tbuckley/cabot-search huggingface dataset:
CD8+ Enriched “Young” Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma
Authors: Mark E. Dudley, Colin A. Gross, Michelle M. Langhan, Marcos R. Garcia, Richard M. Sherry, James C. Yang, Giao Q. Phan, Udai S. Kammula, Marybeth S. Hughes, Deborah E. Citrin, Nicholas P. Restifo, John R. Wunderlich, Peter A. Prieto, Jenny J. Hong, Russell C. Langan, Daniel A. Zlott, Kathleen E. Morton, Donald E. White, Carolyn M. Laurencot, Steven A. Rosenberg
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Tumor-infiltrating lymphocytes (TIL) and interleukin (IL)-2 administered following lymphodepletion can cause the durable complete regression of bulky metastatic melanoma in patients refractory to approved treatments. However, the generation of a unique tumor-reactive TIL culture for each patient may be prohibitively difficult. We therefore investigated the clinical and immunologic impact of unscreened, CD8+ enriched “young” TIL. Experimental Design: Methods were developed for generating TIL that minimized the time in culture and eliminated the individualized tumor-reactivity screening step. Thirty-three patients were treated with these CD8+ enriched young TIL and IL-2 following nonmyeloablative lymphodepletion (NMA). Twenty-three additional patients were treated with CD8+ enriched young TIL and IL-2 after lymphodepletion with NMA and 6 Gy of total body irradiation. Results: Young TIL cultures for therapy were successfully established from 83% of 122 consecutive melanoma patients. Nineteen of 33 patients (58%) treated with CD8+ enriched young TIL and NMA had an objective response (Response Evaluation Criteria in Solid Tumors) including 3 complete responders. Eleven of 23 patients (48%) treated with TIL and 6 Gy total body irradiation had an objective response including 2 complete responders. At 1 month after TIL infusion the absolute CD8+ cell numbers in the periphery were highly correlated with response. Conclusions: This study shows that a rapid and simplified method can be used to reliably generate CD8+ enriched young TIL for administration as an individualized therapy for advanced melanoma, and may allow this potentially effective treatment to be applied at other institutions and to reach additional patients. Clin Cancer Res; 16(24); 6122–31. ©2010 AACR.
The neurology of syntax: Language use without Broca's area
Authors: Yosef Grodzinsky
Journal: Behavioral and Brain Sciences (2000)

A new view of the functional role of the left anterior cortex in language use is proposed. The experimental record indicates that most human linguistic abilities are not localized in this region. In particular, most of syntax (long thought to be there) is not located in Broca's area and its vicinity (operculum, insula, and subjacent white matter). This cerebral region, implicated in Broca's aphasia, does have a role in syntactic processing, but a highly specific one: It is the neural home to receptive mechanisms involved in the computation of the relation between transformationally moved phrasal constituents and their extraction sites (in line with the Trace-Deletion Hypothesis). It is also involved in the construction of higher parts of the syntactic tree in speech production. By contrast, basic combinatorial capacities necessary for language processing – for example, structure-building operations, lexical insertion – are not supported by the neural tissue of this cerebral region, nor is lexical or combinatorial semantics. The dense body of empirical evidence supporting this restrictive view comes mainly from several angles on lesion studies of syntax in agrammatic Broca's aphasia. Five empirical arguments are presented: experiments in sentence comprehension, cross-linguistic considerations (where aphasia findings from several language types are pooled and scrutinized comparatively), grammaticality and plausibility judgments, real-time processing of complex sentences, and rehabilitation. Also discussed are recent results from functional neuroimaging and from structured observations on speech production of Broca's aphasics. Syntactic abilities are nonetheless distinct from other cognitive skills and are represented entirely and exclusively in the left cerebral hemisphere. Although more widespread in the left hemisphere than previously thought, they are clearly distinct from other human combinatorial and intellectual abilities. The neurological record (based on functional imaging, split-brain and right-hemisphere-damaged patients, as well as patients suffering from a breakdown of mathematical skills) indicates that language is a distinct, modularly organized neurological entity. Combinatorial aspects of the language faculty reside in the human left cerebral hemisphere, but only the transformational component (or algorithms that implement it in use) is located in and around Broca's area.
Negative prognostic value of glutathione S-transferase(GSTM1 and GSTT1) deletions in adult acute myeloid leukemia
Authors: Maria Teresa Voso, Francesco D'Alo', Rossana Putzulu, Luca Mele, Alessandra Scardocci, Patrizia Chiusolo, Roberto Latagliata, Francesco Lo-Coco, Sergio Rutella, Livio Pagano, Stefan Hohaus, Giuseppe Leone
Journal: Blood (2002)
Handbook of Biological Psychiatry, Part I: Disciplines Relevant to Biological Psychiatry; Handbook of Biological Psychiatry, Part III: Brain Mechanisms and Abnormal Behavior—Genetics and Neuroendocrinology; Handbook of Biological Psychiatry, Part IV: Brain Mechanisms and Abnormal Behavior—Chemistry; Handbook of Biological Psychiatry, Part V: Drug Treatment in Psychiatry—Psychotropic Drugs; Handbook of Biological Psychiatry, Part VI: Practical Applications of Psychotropic Drugs and Other …
Authors: ROBERT T. RUBIN
Journal: American Journal of Psychiatry (1982)
Angiopoietin-1 mediates inhibition of hypertension-induced release of angiopoietin-2 from endothelial cells
Authors: Thomas Korff, Evelyn Ernst, Rainer Nobiling, Anja Feldner, Yvonne Reiss, Karl H. Plate, Ulrike Fiedler, Hellmut G. Augustin, Markus Hecker
Journal: Cardiovascular Research (2012)

Adequate endothelial cell stimulation is a prerequisite for the adaptive remodelling of macro- and microvessels. A pivotal autocrine mechanism following endothelial cell activation is the release of angiopoietin-2 (Ang-2), which subsequently antagonizes the binding of Ang-1 to the Tie-2 receptor, thus sensitizing the endothelial cells to pro-angiogenic and/or pro-inflammatory stimuli. Based on the observation that hypertension in mice reduces the abundance of Ang-2 stored in arterial endothelial cells, this study was aimed at testing the hypothesis that an increase in wall stress (WS) or stretch—a hallmark of hypertension—is sufficient to release Ang-2 from endothelial cells. In fact, stretching of isolated perfused mouse arteries or human cultured endothelial cells rapidly elicited an increased release of Ang-2. In the cultured endothelial cells, this was preceded by a transient rise in intracellular free calcium, abrogated through calcium chelation and accompanied by a decrease in Tie-2 phosphorylation. Interestingly, Ang-1 abolished the stretch-induced release of Ang-2 from both cultured and native endothelial cells through inhibiting the stretch-dependent mobilization of intracellular calcium. Collectively, these results indicate that increased WS or stretch facilitates the release of Ang-2 from endothelial cell Weibel–Palade bodies, and that Ang-1 can block this by attenuating the stretch-mediated rise in intracellular calcium.
Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing
Authors: S. Esposito, F. Blasi, C. Arosio, L. Fioravanti, L. Fagetti, R. Droghetti, P. Tarsia, L. Allegra, N. Principi
Journal: European Respiratory Journal (2000)

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae in reactive airway disease, 71 children aged 2-14 yrs with an acute episode of wheezing and 80 age-matched healthy children were studied. Sera for the determination of specific antibody levels and nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae deoxyribonucleic acid were obtained on admission and after 4-6 weeks. All children with wheezing received a standard therapy with inhaled corticosteroids and bronchodilators for 5-7 days; when antibiotic was added on the basis of the judgement of the paediatrician in charge, clarithromycin 15 mg.kg body weight(-1).day(-1) for 10 days was used. Acute M. pneumoniae and C. pneumoniae infections were detected significantly more often in children with wheezing than in controls. In patients infected with one of the two pathogens, a history of recurrent wheezing was significantly more frequent than in those without either infection. During a 3-month follow-up period, among nonantibiotic-treated children, those with acute M. pneumoniae and/or C. pneumoniae infection showed a significantly higher recurrence of wheezing than those without acute M. pneumoniae and/or C. pneumoniae infection (p=0.03). These results highlight the apparently significant relationship of Mycoplasma pneumoniae and Chlamydia pneumoniae with wheezing in children, particularly in subjects with a history of recurrent episodes, and the possible improvement in the course of reactive airway disease within paediatric patients with acute Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection.
Changes in Features of the Metabolic Syndrome and Incident Impaired Glucose Regulation or Type 2 Diabetes in a Chinese Population
Authors: Jian-jun Wang, Gang Hu, Jani Lappalainen, Maija E. Miettinen, Qing Qiao, Jaakko Tuomilehto
Journal: Diabetes Care (2005)

The current understanding of the pathogenesis of type 2 diabetes is mainly based on a large number of cross-sectional and prospective studies (1– 4) in which nondiabetic individuals were followed for several years to determine incident cases of diabetes without repeating assessment of other metabolic characteristics except for assay of plasma glucose during follow-up. In fact, only the studies in the Pima Indian population (5–7) have examined the changes in anthropometric characteristics, insulin secretion, and insulin action during the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to diabetes. Thus far, no study has directly addressed the effects of changes in the components of the metabolic syndrome on the transition to diabetes in other populations. The purpose of this study was to investigate the changes in the features of the metabolic syndrome during the transition from one state of glucose homeostasis to another in a cohort of Chinese people and to understand the relative contributions of these changes to the development of impaired glucose regulation (IGR) or type 2 diabetes. RESEARCH DESIGN AND METHODS — A total of 627 subjects without diabetes at baseline who participated in the National Diabetes Survey in 1994 and the follow-up survey in 1999 in the Beijing area (8) were included in this study. All of the subjects had measurements of BMI, blood pressure, fasting serum total cholesterol, triglecerides, insulin, plasma fasting glucose, and 2-h postload glucose (2-hPG) at baseline and follow-up separately. Past medical history, family history of diabetes, history of pharmacological treatment, smoking status, education, and occupation were determined with a standardized questionnaire. Obesity was defined as BMI 25.0 kg/m 2 , according to the recommendations for Asians (9). Hy
Lectures on the Compressed Air Bath and its Uses in the Treatment of Disease
Authors: C. T. Williams
Journal: BMJ (1885)

The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from TLRs and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes and conventional and plasmacytoid dendritic cells produced less IL-12p70 and IFN-α (and consequently induced less IFN-γ), moderately less TNF-α, but as much or even more IL-1β, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs the adult white-blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.
Clinical Profiles and Outcomes of Acute Type B Aortic Dissection in the Current Era: Lessons From the International Registry of Aortic Dissection (IRAD)
Authors: Toru Suzuki, Rajendra H. Mehta, Hüseyin Ince, Ryozo Nagai, Yasunari Sakomura, Frank Weber, Tetsuya Sumiyoshi, Eduardo Bossone, Santi Trimarchi, Jeanna V. Cooper, Dean E. Smith, Eric M. Isselbacher, Kim A. Eagle, Christoph A. Nienaber
Journal: Circulation (2003)

Clinical profiles and outcomes of patients with acute type B aortic dissection have not been evaluated in the current era.Accordingly, we analyzed 384 patients (65+/-13 years, males 71%) with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD). A majority of patients had hypertension and presented with acute chest/back pain. Only one-half showed abnormal findings on chest radiograph, and almost all patients had computerized tomography (CT), transesophageal echocardiography, magnetic resonance imaging (MRI), and/or aortogram to confirm the diagnosis. In-hospital mortality was 13% with most deaths occurring within the first week. Factors associated with increased in-hospital mortality on univariate analysis were hypotension/shock, widened mediastinum, periaortic hematoma, excessively dilated aorta (>or=6 cm), in-hospital complications of coma/altered consciousness, mesenteric/limb ischemia, acute renal failure, and surgical management (all P<0.05). A risk prediction model with control for age and gender showed hypotension/shock (odds ratio [OR] 23.8, P<0.0001), absence of chest/back pain on presentation (OR 3.5, P=0.01), and branch vessel involvement (OR 2.9, P=0.02), collectively named 'the deadly triad' to be independent predictors of in-hospital death.Our study provides insight into current-day profiles and outcomes of acute type B aortic dissection. Factors associated with increased in-hospital mortality ("the deadly triad") should be identified and taken into consideration for risk stratification and decision-making.
Trends in Tracheostomy for Mechanically Ventilated Patients in the United States, 1993–2012
Authors: Anuj B. Mehta, Sohera N. Syeda, Lisa Bajpayee, Colin R. Cooke, Allan J. Walkey, Renda Soylemez Wiener
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: National trends in tracheostomy for mechanical ventilation (MV) patients are not well characterized.Objectives: To investigate trends in tracheostomy use, timing, and outcomes in the United States.Methods: We calculated estimates of tracheostomy use and outcomes from the National Inpatient Sample from 1993 to 2012. We used hierarchical models to determine factors associated with tracheostomy use among MV patients.Measurements and Main Results: We identified 1,352,432 adults who received tracheostomy from 1993 to 2012 (9.1% of MV patients). Tracheostomy was more common in surgical patients, men, and racial/ethnic minorities. Age-adjusted incidence of tracheostomy increased by 106%, rising disproportionately to MV use. Among MV patients, tracheostomy rose from 6.9% in 1993 to 9.8% in 2008, and then it declined to 8.7% in 2012 (P < 0.0001). Increases in tracheostomy use were driven by surgical patients (9.5% in 1993; 15.0% in 2012; P < 0.0001), with little change among nonsurgical patients (5.8% in 1993; 5.9% in 2012; P < 0.0001). Over time, tracheostomies were performed earlier (median, 11 d in 1998; 10 d in 2012; P < 0.0001), whereas hospital length of stay declined (median, 39 d in 1993; 26 d in 2012; P < 0.0001), discharges to long-term facilities increased (40.1% vs. 71.9%; P < 0.0001), and hospital mortality declined (38.1% vs. 14.7%; P < 0.0001).Conclusions: Over the past two decades, tracheostomy use rose substantially in the United States until 2008, when use began to decline. The observed dramatic increase in discharge of tracheostomy patients to long-term care facilities may have significant implications for clinical care, healthcare costs, policy, and research. Future studies should include long-term facilities when analyzing outcomes of tracheostomy.
On the Treatment of Nocturnal Enuresis and Spermatic Incontinence
Authors: D. C. Black
Journal: BMJ (1871)

THE BRITISH MEDICAL 7OURNAL.609-and in the woman with spinal disease, of IO per minute.Tern5erature.In four cases, it was observed in the rectum.In three of these, there was no change ; in one, there was a decrease of o.8 deg.In the case of spinal disease observed (in the axilla), there was also a decrease of o.8 deg.'espiration.-Byan unfortunate omission, the respirations were not counted, except in two cases; in one of these, no change was
Minocycline in Rheumatoid Arthritis: A 48-Week, Double-Blind, Placebo-Controlled Trial
Authors: Barbara C. Tilley
Journal: Annals of Internal Medicine (1995)

Objective: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. Design: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. Setting: 6 clinical centers in the United States. Patients: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. Measurements: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. Results: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. Conclusions: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined. For current author affiliations, see end of text. *For members of the MIRA Trial Group, see the Appendix. For current author affiliations, see end of text. †Deceased.
Epigenetic silencing of RASSF1A deregulates cytoskeleton and promotes malignant behavior of adrenocortical carcinoma
Authors: Reju Korah, James M Healy, John W Kunstman, Annabelle L Fonseca, Amir H Ameri, Manju L Prasad, Tobias Carling
Journal: Molecular Cancer (2013)

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high mutational heterogeneity and a generally poor clinical outcome. Despite implicated roles of deregulated TP53, IGF-2 and Wnt signaling pathways, a clear genetic association or unique mutational link to the disease is still missing. Recent studies suggest a crucial role for epigenetic modifications in the genesis and/or progression of ACC. This study specifically evaluates the potential role of epigenetic silencing of RASSF1A, the most commonly silenced tumor suppressor gene, in adrenocortical malignancy.Using adrenocortical tumor and normal tissue specimens, we show a significant reduction in expression of RASSF1A mRNA and protein in ACC. Methylation-sensitive and -dependent restriction enzyme based PCR assays revealed significant DNA hypermethylation of the RASSF1A promoter, suggesting an epigenetic mechanism for RASSF1A silencing in ACC. Conversely, the RASSF1A promoter methylation profile in benign adrenocortical adenomas (ACAs) was found to be very similar to that found in normal adrenal cortex. Enforced expression of ectopic RASSF1A in the SW-13 ACC cell line reduced the overall malignant behavior of the cells, which included impairment of invasion through the basement membrane, cell motility, and solitary cell survival and growth. On the other hand, expression of RASSF1A/A133S, a loss-of-function mutant form of RASSF1A, failed to elicit similar malignancy-suppressing responses in ACC cells. Moreover, association of RASSF1A with the cytoskeleton in RASSF1A-expressing ACC cells and normal adrenal cortex suggests a role for RASSF1A in modulating microtubule dynamics in the adrenal cortex, and thereby potentially blocking malignant progression.Downregulation of RASSF1A via promoter hypermethylation may play a role in the malignant progression of adrenocortical carcinoma possibly by abrogating differentiation-promoting RASSF1A- microtubule interactions.
Whole body muscle hypertrophy from resistance training: distribution and total mass
Authors: T Abe, K Kojima, C F Kearns, H Yohena, J Fukuda
Journal: British Journal of Sports Medicine (2003)

To examine the absolute and relative changes in skeletal muscle (SM) size using whole body magnetic resonance imaging (MRI) in response to heavy resistance training (RT).Three young men trained three days a week for 16 weeks.MRI measured total SM mass and fat free mass (FFM) had increased by 4.2 kg and 2.6 kg respectively after resistance training.RT induces larger increases in SM mass than in FFM. RT induced muscle hypertrophy does not occur uniformly throughout each individual muscle or region of the body. Therefore the distribution of muscle hypertrophy and total SM mass are important for evaluating the effects of total body RT on muscle size.
Central sleep apnoea syndrome in patients with chronic heart disease: a critical review of the current literature
Authors: T Kohnlein
Journal: Thorax (2002)

The prevalence, prognosis, clinical presentation, pathophysiology, diagnosis, and treatment of the central sleep apnoea syndrome (CSAS) are reviewed and its relationship with congestive heart failure (CHF) is discussed. Adequately powered trials are needed with survival and health status as end points to establish whether correction of sleep related breathing abnormalities improves the outcome in patients with CHF.