tbuckley/cabot-search huggingface dataset:
Synergy of a Herpes Oncolytic Virus and Paclitaxel for Anaplastic Thyroid Cancer
Authors: Shu-Fu Lin, Sizhi Paul Gao, Daniel L. Price, Sen Li, Ting-Chao Chou, Paramjeet Singh, Yu-Yao Huang, Yuman Fong, Richard J. Wong
Journal: Clinical Cancer Research (2008)

Novel therapeutic regimens are needed to improve the dismal outcomes of patients with anaplastic thyroid cancer (ATC). Oncolytic herpes simplex virus have shown promising activity against human ATC. We studied the application of oncolytic herpes simplex virus (G207 and NV1023) in combination with currently used chemotherapeutic drugs (paclitaxel and doxorubicin) for the treatment of ATC.All four agents showed dose-response cytotoxicity in vitro for the human ATC cell lines KAT4 and DRO90-1. G207, combined with paclitaxel, showed synergistic cytotoxicity. Chou-Talalay combination indices ranged from 0.56 to 0.66 for KAT4, and 0.68 to 0.74 for DRO90-1 at higher affected fractions. Paclitaxel did not enhance G207 viral entry and early gene expression or G207 viral replication. Paclitaxel combined with G207 compared with single-agent treatment or controls showed significantly increased microtubule acetylation, mitotic arrest, aberrant chromatid separation, inhibition of metaphase to anaphase progression, and apoptosis. A single i.t. injection of G207 combined with biweekly i.p. paclitaxel injections in athymic nude mice bearing KAT4 flank tumors showed significantly reduced mean tumor volume (74 +/- 38 mm(3)) compared with G207 alone (388 +/- 109 mm(3)), paclitaxel alone (439 +/- 137 mm(3)), and control (520 +/- 160 mm(3)) groups at 16 days. There was no morbidity in vivo attributable to therapy.Mechanisms of paclitaxel antitumoral activity, including microtubule acetylation, mitotic block, and apoptosis, were enhanced by G207, which also has direct oncolytic effects. Combination of G207 and paclitaxel therapy is synergistic in treating ATC and holds promise for patients with this fatal disease.
Prevention of Venous Thrombosis and Pulmonary Embolism
Authors: T. Michael White
Journal: JAMA (1981)

My initial impression in reviewing J. G. Sharnoff's<i>Prevention of Venous Thrombosis and Pulmonary Embolism</i>was that it was a somewhat evangelical attempt by the author to excite the heparin-thromboembolism establishment into a mystical realization that there is a difference between small-dose (his) and lowdose (theirs) heparin prophylaxis. Then I spent a morning reviewing references (the monograph is well referenced) and my skepticism abated. The author, beginning in 1956, took a piece of pathological data (increased pulmonary megakaryocytes) and rudimentary laboratory data (increased platelets and decreased Lee-White clotting times in postoperative patients) and developed a theory (postoperative hypercoagulable state secondary to thrombocytosis related to stress of surgery and exacerbated by mobilization) that explained to him the high incidence of postoperative morbidity and mortality related to thromboembolic disease. His theory led him to the institution of a trial of prophylactic heparinization in which he strove to prevent hypercoagulable or hypocoagulable states
Severe steatohepatitis with hepatic decompensation resulting from malnutrition after pancreaticoduodenectomy
Authors: Eun Hui Sim, Jung Hyun Kwon, Se Young Kim, Seung Min Jung, Lee-So Maeng, Jeong Won Jang, Kyu Won Chung
Journal: Clinical and Molecular Hepatology (2012)

The most common finding related to nonalcoholic steatohepatitis is obesity, but a status of severe malnutrition can also induce the steatohepatitis. The authors report a rare case of steatohepatitis leading to hepatic decompensation caused by malnutrition after pancreaticoduodenectomy. A 68-year-old female patient who had been previously diagnosed with pancreatic cancer and had undergone pancreaticoduodenectomy 5 months previously presented with abdominal distension. Routine CT performed 3 months after the surgery revealed severe fatty liver without evidence of tumor recurrence. After undergoing pancreaticoduodenectomy her food intake had reduced, and as a result she had lost 7 kg of body weight over 2 months. At this admission, CT revealed moderate amounts of ascites without tumor recurrence. Furthermore, her albumin and lipid profile levels were markedly decreased, and she had a flapping tremor and slurred speech suggestive of hepatic encephalopathy. Her liver biopsy findings were consistent with steatohepatitis and disclosed macrovesicular steatosis without definite fibrosis. After careful nutritional control, her symptoms disappeared and her laboratory findings improved. Keywords: Nonalcoholic steatohepatitis; Malnutrition; Pancreaticoduodenectomy; Pancreatic cancer; Hepatic decompensation
p53 centrosomal localization diagnoses ataxia-telangiectasia homozygotes and heterozygotes
Authors: Andrea Prodosmo, Andrea De Amicis, Cecilia Nisticò, Mario Gabriele, Giuliana Di Rocco, Laura Monteonofrio, Maria Piane, Enrico Cundari, Luciana Chessa, Silvia Soddu
Journal: Journal of Clinical Investigation (2013)

Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder characterized by radiosensitivity, genomic instability, and predisposition to cancer. A-T is caused by biallelic mutations in the ataxia-telangiectasia mutated (ATM) gene, but heterozygous carriers, though apparently healthy, are believed to be at increased risk for cancer and more sensitive to ionizing radiation than the general population. Despite progress in functional and sequencing-based assays, no straightforward, rapid, and inexpensive test is available for the identification of A-T homozygotes and heterozygotes, which is essential for diagnosis, genetic counseling, and carrier prediction. The oncosuppressor p53 prevents genomic instability and centrosomal amplification. During mitosis, p53 localizes at the centrosome in an ATM-dependent manner. We capitalized on the latter finding and established a simple, fast, minimally invasive, reliable, and inexpensive test to determine mutant ATM zygosity. The percentage of mitotic lymphoblasts or PBMCs bearing p53 centrosomal localization clearly discriminated among healthy donors (>75%), A-T heterozygotes (40%–56%), and A-T homozygotes (<30%). The test is specific for A-T, independent of the type of ATM mutations, and recognized tumor-associated ATM polymorphisms. In a preliminary study, our test confirmed that ATM is a breast cancer susceptibility gene. These data open the possibility of cost-effective, early diagnosis of A-T homozygotes and large-scale screenings for heterozygotes.
Perspectives in spina bifida
Authors: J N Thompson
Journal: BMJ (1978)

parison we recorded our results in the same way as Drs Lunn and Johnson.Forty-four of the 60 persons with positive Mantoux tests had a positive and 10 a doubtful tine test.We even found 9",, positive tine tests in Mantoux-negative patients, a fact we explain by the difficulty of strictly intracutane- ous application of the Mantoux test in older persons with very thin skin.In our practice the tine test is an accurate and easily performed screening test for tuberculosis.
Disruption of Striated Preferentially Expressed Gene Locus Leads to Dilated Cardiomyopathy in Mice
Authors: Xiaoli Liu, Tripurasundari Ramjiganesh, Yen-Hsu Chen, Su Wol Chung, Sean R. Hall, Scott L. Schissel, Robert F. Padera, Ronglih Liao, Kate G. Ackerman, Jan Kajstura, Annarosa Leri, Piero Anversa, Shaw-Fang Yet, Matthew D. Layne, Mark A. Perrella
Journal: Circulation (2009)

The striated preferentially expressed gene (Speg) generates 4 different isoforms through alternative promoter use and tissue-specific splicing. Depending on the cell type, Speg isoforms may serve as markers of striated or smooth muscle differentiation.To elucidate function of Speg gene isoforms, we disrupted the Speg gene locus in mice by replacing common exons 8, 9, and 10 with a lacZ gene. beta-Galactosidase activity was detected in cardiomyocytes of the developing heart starting at day 11.5 days post coitum (dpc). beta-Galactosidase activity in other cell types, including vascular smooth muscle cells, did not begin until 18.5 dpc. In the developing heart, protein expression of only Spegalpha and Spegbeta isoforms was present in cardiomyocytes. Homozygous Speg mutant hearts began to enlarge by 16.5 dpc, and by 18.5 dpc, they demonstrated dilation of right and left atria and ventricles. These cardiac abnormalities in the absence of Speg were associated with a cellular hypertrophic response, myofibril degeneration, and a marked decrease in cardiac function. Moreover, Speg mutant mice exhibited significant neonatal mortality, with increased death occurring by 2 days after birth.These findings demonstrate that mutation of the Speg locus leads to cardiac dysfunction and a phenotype consistent with a dilated cardiomyopathy.
Chikungunya infection confirmed in a Belgian traveller returning from Phuket (Thailand)
Authors: E Bottieau, M Van Esbroeck, L Cnops, J Clerinx, A Van Gompel
Journal: Eurosurveillance (2009)

Chikungunya infection has been increasingly reported in international travellers following its epidemic re-emergence in the Indian Ocean islands in 2006 and its spread to southern Asia thereafter. We describe the first case of chikungunya in a Belgian traveller returning from Phuket, Thailand and discuss the potential implications of chikungunya cases imported to European countries for patient management and public health.
Management of Infections Caused by Antibiotic-Resistant Streptococcus Pneumoniae
Authors: Alastair J.J. Wood, Ian R. Friedland, George H. McCracken
Journal: New England Journal of Medicine (1994)

The increasing resistance of S. pneumoniae to antimicrobial agents is a cause for concern. Although a number of therapeutic strategies are possible, local patterns of resistance must be considered. It is essential to determine the susceptibility of individual strains to penicillin and other antimicrobial agents that could be used for therapy. Communication between the clinician and the laboratory is vital to determine the best therapeutic options. The recent recognition of cephalosporin-resistant strains emphasizes the need to determine susceptibility to cephalosporins. Clinical laboratories should be aware of the recently proposed changes in the definition of cephalosporin resistance, and clinicians need to be aware of how these changes affect the choice of antibiotic therapy. Until pneumococcal disease can be effectively prevented, we can expect resistant pneumococcal infections to continue to pose therapeutic difficulties.
The Quest Toward Unsupervised Practice
Authors: Daniel J. Schumacher, Corinne Bria, John G. Frohna
Journal: JAMA (2013)

The ultimate goal of graduate medical education has often been described as supporting learners in the pursuit of independent practice. To achieve this goal, learners and supervisors attempt to balance autonomy vs supervision, defining autonomy as allowing a learner to make decisions in the absence of a supervisor, and supervision as ensuring that ultimate care decisions are in the control of a more experienced physician. These definitions are not only outmoded but perhaps were never correct. Instead, training must prepare learners for unsupervised practice, in which they interact with others (not act independently) and are afforded appropriate autonomy and levels of supervision during training. Indeed, this concept is now reflected in the educational competencies that have been developed by the Accreditation Council for Graduate Medical Education. It is not simply a matter of semantics. Overemphasis on independent practice as the goal beyond training threatens the openness of learners to seeking help when needed and misstates the goal they must strive to achieve. Without defining the intended goal— unsupervised practice—learners and supervisors risk losing focus on ensuring that learners make appropriate de
Proton Pump Inhibitors and the Risk for &lt;emph type="ital"&gt;Clostridium difficile&lt;/emph&gt; Infection—Reply
Authors: Ciarán P. Kelly
Journal: JAMA (2009)

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
THE SENSORY DISTRIBUTION OF THE TRIGEMINAL NERVE
Authors: WALTER MAX KRAUS
Journal: JAMA (1918)

The charts used to indicate the place, extent and nature of sensory changes due to disease of the nervous system fall into two groups: those showing the distribution of peripheral nerves, and those showing the distribution of the spinal segments or posterior roots. The distribution of the trigeminal nerve is sometimes included in both these groups. When it is, it is usually that of the entire nerve root (Fig. 2) or that of the three main branches entering the gasserian ganglion (Fig. 3). The use of the word "segmental" is somewhat confusing. The terms "segmental" and "radicular" are often used interchangeably, and justly so when they apply to the spinal cord. This cannot be done in the case of the trigeminal, as will be shown presently. The word "segmental" should be limited to distributions of intramedullary origin. Some confusion arises from the fact that the first two of the three
Transcriptional regulation of the Th17 immune response by IKKα
Authors: Li Li, Qingguo Ruan, Brendan Hilliard, Jennifer DeVirgiliis, Michael Karin, Youhai H. Chen
Journal: The Journal of Experimental Medicine (2011)

Th17 cells are a subset of T cells that play crucial roles in the pathogenesis of many inflammatory diseases. We report here the identification of IKKα (inhibitor of NF-κB kinase-α) as a key transcriptional regulator of the Th17 lineage. T cells expressing a nonactivatable form of IKKα were significantly compromised in their ability to produce IL-17 and to initiate neural inflammation. IKKα is present in the nuclei of resting CD4+ T cells. Upon Th17 differentiation, IKKα selectively associated with the Il17a locus, and promoted its histone H3 phosphorylation and transcriptional activation in a NF-κB–independent manner. These findings indicate that nuclear IKKα maintains the Th17 phenotype by activating the Il17a gene.
Implanted Cardiac Pacemakers of Variable Frequency
Authors: George J. Haupt
Journal: JAMA (1963)

Studies were made to assess the advantages of variable frequency control in two patients with complete heart block in whom cardiac pacemakers had been inserted. Ventricular rate could be varied electromagnetically by use of an external induction coil. With the patient at rest, cardiac output was relatively independent of the ventricular rate of between 66 and 120. One patient, exercised at a fixed ventricular rate of 66, showed an increase in cardiac output from augmented stroke volume alone. A further increase in cardiac output, despite a decrease in stroke volume, occurred when the ventricular rate was set at the "physiological" level compatible with the exercise load. This effectively differentiates the role of heart rate and stroke volume as determinants of cardiac output.
Delineation of a novel hepatic route for the selective transfer of unesterified sterols from high-density lipoproteins to bile: Studies using the perfused rat liver
Authors: Sander J. Robins, Joan M. Fasulo
Journal: Hepatology (1999)

Cholesterol is principally excreted from the body in bile as unesterified cholesterol (UC). Using the unesterified plant sterol, sitostanol (SIT), as a nonexchangeable analog for UC, we have found that high–density lipoproteins (HDL), but not low–density lipoproteins, provide a vehicle for the direct delivery of cholesterol to bile. To determine the mechanism for preferential cholesterol transport from HDL to bile, isolated rat livers were perfused with a reconstituted HDL, made with radiolabeled unesterified SIT, UC, and cholesteryl esters (CE). Total biliary sterol secretion was independent of the concentration of HDL added to perfusions, but with increasing HDL–SIT perfused, the proportion of SIT to cholesterol in bile was linearly increased. Biliary SIT secretion was rapid (detected within 2 to 4 minutes after reconstituted HDL was added to perfusions) and was dependent on the immediate presence of SIT in the perfusate, but independent of the amount of SIT that had accumulated in the liver. The ratio of SIT to UC was seven– to ninefold greater in bile than in the liver, consistent with preferential mobilization of membrane sterols delivered from HDL. Although radiolabeled UC as well as SIT was taken up from HDL by the liver and secreted in bile, net UC uptake could not be quantitated because of both UC exchange and a sizable enrichment of HDL with UC mass that approximated the SIT removed during the passage of HDL through the liver. These results are consistent with sterol transport to bile from HDL by a direct plasma membrane pathway and by a mechanism that appears to involve substitution of unesterified (exogenous) sterol from HDL for plasma membrane UC during transport. By this process, HDL can promote reverse cholesterol transport from peripheral tissues to bile, even without an increase in biliary cholesterol secretion.
Pancreatic Growth and Regeneration
Authors: E W BENBOW
Journal: Gut (1998)

Pancreatic Growth and Regeneration. Edited by Sarvetnick N. (Pp 25; illustrated; US$98.00.) Karger Landes Systems, 1997. ISBN 3 8055 6618 2.

I may get a reputation for this, but I’m going to do it anyway. I reviewed a book for Gut a few months ago, and grumbled vociferously about the title; specifically, I didn’t like the phrase “clinical pathology” in its title because I didn’t know what the authors would mean by “clinical pathology”. This time, the title is easily understood; it’s just that it’s …
Effect of <i>Bordetella pertussis</i> Vaccination in Mice and the Isolated Tracheal Response to Isoprenaline
Authors: Thad E. Bartell, William W. Busse
Journal: Allergy (1980)

The administration of Bordetella pertussis vaccine to mice has been associated with the development of an impaired beta‐adrenoceptor responsiveness and in many respects has resembled human asthma. Trachea ( n =12) were isolated from Swiss‐Webster mice 5 days following the intraperitoneal administration of 2 × 10 9 B. pertussis organisms. The tracheal smooth muscle response to carbachol was measured and compared with that found in trachea from unvaccinated mice ( n =15). The contractile response was similar in both groups. The tracheal smooth muscle relaxant effects of isoproterenol were measured in these two groups. The EC 50 value for isoprenaline (6.5 × 10 –7 M) in trachea from B. pertussis treated mice was significantly ( P 0.05) greater than that noted in the control animals (2.3 × 10 −7 M). These studies demonstrated that in tracheal smooth muscle isolated from B. pertussis vaccinated mice, the relaxant effects of isoprenaline are impaired.
Evaluation of the 8q24 Prostate Cancer Risk Locus and <i>MYC</i> Expression
Authors: Mark M. Pomerantz, Christine A. Beckwith, Meredith M. Regan, Stacia K. Wyman, Gyorgy Petrovics, Yongmei Chen, Dorota J. Hawksworth, Fredrick R. Schumacher, Lorelei Mucci, Kathryn L. Penney, Meir J. Stampfer, Jennifer A. Chan, Kristin G. Ardlie, Brian R. Fritz, Rachael K. Parkin, Daniel W. Lin, Michelle Dyke, Paula Herman, Steve Lee, William K. Oh, Philip W. Kantoff, Muneesh Tewari, David G. McLeod, Shiv Srivastava, Matthew L. Freedman
Journal: Cancer Research (2009)

Abstract Polymorphisms at 8q24 are robustly associated with prostate cancer risk. The risk variants are located in nonprotein coding regions and their mechanism has not been fully elucidated. To further dissect the function of this locus, we tested two hypotheses: (a) unannotated microRNAs (miRNA) are transcribed in the region, and (b) this region is a cis-acting enhancer. Using next generation sequencing, 8q24 risk regions were interrogated for known and novel miRNAs in histologically normal radical prostatectomy tissue. We also evaluated the association between the risk variants and transcript levels of multiple genes, focusing on the proto-oncogene, MYC. RNA expression was measured in histologically normal and tumor tissue from 280 prostatectomy specimens (from 234 European American and 46 African American patients), and paired germline DNA from each individual was genotyped for six 8q24 risk single nucleotide polymorphisms. No evidence was found for significant miRNA transcription within 8q24 prostate cancer risk loci. Likewise, no convincing association between RNA expression and risk allele status was detected in either histologically normal or tumor tissue. To our knowledge, this is one of the first and largest studies to directly assess miRNA in this region and to systematically measure MYC expression levels in prostate tissue in relation to inherited risk variants. These data will help to direct the future study of this risk locus. [Cancer Res 2009;69(13):5568–74]
Selective bowel decontamination of recipients for prevention against liver injury following orthotopic liver transplantation: Evaluation with rat models
Authors: Masahiro Arai, Satoshi Mochida, Akihiko Ohno, Shin Arai, Kenji Fujiwara
Journal: Hepatology (1998)

Gut-derived substances can activate Kupffer cells to provoke hepatic necrosis after partial hepatectomy in rats. A similar situation may occur during orthotopic liver transplantation (OLT), as congestion in the intestinal wall, caused by portal vein occlusion, is inevitable during the operation. The contribution of such substances to liver injury following OLT was investigated in rats. Oral administration of polymyxin B sulfate for 7 days significantly altered intestinal bacterial flora in rats; Enterobacteriaceae diminished and anaerobes such as Bifidobacterium , Lactobacillus, Bacteroides, and Eubacterium increased in number, compared with the control rats. Also, this treatment significantly reduced endotoxin concentration in the portal blood 30 minutes after blood reflow following portal vein occlusion. When OLT was performed in rats using the liver preserved in cold University of Wisconsin solution for 18 hours, tissue factor activity in Kupffer cells (KC) isolated from the transplanted liver 1 hour after the operation was significantly higher than in that of normal rats. This increase was significantly reduced by pretreatment of the recipients with polymyxin B sulfate. In these recipients, serum alanine aminotransferase activity, tumor necrosis factor alpha (TNF alpha) concentration, and histological extent of liver necrosis were significantly attenuated at 24 hours after the operation compared with those of control rats. We conclude that the substances derived from bacilli sensitive to polymyxin B sulfate in the gut may be a contributing factor to liver injury following OLT in rats; we feel that this probably occurs by entering of the substances into the portal blood during the ahepatic phase of the operation to activate KC. Selective bowel decontamination of recipients with polymyxin B sulfate would be a candidate for protection against early graft failure following OLT.