tbuckley/cabot-search huggingface dataset:
Histopathologic heterogeneity in chronic hepatitis C virus infection: Are two liver biopsy specimens better than one? Division of Gastroenterology and Dept. of Pathology, Beth Israel Hospital, Harvard Medical School, Boston, MA
Journal: Hepatology (1995)

Successful encapsidation of hepadnaviral pregenomic RNA requires the orchestrated interaction of the viral capsid and polymerase proteins with each other and with the RNA packaging substrate. The early steps of this process involve binding of the polymerase to the encapsidation signal, ϵ, and are already understood in some detail. However, the underlying macromolecular interactions resulting in the subsequent encapsidation of this polymerase–ϵ complex by capsid proteins are less clearly defined. To approach this issue we have examined the ability of two different hepadnaviruses to encapsidate each other's pregenomic RNA. H. Okamotoet al.((1990)J. Gen. Virol.71, 959–963) have previously demonstrated that WHV polymerase could encapsidate an HBV pregenome, but the origin of the capsid proteins (i.e., HBV- or WHV-derived) required for this reaction was not clear; some evidence suggested that heterologous capsid and polymerase proteins might not be capable of interaction. To clarify this, we analyzed encapsidated RNA isolated from cytoplasmic cores produced following transient transfection of HepG2 cells with different combinations of plasmids encoding HBV or WHV core and polymerase genes. We found that (i) the essential encapsidation signal of WHV is comprised of a short region including ϵ, as in HBV; (ii) HBV and WHV polymerases are each competent to recognize both HBV and WHV packaging signals; therefore the encapsidation signals are functionally interchangeable; and (iii) HBV capsids encapsidate a WHV polymerase–ϵ complex, and vice versa, although the efficiency of heterologous packaging is slightly lower than that of homologous encapsidation. Our results underscore the close relationship of these two mammalian hepadnaviruses.
KEYNOTE-177: First-line, open-label, randomized, phase 3 study of pembrolizumab versus investigator-choice chemotherapy for mismatch repair-deficient or microsatellite instability-high metastatic colorectal carcinoma.
Authors: Luis A. Diaz, Dung T. Le, Takayuki Yoshino, Thierry Andre, Johanna C. Bendell, Minori Koshiji, Yinghua Zhang, S. Peter Kang, Baohoang Lam, Dirk Jäger
Journal: Journal of Clinical Oncology (2016)

TPS3639 Background: Mismatch repair–deficient (dMMR) tumors are characterized by high mutational load and lymphocyte infiltration and may be good candidates for immune checkpoint blockade. Pembrolizumab is a monoclonal antibody against PD-1 that is designed to block its interaction with PD-L1 and PD-L2 and thus allow an antitumor immune response. In the KEYNOTE-016 proof-of-concept study, pembrolizumab showed promising antitumor activity against dMMR tumors in patients (pts) with treatment-refractory metastatic colorectal carcinoma (mCRC). KEYNOTE-177 is an international, randomized trial designed to evaluate the efficacy and safety of pembrolizumab compared with standard-of-care (SOC) chemotherapy in the first-line setting for dMMR or microsatellite instability–high (MSI-H) mCRC. Methods: Key eligibility criteria include age ≥ 18 y, confirmed MSI-H or dMMR mCRC, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for metastatic disease. Pts are to be randomized 1:1 to receive either pembrolizumab 200 mg Q3W or investigator’s choice of SOC chemotherapy. Chemotherapy must be chosen prior to randomization; options include mFOLFOX6 or FOLFIRI alone or in combination with bevacizumab or cetuximab. Treatment is to continue until PD, unacceptable toxicity, pt/investigator decision, or completion of 35 cycles (pembrolizumab only). Response is to be evaluated every 9 wk per RECIST v1.1 by central imaging vendor review and per RECIST adapted for immunotherapy response patterns. Eligible pts may continue pembrolizumab beyond initial RECIST-defined progression. Pts in the SOC arm who have PD and meet crossover criteria may be eligible to receive pembrolizumab for up to 17 treatment cycles. AEs are to be assessed throughout treatment and for 30 d thereafter (90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts are to be followed for survival every 9 wk. PFS per RECIST v1.1 is the primary end point; OS and ORR are key secondary end points; others include duration of response and health-related quality of life. Planned enrollment in KEYNOTE-177 is 270 pts. Clinical trial information: NCT02563002.
Abstract 478: Cell-type Specific Surface Markers Effectively Isolate Cardiac Cell Sub-populations
Authors: Jordan D Prahl, Matthew Weiland, Hsiaoyun Milliron, Eric J Kort, Stefan Jovinge
Journal: Circulation Research (2017)

Cardiomyocytes comprise only 20-30% of the cells in the heart. To enable downstream applications requiring live cells (including clinical application), identification of surface markers unique to all cardiac subpopulations is needed. Development of such strategies would create a powerful technique to tease apart the multiple cell populations that make up the heart and their role in complex heart diseases. Our hypothesis was that surface markers could be identified in neonatal mice to distinguish smooth muscle cells (SMC), cardiomyocytes (CM), fibroblasts (FB) and endothelial cells (EC), enabling sorting by flow cytometry and analysis of these subpopulations of heart cells. Hearts were surgically removed from one litter of neonatal (Day 0-2) C57BL/6J mice and three litters of transgenic mice with mCherry α-myosin heavy chain promoter (αMHC-mCherry), then digested with trypsin overnight followed by collagenase/dispase and gentle mechanical dissociation. Surface marker staining for Cadherin-2 (Cdh2) showed congruence with αMHC-mCherry positivity. Cells were sorted using fluorescent activated cell sorting with antibodies against the following surface markers: Cdh2 (CM), CD31 (EC), CD90.2 (FB) and CD49a (SMC). Enrichment of these cell populations was then evaluated by qRT-PCR for known intracellular and extracellular markers specific to each cell: EC (CD31 + vWf), CM (TNNT2 + Myh6), FB (CD90) and SMC (Myh10/11 + Tagln). Our panel of surface markers enabled enrichment of four subpopulations of heart cells which will be verified further in coming experiments. In the future, this strategy will enable sorting of cells from each subpopulation for downstream analysis.
Abstract 1737: Association of inherited variants with chromosomal breaks in cancer
Authors: Meng Xiao He, Sahar Shahamatdar, Amaro Taylor-Weiner, Travis Zack, Sohini Ramachandran, Eliezer Van Allen
Journal: Cancer Research (2019)

Abstract Background: Cancer cells frequently harbor genomic rearrangements and somatic copy number alterations that result from chromosome breaks, which vary in frequency across the genome. The distribution of breakpoint locations depends on features of the local genomic context, such as presence of certain retrotransposons. Moreover, inherited variants have been associated with specific chromosomal alterations in myeloproliferative neoplasms and in blood from cancer-free individuals. Here, we developed and applied computational methodology to broadly identify associations between inherited variants and the location of somatic breakpoints across cancers. Methods: We analyzed TCGA Affymetrix Genome-Wide Human SNP Array 6.0 data from matched tumor-normal pairs (n = 5,923 samples remaining after quality control and selecting for individuals of predominantly European ancestry). Germline genotypes were called from normal samples using Birdseed v2. Allele-specific copy number analysis using both normal and tumor samples for each individual was performed using ASCAT v2.5.1. Breakpoints were inferred as the intervals between ASCAT-called somatic chromosomal segments. We assigned individuals binary phenotypes corresponding to whether a somatic breakpoint was detected in non-overlapping 5 megabase bins of the genome. We then performed an association analysis between each phenotype and variants located on the same chromosome as the corresponding bin, adjusting for sex and ancestry via logistic regression with plink2. Analyses were performed separately for each disease type followed by a meta-analysis of association summary statistics with METAL. Results and Conclusions: We identify several candidate associations between inherited variants and the presence of somatic breakpoints in specific regions of the genome (using a p-value cutoff of 5e-8 for each phenotype). Our results suggest that heritable genetic variation may be associated with risk of development of localized chromosome breaks in somatic cells. Ongoing work is aimed at validating the putative associations (for example using data from the PanCancer Analysis of Whole Genomes study) and identifying potential mechanisms associated with putative risk alleles. Citation Format: Meng Xiao He, Sahar Shahamatdar, Amaro Taylor-Weiner, Travis Zack, Sohini Ramachandran, Eliezer Van Allen. Association of inherited variants with chromosomal breaks in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1737.
Medical Greek and Latin at a Glance
Journal: JAMA (1935)

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
Pneumonia, Its Pathology, Diagnosis, Prognosis and Treatment.
Journal: JAMA (1926)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Public Health AND POOR LAW MEDICAL SERVICES
Authors: -H Moore, T Staunto-, A Kilbride, J Dempsey, D Denvir, T Maguire, J Llotliwell
Journal: BMJ (1912)

College, Edinburgh, shall qualify pro taoto for admission to the university examinations for the degrees.The founder of the college, Mr. William Dick, bequeathed the college buildings for the use of the public, while his sister left her fortune to endow a chair of physiology in the college, and also a chair of com- parative anatomy in the University of Edinburghl.In 1905 these
Progress in Neurological Surgery
Authors: Oscar Sugar
Journal: JAMA (1975)

Human stereotactic surgery is<i>not</i>dead, although one might have assumed so from the dearth of articles in English-language journals since levodopa became a treatment for parkinsonism. This medical therapy is described by Siegfried (Zurich) as the last article in this neurosurgical volume. The remainder deals with the activities of some of the main centers of stereotactic surgery—Riechert in Freiburg, Bertrand and co-workers in Montreal, Cooper in New York, and Guiot in Suresnes-Paris. Each group describes in detail their own techniques for reaching the depths of the brain and for making lesions. More and more emphasis is placed on neurophysiologic tests for localization of target (Maressero of Milan) while using detailed anatomical atlases for cruder placement. Among other uses of stereotactic surgery described is the attack on behavior disorders by Narabayashi (Tokyo), whose pioneering work began in 1958, and who describes the follow-up in cases of aggressiveness, violence, and uncontrollable
Overprescribing Antipsychotics
Authors: Mike Mitka
Journal: JAMA (2012)

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
Poetry and Medicine
Authors: Jack Coulehan
Journal: JAMA (1997)

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
Excretion and Tissue Disposition of Dichloroacetonitrile in Rats and Mice
Authors: Mark R. Roby, Sigrid Carle, Michael A. Pereira, Dean E. Carter
Journal: Environmental Health Perspectives (1986)

The excretion and tissue distribution of [1-14C]dichloroacetonitrile and [2-14C]dichloroacetonitrile were studied in male Fischer 344 rats and male B6C3F1 mice. Three dose levels of dichloroacetonitrile (DCAN) (0.2, 2, or 15 mg/kg) were administered to rats and two dose levels of DCAN (2 or 15 mg/kg) to mice. Daily excreta including exhaled volatiles and radiolabeled carbon dioxide (14CO2) were analyzed for radiolabeled carbon (14C) until greater than 70% of the radioactivity was excreted. At that time the animals were sacrificed and tissues were collected. Tissues and excreta were analyzed for 14C by combustion and liquid scintillation counting. Rats administered [1-14C]DCAN excreted 62 to 73% of the 14C in 6 days, with 42 to 45% in urine, 14 to 20% in feces, and 3 to 8% as CO2. Rats administered [2-14C]DCAN excreted 82 to 86% of the 14C in 48 hr, with 35 to 40% in urine, 33 to 34% as CO2, and 10 to 13% in feces. Mice administered [1-14C]DCAN excreted 83 to 85% of the 14C in 24 hr, with 64 to 70% in urine, 9 to 13% in feces, and 5 to 6% as CO2. Mice administered [2-14C]DCAN excreted 84 to 88% of the 14C in 24 hr with 42 to 43% in urine, 8 to 11% in feces, and 31 to 37% as CO2. Liver tissues retained the most 14C in all studies except the study of [1-14C]DCAN in rats, where blood contained the most 14C. These results indicate that DCAN was absorbed rapidly after oral administration in water. The differences in the route of excretion of [1-14C]DCAN compared to [2-14C]DCAN indicated that the molecule was being cleaved in the body and metabolized by different mechanisms.
A Manual of Modern Surgery. An Exposition of the accepted Doctrines and approved Operative Procedures of the Present Time, for the Use of Students and Practitioners.
Journal: JAMA (1891)

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
Abstract SY02-03: Studying tumor evolution in mouse models of cancer
Authors: Tyler Jacks
Journal: Cancer Research (2010)

Abstract Like other solid tumors, lung adenocarcinoma progresses through multiple stages including tumor initiation, expansion in the lung, and metastasis of the primary tumor to distant organs. Dissection of this process requires quantitative and tractable models that recapitulate the human disease at the genetic and histological level. We have employed autochthonous mouse models of lung adenocarcinoma that recapitulate tumor initiation, progression and metastasis in the human disease both genetically, and pathologically. We have established oncogenic Kras as the initiating event in lung adenoma and amplification of the oncogenic signaling is associated with progression to adenocarcinoma. The p53 tumor suppressor limits tumor progression in this model. Restoration of the Trp53 locus has pinpointed the adenoma-adenocarcinoma transition as the stage in which p53 function is critical for tumor suppression. Expression of oncogenic Kras in the absence of p53 leads to the development of distant metastases after long latency. Identification of the lentiviral integration site in each tumor allows the clonal relationship between metastases and the primary tumors to be unequivocally established. Gene expression and DNA copy number analyses of metastasis-derived cell lines and primary lung tumors have uncovered a metastasis associated gene expression signature and recurrent genomic alterations. Integration of these datasets, other genome-wide analyses and human tumor data are providing insights into the molecular mechanism and biology of lung cancer progression and metastasis. Citation Format: Tyler Jacks. Studying tumor evolution in mouse models of cancer [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY02-03
Abstract 1134: Crucial Role of Cu/Zn-SOD in the Synthesis of Endothelium-Derived Hyperpolarizing Factor (EDHF) during Reactive Hyperemia in Mouse Mesenteric Microcirculation in Vivo
Authors: Toyotaka Yada, Hiroaki Shimokawa, Keiko Morikawa, Aya Takaki, Yoshiro Shinozaki, Hidezo Mori, Masami Goto, Yasuo Ogasawara, Fumihiko Kajiya
Journal: Circulation (2007)

Background: We have recently demonstrated that endothelial Cu/Zn-superoxide dismutase (SOD) plays an important role as an EDHF synthase. In this study, we examined the possible role of Cu/Zn-SOD in the synthesis of EDHF/H 2 O 2 during reactive hyperemia (RH) in mouse mesenteric microcirculation in vivo. Methods: Mesenteric arterioles from wild-type (wild) and Cu/Zn-SOD −/− mice (SOD-KO) (n=5 each, 22– 60 μm) were continuously observed with a pencil-typed intravital microscope (×600 magnification) during acetylcholine (ACh)-induced vasodilatation and RH (reperfusion after 60 sec of mesenteric artery occlusion) under cyclooxygenase blockade (indomethacin) under the following 3 conditions; control, NO synthase inhibitor (L-NMMA) and L-NMMA+catalase (a specific decomposer of H 2 O 2 ). Results: In mesenteric arterioles of wild-type mice, endothelium-dependent relaxations to ACh (34±4%) and vasodilatation during RH (40±5%) were resistant to L-NMMA (ACh 23±7% and RH 20±5%, both P&lt;0.05), but were markedly inhibited by L-NMMA+catalase (ACh, 8±2% and RH, 4±3%, both P&lt;0.01 vs. control). In mesenteric arterioles of SOD-KO mice, L-NMMA markedly inhibited the relaxations to ACh (30±4% to 8±2%, P&lt;0.01) and vasodilatation during RH (40±5% to 5±2%, P&lt;0.01), and the responses were not inhibited by the addition of catalase (ACh, 3±2% and RH, 4±2%, not significant vs. control). In the presence of L-NMMA, RH-induced increase in blood flow was 330±5% of baseline in the wild-type mice, whereas in the SOD-KO mice, the response was significantly reduced to 145±23% (P&lt;0.01). In the mesenteric arterioles of SOD-KO mice, tempol, an SOD mimetic, significantly increased the ACh-induced vasodilation, which effect was abolished by catalase. Vascular H 2 O 2 production in response to ACh in mesenteric arterioles (fluorescent method) was significantly increased in wild-type mice but was markedly impaired in SOD-KO mice. By contrast, vascular NO production was significantly increased in wild-type mice and was unaltered in SOD-KO mice. Vascular level of BH 4 in the aorta was comparable between the two genotypes. Conclusions: These results indicate that endothelial Cu/Zn-SOD plays an important role as an EDHF synthase during RH in mouse mesenteric microcirculation in vivo.