88, 0.85 to 0.90; 0.82, 0.80 to 0.84). <b>Conclusions</b> Mortality was slightly higher in Porton Down than non-Porton Down veterans. With lack of information on other important factors, such as smoking or service overseas, it is not possible to attribute the small excess mortality to chemical exposures at Porton Down.
Stem Cells: Reconstituting Vascular Microenvironment of Neural Stem Cell Niche in Three-Dimensional Extracellular Matrix (Adv. Healthcare Mater. 9/2014)
Authors: Yoojin Shin, Kisuk Yang, Sewoon Han, Hyun‐Ji Park, Yun Seok Heo, Seung‐Woo Cho, Seok Chung
Journal: Advanced Healthcare Materials (2014)

On page 1457 S.-W. Cho, S. Chung, and co-workers show that neural stem cell (NSC)-vascular niche consisting of a brain vasculature and 3D extracellular matrix (ECM) is reconstituted in a microfluidic system. The in vivo-like microenvironment reconstituted in this system allows NSCs to adopt physiologically relevant phenotypes through the combined effects of 3D ECM and vasculature.