tbuckley/cabot-search huggingface dataset:
Elevated Plasma Inflammatory Markers in Individuals With Intermittent Explosive Disorder and Correlation With Aggression in Humans
Authors: Emil F. Coccaro, Royce Lee, Mary Coussons-Read
Journal: JAMA Psychiatry (2013)

Neurochemical studies in human aggression point to a modulatory role for a variety of central neurotransmitters. Some of these neurotransmitters play an inhibitory role, while others play a facilitatory role modulating aggression. Preclinical studies suggest a facilitatory role for inflammatory markers in aggression. Despite this, to our knowledge, no studies of aggression and inflammatory markers have been reported in psychiatric patients or in individuals with recurrent, problematic, impulsive aggressive behavior.To test the hypothesis that plasma inflammatory markers will correlate directly with aggression and will be elevated in individuals with recurrent, problematic, impulsive aggressive behavior. DESIGN, SETTING, AND PARTICIPANTS Case-control study in a clinical research program in impulsive aggressive behavior at an academic medical center. Participants were physically healthy individuals with intermittent explosive disorder (n = 69), nonaggressive individuals with Axis I and/or II disorders (n = 61), and nonaggressive individuals without history of an Axis I or II disorder (n = 67).Plasma levels of C-reactive protein and interleukin 6 were examined in the context of measures of aggression and impulsivity and as a function of intermittent explosive disorder.Both plasma C-reactive protein and interleukin 6 levels were significantly higher in participants with intermittent explosive disorder compared with psychiatric or normal controls. In addition, both inflammatory markers were directly correlated with a composite measure of aggression and, more specifically, with measures reflecting history of actual aggressive behavior in all participants.These data suggest a direct relationship between plasma inflammatory processes and aggression in humans. This finding adds to the complex picture of the central neuromodulatory role of aggression in humans.
Hyperbaric Oxygenation Accelerates the Healing Rate of Nonischemic Chronic Diabetic Foot Ulcers
Authors: Laurence Kessler, Pascal Bilbault, Francoise Ortéga, Claire Grasso, Raphael Passemard, Dominique Stephan, Michel Pinget, Francis Schneider
Journal: Diabetes Care (2003)

To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers.From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline.HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group.In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.
Antidepressants May Mitigate the Effects of Prenatal Maternal Anxiety on Infant Auditory Sensory Gating
Authors: Sharon K. Hunter, Jordan H. Mendoza, Kimberly D'Anna, Gary O. Zerbe, Lizbeth McCarthy, Camille Hoffman, Robert Freedman, Randal G. Ross
Journal: American Journal of Psychiatry (2012)

Objective: Prenatal maternal anxiety has detrimental effects on the offspring's neurocognitive development, including impaired attentional function. Antidepressants are commonly used during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. The authors used P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, to assess the impact of maternal anxiety and antidepressant use. Method: A total of 242 mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean age of 76 days (SD=38). Results: In the absence of prenatal antidepressant exposure, infants whose mothers had a history of anxiety diagnoses had diminished P50 sensory gating. Prenatal antidepressant exposure mitigated the effect of anxiety. The effect of maternal anxiety was limited to amplitude of response to the second stimulus, while antidepressant exposure had an impact on the amplitude of response to both the first and second stimulus. Conclusions: Maternal anxiety disorders are associated with less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant exposure. This effect may be important in considering the risks and benefits of antidepressant use during pregnancy. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects, although the cholinergic receptors involved are likely different for anxiety and antidepressant effects.
Interrelations between interleukin-6, interleukin-1 beta, plasma C-reactive protein values, and in vitro C-reactive protein generation in patients with inflammatory bowel disease.
Authors: M Z Mazlam, H J Hodgson
Journal: Gut (1994)

Acute phase proteins are released from the liver in response to cytokines, and measurement of serum concentrations offers a valuable means of assessing inflammatory bowel disease. C-reactive protein (CRP) is a participating prominent component of the acute phase response in active Crohn's disease. This study aimed at determining the comparative role of the cytokines interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6), in driving CRP production in inflammatory bowel disease, and to test the hypothesis that there is a difference in the profile of cytokines generated in these two conditions. Serum CRP, the release of the cytokines IL-1 beta and IL-6 from monocytes, and the ability of monocyte conditioned medium to stimulate CRP synthesis by hepatocytes in an in vitro system was measured in patients with ulcerative colitis and Crohn's disease. Monocytes from patients with Crohn's disease produced more 1L beta-1 than monocytes from patients with ulcerative colitis or normal controls. There was no increased tendency for monocytes from Crohn's disease patients to produce more 1L-6, so the greater circulating values of IL-6 reported by a number of authors in Crohn's disease may reflect the participation of a larger number of cells of the monocyte-macrophage series, or production of IL-6 by other cell types. Correlation of cytokine production by monocytes with in vitro CRP release from cultured hepatocytes in response to monocyte conditioned medium showed that, in that system, IL-1 beta was the stronger stimulus to CRP production. Some of the differences in the inflammatory processes of ulcerative colitis and Crohn's disease may reflect differences in the amount of IL-1beta and IL-6 generated from macrophages and monocytes.
Tendon Healing: Repair and Regeneration
Authors: Pramod B. Voleti, Mark R. Buckley, Louis J. Soslowsky
Journal: Annual Review of Biomedical Engineering (2012)

Injury and degeneration of tendon, the soft tissue that mechanically links muscle and bone, can cause substantial pain and loss of function. This review discusses the composition and function of healthy tendon and describes the structural, biological, and mechanical changes initiated during the process of tendon healing. Biochemical pathways activated during repair, experimental injury models, and parallels between tendon healing and tendon development are emphasized, and cutting-edge strategies for the enhancement of tendon healing are discussed.
Histamine induced pulmonary vasodilatation in the rat: site of action and changes in chronic hypoxia
Authors: PC Russell, CE Wright, GR Barer, P Howard
Journal: European Respiratory Journal (1994)

Histamine constricts postcapillary lung vessels and also causes dilatation, site unknown. In chronically hypoxic rats, pulmonary arterioles are muscularized and histamine-containing mast cells increase. We wanted to determine a) whether vasoreactivity to histamine changes in chronic hypoxia; b) whether dilatation is due to H2 receptors; and c) which vessels dilate. We perfused isolated lungs of normal (C) and chronically hypoxic (CH) rats. Histamine was tested during hypoxic vasoconstriction. To examine effects on arteries alone, we raised alveolar (inflation) pressure above outflow pressure; during inflation, pressure/flow (P/Q) lines were measured during normoxia, and hypoxia, and after histamine during continued hypoxia. Dose-related dilatation was seen, which was abolished by cimetidine and enhanced in CH rats. A mast cell-discharging agent, but not exogenous histamine, caused constriction, which was abolished by chlorpheniramine. P/Q lines differed in C and CH rats in a manner which suggests that hypoxia constricts larger "extra-alveolar" vessels in C rats, but mainly muscularized arterioles exposed to alveolar pressure in CH rats. Histamine restored the P/Q line to nearly its normoxic position; it therefore dilated those vessels which constrict in hypoxia in each rat group. It is concluded that histamine has a strong H2 dilator effect, enhanced in chronic hypoxia, which might be an important attenuating factor in hypoxic pulmonary hypertension.
Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia
Authors: Atsushi Takata, Maiko Kato, Masayuki Nakamura, Takeo Yoshikawa, Shigenobu Kanba, Akira Sano, Tadafumi Kato
Journal: Genome biology (2011)

Abstract Background Whole-exome sequencing using next-generation technologies has been previously demonstrated to be able to detect rare disease-causing variants. Progressive external ophthalmoplegia (PEO) is an inherited mitochondrial disease that follows either autosomal dominant or recessive forms of inheritance (adPEO or arPEO). AdPEO is a genetically heterogeneous disease and several genes, including POLG1 and C10orf2 /Twinkle, have been identified as responsible genes. On the other hand, POLG1 was the only established gene causing arPEO with mitochondrial DNA deletions. We previously reported a case of PEO with unidentified genetic etiology. The patient was born of a first-cousin marriage. Therefore, the recessive form of inheritance was suspected. Results To identify the disease-causing variant in this patient, we subjected the patient's DNA to whole-exome sequencing and narrowed down the candidate variants using public data and runs of homozygosity analysis. A total of 35 novel, putatively functional variants were detected in the homozygous segments. When we sorted these variants by the conservation score, a novel missense variant in RRM2B , whose heterozygous rare variant had been known to cause adPEO, was ranked at the top. The list of novel, putatively functional variants did not contain any other variant in genes encoding mitochondrial proteins registered in MitoCarta. Conclusions Exome sequencing efficiently and effectively identified a novel, homozygous missense variant in RRM2B , which was strongly suggested to be causative for arPEO. The findings in this study indicate arPEO to be a genetically heterogeneous disorder, as is the case for adPEO.
GENETIC CONTROL OF THYMUS-DERIVED CELL FUNCTION
Authors: R. Michael Williams, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1972)

Concanavalin A- or phytohemagglutinin-stimulated DNA synthetic responses of 1 million normal mouse spleen cells in vitro were significantly different among various inbred strains. BALB/cJ (H-2(d)) responded better than C57BL/6J (H-2(b)) spleen cells, and the responses of C3H/HeJ or AKR/J (both H-2(k)) cells were intermediate. These responses, measured as the increment in thymidine-(3)H incorporation of mitogen-stimulated compared with unstimulated cultures, varied according to the number of cells cultured or the mitogen concentration. BALB/c spleens had the highest proportion of theta-positive cells, but no direct relationship between the proportion of theta-positive cells and the DNA synthetic response was observed. (BALB/cJ x C57BL/6)F(1) spleen cells responsed as well as BALB/c cells. Responses of spleen cells from (F(1) x C57BL/6) backcross littermates varied over a range equal to, or greater than, that of BALB/c and C57BL/6 cells. There was no correlation between H-2 specificity (H-2(bd) or H-2(bb)) or sex and the mitogen-stimulated DNA synthetic response of backcross animals. Con A- and PHA-stimulated responses of individual backcross animals were positively correlated with the level of thymidine-(8)H incorporation by unstimulated spleen cells. These results are consistent with autosomal dominant, non-H-2-linked, polygenic control of the mitogen-stimulated in vitro DNA synthetic response of mouse spleen cells.
Evidence for the presence of functional protease activated receptor 4 (PAR4) in the rat colon
Authors: F Mulè, R Pizzuti, A Capparelli, N Vergnolle
Journal: Gut (2004)

<b>Background and aims:</b> Protease activated receptors (PARs) have been postulated to play a role during intestinal inflammation. The presence and role played by PAR<sub>4</sub> in gastrointestinal functions have not been fully clarified. The aims of this study were: (i) to examine expression of PAR<sub>4</sub> in rat proximal colon; (ii) to determine the mechanical effects induced by PAR<sub>4</sub> activation in longitudinal muscle; and (iii) to characterise the underlying mechanisms. <b>Methods:</b> PAR<sub>4</sub> expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Mechanical activity was recorded as changes in isometric tension. <b>Results:</b> A PCR product corresponding to the predicted size of the PAR<sub>4</sub> signal was amplified from RNA prepared from the colon of rats, showing the presence of PAR<sub>4</sub> in those tissues. Immunohistochemistry revealed that PAR<sub>4</sub> protein was expressed on epithelial surfaces and submucosa. PAR<sub>4</sub> activating peptides, GYPGKF-NH<sub>2</sub> and AYPGKG-NH<sub>2</sub>, produced concentration dependent contractile effects on longitudinal muscle. Tetrodotoxin (TTX) or atropine significantly reduced the contractile responses to AYPGKG-NH<sub>2</sub>, and atropine after TTX did not cause any further reduction. NK<sub>1</sub> receptor antagonist, SR140333, or NK<sub>2</sub> receptor antagonist, SR48968, alone or in combination, produced a reduction in PAR<sub>4</sub> induced contractile effect, and when coadministered with TTX abolished it. Capsaicin markedly reduced the contractions evoked by AYPGKG-NH<sub>2</sub>. <b>Conclusions:</b> The present results suggest that PAR<sub>4</sub> is functionally expressed in rat colon and its activation induces contraction of the longitudinal muscle both through TTX sensitive release of acetylcholine and release of tachykinins, probably from sensory nerves. These actions may contribute to motility disturbances during intestinal trauma and inflammation.
A STUDY IN VITRO OF COMPONENTS IN THE TRANSMISSION CYCLE OF SWINE INFLUENZA VIRUS
Authors: W. D. Peterson, Fred M. Davenport, Thomas Francis
Journal: The Journal of Experimental Medicine (1961)

Swine lungworm extracts and suspensions of swine lungworms contain receptor-like substances capable of adsorbing influenza virus, a result consonant with the hypothesis (5-8) that the lungworm may be involved in the swine influenza cycle. Yet no evidence for multiplication of virus or even persistence of infectious virus in lungworms at undimished titer was found. Clearly much more information is needed, and it is hoped that the present demonstration of the practicality of studying the components of the transmission cycle proposed by Shope, will provide important tools requisite for further investigation of this problem. Studies on the role of the earthworm in the transmission of swine influenza suggest that, at best, that role would be a passive one.
Anti-CD43 Inhibition of T Cell Homing
Authors: Leslie M. McEvoy, Hailing Sun, John G. Frelinger, Eugene C. Butcher
Journal: The Journal of Experimental Medicine (1997)

The homing of lymphocytes from the blood is controlled by specialized processes of lymphocyte–endothelial cell interaction. Interference with these processes offers the potential to manipulate lymphocyte traffic, and thus to modulate normal and pathologic immune and inflammatory responses. We selected antilymphocyte monoclonal antibodies (mAbs) for inhibition of lymphocyte binding in vitro to lymph node high endothelial venules (HEV), specialized vessels that support lymphocyte recruitment into lymph nodes. mAb L11 blocks T cell binding to lymph node and Peyer's patch HEV and inhibits T cell extravasation from the blood into organized secondary lymphoid tissues. In contrast, L11 has no effect on lymphocyte binding to purified vascular ligands for L-selectin, α4β7, or LFA-1, suggesting that it inhibits by a novel mechanism. The L11 antigen is CD43, a sialomucin implicated in vitro in regulation of lymphocyte activation, whose expression is often dysregulated in the Wiskott-Aldrich syndrome. CD43 represents a novel target for experimental and therapeutic manipulation of lymphocyte traffic and may help regulate T cell distribution in vivo.
An Oncogenic Role for <i>ETV1</i> in Melanoma
Authors: Judit Jané-Valbuena, Hans R. Widlund, Sven Perner, Laura A. Johnson, Aurora C. Dibner, William M. Lin, Alissa C. Baker, Rosalynn M. Nazarian, Krishna G. Vijayendran, William R. Sellers, William C. Hahn, Lyn M. Duncan, Mark A. Rubin, David E. Fisher, Levi A. Garraway
Journal: Cancer Research (2010)

Copy gains involving chromosome 7p represent one of the most common genomic alterations found in melanomas, suggesting the presence of "driver" cancer genes. We identified several tumor samples that harbored focal amplifications situated at the peak of common chromosome 7p gains, in which the minimal common overlapping region spanned the ETV1 oncogene. Fluorescence in situ hybridization analysis revealed copy gains spanning the ETV1 locus in >40% of cases, with ETV1 amplification (>6 copies/cell) present in 13% of primary and 18% of metastatic melanomas. Melanoma cell lines, including those with ETV1 amplification, exhibited dependency on ETV1 expression for proliferation and anchorage-independent growth. Moreover, overexpression of ETV1 in combination with oncogenic NRAS(G12D) transformed primary melanocytes and promoted tumor formation in mice. ETV1 overexpression elevated microphthalmia-associated transcription factor expression in immortalized melanocytes, which was necessary for ETV1-dependent oncogenicity. These observations implicate deregulated ETV1 in melanoma genesis and suggest a pivotal lineage dependency mediated by oncogenic ETS transcription factors in this malignancy.
Letters Regarding Article by Bloomfield et al, “Microvolt T-Wave Alternans Distinguishes Between Patients Likely and Patients Not Likely to Benefit From Implanted Cardiac Defibrillator Therapy”
Authors: Michael Jachuck, Duwarakan K. Satchithananda
Journal: Circulation (2005)

The recent article by Bloomfield and colleagues described the use of microvolt T-wave alternans (MTWA) testing for identifying groups at high and low risk of dying among heart failure patients who met Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) criteria for implantable cardioverterdefibrillator (ICD) prophylaxis. 1 Their study adds to the current literature and suggests that MTWA testing may be a useful guide to mortality prediction.The authors emphasize the potential impact on resources that the MADIT-II findings could have if applied to current clinical practice and the need for additional, noninvasive risk-stratification tools.Their results complement a recent meta-analysis in The Lancet, which proposed that a normal MTWA result identified a low-risk group among MADIT-II patients who may benefit less from defibrillator therapy. 2 MTWA testing may be helpful in delivering ICD implantation to those with the greatest need; however, uncertainties remain regarding the timing of testing after myocardial infarction (MI) and the effects of medical treatment on the result.The authors' report 74% of patients in their study were taking ␤-blockers; additional data on drug doses, resting heart rate, and blood pressure may have indicated whether there was scope to further increase medical treatment before testing and how this influenced the result.Activation of the sympathetic nervous system augments MTWA, with Klingenheben and colleagues having previously shown that selective ␤-adrenergic blockade with metoprolol or sotalol significantly reduced MTWA magnitude in patients susceptible to ventricular arrhythmias (PՅ0.001). 3 Bloomfield and coworkers reported a mean time of Ϸ5 years after MI before testing, although temporal variations in MTWA levels post-MI have been demonstrated previously, and the optimal time for testing to maximize its predictive accuracy has not yet been identified. 4 The primary end point in both the Bloomfield et al study and MADIT-II was all-cause mortality.In terms of ICD screening, however, the proportion of arrhythmic deaths relative to heart failure and ischemic deaths would be of greater relevance in determining the usefulness of MTWA.It has been suggested that an alternative interpretation of a positive MTWA test could be that it identifies a high-risk group of patients who are not yet optimally medically treated 5 and that MTWA testing should be performed only after optimization of pharmacological therapy.Further studies are therefore needed before establishing the precise role of MTWA testing in screening for ICD prophylaxis.
Implications of continued response after autologous stem cell transplantation for multiple myeloma
Authors: Wilson I. Gonsalves, Morie A. Gertz, Angela Dispenzieri, Martha Q. Lacy, Yi Lin, Preet P. Singh, Vinay Gupta, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Prashant Kapoor, Arleigh R. McCurdy, Shaji K. Kumar
Journal: Blood (2013)