tbuckley/cabot-search huggingface dataset:
Immune function of successfully treated lymphoma patients.
Authors: G W King, B Yanes, P E Hurtubise, S P Balcerzak, A F LoBuglio
Journal: Journal of Clinical Investigation (1976)

Immunologic function was evaluated in 12 patients with Hodgkin's disease and 5 patients with lymphocytic lymphoma who had been successfully treated with either chemotherapy, radiation therapy, or both of these modalities 3-42 mo previously. Only two of the patients were found to have total anergy to a battery of six recall skin test antigens and all were responsive to skin testing with phytohemagglutinin. However, 10 of 16 patients were unable to develop delayed cutaneous hypersensitivity to either of the neoantigens dinitrochlorobenzene or keyhole limpet hemocyanin. Four other patients developed reactivity to only one of these neoantigens for a total of 14 of 16 (88%) of the patients demonstrating some impairment in neoantigen response. Total lymphocyte, T-lymphocyte, B-lymphocyte, and null cell numbers, as well as serum immunoglobulins were quantitatively normal. Monocyte numbers, chemotaxis, and Fc receptor activity were normal. Monocyte staphylocidal activity at 60 min was modestly depressed and candidacidal activity was depressed in those receiving both chemotherapy and radiation therapy. Spontaneous (unstimulated) lymphocyte [3H]thymidine incorporation was low in the patients as a group and lymphoblastic transformation to specific antigens was impaired in 11 of 17 patients who had positive skin test reactions to the same antigen. Highly significant suppression of lymphoblastic transformation was noted after stimulation by the mitogens phytohemagglutinin, pokeweed, and concanavalin-A. The greatest impairment of mitogen response was seen in those patients receiving both chemotherapy and radiation therapy. These data demonstrate specific impairments of neoantigen processing, lymphocyte function, and to a lesser extent monocyte function in successfully treated patients with lymphoma. These impairments may contribute to the increased incidence of infections and second primary malignancies in these patients.
Biological and Biomaterial Approaches for Improved Islet Transplantation
Authors: Ajit S. Narang, Ram I. Mahato
Journal: Pharmacological Reviews (2006)

Islet transplantation may be used to treat type I diabetes. Despite tremendous progress in islet isolation, culture, and preservation, the clinical use of this modality of treatment is limited due to post-transplantation challenges to the islets such as the failure to revascularize and immune destruction of the islet graft. In addition, the need for lifelong strong immunosuppressing agents restricts the use of this option to a limited subset of patients, which is further restricted by the unmet need for large numbers of islets. Inadequate islet supply issues are being addressed by regeneration therapy and xenotransplantation. Various strategies are being tried to prevent β-cell death, including immunoisolation using semipermeable biocompatible polymeric capsules and induction of immune tolerance. Genetic modification of islets promises to complement all these strategies toward the success of islet transplantation. Furthermore, synergistic application of more than one strategy is required for improving the success of islet transplantation. This review will critically address various insights developed in each individual strategy and for multipronged approaches, which will be helpful in achieving better outcomes.
Exome Sequencing of Neonatal Blood Spots and the Identification of Genes Implicated in Bronchopulmonary Dysplasia
Authors: Jingjing Li, Kun-Hsing Yu, John Oehlert, Laura L. Jeliffe-Pawlowski, Jeffrey B. Gould, David K. Stevenson, Michael Snyder, Gary M. Shaw, Hugh M. O’Brodovich
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Bronchopulmonary dysplasia (BPD), a prevalent severe lung disease of premature infants, has a strong genetic component. Large-scale genome-wide association studies for common variants have not revealed its genetic basis.Objectives: Given the historical high mortality rate of extremely preterm infants who now survive and develop BPD, we hypothesized that risk loci underlying this disease are under severe purifying selection during evolution; thus, rare variants likely explain greater risk of the disease.Methods: We performed exome sequencing on 50 BPD-affected and unaffected twin pairs using DNA isolated from neonatal blood spots and identified genes affected by extremely rare nonsynonymous mutations. Functional genomic approaches were then used to systematically compare these affected genes.Measurements and Main Results: We identified 258 genes with rare nonsynonymous mutations in patients with BPD. These genes were highly enriched for processes involved in pulmonary structure and function including collagen fibril organization, morphogenesis of embryonic epithelium, and regulation of Wnt signaling pathway; displayed significantly elevated expression in fetal and adult lungs; and were substantially up-regulated in a murine model of BPD. Analyses of mouse mutants revealed their phenotypic enrichment for embryonic development and the cyanosis phenotype, a clinical manifestation of BPD.Conclusions: Our study supports the role of rare variants in BPD, in contrast with the role of common variants targeted by genome-wide association studies. Overall, our study is the first to sequence BPD exomes from newborn blood spot samples and identify with high confidence genes implicated in BPD, thereby providing important insights into its biology and molecular etiology.
Twelfth Biannual Report of the Cochrane Haematological Malignancies Group--Focus on Tyrosine Kinase Inhibitors
Authors: N. Skoetz, S. Kluge, I. Monsef, K. Bauer, H. Siebert, K.-A. Kreuzer, A. Engert
Journal: JNCI Journal of the National Cancer Institute (2011)

This 12th biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials in the field of hemato-oncology, covering the publication period from September 1, 2009, through June 30, 2010. Implication for clinical practice and methodological aspects are the main principles used to select trials for this report. Studies on tyrosine kinase inhibitors for patients with chronic myeloid leukemia were identified through electronic search of MEDLINE with a broad search filter that covered all topics in hemato-oncology combined with a highly sensitive search filter for randomized studies as described in the Cochrane Handbook for Systematic Reviews of Interventions.
TCR-dependent transformation of mature memory phenotype T cells in mice
Authors: Xi Wang, Miriam B.F. Werneck, Boris G. Wilson, Hye-Jung Kim, Michael J. Kluk, Christopher S. Thom, Jonathan W. Wischhusen, Julia A. Evans, Jonathan L. Jesneck, Phuong Nguyen, Courtney G. Sansam, Harvey Cantor, Charles W.M. Roberts
Journal: Journal of Clinical Investigation (2011)

A fundamental goal in cancer research is the identification of the cell types and signaling pathways capable of initiating and sustaining tumor growth, as this has the potential to reveal therapeutic targets. Stem and progenitor cells have been implicated in the genesis of select lymphoid malignancies. However, the identity of the cells in which mature lymphoid neoplasms are initiated remains unclear. Here, we investigate the origin of peripheral T cell lymphomas using mice in which Snf5, a chromatin remodelling–complex subunit with tumor suppressor activity, could be conditionally inactivated in developing T cells. In this model of mature peripheral T cell lymphomas, the cell of origin was a mature CD44hiCD122loCD8+ T cell that resembled a subset of memory cells that has capacity for self-renewal and robust expansion, features shared with stem cells. Further analysis showed that Snf5 loss led to activation of a Myc-driven signaling network and stem cell transcriptional program. Finally, lymphomagenesis and lymphoma proliferation depended upon TCR signaling, establishing what we believe to be a new paradigm for lymphoid malignancy growth. These findings suggest that the self-renewal and robust proliferative capacities of memory T cells are associated with vulnerability to oncogenic transformation. Our findings further suggest that agents that impinge upon TCR signaling may represent an effective therapeutic modality for this class of lethal human cancers.
Physician and Nurse Use of Psychosocial Strategies in Diabetes Care
Authors: Mark Peyrot, Richard R. Rubin, Linda M. Siminerio
Journal: Diabetes Care (2006)

To determine the use of psychosocial strategies by health care providers in treating patients with diabetes and the factors associated with use of these strategies.Cross-sectional survey of national samples of generalist and diabetes specialist physicians (n = 2,705) and nurses (n = 1,122) from the multinational study of Diabetes Attitudes, Wishes and Needs. Respondents were from 13 countries in Asia, Australia, Europe, and North America. Two psychosocial strategies were examined: provider psychosocial care, which provides psychosocial support by diabetes care providers to their own patients, and psychosocial specialist care, which refers diabetic patients to psychosocial specialists.Compared with physicians, nurses perceived significantly higher prevalence and severity of psychosocial problems and used psychosocial strategies significantly more frequently, even though they rated their own psychosocial skills lower. Among both physicians and nurses, diabetes specialists were significantly more likely than generalists to utilize psychosocial strategies. Physicians and nurses used psychosocial strategies significantly more when they believed that more patients have psychosocial problems and that problems interfere more with diabetes control. Referral to psychosocial specialists was significantly more likely when physicians and nurses perceived that professional psychological resources were more available. There were substantial country differences in all factors studied. Compared with other countries, U.S. providers provided more psychosocial care themselves but were less likely to refer to psychosocial specialists.Psychosocial strategies are important parts of the diabetes care provider repertoire; understanding their determinants may facilitate efforts to increase their use.
Randomized Trial of Adjuvant 13-<i>cis</i>-Retinoic Acid and Interferon Alfa for Patients With Aggressive Skin Squamous Cell Carcinoma
Authors: Abenaa M. Brewster, J. Jack Lee, Gary L. Clayman, John L. Clifford, Mary Jo T. Necesito Reyes, Xian Zhou, Anita L. Sabichi, Sara S. Strom, Robert Collins, Christina A. Meyers, Scott M. Lippman
Journal: Journal of Clinical Oncology (2007)

Purpose To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-α) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC. Patients and Methods Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-α (3 × 10 6 U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation. Results At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-α was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities. Conclusion Results of this phase III trial do not support 13cRA plus IFN-α for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.
Partial mid-portion Achilles tendon ruptures: new sonographic findings helpful for diagnosis
Authors: Håkan Alfredson, Lorenzo Masci, Lars Öhberg
Journal: British Journal of Sports Medicine (2009)

Background Partial Achilles tendon ruptures are not always easy to diagnose. A history including a sudden onset of pain and/or relative weakness in plantar flexion force is an indicator. The most loaded side of the Achilles tendon is the dorsal side (skin side). Objective The aim of this study was to evaluate the ultrasound (US) and colour Doppler (CD) findings in patients with a suspected partial rupture in the Achilles tendon. Materials and Methods Seventeen patients (16 men and 1 woman) with a mean age of 36 years (range 23–71 years) were examined clinically and by US+CD because of mid-portion Achilles tendon pain. There was an acute onset in 14 of 17 patients, and all had painful weakness during tendon loading activity. Results In all patients, the US examination showed a partial Achilles tendon rupture, presented as a disrupted dorsal (skin side) tendon line and an irregular tendon structure mainly located in the dorsal and mid-tendon. The size of the rupture varied from 1/3 to 2/3 of the tendon thickness. In the dorsal part of the tendon, corresponding to the region with disrupted tendon line and irregular structure, CD examination showed high blood flow—most often of a longitudinal character. Six of the patients were surgically treated, and macroscopical examination verified the US findings showing disruption on the dorsal side and a partial rupture in the dorsal and mid-tendon. Conclusions US and Doppler examination can be helpful tools to diagnose partial mid-portion Achilles tendon ruptures. The characteristic findings of a disrupted dorsal tendon line and high blood flow in the structurally abnormal dorsal tendon indicate a partial rupture.
Clara cell protein as a marker of Clara cell damage and bronchoalveolar blood barrier permeability
Authors: C. Hermans, B. Knoops, M Wiedig, K Arsalane, G Toubeau, P Falmagne, A Bernard
Journal: European Respiratory Journal (1999)

The 16 kDa Clara cell protein (CC16), an abundant component of airway secretions, has recently been proposed in humans as a pulmonary marker measurable not only in bronchoalveolar lavage fluid (BALF) but also in serum. The aim of the present study was to investigate the changes and determinants of CC16 concentrations in these fluids in normal rats and rats with lung injury. Female Sprague-Dawley rats were given a single i.p. injection of arachis oil (n=20) or chemicals in arachis oil (n=10) that mainly damage Clara cells (4-ipomeanol (IPO) 8 mg x kg(-1) and methylcyclopentadienyl manganese tricarbonyl (MMT) 5 mg x kg(-1)) or endothelial cells (alpha-naphthylthiourea (ANTU) 5 mg x kg(-1)). CC16 concentration (mean+/-sD in microg x L(-1)), measured by a sensitive latex immunoassay, was significantly reduced in BALF of all treated groups (IPO 380+/-100; MMT 730+/-200; ANTU 1,070+/-200; controls 1,700+/-470). The same pattern of decrease was observed in the labelling of Clara cells with an anti-CC16 antiserum as well as in the CC16 messenger ribonucleic acid levels assessed by Northern enzyme-linked immunosorbent assay. In serum, by contrast, CC16 was significantly increased in all treated groups (IPO 31+/-7; MMT 22+/-12; ANTU 52+/-24; controls 15+/-6). This rise of CC16 in serum was associated with an elevation of albumin in BALF which is an index of increased bronchoalveolar/blood barrier permeability. In conclusion, lung injury induces a decrease of the 16 kDa Clara cell protein in bronchoalveolar lavage fluid owing to a reduced production by damaged Clara cells, and an increase in serum protein levels resulting from its enhanced leakage across the bronchoalveolar/blood barrier. This study provides new insights into the understanding of the changes of lung secretory proteins in bronchoalveolar lavage fluid and serum.
Francis (“Frank”) Joseph O'Kelly
Authors: Frank O'Kelly
Journal: BMJ (2006)

​FormerFormer surgeon rear admiral of both ships and establishments Plymouth and Naval Hospitals at Haslar, Gosport (b 1921, q University College Dublin 1945; OBE, FFOM, FACOM), died from lung cancer on 11 November 2005.



Figure 1



Francis Joseph O'Kelly (“Frank”) completed commando training and saw active service with the Royal Marines in the Far East. For 32 years he enjoyed all aspects of naval life: at sea, with the Fleet Air Arm, as senior medical officer in the dockyards in Singapore and Rosyth, and staff medical officer at Royal Naval Hospital, Gibraltar. Frank was also a consultant in occupational medicine, an honorary physician to the Queen, and commander in the Order of St John. On retirement from the navy in 1980 he was consultant in occupational health to the Hong Kong government for six years. He leaves a wife, Terry; four children; and 11 grandchildren.
Relative importance of pacing strategy and mean power output in 1500-m self-paced cycling
Authors: F J Hettinga, J J de Koning, M Hulleman, C Foster
Journal: British Journal of Sports Medicine (2009)

Both mean power output (MPO) and the distribution of the available energy over the race, that is, pacing strategy, are critical factors in performance. The purpose of this study was to determine the relative importance of both pacing strategy and MPO to performance.Six well-trained, regionally competitive cyclists performed four 1500-m ergometer time trials (∼2 min). For each subject, the fastest (Fast) and slowest (Slow) time trials were compared and the relative importance of differences in power output and pacing strategy were determined with an energy flow model.The difference in final time between Fast and Slow was 4.0 (2.5) s. Fast was performed with a higher MPO (437.8 (32.3) W vs 411.3 (39.0) W), a higher aerobic peak power (295.3 (36.8) vs 287.5 (34.7) W) and a higher anaerobic peak power (828.8 (145.4) W vs 649.5 (112.2) W) combined with a relatively higher, but not statistically different anaerobic rate constant (0.051 (0.016) vs 0.041 (0.009) W). The changes in MPO (63% anaerobic, 37% aerobic) largely explained the differences in final times. Athletes chose a different pacing strategy that was close to optimal for their physiological condition in both Fast and Slow.Differences in intraindividual performance were mainly caused by differences in MPO. Athletes seemed to be able to effectively adjust their pacing profile based on their "status of the day". Keywords modelling performance, energy expenditure, aerobic, anaerobic, sports.
Family characteristics of 105 patients with bulimia
Authors: Craig Johnson, Anna Flach
Journal: American Journal of Psychiatry (1985)

The authors compared 105 patients who met DSM-III criteria for bulimia with 86 control subjects on measures of family environment and presence of eating disorders. Bulimic patients' perceptions of their families included low cohesiveness, a lack of emphasis on independent and assertive behavior, and a high level of conflict coupled with a low emphasis on open expression of feelings. Families of bulimic subjects had achievement expectations comparable to those of control families, but the former placed less emphasis on intellectual and recreational activities. The high disorganization of the families of bulimic subjects was associated with severity of symptoms.
Endothelial Indoleamine 2,3-Dioxygenase Protects against Development of Pulmonary Hypertension
Authors: Yongguang Xiao, Helen Christou, Li Liu, Gary Visner, S. Alex Mitsialis, Stella Kourembanas, Hanzhong Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: A proliferative and apoptosis-resistant phenotype in pulmonary arterial smooth muscle cells (PASMCs) is key to pathologic vascular remodeling in pulmonary hypertension (PH). Expression of indoleamine-2,3-dioxygenase (IDO) by vascular endothelium is a newly identified vasomotor-regulatory mechanism also involved in molecular signaling cascades governing vascular smooth muscle cell (vSMC) plasticity.Objectives: To investigate the therapeutic potential of enhanced endothelial IDO in development of PH and its associated vascular remodeling.Methods: We used loss and gain of function in vivo studies to establish the role and determine the therapeutic effect of endothelial IDO in hypoxia-induced PH in mice and monocrotaline-induced PH in rats. We also studied PASMC phenotype in an IDO-high in vivo and in vitro tissue microenvironment.Measurements and Main Results: The endothelium was the primary site for endogenous IDO production within mouse lung, and the mice lacking this gene had exaggerated hypoxia-induced PH. Conversely, augmented pulmonary endothelial IDO expression, through a human IDO-encoding Sleeping Beauty (SB)-based nonviral gene-integrating approach, halted and attenuated the development of PH, right ventricular hypertrophy, and vascular remodeling in both preclinical models of PH. IDO derived from endothelial cells promoted apoptosis in PH-PASMCs through depolarization of mitochondrial transmembrane potential and down-regulated PH-PASMC proliferative/synthetic capacity through enhanced binding of myocardin to CArG box DNA sequences present within the promoters of vSMC differentiation–specific genes.Conclusions: Enhanced endothelial IDO ameliorates PH and its associated vascular structural remodeling through paracrine phenotypic modulation of PH-PASMCs toward a proapoptotic and less proliferative/synthetic state.
ON THE RELATION OF INFLAMMATION TO THE CHEMICAL CONSTITUTION OF INJURIOUS AGENTS. ON THE PHARMACOLOGY OF INFLAMMATION
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1963)

Changes characteristic of an inflammatory reaction caused by the injection of an injurious agent into the peritoneal cavity were measurable by the quantity of peritoneal fluid, by the number of leucocytes that entered the cavity, and by the abundance of exuded protein. Inflammation increased in severity along with ion dissociation and increase of the valence of electrolytes. With chlorides, sulfates, and nitrates it increased in each instance with the valence of their basic ions. The reactions caused by sodium chloride, sodium sulfate, and sodium citrate increased with the valence of their acid ions. Salts of heavy metals which fix and precipitate proteins caused more active inflammation than did other electrolytes. Histamine and arginine caused active inflammatory reactions with similar characteristics. The amino compounds, urea, citrulline, and creatinine, glycine, alanine, histidine, arginine, and histamine, produced inflammatory reaction in the order of severity with which, in foregoing experiments, they had caused necrosis when injected into the dermis. The acids and alkalis that were tested caused active inflammation when their acidity approached pH 1 or their alkalinity pH 11 respectively, but with approximate neutrality the inflammatory reaction became scant. These changes were in accord with the extent of necrosis when acid or alkalis, in foregoing experiments, were injected into the dermis. When histamine or arginine combines with hydrochloric acid to form histamine dihydrochloride or arginine monohydrochloride alkalinity is lost and inflammatory reactions caused by the hydrochlorides are relatively mild. The characteristic changes which accompany histamine and arginine do not occur. The combination of histamine with phosphoric acid to form histamine acid phosphate has similar relation to histamine. Inflammatory reactions caused by monobasic, dibasic, and tribasic sodium phosphate increased in activity in accord with increasing alkalinity referable to the basic ions of these salts. The activity of inflammatory reactions has been found to vary in accord with the chemical constitution of the injurious agents that have been tested.