tbuckley/cabot-search huggingface dataset:
Acute interstitial pneumonia
Authors: D. Bouros, A.C. Nicholson, V Polychronopoulos, R.M du Bois
Journal: European Respiratory Journal (2000)

The term "acute interstitial pneumonia" (AIP) describes an idiopathic clinicopathological condition, characterized clinically by an interstitial lung disease causing rapid onset of respiratory failure, which is distinguishable from the other more chronic forms of interstitial pneumonia. It is synonymous with Hamman-Rich syndrome, occurring in patients without pre-existing lung disease. The histopathological findings are those of diffuse alveolar damage. AIP radiologically and physiologically resembles acute respiratory distress syndrome (ARDS) and is considered to represent the small subset of patients with idiopathic ARDS. It is frequently confused with other clinical entities characterized by rapidly progressive interstitial pneumonia, especially secondary acute interstitial pneumonia, acute exacerbations and accelerated forms of cryptogenic fibrosing alveolitis . Furthermore, many authors use the above terms, both erroneously and interchangeably. It has a grave prognosis with >70% mortality in 3 months, despite mechanical ventilation. This review aims to clarify the relative clinical and pathological issues and terminology.
XIAP Reduces Muscle Proteolysis Induced by CKD
Authors: Junping Hu, Jie Du, Liping Zhang, S. Russ Price, Janet D. Klein, Xiaonan H. Wang
Journal: Journal of the American Society of Nephrology (2010)

X-chromosome-linked inhibitor of apoptosis protein (XIAP) is an endogenous caspase inhibitor. Caspase-3 contributes to the muscle wasting associated with chronic kidney disease (CKD) and other systemic illnesses, but whether XIAP modulates muscle wasting in CKD is unknown. Here, overexpression of XIAP in cultured skeletal muscle cells decreased protein degradation induced by serum deprivation, suggesting that caspase-mediated proteolysis contributes to muscle atrophy. We generated transgenic mice that overexpress human XIAP specifically in skeletal muscle (mXIAP) and evaluated muscle protein degradation induced by CKD. mXIAP mice with normal kidney function exhibited mild skeletal muscle hypertrophy. Muscle weights of mXIAP mice with CKD (mXIAP-CKD) were indistinguishable from wild-type mice, suggesting that overexpression of XIAP in skeletal muscle protects from CKD-induced muscle atrophy. The rate of total protein degradation, proteasome chymotrypsin-like activity, and caspase-3-mediated actin cleavage all were lower in muscle isolated from mXIAP-CKD mice compared with wild-type CKD mice. Concomitant with the reduction in overall proteolysis, mRNA levels of ubiquitin, muscle-specific ring finger 1, and atrogin-1/muscle atrophy F-box were lower in mXIAP-CKD mice, suggesting that decreased expression of the ubiquitin-proteasome pathway components may contribute to the protein-sparing effects of XIAP. In summary, these results demonstrate that XIAP inhibits multiple aspects of protein degradation in skeletal muscle during CKD.
Severe Intractable Postprandial Chest Pain
Authors: Conall Fitzgerald, Orla Mc Cormack, John V. Reynolds
Journal: JAMA (2013)

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Brain-derived neurotrophic factor amplifies neurotransmitter responses and promotes synaptic communication in the enteric nervous system
Authors: W Boesmans, P Gomes, J Janssens, J Tack, P V. Berghe
Journal: Gut (2007)

<h3>Background:</h3> Besides its role in neuronal growth and differentiation, brain-derived neurotrophic factor (BDNF) has been implicated in the control of peristalsis where it serves to enhance gastrointestinal motility. <h3>Aim:</h3> To unravel the cellular mechanisms governing BDNF's effect on motility. <h3>Methods:</h3> Studies were performed in primary myenteric neuron cultures and whole-mount preparations derived from guinea pig ileum. Expression of BDNF and its tropomyosin-related kinase B (TrkB) receptor was assessed by immunohistochemistry. Intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) changes in myenteric neurons were monitored using Fluo-4, and neurotransmitter release kinetics at enteric synapses were evaluated with FM1-43 imaging. <h3>Results:</h3> Immunohistochemistry revealed the presence of BDNF and TrkB in mucosa, submucosal plexus and myenteric ganglia. Primary cultures also expressed BDNF and TrkB and were used to study the physiological effects of BDNF. None of the neurons studied displayed a [Ca<sup>2+</sup>]<sub>i</sub> change when challenged with BDNF. However, BDNF exposure caused an enhancement of Ca<sup>2+</sup> transients induced by serotonin and substance P, which was reversed by the Trk receptor blocker K-252a (0.1 μM). BDNF exposure also resulted in an amplification of spontaneous network activity which was reflected in an increased number of synaptic vesicle clusters. Furthermore, BDNF treatment facilitated FM1-43-labelled vesicle destaining in enteric terminals during field stimulation. <h3>Conclusions:</h3> The findings demonstrate that BDNF is able to enhance rather than directly activate enteric nervous system signalling. Therefore, the promotion of motility by BDNF seems to result from its potent modulating role on enteric neuronal activity and synaptic communication.
Ca <sup>2+</sup> -Related Signaling and Protein Phosphorylation Abnormalities Play Central Roles in a New Experimental Model of Electrical Storm
Authors: Yukiomi Tsuji, Mayumi Hojo, Niels Voigt, Ali El-Armouche, Yasuya Inden, Toyoaki Murohara, Dobromir Dobrev, Stanley Nattel, Itsuo Kodama, Kaichiro Kamiya
Journal: Circulation (2011)

Background— Electrical storm (ES), characterized by recurrent ventricular tachycardia/fibrillation, typically occurs in implantable cardioverter-defibrillator patients and adversely affects prognosis. However, the underlying molecular basis is poorly understood. In the present study, we report a new experimental model featuring repetitive episodes of implantable cardioverter-defibrillator firing for recurrent ventricular fibrillation (VF), in which we assessed involvement of Ca 2+ -related protein alterations in ES. Methods and Results— We studied 37 rabbits with complete atrioventricular block for ≈80 days, all with implantable cardioverter-defibrillator implantation. All rabbits showed long-QT and VF episodes. Fifty-three percent of rabbits developed ES (≥3 VF episodes per 24-hour period; 103±23 VF episodes per rabbit). Expression/phosphorylation of Ca 2+ -handling proteins was assessed in left ventricular tissues from rabbits with the following: ES; VF episodes but not ES (non-ES); and controls. Left ventricular end-diastolic diameter increased comparably in ES and non-ES rabbits, but contractile dysfunction was significantly greater in ES than in non-ES rabbits. ES rabbits showed striking hyperphosphorylation of Ca 2+ /calmodulin-dependent protein kinase II, prominent phospholamban dephosphorylation, and increased protein phosphatase 1 and 2A expression versus control and non-ES rabbits. Ryanodine receptors were similarly hyperphosphorylated at Ser2815 in ES and non-ES rabbits, but ryanodine receptor Ser2809 and L-type Ca 2+ channel α-subunit hyperphosphorylation were significantly greater in ES versus non-ES rabbits. To examine direct effects of repeated VF/defibrillation, VF was induced 10 times in control rabbits. Repeated VF tissues showed autophosphorylated Ca 2+ /calmodulin-dependent protein kinase II upregulation and phospholamban dephosphorylation like those of ES rabbit hearts. Continuous infusion of a calmodulin antagonist (W-7) to ES rabbits reduced Ca 2+ /calmodulin-dependent protein kinase II hyperphosphorylation, suppressed ventricular tachycardia/fibrillation, and rescued left ventricular dysfunction. Conclusions— ES causes Ca 2+ /calmodulin-dependent protein kinase II activation and phospholamban dephosphorylation, which can explain the vicious cycle of arrhythmia promotion and mechanical dysfunction that characterizes ES.
RECEPTOR FOR SOLUBLE C3 AND C3b ON HUMAN LYMPHOBLASTOID (RAJI) CELLS
Authors: Argyrios N. Theofilopoulos, Viktor A. Bokisch, Frank J. Dixon
Journal: The Journal of Experimental Medicine (1974)

This study describes the presence of a receptor for fluid phase human C3 and C3b on Raji cell membranes. The binding of C3 and C3b was demonstrated indirectly by a fluoresceinated anti-C3 serum and directly by using radioiodinated proteins. No other complement proteins or serum factors were needed to mediate binding of C3 and C3b to the receptor. The possibility of enzymatic cleavage of C3 before or after its attachment on the cell membrane was ruled out by the demonstration of antigenically intact C3 on Raji cells. Inhibition and dissociation of Raji cell-EAC1423 rosettes by C3 and C3b indicated that both of these proteins bind to the same receptor site or closely associated receptor sites on Raji cells. C3b-bearing Raji cells were immune adherence negative, indicating that C3b binding to the receptor is brought about through the immune adherence region of the molecule and not the C3d portion. The C3 receptor on Raji cell membranes is uniformly distributed and can move on the membrane plane. Approximately 4 x 105 molecules of C3 or C3b bind per Raji cell. The receptor had a higher affinity for C3 than C3b, as was shown by uptake experiments and inhibition of Raji cell-EAC1423 rosette formation. Apart from the described receptor for C3 and C3b another specific receptor for C3b inactivator-cleaved C3b (C3d) bound to red cells was shown to be present on Raji cells. Raji cells cultured in medium containing fresh normal human serum and cobra venom factor were lysed. Similar results were obtained when C3b-bearing Raji cells were cultured in medium with fresh normal human serum. The lytic effect could be abolished by inactivating serum C3 proactivator (C3PA) and required C6. It was concluded that C3b bound to the Raji cell membrane activates the complement system through the alternate pathway and results in membrane damage and cytolysis. It is postulated that cell destruction by this mechanism may play an important role in vivo in controlling cell growth.
Outcome of Burkholderia (Pseudomonas) cepacia colonisation in children with cystic fibrosis following a hospital outbreak.
Authors: M L Whiteford, J D Wilkinson, J H McColl, F M Conlon, J R Michie, T J Evans, J Y Paton
Journal: Thorax (1995)

BACKGROUND--While there are reports on the outcome in adults and teenagers with cystic fibrosis of colonisation with Burkholderia (Pseudomonas) cepacia, there is little information in children. METHODS--In December 1991 only one of 115 children with cystic fibrosis attending a paediatric centre was colonised with B cepacia. Over the next 12 months there was a rapid increase with 23 (20%) becoming colonised; eighteen (79%) of these became colonised in hospital at a time that overlapped with the admission of a B cepacia positive child. Three different bacteriocin types were isolated, with one type (S22/PO) being present in 17 (74%) patients. The outcome for children who became colonised with B cepacia was compared with that in 33 children who continued to be colonised with Pseudomonas aeruginosa alone. RESULTS--Children colonised with B cepacia were older and more poorly nourished than those colonised with P aeruginosa, but did not have poorer pulmonary function. After colonisation, the forced expiratory volume in one second (FEV1) deteriorated between consecutive annual tests, with the average deterioration being greater in those with higher initial levels. Five children with B cepacia died from respiratory failure although none showed a fulminant deterioration. Introduction of segregation measures within hospital led to a dramatic decrease in the number of newly colonised patients. CONCLUSIONS--This study provides further evidence for person-to-person spread of B cepacia and confirms the effectiveness of simple isolation measures in interrupting spread. Colonisation with B cepacia and P aeruginosa in children is associated with a more rapid decline in lung function and a significantly increased mortality compared with cases colonised with P aeruginosa alone.
The Insulin Analog Aspart: A Safe Alternative in Insulin Allergy
Authors: Lorena Airaghi, Maurizio Lorini, Alberto Tedeschi
Journal: Diabetes Care (2001)

The introduction of human recombinant insulin has considerably lowered, but not eliminated, adverse reactions to insulin administration. Several reports indicate that human recombinant insulin can also induce IgE- and non–IgE-mediated local or systemic reactions (1,2). However, in most patients with allergy to human recombinant insulin, insulin lispro—a genetically engineered insulin analog (Humalog; Lilly, Indianapolis, IN)—is well tolerated and can be safely used (3,4,5). Although the main immunogenic insulin epitopes remain unchanged in the lispro molecule, it has been suggested that this analog has reduced immunogenicity because of its rapid dissociation in monomers (6).

Here we report the case of cutaneous hypersensitivity to human insulin, successfully treated with the human insulin analog aspart (NovoRapid; Novo Nordisk, Bagsvaerd, Denmark). This rapid-acting insulin analog is produced by recombinant technology that replaces the proline at position 28 on the …
Novel scoring system and algorithm for classifying chronic rhinosinusitis: the <scp>JESREC</scp> Study
Authors: T. Tokunaga, M. Sakashita, T. Haruna, D. Asaka, S. Takeno, H. Ikeda, T. Nakayama, N. Seki, S. Ito, J. Murata, Y. Sakuma, N. Yoshida, T. Terada, I. Morikura, H. Sakaida, K. Kondo, K. Teraguchi, M. Okano, N. Otori, M. Yoshikawa, K. Hirakawa, S. Haruna, T. Himi, K. Ikeda, J. Ishitoya, Y. Iino, R. Kawata, H. Kawauchi, M. Kobayashi, T. Yamasoba, T. Miwa, M. Urashima, M. Tamari, E. Noguchi, T. Ninomiya, Y. Imoto, T. Morikawa, K. Tomita, T. Takabayashi, S. Fujieda
Journal: Allergy (2015)

Abstract Background Chronic rhinosinusitis ( CRS ) can be classified into CRS with nasal polyps ( CRS w NP ) and CRS without nasal polyps ( CRS s NP ). CRS w NP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS ( ECRS ), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS . Methods This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis ( JESREC ). We evaluated patients with CRS treated with endoscopic sinus surgery ( ESS ), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS . Results We analyzed 1716 patients treated with ESS . To diagnose ECRS , the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography ( CT ) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (&gt;5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti‐inflammatory drugs intolerance were associated significantly with recurrence. Conclusion We subdivided CRS w NP in non‐ ECRS , mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.
Vascular smooth muscle cell activation by C-reactive protein
Authors: Y HATTORI, M MATSUMURA, K KASAI
Journal: Cardiovascular Research (2003)

Objective: C-reactive protein (CRP) is an important cardiovascular risk factor. Although the role of CRP has been implicated in atherogenesis, its direct effects on vascular cells are poorly defined. Methods: We investigated the responses to CRP in vascular smooth muscle cells (VSMC). Results: The present study shows that CRP induces parallel activation of the redox-responsive transcription factors NF-kappa B (NF-κB) and AP-1 and increases the activity of the MAP kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38MAPK, in VSMC. C-reactive protein increased the expression of early response genes, c-fos and c-jun and inflammatory genes, monocyte chemoattractant peptide (MCP-1) and interleukin-6 (IL-6). When VSMC were incubated with CRP, the inducible nitric oxide synthase (iNOS) promoter was activated. CRP alone was a weak inducer of NO production in VSMC as measured by determining nitrite levels, and interferon-γ alone was totally ineffective, whereas CRP plus interferon-γ was a powerful stimulus. This synergy for NO production corresponded to the results of iNOS mRNA expression analyzed by Northern blotting. The NF-κB activation caused by CRP was inhibited by 15-deoxy-12,14-prostaglandin J2 and the PPARγ activators, rosiglitazone and pioglitazone. Fluvastatin and cerivastatin also reduced the activation of NF-κB by CRP. Conclusions: CRP causes NF-κB activation which could lead to the induction of MCP-1, IL-6, and iNOS gene expression. CRP also activates the MAPK→c-Fos/cJun→AP-1 pathway. Thus, CRP may play a role in atherogenesis by activating VSMC.
Effects of High-Dose IFNα2b on Regional Lymph Node Metastases of Human Melanoma: Modulation of STAT5, FOXP3, and IL-17
Authors: Wenjun Wang, Howard D. Edington, Uma N.M. Rao, Drazen M. Jukic, Arash Radfar, Hong Wang, John M. Kirkwood
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Signal transducer and activator of transcription 5 (STAT5) and STAT3 oppose one another in regulation of the reciprocal development of CD4+CD25+FOXP3+ regulatory T cells (Treg) and T helper 17 (Th17). A reduction in STAT3 is associated with up-regulation of Treg, and STAT5 activation promotes Treg differentiation or function while constraining Th17 generation. The effects of IFNα on STAT signaling in relation to tumor tissue Treg and Th17 have not been documented in humans beyond the observations that IFNα2b down-regulates STAT3. Experimental Design: Following diagnostic biopsy and before definitive surgery, 20 doses of high-dose IFNα2b (HDI) were administered to patients with stage IIIB melanoma who gave written informed consent. Lymph node biopsies, in which both total STAT3 and phosphorylated STAT3 were down-regulated by HDI, were probed with STAT5, FOXP3, CD4, and interleukin 17 (IL-17) with immunohistochemistry and/or immunofluorescence techniques. Results: The percentage of FOXP3+ lymphocytes determined by immunohistochemistry was up-regulated from 3.06 ± 0.65% to 9.86 ± 1.27% (n = 13, P = 0.0002), and this observation was confirmed by immunofluorescence evaluation of CD4+FOXP3+ Tregs. HDI induced STAT5 up-regulation (five cases observed) in melanoma cells and lymphocytes but did not induce the generation of IL-17–expressing lymphocytes. Increased STAT5 expression was associated with increased FOXP3 expression among lymphocytes, and STAT5 was constitutively activated among both melanoma cells and lymphocytes. Conclusion: IFNα2b up-regulates STAT5 and down-regulates STAT3, in conjunction with up-regulation of Treg and inhibition of IL-17–expressing lymphocytes in melanoma tissues. These findings suggest that the effects of IFNα may be potentiated through interference with the response of Tregs and/or STAT5.
RESULTS OF EXPERIMENTAL INTESTINAL STRANGULATION OBSTRUCTION IN GERMFREE RATS
Authors: Egil Amundsen, Bengt E. Gustafsson
Journal: The Journal of Experimental Medicine (1963)

Experimental low ileal strangulation obstruction has been produced in germfree and conventional rats. The mean survival time was 240 hours in the germfree rats and 44 hours in the conventional controls. 4 of the 10 germfree rats survived 15 or more days, whereas the 10 conventional animals were all dead within 2(1/2) days. The strangulation obstruction fluid from the germfree animals was sterile and non-toxic when injected into mice even after a fourfold concentration. The same fluid from the conventional animals contained a great number of microorganisms and caused death within 24 hours when injected intraperitoneally into mice.
Reprogramming CD19-Specific T Cells with IL-21 Signaling Can Improve Adoptive Immunotherapy of B-Lineage Malignancies
Authors: Harjeet Singh, Matthew J. Figliola, Margaret J. Dawson, Helen Huls, Simon Olivares, Kirsten Switzer, Tiejuan Mi, Sourindra Maiti, Partow Kebriaei, Dean A. Lee, Richard E. Champlin, Laurence J.N. Cooper
Journal: Cancer Research (2011)

Improving the therapeutic efficacy of T cells expressing a chimeric antigen receptor (CAR) represents an important goal in efforts to control B-cell malignancies. Recently an intrinsic strategy has been developed to modify the CAR itself to improve T-cell signaling. Here we report a second extrinsic approach based on altering the culture milieu to numerically expand CAR(+) T cells with a desired phenotype, for the addition of interleukin (IL)-21 to tissue culture improves CAR-dependent T-cell effector functions. We used electrotransfer of Sleeping Beauty system to introduce a CAR transposon and selectively propagate CAR(+) T cells on CD19(+) artificial antigen-presenting cells (aAPC). When IL-21 was present, there was preferential numeric expansion of CD19-specific T cells which lysed and produced IFN-γ in response to CD19. Populations of these numerically expanded CAR(+) T cells displayed an early memory surface phenotype characterized as CD62L(+)CD28(+) and a transcriptional profile of naïve T cells. In contrast, T cells propagated with only exogenous IL-2 tended to result in an overgrowth of CD19-specific CD4(+) T cells. Furthermore, adoptive transfer of CAR(+) T cells cultured with IL-21 exhibited improved control of CD19(+) B-cell malignancy in mice. To provide coordinated signaling to propagate CAR(+) T cells, we developed a novel mutein of IL-21 bound to the cell surface of aAPC that replaced the need for soluble IL-21. Our findings show that IL-21 can provide an extrinsic reprogramming signal to generate desired CAR(+) T cells for effective immunotherapy.