tbuckley/cabot-search huggingface dataset:
Biofeedback-Assisted Relaxation in Type 2 Diabetes
Authors: Ronald A. McGinnis, Angele McGrady, Stephen A. Cox, Kimber A. Grower-Dowling
Journal: Diabetes Care (2005)

OBJECTIVE—The objective of this randomized controlled study was to determine the effects of biofeedback and relaxation on blood glucose and HbA1c (A1C) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes were randomized to either 10 sessions of biofeedback (electromyograph and thermal) and relaxation or 3 sessions of education. All sessions were individual. A total of 39 participants were entered, and 30 completed the 3-month protocol. Average blood glucose, A1C, forehead muscle tension, and peripheral skin temperature were assessed, and inventories measuring depression and anxiety were administered prerandomization and after completion of treatment/control. RESULTS—Biofeedback and relaxation were associated with significant decreases in average blood glucose, A1C, and muscle tension compared with the control group. At 3-month follow-up, the treatment group continued to demonstrate lower blood glucose and A1C. Both groups decreased scores on the depression and anxiety inventories. Patients with depression had higher blood glucose levels and tended to drop out of the study. CONCLUSIONS—This study supports the use of biofeedback and relaxation in patients with type 2 diabetes for up to 3 months after treatment. Further research is necessary to determine the long-term effects of biofeedback and the effects of mood on patients’ responses to treatment.
Nocturnal asthma: effects of slow-release terbutaline on spirometry and arterial blood-gases
Authors: L Eriksson, B Jonson, G Eklundh, G Persson
Journal: European Respiratory Journal (1988)

The effect of terbutaline, in a slow-release preparation, on spirometry and arterial blood-gases, was studied in fourteen patients with nocturnal asthma. The patients were treated with either 15 mg of slow-release terbutaline or placebo given as a single dose at 10 pm for eight days in a double-blind crossover trial. The patients were studied in the hospital for one night at the end of each treatment period. During active treatment the patients had a significantly higher FEV1 and PaO2 compared with placebo. Tolerance to the high single dose was good and none of the patients discontinued treatment because of side-effects. In patients with nocturnal asthma treatment with a high dose of slow-release terbutaline given as a single dose in the evening appears to be effective.
Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance
Authors: Juan Dubrot, Fernanda V. Duraes, Lambert Potin, Francesca Capotosti, Dale Brighouse, Tobias Suter, Salomé LeibundGut-Landmann, Natalio Garbi, Walter Reith, Melody A. Swartz, Stéphanie Hugues
Journal: The Journal of Experimental Medicine (2014)

Dendritic cells (DCs), and more recently lymph node stromal cells (LNSCs), have been described to tolerize self-reactive CD8+ T cells in LNs. Although LNSCs express MHCII, it is unknown whether they can also impact CD4+ T cell functions. We show that the promoter IV (pIV) of class II transactivator (CIITA), the master regulator of MHCII expression, controls endogenous MHCII expression by LNSCs. Unexpectedly, LNSCs also acquire peptide–MHCII complexes from DCs and induce CD4+ T cell dysfunction by presenting transferred complexes to naive CD4+ T cells and preventing their proliferation and survival. Our data reveals a novel, alternative mechanism where LN-resident stromal cells tolerize CD4+ T cells through the presentation of self-antigens via transferred peptide–MHCII complexes of DC origin.
Tumor Cell-Microenvironment Interaction Models Coupled with Clinical Validation Reveal CCL2 and SNCG as Two Predictors of Colorectal Cancer Hepatic Metastasis
Authors: Hai Hu, Lichao Sun, Chunguang Guo, Qian Liu, Zhuan Zhou, Liang Peng, Jian Pan, Long Yu, Jinning Lou, Zhihua Yang, Ping Zhao, Yuliang Ran
Journal: Clinical Cancer Research (2009)

This study aimed to identify novel biological markers for the prediction of colorectal cancer liver metastasis.We established two models that mimicked the interactions between colorectal tumor cells and the liver microenvironment. From these models we established subcell lines that had an enhanced ability to metastasize to the liver. Genes that related to hepatic metastasis were screened by microarray. The candidate markers were tested by immunohistochemistry, and their predictive accuracy was assessed by the cross-validation method and an independent test set.Highly metastatic colon cancer cell sublines SW1116p21 and SW1116v3 were established from the tumor cell-microenvironment interaction models. Seven of the up-regulated genes in the sublines were selected as candidate markers for predicting metastatic potential. A total of 245 colorectal cancer samples were divided into a training set containing 117 cases and a test set containing 128 cases. In the training set, immunohistochemical analysis showed CCL2 and SNCG expression was higher in the hepatic metastasis group than in the nonmetastasis group, and was correlated with poor survival. Logistic regression analysis revealed that CCL2 and SNCG levels in primary tumors, serum carcinoembryonic antigen level, and lymph node metastasis status were the only significant (P < 0.05) parameters for detecting liver metastasis. In leave-one-out-cross-validation, the two markers, when combined with clinicopathologic features, resulted in 90.5% sensitivity and 90.7% specificity for hepatic metastasis detection. In an independent test set, the combination achieved 87.5% sensitivity and 82% specificity for predicting the future hepatic metastasis of colorectal cancer.Our results suggest that these models are able to mimic the interactions between colorectal cancer cells and the liver microenvironment, and may represent a promising strategy to identify metastasis-related genes. CCL2 and SNCG, combined with clinicopathologic features, may be used as accurate predictors of liver metastasis in colorectal cancer.
Nitric Oxide and Its Gatekeeper Thrombospondin-1 in Tumor Angiogenesis
Authors: David D. Roberts, Jeffery S. Isenberg, Lisa A. Ridnour, David A. Wink
Journal: Clinical Cancer Research (2007)

Nitric oxide (NO) plays a central role in angiogenesis as a mediator of signaling by vascular endothelial growth factor and other angiogenic factors. Low concentrations of NO produced in response to angiogenic factors stimulate angiogenesis, whereas higher concentrations typical of inflammatory responses inhibit angiogenesis. The proangiogenic activity of NO is mediated by activation of soluble guanylyl cyclase, leading to cyclic guanosine 3',5'-monophosphate accumulation and activation of its target kinases and ion channels. The four angiogenesis inhibitors currently approved for clinical use target components of the signaling cascade upstream of NO. New research has identified components downstream of NO as the primary target of the endogenous angiogenesis inhibitor thrombospondin-1 and has shown that circulating levels of thrombospondin-1 are sufficient to limit angiogenic responses by antagonizing NO signaling. This provides new insights into the significance of the widespread loss of thrombospondin-1 expression during malignant progression. Although clinical trials suggest that blocking NO signaling can inhibit tumor angiogenesis, this approach also inactivates inhibitory signaling from thrombospondin-1. We discuss the implications of the balance between these pathways for applying thrombospondin-1 mimetics and redox modifiers as cancer therapeutics.
Pkd1 Inactivation Induced in Adulthood Produces Focal Cystic Disease
Authors: Ayumi Takakura, Leah Contrino, Alexander W. Beck, Jing Zhou
Journal: Journal of the American Society of Nephrology (2008)

Autosomal dominant polycystic kidney disease, the most common monogenetic disorder, is characterized by gradual replacement of normal renal parenchyma by fluid-filled cysts. Mutations in either <i>PKD1</i> or <i>PKD2</i> cause autosomal dominant polycystic kidney disease. <i>Pkd1</i><sup>−/−</sup> or <i>Pkd2</i><sup>−/−</sup> mice develop rapid renal cystic disease and exhibit embryonic lethality; this supports the “two-hit” hypothesis, which proposes that a germline mutation in <i>PKD1</i> (or <i>PKD2</i>) followed by a second somatic mutation later in life is responsible for the phenotype. Here, for investigation of the loss of <i>Pkd1</i> at specific times of development, an inducible <i>Pkd1</i>-knockout mouse model was generated. Inactivation of <i>Pkd1</i> in 5-wk-old mice resulted in formation of only focal renal cysts 6 to 9 wk later but in a severe polycystic phenotype nearly 1 yr later. Cysts derived from either collecting tubules or distal tubules but not from proximal tubules, which correlated with sites of Cre-mediated recombination. Inactivation of <i>Pkd1</i> in 1-wk-old mice, however, resulted in massive cyst disease 6 wk later, despite a similar pattern of Cre-mediated recombination between 1- and 5-wk-old kidneys. Moreover, a germline heterozygous <i>Pkd1</i> mutation facilitated cyst formation when a somatic <i>Pkd1</i> mutation was induced. A marked increase in proliferating cell nuclear antigen expression was observed in cyst-lining epithelia and in normal-looking tubules adjacent to but not in those distant from cysts. These data suggest that <i>Pkd1</i> inactivation is not sufficient to initiate the cell proliferation necessary for cyst formation; a paracrine mechanism may account for focal cell proliferation and regional disease progression. We propose that an additional genetic or nongenetic “third hit” may be required for rapid development of cysts in polycystic kidney disease.
IFR-9/STAT2 Functional Interaction Drives Retinoic Acid–Induced Gene G Expression Independently of STAT1
Authors: Ye-Jiang Lou, Xiao-Rong Pan, Pei-Min Jia, Dong Li, Shu Xiao, Zhang-Lin Zhang, Sai-Juan Chen, Zhu Chen, Jian-Hua Tong
Journal: Cancer Research (2009)

Retinoic acid-induced gene G (RIG-G), a gene originally identified in all-trans retinoic acid-treated NB4 acute promyelocytic leukemia cells, is also induced by IFNalpha in various hematopoietic and solid tumor cells. Our previous work showed that RIG-G possessed a potent antiproliferative activity. However, the mechanism for the transcriptional regulation of RIG-G gene remains unknown. Here, we report that signal transducer and activator of transcription (STAT) 2 together with IFN regulatory factor (IRF)-9 can effectively drive the transcription of RIG-G gene by their functional interaction through a STAT1-independent manner, even without the tyrosine phosphorylation of STAT2. The complex IRF-9/STAT2 is both necessary and sufficient for RIG-G gene expression. In addition, IRF-1 is also able to induce RIG-G gene expression through an IRF-9/STAT2-dependent or IRF-9/STAT2-independent mechanism. Moreover, the induction of RIG-G by retinoic acid in NB4 cells resulted, to some extent, from an IFNalpha autocrine pathway, a finding that suggests a novel mechanism for the signal cross-talk between IFNalpha and retinoic acid. Taken together, our results provide for the first time the evidence of the biological significance of IRF-9/STAT2 complex, and furnish an alternative pathway modulating the expression of IFN-stimulated genes, contributing to the diversity of IFN signaling to mediate their multiple biological properties in normal and tumor cells.
Identification of the Mechanism Mediating Genioglossus Muscle Suppression in REM Sleep
Authors: Kevin P. Grace, Stuart W. Hughes, Richard L. Horner
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Inhibition of pharyngeal motoneurons accompanies REM sleep and is a cause of hypoventilation and obstructive sleep apnea in humans. One explanation posits that the neurotransmitters glycine and γ-aminobutyric acid are responsible for REM sleep motor inhibition. However, blockade of that mechanism at cranial motor nuclei increases motor activity in all sleep-wake states, and least of all in REM sleep, arguing against it as a major mechanism of REM sleep pharyngeal motor inhibition.To identify the mechanism of REM sleep inhibition at the hypoglossal motor pool.Genioglossus and diaphragm activities were recorded in 34 rats across sleep-wake states. Microdialysis probes were implanted into the hypoglossal motor pool.Here we show that muscarinic receptor antagonism at the hypoglossal motor pool prevents the inhibition of genioglossus activity throughout REM sleep; likewise, with G-protein-coupled inwardly rectifying potassium (GIRK) channel blockade. Importantly, the genioglossus activating effects of these interventions were largest in REM sleep and minimal or often absent in other sleep-wake states. Finally, we showed that muscarinic inhibition of the genioglossus is functionally linked to GIRK channel activation.We identify a powerful cholinergic-GIRK channel mechanism operating at the hypoglossal motor pool that has its largest inhibitory influence in REM sleep and minimal or no effects in other sleep-wake states. This mechanism is the major cause of REM sleep inhibition at a pharyngeal motor pool critical for effective breathing.
Genes within Genes: Multiple LAGLIDADG Homing Endonucleases Target the Ribosomal Protein S3 Gene Encoded within an rnl Group I Intron of Ophiostoma and Related Taxa
Authors: J. Sethuraman, A. Majer, N. C. Friedrich, D. R. Edgell, G. Hausner
Journal: Molecular Biology and Evolution (2009)

In some ascomycete fungi, ribosomal protein S3 (Rps3) is encoded within a group I intron (mL2449) that is inserted in the U11 region of the mitochondrial large subunit rDNA (rnl) gene. Previous characterization of the mL2449 intron in strains of Ophiostoma novo-ulmi subspecies americana (Dutch Elm Disease) revealed a complex genes-within-genes arrangement whereby a LAGLIDADG homing endonuclease gene (HEG) is inserted into the RPS3 gene near the 3′ terminus, creating a hybrid Rps3–LAGLIDADG fusion protein. Here, we examined 119 additional strains of Ophiostoma and related taxa representing 85 different species by a polymerase chain reaction– based survey and detected both short (∼1.6 kb) and long (>2.2 kb) versions of the mL2449 intron in 88 and 31 strains, respectively. Among the long versions encountered, 21 were sequenced, revealing the presence of either intact or degenerated HEG-coding regions inserted within the RPS3 gene. Surprisingly, we identified two new HEG insertion sites in RPS3; one near the original C-terminal insertion site and one near the N-terminus of RPS3. In all instances, the HEGs are fused in-frame with the RPS3-coding sequences to create fusion proteins. However, comparative sequence analysis showed that upon insertion, the HEGs displaced a portion of the RPS3-coding region. Remarkably, the displaced RPS3-coding segments are duplicated and fused in-frame to the 3′ end of RPS3, restoring a full-length RPS3 gene. We cloned and expressed the LAGLIDADG portion of two Rps3–HEG fusions, and showed that I-OnuI and I-LtrI generate 4 nucleotide (nt), 3′ overhangs, and cleave at or 1 nt upstream of the HEG insertion site, respectively. Collectively, our data indicate that RPS3 genes are a refuge for distinct types of LAGLIDADG HEGs that are defined by the presence of duplicated segments of the host gene that restore the RPS3 gene, thus minimizing the impact of the HEG insertion on Rps3 function.
Role of surgical resection in pelvic Ewing's sarcoma.
Authors: S P Scully, H T Temple, R J O'Keefe, M T Scarborough, H J Mankin, M C Gebhardt
Journal: Journal of Clinical Oncology (1995)

The improved survival in patients with Ewing's sarcoma over the past two decades has placed increased importance on achievement of local disease control. Ewing's sarcoma that arises in the pelvis has been recognized to have a worse prognosis than that in the appendicular skeleton, and the role of surgical resection in these cases remains controversial. The current study attempts to identify a benefit to surgical resection in these patients.We retrospectively examined 39 patients who presented with Ewing's sarcoma in a pelvic location, all of whom were treated systemically with chemotherapy. Twenty patients received radiation only as a means of local control, and 19 underwent resection with or without radiation therapy. The patients were evaluated with end points of disease-free survival and overall survival for a minimum of 24 months and a mean of 58 months.There was an even distribution among patients who underwent surgical resection for local control as compared with those who received only radiation therapy with respect to age, site, date of treatment, and stage of disease. Despite uncontrolled biases including tumor size and response to chemotherapy that would be expected to favor patients who undergo resection, surgery in addition to or in substitution for radiation therapy did not result in a statistically significant increase in disease-free survival or overall survival. Local disease control was comparable between those who underwent resection and those who did not: three patients in each group developed a local recurrence.Currently, morbidity of surgical resection should be weighed against the efficacy and secondary complications of radiation therapy in the decision-making process for local disease control. The issue of whether overall survival and local disease control is improved in patients who undergo surgical resection remains controversial and may require a prospective randomized trial to be answered definitively.
CONGENITAL PROTEIN HYPERSENSITIVENESS IN TWO GENERATIONS
Authors: Bret Ratner, Helen Lee Gruehl
Journal: The Journal of Experimental Medicine (1931)

Hypersensitivity actively induced in utero is shown to persist for a longer period than passive sensitization. The degree of hypersensitivity, its duration, and its transmissibility appear to be influenced by the time elapsing between the original injection of the parent and parturition. A pregnant guinea pig receiving a parenteral injection of antigen 2 to 4 days prior to parturition transmits a state of hypersensitivity to two succeeding generations. The sensitization of the FI generation is due to the passage of antigen. The sensitization of the FII generation is due to the passage of antibodies formed in the FI generation. This prevents any further transfer of the hypersensitive state. Though hypersensitivity occurs in two successive generations, the phenomenon is congenital and not hereditary. We believe that this phenomenon demonstrated in the guinea pig is fundamentally related to the problem of congenital sensitization of the human being.
Spread of β-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic
Authors: Katharine Cheng, Rosalind L Smyth, John RW Govan, Catherine Doherty, Craig Winstanley, Nessa Denning, David P Heaf, Hendrik van Saene, C Anthony Hart
Journal: The Lancet (1996)
Why are Dutch rheumatologists reluctant to use the COBRA treatment strategy in early rheumatoid arthritis?
Authors: L. H D van Tuyl, A. M. C Plass, W. F Lems, A. E Voskuyl, B. A C Dijkmans, M. Boers
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow-up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. <b>Objective:</b> To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. <b>Methods:</b> A short structured questionnaire based on social–psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). <b>Results:</b> The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high-dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. <b>Conclusion:</b> The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient-related consequences of the therapy.
Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors
Authors: Helen Stone
Journal: Thorax (2007)

▴ Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Hatakeyama S, Sugaya N, Ito M, et al . JAMA2007;297:1435–42.

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



Oseltamivir is a neuraminidase inhibitor effective in the treatment of influenza. In this Japanese study, the sensitivity of influenza B virus to neuraminidase inhibitors was assessed in 74 children before and after treatment with oseltamivir, and in a further 348 untreated patients, 66 of whom were adults. …

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Kenneth Willoughby Heaton
Authors: C. B.-C. T. Paine
Journal: BMJ (2013)

Kenneth Willoughby Heaton (“Ken”) was born and brought up by Christian missionary parents in Shillong, Meghalaya, India.

By sustained meticulous work at Duke University and Bristol he fulfilled his ambition to study the effects of food and the environment on gastrointestinal function. He unravelled the origins of gallstones and irritable bowel syndrome, …
Dietary Proteins as Environmental Modifiers of Type 1 Diabetes Mellitus
Authors: David E. Lefebvre, Karen L. Powell, Alexander Strom, Fraser W. Scott
Journal: Annual Review of Nutrition (2006)

Type 1 diabetes is an autoimmune disease in which the patient's immune system destroys the insulin-secreting beta-cells in the pancreatic islets of Langerhans. A majority of cases is thought to occur as a result of gene-environment interactions. The identity of the environmental factors remains unknown mainly because of the difficulty in linking past exposures with later disease development. Overall, the data suggest a model in which individuals develop diabetes by several different pathways, each influenced by numerous genetic and environmental variables. The most investigated environmental factors are diet and viruses. In this review, we examine the evidence that the source of dietary proteins can modify diabetes outcome, describe new approaches to identify candidate diabetes-related dietary agents, examine possible links with gut dysfunction, discuss some of the limitations, and propose a multifactorial model for dietary modification of diabetes. The key to diabetes pathogenesis, its prevention, and the ultimate success of beta-cell replacement therapies lies in understanding how the environment controls disease expression. Dietary proteins could be one of these keys.