tbuckley/cabot-search huggingface dataset:
Long-Term Medical Outcomes and Quality-of-Life Assessment of Patients With Chronic Myeloid Leukemia Followed at Least 10 Years After Allogeneic Bone Marrow Transplantation
Authors: T.L. Kiss, M. Abdolell, N. Jamal, M.D. Minden, J.H. Lipton, H.A. Messner
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Benchmark analysis of patients with chronic myeloid leukemia (CML) alive for more than 10 years after allogeneic bone marrow transplantation (BMT) including data on disease status, bone marrow reserve, long-term complications, and quality of life (QOL). PATIENTS AND METHODS: Eighty-nine patients (46 in first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML during the study period. Medical outcomes and QOL of patients were analyzed retrospectively. RESULTS: Twenty-eight (31.5%) of 89 patients were alive at 10 years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors never relapsed. Fifteen patients relapsed between 0.5 and 16 years after transplantation. Ten patients showed a hematologic relapse and received salvage treatment. Five patients showed transient low levels of BCR-ABL–positive cells by Southern blot with no subsequent hematologic relapse. One of the 28 patients died in blast crisis at 12 years. The most frequent long-term complications were chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of clonogenic progenitors remained persistently decreased. QOL assessment yielded lower scores in physical performance as compared with an age-matched normative population, whereas social functioning was equivalent. A high degree of satisfaction was noted with interpersonal relationships. CONCLUSION: Patients with CML surviving their BMT long term do well in terms of medical outcomes. A constant rate of relapse was noted, with a high salvage rate of affected patients, suggesting the need for lifelong monitoring. QOL is perceived as good, particularly as related to social functioning; however, it is inferior to a normative population with regard to physical performance.
A 26‐yr-old female with persistent cough
Authors: S. Baser, F.E. Fisekci, S. Ozkurt, G. Kiter, S. Kirac, H. Alper
Journal: European Respiratory Journal (2003)

Case historyA 26-yr-old female was referred to the Chest Dept of the Pamukkale University Medical School, Turkey, for the investigation of coughing and abnormal chest roentgenogram.She suffered flu 3 weeks prior to this and her coughing was persisting since then.She denied fever, phlegm, dyspnoea, wheeze, night sweats and haemoptysis.Before a splenectomy at aged 18 yrs, blood transfusions had been applied monthly.Physical examination revealed a blood pressure of 120/ 80 mmHg, pulse rate of 96 beats per min, respiratory rate of 21 breaths per min and marked hepatomegaly.Chest examination results were normal.Haematological examination showed a haemoglobin level of 1.38 mmol?L -1 (89.3 g?L -1 ), haematocrit value of 0.19, mean corpuscular volume of 91.4 fL, mean corpuscular haemoglobin concentration of 466 g?L -1 , red blood cell count of 2.1610 12 cells?L -1 , reticulocyte count of 0.14, white blood cell count of 23610 9 cells?L -1 , and platelet count of 1072610 9 platelets?L -1 .Serum biochemical findings were as follows: aspartate aminotransferase 85 U?L -1 , alanine aminotransferase 84 U?L -1 , blood urea nitrogen 1.33 mmol urea?L -1 , total protein 73 g?L -1 , total bilirubin 30.8 mmol?L -1 , iron 36.7 mmol?L -1 , ferritin 2.3 g?L -1 , and total iron binding capacity 40.3 mmol?L -1 .The chest radiographs (fig.1a and1b), computed tomography (CT) of the chest (fig.2), thoracic single photon emission computed tomography (SPECT) study with TC-99M (fig.3) and peripheral blood smear (fig.4) were as shown.
PEMer: a computational framework with simulation-based error models for inferring genomic structural variants from massive paired-end sequencing data
Authors: Jan O Korbel, Alexej Abyzov, Xinmeng Jasmine Mu, Nicholas Carriero, Philip Cayting, Zhengdong Zhang, Michael Snyder, Mark B Gerstein
Journal: Genome biology (2009)

Abstract Personal-genomics endeavors, such as the 1000 Genomes project, are generating maps of genomic structural variants by analyzing ends of massively sequenced genome fragments. To process these we developed Paired-End Mapper ( PEMer ; http://sv.gersteinlab.org/pemer ). This comprises an analysis pipeline, compatible with several next-generation sequencing platforms; simulation-based error models, yielding confidence-values for each structural variant; and a back-end database. The simulations demonstrated high structural variant reconstruction efficiency for PEMer 's coverage-adjusted multi-cutoff scoring-strategy and showed its relative insensitivity to base-calling errors.
The need to change the method for defining mild airway obstruction
Authors: P.H. Quanjer, P.L. Enright, M.R. Miller, J. Stocks, G. Ruppel, M.P. Swanney, R.O. Crapo, O.F. Pedersen, E. Falaschetti, J.P. Schouten, R.L. Jensen
Journal: European Respiratory Journal (2011)

The need to change the method for defining mild airway obstruction Dear colleagues, members of GOLD committee, This letter arises from discussions and correspondence between colleagues involved in respiratory research or the diagnosis and treatment of lung diseases, as well as from a review of the literature on chronic obstructive pulmonary disease (COPD).As discussed below, it is written in the hope that we can persuade members of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee to vote to change the method by which mild airway obstruction is defined by the GOLD guidelines.We very much welcome the continued efforts of the GOLD group to stimulate interest and awareness of the high prevalence of COPD, its morbidity, effects on quality of life and on mortality.There is no doubt that COPD is a major public health problem of which the public, health workers and health authorities were insufficiently aware.It is therefore an important achievement that the World Health Organization (WHO), the European Respiratory Society (ERS), the American Thoracic Society (ATS), the Asian Pacific Society of Respirology (APSR), the Asociacio ´n Latinoamericana de To ´rax (ALAT), and the World Organization of Family Doctors (WONCA) and many distinguished individuals have joined forces to increase awareness about the burden of disease, by publishing reports and guidelines for diagnostic procedures and interventions which have been adopted by numerous international and national organisations.
Dual concerns with the dualist approach
Authors: David A. Lagnado, David R. Shanks
Journal: Behavioral and Brain Sciences (2007)

Abstract Barbey &amp; Sloman (B&amp;S) attribute all instances of normative base-rate usage to a rule-based system, and all instances of neglect to an associative system. As it stands, this argument is too simplistic, and indeed fails to explain either good or bad performance on the classic Medical Diagnosis problem.
Familial Aggregation of Severity of Diabetic Retinopathy in Mexican Americans From Starr County, Texas
Authors: D. Michael Hallman, J. Charles Huber, Victor H. Gonzalez, Barbara E.K. Klein, Ronald Klein, Craig L. Hanis
Journal: Diabetes Care (2005)

OBJECTIVE—Diabetic retinopathy is a major cause of blindness. To determine whether retinopathy itself or only its severity aggregates in families, we examined the occurrence and severity of diabetic retinopathy in Mexican-American siblings with type 2 diabetes. RESEARCH DESIGN AND METHODS—Using stereoscopic fundus photography of seven standard fields, we measured retinopathy in 656 type 2 diabetic patients from 282 Mexican-American families from Starr County, Texas. Retinopathy severity was scored using the Early Treatment of Diabetic Retinopathy Study system and classified as no retinopathy, early nonproliferative diabetic retinopathy (NPDR-E), moderate-to-severe nonproliferative diabetic retinopathy (NPDR-S), or proliferative diabetic retinopathy (PDR). RESULTS—Of 249 siblings of randomly selected probands with retinopathy, 169 (67.9%) had retinopathy, compared with 95 of 125 siblings of unaffected probands (76.0%; P = 0.11). Proband retinopathy class was associated (P = 0.03) with sibling retinopathy class, with significant odds ratios (ORs) for NPDR-E versus no retinopathy (OR 0.57 [95% CI 0.35–0.93]) and PDR versus NPDR-E (2.02 [1.13–3.63]); the contrast of NPDR-S versus NPDR-E approached significance (1.78 [0.99–3.20]). With the more severe classes (PDR and NPDR-S) combined in one group and the less severe ones (none and NPDR-E) in another, more severe proband retinopathy was associated with more severe sibling retinopathy (1.72 [1.03–2.88]). CONCLUSIONS—More severe diabetic retinopathy showed evidence of familial aggregation, but the occurrence of diabetic retinopathy per se did not. The factors involved in the onset of diabetic retinopathy may differ from those involved in its progression to more severe forms.
Jogger's Whiplash
Authors: R. Peter Rosier
Journal: JAMA (1978)

To the Editor.—  To our knowledge, this is the first recorded case of jogger's whiplash. While running east 75 minutes before dusk on a macadam road in good repair on a windless day (0 to 5 knots northeast), a 35-year-old well-developed, well-nourished pathologist stepped onto the shoulder rather casually to avoid collision with an oncoming motorist. The subject experienced sudden, severe, sharp, transverse localized pain in the midline posteriorly between C-5 and C-7. The pain was described as similar to that experienced as if hit in the back of the neck with an axe.  The jogger slowed from his 5 min/km pace but did not stop for two reasons. First, he was 2.4 km into an 8-km run and thus was in the middle of nowhere. Secondly, 75% of maximal cardiac rate had to be maintained to ensure optimum cardiovascular exercise. Fortunately, at the end of the third kilometer, the
Podocyte Hypertrophy, “Adaptation,” and “Decompensation” Associated with Glomerular Enlargement and Glomerulosclerosis in the Aging Rat
Authors: Jocelyn E. Wiggins, Meera Goyal, Silja K. Sanden, Bryan L. Wharram, Kerby A. Shedden, David E. Misek, Rork D. Kuick, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2005)

Whether podocyte depletion could cause the glomerulosclerosis of aging in Fischer 344 rats at ages 2, 6, 17, and 24 mo was evaluated. Ad libitum-fed rats developed proteinuria and glomerulosclerosis by 24 mo, whereas calorie-restricted rats did not. No evidence of age-associated progressive linear loss of podocytes from glomeruli was found. Rather, ad libitum-fed rats developed glomerular enlargement over time. To accommodate the increased glomerular volume, podocytes principally underwent hypertrophy, whereas other glomerular cells underwent hyperplasia. Stages of hypertrophy through which podocytes pass en route to podocyte loss and glomerulosclerosis were identified: Stage 1, normal podocyte; stage 2, nonstressed podocyte hypertrophy; stage 3, "adaptive" podocyte hypertrophy manifest by changes in synthesis of structural components (e.g., desmin) but maintenance of normal function; stage 4, "decompensated" podocyte hypertrophy relative to total glomerular volume manifest by reduced production of key machinery necessary for normal podocyte function (e.g., Wilms' tumor 1 protein [WT1], transcription factor pod1, nephrin, glomerular epithelial protein 1, podocalyxin, vascular endothelial growth factor, and alpha5 type IV collagen) and associated with widened foot processes and decreased filter efficiency (proteinuria); and stage 5, podocyte numbers decrease in association with focal segmental glomerulosclerosis. In contrast, in calorie-restricted rats, glomerular enlargement was minor, significant podocyte hypertrophy did not occur, podocyte machinery was unchanged, there was no proteinuria, and glomerulosclerosis did not develop. Glomerular enlargement therefore was associated with podocyte hypertrophy rather than hyperplasia. Hypertrophy above a certain threshold was associated with podocyte stress and then failure, culminating in reduced podocyte numbers in sclerotic glomeruli. This process could be prevented by calorie restriction.
Expression Profiling of Mucinous Tumors of the Ovary Identifies Genes of Clinicopathologic Importance
Authors: Fred W. Wamunyokoli, Tomas Bonome, Ji-Young Lee, Colleen M. Feltmate, William R. Welch, Mike Radonovich, Cindy Pise-Masison, John Brady, Ke Hao, Ross S. Berkowitz, Samuel Mok, Michael J. Birrer
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To elucidate the molecular mechanisms contributing to the unique clinicopathologic characteristics of mucinous ovarian carcinoma, global gene expression profiling of mucinous ovarian tumors was carried out. Experimental Design: Gene expression profiling was completed for 25 microdissected mucinous tumors [6 cystadenomas, 10 low malignant potential (LMP) tumors, and 9 adenocarcinomas] using Affymetrix U133 Plus 2.0 oligonucleotide microarrays. Hierarchical clustering and binary tree prediction analysis were used to determine the relationships among mucinous specimens and a series of previously profiled microdissected serous tumors and normal ovarian surface epithelium. PathwayAssist software was used to identify putative signaling pathways involved in the development of mucinous LMP tumors and adenocarcinomas. Results: Comparison of the gene profiles between mucinous tumors and normal ovarian epithelial cells identified 1,599, 2,916, and 1,765 differentially expressed in genes in the cystadenomas, LMP tumors, and adenocarcinomas, respectively. Hierarchical clustering showed that mucinous and serous LMP tumors are distinct. In addition, there was a close association of mucinous LMP tumors and adenocarcinomas with serous adenocarcinomas. Binary tree prediction revealed increased heterogeneity among mucinous tumors compared with their serous counterparts. Furthermore, the cystadenomas coexpressed a subset of genes that were differentially regulated in LMP and adenocarcinoma specimens compared with normal ovarian surface epithelium. PathwayAssist highlighted pathways with expression of genes involved in drug resistance in both LMP and adenocarcinoma samples. In addition, genes involved in cytoskeletal regulation were specifically up-regulated in the mucinous adenocarcinomas. Conclusions: These data provide a useful basis for understanding the molecular events leading to the development and progression of mucinous ovarian cancer.
Thioesterase II, a New Marker Enzyme for Human Cells of Breast Epithelial Origin2
Authors: Stuart Smith, David Pasco, Jan Pawlak, Betty J. Thompson, Martha Stampfer, Satyabrata Nandi
Journal: JNCI Journal of the National Cancer Institute (1984)

Metabolic, enzymologic, and immunohistochemical techniques have been used to show that a human cell line of breast epithelial origin synthesized medium chain fatty acids via the ubiquitous fatty acid synthetase and a mammary-specific chain-terminating enzyme, thioesterase II. Previous studies in our laboratory with rodents indicated that thioesterase II is expressed exclusively in mammary epithelial cells, an observation consistent with the physiologic role of the enzyme in milk fat synthesis. Results of the present study suggest that the enzyme exhibits a similar cell specificity in its expression in humans and that the specificity is maintained in normal and neoplastic tissues. Thus thioesterase II was detected immunohistochemically in normal human breast epithelia derived from both lactating and nonlactating breast tissue, in cultured cells derived from both primary breast epithelial tumors and from a metastatic tumor of breast origin, and in several human breast epithelial cell lines; the enzyme could not be detected in HeLa cells, in a colon carcinoma, or in a mammary myoepithelial cell line. These findings raise the possibility that thioesterase II may be of use as a diagnostic tool to identify human tumors of breast epithelial origin.
Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab
Authors: Venky Ramakrishna, Karuna Sundarapandiyan, Biwei Zhao, Max Bylesjo, Henry C. Marsh, Tibor Keler
Journal: Journal for ImmunoTherapy of Cancer (2015)

Clinical targeting of TNFR family of receptors (CD40, CD134 and CD137) with immunostimulatory monoclonal antibodies has been successful in cancer immunotherapy. However, targeting of CD27 with a mAb is a relatively new approach to provide costimulation of immune cells undergoing activation. Thus, activation of human CD27 (TNFRSF7) with a monoclonal antibody (varlilumab) has previously been demonstrated to result in T cell activation and anti-tumor activity in preclinical models, and is currently in early phase clinical trials in patients with advanced malignancies. In this study we used an in vitro system using human peripheral blood T cells to characterize the varlilumab-mediated costimulatory effects in combination with TCR stimulation in terms of phenotypic, transcriptional and functionality changes.T cells were isolated from normal volunteer PBMCs using magnetic bead isolation kits and stimulated in vitro with plate bound anti-CD3 Ab (OKT3) and varlilumab or control Ab for 72 h. Activation profiles were monitored by ELISA or Luminex-based testing cytokine/chemokine releases, cell surface phenotyping for costimulatory and coinhibitory markers and CFSE dye dilution by proliferating T cells and Tregs. Changes in gene expression and transcriptome analysis of varlilumab-stimulated T cells was carried on Agilent Human whole genome microarray datasets using a suite of statistical and bioinformatic software tools.Costimulation of T cells with varlilumab required continuous TCR signaling as pre-activated T cells were unable to produce cytokines with CD27 signaling alone. Analysis of T cell subsets further revealed that memory CD4+ and CD8+ T cells were specifically activated with a bias toward CD8+ T lymphocyte proliferation. Activation was accompanied by upregulated cell surface expression of costimulatory [4-1BB, OX40, GITR and ICOS] and coinhibitory [PD-1] molecules. Importantly, varlilumab costimulation did not activate purified Tregs as measured by cytokine production, proliferation and suppression of dividing non-Treg T cells. Analysis of changes in gene expression during varlilumab stimulation of T cells revealed modulation of pro-inflammatory signatures consistent with cellular activation and proliferation, with the IL-2 pathway showing the highest frequency of gene modulation.Altogether, the data reveal the requirements and T cell subtype-specific effects of CD27 costimulation, and helps select relevant biomarkers for studying the effects of varlilumab in patients.
Investigation of mycobacterial colonisation and invasion of the respiratory mucosa
Authors: A M Middleton
Journal: Thorax (2003)

The pathogenesis of Mycobacterium avium complex and Mycobacterium tuberculosis in the respiratory tract is poorly understood, as are the reasons for their differing virulence. We have previously shown that their initial adherence to the mucosa is identical.The interaction of M avium complex, M tuberculosis, and M smegmatis with human respiratory tissue was investigated in an organ culture model with an air interface. Tissue was infected for intervals up to 14 days and assessed by scanning electron microscopy for adherent bacteria or cultured for recoverable bacteria.The mean number of adherent bacteria/mm(2) (and the viable count of macerated tissue, cfu/ml) at 15 minutes, 3 and 24 hours, 7 and 14 days were: M avium complex 168 (153), 209 (136), 289 (344), 193 (313), 14140 (16544); M tuberculosis 30 (37), 39 (23), 48 (53), 1 (760), 76 (2186); M smegmatis 108 (176), 49 (133), 97 (81), 114 (427), 34 (58), (n=6). There was no significant change in morphology between infected and uninfected tissue or tissue infected with the different species over 14 days. The number of M avium complex on the mucosa and recovered from tissue increased over time (p=0.03). M tuberculosis decreased on the surface, but recoverable bacteria increased (p=0.01). M smegmatis numbers on the mucosa and recovered from tissue decreased. Sectioned tissue showed M avium complex and M tuberculosis in submucosal mucus glands and M tuberculosis penetrating epithelial cells in one experiment.The initial adherence to the mucosa of the three species was similar, but after 14 days they varied in their interaction with the tissue in a manner compatible with their pathogenicity.
Proteome analysis of stratum corneum from atopic dermatitis patients by hybrid quadrupole-orbitrap mass spectrometer
Authors: Jun-Ichi Sakabe, Koji Kamiya, Hayato Yamaguchi, Shigeki Ikeya, Takahiro Suzuki, Masahiro Aoshima, Kazuki Tatsuno, Toshiharu Fujiyama, Masako Suzuki, Tsuyoshi Yatagai, Taisuke Ito, Toshiyuki Ojima, Yoshiki Tokura
Journal: Journal of Allergy and Clinical Immunology (2014)
Initial Effects of the Left Ventricular Repair by Plication May Not Last Long in a Rat Ischemic Cardiomyopathy Model
Authors: T Nishina, K Nishimura, S Yuasa, S Miwa, T Nomoto, Y Sakakibara, N Handa, I Hamanaka, Y Saito, M Komeda
Journal: Circulation (2001)

Long term effects of left ventricle (LV) repair surgery (LVR) for ischemic cardiomyopathy are not well understood.Sixty-nine rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after the left anterior descending artery was ligated. In a second surgery 4 weeks later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group), and 36 underwent rethoracotomy alone (sham group). No medication was used in either group. All rats survived the second surgery. LV end-diastolic dimension as measured by echocardiography, LV fractional shortening, and the maximal end-systolic pressure-volume relationship (E(max)) as calculated from the data by catheter-tipped manometer and echocardiography improved in the LVR group after the second surgery, but LV end-diastolic dimension and E(max) gradually deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks postoperatively.Initial improvement in LV function and neurohormonal status after LVR did not last for 4 weeks in this rat model when untreated medically. The mechanism of deterioration should be elucidated to improve long-term results of LVR.
Right Prefrontal Repetitive Transcranial Magnetic Stimulation in Obsessive-Compulsive Disorder: A Double-Blind, Placebo-Controlled Study
Authors: P Alonso, J Pujol, N Cardoner, L Benlloch, J Deus, J M Menchón, A Capdevila, J Vallejo
Journal: American Journal of Psychiatry (2001)

The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex for patients with obsessive-compulsive disorder (OCD) was studied under double-blind, placebo-controlled conditions.Patients were randomly assigned to 18 sessions of real (N=10) or sham (N=8) rTMS. Treatments lasted 20 minutes, and the frequency was 1 Hz for both conditions, but the intensity was 110% of motor threshold for real rTMS and 20% for the sham condition.No significant changes in OCD were detected in either group after treatment. Two patients who received real rTMS, with checking compulsions, and one receiving sham treatment, with sexual/religious obsessions, were considered responders.Low-frequency rTMS of the right prefrontal cortex failed to produce significant improvement of OCD and was not significantly different from sham treatment. Further studies are indicated to assess the efficacy of rTMS in OCD and to clarify the optimal stimulation characteristics.