tbuckley/cabot-search huggingface dataset:
A Randomized, Prospective Trial Comparing the Efficacy of Continuous Subcutaneous Insulin Infusion With Multiple Daily Injections Using Insulin Glargine
Authors: Elizabeth A. Doyle (Boland), Stuart A. Weinzimer, Amy T. Steffen, Jo Ann H. Ahern, Miranda Vincent, William V. Tamborlane
Journal: Diabetes Care (2004)

OBJECTIVE—The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA1c levels in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Thirty-two youth with type 1 diabetes (age 8–21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA1c. HbA1c, total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy. RESULTS—While there was no significant change in the glargine group (HbA1c 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA1c levels, from 8.1 to 7.2% after 16 weeks of therapy (P &amp;lt; 0.02 vs. baseline and &amp;lt;0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P &amp;lt; 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group (P &amp;lt; 0.01). CONCLUSIONS—Lower HbA1c and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes.
Inflammation, new bone formation and treatment options in axial spondyloarthritis
Authors: Joachim Sieper, Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2014)

How and whether ankylosis is connected with inflammation has been discussed for a long time.1 There are two major reasons for this debate. First, no effective anti-inflammatory treatment was available in the past for ankylosing spondylitis (AS) as salicylates, which have been used to treat inflammatory rheumatic diseases for over 100 years, were not effective. However, the first non-steroidal anti-inflammatory drug (NSAID), phenylbutazone, was introduced into clinical practice around 1949 and was highly effective in patients with active AS. It was followed in subsequent decades by many other NSAIDs. The good therapeutic efficacy of NSAIDs was used to differentiate AS from degenerative causes of back pain2 due to their good anti-inflammatory properties. Nonetheless, NSAIDs for the treatment of AS are still often regarded incorrectly by the public as just ‘painkillers’ which should be avoided.3 Furthermore, conventional anti-inflammatory disease-modifying anti-rheumatic drugs (DMARDs) which are highly effective in many chronic rheumatic diseases such as rheumatoid arthritis, are not effective in AS,4 similarly to low or moderate doses of glucocorticoids, which also show lack of efficacy.5 All this contributed to the assumption that inflammation does not play a major role in AS, which was believed to be rather dominated by new bone formation and ankylosis.

Approximately 14 years ago, the dramatic efficacy of tumour necrosis factor (TNF) blockers was demonstrated in patients with active AS.6 The debate on the interaction between inflammation and new bone formation was fuelled again by the finding that treatment of patients with active AS with TNF blockers for 2 years, despite the good effect on signs and symptoms, C-reactive protein (CRP) and inflammation as detected by MRI, did not prevent new bone formation in the spine.7 This is the second major reason for the ongoing discussion on the association between inflammation and new bone …
Using routine spirometry to obtain sputum samples in the respiratory clinic
Authors: Anilkumar Pillai, Beverley Davies, Vicky Turner, David Smith
Journal: European Respiratory Journal (2011)

Background: Analysis of sputum is helpful in diagnosis and management. Not all patients produce sputum on request. However most undergo spirometry during their clinic visit. We had noticed that many patients appear to produce sputum during spirometry which was often swallowed and wondered if this might be an opportunity to obtain a sample.

Method: 303 consecutive patients performing nurse led spirometry in our chest clinic at the North Bristol Lung Centre from 1st November 2010 to 31st January 2011 were studied. Initial 139 patients were not informed prior to spirometry that a sputum specimen was required; subsequent 164 patients were asked to provide a specimen if possible.Nature of the sputum (mucoid/purulent) was recorded by the nurse.

Results: Of the initial 139 patients, 14 (10%) produced sputum spontaneously. 19 (12%)of the subsequent 164 were able to produce sputum on request during spirometry. Many patients in both groups swallowed sputum during spirometry.

Among the 303 patients, 66 (22%) had bronchiectasis, 65 (21%) had asthma and 53 (18%) had chronic obstructive pulmonary disease (COPD). Among those who produced sputum at spirometry, 22 (17 purulent) had bronchiectasis, 5 had COPD and 4 asthma.

22/33 sputum samples collected were sent to the laboratory. Sputum assessment by the clinic nursing staff matched that of the lab in 18 (82%) of the 22 cases.

Conclusion: Performing spirometry provides an opportunity to gain sputum. Forewarning the patient appears to have no effect on giving a sputum specimen. Nurses' categorisation of sputum nature correlates well with microbiology laboratory assessment. Categorisation as mucoid may enable fewer samples to be submitted for microbiology assessment.
Risk Group and Death From Prostate Cancer
Authors: Ann C. Raldow, Danjie Zhang, Ming-Hui Chen, Michelle H. Braccioforte, Brian J. Moran, Anthony V. D’Amico
Journal: JAMA Oncology (2015)

Active surveillance (AS), per the National Comprehensive Cancer Network (NCCN) guidelines, is considered for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, given the grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may be appropriate for men presenting with favorable intermediate-risk PC.To estimate and compare the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM) following brachytherapy among men with low and favorable intermediate-risk PC.Prospective cohort study of 5580 consecutively treated men (median age, 68 years) with localized adenocarcinoma of the prostate treated with brachytherapy at the Prostate Cancer Foundation of Chicago between October 16, 1997, and May 28, 2013.Standard of practice per the NCCN guidelines.Fine and Gray competing risks regression and Cox regression analyses were used to assess whether the risks of PCSM and ACM, respectively, were increased in men with favorable intermediate-risk vs low-risk PC. Analyses were adjusted for age at brachytherapy, year of treatment, and known PC prognostic factors.After median follow-up of 7.69 years, 605 men had died (10.84% of total cohort), 34 of PC (5.62% of total deaths). Men with favorable intermediate-risk PC did not have significantly increased risk of PCSM and ACM compared with men with low-risk PC (adjusted hazard ratio [HR], 1.64; 95% CI, 0.76-3.53; P = .21 for PCSM; adjusted HR, 1.11; 95% CI, 0.88-1.39; P = .38 for ACM). Eight-year adjusted point estimates for PCSM were low: 0.48% (95% CI, 0.23%-0.93%) and 0.33% (95% CI, 0.19%-0.56%) for men with favorable intermediate-risk PC and low-risk PC, respectively. The respective estimates for ACM were 10.45% (95% CI, 8.91%-12.12%) and 8.68% (95% CI, 7.80%-9.61%).Men with low-risk PC and favorable intermediate-risk PC have similarly low estimates of PCSM and ACM during the first decade following brachytherapy. While awaiting the results of ProtecT, the randomized trial of AS vs treatment, our results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC.
Obesity and Fatty Pancreatic Infiltration Are Risk Factors for Pancreatic Precancerous Lesions (PanIN)
Authors: Vinciane Rebours, Sébastien Gaujoux, Gaspard d'Assignies, Alain Sauvanet, Philippe Ruszniewski, Philippe Lévy, Valérie Paradis, Pierre Bedossa, Anne Couvelard
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The roles of intravisceral and subcutaneous fat are unknown, and the prevalence of precancerous lesions in obese patients was never evaluated. This study aims to assess the frequency and severity of pancreatic intraepithelial neoplasia (PanIN) and to correlate pathologic findings with metabolic abnormalities, type of fat, and fatty pancreatic infiltration. Experimental Design: Normal pancreatic tissue from surgical specimens was analyzed. Fatty infiltration and fibrosis in intra- and extralobular locations and PanIN lesions were assessed. General characteristics were collected: body mass index (BMI), diabetes, and tobacco intake. Liver steatosis and subcutaneous and intravisceral fat were assessed by CT scan (ImageJ software). Results: Of note, 110 patients were included [median age, 53.8 (17–85) years]. Arterial hypertension, diabetes, and tobacco intake were found in 19%, 9%, and 23%, respectively. Median BMI was 24 (16–37; BMI &amp;lt; 25: 45%, 25 ≤ 30: 24%, ≥30: 11%). Overall, PanIN lesions were found in 65% (type I, II, and III PanIN in 62%, 38%, and 1%, respectively). Fibrosis and fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and in 30% and 51%, respectively. A correlation was observed between PanIN lesions and fatty pancreas [extralobular (0.01) and intralobular (&amp;lt;0.0001)], intralobular fibrosis (0.003), high BMI (P = 0.02), and subcutaneous (P = 0.02) and intravisceral fat (P = 0.02). The number of PanIN lesions was correlated with intravisceral fat (r = 0.22, P = 0.04), but not with subcutaneous fat (r = 0.14, P = 0.22). In multivariate analysis, PanIN lesions were associated with intralobular fibrosis [OR, 5.61; 95% confidence interval (CI), 1.18–42.99] and intralobular fat (OR, 17.86; 95% CI, 4.935–88.12). Conclusions: Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions. Clin Cancer Res; 21(15); 3522–8. ©2015 AACR. See related commentary by Wang et al., p. 3369
Delayed-Onset Posttraumatic Stress Disorder: A Systematic Review of the Evidence
Authors: Bernice Andrews, Chris R. Brewin, Rosanna Philpott, Lorna Stewart
Journal: American Journal of Psychiatry (2007)

Objective: Since the diagnosis of delayed-onset posttraumatic stress disorder (PTSD) was introduced in DSM-III, there has been controversy over its prevalence and even its existence. The authors sought to resolve discrepant findings concerning the prevalence of delayed-onset PTSD by conducting a systematic review of the evidence. Method: A literature search was conducted for case reports and group studies with adequate measurement of delayed-onset PTSD according to DSM criteria. Studies that met inclusion criteria were examined for the defined length of delay for delayed-onset PTSD, presence of symptoms before full diagnostic criteria were met, length of follow-up, prevalence estimates, and other variables. Studies were also examined for differences between immediate-onset PTSD, delayed-onset PTSD, and no-PTSD cases. Results: Ten case studies and 19 group studies met criteria for inclusion in the review. Studies consistently showed that delayed-onset PTSD in the absence of any prior symptoms was rare, whereas delayed onsets that represented exacerbations or reactivations of prior symptoms accounted on average for 38.2% and 15.3%, respectively, of military and civilian cases of PTSD. Conclusions: The discrepant findings in the literature concerning prevalence can be largely, but not completely, explained as being due to definitional issues. Little is known about what distinguishes the delayed-onset and immediate-onset forms of the disorder. Continuing scientific study of delayed-onset PTSD would benefit if future editions of DSM were to adopt a definition that explicitly accepts the likelihood of at least some prior symptoms.
Extensive facial hemangioma associated with cardiac and abdominal anomalies
Authors: Sandeep D. Patel, Bernard A. Cohen, Jean S. Kan
Journal: Journal of the American Academy of Dermatology (1997)

Various cutaneous and visceral anomalies have been associated with cutaneous vascular lesions in infants and children. We describe a newborn girl with an extensive facial hemangioma, laryngeal and duodenal hemangiomas, a midline abdominal defect, and a right-sided coarctation of the aorta.
Non-Hodgkin's lymphoma with CFA
Authors: A. NICHOLSON, B. CORRIN;, T R ORCHARD, C D ERAUT, A G DAVISON
Journal: Thorax (1998)

We read with interest the case report by Orchard et al on non-Hodgkin’s lymphoma arising in cryptogenic fibrosing alveolitis (CFA).1 Although the authors state that this has not been described previously, we recently reported six cases of pulmonary B cell …
Soluble TRAIL concentrations are raised in patients with systemic lupus erythematosus
Authors: M N Lub-de Hooge, E G E de Vries, S de Jong, M Bijl
Journal: Annals of the Rheumatic Diseases (2004)

Increased apoptosis may induce autoimmune conditions. Apoptosis is induced by binding of death receptor ligands, members of the tumour necrosis factor (TNF) superfamily, to their cognate receptors. The Fas-Fas ligand pathway has been studied extensively in relation to systemic lupus erythematosus (SLE). However, other death pathways are also considered important. TNF related apoptosis inducing ligand (TRAIL), another ligand of the TNF superfamily, induces apoptosis in sensitive cells.To assess soluble (s) TRAIL concentrations in sera of SLE patients.40 SLE patients were studied (20 with active and 20 with inactive disease). Serum sTRAIL concentrations were measured by a solid phase sandwich enzyme linked immunosorbent assay. Levels in SLE patients were compared with those in patients with rheumatoid arthritis (n = 20), Wegener's granulomatosis (n = 20), and healthy controls (n = 20).Mean (SEM) serum sTRAIL concentration in SLE patients (936.0 (108.2) pg/ml) was higher than in healthy controls (509.4 (33.8) pg/ml; p<0.01) or in disease control patients with rheumatoid arthritis (443.8 (36.1) pg/ml, p<0.001) or Wegener's granulomatosis (357.1 (32.2) pg/ml; p<0.001). The mean serum sTRAIL concentration was 1010.2 (168.0) pg/ml for patients with inactive disease and 861.8 (138.7) pg/ml for those with active disease. sTRAIL values were not correlated with specific manifestations of the disease, such as leucopenia or lymphopenia, or with SLE disease activity index.Serum sTRAIL concentrations are increased SLE patients. This seems to be disease specific and could indicate a role for TRAIL in SLE pathophysiology.
The Tumor Suppressor Protein Menin Inhibits AKT Activation by Regulating Its Cellular Localization
Authors: Yan Wang, Atsushi Ozawa, Shadia Zaman, Nijaguna B. Prasad, Settara C. Chandrasekharappa, Sunita K. Agarwal, Stephen J. Marx
Journal: Cancer Research (2010)

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder associated mainly with tumors of multiple endocrine organs. Mutations in the MEN1 gene that encodes for the menin protein are the predominant cause for hereditary MEN1 syndrome. Though menin is a tumor suppressor, its molecular mechanism of action has not been defined. Here, we report that menin interacts with AKT1 in vitro and in vivo. Menin downregulates the level of active AKT and its kinase activity. Through interaction with AKT1, menin suppresses both AKT1-induced proliferation and antiapoptosis in nonendocrine and endocrine cells. Confocal microscopy analysis revealed that menin regulates AKT1 in part by reducing the translocation of AKT1 from the cytoplasm to the plasma membrane during growth factor stimulation. Our findings may be generalizable to other cancers, insofar as we found that loss of menin expression was also associated with AKT activation in a mouse model of pancreatic islet adenoma. Together, our results suggest menin as an important novel negative regulator of AKT kinase activity.
Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets
Authors: Emma C. Josefsson, Chloé James, Katya J. Henley, Marlyse A. Debrincat, Kelly L. Rogers, Mark R. Dowling, Michael J. White, Elizabeth A. Kruse, Rachael M. Lane, Sarah Ellis, Paquita Nurden, Kylie D. Mason, Lorraine A. O’Reilly, Andrew W. Roberts, Donald Metcalf, David C.S. Huang, Benjamin T. Kile
Journal: The Journal of Experimental Medicine (2011)

It is believed that megakaryocytes undergo a specialized form of apoptosis to shed platelets. Conversely, a range of pathophysiological insults, including chemotherapy, are thought to cause thrombocytopenia by inducing the apoptotic death of megakaryocytes and their progenitors. To resolve this paradox, we generated mice with hematopoietic- or megakaryocyte-specific deletions of the essential mediators of apoptosis, Bak and Bax. We found that platelet production was unperturbed. In stark contrast, deletion of the prosurvival protein Bcl-x(L) resulted in megakaryocyte apoptosis and a failure of platelet shedding. This could be rescued by deletion of Bak and Bax. We examined the effect on megakaryocytes of three agents that activate the intrinsic apoptosis pathway in other cell types: etoposide, staurosporine, and the BH3 mimetic ABT-737. All three triggered mitochondrial damage, caspase activation, and cell death. Deletion of Bak and Bax rendered megakaryocytes resistant to etoposide and ABT-737. In vivo, mice with a Bak(-/-) Bax(-/-) hematopoietic system were protected against thrombocytopenia induced by the chemotherapeutic agent carboplatin. Thus, megakaryocytes do not activate the intrinsic pathway to generate platelets; rather, the opposite is true: they must restrain it to survive and progress safely through proplatelet formation and platelet shedding.
MICA Expressed by Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance Plasma Cells Costimulates Pamidronate-Activated γδ Lymphocytes
Authors: Stefania Girlanda, Claudio Fortis, Daniela Belloni, Elisabetta Ferrero, Paolo Ticozzi, Clara Sciorati, Moreno Tresoldi, Aurelio Vicari, Thomas Spies, Veronika Groh, Federico Caligaris-Cappio, Marina Ferrarini
Journal: Cancer Research (2005)

Amino-biphosphonates (like pamidronate) activate human Vgamma9/Vdelta2 T lymphocytes and promote their cytotoxicity against multiple myeloma cells. T-cell receptor (TCR)-mediated effector functions of gammadelta cells are enhanced upon triggering of the activating receptor NKG2D by MICA, a stress-inducible antigen expressed by epithelial and some hematopoietic tumors, including multiple myeloma. Here we show that MICA was expressed not only by myeloma cell lines and by 6 of 10 primary multiple myeloma cells from patients but also by bone marrow plasma cells from all (six of six) patients with preneoplastic gammopathy (monoclonal gammopathy of undetermined significance, MGUS), a direct precursor of multiple myeloma. Moreover, compared with multiple myeloma plasma cells, MICA was expressed by MGUS plasma cells at significantly (P < 0.05) higher levels. MICA expressed by myeloma cell lines contributed to killing and IFN-gamma production by Vgamma9/Vdelta2 cells only upon pamidronate treatment, suggesting a dual interaction between Vgamma9/Vdelta2 lymphocytes and multiple myeloma plasma cells involving both TCR triggering and NKG2D-mediated signals. Finally, MICA enhanced killing of freshly derived, pamidronate-treated multiple myeloma cells from patients by gammadelta cells, as indicated by the significantly (P < 0.05) higher gammadelta cytotoxicity against MICA-positive rather than MICA-negative multiple myeloma cells. Our results indicate that MICA expressed by monoclonal plasma cells is functional and correlates with disease stages, suggesting a role for the molecule in the immune surveillance against multiple myeloma. Moreover, pamidronate-activated Vgamma9/Vdelta2 lymphocytes can be exploited in the immune therapy of early stages multiple myeloma and possibly of premalignant disease.
Natural Selection on Gene Order in the Genome Reorganization Process After Whole-Genome Duplication of Yeast
Authors: R. P. Sugino, H. Innan
Journal: Molecular Biology and Evolution (2011)

A genome must locate its coding genes on the chromosomes in a meaningful manner with the help of natural selection, but the mechanism of gene order evolution is poorly understood. To explore the role of selection in shaping the current order of coding genes and their cis-regulatory elements, a comparative genomic approach was applied to the baker's yeast Saccharomyces cerevisiae and its close relatives. S. cerevisiae have experienced a whole-genome duplication followed by an extensive reorganization process of gene order, during which a number of new adjacent gene pairs appeared. We found that the proportion of new adjacent gene pairs in divergent orientation is significantly reduced, suggesting that such new divergent gene pairs may be disfavored most likely because their coregulation may be deleterious. It is also found that such new divergent gene pairs have particularly long intergenic regions. These observations suggest that selection specifically worked against deletions in intergenic regions of new divergent gene pairs, perhaps because they should be physically kept away so that they are not coregulated. It is indicated that gene regulation would be one of the major factors to determine the order of coding genes. gene order, whole genome duplication, budding yeast, gene regulation.
Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays.
Authors: S L Swain, M Howard, J Kappler, P Marrack, J Watson, R Booth, G D Wetzel, R W Dutton
Journal: The Journal of Experimental Medicine (1983)

Several previously described B cell growth factor (BCGF) activities from a number of mouse monoclonal T cell sources were compared in different functional assays. The results indicate that there are two distinct classes of BCGF defined by functional activity and source. BCGF I, whose prototype is (EL4)BCGF, synergized with anti-Ig in the proliferation of normal splenic B cells but had no activity when dextran sulfate (DXS), rather than anti-Ig, was used to costimulate the same source of B cells. BCGF I also failed to directly stimulate BCL1 tumor B cells. In contrast, BCGF II, whose prototype is (DL)BCGF, showed a reciprocal pattern of activity. BCGF II failed to synergize with anti-Ig-costimulated normal B cells to give good proliferative responses. Sources of BCGF II also directly stimulated (no anti-Ig or DXS added) B cells of the BCL1 tumor-carrying mice. These results suggest that the two BCGF may have activity on two subsets of B cells that respond differentially to induction with the two polyclonal B cell activators, anti-Ig and DXS. The possibilities that these different patterns of response occur in separate lineages of B cells and/or in B cells in different states of differentiation is discussed.