tbuckley/cabot-search huggingface dataset:
Induction of a Novel Ca 2+-Dependent Chymotrypsin-Like Serine Protease by Tumor Promoters in Rat Livers&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: A Kaneko, K Enomoto, M Oyamada, N Sawada, K Dempo, M Mori
Journal: JNCI Journal of the National Cancer Institute (1986)

Induction of a microsomal Ca2+-dependent serine protease by hepatic tumor promoters was studied. Male F344 rats were fed a diet containing one of the following promoting agents: phenobarbital (CAS: 50-06-6), dichlorophenyltrichloroethane (CAS: 50-29-3), butylated hydroxytoluene, ethyl-alpha-chlorophenoxyisobutyrate (CAS: 128-95-0), or 17-alpha-ethynylestradiol (CAS: 57-63-6) or a nonpromoting agent, diphenylhydantoin (CAS: 57-41-0), for 1 week. By treatment with promoters, the protease activity in the microsomal fraction was increased to threefold to fivefold that of control, whereas only a slight increase of activity was found after diphenylhydantoin treatment. The Ca2+-dependent protease activity was determined with the use of N-benzoyl-L-tyrosine ethyl ester as the substrate in a medium containing 50 mM CaCl2 for its maximal activity. This protease was preferentially localized in the smooth microsomal membrane and strongly inhibited by diisopropyl phosphorofluoridate (CAS: 55-91-4), and the optimum pH of the activity was 7.8. It appears that the Ca2+-dependent serine protease measured by using a chymotrypsin substrate is a novel protease, and induction of its activity by hepatic tumor-promoting agents is a common and specific phenomenon.
Antisense oligonucleotides to proliferating cell nuclear antigen and Ki-67 inhibit human mesangial cell proliferation.
Authors: Y Maeshima, N Kashihara, H Sugiyama, H Makino, Z Ota
Journal: Journal of the American Society of Nephrology (1996)

Proliferating cell nuclear antigen (PCNA) and Ki-67 are cell cycle-associated nuclear proteins and are used as markers for proliferating cells. This study attempted to inhibit glomerular mesangial cell (MC) proliferation, which is the hallmark of many forms of glomerular disease, by inhibiting these nuclear proteins with antisense oligodeoxynucleotides. The antisense and sense phosphorothioate oligodeoxynucleotides complementary to PCNA and Ki-67 mRNA, including the initiation codon, were synthesized. Human MC were cultured in growth medium in the presence of sense or antisense oligodeoxynucleotides, and the effects of these oligodeoxynucleotides on mesangial cell proliferation were evaluated by direct cell count. Both PCNA and Ki-67 antisense oligodeoxynucleotides significantly inhibited mesangial cell proliferation as compared with sense oligodeoxynucleotides. Antisense oligodeoxynucleotides (10 microM) for PCNA and Ki-67 inhibited mesangial cell growth by greater than 50%. The effect of antisense oligodeoxynucleotides on target protein expression was examined by immunocytochemistry using specific monoclonal antibodies. Reverse transcription-polymerase chain reaction also was performed to evaluate the effect of antisense oligodeoxynucleotides on PCNA and Ki-67 mRNA expression. Studies of target protein and mRNA expression revealed that the inhibitory effects of the antisense oligonucleotides were mediated through decreases in the expression of both mRNA and protein. Sense oligodeoxynucleotides produced little effect. These results indicate that antisense oligodeoxynucleotides targeting PCNA and Ki-67 mRNA reduce the expression of these gene products and inhibit mesangial cell proliferation. Moreover, these results suggest the feasibility of antisense strategies designed to inhibit PCNA and Ki-67 expression for the inhibition of mesangial cell proliferation in vivo.
Abstract 219: Cardiac Autophagy in Response to Fasting is Impaired in Mice with Metabolic Syndrome
Authors: Bruce R Ito, Nandini Ravindran, Allen M Andres, Roberta A Gottlieb, Robert M Mentzer
Journal: Circulation Research (2014)

Introduction: Macroautophagy (autophagy) is highly responsive to nutrient/energy status and cellular stress. It plays an adaptive role in limiting ischemia/reperfusion (I/R) injury in the heart. Nutrient depletion is a potent inducer of autophagy and is mediated by reciprocal regulation of AMPK and mTOR pathways which in turn regulate autophagy initiation via ULK1/Atg1. Autophagy is reduced in the setting of obesity, dyslipidemia, and insulin resistance associated with metabolic syndrome (MetS). The purpose of this study was determine whether impaired autophagy in MetS is due to altered upstream signaling or a disruption in the autophagic pathway. Methods: Mice were ad-lib fed a chow (Lean) or a high fat diet (HFD) (D12492, 60% fat) for 18 weeks. In both groups, half of the mice were freely fed with the other half fasted for 24 hours prior to cardiac harvest. Protein levels were determined with Western blotting and gene expression with quantitative PCR. Results: Consistent with previous data, HFD animals exhibited obesity and insulin resistance as reflected by increased body weight, and elevated serum insulin/HOMA compared to Lean animals. Fasting resulted in a marked reduction in serum insulin in both Lean (p=0.013) and HFD (p =0.002) animals. This was accompanied by marked increases in cardiac AMPK activation as reflected by increased phosphorylation in both Lean (p =0.002) and HFD (p=0.002) groups with parallel reciprocal suppression of mTOR activity as reflected by decreased pS6K and pS6. As expected, the Lean group exhibited a fasting-induced increase in LC3-II (p=0.020) indicating an increase in autophagy. This did not occur in the HFD group despite a similar induction in LC3B and p62 gene expression. This lack of autophagy stimulation with fasting in HFD animals was not explained by differences in autophagy initiation as the phosphorylation status of ULK1 decreased similarly with fasting in both groups. Conclusions: These data indicate that the impairment of cardiac autophagy in the presence of MetS is not attributable to abnormal upstream nutrient sensing pathways. The findings suggest a MetS-associated defect in the autophagy/lysosomal fusion pathway. This could explain the increased vulnerability of the heart to I/R injury in the setting of MetS.
Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression
Authors: A Roy, H Agren, D Pickar, M Linnoila, A R Doran, N R Cutler, S M Paul
Journal: American Journal of Psychiatry (1986)

Depressed patients who had attempted suicide (N = 19) had significantly lower CSF homovanillic acid (HVA) levels than patients who had not attempted suicide (N = 8) and control subjects (N = 41). Intergroup levels of 5-hydroxyindoleacetic acid (5-HIAA) were not significantly different. The ratio of CSF HVA to CSF 5-HIAA was significantly lower in both patient groups than in control subjects, and patients who had attempted suicide had CSF HVA/5-HIAA ratios that were nearly 50% those of the control subjects. The combinations of nonsuppression on the dexamethasone suppression test and either a low CSF HVA level or a low CSF HVA/5-HIAA ratio were significantly more common among patients who had attempted suicide than among those who had not.
Abstract 36: Acute Inhibition Of O-GlcNAc Signaling Rescues Inotropic Responsiveness In Type 1 Diabetic Rat Hearts
Authors: Chengxue Qin, Rochelle S S Sleaby, Lea M Delbridge, Amy J Davidoff, John C Chatham, Rebecca H Ritchie
Journal: Circulation Research (2014)

Metabolism of excess glucose is an important component of the aetiology of type 1 diabetes. The cardiac phenotype includes left ventricular (LV) remodelling and LV dysfunction. Increased hexosamine biosythesis (HBP) and downstream upregulation of protein O-GlcNAcylation has been linked to diabetic complications in many organs. Its impact on LV contractile responsiveness is however not well understood. This study aimed to test the hypothesis that acute inhibition of O-GlcNAc signaling protects inotropic responsiveness in type 1 diabetic heart. Hearts isolated from adult Sprague-Dawley male rats were Langendorff-perfused (constant flow, 10ml/min). Baseline and phenylephrine-stimulated (PE, 10μmol/L) LV function was determined in diabetic (8wks post-streptozotocin diabetes, 55mg/kg i.v.) versus non-diabetic sham rats in the presence of pharmacological inhibitors of HBP/O-GlcNAc including 6-diazo-5-oxo-L-norleucine (DON, 20μM) and alloxan (5mM). Diabetic rats exhibited a marked reduction in inotropic responsiveness to PE (Table, mean±SEM, one-way ANOVA, #P&lt;0.05 vs non-diabetic vehicle rats, *P&lt;0.05 vs diabetic vehicle, at 40 mins). Acute interruption of cardiac HBP/O-GlcNAc by DON and Alloxan significantly rescued LV responsiveness to PE in type 1 diabetic rat hearts. These results support further assessment of the impact of upregulated protein O-GlcNAcylation on LV function, particularly in the diabetic heart. Treatment strategies that target HBP may provide significant benefits alone or in combination with current standard treatments, to reduce progression of heart failure and death in type 1 diabetic patients.
Medical Marijuana Use in Oncology
Authors: Gianna Wilkie, Bachir Sakr, Tina Rizack
Journal: JAMA Oncology (2016)

Medicinal marijuana use is currently legal in 23 states and the District of Columbia. As more states approve marijuana use for medical indications, physicians will be asked by their patients for more information regarding the risks and benefits of use. This article reviews the history, adverse effects, and proposed mechanisms of action of marijuana and summarizes the available literature regarding symptom relief and therapeutic value in patients with cancer.Marijuana in oncology may have potential for use as an antiemetic, for refractory cancer pain, and as an antitumor agent. However, much of the data are based on animal data, small trials, or are outdated.More research is needed in all areas related to the therapeutic use of marijuana in oncology.
Abstract 15832: Suppression of Rad Activity Regulates L-type Ca2+ Channels and Causes Triggered Activities in Mouse Hearts
Authors: Tomoyuki Suzuki, Mitsushige Murata, Hiroyuki Yamakawa, Mika Mizusawa, Shugo Thoyama, Yasuyuki Ohgino, Shinsuke Yuasa, Shinji Makino, Motoaki Sano, Kaichiro Kamiya, Keiichi Fukuda
Journal: Circulation (2010)

Background: We have reported that the ras-related small G-protein Rad plays a critical role in generating arrhythmias. However, its mechanism has not been fully understood. This study was designed ...
Football-Related Spinal Cord Injuries Among High School Players — Louisiana, 1989
Journal: JAMA (1990)

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Jean Elizabeth Clark
Authors: C. Smalley, J. Mann
Journal: BMJ (2015)

The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain–containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells. Collectively, these findings point to ILDR2 as a novel negative regulator for T cells, with potential roles in the development of immune-related diseases, including autoimmunity and cancer.
Update:<i>New England Journal of Medicine</i>publishes correction to 2012 CHEST trial of hydroxyethyl starch versus colloids
Authors: Peter Doshi
Journal: BMJ (2016)

After publication of my article,1 the New England Journal of Medicine ( NEJM ) published a correction to the 2012 CHEST trial of hydroxyethyl starch versus colloids.2 3 A new P value of 0.006 was provided for the comparison of treatment related adverse events between hydroxyethyl starch (HES) and saline groups (180/3871 (4.6%) v 95/2870 (3.3%)). Before the correction, this was reported as 180/3416 (5.3%) …
PWE-069 Differences in luminal distribution and clinical characteristics of ulcerative colitis in south asians and white british in the north of england: Abstract PWE-068 Table 1
Authors: MA Khan, W Newman, J Hill
Journal: Gut (2015)

<h3>Introduction</h3> Inflammatory bowel diseases (IBD) are inflammatory conditions that affect the gastrointestinal tract and may have extra intestinal manifestations. The two main subtypes are Crohn’s disease (CD) and ulcerative colitis (UC). The incidence of IBD has traditionally been higher in Caucasian populations in Europe, North America and Australia compared to other regions of the world. There is now evidence of increasing incidence in all populations worldwide. Studies from the UK, North America, Malaysia and Singapore have observed a 2–3 times higher incidence of IBD in South Asian immigrant populations compared to local cohorts. However, few studies have described the disease phenotype and mucosal distribution in the South Asian immigrant population. <h3>Method</h3> Ethics approval was obtained ref: O5/Q1407/274. Patients were recruited prospectively in 11 centres in the North Of England. Inclusion criteria were diagnosis of UC and age &gt;16 years. Exclusion criteria were Diagnosis of IBDU or IDC and Age &lt;16 years. Information was collected on a standard clinical proforma. Data was stored on a FileMaker Pro database. Chi Squared analysis was used to compare groups. <h3>Results</h3> In total 186 South Asians (SA) and 535 White British (WB). In the South Asian cohort males were more likely to be affected compared to White British. South Asians had a younger average age of diagnosis 30 vs. 40 for White British. There were differences in luminal distribution with South Asians more likely to have Extensive Colitis (45% vs. 26%) or Left sided colitis (42% vs. 22%) and White British more likely to have Proctitis (13% vs. 52%). The differences in luminal distribution between groups were highly statistically significant. There was no statistical difference in family history between groups with 21% of South Asians vs. 27% for White British. There was also no statistical difference in need for colectomy between groups (5% for SA vs. 3% for White British). Also there was no statistical difference in the presence of EIM’s 6% for SA vs. 5% for White British. <h3>Conclusion</h3> There are significant differences in luminal distribution and age of diagnosis between groups. South Asians had a younger age of onset and more extensive colitis, but the relatively low rate of colectomy and EIM’s which suggest a less severe disease phenotype. In addition the younger age of onset and extensive disease in South Asians may influence risk of colorectal cancer in the future. These differences may represent differences in disease pathogenesis in particular genetic susceptibility or environmental factors. This information will help inform current and future genotype studies. <h3>Disclosure of interest</h3> None Declared.
Eosinophilic, Polymorphic, and Pruritic Eruption Associated With Radiotherapy on the Skin of the Right Breast
Authors: Marloes S. van Kester, Koen D. Quint
Journal: JAMA Oncology (2016)

A 72-year-old woman was treated with postoperative radiotherapy after lumpectomy of a cT1bN0M0 mammary carcinoma; 2 months later she developed pruritic, pustules and papules on the skin of the ipsilateral right breast. What is your diagnosis?
Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability
Authors: Bernhard Mlecnik, Gabriela Bindea, Helen K. Angell, Pauline Maby, Mihaela Angelova, David Tougeron, Sarah E. Church, Lucie Lafontaine, Maria Fischer, Tessa Fredriksen, Maristella Sasso, Amélie M. Bilocq, Amos Kirilovsky, Anna C. Obenauf, Mohamad Hamieh, Anne Berger, Patrick Bruneval, Jean-Jacques Tuech, Jean-Christophe Sabourin, Florence Le Pessot, Jacques Mauillon, Arash Rafii, Pierre Laurent-Puig, Michael R. Speicher, Zlatko Trajanoski, Pierre Michel, Richard Sesboüe, Thierry Frebourg, Franck Pagès, Viia Valge-Archer, Jean-Baptiste Latouche, Jérôme Galon
Journal: Immunity (2016)
Comparison of p53 antibody status and carcinoembryonic antigen (CEA) levels and their clinical impact as diagnostic markers in colorectal cancer patients
Authors: M. Gasser, M. Bueter, D. Meyer, A. Mueller, N. Schramm, A. M. Gassel, A. Trumpfheller, C. Gerstlauer, A. Thiede, A. M. Waaga-Gasser
Journal: Journal of Clinical Oncology (2004)

9725 Background: The purpose of this study was to evaluate the clinical impact of p53 antibodies, suggested to be associated with advanced tumor state and poor survival rate. Methods: We analyzed the frequency of circulating anti-p53 antibodies, levels of free p53 protein, and concentration of CEA in sera of colorectal cancer patients (n=48, ELISA) as well as expression of p53/CEA in the tumor (immunohistology) and correlated with the UICC stage. Results: 39.6% of all tested patients (n=19/48) expressed wild-type (wt) p53-specific-IgG-antibodies: 26% in UICC I (n=5/19), 16% in UICC II (n=3/19), 21% in UICC III (n=4/19), and 37% in UICC IV (n=7/19). 31.3% (n=15/48) showed a negative response to p53 and 29.2% (n=14/48) were within the critical range. In addition, similar levels of p53-IgG1/IgG2-subtypes were observed in patients with p53 antibodies (ELISA). No correlation was found between levels of free p53 protein and antibody levels. Immunohistologically 62.5% of the tumors (n=10/16) overexpressed p53 (clone DO-7) independent of UICC stage. The presence of wt p53-IgG-antibodies was correlated with strong p53 staining within the tumor. In addition, 29.2% (n=14/48) of the patients expressed high CEA levels depending on their UICC stage (n=0/6 UICC I, n=0/12 UICC II, n=2/9 UICC III, and n=12/21 UICC IV, ELISA). CEA expression within the tumor and UICC stage was strongly correlated (75%, n=12/16). Five different point mutations at 5 different positions of wt p53 sequence (4 in DNA-binding core domain) were observed in tumors (n=16, RT-PCR), indicating no association with the p53 humoral response and UICC stage. Conclusions: This study suggests that a humoral response to p53 is strongly correlated with intracellular accumulation of p53 within the tumor but independent from free p53 protein serum levels and p53 gene mutations. In contrast to CEA, presence of p53 auto-antibodies is not correlated with UICC stage. p53 auto-antibodies seem not to be predictive in poor outcome and irrelevant in colorectal cancer diagnosis. No significant financial relationships to disclose.
Problems of psychiatric practice in community mental health centers
Authors: C M Donovan
Journal: American Journal of Psychiatry (1982)

Initial enthusiasm about community mental health centers (CMHCs) has diminished. The participation of psychiatrists in CMHCs declined in the 1970s and may decline further. The author describes one center to highlight problems encountered by community psychiatrists: 1) unrealistic treatment expectations, 2) limitations of psychiatric knowledge, 3) need for a broad range of clinical expertise, 4) supervision of other CMHC clinicians, 5) limited funds and rehabilitation facilities, 6) complex medical and legal problems, and 7) lack of adequate training in administration. She suggests that the public be reeducated regarding realistic treatment goals, that CMHCs be allied with university departments of psychiatry, that funding be stabilized, and that community psychiatrists be given more support.
Relationship between the cancer-specific comprehensive score for financial toxicity (COST), patient-reported outcome, and health-related quality of life (HRQOL) in patients with advanced cancers.
Authors: Jonas A. De Souza, Bonnie J. Yap, Fay J. Hlubocky, Christopher Daugherty
Journal: Journal of Clinical Oncology (2014)

222 Background: Financial toxicity is an important Patient Reported Outcome (PRO). Its relationship with HRQOL has not been previously described. Therefore, we report the relationship between financial toxicity and HRQOL in patients with advanced cancers. Methods: HRQOL was measured by the EORTC QLC-C30 global health status and its functional scales. Financial toxicity was assessed by the COST (COmprehensive Score for financial Toxicity), a cancer-specific PRO measure developed in 155 patients with advanced cancers. The Personal Financial Wellness Scale (PFW), a non-cancer specific financial measure, as well as the EORTC perceived financial impact (FI), were used to assess convergent validity. The Marlowe-Crowne Social Desirability Scale and the Brief Profile of Mood States were included to demonstrate divergent validity (i.e., no significant relationship should exist between self-reported financial toxicity and social desirability and total mood disturbance). Spearman’s correlation coefficients were used to assess the strength of relationships. Results: Fifty patients were assessed. All participants were diagnosed with advanced cancers, were receiving treatment at the time of participation, and had received treatment for at least 3 months. A negative correlation existed between the COST and HRQOL as measured by the EORTC (r = -0.32, p &lt; 0.05). The highest correlation was found between COST and the EORTC Emotional Functioning Scale (r = - 0.34, p &lt; 0.05). The COST had high correlations with the PFW scale (r = 0.86, p&lt;0.0001) and FI (r = 0.74, p &lt; 0.0001), indicating convergent validity. The association between financial toxicity and social desirability and mood states were not statistically significant (r = 0.16, p = 0.28 and 0.20, p = 0.15, respectively), indicating divergent validity. Conclusions: Results demonstrate an inverse relationship between patient-reported HRQOL and financial toxicity, suggesting that higher financial toxicity is associated with worse HRQOL in this small sample of patients. There was no correlation between COST and social desirability and mood disturbances, as expected.