tbuckley/cabot-search huggingface dataset:
State of the Translational Science
Authors: Arthur Zelent, Samuel Waxman, Michael Carducci, John Wright, James Zweibel, Steven D. Gore
Journal: Clinical Cancer Research (2004)

Abstract A workshop was held in Baltimore, Maryland in January 2003 to discuss translational aspects of cancer therapies targeted at impacting aberrant gene transcription due to epigenetic changes. The mission of the meeting was the development of strategies for scientifically sound, clinically feasible applications targeting epigenetics in cancer therapy. Sessions included preclinical discussions of DNA methylation, the histone code, chromatin remodeling, and transcriptional control. Data on the histone deacetylase and DNA methyltransferase inhibitors under preclinical and clinical investigation were presented and discussed. The optimal correlative laboratory studies for monitoring clinical trials with these agents remain controversial. DNA methyltransferase and histone deacetylase inhibitors will be combined with each other to maximally re-express genes silenced through promoter methylation. Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs.
Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 immunity by licensing host dendritic cells to produce IL-12
Authors: Brian M. Janelsins, Tina L. Sumpter, Olga A. Tkacheva, Darling M. Rojas-Canales, Geza Erdos, Alicia R. Mathers, William J. Shufesky, Walter J. Storkus, Louis D. Falo, Adrian E. Morelli, Adriana T. Larregina
Journal: Blood (2013)
Abstract IA4: Outcome prediction from the pattern of aberrations in prostate cancer genomes
Authors: Barry S. Taylor, Haley Hieronymus, Nikolaus Schultz, Charles L. Sawyers
Journal: Cancer Research (2012)

Abstract One of the greatest challenges in prostate cancer care is distinguishing men with high-risk disease requiring aggressive therapy from those who can be managed with active surveillance. Therefore, we are pursuing an ongoing integrative genomic analysis of human primary and metastatic prostate cancers. We explore the clinical importance and pathogenicity of genomic lesions and their association with canonical features of prostate cancer biology. Previously, we found that global patterns of DNA copy number alterations (CNAs) in primary tumors were associated with disease recurrence after radical prostatectomy. Here, we will discuss our efforts to extend this discovery by validating the clinical importance of CNAs and structural rearrangements in independent cohorts, at multiple scales, and with orthogonal methods. Our principal goal is to deliver a clinical diagnosis informed by genomic abnormalities that impacts definitive treatment decisions in men diagnosed with prostate cancer. Citation Format: Barry S. Taylor, Haley Hieronymus, Nikolaus Schultz, Charles L Sawyers, on behalf of the MSKCC Prostate Cancer Oncogenome Group. Outcome prediction from the pattern of aberrations in prostate cancer genomes [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA4.
Inexpensive probes for the determination of body temperature.
Authors: C J Gore, R T Withers, G F Woods, L Day
Journal: British Journal of Sports Medicine (1987)

Two-terminal integrated circuit temperature transducers (Analog Devices' AD 590) were used to fabricate skin and rectal probes for the monitoring of mean body temperature. They are inexpensive, robust, easily constructed and of low mass. The skin sensor system described is capable of being solidly attached regardless of the body contour such that it remains integral throughout profuse sweating and vigorous movement. Both types of probe are stable, accurate to within +/- 0.05 degree C over the physiological range of measurement and exhibit 100% response times of approximately 60 s to a square wave stimulus of 10 degrees C.
A NORMAL RELATIVE CORONARY FLOW RESERVE IS ASSOCIATED WITH A LOWER MORTALITY IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE.
Authors: Martijn Meuwissen, Steven AJ Chamuleau, Karel T. Koch, Robbert J. de Winter, Marije M. Vis, Jan Baan, Jan GP Tijssen, Jose PS Henriques, Jan J. Piek
Journal: Journal of the American College of Cardiology (2010)
Changes Induced by Exposure of the Human Lung to Glass Fiber–Reinforced Plastic
Authors: Carmelo Abbate, Concetto Giorgianni, Renato Brecciaroli, Giovanni Giacobbe, Chiara Costa, Vittorio Cavallari, Francesca Albiero, Stefania Catania, Maria Antonietta Tringali, Lucia Barbaro Martino, Simona Abbate
Journal: Environmental Health Perspectives (2006)

The inhalation of glass dusts mixed in resin, generally known as glass fiber-reinforced plastic (GRP), represents a little-studied occupational hazard. The few studies performed have highlighted nonspecific lung disorders in animals and in humans. In the present study we evaluated the alteration of the respiratory system and the pathogenic mechanisms causing the changes in a group of working men employed in different GRP processing operations and exposed to production dusts. The study was conducted on a sample of 29 male subjects whose mean age was 37 years and mean length of service 11 years. All of the subjects were submitted to a clinical check-up, basic tests, and bronchoalveolar lavage (BAL); microscopic studies and biochemical analysis were performed on the BAL fluid. Tests of respiratory function showed a large number of obstructive syndromes; scanning electron microscopy highlighted qualitative and quantitative alterations of the alveolar macrophages; and transmission electron microscopy revealed the presence of electron-dense cytoplasmatic inclusions indicating intense and active phlogosis (external inflammation). Biochemical analyses highlighted an increase in protein content associated with alterations of the lung oxidant/antioxidant homeostasis. Inhalation of GRP, independent of environmental concentration, causes alterations of the cellular and humoral components of pulmonary interstitium; these alterations are identified microscopically as acute alveolitis.
Clinical Onset Characteristics of Familial Versus Nonfamilial Cases in a Large Population-based Cohort of Childhood-Onset Diabetes Patients
Authors: Gisela G Dahlquist, Lena R Mustonen
Journal: Diabetes Care (1995)

OBJECTIVE To compare characteristics at clinical onset of childhood-onset diabetes patients with and without a first-degree relative with childhood-onset insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS In a nationwide continuous incident diabetes register covering patients from 0 to 14 years of age with a high level of ascertainment, we compared 687 patients who at onset had at least one first-degree relative with insulin-treated diabetes with 5,137 patients without such relatives. RESULTS The pattern of change over the 15-year period was similar among familial- and sporadic-case patients. The seasonal pattern, with a lower incidence during the warmer period of the year, was similar in both groups. Age at clinical onset was also similar in both groups in either sex. When the proband had a sibling who already had the disease, the mean age at onset was significantly higher when compared with sporadic-case or other familial-case patients. CONCLUSIONS This analysis of a very large set of population-based cases of childhood diabetes showed that patients who had one first-degree relative with insulin-treated diabetes at onset shared the onset characteristics of those without such family members, including age at onset, sex ratio, seasonality, and secular trend. The findings may indicate that the complex interactions between genetic and nongenetic risk factors subsequently leading to IDDM are mainly shared by familial- and sporadic-case patients.
Myocardial Glucose Transport and Utilization in Patients With Type 2 Diabetes Mellitus, Left Ventricular Dysfunction, and Coronary Artery Disease
Authors: David P. Dutka, Michael Pitt, Domenico Pagano, Marco Mongillo, David Gathercole, Robert S. Bonser, Paolo G. Camici
Journal: Journal of the American College of Cardiology (2006)
Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells
Authors: Gang Lu, Haipeng Sun, Pengxiang She, Ji-Youn Youn, Sarah Warburton, Peipei Ping, Thomas M. Vondriska, Hua Cai, Christopher J. Lynch, Yibin Wang
Journal: Journal of Clinical Investigation (2009)

The branched-chain amino acids (BCAA) are essential amino acids required for protein homeostasis, energy balance, and nutrient signaling. In individuals with deficiencies in BCAA, these amino acids can be preserved through inhibition of the branched-chain-alpha-ketoacid dehydrogenase (BCKD) complex, the rate-limiting step in their metabolism. BCKD is inhibited by phosphorylation of its E1alpha subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates. Loss of PP2Cm completely abolished substrate-induced E1alpha dephosphorylation both in vitro and in vivo. PP2Cm-deficient mice exhibited BCAA catabolic defects and a metabolic phenotype similar to the intermittent or intermediate types of human maple syrup urine disease (MSUD), a hereditary disorder caused by defects in BCKD activity. These results indicate that PP2Cm is the endogenous BCKD phosphatase required for nutrient-mediated regulation of BCKD activity and suggest that defects in PP2Cm may be responsible for a subset of human MSUD.
Multiple lipolysis defects in the insulin resistance (metabolic) syndrome.
Authors: S Reynisdottir, K Ellerfeldt, H Wahrenberg, H Lithell, P Arner
Journal: Journal of Clinical Investigation (1994)

Bearing in mind the importance of upper-body obesity for the insulin resistance (or metabolic) syndrome and the abnormalities in free fatty acid metabolism associated with this disorder, the regulation of lipolysis in isolated subcutaneous adipocytes was investigated in 13 72-yr old upper-body obese men with insulin resistance and glucose intolerance and in 10 healthy 72-yr-old men. There was a marked resistance to the lipolytic effect of noradrenaline in the metabolic syndrome due to defects at two different levels in the lipolytic cascade. First, an 80-fold decrease in sensitivity to the beta 2-selective agonist terbutaline (P < 0.001) which could be ascribed to a 50% reduced number of beta 2-receptors (P < 0.005) as determined with radioligand binding. The groups did not differ as regards dobutamine (beta 1) or clonidine (alpha-2) sensitivity, nor beta 1-receptor number. The mRNA levels for beta 1- and beta 2-receptors were similar in the two groups. Second, the maximum stimulated lipolytic rate was markedly reduced in the metabolic syndrome. This was true for isoprenaline (nonselective beta-agonist), forskolin (activating adenylyl cyclase), and dibutyryl cAMP (activating protein kinase). In regression analysis, the observed abnormalities in lipolysis regulation correlated in an independent way with the degree of glucose intolerance (r = -0.67) and beta 2-receptor number with insulin resistance (r = 0.67). In conclusion, the results of this study indicate the existence of lipolytic resistance to catecholamines in the adipose tissue of elderly men with the metabolic syndrome, which may be of importance for impaired insulin action and glucose intolerance. The resistance is located at a posttranscriptional level of beta 2-receptor expression and at the protein kinase-hormone sensitive lipase level.
UK paediatric surgeon wins libel damages
Authors: C. Dyer
Journal: BMJ (1998)

Haemophagocytic lymphohistiocytosis (HLH) is a rare condition of uncontrolled immune activation as a result of an inherited genetic defect or in response to malignancy, autoimmune disease, rheumatological disease, AIDS infection or post-transplant immunosuppression. Described here is the case of a 19-year-old Caucasian man who presented with complaints of worsening fever, new-onset jaundice and lethargy after failing treatment for suspected infectious mononucleosis. Physical examination was significant for fever and splenomegaly while laboratory results revealed transaminitis, cytopaenia, indirect hyperbilirubinaemia and elevated ferritin, raising the likelihood of both autoimmune haemolytic anaemia and HLH. He tested positive for Epstein-Barr virus (EBV), and bone marrow biopsy revealed hypercellular marrow with haemophagocytosis and no evidence of malignancy. High dose steroids were initiated with significant improvement in haemoglobin, resulting in a final diagnosis of HLH secondary to acute EBV infection. The patient was discharged on continued high-dose prednisone with planned taper and consideration of outpatient rituximab therapy for 4 weeks. High clinical suspicion and prompt evaluation were critical to early treatment and decreased morbidity.
Minister orders new checks on private care homes after regulator failed to act on abuse
Authors: C. Dyer
Journal: BMJ (2011)

The UK government has ordered an urgent review of private hospitals caring for adults with learning disabilities and four care workers have been arrested after an undercover TV programme exposed abuse described by a clinical psychologist as “torture.”

Three men and a woman working at Winterbourne View in Bristol were arrested and bailed by police after a reporter for the BBC Panorama programme secretly filmed workers over a four week period slapping and kicking residents, taunting them, pinning them under chairs, and drenching them with cold water.

Care services minister Paul Burstow announced that the Care Quality Commission (CQC), …
A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis
Authors: Vlad Ratziu, Victor de Ledinghen, Fréderic Oberti, Philippe Mathurin, Claire Wartelle-Bladou, Christophe Renou, Philippe Sogni, Marianne Maynard, Dominique Larrey, Lawrence Serfaty, Dominique Bonnefont-Rousselot, Jean-Philippe Bastard, Marc Rivière, Jean Spénard
Journal: Journal of Hepatology (2010)
Doses of Nicotine and Lung Carcinogens Delivered to Cigarette Smokers
Authors: Mirjana V. Djordjevic, Steven D. Stellman, Edith Zang
Journal: JNCI Journal of the National Cancer Institute (2000)

Cigarette smoke yields of tar and nicotine obtained under the Federal Trade Commission (FTC)-specified machine-smoking protocol (35-mL puff volume drawn for 2 seconds once per minute) may not accurately reflect the delivery of toxins and carcinogens to the smoker. We conducted this study to obtain more realistic estimates of exposure to components of cigarette smoke that affect lung cancer risk.We used a pressure transducer system to evaluate puffing characteristics for 133 smokers of cigarettes rated by the FTC at 1.2 mg of nicotine or less (56 smokers of low-yield cigarettes [</=0.8 mg of nicotine per cigarette] and 77 smokers of medium-yield cigarettes [0.9-1.2 mg of nicotine per cigarette]). We programmed measurements from a randomly chosen subset of 72 of these smokers into a piston-type machine to generate smoke from each smoker's usual brand of cigarettes for assays of nicotine, carbon monoxide, tar, and the lung cancer-causing agents 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene. The FTC protocol was also used to assess levels of targeted components in the 11 brands most frequently smoked by study subjects.Compared with the FTC protocol values, smokers of low- and medium-yield brands took in statistically significantly larger puffs (48.6 and 44.1 mL, respectively) at statistically significantly shorter intervals (21.3 and 18.5 seconds, respectively), and they drew larger total smoke volumes than specified in the FTC parameters. They received, respectively, 2.5 and 2.2 times more nicotine and 2.6 and 1.9 times more tar than FTC-derived amounts, as well as about twofold higher levels of benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Smokers of medium-yield cigarettes compared with smokers of low-yield cigarettes received higher doses of all components.The FTC protocol underestimates nicotine and carcinogen doses to smokers and overestimates the proportional benefit of low-yield cigarettes. Thus, FTC-based nicotine medication doses prescribed/recommended for smoking cessation may need to be reassessed.
DNA Damage Triggers a Chronic Autoinflammatory Response, Leading to Fat Depletion in NER Progeria
Authors: Ismene Karakasilioti, Irene Kamileri, Georgia Chatzinikolaou, Theodoros Kosteas, Eleni Vergadi, Andria Rasile Robinson, Iannis Tsamardinos, Tania A. Rozgaja, Sandra Siakouli, Christos Tsatsanis, Laura J. Niedernhofer, George A. Garinis
Journal: Cell Metabolism (2013)
Chloroform in Hydrophobia
Authors: S. B. Denton
Journal: BMJ (1849)

on his way to the infant school, on the 16th of October, 1848, was bitten by a dog through the under lip.The wound was quite free from pain, and soon healed.The child betrayed no symptom of indisposition until the expiration of a month.On Sunday, the 12th of November, the child went to school as usual, and nothing uncommon was nioticed until dinner time, when he refusecl to eat anything.His mother asked him why he did not eat his dinner.He replied that he felt sick and weary, and had been so the whole day, accompanied by unusuial perspiration.She prevailed
The ethics of placebo treatment for patients with acute exacerbation of chronic hepatitis B
Authors: Gin-Ho Lo
Journal: Hepatology (2011)

I read with interest the article by Garg et al.,1 who showed that tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B virus (HBV) presenting as acute-on-chronic liver failure (ACLF). As indicated by the authors, the short-term prognosis of patients with spontaneous severe acute exacerbation of chronic hepatitis B leading to ACLF-like presentation is extremely poor, with a mortality rate ranging from 30%-70%. The current study showed that mortality rate was 43% in the tenofovir group and up to 85% in the placebo group. Prior to the start of the trial by Garg et al., Chien et al.2 demonstrated that the use of lamivudine is definitely beneficial for these patients, with an improved survival compared to historic controls. Moreover, this study showed that patients with serum bilirubin lower than 20 mg/dL could usually be rescued with the use of lamivudine. As a consequence, the HBV management guidelines proposed by organizations such as the Asian Pacific Association for the Study of the Liver (APASL)3 as well as the American Association for the Study of Liver Diseases (AASLD)4 consistently recommend that when patients with HBV who have ACLF are treated, antiviral drugs should be promptly instituted. The trial by Garg et al., which used placebo drug as a control, leading to an appreciably high mortality in this group, in order to demonstrate the efficacy of tenofovir in treating patients with HBV who have ACLF, was apparently medically unethical. Similar studies should be strongly discouraged. Gin-Ho Lo M.D.*, * Department of Medical Education, Digestive Center, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan.
IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes
Authors: Yasunori Nakagawa, Shinya Abe, Morito Kurata, Maki Hasegawa, Kouhei Yamamoto, Miori Inoue, Tamiko Takemura, Kenshi Suzuki, Masanobu Kitagawa
Journal: American Journal of Hematology (2006)

Multidrug-resistant (MDR) multiple myeloma (MM) patients who fail chemotherapy frequently express MDR1 protein, which serves as an efflux pump that protects neoplastic cells. The expression of lung resistance protein (LRP), which mediates intercellular and nucleocytoplasmic transport, is also correlated with chemotherapy resistance and shorter survival of MM patients. Here, we investigated the chemotherapy-induced change of MDR expression in MM patients using quantitative RT-PCR. Overall expression levels of MDR1 and LRP in MM patients were significantly higher than those in control subjects and increased after chemotherapy. More than half of the patients exhibited increased expression of MDR1 (14/26) or LRP (17/26) after chemotherapy. Also, the expression of inhibitor of apoptosis proteins (IAP) was determined in association with the prognosis of the patients. Among patients with increased MDR1-expression after chemotherapy, those with a poor outcome exhibited significant increases in survivin, cIAP1, cIAP2, and XIAP expression by chemotherapy compared with those with a good prognosis. Similarly, in the LRP expression-increased group, patients with a poor outcome showed significant increases of cIAP1 and cIAP2 expression compared with those with longer survival. In patients with reduced-MDR1 or LRP expression after chemotherapy, changes in the expression of IAPs induced by chemotherapy did not correlate with their prognosis. These findings indicate that IAP family proteins might play a role in worsening the prognosis of MM patients in association with chemotherapy-induced overexpression of MDR1 or LRP. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc.
CONVEYANCE OF INFECTION THROUGH THE MEDIUM OF THE EAR SYRINGE: A REMEDY.
Authors: FRANK C. TODD
Journal: JAMA (1899)

Inflammation of the middle ear may result from various affections of the nose and throat or from infection externally, and may terminate in recovery without treatment. With modern treatment many cases undergo a speedy recovery, running a course of from a few days to two months, while others under similar conditions and with the same treatment result in a most violent inflammation involving the mastoid and surrounding structures, or lapse into chronic suppuration. The variation in severity and chronicity is in a large degree due to the character of the bacterium or bacteria causing the infection. "Whether the disease shall promptly run its course or change into the chronic form depends upon the continued activity of the germs present or upon the gradual dying out of the first culture and implantation of new varieties upon the now affected membrane." (C. R. Holmes.) The germs commonly causing inflammation of the middle
Intussusception Secondary to Meckel's Diverticulum Detection With Tc-99m Monoclonal Antibodies to Granulocytes (LeukoScan®)
Authors: BRUCE J. BARRON, DAVID B. ROBINS, LAMK M. LAMKI, WILLIAM DANIELS, LUCKY CHOPRA, C. THOMAS BLACK
Journal: Clinical Nuclear Medicine (1996)

A case of Meckel's diverticulum causing intussusception in an 8-year-old boy is presented. The Meckel's diverticulum was detected by using a Tc-99m-labeled antigranulocyte monoclonal antibody MN3 (Leukoscan®; Immunomedics, Morris Plains, NJ), which is under clinical evaluation for the detection of atypical appendicitis at the authors' institution. Pathologic evaluation confirmed Meckel's diverticulitis with ileal-ileal intussusception.