tbuckley/cabot-search huggingface dataset:
Stability of the Diagnosis of Deficit Syndrome in Schizophrenia
Authors: Xavier F. Amador, Brian Kirkpatrick, Robert W. Buchanan, William T. Carpenter, Lynn Marcinko, Scott A. Yale
Journal: American Journal of Psychiatry (1999)

Primary, enduring negative symptoms have been distinguished from negative symptoms more generally and are used to define the deficit syndrome of schizophrenia. Although the validity of the deficit syndrome has been demonstrated by using brain imaging, neuropsychological, illness outcome, and developmental history data, the stability of this diagnostic category has not been tested prospectively by using direct patient assessments.Forty-three outpatients with schizophrenia and schizoaffective disorder were categorized into deficit and nondeficit groups an average of 3.8 years after having been previously categorized.There was 83% agreement between initial and blind follow-up designations of deficit status and 88% agreement on the nondeficit categorization.These results provide evidence for the long-term stability of the deficit syndrome in patients with schizophrenia and the reliability of the deficit/nondeficit categorization when diagnosed by those with appropriate training. Furthermore, they validate the method of categorizing deficit patients by using cross-sectional and retrospective data.
Ceramide Reduces Endothelium-Dependent Vasodilation by Increasing Superoxide Production in Small Bovine Coronary Arteries
Authors: David X. Zhang, Ai-Ping Zou, Pin-Lan Li
Journal: Circulation Research (2001)

Abstract —Ceramide serves as a second messenger in a variety of mammalian cells. Little is known regarding the role of ceramide in the regulation of vascular endothelial function. The present study was designed to determine whether ceramide affects endothelium-dependent vasodilation in coronary arteries and to explore the mechanism of action of ceramide. In isolated and pressurized small bovine coronary arteries, cell-permeable C 2 -ceramide (10 − 5 mol/L) markedly attenuated vasodilator responses to bradykinin and A23187 (by 40% and 60%, respectively). In the presence of K G -nitro- l -arginine methyl ester, ceramide produced no further inhibition on the vasodilation induced by these vasodilators. Ceramide had no effect on DETA NONOate–induced vasodilation. By use of a fluorescence NO indicator (4,5-diaminofluorescein diacetate), intracellular NO was measured in the endothelium of freshly isolated small coronary arteries. It was found that ceramide significantly inhibited bradykinin-induced NO increase within endothelial cells. However, it had no effect on the activity of arterial or endothelial NO synthase. Pretreatment of the arteries with sodium dihydroxybenzene disulfonate (Tiron, 10 − 3 mol/L), a cell-permeable superoxide scavenger, or polyethylene glycol superoxide dismutase (100 U/mL) largely restored the inhibitory effects of ceramide on the vasodilation and NO increase induced by bradykinin or A23187. Moreover, ceramide time-dependently increased intracellular superoxide (O 2 − · ) in the endothelium, as measured by a fluorescent O 2 − · indicator, dihydroethidium. These results demonstrate that ceramide inhibits endothelium-dependent vasodilation in small coronary arteries by decreasing NO in vascular endothelial cells and that this decrease in NO is associated with increased O 2 − · but not with the inhibition of NO synthase activity within these cells.
Influence of ursodeoxycholate-enriched diet on liver tumor growth in HBV transgenic mice
Authors: Michele Barone, Eugenio Maiorano, Roberta Ladisa, Rosario Cuomo, Antonia Pece, Pasquale Berloco, Maria Lucia Caruso, Anna Maria Valentini, Achille Iolascon, Antonio Francavilla, Alfredo Di Leo, Enzo Ierardi
Journal: Hepatology (2003)

Hepatitis B virus (HBV) transgenic mice (official designation, Tg [Alb-1 HBV] Bri 44) invariably develop macroscopically evident tumors within the 20th month of life. Sustained proliferative activity seems to play an important role in the development of these lesions. We previously showed that ursodeoxycholate (UDC) stimulates hepatocyte proliferation in various experimental settings. Herein, we tested the assumption that biological factors able to further increase liver cell proliferation, such as UDC, could accelerate tumor development in this animal model. For this study, 22 eight-week-old male transgenic mice were divided into 2 groups; 11 animals received a standard diet, and 11 received a UDC-enriched diet. The 2 groups were further divided into 2 subgroups of 5 and 6 animals each and were sacrificed at 3 and 15 months of age, respectively. These different times were chosen to exclude diet-related toxicity (in 3-month-old mice) and evaluate tumor growth (in 15-month-old mice). In addition, hepatocyte proliferation was assessed in all animals. In 3-month-old mice receiving UDC, cholestatic and cytolytic indices as well as liver histology were comparable to those in controls. At 15 months, all UDC-treated mice showed large multinodular tumors whereas only 33% of controls developed smaller uninodular neoplasms. Hepatocyte proliferation was increased in all animals receiving UDC compared with controls. In conclusion, the increase in serum UDC (undetectable in mice fed a standard diet), in the absence of any toxic effect on the liver, suggests the involvement of this bile salt in the stimulation of hepatocyte proliferation and tumor growth.
Sphingosine-1-Phosphate, a Platelet-Derived Lysophospholipid Mediator, Negatively Regulates Cellular Rac Activity and Cell Migration in Vascular Smooth Muscle Cells
Authors: Yasuji Ryu, Noriko Takuwa, Naotoshi Sugimoto, Sotaro Sakurada, Soichiro Usui, Hiroyuki Okamoto, Osamu Matsui, Yoh Takuwa
Journal: Circulation Research (2002)

Previous studies demonstrated that sphingosine-1-phosphate (S1P) induced migration of human umbilical vein endothelial cells (HUVECs) whereas it inhibited that of vascular smooth muscle cells (SMCs). This study explored the molecular mechanisms underlying the contrasting S1P actions on vascular cell motility. In rat and human aortic SMCs, the chemoattractant platelet-derived growth factor B-chain (PDGF) induced rapid 5- to 6-fold increases in the cellular amount of GTP-bound, active form of Rac. S1P did not affect PDGF-stimulated tyrosine phosphorylation of PDGF-β receptor, but strongly inhibited PDGF-induced Rac activation, with a dose-response relationship similar to that for inhibition of PDGF-elicited chemotaxis. Dihydrosphingosine-1-phosphate, which is a weaker agonist for the S1P receptors, but not an inactive ligand sphingosine, also inhibited PDGF-stimulated chemotaxis and Rac activation although to lesser extents compared with S1P, suggesting that negative regulation by S1P of both chemotaxis and Rac was a receptor-mediated process. In contrast, S1P by itself stimulated Rac activity in HUVECs. Among the five S1P receptor isoforms, SMCs prominently expressed Edg-5 mRNA, whereas HUVECs expressed abundant Edg-1 mRNA but lacked detectable expression of Edg-5 mRNA. Adenovirus-mediated expression of a dominant-negative form of either Rac or Cdc42, but not RhoA, markedly attenuated chemotaxis of SMCs and HUVECs toward PDGF and S1P, respectively. Overexpression of Edg-1 in SMCs and Edg-5 in HUVECs reduced S1P-induced inhibition and stimulation, respectively, of Rac activity and migration. These results together indicate that Edg isoform-specific, negative or positive regulation of cellular Rac activity is critically involved in S1P-mediated bimodal regulation of cell motility in SMCs and HUVECs.
Chymase Is Upregulated in Diabetic Nephropathy
Authors: Xiao R. Huang, Wei Y. Chen, Luan D. Truong, Hui Y. Lan
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Angiotensin II (AngII) has been shown to play a critical role in diabetic nephropathy and vasculopathy. Although it is well recognized that an angiotensin-converting enzyme (ACE)–dependent AngII-generating system is a major source of intrarenal AngII production, it is here reported that the chymase-dependent AngII-generating system is upregulated in the human diabetic kidney. This becomes particularly strong in those with hypertension. In the normal kidney, while ACE was constitutively expressed by most kidney cells, chymase was weakly expressed by mesangial cells (MC) and vascular smooth muscle cells (VSMC) only. In the diabetic kidney, while ACE expression was significantly upregulated (1 to 3-fold) by tubular epithelial cells (TEC) and infiltrating mononuclear cells, there was also markedly increased chymase expression (10 to 15-fold) by both MC and VSMC, with strong deposition in the collagen-rich extracellular matrix including both diffuse and nodular glomerulosclerosis, tubulointerstitial fibrosis, and vascular sclerosis. Interestingly, while ACE expression showed no difference in patients with or without hypertension, upregulation of chymase in hypertensive patients was much stronger than that seen in those without hypertension (4 to 7-fold, <i>P</i> &lt; 0.001). Correlation analysis showed that, in contrast to the ACE expression, upregulation of chymase correlated significantly with the increase in BP and the severity of collagen matrix deposition within the glomerulus, tubulointerstitium, and arterial walls (all with <i>P</i> &lt; 0.001). In conclusion, the present study demonstrates that chymase, as an alternative AngII-generating enzyme, is markedly upregulated in the diabetic kidney and may be associated with the development of diabetic/hypertensive nephropathy. In addition, differential expression of ACE and chymase in the diabetic kidney indicates that both ACE and chymase may be of equal importance for AngII-mediated diabetic nephropathy and vascular disease. Results from this study suggest that blockade of both AngII-generating pathways may provide additional beneficial effect on diabetic nephropathy. E-mail: hlan@bcm.tmc.edu
Prostate cancer screening and the management of clinically localized disease
Authors: T. J. Wilt, H. U. Ahmed
Journal: BMJ (2013)

Prostate cancer is an important health problem.More than 40 000 incident cases of prostate cancer and more than 10 000 prostate cancer related deaths occur each year in the United Kingdom. 1 Prevention, detection, and treatment of localized prostate cancer remain controversial.Although screening for prostate cancer with serum prostate specific antigen (PSA) testing is not approved in the UK, informal screening is common and has led to a threefold increase in the incidence of prostate cancer.In the United States, since the introduction of PSA screening more than 1.3 million men have been diagnosed with prostate cancer and one million of these have undergone treatment. 2We update a previous review, highlighting new findings that deal with clinical questions and future research needs for the prevention, detection, and treatment of clinically localized prostate cancer.
GANCICLOVIR FOR CYTOMEGALOVIRUS INFECTION IN RENAL TRANSPLANT RECIPIENTS
Authors: C. Hiesse, C. Farquet, E. Dussaix, B. Charpentier, D. Fries, P. Gianello, M. Stoffel, J.P. Squifflet, Y. Pirson, G.P.J. Alexandre, M. Reynaert
Journal: The Lancet (1989)
Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer
Authors: David Cunningham, Yves Humblet, Salvatore Siena, David Khayat, Harry Bleiberg, Armando Santoro, Danny Bets, Matthias Mueser, Andreas Harstrick, Chris Verslype, Ian Chau, Eric Van Cutsem
Journal: New England Journal of Medicine (2004)

The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan.We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment.The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combination-therapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone.Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.
The Brain-Gut Axis in Abdominal Pain Syndromes
Authors: Emeran A. Mayer, Kirsten Tillisch
Journal: Annual Review of Medicine (2010)

The importance of bidirectional brain-gut interactions in gastrointestinal (GI) illness is increasingly recognized, most prominently in the area of functional GI syndromes such as irritable bowel syndrome (IBS), functional dyspepsia, and functional chest pain. The brain receives a constant stream of interoceptive input from the GI tract, integrates this information with other interoceptive information from the body and with contextual information from the environment, and sends an integrated response back to various target cells within the GI tract. This system is optimized to assure homeostasis of the GI tract during physiological perturbations and to adapt GI function to the overall state of the organism. In health, the great majority of interoceptive information reaching the brain is not consciously perceived but serves primarily as input to autonomic reflex pathways. In patients with functional abdominal pain syndromes, conscious perception of interoceptive information from the GI tract, or recall of interoceptive memories of such input, can occur in the form of constant or recurrent discomfort or pain. This is often associated with alterations in autonomic nervous system output and with emotional changes. A model is proposed that incorporates reported peripheral and central abnormalities in patients with IBS, extrapolates similar alterations in brain-gut interactions to patients with other chronic abdominal pain syndromes, and provides novel treatment targets.
Insufficiency fracture of the sacrum revealing a pregnancy associated osteoporosis. First case report
Authors: V Breuil, O Brocq, L Euller-Ziegler, A Grimaud
Journal: Annals of the Rheumatic Diseases (1997)

Osteoporosis of pregnancy, usually responsible for spinal or femoral fracture,1 is rare as is insufficiency fracture of the sacrum, usually occurring in the elderly.2Magnetic resonance imaging (MRI) permitted during pregnancy, led us to diagnose an insufficiency fracture of the sacrum revealing a pregnancy associated osteoporosis, never previously reported to the best of our knowledge. Rheumatologists need to be aware of this new cause of pelvic pain during pregnancy.

A 29 year old pregnant (seventh month) woman presented with a spontaneous acute claudication in conjunction with a left hyperalgesic buttock pain. Her past medical history showed: low back pain, since the second month of her pregnancy, relieved by rest and paracetamol; smoking (10 packet years) stopped at the sixth month of pregnancy; one spontaneous miscarriage at six months responsible for …
Homeopathy in childhood asthma
Authors: A M Li
Journal: Thorax (2003)

We read with interest the article by White et al on the use of homeopathy as an adjunct in the treatment of childhood asthma.1 We also obtained negative findings in an open study in which we assessed the effects of homeopathy on spirometry and exhaled nitric oxide (eNO) in children with stable asthma.

Twelve asthmatic children (4 boys, median age 13.5 years, range 7–18) who satisfied the following inclusion criteria were recruited: (1) stable asthma with no clinical indication for change in treatment, on any dose of inhaled corticosteroid and any other asthma medications; (2) raised eNO level at the start of the study despite clinical stability; (3) identifiable sensitivity to house dust mite (HDM, n=3) or cat and HDM (n=9) by history and skin prick test (SPT); (4) no hospital admission or emergency department attendance for asthma in the previous 3 months; (5) no history of consumption of oral corticosteroid in the previous 3 months; (6) no homeopathic treatment within the previous 6 months, allergen desensitisation within the previous year, or HDM avoidance measures or removal of household pet to which the subject had a positive SPT in the previous 3 months.

At baseline all recruited patients underwent SPT if this had not been done within the previous 2 years, eNO measurement (NIOX, Aerocrine, Sweden), and spirometric testing (Vitalograph, Buckingham, UK) measuring forced expiratory volume in 1 second (FEV1). The mean of three best efforts was recorded and the result was expressed as percentage predicted. The homeopathic remedy was prescribed according to the child’s SPT result. This was a preparation of HDM or cat dander (or both, if appropriate) in the form of two lactose globules. The preparation was made up according to the principles laid out in the British Homeopathic Pharmacopoeia. The patients were told to …
Mild ovarian stimulation for IVF
Authors: M.F.G. Verberg, N.S. Macklon, G. Nargund, R. Frydman, P. Devroey, F.J. Broekmans, B.C.J.M. Fauser
Journal: Human Reproduction Update (2008)

BACKGROUNDMild ovarian stimulation for in vitro fertilization (IVF) aims to achieve cost-effective, patient-friendly regimens which optimize the balance between outcomes and risks of treatment.
Negative Selection of Immature B Cells by Receptor Editing or Deletion Is Determined by Site of Antigen Encounter
Authors: Peter C Sandel, John G Monroe
Journal: Immunity (1999)

Immature B cells that encounter self-antigen are eliminated from the immune repertoire by negative selection. Negative selection has been proposed to take place by two distinct mechanisms: deletion by apoptosis or alteration of the antigen receptor specificity by receptor editing. While convincing evidence exists for each, the two models are inherently contradictory. In this paper, we propose a resolution to this contradiction by demonstrating that the site of first antigen encounter dictates which mechanism of negative selection is utilized. We demonstrate that the bone marrow microenvironment provides signals that block antigen-induced deletion and promote RAG reinduction. In the periphery, the absence of these signals allows the immature B cell to default to apoptosis as a result of BCR engagement.
Ongoing airway inflammation in patients with COPD who do not currently smoke
Authors: S. R. Rutgers, D. S. Postma, N. H. T. Ten Hacken, H. F. Kauffman, T. W. Van Der Mark, G. H. Koëter, W. Timens
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Inflammatory changes in the airways in chronic obstructive pulmonary disease (COPD) are largely attributed to smoking, yet they may be present even if patients do not currently smoke. The differences in inflammatory cells and the factors contributing to these differences were examined in the airways of patients with COPD who do not currently smoke. <h3>METHODS</h3> Eighteen non-atopic subjects with COPD (14 men) of mean (SD) age 62 (8) years and forced expiratory volume in one second (FEV<sub>1</sub>) 59 (13)% predicted and 11 non-atopic healthy subjects (eight men) of mean (SD) age 58 (8) years, FEV<sub>1</sub> 104 (11)% predicted were studied. Sputum induction and bronchoscopy with bronchoalveolar lavage (BAL) and biopsies were performed. <h3>RESULTS</h3> Patients with COPD had more mucosal EG2+ cells (eosinophils) (median (range) 40 (0–190) versus 5 (0–40) cells/mm<sup>2</sup>, p = 0.049) and CD68+ cells (1115 (330–2920) versus 590 (450–1580) cells/mm<sup>2</sup>, p = 0.03), and a tendency towards more CD4+ but not CD8+ lymphocytes than healthy controls. Furthermore, patients with COPD had higher percentages of sputum neutrophils (77 (29–94) versus 36 (18–60)%, p = 0.001) and eosinophils (1.2 (0–8.5) versus 0.2 (0–3.1)%, p = 0.008), BAL fluid eosinophils (0.4 (0–1.7) versus 0.2 (0–0.5)%, p = 0.03), and higher concentrations of sputum eosinophilic cationic protein (ECP) (838 (115–23 760) versus 121 (35–218) ng/ml, p&lt;0.001). Concentrations of ECP expressed per eosinophil were not higher. Patients with COPD with high mucosal EG2+ cell numbers also had high mucosal CD4+ cell numbers. Sputum eosinophilia was associated with a decrease in FEV<sub>1</sub>/VC and BAL fluid eosinophilia with a decrease in mucosal NP57+ cells (neutrophils). <h3>CONCLUSIONS</h3> Subjects with COPD who do not currently smoke have increased numbers of inflammatory cells. Eosinophils are increased in number in the airways in COPD but do not seem to be activated. The increased eosinophil numbers are probably due to recruitment as a result of ongoing inflammation. Macrophages and lymphocytes may play a part in this inflammation.
IL-17A inhibits airway reactivity induced by respiratory syncytial virus infection during allergic airway inflammation
Authors: Dawn Catherine Newcomb, Madison G Boswell, Sara Reiss, Weisong Zhou, Kasia Goleniewska, Shinji Toki, Melissa T Harintho, Nicholas W Lukacs, Jay K Kolls, R Stokes Peebles
Journal: Thorax (2013)

<h3>Background</h3> Viral infections are the most frequent cause of asthma exacerbations and are linked to increased airway reactivity (AR) and inflammation. Mice infected with respiratory syncytial virus (RSV) during ovalbumin (OVA)-induced allergic airway inflammation (OVA/RSV) had increased AR compared with OVA or RSV mice alone. Furthermore, interleukin 17A (IL-17A) was only increased in OVA/RSV mice. <h3>Objective</h3> To determine whether IL-17A increases AR and inflammation in the OVA/RSV model. <h3>Methods</h3> Wild-type (WT) BALB/c and IL-17A knockout (KO) mice underwent mock, RSV, OVA or OVA/RSV protocols. Lungs, bronchoalveolar lavage (BAL) fluid and/or mediastinal lymph nodes (MLNs) were harvested after infection. Cytokine expression was determined by ELISA in the lungs or BAL fluid. MLNs were restimulated with either OVA (323–229) peptide or RSV M2 (127–135) peptide and IL-17A protein expression was analysed. AR was determined by methacholine challenge. <h3>Results</h3> RSV increased IL-17A protein expression by OVA-specific T cells 6 days after infection. OVA/RSV mice had decreased interferon-β protein expression compared with RSV mice. OVA/RSV mice had increased IL-23p19 mRNA expression in lung homogenates compared with mock, OVA or RSV mice. Unexpectedly, IL-17A KO OVA/RSV mice had increased AR compared with WT OVA/RSV mice. Furthermore, IL-17A KO OVA/RSV mice had increased eosinophils, lymphocytes and IL-13 protein expression in BAL fluid compared with WT OVA/RSV mice. <h3>Conclusions</h3> IL-17A negatively regulated AR and airway inflammation in OVA/RSV mice. This finding is important because IL-17A has been identified as a potential therapeutic target in asthma, and inhibiting IL-17A in the setting of virally-induced asthma exacerbations may have adverse consequences.