tbuckley/cabot-search huggingface dataset:
Peptidome from Renal Cell Carcinoma Contains Antigens Recognized by CD4+ T Cells and Shared among Tumors of Different Histology
Authors: Elena Tassi, Valeria Facchinetti, Samantha Seresini, Anna Borri, Giacomo Dell'Antonio, Claudio Garavaglia, Giulia Casorati, Maria Pia Protti
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Renal cell carcinoma (RCC) is considered immunogenic; nonetheless, rare tumor-associated antigens have been identified or are expressed in RCC. Peptidome (i.e., the total content of natural peptides of whole cells) from other tumors, such as melanoma, has proved to be immunogenic. The aims of this study were to determine whether peptidome from RCC is immunogenic and whether it contains tumor peptides shared among allogenic RCCs. Experimental Design: Autologous dendritic cells pulsed with RCC peptidome were used to activate in vitro CD4+ T cells from healthy donors and a metastatic RCC patient. CD4+ T-cell polyclonal lines and clones were characterized for tumor cell recognition by proliferation assay, killing activity, and cytokine secretion. Results: CD4+ T-cell lines and clones recognized HLA-DR-matched allogenic RCC and, for the patient, the autologous tumor. RCC-reactive CD4+ T cells showed a heterogeneous Th1 or Th0/Th2 pattern of cytokine secretion. Moreover, RCC-reactive CD4+ T cells recognized also melanoma, colon carcinoma, cervical carcinoma, pancreas carcinoma, lung carcinoma, gastric carcinoma, and lymphoma cells but not autologous T-cell blasts. Conclusions: Our results show that (a) the RCC peptidome contain antigens recognized by CD4+ T cells and (b) shared among tumors of different histology and (c) it induces both Th1-type and Th2/Th0-type immune responses. These data support the use of the peptidome from allogenic RCC for specific immunotherapy in RCC and possibly in other neoplastic diseases. Moreover, the CD4+ T-cell clones generated here are useful tools for tumor antigen identification.
The In Vitro Effect of Calcitriol on Parathyroid Cell Proliferation and Apoptosis
Authors: ANTONIO CANALEJO, YOLANDA ALMADÉN, VICENTE TORREGROSA, JOSE C. GOMEZ-VILLAMANDOS, BLANCA RAMOS, JOSE M. CAMPISTOL, ARNOLD J. FELSENFELD, MARIANO RODRÍGUEZ
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Calcitriol treatment is used to reduce parathyroid hormone levels in azotemic patients with secondary hyperparathyroidism (HPT). Whether long-term calcitriol administration reduces parathyroid gland size in patients with severe secondary hyperparathyroidism is not clear. The aim of the study was to evaluate in vitro the effect of calcitriol on parathyroid cell proliferation and apoptosis in normal parathyroid glands and in adenomatous and hyperplastic human parathyroid glands. Freshly harvested parathyroid glands from normal dogs and hyperplastic and adenomatous glands from patients with secondary (2°) and primary (1°) HPT undergoing parathyroidectomy were studied. Flow cytometry was used to quantify the cell cycle and apoptosis of parathyroid cells. Apoptosis was also evaluated by DNA electrophoresis and light and electron microscopy. In normal dog parathyroid glands, culture with calcitriol (10 -10 to 10 -7 M) for 24 h produced a dose-dependent inhibitory effect on the progression of cells into the cell cycle and into apoptosis. When glands from patients with 2°HPT were cultured for 24 h, only high calcitriol concentrations (10 -7 M) inhibited the progression through the cell cycle and the induction of apoptosis. In parathyroid adenomas (1°HPT), even a high concentration of calcitriol (10 -7 M) had no significant effect on the cell cycle or apoptosis. The present study shows that in vitro , calcitriol inhibits in a dose-dependent manner in normal parathyroid glands both parathyroid cell proliferation and apoptosis. However, in secondary hyperplasia, only high concentrations of calcitriol inhibited cell proliferation and apoptosis. In 1°HPT, even high concentrations of calcitriol had no effect. Because calcitriol simultaneously inhibits both cell proliferation and apoptosis, a reduction in the parathyroid gland mass may not occur as a direct effect of calcitriol treatment.
Gene Therapy via Blockade of Monocyte Chemoattractant Protein-1 for Renal Fibrosis
Authors: Takashi Wada, Kengo Furuichi, Norihiko Sakai, Yasunori Iwata, Kiyoki Kitagawa, Yuko Ishida, Toshikazu Kondo, Hiroyuki Hashimoto, Yoshiro Ishiwata, Naofumi Mukaida, Naohisa Tomosugi, Kouji Matsushima, Kensuke Egashira, Hitoshi Yokoyama
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Monocyte chemoattractant protein (MCP)-1, also termed monocyte chemotactic and activating factor (MCAF)/CCL2, plays an important role in progressive organ fibrosis. It was hypothesized that MCP-1, through its cognate receptor, CCR2, regulates the pathogenesis and is therapeutically of importance for renal fibrosis. To achieve this goal, the therapeutic efficacy and efficiency in renal fibrosis induced by a unilateral ureteral obstruction nephropathy model in mice by the blockade of MCP-1/CCR2 signaling was studied. The delivery of N-terminal deletion mutant of the human MCP-1 gene, 7ND, into a skeletal muscle ameliorated renal fibrosis by resulting in decrease in the deposit of type I collagen and in reduced expression of TGF-β. Concomitantly, gene transfer of 7ND reduced the cell infiltration, most of which were CCR2-positive macrophages, followed by the decrease in MCP-1 expression in the diseased kidneys. These observations suggest that MCP-1 through CCR2 signaling is responsible for Mφ recruitment, which augments downstream events, resulting in renal fibrosis. Moreover, these findings imply that gene therapy against MCP-1/CCR2 signaling via the mutant gene transferred strategy may serve a beneficial therapeutic application for renal fibrosis.
Vitamin B-6: food or medicine?
Authors: J. Collier
Journal: BMJ (1998)

The recent spat between the House of Commons Agriculture Select Committee and the government's Food Advisory Committee about vitamin B-6 was inevitable.1 The problem started in June 1997 when the Food Advisory Committee, on the advice of the Department of Health's Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment, recommended that vitamin B-6 should be seen either as a food supplement, in which case the daily dose would be limited to 10 mg, or as a medicine, when it could be available in higher doses. The draft regulations, issued in April 1998 with a 26 June deadline for comments, stipulated that over the counter sales of vitamin B-6 from pharmacies should be limited to daily doses of 11-49 mg; for doses of 50 mg and over the vitamin would have to be prescribed. This position was fiercely contested by the Agriculture Select Committee in its report, conveniently published on 23 June. This argued that limiting the daily “food” dose to 10 mg/day was scientifically unsound and infringed individuals' rights to decide what they ate.2

Whether or not the Food Advisory Committee has got it right—and it probably has—some guidelines were certainly needed. The daily dietary requirement of pyridoxine, …
Plasma and urinary levels of beta2 microglobulin in rheumatoid arthritis.
Authors: D Manicourt, H Brauman, S Orloff
Journal: Annals of the Rheumatic Diseases (1978)

Plasma and urinary levels of beta2 microglobulin have been investigated in 21 patients suffering from rheumatoid arthritis (RA). Despite a normal renal glomerular function in all patients 50% of them had supranormal plasma beta2 microglobulin levels and 30% had a higher than normal urinary output of beta2 microglobulin generally related to the high plasma level. Plasma beta2 microglobulin levels paralleled closely the lymphocytosis and the 'joint count' both indexes of the severity of the disease. beta2 Microglobulin was normally secreted by the lymphoid tissue and it is suggested that it reflects the increase of the total mass and/or membrane turnover of the lymphoid tissue in RA. beta2 Microglobulin may be considered as a good parameter of the degree of severity of the joint and extra-articular involvement as well as a useful tool for the evaluation of drug efficacy in rheumatoid arthritis.
A method for high-throughput gene expression signature analysis.
Authors: David Peck, Emily D Crawford, Kenneth N Ross, Kimberly Stegmaier, Todd R Golub, Justin Lamb
Journal: Genome biology (2006)

Abstract Genome-wide transcriptional profiling has shown that different biologic states (for instance, disease and response to pharmacologic manipulation) can be recognized by the expression pattern of relatively small numbers of genes. However, the lack of a practical and cost-effective technology for detection of these gene expression 'signatures' in large numbers of samples has severely limited their exploitation in important medical and pharmaceutical discovery applications. Here, we describe a solution based on the combination of ligation-mediated amplification with an optically addressed microsphere and flow cytometric detection system.
Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2)
Authors: Gérald Simonneau, Andrea M. D’Armini, Hossein-Ardeschir Ghofrani, Friedrich Grimminger, Marius M. Hoeper, Pavel Jansa, Nick H. Kim, Chen Wang, Martin R. Wilkins, Arno Fritsch, Neil Davie, Pablo Colorado, Eckhard Mayer
Journal: European Respiratory Journal (2014)

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year.
In vivo and in vitro release of lysozyme from cross-linked gelatin hydrogels: a model system for the delivery of antibacterial proteins from prosthetic heart valves
Authors: A.J Kuijpers, P.B van Wachem, M.J.A van Luyn, G.H.M Engbers, J Krijgsveld, S.A.J Zaat, J Dankert, J Feijen
Journal: Journal of Controlled Release (2000)
Characterisation of natural killer cells and CD56+ T-cells in sarcoidosis patients
Authors: K. Katchar, K. Söderström, J. Wahlstrom, A. Eklund, J. Grunewald
Journal: European Respiratory Journal (2005)

The aim of the current study was to investigate the frequency, phenotype and functional activity of natural killer (NK) cells and CD56+ T-cells in the bronchoalveolar lavage fluid and peripheral blood of patients with pulmonary sarcoidosis when compared with healthy volunteers, using staining with a panel of monoclonal antibodies followed by flow cytometry. The results revealed that the majority of the lung NK cell subpopulation expressed CD56 bright . In contrast, there was a predominant CD56 dim subset in the blood of both patients and healthy controls. Most lung NK cells expressed C-type lectin-like human leukocyte antigen (HLA)-E-specific inhibitory receptor ( i.e. CD94/NKG2A), but only a few lung NK cells expressed killer cell immunoglobulin-like inhibitory receptors specific for HLA-A, -B or -C molecules. In addition, a significantly increased number of CD56+ T-cells were observed in the blood of patients when compared with controls. Upon in vitro stimulation, both lung NK and CD56+ T-cells produced considerable amounts of interferon-γ and tumour necrosis factor-α. Thus, in the lungs of patients with pulmonary sarcoidosis, a distinct phenotype of natural killer cells with the capacity to produce cytokines and actively participate in the T-helper 1-like inflammatory response associated with sarcoidosis was identified.
Implementing a Death with Dignity Program at a Comprehensive Cancer Center
Authors: Elizabeth Trice Loggers, Helene Starks, Moreen Shannon-Dudley, Anthony L. Back, Frederick R. Appelbaum, F. Marc Stewart
Journal: New England Journal of Medicine (2013)

The majority of Death with Dignity participants in Washington State and Oregon have received a diagnosis of terminal cancer. As more states consider legislation regarding physician-assisted death, the experience of a comprehensive cancer center may be informative.We describe the implementation of a Death with Dignity program at Seattle Cancer Care Alliance, the site of care for the Fred Hutchinson-University of Washington Cancer Consortium, a comprehensive cancer center in Seattle that serves the Pacific Northwest. Institution-level data were compared with publicly available statewide data from Oregon and Washington.A total of 114 patients inquired about our Death with Dignity program between March 5, 2009, and December 31, 2011. Of these, 44 (38.6%) did not pursue the program, and 30 (26.3%) initiated the process but either elected not to continue or died before completion. Of the 40 participants who, after counseling and upon request, received a prescription for a lethal dose of secobarbital (35.1% of the 114 patients who inquired about the program), all died, 24 after medication ingestion (60% of those obtaining prescriptions). The participants at our center accounted for 15.7% of all participants in the Death with Dignity program in Washington (255 persons) and were typically white, male, and well educated. The most common reasons for participation were loss of autonomy (97.2%), inability to engage in enjoyable activities (88.9%), and loss of dignity (75.0%). Eleven participants lived for more than 6 months after prescription receipt. Qualitatively, patients and families were grateful to receive the lethal prescription, whether it was used or not.Overall, our Death with Dignity program has been well accepted by patients and clinicians.
Urine Podocyte mRNAs, Proteinuria, and Progression in Human Glomerular Diseases
Authors: Larysa Wickman, Farsad Afshinnia, Su Q. Wang, Yan Yang, Fei Wang, Mahboob Chowdhury, Delia Graham, Jennifer Hawkins, Ryuzoh Nishizono, Marie Tanzer, Jocelyn Wiggins, Guillermo A. Escobar, Bradley Rovin, Peter Song, Debbie Gipson, David Kershaw, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2013)

Model systems demonstrate that progression to ESRD is driven by progressive podocyte depletion (the podocyte depletion hypothesis) and can be noninvasively monitored through measurement of urine pellet podocyte mRNAs. To test these concepts in humans, we analyzed urine pellet mRNAs from 358 adult and pediatric kidney clinic patients and 291 controls (n=1143 samples). Compared with controls, urine podocyte mRNAs increased 79-fold (P<0.001) in patients with biopsy-proven glomerular disease and a 50% decrease in kidney function or progression to ESRD. An independent cohort of patients with Alport syndrome had a 23-fold increase in urinary podocyte mRNAs (P<0.001 compared with controls). Urinary podocyte mRNAs increased during active disease but returned to baseline on disease remission. Furthermore, urine podocyte mRNAs increased in all categories of glomerular disease evaluated, but levels ranged from high to normal, consistent with individual patient variability in the risk for progression. In contrast, urine podocyte mRNAs did not increase in polycystic kidney disease. The association between proteinuria and podocyturia varied markedly by glomerular disease type: a high correlation in minimal-change disease and a low correlation in membranous nephropathy. These data support the podocyte depletion hypothesis as the mechanism driving progression in all human glomerular diseases, suggest that urine pellet podocyte mRNAs could be useful for monitoring risk for progression and response to treatment, and provide novel insights into glomerular disease pathophysiology.
Influence of Cortisone and Prednisolone in Hyperbilirubinemia
Authors: Ricardo Katz, Héctor Ducci, Hernán Alessandri
Journal: Journal of Clinical Investigation (1957)

ence of ACTH on the icteric index in cases of hepatitis and of post-hepatic jaundice. In the former, it dropped very rapidly but in the latter it was not significantly influenced. They believed that the different response of both types of jaundice could be used in the differential diagnosis.
Ultrasound-detected synovial abnormalities are frequent in clinically inactive juvenile idiopathic arthritis, but do not predict a flare of synovitis
Authors: Silvia Magni-Manzoni, Carlo Alberto Scirè, Angelo Ravelli, Catherine Klersy, Silvia Rossi, Valentina Muratore, Chiara Visconti, Stefano Lanni, Pietro Merli, Carlomaurizio Montecucco
Journal: Annals of the Rheumatic Diseases (2012)

To investigate whether children with juvenile idiopathic arthritis (JIA) in clinical remission have subclinical synovial disease on ultrasound, and whether ultrasound abnormalities predict an early flare of synovitis.Thirty-nine consecutive children who had clinically defined inactive disease (ID) for a minimum of 3 months underwent ultrasound assessment of 52 joints. All joints were scanned for synovial hyperplasia, joint effusion, power Doppler (PD) signal and tenosynovitis. Patients were then followed clinically for up to 2 years until a flare of synovitis occurred in one or more joints, or until the 2-year visit if the disease remained in clinical remission.Synovial hyperplasia, joint effusion, PD signal and tenosynovitis in at least one joint were detected in 76.9%, 66.7%, 33.3% and 15.4% of patients, respectively. During the 2-year follow-up, 24 patients (61.5%) experienced sustained ID, whereas 15 patients (38.5%) had a flare of synovitis in a total of 45 joints after a median of 10.6 months (range 6.3-13.7 months). At study entry, the rate of synovial hyperplasia, joint effusion and tenosynovitis was comparable between patients with persistent ID and patients with synovitis flare, whereas patients with persistent ID had a greater frequency of PD signal than patients with synovitis flare. Only 17 of the 45 flared joints had ultrasound abnormalities at study entry.The authors found that ultrasound-detected synovial abnormalities are common in children with JIA in clinical remission. However, the presence of ultrasound pathology did not predict an early flare of synovitis in the affected joints.
Plague, rats and the Bible again
Authors: W M S Russell
Journal: Journal of the Royal Society of Medicine (2005)

Plague, rats and the Bible againWhen discussing the 'plague' of the Philistines, I postulated that the black rat only reached Egypt, and hence Palestine, from southern India after the Greeks discovered the monsoon in the second or first century BC. [1][2][3] The new finds described by Freemon prove that the black rat and its fleas arrived in Egypt over a millennium earlier. 4 Either they came the long coastal way round, or someone knew about the monsoon long before the Greeks.But, whether the epidemic was bubonic plague 4 or bacillary dysentery, 5 I must still insist that the rodents mentioned were not vectors but crop pests, being 'mice that mar the land' (1 Samuel, 6:5).The Philistines hoped that the God of Israel would lighten his hand from off them and from off their land.
Interstitial lung diseases in a lung cancer screening trial
Authors: N. Sverzellati, L. Guerci, G. Randi, E. Calabrò, C. La Vecchia, A. Marchianò, A. Pesci, M. Zompatori, U. Pastorino
Journal: European Respiratory Journal (2011)

We assessed the prevalence of interstitial lung disease (ILD) in a cohort of smokers included in a lung cancer screening trial. Two observers independently reviewed, for the presence of findings consistent with ILD, the computed tomography (CT) examinations of 692 heavy smokers recruited by the Multicentric Italian Lung Detection (MILD) trial. Four CT patterns were considered: usual interstitial pneumonia (UIP), other chronic interstitial pneumonia (OCIP), respiratory bronchiolitis (RB) and indeterminate. Subsequently, the evolution of ILD in those subjects who had undergone a repeat CT examination after 3 yrs was assessed. The UIP pattern and the OCIP pattern were identified in two (0.3%) out of 692 and 26 (3.8%) out of 692 patients, respectively; 109 (15.7%) out of 692 patients showed CT abnormalities consistent with RB, while an indeterminate CT pattern was reported in 21 out of 692 (3%) patients. Age, male sex and current smoking status were factors associated with the presence of OCIP and UIP (combined) pattern, although the relationship did not attain statistical significance. A progression of the disease was observed in three (25%) out of 12 subjects with OCIP who underwent repeat CT after 3 yrs. Thin-section CT features of ILD, probably representing smoking-related ILD, are not uncommon in a lung cancer screening population and should not be overlooked.
Laparoscopic or conventional Nissen fundoplication for gastrooesophageal reflux disease: randomised clinical trial
Authors: JE Bais, JFWM Bartelsman, HJ Bonjer, MA Cuesta, PMNYH Go, EC Klinkenberg-Knol, JJB van Lanschot, JHSM Nadorp, AJPM Smout, Y van der Graaf, HG Gooszen
Journal: The Lancet (2000)
Shielding the cationic charge of nanoparticle-formulated dermal DNA vaccines is essential for antigen expression and immunogenicity
Authors: Joost H. van den Berg, Koen Oosterhuis, Wim E. Hennink, Gert Storm, Leonardus J. van der Aa, Johan F.J. Engbersen, John B.A.G. Haanen, Jos H. Beijnen, Ton N. Schumacher, Bastiaan Nuijen
Journal: Journal of Controlled Release (2009)
White Racism: Its Root, Form, and Function
Authors: JAMES P. COMER
Journal: American Journal of Psychiatry (1969)

The author traces the development of white racism in the United States back to the social and religious environment of 16th century Europe and the later Revolutionary era in America. He outlines the functions it has served and its transmission from one generation to the next. Without a significant reduction in white racism now, he concludes, black reaction can only be intensified and form the basis for a more widespread and malignant type of black racism.