tbuckley/cabot-search huggingface dataset:
Evaluation of Dr. John Tileston Edsall's Contribution to Science
Authors: J. Lawrence Oncley
Journal: JAMA (1966)

I am delighted to have been asked to take part in this happy occasion when we honor Prof John Tileston Edsall by the presentation of the 1966 Passano Award. It is especially interesting to me, and I am sure to Professor Edsall, that the first Passano Award, in 1945, was presented to Edwin Joseph Cohn, then professor of biochemistry and head of the Department of Physical Chemistry at Harvard Medical School. Professor Edsall was introduced to that department in 1926 while a medical student at Harvard, and after graduation from the Harvard Medical School in 1928 he started his professional career there. Over 25 of the "Forty Years Among the Proteins" were spent in that laboratory. I should not pass on from this early introduction of Professor Edsall's to the Department of Physical Chemistry at Harvard Medical School without calling attention to other members of the very distinguished group who
Natural Killer T Cell Ligand α-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines
Authors: Gloria Gonzalez-Aseguinolaza, Luc Van Kaer, Cornelia C. Bergmann, James M. Wilson, John Schmieg, Mitchell Kronenberg, Toshinori Nakayama, Masaru Taniguchi, Yasuhiko Koezuka, Moriya Tsuji
Journal: The Journal of Experimental Medicine (2002)

The important role played by CD8+ T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8+ T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, α-galactosylceramide (α-GalCer), causes bystander activation of NK, B, CD4+, and CD8+ T cells. Our study shows that coadministration of α-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of α-GalCer with various different immunogens strongly enhances antigen-specific CD8+ T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of α-GalCer require CD1d molecules, Vα14 NKT cells, and interferon γ. As α-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.
Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis
Authors: Jasper V. Been, Marlies J. Lugtenberg, Eline Smets, Constant P. van Schayck, Boris W. Kramer, Monique Mommers, Aziz Sheikh
Journal: PLoS Medicine (2014)

Background Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. Methods and Findings Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding. Conclusions There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions. Review Registration PROSPERO CRD42013004965 Please see later in the article for the Editors' Summary
The Glycogenolytic Activity of Immunoreactive Pancreatic Glucagon in Plasma
Authors: Jose Marco, Gerald R. Faloona, Roger H. Unger
Journal: Journal of Clinical Investigation (1971)

Conclusions concerning the physiologic role of pancreatic glucagon in health and its contribution to disorders of carbohydrate metabolism, such as diabetes mellitus, are based entirely on measurements of plasma glucagon by radioimmunoassay. The changes in plasma immunoreactive glucagon can have the metabolic and clinical significance which has been implied, only if the glucagon detected by immunoassay has biological activity. The present study was designed to determine if a relationship between the immunoassayable glucagon and glycogenolytic activity of plasma could be demonstrated. Plasma specimens obtained from normal and diabetic subjects under widely varying circumstances of alpha cell activity were extracted by a modification of the Kenny technique and the recovery of immunoreactive glucagon was calculated. Glycogenolytic activity of each extract was determined by perfusion in the Mortimore rat liver system, modified so as to detect as little as 1 ng of crystalline glucagon.A significant correlation between the calculated quantity of immunoreactive glucagon and the glycogenolytic activity of plasma extracts was observed for both normal and diabetic subjects. Most of the glycogenolytic activity was abolished by incubating the extract with antiglucagon serum. It was concluded that the glycogenolytic activity of extractable glucagon is proportional to its immunoreactivity as calculated from its original concentration in plasma. This would tend to support the view that all or most of the immunoreactive glucagon of plasma is biologically active.
C<scp>HALLENGES AND</scp>A<scp>PPROACHES TO</scp>R<scp>EDUCING</scp>F<scp>OODBORNE</scp>I<scp>LLNESS</scp>
Authors: Catherine E. Woteki, Brian D. Kineman
Journal: Annual Review of Nutrition (2003)

Microorganisms have successfully adapted to changes in food production, processing, and preservation techniques, resulting in a number of new and emerging foodborne pathogens and the re-emergence of organisms that have been problematic in the past. To protect public health, science must meet the challenges that result from the remarkable adaptability of foodborne pathogens. However, not all of the challenges of preventing foodborne illness reside in the realm of science. Food safety policy must evolve in response to new scientific understanding of hazards in the food supply and an ever-changing food processing industry. The laws, regulations, and organizations comprising the food safety system frequently lag behind current scientific knowledge of the risks posed by foodborne pathogens. Future systemic changes to enhance food safety will require better understanding of risks associated with specific pathogens occurring in the food supply and the costs and benefits of implementing mitigation strategies.
A simple method for the derivation of the international normalized ratio for the reporting of prothrombin time results
Authors: F. Habibzadeh, M. Yadollahie
Journal: American Journal of Hematology (1995)

Abstract In order to harmonize the prothrombin time (PT) reporting systems, the World Health Organization, in collaboration with the International Committee on Thrombosis and Hemostasis, and the International Council on the Standardization in Hematology proposed a reporting system, the so‐called international normalized ratio (INR). As the calculation of the INR depends on mathematical formula requiring a special calculator or mathematic tables, its derivation is associated with some difficulties and errors. In this article a nomogram is presented, by which derivation of the INR from different PT reporting methods can be easily done within a few seconds.
Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool
Authors: J. Christoph Vahl, Christoph Drees, Klaus Heger, Sylvia Heink, Julius C. Fischer, Jelena Nedjic, Naganari Ohkura, Hiromasa Morikawa, Hendrik Poeck, Sonja Schallenberg, David Rieß, Marco Y. Hein, Thorsten Buch, Bojan Polic, Anne Schönle, Robert Zeiser, Annette Schmitt-Gräff, Karsten Kretschmer, Ludger Klein, Thomas Korn, Shimon Sakaguchi, Marc Schmidt-Supprian
Journal: Immunity (2014)
Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men
Authors: Sharon Ooms, Sebastiaan Overeem, Kees Besse, Marcel Olde Rikkert, Marcel Verbeek, Jurgen A. H. R. Claassen
Journal: JAMA Neurology (2014)

Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease. A previous study found an effect of sleep on β-amyloid (Aβ), which is a key protein in Alzheimer disease pathology.To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid Aβ42 protein levels in healthy middle-aged men.The Alzheimer, Wakefulness, and Amyloid Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical trial that took place between June 1, 2012, and October 1, 2012. Participants were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n = 26) recruited from the local population.Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13).Sleep was monitored using continuous polysomnographic recording from 3 pm until 10 am. Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral Aβ42 concentrations between evening and morning.A night of unrestricted sleep led to a 6% decrease in Aβ42 levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation counteracted this decrease. When accounting for the individual trajectories of Aβ42 over time, a difference of 75.8 pg/mL of Aβ42 was shown between the unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04). The individual trajectories of evening and morning Aβ42 concentrations differed between the unrestricted sleep and sleep deprivation groups (P = .04) in contrast to stable Aβ40, tau, and total protein levels.Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in Aβ42. We hypothesize that chronic sleep deprivation increases cerebral Aβ42 levels, which elevates the risk of Alzheimer disease.clinicaltrials.gov Identifier: NCT01194713.
Adherence to Surveillance Among Patients With Superficial Bladder Cancer
Authors: D. Schrag, L. J. Hsieh, F. Rabbani, P. B. Bach, H. Herr, C. B. Begg
Journal: JNCI Journal of the National Cancer Institute (2003)

Patients diagnosed with superficial bladder cancer who have not undergone total cystectomy are at high risk for recurrence, and bladder surveillance with cystoscopy is recommended for such patients every 3-6 months. We examined the degree to which bladder cancer patients undergo the recommended surveillance procedures and identified patient and primary care provider characteristics associated with nonadherence to these recommendations.We used information obtained from the Surveillance, Epidemiology, and End Results (SEER) Program-Medicare-linked database to identify 6717 patients aged 65 years or older who were diagnosed with superficial bladder cancer from 1992 through 1996 and who survived for at least 3 years after diagnosis but did not have a total cystectomy. We used information obtained from Medicare claims forms to examine the frequency with which these patients had a surveillance examination of the bladder during each of five contiguous 6-month intervals from month 7 to month 36 following diagnosis. We examined characteristics of patients and their physicians that were associated with low-intensity surveillance (defined as having an examination during fewer than two of the five possible follow-up intervals). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided.Only 40% of the entire cohort had an examination during all five intervals; 1216 patients (18.1%) had low-intensity surveillance. Patient characteristics that were independently associated with low-intensity surveillance were being age 75 years or older (adjusted OR = 1.54, 95% CI = 1.35 to 1.74), nonwhite (adjusted OR = 1.94, 95% CI = 1.57 to 2.40), and having favorable tumor histology (adjusted OR = 0.59, 95% CI = 0.48 to 0.72 for poorly differentiated versus referent well-differentiated tumor grade) and high comorbidity (adjusted OR = 1.72, 95% CI = 1.30 to 2.27). Residence in an urban area or in a census tract with low median income was also associated with low-intensity surveillance.The actual practice of surveillance for patients with superficial bladder cancer differs substantially from the standards recommended in clinical guidelines.
Physiological Importance of First-Phase Insulin Release in Elderly Patients With Diabetes
Authors: Graydon S Meneilly, Dariush Elahi
Journal: Diabetes Care (1998)

OBJECTIVE To assess the physiological role of first-phase insulin release in obese elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Moderately obese elderly patients (n = 14, mean age 77 ± 2 years, BMI 28.4 ± 0.7 kg/m2) with type 2 diabetes underwent three 180-min hyperglycemic clamp studies. In the control study, glucose alone was infused. In the first-phase study, human insulin was infused for the first 4 min at 12 mU/m2 to mimic first-phase insulin release. In the first-phase enhanced study, insulin was infused for the first 4 min at 24 mU · m−2 · min−1. Tritiated glucose methodology was used in all studies to measure glucose production and disposal rates. RESULTS Glucose values were similar in all studies. In the control study, first-phase insulin response was absent. The peak insulin response occurred at 4 min in the first-phase and first-phase enhanced studies, but insulin values were substantially higher in the latter study (528 ± 40 vs. 340 ± 24 pmol/l, P &amp;lt; 0.0001). Second-phase insulin responses were not different among the studies. Glucose production and disposal rates were not significantly different among the studies. CONCLUSIONS While absent first-phase insulin secretion is a marker of abnormal pancreatic function in obese elderly patients with type 2 diabetes, it is not important in the regulation of hepatic glucose output or peripheral glucose disposal.
Prognostic Value of Tumor-Infiltrating Dendritic Cells in Colorectal Cancer: Role of Maturation Status and Intratumoral Localization
Authors: Maro H. Sandel, Alisher R. Dadabayev, Anand G. Menon, Hans Morreau, Cornelis J.M. Melief, Rienk Offringa, Sjoerd H. van der Burg, Connie M. Janssen-van Rhijn, N. Geeske Ensink, Rob A.E.M. Tollenaar, Cornelis J.H. van de Velde, Peter J.K. Kuppen
Journal: Clinical Cancer Research (2005)

The clinical significance of tumor-infiltrating dendritic cells has been reported in a variety of human solid tumors as shown by the correlations found between the presence of tumor-infiltrating dendritic cells and clinical prognosis. In this study, we evaluated whether there is an association between the presence and maturation status of tumor-infiltrating dendritic cells, T lymphocytes, and clinical course in 104 primary tumor samples of patients with colorectal cancer. Dendritic cells were identified with four different markers (S-100, HLA class II, CD208, and CD1a) in double immunohistochemistry, with laminin as second marker to support the exact localization. Tumor-infiltrating dendritic cells showed a distinct infiltration pattern based on their maturation status. CD1a-positive dendritic cells resided in the advancing tumor margins in relatively high numbers, whereas mature CD208-positive dendritic cells were sparsely present in the tumor epithelium but mainly distributed in the tumor stroma and advancing tumor margin. Furthermore, high infiltration of CD1a-positive dendritic cells in the tumor epithelium was significantly correlated to the infiltration of CD4 lymphocytes (P = 0.006). Patients with relatively high numbers of mature CD208-positive infiltrating dendritic cells in the tumor epithelium had a shorter overall survival (P = 0.004). In addition, patients with relatively high numbers of CD1a-positive dendritic cells in the advancing margin of the tumor had a shorter disease-free survival (P = 0.03). We found that tumor-infiltrating dendritic cells had preferential infiltration sites within a tumor, affected local tumor cell-immune cell interactions, and correlated to the clinical prognosis of colorectal cancer patients.
Neural respiratory drive as a physiological biomarker to monitor change during acute exacerbations of COPD
Authors: P. B. Murphy, A. Kumar, C. Reilly, C. Jolley, S. Walterspacher, F. Fedele, N. S. Hopkinson, W. D.-C. Man, M. I. Polkey, J. Moxham, N. Hart
Journal: Thorax (2011)

<h3>Background</h3> Acute exacerbations of chronic obstructive pulmonary disease have a significant negative impact on both patients and healthcare systems. Currently, there are no physiological biomarkers that effectively monitor clinical change or predict respiratory readmission. Acute exacerbations impose a change in the respiratory muscle load-capacity-drive relationship. It was hypothesised that lack of a fall in neural respiratory drive would identify patients at risk of treatment failure and early hospital readmission. <h3>Methods</h3> An observational study was performed at two UK teaching hospitals. Routine clinical physiological parameters and neural respiratory drive index (NRDI), calculated as the product of second intercostal space parasternal electromyography (EMG) activity normalised to the peak EMG activity during a maximum inspiratory sniff manoeuvre and respiratory rate, were recorded daily from admission to discharge. <h3>Results</h3> 30 acutely unwell patients of mean (SD) age 72 (10) years, forced expiratory volume in 1 s 0.60 (1.65) l, NRDI 455 (263) AU and median length of stay 6 days were studied. Changes in NRDI correlated with changes in Borg score (r=+0.60; p&lt;0.001), discriminated between patients deemed to have clinically improved rather than deteriorated (mean difference 339 AU; 95% CI 234 to 444; p&lt;0.001) and identified those patients readmitted within 14 days (mean difference 203 AU; 95% CI 39 to 366; p=0.017). <h3>Conclusions</h3> NRDI is a feasible clinical physiological parameter in patients with an acute exacerbation of chronic obstructive pulmonary disease and can provide useful information on treatment response and risk of readmission.
Spinal Cord Penetration of Intrathecally Administered Cytarabine and Methotrexate: A Quantitative Autoradiographic Study
Authors: P. A. Burch, S. A. Grossman, C. S. Reinhard
Journal: JNCI Journal of the National Cancer Institute (1988)

Carcinomatous meningitis is an increasingly common complication of systemic cancer. Treatment usually involves the use of intrathecal methotrexate or cytarabine, which have been reported to be toxic to the spinal cord. This study was performed to determine the penetration and distribution of intrathecally administered chemotherapy within the spinal cord. Tritiated methotrexate and cytarabine were administered intraventricularly and by lumbar puncture to New Zealand White rabbits. The extent and pattern of penetration of drug into the spinal cord were determined using quantitative autoradiographic techniques. The results demonstrate that 1 hour after administration 67%-99% of the total area of the spinal cord sections were exposed to these intrathecally administered agents. The pattern of distribution of the labeled drugs was inhomogeneous and was not dependent on the agent or the route of administration. High drug levels were seen in the area of the substantia gelatinosa and peripheral white matter which correspond to the location of pathological changes seen in the spinal cords of patients with neurotoxicity from intrathecal chemotherapy. This rapid and extensive penetration of intrathecally administered chemotherapy may offer insight into the myelopathy observed with these treatments.
Disclosing Harmful Medical Errors to Patients
Authors: Thomas H. Gallagher, David Studdert, Wendy Levinson
Journal: New England Journal of Medicine (2007)

Historically, fear of malpractice litigation made clinicians cautious about informing patients when they made mistakes in their care. This article reviews recent efforts by regulators, hospitals, accreditation organizations, and legislators to encourage and facilitate discussions between health care providers and patients when patients are harmed by medical errors.
DNA Microarray Analysis of Complex Biologic Processes
Authors: MANJULA KURELLA, LI-LI HSIAO, TAKUMI YOSHIDA, JEFFREY D. RANDALL, GARY CHOW, SATINDER S. SARANG, RODERICK V. JENSEN, STEVEN R. GULLANS
Journal: Journal of the American Society of Nephrology (2001)

Abstract. DNA microarrays, or gene chips, allow surveys of gene expression, ( i.e. , mRNA expression) in a highly parallel and comprehensive manner. The pattern of gene expression produced, known as the expression profile, depicts the subset of gene transcripts expressed in a cell or tissue. At its most fundamental level, the expression profile can address qualitatively which genes are expressed in disease states. However, with the aid of bioinformatics tools such as cluster analysis, self-organizing maps, and principle component analysis, more sophisticated questions can be answered. Microarrays can be used to characterize the functions of novel genes, identify genes in a biologic pathway, analyze genetic variation, and identify therapeutic drug targets. Moreover, the expression profile can be used as a tissue or disease “fingerprint.” This review details the fabrication of arrays, data management tools, and applications of microarrays to the field of renal research and the future of clinical practice.