tbuckley/cabot-search huggingface dataset:
Gene complementation. Neither Ir-GLphi gene need be present in the proliferative T cell to generate an immune response to Poly(Glu55Lys36Phe9)n.
Authors: D L Longo, R H Schwartz
Journal: The Journal of Experimental Medicine (1980)

The cellular requirements for immune response (Ir) gene expression in a T cell proliferative response under dual Ir gene control were examined with radiation-induced bone marrow chimeras. The response to poly(Glu55Lys36Phe9)n (GLphi) requires two responder alleles that in the [B10.A X B10.A(18R)]F1 map in I-Ab and I-Ek/Cd. Chimeras in which a mixture of the nonresponder B10.A parental cells (which possess only I-Ek/Cd) and the nonresponder B10.A(18R) parental cells (which possess only I-Ab) were allowed to mature in a responder F1 environment did not respond to GLphi, which suggests that at least one cell participating in the response needed to possess both responder alleles to function. When T cells from such A + 18R leads to F1 chimeras were primed in the presence of responder antigen-presenting cells (APC), the chimeric T cells responded to GLphi, which suggests that both responder alleles must be expressed in the APC but not necessarily in the T cell. Interestingly, acutely irradiated F1 animals were found not to be an adequate source of responder APC for priming the proliferating T cell because of the rapid turnover of peripheral APC after irradiation. In adoptive transfer experiments, T cell-depleted bone marrow had to be used as a source of responder APC. When bone marrow cells from (B10.A X B10)F1 responder animals were allowed to mature in a low-responder B10 of B10.A parental environment, neither chimera, F1 leads to A or F1 leads to B, could respond to GLphi. This demonstrated that the presence of high-responder APC, which derive from the donor bone marrow, was not sufficient to generate a GLphi response. It appears that in addition it is essential for the T lymphocytes to mature in a high-responder environment. Finally, B10.A(4R) T cells, which possess neither Ir-GLphi responder allele, could be educated to mount a GLphi-proliferative response provided that they matured in a responder environment and were primed with APC expressing both responder alleles. Therefore, the gene products of the complementing Ir-GLphi responder alleles appear to function as a single restriction element at the level of the APC. T cells that do not possess responder alleles are not intrinsically defective, because they could be made phenotypic responders if they developed in an environment in which responder major histocompatibility complex (MHC) products were learned as self and if antigen was presented to them by APC expressing responder MHC products.
Upregulation of Ciliary Neurotrophic Factor (CNTF) and CNTF Receptor α in Rat Kidney with Ischemia-Reperfusion Injury
Authors: CHUL WOO YANG, SUN WOO LIM, KI WHAN HAN, HEE JONG AHN, JUNG HEE PARK, YOUNG HEE KIM, MATTHIAS KIRSH, JUNG HO CHA, JOO HYUN PARK, YONG SOO KIM, JIN KIM, BYUNG KEE BANG
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Ciliary neurotrophic factor (CNTF) is presumed to play a role as a survival factor in neuronal cells, but little is known about its role in the kidney. To investigate this, the expression of CNTF and CNTF receptor α (CNTFR α) was analyzed in the ischemic rat kidney. An ischemia/reperfusion (I/R) injury was induced by clamping both renal arteries for 45 min. Animals were killed at 1, 2, 3, 5, 7, 14, and 28 d after ischemia. The expression of CNTF and CNTFR α was monitored by reverse transcription-PCR, in situ hybridization, immunoblotting, immunohistochemistry, and electron microscopy. In sham-operated rat kidneys, CNTF expression was weak and limited to the descending thin limb of the loop of Henle. With I/R injury, CNTF mRNA and protein expressions were strikingly increased as compared with the sham-operated rat kidney, and the immunoreactivity of CNTF was mainly observed in the regenerating proximal tubules. The expression of CNTFR α mRNA was also increased after I/R injury, and its location and expression patterns were similar to the expression of CNTF. These findings suggest a possible role of CNTF as a growth factor during renal tubular repair processes after I/R injury and an autocrine or paracrine function of CNTF acting against CNTFR α.
Influenza virus infection of human ciliated respiratory epithelial cells in culture
Authors: Claire Smith, Hemant Kulkarni, Hirst Robert, Gwyneth Williams, Peter Andrew, Andrew Easton, Chris O'Callaghan
Journal: European Respiratory Journal (2013)

Introduction: Influenza is a major cause of paediatric respiratory disease initially infecting and replicating in the respiratory epithelium. Data is limited on the initial effects of influenza A virus on human ciliated respiratory epithelium. In this study we investigated the earliest stages of infection of ciliated epithelial cultures from healthy individuals.  Methods Ciliated epithelial cells were cultured from nasal brush biopsies (n=7). Cells were infected with Influenza A/PR8 for up to 24h. Cilia were videoed using a high speed digital camera and the number of motile ciliated cells in each sample area was counted, half of which were used to determine the average CBF. Apical fluid was removed for evaluation of cytokine and chemokine response before and after infection. Cells were fixed and stained using anti-influenza HA antigen (Alexa594) and anti-β tubulin (FITC) antibodies. Confocal optical sectioning of stained slides was performed.  Results Ciliary beat frequency was unaffected by influenza A infection over 24 hours, however, the number of motile ciliated cells (median (IQR)) was significantly decreased from 13 (6-14) to 5 (5-7) cells/4.2mm2 following infection. Influenza A infection caused a significant (P  Conclusion Ciliary beat frequency was unaffected by influenza A infection over 24 hours, however, a significant reduction in cells with beating cilia was observed.
Reversal of Collapsing Glomerulopathy in Mice with the Cyclin-Dependent Kinase Inhibitor CYC202
Authors: Dana Gherardi, Vivette D’Agati, Te-Hua Tearina Chu, Anna Barnett, Athos Gianella-Borradori, Irwin H. Gelman, Peter J. Nelson
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Collapsing glomerulopathy (CG) has become an important cause of end-stage renal disease. Whether associated with HIV-1 or other potential etiologies, the pathogenesis of CG converges to induce aberrant proliferation of renal epithelium along the entire nephron. This raises the possibility that targeting cell-cycle progression may be an effective therapeutic strategy for CG. Here, we ask whether the cyclin-dependent kinase (CDK) inhibitor, CYC202 (R-roscovitine), could attenuate or reverse existing renal disease in Tg26 mice, a well characterized HIV-1 transgenic mouse model of CG. Tg26 mice were age and disease matched through analysis of urine (protein/creatinine) to generate 12 treatment pairs covering a range of mild to severe CG. One mouse from each pair received either vehicle or 75 mg/kg of CYC202 every 12 h for 20 d, a dose 20% above that needed to prevent the development of CG. After treatment, urinary, serologic, and histopathologic indices of nephrosis showed reversal of CG in 8 of 12 CYC202-treated mice compared with progression of CG in 10 of 12 vehicle-treated mice, demonstrating a significant therapeutic benefit from CYC202 (<i>P</i> &lt; 0.05). Pharmacokinetic profiles showed that concentrations of CYC202 known to inhibit cell-cycle and transcriptional CDK <i>in vitro</i> were achieved in plasma at efficacious doses. However, amelioration of CG by CYC202 did not correlate with decreases in kidney HIV-1 transgene expression, indicating that suppression of HIV-1 transcription was not a prerequisite for the antiproliferative activity of CYC202. These results demonstrate a novel therapeutic strategy for CG.
Peroxisome Proliferator-Activated Receptor α Reduces Cholesterol Esterification in Macrophages
Authors: G. Chinetti, S. Lestavel, J.-C. Fruchart, V. Clavey, B. Staels
Journal: Circulation Research (2003)

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor activated by fatty acid derivatives and hypolipidemic drugs of the fibrate class. PPARalpha is expressed in monocytes, macrophages, and foam cells, suggesting a role for this receptor in macrophage lipid homeostasis with consequences for atherosclerosis development. Recently, it was shown that PPARalpha activation promotes cholesterol efflux from macrophages via induction of the ABCA1 pathway. In the present study, the influence of PPARalpha activators on intracellular cholesterol homeostasis was investigated. In human macrophages and foam cells, treatment with fibrates, synthetic PPARalpha activators, led to a decrease in the cholesteryl ester (CE):free cholesterol (FC) ratio. In these cells, PPARalpha activation reduced cholesterol esterification rates and Acyl-CoA:cholesterol acyltransferase-1 (ACAT1) activity. However, PPARalpha activation did not alter ACAT1 gene expression, whereas mRNA levels of carnitine palmitoyltransferase type 1 (CPT-1), a key enzyme in mitochondrial fatty acid catabolism, were induced. Finally, PPARalpha activation blocked CE formation induced by TNF-alpha, possibly due to the inhibition of neutral sphingomyelinase activation by TNF-alpha. In conclusion, our results identify a role for PPARalpha in the control of cholesterol esterification in macrophages, resulting in an enhanced availability of FC for efflux through the ABCA1 pathway.
Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups
Authors: Martin Schaefer, Folkhard Schmidt, Christian Folwaczny, Reinhard Lorenz, Gaby Martin, Norbert Schindlbeck, Walter Heldwein, Michael Soyka, Heinz Grunze, August Koenig, Klaus Loeschke
Journal: Hepatology (2003)

Psychiatric disorders or drug addiction are often regarded as contraindications against the use of interferon alfa (IFN-α) in patients with chronic hepatitis C. Our aim was to obtain prospective data on adherence to as well as efficacy and mental side effects of treatment with IFN-α in different psychiatric risk groups compared with controls. In a prospective trial, 81 patients with chronic hepatitis C (positive hepatitis C virus[HCV] RNA and elevated alanine aminotransferase[ALT] level) and psychiatric disorders (n = 16), methadone substitution (n = 21), former drug addiction (n = 21), or controls without a psychiatric history or drug addiction (n = 23) were treated with a combination of IFN-α-2a 3 MU 3 times weekly and ribavirin (1,000-1,200 mg/d). Sustained virologic response (overall, 37%) did not differ significantly between subgroups. No significant differences between groups were detected with respect to IFN-α-related development of depressions during treatment. However, in the psychiatric group, significantly more patients received antidepressants before and during treatment with IFN-α ( P &lt; .001). Most of those who dropped out of the study were patients with former drug addiction (43%; P = .04) compared with 14% in the methadone group, 13% in the control group, and 18% in the psychiatric group. No patient in the psychiatric group had to discontinue treatment because of psychiatric deterioration. In conclusion, our data do not confirm the supposed increased risk for IFN-α-induced mental side effects and dropouts in psychiatric patients if interdisciplinary care and antidepressant treatment are available. Preexisting psychiatric disorders or present methadone substitution should no longer be regarded as contraindications to treatment of chronic hepatitis C with IFN-α and ribavirin in an interdisciplinary setting.
In digging up the past of this 90-year-old man, a recent Eastern European immigrant to the USA, what is a historical treatment for an ongoing endemic disease he might have received?
Authors: George Apergis, Francois Abi-Fadel, Padmanabhan Krishnan
Journal: Thorax (2012)

Images in ThoraxIn digging up the past of this 90-yearold man, a recent Eastern European immigrant to the USA, what is a historical treatment for an ongoing endemic disease he might have received?Answer: Oleothorax with expansion.This 90-year-old man presented for an incidental finding on a chest radiograph of an opacification of the entire left hemithorax.He denied chest pain, haemoptysis, cough, fever, weight loss, night sweats or dyspnoea.Review of the patient's history revealed that 60 years ago he was treated in a sanatorium in Russia, and recollects that his 'lung was collapsed'.CT imaging revealed a well-defined pleural homogenous opacity with sharp margins, partly calcified, occupying most of the left hemithorax.The density of the opacity measured e36 Hounsfield units.The expansion in the volume of this lipid density fluid is evident from the generalised compression of the lung parenchyma and airways, and contralateral displacement of the mediastinum (figure 1).Collapse therapy was the cornerstone of treatment for pulmonary tuberculosis up until the 1950s, and was used in up to 70% of all sanatorium patients. 1This was achieved by several techniques, such as artificial pneumothorax, artificial pneumoperitoneum, diaphragmatic paralysis, plombage or by thoracoplasty.In our patient, it was done by pleural space injection of oil.Chronic expansion of the oleothorax is best explained by stimulation of pleural fluid production by the oil. 2 This expansion may occur chronically after the oleothorax has been stable for years and is frequently asymptomatic.Less commonly, the expansion may be acute causing respiratory compromise and requiring removal.As our patient was asymptomatic, no interventions were deemed necessary.Recognition of oleothorax using Chest CT imaging will allow for appropriate management if there are complications, such as loculated pleural effusions, empyema, or tuberculosis reactivation, and avoiding unnecessary interventions when patients are asymptomatic and no complications suspected.
Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials
Authors: Yaa-Hui Dong, Hsien-Ho Lin, Wen-Yi Shau, Yun-Chun Wu, Chia-Hsuin Chang, Mei-Shu Lai
Journal: Thorax (2012)

<h3>Background</h3> The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD. <h3>Methods</h3> Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison. <h3>Results</h3> 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model. <h3>Conclusion</h3> Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.
Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study
Authors: Eric A. J. Hoste, Sean M. Bagshaw, Rinaldo Bellomo, Cynthia M. Cely, Roos Colman, Dinna N. Cruz, Kyriakos Edipidis, Lui G. Forni, Charles D. Gomersall, Deepak Govil, Patrick M. Honoré, Olivier Joannes-Boyau, Michael Joannidis, Anna-Maija Korhonen, Athina Lavrentieva, Ravindra L. Mehta, Paul Palevsky, Eric Roessler, Claudio Ronco, Shigehiko Uchino, Jorge A. Vazquez, Erick Vidal Andrade, Steve Webb, John A. Kellum
Journal: Intensive Care Medicine (2015)
Hepatic manifestations of total parenteral nutrition: Need for prospective investigation
Authors: K. N. Jeejeebhoy
Journal: Hepatology (1988)

Total parenteral nutrition is now widely used in the treatment of nutritional depletion. Among problems that persist in the use of this technique, the development of hepatic abnormalities has received increasing attention. In this review, the current understanding of the pathogenesis and management of liver injury during short-term total parenteral nutrition is summarized. These complications include fatty liver, cholestasis, and nonspecific triaditis. The experience with hepatic complications during long-term total parenteral nutrition is also reviewed. Evidence that progressive liver injury develops in some patients requiring lifelong total parenteral nutrition raises a serious dilemma for both patients and physicians. Better understanding of the pathogenesis is required before appropriate treatment can be prescribed.
Significance of NS3 and NS5 antigens in screening for HCV antibody
Authors: K Vernelen, H Claeys, H Verhaert, A Volckaerts, C Vermylen, Anne-Marie Courouce, Françoise Bouchardeau, Annie Girault, NadineLe Marrec, Eric Goffin, Yves Pirson, Chantal Cornu, Michel Jadoul, Charles van Ypersele de Strihou
Journal: The Lancet (1994)
A Plague on Host Defense
Authors: Elizabeth Kopp, Ruslan Medzhitov
Journal: The Journal of Experimental Medicine (2002)

“ … the plague bacillus never dies or disappears for good; … it bides its time in bedrooms, cellars, trunks, and bookshelves; and perhaps the day would come when, for the bane and the enlightening of men, it would rouse up its rats again and send them forth to die in a happy city.” Albert
Basal cell carcinomas in a tertiary referral centre: a systematic analysis
Authors: J. Dreier, P.F. Cheng, I. Bogdan Alleman, A. Gugger, J. Hafner, A. Tschopp, S.M. Goldinger, M.P. Levesque, R. Dummer
Journal: British Journal of Dermatology (2014)

Background Basal cell carcinoma (BCC) is the most frequent skin cancer with increasing incidence and generally high cure rates. BCC can be quite aggressive and is difficult to treat. Objectives To investigate BCCs with a focus on histological subtypes, treatment procedures and correlation to clinical progress to collect further information on complex BCC cases. Methods In this retrospective single-centre analysis the dermatopathology database, a network of cooperating dermatological surgeons, was queried for BCC cases between January 2007 and December 2011. Of 14 423 samples from a total of 9652 patients initially identified, 2938 patients were treated at the University Hospital Zurich and had corresponding local electronic patient records. Results Patients (n = 2938) (with 4769 diagnoses, 2006 re-excisions with 1180 microscopically controlled surgeries) were classified based on severity estimations into 2240 simple, 640 moderate, and 58 severe cases, including one BCC-treatment-associated death and 11 patients with subsequent participation in a clinical trial. In moderate and severe cases (n = 698), there were significantly higher rates of unique histological diagnoses (n = 2·5; P < 0·0001), higher association with basosquamous carcinoma [odds ratio (OR) 3·6; P < 0·0001] and sclerosing BCC (OR 2·48; P < 0·0001). Of the patients with basosquamous carcinoma 82·6% had a previous history of BCC. Conclusions This is the first study that analyses the frequency of complicated BCCs in a tertiary referral centre. There were 6·6% moderate (640 of 9652) and 0·6% (58 of 9652) severe cases. We found significantly more varying histological diagnoses and significant association with aggressive subtypes in moderate and severe cases. These patients might especially benefit from new therapeutic options.
A Non–Cancer-Related Survival Benefit Is Associated With Partial Nephrectomy
Authors: Maxine Sun, Quoc-Dien Trinh, Marco Bianchi, Jens Hansen, Nawar Hanna, Firas Abdollah, Shahrokh F. Shariat, Alberto Briganti, Francesco Montorsi, Paul Perrotte, Pierre I. Karakiewicz
Journal: European Urology (2011)
Dying to know
Authors: L. Farrell
Journal: BMJ (1996)

The demise of the Lisa Sainsbury Foundation was a matter of great regret to me. Five years ago I attended one of its three day workshops on palliative care, and it was a formative experience for me; not just the message, but the way it was taught. I was so enthusiastic that I organised another workshop for my own practice team in Crossmaglen. The foundation agreed to send two of its tutors, which was especially gratifying as at that time the troubles were at their height and Crossmaglen had a particularly malign if ill deserved name.

So we wanted to put on …
Recovered Pulmonary Vein Conduction as a Dominant Factor for Recurrent Atrial Tachyarrhythmias After Complete Circular Isolation of the Pulmonary Veins
Authors: Feifan Ouyang, Matthias Antz, Sabine Ernst, Hitoshi Hachiya, Hercules Mavrakis, Florian T. Deger, Anselm Schaumann, Julian Chun, Peter Falk, Detlef Hennig, Xingpeng Liu, Dietmar Bänsch, Karl-Heinz Kuck
Journal: Circulation (2004)

Atrial tachyarrhythmias (ATa) can recur after continuous circular lesions (CCLs) around the ipsilateral pulmonary veins (PVs) in patients with atrial fibrillation (AF). This study characterizes the electrophysiological findings in patients with and without ATa after complete PV isolation.Twenty-nine of 100 patients had recurrent ATa after complete PV isolation by use of CCLs during a mean follow-up of approximately 8 months. A repeat procedure was performed in 26 patients with ATa and in 7 volunteers without ATa at 3 to 4 months after CCLs. No recovered PV conduction was demonstrated in the 7 volunteers, whereas recovered PV conduction was found in 21 patients with recurrent ATa (right-sided PVs in 9 patients and left-sided PVs in 16 patients). The interval from the onset of the P wave to the earliest PV spike was 157+/-66 ms in the right-sided PVs and 149+/-45 ms in the left-sided PVs. During the procedure, PV tachycardia activated the atrium and resulted in atrial tachycardia (AT) in 10 patients. All conduction gaps were successfully closed with segmental RF ablation. After PV isolation, macroreentrant AT was induced and ablated in 3 patients. In the 5 patients without PV conduction, focal AT in the left atrial roof in 2 patients and non-PV foci in the left atrium in 1 patient were successfully abolished; in the remaining 2 patients, no ablation was performed because of noninducible arrhythmias. During a mean follow-up of approximately 6 months, 24 patients were free of ATa without antiarrhythmic drugs.In patients with recurrent ATa after CCLs, recovered PV conduction is a dominant finding in approximately 80% of patients and can be successfully eliminated by segmental RF ablation. Also, mapping and ablation of non-PV arrhythmias can improve clinical success.
<i>TP53</i> Mutation Spectrum in Breast Cancer Is Subtype Specific and Has Distinct Prognostic Relevance
Authors: Laxmi Silwal-Pandit, Hans Kristian Moen Vollan, Suet-Feung Chin, Oscar M. Rueda, Steven McKinney, Tomo Osako, David A. Quigley, Vessela N. Kristensen, Samuel Aparicio, Anne-Lise Børresen-Dale, Carlos Caldas, Anita Langerød
Journal: Clinical Cancer Research (2014)

In breast cancer, the TP53 gene is frequently mutated and the mutations have been associated with poor prognosis. The prognostic impact of the different types of TP53 mutations across the different molecular subtypes is still poorly understood. Here, we characterize the spectrum and prognostic significance of TP53 mutations with respect to the PAM50 subtypes and integrative clusters (IC).