tbuckley/cabot-search huggingface dataset:
<i>RRM1</i> Modulated In Vitro and In Vivo Efficacy of Gemcitabine and Platinum in Non–Small-Cell Lung Cancer
Authors: Gerold Bepler, Irina Kusmartseva, Swati Sharma, Ashish Gautam, Alan Cantor, Anupama Sharma, George Simon
Journal: Journal of Clinical Oncology (2006)

Purpose RRM1 encodes the regulatory subunit of ribonucleotide reductase and is a molecular target of gemcitabine. Previous studies showed increased RRM1 expression on continuous exposure of cell lines to gemcitabine and suggested improved survival for patients with low as opposed to high tumoral RRM1 expression when treated with gemcitabine-containing chemotherapy. However, the principal hypothesis that intratumoral levels of gene expression are associated with disease response has not been addressed. Patients and Methods We constructed genetically modified lung cancer cell lines with increased and decreased RRM1 expression to investigate the in vitro 50% inhibitory concentration (IC 50 ) for gemcitabine, cisplatin, and carboplatin. A prospective phase II clinical trial in patients with locally advanced non–small-cell lung cancer was conducted with pretreatment tumor collection for determination of RRM1 and ERCC1 expression by real-time reverse transcriptase polymerase chain reaction. The levels of gene expression were correlated with tumor response after two cycles of gemcitabine and carboplatin. Results In cell lines with a genetically engineered 15-fold RRM1 expression range, the gemcitabine IC 50 had a 100-fold range, and the cisplatin and carboplatin IC 50 had a two-fold range. They were highest in constructs with high RRM1 expression. In the prospective clinical trial, RRM1 expression was significantly (P = .002) and inversely correlated (r = −0.498) with disease response. ERCC1 expression showed a similar trend (P = .099). Conclusion The results strongly suggest that tumoral RRM1 expression is a major predictor of disease response to gemcitabine/platinum chemotherapy. ERCC1 expression is predictive of response albeit to a lesser degree.
Incidence, Prevalence, and Clinical Significance of Abnormal Hematologic Indices in Compensated Cirrhosis
Authors: Amir A. Qamar, Norman D. Grace, Roberto J. Groszmann, Guadalupe Garcia–Tsao, Jaime Bosch, Andrew K. Burroughs, Cristina Ripoll, Rie Maurer, Ramon Planas, Angels Escorsell, Juan Carlos Garcia–Pagan, David Patch, Daniel S. Matloff, Robert Makuch, Gabriel Rendon
Journal: Clinical Gastroenterology and Hepatology (2009)
Spontaneous Recurrence of Marihuana Effect
Authors: MARTIN H. KEELER, CLIFFORD B. REIFLER, MYRON B. LIPTZIN
Journal: American Journal of Psychiatry (1968)

Four individuals reported the recurrence, in a drug-free state, of unusual visual or somatic sensations previously experienced during marihuana reaction. None had used other hallucinogens. Two of the four were distressed by these recurrences. Such events should be distinguished from the recurrence of clinical psychopathology first experienced during marihuana reaction and from reports of nonspecific heightening of perception subsequent to marihuana use.
Protein kinase C inhibits cyclic adenosine monophosphate generation by histamine and truncated glucagon like peptide 1 in the human gastric cancer cell line HGT-1.
Authors: P McKenna, J M Williams, C P Gespach, P J Hanson
Journal: Gut (1993)

The HGT-1 gastric cancer cell line was used to determine the actions of protein kinase C on the stimulation of adenylate cyclase by the human histamine H2 receptor, and the receptors for gastric inhibitory polypeptide and truncated glucagon like peptide 1 (TGLP-1). Suspensions of HGT-1 cells were preincubated with the activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nmol/l), for 10 minutes. The subsequent cyclic adenosine monophosphate (AMP) response to 0.5 mmol/l histamine or 100 nmol/l TGLP-1 was reduced by comparison with control cells preincubated in the absence of TPA. The cyclic AMP response to 100 nmol/l gastric inhibitory polypeptide was enhanced by preincubation with TPA, while the responses to cholera toxin and forskolin were unaffected. Preincubation with pertussis toxin prevented the enhancement of the gastric inhibitory polypeptide response by TPA, suggesting an involvement of an inhibitory guanine nucleotide regulatory subunit of the Gi class, but did not change the inhibition of histamine stimulation. In conclusion, activation of protein kinase C produces a specific inhibition of the effects of histamine and TGLP-1 on adenylate cyclase activity in a human gastric cancer cell line by acting at a site close to their receptors.
Antigen-specific regulatory T cells develop via the ICOS–ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity
Authors: Omid Akbari, Gordon J. Freeman, Everett H. Meyer, Edward A. Greenfield, Tammy T. Chang, Arlene H. Sharpe, Gerald Berry, Rosemarie H. DeKruyff, Dale T. Umetsu
Journal: Nature Medicine (2002)
Highlights of the 2010 North American Cystic Fibrosis Conference
Authors: Kevin W Southern
Journal: Journal of the Royal Society of Medicine (2011)

The 24th North American Cystic Fibrosis (CF) Conference was held in Baltimore, Maryland. The meeting did not have the heightened level of excitement of the past couple of years, but there was an air of anticipation relating to the number of ongoing trials of new therapies. In addition, novel therapies are emerging rapidly and it is clear that CF teams will need to reflect carefully on how these fit into their management strategies. The three plenary sessions are available on the CFF website:
BRCA1 Deficiency Exacerbates Estrogen-Induced DNA Damage and Genomic Instability
Authors: Kienan I. Savage, Kyle B. Matchett, Eliana M. Barros, Kevin M. Cooper, Gareth W. Irwin, Julia J. Gorski, Katy S. Orr, Jekaterina Vohhodina, Joy N. Kavanagh, Angelina F. Madden, Alexander Powell, Lorenzo Manti, Simon S. McDade, Ben Ho Park, Kevin M. Prise, Stuart A. McIntosh, Manuel Salto-Tellez, Derek J. Richard, Christopher T. Elliott, D. Paul Harkin
Journal: Cancer Research (2014)

Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell-cycle arrest, and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here, we report that estrogen and estrogen metabolites can cause DNA double-strand breaks (DSB) in estrogen receptor-α-negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolizing enzymes, such as CYP1A1, in breast cells. Finally, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumors in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.
Rupture of the normal aortic valve after blunt chest trauma.
Authors: S Chi, T C Blair, L Gonzalez-Lavin
Journal: Thorax (1977)

Rupture of the normal aortic valve after blunt trauma to the chest is seen infrequently. With the ever-increasing incidence of car and motorcycle accidents, this injury should be considered during the initial examination of an accident victim. Any patient without a history of heart disease presenting with heart murmurs after severe blunt trauma to the chest should give rise to the suspicion of aortic valve damage. When the diagnosis is proved, aortic valve expoloration is necessary. Review of the published cases establishes that valve replacement is the treatment of choice.
P238 Characteristics, treatment patterns and outcomes of patients with non-CF bronchiectasis: a single institution district general hospital (DGH) analysis
Authors: M. J. McDonnell, C. Mashamba, A. Foden
Journal: Thorax (2010)

<h3>Introduction</h3> Non-CF bronchiectasis has been the subject of analysis for several years with limited guidelines available regarding appropriate investigation and management strategies to optimise patient care. Non-CF bronchiectasis is common and, unlike CF, is often managed by general respiratory physicians in a DGH setting. BTS consensus, based largely on case-control series and cohort studies, has recently been published to aid clinicians in diagnosis and management. <h3>Objectives</h3> The aim of this retrospective study is to present data on patient characteristics, treatment patterns, and treatment results in an unselected patient group with non-CF bronchiectasis over a 9-year period. <h3>Methods</h3> From January 2000 to December 2009, we reviewed the clinical, radiological, microbiological, and physiological findings in 73 well-studied patients with proven non-CF bronchiectasis. We collected data on drug and non-drug management, including side effects and response to treatment-measured as improvement in pulmonary lung function (PFTs). <h3>Results</h3> There was a male:female ratio of 1:2 with mean age of 51.4 years (range 3–81); 46.6% were lifetime non-smokers. Idiopathic bronchiectasis was confirmed in 54.7% patients on completion of full bronchial sepsis screen. Of the idiopathic group, 42.5% were smokers; 22.5% of these were confirmed to have COPD prior to diagnosis of bronchiectasis. HRCT confirmed diagnosis of bronchiectasis in 82.2% of patients with bibasal predominance in majority. Initial CXR was abnormal in 62.8%. PFTs documented airway obstruction in 54% of lifetime non-smokers. Smokers had greater degree of airway obstruction than non-smokers and greater number of exacerbations/patient/year. Pathologic microbial flora isolated from sputum included Haemophilus influenza and other opportunistic organisms. 17.8% patients were colonised with <i>Pseudomonas aeruginosa</i> and treated with prophylactic nebulised antibiotics. There was no relationship between COPD and pseudomonas colonisation. 5.5% patients were treated with prophylactic oral antibiotics. Side-effects occurred in 4.1% overall (<i>Clostridium difficile</i>). Factors contributing to worsening of PFTs include increased number of exacerbations/patient/year, pseudomonas colonisation and smoking status. <h3>Conclusion</h3> We provide a comprehensive analysis of a contemporary patient population. Treatment patterns fit well in the context of current consensus based on international trials. We suggest a likely correlation between the pathophysiology of COPD and bronchiectasis which warrants further investigation with randomised controlled trials.
Soft Skills Matter
Authors: Diana L. Farmer
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Lethal host-versus-graft disease and hypereosinophilia in the absence of MHC I–T-cell interactions
Authors: Jérôme D. Coudert, Gilles Foucras, Cécile Demur, Christiane Coureau, Catherine Mazerolles, Georges Delsol, Philippe Druet, Jean-Charles Guéry
Journal: Journal of Clinical Investigation (2000)

Neonatal injection of semiallogeneic spleen cells in BALB/c mice induces a self-limited state of chimerism that promotes the differentiation of donor-specific CD4 T cells toward the Th2 phenotype. Here we show that injection of spleen cells from β2-microglobulin–deficient (BALB/c × C57BL/6) F1 mice into BALB/c newborns with a disrupted β2-microglobulin (β2m) gene results in a lethal lymphoproliferative disorder associated with uncontrolled Th2 response, long-term persistence of donor B cells, and sustained blood eosinophilia. Autoimmune manifestations are also enhanced and characterized by a severe autoantibody-mediated glomerulonephritis. Histological examination of the spleen shows a hyperplasia of periarteriolar lymphoid sheaths, with accumulation of eosinophils and basophils, and variable degree of fibrosis. Perivascular lymphoid infiltrates with eosinophils are also found in the lung and are correlated with disease severity. Such abnormalities are almost absent using β2m-sufficient mice. These data demonstrate that induction of lymphoid chimerism in the absence of MHC class I–T-cell interactions results in a lethal form of host-versus-graft disease that represents a unique model of Th2-dependent chronic inflammatory disease associated with an hypereosinophilic syndrome in mice.
Parvovirus B19 as a possible causative agent of fulminant liver failure and associated aplastic anemia
Authors: Alan N. Langnas, Rodney S. Markin, Mark S. Cattral, Stanley J. Naides
Journal: Hepatology (1995)

We recently observed that more than one third of pediatric patients who presented with non-A, non-B fulminant liver failure (FLF) also developed aplastic anemia (AA) either before or shortly after liver transplantation. Factors involved in the suppression of bone marrow could be the same as those causing hepatic failure. We considered parvovirus B19 a candidate etiologic agent because of the known tropism of B19 for erythroid precursors. Archived liver and serum from six patients undergoing liver transplantation for non-A, non-B, non-C FLF with associated AA were analyzed for the presence of B19 DNA and anti-B19 serology. An age- and gender-matched control group (N = 44) was analyzed in parallel. B19 DNA studies and anti-B19 serology were performed in a blinded fashion. B19 serologies were performed by antibody capture enzyme-linked immunosorbent assay (ELISA). B19 DNA was detected after polymerase chain reaction (PCR) amplification of target B19 DNA sequences in liver and serum. Liver tissue showed evidence of B19 DNA in four of six (66%) patients with FLF and associated AA. Two of 4 patients with cryptogenic FLF but without AA had B19 DNA detected in the liver tissue. Of the 34 remaining controls, only 5 (15%) showed evidence of B19 DNA in liver tissue (66% vs. 15%, P = .016). B19 DNA was not detected in any of the test or control sera. This study provides evidence to support the role of parvovirus B19 in the development of FLF and associated AA.
Boosting T Cell-Mediated Immunity to Tyrosinase by Vaccinia Virus-Transduced, CD34+-Derived Dendritic Cell Vaccination
Authors: Massimo Di Nicola, Carmelo Carlo-Stella, Roberta Mortarini, Paola Baldassari, Anna Guidetti, Gian Francesco Gallino, Michele Del Vecchio, Fernando Ravagnani, Michele Magni, Paul Chaplin, Natale Cascinelli, Giorgio Parmiani, Alessandro M. Gianni, Andrea Anichini
Journal: Clinical Cancer Research (2004)

Six American Joint Committee on Cancer stage IV melanoma patients were enrolled into a Phase I study of vaccination with autologous CD34(+)-derived dendritic cells transduced with a modified vaccinia Ankara virus encoding human tyrosinase gene (MVA-hTyr).Patients received a first intravenous injection of 1 x 10(8) MVA-hTyr-transduced dendritic cells, followed by three s.c. injections at a 14-day interval.Treatment was well tolerated, except for low-grade fever (three of six patients), mild erythema at injection site (five of six), and vitiligo (two of six). A partial response, involving shrinkage of an s.c. nodule, later surgically removed, was observed in 1 patient, who then remained disease-free (>850 days). By human lymphocyte antigen tetramer analysis, significant and often long-lasting increases in frequency of T cells directed to tyrosinase(368-376) but not to gp100(209-217) were documented in periphery of 4 of 5 HLA-A*0201+ patients, a few days after vaccine administration. In addition, maturation phenotype of tyrosinase-specific T cell shifted toward the T effector memory/T terminally differentiate stages (CCR7(-)CD45RA(-/+)) in synchrony with the T-cell frequency peaks. By enzyme-linked immunospot in peripheral blood of five HLA-A*0201+ patients, we found that the vaccine could induce interferon gamma-releasing effector cells directed to HLA-A*0201/tyrosinase(368-376) and to vaccinia virus HLA-A*0201/H3L(184-192) epitopes. Moreover, an interferon gamma response after vaccination was elicited even against the HLA-DRB1-1501/tyrosinase(386-406) epitope in one out of two HLA-A* DRB1-01501+ patients.These results indicate that vaccination with MVA-hTyr-transduced dendritic cells is well tolerated, can possibly produce clinical responses, and activates tyrosinase- and vaccinia virus-specific T cells in vivo. These data suggest a broad utility of the MVA vector for targeting tumor-associated antigens to dendritic cells for tumor immunotherapy.
Dislocation of the Knee-Joint
Authors: T. O. Ward
Journal: BMJ (1863)

was hardly perceptible; the body was bathed in sweat.It was evident to all that he was fast sinking; and hE died at about 11 o'clock, five days after the first appear- ance of the vesicle.The general treatment consisted chiefly in the liberal administration of good beef-tea, brandy, and ammonia.[To be continued.
Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials
Authors: Tullio Palmerini, Umberto Benedetto, Letizia Bacchi-Reggiani, Diego Della Riva, Giuseppe Biondi-Zoccai, Fausto Feres, Alexandre Abizaid, Myeong-Ki Hong, Byeong-Keuk Kim, Yangsoo Jang, Hyo-Soo Kim, Kyung Woo Park, Philippe Genereux, Deepak L Bhatt, Carlotta Orlandi, Stefano De Servi, Mario Petrou, Claudio Rapezzi, Gregg W Stone
Journal: The Lancet (2015)
Plasma Etoposide Catechol Increases in Pediatric Patients Undergoing Multiple-Day Chemotherapy with Etoposide
Authors: Naiyu Zheng, Carolyn A. Felix, Shaokun Pang, Ray Boston, Peter Moate, Jennifer Scavuzzo, Ian A. Blair
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to determine inter- and intrapatient differences in the pharmacokinetic profiles of etoposide and its genotoxic catechol metabolite during conventional multiple-day dosing of etoposide in pediatric patients. Experimental Design: Seven pediatric patients with various malignancies received etoposide at a dose of 100 mg/m2 i.v. over 1 h daily for 5 days. Blood samples were taken at selected time points on days 1 and 5. Plasma and protein-free plasma concentrations of etoposide and etoposide catechol were determined using a validated liquid chromatography/tandem mass spectrometry assay. Pharmacokinetic parameters of both etoposide and etoposide catechol were calculated using the WinSAAM modeling program developed at NIH. Results: The mean maximum concentration (Cmax) for total (0.262 ± 0.107 μg/ml) and free catechol (0.0186 ± 0.0082 μg/ml) on day 5 were higher than the mean Cmax for total (0.114 ± 0.028 μg/ml) and free catechol (0.0120 ± 0.0091 μg/ml) on day 1. The mean area under the plasma concentration-time curve (AUC)24h for total (105.4 ± 49.1 μg.min/ml) and free catechol (4.89 ± 2.23 μg.min/ml) on day 5 were much greater (P &amp;lt; 0.05) than those for total (55.9 ± 16.1 μg.min/ml) and free catechol (3.04 ± 1.04 μg.min/ml) on day 1. In contrast, the AUC24h for etoposide was slightly lower on day 5 than on day 1. Conclusions: The Cmax and AUC24h for etoposide catechol were significantly higher on day 5 than on day 1. This suggests that metabolism of etoposide to its catechol metabolite increases in pediatric patients receiving multiple-day bolus etoposide infusions. These findings may be relevant to future reduction of the risk of leukemia as a treatment complication, because etoposide and etoposide catechol are both genotoxins.
Brachytherapy: Where Has It Gone?
Authors: Daniel G. Petereit, Steven J. Frank, Akila N. Viswanathan, Beth Erickson, Patricia Eifel, Paul L. Nguyen, David E. Wazer
Journal: Journal of Clinical Oncology (2015)

Daniel G. Petereit, Rapid City Regional Cancer Center, Rapid City, SD Steven J. Frank, University of Texas MD Anderson Cancer Center, Houston, TX Akila N. Viswanathan, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Beth Erickson, Medical College of Wisconsin, Milwaukee, WI Patricia Eifel, University of Texas MD Anderson Cancer Center, Houston, TX Paul L. Nguyen, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA David E. Wazer, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, and Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI
Myocardial viability inchronic ischemic heart disease
Authors: Harald P. Kühl, Aernout M. Beek, Arno P. van der Weerdt, Mark B.M. Hofman, Cees A. Visser, Adriaan A. Lammertsma, Nicole Heussen, Frans C. Visser, Albert C. van Rossum
Journal: Journal of the American College of Cardiology (2003)
Age dependence of oval cell responses and bile duct carcinomas in male fischer 344 rats fed a cyclic choline-deficient, ethionine-supplemented diet
Authors: Ian Guest, Zoran Ilic, Stewart Sell
Journal: Hepatology (2010)

The age dependence of the oval cell response and bile duct carcinomas of male F344 rats exposed to a cyclic choline deficiency-ethionine (CDE) diet (2 weeks on, 1 week off) supports the concept of loss of potential of liver stem cells to form cancers with aging. Livers of rats exposed at 3 weeks of age demonstrated a robust and widespread oval cell proliferation followed by cholangiofibrosis and bile duct metaplasia with extensive mucinous cysts throughout all lobes, and induction of cholangiocarcinomas (CCAs) in seven of eight rats. Livers of rats exposed beginning at 8 weeks of age had much less oval cell response and cholangiofibrosis with only 1 of 15 rats developing a CCA. Livers in old (10-12 months when started) rats remained virtually unaffected, with minimal oval cell proliferation, only occasional and small foci of ductular dysplasia, and none of 16 rats developed CCAs. In contrast to most published studies using uninterrupted choline deficiency plus a carcinogen, hepatocellular carcinoma (HCC) was not observed under the conditions of this study. Conclusion: With aging, male F344 rats exposed to cyclic CDE diet display a diminished oval cell response and fewer CCAs. The absence of HCC is possibly due to the fact that during cyclic CDE, the week off may allow putative liver stem cells to avoid death or differentiation and survive to give rise to CCAs, whereas with continuous CDE exposure, the stem cells are forced to differentiate and develop into HCCs with relatively few CCAs. Hepatology 2010