tbuckley/cabot-search huggingface dataset:
Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography
Authors: John Terrovitis, Keng Fai Kwok, Riikka Lautamäki, James M. Engles, Andreas S. Barth, Eddy Kizana, Junichiro Miake, Michelle K. Leppo, James Fox, Jurgen Seidel, Martin Pomper, Richard L. Wahl, Benjamin Tsui, Frank Bengel, Eduardo Marbán, M. Roselle Abraham
Journal: Journal of the American College of Cardiology (2008)
Effect of acidic reperfusion on prolongation of intracellular acidosis and myocardial salvage
Authors: J. Inserte, I. Barba, V. Hernando, A. Abellan, M. Ruiz-Meana, A. Rodriguez-Sinovas, D. Garcia-Dorado
Journal: Cardiovascular Research (2007)

It has been proposed that intracellular acidosis may be the basis of the cardioprotection of different interventions, including postconditioning. However, contradictory reports exist on the effects of acidic reperfusion on myocardial salvage. Here we characterized the effect of lowering the pH of the reperfusion media (pHo) on intracellular pH (pHi) and cell death.The effect of acidic perfusion on reperfusion injury was studied in isolated rat hearts submitted to 40 min of ischaemia and 30 min of reperfusion, and its effect on the Na(+)/Ca(2+)-exchanger (NCX) was analysed in isolated myocytes. pHi and phosphocreatine (PCr) were monitored by nuclear magnetic resonance spectroscopy. Lowering pHo to 6.4 during the initial 3 min of reperfusion delayed pHi normalization, improved PCr recovery, and markedly reduced (P < 0.001) lactate dehydrogenase release and infarct size (tetrazolium reaction). This cardioprotection was attenuated as pHo was increased, and was lost at pH0 7.0. Extending acidic reperfusion to the first 15 or 30 min of reflow did not result in further delay of pHi normalization and abolished the protection afforded by the initial 3 min of acidic reperfusion unless the Na(+)/H(+)-exchanger (NHE) blocker cariporide was added to the acidic perfusate and HCO(3)(-) substituted for N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulphonic acid]. In experiments performed in fura-2-loaded myocytes exposed to low Na(+) buffer adjusted to pH 6.4, the lower Ca(2+) uptake indicated an inhibitory effect of acidosis on NCX.Acidic reperfusion for 3 min delays normalization of pHi and enhances myocardial salvage, but extending it beyond this period fails to further delay pHi recovery. This is probably due to persisting NHE and Na(+)/HCO(3)(-)-cotransporter activities, and it is detrimental, possibly through prolonged NCX inhibition.
Regulation of Connective Tissue Growth Factor Activity in Cultured Rat Mesangial Cells and Its Expression in Experimental Diabetic Glomerulosclerosis
Authors: BRUCE L. RISER, MARK DENICHILO, PEDRO CORTES, CATHRYN BAKER, JANET M. GRONDIN, JERRY YEE, ROBERT G. NARINS
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Connective tissue growth factor (CTGF) is a peptide secreted by cultured endothelial cells and fibroblasts when stimulated by transforming growth factor-β (TGF-β), and is overexpressed during fibrotic processes in coronary arteries and in skin. To determine whether CTGF is implicated in the pathogenesis of diabetic glomerulosclerosis, cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli were examined from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to recombinant human CTGF significantly increased fibronectin and collagen type I production. Furthermore, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36 to 38 kD) into the media. However, sodium heparin treatment resulted in a greater than fourfold increase in media-associated CTGF, suggesting that the majority of CTGF produced was cell- or matrix-bound. Exposure of MC to TGF-β, increased glucose concentrations, or cyclic mechanical strain, all causal factors in diabetic glomerulosclerosis, markedly induced the expression of CTGF transcripts, while recombinant human CTGF was able to autoinduce its own expression. TGF-β and high glucose, but not mechanical strain, stimulated the concomitant secretion of CTGF protein, the former also inducing abundant quantities of a small molecular weight form of CTGF (18 kD) containing the heparin-binding domain. The induction of CTGF protein by a high glucose concentration was mediated by TGF-β, since a TGF-β-neutralizing antibody blocked this stimulation. In vivo studies using quantitative reverse transcription-PCR demonstrated that although CTGF transcripts were low in the glomeruli of control mice, expression was increased 28-fold after approximately 3.5 mo of diabetes. This change occurred early in the course of diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced elevation of CTGF mRNA (twofold) observed in whole kidney cortices indicated that the primary alteration of CTGF expression was in the glomerulus. These results suggest that CTGF upregulation is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis, acting downstream of TGF-β.
Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma
Authors: Michael A. Postow, Jason Chesney, Anna C. Pavlick, Caroline Robert, Kenneth Grossmann, David McDermott, Gerald P. Linette, Nicolas Meyer, Jeffrey K. Giguere, Sanjiv S. Agarwala, Montaser Shaheen, Marc S. Ernstoff, David Minor, April K. Salama, Matthew Taylor, Patrick A. Ott, Linda M. Rollin, Christine Horak, Paul Gagnier, Jedd D. Wolchok, F. Stephen Hodi
Journal: New England Journal of Medicine (2015)

In a phase 1 dose-escalation study, combined inhibition of T-cell checkpoint pathways by nivolumab and ipilimumab was associated with a high rate of objective response, including complete responses, among patients with advanced melanoma.
Oxidised LDL and progression of atherosclerosis
Authors: Markku Laakso, Kari Poikolainen, Kalevi Pyörälä, Michele Mercuri, Meir Strahilevitz, Simon Roselaar, John Cunningham, JukkaT. Salonen, Heikki Korpela, Riitta Salonen, Kristiina Nyyssönen, Seppo Ylā-Herttuala, Robert Yamamato, Susan Butler, Wulf Palinski, JosephL. Witztum
Journal: The Lancet (1992)
Decrease of CD56+T Cells and Natural Killer Cells in Cirrhotic Livers With Hepatitis C May Be Involved in Their Susceptibility to Hepatocellular Carcinoma
Authors: Nobuaki Kawarabayashi, Shuhji Seki, Kazuo Hatsuse, Takashi Ohkawa, Yuji Koike, Tsukasa Aihara, Yoshiko Habu, Ryusuke Nakagawa, Katsunori Ami, Hoshio Hiraide, Hidetaka Mochizuki
Journal: Hepatology (2000)

CD56(+)T cells and CD56(+)natural killer (NK) cells are abundant in the human liver. The aim of this study was the further characterization of these cells in the liver with or without hepatitis C virus (HCV) infection. Liver mononuclear cells (MNC) were isolated from liver specimens obtained from the patients during abdominal surgery. In addition to a flow cytometric analysis, liver MNC and PBMC were cultured with the immobilized anti-CD3 Ab, IL-2, or a combination of IL-2 and IL-12 and their IFN-gamma production and the antitumor cytotoxicity were assessed. The liver MNC of HCV (-) patients contained 20% CD56(+)T cells whereas the same proportions decreased to 11% in chronic hepatitis livers and to 5% in cirrhotic livers. The proportion of NK cells also decreased in the cirrhotic livers. On the other hand, the populations of these cells in PBMC did not significantly differ among patient groups. The IFN-gamma production and the cytotoxicity against K562 cells, Raji cells, and a hepatocellular carcinoma, HuH-7 cells, greatly decreased in the cirrhotic liver MNC. In contrast, the cytotoxicity in PBMC did not significantly differ among the patient groups and was lower than that in the liver MNC of HCV (-) patients. CD56(+)T cells and NK cells but not regular T cells purified from liver MNC cultured with cytokines showed potent cytotoxicities against HuH-7 cells. These results suggest that a decreased number of CD56(+)T cells and NK cells in cirrhotic livers may be related to their susceptibility to hepatocellular carcinoma.
Cystic dilatation of peribiliary glands in livers with adult polycystic disease and livers with solitary nonparasitic cysts: An autopsy study
Authors: Tetsuji Kida, Yasuni Nakanuma, Tadashi Terada
Journal: Hepatology (1992)

Cystic dilatation of peribiliary glands of intrahepatic and extrahepatic bile ducts was investigated in autopsied livers with adult polycystic disease (n = 8), in autopsied livers with solitary nonparasitic cysts (n = 18) and in normal autopsied livers (n = 23). In normal livers, cystic dilatation of intrahepatic peribiliary glands was absent or slight, when present. In livers with solitary nonparasitic cysts, cystic dilatation of intrahepatic peribiliary glands was present in varying degrees. In livers with adult polycystic disease, intrahepatic peribiliary glands showed frequent and severe cystic dilatation so marked that it was grossly recognizable. In contrast, peribiliary glands of the extrahepatic bile ducts showed no cystic dilatation in most cases, regardless of the three conditions examined. Liver parenchymal cysts were numerous in livers with adult polycystic disease, few in livers with solitary nonparasitic cysts and nonexistent in normal livers. Von Meyenburg complexes were present in 87.5% of livers with adult polycystic disease, in 16.7% of livers with solitary nonparasitic cysts and in 4.3% of normal livers. These findings suggest that intrahepatic peribiliary glands undergo cystic dilatation in livers with adult polycystic disease-and, to a lesser degree and frequency in livers with solitary nonparasitic cysts, probably because of congenital or genetic factors-and that these cystic changes may comprise a part of numerous cysts of adult polycystic disease.
Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD
Authors: R A O'Donnell
Journal: Thorax (2004)

Considerable research has been conducted into the nature of airway inflammation in chronic obstructive pulmonary disease (COPD) but the relationship between proximal airways inflammation and both dynamic collapse of the peripheral airways and HRCT determined emphysema severity remains unknown. A number of research tools have been combined to study smokers with a range of COPD severities classified according to the GOLD criteria.Sixty five subjects (11 healthy smokers, 44 smokers with stage 0-IV COPD, and 10 healthy non-smokers) were assessed using lung function testing and HRCT scanning to quantify emphysema and peripheral airway dysfunction and sputum induction to measure airway inflammation.Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio (both indicators of peripheral airway dysfunction) correlated more closely in smokers with the severity of airflow obstruction (r = -0.64, p<0.001) than did inspiratory HRCT measurements (which reflect emphysema severity; r = -0.45, p<0.01). Raised sputum neutrophil counts also correlated strongly in smokers with HRCT indicators of peripheral airway dysfunction (r = 0.55, p<0.001) but did not correlate with HRCT indicators of the severity of emphysema.This study suggests that peripheral airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of COPD severity. Airway neutrophilia, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD but is not related to the overall severity of emphysema as measured by HRCT.
Joint hypermobility and fibromyalgia in schoolchildren.
Authors: A Gedalia, J Press, M Klein, D Buskila
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To test the hypothesis that joint hypermobility may play a part in the pathogenesis of pain in fibromyalgia, schoolchildren were examined for the coexistence of joint hypermobility and fibromyalgia. METHODS--The study group consisted of 338 children (179 boys, 159 girls; mean age 11.5 years, range 9-15 years) from one public school in Beer-Sheva, Israel. In the assessment of joint hypermobility, the criteria devised by Carter and Bird were used. Any child who met at least three of five criteria was considered to have joint hypermobility. Children were considered to have fibromyalgia if they fulfilled the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia, namely, widespread pain in combination with tenderness of 11 or more of the 18 specific tender point sites. The blind assessments of joint hypermobility (by AG) and fibromyalgia (by DB) were carried out independently. RESULTS--Of the 338 children 43 (13%) were found to have joint hypermobility and 21 (6%) fibromyalgia; 17 (81%) of the 21 with fibromyalgia had joint hypermobility and 17 (40%) of the 43 with joint hypermobility had fibromyalgia. Using chi 2 statistical analysis, joint hypermobility and fibromyalgia were found to be highly associated. CONCLUSIONS--This study suggests that there is a strong association between joint hypermobility and fibromyalgia in schoolchildren. It is possible that joint hypermobility may play a part in the pathogenesis of pain in fibromyalgia. More studies are needed to establish the clinical significance of this observation.
Loss of the Podocyte-Expressed Transcription Factor Tcf21/Pod1 Results in Podocyte Differentiation Defects and FSGS
Authors: Yoshiro Maezawa, Tuncer Onay, Rizaldy P. Scott, Lindsay S. Keir, Henrik Dimke, Chengjin Li, Vera Eremina, Yuko Maezawa, Marie Jeansson, Jingdong Shan, Matthew Binnie, Moshe Lewin, Asish Ghosh, Jeffrey H. Miner, Seppo J. Vainio, Susan E. Quaggin
Journal: Journal of the American Society of Nephrology (2014)

Podocytes are terminally differentiated cells with an elaborate cytoskeleton and are critical components of the glomerular barrier. We identified a bHLH transcription factor, Tcf21, that is highly expressed in developing and mature podocytes. Because conventional Tcf21 knockout mice die in the perinatal period with major cardiopulmonary defects, we generated a conditional Tcf21 knockout mouse to explore the role of this transcription factor in podocytes in vivo. Tcf21 was deleted from podocytes and podocyte progenitors using podocin-cre (podTcf21) and wnt4-cre (wnt4creTcf21) driver strains, respectively. Loss of Tcf21 from capillary-loop stage podocytes (podTcf21) results in simplified glomeruli with a decreased number of endothelial and mesangial cells. By 5 weeks of age, 40% of podTcf21 mice develop massive proteinuria and lesions similar to FSGS. Notably, the remaining 60% of mice do not develop proteinuria even when aged to 8 months. By contrast, earlier deletion of Tcf21 from podocyte precursors (wnt4creTcf21) results in a profound developmental arrest of podocyte differentiation and renal failure in 100% of mice during the perinatal period. Taken together, our results demonstrate a critical role for Tcf21 in the differentiation and maintenance of podocytes. Identification of direct targets of this transcription factor may provide new therapeutic avenues for proteinuric renal disease, including FSGS.
Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial
Authors: Heather Ciliberto, Michael Ciliberto, Andreé Briend, Per Ashorn, Dennis Bier, Mark Manary
Journal: BMJ (2005)

Objective To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Design Prospective, double blind, placebo controlled trial randomised by household. Setting 8 villages in rural southern Malawi. Participants 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Intervention Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. Main outcome measures The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. Results 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Conclusions Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor.
Neuropeptide Function: The Invertebrate Contribution
Authors: Michael O'Shea, Martin Schaffer
Journal: Annual Review of Neuroscience (1985)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Add-on Treatment of Benzoate for Schizophrenia
Authors: Hsien-Yuan Lane, Ching-Hua Lin, Michael F. Green, Gerhard Hellemann, Chih-Chia Huang, Po-Wei Chen, Rene Tun, Yue-Cung Chang, Guochuan E. Tsai
Journal: JAMA Psychiatry (2013)

IMPORTANCEIn addition to dopaminergic hyperactivity, hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia.Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach.To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition.Another method to enhance NMDA function is to raise the levels of D-amino acids by blocking their metabolism.Sodium benzoate is a D-amino acid oxidase inhibitor.OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. DESIGN, SETTING, AND PARTICIPANTSA randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. MAIN OUTCOMES AND MEASURESThe primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score.Clinical efficacy and adverse effects were assessed biweekly.Cognitive functions were measured before and after the add-on treatment.RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning.Benzoate was well tolerated without significant adverse effects.CONCLUSIONS AND RELEVANCE Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia.The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia.
Modification of T cell antinuclease idiotype expression by in vivo administration of anti-idiotype.
Authors: G G Miller, P I Nadler, R J Hodes, D H Sachs
Journal: The Journal of Experimental Medicine (1982)

Immunization of BALB/c mice with nuclease leads to the production of anti-nuclease antibodies bearing a set of cross-reactive idiotypes (Id) distinct from those produced by B10.D2 mice after similar immunization. In both strains, such immunization with nuclease also leads to the production of splenic T helper cells (TH), which provide nuclease-specific help in an in vitro plaque-forming cell response to nuclease-TNP. Pig anti-(BALB/c antinuclease) anti-idiotypic antibodies (pig anti-BALB/c Id) react only with TH of nuclease-primed BALB/c and not with B10.D2 animals. After administration of pig anti-BALB/c Id in complete Freund's adjuvant to BALB/c and B10.D2 mice, Id-bearing nonantigen-binding molecules were induced in both strains. Such treatment also resulted in the induction of nuclease-specific splenic TH cells in both strains. BALB/c TH cells induced by anti-Id, like the majority of nuclease-primed BALB/c TH cells, bore BALB/c Id, as shown by their functional elimination with anti-Id plus complement. B10.D2 TH cells induced by anti-Id, unlike TH cells from nuclease-primed B10.D2 mice, also bore BALB/c idiotypic determinants by the same criterion. Thus, it appears that one can manipulate the expression of Id on serum immunoglobulins and on antigen-specific TH cells by administration of exogenous anti-Id reagents. These results have implications both for network interactions in the immune response and for the genetic basis of Igh-C linked Id expression.
Antiatherogenic Mitochondrial Genotype in Patients With Type 2 Diabetes
Authors: Hajime Matsunaga, Yasushi Tanaka, Masashi Tanaka, Jian-Sheng Gong, Jin Zhang, Takashi Nomiyama, Osamu Ogawa, Takeshi Ogihara, Yoshiji Yamada, Kunio Yagi, Ryuzo Kawamori
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C → A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—Mt5178 typing was done by polymerase chain reaction–restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C. RESULTS—The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mt5178A group than in the Mt5178C group (0.906 ± 0.018 vs. 0.995 ± 0.021 mm, mean ± SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis. CONCLUSIONS—The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.