tbuckley/cabot-search huggingface dataset:
CD28 negative T cells are enriched in granulomatous lesions of the respiratory tract in Wegener's granulomatosis
Authors: P Lamprecht
Journal: Thorax (2001)

Lack of CD28 expression on peripheral blood CD4+ and CD8+ T cells has been reported in patients with Wegener's granulomatosis (WG), suggesting a pathogenetic role of CD28- T cells in WG.Ten patients with WG and six with sarcoidosis (disease control) were analysed. Fluorescence activated cell sorter (FACS) analysis was used to detect CD28 expression on T cells from peripheral venous blood and from bronchoalveolar lavage (BAL) fluid. T cells in biopsy specimens from granulomatous lesions of the upper respiratory tract were analysed for CD28 expression by double immunofluorescence staining.A significantly higher fraction of CD28- T cells was found in the CD4+ and CD8+ T cell compartment in BAL fluid (65.6 (5.4)% and 76.3 (4.1)%, respectively) than in blood (13.4 (6.2)% and 42.9 (6.2)%; p<0.001) in patients with WG but not in those with acute sarcoidosis (6.7 (2.2)% and 53.4 (7.3)% in BAL fluid v 4.1 (2.5)% and 52.0 (9.4)% in blood). The total number of CD4+/CD28- T cells but not of CD8+/CD28- T cells was also significantly higher in BAL fluid than in blood in patients with WG (p<0.05). Patients with WG had a significantly higher fraction of CD28- T cells in the CD4+ and CD8+ T cell compartment in BAL fluid than patients with acute sarcoidosis (65.6 (5.4)% v 6.7 (2.2)%; p<0.001; and 76.3 (4.1)% v 53.4 (7.3)%; p<0.05). The total number of CD4+/CD28- and CD8+/CD28- T cells was also significantly higher in patients with WG than in those with sarcoidosis (p<0.01). An abundance of CD28- T cells was found in granulomatous lesions by double immunofluorescence staining in patients with WG.Our data indicate enrichment of CD28- T cells in BAL fluid and suggest recruitment of CD28- T cells into granulomatous lesions in WG. Further analysis of the phenotype and function of T cell subsets in WG is needed to better understand leucocyte homing in WG and to find new therapeutic targets.
Determination of Red Blood Cell Life Span
Authors: Nathaniel I. Berlin
Journal: JAMA (1964)

ALL VARIATIONS in the total volume of circulating red blood cells (RBC) can be thought of as resulting from an alteration in either the rate of production of cells or the cell life span. Methods for the determination of the rate of cell production have been described elsewhere.<sup>1</sup>This review will be concerned with the measurement of the red cell life span in man. <h3>Methods</h3> There are two classes of direct methods for measurement of red cell life span, cohort and random labeling. The cohort methods require the biosynthetic introduction of a label into a group of newly synthesized cells and the quantitative determination of the persistence of the label in the circulating erythrocytes. The precursors used are glycine C<sup>14</sup>,<sup>2</sup>glycine N<sup>15</sup>,<sup>3</sup>glycine H<sup>3</sup>,<sup>4</sup>and a radioactive iron (Fe<sup>59</sup>) compound.<sup>5</sup>(A cohort of labeled cells has been prepared in the dog
Enhanced Leukemia Cell Detection Using a Novel Magnetic Needle and Nanoparticles
Authors: Jason E. Jaetao, Kimberly S. Butler, Natalie L. Adolphi, Debbie M. Lovato, Howard C. Bryant, Ian Rabinowitz, Stuart S. Winter, Trace E. Tessier, Helen J. Hathaway, Christian Bergemann, Edward R. Flynn, Richard S. Larson
Journal: Cancer Research (2009)

Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. Although bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that utilizes antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPION) and directed against the acute leukemia antigen CD34, coupled with a "magnetic needle" biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34-conjugated SPIONs. Three separate approaches including microscopy, superconducting quantum interference device magnetometry, and in vitro magnetic needle extraction were then used to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by 10-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared with the current standard of care.
Three more government drug advisers resign
Authors: C. Dyer
Journal: BMJ (2009)

The row between the UK government and its advisory council on the misuse of drugs has deepened, with the resignations of three further members, leaving it without some of the representatives required by statute for it to do its work.

Their resignations bring to five the total who have quit in protest at the sacking of the council’s head, David Nutt. It is now short of the representatives from pharmacy, the pharmaceutical industry, and chemistry, which are required by the Misuse of Drugs Act, and is likely to face reluctance on the part of scientists to take up the unpaid posts.

Professor Nutt, a neuropsychopharmacologist from Imperial College, London, and Bristol University, was dismissed by …
What Are the Extrapulmonary Manifestations of Bronchogenic Carcinoma?
Authors: Lloyd H. Smith
Journal: JAMA (1966)

Bronchogenic carcinoma may produce signs and symptoms by three different mechanisms: (1) local extension within the lung, (2) metastasis, or (3) by producing systemic effects unrelated to the spread of the tumor.<sup>14-16</sup>This brief review will outline some of these systemic effects, which may occasionally represent the first manifestation of the disease. None of these systemic manifestations is specific, in that all may be found in association with malignant lesions of other organs. An arbitrary classification is given in Table 3. <h3>Metabolic Manifestations</h3> The most frequent metabolic abnormality found in carcinoma of the lung is wasting of the host. The cause of the marked weakness and weight loss which may accompany a small, localized malignancy is not clear. Most recent attention has been directed to a number of rather well-defined endocrine syndromes which may be produced by nonendocrine tumors, of which bronchogenic carcinoma is one of the most frequent.
Emergence and Transmission of Arbovirus Evolutionary Intermediates with Epidemic Potential
Authors: Kenneth A Stapleford, Lark L Coffey, Sreyrath Lay, Antonio V Bordería, Veasna Duong, Ofer Isakov, Kathryn Rozen-Gagnon, Camilo Arias-Goeta, Hervé Blanc, Stéphanie Beaucourt, Türkan Haliloğlu, Christine Schmitt, Isabelle Bonne, Nir Ben-Tal, Noam Shomron, Anna-Bella Failloux, Philippe Buchy, Marco Vignuzzi
Journal: Cell Host & Microbe (2014)
P204 The Burden of repeated asthma admissions and associations with psychiatric comorbidity
Authors: H. Burke, Z. Pond, C. Duffus, R. J. Kurukulaaratchy
Journal: Thorax (2011)

<h3>Rationale and Objectives</h3> While only 10% of asthmatics have “Difficult Asthma” they account for 80% of asthma-related expenditure. Aggravating comorbidities are common in patients with Difficult Asthma including Psychiatric disorders, such as major depression, which is present in 29%.1 We sought to characterise the annual burden of repeated asthma admissions to our Hospital and assess the influence of psychiatric comorbidity on this group with Difficult Asthma. <h3>Methods</h3> We systematically searched the hospital database for patients who had been acutely admitted on two or more occasions in 2010 for asthma at Southampton General Hospital (Southampton, UK). Data were collected retrospectively and covered patient demographics, admission details, asthma severity, physical and psychiatric co-morbidity. Coding data for each admission was analysed to determine admission costs. Data were analysed using SPSS (V.19.0) to determine significant characteristics of this Difficult Asthma group and to assess the influence of psychiatric comorbidity on those parameters. <h3>Results</h3> There were 396 admissions for acute asthma in 2010, involving 305 patients. Of these, 36 (11.8%) patients were admitted on =2 occasions, accounting for 32.1% of admissions. Repeated admission patients consumed 895 bed-days and were predominantly female (72.2%; p=0.012). They commonly had aggravating comorbidities, the most predominant being diagnosed psychiatric disease (69.4%; p=0.03). Those patients with psychiatric comorbidity showed significantly higher Body Mass Index (p=0.012), plus greater prevalence of obesity (p=0.05) and dysfunctional breathing (p=0.012) than patients without psychiatric comorbidity. They also showed trends for higher prevalence of other aggravating comorbidity like Gastro-Oesophageal Reflux Disease (p=0.07) and for greater median bed-days/length of stay. The annual cost for repeated asthma admission was £226 536 of which patients with psychiatric comorbidity consumed £164 660 (72.7% of costs). <h3>Conclusions</h3> A significant proportion of patients with repeated asthma admission have psychiatric comorbidity. When present in such patients, psychiatric comorbidity is associated with obesity and dysfunctional breathing. Patients with Difficult Asthma and psychiatric comorbidity pose a significant burden on Secondary Healthcare resources. Optimal asthma care could benefit from targeting support and treatment for underlying psychiatric illness.
Mrp2 modulates the activity of chloride channels in isolated hepatocytes
Authors: Xinhua Li, Steven A. Weinman
Journal: Hepatology (2002)

Adenosine triphosphate binding cassette family transport proteins are important organic ion transporters in hepatocytes but these molecules may also exhibit other functions. In the present study we have measured the effects of substrates of the canalicular organic ion transporter multidrug resistance associated protein 2 (Mrp2) on chloride channel activation and cell volume regulation. We found that substrates such as leukotriene D 4 , 17-β-estradiol glucuronide, and the leukotriene inhibitor MK-571 accelerated the activation of chloride channels by cell swelling and activated chloride channels in cytokine-pretreated hepatocytes. Two conjugated estrogens that are not Mrp2 substrates did not produce this effect. Hepatocytes derived from a strain of transport-deficient rats (TR − ), which lack Mrp2 expression, showed none of these substrate effects. Coincident with their ability to activate channels, the Mrp2 substrates increased the rate of volume regulatory decrease by approximately 50% ( P &lt; .01), confirming that enhanced channel activation under this condition stimulated volume regulation. In TR-hepatocytes the Mrp2 substrate had no effect on volume regulation. In conclusion, Mrp2 plays a role in regulation of chloride channel function by reducing the lag time necessary for channel activation and consequently accelerating the process of cell volume regulation. Substrates of Mrp2 affect the ability of the protein to interact with chloride channels. These findings represent an alternative function of Mrp2 in hepatocytes.
Environmental Hazards
Authors: William H. Drury
Journal: New England Journal of Medicine (1966)

A RECENT report by a panel of environmental scientists who had reviewed the American condition was titled "Restoring the Quality of Our Environment" (the White House, 1965).Staff members of the Massachusetts Audubon Society noted a familiar ring to that title. Indeed, we not only have been using that title as a slogan for several decades, but also find in it a definition — as far as a definition is possible — of the modern conservation concept.It may surprise those with little training in biology that a wildlife conservation group could recommend the environmental report as a rather comprehensive . . .
Aberrant immunoglobulin synthesis in light chain amyloidosis. Free light chain and light chain fragment production by human bone marrow cells in short-term tissue culture.
Authors: J Buxbaum
Journal: Journal of Clinical Investigation (1986)

Bone marrow cells obtained from 14 patients with light chain amyloid (AL) deposition were examined by biosynthetic labeling techniques. These analyses identified free monoclonal light chain (L-chain) synthesis even in those patients whose serum or urine contained no M protein or free L-chains or only an intact M protein. The experiments also identified a subset of patients whose plasma cells synthesized polypeptides bearing constant region antigenic determinants that migrated more rapidly than intact L-chains on polyacrylamide gels. Since most AL fibrils contain L-chain fragments rather than intact L-chains, these studies suggested that the genesis of the fibril components may reflect aberrant synthesis, proteolytic processing, or both. We also noted that in some individuals the pattern of Ig synthesis normalized after several courses of cytotoxic therapy. Thus, we could use bone marrow Ig synthesis as a sensitive biochemical parameter for monitoring therapy. Finally, the presence of aberrant synthetic products in these clones raised questions about their origin with respect to the normal processes of transcription, translation, and posttranslational modification in Ig-producing cells.
Simpler for evolution: Secondary representation in apes, children, and ancestors
Authors: Thomas Suddendorf
Journal: Behavioral and Brain Sciences (1998)

Great apes show behavioral evidence for secondary representation similar to that of children of about two years of age. However, there is no convincing evidence for metarepresentation in apes. A good evolutionary interpretation should be parsimonious and must bring developmental and comparative data in accord. I propose a model based on the work of Perner (1991) and close by pointing out a logical flaw in Heyes's second proposed experiment.
Anand Mohan Sur
Authors: Poorvaali Sur
Journal: BMJ (2007)

Anand Sur was a pioneering paediatrician in India, founding the department of paediatrics at the Government Medical College in Nagpur. He made paediatrics a separate subject to be studied at final MB BS level for the first time in India.

He was the youngest son of Rai Saheb Rajendranath Sur, a civil engineer responsible for the Mahanadi dam project. A man of great charm and …
American Psychiatry: Past, Present, and Future
Authors: Thomas H. Jobe
Journal: JAMA (1976)

This volume, commemorating the 200th anniversary of Eastern State Hospital in Williamsburg, Va, the first public hospital for the insane in America, contains 13 papers presented at a conference held in Williamsburg, as well as a general discussion by the participants. The collection offers a concise, brief, and current overview of American psychiatry presented by leading authorities both inside and outside the profession. Norman Dain shows historically how psychiatry tends to be cyclic rather than linear in development. Judge David L. Bazelon cites some reasons for the defensiveness of psychiatrists in the courtroom. Morris S. Schwartz challenges psychiatrists to be more active for social change, and Charles E. Rosenburg warns the profession about its present crisis in social legitimacy. The profession itself is well represented with articles by Seymour S. Kety, Melvin Sabshin, Lawrence C. Kolb, Roy R. Grinker, Sr, and John P. Spiegel. They discuss a number of issues,
Hormesis and Its Place in Nonmonotonic Dose–Response Relationships: Some Scientific Reality Checks
Authors: Paul Mushak
Journal: Environmental Health Perspectives (2007)

ObjectiveThis analysis is a critical assessment of current hormesis literature. I discuss definitions, characterization, generalizability, mechanisms, absence of empirical data specific for hormesis hypothesis testing, and arguments that hormesis be the "default assumption" in risk assessment.Data sourcesHormesis, a biological phenomenon typically described as low-dose stimulation from substances producing higher-dose inhibition, has recently garnered interest in several quarters. The principal sources of published materials for this analysis are the writings of certain proponents of hormesis. Surprisingly few systematic critiques of current hormesis literature exist. Limits to the phenomenon's appropriate role in risk assessment and health policy have been published.Data synthesisSerious gaps in scientific understanding remain: a stable definition; generalizability, especially for humans; a clear mechanistic basis; limitations in the presence of multiple toxic end points, target organs, and mechanisms. Absence of both arms-length, consensus-driven, scientific evaluations and empirical data from studies specifically designed for hormesis testing have limited its acceptance.ConclusionsDefinition, characterization, occurrence, and mechanistic rationale for hormesis will remain speculative, absent rigorous studies done specifically for hormesis testing. Any role for hormesis in current risk assessment and regulatory policies for toxics remains to be determined.
The Computer-Stored Medical Record-Reply
Authors: Clement J. McDonald
Journal: JAMA (1989)

<h3>In Reply. —</h3> We agree fully that our failure to mention Dr Weed's pioneering work in computer-stored medical records and his seminal analysis of the purpose of medical records was a major oversight. We cannot justify it, but we can explain it. The PROMIS system was not discussed among the example medical record systems because it is not currently operative and did not achieve the institutional penetration—in terms of geographic scope or support—that the example systems did. It was not cited among the discussion of the advantages of medical record systems because we were emphasizing controlled trials of the use of medical record systems, and we knew of no such studies about the PROMIS system. The PROMIS system was not the progenitor of major existing medical record systems. Many of these were developed in the early 1970s in the same time frame as PROMIS. However, it was an exemplary achievement
Statin Reverses Smoke-induced Pulmonary Hypertension and Prevents Emphysema but Not Airway Remodeling
Authors: Joanne L. Wright, Steven Zhou, Olena Preobrazhenska, Caroline Marshall, Don D. Sin, Ismail Laher, Saeid Golbidi, Andrew M. Churg
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

the potential role of statins in treating chronic obstructive pulmonary disease (COPD) is controversial, and it is unclear what anatomic COPD lesions statins affect.to determine whether an intervention of simvastatin could alter cigarette smoke-induced pulmonary hypertension.we exposed guinea pigs to cigarette smoke for 6 months. In half the animals, simvastatin therapy was initiated after 3 months of smoke exposure. Pulmonary arterial systolic pressures were monitored weekly with a radiotelemetric catheter; additional physiologic and morphologic measurements were made at sacrifice after 6 months. Precision-cut lung explants were assessed for evidence of endothelial dysfunction, and in situ vascular nitric oxide generation was measured with 4,5-diaminofluorescein diacetate.cigarette smoke increased the pulmonary arterial systolic pressure after approximately 4 weeks. Simvastatin returned the pressure to control levels within 4 weeks of starting treatment, and ameliorated smoke-induced small arterial remodeling as well as emphysema measured both physiologically and morphometrically at 6 months, but did not prevent smoke-induced small airway remodeling either physiologically or morphologically. In precision-cut lung slices simvastatin reversed small arterial endothelial dysfunction, and partially reversed smoke-induced loss of vascular nitric oxide generation.simvastatin, as an intervention therapy, reverses the pulmonary vascular effects of cigarette smoke, including pulmonary hypertension, and prevents smoke-induced emphysema, but does not prevent small airway remodeling. This is the first demonstration that an intervention can reverse a COPD-associated cigarette smoke-induced anatomic abnormality. The study also shows the importance of examining all three anatomic lung compartments when assessing the effects of a potential drug intervention in patients with COPD.
Endogenous antibodies to bovine lactoperoxidase in children and adolescents
Authors: U.‐B. Ericsson, S. A. Ivarsson
Journal: Allergy (1987)

Sera from 146 children and adolescents (70 girls and 76 boys, median age 6 years; range 8 months ‐ 18 years) were analysed for the presence of antibodies to bovine lactoperoxidase (LPO) using a solid‐phase immunosorbent radioassay. LPO antibodies were present in all but one serum. The antibody titres varied from 1/5 to &gt; 1/5000 (final dilutions). Most of the individuals had antibody titres between 1/50 to 1/5000. Because of the frequent occurrence of LPO antibodies in human beings, the presence of LPO antibodies in the serum must be regarded as a physiological phenomenon.
Interaction of reelin signaling and Lis1 in brain development
Authors: Amir H Assadi, Guangcheng Zhang, Uwe Beffert, Robert S McNeil, Amy L Renfro, Sanyong Niu, Carlo C Quattrocchi, Barbara A Antalffy, Michael Sheldon, Dawna D Armstrong, Anthony Wynshaw-Boris, Joachim Herz, Gabriella D'Arcangelo, Gary D Clark
Journal: Nature Genetics (2003)
Outcomes of Phase II Clinical Trials with Single-Agent Therapies in Advanced/Metastatic Non–Small Cell Lung Cancer Published between 2000 and 2009
Authors: Filip Janku, Donald A. Berry, Jing Gong, Henrique A. Parsons, David J. Stewart, Razelle Kurzrock
Journal: Clinical Cancer Research (2012)

Abstract Purpose: We analyzed the outcomes of single-agent phase II clinical trials in non–small cell lung cancer (NSCLC) to determine trial parameters that predicted clinical activity. Exoerimental Design: Data on response rate (RR), progression-free survival (PFS), and overall survival (OS) from all English language, single-agent phase II trials in advanced/metastatic NSCLC indexed by PubMed (January 2000 through December 2009) were abstracted. Results: A total of 143 single-agent phase II trials (7,701 patients) were identified. The median RR was 10%, PFS 2.8 months, and OS 7.6 months. RR and PFS correlated with OS (r = 0.46, P &amp;lt; 0.001, r = 0.52, P &amp;lt; 0.001, respectively) and RR correlated with PFS (r = 0.61, P &amp;lt; 0.001). Treatment arms enriched for patients with molecular targets had a higher median RR (48.8% vs. 9.7%, P = 0.005), longer median PFS (6 vs. 2.8 months, P = 0.005), and OS (11.3 vs. 7.5 months, P = 0.05) as compared with those of unselected patients. In multivariate analysis, only studies enriched for patients with molecular targets or including drugs that eventually gained FDA/EMA approval were associated with a higher RR, and longer PFS/OS. Conclusions: In phase II trials in NSCLC, RR and PFS correlated with OS. Studies enriched for patients with putative molecular drug targets were associated with higher therapeutic benefit as compared with those of unselected populations. Clin Cancer Res; 18(22); 6356–63. ©2012 AACR.