tbuckley/cabot-search huggingface dataset:
Sperm-Derived SPANX-B Is a Clinically Relevant Tumor Antigen That Is Expressed in Human Tumors and Readily Recognized by Human CD4+ and CD8+ T Cells
Authors: Giovanni Almanzar, Purevdorj B. Olkhanud, Monica Bodogai, Chiara Dell'Agnola, Dolgor Baatar, Stephen M. Hewitt, Claudio Ghimenton, Mohan K. Tummala, Ashani T. Weeraratna, Keith Sean Hoek, Natalay Kouprina, Vladimir Larionov, Arya Biragyn
Journal: Clinical Cancer Research (2009)

The sperm-derived SPANX family proteins can be found expressed in human tumors. Here, we aimed to perform a comprehensive study to evaluate immunotherapeutic relevance of one of its members, SPANX-B. We wanted to test its expression pattern in human tumors and to evaluate CD4(+) and CD8(+) T-cell responses in healthy humans after in vitro immunizations.Expression of SPANX-B in human malignancies, including a multitumor tissue array of 145 primary tumors, was assessed using reverse transcription-PCR, Western blotting, and immunohistochemical analysis. T-cell immunogenicity and immunodominant epitopes of SPANX-B were studied using in vitro immunizations of healthy human donor-derived leukocytes.SPANX-B was abundantly expressed in melanoma and carcinomas of lung, ovary, colon, and breast. In melanoma, tissue array data indicated that it was expressed in advanced and metastatic disease. Unlike most tumor-associated antigens, SPANX-B was an immunogenic antigen that was recognized by circulating T-cell precursors in healthy humans. Importantly, these T cells were readily expanded to generate SPANX-B-specific helper CD4(+) and cytolytic CD8(+) T cells that recognized unique immunodominant epitopes: at least one HLA-DR-restricted Pep-9 epitope (SPANX-B(12-23)) and two HLA-A2-restricted Pep-2 and Pep-4 epitopes (SPANX-B(23-31) and SPANX-B(57-65), respectively). CD8(+) T cells were fully functional to recognize and lyse HLA-A2-expressing tumors, including primary human melanomas.SPANX-B is an immunogenic sperm-derived antigen that is expressed in several human tumors. SPANX-B is also efficiently recognized by the human T-cell immune arm, indicating its significant value for the development of protective and therapeutic cancer vaccines.
Risk factors for avascular necrosis of bone in patients with systemic lupus erythematosus: Is there a role for antiphospholipid antibodies?
Authors: M Y Mok, V T Farewell, D A Isenberg
Journal: Annals of the Rheumatic Diseases (2000)

Avascular necrosis of bone (AVN) is a well known complication in patients with systemic lupus erythematosus (SLE).To investigate the role of antiphospholipid antibody status (IgM and IgG anticardiolipin antibodies and lupus anticoagulant) with adjustment for corticosteroid use as risk factors for the development of AVN.A cohort of 265 patients receiving long term follow up in our SLE clinic from 1978 to 1998 was analysed. Patients with AVN complications were detected and then matched for age, sex, ethnicity, duration of disease, and organ disease with two other patients with SLE. A further 31 patients were chosen at random for the analysis.Eleven patients had AVN, giving a point prevalence of 4%. There were no significant differences demonstrable in the presence of individual antiphospholipid antibodies (aPL) or their combination between the group with AVN or the two control groups.Incorporating an adjustment for corticosteroid use we were unable to show a link between the presence of aPL and the development of AVN in patients with SLE.
Commentaries on the end of year editorial on the definition of ischaemia in last December's issue
Authors: R. Chapman
Journal: Cardiovascular Research (1995)

Commentaries on the end of year editorial on the definition of ischaemia in last December's issue Get access RA Chapman, Professor RA Chapman, Professor Department of Physiology, School of Veterinary Science, Southwell St, Bristol, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 2, February 1995, Page 284, https://doi.org/10.1016/S0008-6363(95)90005-5 Published: 01 February 1995
Positive Selection and Subfunctionalization of Duplicated CCT Chaperonin Subunits
Authors: M. A. Fares
Journal: Molecular Biology and Evolution (2003)

To reach a functional and energetically stable conformation, many proteins need molecular helpers called chaperonins. Among the group II chaperonins, CCT proteins provide crucial machinery for the stabilization and proper folding of several proteins in the cytosol of eukaryotic cells through interactions that are subunit-specific and geometry-dependent. CCT proteins are made up of eight different subunits, all with similar sequences, positioned in a precise arrangement. Each subunit has been proposed to have a specialized function during the binding and folding of the CCT protein substrate. Here, we demonstrate that functional divergence occurred after several CCT duplication events due to the fixation of amino acid substitutions by positive selection. Sites critical for ATP binding and substrate binding were found to have undergone positive selection and functional divergence predominantly in subunits that bind tubulin but not actin. Furthermore, we show clear functional divergence between CCT subunits that bind the C-terminal domains of actin and tubulin and those that bind the N-terminal domains. Phylogenetic analyses could not resolve the deep relationships between most subunits, except for the groups alpha/beta/eta and delta/epsilon, suggesting several almost simultaneous ancient duplication events. Together, the results support the idea that, in contrast to homo-oligomeric chaperonins such as GroEL, the high divergence level between CCT subunits is the result of positive selection after each duplication event to provide a specialized role for each CCT subunit in the different steps of protein folding.
ASSOCIATION BETWEEN ELECTROCARDIOGRAPHIC FINDINGS, RIGHT HEART STRAIN AND SHORT-TERM ADVERSE CLINICAL EVENTS IN PATIENTS WITH ACUTE PULMONARY EMBOLISM
Authors: Praveen Hariharan, David Dudzinski, Ikenna Okechukwu, James Takayesu, Yuchiao Chang, Christopher Kabrhel
Journal: Journal of the American College of Cardiology (2014)
Atrial Fibrillation and the Risk of Sudden Cardiac Death
Authors: Lin Y. Chen, Nona Sotoodehnia, Petra Bůžková, Faye L. Lopez, Laura M. Yee, Susan R. Heckbert, Ronald Prineas, Elsayed Z. Soliman, Selcuk Adabag, Suma Konety, Aaron R. Folsom, David Siscovick, Alvaro Alonso
Journal: JAMA Internal Medicine (2012)

It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts.In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2% women; and 26.6% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, ≥65 years; 58.2% women; and 15.4% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors.In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively.Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted.
Whipple's disease complicated by a retinal Jarisch-Herxheimer reaction: a case report.
Authors: R J Playford, E Schulenburg, C S Herrington, H J Hodgson
Journal: Gut (1992)

A 36 year old white man was diagnosed as having Whipple9s disease after a prolonged illness of lethargy, night sweats, and weight loss associated with lymphadenopathy and splenomegaly. Biopsy specimen of an inguinal lymph node confirmed the presence of periodic acid Schiff positive macrophages and culture gave a pure growth of Corynebacterium jeikeium. Twelve hours after the introduction of oral co-trimoxazole and streptomycin the patient9s condition deteriorated. He became confused, feverish, and developed florid retinal vasculitis with associated visual impairment. Both the systemic symptoms and the retinal vasculitis responded to treatment with corticosteroids and his vision returned to normal. We think this was a Jarisch-Herxheimer reaction not previously described in Whipple9s disease and advise inspection of the fundi of such patients before starting treatment.
Acute effects of smoking on lung airways resistance in normal and bronchitic subjects.
Authors: M McDermott, M M Collins
Journal: Thorax (1965)

The increase in airways resistance produced when a subject smokes a single cigarette has been investigated by us and others, particularly Nadel and Comroe (1961).These laboratory studies suggested a method of comparing the cumulative effect over years of an inhaled irritant with an individual's acute response.The consistent epidemiological findings of many workers (Palmer, 1954; Doll and Hill, 1956;
Sphingosine-1-Phosphate Links Persistent STAT3 Activation, Chronic Intestinal Inflammation, and Development of Colitis-Associated Cancer
Authors: Jie Liang, Masayuki Nagahashi, Eugene Y. Kim, Kuzhuvelil B. Harikumar, Akimitsu Yamada, Wei-Ching Huang, Nitai C. Hait, Jeremy C. Allegood, Megan M. Price, Dorit Avni, Kazuaki Takabe, Tomasz Kordula, Sheldon Milstien, Sarah Spiegel
Journal: Cancer Cell (2012)
Triptolide-Induced Transcriptional Arrest Is Associated with Changes in Nuclear Substructure
Authors: Stephanie J. Leuenroth, Craig M. Crews
Journal: Cancer Research (2008)

Abstract Triptolide, an active component of the medicinal herb lei gong teng, is a potent anticancer and anti-inflammatory therapeutic. It potently inhibits nuclear factor-κB transcriptional activation after DNA binding, although a precise mechanism is as yet unknown. Here, we report that triptolide also induces distinct nuclear substructural changes in HeLa cells. These changes in the nucleolus and nuclear speckles are reversible and dependent on both time and concentration. Furthermore, nuclear changes occurred within hours of triptolide treatment and were calcium and caspase independent. Rounding of nuclear speckles, an indication of transcriptional arrest, was evident and was associated with a decrease in RNA polymerase II (RNA Pol II) COOH-terminal domain Ser2 phosphorylation. Additionally, the nucleolus disassembled and RNA Pol I activity declined after RNA Pol II inhibition. We therefore conclude that triptolide causes global transcriptional arrest as evidenced by inactivity of RNA Pol I and II and the subsequent alteration in nuclear substructure. [Cancer Res 2008;68(13):5257–66]
Interleukin 16 expression and phenotype of interleukin 16 producing cells in Crohn's disease
Authors: P Middel
Journal: Gut (2001)

The mechanisms involved in the initiation and maintenance of Crohn's disease are poorly understood. Previous studies have demonstrated an increased number of infiltrating CD4+ T cells within the inflammatory affected bowel wall in Crohn's disease. Novel therapy approaches using anti-CD4 antibodies are thought to be effective in Crohn's disease.Interleukin 16 (IL-16) has been characterised as a chemokine with selective chemoattraction for CD4+ inflammatory T cells. In this study, cellular expression of IL-16 in Crohn's disease and ulcerative colitis was investigated.Expression of IL-16 was analysed in tissue samples of Crohn's disease, ulcerative colitis, and normal controls by applying reverse transcription-polymerase chain reaction, non-radioactive in situ hybridisation, and immunohistochemistry. Double staining methods were used to characterise cells expressing IL-16. The amount of infiltrating CD4+ cells was determined by immunohistochemistry and correlated with the corresponding IL-16+ cell number by step sections.An increased number of IL-16+ cells in Crohn's disease in comparison with ulcerative colitis and control probes was demonstrated. IL-16 was expressed by CD4 and CD8 positive T cells. In addition, in active Crohn's disease there was a substantial number of IL-16 positive mast cells. The increased number of CD4+ lymphocytes correlated positively with the increased number of IL-16 positive cells in Crohn's disease.Our results demonstrate that increased expression of IL-16 in T cells and mast cells in active Crohn's disease is associated with increased numbers of CD4+ lymphocytes. Local expression of IL-16 seems to play a significant role in the initiation and persistence of the inflammatory process in Crohn's disease, presumably by IL-16 mediated recruitment of CD4+ cells, mostly lymphocytes, into the bowel wall.
Long-term Acute Care Hospital Utilization After Critical Illness
Authors: Jeremy M. Kahn, Nicole M. Benson, Dina Appleby, Shannon S. Carson, Theodore J. Iwashyna
Journal: JAMA (2010)

Long-term acute care hospitals have emerged as a novel approach for the care of patients recovering from severe acute illness, but the extent and increases in their activity at the national level are unknown.To examine temporal trends in long-term acute care hospital utilization after an episode of critical illness among fee-for-service Medicare beneficiaries aged 65 years or older.Retrospective cohort study using the Medicare Provider Analysis and Review files from 1997 to 2006. We included all Medicare hospitalizations involving admission to an intensive care unit of an acute care, nonfederal hospital within the continental United States.Overall long-term acute care utilization, associated costs, and survival following transfer.The number of long-term acute care hospitals in the United States increased at a mean rate of 8.8% per year, from 192 in 1997 to 408 in 2006. During that time, the annual number of long-term acute care admissions after critical illness increased from 13,732 to 40,353, with annual costs increasing from $484 million to $1.325 billion. The age-standardized population incidence of long-term acute care utilization after critical illness increased from 38.1 per 100,000 in 1997 to 99.7 per 100,000 in 2006, with greater use among male individuals and black individuals in all periods. Over time, transferred patients had higher numbers of comorbidities (5.0 in 1997-2000 vs 5.8 in 2004-2006, P < .001) and were more likely to receive mechanical ventilation at the long-term acute care hospital (16.4% in 1997-2000 vs 29.8% in 2004-2006, P < .001). One-year mortality after long-term acute care hospital admission was high throughout the study period: 50.7% in 1997-2000 and 52.2% in 2004-2006.Long-term acute care hospital utilization after critical illness is common and increasing. Survival among Medicare beneficiaries transferred to long-term acute care after critical illness is poor.
Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP)-targeted delivery of soluble TRAIL potently inhibits melanoma outgrowth in vitro and in vivo
Authors: Marco de Bruyn, Anna A Rybczynska, Yunwei Wei, Michael Schwenkert, Georg H Fey, Rudi AJO Dierckx, Aren van Waarde, Wijnand Helfrich, Edwin Bremer
Journal: Molecular Cancer (2010)

Abstract Background Advanced melanoma is characterized by a pronounced resistance to therapy leading to a limited patient survival of ~6 - 9 months. Here, we report on a novel bifunctional therapeutic fusion protein, designated anti-MCSP:TRAIL, that is comprised of a melanoma-associated chondroitin sulfate proteoglycan (MCSP)-specific antibody fragment (scFv) fused to soluble human TRAIL. MCSP is a well-established target for melanoma immunotherapy and has recently been shown to provide important tumorigenic signals to melanoma cells. TRAIL is a highly promising tumoricidal cytokine with no or minimal toxicity towards normal cells. Anti-MCSP:TRAIL was designed to 1 . selectively accrete at the cell surface of MCSP-positive melanoma cells and inhibit MCSP tumorigenic signaling and 2 . activate apoptotic TRAIL-signaling. Results Treatment of a panel of MCSP-positive melanoma cell lines with anti-MCSP:TRAIL induced TRAIL-mediated apoptotic cell death within 16 h. Of note, treatment with anti-MCSP:sTRAIL was also characterized by a rapid dephosphorylation of key proteins, such as FAK, implicated in MCSP-mediated malignant behavior. Importantly, anti-MCSP:TRAIL treatment already inhibited anchorage-independent growth by 50% at low picomolar concentrations, whereas &gt; 100 fold higher concentrations of non-targeted TRAIL failed to reduce colony formation. Daily i.v. treatment with a low dose of anti-MCSP:TRAIL (0.14 mg/kg) resulted in a significant growth retardation of established A375 M xenografts. Anti-MCSP:TRAIL activity was further synergized by co-treatment with rimcazole, a σ-ligand currently in clinical trials for the treatment of various cancers. Conclusions Anti-MCSP:TRAIL has promising pre-clinical anti-melanoma activity that appears to result from combined inhibition of tumorigenic MCSP-signaling and concordant activation of TRAIL-apoptotic signaling. Anti-MCSP:TRAIL alone, or in combination with rimcazole, may be of potential value for the treatment of malignant melanoma.
Symptoms of asthma, bronchial responsiveness and atopy in immigrants and emigrants in Europe
Authors: A. Tobias, J.B. Soriano, S. Chinn, J.M. Anto, J. Sunyer, P. Burney
Journal: European Respiratory Journal (2001)

Migration studies on asthma may provide information on its environmental causes. The European Community Respiratory Health Survey has potential advantages due to the number of countries involved, standardized collection of information, assessment of directionality of migration, and availability of physiological data on bronchial responsiveness and atopy. Prevalence rates of symptoms associated with asthma were compared for immigrants, emigrants and nonmigrants living in centres mostly in western Europe. Similar analyses were carried out for bronchial responsiveness (provocative concentration causing a 20% fall in forced expiratory volume in one second and slope) and atopy. Medication and use of health services were also explored. Overall, 1,678 (8.6%) of 19,516 participants were immigrants in the 18 countries participating in the study, of whom 581 were emigrants from one of the participating countries. Rates of asthma symptoms were higher in immigrants (odds ratio (OR): 1.21, 95% confidence interval (CI): 1.00–1.51) and emigrants (OR: 1.31, 95% CI: 0.96–1.51) compared to nonmigrants after controlling for area, sex, age and smoking status. However, bronchial responsiveness and atopy were equally distributed between immigrants, emigrants and nonmigrants. Use of health services was observed to be similar in migrants and nonmigrants with asthma. In the European Community Respiratory Health Survey, migrants reported more asthma symptoms, but had similar bronchial responsiveness, atopy, and use of health services when compared with the nonmigrant population.
Susceptibility of Nonpromoter CpG Islands to De Novo Methylation in Normal and Neoplastic Cells
Authors: C. Nguyen, G. Liang, T. T. Nguyen, D. Tsao-Wei, S. Groshen, M. Lubbert, J.-H. Zhou, W. F. Benedict, P. A. Jones
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Many cancers display alterations in methylation patterns of CpG islands—stretches of DNA rich in CpG dinucleotides often associated with gene promoters that are involved in initiation of gene transcription. This methylation may perturb expression of genes critical to the regulation of cell proliferation. Aberrant methylation is not limited to a few genes or to promoter regions but has been found on a genome-wide scale in a variety of neoplasias, including colorectal cancer and acute myelogenous leukemia. Our goal was to characterize, in a quantitative manner, the profiles of abnormally methylated genes that may be specific for different cancers. Methods: Using a quantitative assay, methylation-sensitive single nucleotide primer extension (MS-SNuPE), we have analyzed the methylation levels of promoter and exonic (coding region) CpG islands of two cyclin-dependent kinase inhibitors [p15(INK4B) and p16(INK4A)] and the PAX6 gene, which encodes a transcriptional factor involved in neuronal proliferation, in DNA samples taken from patients with chronic myelogenous leukemia, acute myelogenous leukemia, myelodysplastic syndrome, and colorectal cancer. Results: De novo methylation of all three exonic loci in tumors—relative to baseline levels found in nontumor tissue or blood—was observed in hematologic neoplasias and in solid tumors as well as in normal colonic tissue. However, methylation of promoter regions was more limited. Moreover, two different patterns of promoter methylation distinguished the leukemias from colorectal cancer: p15 promoter hypermethylation was found only in the leukemias, and p16 promoter hypermethylation occurred only in colon tumors. However, we did not address this issue prospectively; therefore, such an observation is only hypothesis generating. Conclusions: The methylation patterns that we observed suggest that exonic CpG islands are more susceptible to de novo methylation than promoter islands and that methylation may be seeded in exonic regions, from which it can spread to other islands, including promoter regions. Subsequent selection of cells with a growth advantage conferred by spread of methylation into and inactivation of a particular promoter might then contribute to the genesis of a specific type of cancer.
Expansion of microvascular networks in vivo by phthalimide neovascular factor 1 (PNF1)
Authors: Kristen A. Wieghaus, Meghan M. Nickerson, Caren E. Petrie Aronin, Lauren S. Sefcik, Richard J. Price, Mikell A. Paige, Milton L. Brown, Edward A. Botchwey
Journal: Biomaterials (2008)