tbuckley/cabot-search huggingface dataset:
Modulating the intestinal immune system: the role of lymphotoxin and GALT organs
Authors: T W Spahn
Journal: Gut (2004)

he gut associated immune system fences off potentially harmful intestinal antigens from the systemic circulation and induces systemic tolerance against luminal antigens.Intestinal immune responses against luminal antigens include IgA secretion and induction of regulatory cells.Unlike few other cytokines, lymphotoxin a/b regulates the development of intestinal lymphoid organs.The embryonic development of Peyer's patches, postnatal lamina propria B cell development, and isolated lymphoid follicle development all depend on lymphotoxin b receptor interactions.Lymphotoxin a/b signalling also contributes to the development of mesenteric lymph nodes.In addition, intestinal inflammation is suppressed by inhibition of lymphotoxin b signalling, an observation which has initiated clinical studies using this treatment principal.Intestinal follicular lymphoid organs are sites of antigen presentation.Antigen presenting cells tune the delicate balance between intestinal immune tolerance and inflammation.Therefore, gut associated lymphatic organs and factors regulating their development are critical for the prevention of adverse immune reactions to intestinal antigens.This review provides an overview on the role of lymphotoxin and the gut associated lymphatic organs in the regulation of oral tolerance and intestinal inflammation.
ACC/AHA Key Data Elements and Definitions for Measuring the Clinical Management and Outcomes of Patients With Atrial Fibrillation
Authors: Robert L. McNamara, Lawrence M. Brass, Joseph P. Drozda, Alan S. Go, Jonathan L. Halperin, Charles R. Kerr, Samuel Lévy, David J. Malenka, Suneet Mittal, Frank Pelosi, Yves Rosenberg, Daniel Stryer, D. George Wyse, Martha J. Radford, David C. Goff, Frederick L. Grover, Paul A. Heidenreich, David J. Malenka, Eric D. Peterson, Rita F. Redberg
Journal: Circulation (2004)

than ever before.
The fat droplet in hepatocellular ballooning and implications for scoring nonalcoholic steatohepatitis therapeutic response
Authors: Curtis K. Argo, Yoshihiro Ikura, Carolin Lackner, Stephen H. Caldwell
Journal: Hepatology (2015)

Potential conflict of interest: Dr. Caldwell consults for Wellstat and received grants from Gilead, Immuron, and NGM. To the Editor: Histopathology serves as the cornerstone for translating disease pathophysiology. We were excited to see several articles in Hepatology involving hepatocellular ballooning, Sonic Hedgehog (SHH) expression, PNPLA3, and TM6 genetic variation, all of which seem to converge on the fat droplet.1 These findings support the previously reported association between fat droplet accumulation, hepatocyte enlargement, loss of keratin‐8,18 staining, and the presence of Mallory‐Denk bodies.7 We postulated that oxidative injury to fat droplets' phospholipid membrane impairs function of the proteins that govern insulin‐mediated access to the droplet, disrupts directional droplet trafficking along the cytoskeleton, and impedes small droplets' coalescence into stable macrovesicular droplets.9 We speculated that impaired droplet coalescence resulting from oxidative injury leads to "derelict" droplets prone ultimately to rancidification—a fitting component of the "undead" ballooned hepatocytes.10 The proposed TM6‐mediated reciprocal relationship between nonalcoholic steatohepatitis (NASH) and systemic dyslipidemia hearkens further to earlier fat droplet studies in alcoholic steatosis by Cairns et al.11 In contrast, we were disappointed to note perpetuation of misconceptions from the PIVENS trial in two of the articles, which dismissed pioglitazone as ineffective in NASH.1 The inconsistency in assessing ballooning by conventional hematoxylin and eosin staining and its marked effect on nonalcoholic fatty liver disease activity score (NAS) negatively affect the utility of a 2‐point NAS reduction as an outcome.13 In PIVENS, post‐hoc analysis of biopsies resulted in approximately 20% of all subjects not meeting entry criteria for ballooning.13 Based on the predetermined primary outcome of 2‐point NAS reduction, which was developed in a consensus conference and has never been validated,16 vitamin E was superior to pioglitazone. However, using the more reliable and meaningful histological endpoint, absence of definite NASH,17 pioglitazone was approximately twice as effective as vitamin E. The 2‐point NAS reduction as the primary outcome in NASH perpetuates a problematic, arbitrary endpoint. Clearly, ballooning is a critical pathophysiological finding and likely occurs across a spectrum in NASH. Future studies should consider how to better assess this key parameter and determine the most reproducible, clinically useful outcome related to disease pathophysiology.
Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review
Authors: N P Rowell
Journal: Thorax (2001)

To determine the effectiveness of radical radiotherapy in medically inoperable stage I/II non-small cell lung cancer (NSCLC) and the extent of treatment related morbidity.Randomised trials were sought by electronically searching the Cochrane Clinical Trials Register, and both randomised and non-randomised trials were sought by searching Medline and Excerpta Medica (Embase). Further studies were identified from references cited in those papers already identified by electronic searching. The studies included were those of patients of any age with stage I/II NSCLC receiving radiotherapy at a dose of >40 Gy in 20 fractions over 4 weeks or its radiobiological equivalent.Two randomised and 35 non-randomised studies were identified. One randomised and nine non-randomised studies did not meet the selection criteria, leaving one randomised and 26 non-randomised studies for analysis. In the randomised trial 2 year survival was higher following continuous hyperfractionated accelerated radiotherapy (CHART; 37%) than following 60 Gy in 30 fractions over 6 weeks (24%). An estimated 2003 patients were included in the 26 non-randomised studies; overall survival was 22-72% at 2 years, 17-55% at 3 years, and 0-42% at 5 years. Following treatment, 11-43% of patients died from causes other than cancer. Cancer specific survival was 54-93% at 2 years, 22-56% at 3 years, and 13-39% at 5 years. Complete response rates were 33-61% and local failure rates were 6-70%. Distant metastases developed in approximately 25% of patients. Better response rates and survival were seen in those with smaller tumours and in those receiving higher doses although the reasons for prescribing higher doses were not clearly stated. The outcome was worse in those with prior weight loss or poor performance status. Assessment of treatment related morbidity and effects on quality of life and symptom control were inconclusive because of the lack of prospective evaluation and paucity of data.No randomised trials compared a policy of immediate radical radiotherapy with palliative radiotherapy given when patients develop symptoms. In the absence of such trials, radical radiotherapy appears to result in a better survival than might be expected had treatment not been given. A substantial, though variable, proportion of patients died during follow up from causes other than cancer. The optimal radiation dose and treatment technique (particularly with respect to mediastinal irradiation) remain uncertain.
Distribution and Evolution of the Mobile vma-1b Intein
Authors: Kristen S. Swithers, Shannon M. Soucy, Erica Lasek-Nesselquist, Pascal Lapierre, Johann Peter Gogarten
Journal: Molecular Biology and Evolution (2013)

Inteins are self-splicing parasitic genetic elements found in all domains of life. These genetic elements are found in highly conserved positions in conserved proteins. One protein family that has been invaded by inteins is the vacuolar and archaeal catalytic ATPase subunits (vma-1). There are two intein insertion sites in this protein, “a” and “b.” The b site was previously thought to be only invaded in archaeal lineages. Here we survey the distribution and evolutionary histories of the b site inteins and show that the intein is present in more lineages than previously annotated, including a bacterial lineage, Mahella australiensis 50-1 BON. We present evidence, through ancestral character state reconstruction and substitution ratios between host genes and inteins, for several transfers of this intein between divergent species, including an interdomain transfer between the archaea and bacteria. Although inteins may persist within a single population or species for long periods of time, transfer of the vma-1b intein between divergent species contributed to the distribution of this intein.
Exacerbation frequency and FEV1 decline of COPD: is it geographic?
Authors: Terence A.R. Seemungal, Jadwiga A. Wedzicha
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) exacerbations are episodes of symptom worsening that have major impacts on a variety of health outcomes, including quality of life, hospital admission and death [1]. Exacerbation reduction is now a key outcome for pharmacological therapies in COPD and, thus, if exacerbation can be prevented how does this affect disease progression and lung function decline?

The issue of the importance of lung function decline in COPD first arose when Fletcher and Peto [2] explored lung function in a cohort of 792 male British postal workers. These subjects were studied over 8 years and it was found that exacerbations were associated with the ratio of forced expiratory volume in 1 s (FEV1) to the cube of the height, although the exacerbation definition was limited at that time. This work was followed in close succession by a study from Utah in which Kanner et al. [3] showed that exacerbation frequency was related to COPD severity, thus implicating exacerbation frequency as a factor in FEV1 decline. However, detecting the relationship proved elusive until the Lung Health Study showed that in smokers and intermittent quitters each additional exacerbation reported to physicians caused a greater annual decline of 7 mL [4]. The following …
Formation of a Free Floating Left Atrial Thrombus Despite Three Weeks of Anticoagulation
Authors: M. Timur Selcuk, Hatice Selcuk, Bilal Geyik, Irfan Sabah
Journal: Circulation (2002)

A 46-year-old woman with exertional dyspnea conse- quent to severe rheumatic mitral valvular stenosis had a small thrombus in the left atrial appendage documented by transesophageal echocardiography.Warfarin and aspirin therapy was instituted, and she was referred for elective surgical repair.Three weeks later she was admitted for acute pulmonary edema.An immediate echocardiogram revealed a 2.8ϫ2.9-cmfree-floating, spheric-shaped thrombus within the left atrial cavity.The thrombus was free from the atrial wall, moving within the cavity.It had a recurring, rhythmic motion in the left atrium while intermittently obstructing the mitral orifice (Figures 1 and
Familial Pulmonary <i>Mycobacterium avium</i>Complex Disease
Authors: EISAKU TANAKA, TERUMI KIMOTO, HISAKO MATSUMOTO, KAZUNARI TSUYUGUCHI, KATSUHIRO SUZUKI, SONOKO NAGAI, MITSUNOBU SHIMADZU, HIDEAKI ISHIBATAKE, TAKAKO MURAYAMA, RYOICHI AMITANI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We report two Japanese families affected by pulmonary Mycobacterium avium complex (MAC) disease, involving an older brother and younger sister in one family and two brothers in the second family. We investigated whether defects in the natural resistance-associated macrophage protein gene (NRAMP1) underlay susceptibility to MAC in these cases. All of the patients had computed tomographic findings of peripheral nodules and bronchiectasis. Pulse-field gel electrophoresis patterns of mycobacterial genomic DNA restriction fragments revealed that none of the MAC strains isolated from the patients was epidemiologically related to any of the others. Direct sequencing of the complementary DNA of the patients' NRAMP1 revealed a nonconservative missense mutation at codon 419 in one patient, which was heterozygous and was not seen in his affected sibling. No variations similar to those found in mice that show susceptibility to MAC were found. The results suggest an underlying genetic defect in host defense rather than exposure to an unusually virulent strain of MAC as the pathogenetic factor in MAC disease; however, alterations in the coding region of NRAMP1 do not appear to explain the susceptibility to MAC.
Patient perception of the benefit of a BRAF inhibitor in metastatic melanoma: quality-of-life analyses of the BREAK-3 study comparing dabrafenib with dacarbazine
Authors: J.-J. Grob, M.M. Amonkar, S. Martin-Algarra, L.V. Demidov, V. Goodman, K. Grotzinger, P. Haney, E. Kämpgen, B. Karaszewska, C. Mauch, W.H. Miller, M. Millward, B. Mirakhur, P. Rutkowski, V. Chiarion-Sileni, S. Swann, A. Hauschild
Journal: Annals of Oncology (2014)
The Metastasis-Associated microRNA miR-516a-3p Is a Novel Therapeutic Target for Inhibiting Peritoneal Dissemination of Human Scirrhous Gastric Cancer
Authors: Yoshifumi Takei, Misato Takigahira, Keichiro Mihara, Yuzo Tarumi, Kazuyoshi Yanagihara
Journal: Cancer Research (2010)

Although aberrant microRNA (miRNA) is expressed in different types of human cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and metastasis are still largely unknown. Here, we defined miRNAs involved in cancer metastasis (metastamirs) using an established mouse model for peritoneal dissemination of human scirrhous gastric carcinoma cells. Highly metastatic derivatives (44As3 cells) were derived from the parental cells originally isolated from patients (HSC-44PE cells). Using microarray analysis to identify differentially expressed miRNAs in 44As3 and HSC-44PE cells, we focused on miR-516a-3p as a candidate antimetastatic miRNA (antimetastamir) whose functions in cancer had not been studied. We confirmed attenuated expression of miR-516a-3p in 44As3 cells compared with HSC-44PE cells by Northern blot analysis and quantitative reverse transcriptase PCR. Stable ectopic overexpression in 44As3-miR-516a-3p cells permitted identification of sulfatase 1 as a direct target of the miRNA, through use of the isobaric tagging reagent iTRAQ and the QSTAR Elite Hybrid LC-MS/MS system. Sulfatase 1 is known to remove 6-O-sulfates from heparan sulfate proteoglycans on the cell surface, causing release of membrane-bound Wnt ligands from cells. Consistent with this function, Western blot analyses revealed high levels of Wnt3a, Wnt5a, and nuclear β-catenin accumulation in 44As3 cells but relatively reduced levels in 44As3-miR-516a-3p cells. Notably, orthotopic inoculation of nude mice with 44As3-miR-516a-3p cells yielded significantly longer survival periods compared with mice inoculated with control 44As3 cells. Through atelocollagen-mediated delivery of an miR-516a-3p expression vector into orthotopic 44As3 tumors, we documented its feasibility as a treatment agent. Our findings define the miRNA miR-516-3p as an antimetastamir with potential therapeutic applications in blocking metastatic dissemination of gastric cancers.
RESISTANCE TO PUERPERAL INFECTION
Authors: A. R. Gunn
Journal: BMJ (1909)

<h3>Introduction</h3> In our previous pilot study on the internet I Want The Kit (IWTK) home self-collection program for sexually transmitted infections (STIs), a voluntary risk score tool predicted STIs well for the female volunteers but not for the males. We investigated the association of IWTK risk score and the presence of STIs in male users when the risk score quiz became mandatory for the program. <h3>Methods</h3> A six-question quiz which includes demographic and sexual risk behaviour became a mandatory part of IWTK in August 2103. This analysis was restricted to male participants living in Maryland and Washington DC using IWTK August 2013–April 2015. Cochran-Armitage trend test was performed to determine if the prevalence of STIs (chlamydia, gonorrhoea, or trichomonas infection) increased with the higher score of risk score category. <h3>Results</h3> Overall, 592 male participants submitted specimens for STI testing and completed risk score quizzes. The majority (57%) were &lt; 30 years (mean: 30.1 ± 9.3 years); 42% white, 42% black, and 16% other races. 203 (34.3%) resided in zip codes of Baltimore City. The majority (53%) of the participants had risk score of 4–6, followed by scores of 0–3 (25%), and &nbsp;7–10 (22%). The overall prevalence of STIs was 10.5% (62/592). The prevalence of STIs was 6.2% for users with risk score of 0–3, 10.9% for those with 4–6, and 14.3% for those with &nbsp;7–10 (trend test: p = 0.026). 52% (13/25) of STI positive participants resided in three zip codes located in central and northeast Baltimore City and participants in these three zip codes had a marginally higher risk score than others (p = 0.082). <h3>Conclusions</h3> After excluding potential selection bias, IWTK risk score tool predicted the presence of STIs for male users and could potentially be used for identifying hotspots for STI intervention. <h3>Disclosure of interest statement</h3> The research group has received research funding from U54EB007958, NIBIB, NIH; AI068613–01, NIH, NIAID.
Frequency and Severity of Enlarged Cavum Septi Pellucidi in Childhood-Onset Schizophrenia
Authors: P C Nopoulos, J N Giedd, N C Andreasen, J L Rapoport
Journal: American Journal of Psychiatry (1998)

Patients with schizophrenia have been reported to have a higher frequency of enlarged cavum septi pellucidi (CSP) in comparison with normal subjects. Neurodevelopmental models of schizophrenia suggest that the more severe the brain dysgenesis, the earlier the onset of psychotic symptoms. Study of patients with childhood-onset schizophrenia allows the opportunity to test this hypothesis.Two groups of subjects were evaluated: healthy volunteers (N=95, mean age=11.7 years) and patients with childhood-onset schizophrenia (N=24, mean age=14.6 years). Magnetic resonance images of 1-mm resampled contiguous brain slices were rated blind to diagnosis. The size of the CSP was recorded as the number of consecutive slices in which the CSP was present. Abnormal enlargement was defined as a CSP greater than 6 mm in length.The frequency of an enlarged CSP was significantly higher in the patient group: 12.5% (three of 24 subjects) versus 1.1% (one of 95 subjects). Also, two of the three patients with an enlarged CSP had complete nonfusion of the septal leaflets, a more severe anomaly than was found in the one comparison subject with an enlarged CSP and typically more severe than anomalies seen in groups with adult-onset schizophrenia.These findings suggest that patients with extremely early-onset (childhood) forms of schizophrenia may have more severe developmental brain anomalies than those with adult onset.
gp72, the 72 kilodalton glycoprotein, is the membrane acceptor site for C3 on Trypanosoma cruzi epimastigotes.
Authors: K Joiner, S Hieny, L V Kirchhoff, A Sher
Journal: The Journal of Experimental Medicine (1985)

We examined the interaction of complement component C3 with surface molecules on Trypanosoma cruzi. Five- to six-fold more C3 was bound to epimastigotes (Epi) than to metacyclic trypomastigotes (CMT) of strain M88. Epi and CMT were surface iodinated, then incubated in C8-deficient serum, and detergent lysates were applied to anti-C3 antibody that had been coupled to Sepharose. We found that 9.20-10.24% of applied 125I-Epi protein bound to anti-C3-sepharose, compared to 2.64% binding of 125I-CMT protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that C3 was attached to 125I-Epi protein by a covalent bond. Samples eluted from anti-C3-sepharose with hydroxylamine revealed a single, major, 72 kD band, suggesting that C3b attaches almost exclusively to the 72 kD glycoprotein of Epi by a hydroxylamine-susceptible ester bond. An antiserum was prepared from lysates of serum-treated Epi that had been affinity-purified on anti-C3-sepharose. This antiserum immunoprecipitated a single 72 kD component (gp72) from surface-iodinated Epi, and specifically recognized only gp72 from Epi in immunoblots. In contrast to the results with Epi, gp72 on CMT was not found to be an efficient acceptor molecule for C3 deposition. The results are the first to evaluate the acceptor site for C3 deposition on a parasite, and they show that gp72 on Epi, but not gp72 on CMT, serves as the preferential acceptor for C3 during antibody-independent alternative complement pathway activation.
Hamartoma of the thoracic wall
Authors: S. Gupta, N. C. Pal
Journal: Thorax (1972)

A 16-year-old boy presented with a slowly growing tumour of the chest wall involving the posterior ends of the second and third ribs on the left side and the corresponding vertebrae. The tumour on excision was a well-localized growth with a bony shell, the second and third ribs originating from its anterior end. Histological studies showed a benign tumour with haphazard distribution of bony spicules, smooth muscle, adipose tissue, angiomatous tissue, nerve bundles, and lymph follicles. This was diagnosed as a hamartoma of the thoracic wall.
Racial/Ethnic and Gender Gaps in the Use of and Adherence to Evidence-Based Preventive Therapies Among Elderly Medicare Part D Beneficiaries After Acute Myocardial Infarction
Authors: Julie C. Lauffenburger, Jennifer G. Robinson, Christine Oramasionwu, Gang Fang
Journal: Circulation (2013)

It is unclear whether gender and racial/ethnic gaps in the use of and patient adherence to β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins after acute myocardial infarction have persisted after establishment of the Medicare Part D prescription program.
Motor Functions of the Superior Colliculus
Authors: Neeraj J. Gandhi, Husam A. Katnani
Journal: Annual Review of Neuroscience (2011)

The mammalian superior colliculus (SC) and its nonmammalian homolog, the optic tectum, constitute a major node in processing sensory information, incorporating cognitive factors, and issuing motor commands. The resulting action-to orient toward or away from a stimulus-can be accomplished as an integrated movement across oculomotor, cephalomotor, and skeletomotor effectors. The SC also participates in preserving fixation during intersaccadic intervals. This review highlights the repertoire of movements attributed to SC function and analyzes the significance of results obtained from causality-based experiments (microstimulation and inactivation). The mechanisms potentially used to decode the population activity in the SC into an appropriate movement command are also discussed.