tbuckley/cabot-search huggingface dataset:
Insulin-Like Growth Factor Binding Protein-5 Is a Target of Matrix Metalloproteinase-7: Implications for Epithelial-Mesenchymal Signaling
Authors: Elaine Hemers, Cedric Duval, Catherine McCaig, Mark Handley, Graham J. Dockray, Andrea Varro
Journal: Cancer Research (2005)

Matrix metalloproteinase-7 (MMP-7) is localized to epithelial cells and is up-regulated in many cancers and in inflammation. We now report that MMP-7 targets a key mesenchymal cell type, the myofibroblast. Recombinant MMP-7 stimulated the proliferation and migration of human colonic myofibroblasts. These responses were partly attributable to activation of other MMPs, notably MMP-3 and MMP-8, and to stimulation of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Using a proteomic approach, we identified insulin-like growth factor binding protein-5 (IGFBP-5) as a previously unsuspected target of MMP-7 produced by colonic myofibroblasts. We present evidence that the MMP-7 cleavage of IGFBP-5 liberates IGF-II that functions as an autocrine myofibroblast growth factor. Thus, MMP-7 may act as a signal from epithelial cells for local recruitment of myofibroblasts and stimulation of their proliferation. Similar effects of MMP-7 produced in epithelial tumors might account for the expansion of stroma through activation of myofibroblasts.
Complementary therapy used by patients with cancer
Authors: E Ernst
Journal: BMJ (1994)

and for their mothers collected the information shown in the table and other data such as place of birth, number of other children in the household, and parental social class and smoking.Finally, we are aware that the accuracy of breast feeding recall may represent a problem after so many years, but why should we suspect a differential recall between the two study groups?We agree that our results must be treated with caution until other evidence supports them.Among our study groups the mothers of low socioeconomic status were more likely to have breast fed their infants.Thus, it is possible that infants who were breast fed longer were also exposed early in life to some viruses, but after our data were stratified by social class, the association between breast feeding and multiple sclerosis did not change.An intriguing point is that the fatty acid composition of human milk may be influenced by maternal diet,4 and diet may vary in mothers of differing socioeconomic status and from different countries.
Electrocardiographic Changes in Pulmonary Collapse Therapy
Authors: CHARLES SILVERBERG, DAVID FELDMAN
Journal: Circulation (1950)

The effect of thoracoplasty and phrenemphraxis upon the electrocardiographic pattern of tuberculous patients was studied. Alteration in the size of QRS complexes resulted in variable changes in the mean electrical axis. Some alterations in T waves occurred in all leads, occasionally resulting in inversion of the T waves in Leads CF 2 , CF 4 and/or CF 5 . There was no pattern characteristic of any of the collapse procedures studied.
Abstract 1365: Epigenetic modification of LY6K in CGI shore and CGI regulates LY6K gene activation and metastatic function in breast cancer
Authors: Hyun Kyung Kong, Sae Jeong Park, Ye Sol Kim, Jong Hoon Park
Journal: Cancer Research (2014)

Abstract Lymphocyte antigen 6 complex locus K (LY6K) is associated with development of the immune response and carcinogenesis. Elevated LY6K by AP-1 activation induces cell invasion and metastasis through activating the Raf-1/MEK/ERK signaling pathway. However, the exact epigenetic mechanism of LY6K gene expression has yet to be clarified. To elucidate the epigenetic mechanism of LY6K gene regulation and expression, CpG island and 5′CGI shore in the region around transcription start site of the LY6K were predicted using UCSC genome browser and Methprimer software. We performed MSP, bisulfite pyro-sequnecing, and bisulfite sequencing to investigate the DNA methylation status of CpG sites from -400 to +500 on the LY6K CGI and 5′CGI shore. Breast cancer cells with low LY6K expression were highly methylated in the both CGI and 5′CGI shore region, whereas high LY6K expression cell lines had low methylation levels. Moreover, 5-Aza-dC, demethylaing agent, treatment of cells with low LY6K expression caused elevation of LY6K expression and finally leads wound healing. To further validate the inverse correlation between LY6K 5′CGI shore methylation and LY6K expression in vivo seen in breast cancer cell lines, we performed bisulfite pyro-sequencing and tissue microarray using breast carcinoma samples. LY6K expression inversely correlates with methylation status and histone modification of 5′CGI shore in the LY6K promoter in human breast cancers. An understanding of epigenetic changes in LY6K may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with breast cancer. Citation Format: Hyun Kyung Kong, Sae Jeong Park, Ye Sol Kim, Jong Hoon Park. Epigenetic modification of LY6K in CGI shore and CGI regulates LY6K gene activation and metastatic function in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1365. doi:10.1158/1538-7445.AM2014-1365
THE COMPARATIVE PATHOLOGY OF HYPERPLASTIC AND SUPPURATIVE ETHMOIDITIS
Authors: ROSS HALL SKILLERN
Journal: JAMA (1910)

Last year, when the subject of hyperplastic ethmoiditis, in contradistinction to the suppurative type, was presented before one of our laryngologic societies, the question was raised as to whether these conditions were not identical, or that one was merely a sequela or a complication of the other, as the case might be. It is my intention to bring before you to-day the microscopic pathology of these two conditions and show that the ethmoidal structures and their components are, under certain conditions, dissimilarly affected, and, indeed, often in dia-metrically
Almost a Revolution: Mental Health Law and the Limits of Change
Authors: Landy F. Sparr
Journal: JAMA (1995)

As a prominent commentator and major investigator in the development of forensic psychiatry, Dr Paul Appelbaum has witnessed a profound change in the relationship between mental illness and the law. The civil rights movement of the 1960s not only dealt with racial equality but also extended to the mentally ill, as early optimism about benefits of psychiatric treatment gave way to doubts. Appelbaum, who experienced firsthand the "swirl of events," was a key participant in this "unprecedented epoch of change." Now, in the 1990s, as cries for change have subsided, Appelbaum looks back at a tumultuous era and assesses four important mental health law reforms: (1) changes in civil commitment laws that included strict procedural protections for patients; (2) the imposition of liability on mental health professionals for violent acts committed by their patients; (3) a recognition of the right of psychiatric patients to refuse treatment, particularly with antipsychotic medications;
Malnutrition linked to literacy problems in quarter of world's schoolchildren
Authors: A. O'Dowd
Journal: BMJ (2013)

Experts have warned that around a quarter of schoolchildren globally could have serious literacy problems as a result of malnutrition.

A report published by the charity Save the Children on 28 May claims that a child’s ability to read and write simple sentences and answer basic mathematical questions correctly is severely damaged if they do not have a nutritious diet.

The report Food for Thought contains new research that involved following …
Duodenal adenomatosis in familial adenomatous polyposis
Authors: S Bulow
Journal: Gut (2004)

The prevalence of duodenal carcinoma is much higher in familial adenomatous polyposis (FAP) than in the background population, and duodenal adenomatosis is found in most polyposis patients.To describe the long term natural history of duodenal adenomatosis in FAP and evaluate if cancer prophylactic surveillance of the duodenum is indicated.A prospective five nation study was carried out in the Nordic countries and the Netherlands.A total of 368 patients were examined by gastroduodenoscopy at two year intervals during the period 1990-2001.At the first endoscopy, 238 (65%) patients had duodenal adenomas at a median age of 38 years. Median follow up was 7.6 years. The cumulative incidence of adenomatosis at age 70 years was 90% (95% confidence interval (CI) 79-100%), and of Spigelman stage IV 52% (95% CI 28-76%). The probability of an advanced Spigelman score increased during the study period (p<0.0001) due to an increasing number and size of adenomas. Two patients had asymptomatic duodenal carcinoma at their first endoscopy while four developed carcinoma during the study at a median age of 52 years (range 26-58). The cumulative incidence rate of cancer was 4.5% at age 57 years (95% CI 0.1-8.9%) and the risk was higher in patients with Spigelman stage IV at their first endoscopy than in those with stages 0-III (p<0.01).The natural course of duodenal adenomatosis has now been described in detail. The high incidence and increasing severity of duodenal adenomatosis with age justifies prophylactic examination, and a programme is presented for upper gastrointestinal endoscopic surveillance.
Hepatocellular Neoplasms Induced by Low-Number Pancreatic Islet Transplants in Autoimmune Diabetic BB/Pfd Rats
Authors: Frank Dombrowski, Chantal Mathieu, Matthias Evert
Journal: Cancer Research (2006)

Abstract It has been shown that combined high local hyperinsulinism and hyperglycemia after low-number islet transplantation into the livers of streptozotocin-diabetic rats lead to the development of hepatocellular neoplasms but a substantial cocarcinogenic effect of genotoxic streptozotocin could not be ruled out completely. Thus, we herein investigated this model in BB/Pfd rats (n = 805; nine experimental groups), which develop spontaneous autoimmune diabetes similar to human type 1 diabetes. After low-number islet transplantation (n = 450), the liver acini downstream of the islets show insulin-induced alterations: massive glycogen and/or fat accumulation, translocation of the insulin receptor, decrease in glucose-6-phosphatase activity, increase in expression of insulin-like growth factor (IGF)-I, IGF-II/mannose-6-phosphate receptor, insulin receptor substrate-1, Raf-1, and Mek-1, corresponding to clear cell preneoplastic foci of altered hepatocytes known from chemical hepatocarcinogenesis and identical to that in streptozotocin-diabetic Lewis rats. After 6 months, many altered liver acini progressed to other types of preneoplasias often accompanied by an overexpression of the glutathione-S transferase (placental form), IGF-I receptor, and transforming growth factor (TGF)-α. After 12 to 15 and 15 to 18 months, 52% and 100% of the animals showed one or multiple hepatocellular adenomas or hepatocellular carcinomas (HCCs), respectively. Conclusively, this study identifies combined hyperinsulinism and hyperglycemia as a carcinogenic mechanism for the development of HCCs in diabetic rats. Hepatocarcinogenesis is independent from additional genotoxic compounds (i.e., streptozotocin), but is primarily triggered by increased intracellular insulin signaling via pathways associated with cell growth and proliferation, such as the Ras-Raf-mitogen-activated protein kinase pathway and the IGF system, and secondarily involves other growth factors, such as TGF-α. (Cancer Res 2006; 66(3): 1833-43)
Predictors of Overweight During Childhood in Offspring of Parents With Type 1 Diabetes
Authors: Sandra Hummel, Maren Pflüger, Susanne Kreichauf, Michael Hummel, Anette-G. Ziegler
Journal: Diabetes Care (2009)

We thank Rodekamp et al. (1) for their interest in our article (2) on predictors of overweight during childhood in offspring of parents with type 1 diabetes. In our study, we analyzed overweight risk in children participating in the German BABYDIAB study, including both the offspring of mothers with and without type 1 diabetes. Plagemann et al. (3) have previously suggested that the beneficial effects of breast-feeding on childhood obesity are lost when mothers are affected by diabetes. The authors have advised caution with respect to encouraging breast-feeding in mothers with diabetes. Rodekamp et al. have raised some questions on this issue, which we will attempt to answer by reporting data on …
Evaluation of Vascular Delivery Methodologies to Enhance rAAV6-mediated Gene Transfer to Canine Striated Musculature
Authors: Paul Gregorevic, Brian R Schultz, James M Allen, Jeffrey B Halldorson, Michael J Blankinship, Norman A Meznarich, Christian S Kuhr, Caitlin Doremus, Eric Finn, Denny Liggitt, Jeffrey S Chamberlain
Journal: Molecular Therapy (2009)

A growing body of research supports the development of recombinant adeno-associated viral (rAAV) vectors for delivery of gene expression cassettes to striated musculature as a method of treating severe neuromuscular conditions. However, it is unclear whether delivery protocols that achieve extensive gene transfer in mice can be adapted to produce similarly extensive gene transfer in larger mammals and ultimately patients. Consequently, we sought to investigate methodological modifications that would facilitate rAAV-mediated gene transfer to the striated musculature of canines. A simple procedure incorporating acute (i) occlusion of limb blood flow, (ii) exsanguination via compression bandage, and (iii) vector "dwell" time of <20 minutes, markedly enhanced the transduction of limb muscles, compared with a simple bolus limb infusion of vector. A complementary method whereby vector was infused into the jugular vein led to efficient transduction of cardiomyocytes and to a lesser degree the diaphragm. Together these methods can be used to achieve transgene expression in heart, diaphragm, and limb muscles of juvenile dogs using rAAV6 vectors. These results establish that rAAV-mediated gene delivery is a viable approach to achieving systemic transduction of striated musculature in mammals approaching the dimensions of newborn humans. A growing body of research supports the development of recombinant adeno-associated viral (rAAV) vectors for delivery of gene expression cassettes to striated musculature as a method of treating severe neuromuscular conditions. However, it is unclear whether delivery protocols that achieve extensive gene transfer in mice can be adapted to produce similarly extensive gene transfer in larger mammals and ultimately patients. Consequently, we sought to investigate methodological modifications that would facilitate rAAV-mediated gene transfer to the striated musculature of canines. A simple procedure incorporating acute (i) occlusion of limb blood flow, (ii) exsanguination via compression bandage, and (iii) vector "dwell" time of <20 minutes, markedly enhanced the transduction of limb muscles, compared with a simple bolus limb infusion of vector. A complementary method whereby vector was infused into the jugular vein led to efficient transduction of cardiomyocytes and to a lesser degree the diaphragm. Together these methods can be used to achieve transgene expression in heart, diaphragm, and limb muscles of juvenile dogs using rAAV6 vectors. These results establish that rAAV-mediated gene delivery is a viable approach to achieving systemic transduction of striated musculature in mammals approaching the dimensions of newborn humans.
Methotrexate versus Cyclosporine in Moderate-to-Severe Chronic Plaque Psoriasis
Authors: Vera M.R. Heydendael, Phyllis I. Spuls, Brent C. Opmeer, Corianne A.J.M. de Borgie, Johannes B. Reitsma, Wouter F.M. Goldschmidt, Patrick M.M. Bossuyt, Jan D. Bos, Menno A. de Rie
Journal: New England Journal of Medicine (2003)

Methotrexate and cyclosporine are well-known systemic therapies for moderate-to-severe chronic plaque psoriasis. We conduced a randomized, controlled trial comparing methotrexate and cyclosporine in terms of effectiveness, side effects, and the quality of life.
Tension and Hypertension
Authors: Thomas G. Pickering
Journal: JAMA (1993)

Many patients with high blood pressure consider that the term<i>hypertension</i>refers to an elevation of nervous as well as physical tension, an idea first proposed in 1905 by Gaisböck, who observed that in men with high systolic pressure "one finds an unusual frequency of those who as directors of big enterprises had a great deal of responsibility and who, after long periods of psychic overwork, became nervous."<sup>1</sup>Many physicians, on the other hand, doubt that mental factors play any significant role in the development of hypertension. The study by Markovitz et al<sup>2</sup>in this issue ofTHE JOURNALoffers support for the patients' viewpoint. The concept of a "hypertensive personality" has been debated for about 50 years, but there is still no consensus as to whether it really exists or, if it does, how it should be defined or measured. Three views have been advocated: first, that
Ustekinumab induces rapid clearing of erythrodermic psoriasis after failure of antitumour necrosis factor therapies
Authors: J. Santos-Juanes, P. Coto-Segura, A. Mas-Vidal, C. Galache Osuna
Journal: British Journal of Dermatology (2010)

Journal Article Ustekinumab induces rapid clearing of erythrodermic psoriasis after failure of antitumour necrosis factor therapies Get access J. Santos‐Juanes, J. Santos‐Juanes Service of Dermatology II, Facultad de Medicina, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain Search for other works by this author on: Oxford Academic Google Scholar P. Coto‐Segura, P. Coto‐Segura Service of Dermatology II, Facultad de Medicina, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Mas‐Vidal, A. Mas‐Vidal Service of Dermatology II, Facultad de Medicina, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain Search for other works by this author on: Oxford Academic Google Scholar C. Galache Osuna C. Galache Osuna Section of Dermatology, Hospital of Cabueñes, Gijón, Spain E‐mail: jsantosj@hca.es Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 5, 1 May 2010, Pages 1144–1146, https://doi.org/10.1111/j.1365-2133.2010.09669.x Published: 01 May 2010
Screening and brief intervention for alcohol use disorders in primary care
Authors: E. Murray
Journal: BMJ (2013)

Simple screening and provision of written information may be enough for most patients 

Excess alcohol consumption is a growing public health problem, causing around 5.3% of deaths in those aged under 60 years worldwide.1 In England, about one in four adults aged 16-65 (about seven million people) drink hazardously or harmfully.2 Alcohol accounts for 10% of disability adjusted life years (DALYs) and costs to the NHS of around £3bn (€3.7bn; $4.8bn) each year.3 High alcohol consumption is one of the top modifiable risk factors for premature morbidity and mortality, along with smoking and hypertension, yet much less research has been done on alcohol use disorders than on smoking or hypertension. The publication of Kaner and colleagues’ linked paper (doi:10.1136/bmj.e8501), which reports the findings of the SIPS (Screening and Intervention Programme for Sensible drinking) trial in primary care, is therefore welcome.4

Although screening and brief intervention reduce alcohol consumption by …
Pancreatic Cancer Risk and Nutrition-Related Methyl-Group Availability Indicators in Male Smokers
Authors: R. Z. Stolzenberg-Solomon, D. Albanes, F. J. Nieto, T. J. Hartman, J. A. Tangrea, M. Rautalahti, J. Sehlub, J. Virtamo, P. R. Taylor
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Few risk factors for pancreatic cancer have been identified, with age and cigarette smoking being the most consistent. The protective effect associated with consumption of fruits and vegetables—the major dietary sources of folate—is suggestive of a role for factors influencing cellular methylation reactions; however, to our knowledge, no study has investigated this relationship. Whether biochemical indicators of methyl-group availability are associated with exocrine pancreatic cancer risk was the focus of this investigation. METHODS: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years. One hundred twenty-six subjects with incident exocrine pancreatic cancer were matched by date of baseline blood draw (±30 days), study center, age (±5 years), trial intervention group, and completion of dietary history to 247 control subjects, who were alive and free from cancer at the time the case subjects were diagnosed. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined by use of conditional logistic regression. Reported P values are two-tailed. RESULTS: Serum folate and pyridoxal-5′-phosphate (PLP) concentrations showed statistically significant inverse dose-response relationships with pancreatic cancer risk, with the highest serum tertiles having approximately half the risk of the lowest (folate: OR = 0.45; 95% CI = 0.24-0.82; P for trend = .009, and PLP: OR = 0.48; 95% CI = 0.26-0.88; P for trend = .02). An increased pancreatic cancer risk was also observed with greater exposure to cigarettes (e.g., pack-years [number of packs smoked per day × number of years of smoking], highest versus lowest quartile: OR = 2.13; 95% CI = 1.13-3.99; P for trend = .04). CONCLUSIONS: These results support the hypothesis that maintaining adequate folate and pyridoxine status may reduce the risk of pancreatic cancer and confirm the risk previously associated with cigarette smoking.
BMA meeting: Scotland closes loophole to prevent GP surgeries being run by private firms
Authors: Z. Kmietowicz
Journal: BMJ (2008)

Ministers in Scotland are planning to amend the general practitioner contract to make it illegal for private companies to run primary care services in the country.

Nicola Sturgeon, the Scottish health secretary, was greeted by rapturous applause when she told the BMA’s annual representatives’ meeting that the “legal loopholes” allowing private firms to bid to run general practices in Scotland would be closed.

Currently no general practices in Scotland are run by …
Contact Photodermatitis Due to Bithionol and Related Compounds
Authors: Silas E. O'Quinn
Journal: JAMA (1967)

Chemical antibacterial compounds used in soaps and cosmetics were the causative agent in the majority of patients seen with contact photodermatitis. Clinical examinations and patch tests were given to a group of 20 patients with contact photodermatitis due to bithionol and three patients with contact photodermatitis due to hexachlorophene. This problem of photosensitivity presents similar clinical findings and occurs with equal severity in both white and Negro patients. Persistent photosensitivity has occurred in approximately one third of our patients.
Derivation of Serum Transferrin
Authors: Sidney F. Miller
Journal: JAMA (1981)

<h3>To the Editor:—</h3> We would like to comment briefly on the article by Eriksson and Douglass (1980; 243:2049). Our findings are in agreement with their general conclusion that transferrin is useful as an indicator of nutritional status and that it has prognostic value. Unfortunately, their investigation is predicated on an assumption that, if wrong, challenges the validity and clinical applicability of their results. The method used in their study for determining transferrin (serum transferrin=0.8 total iron-binding capacity [TIBC]—43) is a widely propagated formula.<sup>1-3</sup>It has become a commonly accepted conversion owing to the fact that actual serum transferrin quantification requires equipment not yet routinely available. We respectfully wish to question this calculation. In our preliminary investigation, 93 studies were carried out in 33 burn patients. Actual serum transferrin measurements were determined by radial immunodiffusion. Transferrin was also derived in the same group of patients by determining the serum TIBC