tbuckley/cabot-search huggingface dataset:
Social Influences on Clinical Outcomes of Patients With Ovarian Cancer
Authors: Susan K. Lutgendorf, Koen De Geest, David Bender, Amina Ahmed, Michael J. Goodheart, Laila Dahmoush, M. Bridget Zimmerman, Frank J. Penedo, Joseph A. Lucci, Parvin Ganjei-Azar, Premal H. Thaker, Luis Mendez, David M. Lubaroff, George M. Slavich, Steven W. Cole, Anil K. Sood
Journal: Journal of Clinical Oncology (2012)

Previous research has demonstrated relationships of social support with disease-related biomarkers in patients with ovarian cancer. However, the clinical relevance of these findings to patient outcomes has not been established. This prospective study examined how social support relates to long-term survival among consecutive patients with ovarian cancer. We focused on two types of social support: social attachment, a type of emotional social support reflecting connections with others, and instrumental social support reflecting the availability of tangible assistance.Patients were prospectively recruited during a presurgical clinic visit and completed surveys before surgery. One hundred sixty-eight patients with histologically confirmed epithelial ovarian cancer were observed from the date of surgery until death or December 2010. Clinical information was obtained from medical records.In a Cox regression model, adjusting for disease stage, grade, histology, residual disease, and age, greater social attachment was associated with a lower likelihood of death (hazard ratio [HR], 0.87; 95% CI, 0.77 to 0.98; P = .018). The median survival time for patients with low social attachment categorized on a median split of 15 was 3.35 years (95% CI, 2.56 to 4.15 years). In contrast, by study completion, 59% of patients with high social attachment were still alive after 4.70 years. No significant association was found between instrumental social support and survival, even after adjustment for covariates.Social attachment is associated with a survival advantage for patients with ovarian cancer. Clinical implications include the importance of screening for deficits in the social environment and consideration of support activities during adjuvant treatment.
Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients.
Authors: O Levran, R J Desnick, E H Schuchman
Journal: Journal of Clinical Investigation (1991)

Types A and B Niemann-Pick disease both result from the deficient activity of the lysosomal hydrolase, acid sphingomyelinase (E.C. 3.1.4.12). Type A Niemann-Pick disease is a severe neurodegenerative disorder of infancy which leads to death by three years of age, whereas Type B disease has a later age at onset, little or no neurologic involvement, and most patients survive into adulthood. To investigate the molecular basis for the remarkable phenotypic heterogeneity, the nature of the mutations causing Type B Niemann-Pick disease in Ashkenazi Jewish patients was determined. The entire acid sphingomyelinase coding region from an Ashkenazi Jewish Type B patient was polymerase chain reaction-amplified, subcloned, and completely sequenced. A three-base deletion was identified of nucleotides 1821-1823 in the cDNA which predicted the removal of an arginine residue from position 608 of the acid sphingomyelinase polypeptide (delta R608). The other cDNA clones from this patient had the R496L mutation previously identified in Type A Niemann-Pick disease patients. Both Ashkenazi Jewish Type B patients were heteroallelic for the delta R608 mutation, whereas this allele was not present in 15 unrelated non-Jewish Type B patients, with the notable exception of one mildly affected patient of Arabic descent who was homoallelic for the delta R608 mutation. These results indicate that the delta R608 mutation predicts the Type B Niemann-Pick disease phenotype, even in the presence of the R496L Type A allele, thereby providing the first genotype/phenotype correlation for this lysosomal storage disease. Although only two patients have been studied, it appears that the delta R608 mutation occurs frequently in Type B Niemann-Pick disease patients of Ashkenazi Jewish descent.
Treatment with Continuous Positive Airway Pressure Is Not Effective in Patients with Sleep Apnea but No Daytime Sleepiness
Authors: Ferran Barbé, Lola R. Mayoralas, Joaquin Duran, Juan F. Masa, Andreu Maimó, Josep M. Montserrat, Carmen Monasterio, Margalida Bosch, Antoni Ladaria, Manuela Rubio, Ramon Rubio, Magdalena Medinas, Lourdes Hernandez, Silvia Vidal, Neil J. Douglas, Alvar G.N. Agustí
Journal: Annals of Internal Medicine (2001)

Background: The sleep apnea–hypopnea syndrome is defined by a pathologic number of respiratory events during sleep (the apnea–hypopnea index, defined as the number of apnea and hypopnea episodes per hour) and daytime symptoms (mostly, excessive sleepiness). In patients with the sleep apnea syndrome, treatment with continuous positive airway pressure (CPAP) normalizes both the apnea–hypopnea index and diurnal symptoms. However, the effect of CPAP in persons with a pathologic apnea–hypopnea index without daytime sleepiness is unclear. Objective: To investigate the short-term effects of CPAP on quality of life, objective sleepiness, cognitive function, and arterial blood pressure in nonsleepy patients with a pathologic apnea–hypopnea index. Design: Multicenter randomized, placebo-controlled, parallel-group study. Setting: Six teaching hospitals in Spain. Patients: 55 patients with an apnea–hypopnea index of 30 or greater who did not have daytime sleepiness (Epworth Sleepiness Scale score ≤ 10). Intervention: Patients were randomly assigned to receive optimal (n = 29) or sham (n = 25) CPAP and were observed for 6 weeks. Measurements: Quality of life, objective sleepiness (Multiple Sleep Latency Test score), cognitive function, and arterial blood pressure. Results: The intervention and control groups were similar in terms of mean (±SE) age (54 ± 2 vs. 52 ± 2 years), apnea–hypopnea index (54 ± 3 vs. 57 ± 4), Epworth Sleepiness Scale score (7.0 ± 0.4 vs. 7.0 ± 0.4) and adherence to CPAP treatment (5.0 ± 0.4 vs. 4.0 ± 0.5 hours/d). Other variables, such as quality of life, cognitive function, and arterial blood pressure, were also similar in both groups before treatment. After 6 weeks of CPAP or sham CPAP, none of these variables changed significantly. Conclusion: In patients with an apnea–hypopnea index of 30 or greater and no subjective daytime sleepiness, CPAP does not modify quality of life, objective sleepiness, vigilance, attention, memory, information processing, visuomotor coordination, or arterial blood pressure. Treatment with CPAP is therefore not indicated in nonsleepy patients with a pathologic apnea–hypopnea index.
Sirtuins and Pyridine Nucleotides
Authors: Maha Abdellatif
Journal: Circulation Research (2012)

The silencer information regulator (Sir) family of proteins has attracted much attention during the past decade due to its prominent role in metabolic homeostasis in mammals. The Sir1-4 proteins were first discovered in yeast as nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases, which through a gene silencing effect promoted longevity. The subsequent discovery of a homologous sirtuin (Sirt) family of proteins in the mammalian systems soon led to the realization that these molecules have beneficial effects in metabolism- and aging-related diseases. Through their concerted functions in the central nervous system, liver, pancreas, skeletal muscle, and adipose tissue, they regulate the body's metabolism. Sirt1, -6, and -7 exert their functions, predominantly, through a direct effect on nuclear transcription of genes involved in metabolism, whereas Sirt3-5 reside in the mitochondrial matrix and regulate various enzymes involved in the tricarboxylic acid and urea cycles, oxidative phosphorylation, as well as reactive oxygen species production. An interesting aspect of the functionality of sirtuin involves their regulation by the circadian rhythm, which affects their function via cyclically regulating systemic NAD(+) availability, further establishing the link of these proteins to metabolism. In this review, we will discuss the relation of sirtuins to NAD(+) metabolism, their mechanism of function, and their role in metabolism and mitochondrial functions. In addition, we will describe their effects in the cardiovascular and central nervous systems.
Resuscitative laser photoresection of a tracheal tumour before elective surgery.
Authors: P J George, C P Garrett, P Goldstraw, M R Hetzel, A D Ramsay
Journal: Thorax (1986)

The palliative role of the neodymium yttrium-aluminiumgarnet (Nd YAG) laser in the management of tracheo- bronchial tumours is already established.' 2 We report a patient with a tracheal tumour, nearly occluding the lumen, in whom laser photoresection restored an adequate airway and thereby facilitated elective surgery. Case reportA 66 year old man was admitted to another hospital with a four month history of breathlessness, non-productive cough,
A Telephone-Based Program to Provide Symptom Monitoring Alone vs Symptom Monitoring Plus Care Management for Late-Life Depression and Anxiety
Authors: Shahrzad Mavandadi, Amy Benson, Suzanne DiFilippo, Joel E. Streim, David Oslin
Journal: JAMA Psychiatry (2015)

Mental health (MH) conditions are undertreated in late life. It is important to identify treatment strategies that address variability in treatment content and delivery and take individual-specific symptoms into account, particularly among low-income, community-dwelling older adults.To evaluate program feasibility and MH outcomes among community-dwelling older adults randomized to 1 of 2 treatment arms of varying intensity of evidence-based, collaborative MH care management services (ie, the Supporting Seniors Receiving Treatment and Intervention [SUSTAIN] program) that provide standardized, measurement-based, software-aided MH assessment and symptom monitoring and connection to community resources via telephone.Trial participants were 1018 older, community-dwelling, low-income adults prescribed an antidepressant or anxiolytic by a primary care or non-MH professional and experiencing clinically significant MH symptoms at intake. The participant subsample was drawn from a larger parent sample of older adults enrolled in the SUSTAIN program. Individuals were randomized to receive MH symptom monitoring alone (hereafter monitoring alone) or MH symptom monitoring plus care management (hereafter care management) provided by an MH professional. Baseline characteristics were examined, and changes in clinical MH outcomes were evaluated at 3-month and 6-month follow-up. The study dates were August 5, 2010, to May 5, 2014.Monitoring alone or care management delivered by an MH professional.Overall MH functioning (primary) and depressive and anxiety symptoms.A total of 509 participants were randomized to the monitoring alone group and 509 to the care management group; 377 and 401 completed ≥2 research assessments in the monitoring alone and case management groups, respectively. Compared with those randomized to monitoring alone, individuals randomized to care management showed greater improvements in the 3 domains of MH functioning (β [SE], 0.36 [0.12]; 95% CI, 0.12 to 0.60; P = .004), depressive symptoms (β [SE], -0.20 [0.06]; 95% CI, -0.32 to -0.09; P < .001), and anxiety symptoms (β [SE], -0.23 [0.05]; 95% CI, -0.33 to -0.14; P < .001) over time.The SUSTAIN program, which provides assessment, monitoring, care management, and brief therapies for MH symptoms and needs in primary care settings, is feasible and scalable. A more intense level of care (ie, symptom monitoring plus care management) is associated with more favorable individual outcomes for low-income, community-dwelling older adults experiencing clinically significant MH symptoms.clinicaltrials.gov Identifier: NCT02440594.
Infant Feeding in Relation to Islet Autoimmunity and Type 1 Diabetes in Genetically Susceptible Children: The MIDIA Study
Authors: Nicolai A. Lund-Blix, Lars C. Stene, Trond Rasmussen, Peter A. Torjesen, Lene F. Andersen, Kjersti S. Rønningen
Journal: Diabetes Care (2014)

OBJECTIVE We aimed to study the association of breast-feeding duration and age at the introduction of solid foods with the risk of islet autoimmunity and type 1 diabetes in genetically susceptible children. RESEARCH DESIGN AND METHODS Newborns were recruited from the Norwegian general population during 2001–2007. After genetic screening of nearly 50,000 newborns, 908 children with the high-risk HLA genotype were followed up with blood samples and questionnaires at age 3, 6, 9, and 12 months and then annually. Complete infant diet data were available for 726 children. RESULTS Any breast-feeding for 12 months or longer predicted a decreased risk of developing type 1 diabetes compared with any breast-feeding for less than 12 months before and after adjusting for having a first-degree relative with type 1 diabetes, vitamin D supplementation, maternal education, sex, and delivery type (hazard ratio 0.37 [95% CI 0.15–0.93]). Any breast-feeding for 12 months or longer was not associated with islet autoimmunity but predicted a lower risk of progression from islet autoimmunity to type 1 diabetes (hazard ratio 0.35 [95% CI 0.13–0.94]). Duration of full breast-feeding was not significantly associated with the risk of islet autoimmunity or type 1 diabetes nor was age at introduction of solid foods or breast-feeding at the time of introduction of any solid foods. CONCLUSIONS These results suggest that breast-feeding for 12 months or longer predict a lower risk of progression from islet autoimmunity to type 1 diabetes among genetically predisposed children.
Effects of exercise on free serum cholesterol.
Authors: D. L. Montgomery, A. H. Ismail
Journal: British Journal of Sports Medicine (1977)

Two age groups (young and old, n = 12) matched for physical fitness and two physical fitness groups (high and old, n = 12) matched for age participated in a four month physical fitness programme. Blood samples were drawn at four stages of metabolic stress at the pre-test and five stages at the post-test. The blood samples were analyzed by colorimetric methods for total cholesterol and free cholesterol. Statistical analysis revealed that: (1) Short-term exercise increased total cholesterol, free cholesterol, and the percent free cholesterol from the resting state to the submaximal and maximal exercise states. (2) There was no change in free serum cholesterol from the pre- to post-tests. (3) The high-fit group, compared with the low-fit group, had a lower free cholesterol level but had similar percent free cholesterol values. (4) There was no significant difference between age groups for either total serum cholesterol, free cholesterol, or the percent free cholesterol levels.
Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study
Authors: Markus Ketteler, Philipp Bongartz, Ralf Westenfeld, Joachim Ernst Wildberger, Andreas Horst Mahnken, Roland Böhm, Thomas Metzger, Christoph Wanner, Willi Jahnen-Dechent, Jürgen Floege
Journal: The Lancet (2003)
Bronchoscopic Volume Reduction
Authors: EDWARD P. INGENITO, JOHN J. REILLY, STEVEN J. MENTZER, SCOTT J. SWANSON, RON VIN, HEIKE KEUHN, ROBERT L. BERGER, ANDREW HOFFMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung, has been shown to improve respiratory function in many patients with end-stage emphysema. We report the results of an animal study using a new transbronchoscopic alternative to LVRS in which a washout solution and fibrin-based glue are used to collapse, seal, and scar target regions of abnormal lung. Twelve sheep had static and dynamic lung functions measured at baseline. Emphysema was produced by inhaled papain (7,000 U/wk × 4 wk), resulting in a significant increase of lung volumes, compliance, and airway resistance. The animals were then divided into three treatment groups of four animals, and underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR), or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to 12 wk after treatment by measuring lung function and examining lung tissue. BVR and SVR groups responded with significant and similar decreases in TLC and residual volume (RV). Tissue examination demonstrated that BVR caused collapse of the lung with focal scarring in 11 of 20 target territories (55% success rate). Three of the 11 target zones developed sterile abscesses. Postprocedure complications were less frequent with BVR than with SVR. This pilot study suggests that lung volume reduction can be achieved in animals without surgery using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans.Keywords: lung volume reduction therapy; emphysema; interventional bronchoscopy
Cardioscopic catheter ablation with non-contact, pulsed Nd:YAG laser using saline inflated balloon catheter
Authors: H. Nakagawa, S.D. Savage, G. Brucker, S. Imai, W.S. Yamanashi, J.V. Pitha, B. Cambell, M. Arruda, K. Otomo, R. Lazzara, W.M. Jackman
Journal: Journal of the American College of Cardiology (1998)
Functional expression of an inactivating potassium channel (Kv4.3) in a mammalian cell line
Authors: L Franqueza
Journal: Cardiovascular Research (1999)

Objective: The goal of this study was to characterize the electrophysiological properties of the Kv4.3 channels expressed in a mammalian cell line. Methods: Currents were recorded using the whole-cell voltage clamp technique. Results: The threshold for activation of the expressed Kv4.3 current was approximately −30 mV. The dominant time constant for activation was 1.71±0.16 ms (n=10) at +60 mV. The current inactivated, this process being incomplete, resulting in a sustained level which contributed 15±2% (n=25) of the total current. The time course of inactivation was fit by a biexponential function, the fast component contributing 74±5% (n=9) to the overall inactivation. The fast time constant was voltage-dependent [27.6±2.0 ms at +60 mV (n=10) versus 64.0±3.6 ms at 0 mV (n=10); P<0.01], whereas the slow was voltage-independent [142±15 ms at +60 mV (n=10) versus 129±33 ms at 0 mV (n=6) P>0.05]. The voltage-dependence of inactivation exhibited midpoint and slope values of −26.9±1.5 mV and 5.9±0.3 mV (n=21). Recovery from inactivation was faster at more negative membrane potentials [203±17 ms (n=13) and 170±19 ms (n=4), at −90 and −100 mV]. Bupivacaine block of Kv4.3 channels was not stereoselective (KD∼31 μM). Conclusions: The functional profile of Kv4.3 channels expressed in Ltk− cells corresponds closely to rat ITO, although differences in recovery do not rule out association with accessory subunits. Nevertheless, the sustained component needs to be considered with respect to native ITO.
Nasal Ventilation Alters Mesenchymal Cell Turnover and Improves Alveolarization in Preterm Lambs
Authors: Brent Reyburn, Marlana Li, Drew B. Metcalfe, Nicholas J. Kroll, Jeremy Alvord, Albert Wint, Mar Janna Dahl, Jiancheng Sun, Li Dong, Zheng-ming Wang, Christopher Callaway, Robert A. McKnight, Laurie Moyer-Mileur, Bradley A. Yoder, Donald M. Null, Robert H. Lane, Kurt H. Albertine
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Bronchopulmonary dysplasia (BPD) is a frequent cause of morbidity in preterm infants that is characterized by prolonged need for ventilatory support in an intensive care environment. BPD is characterized histopathologically by persistently thick, cellular distal airspace walls. In normally developing lungs, by comparison, remodeling of the immature parenchymal architecture is characterized by thinning of the future alveolar walls, a process predicated on cell loss through apoptosis.Objectives: We hypothesized that minimizing lung injury, using high-frequency nasal ventilation to provide positive distending pressure with minimal assisted tidal volume displacement, would increase apoptosis and decrease proliferation among mesenchymal cells in the distal airspace walls compared with a conventional mode of support (intermittent mandatory ventilation).Methods: Accordingly, we compared two groups of preterm lambs: one group managed by high-frequency nasal ventilation and a second group managed by intermittent mandatory ventilation. Each group was maintained for 3 days.Measurements and Main Results: Oxygenation and ventilation targets were sustained with lower airway pressures and less supplemental oxygen in the high-frequency nasal ventilation group, in which alveolarization progressed. Thinning of the distal airspace walls was accompanied by more apoptosis, and less proliferation, among mesenchymal cells of the high-frequency nasal ventilation group, based on morphometric, protein abundance, and mRNA expression indices of apoptosis and proliferation.Conclusions: Our study shows that high-frequency nasal ventilation preserves the balance between mesenchymal cell apoptosis and proliferation in the distal airspace walls, such that alveolarization progresses.
Endosomal Proteases Influence the Repertoire of MAGE-A3 Epitopes Recognized<i>In vivo</i>by CD4+ T Cells
Authors: Jill Marturano, Renato Longhi, Vincenzo Russo, Maria Pia Protti
Journal: Cancer Research (2008)

Abstract Little is known about the repertoire of MAGE-A3 CD4+ T-cell epitopes recognized in vivo by neoplastic patients and how antigen processing influences epitope formation. Here, we first show that MAGE-A3–specific CD4+ T cells are present in the blood of advanced melanoma patients. MAGE-A3111-125, MAGE-A3191-205, and MAGE-A3281-300 were recognized by 7, 6, and 5 of the 11 patients tested, respectively. MAGE-A3146-160 and MAGE-A3171-185 were also recognized in two and one cases, whereas no recognition of MAGE-A3161-175 and MAGE-A3243-258 was observed. Cytokines produced were mainly interleukin 5 and/or granulocyte macrophage colony-stimulating factor, suggesting impairment of productive polarized Th1 responses. Secondly, proteases inhibitors were used to modulate in vitro the recognition by CD4+ T-cells clones of dendritic cells loaded with MAGE-A3–expressing cell lysates. We found that formation of MAGE-A3111-125 depended on both leupeptin-sensitive and pepstatin-sensitive proteases. In contrast, we found that MAGE-A3161-175, which was never recognized ex vivo, was formed by leupeptin but destroyed by pepstatin-sensitive proteases. Collectively, our results show that (a) anti–MAGE-A3 CD4+ T-cell immunity develops in vivo in neoplastic patients and is focused toward immunodominant epitopes, (b) the response in advanced disease is skewed toward a Th2 type, and (c) endosomal/lysosomal proteases in dendritic cells influence the repertoire of the epitopes recognized. [Cancer Res 2008;68(5):1555–62]
A new gene that controls the type of leukemia induced by Friend murine leukemia virus.
Authors: J E Silver, T N Fredrickson
Journal: The Journal of Experimental Medicine (1983)

NB tropic Friend murine leukemia virus (F-MuLV) replicates equally well in BALB/c and C57BL mice inoculated as neonates but causes almost exclusively erythroblastosis in BALB/c mice and nonerythroid (lymphoid and myelogenous) leukemias in C57BL mice. The C57BL resistance to erythroblastosis appears to be controlled by a single dominant gene in first and second backcrosses to BALB/c. This resistance to erythroblastosis is distinct from other genes known to affect susceptibility to Friend virus including Fv-1, Fv-2, H-2, Rfv-3, Fv-4, and Rmcf. We suggest the name Fhe for the new gene controlling susceptibility to Friend helper virus erythroblastosis.