tbuckley/cabot-search huggingface dataset:
Natural Autoantibody to MUC1 Is a Prognostic Indicator for Non–Small Cell Lung Cancer
Authors: YUTAKA HIRASAWA, NOBUOKI KOHNO, AKIHITO YOKOYAMA, KEIICHI KONDO, KUNIO HIWADA, MASAYUKI MIYAKE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

A great deal of attention has been focused on the antitumor effects of anti-MUC1 humoral and cellular responses. We examined whether anti-MUC1 antibody is present in patients with lung cancer, and evaluated its prognostic value. Serum was obtained from 30 patients with nonresectable, non–small cell lung cancer (NSCLC) and 60 healthy volunteers. The presence of anti-MUC1 antibody was determined by enzyme-linked immunosorbent assay. The patients were observed for a median follow-up time of 54.0 mo. Overall survival was estimated by the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional hazards regression model. Anti-KL-6/MUC1 antibody levels of the patients were significantly lower than those of normal individuals (p < 0.001). One-year survival rate of patients with high concentrations of anti-KL-6/MUC1 antibody was significantly higher than that of patients with low levels of anti-KL-6/MUC1 antibody (90.9% versus 21.1%, p < 0.001). Anti-KL-6/MUC1 antibody status was most strongly correlated with mortality, followed by lymph node status and albumin levels, whereas sex, serum lactate dehydrogenase (LDH), and carcinoembryonic antigen (CEA) levels, and metastasis status did not correlate with mortality. These preliminary results indicate that the degree of decrease in antibody level may be associated with a patient's prognosis. Hirasawa Y, Kohno N, Yokoyama A, Kondo K, Hiwada K, Miyake M. Natural autoantibody to MUC1 is a prognostic indicator for non–small cell lung cancer.
Cost effectiveness of two therapeutic regimens of infliximab in ankylosing spondylitis: economic evaluation within a randomised controlled trial
Authors: B Fautrel, M Benhamou, M Breban, C Roy, C Lenoir, G Trape, A Baleydier, P Ravaud, M Dougados
Journal: Annals of the Rheumatic Diseases (2009)

Objective: To determine the incremental cost-effectiveness ratios (ICERs) of two therapeutic regimens of infliximab for ankylosing spondylitis (AS). Methods: 230 patients with active AS who were participating in a randomised controlled trial comparing two infliximab infusion modalities—every 6 weeks (Q6) and on demand (DEM)—were included in an economic evaluation within the trial. Data were collected by phone every 3 months for 1 year. Direct and indirect costs were calculated from a payer perspective. Health-related quality of life was assessed with a general health rating scale. ICERs were calculated for one 20% improvement (ASAS20), for one partial remission and for one quality-adjusted life year (QALY) gained. Results: The Q6 regimen was significantly more efficacious than the DEM regimen but also more costly (€22 388 vs €17 596; p&lt;0.001), because it required significantly more infliximab infusions per patient (8.4 vs 6.2). The ICERs of the Q6 to DEM regimen were €15 841 for one ASAS20 response, €23 296 for one partial remission and €50 760 for one QALY gained. Conclusion: The administration of infliximab every 6 weeks is cost effective as compared with a DEM regimen; however, the ICER is close to the acceptability threshold of €50 000 for one QALY gained. Trial registration number: NCT 00439283.
STUDIES ON NATURAL IMMUNITY TO PNEUMOCOCCUS TYPE III
Authors: John F. Enders, Morris F. Shaffer, Chao-Jen Wu
Journal: The Journal of Experimental Medicine (1936)

AMONG THE EXPERIMENTAL FINDINGS REPORTED IN THIS PAPER TO WHICH WE WISH TO GIVE PARTICULAR EMPHASIS ARE THE FOLLOWING: 1. The results which follow the intravenous injection into rabbits of two strains of Pneumococcus Type III of different degrees of virulence vary with the state of the capsule. Thus when this structure is completely developed both remain in the blood. A culture of either strain begins to become susceptible to the blood-clearing mechanism contemporaneously with the onset of capsular degeneration and the initiation of other concomitant changes at the surface of the organism (cf Paper II), which occur much earlier with the less virulent strain. 2. When, in either case, removal from the blood stream occurs, this is effected by the phagocytic cells of the body. There is no suggestion that a new or unknown mechanism is involved. The greatest share of the burden is borne by the fixed phagocytic cells of the liver and spleen, and to a less extent by those of the lung and bone marrow. Nevertheless, it has been demonstrated that the polymorphonuclear leucocytes may also participate. 3. Phagocytosis by the leucocytes of the normal animal either in intro or in vivo has been observed only at such a time as the capsule has become impaired. Ingestion of the organisms by the fixed tissue cells appears also to be effective only under the same condition and is accordingly observed with much younger cultures of the less virulent strain. 4. Following their removal from the blood and their accumulation within the fixed phagocytes of the organs, destruction of most of the cocci proceeds within 2 to 4 hours. Both strains are destroyed provided they are in the state favorable to phagocytic attack. 5. Evidence has been presented which indicates that just as in vitro, so in a local area of inflammation within the body, aging with attendant capsular loss and increasing susceptibility to phagocytosis may take place. 6. With organisms from either strain a variable period of lag follows their injection into the blood stream, even when they are introduced in a state of active multiplication and complete encapsulation. 7. Differences in virulence for rabbits of two strains of Pneumococcus Type III do not imply that this animal possesses a defensive mechanism which is absent in other species, since it has been possible to demonstrate similar differences when the organisms are injected intravenously into mice. This fact indicates that the factors determining the degree of virulence of these strains are to be sought in the organisms themselves, rather than in the kind of host.
PULMONARY DIFFUSING CAPACITY: A COMPARISON OF BREATH-HOLDING AND STEADY STATE METHODS USING CARBON MONOXIDE
Authors: G. H. Apthorp, R. Marshall
Journal: Journal of Clinical Investigation (1961)

ing the diffusing capacity of the lungs for carbon monoxide (DL). Two of these are steady state methods, and they differ in the methods used to calculate the mean alveolar carbon monoxide tension. Filley, MacIntosh and Wright (1) calculate the alveolar Pco indirectly, assuming the physiological dead space for carbon dioxide to be the same as that for carbon monoxide, while Bates, Boucot and Dormer (2) use the end-tidal Pco as the mean alveolar Pco. The third method is the single breath method of Krogh and Krogh (3) as modified by Ogilvie, Forster, Blakemore and Morton (4). Each method in theory measures the total resistance to gas diffusion offered by the structures that lie between the gas in the alveoli and the hemoglobin within the red cells of the pulmonary capillaries. The results obtained by each method differ in normal subjects; and in disease states, such as emphysema, the differences may be great. While the different results obtained in similar subjects by the two steady state methods can largely be explained by the different methods of estimating the mean alveolar Pco (5), the breath-holding method consistently gives higher results than either of the steady state methods (6). Marshall (7) has recently compared the breath-holding method of
Carcinogenic Properties of Increased Oxygen Tensions. I. Effects on Radiation-Induced Mammary Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Cornelia M. Dettmer, Simon Kramer, Sheldon F. Gottlieb, Gonzalo E. Aponte
Journal: JNCI Journal of the National Cancer Institute (1968)

It has been reported that exposure to increased oxygen concentrations will enhance the incidence of chemically induced tumors in the lungs of mice. Such effects of oxygen on neoplastic transformation are important in hyperbaric medicine and space programs. To investigate more fully the carcinogenic-enhancing properties of oxygen, we studied the relationship of increased oxygen tensions on radiation-induced mammary tumors in the female Sprague-Dawley rat. The animals were exposed to the following regimen 1 week after 400 rads whole-body irradiation: 1 hour daily, 5 consecutive days a week for 6 weeks to either 1 atmospheres absolute (ATA) air (Po2 152 mm Hg), 3 ATA air (Po2 456 mm Hg), 1 ATA oxygen (Po2 760 mm Hg), or 3 ATA oxygen (Po2 2280 mm Hg). The data indicate that increased oxygen tensions speed up the time of emergence of the primary tumors and enhance the incidence of tumors. Increases in the total number of tumors as well as the number of second tumors per animal were noted. The higher oxygen tensions produced no changes in location or histologic type of tumor.
A Follow-up Study of Colonic Epithelial Proliferation as a Biomarker in a Native-American Family with Hereditary Nonpolyposis Colon Cancer
Authors: P. M. Lynch, M. J. Wargovich, H. T. Lynch, C. Palmer, S. Lanspa, T. Drouhard, J. Lynch
Journal: JNCI Journal of the National Cancer Institute (1991)

A 7-year follow-up study of colonic mucosa proliferation markers was conducted on members of a Native-American family with hereditary nonpolyposis colon cancer. Reproducibility of a tritiated thymidine autoradiography assay for labeling indexes during this 7-year biologically significant time frame was established. A good correlation between tritiated thymidine and a newer technique, bromodeoxyuridine immunoperoxidase staining, was seen. No confounding effect could be attributed to standard colon preparation. On average, both baseline and follow-up values for epithelial proliferation were within the accepted normal range. The presence of essentially normal labeling indexes among colon cancer patients and their high-risk offspring suggests the possibility of the significant effect of dietary factors in reducing proliferation. Such factors may account for the low risk of colon cancer that characterizes the Native-American population in the American Southwest.
Diabetes in relation to breast cancer relapse and all-cause mortality in elderly breast cancer patients: a FOCUS study analysis
Authors: M. Kiderlen, N.A. de Glas, E. Bastiaannet, C.C. Engels, W. van de Water, A.J.M. de Craen, J.E.A. Portielje, C.J.H. van de Velde, G.J. Liefers
Journal: Annals of Oncology (2013)

BackgroundIn developed countries, 40% of breast cancer patients are >65 years of age at diagnosis, of whom 16% additionally suffer from diabetes. The aim of this study was to assess the impact of diabetes on relapse-free period (RFP) and overall mortality in elderly breast cancer patients.Patients and MethodsPatients were selected from the retrospective FOCUS cohort, which contains detailed information of elderly breast cancer patients. RFP was calculated using Fine and Gray competing risk regression models for patients with diabetes versus patients without diabetes. Overall survival was calculated by Cox regression models, in which patients were divided into four groups: no comorbidity, diabetes only, diabetes and other comorbidity or other comorbidity without diabetes.ResultsOverall, 3124 patients with non-metastasized breast cancer were included. RFP was better for patients with diabetes compared with patients without diabetes (multivariable HR 0.77, 95% CI 0.59–1.01), irrespective of other comorbidity and most evident in patients aged ≥75 years (HR 0.67, 95% CI 0.45–0.98). The overall survival was similar for patients with diabetes only compared with patients without comorbidity (HR 0.86, 95% CI 0.45-0.98), while patients with diabetes and additional comorbidity had the worst overall survival (HR 1.70, 95% CI 1.44–2.01).ConclusionWhen taking competing mortality into account, RFP was better in elderly breast cancer patients with diabetes compared with patients without diabetes. Moreover, patients with diabetes without other comorbidity had a similar overall survival as patients without any comorbidity. Possibly, unfavourable effects of (complications of) diabetes on overall survival are counterbalanced by beneficial effects of metformin on the occurrence of breast cancer recurrences.
LOS ANGELES SUICIDE PREVENTION CENTER
Authors: ROBERT E. LITMAN, EDWIN S. SHNEIDMAN, NORMAN L. FARBEROW
Journal: American Journal of Psychiatry (1961)

Suicidal reactions represent a complicated synthesis of mental illness and interpersonal or social-living problems. Many potentially suicidal persons can be greatly helped by appropriate psychiatric treatment. Often pre-suicidal behavior is associated with strong defensive efforts (in patient and relatives) to deny the problems and avoid facing the illness. Opportunities to circumvent the resistance should be seized whenever possible. Some benefits of a Suicide Prevention Center are: 1. Some pre-suicidal persons get appropriate treatment who might not otherwise get treatment. 2. Much needed data, especially longitudinal studies of the lives of pre-suicidal persons, are collected and analyzed. 3. The S.P.C. facilitates the functioning of a number of different agencies and community resources where they are concerned with suicide, leading to smoother handling of pre-suicidal persons. 4. The S.P.C. helps provide educational information for police, physicians, judges and others in a position to recognize pre-suicidal persons. 5. Proper publicity might help overcome the popular prejudice against psychiatric hospitalization. 6. The S.P.C. offers an opportunity for experimental activities such as psychiatric emergency call service and the use of supervised volunteers in emergency situations. Finally, it should be said that there is more to suicide than mental illness. In a sense, self-destruction reflects the relationship of the individual to his community and his civilization. It may be that a certain minimal level or rate of suicide is "built in" to our competitive culture, part of the price we pay for our prized individual freedom to dispose of our lives as we wish. As the Suicide Prevention Center develops we hope to increase our knowledge of suicide, sharpen our diagnostic accuracy and contribute answers to some of the questions we have raised, but as far as we can see into the future, suicide and suicide prevention will continue to present new problems.
Collecting Duct-Derived Cells Display Mesenchymal Stem Cell Properties and Retain Selective In Vitro and In Vivo Epithelial Capacity
Authors: Joan Li, Usukhbayar Ariunbold, Norseha Suhaimi, Nana Sunn, Jinjin Guo, Jill A. McMahon, Andrew P. McMahon, Melissa Little
Journal: Journal of the American Society of Nephrology (2014)

We previously described a mesenchymal stem cell (MSC)-like population within the adult mouse kidney that displays long-term colony-forming efficiency, clonogenicity, immunosuppression, and panmesodermal potential. Although phenotypically similar to bone marrow (BM)-MSCs, kidney MSC-like cells display a distinct expression profile. FACS sorting from Hoxb7/enhanced green fluorescent protein (GFP) mice identified the collecting duct as a source of kidney MSC-like cells, with these cells undergoing an epithelial-to-mesenchymal transition to form clonogenic, long-term, self-renewing MSC-like cells. Notably, after extensive passage, kidney MSC-like cells selectively integrated into the aquaporin 2-positive medullary collecting duct when microinjected into the kidneys of neonatal mice. No epithelial integration was observed after injection of BM-MSCs. Indeed, kidney MSC-like cells retained a capacity to form epithelial structures in vitro and in vivo, and conditioned media from these cells supported epithelial repair in vitro. To investigate the origin of kidney MSC-like cells, we further examined Hoxb7(+) fractions within the kidney across postnatal development, identifying a neonatal interstitial GFP(lo) (Hoxb7(lo)) population displaying an expression profile intermediate between epithelium and interstitium. Temporal analyses with Wnt4(GCE/+):R26(tdTomato/+) mice revealed evidence for the intercalation of a Wnt4-expressing interstitial population into the neonatal collecting duct, suggesting that such intercalation may represent a normal developmental mechanism giving rise to a distinct collecting duct subpopulation. These results extend previous observations of papillary stem cell activity and collecting duct plasticity and imply a role for such cells in collecting duct formation and, possibly, repair.
Additive preventive effect of influenza and pneumococcal vaccines in elderly persons
Authors: B. Christenson, J. Hedlund, P. Lundbergh, Å. Örtqvist
Journal: European Respiratory Journal (2004)

In 1999, all individuals ≥65 yrs of age (n=258,754) in Stockholm County, Sweden, were offered influenza and pneumococcal vaccination in a prospective study on the effectiveness of these vaccines in reducing the need for hospital treatment and death due to influenza, pneumonia and invasive pneumococcal disease (IPD). Data on hospitalisation and mortality during 1 yr were obtained from the administrative database in Stockholm County Council. Vaccination was performed in 124,702 (48%) subjects; 72,107 had both vaccines, 29,346 only had the influenza vaccine and 23,249 only had the pneumococcal vaccine. Compared with the unvaccinated cohort, a lower incidence of hospitalisation for all end-point diagnoses was seen in vaccinated persons. An additive effectiveness of vaccination was seen when both vaccines were given, with a reduction of hospital admissions for influenza (37%), pneumonia (29%) and IPD (44%). In-hospital mortality for pneumonia was significantly lower in those who received both vaccines, than in unvaccinated persons. To conclude, vaccination with influenza and pneumococcal vaccines together was effective in reducing the need for hospital admission for influenza and pneumonia. There was a strong indication that pneumococcal vaccination alone, was effective not only in the prevention of invasive pneumococcal disease, but also of pneumonia overall, although to a low degree.
Pegylated (40 KDA) interferon alfa-2a (PEGASYS®) in new combination therapies: a report of a randomized, multicenter efficacy and safety study
Authors: A.M. Di Bisceglie, D.E. Bernstein, V.R. Rustgi, N. Gitlin, L.J. Jeffers, D. Simon, J. Campagna, S.C. Pappas
Journal: Journal of Hepatology (2001)
Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants
Authors: W Anees
Journal: Thorax (2002)

Background: Despite having a work related deterioration in peak expiratory flow (PEF), many workers with occupational asthma show a low degree of within day diurnal variability atypical of non-occupational asthma. It was hypothesised that these workers would have a neutrophilic rather than an eosinophilic airway inflammatory response. Methods: Thirty eight consecutive workers with occupational asthma induced by low molecular weight agents underwent sputum induction and assessment of airway physiology while still exposed at work. Results: Only 14 (36.8%) of the 38 workers had sputum eosinophilia (&gt;2.2%). Both eosinophilic and non-eosinophilic groups had sputum neutrophilia (mean (SD) 59.5 (19.6)% and 55.1 (18.8)%, respectively). The diurnal variation and magnitude of fall in PEF during work periods was not significantly different between workers with and without sputum eosinophilia. Those with eosinophilia had a lower forced expiratory volume in 1 second (FEV<sub>1</sub>; 61.4% <i>v</i> 83% predicted, mean difference 21.6, 95% confidence interval (CI) 9.2 to 34.1, p=0.001) and greater methacholine reactivity (geometric mean PD<sub>20</sub> 253 μg <i>v</i> 1401 μg, p=0.007). They also had greater bronchodilator reversibility (397 ml <i>v</i> 161 ml, mean difference 236, 95% CI of difference 84 to 389, p=0.003) which was unrelated to differences in baseline FEV<sub>1</sub>. The presence of sputum eosinophilia did not relate to the causative agent, duration of exposure, atopy, or lack of treatment. Conclusions: Asthma caused by low molecular weight agents can be separated into eosinophilic and non-eosinophilic pathophysiological variants with the latter predominating. Both groups had evidence of sputum neutrophilia. Sputum eosinophilia was associated with more severe disease and greater bronchodilator reversibility but no difference in PEF response to work exposure.
EULAR recommendations for the management of knee osteoarthritis
Authors: A S M JAWAD
Journal: Annals of the Rheumatic Diseases (2001)

EULAR recommendations for the management of knee osteoarthritisI welcome the publication of the EULAR recommendations for the management of knee osteoarthritis by the EULAR Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). 1However, it is out of date and has been superseded by other more up to date publications such as the recommendations for the medical management of osteoarthritis of the hip and knee by the American College of Rheumatology (ACR) Subcommittee on Osteoarthritis Guidelines 2 and another review of the medical management of osteoarthritis. 3 The newer COX-1 sparing nonsteroidal anti-inflammatory drugs, rofecoxib and celecoxib are not discussed in the EULAR recommendations, but they have been included in the other reviews. 2 3 My second criticism of the report is that it contains statements such as " SYSADOA... may possess structure modification properties", which is misleading and may lead to widespread use of these drugs in the absence of good evidence.Although the Annals of the Rheumatic Diseases is the oYcial EULAR journal, EULAR reports should be peer reviewed before publication.The ACR recommendations for the management of osteoarthritis of the hip and knee were only accepted in a revised format.
Mechanism of Doxorubicin-Induced Inhibition of Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Gene Transcription
Authors: Masashi Arai, Akemi Yoguchi, Takako Takizawa, Tomoyuki Yokoyama, Tsugiyasu Kanda, Masahiko Kurabayashi, Ryozo Nagai
Journal: Circulation Research (2000)

Doxorubicin (DOX)-induced cardiomyopathy has been found to be associated with impaired Ca(2+) handling in the sarcoplasmic reticulum (SR), leading to reduced cardiac function. We have recently demonstrated that expression of mRNA encoding sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2), a major Ca(2+) transport protein in SR, is markedly decreased in DOX-treated hearts. To extend this observation, we have dissected the molecular mechanisms by which DOX downregulates SERCA2 gene transcription. Using cultured rat neonatal cardiac myocytes, we found that the antioxidant N-acetylcysteine blocked the DOX-induced decrease in SERCA2 mRNA levels, as well as the DOX-induced increase in H(2)O(2) concentration; thus, H(2)O(2) is an intracellular mediator of DOX activity. Using a luciferase reporter assay, we found that the sequence from -284 to -72 bp in the 5' flanking region of the SERCA2 gene has a DOX-responsive element. Although several transcription factors have putative binding motifs in this region of the SERCA2 gene, only the expression of Egr-1 mRNA and the binding of Egr-1 protein to the 5' regulatory sequence of SERCA2 gene increased markedly after DOX administration. We also found that overexpression of Egr-1 was associated with a significant reduction in SERCA2 gene transcription. In addition, Egr-1 antisense oligonucleotides blocked the DOX-induced reduction in SERCA2 mRNA, suggesting that Egr-1 is a transcriptional inhibitor of the SERCA2 gene in DOX-induced cardiomyopathy. We observed activation of 3 mitogen-activated protein kinases (MAPKs), p44/42 MAPK, p38 MAPK, and stress-activated MAPK/Jun N-terminal kinase, by DOX, but only a specific inhibitor of the p44/42 MAPK kinase suppressed the effects of DOX on Egr-1 and SERCA2 mRNA expression. These findings indicate that reactive oxygen intermediates, the transcription factor Egr-1, and p44/42 MAPK are critical elements in the transcriptional regulation of the SERCA2 gene in response to DOX.