tbuckley/cabot-search huggingface dataset:
How free of germs is germ-free? Detection of bacterial contamination in a germ free mouse unit
Authors: Clinton A Fontaine, Anna M Skorupski, Chriss J Vowles, Natalie E Anderson, Sara A Poe, Kathryn A Eaton
Journal: Gut Microbes (2015)

Management of germ free animals has changed little since the beginning of the 20th century. The current upswing in their use, however, has led to interest in improved methods of screening and housing. Traditionally, germ free colonies are screened for bacterial colonization by culture and examination of Gram stained fecal samples, but some investigators have reported using PCR-based methods of microbial detection, presumably because of perceived increased sensitivity. The accuracy and detection limit for traditional compared to PCR-based screening assays are not known. The purpose of this study was to determine the limit of detection of bacterial contamination of mouse feces by aerobic and anaerobic culture, Gram stain, and qPCR, and to compare the accuracy of these tests in the context of a working germ free mouse colony. We found that the limit of detection for qPCR (approximately 105 cfu/g of feces) was lower than for Gram stain (approximately 109 cfu/g), but that all 3 assays were of similar accuracy. Bacterial culture was the most sensitive, but the least specific, and qPCR was the least sensitive and most specific. Gram stain but not qPCR detected heat-killed bacteria, indicating that bacteria in autoclaved diet are unlikely to represent a potential confounding factor for PCR screening. We conclude that as a practical matter, bacterial culture and Gram stain are adequate for screening germ free mouse colonies for bacterial contaminants, but that should low numbers of unculturable bacteria be present, they would not be detected with any of the currently available means.
Abstract 428: HIC-1: A gene silenced in cancer stem cells of glioma
Authors: Mohita Bhagat, Subrata Sinha, Parthaprasad Chattopadhyay
Journal: Cancer Research (2014)

Abstract Background : According to the cancer stem cell hypothesis, tumors contain and are driven by a minority cellular population which has retained or re-established key stem-cell properties. Studies have demonstrated frequent hypermethylation of the HIC-1 locus in human cancers and recent work has demonstrated hypermethylation of HIC-1 in ES cells. Targeted methylation of HIC-1 has been shown to transform mesenchymal stem cells into cancer stem/initiating cells. However, so far no study has established the epigenetic role/status of HIC-1 in cancer stem cells. Methods and Results: U87MG, a glioblastoma cell line, showed a consistent decrease of HIC-1 expression in gliomaspheres obtained in Stem cell media compared to same tumor cells grown in normal media. To examine for the role of HIC-1 in regulating stemness (Sox-2, Oct-4, Nanog), we established a U87 cell line with dominant negative p53 (dn-U87) expressing low HIC-1 levels. Increase in expression of stemness markers was observed in dn-U87 compared to wt-U87.Moreover,effect of hypoxia in increasing stemness was more pronounced in the dn-U87 cell line. Knockdown of HIC-1 in U87MG grown in normal or stem cell media exhibited an increase in expression of stemness markers (Sox2, Oct4, Nanog and Nestin) under both conditions compared to Mock and control, further confirming role of HIC-1 in modulating stemness expression . Also, gliomaspheres were obtained much earlier (i.e. on Day 4) in HIC-1 knockdown samples grown in stem cell media compared to both Mock and Control (Day7). To look for the difference in epigenetic signature of HIC-1 gene between gliomaspheres and tumor cells, we checked for changes in methylation and chromatin accessibility in the two cell populations. MNAse assay ascertained heterochromatization of the HIC-1 promoter in gliomaspheres compared to normal U87 cells, while bisulfite sequencing or High Resolution Melt PCR could not detect any change in methylation pattern of the HIC-1 promoter in the two cell populations studied. Interpretation and Conclusion: Down-regulation of HIC-1, by i) epigenetic changes or ii) knockdown by siRNA or iii) using mutant p53 cell line, may be responsible for contributing to stem cell-like properties to tumor cells. Since HIC-1 is a tumor suppressor gene silenced in many cancers as a result of promoter hypermethylation, it could by itself be a new target for epigenetic therapy. Moreover, increase in stemness on knockdown of HIC-1 could provide new insights into the behavior of cancer-initiating stem cells. Citation Format: Mohita Bhagat, Subrata Sinha, Parthaprasad Chattopadhyay. HIC-1: A gene silenced in cancer stem cells of glioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 428. doi:10.1158/1538-7445.AM2014-428
Health Care Delivery in the Texas Prison System
Authors: Christian T Sinclair, Karin Porter-Williamson
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
FDA OKs Nonprescription Defibrillators
Authors: Mike Mitka
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Continuity of care for chronic mental patients: a conceptual analysis
Authors: L L Bachrach
Journal: American Journal of Psychiatry (1981)

The author discusses seven dimensions of continuity of care, a basic concept in planning services for chronic mental patients. Continuity of care in psychiatry is distinguished from that in other medical specialties by the unique needs of chronic mental patients. Different approaches to continuity must be used for chronic mental patients with different institutional histories and specialized service needs.
Transfusion Thresholds in High-Risk Patients after Hip Surgery
Authors: Patrick Meybohm, Kai Zacharowski
Journal: New England Journal of Medicine (2012)

transfusion strategy in patients with anemia after hip-fracture surgery. A major limitation of this trial (and of others that have addressed transfusion thresholds 2 ) is the failure to take into account the different causes of the patients’ anemia. This is analogous to conducting a trial of aggressive fluid resuscitation in unselected patients with hypotension: although volume expansion will benefit patients with hemorrhage or sepsis, it may harm those with heart failure. A more liberal transfusion strategy could benefit patients with anemia caused by acute blood loss, since levels of erythrocyte 2,3-bisphosphoglyceric acid may be depleted in such patients. Conversely, in patients whose anemia is predominantly the anemia of chronic disease, transfusion may be harmful. Raising hemoglobin levels may increase mortality in patients in whom anemia of chronic disease is likely to be prevalent, including those in critical care 2 or with renal failure 3 or cancer, 4 since in such patients anemia may be an adaptive response to inflammation. 5 We suggest that Carson and colleagues analyze their data according to subgroups on the basis of the cause of anemia.
Mechanism-based biomarkers of activity for a novel HDAC inhibitor PCI-24781 in solid and hematologic malignancies
Authors: Sriram Balasubramanian, Shanthi Adimoolam, Mint Sirisawad, Joseph Buggy
Journal: Clinical Cancer Research (2007)

C24   Broad-spectrum histone deacetylase (HDAC) inhibitors are currently showing promise in clinical trials for treating a variety of neoplastic malignancies. One such compound, PCI-24781, is a novel, orally bioavailable HDAC inhibitor that effectively inhibits the enzymatic activity of most of the eleven known HDAC isoforms. PCI-24781 is active against many tumors in preclinical models including cell lines, mouse xenograft models and in primary human tumors cultured  ex vivo  with mean GI50 values of 0.1 -0.5 uM, depending on tumor type. One of the mechanisms of activity of this compound involves inhibition of DNA repair pathways. When samples from these experiments were examined by a combination of whole genome expression profiling, Western blotting for key proteins, and biochemical pathway analysis, we found a correlation between activity and expression changes in several key DNA repair genes, including RAD51. This protein is essential for DNA repair by homologous recombination (HR), and interestingly, we found that PCI-24781 can synergize with poly (ADP-ribose) polymerase (PARP) inhibitor PJ34, an agent thought to produce lesions repaired by HR. Further, we found that RAD51 is downregulated at both protein and mRNA levels by PCI-24781 in both solid and hematopoietic cell lines and tumors, leading to inhibition of DNA repair and RAD51 foci formation, eventually leading to apoptosis. The decrease in RAD51 levels upon PCI-24781 treatment showed a significant correlation with activity in these models. When the differences between sensitive and resistant tumors were analyzed, it was observed that sensitive tumors showed a consistent decrease of >2-fold in RAD51 levels, whereas resistant tumors did not. Thus, RAD51 appears to be a good biomarker of sensitivity in both solid and hematologic tumors. In addition, from the primary colon tumors, we have also identified a set of genes previously associated with chemoresistance that were expressed at 3-15 fold higher levels in the resistant tumors. This signature was confirmed by Taqman (RT-PCR) analysis, and was further validated in an independent set of primary colon tumors. These markers of sensitivity and resistance will be used to identify likely responders in clinical trials with PCI-24781.
Correction and transparency of BNF risk charts
Authors: R. A Payne, D. J Webb, S. R J Maxwell
Journal: BMJ (2009)

The Joint British Societies’ (JBS) charts use a “traffic lights” system to emphasise different categories of cardiovascular risk.1 They were published in 2005 in conjunction with the societies’ guidelines2 and are reproduced biannually in the BNF .

We recently observed that the green (<10% risk) area was missing from the charts for non-diabetic male non-smokers aged 50-59, and …
Fanconi anemia gene variants in therapy-related myeloid neoplasms
Authors: M T Voso, E Fabiani, Z Zang, L Fianchi, G Falconi, A Padella, M Martini, S Li Zhang, R Santangelo, L M Larocca, M Criscuolo, A La Brocca, I Cutcutache, S Rozen, G Simonetti, M Manfrini, G Martinelli, S Hohaus, G Leone, P Tan, D G Tenen
Journal: Blood Cancer Journal (2015)

Therapy-related myeloid neoplasms (t-MN) include myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) occurring as a late effect of chemotherapy and/or radiotherapy for a primary malignancy or for autoimmune diseases.1, 2 The incidence of this complication has been raising in the past years because of the prolonged survival and the higher number of treated patients. Still, <5% of patients exposed to cytotoxic drugs and radiotherapy develop a t-MN, suggesting an underlying individual susceptibility. Primary malignancies most frequently associated to t-MN are breast cancer and lymphoproliferative diseases. Other recurrent clinical characteristics are presence of multiple primary neoplasms in the same individual and cancer familiarity.2 So far, higher frequency of single-nucleotide variants of detoxification and DNA-repair enzymes, alone or in association, have been reported in t-MN, but none has been validated as significant risk factor in large patient groups.3, 4, 5, 6
PKC activators phorbol 12-myristate 13-acetate (PMA) and N-benzyladriamycin-14-valerate (AD 198) exert different cellular effects based upon sub-cellular localization.
Authors: Leonard Lothstein, Luydmila Savranskaya, Trevor Sweatman
Journal: Cancer Research (2007)

5405   The phorbol ester PMA and  N -benzyladriamycin-14-valerate (AD 198) possess similar mechanisms of action; i.e., binding to the C1b regulatory domain of conventional and novel isoforms of the C family of protein kinases (PKC). However, the functional consequences may either be the same or vary with cell type. In cardiac myocytes, both agents activate PKC-ϵ to trigger cardioprotective signaling. Both agents are also capable of triggering apoptosis through activation of both PKC-δ and PKC-ϵ. In K562 human leukemia cells, AD 198 triggers rapid apoptosis through PKC-δ activation in a manner that is unaffected by the proliferative effects of Bcr-Abl expression. In contrast, PMA inhibits K562 cell proliferation through the induction of the differentiation pathway leading to megakaryocyte formation, but does not induce apoptosis, even at a concentration 50-fold higher than required to induce differentiation. At sub-cytotoxic levels, AD 198 triggers neither erythroid nor megakaryocyte differentiation of K562. PMA-mediated megakaryocyte formation is associated with the increased expression and activation of PKC-ϵ, as observed by increased PKC-ϵ associated with total cell membrane fractions. Low dose AD 198 induces expression of PKC-ϵ in K562 cells but does not induce PKC-ϵ activation, as shown by the absence of PKC-ϵ translocation from cytosol to membrane. RACK2, a PKC-ϵ-specific receptor of activated PKC, promotes spatial orientation of PKC-ϵ with its specific substrates. We observe an increase in RACK2 protein following treatment of K562 cells with either 250 nM AD 198 or 20 nM PMA. However, RACK2 protein remains in the cytoplasm of AD 198-treated cells, but migrates to the nuclei of PMA-treated cells. In addition to its correlation with K562 differentiation, PMA-mediated PKC-ϵ activity and RACK2 distribution also correlate with increased K562 sensitivity to a variety of antitumor agents. PMA increases the sensitivity of K562 cells 7-fold to the metabolically stable PKC activator  N -benzyladriamycin-14-pivalate (AD 445), 2-fold to the topoisomerase II catalytic inhibitor  N -benzyladriamycin (AD 288) and 0.5-fold to vinblastine. In contrast, 250 nM AD 198 did not sensitize the cells to any of these agents. The localization of AD 198 principally in the cytoplasm as opposed to the distribution of PMA in both the cytoplasm and nucleoplasm suggests that the differential effects of two compounds with the same PKC binding sites correlates, at least in part, with the nuclear distribution of PMA in conjunction with similar localization of PKC-ϵ and RACK2. (Supported by NCI grant CA100093).
Abstract P393: Consumption of Bread and Tortilla and Incidence of Self-Reported Hypertension in Mexican Women
Authors: Adriana Monge, Tonatiuh Barrientos, Isabelle Romieu, Ruy Lopez-Ridaura, Martin Lajous
Journal: Circulation (2014)

Background: Mexico is undergoing a fast-paced epidemiologic and nutritional transition and hypertension affects 31% of Mexicans. Bread and wheat tortilla have almost three times more sodium than corn tortillas and long-term sodium intake may increase the risk of hypertension. Methods and Results: We investigated the relation between bread and tortilla intake and the incidence of self-reported hypertension in 43,619 women from the Mexican Teachers’ Cohort who were free of hypertension at baseline in 2008 when diet was assessed using a food frequency questionnaire. Between baseline and 2011 we identified 2,699 incident cases of self-reported hypertension. Total bread (white and whole grain) and corn and wheat tortilla consumption were categorized into energy-adjusted quintiles and logistic regression models were fit. Median servings per week for extreme categories were 2.0 and 12.5 for total bread (1.4 and 11.0 for white bread; 0.2 and 3.0 for whole grain), 3.0 and 17.5 for corn tortilla, and 0.2 and 3.0 for wheat tortilla, respectively. The multivariable-adjusted odds of hypertension in the highest quintile of intake of total bread were 18% higher than the odds for individuals in the lowest quintile (OR=1.18; 95%CI=1.03-1.35; P-trend=0.12); corn tortilla intake was not significantly associated with hypertension (OR=0.88; 95%CI=0.76-1.01; P-trend=0.05). White bread appeared to be responsible for the observed association, the OR comparing extreme quintiles was 1.18 (OR=1.18; 95%CI=1.03-1.35; P-trend=0.0007). We did not observe an association between whole grain bread and wheat tortilla and hypertension. Conclusion: Bread consumption may affect the incidence of hypertension, while corn tortilla, a substitute for bread in the Hispanic population was not associated with incident hypertension. Results need to be confirmed with extended follow-up.
Abstract 1476: Hypermethylation of a TGF-β regulated micro-RNA, miR-193a, predicts prognosis in ovarian cancer
Authors: Frank Hsueh-Che Cheng, Gary C.W. Chen, Jian-Liang Chou, Ya-Wen Lin, Lin-Yu Chen, Hung-Cheng Lai, Chin Li, Michael W.Y. Chan
Journal: Cancer Research (2014)

Abstract Ovarian cancer is one of the most lethal cancers in the female reproductive system. One of the hypotheses suggests that ovarian cancer arises from cancer stem/progenitor cell with surface antigen CD117 (or c-kit). In order to identify microRNAs (miRNAs) that can regulate the expression of c-kit, bioinformatic prediction was performed and identified miR-193a as one of the regulators. Expression analysis showed that miR-193a was up-regulated upon TGF-β treatment in immortalized ovarian surface epithelial cells (IOSE) cells. On the contrary, expression of miR-193a cannot be detected in a panel of ovarian cancer cell lines (SKOV3, A2780, CP70, MCP2, MCP3). Bisulphite pyrosequencing revealed that promoter CpG island of miR-193a was not methylated in IOSE cell but hypermethylated in the ovarian cancer cells showing down-regulation of miR-193a. Treatment of 5azaDC, a DNMT inhibitor, partially restored miR-193a expression in the ovarian cancer cells, thus suggesting DNA hypermethylation may be responsible for the down-regulation of miR-193a in ovarian cancer. Further clinical studies using bisulphite pyrosequencing found that promoter region of miR-193a was heavily methylated in 109 ovarian cancer patient samples but not in normal OSE samples. Kaplan-meier analysis revealed that patients with higher methylation of miR-193a was significantly associated with shorter overall survival and progression-free survival. Taken together, miR-193a may be a TGF-β regulated tumor suppressor micro-RNA and is epigenetically silenced in ovarian cancer. Methylation of miR-193a may be able to predict prognosis in ovarian cancer patients. Citation Format: Frank Hsueh-Che Cheng, Gary C.W. Chen, Jian-Liang Chou, Ya-Wen Lin, Lin-Yu Chen, Hung-Cheng Lai, Chin Li, Michael W.Y. Chan. Hypermethylation of a TGF-β regulated micro-RNA, miR-193a, predicts prognosis in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1476. doi:10.1158/1538-7445.AM2014-1476
Pitfalls of Converting Practice Guidelines Into Quality Measures—Reply
Authors: Louise C. Walter, Paul A. Heineken, Kenneth E. Covinsky
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal