tbuckley/cabot-search huggingface dataset:
A comparison of the small ribosomal RNA genes from the mitochondrial DNA of the great apes and humans: sequence, structure, evolution, and phylogenetic implications.
Authors: James E. Hixson, Wesley M. Brown
Journal: Molecular Biology and Evolution (1986)

Restriction endonuclease fragments produced by EcoRI/AvaI or KpnI digestion and containing the small (12S) ribosomal RNA (rRNA) genes from the mitochondrial DNAs (mtDNAs) of the common chimpanzee, pygmy chimpanzee, gorilla, and orangutan were inserted into the plasmids pBR322 or pADD1. After species verification the inserted fragments were digested with SauIIIA, subcloned into M13mp7 vectors, and sequenced. The small rRNA gene sequences were compared with each other and with the published human sequence (Anderson et al. 1981). Substitutions were detected at 118 of the 955 nucleotide positions compared. Pairwise, the sequence differences ranged from 1% (between the chimpanzee species) to 9% (comparisons involving the orangutan); the proportion that were transitions ranged from 87% to 100%. Deletions and/or additions were noted at seven locations. With respect to evolutionary sequence lability, kinetic analysis indicated the presence of at least two classes of nucleotide positions; the more labile class occurs in sequences thought to form self-complementary duplexes (stems) in the mature rRNA. The high frequency of compensating substitutions, which maintain base-pairing within these sequences, corroborates their inferred structure. Phylogenetic inferences drawn from the sequence comparisons support the notion of an approximately equidistant relationship among chimpanzees, gorilla, and man, with the orangutan much less closely related. However, inference from a shared deletion suggests that the gorilla and the chimpanzees may be more closely related to one another than they are to man.
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo
Authors: Yi-Fan Hsu, Daniel Ajona, Leticia Corrales, Jose M Lopez-Picazo, Alfonso Gurpide, Luis M Montuenga, Ruben Pio
Journal: Molecular Cancer (2010)

Cetuximab, an antibody targeting the epidermal growth factor receptor (EGFR), increases survival in patients with advanced EGFR-positive non-small cell lung cancer when administrated in combination with chemotherapy. In this study, we investigated the role of complement activation in the antitumor mechanism of this therapeutic drug.EGFR-expressing lung cancer cell lines were able to bind cetuximab and initiate complement activation by the classical pathway, irrespective of the mutational status of EGFR. This activation led to deposition of complement components and increase in complement-mediated cell death. The influence of complement activation on the activity of cetuximab in vivo was evaluated in xenografts of A549 lung cancer cells on nude mice. A549 cells express wild-type EGFR and have a KRAS mutation. Cetuximab activity against A549 xenografts was highly dependent on complement activation, since complement depletion completely abrogated the antitumor efficacy of cetuximab. Moreover, cetuximab activity was significantly higher on A549 cells in which a complement inhibitor, factor H, was genetically downregulated.We demonstrate for the first time that the in vivo antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response.
Minor hazard of amniocentesis.
Authors: R L Neu, J T Lanman, M Wingate, R M Bannerman
Journal: BMJ (1979)

incidence of allergic complications than those with no detected antigen in blood.3Furthermore, high concentrations of antigen in CSF at diagnosis with slow disappearance of antigen were associated with neurological damage.Thus, while I agree with the authors' two conclusions, which, I respectfully submit, are self-evident, there are well-known immuno- logical techniques which can improve diagnostic accuracy and which also have some prognostic and epidemiological value.
Oestrogen plays a permissive role in cardioprotection
Authors: M. V. Cohen, J. M. Downey
Journal: Cardiovascular Research (2008)

Ischaemic preconditioning (IPC) is a powerful cardioprotective intervention. It can salvage upwards of 75% of the myocardium destined to otherwise infarct. This potent cardioprotective strategy has been observed in all animal species examined to date including mammals and birds.1 We have observed IPC's protection in non-human primates (unpublished observation) and strong evidence exists of its efficacy in man.2,3 Since the initial description of IPC in 1986 by Murry et al. ,4 many investigators have toiled to uncover its mechanism in the hopes of being able to apply the strategy clinically. As a result, much is now known concerning its mechanism.5

The protection results from signal transduction pathways emanating from surface receptors. During the preconditioning ischaemia, the receptor agonists bradykinin, opioid, and adenosine are released. The first two bind to Gi-coupled receptors that trigger a complex cascade that involves nitric oxide production and opening of potassium channels in the mitochondria with subsequent redox signalling, which activates an important signalling molecule called protein kinase C (PKC). Adenosine, the third receptor agonist released by ischaemic myocardium, binds to its Gi-coupled receptor, but its signalling bypasses the above … 

*Corresponding author. Tel: +1 251 460 6812; fax: +1 251 460 6386. E-mail address: mcohen{at}usouthal.edu
Is Choice of Physician and Hospital an Essential Benefit?
Authors: Robert H. Brook
Journal: JAMA (2011)

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
Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine
Authors: Ming-Chen Yang, Hao-Chen Wang, Ya-Chin Hou, Hui-Ling Tung, Tai-Jan Chiu, Yan-Shen Shan
Journal: Molecular Cancer (2015)

Cancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer and has been implicated in cytoprotection and tumor promotion. This study aimed to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer. The correlation between autophagy and CSCs and its clinical significance were analyzed using pancreatic cancer tissue microarrays. Genetic and pharmacological approaches were applied to explore the function of autophagy on CSC activity and gemcitabine resistance of pancreatic cancer cells in vitro and in vivo. LC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44, and CD133 in pancreatic cancer tissues. High coexpression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5, ATG7, and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation, and resistance to gemcitabine in vitro and in vivo. Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44, and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170–82, could effectively counteract OPN-induced autophagy and CSC activity. According to the histochemical results, pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/CD133 had poor survival. Induction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. Combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for pancreatic cancer.
Risk of Breast Cancer Among Young Women: Relationship to Induced Abortion
Authors: Janet R. Daling, Kathleen E. Malone, Lynda F. Voigt, Emily White, Noel S. Weiss
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Risk of Breast Cancer Among Young Women: Relationship to Induced Abortion Get access Janet R. Daling, Janet R. Daling Search for other works by this author on: Oxford Academic PubMed Google Scholar Kathleen E. Malone, Kathleen E. Malone Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynda F. Voigt, Lynda F. Voigt Search for other works by this author on: Oxford Academic PubMed Google Scholar Emily White, Emily White Search for other works by this author on: Oxford Academic PubMed Google Scholar Noel S. Weiss Noel S. Weiss Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 21, 2 November 1994, Pages 1584–1592, https://doi.org/10.1093/jnci/86.21.1584 Published: 02 November 1994 Article history Received: 09 March 1994 Revision received: 29 July 1994 Accepted: 12 August 1994 Published: 02 November 1994
Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy
Authors: José Baselga, Karen A. Gelmon, Shailendra Verma, Andrew Wardley, PierFranco Conte, David Miles, Giulia Bianchi, Javier Cortes, Virginia A. McNally, Graham A. Ross, Pierre Fumoleau, Luca Gianni
Journal: Journal of Clinical Oncology (2010)

PURPOSE; Pertuzumab, a human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibody, potently inhibits HER2 dimerization and HER-mediated signaling pathways. Pertuzumab and the approved HER2-targeted monoclonal antibody trastuzumab have complementary mechanisms of action and result in enhanced antitumor activity when combined. This phase II trial assessed the efficacy and safety profile of the combination in patients with HER2-positive breast cancer whose disease had progressed during prior trastuzumab-based therapy.This was a multicenter, open-label, single-arm, Simon two-stage study. Patients with advanced HER2-positive breast cancer in whom disease progression had occurred during prior trastuzumab-based therapy received trastuzumab weekly (4 mg/kg loading dose, then 2 mg/kg every week) or every 3 weeks (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) and pertuzumab every 3 weeks (840 mg loading dose, then 420 mg every 3 weeks). Treatment continued until disease progression or excessive toxicity.All 66 patients were assessable for efficacy and safety. The objective response rate was 24.2%, and the clinical benefit rate was 50%. Five patients (7.6%) experienced a complete response, 11 patients (16.7%) experienced a partial response, and 17 patients (25.8%) experienced stable disease of > or = 6 months. Median progression-free survival was 5.5 months. Overall, the combination of pertuzumab and trastuzumab was well tolerated, and adverse events were mild to moderate. Cardiac dysfunction was minimal, and no patients withdrew as a result of cardiac-related adverse events.The combination of pertuzumab and trastuzumab is active and well tolerated in patients with metastatic HER2-positive breast cancer who had experienced progression during prior trastuzumab therapy.
Differential p53 Engagement in Response to Oxidative and Oncogenic Stresses in Fanconi Anemia Mice
Authors: Reena Rani, Jie Li, Qishen Pang
Journal: Cancer Research (2008)

Abstract Members of the Fanconi anemia (FA) protein family are involved in repair of genetic damage caused by DNA cross-linkers. It is not clear whether the FA proteins function in oxidative DNA damage and oncogenic stress response. Here, we report that deficiency in the Fanca gene in mice elicits a p53-dependent growth arrest and DNA damage response to oxidative DNA damage and oncogenic stress. Using a Fanca−/−Trp53−/− double knockout model and a functionally switchable p53 retrovirus, we define the kinetics, dependence, and persistence of p53-mediated response to oxidative and oncogenic stresses in Fanca−/− cells. Notably, oxidative stress induces persistent p53 response in Fanca−/− cells, likely due to accumulation of unrepaired DNA damage. On the other hand, whereas wild-type cells exhibit prolonged response to oncogene activation, the p53-activating signals induced by oncogenic ras are short-lived in Fanca−/− cells, suggesting that Fanca may be required for the cell to engage p53 during constitutive ras activation. We propose that the FA proteins protect cells from stress-induced proliferative arrest and tumor evolution by acting as a modulator of the signaling pathways that link FA to p53. [Cancer Res 2008;68(23):9693–702]
Human T cell leukaemia/lymphoma virus infection in pregnant women in the United Kingdom: population study
Authors: A E Ades
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To assess the prevalence of human T cell leukaemia/lymphoma virus (HTLV) infection in pregnant women in the United Kingdom. <b>Design:</b> Population study. <b>Subjects:</b> Guthrie card samples from babies born in 1997-8.Samples were linked to data on mother9s age and ethnic status and parents9 country of birth and then anonymised. <b>Setting:</b> North Thames Regional Health Authority. <b>Main outcome measures:</b> Presence of antibodies against HTLV in eluates tested by gelatin particle agglutination assay and results confirmed by immunoblot. <b>Results:</b> Of 126 010 samples tested, 67 had confirmed antibodies to HTLV (59 HTLV-I, 2 HTLV-II, 6 untyped) and six had indeterminate results. Seroprevalence was 17.0 per 1000 (95% confidence interval 9.2 to 28.3) in infants whose mothers were born in the Caribbean, 3.2/1000 (1.5 to 5.9) with mothers born in west and central Africa, and 6.8/1000 (3.1 to 12.9) in infants of black Caribbean mothers born in non-endemic regions. In infants with no known risk (both parents born in non-endemic regions and mother not black Caribbean) seroprevalence was 0.06-0.12 per 1000. Mother9s country of birth, father9s country of birth, and mother9s ethnic status were all independently associated with neonatal seroprevalence. An estimated 223 (95% confidence interval 110 to 350) of the 720 000 pregnant women each year in the United Kingdom are infected with HTLV. <b>Conclusions:</b> The prevalence of HTLV and HIV infections in pregnant women in the United Kingdom are comparable. The cost effectiveness of antenatal HTLV screening should be evaluated, and screening of blood donations should be considered.
Smartphone and tablet apps for concussion road warriors (team clinicians): a systematic review for practical users
Authors: Hopin Lee, S John Sullivan, Anthony G Schneiders, Osman Hassan Ahmed, Arun Prasad Balasundaram, David Williams, Willem H Meeuwisse, Paul McCrory
Journal: British Journal of Sports Medicine (2014)

Background Mobile technologies are steadily replacing traditional assessment approaches for the recognition and assessment of a sports concussion. Their ease of access, while facilitating the early identification of a concussion, also raises issues regarding the content of the applications (apps) and their suitability for different user groups. Aim To locate and review apps that assist in the recognition and assessment of a sports concussion and to assess their content with respect to that of internationally accepted best-practice instruments. Methods A search of international app stores and of the web using key terms such as ‘concussion’, ‘sports concussion’ and variants was conducted. For those apps meeting the inclusion criteria, data were extracted on the platform, intended users and price. The content of each app was benchmarked to the Sport Concussion Assessment Tool 2 (SCAT2) and Pocket SCAT2 using a custom scoring scheme to generate a percentage compliance statistic. Results 18 of the 155 apps identified met the inclusion criteria. Almost all (16/18) were available on an iOS platform and only five required a payment to purchase. The apps were marketed for a wide range of intended users from medical professionals to the general public. The content of the apps varied from 0% to 100% compliance with the selected standard, and ‘symptom evaluation’ components demonstrated the highest level of compliance. Conclusions The surge in availability of apps in an unregulated market raises concerns as to the appropriateness of their content for different groups of end users. The consolidation of best-practice concussion instruments now provides a framework to inform the development of future apps.
Hemin decreases cardiac oxidative stress and fibrosis in a rat model of systemic hypertension via PI3K/Akt signalling
Authors: M.-E. Worou, K. Belmokhtar, P. Bonnet, P. Vourc'h, M.-C. Machet, G. Khamis, V. Eder
Journal: Cardiovascular Research (2011)

Angiotensin II induces cardiac myocyte apoptosis and hypertrophy, which contribute to heart failure, possibly through enhanced oxidative stress. The aim of this work was to assess the impact of hemin (heme oxygenase-1 inducer) on NADPH oxidase activation, cardiac oxidative stress, and development of fibrosis in a rat model of renovascular hypertensive cardiomyopathy in comparison to an anti-hypertensive reference treatment with losartan. A 3week hemin treatment was tested in an angiotensin II-dependent hypertensive rat model and a cellular model of neonatal rat cardiomyocytes stimulated by angiotensin II. Our findings demonstrate that hemin prevented development of intercellular fibrosis, expression of collagen I, and disorganization of intracellular fibres. Oxidative stress and apoptosis evaluated in hypertensive myocardial tissue were decreased by hemin. The reference treatment with the angiotensin II receptor (AT1) antagonist (losartan) was less effective than hemin in prevention of fibrosis and oxidative stress, although it was more effective in reducing hypertension. Rac-1 activation and, subsequently, NADPH oxidase activity were further decreased with hemin than with losartan. Hemin enhanced the expression of phosphoinositide 3-kinase (PI3K) p85 regulatory subunit, in contrast to losartan. The PI3K/Akt signalling pathway activation by hemin was related to heme oxygenase-1 activation and an increase in biliverdin reductase, and its inhibition by LY294002 reversed the effects of hemin on collagen I and caspase-3 expression. Finally, hemin increased Akt activation, and concomitantly decreased RhoA and p38 mitogen-activated protein kinase activation. We confirmed a positive effect of hemin on oxidative cardiac damage, apoptosis, and fibrosis induced by hypertension by modulating the NADPH oxidase activation through enhanced expression of the PI3K p85 regulatory subunit.
Respiratory problems in late onset Pompe disease
Authors: Mehtap Ertas, Zuleyha Bingol, Gulfer Okumus, Piraye Serdaroglu, Esen Kiyan
Journal: European Respiratory Journal (2012)

Introduction: Pompe disease (glycogen storage disorder type II) is associated with functional deficiencies in skeletal, heart and respiratory muscles due to glycogen deposition. While progression and mortality rates are fast in early onset (first year) Pompe disease, late onset (adult) Pompe disease is related with slow progression and proximal myopathy. In this disease respiratory muscle involvement is independent from severity of skeletal muscle weakness. Here, we present the respiratory evaluation of 10 patients with Pompe disease who are followed up in our clinic.

Table 1: Characteristics ot the patients.

View this table:



Conclusion: Respiratory muscle involvement especially diaphragm muscle dysfunction and respiratory disorders in sleep are common in late onset Pompe disease even the respiratory symptoms are recessive.
Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations
Authors: M. Attur, H.-Y. Wang, V. B. Kraus, J. F. Bukowski, N. Aziz, S. Krasnokutsky, J. Samuels, J. Greenberg, G. McDaniel, S. B. Abramson, K. S. Kornman
Journal: Annals of the Rheumatic Diseases (2009)

A lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs.To determine whether inflammatory genetic markers could stratify patients with knee OA into high and low risk for destructive disease.Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen single nucleotide polymorphisms (SNPs) in six inflammatory genes were evaluated for association with radiographic severity and with synovial fluid mediators in a subset of the patients.Interleukin 1 receptor antagonist (IL1RN) SNPs (rs419598, rs315952 and rs9005) predicted Kellgren-Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR=0.15; 95% CI 0.065 to 0.349; p<0.0001), greater joint space width and lower synovial fluid cytokine levels. Carriage of the IL1RN haplotype influenced the age relationship with severity.IL1RN polymorphisms reproducibly contribute to disease severity in knee OA and may be useful biomarkers for patient selection in disease-modifying OA drug trials.
Positron Emission Tomography (PET) Imaging of Prostate Cancer with a Gastrin Releasing Peptide Receptor Antagonist - from Mice to Men
Authors: Gesche Wieser, Rosalba Mansi, Anca L. Grosu, Wolfgang Schultze-Seemann, Rebecca A. Dumont-Walter, Philipp T. Meyer, Helmut R. Maecke, Jean Claude Reubi, Wolfgang A. Weber
Journal: Theranostics (2014)

Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy.Methods: Biodistribution, dosimetry and tumor uptake of the GRPr antagonist 64 Cu-CB-TE2A-AR06 [( 64 Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG 4 -D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH 2 ] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7).Results: No adverse events were observed after injection of 64 Cu-CB-TE2A-AR06.Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9).Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time.Conclusion: 64 Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer.Future studies evaluating 64 Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.