tbuckley/cabot-search huggingface dataset:
Evaluation of the Combined Effect of p53 Codon 72 Polymorphism and Hotspot Mutations in Response to Anticancer Drugs
Authors: Faina Vikhanskaya, Mobin M. Siddique, Ming Kei Lee, Massimo Broggini, Kanaga Sabapathy
Journal: Clinical Cancer Research (2005)

Abstract Mutations in p53 are common events during carcinogenesis and have been suggested to affect sensitivity to chemotherapy. Recently, the common polymorphism at codon 72, resulting in either an arginine (72R) or proline (72P) residue, was shown to differentially affect the response to anticancer drugs. Here, we have generated isogenic lung cancer cell lines to evaluate the effect of six p53 hotspot mutations (R175H, G245S, R248W, R249S, R273H, and R282W) in conjunction with the codon 72 polymorphism, for their response to a variety of anticancer drugs, either alone or in combination. The data indicate that 72R mutations do not confer general resistance to cisplatin, etoposide, gemcitabine, vinblastine, and taxol. For doxorubicin, cells expressing 249-72R were more resistant than the 249-72P cells. Combined treatment with cisplatin + etoposide resulted in an additive effect in cells expressing most 72R and 72P mutations, except for the 175-72R cells which were refractory to combined treatment. However, combined treatment with cisplatin + gemcitabine resulted in the absence of an additive effect in cells expressing the 273-72R and 282-72R mutants, unlike their 72P counterparts. Nonetheless, all p53 mutants (72R or 72P) equally inhibited p73-mediated transcriptional activity in lung cancer cells, suggesting that the selective resistance conferred by some 72R mutants to certain drugs is probably due to other p73-independent effects of these mutants. Together, the data show that the status of codon 72 polymorphism and p53 mutations can be used as a means for prediction of treatment response, although variables for each cancer type requires detailed evaluation.
A comparison of the clinical efficacy and safety of intranasal fluticasone propionate and antihistamines in the treatment of rhinitis
Authors: A. Foresi
Journal: Allergy (2000)

Adequate management of allergic rhinitis is needed to avoid its considerable adverse social, clinical, and economic impact. Both topical intranasal steroids and oral or topical antihistamines are recognised as effective treatments for this condition. In comparative studies, however, intranasal steroids and, in particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded consistently better symptomatic relief, and have a greater beneficial effect on quality of life. Furthermore, the addition of an antihistamine to FPANS therapy has generally produced little further benefit. Intranasal administration is associated with a low systemic absorption of fluticasone propionate and, following regular use of FPANS, placebo, or an oral antihistamine, no significant differences were seen between treatment groups in plasma or urinary cortisol. Overall, therefore, the data indicate that FPANS is superior to second‐generation antihistamines in the management of allergic rhinitis.
Impact of Moderate Functional Mitral Insufficiency in Patients Undergoing Surgical Revascularization
Authors: Eugene A. Grossi, Gregory A. Crooke, Paul L. DiGiorgi, Charles F. Schwartz, Ulrich Jorde, Robert M. Applebaum, Greg H. Ribakove, Aubrey C. Galloway, Juan B. Grau, Stephen B. Colvin
Journal: Circulation (2006)

Background— Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG). Methods and Results— From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance ( P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expβ = 1.49; P =0.007) and mild MR (expβ = 1.34; P =0.033). Conclusions— Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.
Abstract P4-06-09: Genetic Signature Discriminating Metastatic from Non-Metastatic Small Tumors
Authors: RE Ellsworth, AL Valente, LA Field, JL Kane, B Love, L Tafra, CD. Shriver
Journal: Cancer Research (2010)

Abstract Background: The widespread use of mammographic screening resulted in increased diagnosis of small (&amp;lt;2 cm; T1) tumors. Small tumors are associated with better prognosis, including a lower likelihood of developing metastasis, than larger tumors. Although this lower propensity to metastasize suggests that less aggressive treatments may be warranted in patients with T1 tumors, a subset of patients with small tumors (10-20%) will be diagnosed with lymph node metastasis. Methods: Frozen breast specimens were collected from women with T1 tumors and either negative (n=29) or positive (n=15) lymph node status. RNA was isolated from pure tumor cell populations after laser microdissection. Gene expression data was generated using HG U133A 2.0 arrays (Affymetrix). Differential expression was determined using Mann-Whitney testing using a P-value &amp;lt; 0.001 to define significance. Results for ESR1 were validated by immunohistochemistry. Results: Tumor characteristics did not differ significantly between groups in terms of age at diagnosis, grade, HER2 or PR status; however, tumors from patients with positive lymph nodes (47%) were significantly (P&amp;lt;0.05) more frequently ER negative compared to node negative (14%) patients. Gene expression analysis revealed 17 genes that were differentially expressed between node negative and node positive tumors: 6 with higher expression in node positive, including AURKA, and 11 with higher expression in node negative patients, including ESR1 and EPHX2. Of note, ESR1 was expressed at &amp;gt;4X higher levels in tumors without metastasis, in agreement with IHC findings. Conclusions: Small metastatic tumors differ in gene expression from those without metastasis. EPHX2 has been implicated as a metastasis suppressor while AURKA has been implicated as a metastasis promoter. These results suggest that small tumors have different propensities to metastasize and the genetic signature may serve as a new molecular tool to discriminate metastatic and non-metastatic small tumors, allowing appropriate treatment and risk assessment to be performed. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-06-09.
Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis.
Authors: J J Goronzy, P Bartz-Bazzanella, W Hu, M C Jendro, D R Walser-Kuntz, C M Weyand
Journal: Journal of Clinical Investigation (1994)

Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4+ T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4+ populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1*04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for V beta 3+, V beta 14+, and V beta 17+CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V beta 17+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation. The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint.
-GENESIS, NOT -GENOLYSIS
Authors: O'NEILL BARRETT
Journal: Annals of Internal Medicine (1967)

Letters and Comments1 January 1967-GENESIS, NOT -GENOLYSISO'NEILL BARRETTO'NEILL BARRETTSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-1-237_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:I would suppose that by now you have been deluged with letters from well-intentioned readers of the ANNALS, pointing out a discrepancy in the August issue. If so, perhaps this one of mine will be of no statistical import, but if not perhaps it will be of some value. My reference is to the article by Drs. Hutchings, Hegstrom, and Scribner entitled "Glucose Intolerance in Patients on Long-term Intermittent Dialysis." In this very excellent paper the discussion of the site of abnormality responsible for glucose intolerance is suggested as being a decreased rate of glycogenesis, as described... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: MC Department of Medicine Letterman General Hospital Department of the Army San Francisco, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1967Volume 66, Issue 1Page: 237-238KeywordsGlucose intoleranceMedical dialysis Issue Published: 1 January 1967 PDF downloadLoading ...
IS BICEPS FEMORIS LONG HEAD APONEUROSIS SIZE A RISK FACTOR FOR HAMSTRING STRAIN INJURY?
Authors: PE Evangelidis, GJ Massey, MT Pain, JP Folland
Journal: British Journal of Sports Medicine (2014)

Background Biceps femoris long head (BFlh) proximal aponeurosis (PA) size appears to be highly variable between individuals (Handsfield et al. , 2010) and may not be proportional to muscle size and strength. Individuals with a relatively small aponeurosis may be at higher risk of strain injury (Fiorentino et al. , 2012), and this could be an important intrinsic risk factor. Objective To examine the relationship of BFlh PA area with BFlh muscle size (volume and maximal anatomical cross-sectional area, ACSAmax) and hamstrings voluntary maximal isometric strength (MIS). Design Cross-sectional study. Setting Laboratory. Participants Thirty healthy, recreationally active participants (age: 20.7±2.6 yrs, height: 179.3±7.0 cm, body mass: 72.2±7.2 kg, mean±s) with no history of hamstrings injury. Risk factor assessment The dominant thigh was scanned (1.5T MRI scanner) and axial plane images (slice thickness: 5 mm) were used to measure BFlh muscle ACSAmax and volume. PA area was calculated as the sum of aponeurosis to muscle contact distance within each image (external and internal) multiplied by the slice thickness. MIS was measured in a prone position (hip and knee joint angles of 150°;full extension=180°). Main outcome measurements BFlh muscle volume, BFlh ACSAmax, BFlh PA area, MIS. Results BFlh PA area varied considerably across participants (mean=20.4±5.4 cm 2 , range=7.5-33.5 cm 2 , CV=26.6%) and it was not related to BFlh ACSAmax (r=0.041, P=.830) or volume (r=0.354, P=.055). Also, BFlh PA area was not related to MIS (r=0.178, P=.347). BFlh PA relative size (ratio to ACSAmax) was &gt;4 times smaller in some individuals than others (CV=38%). Conclusions BFlh PA area was not related to BFlh muscle size or hamstrings strength. Our results confirm the large aponeurosis size variability previously reported (Handsfield et al. , 2010) and support the notion that this could be a risk factor for hamstrings strain injury.
Cardiac Effects of Anticancer Therapy in the Elderly
Authors: Melissa K. Accordino, Alfred I. Neugut, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2014)

Cancer incidence increases with age, and as life expectancy increases, the number of elderly patients with cancer is increasing. Cancer treatments, including chemotherapy and radiotherapy, have significant short- and long-term effects on cardiovascular function. These cardiotoxic effects can be acute, such as changes in electrocardiogram (ECG), arrhythmias, ischemia, and pericarditis and/or myocarditis-like syndromes, or they can be chronic, such as ventricular dysfunction. Anticancer therapies can also have indirect effects, such as alterations in blood pressure, or can cause metabolic abnormalities that subsequently increase risk for cardiac events. In this review, we explore both observational and clinical trial evidence of cardiac risk in the elderly. In both observational and clinical trial data, risk of cardiotoxicity with anthracycline-based chemotherapy increases with age. However, it is less clear whether the association between age and cardiotoxicity exists for newer treatments. The association may not be well demonstrated as a result of under-representation of elderly patients in clinical trials and avoidance of these therapies in this population. In addition, we discuss strategies for surveillance and prevention of cardiotoxicity in the elderly. In the elderly, it is important to be aware of the potential for cardiotoxicity during long-term follow-up and to consider both prevention and surveillance of these late effects.
Early Detection of Rasmussen??s Syndrome by Brain SPECT Imaging
Authors: GEROGE J. BURKE, S ANNE FIFER, JEAN YODER
Journal: Clinical Nuclear Medicine (1992)

The authors describe a patient with Rasmussen's syndrome detected by grossly abnormal results of Tc-99m HMPAO SPECT brain imaging obtained with a singleheaded camera. Results of magnetic resonance imaging and cerebrospinal fluid examinations were normal.
Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies
Authors: Reinhard Marks, Karin Potthoff, Joachim Hahn, Gabriele Ihorst, Hartmut Bertz, Alexandros Spyridonidis, Ernst Holler, Jürgen M. Finke
Journal: Blood (2008)
Fibrosis correlates with a ductular reaction in hepatitis C
Authors: Andrew D. Clouston, Elizabeth E. Powell, Meagan J. Walsh, Michelle M. Richardson, A. Jake Demetris, Julie R. Jonsson
Journal: Hepatology (2005)

The mechanisms for progressive fibrosis and exacerbation by steatosis in patients with chronic hepatitis C (HCV) are still unknown. We hypothesized that proliferative blockade in HCV-infected and steatotic hepatocytes results in the default activation of hepatic progenitor cells (HPC), capable of differentiating into both biliary and hepatocyte lineages, and that the resultant ductular reaction promotes portal fibrosis. To study this concept, 115 liver biopsy specimens from subjects with HCV were scored for steatosis, inflammation, and fibrosis. Biliary epithelium and HPC were decorated by cytokeratin 7 immunoperoxidase, and the replicative state of hepatocytes was assessed by p21 and Ki-67 immunohistochemistry. A ductular reaction at the portal interface was common. There was a highly significant correlation between the area of ductular reaction and fibrosis stage (r = 0.453, P < .0001), which remained independently associated after multivariate analysis. HPC numbers also correlated with fibrosis (r = 0.544, P < .0001) and the ductular area (r = 0.624, P < .0001). Moreover, steatosis correlated with greater HPC proliferation (r = 0.372, P = .0004) and ductular reaction (r = 0.374, P < .0001) but was not an obligate feature. Impaired hepatocyte replication by p21 expression was independently associated with HPC expansion (P = .002) and increased with the body mass index (P < .001) and lobular inflammation (P = .005). In conclusion, the strong correlation between portal fibrosis and a periportal ductular reaction with HPC expansion, the exacerbation by steatosis, and the associations with impaired hepatocyte replication suggest that an altered regeneration pathway drives the ductular reaction. We believe this triggers fibrosis at the portal tract interface. This may be a stereotyped response of importance in other chronic liver diseases. (HEPATOLOGY 2005;41:809–818.)
Actomyosin-Mediated Cellular Tension Drives Increased Tissue Stiffness and β-Catenin Activation to Induce Epidermal Hyperplasia and Tumor Growth
Authors: Michael S. Samuel, Jose I. Lopez, Ewan J. McGhee, Daniel R. Croft, David Strachan, Paul Timpson, June Munro, Ewald Schröder, Jing Zhou, Valerie G. Brunton, Nick Barker, Hans Clevers, Owen J. Sansom, Kurt I. Anderson, Valerie M. Weaver, Michael F. Olson
Journal: Cancer Cell (2011)
Gastrointestinal Symptoms in 3181 Volunteers Ingesting Snack Foods Containing Olestra or Triglycerides for 6 Weeks
Authors: Robert S. Sandler
Journal: Annals of Internal Medicine (1999)

Background: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. Objective: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. Design: 6-week, double-blind, randomized, parallel, placebo-controlled trial. Setting: General community. Participants: 3181 volunteers 2 to 89 years of age. Intervention: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). Measurement: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. Results: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, −3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, −2.7 percentage points [CI, −4.9 to −0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. Conclusions: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.
Incompatibility between Sulfamethizole and Methenamine Mandelate
Authors: Joseph H. Lipton
Journal: New England Journal of Medicine (1963)

MARKED turbidity was noted in the urine of 9 of 32 patients during the clinical trial of a preparation containing methenamine mandelate and sulfamethizole.* This trial had been initiated in an attempt to duplicate the outstanding therapeutic response reported1 to occur with the use of this preparation in patients with resistant urinary-tract infections. Turbidity of the urine, which varied from a mild cloudiness to "buttermilk" flocculency, was referred to in the original report and, although disturbing to the patient, was cited as having no apparent adverse effect on the outcome of therapy. The reaction appeared to be related to pH, . . .
Autophagy‐Sensitized Cytotoxicity of Quantum Dots in PC12 Cells
Authors: Xiaoming Li, Nan Chen, Yuanyuan Su, Yao He, Min Yin, Min Wei, Lianhui Wang, Wei Huang, Chunhai Fan, Qing Huang
Journal: Advanced Healthcare Materials (2013)

Both CdTe and CdTe/CdS/ZnS quantum dots induce similar levels of autophagy in PC12 and HEK293 cells, while the former exhibits higher toxicity. Low levels of cadmium ions are not sufficient to induce either autophagy or cytotoxicity by themselves. Interestingly, the combination of cadmium ions and CdTe/CdS/ZnS mimics the toxic effect of CdTe, suggesting that autophagy sensitizes cells to cadmium ions.
An Intervention to Delay Nursing Home Placement-Reply
Authors: John C. Beck
Journal: JAMA (1997)

<h3>In Reply.</h3> —Our Editorial was not directed toward minimizing the significance of the findings in the article by Dr Mittelman and colleagues.<sup>1</sup>The specific comments to which Dr Butler refers were from our perspective to emphasize the importance of considering the differences between efficacy of an intervention trial vs effectiveness of replications in the community. The last paragraph of the editorial addresses this issue in greater detail. The financial and other barriers to nursing home admission (for example, spousal or family choice or medical necessity) are difficult to generalize from state to state. I personally find the "spend-down" regulation onerous. However, in frail elderly individuals with dementia, there is little or no evidence of a greater obstacle to nursing home admission than with nondemented persons, although anecdotal reports have occurred (oral communication, Katie Maslow, Alzheimer's Association of America, and oral communication, Lori Smetanka, The National Citizens Coalition for Nursing Home Reform,
IMPROVED BREAST AND ABDOMINAL BINDERS FOR MATERNITY PATIENTS
Authors: Ira Wilens
Journal: JAMA (1930)

The maternity binders used at present in most hospitals, although efficient, have certain inherent objections. First, they are difficult to put on. Secondly, it takes a long time to adjust them properly. Next, the nurses often stick their fingers, and occasionally the patient, with safety pins when applying the binder. After the binder has been beautifully put on by the nurse, the doctor comes along and takes it off, and another ten minutes is required to replace it. Lastly, the abdominal binder never stays below the hips but has a tendency to roll up on the abdomen.  In order to overcome these defects, the binders described here were devised.  AN IMPROVED BREAST BINDER  The binder is made of preshrunk ordinary unbleached muslin and comes in two sizes, small and large. It is cut along the regulation pattern. The following is a description of the large size: Ten inches from the