tbuckley/cabot-search huggingface dataset:
Histocompatibility alloantigens in psoriasis and psoriatic arthritis. Evidence for the influence of multiple genes in the major histocompatibility complex.
Authors: C Murray, D L Mann, L N Gerber, W Barth, S Perlmann, J L Decker, T P Nigra
Journal: Journal of Clinical Investigation (1980)

The frequency of HLA-A, B, and Cw antigens as well as the antigens expressed preferentially on B cells and monocytes (DRw and Ia-like) was examined in a normal population and two related disease populations, psoriasis and psoriatic arthritis. HLA antigens distinguishing the two disease populations were found. Psoriatic patients demonstrated an increase in frequency of HLA-A1, B17, and B13. Patients with psoriatic arthritis demonstrated an increased frequency of HLA-A26, B38, and DRw4. Antigens showing a common increase in frequency in the two disease populations were HLA-Cw6, DRw7, and Ia744. These results demonstrate genetic differences as well as similarities in the two populations of patients with the common clinical feature of psoriasis. In addition to the above analysis, we examined the association of individual alloantigens elevated in frequency in the diseased population. These same alloantigens were examined for association in the normal population. This analysis revealed HLA antigen associations in the two disease groups that differed from the association of several antigens in the normal population. The results suggest that at least two genetic factors, one mapping in the HLA-A, C-B region and one mapping in the HLA-B-DRw region are associated with the disease states. Thus, multiple factors controlled by genes in the major histocompatibility complex appear to contribute to the disease entities under investigation.
CURARE: A PREVENTIVE OF TRAUMATIC COMPLICATIONS IN CONVULSIVE SHOCK THERAPY
Authors: A. E. BENNETT
Journal: American Journal of Psychiatry (1941)

1. Convulsive shock therapy has proved most useful as a means of terminating chronic resistant affective psychoses. 2. The usefulness of this therapy has been restricted and has been in danger of abandonment because of the severity of the convulsive shock with the hazards of traumatic complications. 3. There is something fundamentally sound in the application of this therapy. The problem has been to eliminate the traumatic hazards. 4. Previous attempts to eliminate traumatic complications have not been successful. 5. The principle of preliminary curarization before induction of metrazol shock has proved successful in eliminating all traumatic hazards. 6. A uniform standardized curare preparation has now been perfected that is non-toxic in physiologic doses and has proved to be a safe treatment. 7. The physiologic and pharmacologic effects of the drug have been discussed. The technic of this combined therapy is described. 8. Roentgenographic evidence and electro-encephalographic evidence are presented to show that the curare protects from traumatic complications, yet leaves the therapeutic effectiveness of metrazol undisturbed. 9. The results of previous metrazol therapy in affective psychoses re compared with curare-metrazol results to show the same therapeutic results are obtained without complication. Other investigators have confirmed our results with this new treatment. 10. A series of cases of depressive psychoses complicated with severe organic diseases are shown that widen the scope of usefulness of this modified therapy. A number of cases can now be salvaged that formerly could not have taken the treatment. 11. Curare is "tailor made" as a "shock absorber" for convulsive shock therapy. 12. A synthetic curare-like drug, quinine methochloride, has been prepared that has been shown to have a strong curare-like action. After intravenous injection it produces effective motor paresis sufficient to prevent traumatic complications of convulsive shock therapy. Further experimentation will be necessary, however, to determine the safety factor, before its use can be recommended. 13. If a continued, sustained supply of pure curare or a safe synthetic curare-like drug can be obtained, it will soon be illegitimate to administer convulsive shock therapy without this safeguard against the all too frequent and serious traumatic accidents.
Cancer Progression in the Transgenic Adenocarcinoma of Mouse Prostate Mouse Is Related to Energy Balance, Body Mass, and Body Composition, but not Food Intake
Authors: Derek M. Huffman, Maria S. Johnson, Amanda Watts, Ada Elgavish, Isam A. Eltoum, Tim R. Nagy
Journal: Cancer Research (2006)

Calorie restriction can inhibit or delay carcinogenesis, reportedly due to a reduction in calorie intake rather than by concurrent changes in body mass and/or composition. Our objective was to test the hypothesis that body mass and/or composition have an important effect, independent of energy intake, on the benefits or hazards associated with calorie restriction or overeating, respectively. In the first experiment, transgenic mice that spontaneously develop prostate cancer [transgenic adenocarcinoma of mouse prostate (TRAMP)] were housed at 27 degrees C or 22 degrees C and pair fed the same diet for 21 weeks (95% of ad libitum intake at 27 degrees C). In the second experiment, TRAMP mice were housed at 27 degrees C or 22 degrees C and fed the same diet ad libitum for 21 weeks. Despite a similar calorie intake, pair-fed mice at 27 degrees C (PF27) were heavier (28.3 +/- 3.3 versus 17.6 +/- 1.6 g at 21 weeks; P < 0.001; mean +/- SD) and had greater fat (6.4 +/- 2.1 versus 1.9 +/- 0.3 g; P < 0.001) and lean mass (P < 0.001) than pair-fed mice at 22 degrees C. Furthermore, PF27 mice had greater levels of serum leptin (P < 0.001), lower levels of adiponectin (P < 0.05), and a greater frequency of prostatic adenocarcinoma (P < 0.05). In contrast, ad libitum-fed mice housed at 22 degrees C consumed approximately 30% more calories than ad libitum-fed mice at 27 degrees C, but there was no difference between groups in body composition or cancer progression. These results imply that the ability of calorie restriction to inhibit or delay cancer incidence and progression is mediated in part by changes in energy balance, body mass, and/or body composition rather than calorie intake per se, suggesting that excess calorie retention, rather than consumption, confers cancer risk.
The Relationship between Levels of PCBs and Pesticides in Human Hair and Blood: Preliminary Results
Authors: Larisa Altshul, Adrian Covaci, Russ Hauser
Journal: Environmental Health Perspectives (2004)

Human hair as a biologic measure of exposure to persistent organic pollutants (POPs) has some advantages over the more commonly used blood and adipose tissue samples. However, one of the primary limitations is the difficulty in distinguishing between exogenous and endogenous contamination. In addition, there are currently no standardized methods for hair sample collection, washing, and chemical analysis. There is also very limited information describing the correlation between levels of organic contaminants in hair and other body compartments. To explore levels of POPs in blood and hair, samples from 10 volunteers were collected and analyzed for select organochlorine pesticides and 57 individual polychlorinated biphenyl (PCB) congeners. We demonstrated that the method for analyzing organic contaminants in human hair was reliable and reproducible. Washing hair with shampoo decreased levels of PCBs, pesticides, and lipids by 25-33% on average and up to 62% for low-chlorinated congeners. The percentage of lipids and the levels of organochlorines in hair were higher than in serum. We found strong correlation (r = 0.8) between p,p -DDE (dichlorodiphenyldichloroethylene) levels in hair and blood and moderate correlations for the more persistent PCB congeners, but no correlations or weak correlations for other organochlorines. The present study provides preliminary evidence on the utility of hair analysis for POPs; however, further larger studies are recommended before hair analysis can be successfully applied in epidemiologic studies on POPs.
Modelling imitation with sequential games
Authors: Andrew M. Colman
Journal: Behavioral and Brain Sciences (1998)

A significant increase in the probability of an action resulting from observing that action performed by another agent cannot, on its own, provide persuasive evidence of imitation. Simple models of social influence based on two-person sequential games suggest that both imitation and pseudo-imitation can be explained by a process more fundamental than priming, namely, subjective utility maximization.
Experience With Single-Lung Transplantation for Pulmonary Fibrosis
Authors: Joel D. Cooper
Journal: JAMA (1988)

Repeated success has now been obtained with single-lung transplantation for end-stage pulmonary fibrosis. Potential candidates for this procedure are individuals who are less than 60 years of age and who have progressive pulmonary deterioration with limited life expectancy. Since November 1983, eleven such transplantations have been performed; nine patients achieved discharge from the hospital and eight patients have remained alive up to 44 months after surgery. All of these recipients have good oxygenation on room air and good exercise tolerance and are capable of performing routine activities, including a return to previous employment. From our experience, it appears likely that single-lung transplantation can achieve the same success rates as other major organ transplantations. (<i>JAMA</i>1988;259:2258-2262)
Axillary Treatment in Women With One or Two Sentinel Nodes With Macrometastases: More Evidence Is Needed to Inform Practice
Authors: Amit Goyal, David Dodwell, Malcolm W. Reed, Robert E. Coleman
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: The benefits of eliminating the morbidity of axillary lymph node dissection (ALND) or axillary radiotherapy (ART) in early breast cancer—if achievable without compromising long-term cancer outcomes— are obvious, but the recommendation from the American Society of Clinical Oncology update committee 1 that ALND can be safely avoided in patients with one or two sentinel lymph node (SLN) macrometastases who will undergo breastconserving surgery with conventional whole-breast radiotherapy (RT) is premature and based entirely on the results of the American College of Surgeons Oncology Group Z11 trial. 2 The shortfalls associated with this study have been previously described 3 but include the following: recruitment rates were poor (50% of original target); patients recruited to the study had generally low-risk cancers; axillary recurrence was not the predefined primary trial end point; approximately 50% of patients had micrometastases; a significant proportion of patients had unknown nodal status; a high proportion of patients were lost to follow-up (21% in the ALND group and 17% in the SLN group); there was a significant amount of missing data, and there was no prospective RT quality assurance programtomitigateanybiasinRTtargetvolumedefinition.Themost critical issue relates to the generalizability of trial results to many patients with cancers who would have met the eligibility criteria but were not represented in the cohort of patients in the trial. Ultimately, the American Society of Clinical Oncology recommendationthatALNDcanbeavoidedinpatientswithoneortwoSLN macrometastases,reflectingtheeligibilitycriteriaofZ11,isbasedona comparisonof228patientsversus202patientsandthisissignificantly short of a persuasive evidence base. Additional clinical trials are needed to define the role of axillary intervention in patients with macrometastases in the SLNs before avoidance of further axillary intervention in this patient group can be routinely recommended. The POSNOC (Positive Sentinel Node: Adjuvant Therapy Alone Versus Adjuvant Therapy Plus Clearance or Axillary Radiotherapy) trial in the United Kingdom is asking thisquestionandwillprovideamoresolidevidencebasetoinform clinical practice. 4
Effects of environmental endotoxin and Can f1 on interleukin-10 responses in infancy*1
Authors: C.L. Reardon, J. Kohls, Z. Li, K.A. Roberg, E. Anderson, C. Tisler, D. DaSilva, R. Gangnon, H. Hiemke, A.H. Liu, P.A. Eggleston, R.F. Lemanske, J.E. Gern
Journal: Journal of Allergy and Clinical Immunology (2004)
Measurement of inspiratory muscle performance with incremental threshold loading: a comparison of two techniques.
Authors: P A Bardsley, S Bentley, H S Hall, S J Singh, D H Evans, M D Morgan
Journal: Thorax (1993)

BACKGROUND--Incremental threshold loading (ITL) is a test of inspiratory muscle performance which is usually performed by breathing through a weighted inspiratory plunger, the load on the inspiratory muscles being increased by externally adding weights to the intake valve. This is not a true threshold device and may be inaccurate. This method was compared with a true threshold device consisting of a solenoid valve which only opens to supply air at a predetermined negative mouth pressure. METHODS--Six naive, normal subjects (three men and three women) aged 22-24 years underwent three tests using each system. The inspiratory loads were increased every minute by equivalent amounts, -10 cm H2O with the solenoid valve and by 50 g with the weighted plunger, until the subjects could not inspire or sustain inspiration for a full minute. Six experienced subjects (four men and two women) aged 23-41 years were subsequently randomised to perform ITL with the solenoid valve, twice with the breathing pattern fixed and twice free. RESULTS--The solenoid valve generated a more accurate mouth pressure response and was less variable at higher loads than the weighted plunger. The work performed (expressed as the pressure-time product) was less with the solenoid valve but was more reproducible. ITL with the solenoid valve was not influenced by controlling the breathing pattern of the subjects. CONCLUSIONS--The solenoid valve has several features that make it superior to the weighted plunger as a device for ITL. It generates a more accurate mouth pressure response which is less variable at higher loads. Increases in load are smoother and quicker to introduce. ITL with the solenoid valve is not influenced by varying breathing patterns and does not require any external regulation.
Evidence for function of Ia molecules on gut epithelial cells in man.
Authors: L Mayer, R Shlien
Journal: The Journal of Experimental Medicine (1987)

Using freshly isolated Ia+ gut epithelial cells we have been able to demonstrate that these cells can function as accessory cells in an immune response. The cells can act as stimulators in both autologous and allogeneic MLRs. More importantly, these cells are capable of taking up the soluble antigen, tetanus toxoid, processing it, and presenting it to tetanus-primed T cells. These functions appear to relate to the presence of surface Ia in that a hetero-anti-Ia antibody can block these effects. Noteworthy is the finding that the subpopulation of T cells stimulated when epithelial cells are used as accessory cells is the T8+, 9.3-T cell. These cells function as potent antigen-nonspecific suppressor cells in both MLR, T cell antigen responses, and induction of B cell differentiation by PWM. These findings have significant implications in local gut immune responses and may help explain several poorly characterized phenomena of mucosal immunity.
Carvedilol Decreases Elevated Oxidative Stress in Human Failing Myocardium
Authors: Kazufumi Nakamura, Kengo Kusano, Yoichi Nakamura, Mikio Kakishita, Keiko Ohta, Satoshi Nagase, Mika Yamamoto, Katsumasa Miyaji, Hironori Saito, Hiroshi Morita, Tetsuro Emori, Hiromi Matsubara, Shinya Toyokuni, Tohru Ohe
Journal: Circulation (2002)

Background — Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating β-blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results — Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects ( P &lt;0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9±4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22±8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% ( P &lt;0.005) along with amelioration of heart failure. Conclusions — Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.
Severe Hypoglycemia and Risks of Vascular Events and Death
Authors: Sophia Zoungas, Anushka Patel, John Chalmers, Bastiaan E. de Galan, Qiang Li, Laurent Billot, Mark Woodward, Toshiharu Ninomiya, Bruce Neal, Stephen MacMahon, Diederick E. Grobbee, Andre Pascal Kengne, Michel Marre, Simon Heller
Journal: New England Journal of Medicine (2010)

Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes.
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Authors: F. Stephen Hodi, Steven J. O'Day, David F. McDermott, Robert W. Weber, Jeffrey A. Sosman, John B. Haanen, Rene Gonzalez, Caroline Robert, Dirk Schadendorf, Jessica C. Hassel, Wallace Akerley, Alfons J.M. van den Eertwegh, Jose Lutzky, Paul Lorigan, Julia M. Vaubel, Gerald P. Linette, David Hogg, Christian H. Ottensmeier, Celeste Lebbé, Christian Peschel, Ian Quirt, Joseph I. Clark, Jedd D. Wolchok, Jeffrey S. Weber, Jason Tian, Michael J. Yellin, Geoffrey M. Nichol, Axel Hoos, Walter J. Urba
Journal: New England Journal of Medicine (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma.
Concurrent Doxorubicin Plus Docetaxel Is Not More Effective Than Concurrent Doxorubicin Plus Cyclophosphamide in Operable Breast Cancer With 0 to 3 Positive Axillary Nodes: North American Breast Cancer Intergroup Trial E 2197
Authors: Lori J. Goldstein, Anne O'Neill, Joseph A. Sparano, Edith A. Perez, Lawrence N. Shulman, Silvana Martino, Nancy E. Davidson
Journal: Journal of Clinical Oncology (2008)

Purpose The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant regimen. Doxorubicin and docetaxel (AT) is one of the most active cytotoxic regimens for metastatic breast cancer. The purpose of this trial was to determine whether adjuvant AT improved disease-free survival compared with AC in operable breast cancer. Patients and Methods Women with invasive breast cancer were eligible if there were one to three positive lymph nodes or if the node-negative tumor was greater than 1 cm. Patients were randomly assigned after surgery to receive doxorubicin (60 mg/m 2 ) plus either cyclophosphamide (600 mg/m 2 ; AC) or docetaxel (60 mg/m 2 ; AT) given every 3 weeks for four cycles, followed by hormone therapy for patients with estrogen receptor (ER) and/or progesterone receptor (PR)–positive tumors. Results There were 2,882 eligible patients enrolled. After a median follow-up of 79.5 months, there was no significant difference in disease-free survival (DFS; 85% in both arms) or overall survival (91% v 92%) at 5 years. The hazard ratio for AC versus AT was 1.02 (95% CI for DFS, 0.86 to 1.22; P = .78). In an exploratory analysis of prespecified stratification factors by ER and PR expression there were trends toward improved DFS for AT in ER/PR-negative disease. Grade 3 neutropenia associated with fever or infection occurred more often with AT (26% v 10%; P &lt; .05). Conclusion AT did not improve DFS or overall survival in this population, and was associated with more toxicity.
Cardiovascular Consequences When Nitric Oxide and Lipid Signaling Converge
Authors: Volker Rudolph, Bruce A. Freeman
Journal: Circulation Research (2009)

The identification of nitric oxide ((*)NO) as an endogenously produced free radical mediator of endothelial-dependent relaxation and host defense has fundamentally changed concepts of cell signal transduction. Ligand-receptor oriented paradigms of cell signaling were originally centered on the concept of a high affinity and specific interaction between a ligand and its receptor, resulting in the activation of secondary signaling events such as gene expression or modulation of catalytic protein function. While (*)NO ligation of the heme iron of soluble guanylate cyclase is consistent with this perspective, the readily diffusible and broadly reactive (*)NO is increasingly appreciated to react with a vast array of target molecules that mediate paracrine vasodilator actions, inhibition of thrombosis and neointimal proliferation, and both pro- and antiinflammatory signaling reactions that are not affected by inhibitors of soluble guanylate cyclase. There is an expanding array of functionally significant "off target" collateral reactions mediated by (*)NO that are guanylate cyclase-independent and rather are dictated by anatomic distribution and the formation of secondary (*)NO-derived species. These reactions are a critical element of redox-regulated signaling and are addressed herein in the context of the oxidation of unsaturated fatty acids to vascular and inflammatory signaling mediators. Because of their abundance and the intrinsic reactivity of unsaturated lipid intermediates and eicosanoid metabolism enzymes with (*)NO and other oxides of nitrogen, lipid signaling mechanisms are a significant target for regulation by (*)NO in the vascular compartment. This convergence of (*)NO and lipid signaling pathways thus adds another level of regulation to physiological responses such as vasodilation, thrombosis, and inflammation. Herein, interactions between (*)NO and lipid signaling events are placed in the context of cardiovascular regulation.