tbuckley/cabot-search huggingface dataset:
Effect of Cyclophosphamide upon the Immune Response in Wegener's Granulomatosis
Authors: Anthony S. Fauci, Sheldon M. Wolff, John S. Johnson
Journal: New England Journal of Medicine (1971)

Abstract Nine patients with Wegener's granulomatosis were studied before and after treatment with cyclophosphamide alone. The study was undertaken to determine any immunologic abnormalities associated with the disease, to observe the effect of cyclophosphamide on the clinical course, as well as on the immune response in man, and to observe any correlation between clinical response and immunosuppression. Untreated patients had elevated mean serum IgA levels of 470 as compared with 200 mg per 100 ml in normal controls and elevated mean parotid-fluid secretory IgA levels of 4.7 as compared with 1.8 mg per 100 ml in normal controls. Seven of nine patients receiving cyclophosphamide had undetectable humoral and delayed hypersensitivity responses to a new antigenic stimulus, and five of the seven retained previously established delayed hypersensitivity. A favorable clinical response to cyclophosphamide and immunosuppression appeared to be correlated.
Isoproterenol infusion causes ST-segment elevation without increased magnitude of the solid angle in post myocardial infarction
Authors: Toshio Miyazaki, Keizo Yamashita, Tadahiko Yamamoto, Tatsu Inoki, Yoshihide Sakaguchi, Yutaka Hirano, Toshiyuki Shibutani, Kinji Ishikawa, Ryo Katori
Journal: Journal of the American College of Cardiology (1991)
Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine.
Authors: D D Kerrigan, Y F Mangnall, N W Read, A G Johnson
Journal: Gut (1991)

The commonly accepted model for gastric emptying suggests that the 9antral mill9 is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid-pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach.
Abstract 1192: Regulation of CCND2, HMGA2, and the IGF pathway by LIN28B in HPV negative head and neck squamous cell carcinoma (HNSCC)
Authors: Nehad M. Alajez, Dennis Wong, Wei Shi, Michelle Lenarduzzi, Fei-Fei Liu
Journal: Cancer Research (2011)

Abstract Background: Lin28 and Lin28B have recently been implicated in the post-transcriptional regulation of Let-7/miR-98 biogenesis. While Lin28B over-expression has been associated with worse clinical outcome in several human cancers, the prognostic significance of Lin28B expression and the molecular mechanism(s) by which it drives tumour progression remains largely unknown. Methods: Let-7-Resist Lin28B-expression plasmid was stably transfected into the FaDu human hypopharyngeal squamous cell carcinoma line. MicoRNA expression profiling was conducted using the Nanostring nCounter Analysis System. Genome-wide micro-array and in silico analyses were utilized to identify Let-7/miR-98 targets. Cell viability and apoptosis were measured using MTS assay and flow cytometry, respectively. In vivo experiments were conducted using SCID mice. Results: qRT-PCR analysis of genes involved in the miRNA biogenesis pathway (DICER, LIN28, LIN28B, and TUT4) suggested an inverse relationship between the expression of Lin28B and mature Let-7 miRNA. Over-expression of Lin28B mediated significant increase in the migration of FaDu cells in vitro, and tumor growth in SCID mice, which in turn, was associated with marked reduction in the Let-7 family of microRNAs. Using a tri-Pronged approach by combining prediction algorithms, experimentally-derived mRNA profiling, along with gene expression data in primary HNSCC samples identified several upregulated Let-7/miR98 gene targets in Lin28B-FaDu cells, including CCND2, HMGA2, and regulators of the insulin growth factor (IGF) mitogenic pathway. Concordantly, treating FaDu-Lin28B cells with IGF (10-50 nM) led to a 26% and 50% increase in cell viability under stress conditions (serum starvation), whereas treating FaDu-GFP cells with IGF had no effect on viability, suggesting the relevance of the IGF axis in FaDu-Lin28B cells. Furthermore, analyzing publicly available data sets on primary HPV positive vs. HPV negative HNSCC samples revealed a significantly higher expression of HMGA2, and genes that regulate the IGF pathway in the latter group of tumours, suggesting a possible role for Lin28B, Let-7/miR-98 and their downstream targets in mediating the more aggressive behavior of HPV negative HNSCC. Conclusions: Our data report for the first time, a potentially important role for Lin28B in regulating the IGF mitogenic pathway, as one possible mechanism in driving the biological behaviour of HPV negative HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1192. doi:10.1158/1538-7445.AM2011-1192
"One Dr. Eastman."
Authors: Joseph Rilus Eastman
Journal: JAMA (1898)

Indianapolis, Ind., Jan. 6, 1898. <h3>To the Editor:</h3> —In the issue of theJournalfor December 25, Dr. M. Price of Philadelphia, discussing extra-uterine pregnancy, observes: "My case at term, reported some five years ago, was in the tenth month of gestation and in the amniotic sac. The mother and child are today both living and well, the child a beautiful little girl. This case is reported in "Greig Smith's system of Abdominal Surgery' as operated by one Dr. Eastman. No one of the name is known to belong to the profession of Philadelphia. This goes to illustrate the worthless character of the statistics of even eminent authority. This case is stated by Smith to be the only one in America where mother and child both lived." At the onset we will disclaim any intention to champion the accuracy of Greig Smith's statistics, since indeed a typographic error in the
Quantitative hepatitis C virus RNA and liver histology in chronic hepatitis C patients treated with interferon alfa.
Authors: G Yamada, M Takahashi, H Endo, T Doi, R Miyamoto, H Shimomura, K Yamamoto, T Tsuji
Journal: Gut (1993)

Seventy patients with hepatitis C virus (HCV) infection received alpha interferon at doses ranging from 3 to 10 million units (MU) daily for eight weeks, three times weekly for 12-24 weeks, or daily and three times weekly for 12-24 weeks. The efficacy of interferon was closely related to the initial blood HCV-RNA values in that these were lower in those who responded completely and partially compared with non-responders. Continuous reductions in HCV-RNA and improvements in the histology activity index score were seen in those who responded completely. In contrast, most of the partial and non-responders remained HCV-RNA positive.
Navigating to Knowledge&lt;subtitle&gt;Tools for Finding Information on the Internet&lt;/subtitle&gt;
Authors: Richard Peters
Journal: JAMA (1997)

A physician sees a patient with newly diagnosed HIV infection who has just moved to town. The next day, the patient calls the physician's office to ask about a television news report concerning the use of protease inhibitors in early-stage HIV disease. The physician was unaware of the report and realizes that she is not as up-to-date as she would like to be about the latest recommendations for treatment of HIV disease. The physician also wants to discuss the patient's case with his previous primary care physician, but the patient had seen that clinician for only a short time before moving and does not have the telephone number or address at hand.
Landry-Guillain-Barrù Syndrome after Chicken Pox
Authors: S. M. Rab, G. M. Choudhury
Journal: New England Journal of Medicine (1963)

CHICKEN pox is usually a benign disease of children with virtually few, if any, complications. Bullowa and Wishik,1 in an analysis of 2534 hospitalized patients with this disease, found an incidence of 5 per cent complicated cases; in these nervoussystem complications were very rare, occurring in 5 cases. Rotem,2 reporting over a ten-year period from a hospital that admits patients from a population of 1,000,000, could collect only 12 complicated cases. Of these only 5 were neurologic.The purpose of this communication is to report an unusual neurologic complication of varicella that is perhaps the rarest recorded so far.Case . . .
Points from Letters: Looking after Schizophrenics
Authors: N. Hutchens
Journal: BMJ (1974)

some extent those retiring between 1969 and 1972 will be given less than their olleagues who retired after 24 March 1972.This means that there has to be for them a different formula from that for general practitioners retiring after 24 March 1972 and it is on this that there have been some-what protracted negotiations with the De- partment.We have certainly put every pressure on the Department to expedite matters and we hope that with the help of our professional expert advisers we -may be able to reach an early settlement."-ED.,
Abstract B19: Tumor-specific structural rearrangements as potential targets for anticancer vaccines.
Authors: Spencer David Martin, Darin A. Wick, John R. Webb, Robert A. Holt, Brad H. Nelson
Journal: Cancer Research (2013)

Abstract A hallmark of cancer is the accumulation of mutations that allow cells to proliferate uncontrollably. Every tumor has a unique set of somatic mutations, which can be identified with next generation sequencing. In theory, CD8+ T cells can recognize mutated proteins present in human cancers if the mutations are presented as peptides bound to MHC class I molecules. We hypothesize that personalized, tumor-specific peptide vaccines will activate CD8+ T cells and induce tumor regression. To test this concept, we subjected four mouse mammary tumors to RNA sequencing using the Illumina sequencing platform. We identified 14 somatic point mutations and one fusion transcript unique to these tumors. In addition, we have optimized a vaccination strategy involving long peptides and the adjuvant poly (I:C) that results in massive proliferation of antigen-specific CD8+ T cells. When we used this optimized vaccination protocol to target tumor specific mutations, a strong T cell response was elicited towards the fusion protein, but only weak responses or no responses were elicited towards the point mutations. Currently, we are vaccinating mice with immunogenic mutated-peptides, and assessing whether the T cell response elicited by the vaccines causes regression or rejection of established tumors that harbor the same mutations. As the cost of sequencing the human genome continues to decrease, personalized vaccines that target tumor-specific mutations may become a treatment strategy that is clinically feasible. Citation Format: Spencer David Martin, Darin A. Wick, John R. Webb, Robert A. Holt, Brad H. Nelson. Tumor-specific structural rearrangements as potential targets for anticancer vaccines. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B19.
Bid Agonist Regulates Murine Hepatocyte Proliferation by Controlling Endoplasmic Reticulum Calcium Homeostasis
Authors: Hong-Min Ni, Catherine J. Baty, Na Li, Wen-Xing Ding, Wentao Gao, Min Li, Xiaoyun Chen, Jianjie Ma, George K. Michalopoulos, Xiao-Ming Yin
Journal: Hepatology (2010)

BH3-interacting domain death agonist (Bid), a BH3-only B cell lymphoma 2 family molecule, is generally known for its importance in activating the mitochondrial apoptosis pathway after death receptor engagement, particularly in hepatocytes. However, Bid also promotes hepatocyte proliferation during liver regeneration and carcinogenesis. This study was designed to examine the hypothesis that Bid regulates endoplasmic reticulum calcium concentration ([Ca2+]ER) homeostasis to affect hepatocyte proliferation. We found that serum-stimulated hepatocyte proliferation was dependent on calcium, and the depletion of calcium with thapsigargin or ethylene glycol tetraacetic acid (EGTA) inhibited the proliferation. Subcellular fractionation showed that a portion of Bid was inserted into the endoplasmic reticulum (ER)–enriched membranes, and single-cell calcium imaging indicated that Bid was important for maintaining the [Ca2+]ER level. Bid-deficient hepatocytes manifested delayed and reduced serum-stimulated proliferation, which was corrected by ionomycin or reconstitution of Bid, particularly an ER-targeted Bid. Finally, B cell lymphoma 2–associated X protein (Bax) could also be found in the ER-enriched membranes, and Bax deficiency caused the same proliferation defect. However, Bid/Bax double deletion in hepatocytes did not further augment the defect, which suggested that Bid and Bax worked by the same regulatory mechanism in [Ca2+]ER control. Conclusion: Bid regulates hepatocyte proliferation by positively affecting [Ca2+]ER homeostasis, and this could be important for liver regeneration and carcinogenesis. (Hepatology 2010)
Assessment of Myocardial Viability With <sup>99m</sup> Tc-Sestamibi Tomography Before Coronary Bypass Graft Surgery
Authors: Habib Abbas Dakik, Jimmy F. Howell, Gerald M. Lawrie, Rafael Espada, Donald G. Weilbaecher, Zuo-Xiang He, John J. Mahmarian, Mario S. Verani
Journal: Circulation (1997)

Assessment of myocardial viability by 99mTc-sestamibi remains controversial. Accordingly, we investigated the use of sestamibi as a marker of myocardial viability, defined by histopathology, and for predicting improvement of myocardial function after coronary artery bypass graft surgery (CABG).99mTc-sestamibi perfusion tomography and radionuclide angiography were performed within 2 days before CABG in 21 patients with > or = 75% stenosis of the left anterior descending coronary artery and resting anterior wall dyssynergy. During CABG, transmural myocardial biopsies were obtained from the dyssynergic anterior wall and from normal myocardial segments to determine the extent of viable myocardium by histopathology. Improvement of regional left ventricular function was evaluated by radionuclide angiography at 6 to 8 weeks after CABG. There was a good correlation (r=.85, P<.001) between the quantified sestamibi activity and the extent of viable myocardium determined morphometrically. Among 21 biopsied dyssynergic myocardial segments, 11 improved their function after CABG and 10 failed to improve. Biopsied segments with improved postoperative function had significantly higher sestamibi activity (81+/-5% versus 49+/-16%, P<.0001) and significantly lower extent of interstitial fibrosis (7+/-4% versus 31+/-21%, P=.0002) than segments that failed to improve. A 55% threshold of 99mTc-sestamibi activity had positive and negative predictive values of 79% and 100%, respectively, for recovery of function after CABG in the biopsied segments.Myocardial 99mTc-sestamibi activity correlates well with the extent of viable myocardium and predicts improvement in regional function after CABG. This lends support to the use of sestamibi as a myocardial viability agent.
Estrogen regulation of p53 isoforms in the human breast cancer cell line MCF7.
Authors: JA Vendrell, J Bourdon, PA Cohen, AM Thompson
Journal: Cancer Research (2009)

Abstract Abstract #4067 Background: p53, a transcription factor activated in response to different cellular stresses, is involved in the majority of cancers. Recently, we have shown that the p53 gene, due to alternative splicing, encodes for 9 different p53 proteins (isoforms) expressed in a tissue-dependent manner. Moreover, p53 isoforms bind preferentially some p53 target gene promoters, increasing the complexity of the p53 pathway. Preliminary results indicate that p53 isoforms are differentially expressed in breast tumours and are associated with survival.&amp;#x2028; Methods and Results: As some p53 isoform expression is also associated with ERa status in breast cancer, we aimed to investigate the effect of 17b-estradiol (E2) on the expression of p53 isoforms in MCF7 cells. We observed that E2 regulated the expression of the p53b isoforms at the protein level but not at the mRNA level. To investigate whether E2 confers resistance to genotoxic stress, we treated cells with doxorubicin, a commonly used chemotherapeutic agent. E2 sensitises MCF7 cells to doxorubicin treatment after a long exposure (3 days). However, we observed that E2 protects MCF7 cells from cell death following short exposure (1 hour) to doxorubicin in a p53-dependent manner. p53 isoforms are differentially expressed after 1h or 3 days treatment with doxorubicin, suggesting their involvement in the response to doxorubicin. These data are consistent with our findings in primary breast cancer, linking p53 isoforms to prognosis.&amp;#x2028; Conclusion: Our data demonstrated that E2 may influence p53 isoforms and response to doxorubicin in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4067.
Mechanism of Mitral Regurgitation in Hypertrophic Cardiomyopathy
Authors: Ehud Schwammenthal, Satoshi Nakatani, Shengqiu He, Joanne Hopmeyer, Alex Sagie, Arthur E. Weyman, Harry M. Lever, Ajit P. Yoganathan, James D. Thomas, Robert A. Levine
Journal: Circulation (1998)

Background —In hypertrophic cardiomyopathy, a spectrum of mitral leaflet abnormalities has been related to the mechanism of mitral systolic anterior motion (SAM), which causes both subaortic obstruction and mitral regurgitation. In the individual patient, SAM and regurgitation vary in parallel; clinically, however, great interindividual differences in mitral regurgitation can occur for comparable degrees of SAM. We hypothesized that these differences relate to variations in posterior leaflet length and mobility, restricting its ability to follow the anterior leaflet (participate in SAM) and coapt effectively. Methods and Results —Different mitral geometries produced surgically in porcine valves were studied in vitro. Comparable degrees of SAM resulted in more severe mitral regurgitation for geometries characterized by limited posterior leaflet excursion. Mitral geometry was also analyzed in 23 patients with hypertrophic cardiomyopathy by intraoperative transesophageal echocardiography. All had typical anterior leaflet SAM with significant outflow tract gradients but considerably more variable mitral regurgitation; therefore, regurgitation did not correlate with obstruction. In contrast, mitral regurgitation correlated inversely with the length over which the leaflets coapted ( r =−0.89), the most severe regurgitation occurring with a visible gap. Regurgitation increased with increasing mismatch of anterior to posterior leaflet length ( r =0.77) and decreasing posterior leaflet mobility ( r =−0.79). Conclusions —SAM produces greater mitral regurgitation if the posterior leaflet is limited in its ability to move anteriorly, participate in SAM, and coapt effectively. This can explain interindividual differences in regurgitation for comparable degrees of SAM. Thus, the spectrum of leaflet length and mobility that affects subaortic obstruction also influences mitral regurgitation in patients with SAM.
Reinforcing Doses of Diphtheria Toxoid Absorbed Through the Buccal Mucosa
Authors: W. Chas. Cockburn, C. M. P. Bradstreet, M. E. Bailey, J. Ungar
Journal: BMJ (1961)

A case of false aneurysm originating from the ascending aortic cannulation site in the absence of mediastinal infection is described. Surgical treatment was carried out by means of limited cardiopulmonary bypass and hypothermic circulatory arrest, but the patient died early in the postoperative period. The technical failures responsible for the unsuccessful outcome are emphasized.
Prospective Evaluation of Pregnancy-Associated Plasma Protein-A and Outcomes in Patients With Acute Coronary Syndromes
Authors: Marc P. Bonaca, Benjamin M. Scirica, Marc S. Sabatine, Petr Jarolim, Sabina A. Murphy, Janna S. Chamberlin, Daniel W. Rhodes, Paula C. Southwick, Eugene Braunwald, David A. Morrow
Journal: Journal of the American College of Cardiology (2012)
Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial
Authors: Albert Parés, Ramón Planas, Miguel Torres, Joan Caballería, Josep M. Viver, Doroteo Acero, Juliá Panés, Joaquim Rigau, Justiniano Santos, Joan Rodés
Journal: Journal of Hepatology (1998)
Quantitative Assessment of the Spatial Organization of Atrial Fibrillation in the Intact Human Heart
Authors: Gregory W. Botteron, Joseph M. Smith
Journal: Circulation (1996)

Atrial activation during atrial fibrillation (AF) is frequently described as random or chaotic. We propose that activation during AF is constrained by the principles of reentrant excitation; that these constraints impart a measurable spatial organization to activation during AF; and that the distance over which activation sequences remain well correlated can be readily measured and related both to the propensity of AF to sustain itself as well as to atrial tissue wavelength.We describe a novel signal-processing technique that quantifies the correlation in activation sequences recorded from five equally spaced sites in the right atrium in patients undergoing electrophysiology studies. In 20 patients in AF (12 with paroxysmal AF, 5 with chronic AF, and 3 with no clinical history of AF), the average correlation was 0.54 +/- 0.12 at 11 mm and 0.32 +/- 0.11 at 44 mm, compared with 0.95 +/- .023 and 0.91 +/- .023 in sinus rhythm. In AF, the correlation versus distance relation was monotonically decreasing, well fit by a decaying exponential function. The space constant of this exponential function, termed the activation space constant, provides a single objective metric of the spatial organization of activation during AF. The mean activation space constant for the group was 2.6 +/- 1.15 cm. Chronic AF had the lowest mean activation space constant (1.84 +/- 0.36 cm) and AF in patients with no prior history of AF had the highest (3.06 +/- 0.40 cm) (P < .05), with paroxysmal AF characterized by intermediate values (2.80 +/- 1.4 cm).Using a novel method to measure the spatial organization of atrial activation during AF, we have demonstrated that AF in the intact human heart is organized over a length scale consistent with reentrant excitation. Preliminary results suggest a relationship between measured spatial organization and the clinical course of the arrhythmia. Further work is needed to determine whether measurement of spatial organization may be useful in prospective patient-specific selection of therapeutic options.