tbuckley/cabot-search huggingface dataset:
A Mechanism for the Major Histocompatibility Complex–linked Resistance to Autoimmunity
Authors: Dennis Schmidt, Joan Verdaguer, Nuzhat Averill, Pere Santamaria
Journal: The Journal of Experimental Medicine (1997)

Certain major histocompatibility complex (MHC) class II haplotypes encode elements providing either susceptibility or dominant resistance to the development of spontaneous autoimmune diseases via mechanisms that remain undefined. Here we show that a pancreatic beta cell–reactive, I-Ag7–restricted, transgenic TCR that is highly diabetogenic in nonobese diabetic mice (H-2g7) undergoes thymocyte negative selection in diabetes-resistant H-2g7/b, H-2g7/k, H-2g7/q, and H-2g7/nb1 NOD mice by engaging antidiabetogenic MHC class II molecules on thymic bone marrow–derived cells, independently of endogenous superantigens. Thymocyte deletion is complete in the presence of I-Ab, I-Ak + I-Ek or I-Anb1 + I-Enb1 molecules, partial in the presence of I-Aq or I-Ak molecules alone, and absent in the presence of I-As molecules. Mice that delete the transgenic TCR develop variable degrees of insulitis that correlate with the extent of thymocyte deletion, but are invariably resistant to diabetes development. These results provide an explanation as to how protective MHC class II genes carried on one haplotype can override the genetic susceptibility to an autoimmune disease provided by allelic MHC class II genes carried on a second haplotype.
The universal basis of local linguistic exceptionality
Authors: Daniel Harbour
Journal: Behavioral and Brain Sciences (2009)

Abstract Evans &amp; Levinson (E&amp;L) claim Kiowa number as a prime example of the semantically unexpected, threatening both Universal Grammar and Linguistic Universals. This commentary, besides correcting factual errors, shows that the primitives required for Kiowa also explain two unrelated semantically unexpected patterns and derive two robust Linguistic Universals. Consequently, such apparent exceptionality argues strongly for Universal Grammar and against E&amp;L.
Benzodithiophenes Induce Differentiation and Apoptosis in Human Leukemia Cells
Authors: Yongkui Jing, Nella Hellinger, Lijuan Xia, Anne Monks, Edward A. Sausville, Arthur Zelent, Samuel Waxman
Journal: Cancer Research (2005)

Abstract All-trans retinoic acid (ATRA) induces clinical remission in patients with t(15;17) acute promyelocytic leukemia (APL) carrying leukemogenic promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion protein by overcoming PML-RARα transcriptional repression and inducing myeloid differentiation. To identify more potent chemical differentiation inducers, a screening assay was developed utilizing an ATRA-insensitive NB4 cell line (NB4-c) in which differentiation could be measured after 48 hours when primed with ATRA followed by other potential inducers. Over 300 cytostatic agents selected from the National Cancer Institute library were screened using this established method. Three compounds, NSC656243, NSC625748, and NSC144168, were identified to amplify ATRA-induced differentiation with acceptable cytotoxicity in NB4-c cells. In the absence of ATRA, these compounds also induced HL-60 and murine erythroleukemia cells to undergo partial differentiation. NSC656243, a benzodithiophene compound, was selected for further studies to examine the underlying mechanism of action. The differentiation effect of NSC656243 was associated with enhanced ATRA-mediated up-regulation of cell cycle regulatory proteins p21waf1 and p27kip1, retinoblastoma dephosphorylation, expression of RIG-E and RIG-G, and myelomonocytic differentiation–specific down-regulation of the myeloperoxidase (MPO) gene. Moreover, at 2- to 3-fold higher concentrations than those used to synergize with ATRA, NSC656243 induced apoptosis in NB4-c cells by reactive oxygen species–mediated pathways. The dual effects of benzodithiophenes (i.e., differentiation and apoptosis induction) support further development of these compounds as therapeutic agents for leukemia.
Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms?
Authors: T. M. Maher, A. U. Wells, G. J. Laurent
Journal: European Respiratory Journal (2007)

Idiopathic pulmonary fibrosis (IPF) is a devastating condition that carries a prognosis worse than that of many cancers. A recent classification of the idiopathic interstitial pneumonias has redefined the diagnostic criteria necessary to determine a diagnosis of IPF. The present authors believe that this redefinition is incorrect, relying as it does on subtle histological differences for the definition of separate disease categories. A further issue affecting IPF research is the polarisation of views around two competing pathogenetic hypotheses. One argues for the primacy of inflammation as the trigger that initiates fibrosis, and the other proposes that fibrosis arises as a consequence of chronic epithelial injury and failure of repair due to aberrant epithelial–mesenchymal interactions. The present authors believe that this schism is hampering understanding of IPF and skewing research priorities. It is argued here, instead, that abnormalities in multiple pathways involved in wound healing and inflammation lead to the development of idiopathic pulmonary fibrosis, and it is suggested that a new rationale for clinical classification and pathogenesis may be more productive in driving the search for novel therapies in the future.
The natural course of serrated lesions: a difficult enigma to resolve
Authors: J E G IJspeert, B A J Bastiaansen, P Fockens, E Dekker
Journal: Gut (2015)

Two types of sensory hair cells in the mammalian cochlea signal through anatomically distinct populations of spiral ganglion afferent neurons. The solitary inner hair cell ribbon synapse uses multivesicular release to trigger action potentials that encode acoustic timing, intensity, and frequency in each type I afferent. In contrast, cochlear outer hair cells (OHCs) have a far weaker effect on their postsynaptic targets, the type II spiral ganglion afferents. OHCs typically release single vesicles with low probability so that extensive summation is required to reach the relatively high action potential initiation threshold. These stark differences in synaptic transfer call into question whether type II neurons contribute to the cognitive perception of sound. Given the sparse and weak synaptic inputs from OHCs, the electrical properties of type II afferents are crucial in determining whether synaptic responses can sum to evoke an action potential to convey information to the cochlear nucleus. In the present work, dual-electrode recordings determined that type II afferents of rats have length constants that exceed the length of the distal, spiral process, enabling spatial summation from widespread OHCs. Focal application of tetrodotoxin localized the spike initiation zone to the type II proximal, radial process, near the spiral ganglion, in agreement with the high voltage threshold measured in the spiral process. These measured membrane properties were incorporated into a compartmental model of the type II neuron to demonstrate that neurotransmitter release from at least six OHCs is required to trigger an action potential in a type II neuron.
Risk Management: Extreme Honesty May Be the Best Policy
Authors: Steve S. Kraman, Ginny Hamm
Journal: Annals of Internal Medicine (1999)

This paper reviews a humanistic risk management policy that includes early injury review, steadfast maintenance of the relationship between the hospital and the patient, proactive full disclosure to patients who have been injured because of accidents or medical negligence, and fair compensation for injuries. The financial consequences of this type of policy are not yet known; however, one Veterans Affairs medical center, which has been using humanistic risk management since 1987, has had encouragingly moderate liability payments. The Department of Veterans Affairs now requires such a policy for all of its facilities; therefore, comprehensive experience may be only a few years away.
Manovolumetry: a new method for investigation of anorectal function.
Authors: S Akervall, S Fasth, S Nordgren, T Oresland, L Hulten
Journal: Gut (1988)

A new technique for manovolumetric investigation of rectoanal function allowing for simultaneous recording of rectal volume, anal pressure and external sphincter EMG in response to graded rectal distension was developed. Distension pressure was generated by a water column between two reservoirs. Volume was recorded as shifts of water between the reservoirs. Anal pressure was recorded with a cylindrical balloon and electromyographic activity of the external sphincter by means of a needle electrode. It could be shown that although reduction of preset pressure was minimal, this factor had to be taken into account when rectal compliance is high. The position of the patients during the investigation has to be defined, because rectal volume changed with body position. Pull through studies of anal pressure indicated low sensitivity to displacement of the cylindrical anal probe. A pressure adaptation to the anal probe during eight minutes was noted. Representative recordings of the anorectal response to different isobaric pressures are presented. The present system offers new possibilities for investigation of rectoanal physiology in man.
Influence of Fat and Carbohydrate Proportions on the Metabolic Profile in Patients With Type 2 Diabetes: A Meta-Analysis
Authors: Satoru Kodama, Kazumi Saito, Shiro Tanaka, Miho Maki, Yoko Yachi, Mutsumi Sato, Ayumi Sugawara, Kumiko Totsuka, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada, Hirohito Sone
Journal: Diabetes Care (2009)

The effects of dietary macronutrient composition on metabolic profiles in patients with type 2 diabetes have been inconsistent. This meta-analysis aimed to elucidate the effect of replacing dietary fat with carbohydrate on glucose and lipid parameters in patients with type 2 diabetes.We searched for randomized trials that investigated the effects of two kinds of prescribed diets (a low-fat, high-carbohydrate [LFHC] diet and a high-fat, low-carbohydrate [HFLC] diet); in these studies, energy and protein intake did not differ significantly between the two dietary groups. Nineteen studies that included 306 patients met our inclusion criteria. Median diet composition of carbohydrate/fat in the LFHC and HFLC diets was 58%/24% and 40%/40%, respectively.Changes in values for A1C, fasting plasma glucose (FPG), and total and LDL cholesterol did not differ significantly between the LFHC and HFLC groups. However, the LFHC diet significantly increased fasting insulin and triglycerides by 8% (P = 0.02) and 13% (P < 0.001), respectively, and lowered HDL cholesterol by 6% (P < 0.001) compared with the HFLC diet. There were positive associations among the magnitude of changes in FPG, fasting insulin, and triglycerides for the diets analyzed. However, stratified analysis indicated that the increase in triglycerides was insignificant when accompanied by energy intake restriction.Our findings suggested that replacing fat with carbohydrate could deteriorate insulin resistance while the adverse effect on triglycerides from the LFHC diet could be avoided by restricting energy intake to a degree sufficient for the attainment of weight reduction.
Combination of interferon alpha and ribavirin in chronic hepatitis C non responders to interferon monotherapy: role of genotype and age
Authors: S. Fargion, S. Bruno, M. Borzio, F. Bissoli, M. Zuin, A. Orlandi, P. Battezzati, A. Maraschi, A. Chiesa, G. Fiorelli, M. Podda
Journal: Journal of Hepatology (2001)
Kras, Pten, NF-κB, and Inflammation: Dangerous Liaisons
Authors: Paul J. Chiao, Jianhua Ling
Journal: Cancer Discovery (2011)

Abstract Ying and colleagues identify a novel function of Pten as a haploinsufficient tumor suppressor in human pancreatic cancer development. Genomic, genetic, and biochemical data reveal that Pten loss and Kras mutation cooperate to accelerate pancreatic cancer development by altering PI3K regulation to enhance NF-κB activation and upregulate downstream cytokine genes; this provides a protumorigenic and metastatic microenvironment. Cancer Discovery; 1(2); 103–5. ©2011 AACR. Commentary on Ying et al., p. 158
Human Papillomavirus 16 E5 Oncogene Contributes to Two Stages of Skin Carcinogenesis
Authors: John P. Maufort, Sybil M. Genther Williams, Henry C. Pitot, Paul F. Lambert
Journal: Cancer Research (2007)

Abstract High-risk human papillomaviruses (HPVs), which cause the vast majority of cervical cancer, other anogenital cancers, and a subset of head and neck squamous cell carcinomas, encode three oncogenes: E5, E6, and E7. To determine the oncogenic properties of HPV16 E5 in vivo, we previously generated K14E5 transgenic mice, in which expression of E5 was directed to the basal compartment of stratified squamous epithelia. In these mice, E5 induced epidermal hyperplasia and spontaneous skin tumors. In the current study, we determined how E5 contributes to tumor formation in the skin using a multistage model for skin carcinogenesis that specifies the role of genes in three stages: initiation, promotion, and malignant progression. Both initiation and promotion are required steps for papilloma formation. K14E5 mice treated with the initiating agent 7,12-dimethylbenz(a)anthracene (DMBA) developed more papillomas than like-treated nontransgenic mice, whereas neither K14E5 nor nontransgenic mice treated with the promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) developed papillomas. K14E5 mice treated with both DMBA and TPA to induce large numbers of papillomas had a higher incidence and earlier onset of carcinoma progression compared with like-treated nontransgenic mice. Thus, HPV16 E5 contributes to two stages of skin carcinogenesis: promotion and progression. The progressive neoplastic disease in K14E5 mice differed from that in nontransgenic mice in that benign tumors converted from exophytic to endophytic papillomas before progressing to carcinomas. Initial genetic and immunohistopathologic analyses did not determine the underlying basis for this distinct morphology, which correlates with a highly penetrant neoplastic phenotype. [Cancer Res 2007;67(13):6106–7]
Race and Insurance Differences in the Receipt of Adjuvant Chemotherapy Among Patients With Stage III Colon Cancer
Authors: Caitlin C. Murphy, Linda C. Harlan, Joan L. Warren, Ann M. Geiger
Journal: Journal of Clinical Oncology (2015)

Purpose Although the incidence and mortality of colon cancer in the United States has declined over the past two decades, blacks have worse outcomes than whites. Variations in treatment may contribute to mortality differentials. Methods Patients diagnosed with stage III colon cancer were randomly sampled from the SEER program from the years 1990, 1991, 1995, 2000, 2005, and 2010. Patients were categorized as non-Hispanic white (n = 835) or black (n = 384). Treatment data were obtained from a review of the medical records, and these data were verified through contact with the original treating physicians. Log-binomial regression models were used to estimate the association between race and receipt of adjuvant chemotherapy. Effect modification by insurance was assessed with use of single referent models. Results Receipt of adjuvant chemotherapy among both white and black patients increased from the period encompassing the years 1990 and 1991 (white, 58%; black, 45%) to the year 2005 (white, 72%; black, 71%) and then decreased in the year 2010 (white, 66%; black, 57%). There were marked racial disparities in the time period of 1990 to 1991 and again in 2010, with black patients less likely to receive adjuvant chemotherapy as compared with white patients (risk ratio [RR], .82; 95% CI, .72 to .93). For black patients, receipt of adjuvant chemotherapy did not differ across insurance categories (RR for private insurance, .80; 95% CI, .69 to .93; RR for Medicare, .84; 95% CI, .69 to 1.02; and RR for Medicaid, .84; 95% CI, .69 to 1.02), although a larger proportion had Medicaid in all years of the study as compared with white patients. Conclusion The chemotherapy differential narrowed after the time period of 1990 to 1991, but our findings suggest that the disparity reemerged in 2010. Recent decreases in chemotherapy use may be due, in part, to the economic downturn and an increase in Medicaid coverage.
Overexpression of<i>LAMP3/TSC403/DC-LAMP</i>Promotes Metastasis in Uterine Cervical Cancer
Authors: Hiroyuki Kanao, Takayuki Enomoto, Toshihiro Kimura, Masami Fujita, Ryuichi Nakashima, Yutaka Ueda, Yuko Ueno, Takashi Miyatake, Tatsuo Yoshizaki, Gregory S. Buzard, Akira Tanigami, Kiyoshi Yoshino, Yuji Murata
Journal: Cancer Research (2005)

LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer.
194 THE NATURAL HISTORY OF HEPATIC MACROREGENERATIVE NODULES DEVELOPING IN CIRRHOTIC PATIENTS DURING SURVEILLANCE WITH ULTRASOUND
Authors: A. Sangiovanni, C. Della Corte, M.A. Manini, M. Iavarone, S. Vavassori, R. Romeo, M. Fraquelli, A. Aghemo, M. Colombo
Journal: Journal of Hepatology (2010)
New Method for the Rapid Quantitation of Immunofluorescence 2
Authors: J. S. Haskill, M. J. Raymond
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article New Method for the Rapid Quantitation of Immunofluorescence Get access J. S. Haskill, J. S. Haskill Department of Pathology, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Raymond M. J. Raymond Department of Pathology, Queen's University and Kingston General Hospital, Kingston, Ontario, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 159–163, https://doi.org/10.1093/jnci/51.1.159 Published: 01 July 1973 Article history Received: 13 December 1972 Accepted: 06 March 1973 Published: 01 July 1973
Thrombin and plasmin generation in patients with liver disease
Authors: Hoyu Takahashi, Wataru Tatewaki, Ken Wada, Akira Yoshikawa
Journal: American Journal of Hematology (1989)

Abstract Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin‐antithrombin III complex (TAT) and plasmin‐α2‐antiplasmin complex (PAP) were measured together with cross‐linked fibrin derivatives (XDP), tissue‐type plasminogen activator (t‐PA), and plasminogen activator inhibitor (PAI‐1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 ± SD 4.0 μg/L), PAP (0.7 ± 0.7 mg/L), and XDP (374 ± 518 μg/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 ± 0.3 μg/L, PAP of 0.2 ± 0.1 mg/L, and XDP of 30 ± 14 μg/L; P &lt; 0.005). Plasma concentrations of t‐PA and PAI‐1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t‐PA/PAI‐1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.
ANGIOPOIETIN-LIKE 4 SERUM LEVELS ON ADMISSION FOR ACUTE MYOCARDIAL INFARCTION ARE ASSOCIATED WITH NO-REFLOW ASSESSED BY MAGNETIC RESONANCE IMAGING
Authors: Claire Bouleti, Jean Michel Serfaty, Thomas Mathivet, Nicolas Vignolles, Elodie Berland, Philippe Cluzel, Philippe Steg, Gilles Montalescot, Stephane Germain
Journal: Journal of the American College of Cardiology (2014)
Circulatory basophilia in guinea pigs with delayed‐type hypersensitivity
Authors: D. Sompolinsky, T. Katzenstein, L. Lundberg
Journal: Allergy (1992)

Circulatory basophilia could be induced in inbred guinea pigs systematically immunized with ovalbumin and consequently provoked repeatedly with dissolved ovalbumin applied onto the mucosa of the nares or the outer eye. The degree of the increase in circulatory basophil granulocytes depended on the adjuvant used and was significantly more pronounced after immunization with Freund's complete adjuvant than with alhydrogel (A1(OH)3). The degree of basophilia was also dependent on the animal strain, but different in two strains selected for high‐asthma trait.
Safety and tolerability of acute dosing of beta-blockers in asthma
Authors: Philip Short, William Anderson, Peter Williamson, Brian Lipworth
Journal: European Respiratory Journal (2013)

Objectives

We wished to assess the safety and tolerability of acute dosing of both propranolol and esmolol in mild-to-moderate asthmatics.

Methods

A secondary analysis of a double-blind randomised placebo controlled trial was performed ([NCT01074853][1]). Participants underwent dose titrations of propranolol (10mg BD, 20mg BD, 80mg OD). Prior to randomisation participants received an intravenous bolus dose of esmolol (0.5mg/kg). Spirometry, impulse oscillomtery and heart rate were recorded. For each dose titration of propranolol, tiotropium was given concurrently.

Results

12 participants completed: mean (SEM); age 37(5), FEV1% 93 (2), R5% 127 (12), ICS ug/day 390 (67) No significant difference was seen for FEV1% predicted or R5% predicted following esmolol use.

![Figure][2] 



There were reductions in heart rate, 2 minutes post esmolol, mean difference 4bpm (95%CI 1.2 -7.5). There were significant worsening of FEV1% (mean difference 4.1% (95%CI 0.22 – 7.9) and R5% 38.3% (95%CI 20.5 - 56.1) 45 minutes post 10mg propranolol. Tiotropium prevented any further bronchoconstriction post 45 minutes and also at each subsequent up-titration visit.

Conclusions

Acute esmolol dosing did not cause any worsening of pulmonary function within our cohort of asthmatics.

Acute propranolol dosing caused evidence of bronchoconstriction with a greater signal seen with impulse oscillometry.

Tiotropium prevented any further bronchoconstriction at up-titration visits.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01074853&atom=%2Ferj%2F42%2FSuppl_57%2FP3646.atom
 [2]: pending:yes