tbuckley/cabot-search huggingface dataset:
Sites for Antagonism on the N-Methyl-D-Aspartate Receptor Channel Complex
Authors: E H Wong, J A Kemp
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Antibacterial Components in Bronchoalveolar Lavage Fluid from Healthy Individuals and Sarcoidosis Patients
Authors: BIRGITTA AGERBERTH, JOHAN GRUNEWALD, ESMERALDA CASTAÑOS-VELEZ, BERIT OLSSON, HANS JÖRNVALL, HANS WIGZELL, ANDERS EKLUND, GUDMUNDUR H. GUDMUNDSSON
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Antibacterial peptides and proteins are an integral part of the epithelial defense barrier that provides immediate protection against bacterial invasion. In humans, α -defensins are mainly bactericidal effectors in circulating granulocytes, β -defensin-1 is synthesized in epithelial cells, and LL-37 is produced in granulocytes but is also induced in skin epithelia during inflammation. To investigate the importance of these defense effectors in disease, we analyzed bronchoalveolar lavage fluid (BALF) for bactericidal activity. Antibacterial activity was found in BALF material from healthy individuals and sarcoidosis patients, with enhanced activity in BALF from the patients. The activity was present as several antibacterial components, of which we have so far characterized LL-37, lysozyme, α -defensins, and antileukoprotease. In addition, the antibacterial peptide LL-37 was located in alveolar macrophages, bronchial epithelial cells, and bronchial glands, suggesting that it has a defensive role in airway mucosa. In conclusion, the airway epithelium is protected by a complex antibacterial defense system. This is activated in sarcoidosis, and may explain why these patients seldom develop severe respiratory tract infections.
Kidney Stones Associate with Increased Risk for Myocardial Infarction
Authors: Andrew D. Rule, Veronique L. Roger, L. Joseph Melton, Eric J. Bergstralh, Xujian Li, Patricia A. Peyser, Amy E. Krambeck, John C. Lieske
Journal: Journal of the American Society of Nephrology (2010)

Kidney stones are a risk factor for chronic kidney disease (CKD), which, in turn, is a risk factor for myocardial infarction (MI). The objective of this study was to determine whether kidney stones associate with an increased risk for MI. We matched 4564 stone formers (1984 through 2003) on age and gender with 10,860 control subjects among residents in Olmsted County, Minnesota. We identified incident MI by diagnostic codes and validated events by chart review through 2006. We used diagnostic codes to determine incidence of kidney stones and presence of comorbidities (CKD, hypertension, diabetes, obesity, dyslipidemia, gout, alcohol dependence, and tobacco use). During a mean of 9 years of follow-up, stone formers had a 38% (95% confidence interval 7 to 77%) increased risk for MI, which remained at 31% (95% confidence interval 2% to 69%) after adjustment for CKD and other comorbidities. In conclusion, kidney stone formers are at increased risk for MI, and this risk is independent of CKD and other risk factors.
Periodontal disease immunology: ‘double indemnity’ in protecting the host
Authors: Jeffrey L. Ebersole, Dolphus R. Dawson, Lorri A. Morford, Rebecca Peyyala, Craig S. Miller, Octavio A. Gonzaléz
Journal: Periodontology 2000 (2013)

Abstract During the last two to three decades our understanding of the immunobiology of periodontal disease has increased exponentially, both with respect to the microbial agents triggering the disease process and the molecular mechanisms of the host engagement maintaining homeostasis or leading to collateral tissue damage. These foundational scientific findings have laid the groundwork for translating cell phenotype, receptor engagement, intracellular signaling pathways and effector functions into a ‘picture’ of the periodontium as the host responds to the ‘danger signals’ of the microbial ecology to maintain homeostasis or succumb to a disease process. These findings implicate the chronicity of the local response in attempting to manage the microbial challenge, creating a ‘Double Indemnity’ in some patients that does not ‘insure’ health for the periodontium. As importantly, in reflecting the title of this volume of Periodontology 2000 , this review attempts to inform the community of how the science of periodontal immunology gestated, how continual probing of the biology of the disease has led to an evolution in our knowledge base and how more recent studies in the postgenomic era are revolutionizing our understanding of disease initiation, progression and resolution. Thus, there has been substantial progress in our understanding of the molecular mechanisms of host–bacteria interactions that result in the clinical presentation and outcomes of destructive periodontitis. The science has embarked from observations of variations in responses related to disease expression with a focus for utilization of the responses in diagnosis and therapeutic outcomes, to current investigations using cutting‐edge fundamental biological processes to attempt to model the initiation and progression of soft‐ and hard‐tissue destruction of the periodontium. As importantly, the next era in the immunobiology of periodontal disease will need to engage more sophisticated experimental designs for clinical studies to enable robust translation of basic biologic processes that are in action early in the transition from health to disease, those which stimulate microenvironmental changes that select for a more pathogenic microbial ecology and those that represent a rebalancing of the complex host responses and a resolution of inflammatory tissue destruction.
Motivation and satisfaction among polyclinic volunteers at the 2002 Winter Olympic and Paralympic Games
Authors: J C Reeser, R L Berg, D Rhea, S Willick
Journal: British Journal of Sports Medicine (2005)

The Olympic and Paralympic Games rely heavily on volunteers to provide many essential services, including medical care of athletes.This preliminary investigation sought to characterise the motivational influences and factors responsible for the satisfaction of Olympic and Paralympic healthcare volunteers.The 2002 Winter Games polyclinic healthcare volunteers were asked to complete a questionnaire designed to elicit information about their motives for volunteering and the factors that contributed to their satisfaction with their volunteer experience.There was no significant difference in the motivation or satisfaction summary scores based on event worked. There was a strong positive correlation between motivation and satisfaction. Physician respondents had a lower mean motivation score than did non-physician volunteers.There were no significant motivational differences between Olympic and Paralympic volunteers, but there were several differences noted between physician and non-physician volunteers. The 2002 polyclinic volunteers appear to have been motivated by a complex process best described as "enlightened self interest," and all were generally well satisfied with their experience. These results may assist organisers of future Games in selecting appropriately motivated volunteer personnel and creating rewarding work environments for them.
Epithelial Damage and Angiogenesis in the Airways of Children with Asthma
Authors: Angelo Barbato, Graziella Turato, Simonetta Baraldo, Erica Bazzan, Fiorella Calabrese, Cristina Panizzolo, Maria Elena Zanin, Renzo Zuin, Piero Maestrelli, Leonardo M. Fabbri, Marina Saetta
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Airway remodeling and inflammation are characteristic features of adult asthma that are still poorly investigated in childhood asthma.To examine epithelial and vascular changes as well as the inflammatory response in airways of children with asthma.We analyzed bronchial biopsies obtained from 44 children undergoing bronchoscopy for appropriate clinical indications other than asthma: 17 with mild/moderate asthma (aged 2-15 yr), 12 with atopy without asthma (1-11 yr), and 15 control children without atopy or asthma (1-14 yr). By histochemistry and immunohistochemistry, we quantified epithelial loss, basement membrane thickness, number of vessels, and inflammatory cells in subepithelium.Epithelial loss and basement membrane thickness were increased in children with asthma compared with control subjects (p = 0.005 and p = 0.0002, respectively) and atopic children (p = 0.002 and p = 0.005, respectively). The number of vessels and eosinophils was increased not only in asthmatic children (p = 0.03 and p = 0.0002, respectively) but also in atopic children without asthma (p = 0.03 and p = 0.008, respectively) compared with control subjects. When we stratified the analysis according to age, we observed that children with asthma younger than 6 yr had increased epithelial loss, basement membrane thickening, and eosinophilia compared with control subjects of the same age.Epithelial damage and basement membrane thickening, which are pathologic features characteristic of adult asthma, are present even in childhood asthma. Other changes, such as airway eosinophilia and angiogenesis, were also observed in atopic children without asthma. These observations suggest that pathologic changes occur early in the natural history of asthma and emphasize the concept that some of these lesions may characterize atopy even in the absence of asthmatic symptoms.
Methods for analyzing deep sequencing expression data: constructing the human and mouse promoterome with deepCAGE data
Authors: Piotr J Balwierz, Piero Carninci, Carsten O Daub, Jun Kawai, Yoshihide Hayashizaki, Werner Van Belle, Christian Beisel, Erik van Nimwegen
Journal: Genome biology (2009)

With the advent of ultra high-throughput sequencing technologies, increasingly researchers are turning to deep sequencing for gene expression studies. Here we present a set of rigorous methods for normalization, quantification of noise, and co-expression analysis of deep sequencing data. Using these methods on 122 cap analysis of gene expression (CAGE) samples of transcription start sites, we construct genome-wide 'promoteromes' in human and mouse consisting of a three-tiered hierarchy of transcription start sites, transcription start clusters, and transcription start regions.
Intensive glucose control did not reduce a composite of microvascular events more than standard control in type 2 diabetes
Authors: David C Aron, Leonard M Pogach
Journal: Annals of Internal Medicine (2010)

Source Citation Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419-30. 20594588
Post-operative Pneumoperitoneum and Pulmonary Collapse
Authors: P. G. Bevan
Journal: BMJ (1961)

operative pneumoperitoneum may cause basal collapse of the lung.This has been made the subject of a separate study (Bevan, 1961).3. Dehiscence.-An abdomen containing air is more liable to dehiscence of a surgical incision.Distension of the abdomen exaggerates the pressure responses of activities such as coughing and vomiting (Drye, 1948), and in this way intraperitoneal air may lead to dehiscence.4. Subphrenic Abscess.-Pneumoperitoneumencourages the spread of intra-abdominal infection by opening up the subphrenic space (Harley, 1955), and thus, with the patient erect, subhepatic infection is aspirated into the suprahepatic space (Spalding, 1946).5. Phlebothrombosis and Pulmonary Embolism.-Ithas been shown by rabbit experiments that pneumoperitoneum increases the pressure in the veins of the leg (Bevan, 1958).Venous return along the inferior vena cava is facilitated by the negative intrathoracic pressure cranially and the positive abdominal pressure caudally.This " abdomino- thoracic pump" is impeded by a subphrenic pneumoperitoneum which leads to increased pressure and stasis in the deep veins of the pelvis and legs.In this series there were three examples of thrombo-embolism-two associated with grade 2 and one with a grade 3 pneumoperitoneum.6. Delayed Restoration in Gastro-intestinal Function.-In the group of gastric operations, the average post-operative day of withdrawal of Ryle's tube was 5.0 in those cases with considerable pneumoperitoneum, and 2.6 in cases with no pneumoperitoneum. (In all cases Ryle's tube was used routinely, being removed as soon as the oral intake exceeded the aspirates.)In the whole series the mean post-operative day on which the first bowel action occurred was 4.67 in the group of nine grade 4 pneumoperitoneums, and 4.25 in the group of cases with no pneumoperitoneum.Post- operative pneumoperitoneum appears to be associated with marked delay in gastric emptying after partial gastrectomy and slight delay in return of bowel function. SummarySerial radiographs have shown that air occurs in the peritoneal cavity in 76.8 % of cases in a series of abdominal operations.The incidence of the larger amounts of pneumoperitoneum is higher after partial gastrectomy than in the other surgical groups-upper and lower abdominal and pelvic operations.The distribution, amounts, and duration of post-operative pneumoperitoneum are discussed.It is suggested that residual air in the peritoneal cavity may be associated with various post-operative complications.I am indebted to Professor F. A. R. Stammers for his help and encouragement; most of the patients studied were under his care.I owe
Hypoglycemia in Type 1 Diabetes
Authors: Shlomit Shalitin, Moshe Phillip
Journal: Diabetes Care (2008)

The Diabetes Control and Complications Trial demonstrated that in patients with type 1 diabetes, tight metabolic control achieved with intensive insulin therapy can reduce the risk of long-term microvascular complications. However, strict glycemic control carries an increased risk of severe hypoglycemia. Recurrent episodes of hypoglycemia, especially at young ages, can lead to hypoglycemia unawareness, exert adverse effects on neurocognitive function, and cause significant emotional morbidity in the child and parents. Although the introduction of the new insulin analogs in diabetes therapy and the use of continuous subcutaneous insulin infusion raised hopes for a solution to this problem, these modalities have not been associated with the expected reduction in hypoglycemic episodes. The findings suggest that the prevention of hypoglycemia in patients with type 1 diabetes lies in biologically controlled insulin secretion, as in islet transplantation, or the development of an autonomous closed-loop system that efficiently mimics the action of the pancreatic beta-cells and maintains blood glucose levels within the desired range.
Transient ischaemic colitis following an aeroplane flight: two case reports and review of the literature
Authors: J H Butcher
Journal: Gut (2002)

Boley et al documented the first cases of reversible colonic injury resulting from ischaemia of the colon in 1963.1 At least 50 further cases have subsequently been reported in the literature with as yet no common aetiological factors elicited.2–10 This report documents two extensively investigated cases with no obvious precipitant except for a preceding aeroplane flight.

A 43 year old woman took a 10 hour flight to the USA. A few hours after arrival she developed vomiting, diarrhoea, and abdominal pain. She collapsed and was admitted to hospital where she had a further episode of diarrhoea with some fresh rectal bleeding. A diagnosis of gastroenteritis was made and she was discharged. Twenty four hours later she was admitted to another hospital with further rectal bleeding, abdominal pain, and a vasovagal episode. There were no abnormal physical findings. She underwent urgent colonoscopy which showed oedema, friability, and cobblestoning from the distal transverse colon to the descending colon (fig 1). Biopsies were taken from this area (fig 2) and showed a surface acute inflammatory cell exudate, mucosal haemorrhage, and gland dropout consistent with the effects of ischaemic damage. The rest of the large bowel was normal and ischaemic colitis was diagnosed. Her symptoms settled and she returned to the UK where she was referred as an outpatient. There was no past history of coagulopathy or cardiac abnormalities and she did not smoke. She had not been taking any medication (including herbal remedies and oral contraceptives). Examination revealed no evidence of peripheral emboli or vasculitis. Heart sounds were normal and blood pressure was 115/70. Abdominal examination revealed mild right iliac fossa tenderness …
Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial
Authors: Stephen J Allen, Kathie Wareham, Duolao Wang, Caroline Bradley, Hayley Hutchings, Wyn Harris, Anjan Dhar, Helga Brown, Alwyn Foden, Michael B Gravenor, Dietrich Mack
Journal: The Lancet (2013)

Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result.We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204.Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial.We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies.Health Technology Assessment programme; National Institute for Health Research, UK.
The role of telomeres and telomerase in hematologic malignancies and hematopoietic stem cell transplantation
Authors: Limengmeng Wang, Haowen Xiao, Xing Zhang, Chong Wang, He Huang
Journal: Journal of Hematology & Oncology (2014)

Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related factors should be taken into consideration because of their impacts on telomere homeostasis. As activation of telomerase is widespread in tumor cells, it has been employed as a target point in the treatment of neoplastic hematologic disorders. In this review, the characteristics and roles of telomeres and telomerase both in hematologic malignancies and in HSCT will be summarized. The current status of telomerase-targeted therapies utilized in the treatment of hematologic malignancies will also be reviewed.
The slow component of V̇o<sub>2</sub>in professional cyclists
Authors: Alejandro Lucía, Jesús Hoyos, José L Chicharro
Journal: British Journal of Sports Medicine (2000)

Objectives —To analyse the slow component of oxygen uptake (V̇ o 2 ) in professional cyclists and to determine whether this phenomenon is due to altered neuromuscular activity, as assessed by surface electromyography (EMG). Methods —The following variables were measured during 20 minute cycle ergometer tests performed at about 80% of V̇ o 2 max in nine professional road cyclists (mean (SD) age 26 (2) years; V̇ o 2 max 72.6 (2.2) ml/kg/min): heart rate (HR), gas exchange variables (V̇ o 2 , ventilation (V̇ e) , tidal volume (V T ), breathing frequency (f b ), ventilatory equivalents for oxygen and carbon dioxide (V̇ e /V̇ o 2 and V̇ e /V̇ co 2 respectively), respiratory exchange ratio (RER), and end tidal P o 2 and P co 2 (P eto 2 and P etco 2 respectively)), blood variables (lactate, pH, and [HCO 3 − ]) and EMG data (root mean from square voltage (rms-EMG) and mean power frequency (MPF)) from the vastus lateralis muscle. Results —The mean magnitude of the slow component (from the end of the third minute to the end of exercise) was 130 (0.04) ml in 17 minutes or 7.6 ml/min. Significant increases from three minute to end of exercise values were found for the following variables: V̇ o 2 (p&lt;0.01), HR (p&lt;0.01), V̇ e (p&lt;0.05), f b (p&lt;0.01), V̇ e /V̇ o 2 (p&lt;0.05), V̇ e /V̇ co 2 (p&lt;0.01), P eto 2 (p&lt;0.05), and blood lactate (p&lt;0.05). In contrast, rms-EMG and MPF showed no change (p&gt;0.05) throughout the exercise tests. Conclusions —A significant but small V̇ o 2 slow component was shown in professional cyclists during constant load heavy exercise. The results suggest that the primary origin of the slow component is not neuromuscular factors in these subjects, at least for exercise intensities up to 80% of V̇ o 2 max .