tbuckley/cabot-search huggingface dataset:
Signaling pathways in the development of infantile hemangioma
Authors: Yi Ji, Siyuan Chen, Kai Li, Li Li, Chang Xu, Bo Xiang
Journal: Journal of Hematology & Oncology (2014)

Infantile hemangioma (IH), which is the most common tumor in infants, is a benign vascular neoplasm resulting from the abnormal proliferation of endothelial cells and pericytes. For nearly a century, researchers have noted that IH exhibits diverse and often dramatic clinical behaviors. On the one hand, most lesions pose no threat or potential for complication and resolve spontaneously without concern in most children with IH. On the other hand, approximately 10% of IHs are destructive, disfiguring and even vision- or life-threatening. Recent studies have provided some insight into the pathogenesis of these vascular tumors, leading to a better understanding of the biological features of IH and, in particular, indicating that during hemangioma neovascularization, two main pathogenic mechanisms prevail, angiogenesis and vasculogenesis. Both mechanisms have been linked to alterations in several important cellular signaling pathways. These pathways are of interest from a therapeutic perspective because targeting them may help to reverse, delay or prevent hemangioma neovascularization. In this review, we explore some of the major pathways implicated in IH, including the VEGF/VEGFR, Notch, β-adrenergic, Tie2/angiopoietins, PI3K/AKT/mTOR, HIF-α-mediated and PDGF/PDGF-R-β pathways. We focus on the role of these pathways in the pathogenesis of IH, how they are altered and the consequences of these abnormalities. In addition, we review the latest preclinical and clinical data on the rationally designed targeted agents that are now being directed against some of these pathways.
Irradiation induces diverse changes in invasive potential in cancer cell lines
Authors: Mayumi Fujita, Shigeru Yamada, Takashi Imai
Journal: Seminars in Cancer Biology (2015)

Cancer patients without metastasis are generally considered as candidates for curative localized radiation therapy. However, while the benefits of localized radiation have been demonstrated by many clinical studies, recurrences or distant metastases that develop after local treatment remain a major therapeutic challenge. Several in vitro and in vivo studies have reported that irradiation may subsequently alter tumor aggression by reducing or promoting the invasiveness of the remaining cancer cells after radiation, which appears to differ depending on the form of radiation, as well as the investigated cell lines. Cell lines recapitulate cancer heterogeneity based on the characteristics reflected in their genetic abnormalities, and thus can be used as a tool to investigate the genetic basis of cancer aggression. Importantly, molecular insights into this process would allow us to tailor drug treatments for use in combination with local radiation treatment. This review summarizes the diverse responses of cancer cell invasiveness induced by radiation, and discusses the possible molecular pathways and the genetic variations that may affect radiation-altered invasion.
Falling through the Cracks — Virginia Tech and the Restructuring of College Mental Health Services
Authors: Miriam Shuchman
Journal: New England Journal of Medicine (2007)

Interview with Mark Reed on mental illness among college students and mental health care on campus. (07:16)Download Since April 16, when Virginia Tech student Seung-Hui Cho gunned down 27 fellow students and 5 faculty members and injured 24 other people before taking his own life, some disturbing facts about his mental health history have emerged. At various points during Cho's college career, Virginia Tech police officers, professors, and students recognized that he was mentally troubled, but although state psychiatric evaluators once briefly committed him to a psychiatric hospital, it is unclear whether anyone from the school monitored him after his release. These discoveries have left investigators wondering whether the killings could have been prevented — and college . . .
Antibodies Directed against Lewis-Y Antigen Inhibit Signaling of Lewis-Y Modified ErbB Receptors
Authors: Markus Klinger, Hesso Farhan, Herwig Just, Helmut Drobny, Gottfried Himmler, Hans Loibner, Geert C. Mudde, Michael Freissmuth, Veronika Sexl
Journal: Cancer Research (2004)

Abstract The majority of cancer cells derived from epithelial tissue express Lewis-Y (LeY) type difucosylated oligosaccharides on their plasma membrane. This results in the modification of cell surface receptors by the LeY antigen. We used the epidermal growth factor (EGF) receptor family members ErbB1 and ErbB2 as model systems to investigate whether the sugar moiety can be exploited to block signaling by growth factor receptors in human tumor cells (i.e., SKBR-3 and A431, derived from a breast cancer and a vulval carcinoma, respectively). The monoclonal anti-LeY antibody ABL364 and its humanized version IGN311 immunoprecipitated ErbB1 and ErbB2 from detergent lysates of A431 and SKBR-3, respectively. ABL364 and IGN311 blocked EGF- and heregulin-stimulated phosphorylation of mitogen-activated protein kinase [MAPK = extracellular signal-regulated kinase 1/2] in SKBR-3 and A431 cells. The effect was comparable in magnitude with that of trastuzumab (Herceptin) and apparently noncompetitive with respect to EGF. Stimulation of MAPK by ErbB was dynamin dependent and contingent on receptor internalization. ABL364 and IGN311 changed the intracellular localization of fluorescent EGF-containing endosomes and accelerated recycling of intracellular [125I]EGF to the plasma membrane. Taken together, these observations show that antibodies directed against carbohydrate side chains of ErbB receptors are capable of inhibiting ErbB-mediated signaling. The ability of these antibodies to reroute receptor trafficking provides a mechanistic explanation for their inhibitory action.
Needle-Free Jet Injection of Rapid-Acting Insulin Improves Early Postprandial Glucose Control in Patients With Diabetes
Authors: Elsemiek E.C. Engwerda, Cees J. Tack, Bastiaan E. de Galan
Journal: Diabetes Care (2013)

Clamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes.In a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles.Insulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L(-1); P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes.The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.
Validity of spirometry performed in the primary care setting
Authors: Mohammed Harris, Sue Church, Sanjeev Agarwal
Journal: European Respiratory Journal (2012)

Background: Spirometry is a valuable diagnostic tool in the identification of patients with Chronic Obstructive Pulmonary Disease (COPD) in the community.In the primary care setting, low acceptability of spirometric manoeuvres has been reported which may affect the interpretation of results and clinical decision making. T R Schermer et al had demonstrated in the Netherlands that spirometric indices performed by trained general practice staff were marginally but statistically significantly higher than those measured in pulmonary function laboratories. He concluded laboratory and general practice values should not be used interchangeably.  Aims: To evaluate the validity of spirometric testing performed in the community.  Methods: Retrospective study of 405 patients found to have abnormal screening spirometry performed in the community. Screening criteria included adults with a history of smoking. This was followed by repeat spirometry in the hospital pulmonary function laboratory. Data was analyses using SPSS.  Results: N=405, mean age 54 years (range 22 to 78), 46 % (187) and 41% (165) were current and ex-smoker respectively. 78% (318) were using short-acting beta agonist 60% (242) were already on inhaled steroids.0.7% (3) were on oral steroids. 82% (331) had obstructive spirometry. Majority (45%) of them had moderate COPD. 32% and 11% were found to have severe and very severe COPD respectively. The Mean FEV1 in the community (1.52 liters) was slightly higher than the pulmonary function laboratory (1.49 liters).Paired t test study showed the results to be in concordance to the results demonstrated by T R Schermer et al.  Conclusions: This study validates the results published in the Netherlands by T R Schermer et al.
Damp housing and adult respiratory symptoms
Authors: B. Brunekreef
Journal: Allergy (1992)

The relationship between home dampness and adult respiratory symptoms was investigated using data from a parent‐administered questionnaire on childhood respiratory symptoms that also included questions on parental respiratory symptoms. Questionnaires were returned by the parents of 3344 children living in the town of Helmond, The Netherlands. The response was 73%. Home dampness was characterized by reports of damp stains or mould growth on indoor surfaces and was reported by 23.6% and 15.0% of the study population, respectively. Of the homes, 25.4% had dampness and/or mould. Information about respiratory symptoms was collected for the mothers and fathers of a population of 6–12‐year‐old schoolchildren. Symptoms analysed were cough, phlegm, wheeze, asthma, and allergy to pollen or house dust. Cough and phlegm in both men and women were found to be strongly associated with living in a damp home. Weaker associations were found for wheeze and asthma, and there was little association between living in a damp home and allergy to pollen or house dust. Current smoking was strongly associated with cough, phlegm and wheeze in both men and women. Smoking was inversely associated with allergy to pollen or house dust, suggesting that allergic subjects do not start smoking, or give up the habit. The results suggest that the association between home dampness and respiratory symptoms previously reported for children also applies to adults. Suggested mechanisms include exposure to biological contaminants produced by fungi or house dust mites, but it has not yet been documented to what extent these exposures are responsible. Also, the effects of potential biases related to selective migration or home amelioration, or to over‐reporting of symptoms among subjects living in damp homes, or to over‐reporting of home dampness by symptomatic subjects, need further investigation.
Prevalence of haemoglobinopathy in sportsmen in qatar
Authors: C Tremblay, B Hamilton, M Sala, J Paoloni, H Chalabi
Journal: British Journal of Sports Medicine (2011)

Background Haemoglobinopathy are the most common genetically inherited disease in many parts of the world. Both health and athletic performance may be affected in athletes training at high intensity and in extreme conditions. Objective This retrospective study evaluates the prevalence of haemoglobinopathy in sportmen of Qatar. Design and setting 712 male athletes (age 14–36 years) of all levels were medically screened in our sports hospital during the period of January 2008 to April 2009. Athletes with a low Mean Cell Volume (Value) and low Mean Cell Haemoglobin (Hb value) were investigated for haemoglobinopathy with an electrophoresis screen and DNA analysis in the event of a normal electrophoresis, and unexplained low MCV/MCH. Intervention 112 athletes (15.7%) met the criteria for investigation. 93 (83.04%) of these underwent electrophoresis and 76 (81.7%) had a normal result. Results Abnormal results included nine â-thalassemia minor, four sickle cell trait, one Hb D Los Angeles and three subtypes of HbX. 49 (64.7%) of the 76 normal Hb electrophoresis were further tested with DNA analysis. 45 DNA results were subsequently abnormal for three subforms of alpha thalassemia minor. Main outcome measurements Overall, no athletes were found to have thalassaemia major but 8.85% of total number of athletes in this cohort were positive for thalassaemia minor. Nearly 2/3 of the positive results were in Qatari athletes, with the remainder being from other Gulf, Asian and African countries. Conclusion Thus we conclude that there is a high prevalence of haemoglobinopathies in Qatar sportsmen. The use of electrophoresis as a screening tool is challenged by the high rate of false negative observed in this study. Screening, education and counselling is needed to prevent possible health hazards and to optimise performance in this group of athletes often performing in extreme environmental conditions.
Myocardial Osteopontin Expression Is Associated With Left Ventricular Hypertrophy
Authors: Kristof Graf, Yung S. Do, Naoto Ashizawa, Woerner P. Meehan, Cecilia M. Giachelli, Charles C. Marboe, Eckart Fleck, Willa A. Hsueh
Journal: Circulation (1997)

Osteopontin (OP) has been identified in cultured rat cardiac fibroblasts, where it contributes to angiotensin II (AII)-induced remodeling processes; in cultured cardiomyocytes; and in macrophages in cardiac tissues with inflammation. However, the presence of OP has not been reported in histological sections of myocardial tissue. In the present study, we investigated (1) the regulation of OP mRNA expression in cultured rat cardiomyocytes; (2) the localization of OP mRNA in neonatal and adult normal and hypertrophied rat hearts; and (3) the histology of OP expression in myocardial specimens from humans either with myocyte hypertrophy or with no pathological changes.Cultured neonatal cardiomyocytes expressed OP mRNA and were immunoreactive for OP. Endothelin-1 (ET-1) and norepinephrine (NE) increased both OP and atrial natriuretic peptide (ANP) mRNA levels twofold to threefold (P<.01). OP mRNA was prominent in ventricular tissue from neonatal and adult rats with renovascular hypertension and aortic banding, whereas barely detectable levels were observed in normal adult cardiac tissue. ANP and OP mRNA levels in normal and hypertrophied ventricles correlated (r2=.87, P<.001). OP immunoreactivity and mRNA transcripts were predominantly found in cardiomyocytes not associated with inflammatory cells in sections from neonatal and adult hypertrophied hearts. No staining was detectable in normal adult hearts. Human myocardium with extensive fibrosis and cardiomyocyte hypertrophy obtained from explanted hearts with either idiopathic (n=5) or ischemic cardiomyopathy (n=7) demonstrated substantial myocyte immunoreactivity for both OP and ANP in right and left ventricles that was not associated with leukocyte infiltration. In situ hybridization identified cardiomyocytes as the major source of OP mRNA transcripts in these hearts. In contrast, OP immunoreactivity was not detectable in four of five endomyocardial biopsies with normal histology.The present study provides the first evidence that cardiomyocytes are a prominent source of OP in vivo and suggests that induction of OP expression is strongly associated with ventricular hypertrophy.
The Tumor-Suppressive Function of Connexin43 in Keratinocytes Is Mediated in Part via Interaction with Caveolin-1
Authors: Stéphanie Langlois, Kyle N. Cowan, Qing Shao, Bryce J. Cowan, Dale W. Laird
Journal: Cancer Research (2010)

Connexin43 (Cx43) is known to have tumor-suppressive effects, but the underlying mechanisms are still poorly understood. In keratinocytes, we previously showed that the COOH-terminal domain of Cx43 directly interacts with the tumor suppressor Cav-1. We now show that rat epidermal keratinocytes (REK) that are reduced in Cx43 present features of epithelial-to-mesenchymal transition and are more invasive than their control counterparts, whereas overexpression of Cx43 inhibited the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- and epidermal growth factor (EGF)-induced invasive properties. Carbenoxolone did not alter the inhibitory effect of Cx43 against TPA- and EGF-induced cell invasion, indicating the involvement of a gap junctional intercellular communication-independent mechanism. Interestingly, the association of Cx43 with Cav-1 was found to be reduced after TPA and EGF treatment. Accordingly, the colocalization of Cx43 with Cav-1 was diminished in cells from a human epidermal squamous cell carcinoma, as well as in sections from human keratinocyte tumors, suggesting that Cx43/Cav-1 interaction plays a protective role against keratinocyte transformation. As opposed to cells that overexpress Cx43-GFP, invasion could be induced in rat epidermal keratinocytes that overexpressed a GFP-tagged truncated mutant of Cx43 (Delta244-GFP) that we previously showed not to interact with Cav-1, as well as in cells that overexpressed Cx43-GFP but were reduced in Cav-1. Our data show that Cx43 possesses tumor-suppressive properties in keratinocytes and provide the first evidence that the Cx43/Cav-1 interaction is altered in keratinocyte transformation processes, as well as in human keratinocyte tumors, and that this association might play a role in Cx43-mediated tumor suppression.
The emergence of biliary sludge, a new clinical entity
Authors: Thomas R. Holzbach
Journal: Hepatology (1988)

Biliary sludge is a collection of mucus, calcium bilirubinate, and cholesterol crystals that is usually recognized by characteristic echoes on ultrasonography. Its pathogenesis, clinical significance, and ultimate prognosis remain uncertain. We therefore studied the origin of biliary sludge ultrasonic echoes, using an ex vivo liver-gallbladder preparation, and determined the outcome of a group of patients identified to have gallbladder sludge by ultrasonography. Echoes were not generated by either an increase in the total solid concentration or by the graded addition of partially purified mucus glycoprotein. Cholesterol monohydrate crystals (&gt;50 μm) mixed with mucus produced echoes that were indistinguishable from gallbladder sludge observed in patients. To determine the natural evolution of gallbladder sludge in patients, we prospectively followed 96 patients found to have biliary sludge for a mean of 37.8 mo by serial ultrasound scans every 6 mo. In 17 patients (17.7%) biliary sludge disappeared and did not recur for at least 2 years, in 58 patients (60.4%) biliary sludge disappeared and reappeared, and in 8 patients (8.3%) asymptomatic gallstones developed. There were 12 cholecystectomies performed: six were done for symptomatic gallstones (6.3%) and the other six for sludge associated with severe biliary pain attacks with or without recurrent acute pancreatitis. The finding of sludge represented precipitates being formed in bile. In some patients, it was a precursor form of gallstone disease.
Elevated α-foetoprotein and hepatic metastases—it’s not always what it seems!
Authors: G.M. Marx, A. Boyce, D. Goldstein
Journal: Annals of Oncology (2002)

Gastric cancers that secrete α-foetoprotein (AFP) are a rare but well defined entity. These tumours tend to be aggressive with a poor prognosis. Recognition and identification of this group of patients is important in influencing prognosis, treatment options and further clinical research into this entity. We report three cases of gastric cancers associated with elevated AFP. This entity should be considered in patients with hepatic lesions and an elevated AFP without risk factors for hepatocellular carcinoma or in patients with associated gastric symptoms.
Cellophane Perinephritis Hypertension and Its Reversal in Rabbits
Authors: DUNCAN J. CAMPBELL, SANDFORD L. SKINNER, ALLAN J. DAY
Journal: Circulation Research (1973)

Plasma renin activity and renin substrate levels were measured during the development of cellophane perinephritis hypertension induced by either a bilateral renal wrap procedure or a wrap-nephrectomy procedure in 28 rabbits. Unoperated and unilaterally nephrectomized controls were also studied. Plasma renin concentration was derived from plasma renin activity and plasma renin substrate levels using a measured K m of 2.3 x 10 -6 M. All surgical operations were followed by a transient increase in plasma renin substrate levels and a fall in plasma renin concentration. Unilateral nephrectomy in normotensive controls suppressed plasma renin activity and concentration for a 20-day period. Similar suppression occurred during the onset of hypertension in rabbits subjected to the wrap-nephrectomy procedure. Decapsulation accompanied by a fall in blood pressure again suppressed plasma renin activity and concentration. With bilateral wrapping, hypertension developed gradually without a change in renin levels. Decreased renin secretion during the evolution of perinephritis hypertension probably reflects a decreased renal excretory capacity for salt and water that overrides the renin-releasing effect of renal compression.
Informed participation in a randomised controlled trial of computed tomography screening for lung cancer
Authors: K. A. M. van den Bergh, M. L. Essink-Bot, R. J. van Klaveren, H. J. de Koning
Journal: European Respiratory Journal (2009)

The actual lung cancer (screening) knowledge, attitudes, risk perceptions, reasons to participate in or decline participation, and informed decisions of subjects who decided to or decided not to participate in the Dutch-Belgian randomised controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) were evaluated. A total of 2,500 high-risk subjects were asked to complete a questionnaire 3 weeks after they had received a brochure with information about the trial. Differences in knowledge, attitude and risk perception between participants and nonparticipants were analysed with logistic regression analyses adjusted for sex and smoking status. The questionnaire response of trial participants was 80% (n = 889) whereas the response of nonparticipants was low (7%, n = 97) and selective. Participants' responses to knowledge items on lung cancer as a disease were on average more often correct (mean± sd 68±17%) than items on lung cancer screening (49±29%). Participants had adequate knowledge on lung cancer screening (51%) more often than the nonparticipants (38%; p = 0.009). Of the decisions regarding participation, 49% were uninformed, mainly due to insufficient knowledge. Most of the participants (99%) and 64% of the nonparticipants had a positive attitude towards lung cancer screening. Additional efforts are required to improve the knowledge and understanding of subjects who are in the process of decision-making regarding participation in a lung cancer screening trial.