tbuckley/cabot-search huggingface dataset:
Childhood Maltreatment, Altered Limbic Neurobiology, and Substance Use Relapse Severity via Trauma-Specific Reductions in Limbic Gray Matter Volume
Authors: Nicholas T. Van Dam, Kenneth Rando, Marc N. Potenza, Keri Tuit, Rajita Sinha
Journal: JAMA Psychiatry (2014)

IMPORTANCE Substance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown.OBJECTIVES To identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse. DESIGN, SETTING, AND PARTICIPANTSStructural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center.Both groups included individuals with a range of CM experiences.Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity.INTERVENTION Standard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD.MAIN OUTCOMES AND MEASURES Gray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse. RESULTSControlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05;uncorrected P = .001).Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048),while CM-related GMV reductions predicted severity of substance use relapse (P = .04). CONCLUSIONS AND RELEVANCEFindings indicate that CM was related to decreased GMV in limbic regions, which in turn predicted increased risk of relapse in SUD.These results suggest that CM may significantly affect the course of SUD treatment outcomes and that SUD treatment planning may benefit from identifying and addressing CM.
Abstract 4912: Hyperthermia induced NO repressed NFκB regulates IR-induced EMT, CSC self-renewal and pluripotency
Authors: Corinne Dinges, Mohan Natarajan, Sheeja Aravindan, Terence S. Herman, Natarajan Aravindan
Journal: Cancer Research (2014)

Abstract Based on clinical evidence, hyperthermia treatment (HT) in combination with radiation (IR) achieves superior local control for recurrent chest wall breast cancer (BCa). The effect of HT combined with IR is due partly to its independent cytotoxic effects, and partly to its radiosensitizing effect. Recently, we have shown that apoptosis upon hyperthermia of BCa cells is regulated by NO-mediated suppression of NFκB. Also, we have demonstrated that tumor cells that survive a course of IR are instrumental in tumor relapse and progression. Accordingly, we investigated whether HT exerts NO-NFκB axis dependent regulation of IR-induced alterations in factors that drive the EMT, CSCs self-renewal capacity and pluripotency maintenance in surviving BCa Cells. Human breast adenocarcinoma (MCF-7) cells either mock-irradiated or exposed IR (2Gy) with or without HT (43°C for 1h) were analyzed for transcriptional regulation of 93 stem cell related molecules using QPCR profiling. NFκB (p50/p65) overexpression, muting by ΔIκBα (with IR) and NO induction by SNP (with HT) approach were used to delineate the role of HT-induced NO and the selective targeting of IR-induced NFκB. Nanog, Sox-2, ABCG-2, N-Cadherin and Myc expressions were examined with immunoblotting. IR profoundly increased the transactivation of 80 stem-cell related molecules. Interestingly, HT reverted the activation of 79 IR-induced genes. Attenuation of all 80 IR-induced genes observed after blocking NFκB with ΔIκBα and by increasing intracellular NO with SNP demonstrated the significant role of NO dependent NFκB suppression in HT-induced inhibition of IR modulated stem-cell related transcriptome. Expression levels of Nanog, Sox-2, ABCG-2, N-Cadherin and Myc validates the potential of HT in mitigating IR-induced stemness. Together this data demonstrates that HT attenuates IR-induced stemness in BCa cells and further imply that HT induced increase in NO may alleviate stemness by selectively targeting IR-induced NFκB. Citation Format: Corinne Dinges, Mohan Natarajan, Sheeja Aravindan, Terence S. Herman, Natarajan Aravindan. Hyperthermia induced NO repressed NFκB regulates IR-induced EMT, CSC self-renewal and pluripotency. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4912. doi:10.1158/1538-7445.AM2014-4912
Regulation of intracellular pH in the rabbit cortical collecting tubule.
Authors: I D Weiner, L L Hamm
Journal: Journal of Clinical Investigation (1990)

The cortical collecting tubule (CCT) is an important nephron segment for Na+, K+, water and acid-base transport. Differential loading characteristics of the pH sensitive dye 2',7'-bis-(2-carboxyethyl)-5(and-6)carboxyfluorescein (BCECF) and basolateral Cl- removal were used to identify and study intracellular pH (pHi) regulation in each of three cell types involved in this transport. Both principal cells and beta-intercalated cells were found to have a basolateral Na+/H+ exchanger based on the Na+ and amiloride sensitivity of pHi recovery from acid loads. Intercalated cells demonstrated abrupt pHi changes with basolateral Cl- removal. alpha-intercalated cells alkalinized; beta-intercalated cells acidified. In the beta-intercalated cells, luminal Cl- removal blocked changes in pHi in response to changes in luminal HCO3- or peritubular Cl-, providing direct evidence for a luminal Cl-/HCO3- exchanger. In principal cells, brief removal of either peritubular or luminal Cl- resulted in no change in pHi; however, return of peritubular Cl- after prolonged removal resulted in a rapid fall in pHi consistent with a basolateral Cl-/HCO3- exchanger, which may be relatively inactive under baseline conditions. Therefore, Cl-/HCO3- exchange is present in all three cell types but varies in location and activity.
ON THE COERCIVE ADMINISTRATION OF FOOD TO THE INSANE
Authors: Luther V. Bell
Journal: American Journal of Psychiatry (1850)

On Coercive Administration of Food.223 who after having again become sound, under a thousand pains and troubles, are so often abandoned by all the world; stripped of all means by the disease itself, they become again disheartened, and tremble for their future prospects.Likewise br these saEutary exertions must the institution give the first impulse, and although she takes upon herself a new burden thereby, ievertheless she encircles herself with new helj s and blessings: a new band of kindness and confidence, and the most active and friendly sympathy binds her to the world, and strengthens and completes her own efficiency.
Respiratory challenge induces high frequency spiking on the static charge sensitive bed (SCSB)
Authors: T Kirjavainen, O Polo, S McNamara, K Vaahtoranta, CE Sullivan
Journal: European Respiratory Journal (1996)

The static charge sensitive bed (SCSB) is a simple and noninvasive device used for the detection of sleep apnoea. In addition to episodes of apnoea or hypopnoea, heavy snorers commonly present with episodes of high frequency spiking on the SCSB. These spiking episodes have been claimed to represent partial upper airway obstruction during sleep, but the mechanism of their appearance is not known. We studied the SCSB spiking phenomenon in awake subjects during experimental respiratory challenge. One female and five male volunteers were studied whilst breathing freely, during hypoxia, hypercapnia and inspiratory and expiratory loading. Oxygen saturation, end-tidal carbon dioxide tension, minute ventilation, oesophageal pressure, electrocardiographic activity (ECG), blood pressure and the SCSB signals were monitored. During free breathing, the SCSB high frequency signal consisted of low amplitude complexes with close time relationship to the cardiac cycle. During respiratory challenge, spiking occurred. These spikes showed no time relationship to the cardiac cycle, but were time-linked to the onset of inspiration or expiration. Spike amplitude correlated with breathing frequency (r2 = 0.59; p &lt; 0.005) and variation in oesophageal pressure (r2 = 0.57; p &lt; 0.005). We conclude that during quiet, unobstructed breathing the static charge sensitive bed high frequency signal represents cardiac activity (ballistocardiogram), whereas during high-drive breathing high frequency spikes are produced. These spikes are respiratory in origin and are likely to represent fast components of respiratory movements. Our results support the use of static charge sensitive bed spiking as a noninvasive measure of breathing stimulation.
Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury
Authors: Christopher P. Regan, Paul J. Adam, Cort S. Madsen, Gary K. Owens
Journal: Journal of Clinical Investigation (2000)

While it is well established that phenotypic modulation of vascular smooth muscle cells (VSMCs) contributes to the development and progression of vascular lesions, little is known regarding the molecular mechanisms of phenotypic modulation in vivo. Here we show that vascular injury reduces transcription of VSMC differentiation marker genes, and we identify cis regulatory elements that may mediate this decrease. Using a carotid wire-injury model in mice carrying transgenes for smooth muscle α-actin, smooth muscle myosin heavy chain, or a SM22α promoter–β-gal reporter, we collected arteries 7 and 14 days after injury and assessed changes in endogenous protein and mRNA levels and in β-gal activity. Endogenous levels for all markers were decreased 7 days after injury and returned to nearly control levels by 14 days. β-gal staining in all lines followed a similar pattern, suggesting that transcriptional downregulation contributed to the injury-induced decreases. To begin to dissect this response, we mutated a putative G/C-rich repressor in the SM22α promoter transgene and found that this mutation significantly attenuated injury-induced downregulation. Hence, transcriptional downregulation contributes to injury-induced decreases in VSMC differentiation markers, an effect that may be partially mediated through a G/C-rich repressor element.
Cisplatin-Induced Long-Term Hearing Impairment Is Associated With Specific Glutathione <i>S</i>-Transferase Genotypes in Testicular Cancer Survivors
Authors: Jan Oldenburg, Sigrid M. Kraggerud, Milada Cvancarova, Ragnhild A. Lothe, Sophie D. Fossa
Journal: Journal of Clinical Oncology (2007)

Purpose Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs). Patients and Methods We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis. Results The risk of having an inferior audiometric result was more than four times higher in TCSs with 105 Ile/ 105 Ile-GSTP1 or 105 Val/ 105 Ile-GSTP1 compared with 105 Val/ 105 Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P &lt; .001 when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was detrimental for hearing ability. Two combined genotypes were associated with hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and 105 Ile/ 105 Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI, 1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1 positive, and 105 Val/ 105 Val-GSTP1) had better hearing ability than TCSs without this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P &lt; .001, OLR). Conclusion The presence of both alleles of 105 Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified.
Incidence of <scp>ATRX</scp> mutations in myelodysplastic syndromes, the value of microcytosis
Authors: Charles Herbaux, Nicolas Duployez, Catherine Badens, Nicolas Poret, Claude Gardin, Mathieu Decamp, Virginie Eclache, Sylvie Daliphard, Anne Murati, Pascale Cony‐Makhoul, Stéphane Cheze, Blandine Beve, Caroline Lacoste, Thomas Prebet, Mathilde Hunault‐Berger, Frédéric Maloisel, Aline Renneville, Martin Figeac, Aspasia Stamatoullas‐Bastard, Christian Bastard, Pierre Fenaux, Claude Preudhomme, Christian Rose
Journal: American Journal of Hematology (2015)

Acquired α-thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy. Our data confirm the low frequency of ATRX mutations in MDS: 0% in an unselected clinical trial cohort of 80 low risk MDS, 0.2-0.8% in a multicenter registry of 2,980 MDS and 43% of MDS with unexplained microcytosis in this same registry. In addition, we reported four novel mutations of the ATRX gene in ATMDS. This study further determines the frequency of ATRX mutations and highlights the importance of microcytosis to detect ATRX mutations within MDS patients.
Efficacy and Safety of Tumor Necrosis Factor Antagonists in Crohn's Disease: Meta-Analysis of Placebo-Controlled Trials
Authors: Laurent Peyrin–Biroulet, Pierre Deltenre, Nicolas de Suray, Julien Branche, William J. Sandborn, Jean–Frédéric Colombel
Journal: Clinical Gastroenterology and Hepatology (2008)
MMP9 and SCF Protect from Apoptosis in Acute Kidney Injury
Authors: Soraya Bengatta, Catherine Arnould, Emmanuel Letavernier, Matthieu Monge, Héle[Combining Grave Accent]ne Martinan de Préneuf, Zena Werb, Pierre Ronco, Brigitte Lelongt
Journal: Journal of the American Society of Nephrology (2009)

Apoptosis of tubular epithelial cells is a hallmark of acute kidney injury (AKI), but the cellular events preceding apoptosis in this setting are incompletely understood. Because matrix metalloproteinase 9 (MMP9) degrades matrix components involved in cell survival, we studied the role of MMP9 in AKI. In the mouse model of folic acid–induced AKI, we observed a marked increase of MMP9 activity in the S3 segment of the proximal tubule (S3PT), correlating with the apoptotic phase. MMP9 deficiency increased apoptosis and the severity of renal lesions and substantially delayed recovery of renal function. MMP9−/− mice exhibited significant apoptosis in the S3PT and the intercalated cells of the collecting duct (I-CD), whereas wild-type mice exhibited none in these segments. Stem cell factor (SCF), an MMP9 substrate, was identified in the S3PT, and its receptor, c-Kit, was expressed in both the S3PT and I-CD. MMP9 released the soluble form of SCF (sSCF) from kidney cells in vivo and in vitro. In addition, SCF inhibited apoptosis of tubular cells in vitro, rescued MMP9−/− S3PT and I-CD from apoptosis in vivo, and improved renal function. An ischemia-reperfusion model of AKI produced similar results. In patients with AKI, urinary sSCF increased with acute tubular necrosis but not with prerenal azotemia. In conclusion, these data show that MMP9 protects the S3 segment of the proximal tubule and the I-CD from apoptosis in AKI, most likely by releasing sSCF.
A Reversible Defect in Natural Killer T Cell Function Characterizes the Progression of Premalignant to Malignant Multiple Myeloma
Authors: Madhav V. Dhodapkar, Matthew D. Geller, David H. Chang, Kanako Shimizu, Shin-Ichiro Fujii, Kavita M. Dhodapkar, Joseph Krasovsky
Journal: The Journal of Experimental Medicine (2003)

We studied the function of antitumor T and natural killer T (NKT) cells from the blood and tumor bed in 23 patients with premalignant gammopathy, nonprogressive myeloma, or progressive multiple myeloma. We show that antitumor killer T cells can be detected in patients with both progressive or nonprogressive myeloma. Vα24+Vβ11+ invariant NKT cells are detectable in the blood and tumor bed of all cohorts. However, freshly isolated NKT cells from both the blood and tumor bed of patients with progressive disease, but not nonprogressive myeloma or premalignant gammopathy, have a marked deficiency of ligand-dependent interferon-γ production. This functional defect can be overcome in vitro using dendritic cells pulsed with the NKT ligand, α-galactosylceramide (α-GalCer). Fresh myeloma cells express CD1d, and can be efficiently killed by autologous NKT cells. We hypothesize that presentation of tumor derived glycolipids by myeloma cells leads to NKT dysfunction in vivo. These data demonstrate that clinical progression in patients with monoclonal gammopathies is associated with an acquired but potentially reversible defect in NKT cell function and support the possibility that these innate lymphocytes play a role in controlling the malignant growth of this incurable B cell tumor in patients.
The evolution of foresight: What is mental time travel, and is it unique to humans?
Authors: Thomas Suddendorf, Michael C. Corballis
Journal: Behavioral and Brain Sciences (2007)

Abstract In a dynamic world, mechanisms allowing prediction of future situations can provide a selective advantage. We suggest that memory systems differ in the degree of flexibility they offer for anticipatory behavior and put forward a corresponding taxonomy of prospection. The adaptive advantage of any memory system can only lie in what it contributes for future survival. The most flexible is episodic memory, which we suggest is part of a more general faculty of mental time travel that allows us not only to go back in time, but also to foresee, plan, and shape virtually any specific future event. We review comparative studies and find that, in spite of increased research in the area, there is as yet no convincing evidence for mental time travel in nonhuman animals. We submit that mental time travel is not an encapsulated cognitive system, but instead comprises several subsidiary mechanisms. A theater metaphor serves as an analogy for the kind of mechanisms required for effective mental time travel. We propose that future research should consider these mechanisms in addition to direct evidence of future-directed action. We maintain that the emergence of mental time travel in evolution was a crucial step towards our current success.
Surgical treatment of idiopathic mediastinal fibrosis: report of five cases.
Authors: I M Mitchell, N R Saunders, O Maher, S C Lennox, D R Walker
Journal: Thorax (1986)

Idiopathic mediastinal fibrosis is a rare disease of unknown aetiology. It is a benign condition in which abnormal proliferation of fibrous tissue occurs within the mediastinum, leading to constriction and obliteration of local structures, particularly the great veins. It is a rare cause of superior vena caval obstruction (1-2%) but one that is potentially amenable to surgical palliation. The results of venous reconstruction in five patients with superior vena caval obstruction secondary to idiopathic mediastinal fibrosis are reported. Reversed autogenous saphenous vein grafts were used in two patients, woven silicone rubber prostheses in two, and bovine pericardial conduits in one patient. Useful long term results were obtained in three patients, but the bovine pericardial graft and one of the vein grafts failed within a few weeks.
Phase II study of everolimus–erlotinib in previously treated patients with advanced non-small-cell lung cancer
Authors: B. Besse, N. Leighl, J. Bennouna, V.A. Papadimitrakopoulou, N. Blais, A.M. Traynor, J.-C. Soria, S. Gogov, N. Miller, V. Jehl, B.E. Johnson
Journal: Annals of Oncology (2013)
Randomization Reveals Unexpected Acute Leukemias in Southwest Oncology Group Prostate Cancer Trial
Authors: Thomas W. Flaig, Catherine M. Tangen, Maha H.A. Hussain, Walter M. Stadler, Derek Raghavan, E. David Crawford, L. Michael Glodé
Journal: Journal of Clinical Oncology (2008)

Southwest Oncology Group (SWOG) study 9921 is a randomized, phase III, intergroup study to define the role of adjuvant chemotherapy in patients with high-risk prostate cancer.We allocated 983 patients with prostate cancer with high-risk features to receive 2 years of androgen-deprivation therapy (ADT) with or without six cycles of mitoxantrone (12 mg/m(2)) after prostatectomy.In January 2007, SWOG 9921 was closed to further accrual after three cases of acute myelogenous leukemia (AML) were reported of a total of 487 patients in the mitoxantrone treatment arm. The key cytogenetic features of these cases included inv(16) in the first case, t(15;17) in the second, and del(5) in the third case. Time from the start of mitoxantrone to the detection of AML was 13, 48, and 72 months, respectively. Before SWOG 9921, there were no cases of mitoxantrone-induced AML reported in patients treated for prostate cancer.The emergence of this possible pattern of secondary malignancy emphasizes the importance of randomized controlled trials in defining safety and efficacy of new approaches for patients in the adjuvant setting.