tbuckley/cabot-search huggingface dataset:
Defining the roles of perforin, Fas/FasL, and tumour necrosis factor in T cell induced mucosal damage in the mouse intestine
Authors: M Merger, J L Viney, R Borojevic, D Steele-Norwood, P Zhou, D A Clark, R Riddell, R Maric, E R Podack, K Croitoru
Journal: Gut (2002)

<b>Background and aims:</b> Mucosal flattening and epithelial cell apoptosis are typical features of T cell induced inflammatory diseases of the bowel, such as coeliac disease and graft versus host disease. Mice injected with a T cell activating anti-CD3 antibody develop a severe diarrhoeal illness. We describe the histological features of this enteropathy and define the effector mechanisms involved in T cell induced mucosal injury in this in vivo model. <b>Methods:</b> Wild-type and genetically modified mice were injected with the anti-CD3 antibody 3C11 (50 μg). Changes in the murine intestine were characterised by light microscopy analysis and terminal uridine nick-end labelling (TUNEL) assay. The role of perforin, Fas/Fas ligand (FasL), tumour necrosis factor α (TNF-α), and interferon γ (IFN-γ) in T cell induced mucosal damage was assessed using selected immunodeficient mouse strains. <b>Results:</b> T cell activation caused severe damage, including small intestinal mucosal flattening and apoptosis of crypt epithelial cells. Mucosal damage was unaltered in anti-CD3 treated mice lacking IFN-γ, Fas, or TNF-α receptors. In mice lacking TNF-α receptors and Fas (TNF-R1×R2 <i>lpr/lpr</i> strain), enterocyte apoptosis was diminished but there was no significant reduction in tissue damage. Apoptosis and mucosal injury were significantly reduced in perforin knockout mice. Abrogation of both FasL and perforin (perforin KO×<i>gld</i> mice) further significantly reduced tissue damage and apoptotic bodies. <b>Conclusions:</b> T cell induced mucosal injury is mediated by the combined effect of multiple pathways but predominantly by perforin. The redundancy of the mechanisms of tissue damage will have significant impact on therapeutic strategies aimed at specific and targeted inhibition of inflammatory processes.
The dynamic developmental theory of ADHD: Reflections from a cognitive energetic model standpoint
Authors: Joseph A. Sergeant
Journal: Behavioral and Brain Sciences (2005)

“a dynamic developmental theory of attention-deficit/hyperactivity disorder (adhd) predominantly hyperactive/impulsive and combined subtypes” is a major contribution linking comparative psychology with clinical developmental neuropsychopathology. in this commentary, i place some critical remarks concerning the theory's explanation of sleep problems, inhibition, error monitoring, and motor control.
Introducing the non-B DNA Motif Search Tool (nBMST)
Authors: Regina Z Cer, Kevin H Bruce, Duncan E Donohue, Alpay N Temiz, Albino Bacolla, Uma S Mudunuri, Ming Yi, Natalia Volfovsky, Brian T Luke, Jack R Collins, Robert M Stephens
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Elevated HLA class i antigen expression on peripheral blood mononuclear cells of HBsAg carriers with coexistent human immunodeficiency virus infection
Authors: Robert G. Paul, Stanford T. Roodman, Deborah A. Paul, Robert P. Perrillo
Journal: Hepatology (1987)

The density of HLA Class I antigen on peripheral blood mononuclear cells was evaluated by flow cytometry in the following groups of patients: 41 HBsAg carriers; 12 individuals with chronic non-A, non-B hepatitis, and 4 with acute hepatitis B. Fourteen of the carriers were positive for antibody to human immunodeficiency virus, and all were negative for antibody to delta agent. Elevated levels of Class I antigen were observed in only 19% of patients with chronic hepatitis B virus infection alone. In contrast, 86% of HBsAg carriers with coexistent human immunodeficiency virus infection demonstrated increased expression. These data suggest that HBsAg carriers are capable of sustaining a systemic interferon response to another chronic viral infection and further supports the hypothesis that a defective interferon response exists in chronic hepatitis B virus infection.
The Molecular Neurobiology of the Acetylcholine Receptor
Authors: M P McCarthy, J P Earnest, E F Young, S Choe, R M Stroud
Journal: Annual Review of Neuroscience (1986)

The acetylcholine receptor (AChR) is the most thoroughly characterized component ofthe neuromuscular transduction process. Earlier reviews that summarize the structural and biochemical features of the AChR include Popot & Changeux (1984), Stroud (1983), Conti-Tronconi & Raftery (1982), and Karlin (1980). This receptor translates the binding of the neurotrans­ mitter, acetylcholine (ACh), into a rapid increase and subsequent decrease in the permeability of the endplate membrane to the passage of cations. Inward flux of ions through the channel is passive, driven by elec­ trochemical gradients across the receptor-containing membrane. The physiological effect is to temporarily depolarize the endplate, a response that is translated into muscular contraction in the case of a neuromuscular junction, or potentiation of electric tissue in the stacked asymmetric cells of electric organs in Torpedo (a marine elasmobranch) or Electrophorus (a freshwater teleost). The availability of acetylcholine receptors from electric tissue was a fundamental key to molecular characterization. The subunit stoichiometry of the four identified polypeptides has been unequivocally established as 1X2/3yb, and the funnel shape of the molecule has been well characterized with respect to position of the ion channel. Distribution of protein relative to the phospholipid bilayer and some aspects ofthe subunit arrangements in a quasipentameric structure around the ion channel have also been established. The genes for the four subunits that constitute the
Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C
Authors: R.J.H. Massie, N. Poplawski, B. Wilcken, J. Goldblatt, C. Byrnes, C. Robertson
Journal: European Respiratory Journal (2001)

Compound heterozygotes for a severe cystic fibrosis transmembrane conductance regulator (CFTR) mutation and the R117H or R117C mutation (R117H/C) have clinical presentations that vary from classic cystic fibrosis (CF) to an incidental genetic finding. The aim of this study was to assess the influence of the intron-8 polythymidine sequence (IVS8) on the relationship between genotype and phenotype of individuals with R117H/C. All individuals with R117H/C known to CF clinics in Australia and New Zealand were retrospectively studied by collecting information on genotype, age, pancreatic status, sweat electrolytes, sputum microbiology and pulmonary function. Forty-one individuals (39 with R117H and two with R117C), 16 on an IVS8-5T background and 25 on an IVS8-7T background were identified. Twelve individuals presented clinically, four were siblings of known R117H/C compound heterozygotes and 25 were detected by newborn screening. Eleven of 14 of the IVS8-5T group (78%) with sweat chloride results available had sweat Cl&gt;60 mmol·L −1 compared to 5 (20%) of the R117H/7T group (Chi-squared=10.4, p=0.001). Two were pancreatic insufficient, both IVS8-5T. Two IVS8-5T individuals have recently died (aged 43 and 19) and of the 14 surviving IVS8-5T group, 11 (79%) are symptomatic compared to eight (32%) of the IVS8-7T individuals (Chi-squared=6.1, p=0.01). In conclusion, most individuals with R117H/C on a IVS8-5T background have an elevated sweat chloride and clinical cystic fibrosis, which in some cases is severe. Most individuals with R117H/C on an IVS8-7T background do not have clinical cystic fibrosis but should be followed for the development of clinical disease.
Enhancing effect of pretreatment with topical niacin in the treatment of rosacea-associated erythema by 585-nm pulsed dye laser in Koreans: a randomized, prospective, split-face trial
Authors: T.G. Kim, H.J. Roh, S.B. Cho, J.H. Lee, S.J. Lee, S.H. Oh
Journal: British Journal of Dermatology (2010)

Journal Article Enhancing effect of pretreatment with topical niacin in the treatment of rosacea‐associated erythema by 585‐nm pulsed dye laser in Koreans: a randomized, prospective, split‐face trial Get access T.G. Kim, T.G. Kim Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 134 Sinchon‐Dong, Seodaemun‐Gu, Seoul 120‐752, Korea Search for other works by this author on: Oxford Academic Google Scholar H.J. Roh, H.J. Roh Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 134 Sinchon‐Dong, Seodaemun‐Gu, Seoul 120‐752, Korea Search for other works by this author on: Oxford Academic Google Scholar S.B. Cho, S.B. Cho Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 134 Sinchon‐Dong, Seodaemun‐Gu, Seoul 120‐752, Korea Search for other works by this author on: Oxford Academic Google Scholar J.H. Lee, J.H. Lee Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 134 Sinchon‐Dong, Seodaemun‐Gu, Seoul 120‐752, Korea Search for other works by this author on: Oxford Academic Google Scholar S.J. Lee, S.J. Lee Yonsei Star Skin and Laser Clinic, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar S.H. Oh S.H. Oh Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, 134 Sinchon‐Dong, Seodaemun‐Gu, Seoul 120‐752, Korea Sang Ho Oh. E‐mail: oddung93@yuhs.ac Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 3, 1 March 2011, Pages 573–579, https://doi.org/10.1111/j.1365-2133.2010.10174.x Published: 01 March 2011
Changes in Pulmonary Vascular Resistance Following Closure of Ventricular Septal Defects
Authors: C. D. PARK, H. NICODEMUS, J. J. DOWNES, WILLIAM W. MILLER, JOHN A. WALDHAUSEN
Journal: Circulation (1969)

In five patients with pulmonary arterial hypertension (PAH) associated with ventricular septal or endocardial cushion defects, measurements of pulmonary vascular resistance (PVR) were made up to seven days after surgical closure. Before operation, the ratio of mean pulmonary arterial pressure [See Equation in PDF File] to mean systemic arterial pressure [See Equation in PDF File] averaged 0.77 . Catheters placed at operation were used to measure pressure in the pulmonary artery, a systemic artery, and right and left atria. Cardiac output was determined by dye dilution. Controlled mechanical ventilation maintained a normal alveolar ventilation and arterial PO 2 . Postoperative [See Equation in PDF File], [See Equation in PDF File], and PVR were initially elevated, averaging 42 mm Hg, 0.57, and 1,132 dyne sec cm -5 , respectively. These values decreased to 29, 0.38, and 459 in three to seven days in the four survivors, but rose in the single death. With unassisted ventilation and 100% 0 2 , or with acidosis (pH 7.21), [See Equation in PDF File] and PVR increased as much as +177% and 570%, respectively. These studies show the relative pulmonary vasoconstricting effect of systemic acidosis and of spontaneous unassisted breathing with 100% O 2 . In patients with markedly elevated, but reversible, hyperkinetic pulmonary vascular resistance, the beneficial effects of prolonged mechanical ventilation enabled the pulmonary circulation to return toward normal.
Best Supportive Care Compared With Chemotherapy for Unresectable Gall Bladder Cancer: A Randomized Controlled Study
Authors: Atul Sharma, Amit Dutt Dwary, Bidhu Kalyan Mohanti, Surya V. Deo, Sujoy Pal, Vishnu Sreenivas, Vinod Raina, Nootan Kumar Shukla, Sanjay Thulkar, Pramod Garg, Surendra Pal Chaudhary
Journal: Journal of Clinical Oncology (2010)

Purpose We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC). Patients and Methods Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m 2 and FA 20 mg/m 2 intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m 2 and oxaliplatin 80 mg/m 2 IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26). Results Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P &lt; .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P &lt; .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics. Conclusion This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.
Mitochondrias' sense of SNO: pathway to cardioprotection in ischaemic preconditioning
Authors: Tienush Rassaf, Rainer Schulz
Journal: Cardiovascular Research (2015)

This Editorial refers to ‘Ischaemic preconditioning preferentially increases protein S-nitrosylation in subsarcolemmal mitochondria’ by J. Sun et al. , pp. 227–236. 

Ischaemic heart disease (IHD) is the leading cause of death worldwide. The optimal therapy in an acute myocardial infarction is the timely reperfusion of the ischaemic myocardium. This leads to a reduction in infarct size (IS) and improves the prognosis of the patients. The reperfusion of the ischaemic myocardium, however, can cause injury itself and first clinical investigations revealed that up to 50% of the final IS may be caused by reperfusion (for review, see1). As the prevalence of IHD increases and the IS being an important determinant of heart failure, a medical need exists to develop strategies to protect the heart from ischaemia/reperfusion (I/R) injury and thus to improve patients' outcome.2,3

During the last years, different endogenous cardioprotective strategies such as ischaemic preconditioning (IPC), ischaemic …
Enhanced Early Morning Salivary Cortisol in Neuroticism
Authors: Maria J Portella, Catherine J Harmer, Jonathan Flint, Philip Cowen, Guy M Goodwin
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Neuroticism is a predisposing factor for major depression. The increase in salivary cortisol that follows waking provides a reliable measure of adrenocortical activity, and this response is increased in recovered depressed patients. This study compared waking cortisol levels in healthy subjects with high and low levels of neuroticism without a previous history of depression. METHOD: Salivary cortisol levels were measured upon waking and at 15-minute intervals for the next hour in volunteers selected to have high (>19/23) or low (<4/23) neuroticism based on the Eysenck Personality Inventory. RESULTS: Subjects with high neuroticism showed significantly greater levels of salivary cortisol 30 minutes after waking, which were maintained for the next half hour. CONCLUSIONS: Abnormalities in waking cortisol are associated with neuroticism in a way similar to those seen in major depression. Elevated waking cortisol may represent a vulnerability marker for mood disorder.
THE ROLE OF ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODY IN THE PATHOGENESIS OF HUMAN GLOMERULONEPHRITIS
Authors: R. A. Lerner, R. J. Glassock, Frank J. Dixon
Journal: The Journal of Experimental Medicine (1967)

These observations established the presence of anti-GBM antibodies in the sera and/or kidneys of six humans with glomerulonephritis. Further, it seems clear that these antibodies do combine with the host's glomeruli in vivo and with GBM antigen of several species in vitro. Transfer of acute glomerulonephritis to normal recipient monkeys was possible with serum or renal eluate IGG from the three patients with anti-GBM antibodies in whom sufficient material was available. Based on this transfer of nephritis and on the presence of these antibodies at the site of injury in the nephritic kidneys of both the patients and the recipient monkeys, it seems likely that they are at least a contributing, if not primary, cause of the glomerular injury. The frequency of anti-GBM antibodies in human nephritis is not certain, but on the basis of preliminary observations it would appear that they are present in all cases of Goodpasture's nephritis and somewhat less than half of the cases of subacute and chronic glomerulonephritis of adults. The nature and source of immunogen stimulating the production of anti-GBM antibodies is not known, but the presence of potentially nephritogenic GBM antigens in normal urine raises the question of possible autoimmunization. From a practical point of view, it appears that patients forming anti-GBM antibodies may not be good candidates for renal transplantation since they are likely to produce in the transplants the nephritic changes already suffered by their own kidneys.
Altered Kidney Graft High-Energy Phosphate Metabolism in Kidney-Transplanted End-Stage Renal Disease Type 1 Diabetic Patients
Authors: Paolo Fiorina, Gianluca Perseghin, Francesco De Cobelli, Chiara Gremizzi, Alessandra Petrelli, Lucilla Monti, Paola Maffi, Livio Luzi, Antonio Secchi, Alessandro Del Maschio
Journal: Diabetes Care (2007)

Diabetes, hypertension, dyslipidemia, obesity, nephrotoxicity of certain immunosuppressive drugs, and the persistence of a chronic alloimmune response may significantly affect graft survival in end-stage renal disease (ESRD) type 1 diabetic patients who have undergone kidney transplant. The aim of this study was to ascertain the impact of kidney alone (KD) or combined kidney-pancreas (KP) transplantation on renal energy metabolism.We assessed high-energy phosphates (HEPs) metabolism by using, in a cross-sectional fashion, 31P-magnetic resonance spectroscopy in the graft of ESRD type 1 diabetic transplanted patients who received KD (n = 20) or KP (n = 20) transplant long before the appearance of overt chronic allograft nephropathy (CAN). Ten nondiabetic microalbuminuric kidney transplanted patients and 10 nondiabetic kidney transplanted patients with overt CAN were chosen as controls subjects.Simultaneous KP transplantation patients showed a higher beta-ATP/inorganic phosphorus (Pi) ratio (marker of the graft energy status) versus the other groups, and a positive correlation between beta-ATP/Pi phosphorus ratio and A1C was found. In the analysis limited to the subgroup of normoalbuminuric patients, the difference in beta-ATP/Pi was still detectable in KP patients compared with KD transplantation.KP transplantation was associated with better HEPs than in KD transplantation, suggesting that restoration of beta-cell function positively affects kidney graft metabolism.
Mixed chimerism after transplantation: Mechanism or marker of specific tolerance?
Authors: Thomas Judge
Journal: Hepatology (1993)

We have previously reported data from clinical and laboratory animal observations which suggest that organ tolerance after transplantation depends on a state of balanced lymphodendritic cell chimerism between the host and donor graft. We have sought further evidence to support this hypothesis by investigating HLA-mismatched liver allograft recipients. Nine of nine female recipients of livers from male donors had chimerism in their allografts and extrahepatic tissues, according to in-situ hybridisation and molecular techniques 10 to 19 years post-transplantation. In 8 women with good graft function, evidence of the Y chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A ninth patient whose transplant failed after 12 years from recurrent chronic viral hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time of retransplantation. Although cell migration is thought to take place after all types of transplantation, the large population of migratory cells in, and the extent of their seeding from, hepatic grafts may explain the privileged tolerogenicity of the liver compared with other organs.
THE ANTIGENIC COMPOSITION OF INFLUENZA VIRUS MEASURED BY ANTIBODY-ABSORPTION
Authors: Keith E. Jensen, Thomas Francis
Journal: The Journal of Experimental Medicine (1953)

The application of methods herein described for the absorption of antibody from sera by influenza virus adsorbed to erythrocytes has greatly facilitated absorption studies with this virus and has resulted in a more comprehensive demonstration of strain differences and relationships. It is now evident that there are at least 18 different antigenic components which can be measured in Type A strains of influenza virus. Utilization of quantitative absorption technics allows the simultaneous detection of variable quantities of several different antigens so that the antigenic composite of the strain is more clearly defined than was previously possible. The wide sharing of antigenic components leads to the conclusion that no completely new antigens have formed of late nor have the antigenic components of strains isolated several years ago disappeared. Some mechanisms for antigenic variation among strains are suggested, and the significance of the variation in antigenic components is discussed in relation to specifications for an effective vaccine.
Effect of Inhibition of the Lysophosphatidic Acid Receptor 1 on Metastasis and Metastatic Dormancy in Breast Cancer
Authors: Jean-Claude A. Marshall, Joshua W. Collins, Joji Nakayama, Christine E. Horak, David J. Liewehr, Seth M. Steinberg, Mary Albaugh, Fernando Vidal-Vanaclocha, Diane Palmieri, Maryse Barbier, Maximilien Murone, Patricia S. Steeg
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundPrevious studies identified the human nonmetastatic gene 23 (NME1, hereafter Nm23-H1) as the first metastasis suppressor gene. An inverse relationship between Nm23-H1 and expression of lysophosphatidic acid receptor 1 gene (LPAR1, also known as EDG2 or hereafter LPA1) has also been reported. However, the effects of LPA1 inhibition on primary tumor size, metastasis, and metastatic dormancy have not been investigated.