tbuckley/cabot-search huggingface dataset:
Role of T lymphocytes in rat 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis: increased mortality after gammadelta T cell depletion and no effect of alphabeta T cell depletion
Authors: J C Hoffmann
Journal: Gut (2001)

<h3>BACKGROUND AND AIM</h3> Indirect evidence suggests that CD4<sup>+</sup> T cells have a pathogenic while γδ T cells have a protective role in the initiation and perpetuation of inflammatory bowel disease. To define the role of T cell subsets in a rat colitis model (2,4,6-trinitrobenzene sulphonic acid (TNBS)) we analysed colitis severity after effective depletion of T helper cells, αβ Τ cells, or γδ T cells. <h3>METHODS</h3> T helper cells, αβ T cells, or γδ T cells were depleted using previously described monoclonal antibodies directed at the CD4 molecule (OX38), the CD2 molecule (OX34, both depleting CD4<sup>+</sup> T cells), the αβ T cell receptor (R73), and the γδ T cell receptor (V65). Depletion was verified by flow cytometry and/or immunohistology. Colitis was induced using intracolonic application of TNBS. <h3>RESULTS</h3> Surprisingly, depletion of T helper cells or αβ T cells had no influence on survival, macroscopic or microscopic scores, or myeloperoxidase activity following colitis induction. In contrast, depletion of γδ T cells resulted in significantly increased mortality (V65: 73%, n=15) compared with controls (30%, n=13; p&lt;0.03). In addition, colitis was histologically more severe in the γδ T cell depleted group compared with controls (p&lt;0.05). <h3>CONCLUSIONS</h3> T helper cells or αβ T cells did not influence the initiation or perpetuation of rat TNBS colitis. In contrast, γδ T cells had a protective role in rat TNBS colitis as depletion caused increased mortality.
Homology in classical and molecular biology.
Authors: C Patterson
Journal: Molecular Biology and Evolution (1988)

Hypotheses of homology are the basis of comparative morphology and comparative molecular biology. The kinds of homologous and nonhomologous relations in classical and molecular biology are explored through the three tests that may be applied to a hypothesis of homology: congruence, conjunction, and similarity. The same three tests apply in molecular comparisons and in morphology, and in each field they differentiate eight kinds of relation. These various relations are discussed and compared. The unit or standard of comparison differs in morphology and in molecular biology; in morphology it is the adult or life cycle, but with molecules it is the haploid genome. In morphology the congruence test is decisive in separating homology and nonhomology, whereas with molecular sequence data similarity is the decisive test. Consequences of this difference are that the boundary between homology and nonhomology is not the same in molecular biology as in morphology, that homology and synapomorphy can be equated in morphology but not in all molecular comparisons, and that there is no detected molecular equivalent of convergence. Since molecular homology may reflect either species phylogeny or gene phylogeny, there are more kinds of homologous relation between molecular sequences than in morphology. The terms paraxenology and plerology are proposed for two of these kinds--respectively, the consequence of multiple xenology and of gene conversion.
Cell Signaling and Neuronal Death
Authors: Makoto R. Hara, Solomon H. Snyder
Journal: The Annual Review of Pharmacology and Toxicology (2006)

The past few decades have revealed that cell death can be precisely programmed with two principal forms, apoptosis and necrosis. Besides pathophysiological alterations, physiologic processes, such as the pruning of neurons during normal development and the involution of the thymus, involve apoptosis. This review focuses on the role of inter- and intracellular signaling systems in cell death, especially in the nervous system. Among neurotransmitters, glutamate and nitric oxide have been most extensively characterized and contribute to cell death in excitotoxic damage, especially in stroke and possibly in neurodegenerative diseases. Within cells, calcium, the most prominent of all intracellular messengers, mediates diverse forms of cell death with actions modulated by many proteins, including IP3 receptors, calcineurin, calpain, and cytochrome c.
VALENTINE MOTT'S ANEURYSM NEEDLE FOR LIGATURE OF THE INNOMINATE AND SUBCLAVIAN ARTERIES
Authors: A. H. G. Doran
Journal: BMJ (1922)

IMEDICAL JOuRt 63 anus to the birth canal is a source of danger also.Unfor- tunately the vulva and vagina cannot be sterilized.The ante-partunL douche is, even in cases with obvious vaginal discharge, considered dangerous.The severity of-an attack of puerperal infection depends on tlle resistance of the patient, the time of infection, the site of
Bacterial Origin for the Isoprenoid Biosynthesis Enzyme HMG-CoA Reductase of the Archaeal Orders Thermoplasmatales and Archaeoglobales
Authors: Yan Boucher, Harald Huber, Stéphane L'Haridon, Karl O. Stetter, W. Ford Doolittle
Journal: Molecular Biology and Evolution (2001)

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase or HMGR) fulfills an essential role in archaea, as it is required for the synthesis of isoprenoid ethers, the main component of archaeal cell membranes. There are two clearly homologous but structurally different classes of the enzyme, one found mainly in eukaryotes and archaea (class 1), and the other found in bacteria (class 2). This feature facilitated the identification of several cases of interdomain lateral gene transfer (LGT), in particular, the bacterial origin for the HMGR gene from the archaeon Archaeoglobus fulgidus. In order to investigate if this LGT event was recent and limited in its scope or had a broad and long-term impact on the recipient and its related lineages, the HMGR gene was amplified and sequenced from a variety of archaea. The survey covered close relatives of A. fulgidus, the only archaeon known prior to this study to possess a bacterial-like HMGR; representatives of each main euryarchaeal group were also inspected. All culturable members of the archaeal group Archaeoglobales were found to display an HMGR very similar to the enzyme of the bacterium Pseudomonas mevalonii. Surprisingly, two species of the genus Thermoplasma also harbor an HMGR of bacterial origin highly similar to the enzymes found in the Archaeoglobales. Phylogenetic analyses of the HMGR gene and comparisons to reference phylogenies from other genes confirm a common bacterial origin for the HMGRs of Thermoplasmatales and Archaeoglobales. The most likely explanation of these results includes an initial bacteria-to-archaea transfer, followed by a another event between archaea. Their presence in two divergent archaeal lineages suggests an important adaptive role for these laterally transferred genes.
Neonatal Fc Receptor Promotes Immune Complex–Mediated Glomerular Disease
Authors: Florina Olaru, Wentian Luo, Hani Suleiman, Patricia L. St. John, Linna Ge, Adam R. Mezo, Andrey S. Shaw, Dale R. Abrahamson, Jeffrey H. Miner, Dorin-Bogdan Borza
Journal: Journal of the American Society of Nephrology (2013)

The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex–mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex–mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-α3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG.
Direct Estimates of Natural Selection in Iberia Indicate Calcium Absorption Was Not the Only Driver of Lactase Persistence in Europe
Authors: Oddný Ósk Sverrisdóttir, Adrian Timpson, Jamie Toombs, Cecile Lecoeur, Philippe Froguel, Jose Miguel Carretero, Juan Luis Arsuaga Ferreras, Anders Götherström, Mark G. Thomas
Journal: Molecular Biology and Evolution (2014)

Lactase persistence (LP) is a genetically determined trait whereby the enzyme lactase is expressed throughout adult life. Lactase is necessary for the digestion of lactose—the main carbohydrate in milk—and its production is downregulated after the weaning period in most humans and all other mammals studied. Several sources of evidence indicate that LP has evolved independently, in different parts of the world over the last 10,000 years, and has been subject to strong natural selection in dairying populations. In Europeans, LP is strongly associated with, and probably caused by, a single C to T mutation 13,910 bp upstream of the lactase (LCT) gene (-13,910*T). Despite a considerable body of research, the reasons why LP should provide such a strong selective advantage remain poorly understood. In this study, we examine one of the most widely cited hypotheses for selection on LP—that fresh milk consumption supplemented the poor vitamin D and calcium status of northern Europe's early farmers (the calcium assimilation hypothesis). We do this by testing for natural selection on -13,910*T using ancient DNA data from the skeletal remains of eight late Neolithic Iberian individuals, whom we would not expect to have poor vitamin D and calcium status because of relatively high incident UVB light levels. None of the eight samples successfully typed in the study had the derived T-allele. In addition, we reanalyze published data from French Neolithic remains to both test for population continuity and further examine the evolution of LP in the region. Using simulations that accommodate genetic drift, natural selection, uncertainty in calibrated radiocarbon dates, and sampling error, we find that natural selection is still required to explain the observed increase in allele frequency. We conclude that the calcium assimilation hypothesis is insufficient to explain the spread of LP in Europe.
A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E<sub>2</sub>concentrations
Authors: J M Bjordal, R A B Lopes-Martins, V V Iversen
Journal: British Journal of Sports Medicine (2005)

Background: Low level laser therapy (LLLT) has gained increasing popularity in the management of tendinopathy and arthritis. Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action. Objective: To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon. Subjects: Seven patients with bilateral Achilles tendinitis (14 tendons) who had aggravated symptoms produced by pain inducing activity immediately before the study. Method: Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm 2 ) and placebo LLLT (0 J) were administered to both Achilles tendons in random blinded order. Results: Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 (95% confidence interval 0.87 to 0.95). Prostaglandin E 2 concentrations were significantly reduced 75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026) and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after active LLLT compared with placebo LLLT: the mean difference in the change between the groups was 0.40 kg/cm 2 (95% confidence interval 0.10 to 0.70). Conclusion: LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis. LLLT may therefore have potential in the management of diseases with an inflammatory component.
A care-bundles approach to improving standard of care in AECOPD admissions: results of a national project: Table 1
Authors: AM Turner, WS Lim, C Rodrigo, SA Welham, JM Calvert
Journal: Thorax (2015)

This report describes a care bundles implementation project for COPD undertaken during 2013 in England and Wales. High-level data were collected on outcomes of care for 11 748 patients admitted with an acute exacerbation of COPD (AECOPD). Patient-level data on processes and outcomes of care were collected on 3272 COPD admissions, among which 1174 bundles were delivered. Analysis demonstrated a statistically significant reduction in mortality and length of hospital stay from some bundle elements. Outcomes, including bundle completion rates, were better when specialist respiratory review occurred. The results support wider use of care bundles for AECOPD.
Phase II Trial of Idiotype Vaccination in Previously Treated Patients With Indolent Non-Hodgkin’s Lymphoma Resulting in Durable Clinical Responses
Authors: Charles H. Redfern, Troy H. Guthrie, Alberto Bessudo, John J. Densmore, Peter R. Holman, Nalini Janakiraman, John P. Leonard, Richard L. Levy, Richard G. Just, Mitchell R. Smith, Fred P. Rosenfelt, Peter H. Wiernik, William D. Carter, Daniel P. Gold, Teresa J. Melink, John C. Gutheil, John F. Bender
Journal: Journal of Clinical Oncology (2006)

To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin's lymphoma.Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 mug on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated.Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id.This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.
Improving Metabolic Control Leads to Better Working Memory in Adults With Type 2 Diabetes
Authors: Christopher M. Ryan, Martin I. Freed, Julie A. Rood, Alexander R. Cobitz, Brian R. Waterhouse, Mark W.J. Strachan
Journal: Diabetes Care (2006)

The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance.This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery.Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1-2.3 mmol/l). Working memory improved with both rosiglitazone (P < 0.001) and glyburide (P = 0.017). Improvement (25-31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG.Similar and statistically significant cognitive improvement was observed with both rosiglitazone and glyburide therapy, and the magnitude of this effect was correlated with the degree to which FPG improved. These results suggest that a cognitive benefit is achievable with pharmacological interventions targeting glycemic control.
Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease
Authors: I. Comino, A. Real, L. de Lorenzo, H. Cornell, M. A. Lopez-Casado, F. Barro, P. Lorite, M. I. Torres, A. Cebolla, C. Sousa
Journal: Gut (2011)

<h3>Background and aims</h3> Coeliac disease (CD) is triggered by an abnormal reaction to gluten. Peptides resulting from partially digested gluten of wheat, barley or rye cause inflammation of the small intestinal mucosa. Previous contradictory studies suggest that oats may trigger the abnormal immunological response in patients with CD. Monoclonal antibodies (moAbs) against the main immunotoxic 33-mer peptide (A1 and G12) react strongly against wheat, barley and rye but have less reactivity against oats. The stated aim of this study is to test whether this observed reactivity could be related to the potential toxicity of oats for patients with CD. <h3>Methods</h3> In the present study, different oat varieties, controlled for their purity and by their distinct protein pattern, were used to examine differences in moAb G12 recognition by ELISA and western blot. Immunogenicity of oat varieties was determined by 33-mer concentration, T cell proliferation and interferon γ production. <h3>Results</h3> Three groups of oat cultivars reacting differently against moAb G12 could be distinguished: a group with considerable affinity, a group showing slight reactivity and a third with no detectable reactivity. The immunogenicity of the three types of oats as well as that of a positive and negative control was determined with isolated peripheral blood mononuclear T cells from patients with CD by measurement of cell proliferation and interferon γ release. A direct correlation of the reactivity with G12 and the immunogenicity of the different prolamins was observed. <h3>Conclusions</h3> The results showed that the reactivity of the moAb G12 is proportional to the potential immunotoxicity of the cereal cultivar. These differences may explain the different clinical responses observed in patients suffering from CD and open up a means to identify immunologically safe oat cultivars, which could be used to enrich a gluten-free diet.
Lymphocytic Interstitial Pneumonitis
Authors: C. VAUGHN STRIMLAN
Journal: Annals of Internal Medicine (1978)

Thirteen patients with lymphocytic interstitial pneumonitis were seen at the Mayo Clinic from 1966 through 1976. The group included nine women and four men, with a mean age of 50.7 years. Their primary complaints were cough, dyspnea, and loss of weight. Chest roentgenographic features were predominantly basilar, coarse interstitial-alveolar infiltrations. Pulmonary function studies showed restrictive ventilatory impairments with a low CO diffusing capacity in all 13 patients. Lung biopsies in all cases showed diffuse interstitial infiltrations, consisting of mature lymphocytes and plasma cells. Ten of the 13 patients had an associated dysproteinemia, including two patients with hypogammaglobulinemia. Three patients had coexistent Sjögren's syndrome, including two with localized amyloidosis. Although lymphocytic interstitial pneumonitis is a histologically distinct pulmonary lesions, it occurs with a variety of immune disorders.
SG-01 * FEEDBACK ACTIVATION OF EGFR VIA PTPN9 LEADS TO GLIOMA ESCAPE FROM BRAFV600E TARGETED THERAPY
Authors: T.-W. Yao, J. Zhang, M. Prados, W. Weiss, D. James, T. Nicolaides
Journal: Neuro-Oncology (2015)

Mutational activation of BRAF (BRAFV600E) is found in 10-67% of pediatric gliomas (depending on histopathologic subclassification) and drives aberrant MAPK signaling independently of upstream cues. BRAFV600E targeted monotherapy displays efficacy in pre-clinical models of glioma, however xenograft tumors adapt rapidly and escape from the growth-inhibitory effects of BRAF-targeted therapy. Here, we show that intrinsic resistance to a BRAFV600E specific inhibitor stems, in part, from feedback activation of EGFR and downstream signaling pathways. BRAFV600E inhibition suppresses MAPK signaling, which in turn downregulates the EGFR phosphatase PTPN9, resulting in sustained EGFR phosphorylation and enhanced EGFR activity. We further demonstrated that overexpression of PTPN9 reduces EGFR phosphorylation and cooperates with BRAFV600E inhibitor PLX4720 to suppress MAPK and Akt signaling, resulting in decreased glioma cell viability. Moreover, pharmacologic inhibition of EGFR combined with inhibition of BRAFV600E to reduce growth of glioma cell lines and orthotopic glioma xenograft by decreasing tumor cell proliferation while increasing apoptosis, with resultant significant extension of animal subject survival. Our data support clinical evaluation of BRAFV600E and EGFR targeted therapy in treating BRAFV600E glioma.
Complex Role of Histone Deacetylase Inhibitors in the Treatment of Non–Small-Cell Lung Cancer
Authors: Joel W. Neal, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2012)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2011.41.0860 Journal of Clinical Oncology - published online before print April 16, 2012 PMID: 22508823 Complex Role of Histone Deacetylase Inhibitors in the Treatment of Non–Small-Cell Lung Cancer Joel W. NealxJoel W. NealSearch for articles by this author Lecia V. SequistxLecia V. SequistSearch for articles by this author Show More Stanford Cancer Institute, Stanford, CAMassachusetts General Hospital Cancer Center, Boston, MA https://doi.org/10.1200/JCO.2011.41.0860 First Page Full Text PDF Figures and Tables © 2012 by American Society of Clinical Oncology