tbuckley/cabot-search huggingface dataset:
Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues
Authors: R. Pat Bucy, Richard D. Hockett, Cynthia A. Derdeyn, Michael S. Saag, Kathleen Squires, Michael Sillers, Ronald T. Mitsuyasu, J. Michael Kilby
Journal: Journal of Clinical Investigation (1999)

Previous studies proposed a dynamic, steady-state relationship between HIV-mediated cell killing and T-cell proliferation, whereby highly active antiretroviral therapy (HAART) blocks viral replication and tips the balance toward CD4+ cell repopulation. In this report, we have analyzed blood and lymph node tissues obtained concurrently from HIV-infected patients before and after initiation of HAART. Activated T cells were significantly more frequent in lymph node tissue compared with blood at both time points. Ten weeks after HAART, the absolute number of lymphocytes per excised lymph node decreased, whereas the number of lymphocytes in the blood tended to increase. The relative proportions of lymphoid subsets were not significantly changed in tissue or blood by HAART. The expression levels of mRNA for several proinflammatory cytokines (IFN-γ, IL-1β, IL-6, and macrophage inflammatory protein-1α) were lower after HAART. After therapy, the expression of VCAM-1 and ICAM-1 — adhesion molecules known to mediate lymphocyte sequestration in lymphoid tissue — was also dramatically reduced. These data provide evidence suggesting that initial increases in blood CD4+ cell counts on HAART are due to redistribution and that this redistribution is mediated by resolution of the immune activation that had sequestered T cells within lymphoid tissues.
The Value of Assessing Falls in an Elderly Population
Authors: L Z Rubenstein, A S Robbins, K R Josephson, B L Schulman, D Osterweil
Journal: Annals of Internal Medicine (1990)

Objective: To measure the effects of a specialized postfall assessment intended to detect causes and underlying risk factors for falls, and to recommend preventive and therapeutic interventions. Design: Randomized, controlled trial. Setting: A long-term residential care facility for elderly persons. Subjects: Within 7 days of a fall, 160 ambulatory subjects (mean age, 87 years) were randomly assigned to receive either a comprehensive postfall assessment (intervention group, n = 79) or usual care (control group, n = 81). Intervention: The postfall assessment included a detailed physical examination and environmental assessment by a nurse practitioner; laboratory tests; electrocardiogram; and 24-hour Holter monitoring. Probable cause or causes for the fall, identified risk factors, and therapeutic recommendations were given to the patient's primary physician. Measurements and Main Results: Through use of the assessment, many remediable problems (for example, weakness, environmental hazards, orthostatic hypotension, drug side effects, gait dysfunction) were detected. At the end of the 2-year follow-up period, the intervention group had 26% fewer hospitalizations (P < 0.05) and a 52% reduction in hospital days (P < 0.01) compared with controls. Patients in the intervention group had 9% fewer falls and 17% fewer deaths than controls by 2 years, but these trends were not statistically significant. Conclusions: Our study suggests that falls are a marker of underlying disorders easily identifiable by a careful postfall assessment, which in turn can reduce disability and costs.
Infection of monocyte/macrophages by human T lymphotropic virus type III.
Authors: D D Ho, T R Rota, M S Hirsch
Journal: Journal of Clinical Investigation (1986)

Normal blood-derived monocyte/macrophages were found to be susceptible to infection in vitro by human T lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immunodeficiency syndrome. In addition, HTLV-III was recovered from monocyte/macrophages of patients infected with this virus. The above findings raise the possibility that HTLV-III-infected monocyte/macrophages may serve as a vehicle for the dissemination of virus to target organs and as a reservoir for viral persistence, as has been shown for other lentiviruses including visna virus and caprine arthritis encephalitis virus.
Stem Cells and Metastatic Cancer: Fatal Attraction?
Authors: Riccardo Fodde
Journal: PLoS Medicine (2006)

Neural stem cells (NSCs) are generally defined by their dual capacity to self-renew and differentiate into more specialized cell types such as neurons and glia. NSCs have been the object of many studies aimed at neuron replacement therapy in several degenerative conditions of the central nervous system such as Parkinson disease, Alzheimer disease, multiple sclerosis, and amyotrophic lateral sclerosis.

Pathotropism (movement towards diseased areas), a yet incompletely understood characteristic of NSCs, makes them particularly attractive candidates not only to replace damaged tissue in degenerative pathologies, but also to deliver therapeutic molecules in patients with disseminated metastatic cancer [1]. By 2000, several studies had shown that upon intracranial transplantation into animal models of brain cancer, NSCs are able to specifically migrate to sites of neoplasia [2–4], possibly in response to chemotactic signals emanating from cancer cells. Perhaps even more surprisingly, this tropism of neural stem cells can be exploited to target extracranial tumors of both neural and non-neural origins [5].
Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women
Authors: L. Minig, D. Franchi, S. Boveri, C. Casadio, L. Bocciolone, M. Sideri
Journal: Annals of Oncology (2010)
Early Experience with Dual Kidney Transplantation in Adults using Expanded Donor Criteria
Authors: GIUSEPPE REMUZZI, JOSEP GRINYÒ, PIERO RUGGENENTI, MARCO BEATINI, EDWARD H. COLE, EDGAR L. MILFORD, BARRY M. BRENNER
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Dual transplant of marginal kidneys otherwise not considered for single transplant may give access to an expanded pool of cadaveric organs without exposing recipients to the drawbacks of a limited nephron mass supply. This prospective, case-control study compares adverse events and graft outcome in 24 recipients of two marginal kidneys from donors who were &gt;60 yr old or who had diabetes, hypertension, or non-nephrotic proteinuria (cases), with that of 48 age- and gender-matched control subjects who received single ideal grafts at the same center and were given the same immuno-suppressive therapy. Marginal kidneys with no macroscopic abnormalities were selected for the double transplant on the basis of a predefined score of histologic damage. Six-month patient and kidney survival was 100% with both of the procedures. Incidence (20.8% versus 20.8%) and median (range) duration of posttransplant anuria (5 [2 to 12] versus 7 [2 to 13] days) were comparable in cases and control subjects, respectively. Time to normal serum creatinine and mean serum creatinine values at each time visit were comparable as well, but with significantly lower levels in cases compared with control subjects from month 2 to last follow-up (1.56 ± 0.65 versus 1.74 ± 0.73 mg/dl, P = 0.04). Diastolic BP values averaged during the entire posttransplant period were significantly lower in cases than in control subjects (83.2 ± 11.5 versus 85.1 ± 12.5 mmHg, respectively, P = 0.008). Donor/recipient body weight ratio was the only covariate significantly associated at univariate ( P = 0.002) and multivariate ( P = 0.001) analysis with last available serum creatinine concentrations. Incidence of acute allograft rejections (20.8% versus 18.8%) and of major surgical complications was comparable in the two groups. No renal artery or vein thrombosis was reported in either group. Dual transplants of marginal kidneys are as safe and tolerated as single transplants, and possibly offer an improved filtration power without exposing the recipient to enhanced risk of delayed renal function recovery, acute allograft rejection, or major surgical complications.
The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas
Authors: Eva Hernando, Elizabeth Charytonowicz, Maria E Dudas, Silvia Menendez, Igor Matushansky, Joslyn Mills, Nicholas D Socci, Nille Behrendt, Li Ma, Robert G Maki, Pier Paolo Pandolfi, Carlos Cordon-Cardo
Journal: Nature Medicine (2007)
Novel Noncatalytic Role for Caspase-8 in Promoting Src-Mediated Adhesion and Erk Signaling in Neuroblastoma Cells
Authors: Darren Finlay, Kristiina Vuori
Journal: Cancer Research (2007)

Abstract Neuroblastomas are extremely aggressive, although heterogeneous, cancers with a poor prognosis upon metastasis. Some evidence has suggested a correlative silencing of caspase-8 with MYCN amplification in neuroblastoma. A prognostic effect of this silencing, however, has been disputed. We report here hitherto undescribed roles for caspase-8 in the modulation of cell adhesion and subsequent activation of the Erk signaling pathway. Re-expression of caspase-8 in neuroblastoma cells lacking endogenous caspase-8 expression was found to promote cell adhesion to extracellular matrix and to activate adhesion-dependent signaling pathways, such as the Erk kinase cascade. This function of caspase-8 occurred irrespective of its proteolytic activity. Additionally, a pool of caspase-8 was shown to co-localize with the Src tyrosine kinase at the cellular periphery. Furthermore, our studies showed that caspase-8 forms a physical protein complex with Src via its death effector domains (DED) and maintains the complex in a detergent-soluble fraction. We also show that the DEDs of caspase-8 alone are necessary and sufficient to recreate the adhesive and biochemical phenotypes observed with the full-length protein, suggesting that caspase-8 may exert these effects via its association with Src. This protein complex association of caspase-8 and Src, and concomitant downstream signaling events, may help reconcile why a potential tumor suppressor such as caspase-8 is rarely absent in cancers. [Cancer Res 2007;67(24):11704–11]
Trends and Characteristics of Self-reported Case Presentation of Diabetes Diagnosis Among Youth From 2002 to 2010: Findings From the SEARCH for Diabetes in Youth Study
Authors: Sharon H. Saydah, Giuseppina Imperatore, Leora Henkin, Ralph D’Agostino, Jasmin Divers, Elizabeth J. Mayer-Davis, Dana Dabelea, Georgeanna Klingensmith, Catherine Pihoker, Jean M. Lawrence
Journal: Diabetes Care (2015)

Diagnosis of diabetes in youth is increasing in the U.S. (1,2). It is not known how much of this change is due to an increase in diabetes and how much is due to improved case detection, especially for type 2 diabetes. Some researchers have hypothesized that part of the explanation for the increase in diabetes diagnosis in youth is increased screening, resulting in a higher percentage of cases being identified. The objective of this study was to assess whether the change in diabetes could be explained by changes in case identification by examining trends from 2002 to 2010 in self-reported case presentation of diabetes.

Briefly, there were 9,054 youth aged <20 years with newly diagnosed diabetes between 2002 and 2010 in the SEARCH for Diabetes in Youth study (3). Participants were asked, “How did you find out you had diabetes?” Responses were grouped into symptoms, checkup, community screening, or other. Self-reported case presentation patterns were examined in 3-year blocks to assess change over time, reported by diabetes type. We explored trends in self-reported modes of diabetes diagnosis (i.e., symptoms, checkup, screening, and other …
Molecular Staging of Cervical Lymph Nodes in Squamous Cell Carcinoma of the Head and Neck
Authors: Robert L. Ferris, Liqiang Xi, Siva Raja, Jennifer L. Hunt, Jun Wang, William E. Gooding, Lori Kelly, Jesus Ching, James D. Luketich, Tony E. Godfrey
Journal: Cancer Research (2005)

Abstract Clinical staging of cervical lymph nodes from patients with squamous cell carcinoma of the head and neck (SCCHN) has only 50% accuracy compared with definitive pathologic assessment. Consequently, both clinically positive and clinically negative patients frequently undergo neck dissections that may not be necessary. To address this potential overtreatment, sentinel lymph node (SLN) biopsy is currently being evaluated to provide better staging of the neck. However, to fully realize the potential improvement in patient care afforded by the SLN procedure, a rapid and accurate SLN analysis is necessary. We used quantitative reverse transcription–PCR (QRT-PCR) to screen 40 potential markers for their ability to detect SCCHN metastases to cervical lymph nodes. Seven markers were identified with good characteristics for identifying metastatic disease, and these were validated using a set of 26 primary tumors, 19 histologically positive lymph nodes, and 21 benign nodes from patients without cancer. Four markers discriminated between positive and benign nodes with accuracy &amp;gt;97% but only one marker, pemphigus vulgaris antigen (PVA), discriminated with 100% accuracy in both the observed data and a statistical bootstrap analysis. A rapid QRT-PCR assay for PVA was then developed and incorporated into a prototype instrument capable of performing fully automated RNA isolation and QRT-PCR. The automated analysis with PVA provided perfect discrimination between histologically positive and benign lymph nodes and correctly identified two lymph nodes with micrometastatic tumor deposits. These assays were completed (from tissue to result) in ∼30 minutes, thus demonstrating the feasibility of intraoperative staging of SCCHN SLNs by QRT-PCR.
Active and Passive Cigarette Smoking and Acute Lung Injury after Severe Blunt Trauma
Authors: Carolyn S. Calfee, Michael A. Matthay, Mark D. Eisner, Neal Benowitz, Mariah Call, Jean-François Pittet, Mitchell J. Cohen
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Cigarette smoking has been demonstrated in laboratory studies to have effects on lung epithelial and endothelial function similar to those observed in acute lung injury (ALI). However, the association between active and passive cigarette smoke exposure and susceptibility to ALI has not been prospectively studied.We hypothesized that both active and passive cigarette smoke exposure would be associated with increased susceptibility to ALI after severe blunt trauma.We measured levels of cotinine, a metabolite of nicotine and validated biomarker of tobacco use, in plasma samples obtained immediately on arrival at the emergency department from 144 adult subjects after severe blunt trauma. Patients were then followed for the development of ALI.Increasing quartiles of plasma cotinine were associated with the development of ALI (odds ratio [OR] for developing ALI in highest cotinine quartile, 3.25; 95% confidence interval [CI], 1.22-8.68; P = 0.017 for trend across quartiles). Moderate to heavy passive smoke exposure was associated with nearly the same odds of developing ALI as active smoking (OR for moderate to heavy passive smoking compared with no exposure or low level exposure, 3.03; 95% CI, 1.15-8.04; OR for active smoking, 2.77; 95% CI, 1.28-5.99). This association persisted after adjusting for other predictors of ALI, including Injury Severity Score and alcohol abuse.Both moderate to heavy passive smoking and active smoking are independently associated with the development of ALI after severe blunt trauma. This finding has important implications both for public health and for understanding the pathogenesis of ALI.
Death by withdrawal from dialysis
Authors: L U Mailloux, A G Bellucci, B Napolitano, R T Mossey, B M Wilkes, P A Bluestone
Journal: Journal of the American Society of Nephrology (1993)

The reasons for withdrawal from dialysis are not well understood. The goals of this study were to determine the risk of dying by withdrawal from dialysis over time and to elucidate pertinent clinical correlates in 716 long-term dialysis patients. These patients were monitored from the initiation of dialysis through the time of death, transplant or transfer to another program during a 20-yr period from 1970 through 1989. The causes of death in the 340 deceased patients were analyzed. Clinical correlates and associated risk factors were evaluated in the patients who died from withdrawal from dialysis. Withdrawal from dialysis was defined as: "Death with manifestations of uremia because of withdrawal from dialysis. Underlying medical conditions should not have been active, leading to rapid deterioration with imminent death." Withdrawal from dialysis and cardiac events were the second leading cause of death, each accounting for 18.5% of the deaths. Patients stopping dialysis were older at the start of dialysis than were patients dying of other causes (P < 0.0006; Kruskal-Wallis test), with 65.1% of these patients 61 yr of age and older. Cancer, malnutrition, catabolism, and "dissatisfaction with life" were important associations with the decision to withdraw. More than 50% of patients withdrawing from dialysis had either diabetic nephropathy or atherosclerotic renal vascular disease. Withdrawal from dialysis was a common cause of death in these dialysis patients especially if they were over 61 and had systemic diseases such as diabetes mellitus and renal vascular disease. The reasons for a higher incidence of withdrawal in certain programs deserve further study.
A Novel Role for the β2 Integrin CD11b/CD18 in Neutrophil Apoptosis: A Homeostatic Mechanism in Inflammation
Authors: Angela Coxon, Phillipe Rieu, Fern J. Barkalow, Sanaz Askari, Arlene H. Sharpe, Ulrich H. von Andrian, M.Amin Arnaout, Tanya N. Mayadas
Journal: Immunity (1996)
Comparison of elderly people's technique in using two dry powder inhalers to deliver zanamivir: randomised controlled
Authors: P. Diggory
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To determine whether elderly people can learn to use the inhaler used to deliver zanamivir (Relenza Diskhaler) as effectively as the Turbohaler and to identify which aspects of inhaler technique are most problematic. <b>Design:</b> Randomised, controlled, intervention study. <b>Setting:</b> Wards for acute elderly care in a large district general hospital. <b>Participants:</b> 73 patients who were unfamiliar with the use of an inhaler, aged 71 to 99 (mean 83) years. <b>Main outcome measures:</b> Initial scores and changes in scores 24 hours later using a 10 point scoring system of five aspects of inhaler technique. <b>Results:</b> 38 patients were allocated the Relenza Diskhaler and 35 the Turbohaler. The mean total score was significantly greater in the Turbohaler than Diskhaler groups both initially (8.74 <i>v</i> 7.05) and after 24 hours (8.28 <i>v</i> 5.43). The major difference between inhalers was in loading and priming. After tuition 50% (19 of 38) of patients allocated the Diskhaler were unable to load and prime the device and 65% (24 of 37) were unable to do so 24 hours later. Of those allocated the Turbohaler, two patients were unable to load and prime the device after initial review and one after 24 hours. <b>Conclusion:</b> Most elderly people cannot use the inhaler device used to deliver the anti-influenza drug zanamivir. Treatment with this drug is unlikely to be effective in elderly people unless the delivery system is improved
EVI1 Impairs Myelopoiesis by Deregulation of PU.1 Function
Authors: Leopoldo Laricchia-Robbio, Kavitha Premanand, Ciro R. Rinaldi, Giuseppina Nucifora
Journal: Cancer Research (2009)

EVI1 is an oncogene inappropriately expressed in the bone marrow (BM) of approximately 10% of myelodysplastic syndrome (MDS) patients. This disease is characterized by severe anemia and multilineage myeloid dysplasia that are thought to be a major cause of mortality in MDS patients. We earlier reported on a mouse model that constitutive expression of EVI1 in the BM led to fatal anemia and myeloid dysplasia, as observed in MDS patients, and we subsequently showed that EVI1 interaction with GATA1 blocks proper erythropoiesis. Whereas this interaction could provide the basis for the erythroid defects in EVI1-positive MDS, it does not explain the alteration of myeloid differentiation. Here, we have examined the expression of several genes activated during terminal myelopoiesis in BM cells and identified a group of them that are altered by EVI1. A common feature of these genes is their regulation by the transcription factor PU.1. We report here that EVI1 interacts with PU.1 and represses the PU.1-dependent activation of a myeloid promoter. EVI1 does not seem to inhibit PU.1 binding to DNA, but rather to block its association with the coactivator c-Jun. After mapping the PU.1-EVI1 interaction sites, we show that an EVI1 point mutant, unable to bind PU.1, restores the activation of PU.1-regulated genes and allows a normal differentiation of BM progenitors in vitro.
iBsu1103: a new genome-scale metabolic model of Bacillus subtilis based on SEED annotations
Authors: Christopher S Henry, Jenifer F Zinner, Matthew P Cohoon, Rick L Stevens
Journal: Genome biology (2009)

Abstract Background Bacillus subtilis is an organism of interest because of its extensive industrial applications, its similarity to pathogenic organisms, and its role as the model organism for Gram-positive, sporulating bacteria. In this work, we introduce a new genome-scale metabolic model of B. subtilis 168 called i Bsu1103. This new model is based on the annotated B. subtilis 168 genome generated by the SEED, one of the most up-to-date and accurate annotations of B. subtilis 168 available. Results The i Bsu1103 model includes 1,437 reactions associated with 1,103 genes, making it the most complete model of B. subtilis available. The model also includes Gibbs free energy change (Δ r G '°) values for 1,403 (97%) of the model reactions estimated by using the group contribution method. These data were used with an improved reaction reversibility prediction method to identify 653 (45%) irreversible reactions in the model. The model was validated against an experimental dataset consisting of 1,500 distinct conditions and was optimized by using an improved model optimization method to increase model accuracy from 89.7% to 93.1%. Conclusions Basing the i Bsu1103 model on the annotations generated by the SEED significantly improved the model completeness and accuracy compared with the most recent previously published model. The enhanced accuracy of the i Bsu1103 model also demonstrates the efficacy of the improved reaction directionality prediction method in accurately identifying irreversible reactions in the B. subtilis metabolism. The proposed improved model optimization methodology was also demonstrated to be effective in minimally adjusting model content to improve model accuracy.
Aprotinin in the management of Achilles tendinopathy: a randomised controlled trial
Authors: R Brown, J Orchard, M Kinchington, A Hooper, G Nalder
Journal: British Journal of Sports Medicine (2006)

Achilles tendinopathy is a common condition, which can become chronic and interfere with athletic performance. The proteinase inhibitor aprotinin (as injection) has been found to improve recovery in patellar tendinopathy (evidence level 1b) and Achilles tendinopathy. Internationally this therapy is being used based on this limited knowledge base.