tbuckley/cabot-search huggingface dataset:
Abstract P2-08-03: Patterns of somatic mutations in metaplastic carcinoma of the breast
Authors: SA O'Toole, B Yu, CC Ng, CI Selinger, WA Cooper, H Carmalt, C Mak, C Chan, S Lee, R Karim, J Beith, C Cooper
Journal: Cancer Research (2013)

Abstract Introduction Metaplastic carcinoma of the breast (MCB) is a heterogeneous group of malignant tumors comprising less than 1% of all breast carcinomas encompassing tumors with purely epithelial, as well as epithelial and mesenchymal components, which may be entirely metaplastic or admixed with carcinoma. There is no agreed upon optimal treatment regime for these tumors, which overall have a worse prognosis than similar stage invasive ductal carcinoma (IDC). Research into MCB has been limited by the rarity of this tumor; however as the majority of these tumors do not express ER, PR or Her2 (triple negative) and response to traditional chemotherapy is limited, there is a need for further research to identify predictive biomarkers and new targets for treatment. We report our findings of multigene mutation profiling in a series of 21 MCB. Methods DNA was extracted from tumors of twenty one patients with MCB, genotyped using the Oncocarta v1.0 kit a sensitive, high throughput mass spectrometry based assay which detects a panel of 238 specific mutations in 19 oncogenes including KRAS, BRAF, PIK3CA, MET, AKT1 &amp; ERBB2 and processed on the Sequenom compact MassARRAY platform. In the case with heterologous differentiation, separate cores were taken from the spindle cell, osteo- and chrondrosarcomatous areas. Results Histological review revealed three pure spindle cell cases with the remainder showing mixed patterns of spindle, squamous and IDC, no special type. A single case showed heterologous osteosarcomatous and chondrosarcomatous differentiation. Ten mutations were detected in these 21 MCB. PIK3CA gene mutations (six H1047L and one E545K mutation) were seen in seven patients; and KRAS gene mutations (two G12V and one G12A) were observed in three patients. No mutations were detected in the case with heterologous elements in the separate areas of spindle, osteo- and chondrosarcomatous differentiation. Conclusions PIK3CA mutations were seen in 33% and KRAS mutations were seen in 14% of MCB cases in this series. Given the general lack of effective chemotherapies in MCB, these findings suggest that the PI3K pathway may be a promising therapeutic target worthy of further investigation. We plan to also undertake detailed mutational analyses using next generation sequencing to identify further potential therapeutic targets in these rare and difficult to treat malignancies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-08-03.
MAP Kinase-Interacting Kinase 1 Regulates SMAD2-Dependent TGF-β Signaling Pathway in Human Glioblastoma
Authors: Michal Grzmil, Pier Morin, Maria Maddalena Lino, Adrian Merlo, Stephan Frank, Yuhua Wang, Gerald Moncayo, Brian A. Hemmings
Journal: Cancer Research (2011)

Abstract Glioblastoma multiforme (GBM) is the most common aggressive brain cancer with a median survival of approximately 1 year. In a search for novel molecular targets that could be therapeutically developed, our kinome-focused microarray analysis identified the MAP (mitogen-activated protein) kinase-interacting kinase 1 (MNK1) as an attractive theranostic candidate. MNK1 overexpression was confirmed in both primary GBMs and glioma cell lines. Inhibition of MNK1 activity in GBM cells by the small molecule CGP57380 suppressed eIF4E phosphorylation, proliferation, and colony formation whereas concomitant treatment with CGP57380 and the mTOR inhibitor rapamycin accentuated growth inhibition and cell-cycle arrest. siRNA-mediated knockdown of MNK1 expression reduced proliferation of cells incubated with rapamycin. Conversely, overexpression of full-length MNK1 reduced rapamycin-induced growth inhibition. Analysis of polysomal profiles revealed inhibition of translation in CGP57380 and rapamycin-treated cells. Microarray analysis of total and polysomal RNA from MNK1-depleted GBM cells identified mRNAs involved in regulation of TGF-β pathway. Translation of SMAD2 mRNA as well as TGF-β–induced cell motility and vimentin expression was regulated by MNK1 signaling. Tissue microarray analysis revealed a positive correlation between the immunohistochemical staining of MNK1 and SMAD2. Taken together, our findings offer insights into how MNK1 pathways control translation of cancer-related mRNAs including SMAD2, a key component of the TGF-β signaling pathway. Furthermore, they suggest MNK1-controlled translational pathways in targeted strategies to more effectively treat GBM. Cancer Res; 71(6); 2392–402. ©2011 AACR.
Detection of clonal T-cell receptor γ chain gene rearrangements by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE) in archival specimens from patients with early cutaneous T-cell lymphoma: Correlation of histologic findings with PCR/DGGE
Authors: Julide Tok, Matthias J. Szabolcs, David N. Silvers, Jingyao Zhong, Anne Y. Matsushima
Journal: Journal of the American Academy of Dermatology (1998)

Early stages of cutaneous T-cell lymphoma (CTCL) may be difficult to distinguish from benign inflammatory dermatoses by routine histologic examination.Our purpose was to determine whether clonal rearrangements of the T-cell receptor (TCR) gamma gene by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE) could be detected in the early stages of CTCL and to correlate these findings with conventional histopathology.A total of 39 specimens from 12 patients with CTCL were obtained. The slides were evaluated independently by three dermatopathologists, and categorized into three groups: nondiagnostic, suggestive of CTCL, and diagnostic of CTCL. Of the 39 specimens, 33 were tested by PCR/DGGE by means of GC-clamped primers for clonal rearrangement of the TCR gamma gene.The histologic evaluation of the 12 cases showed a significant variation among the three dermatopathologists. The correlation of PCR/DGGE with routine histology was as follows: Clonal TCR gamma gene rearrangements were demonstrated in 73% of the specimens nondiagnostic for CTCL, 71% of those suggestive of CTCL, and 74% of those diagnostic of CTCL.Clonal TCR gamma gene rearrangements may be detected in patients with early CTCL, even when the histologic findings are not unequivocally diagnostic. In patients with multiple biopsy specimens, identical clones were demonstrated in all rearranged samples, indicating the same neoplastic clone was present in the earliest stages of disease.
Long-term Scintigraphic Appearance of Extremities Following Bone Tumor Resection and Allograft Reconstruction
Authors: JOHN T. SMITH, LYNN M. SMITH, LAWRENCE RINSKY, MICHAEL L. GORIS
Journal: Clinical Nuclear Medicine (1991)

The authors retrospectively reviewed the Tc-99m medronate scan findings in six patients who had no evidence of metastatic disease following en bloc resection of a primary osteosarcoma and subsequent limb reconstruction using allograft bone. Persistently increased radionuclide uptake was noted at the junction between the host bone and the graft, while the graft cortical bone showed persistently decreased activity. Radionuclide uptake at the periphery of the graft varied. Over time the youngest patient in the series had increasingly normal scan findings.
PROBLEMS OF PRACTICE
Authors: J. N S Simpson
Journal: BMJ (1995)

Many years ago I was in a country practice during a severe influenza epidemic. One week three of us had 83 new calls on the Monday and 75 on the Tuesday. Things settled down a little and then it was my weekend on. I had about 15 new calls from people who had influenza or thought they did.

I waded through the list, dispensing medicine and reassurance. Towards lunch time I visited a country council house and was duly ushered into a downstairs room. …
Biochemical Correction of X-CGD by a Novel Chimeric Promoter Regulating High Levels of Transgene Expression in Myeloid Cells
Authors: Giorgia Santilli, Elena Almarza, Christian Brendel, Uimook Choi, Chiara Beilin, Michael P Blundell, Sneha Haria, Kathryn L Parsley, Christine Kinnon, Harry L Malech, Juan A Bueren, Manuel Grez, Adrian J Thrasher
Journal: Molecular Therapy (2010)

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase catalytic subunit gp91(phox). A recent clinical trial for X-CGD using a spleen focus-forming virus (SFFV)-based γ-retroviral vector has demonstrated clear therapeutic benefits in several patients although complicated by enhancer-mediated mutagenesis and diminution of effectiveness over time due to silencing of the viral long terminal repeat (LTR). To improve safety and efficacy, we have designed a lentiviral vector that directs transgene expression primarily in myeloid cells. To this end, we created a synthetic chimeric promoter that contains binding sites for myeloid transcription factors CAAT box enhancer-binding family proteins (C/EBPs) and PU.1, which are highly expressed during granulocytic differentiation. As predicted, the chimeric promoter regulated higher reporter gene expression in myeloid than in nonmyeloid cells, and in human hematopoietic progenitors upon granulocytic differentiation. In a murine model of stem cell gene therapy for X-CGD, the chimeric vector resulted in high levels of gp91(phox) expression in committed myeloid cells and granulocytes, and restored normal NADPH-oxidase activity. These findings were recapitulated in human neutrophils derived from transduced X-CGD CD34(+) cells in vivo, and suggest that the chimeric promoter will have utility for gene therapy of myeloid lineage disorders such as CGD.
Ambulatory Management of Thromboembolic Disease During Pregnancy With Continuous Infusion of Heparin
Authors: Michael Carl Brabeck
Journal: JAMA (1987)

THROMBOEMBOLIC events related to pregnancy are not uncommon. Retrospective studies have shown an incidence as high as one in 70 pregnancies when thrombophlebitis of either the superficial or deep venous systems occurring in the antepartum or postpartum period is considered.<sup>1</sup>The following report describes continuous intravenous (IV) infusion of heparin sodium in the ambulatory setting, an uncommon approach to treating these patients. <h3>Report of a Case</h3> A 32-year-old woman with a history of a documented pulmonary embolus while receiving oral contraceptives and a previously uneventful pregnancy was admitted to the hospital in the eighth week of gestation, with pain and swelling of the right lower extremity. Plethysmographic and Doppler study results suggested acute obstruction in the right popliteal system and further diagnostic studies were not pursued. A bolus of 5000 units of heparin sodium was given, followed by a continuous infusion of approximately 1000 U/h for eight days. There
Global Shortage of Health Workers, Brain Drain Stress Developing Countries
Authors: Bridget M. Kuehn
Journal: JAMA (2007)

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
Winiwarter-Buerger Disease ('Thromboangiitis Obliterans') With Cerebral Involvement
Authors: Miles E. Drake
Journal: JAMA (1982)

A patient with clinical and radiological manifestations o Winiwarter-Buerger disease ("thromboangiitis obliterans") in the extremities had three cerebrovascular events during a five-year follow-up. Changes of infarction were confirmed by computed tomographic brain scan and arteriography, but no clinical or laboratory evidence of vasculitis nor a source of recurrent emboli could be found. He had no atherosclerotic risk factors except being a heavy smoker. Cerebrovascular involvement in Buerger's disease is infrequent, but clinical and pathological demonstration has occasionally been found. The existence of Buerger's disease has been questioned, but there appears to be a distinct syndrome of vascular disease that is not atherosclerotic or vasculitic. Stroke maybe a component of this syndrome and may be a complication preventable by cessation of smoking.
Troglitazone Improves Recovery of Left Ventricular Function After Regional Ischemia in Pigs
Authors: Peili Zhu, Li Lu, Ya Xu, Gregory G. Schwartz
Journal: Circulation (2000)

Background —This study determined whether treatment of normal (nondiabetic) pigs with the insulin-sensitizing agent troglitazone improves recovery of left ventricular (LV) function after acute ischemia and whether such effects are associated with altered myocardial substrate metabolism. Methods and Results —Juvenile pigs (n=6) were treated with troglitazone (75 mg · kg −1 · d −1 PO) for 8 weeks. Untreated pigs (n=8) served as controls. Under anesthetized, open-chest conditions, pigs underwent 90 minutes of moderate regional LV ischemia and 90 minutes of reperfusion. Regional LV function was assessed with subendocardial sonomicrometry crystals. Fasting plasma insulin and free fatty acid levels were lower in troglitazone-treated pigs than in untreated pigs, whereas blood glucose did not differ between groups. These findings suggest that treatment enhanced systemic insulin sensitivity. Baseline hemodynamics and regional LV function did not differ between groups. After ischemia and reperfusion, systolic function (external work) of the ischemic region recovered to 44±6% of baseline in troglitazone-treated pigs versus 18±6% of baseline in untreated pigs ( P &lt;0.05). Regional diastolic function (maximum rate of wall expansion) recovered to 78±7% of baseline in treated pigs versus 52±7% of baseline in untreated pigs ( P &lt;0.05). Recovery of global LV systolic and diastolic function was also significantly greater in treated pigs. Myocardial glucose uptake did not differ between groups under any condition; however, net myocardial lactate uptake after reperfusion was 7 times greater in troglitazone-treated pigs than in untreated pigs, suggesting that treatment enhanced myocardial carbohydrate oxidation after reperfusion. Conclusions —In nondiabetic pigs, chronic troglitazone treatment improves recovery of LV systolic and diastolic function after acute ischemia.
On the relation between phenomenal and representational properties
Authors: Güven Güzeldere, Murat Aydede
Journal: Behavioral and Brain Sciences (1997)

We argue that Block's charge of fallacy remains ungrounded so long as the existence of P-consciousness, as Block construes it, is independently established. This, in turn, depends on establishing the existence of “phenomenal properties” that are essentially not representational, cognitive, or functional. We argue that Block leaves this fundamental thesis unsubstantiated. We conclude by suggesting that phenomenal consciousness can be accounted for in terms of a hybrid set of representational and functional properties.
The initial care of newborn infants and subsequent hay fever
Authors: S. M. Montgomery, A. J. Wakefield, D. L. Morris, R. E. Pounder, S. H. Murch
Journal: Allergy (2000)

Background: Patterns of neonatal exposure to microorganisms have changed substantially over the last 100 years, and it has been suggested that this has influenced the risk of immune‐mediated disease. Using a proxy measure, we tested the hypothesis that the initial handling of newborn infants, which is known to affect the pattern of exposure to microorganisms, may alter the risk of developing subsequent atopy, as indicated by hay fever. Methods : Analysis was performed on 5519 members of the 1970 British Cohort Study, a nationally representative birth cohort. Cohort members with hay fever were identified at intervals up to the age of 26 years. Details of neonatal care and childhood circumstances were recorded prospectively. Those who had spent their first night away from their mother in the communal infant nursery were selected as likely to have experienced atypical exposure compared with infants who remained with their mother. Adjustment was made for potential confounding factors in infancy and childhood by multiple logistic regression analysis. Results : Unadjusted relative odds (with 95% CI) for developing hay fever among those spending the first night in the communal nursery, when compared with other infants who remained with the mother, were 1.48 (1.23–1.77), P &lt;0.001. Comprehensive adjustment for the potential confounding factors, including feeding practices on the first day of life, markers of social and material circumstances, and region, did not substantially alter this relationship, with adjusted relative odds of 1.31 (1.08–1.59), P =0.005. Conclusions : While our proxy measure is associated with an increased risk of hay fever, further research is required to confirm that this is due to the pattern of infectious exposure in very early life. The results are consistent with the hypothesis that the first challenges are particularly important in the development of the newborn infant's immune system.
Clinical Experience with the Use of Frozen Blood in Combat Casualties
Authors: Gerald S. Moss, C. Robert Valeri, Charles E. Brodine
Journal: New England Journal of Medicine (1968)

To test the usefulness of frozen Group O, Rh-negative red blood cells in a combat-zone hospital, a frozen-blood facility was established in DaNang. The cells were glycerolized and frozen in Boston and then air-shipped to Vietnam. Total storage time at -80°C ranged from four to eight months. In vitro red blood cell loss was 26.7 per cent (±12.8 per cent), and unit supernatant hemoglobin was 54 mg (±46 mg). Thirty-six acutely injured casualties were given multiple transfusions. Recipient plasma hemoglobin rose 3.68 mg per 100 ml per unit received. Recipient serum bilirubin rose 0.28 mg per 100 ml per unit received. No evidence of impaired renal function related to transfusion was noted. It is concluded that the operation of a frozen-blood bank in a combat-zone hospital is technically feasible and clinically acceptable, and in its present state of development provides a satisfactory alternative to walking donors.
ANGIOTENSIN II TYPE 1 RECEPTOR POLYMORPHISM IS ASSOCIATED WITH BASELINE HEMODYNAMICS AMONG PATIENTS WITH CORONARY ARTERY DISEASE AND EXERCISE INDUCED MYOCARDIAL ISCHEMIA: RESULTS FROM THE PSYCHOPHYSIOLOGICAL INVESTIGATIONS OF MYOCARDIAL ISCHEMIA STUDY
Authors: Catherine Norton, Jonathan Schultz, Ambar Kulshreshtha, Reynaria Nieva, Gina Eubanks, Mustafa Hassan, Julie Johnson, Taimour Langaee, Shaoyong Su, David Sheps
Journal: Journal of the American College of Cardiology (2011)
Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children ( <scp>SONIC</scp> )
Authors: I. Orlow, J.M. Satagopan, M. Berwick, H.L. Enriquez, K.A.M. White, K. Cheung, S.W. Dusza, S.A. Oliveria, M.A. Marchetti, A. Scope, A.A. Marghoob, A.C. Halpern
Journal: British Journal of Dermatology (2014)

Melanocytic naevi are an important risk factor for melanoma. Naevi with distinct dermoscopic patterns can differ in size, distribution and host pigmentation characteristics.We examined MC1R and 85 other candidate loci in a cohort of children to test the hypothesis that the development and dermoscopic type of naevi are modulated by genetic variants.Buccal DNAs were obtained from a cohort of 353 fifth graders (mean age 10·4 years). Polymorphisms were chosen based on a known or anticipated role in naevi and melanoma. Associations between single-nucleotide polymorphisms (SNPs) and baseline naevus count were determined by multivariate regression adjusting for sex, race/ethnicity and sun sensitivity. Dermoscopic images were available for 853 naevi from 290 children. Associations between SNPs and dermoscopic patterns were determined by polytomous regression.Four SNPs were significantly associated with increasing (IRF4) or decreasing (PARP1, CDK6 and PLA2G6) naevus count in multivariate shrinkage analyses with all SNPs included in the model; IRF4 rs12203952 showed the strongest association with log naevus count (relative risk 1·56, P < 0·001). Using homogeneous naevi as the reference, IRF4 rs12203952 and four other SNPs in TERT, CDKN1B, MTAP and PARP1 were associated with either globular or reticular dermoscopic patterns (P < 0·05).Our results provide evidence that subsets of naevi defined by dermoscopic patterns differ in their associations with germline genotypes and support the hypothesis that dermoscopically defined subsets of naevi are biologically distinct. These results require confirmation in larger cohorts. If confirmed, these findings will improve the current knowledge of naevogenesis and assist in the identification of individuals with high-risk phenotypes.
Pseudomonas Endocarditis-Reply
Authors: Joseph S. Alpert
Journal: JAMA (1979)

We appreciate the comments of Drs Reyes and Lerner based on their considerable experience with Pseudomonas endocarditis in heroin addicts. It was not the purpose of our article to suggest that patients whose temperatures defervesce rapidly without therapy never have Pseudomonas endocarditis. Indeed, we specifically stated that such a clinical course does not imply that treatment with appropriate antibiotics should be withheld from addicts with fever, pleuritic chest pain, and heart murmurs, since it is impossible to predict which drug abusers will follow this more benign course. We go on to state that in such patients, the clinical condition should be reevaluated, and the plan of therapy should be reconsidered, particularly when defervescence occurs within 24 hours of the initiation of antibiotic therapy. It may be possible to treat such patients with an abbreviated antibiotic course rather than the full six-week course recommended by Drs Reyes and Lerner.
Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation
Authors: A Sprüssel, J H Schulte, S Weber, M Necke, K Händschke, T Thor, K W Pajtler, A Schramm, K König, L Diehl, P Mestdagh, J Vandesompele, F Speleman, H Jastrow, L C Heukamp, R Schüle, U Dührsen, R Buettner, A Eggert, J R Göthert
Journal: Leukemia (2012)