tbuckley/cabot-search huggingface dataset:
Gender differences in cytokine immune response profiles and wheezing phenotypes during the first three years of life
Authors: S.J. Uekert, G. Akan, M. Evans, Z. Li, K. Roberg, C. Tisler, D. DaSilva, E. Anderson, R. Gangnon, J. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2005)
Abstract 5575: Mass spectrometry analysis of the posttranslational modifications of alpha-enolase from pancreatic ductal adenocarcinoma cells
Authors: Weidong Zhou, Michela Capello, Claudia Fredolini, Francesco Novelli, Lance A. Liotta, Emanuel F. Petricoin
Journal: Cancer Research (2010)

Abstract Enolase is one of the most abundantly expressed cytosolic proteins in many organisms, and it is a key glycolytic enzyme that catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate. Recently, accumulating evidence revealed that, in addition to its innate glycolytic function, the well characterized old enzyme enolase is a multifunctional protein and plays an important role in several biological and pathophysiological processes: 1) by using an alternative start codon, the α-enolase mRNA can be translated into a 37 kDa protein which lacks the first 96 amino acid residues. This protein is localized in the nucleus and can bind to the c-myc P2 promoter and negatively regulate transcription of the proto-oncogene; 2) α-enolase has been detected on the surface of hematopoietic cells such as monocytes, T cells and B cells, neuronal cells and endothelial cells as a strong plasminogen-binding receptor, modulating the pericellular and intravascular fibrinolytic system. The expression of α-enolase on the surface of a variety of eukaryotic cells has been found to be dependent on the pathophysiological conditions of these cells, however, how α-enolase is displayed on the cell surface remains unknown; 3) increased expression of enolase has been reported to correlated with progression of tumors, such as neuroendocrine tumors, neuroblastoma and lung cancers, and enolase has been considered to be a diagnostic marker for many tumors. Our previous studies demonstrated that α-enolase is up-regulated at both the mRNA and protein levels in pancreatic ductal adenocarcinoma (PDAC). PDAC is the fourth leading cause of cancer-related deaths in Western countries. The mean life expectancy is 15-18 months for patients with local and regional disease, and only 3-6 months for those with metastatic disease. In this present work, we further characterized the α-enolase from PDAC by reversed-phase liquid chromatography nanospray tandem mass spectrometry (LC-MS/MS) analysis and an LTQ-Orbitrap instrument, and identified multiple posttranslational modifications of α-enolase, such as phosphorylation, acetylation, and methylation. The mass spectrometer LTQ-Orbitrap provides high accuracy mass measurement that is essential for the validation of modified peptide identifications and the reduction of false positive identifications. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5575.
New criteria for the laboratory diagnosis of nondermatophyte moulds in onychomycosis
Authors: A. Shemer, B. Davidovici, M.H. Grunwald, H. Trau, B. Amichai
Journal: British Journal of Dermatology (2008)

Background Nondermatophyte moulds (NDM) may be found as aetiological agents or as contaminants in onychomycosis. The classic and most used criteria for the diagnosis of NDM are those established by English in 1976. Objectives The aim of this article is to re-evaluate the laboratory criteria for the diagnosis of NDM in onychomycosis. Patients and methods Patients with suspected NDM of the nail underwent five consecutive examinations by both KOH and mycological culture; at the first visit, three samples from the affected nail were taken and were examined separately. Later those patients underwent four consecutive examinations; during this stage only a single sample for both KOH and culture was taken. We compared the culture results obtained from the three nail samples obtained at the first visit with the results from the four consecutive visits. Results We noted a clear trend showing that as the number of positive cultures increases (one to three cultures) during the first examination, the percentage of subsequent positive cultures, taken during the four consecutive visits, also increased. Conclusions We suggest that when NDM infection is found in the first culture, the patient should be re-examined in a subsequent visit in which three separate samples are taken from the affected nail. If NDM is confirmed in all three cultures, the diagnosis of NDM is established. Treatment should be recommended in patients who show positive results in all three cultures.
TCT-205 Mid-term angiographic and clinical outcomes of controlled antegrade and retrograde subintimal tracking (CART) or reverse CART technique for the recanalization of chronic total occlusions
Authors: Akiko Fujino, Satoru Otsuji, Katsuyuki Hasegawa, Shin Takiuchi, Katsuaki Asano, Munemitsu Ibuki, Shinya Nagayama, Kasumi Ishibuchi, Toshikazu Kashiyama, Daisuke Shishikura, Rui Ishii, Masanori Yabuki, Yorihiko Higashino
Journal: Journal of the American College of Cardiology (2014)
Treves and the Royal Star and Garter Home
Authors: John R Silver
Journal: Journal of the Royal Society of Medicine (2011)

In Ramachandran and Aronson's interesting account of Treves' role in the operation for appendicitis, and his role in the description of the Elephant Man in the May issue of the JRSM,1 they omit what was probably Treves' contribution with the most significance today.

Treves' vision was responsible for founding, funding and obtaining royal patronage for the Star and Garter Home in 1915. This Home was set up during World War I to meet the needs of servicemen suffering as a result of amputations and paralysis, and for whom there was no room or role in the established military hospitals. These servicemen were treated at the Royal Star and Garter Home and rehabilitated there. Its contribution was so outstanding that further units were established and to this day, servicemen are continuing to benefit from treatment there.2

It is the only surviving spinal unit from World War I. It has endured till the present day and it is there that competitive sport originated, leading to the founding of the paralympic movement. This enduring contribution, for which countless servicemen are grateful, should be acknowledged.3,4
Patient participation cannot guarantee empowerment
Authors: S. S. Lamont
Journal: BMJ (1999)

EDITOR—Much has been written about the importance of participation in community health projects and the benefits of participatory processes for patients and the local population generally. Becoming an equal partner in the decisions that affect the health of individual people and communities is the ideal constantly trumpeted by many professionals in health and social care, as well as being raised in the eBMJ .1 But how …
A mystery unfolds: Franz-Ulrich Hartl and Arthur L. Horwich win the 2011 Albert Lasker Basic Medical Research Award
Authors: Kathryn Claiborn
Journal: Journal of Clinical Investigation (2011)

Whether enzymatic or structural, the three-dimensional shape into which a protein folds is a critical determinant of all aspects of its function. Proteins fold from an initial chain of amino acids into complex helices and beta-pleated sheets based on intramolecular interactions that favor exposed hydrophilic residues and buried greasy hydrophobic side chains. The 2011 Albert Lasker Basic Medical Research Award recognizes the work of two scientists, Franz-Ulrich Hartl (Max Planck Institute of Biochemistry) and Arthur L. Horwich (Yale University) (Figure ​(Figure1),1), whose collaborative and independent work led to a new understanding of how cells can control this complex process. Their findings not only reveal secrets of basic protein chemistry, but could also have a dramatic impact on the treatment of the many diseases in which protein folding goes awry. 



Figure 1

Franz-Ulrich Hartl (left) and Arthur Horwich (right) are the recipients of the 2011 Albert Lasker Basic Medical Research Award.



Insight into the mystery of how protein folding occurs was in part revealed in the early 1960s, when Christian Anfinsen, working at the NIH, demonstrated that a denatured protein called ribonuclease could spontaneously refold in a test tube. In doing so, he showed that the amino acid sequence of a protein provided the necessary information to allow it to fold properly, dictating its three-dimensional shape and thus its activity (1–3). Following the establishment of this “Anfinsen dogma,” most biologists assumed that all proteins folded spontaneously as they were synthesized on the ribosome. As Hartl recalled in a recent interview with the JCI, “For many years, cell biologists just were not interested in protein folding; it was the domain of biophysicists and biochemists who studied the spontaneous reactions in the test tube.”
Genetic Relatedness of Lymphoid Malignancies: Transformation of Chronic Lymphocytic Leukemia as a Model
Authors: Kenneth A. Foon
Journal: Annals of Internal Medicine (1993)

Objective: Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer. Data Analysis: Analysis of genetic relatedness between the two cancers considered concordance for immunoglobulin gene rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic abnormalities. Conclusions: In the case of large B-cell lymphoma, generally thought to arise from the chronic lymphocytic leukemia clone, approximately one half of the patients had genetically unrelated cancers. In prolymphocytic transformation, all cases studied appeared to evolve from the chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic leukemia and multiple myeloma showed genetic relatedness in some cases and unrelatedness in others. These data indicate that progression to more aggressive B-cell cancers in persons with chronic lymphocytic leukemia can result from either clonal evolution or from an independent transforming event.
The plasma ammonia response to cycle exercise in COPD
Authors: L. D. Calvert, S. J. Singh, P. L. Greenhaff, M. D. Morgan, M. C. Steiner
Journal: European Respiratory Journal (2007)

The plasma ammonia response to exercise in chronic obstructive pulmonary disease (COPD) was examined and the relationship between plasma ammonia concentration and muscle adenine nucleotide metabolism was explored. In total, 25 stable COPD patients and 13 similar-aged controls underwent incremental and constant-work rate cycle exercise tests. Arterialised venous blood was sampled at rest, at 1-min intervals during exercise and ≤5 min after exercise for ammonia and lactate concentration. Peak incremental work rate was significantly less in COPD subjects (67±21 W) than similar-aged controls (156±46 W). In COPD and control subjects, plasma ammonia concentration increased during incremental exercise until 2 min post-exercise and then declined by 5 min post-exercise. However, two distinct patterns were seen in COPD subjects. In one group (n = 16), ammonia increased (42.8±3.3 μmol·L −1 ) by a similar magnitude as the controls (55.5±7.0 μmol·L −1 ). In the second COPD group (n = 9), no ammonia increase was observed despite a similar lactate increase. Ammonia change with incremental and constant-work rate exercise strongly correlated in COPD subjects. Plasma ammonia increase correlated with muscle inosine-5′–monophosphate formation after constant-work rate exercise. Plasma ammonia concentration increases during incremental and constant-work rate cycle exercise in chronic obstructive pulmonary disease subjects at lower absolute work rates compared with similar-aged controls. The plasma ammonia response may provide useful information about adenine nucleotide metabolism and, therefore, muscle fatigue during exercise in patients with chronic obstructive pulmonary disease.
SYNERGISM OF MAGNESIUM SULPHATE AND MORPHIN
Authors: Harry Beckman
Journal: JAMA (1925)

<h3>To the Editor:</h3> —InThe Journal, November 7, appeared an article by Dr. Gwathmey which he describes as a reply to my work on the alleged synergism of magnesium sulphate and morphin. There are three tables. Table 1 furnishes data of a case in which the patient experienced greater relief from pain when given morphin plus magnesium sulphate than when given morphin alone. This mere fact does not, however, constitute proof that simple addition did not bring about this result; indeed, the second longest period of relief was experienced in one of the two instances only in which magnesium sulphate alone was used. Tables 2 and 3 comprise lists of cases in which the time before postoperative sedative was shown to be longer when morphin plus magnesium sulphate was used preoperatively than when morphin was used alone. Here again there is no evidence of synergism. Both experimental and clinical literature
Safety assessment of probiotics for human use
Authors: Mary Ellen Sanders, Louis M.A. Akkermans, Dirk Haller, Cathy Hammerman, James T. Heimbach, Gabriele Hörmannsperger, Geert Huys
Journal: Gut Microbes (2010)

The safety of probiotics is tied to their intended use, which includes consideration of potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are alive when administered, and unlike other food or drug ingredients, possess the potential for infectivity or in situ toxin production. Since numerous types of microbes are used as probiotics, safety is also intricately tied to the nature of the specific microbe being used. The presence of transferable antibiotic resistance genes, which comprises a theoretical risk of transfer to a less innocuous member of the gut microbial community, must also be considered. Genetic stability of the probiotic over time, deleterious metabolic activities, and the potential for pathogenicity or toxicogenicity must be assessed depending on the characteristics of the genus and species of the microbe being used. Immunological effects must be considered, especially in certain vulnerable populations, including infants with undeveloped immune function. A few reports about negative probiotic effects have surfaced, the significance of which would be better understood with more complete understanding of the mechanisms of probiotic interaction with the host and colonizing microbes. Use of readily available and low cost genomic sequencing technologies to assure the absence of genes of concern is advisable for candidate probiotic strains. The field of probiotic safety is characterized by the scarcity of studies specifically designed to assess safety on the one hand contrasted with the long history of safe use of many of these microbes in foods on the other hand.
Growth Factor Regulation of a 26S Proteasomal Subunit in Breast Cancer
Authors: Christopher J. Barnes, Feng Li, Amjad H. Talukder, Rakesh Kumar
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We sought to gain insight into the mechanisms of heregulin-β1 (HRG) action on breast epithelial cells by identifying and characterizing HRG-regulated proteins. Experimental Design: Differential display mRNA screening of human breast cancer cells grown in the presence or absence of HRG was used to identify HRG-regulated genes. Biochemical and functional studies were undertaken to examine the impact of HRG and the therapeutic antibody herceptin on protein expression, localization, and function. Results: We identified the ATPase subunit 4 (S4) of the 26S proteasome as a HRG-regulated target. Both S4 mRNA and protein levels were increased by HRG; however, this HRG-stimulated increase was blocked by the therapeutic antibody herceptin. S4 expression was significantly increased in primary human breast tumors and in estrogen receptor–negative tumors. Coimmunoprecipitation, immunofluorescence, and ATPase activity assays suggested that HRG also induced S4 activity and formation of a functional proteasome complex. Conclusions: This is the first demonstration of growth factor–regulated expression, localization, and activity of the S4 subunit of the 26S proteasome in human breast cancer cells. These findings now provide a potential mechanistic rationale for the use of proteasome inhibitors in breast cancers with active HRG signaling.
Private Practice after Resignation
Authors: N. Hypher
Journal: BMJ (1965)

MBITISHALaction.This decision by a mere 25-strong residents' mess at an 1,100-bed hospital he might consider insignificant, but I have failed to find yet in working in several large hospi- tals a junior hospital doctor who does not consider he is exploited to a greater or less extent.-Iam, etc.,
Mechanisms Producing Color Change in Flat Early Gastric Cancers
Authors: U. Honmyo, A. Misumi, A. Murakami, S. Mizumoto, I. Yoshinaka, M. Maeda, S. Yamamoto, S. Shimada
Journal: Endoscopy (1997)

Although highly refined endoscopes have made it possible to detect not only early gastric cancers with morphological changes, but also flat-type tumors (type IIb) on the basis of the color changes observed in them, the factors responsible for color changes in type IIb carcinomas have not been fully elucidated. The aim of this study was to analyze the potential mechanisms underlying these color changes.Thirteen type IIb cancers were selected from a total of 589 resected gastric cancers detected preoperatively using endoscopic examination. All of the tumors showed color changes alone, without surface changes, and the color changes included redness, discoloration, and spotty bleeding. Detailed histological examination of the resected stomachs revealed twelve more II b lesions that had not been identified at endoscopy. The endoscopic appearance of the IIb cancers were correlated with the degree of tumor differentiation, the extent of wall infiltration, and the number of capillaries.In cases that were detectable by endoscopy, the endoscopic color appearance correlated significantly with both tumor size (P < 0.02) and with the extent of mucosal cancer infiltration (P < 0.02). Histological examination of the IIb lesions revealed that redness and discoloration were significantly more frequent in the differentiated and undifferentiated cancer types, respectively (P < 0.01). There was a significant difference in the number of capillaries between type IIb carcinoma and the adjacent normal mucosa, but not between cancers. The numbers for differences in redness and discoloration were 7.0 +/- 5.6 and -14.0 +/- 8.8, respectively.These results suggest that the main factor underlying color change in type IIb early gastric cancers may be the number of capillaries in the lesions, in comparison with the adjacent mucosa. Whether the lesion is visible on endoscopy, however, depends more on its size than on the number of capillaries.
Treatment of nodular prurigo with cyclosporin (treat the disease, not just the symptoms)
Authors: C. S. Koblenzer
Journal: British Journal of Dermatology (1996)

Journal Article Treatment of nodular prurigo with cyclosporin (treat the disease, not just the symptoms) Get access C. S. Koblenzer C. S. Koblenzer Clinical Professor of Dermatology and Dermatology‐in‐Psychiatry. University of Pennyslavania,1812 Delanecy Place, Philadelphia, PA 19103. U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue 2, 1 August 1996, Page 330, https://doi.org/10.1111/j.1365-2133.1996.tb01175.x Published: 01 August 1996
Aiming for Safe Anticoagulation
Authors: Stephan D. Fihn
Journal: New England Journal of Medicine (1995)

Since its discovery more than 50 years ago, warfarin has endured as a remarkable drug and is now the 14th-largest-selling medication in the United States. The efficacy of oral anticoagulant therapy in treating and providing prophylaxis against venous thromboembolism and in preventing arterial thromboembolism in patients with atrial fibrillation or prosthetic heart valves is generally accepted. Another indication for warfarin was recently approved by the Food and Drug Administration: the prevention of death, venous thromboembolism, and recurrent infarction after acute myocardial infarction. In relation to other widely prescribed medications, warfarin remains inexpensive (when the costs of laboratory monitoring are disregarded). . . .
Epstein–Barr Virus–Associated Lymphoma after Treatment of Macroglobulinemia with Cladribine
Authors: Ruben Niesvizky, Andrew X. Zhu, Diane Louie, Joseph Michaeli
Journal: New England Journal of Medicine (1999)

To the Editor: Purine analogues, including cladribine (2-chlorodeoxyadenosine), are increasingly used in the treatment of Waldenstrom's macroglobulinemia and other hematologic cancers.1 Cladribine ...
Mineralocorticoid Modulation of Cardiac Ryanodine Receptor Activity Is Associated With Downregulation of FK506-Binding Proteins
Authors: Ana María Gómez, Angélica Rueda, Yannis Sainte-Marie, Laetitia Pereira, Spyros Zissimopoulos, Xinsheng Zhu, Roxane Schaub, Emeline Perrier, Romain Perrier, Céline Latouche, Sylvain Richard, Marie-Christine Picot, Frederic Jaisser, F. Anthony Lai, Héctor H. Valdivia, Jean-Pierre Benitah
Journal: Circulation (2009)

The mineralocorticoid pathway is involved in cardiac arrhythmias associated with heart failure through mechanisms that are incompletely understood. Defective regulation of the cardiac ryanodine receptor (RyR) is an important cause of the initiation of arrhythmias. Here, we examined whether the aldosterone pathway might modulate RyR function.Using the whole-cell patch clamp method, we observed an increase in the occurrence of delayed afterdepolarizations during action potential recordings in isolated adult rat ventricular myocytes exposed for 48 hours to aldosterone 100 nmol/L, in freshly isolated myocytes from transgenic mice with human mineralocorticoid receptor expression in the heart, and in wild-type littermates treated with aldosterone. Sarcoplasmic reticulum Ca(2+) load and RyR expression were not altered; however, RyR activity, visualized in situ by confocal microscopy, was increased in all cells, as evidenced by an increased occurrence and redistribution to long-lasting and broader populations of spontaneous Ca(2+) sparks. These changes were associated with downregulation of FK506-binding proteins (FKBP12 and 12.6), regulatory proteins of the RyR macromolecular complex.We suggest that in addition to modulation of Ca(2+) influx, overstimulation of the cardiac mineralocorticoid pathway in the heart might be a major upstream factor for aberrant Ca(2+) release during diastole, which contributes to cardiac arrhythmia in heart failure.