tbuckley/cabot-search huggingface dataset:
Analysis of CD4+ T-Cell Responses to a Novel α-Fetoprotein-Derived Epitope in Hepatocellular Carcinoma Patients
Authors: Akeel Alisa, Annette Ives, Ansar A. Pathan, Cristina V. Navarrete, Roger Williams, Antonio Bertoletti, Shahriar Behboudi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: α-Fetoprotein (AFP) is a tumor-associated antigen in hepatocellular carcinoma and is a target for the development of cancer vaccine. Four immunodominant AFP-derived HLA-A*0201-restricted peptides have been identified and the administration of these peptides with an adjuvant has stimulated AFP-specific CTL responses in hepatocellular carcinoma patients. However, no AFP-derived CD4 T-cell epitope has yet been reported and the status of AFP-specific CD4+ T-cell responses in hepatocellular carcinoma patients is not fully understood. The aim of this study was to analyze naturally occurring CD4+ T-cell responses to AFP. Experimental Design: We analyzed the ability of CD4+ T cells to recognize an HLA-DR-restricted AFP-derived epitope in 41 hepatocellular carcinoma patients and 24 non-hepatocellular carcinoma control patients using intracellular cytokine assays for IFN-γ. Results: Here, for the first time, we report the identification of an AFP-derived CD4+ T-cell epitope that is recognized by circulating lymphocytes from hepatocellular carcinoma patients in association with HLA-DR. The absence of detectable responses in healthy donors and patients with chronic liver disease suggests that AFP-specific CD4+ T cells in the responder patients had been previously expanded in vivo in response to the tumor. The anti-AFP CD4+ T-cell response was only detected in hepatocellular carcinoma patients with normal or mildly elevated serum AFP levels who were in the early stage of disease. Conclusion: Our data will be instrumental in the development of cancer vaccine using AFP-derived immunogens.
Prognostic Significance of Cerebral Metabolic Abnormalities in Patients With Congestive Heart Failure
Authors: Cheol Whan Lee, Jung Hee Lee, Tae-Hwan Lim, Hyun Suk Yang, Myeong-Ki Hong, Jae-Kwan Song, Seong-Wook Park, Seung-Jung Park, Jae-Joong Kim
Journal: Circulation (2001)

Background —Cerebral metabolic abnormalities were proposed as a potential marker of disease severity in congestive heart failure (CHF), but their prognostic significance remains uncertain. Methods and Results —We investigated the prognostic value of cerebral metabolic abnormalities in 130 consecutive patients with advanced CHF (100 men aged 42.6±11.9 years; left ventricular ejection fraction, 22.2±6.2%). Proton magnetic resonance spectroscopy data were obtained from localized regions (≈8 mL) of the occipital gray matter and the parietal white matter. The primary end point was the occurrence of death after the proton magnetic resonance spectroscopy. During follow-up (18.5±14.4 months), 21 patients died and 15 underwent urgent heart transplantation. In the Cox proportional model, occipital metabolites (N-acetylaspartate, creatine, choline, and myoinositol), parietal N-acetylaspartate level, and the duration of CHF symptoms (&gt;12 months) were validated as univariate predictors of death. In multivariate Cox analyses, however, the occipital N-acetylaspartate level was an independent predictor of death (hazard ratio, 0.52; 95% CI, 0.41 to 0.67; P &lt;0.001). An analysis with respect to the combined end point of death or urgent transplantation showed similar results. The best cutoff value (9.0 mmol/kg) for occipital N-acetylaspartate level had 75% sensitivity and 67% specificity to predict mortality. Conclusions —The occipital N-acetylaspartate level is a powerful and independent predictor of CHF mortality, suggesting that cerebral metabolic abnormalities may be used as a new prognostic marker in the assessment of patients with CHF.
Cleft palate and speech.
Authors: Lawrence C. Parish
Journal: JAMA (1963)

The problems of speech correction in cases of cleft palate need to be called to the attention of both the specialist in maxillofacial surgery and the family physician. The latter must be able to advise the parents as to the time when an operation is advisable and what the results may be. He must realize the importance of postoperative therapy. Without proper speech training, the patient cannot benefit from one of the major purposes of the operation. In this text, consideration is given to such subjects as congenital clefts of lips and palate; the anatomy and physiology of the normal palate and palatopharyngeal sphincter; the development of cleftpalate surgery; growth, development, and speech; the evaluation of the speech problem; and methods of treatment for these defects. Because this manual is intended primarily for the speech correctionist, many of its medical concepts will seem overly simplified or
Insights into the evolution of themotilin/ghrelin-associated family and their receptors
Authors: J. He, D. M. Irwin, Y.-p. Zhang
Journal: Molecular Biology and Evolution (2007)

Insights into the evolution of themotilin/ghrelin-associated family and their receptors Jing He, David M. Irwin, and Ya-ping Zhang* Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; The Graduate School, Chinese Academy of Sciences, Beijing 100049, China; Departments of Laboratory Medicine and Pathobiology and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada; and Laboratory for Conservation and Utilization of Bioresource, Yunnan University, Kunming 650091, China
AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress
Authors: Cinzia Perrino, Antonio Feliciello, Gabriele G. Schiattarella, Giovanni Esposito, Rosalia Guerriero, Laura Zaccaro, Annarita Del Gatto, Michele Saviano, Corrado Garbi, Rosa Carangi, Emilio Di Lorenzo, Giuseppe Donato, Ciro Indolfi, Vittorio Enrico Avvedimento, Massimo Chiariello
Journal: Cardiovascular Research (2010)

The aim of the present study was to determine the function and the role of the scaffold protein AKAP121, tethering cAMP dependent protein kinase A to the outer wall of mitochondria, in neonatal ventricular myocytes and the heart.Competitive peptides displacing AKAP121 from mitochondria in the tissue and in the cells were used to investigate the role of AKAP121 in mitochondrial function, reactive oxygen species (ROS) generation, and cell survival. Displacement of AKAP121 from mitochondria by synthetic peptides triggers the death program in cardiomyocytes. Under pathological conditions in vivo, in a rat model of cardiac hypertrophy induced by ascending aorta banding, the levels of AKAP121 are significantly down-regulated. Disappearance of AKAP121 is associated with mitochondrial dysfunction, high oxidative stress, and apoptosis. In vivo delocalization of AKAP121 by competitive peptides replicates some of the molecular signatures induced by pressure overload: mitochondrial dysfunction, increased mitochondrial ROS, and apoptosis.These data suggest that AKAP121 regulates the response to stress in cardiomyocytes, and therefore AKAP121 downregulation might represent an important event contributing to the development of cardiac dysfunction.
Sleep Disturbances as the Hallmark of PTSD: Where Are We Now?
Authors: Anne Germain
Journal: American Journal of Psychiatry (2012)

The hypothesis that rapid eye movement (REM) sleep disturbances are the hallmark of posttraumatic stress disorder (PTSD), proposed by Ross and colleagues in 1989, has stimulated a wealth of clinical, preclinical, and animal studies on the role of sleep in the pathophysiology of PTSD. The present review revisits this influential hypothesis in light of clinical and experimental findings that have since accumulated. Polysomnographic studies conducted in adults with PTSD have yielded mixed findings regarding REM sleep disturbances, and they generally suggest modest and nonspecific sleep disruptions. Prospective and treatment studies have provided more robust evidence for the relationship between sleep disturbances and psychiatric outcomes and symptoms. Experimental animal and human studies that have probed the relationship between REM sleep and fear responses, as well as studies focused more broadly on sleep-dependent affective and memory processes, also provide strong support for the hypothesis that sleep plays an important role in PTSD-relevant processes. Overall, the literature suggests that disturbed REM or non-REM sleep can contribute to maladaptive stress and trauma responses and may constitute a modifiable risk factor for poor psychiatric outcomes. Clinicians need to consider that the chronic sleep disruption associated with nightmares may affect the efficacy of first-line PTSD treatments, but targeted sleep treatments may accelerate recovery from PTSD. The field is ripe for prospective and longitudinal studies in high-risk groups to clarify how changes in sleep physiology and neurobiology contribute to increased risk of poor psychiatric outcomes.
An unusual finding during bowel cancer screening colonoscopy
Authors: Thomas Chapman, Gabrielle Rees, David Gorard
Journal: Gut (2012)

A 63-year-old woman attended for colonoscopy after producing a positive faecal occult blood sample during the National Health Service Bowel Cancer Screening Programme. She was asymptomatic. At her screening colonoscopy, a smooth polypoid mass was seen at the base of the caecum (figure 1). Biopsies were taken (figures 2 and 3).



Figure 1 
Image at colonoscopy.





Figure 2 
Biopsy specimen.





Figure 3 
Chromogranin A staining …
Microbial Exposure in Infancy and Subsequent Appearance of Type 1 Diabetes Mellitus–Associated Autoantibodies
Authors: Suvi M. Virtanen, Hanna-Mari Takkinen, Bright I. Nwaru, Minna Kaila, Suvi Ahonen, Jaakko Nevalainen, Sari Niinistö, Heli Siljander, Olli Simell, Jorma Ilonen, Heikki Hyöty, Riitta Veijola, Mikael Knip
Journal: JAMA Pediatrics (2014)

The role of microbial exposure during early life in the development of type 1 diabetes mellitus is unclear.To investigate whether animal contact and other microbial exposures during infancy are associated with the development of preclinical and clinical type 1 diabetes.A birth cohort of children with HLA antigen-DQB1-conferred susceptibility to type 1 diabetes was examined. Participants included 3143 consecutively born children at 2 hospitals in Finland between 1996 and 2004.The following exposures during the first year of life were assessed: indoor and outdoor dogs and cats, farm animals, farming, visit to a stable, day care, and exposure to antibiotics during the first week of life.Clinical and preclinical type 1 diabetes were used as outcomes. The latter was defined as repeated positivity for islet-cell antibodies plus for at least 1 of 3 other diabetes-associated autoantibodies analyzed and/or clinical type 1 diabetes. The autoantibodies were analyzed at 3- to 12-month intervals since the birth of the child.Children exposed to an indoor dog, compared with otherwise similar children without an indoor dog exposure, had a reduced odds of developing preclinical type 1 diabetes (adjusted odds ratio [OR], 0.47; 95% CI, 0.28-0.80; P = .005) and clinical type 1 diabetes (adjusted OR, 0.40; 95% CI, 0.14-1.14; P = .08). All of the other microbial exposures studied were not associated with preclinical or clinical diabetes: the odds ratios ranged from 0.74 to 1.58.Among the 9 early microbial exposures studied, only the indoor dog exposure during the first year of life was inversely associated with the development of preclinical type 1 diabetes. This finding needs to be confirmed in other populations.
Quantitation and clonal isolation of cytolytic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors.
Authors: K T Brunner, H R MacDonald, J C Cerottini
Journal: The Journal of Experimental Medicine (1981)

A limiting dilution mixed leukocyte-tumor cell microculture system was used to quantitate cytolytic T lymphocytes and their precursors (CTL-P), which infiltrate tumors induced by injection of Moloney sarcoma-leukemia virus (MSV-MoLV) complex into C57BL/6 mice. Leukocyte populations obtained from tumors collected on day 10 after virus injection were found to contain significantly higher frequencies of operationally defined (tumor-specific) CTL-P than either peripheral blood leukocytes (PBL) or spleen cells from the same animals. When these frequencies were normalized according to the content of Lyt-2+ T cells in each tissue, average CTL-P frequencies were found to be 1/9 in tumor-infiltrating cells vs. 1/41 in PBL. These results directly demonstrate selective accumulation of CTL-P in the tumor mass. A number of clonal isolates obtained from tumor-infiltrating leukocyte populations were expanded and studied for cytolytic activity and specificity. Of 11 isolates, 10 were found to have high cytolytic activity, leading to 50% lysis of the syngeneic MoLV-derived tumor target cells in 3.5 h at lymphocyte:target cell ratios ranging from 0.5:1 to 3.2:1. Furthermore, five randomly selected clones showed H-2 restriction by their selective lytic activity against MoLV-derived syngeneic MBL-2 target cells and their lack of activity against either MoLV-derived allogeneic (LSTRA) tumor cells or against syngeneic (EL4) or allogeneic (P815) target cells unrelated to MoLV.
Value of the IUCN Red List
Authors: John Lamoreux, H Resit Akçakaya, Leon Bennun, Nigel J Collar, Luigi Boitani, David Brackett, Amie Bräutigam, Thomas M Brooks, Gustavo A.B da Fonseca, Russell A Mittermeier, Anthony B Rylands, Ulf Gärdenfors, Craig Hilton-Taylor, Georgina Mace, Bruce A Stein, Simon Stuart
Journal: Trends in Ecology & Evolution (2003)
Abciximab (ReoPro) potentiates thrombolysis in ST elevation myocardial infarction: results of TIMI 14 trials
Authors: E.M. Antman, R.P. Giugliano, C.H. McCabe, M. Gibson, A.J.J. Adgey, M. Ghali, P. Coussement, K.M. Anderson, J. Scherer, F. Van de Werf, E. Braunwald
Journal: Journal of the American College of Cardiology (1998)
Serious Infections Among Adult Medicaid Beneficiaries With Systemic Lupus Erythematosus and Lupus Nephritis
Authors: Candace H. Feldman, Linda T. Hiraki, Wolfgang C. Winkelmayer, Francisco M. Marty, Jessica M. Franklin, Seoyoung C. Kim, Karen H. Costenbader
Journal: Arthritis & Rheumatology (2015)

Objective To examine the epidemiology of serious infections, a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide cohort of SLE and lupus nephritis (LN) patients. Methods Using the Medicaid Analytic eXtract database for the years 2000–2006, we identified patients ages 18–64 years who had SLE and the subset who had LN. We ascertained cases of serious hospitalized infections using validated algorithms, and we determined 30‐day mortality rates. Poisson regression was used to calculate infection incidence rates and multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) for the first infection, adjusted for sociodemographic variables, medication use, and an SLE‐specific risk adjustment index. Results We identified 33,565 patients with SLE, 7,113 of whom had LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection incidence rate per 100 person‐years was 10.8 in the SLE cohort and 23.9 in the LN subcohort. In adjusted models for the SLE cohort, we observed increased risks of infection in men as compared to women (HR 1.33 [95% confidence interval (95% CI) 1.20–1.47]), in blacks as compared to whites (HR 1.14 [95% CI 1.06–1.21]), and in users of glucocorticoids (HR 1.51 [95% CI 1.43–1.61]) and immunosuppressive drugs (HR 1.11 [95% CI 1.03–1.20]) as compared to never users. Hydroxychloroquine users had a reduced risk of infection as compared to never users (HR 0.73 [95% CI 0.68–0.77]). The 30‐day mortality rate per 1,000 person‐years among those hospitalized with infections was 21.4 in the SLE cohort and 38.6 in the LN subcohort. Conclusion In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths, particularly among those with LN.
<i>AIP</i>Mutation in Pituitary Adenomas in the 18th Century and Today
Authors: Harvinder S. Chahal, Karen Stals, Martina Unterländer, David J. Balding, Mark G. Thomas, Ajith V. Kumar, G. Michael Besser, A. Brew Atkinson, Patrick J. Morrison, Trevor A. Howlett, Miles J. Levy, Steve M. Orme, Scott A. Akker, Richard L. Abel, Ashley B. Grossman, Joachim Burger, Sian Ellard, Márta Korbonits
Journal: New England Journal of Medicine (2011)

Gigantism results when a growth hormone-secreting pituitary adenoma is present before epiphyseal fusion. In 1909, when Harvey Cushing examined the skeleton of an Irish patient who lived from 1761 to 1783, he noted an enlarged pituitary fossa. We extracted DNA from the patient's teeth and identified a germline mutation in the aryl hydrocarbon-interacting protein gene (AIP). Four contemporary Northern Irish families who presented with gigantism, acromegaly, or prolactinoma have the same mutation and haplotype associated with the mutated gene. Using coalescent theory, we infer that these persons share a common ancestor who lived about 57 to 66 generations earlier.
<i>Cancer Discovery</i> at One Year: The Editors' Interim Analysis
Authors: Lewis C. Cantley, José Baselga
Journal: Cancer Discovery (2012)

Our interim analysis is strikingly positive as Cancer Discovery enters into its second year, and we hope the journal will become an increasingly indispensable resource to both basic and clinical cancer researchers.

![Figure][1] 

As Cancer Discovery approaches its first anniversary, we would like to share with you our initial assessment of the life and health of this young journal of the American Association for Cancer Research (AACR). If we were to analyze the journal in a similar fashion as would be done with a clinical trial for a new and exciting compound, we would call this a prespecified interim analysis, also known as an “early look.” Early looks are by nature tricky. If the findings are positive but do not cross a given boundary, they could simply be false-positive. However, if they are negative to begin with, this does not mean that the study results will be negative after more prolonged follow-up.

First, let us look at the Methods of the journal. The concept behind Cancer Discovery was, and is, to be a …

 [1]: pending:yes
Post-operative Pulmonary Atelectasis
Authors: R. C. Brock
Journal: BMJ (1947)

exertion such as digging or rpowing a rough lawn with an old lawn-mower.The abdominal wall felt icy to the touch, and aftersuch exertion I would have an acute attack as described.It could not be put down to icy water as we had no refrigerator and usually the water remained tepid after boiling.Stools were negative.Apart from these acute attacks I normally had three or four loose stools daily during the hot weather.I eventually found that a " belly pad " consisting of about a square foot of woollen vest, lined on the inside with an old piece of " lock-knit " cotton material, tied round the neck and waist, was almost specific.The Chinese (Hakka) people dress their small children in a "belly pad " in the hot weather.-Iam, etc., Leyburm, Yorks.
Child adoption in the seventeenth century: vignettes from Defoe and Pepys
Authors: A N Williams
Journal: Journal of the Royal Society of Medicine (2003)

In the seventeenth century, between a quarter and one-third of children died in the first year of life and only half reached the age of fifteen. Children born out of wedlock were at even higher risk, partly through infanticide. Indeed, in 1624 Parliament passed an Act ‘to prevent the murthering of bastard children’.2 Many were consigned to the care of a parish, which resented the burden and neglected them. Others went to paid carers; there was no formal system for child adoption, and a mother often made secret arrangements to have the child taken off her hands. In this article I draw attention to two vignettes from the writings of Daniel Defoe (1661–1731) and Samuel Pepys (1633–1703).
Association Between the CCR5 32-bp Deletion Allele and Late Onset of Schizophrenia
Authors: Henrik Berg Rasmussen, Sally Timm, August G. Wang, Karen Søeby, Henrik Lublin, Mogens Fenger, Ralf Hemmingsen, Thomas Werge
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher age at first admission. After age at first admission was analyzed as a continuous variable, it was dichotomized using 40 years as the cutoff. With this approach the authors found that genotype distributions of patients with age at first admission above the cutoff (possible cases of late-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without affecting the disease susceptibility.
Rosai dorfman disease of the orbit
Authors: Geeta K Vemuganti, Milind N Naik, Santosh G Honavar
Journal: Journal of Hematology & Oncology (2008)

To report the clinico-histopathologic features, management and outcome of Rosai-Dorfman disease of the orbit. Non-comparative case series. Rosai-Dorfman disease of the orbit constituted 0.09% of all ocular specimens received at our Institute, presenting with a firm rubbery mass causing proptosis; bilateral in 4 (57%) cases. The median age at presentation was 13 years (range 5–65); median duration of symptoms was 6 (range 3–15) years. Lymphadenopathy was noted in 4 (57%); extranodal involvement in 3 (43%). After biopsy, 3 cases were treated with systemic corticosteroids, 2 cases developed local recurrence that responded to systemic corticosteroid therapy. Polymorphous population of lymphocytes, plasma cells, and characteristic S-100-positive histiocytes showing emperipolesis were pathognomonic histologic features. Rosai-Dorfman disease of the orbit, although rare, should be considered in young individuals with chronic proptosis with rubbery masses. Excision and corticosteroid therapy provide a favorable outcome.