tbuckley/cabot-search huggingface dataset:
Abstract P6-01-04: Ductal Carcinoma In-Situ Associated with Triple-Negative Invasive Breast Carcinoma Is Often Immunohistochemically Distinct from Invasive Component
Authors: RA Simon, TA Karim, C Zhang, MM Steinhoff, CJ Sung, MR. Quddus
Journal: Cancer Research (2010)

Abstract Background: Gene expression profiling studies have identified a sub-set of breast carcinoma known as basal-like carcinoma, which characteristically do not express estrogen receptor (ER), progesterone receptor (PR), or HER2neu (HER2). These triple negative invasive ductal carcinomas (TN-IDC) are associated with an aggressive clinical course and poor prognosis. Little information exists in the literature concerning ductal carcinoma in-situ (DCIS) associated with TN-IDC. We evaluated the frequency, histologic features, and receptor status of DCIS associated with TN-IDC. Design: From our institutional archives between July 2006 and August 2009, we retrieved all cases of intermediate and high grade invasive ductal breast carcinoma. Based on the immunoprofiling, invasive carcinomas were categorized into either TN-IDC or non triple-negative invasive carcinoma (non-TN-IDC). Immunohistochemistry for ER, PR, and HER2 was performed on the DCIS of the TN-IDC group and on some available cases from the non-TN-IDC group. The frequency, receptor status, and nuclear grade of DCIS associated with both groups were noted. Statistical analysis was performed using Fisher Exact Test. Results: Among a total of 224 cases, 56 (25%) were classified as TN-IDC and 168 (75%) as non-TN-IDC. DCIS was seen in 28 (50%) TN-IDC cases and in 150 (89.3%) non-TN-IDC cases (P&amp;lt;0.0001). Sufficient tumor was available for immunohistochemical staining in 23 of 28 cases with DCIS in the TN-IDC group. Within the 23 cases, the DCIS were triple negative in 15 cases (65%). Of the remaining 8 cases (35%), 4 were positive for ER and PR, but negative for HER2, while the other 4 cases were negative for ER and PR but positive for HER2. Ninety-six cases in the non-TN-IDC group had available immunostains for review, 7 of which (7.3%) displayed a different receptor status from their invasive counterparts (p=0.0016, compared with TN-IDC). Two cases of non-TN-IDC showed an associated TN-DCIS. Of the 28 cases of TN-IDC associated with DCIS, 4 (14.3%) showed lower nuclear grade in DCIS than in its invasive counterpart, compared with 22 of 150 (14.7%) non-TN-IDC cases (no significant difference). One TN-IDC case displayed two distinct morphologic patterns of DCIS; neither pattern was triple negative. Conclusion: Our study demonstrated the presence of DCIS in a considerable proportion of TN-IDC although at a significantly lower frequency than in non-TN-IDC. DCIS associated with TN-IDC was significantly more likely to display a different immunoprofile from its invasive counterpart than DCIS associated with non-TN-IDC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-04.
THE INCORPORATION OF ACETATE-1-C14 INTO CHOLESTEROL AND FATTY ACIDS BY SURVIVING TISSUES OF NORMAL AND SCORBUTIC GUINEA PIGS
Authors: H. I. Bolker, S. Fishman, R. D. H. Heard, V. J. O'Donnell, J. L. Webb, G. C. Willis
Journal: The Journal of Experimental Medicine (1956)

The synthesis of cholesterol and fatty acids from acetate-l-C(14) by the isolated liver, adrenal, and aorta of scorbutic and pair-fed control guinea pigs has been studied. It was found that ascorbic acid deficiency does not affect the rate of incorporation of C(14)-acetate into cholesterol and fatty acids by the tissues investigated, under our experimental conditions. The relatively high metabolic activity of the artery with regard to cholesterogenesis and lipogenesis was noted. The elevation of serum cholesterol and hexosamine in scurvy has been confirmed.
Phosphorylation Regulates OLIG2 Cofactor Choice and the Motor Neuron-Oligodendrocyte Fate Switch
Authors: Huiliang Li, Joana Paes de Faria, Paul Andrew, Justyna Nitarska, William D. Richardson
Journal: Neuron (2011)

A fundamental feature of central nervous system development is that neurons are generated before glia. In the embryonic spinal cord, for example, a group of neuroepithelial stem cells (NSCs) generates motor neurons (MNs), before switching abruptly to oligodendrocyte precursors (OLPs). We asked how transcription factor OLIG2 participates in this MN-OLP fate switch. We found that Serine 147 in the helix-loop-helix domain of OLIG2 was phosphorylated during MN production and dephosphorylated at the onset of OLP genesis. Mutating Serine 147 to Alanine (S147A) abolished MN production without preventing OLP production in transgenic mice, chicks, or cultured P19 cells. We conclude that S147 phosphorylation, possibly by protein kinase A, is required for MN but not OLP genesis and propose that dephosphorylation triggers the MN-OLP switch. Wild-type OLIG2 forms stable homodimers, whereas mutant (unphosphorylated) OLIG2S147A prefers to form heterodimers with Neurogenin 2 or other bHLH partners, suggesting a molecular basis for the switch.
Australian team to transplant pig islet cells into patients with unstable diabetes
Authors: S. Mayor
Journal: BMJ (2009)

Australian researchers have been given permission to do a clinical trial in which pig islet cells are transplanted into adult patients with unstable type 1 diabetes in an attempt to cure their disease, it was announced last week.

A research group from the company Living Cell Technologies has been granted approval to conduct the trial in New Zealand because there is a moratorium on xenotransplantation, the transplantation of living animal cells or tissues into humans, in Australia.

In the trial, adults with unstable type 1 diabetes will be given microencapsulated pig islet cells by intraperitoneal injection. The islet cells are coated in a material that allows insulin to pass out into the patient’s bloodstream and nutrients to diffuse into the cells. However, it reduces the risk of rejection by preventing direct contact between the surface of the transplanted …
Depletion of the C3 component of complement enhances the ability of rituximab-coated target cells to activate human NK cells and improves the efficacy of monoclonal antibody therapy in an in vivo model
Authors: Siao-Yi Wang, Suresh Veeramani, Emilian Racila, Jeffrey Cagley, David C. Fritzinger, Carl-Wilhelm Vogel, William St John, George J. Weiner
Journal: Blood (2009)
Gene Expression Profiling of Tumor–Stromal Interactions between Pancreatic Cancer Cells and Stromal Fibroblasts
Authors: Norihiro Sato, Naoki Maehara, Michael Goggins
Journal: Cancer Research (2004)

The interactions between cancer cells and surrounding stroma play a critical role in tumor progression, but their molecular basis is largely unknown. Global gene expression profiling was performed using oligonucleotide microarrays to determine changes in the gene expression of pancreatic cancer cells (CFPAC1) and stromal fibroblasts induced by coculture. This analysis identified multiple genes as differentially expressed in pancreatic cancer cells and in fibroblasts as a consequence of their mutual interactions, including those that encode for proteins associated with tumor invasion, metastasis, and angiogenesis. Among the genes identified, the cyclooxygenase-2 (COX-2)/PTGS2 gene was of particular interest because COX-2 expression was markedly augmented in both cell types (cancer cells and fibroblasts) in response to coculture. Coculture with fibroblasts also induced COX-2 expression in additional pancreatic cancer cells with an unmethylated COX-2 promoter, but not in those with a methylated COX-2 promoter. Using an in vitro invasion assay, we found an increase in the invasive potential of CFPAC1 cells when they were cocultured with fibroblasts, an effect blocked partially by the addition of a selective COX-2 inhibitor, NS-398, or by COX-2 knockdown with small interfering RNA. Thus, COX-2 inhibitors can decrease the invasive properties of pancreatic cancer cells acquired through tumor-stromal interactions.
Adrenal Function and the Inhibition of Allergic Responses Under Hypnosis
Authors: S. Black, M. Friedman
Journal: BMJ (1965)

Initial treatment with one drug only Penicillin ... ... 5 cases (2 changed to chlorampheni- col on second day.One died) Chloramphenicol ... 2 cases (both changed to other effec- tive drugs in second week to avoid toxicity) Intrathecal treatment None ... casesPenicillin one day ... 9Penicillin 2 to 4 days 17PenIcillin 5 to 7 days 10Penicillin 8 to 14 days 5 Streptomycin ... 2 ,, (1 for 1 week, 1 for 1 day) Chloromycetin ...
Foundation trusts in England record overall deficit for first time
Authors: G. Iacobucci
Journal: BMJ (2014)

Almost six in 10 NHS foundation hospital trusts in England reported a deficit in the first quarter of this financial year, as the “unprecedented” financial pressure facing the NHS continues to grow.

The latest quarterly figures from the health sector regulator Monitor show that 86 of England’s 147 foundation trusts reported a deficit totalling £227m (€290m; $370m) between April and June 2014 and that 80% of those posting deficits were acute care trusts.1

Although 61 foundation trusts reported a surplus totalling £60m in this period, the sector as a whole posted a £167m deficit overall, …
IκB kinase–driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease
Authors: Rosalia Gagliardo, Pascal Chanez, Mirella Profita, Anna Bonanno, Giusy Daniela Albano, Angela Marina Montalbano, Flora Pompeo, Cesare Gagliardo, Anna Maria Merendino, Mark Gjomarkaj
Journal: Journal of Allergy and Clinical Immunology (2011)
THE RELATION OF STATES OF APPREHENSION TO CARDIAC DISEASE.
Authors: WILLIAM RUSH DUNTON
Journal: JAMA (1905)

Some time ago an author was quoted in my hearing to the effect that in all cases of alienation which showed apprehension there could be found some cardiac lesion. Unfortunately, I have been unable to trace this statement to the original, but it suggested an inquiry into the milder states of apprehension as distinguished from the anxiety neuroses. This inquiry I am at present following out and the few conclusions which are justifiable at the present time will be given here, while any results which may be derived from further research will be published later. Twenty-five of the most recent admissions to the women's side of the Sheppard and Enoch Pratt Hospital, Who are at present under care, have been taken as a series for this inquiry. Five of these twenty-five cases have shown apprehension in a sufficiently marked degree to leave no doubt as to its
Functional limitation in long standing illness and quality of life: evidence from a national survey
Authors: Gopalakrishnan Netuveli, Richard D Wiggins, Zoe Hildon, Scott M Montgomery, David Blane
Journal: BMJ (2005)

relevant diagnostic investigations-that is, patients in whom treatment is likely to be initiated in everyday practice.In conclusion, several easily obtained clinical parameters and a few additional diagnostic investigationsnotably, natriuretic peptide and electrocardiographymay improve the detection of concomitant heart failure in primary care patients with COPD.The use of these parameters should increase confidence about the diagnosis of heart failure and will help GPs to decide about the need for additional echocardiography or treatment in patients with COPD.We thank the participating patients, general practitioners and their assistants, including the general practices connected to the General Practice Network Utrecht (HNU), the cardiac sonographers Elly Lutgert-Hagman and Ineke Kasteleijn, the pulmonology technicians, especially Paul Munnik, and Pieter Zanen, lung physiologist.Frances Verheij assisted us with the data management.
Age-associated alterations in viscoelastic properties of canine aortic strips.
Authors: F C Yin, H A Spurgeon, C H Kallman
Journal: Circulation Research (1983)

Many studies have delineated the changes in the elastic properties of arterial tissue as a function of age. Despite the fact that viscoelasticity is a prominent feature of these tissues, there is little information or characterization of age-associated changes in viscoelastic properties, over a wide range of smooth muscle activation, particularly in nonhuman tissue where atherosclerosis is not a confounding factor. In the present study, using small sinusoidal length perturbations, we determined the dynamic stiffness properties across a wide range of lengths (stretch ratios from 100 to 135%) and frequencies (from 0.25 to 35 Hz) in strips excised from ascending and descending aortas from six young (2 to 4-year-old) and 12 senescent (10- to 13-year-old) beagles. Studies were performed with the smooth muscle fully activated with calcium and norepinephrine, as well as fully inactivated with cyanide, iodoacetate, and dinitrophenol. There was a cubic nonlinear dependence of stiffness modulus on length only in senescent tissue and, surprisingly, little frequency dependence in tissue of either age. Compared to the young aortas, the three-dimensional surface representing the dependence of stiffness modulus on length and frequency from both the ascending and descending regions of aged aortas was displaced higher on the stiffness axis both with the muscle fully activated and inactivated. This age difference was accentuated at longer lengths. The phase lag between force and length was greater in the young vs. the old strips only in the activated, ascending aortic tissue. We found no age differences in the content of elastin, collagen, or in the collagen/elastin ratio, to account for these mechanical property differences.(ABSTRACT TRUNCATED AT 250 WORDS)
Proinflammatory cytokine–induced and chemical mediator–induced IL-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase–dependent pathway☆☆☆★
Authors: Ken Matsumoto, Shu Hashimoto, Yasuhiro Gon, Tomoko Nakayama, Takashi Horie
Journal: Journal of Allergy and Clinical Immunology (1998)
The histocompatibility restrictions on macrophage T-helper cell interaction determine the histocompatibility restrictions on T-helper cell B-cell interaction.
Authors: U Yamashita, E M Shevach
Journal: The Journal of Experimental Medicine (1978)

To study the histocompatibility restriction between macrophages and helper T cells, carrier primed guinea pig T cells were positively selected in vitro with antigenpulsed macrophages for 7 days and the selected T cells were then mixed with hapten-primed B cells and stimulated with antigen in a modified Mishell-Dutton system. Helper T cells could only be selected with syngeneic, but not allogeneic, antigen-pulsed macrophages and would then collaborate only with syngeneic, but not allogeneic, hapten-primed spleen cells. When F1 T cells were selected with antigen-pulsed parental macrophages they would only collaborate with B cells of the same parental strain as the macrophages used in the selection culture. These results are strongly in support of the view that the primed T cell is activated by carrier determinants of the nominal antigen in association with Ia antigens on macrophages and the helper T cell, in turn, activates B cells which bear the same Ia antigens and determinants of the nominal antigen bound to immunoglobulin receptors on their surface. In addition, in experiments with antigens the response to which is controlled by I-linked genes, we demonstrated that primed (responder X nonresponder)F1 T cells would only collaborate with B cells of the responder parent. The defect appeared to be at the level of the B cell in that the addition to the cultures of antigen-presenting cells of the responder type did not restore the ability of F1 T cells to collaborate with non-responder B cells.
Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor
Authors: Pierre Zoldhelyi, Janice McNatt, Harnath S. Shelat, Yasutaka Yamamoto, Zhi-Qiang Chen, James T. Willerson
Journal: Circulation (2000)

Background —Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor of factor Xa and the coagulant initiator complex tissue factor/factor VIIa. Methods and Results —To study the effects of TFPI gene transfer on thrombus formation, balloon-injured porcine carotid arteries were treated locally with an adenovirus encoding human TFPI (Ad-TFPI) or control virus. Gene transfer of TFPI was confirmed by detection of human TFPI in the conditioned medium of porcine carotid arteries kept in culture after in vivo transduction. When carotid flow was measured with Doppler probe 5 days after surgery, cyclic flow variations (CFVs) developed in 7 of 8 control pigs after constriction of the injured carotid artery by 40%, and all control-treated arteries occluded after 70% constriction. In contrast, CFVs were observed in only 1 of 8 Ad-TFPI–treated pigs after 40% constriction, and only 3 of 8 occluded after constriction by 70% ( P =0.0027 and P =0.007, respectively). None of the 5 TFPI-transduced arteries open after 70% constriction developed CFVs during an incremental epinephrine infusion. Conclusions —Compared with baseline, systemic hemostatic variables and platelet aggregation were unimpaired, suggesting that TFPI gene transfer can prevent arterial thrombosis in the presence of severe shear stress and without detectable hemostatic impairment.
Cardiovascular mortality and water quality.
Authors: G H Martin
Journal: BMJ (1980)

Our trial has shown (after 200 patients) a decrease in infarct size (approximately one- third) and a reduction in the numbers developing complete infarction in those patients given intravenous beta-blockers within 12 hours of the onset of pain.'The treated group needed less diuretics both in hospital and on discharge, suggesting clinical as well as biochemical and electrophysiological benefit.It is important, as Professor Rose points out, not to dismiss (with small trials) therapy which might reduce morbidity and perhaps mortality by, say, 20% as being clinically insignificant in this common condition.
Computerized Prescribing
Authors: Gordon D. Schiff, T. Donald Rucker
Journal: JAMA (1998)

Computerized prescribing in the practice of medicine is a change that is overdue. Virtually all prescriptions in the United States are still handwritten. Instead, medications should be ordered on a computer interacting with 3 databases: patient drug history, scientific drug information and guideline reference, and patient-specific (weight, laboratory) data. Current problems with prescribing on which computerized prescribing could have a positive impact include (1) drug selection; (2) patient role in pharmacotherapy risk-benefit decision making; (3) screening for interactions (drug-drug, drug-laboratory, drug-disease); (4) linkages between laboratory and pharmacy; (5) dosing calculations and scheduling; (6) coordination between team members, particularly concerning patient education; (7) monitoring and documenting adverse effects; and (8) postmarketing surveillance of therapy outcomes. Computerized prescribing is an important component of clinician order entry. Development of this tool has been impeded by a number of conceptual, implementation, and policy barriers. Overcoming these constraints will require clinically and professionally guided vision and leadership.
EG-02 * CORRELATION OF MGMT PROMOTER METHYLATION STATUS ANALYSIS USING 6 MS-MLPA PROBES AND CLINICAL RESPONSE OF TEMOZOLOMIDE IN GLIOBLASTOMA PATIENTS
Authors: M. Fakkert, W. de Leng, R. de Weger, S. Willems, W. Spliet, W. van Hecke, F. de Vos
Journal: Neuro-Oncology (2014)

INTRODUCTION: For patients diagnosed with Glioblastoma Multiforme (GBM) O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is an important predictive factor for treatment with temozolomide (TMZ). MGMT reverses the toxic effect of alkylating chemotherapies like TMZ, therefore absence of the MGMT protein, due to promoter hypermethylation, results in greater tumor response and prolonged survival. MGMT methylation status can be determined using Methylation Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA). Previous research has documented the predictive value of MGMT MS-MLPA probe mix ME011-A1 containing 3 MGMT probes, but no documentation is available for the current commercially available MS-MLPA probe mix ME011-B containing 6 MGMT probes. The aim of this study is to determine the predictive value of MGMT promoter methylation status for GBM patients using the ME011-B probe mix. METHODS: Patients were included if diagnosed with GBM and treated with TMZ. Retrospectively 102 patients were evaluated for MGMT promoter methylation using the MS-MLPA probe mix ME011-B. Methylation status was compared to clinical outcome to determine the predictive value of MS-MLPA promoter methylation status determined by ME011-B probes. Comparison of methylation status with clinical response was also used to determine which combination of probes provides the best prediction of the response to TMZ. RESULTS: Preliminary MS-MLPA results of 79 patients indicate that the number of patients with promoter hypermethylation in tumors ranges from 15%-67% depending on the probe using a cut-off value of >25%. However, when eliminating the lowest and highest probe and calculating the mean, 65% of the tumors show hypermethylation. CONCLUSION: MGMT promoter methylation status was determined using MS-MLPA probe mix ME011-B, results indicate that over half of the patients diagnosed with GBM might benefit from TMZ therapy. Obtaining clinical response of patients and further analysis is necessary to determine the predictive value of MGMT promoter methylation status determined by MS-MLPA ME011-B probes.
Is there any vindication for low dose nonselective β-blocker medication in patients with liver cirrhosis?
Authors: Tae Wan Kim, Hong Joo Kim, Chang Uk Chon, Hyun Sun Won, Jung Ho Park, Dong Il Park, Yong Kyun Cho, Chong Il Sohn, Woo Kyu Jeon, Byung Ik Kim
Journal: Clinical and Molecular Hepatology (2012)

Background/Aims Nonselective Î²-blockers (NSBBs), such as propranolol, reportedly exert a pleiotropic effect in liver cirrhosis. A previous report suggested that survival was higher in patients receiving adjusted doses of NSBBs than in ligation patients. This study investigated whether low-dose NSBB medication has beneficial effects in patients with liver cirrhosis, especially in terms of overall survival. Methods We retrospectively studied 273 cirrhotic patients (199 males; age 53.6Â±10.2 years, meanÂ±SD) who visited our institution between March 2003 and December 2007; follow-up data were collected until June 2011. Among them, 138 patients were given a low-dose NSBB (BB group: propranolol, 20-60 mg/day), and the remaining 135 patients were not given an NSBB (NBB group). Both groups were stratified randomly according to Child-Turcotte-Pugh (CTP) classification and age. Results The causes of liver cirrhosis were alcohol (n=109, 39.9%), hepatitis B virus (n=125, 45.8%), hepatitis C virus (n=20, 7.3%), and cryptogenic (n=19, 7.0%). The CTP classes were distributed as follows: A, n=116, 42.5%; B, n=126, 46.2%; and C, n=31, 11.4%. Neither the overall survival (P=0.133) nor the hepatocellular carcinoma (HCC)-free survival (P=0.910) differed significantly between the BB and NBB groups [probability of overall survival at 4 years: 75.1% (95% CI=67.7-82.5%) and 81.2% (95% CI=74.4-88.0%), respectively; P=0.236]. In addition, the delta CTP score did not differ significantly between the two groups. Conclusions Use of low-dose NSBB medication in patients with liver cirrhosis is not indicated in terms of overall and HCC-free survival. Keywords: Nonselective Î²-blockers; Liver cirrhosis; Overall survival; Child-Turcotte-Pugh