tbuckley/cabot-search huggingface dataset:
Bariatric Surgery and Urinary Incontinence
Authors: Deborah L. Myers
Journal: JAMA Internal Medicine (2015)

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Regulation of CD151 by Hypoxia Controls Cell Adhesion and Metastasis in Colorectal Cancer
Authors: Chun-Wei Chien, Shih-Chieh Lin, Yen-Yu Lai, Bo-Wen Lin, Shao-Chieh Lin, Jenq-Chang Lee, Shaw-Jenq Tsai
Journal: Clinical Cancer Research (2008)

The first step of metastasis is the detachment of cancer cells from the surrounding matrix and neighboring cells; however, how cancer cells accomplish this process remains unclear. Thus, we aimed to investigate the underlying mechanism that controls the early event of metastasis.One hundred and thirty-seven paired colorectal carcinoma and normal colon tissues were examined by immunohistochemical staining and Western blot for the expression of CD151, a member of the tetraspanin family that plays important roles in cell adhesion and motility. The effect of CD151 on cancer cell adhesion was investigated under normoxia and hypoxia conditions.The level of CD151 was down-regulated in colon cancer compared with the paired normal counterparts. Expression of CD151 was negatively regulated by hypoxia inducible factor-1-dependent hypoxic stress. Suppression of CD151 by hypoxia caused the detachment of cancer cells from the surrounding matrix and neighboring cells whereas restoration of CD151 expression during reoxygenation facilitated the adhesion capacity. Clinical examination further showed that metastasized cancer cells expressed a greater level of CD151 compared with that of primary tumor.Regulation of CD151 by oxygen tension may play an important role in cancer metastasis by regulating the detachment from the primary site and homing in the secondary site.
Fatal Pulmonary Lymphangiectasia Manifesting After Repeated Surgeries for Intractable Chylopericardium and Chylothorax in a 20-Month-Old Girl
Authors: Naoki Kamada, Yoshihide Mitani, Kentaro Kihira, Atsushi Iwao, Toshihiko Sinoki, Yukiko Ikeyama, Hirofumi Sawada, Takao Deguchi, Shin Takabayashi, Hideto Shimpo, Yoshihiro Komada
Journal: Circulation (2008)
Clinical and serological comparison of 17 chronic progressive systemic sclerosis (PSS) and 17 CREST syndrome patients matched for sex, age, and disease duration.
Authors: D E Furst, P J Clements, M Saab, M G Sterz, H E Paulus
Journal: Annals of the Rheumatic Diseases (1984)

This study compares the clinical and serological differences between 17 PSS and 17 carefully matched CREST patients. Patients were matched for sex, age by decade, and, importantly, disease duration (11.2 +/- 9.2 vs. 12.0 +/- 9.3 years). Muscular and skin involvement were greater for the PSS groups (p less than 0.02) and pulmonary involvement was also greater (p less than 0.05), at least for non-smoking PSS patients. On the other hand no clinically significant differences were found between groups for other visceral involvement--including comparisons of gastrointestinal, cardiovascular, and renal involvement. There were also no laboratory differences except in anti-RNP antibody (p less than 0.04).
Na <sup>+</sup> Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes
Authors: Colleen E. Clancy, Yoram Rudy
Journal: Circulation (2002)

Background — Complex physiological interactions determine the functional consequences of gene abnormalities and make mechanistic interpretation of phenotypes extremely difficult. A recent example is a single mutation in the C terminus of the cardiac Na + channel, 1795insD. The mutation causes two distinct clinical syndromes, long QT (LQT) and Brugada, leading to life-threatening cardiac arrhythmias. Coexistence of these syndromes is seemingly paradoxical; LQT is associated with enhanced Na + channel function, and Brugada with reduced function. Methods and Results — Using a computational approach, we demonstrate that the 1795insD mutation exerts variable effects depending on the myocardial substrate. We develop Markov models of the wild-type and 1795insD cardiac Na + channels. By incorporating the models into a virtual transgenic cell, we elucidate the mechanism by which 1795insD differentially disrupts cellular electrical behavior in epicardial and midmyocardial cell types. We provide a cellular mechanistic basis for the ECG abnormalities observed in patients carrying the 1795insD gene mutation. Conclusions — We demonstrate that the 1795insD mutation can cause both LQT and Brugada syndromes through interaction with the heterogeneous myocardium in a rate-dependent manner. The results highlight the complexity and multiplicity of genotype-phenotype relationships, and the usefulness of computational approaches in establishing a mechanistic link between genetic defects and functional abnormalities.
Statins and the Risk of Diabetes: Evidence From a Large Population-Based Cohort Study
Authors: Giovanni Corrao, Buthaina Ibrahim, Federica Nicotra, Davide Soranna, Luca Merlino, Alberico L. Catapano, Elena Tragni, Manuela Casula, Guido Grassi, Giuseppe Mancia
Journal: Diabetes Care (2014)

To investigate the relationship between adherence with statin therapy and the risk of developing diabetes.The cohort comprised 115,709 residents of the Italian Lombardy region who were newly treated with statins during 2003 and 2004. Patients were followed from the index prescription until 2010. During this period, patients who began therapy with an antidiabetic agent or were hospitalized for a main diagnosis of type 2 diabetes were identified (outcome). Adherence was measured by the proportion of days covered (PDC) with statins (exposure). A proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% CIs for the exposure-outcome association, after adjusting for several covariates. A set of sensitivity analyses was performed to account for sources of systematic uncertainty.During follow-up, 11,154 cohort members experienced the outcome. Compared with patients with very-low adherence (PDC <25%), those with low (26-50%), intermediate (51-75%), and high (≥75%) adherence to statin therapy had HRs (95% CIs) of 1.12 (1.06-1.18), 1.22 (1.14-1.27), and 1.32 (1.26-1.39), respectively.In a real-world setting, the risk of new-onset diabetes rises as adherence with statin therapy increases. Benefits of statins in reducing cardiovascular events clearly overwhelm the diabetes risk.
Neoadjuvant Chemotherapy Followed by Extrapleural Pneumonectomy in Malignant Pleural Mesothelioma: Is It Safe?
Authors: Güngör Utkan, Bülent Yalçin, Abdullah Büyükçelik, Samet Yalçin
Journal: Journal of Clinical Oncology (2005)

TO THE EDITOR: We read with interest the article by Weder et al. They conducted a pilot study with neoadjuvant gemcitabine and cisplatin followed by extrapleural pneumonectomy in patients with malignant pleural mesothelioma. The response rate to neoadjuvant chemotherapy was 32% and extrapleural pneumonectomy was performed in 16 of 19 patients. Thirteen patients received postoperative radiotherapy. Weder et al concluded that extrapleural pneumonectomy can be performed safely after neoadjuvant chemotherapy in an experienced center. Unfortunately, this conclusion is somewhat incorrect. Although Weder et al reported no perioperative death, the perioperative morbidity rate was quite high. Perioperative morbidity was observed in seven of the 16 patients (43.75%) on whom extrapleural pneumonectomy was performed: pulmonary embolism in one patient, chylothorax in three patients, thrombosis of the brachiocephalic vein in one patient, bronchopleural fistula in one patient, and pyothorax in one patient. Two patients were operated on for the treatment of these operative complications. Two patients were hospitalized for bleeding intrathoracically and retroperitoneally. It is unclear whether neoadjuvant chemotherapy is responsible for this high rate of perioperative morbidity. Therefore, the safety of this treatment modality should be questioned before further studies on uncured malignant pleural mesothelioma. Quality of life related to the treatment becomes more important in this group of patients because of the high rate of perioperative morbidity, and Weder et al should have assessed this in their study. On the other hand, although Weder et al reported in the abstract of their article that the major toxicity of neoadjuvant gemcitabine and cisplatin was thrombocytopenia, if we consider their Table 2, it is seen that grade 3 and 4 leukopenia and neutropenia are more frequent than thrombocytopenia. Gungor Utkan, Bulent Yalcin, and Abdullah Buyukcelik Department of Medical Oncology, Ankara University School of Medicine, Ibni Sina Hospital, Sihhiye, Ankara, Turkey.
Regression discontinuity designs: an approach to the evaluation of treatment efficacy in primary care using observational data
Authors: A. G. O'Keeffe, S. Geneletti, G. Baio, L. D. Sharples, I. Nazareth, I. Petersen
Journal: BMJ (2014)

<h3>Background</h3> JUUL is an electronic cigarette that aerosolises a nicotine-containing liquid, while IQOS heats tobacco to produce an aerosol. Both are marketed to smokers, but their effects have seldom been examined in this population. <h3>Methods</h3> Eighteen cigarette smokers (13 men) with no JUUL or IQOS experience completed a within-subject, laboratory study assessing nicotine delivery and subjective effects after controlled (10 puffs, ~30 s interpuff interval) and ad libitum (90 min) use of JUUL, IQOS or own-brand (OB) cigarettes. <h3>Results</h3> JUUL increased mean plasma nicotine concentration significantly from 2.2 (SD=0.7) ng/mL to 9.8 (4.9) ng/mL after 10 puffs and to 11.5 (9.3) ng/mL after ad libitum use. IQOS increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 12.7 (6.2) ng/mL after 10 puffs and to 11.3 (8.0) ng/mL after ad libitum use. OB increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 20.4 (11.4) ng/mL after 10 puffs and to 21.0 (10.2) ng/mL after ad libitum use. Mean OB plasma nicotine concentration was significantly higher than JUUL and IQOS. OB increased expired carbon monoxide concentration, but IQOS and JUUL did not. ‘Craving a cigarette/nicotine’ and ‘Urges to smoke’ were reduced significantly for all products following the directed bout. <h3>Conclusions</h3> Among smokers, JUUL and IQOS delivered less nicotine than cigarettes. Also, in this sample, IQOS and OB reduced abstinence symptoms more effectively than JUUL. Additional work with experienced JUUL and IQOS users is needed, as their nicotine delivery profiles and subjective experiences may differ.
Early Bactericidal Activity of Isoniazid in Pulmonary Tuberculosis
Authors: RICHARD HAFNER, JOHATHAN A. COHN, DAVID J. WRIGHT, NANCY E. DUNLAP, MERRILL J. EGORIN, MARY E. ENAMA, KATHERINE MUTH, CHARLES A. PELOQUIN, NATAN MOR, LEONID B. HEIFETS
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Early bactericidal activity (EBA) of antituberculosis drugs is the rate of decrease in the concentration of tubercle bacilli sputum during the initial days of therapy. The study reported here was designed to optimize the methodology for obtaining precise EBA measurements. The study compared the results with two versus five treatment days; overnight sputum collections with early morning collections; and quantitative smears for acid-fast bacilli (AFB) with quantitative cultures. Isoniazid (INH) was used as a model drug. Among 28 smear-positive patients enrolled in the study in five cities in the United States, 16 were evaluable (INH-susceptible tuberculosis [TB] and adequate sputum collections). The mean baseline bacterial load was 6.69 log10 cfu/ml (SE = 0.24). Quantitative culture of 10- or 12-h sputum collections obtained on two baseline days and treatment Day 5 was the optimal method for EBA measurement. The mean 5-d EBA was 0.21 log10 cfu/ml/d (SE = 0.03; p < 0.001), and the EBA appeared to be constant during the first five treatment days. On the basis of these data, multiarm studies of investigational drugs will require 25 evaluable subjects per arm to detect (80% power and two-tailed alpha of 0.05) an EBA at least 50% as large as the EBA of INH. In countries with a low incidence of TB, the usefulness of this methodology for rapidly assessing new antituberculosis agents may be limited by the relatively large number of subjects required to compare EBA values across treatment arms.
Deciphering the Signature of Selective Constraints on Cancerous Mitochondrial Genome
Authors: Jia Liu, Li-Dong Wang, Yan-Bo Sun, En-Min Li, Li-Yan Xu, Ya-Ping Zhang, Yong-Gang Yao, Qing-Peng Kong
Journal: Molecular Biology and Evolution (2011)

In accordance with the hypothesis that cancer formation is a process of somatic evolution driven by natural selection, signature of positive selection has been detected on a number of cancer-related nuclear genes. It remains, however, controversial whether a similar selective pressure has also acted on mitochondrial DNA (mtDNA), a small molecule in mitochondrion that may play an important role in tumorigenesis by altering oxidative phosphorylation. To better understand the mutational pattern on cancerous mtDNA and decipher the genetic signature left by natural selection, a total of 186 entire mitochondrial genomes of cancerous and adjacent normal tissues from 93 esophageal cancer patients were obtained and extensively studied. Our results revealed that the observed mutational pattern on the cancerous mtDNAs might be best explained as relaxation of negative selection. Taking into account an additional 1,235 cancerous (nearly) complete mtDNA sequences retrieved from the literature, our results suggested that the relaxed selective pressure was the most likely explanation for the accumulation of mtDNA variation in different types of cancer. This notion is in good agreement with the observation that aerobic glycolysis, instead of mitochondrial respiration, plays the key role in generating energy in cancer cells. Furthermore, our study provided solid evidence demonstrating that problems in some of the published cancerous mtDNA data adequately explained the previously contradictory conclusions about the selective pressure on cancer mtDNA, thus serving as a paradigm emphasizing the importance of data quality in affecting our understanding on the role of mtDNA in tumorigenesis.
A Novel Radiotracer to Image Glycogen Metabolism in Tumors by Positron Emission Tomography
Authors: Timothy H. Witney, Laurence Carroll, Israt S. Alam, Anil Chandrashekran, Quang-Dé Nguyen, Roberta Sala, Robert Harris, Ralph J. DeBerardinis, Roshan Agarwal, Eric O. Aboagye
Journal: Cancer Research (2014)

Abstract The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG–PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that 18F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3]triazole-4-yl)glucosamine (18F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating 18F-NFTG–associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited 18F-NFTG uptake, whereas oncogene (Rab25) activation–associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, 18F-NFTG, but not 18F-FDG uptake, increase proportionally with cell density and G1–G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence. Cancer Res; 74(5); 1319–28. ©2014 AACR.
Effects of Weight Loss Among Metabolically Healthy Obese Men and Women
Authors: Peter M. Janiszewski, Robert Ross
Journal: Diabetes Care (2010)

Weight loss among metabolically healthy obese (MHO) individuals may be unnecessary or result in elevated cardio-metabolic risk. We studied the effects of exercise- or diet-induced weight loss on cardio-metabolic risk among MHO and metabolically abnormal obese (MAO) adults.Participants were 63 MHO and 43 MAO adults who took part in 3 to 6 months of exercise- or diet-induced weight loss intervention. Changes in anthropometry, adipose tissue distribution, and cardio-metabolic risk factors were assessed.Body weight, waist circumference, and total abdominal and visceral adipose tissue were reduced in all subjects (P < 0.05). Improvements in insulin sensitivity were observed in MHO and MAO men and women (P < 0.05), but were greater in the MAO individuals (P < 0.05). Fasting insulin was the only other cardio-metabolic improvement among MHO individuals (P < 0.05).Lifestyle-induced weight loss among MHO subjects is associated with a reduction in total and abdominal obesity and improvement in selected cardio-metabolic risk factors.
The estimation of patient-specific cardiac diastolic functions from clinical measurements
Authors: Jiahe Xi, Pablo Lamata, Steven Niederer, Sander Land, Wenzhe Shi, Xiahai Zhuang, Sebastien Ourselin, Simon G. Duckett, Anoop K. Shetty, C. Aldo Rinaldi, Daniel Rueckert, Reza Razavi, Nic P. Smith
Journal: Medical Image Analysis (2012)

An unresolved issue in patients with diastolic dysfunction is that the estimation of myocardial stiffness cannot be decoupled from diastolic residual active tension (AT) because of the impaired ventricular relaxation during diastole. To address this problem, this paper presents a method for estimating diastolic mechanical parameters of the left ventricle (LV) from cine and tagged MRI measurements and LV cavity pressure recordings, separating the passive myocardial constitutive properties and diastolic residual AT. Dynamic C1-continuous meshes are automatically built from the anatomy and deformation captured from dynamic MRI sequences. Diastolic deformation is simulated using a mechanical model that combines passive and active material properties. The problem of non-uniqueness of constitutive parameter estimation using the well known Guccione law is characterized by reformulation of this law. Using this reformulated form, and by constraining the constitutive parameters to be constant across time points during diastole, we separate the effects of passive constitutive properties and the residual AT during diastolic relaxation. Finally, the method is applied to two clinical cases and one control, demonstrating that increased residual AT during diastole provides a potential novel index for delineating healthy and pathological cases.
Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice.
Authors: G R Gallo, T Caulin-Glaser, M E Lamm
Journal: Journal of Clinical Investigation (1981)

The effect of the charge of circulating immune complexes on glomerular localization was studied in a model of passive serum sickness. Preformed immune complexes of heterogeneous or restricted charge, prepared in vitro from isoelectrically focused or chemically modified proteins, were injected intravenously into mice. The distribution of immune complexes in the kidney was compared by immunofluorescence and electron microscopy. Cationic but not anionic or electrophoretically heterogeneous immune complexes gave rise to diffuse localization in the glomerular basement membrane. The binding in subepithelial and subendothelial sites correlated with the known distribution of structural anionic sites. The observations suggest that electrostatic interactions between fixed anionic sites and immune complexes may be an important factor in glomerular trapping. Alternative mechanisms based on initial localization of excess free cationic antigen cannot be completely excluded and are also considered.
Intestinal absorption of an arginine-containing peptide in cystinuria
Authors: A. M. Asatoor, B. D. W. Harrison, M. D. Milne, D. I. Prosser
Journal: Gut (1972)

Separate tolerance tests involving oral intake of the dipeptide, L-arginyl-L-aspartate, and of a corresponding free amino acid mixture, were carried out in a single type 2 cystinuric patient. Absorption of aspartate was within normal limits, whilst that of arginine was normal after the peptide but considerably reduced after the amino acid mixture. The results are compared with the increments of serum arginine found in eight normal subjects after the oral intake of the free amino acid mixture. Analyses of urinary pyrrolidine and of tetramethylenediamine in urine samples obtained after the two tolerance tests in the patient support the view that arginine absorption was subnormal after the amino acid mixture but within normal limits after the dipeptide.
THE QUESTION OF VERTEBRAL FRACTURES IN CONVULSIVE THERAPY AND IN EPILEPSY
Authors: HARRY J. WORTHING, LOTHAR B. KALINOWSKY
Journal: American Journal of Psychiatry (1942)

1. The considerable percentage of vertebral fractures in the middorsal region during metrazol convulsions can be reduced to a great extent by appropriate chemical or, better, simple mechanical means. 2. Reexamination of eight patients who had severe multiple fractures two years ago, showed no orthopedic or neurological signs of progressive pathology. 3. In electric shock therapy, even without precautions, these fractures are considerably less frequent. By applying an improved technique of extreme hyperextension, they can be avoided as was shown in 60 cases. 4. Seizures in epilepsy do not produce vertebral fractures in the middorsal region as demonstrated by a series of 42 epileptic patients. Fractures in other regions of the spine occur occasionally but they are of a different type and not comparable to the fractures in convulsive treatment. 5. Vertebral fractures in tetanus have the same localization, about the same frequency and multiplicity as those sustained in metrazol convulsive therapy done without precautions. 6. The varying frequency of vertebral fractures in the various convulsive conditions is explained by differences in the onset of the convulsion. 7. No contraindication against shock treatment can be seen in these fractures which can be largely avoided and which, if they do occur, have no clinical importance.