tbuckley/cabot-search huggingface dataset:
Distinct Interactions Between c-Src and c-Met in Mediating Resistance to c-Src Inhibition in Head and Neck Cancer
Authors: Banibrata Sen, Shaohua Peng, Babita Saigal, Michelle D. Williams, Faye M. Johnson
Journal: Clinical Cancer Research (2010)

Abstract Purpose: c-Src inhibition in cancer cells leads to an abrogation of invasion but a variable effect on apoptosis. The pathways downstream of c-Src promoting survival are not well characterized. Because cancer therapy that both decreases invasion and induces significant apoptosis would be ideal, we sought to characterize the mechanisms of resistance to c-Src inhibition. Experimental Design: c-Src was inhibited in a panel of oral cancer cell lines and subsequent survival and signaling measured. The interactions between c-Src and c-Met were evaluated using immunoprecitation and an in vitro kinase assay. Cytotoxicity was measured and the Chou–Talalay combination index calculated. An orthotopic model of oral cancer was used to assess the effects of c-Met and c-Src inhibitors. Results: Inhibition of c-Src resulted in c-Met inhibition in sensitive cells lines, but not in resistant cell lines. Isolated c-Met was a c-Src substrate in both sensitive and resistant cells, but there was no interaction of c-Src and c-Met in intact resistant cells. To examine the biological consequences of this mechanism, we demonstrated synergistic cytotoxicity, enhanced apoptosis, and decreased tumor size with the combination of c-Src and c-Met inhibitors. Conclusions: Sustained c-Met activation can mediate resistance to c-Src inhibition. These data suggest that the differences between c-Met and c-Src signaling in sensitive and resistant cells are due to distinct factors promoting or inhibiting interactions, respectively, rather than to intrinsic structural changes in c-Src or c-Met. The synergistic cytotoxic effects of c-Src and c-Met inhibition may be important for the treatment of head and neck cancers. Clin Cancer Res; 17(3); 514–24. ©2010 AACR.
Parahippocampal Gray Matter Density in Panic Disorder: A Voxel-Based Morphometric Study
Authors: Guillem Massana, Josep Maria Serra-Grabulosa, Pilar Salgado-Pineda, Cristòbal Gastó, Carme Junqué, Joan Massana, José María Mercader
Journal: American Journal of Psychiatry (2003)

The authors examined possible cerebral gray matter abnormalities in patients with panic disorder.Gray matter concentration in 18 panic disorder outpatients and 18 healthy subjects was compared by using a voxel-based morphometry approach.Gray matter density of the left parahippocampal gyrus was significantly lower in patients with panic disorder compared with healthy subjects.This result provides further support for the involvement of the parahippocampal area in the pathophysiology of panic disorder.
Use of viral infections in animal models to assess changes in the immune system.
Authors: E R Kern
Journal: Environmental Health Perspectives (1982)

Viral infections in animal models appear to be ideal systems for determining toxicity to the immune system by environmental substances. Since many viral infections that are utilized in animals produce systemic disease, these models provide an opportunity to evaluate the interaction between virus and components of host resistance. In these infections it is possible to delineate the role of antibody, interferon, cell-mediated immunity, neutrophils and macrophages in response to infection. A change in any of these components responsible for resistance to a particular virus may be correlated with an alteration of mortality an pathogenesis of the viral infection. Three experimental viral infections in mice that are potential candidates for use in determining immunotoxicity are discussed in terms of the response of individual components of resistance to infection and how changes in there components result in alterations of viral pathogenesis. The resistance to encephalomyocarditis virus infection in mice appears to be primarily mediated by antibody and interferon while with herpes simplex virus, infections are mainly controlled through cell-mediated immunity, macrophages, and possible interferon. Cellular immunity also appears to be primarily responsible for resistance to cytomegalovirus infections. Therefore, it is important in the use of these systems for evaluating immunotoxicity to define the pathogenesis of the viral infection and the specific host responses to these infections and to be able to correlate a change in host resistance with an alteration of the viral infection.
Peginterferon Alfa-2a in Patients with Chronic Hepatitis C and Cirrhosis
Authors: E. Jenny Heathcote, Mitchell L. Shiffman, W. Graham E. Cooksley, Geoffrey M. Dusheiko, Samuel S. Lee, Luis Balart, Robert Reindollar, Rajender K. Reddy, Teresa L. Wright, Amy Lin, Joseph Hoffman, Jean De Pamphilis
Journal: New England Journal of Medicine (2000)

Chronic hepatitis C virus (HCV) infection in patients with cirrhosis is difficult to treat. In patients with chronic hepatitis C but without cirrhosis, once-weekly administration of interferon modified by the attachment of a 40-kd branched-chain polyethylene glycol moiety (peginterferon alfa-2a) is more efficacious than a regimen of unmodified interferon. We examined the efficacy and safety of peginterferon alfa-2a in patients with HCV-related cirrhosis or bridging fibrosis.
The path forward in Hungarian neuroscience
Authors: M. Antal, G. Buzsáki, G. Czéh, G. Gaál, B. Gulyás, Z. Horváth, R. Jakab, P. Kabai, J. Kiss, B. Kocsis, S. Komoly, J. Kovách, J. Lendvay, C. Léránth, E. Mezey, Z. Molná, A. Seregi, I. Soltész, P. Somogyi, T. Toth, L. Urbän, C. Vadász
Journal: Trends in Neurosciences (1991)
Abstract 4163: JNK2 reduction increases intestinal tumor susceptibility in Apc+/− mice
Authors: Xiuli Bi, Dong Hu, Nicole M. Pohl, Zhinan Yin, Wancai Yang
Journal: Cancer Research (2010)

Abstract Previous studies have shown distinct functions between c-jun NH2 terminal kinases (JNK) 1 and 2. Indeed, loss of JNK1 causes spontaneous intestinal tumor formation in mice (Tong et al, Am. J. Pathol, 2007; Hu et al, Carcinogenesis, 2008), but loss of JNK2 does not have any phenotype in intestine, although in vitro studies have shown that JNK2, like JNK1, interacts with and inhibits β-catenin signaling, in which GSK3β and proteasome pathway play a critical role (Hu et al, LoS One, 2009). To determine the role of genetic interaction between JNK2 and beta-catenin in intestinal tumorigenesis and to elucidate JNK2-mediated intestinal carcinogenesis, we crossed the JNK2−/−mouse with Apc+/− mice that carry inactivated Apc allele and develops intestinal tumor due to beta-catenin activation and nuclear accumulation. We found that the introduction of mutant JNK2 into Apc+/− did not increase intestinal tumorigenesis when the mice were fed a defined AIN-76A control diet. However, JNK2 reduction significantly increased animal body weight in the Apc+/−/JNK2+/− and Apc+/−/JNK2−/− mice. Interestingly, JNK2 reduction was synergistic with a Western-style high-risk diet (high fat and phosphate, low calcium and vitamin D)(WD) to accelerate intestinal tumorigenesis. Tumor number was significantly increased from 1.89 (AIN-76A diet) to 3.56 (WD) in the Apc+/−/JNK2+/− mice (P&amp;lt;0.01) and to 4.14 (WD) in the Apc+/−/JNK2−/− mice from 1.92 (AIN-76A diet) (P&amp;lt;0.01), even though there was a slight increase of tumor formation in JNK2 wild-type mice (Apc+/−/JNK2+/+) by such a diet (1.55 v.s. 2.0, p=0.4). Therefore, we concluded that JNK2 might have function in controlling fat metabolism, and that loss of JNK2 increases the risk of obesity, the latter synergists with high-fat diet to increase intestinal tumor susceptibility. This data strongly suggests the important role of JNK2 in intestinal carcinogenesis and the essential of dietary manipulation for cancer prevention in the population if their JNK2 is inactivated. The underlying mechanisms are under investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4163.
Clinical significance of upsloping ST segments in exercise electrocardiography.
Authors: R D Rijneke, C A Ascoop, J L Talmon
Journal: Circulation (1980)

Conventional exercise electrocardiographic criteria usually involve patterns with a horizontal or downsloping ST segment. In the present study we present criteria based on upsloping ST segments and compared these criteria with the conventional criteria. Using upsloping ST-segment criteria, the amount of ST-segment depression at 80 msec after the end of the QRS complex is used as a parameter (ST criterion E, with a depression of 100 mV, and ST criterion F, with a depression of 200 mV). In the graded exercise test a bicycle ergometer was used. The ECG leads were CM5 and CC5. The results of exercise electrocardiography were compared with the findings from coronary arteriography. In 623 selected patients (565 males and 58 females), application of conventional ST criteria gave a sensitivity of 56% and a specificity of 94%; with application of the ST criteria E or F, sensitivity was 75% and specificity 90%. In the 58 females use of these new criteria resulted in a sensitivity of 76% and specificity of 88%. Ninety-three patients (15%) could be classified as positive exercise responders by the sole presence of an upsloping ST segment (type E or F). Sixty-eight percent of the patients with type E and 75% with type F had two- or three-vessel disease (coronary obstructions greater their or equal to 50%). We conclude that ST criteria based on upsloping ST segments significantly increase the diagnostic yield of the exercise ECG.
Advances in cardiopuhnonary diseases. Vol I
Authors: Sanford A. Franzblau
Journal: JAMA (1963)

This volume is a potpourri of diverse lectures drawn from papers given in the 1961 courses of the American College of Chest Physicians. Their only common denominator is the chest. The papers, by 22 authors, range in quality from good to poor and in topic from pulmonary function testing to esophageal pathology and aortic disease. There is also an excellent paper on infant resuscitation. It seems to this reviewer that the papers presented could just as well have appeared in already existing and appropriate specialty journals.
Carbohydrate Tolerance and Insulin Responses in Obstructive Jaundice
Authors: N. G. Soler, P. D. Exon, A. Paton
Journal: BMJ (1974)

Twenty-three patients with obstructive jaundice were given a 50-g oral glucose tolerance test (G.T.T.) and an insulin stimulation test with oral glucose and intravenous tolbutamide and glucagon. An abnormal glucose response was as common in patients with carcinoma of the pancreas (seven out of 12) as in patients with “other” causes of obstructive jaundice (six out of 11). Though both groups had a low and delayed insulin response the insulin levels were significantly lower in patients with carcinoma of the pancreas. After the insulin stimulation test patients with obstructive jaundice who did not have carcinoma of the pancreas had a greater and significantly different insulin response from patients with pancreatic cancer. There was, however, considerable overlapping between the results of individual patients in the two groups.
The Safety and Feasibility of Percutaneous Endoscopic Gastrostomy Placement by a Single Physician
Authors: E. Rimon
Journal: Endoscopy (2001)

Percutaneous endoscopic gastrostomy (PEG) has become the procedure of choice for enteral feeding. However, the procedure usually requires two physicians, which makes it more difficult to schedule than procedures performed by a single physician. We investigated whether PEG insertion by a single physician could be done with the same safety and feasibility as by two physicians.This study involved 339 consecutive patients who were referred for PEG. The same single physician, together with a nurse, performed the procedure in all patients, instead of the usual procedure performed by two physicians. Followed up of the patients for 1 month after the procedure was done.Minor complications occurred in 35 patients (10.3%), most frequently self-extubation and skin irritation. Eight patients (2.4%) had severe complications, including apnea in two, and wound infection that needed systemic antibiotics in another three patients. Three patients needed surgery because of peritonitis as a consequence of the procedure. There was no mortality in the first 48 hours after the procedure and only one patient death could be attributed to the procedure.The insertion of PEG by a single experienced physician is as safe as that described in the literature with two physicians. This should not replace the traditional approach with two physicians, but should be reserved for special situations when only one physician is available.
Most doctors see consent from functionalist perspective
Authors: E. Peters, M. Challis
Journal: BMJ (1999)

EDITOR—Alderson and Goodey's article considers the different theoretical perspectives on the practical issue of consent.1 A study recently conducted by a multidisciplinary team at Queen's Medical Centre, Nottingham, supports the authors‘ assertion that consent is understood in different and sometimes conflicting ways by medical staff.

A questionnaire asked preregistration house officers, senior house officers, and nurses from various specialties about training received in obtaining consent, training required, and important issues regarding consent. The questionnaire included vignettes or case studies …
Recent pharmacological advances for treating venous thromboembolism: are we witnessing the demise of warfarin?
Authors: Shankar Kumar, John Howell, Christopher Mattock
Journal: Journal of the Royal Society of Medicine (2013)

Vitamin K antagonists, such as warfarin, have been the mainstay in treatment and prophylaxis of venous thromboembolism. However, warfarin has many disadvantages including a narrow therapeutic window, numerous potential drug interactions, modulation of effect by alcohol and foods containing vitamin K and genetic variation in metabolism of warfarin, all of which contribute to the unpredictability of therapy. This has provided the impetus for developing new oral anticoagulants with a rapid onset of action, wide therapeutic window, predictable and reversible action, with few drug or dietary interactions, no requirement for routine coagulation monitoring or dose adjustment and acceptable cost. No single agent incorporates all these characteristics, but new factor Xa and direct thrombin inhibitors are being introduced into clinical practice that fulfil some of these aims. Here, we briefly discuss the current practice with its limitations and pitfalls, and then review important trials that have launched new oral anticoagulants into clinical practice.
Review: CABG and percutaneous coronary intervention do not differ for long-term mortality in multivessel coronary artery disease
Authors: Laura Rees Willett
Journal: Annals of Internal Medicine (2009)

Source Citation Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet. 2009;373:1190-7. 19303634
THE DECAPSULATION OF THE KIDNEYWITH REFERENCE TO THE CONCOMITANT INTRA-OCULAR COMPLICATIONS IN THE CHRONIC FORMS NEPHRITIS.
Authors: GEORGE F. SUKER
Journal: JAMA (1904)

The object of this paper is to elicit the interest of the members of this Section in determining whether or not the decapsulation of the kidney can be accepted as a curative or as a palliative measure for the various intra-ocular complications accompanying either the diffuse, interstitial or chronic parenchymatous nephritis. The question of decapsulating the kidney<sup>1</sup>still attracts considerable attention,<sup>2</sup>not only from the standpoint of the surgeon but from that of the internist as well. The writer is well aware of the fact that it is rather early to make any definite statements or draw any definite conclusions as to the merits or demerits of the operation from an ophthalmologic point of view.<sup>3</sup>But, if the paper should arouse enough interest in the matter so that before long we might have either a symposium or a more extended report on this subject, as is our wont in such
Relationship between skeletal muscle lipoprotein lipase activity and 24-hour macronutrient oxidation.
Authors: R T Ferraro, R H Eckel, D E Larson, A M Fontvieille, R Rising, D R Jensen, E Ravussin
Journal: Journal of Clinical Investigation (1993)

A low ratio of whole-body 24-h fat/carbohydrate (CHO) oxidation has been shown to be a predictor of subsequent body weight gain. We tested the hypothesis that the variability of this ratio may be related to differences in skeletal muscle metabolism. Since lipoprotein lipase (LPL) plays a pivotal role in partitioning lipoprotein-borne triglycerides to adipose (storage) and skeletal muscle (mostly oxidation), we postulated that a low ratio of fat/CHO oxidation was associated with a low skeletal muscle LPL (SMLPL) activity. As an index of substrate oxidation, 24-h RQ was measured under sedentary and eucaloric conditions in 16 healthy nondiabetic Pima males. During a 6-h euglycemic, hyperinsulinemic clamp, muscle biopsies were obtained at baseline, 3, and 6 h. Heparin-elutable SMLPL activity was 2.92 +/- 0.56 nmol free fatty acids/g.min (mean +/- SD) at baseline, was unchanged (2.91 +/- 0.51) at the third hour, and increased significantly (P < 0.05) to 3.13 +/- 0.57 at the sixth hour of the clamp. The mean (of baseline and 3-h) SMLPL activity correlated inversely with 24-h RQ (r = 0.57, P < 0.03) but not with body size, body composition, or insulin-mediated glucose uptake. Since SMLPL activity is related to the ratio of whole body fat/CHO oxidation rate, a decreased muscle LPL activity may, therefore, predispose to obesity.
Autologous blood products in musculoskeletal medicine
Authors: N. Maffulli
Journal: BMJ (2013)

Although they are trendy money spinners, best evidence shows little effectiveness 

Participation in almost all sports and physical activities benefits individuals and society as a whole because it promotes health and helps prevent conditions such as osteoporosis, cardiovascular disease, and diabetes; it may also lead to improved mental health. Nevertheless, athletes are highly vulnerable to musculoskeletal injuries, sometimes with devastating effects. Sports injuries cost society billions of dollars in direct and indirect costs. Regenerative medicine technologies, such as autologous blood products for the treatment of tendinopathies, hold the promise of improved outcomes for musculoskeletal conditions that currently have limited or no treatment options. In a linked trial (doi:10.1136/bmj.f2310), Bell and colleagues compare the effectiveness of peritendinous injections of autologous blood with standard eccentric exercise in athletes with Achilles tendinopathy.1

Novel treatments that are reported to accelerate recovery from musculoskeletal injuries, without adversely affecting recurrence rate, are increasingly advocated in the lay media and often heavily promoted to athletes and healthcare professionals.2 3 Injections of autologous blood products, including whole blood, platelet rich plasma, and autologous conditioned serum, are increasingly …
CT Angiography: Clearer Picture, Fuzzier Reception
Authors: Mike Mitka
Journal: JAMA (2006)

by the Centers for Disease Control and Prevention, is developing a system that could be used to monitor the emergence of zoonotic diseases in pets (Glickman LT et al. Vector Borne Zoonotic Dis. 2006;6:14-23). The National Companion Animal Surveillance Program uses a centralized database of electronic records from the more than 80 000 animals treated weekly at Banfield pet hospitals, a nationwide chain of veterinary hospitals. Other data have been included from VCA Antech Diagnostics, a nationwide network of laboratories used by 18 000 private veterinary practices. “We think by identifying problems in these pets, we can identify problems such as unusual viral or bacterial infections before they are transmitted to humans—or at least early in the process,” said Larry T. Glickman, DrPH, professor of epidemiology at Purdue University’s School of Veterinary Medicine, West Lafayette, Ind. Glickman said the surveillance system can be used to identify clusters of unusual disease symptoms or to monitor pets for a disease of interest. For example, the system could be used to monitor cats for avian influenza. Cases of highly pathogenic H5N1 avian influenza have been documented in domesticcats inGermanyandAustria,although it isnotknownif theycanspreadthevirus to humans. However, the fact that many domestic cats may hunt wild birds and have close contact with their human owners makes them a potential concern, Glickman said. Banfield’s electronic record system could be used to alertveterinarianstocollectsamples from catswith signsof influenzalike illness for furthertesting.Dataontheresultsof these tests and the geographic location of the animal could be compared with human data to monitor for potential crossspecies transmission. A similar centralizedelectronicdatabaseofpatientrecords might provide valuable information about human disease as well, he said. “It puts primary care physicians and veterinarians at the forefront of disease surveillance where they belong,” Glickman said. CT Angiography: Clearer Picture, Fuzzier Reception