tbuckley/cabot-search huggingface dataset:
Epigenetic Down-Regulation of <i>CDKN1C/p57KIP2</i> in Pancreatic Ductal Neoplasms Identified by Gene Expression Profiling
Authors: Norihiro Sato, Hiroyuki Matsubayashi, Tadayoshi Abe, Noriyoshi Fukushima, Michael Goggins
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is an increasingly identified precursor to infiltrating ductal adenocarcinoma. Although our knowledge of the clinical and pathologic features of IPMNs is increasing, the molecular mechanisms underlying these neoplasms remain poorly understood. Experimental Designs: To provide further insight into the molecular pathobiology of IPMNs, global expression profiling was done to determine genes that are inactivated/down-regulated in IPMNs using oligonucleotide microarrays (Affymetrix). Results: In total, 300 unique transcripts (217 known genes) were identified as highly underexpressed in 12 IPMNs (&amp;lt;10-fold lower and P &amp;lt; 0.05) compared with five normal pancreatic ductal epithelium samples obtained by laser capture microdissection. The differential expression of a selection of genes was confirmed using reverse-transcription PCR. One of the genes underexpressed at both the transcriptional and protein level in a significant proportion of IPMNs was the cyclin-dependent kinase inhibitor, CDKN1C/p57KIP2. CDKN1C expression was also decreased in many pancreatic cancer cell lines and was restored following treatment with a DNA methylation inhibitor (5-aza-2′-deoxycitidine) or, more potently, with a histone deacetylase inhibitor (trichostatin A). Partial methylation of the CDKN1C promoter CpG island was found in most, but not all, pancreatic cancer cell lines with reduced CDKN1C expression, and was also detectable in IPMNs. Furthermore, a subset of pancreatic cancers showed complete hypomethylation of LIT1, an imprinting control region important for the regulation of CDKN1C expression. Complete hypomethylation in these cancers was the result of deletion of the methylated LIT1 allele at 11p15.5 rather than loss of imprinting. Conclusions: These findings suggest that CDKN1C is commonly down-regulated in pancreatic ductal neoplasms through a combination of promoter hypermethylation, histone deacetylation, and loss of the maternal allele expressing CDKN1C.
Intracellular chloride activities in canine tracheal epithelium. Direct evidence for sodium-coupled intracellular chloride accumulation in a chloride-secreting epithelium.
Authors: M J Welsh
Journal: Journal of Clinical Investigation (1983)

Canine tracheal epithelium secretes Cl via an electrogenic transport process that appears to apply to a wide variety of secretory epithelia. To examine the mechanisms involved, intracellular chloride activity, acCl, was measured with Cl-selective intracellular microelectrodes. The results indicate that when the rate of secretion was minimal acCl was 37 mM; with stimulation of secretion the intracellular voltage depolarized, but acCl was not significantly altered, at 39 mM. These findings indicate that: (a) Cl is accumulated across the basolateral membrane under nonsecreting and secreting conditions at an activity 3.8 and 2.4 times, respectively, that predicted for an equilibrium distribution; (b) Cl exit across the apical membrane may be passive with an electrochemical driving force of 22 mV; and (c) stimulation of secretion enhanced the rate of Cl entry across the basolateral membrane, since Cl transport increased without a change in acCl. In the absence of Na in the extracellular fluid, acCl approached the value expected for an equilibrium distribution. This finding suggests that "uphill" entry of Cl into the cell against its electrochemical gradient is dependent upon, and energized by, the entry of Na down its gradient. Submucosal bumetanide, a loop diuretic, also decreased the rate of Cl secretion and decreased acCl, indicating an inhibition of Cl entry. These findings indicate that Cl entry into the cell is directed against its electrochemical gradient and is mediated by a Na-coupled, bumetanide-inhibitable, transport process at the basolateral membrane and that Cl may exit passively down a favorable electrochemical gradient across the apical membrane.
Cumulative trauma disorders of the upper extremities
Authors: P. A. Nathan
Journal: JAMA (1992)

To the Editor.  —We read with interest the communication by Rempel et al.1We have been studying the cause of CTS in industrial workers for 8 years and have found no consistent objective evidence that occupation is a major contributing factor to conduction abnormalities of the median nerve.2,3Rather, we have found the major risk factors for abnormal nerve conduction to be individual characteristics (obesity, age, wrist dimensions, and lack of exercise). In turn, abnormal nerve conduction is by far the most important factor predicting clinical CTS after 5 years.3  We agree with Rempel et al1that it is desirable to reduce the incidence of clinical CTS in industrial workers. What we disagree with is how the reduced incidence is to be achieved. Most of the major risk factors for CTS are also major risk factors for other serious illnesses, such as cardiovascular disease, neuropsychiatric problems
UTERINE ADENOMATA IN THE RABBIT
Authors: Harry S. N. Greene
Journal: The Journal of Experimental Medicine (1941)

An investigation of uterine adenomata in the rabbit revealed an incidence of 16.7 per cent in the total female population over 2 years of age. However, the incidence varied widely in relation to age, breed, and genetic constitution and closely paralleled that of toxemia of pregnancy with reference to the same constitutional factors. In addition, all of the tumor bearing animals suffered attacks of this disease during their earlier breeding history. The facts suggest that the association of the two disorders occurred as a result of the liver damage incident to toxemia which impaired the function of this organ in relation to estrin inactivation and the concentration of this substance in the blood stream subsequently rose to a carcinogenic level. A consideration of the disparity in the distribution of uterine growths in rabbits and women indicated that the absence of squamous epithelium in the cervix of the rabbit and the greater physiological activity of the endometrium of the fundus in this species were the determining factors.
Delayed hypersensitivity to 6‐methyl‐prednisolone in Henoch Schoenlein syndrome
Authors: A. Astone, A. Romano, F. Pietrantonio, A. Garcovich, A. Venuti, C. Barone
Journal: Allergy (1992)

We report a case of allergic reaction to oral 6‐methyl‐prednisolone in a patient with Henoch Schoenlein syndrome. When this syndrome was first diagnosed the patient was started on 6‐methyl‐prednisolone orally and after 4 days he developed a pruriginous generalized maculo‐papular eruption. The rash disappeared 1 week after withdrawal of 6‐methyl‐prednisolone. The skin tests performed 1 month after with main food allergens were negative. Patch test with 0.10 ml of solution containing 6‐methyl‐prednisolone 40 mg/ml was positive after 48 and 72 h. The cutaneous biopsy on the patch tested skin revealed a perivaseular infiltrate of lymphocytes, histiocytes and eosinophils.
How Variability in the Institutional Review Board Review Process Affects Minimal-Risk Multisite Health Services Research
Authors: Laura A. Petersen, Kate Simpson, Richard SoRelle, Tracy Urech, Supicha Sookanan Chitwood
Journal: Annals of Internal Medicine (2012)

Background: The Department of Health and Human Services recently called for public comment on human subjects research protections. Objective: To assess variability in reviews across institutional review boards (IRBs) for a multisite, minimal-risk trial of financial incentives for evidence-based hypertension care and to quantify the effect of review determinations on site participation, budget, and timeline. Design: A natural experiment occurring from multiple IRBs reviewing the same protocol for a multicenter trial (May 2005 to October 2007). Participants: 25 Veterans Affairs (VA) medical centers. Measurements: Number of submissions, time to approval, and costs were evaluated; patient complexity, academic affiliation, size, and location (urban or rural) between participating and nonparticipating VA medical centers were compared. Results: Of 25 eligible VA medical centers, 6 did not meet requirements for IRB review and 2 declined to participate. Of 17 applications, 14 were approved. The process required 115 submissions, lasted 27 months, and cost close to $170 000 in staff salaries. One IRB's concern about incentivizing a particular medication recommended by national guidelines prompted a change in our design to broaden our inclusion criteria beyond uncomplicated hypertension. The change required amending the protocol at 14 sites to preserve internal validity. The IRBs that approved the protocol classified it as minimal risk. The 12 sites that ultimately participated in the trial were more likely to be urban and academically affiliated and to care for more complex patients, which limits the external validity of the trial's findings. Limitation: Because data came from a single multisite trial in the VA system that uses a 2-stage review process, generalizability is limited. Conclusion: Complying with IRB requirements for a minimal-risk study required substantial resources and threatened the study's internal and external validity. The current review of regulatory requirements may address some of these problems. Primary Funding Source: Veterans Affairs Health Services Research and Development and the National Heart, Lung, and Blood Institute.
Pulmonary-Valve Injury and Insufficiency during Pulmonary-Artery Catheterization
Authors: James D. O'Toole, John J. Wurtzbacher, Neal E. Wearner, Abnash C. Jain
Journal: New England Journal of Medicine (1979)

SINCE the flow-directed, balloon-tipped catheter was introduced in 19701 it has been widely used to monitor pulmonary-capillary wedge pressure. Complications associated with its use include transient arrhythmia,1 intravascular knotting,2 balloon rupture,3 infection of the cutdown site,3 persistent arrhythmia,4 , 5 pulmonary embolism or infarction,6 7 8 rupture or perforation of the pulmonary artery,9 10 11 12 13 and both septic14 15 16 and aseptic17 18 19 endocardial vegetation. This catheter has also produced a systolic non-ejection click.20 We report two cases of pulmonary-valve damage and resultant insufficiency occurring with catheterization.Case ReportsCase 1An 18-year-old primapara vomited during delivery and aspirated massive amounts of vomitus; the respiratory-distress syndrome developed. An indwelling . . .
Prediction of significant fibrosis in HBeAg‐positive patients with chronic hepatitis B by a noninvasive model†
Authors: Min‐De Zeng, Lun‐Gen Lu, Yi‐Min Mao, De‐Kai Qiu, Ji‐Qiang Li, Mo‐Bin Wan, Cheng‐Wei Chen, Ji‐Yao Wang, Xiong Cai, Chun‐Fang Gao, Xia‐Qiu Zhou
Journal: Hepatology (2005)

A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2-4 vs. stages 0-1). Consecutive treatment-naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172). Multivariate analysis identified α2-macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Using a cutoff score of <3.0, the presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (86.1% negative predictive value [NPV], 70.1% positive predictive value [PPV], and 94.8% sensitivity) in 43 (21.5%) of 200 patients in the training group, and with the same certainty (90.9% NPV, 64.7% PPV, and 98.0% sensitivity) in 22 (12.8%) of 172 patients in the validation group. Similarly, applying a cutoff score of >8.7, the presence of significant fibrosis could be correctly identified with high accuracy (91.1% PPV, 51.6% NPV, and 95.2% specificity) in 41 (20.5%) of 200 patients in the training group, and with the same certainty (84.8% PPV, 52.4% NPV, and 90.4% specificity) in 39 (22.7%) of 172 patients of the validation group. In conclusion, a predictive model with a combination of easily accessible variables identified HBeAg-positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB. (HEPATOLOGY 2005;42:1437–1445.)
Risk of AIDS to health care workers.
Authors: A M Geddes
Journal: BMJ (1986)

This article reviews evidence on the risk of acquired immunodeficiency syndrome (AIDS) to health workers and suggests guidelines for the clinical care of AIDS patients.  No health worker in the world has yet contracted AIDS from a patient.  However seroconversion to human T-lymphotropic virus type III (HTLV-III) has occurred in a small number.  A serologic study of 1758 US health workers who had direct contact with AIDS patients found HTLV-III antibodies in the blood of 26 (1.5%) but 23 of these workers were in another high-risk group for AIDS (homosexual men).  Similar studies in San Francisco and London that included large numbers of health workers who sustained needlestick injuries while working with AIDS patients have failed to detect seroconversion.  A further study of the siblings children and parents of 39 adult AIDS victims also found no evidence of infection suggesting that AIDS does not occur by casual contact.  HTLV-III appears to be less communicable than the hepatitis B virus which health service staff have contracted from infected blood.  It is recommended that when a patient known to be positive for HTLV-III is admitted to the hospital all specimens from that patient should be labelled with a biohazard sticker.  Specimens should be handled and processed in the same way as those from hepatitis B patients.  Staff should wear gloves and a plastic apron when attending to these patients.  Although isolation is not necessary it is unwise to place patients with HTLV-III in the same ward with patients who are immunocompromised for other reasons given the risk of 2-way transmission of infection.  Finally every effort should be made to maintain confidentiality and lists of HTLV-III-positive patients should not be displayed.
Factors That Affect Pulmonary Artery Pressure in Scleroderma Patients with Pulmonary Hypertensıon
Authors: Uğur Nadir Karakulak, Naresh Maharjan, Elifcan Aladağ, Levent Kılıç, Ali Akdoğan, Ergün Barış Kaya, Lale Tokgözoğlu
Journal: Journal of the American College of Cardiology (2013)
Periosteal Bone Formation — A Neglected Determinant of Bone Strength
Authors: Ego Seeman
Journal: New England Journal of Medicine (2003)

Life forms that have low body mass can hunt for food on the undersurface of branches or along shear cliff faces quite unperturbed by gravity. For larger animals, the hunt for dinner and the struggle to avoid becoming someone else's meal require rapid movement against gravity. This need is met by the lever function of long bones, three-dimensional masterpieces of biomechanical engineering that, by their material composition and structural design, achieve the contradictory properties of stiffness and flexibility, strength and lightness.1 Material stiffness results from the encrusting of the triple-helical structure of collagen type I with hydroxyapatite crystals, which confers . . .
Differences between the lymphocytic population of the liver and the blood: A Study in patients with liver tumors
Authors: M.E. Lafon, J. Saric, A.M. Ferrer, D. Fizet, L. Dubuisson, C. Bedin, L. Boussarie, M. Winnock, A. Quinton, P. Bioulac-Sage, C. Balabaud
Journal: Journal of Hepatology (1989)
Graves's Disease and Total Thyroidectomy
Authors: Sidney C. Werner, Carl R. Feind, Mitsuyasu Aida
Journal: New England Journal of Medicine (1967)

TOTAL thyroidectomy has been offered as a quick and effective treatment1 , 2 for the severe eye changes of Graves's disease.3 The present study was undertaken to assess the value of this proposed method in patients with evident, active, ocular disease, as well as to determine the effect of thyroid removal upon serum long acting thyroid stimulator (LATS).The natural course of the severe eye changes4 is generally a prolonged one, ending ultimately, and unpredictably, in spontaneous remission. Progression of disease may result in serious damage to vision, to extraocular-muscle function or even to loss of the globes, with threat to life. . . .
Epidermolysis bullosa acquisita associated with vesicular cystitis
Authors: CHANG LEE
Journal: British Journal of Dermatology (1988)

A 55-year-old woman with epidermotysis bullosa acquisita (EBA) who had associated vesicular cystitis is described. The clinical, histological and immunohistological features of the skin and mucous membranes were in accordance with previous reports of this disease. The patient also had symptoms of cystitis, and a cystoscopic examination showed areas of erosions and vesicles in the wall of the urinary bladder, Histological and immunopathological studies of the urinary bladder demonstrated sub-mucosal vesicles, and linear deposits of IgG and C3 along the mucosal-lamina propria junction. These bladder changes may be induced by the autoantibodies present in EBA.
P3-07-39: Where To Look for Sentinel Lymph Node in Breast Cancer.
Authors: A Düran
Journal: Cancer Research (2011)

Abstract Hypothesis: The sentinel Lymph node (SLN) is not only the first extra mammary point of metastatic spread, it also undergoes reactive changes. Sonographically this is evident through an increased width of the hypo-echoic cortex of the lymph node. We examined, if it is possible to localize SLN on sono-morphological features, if it is sonographic detection comparable with the radio nuclide tracer method and if false negative rate (FNR) of SLNB can be reduced by ultrsound. Method: From 1/2001 to 5/2003, 117 patients with breast cancer where prospectively examined for SLN localization using sonography in addition to radio nuclide -Tc99m- and/or patent blue-methods. The lymph node identified as the SLN in ultrasound was marked using a hook-wire. The sonographic parameters used to identify the SLN were: The node with the widest hypo echoic cortex, located in the caudal axilla and the closest to the glandular tissue and with the greatest diameter. Results: In all 117 patients, in the region of the caudal axilla, an enlarged, reactive, either tumor free or metastatic SLN could be verified. The location of the SLN was in all cases on the lateral-caudal thoracic wall and consistent with the lymph node group at the lateral border of the pectoralis major. The sonographic detection rate of the SLN was 86%. 70.6% of the sentinel lymph nodes where affected by metastatic spread. In those patients with a pT1a-c-tumor the rate of SLN metastatic spread was 20%. The false negative rate (FNR) for SLN localization with Tc99m/Blau was 10.6 %. Experience has shown that the FNR increases with increasing degree of metastatic spread to the SLN. With the addition of sonography of the axilla the FNR could be decreased to 3.5%. Sonographic SLN detection rate: 86% ( n=101/117) False-negative-rate (Blue/Tc) 10.7% (n=6sln- /56N+) False-negative-rate (Blue/Tc + Sonography) 3.5% (n=2sln-/56N+) Conclusions: The false-negative-rate of detection of suspected lymph nodes can be reduced using sonographic localization of the SLN. Sonography of the axilla should therefore be an integral part of and standard in the sentinel node-biopsy of breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-39.
Intranasal and inhaled fluticasone propionate for pollen‐induced rhinitis and asthma
Authors: R. Dahl, L. P. Nielsen, J. Kips, A. Foresi, P. van Cauwenberge, N. Tudoric, P. Howarth, D. H. Richards, M. Williams, R. Pauwels
Journal: Allergy (2005)

Background: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen‐induced rhinitis and asthma. Methods: A total of 262 patients were randomized to 6 weeks’ treatment with intranasal fluticasone propionate (INFP) 200 μ g o.d., inhaled fluticasone propionate (IHFP) 250 μ g b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double‐blind, parallel‐group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks’ treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. Results: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak‐flow, forced expiratory volume in 1 second (FEV 1 ) and methacholine PD 20 , and the seasonal increase in the sputum eosinophils and methacholine responsiveness. Conclusions: In patients with pollen‐induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.
Mapping of novel peptides of WT-1 and presenting HLA alleles that induce epitope-specific HLA-restricted T cells with cytotoxic activity against WT-1+ leukemias
Authors: Ekaterina Doubrovina, Taissia Carpenter, Dmitry Pankov, Annamalai Selvakumar, Aisha Hasan, Richard J. O'Reilly
Journal: Blood (2012)
Application of Embryonic Lethal or Other Obvious Phenotypes to Characterize the Clinical Significance of Genetic Variants Found in <i>Trans</i> with Known Deleterious Mutations
Authors: Thaddeus Judkins, Brant C. Hendrickson, Amie M. Deffenbaugh, Kristilyn Eliason, Benoît Leclair, Michael J. Norton, Brian E. Ward, Dmitri Pruss, Thomas Scholl
Journal: Cancer Research (2005)

This work describes an approach to characterize the clinical significance of genetic variants detected during the genetic testing of BRCA1 in patients from hereditary breast/ovarian cancer families. Results from transgenic mice and extensive clinical testing support the hypothesis that biallelic BRCA1 mutations result in embryonic lethality. Therefore, it is reasonable to conclude that variants of uncertain clinical significance found to reside in trans with known deleterious mutations impart reduced risk for cancer. This approach was applied to a large data set of 55,630 patients who underwent clinical BRCA1 screening by whole gene direct DNA sequencing. Fourteen common single nucleotide polymorphisms (SNPs) were used to assign 10 previously defined common, recurrent, or canonical haplotypes in 99% of these cases. From a total of 1,477 genetic variants detected in these patients, excluding haplotype-tagging SNPs, 877 (59%) could be unambiguously assigned to one or more haplotypes. In 41 instances, variants previously classified as being of uncertain clinical significance, mostly missense variants, were excluded as fully penetrant mutations due to their coincidence in trans with known deleterious mutations. From a total of 1,150 patients that harbored these 41 variants, 956 carried one as the sole variant of uncertain clinical significance reported. This approach could have widespread application to other disease genes where compound heterozygous mutations are incompatible with life or result in obvious phenotypes. This largely computational technique is advantageous because it relies upon existing clinical data and is likely to prove informative for prevalent genetic variants in large data sets.