tbuckley/cabot-search huggingface dataset:
Community-acquired pneumonia in chronic obstructive pulmonary disease: a Spanish multicenter study.
Authors: A Torres, J Dorca, R Zalacaín, S Bello, M El-Ebiary, L Molinos, M Arévalo, J Blanquer, R Celis, M Iriberri, E Prats, R Fernández, R Irigaray, J Serra
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Community-acquired pneumonia (CAP) is an infectious illness that frequently motivates hospital admission when comorbid conditions are present. However, the epidemiology of CAP in relation to the underlying disease of the patients is not well known. We performed a prospective multicenter study with the aim of assessing the clinical characteristics, etiology, and outcome of chronic obstructive pulmonary disease (COPD) patients with CAP. Between October 1992 and December 1994 we studied 124 COPD patients (mean FEV1 40 +/- 11% of predicted, mean FVC/FEV1 49 +/- 10) admitted because of CAP to one of the participating centers. An attempt to obtain an etiologic diagnosis was performed by means of blood cultures (n = 123), sputum cultures (n = 97), pleural fluid cultures (n = 17), protected specimen brush samples (n = 41), percutaneous transthoracic needle aspiration (n = 41), and serology (n = 106). Etiologic diagnosis was achieved in 80 (64%) of cases, however, diagnosis based upon valid techniques was only possible in 73 (59%) cases. The main causal microorganisms were the following: Streptococcus pneumoniae in 32 (43%), Chlamydia pneumoniae in 9 (12%), Hemophilus influenzae in 7 (9%), Legionella pneumophila in 7 (9%), Streptococcus viridans in 3 (4%), Coxiella burnetii in 3 (4%), Mycoplasma pneumoniae in 2 (3%), Nocordia asteroides 2, Aspergillus ssp. 1, and others 10. In three of these cases the etiology was polymicrobial. Bacteremia was present in 19 (15%) cases; S. pneumoniae was the most frequent isolate (13 cases). Antibiotic treatment was modified in 22 cases due to etiologic findings, and in 9 due to therapeutic failure. Ten patients died (8%), and 22 needed mechanical ventilation, the mortality rate in the latter population being 23%. Total or partial resistance of S. pneumoniae to penicillin was observed in 10 of 32 (31%) isolations, and to erythromycin in 2 (6%). The results of this study are important for the standardization of empiric antibiotic strategies in COPD patients with pneumonia.
Customized Feedback to Patients and Providers Failed to Improve Safety or Quality of Diabetes Care
Authors: Patrick J. O'Connor, JoAnn Sperl-Hillen, Paul E. Johnson, William A. Rush, A. Lauren Crain
Journal: Diabetes Care (2009)

OBJECTIVE To assess whether providing customized clinical information to patients and physicians improves safety or quality of diabetes care. RESEARCH DESIGN AND METHODS Study subjects included 123 primary care physicians and 3,703 eligible adult diabetic patients with elevated A1C or LDL cholesterol, who were randomly assigned to receive customized feedback of clinical information as follows: 1) patient only, 2) physician only, 3) both the patient and physician, or 4) neither patient nor physician. In the intervention groups, patients received customized mailed information or physicians received printed, prioritized lists of patients with recommended clinical actions and performance feedback. Hierarchical models were used to accommodate group random assignment. RESULTS Study interventions did not improve A1C test ordering (P = 0.35) and negatively affected LDL cholesterol test ordering (P &amp;lt; 0.001) in the 12 months postintervention. Interventions had no effect on LDL cholesterol values (P = 0.64), which improved in all groups over time. Interventions had a borderline unfavorable effect on A1C values among those with baseline A1C ≥7% (P = 0.10) and an unfavorable effect on A1C values among those with baseline A1C ≥8% (P &amp;lt; 0.01). Interventions did not reduce risky prescribing events or increase treatment intensification. Time to next visit was longer in all intervention groups compared with that for the control group (P &amp;lt; 0.05). CONCLUSIONS Providing customized decision support to physicians and/or patients did not improve quality or safety of diabetes care and worsened A1C control in patients with baseline A1C ≥8%. Future researchers should consider providing point-of-care decision support with redesign of office systems and/or incentives to increase appropriate actions in response to decision-support information.
Identification of HLA-A24-Restricted CTL Epitope from Cancer-Testis Antigen, NY-ESO-1, and Induction of a Specific Antitumor Immune Response
Authors: Hiroshi Yamaguchi, Fumiaki Tanaka, Mitsuhiko Ohta, Hiroshi Inoue, Masaki Mori
Journal: Clinical Cancer Research (2004)

Abstract Purpose: For the development of peptide-based, cancer-specific immunotherapy, the identification of CTL epitopes from additional tumor antigens is very important. NY-ESO-1, a cancer–testis antigen, is considered to be a promising target of tumor-specific immunotherapy. Because HLA-A24-expressing individuals cover &amp;gt;60% in the population of Japan, we aim at identifying NY-ESO-1-encoded peptide presented by HLA-A24. Experimental Design: In our study, a HLA-A24-restricted CTL epitope was identified by using the following four-step procedure: (a) computer-based epitope prediction from the amino acid sequence of NY-ESO-1 antigen; (b) peptide-binding assay to determine the affinity of the predicted peptide with HLA-A24 molecule; (c) stimulation of primary T-cell response against the predicted peptides in vitro; and (d) testing of the induced CTLs toward various carcinoma cells expressing NY-ESO-1 antigen and HLA-A24. Results: Of the tested peptides, effectors induced by a peptide of NY-ESO-1 at residue position 158–166 lysed three kinds of carcinoma cells expressing both NY-ESO-1 and HLA-A24. Our results indicate that peptide NY-ESO-1 (158–166) (LLMWITQCF) is a new HLA-A24-restricted CTL epitope capable of inducing NY-ESO-1-specific CTLs in vitro mediating HLA class I-restricted manner. Conclusions: We identified a novel HLA-A24-restricted NY-ESO-1-derived epitope peptide (LLMWITQCF) that could induce specific CTLs from the peripheral blood mononuclear cells of HLA-A24+ healthy donors. This peptide would be useful in further evaluating the clinical utility of peptide-based, cancer-specific immunotherapy against various histological tumors.
Racial Variation in CAG Repeat Lengths Within the Androgen Receptor Gene Among Prostate Cancer Patients of Lower Socioeconomic Status
Authors: Charles L. Bennett, Douglas K. Price, Simon Kim, Dachao Liu, Borko D. Jovanovic, Derek Nathan, Margaret E. Johnson, Jeffrey S. Montgomery, Kelly Cude, Justin C. Brockbank, Oliver Sartor, William D. Figg
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate (1) whether there were racial differences in the androgen receptor gene CAG repeat length and in clinical or laboratory attributes of prostate cancer at the time of diagnosis; (2) whether there were differences in race, Gleason score, prostate-specific antigen (PSA) level, and stage at diagnosis by androgen receptor gene CAG repeat length; and (3) whether sociodemographic, clinical, and laboratory based factors might be associated with advanced-stage prostate cancer. To our knowledge, our study is the first to report on CAG repeat lengths in a cohort of prostate cancer patients, which includes large numbers of African-American men. METHODS: CAG repeat lengths on the androgen receptor gene were evaluated for 151 African-American and 168 white veterans with prostate cancer. The χ 2 test, t test, and logistic regression analyses were used to evaluate the associations between CAG repeat lengths and race, stage, histologic grade, and PSA levels at diagnosis. RESULTS: The mean age of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA levels ≥ 10 ng/dL. Mean androgen receptor gene CAG repeat length for white veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans (P = .001). Men with shorter CAG repeats were more likely to have stage D prostate cancer (P = .09) but were not more likely to have a higher PSA concentration or Gleason score. CONCLUSION: In this cohort of men with prostate cancer, short CAG repeat length on the androgen receptor gene was associated with African-American race and possibly with higher stage but not with other clinical or pathologic findings.
Pharmacological Characterization of T Cell-Induce Bronchoconstriction in the Mice
Authors: Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Akemi Ohtomo-Abe, Hiroaki Hayashi, Kentaro Watarai, Chihiro Mitsui, Chiyako Oshikata, Kiyoshi Sekiya, Takahiro Tsuburai, Yuji Maeda, Mamoru Ohtomo, Yuma Fukutomi, Masami Taniguchi, Kazuo Akiyama, Takayuki Ohtomo, Osamu Kaminuma
Journal: Journal of Allergy and Clinical Immunology (2015)
Pituitary adenomas in man and mouse: oncogenic potential of a truncated fibroblast growth factor receptor 4
Authors: Malcolm J. Low
Journal: Journal of Clinical Investigation (2002)

Despite their prevalence and significant morbidity, the etiology of most pituitary adenomas remains an enigma. Hypotheses that regard the growth factor milieu as a primary cause of pituitary oncogenesis have seesawed with others that maintain the primacy of cell-autonomous transforming events. Like other endocrine glands, the pituitary has a remarkable capacity to respond to physiological demands by either hyperplasia or hypoplasia of specific cell types. These reversible changes, mediated by a diverse set of signaling molecules and their corresponding receptors, could set the stage for pathological overgrowth of clonal cell populations within this tissue. Particular interest has settled on members of the fibroblast growth factor (FGF) family as tumorigenic factors. However, very few bona fide molecular pathogenic mechanisms of pituitary adenoma development and progression have stood the tests of time, causality, and replication in independent clinical populations (Table ​(Table11).
Transesophageal echocardiography improves risk assessment of thrombolysis of prosthetic valve thrombosis: results of the international PRO-TEE registry
Authors: Ann T Tong, Raymond Roudaut, Mehmet Özkan, Alex Sagie, Maie S.A Shahid, Sergio C Pontes, Francesc Carreras, Steven E Girard, Samir Arnaout, Raymond F Stainback, Ravi Thadhani, William A Zoghbi
Journal: Journal of the American College of Cardiology (2004)
Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma
Authors: J. J. Parker, K. R. Dionne, R. Massarwa, M. Klaassen, N. K. Foreman, L. Niswander, P. Canoll, B. K. Kleinschmidt-DeMasters, A. Waziri
Journal: Neuro-Oncology (2013)

Tissue invasion is a hallmark of most human cancers and remains a major source of treatment failure in patients with glioblastoma (GBM). Although EGFR amplification has been previously associated with more invasive tumor behavior, existing experimental models have not supported quantitative evaluation of interpatient differences in tumor cell migration or testing of patient-specific responses to therapies targeting invasion. To explore these questions, we optimized an ex vivo organotypic slice culture system allowing for labeling and tracking of tumor cells in human GBM slice cultures. With use of time-lapse confocal microscopy of retrovirally labeled tumor cells in slices, baseline differences in migration speed and efficiency were determined and correlated with EGFR amplification in a cohort of patients with GBM. Slices were treated with gefitinib to evaluate anti-invasive effects associated with targeting EGFR. Migration analysis identified significant patient-to-patient variation at baseline. EGFR amplification was correlated with increased migration speed and efficiency compared with nonamplified tumors. Critically, gefitinib resulted in a selective and significant reduction of tumor cell migration in EGFR-amplified tumors. These data provide the first identification of patient-to-patient variation in tumor cell migration in living human tumor tissue. We found that EGFR-amplified GBM are inherently more efficient in their migration and can be effectively targeted by gefitinib treatment. These data suggest that stratified clinical trails are needed to evaluate gefitinib as an anti-invasive adjuvant for patients with EGFR-amplified GBM. In addition, these results provide proof of principle that primary slice cultures may be useful for patient-specific screening of agents designed to inhibit tumor invasion.
SOME OBSERVATIONS ON THE SPECIFICITY OF BACTERIAL ALLERGY TO CERTAIN OF THE NEISSERIAE
Authors: C. Phillip Miller, Ruth Castles
Journal: The Journal of Experimental Medicine (1933)

By means of the reaction to intracutaneous inoculation with bacterial suspensions in amounts of 0.2 cc., bacterial allergy was demonstrated in rabbits into which had been implanted agar foci containing either gonococci, meningococci, M. catarrhalis, or Bact. lepisepticum. The criterion of hypersensitiveness was the relative size and intensity of reaction evoked by an identical dose in "agar focus" and control rabbits. Rabbits sensitized to gonococci or meningococci usually reacted indistinguishably to either of these organisms, but were less allergic to M. catarrhalis. Similarly, animals sensitized to M. catarrhalis gave moderate but not maximal responses to the two former organisms. Cross-reactions did not occur between Bact. lepisepticum and any of the three Neisseriae. Animals sensitized to the four organisms mentioned reacted no more intensely than did controls to hemolytic streptococci, staphylococci, and rough pneumococci. The hypersensitive state was found to begin early in the 2nd week and to end usually by the 4th week, being at its height in most instances on the 10th to 12th days. The number of organisms contained in the agar focus determined the success of the sensitization only to this extent, that very small and very large inocula failed to evoke the allergic state. Rabbits immunized by intravenous injection of live organisms developed cutaneous reactions indistinguishable from those in controls. The "secondary rise" of Andrewes, Derick, and Swift was rarely observed.
Highly Active Antiretroviral Therapy in AIDS-Associated Kaposi's Sarcoma: Implications for the Design of Therapeutic Trials in Patients With Advanced, Symptomatic Kaposi's Sarcoma
Authors: Susan E. Krown
Journal: Journal of Clinical Oncology (2004)

TO THE EDITOR: The article by Dr Krown provides very appropriate and timely considerations with regard to the management of patients with advanced, symptomatic, AIDS-related Kaposi’s sarcoma (AIDS-KS) in the era of highly active antiretroviral therapy (HAART) and suggests, on the basis of a comprehensive review of the literature, that in T1 (according to the AIDS Clinical Trials Group [ACTG] staging classification) symptomatic KS patients, concomitant chemotherapy should be added to HAART without awaiting a response to HAART. Moreover, the author, referencing our study, states that “T1 and T0 groupings have been associated with distinct survival distribution.” In response, we would like to clarify our data as reported by Dr Krown. We believe that our data may help to better define which group of patients within the T1 category need a timely institution of chemotherapy concomitantly to HAART, and for which group it is too risky to await a possible response to HAART. In our study, we collected clinical and survival data from 211 patients with AIDS-KS enrolled in two prospective cohort studies beginning in 1996, the time when HAART became available in Italy, with the aim of validating the ACTG staging system for AIDS-KS in the HAART era. All patients received HAART. Our analysis identified two different risk categories: a good-risk group (T0S0, T1S0, and T0S1) and a poor-risk group (T1S1). The 3-year survival rate of patients with T1S1 was 53%, significantly lower than the 3-year survival rates of patients with T0S0, T1S0, and T0S1, which were 88%, 80%, and 81%, respectively (P .0001). Therefore, the T category alone does not provide an appropriate survival discrimination, as occurred in the pre-HAART period. When we considered only patients with pulmonary involvement (namely,Tp1) as compared with T1 patients without pulmonary disease (namely,Tp0), the 3-year survival rate was 46% for Tp1 and 77% for Tp0 patients (P .0002), indicating that patients with pulmonary involvement identify the group of patients with the poorest prognosis, independent of the other ACTG variables. Therefore, we believe that we were able to identify, within the T1 category, a specific subgroup of KS patients (ie, T1S1, Tp1) with an unfavorable survival rate in whom HAART and concomitant chemotherapy should be used.
Partial Contribution of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)/TRAIL Receptor Pathway to Antitumor Effects of Interferon-α/5-Fluorouracil against Hepatocellular Carcinoma
Authors: Tameyoshi Yamamoto, Hiroaki Nagano, Masato Sakon, Hisashi Wada, Hidetoshi Eguchi, Motoi Kondo, Bazarragchaa Damdinsuren, Hideo Ota, Masato Nakamura, Hiroshi Wada, Shigeru Marubashi, Atsushi Miyamoto, Keizo Dono, Koji Umeshita, Shoji Nakamori, Hideo Yagita, Morito Monden
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNα and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). Experimental Design: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNα, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNα-induced cytotoxic effects of PBMC on HCC cell lines were examined by 51Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. Results: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNα induced TRAIL on CD4+ T cells, CD14+ monocytes, and CD56+ NK cells. Treatment of effector cells by IFNα and target HCC cells by 5-FU enhanced the cytotoxicity of CD14+ monocytes and CD56+ NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNα/5-FU combination therapy, and TRAIL+ mononuclear cells were found in cancer tissue of a responder. Conclusion: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNα and 5-FU combination therapy.
Effects of dietary fat on postprandial substrate oxidation and on carbohydrate and fat balances.
Authors: J P Flatt, E Ravussin, K J Acheson, E Jéquier
Journal: Journal of Clinical Investigation (1985)

To study the effect of dietary fat on postprandial substrate utilization and nutrient balance, respiratory exchange was determined in seven young men for 1 h before and 9 h after the ingestion of one of three different breakfasts: i.e., bread, jam, and dried meat (482 kcal: 27% protein, 62% carbohydrate, and 11% fat); bread, jam, and dried meat plus 50 g of margarine containing long-chain triglycerides (LCT); or bread, jam, and dried meat plus 40 g medium-chain triglycerides (MCT) and 10 g LCT margarine (858 kcal: 15% protein, 35% carbohydrate, and 50% fat). Plasma glucose concentrations peaked 45 min after the start of the meals. When compared with the low fat meal, the LCT margarine supplement had no effect at any time on circulating glucose and insulin concentrations, nor on the respiratory quotient. When MCTs were consumed, plasma glucose and insulin concentrations remained lower and plasma FFA concentrations higher during the first 2 h. 9 h after the breakfasts, the amounts of substrates oxidized were similar in each case, i.e., approximately 320, 355, and 125 kcal for carbohydrate, fat, and protein, respectively. This resulted in comparable carbohydrate (mean +/- SD = -22 +/- 32, -22 +/- 37, and -24 +/- 22 kcal) and protein balances (-7 +/- 9, +7 +/- 7, and -8 +/- 11 kcal) after the low fat, LCT- and MCT-supplemented test meals, respectively. However, after the low fat meal, the lipid balance was negative (-287 +/- 60 kcal), which differed significantly (P less than 0.001) from the fat balances after the LCT- and MCT-supplemented meals, i.e., +60 +/- 33 and +57 +/- 25 kcal, respectively. The results demonstrate that the rates of fat and of carbohydrate oxidation are not influenced by the fat content of a meal.
Association of complementation group and mutation type with clinical outcome in Fanconi anemia
Authors: Laurence Faivre, Philippe Guardiola, Cathryn Lewis, Inderjeet Dokal, Wolfram Ebell, Ariana Zatterale, Cigdem Altay, Janet Poole, David Stones, Mei Lan Kwee, Margreet van Weel-Sipman, Charmaine Havenga, Neil Morgan, Johan de Winter, Martin Digweed, Anna Savoia, Jan Pronk, Thomas de Ravel, Stander Jansen, Hans Joenje, Eliane Gluckman, Christopher G. Mathew
Journal: Blood (2000)
Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats
Authors: J M Mariadason, A Catto-Smith, P R Gibson
Journal: Gut (1999)

BACKGROUND Dietary fibre influences the turnover and differentiation of the colonic epithelium, but its effects on barrier function are unknown. AIMS To determine whether altering the type and amount of fibre in the diet affects paracellular permeability of intestinal epithelium, and to identify the mechanisms of action. METHODS Rats were fed isoenergetic low fibre diets with or without supplements of wheat bran (10%) or methylcellulose (10%), for four weeks. Paracellular permeability was determined by measurement of conductance and 51 Cr-EDTA flux across tissue mounted in Ussing chambers. Faecal short chain fatty acid (SCFA) concentrations were assessed by gas chromatography, epithelial kinetics stathmokinetically, and mucosal brush border hydrolase activities spectrophotometrically. RESULTS Body weight was similar across the dietary groups. Conductance and 51 Cr-EDTA flux were approximately 25% higher in animals fed no fibre, compared with those fed wheat bran or methylcellulose in the distal colon, but not in the caecum or jejunum. Histologically, there was no evidence of epithelial injury or erosion associated with any diet. The fibres exerted different spectra of effects on luminal SCFA concentrations and pH, and on mucosal indexes, but both bulked the faeces, were trophic to the epithelium, and stimulated expression of a marker of epithelial differentiation. CONCLUSIONS Both a fermentable and a non-fermentable fibre reduce paracellular permeability specifically in the distal colon, possibly by promoting epithelial cell differentiation. The mechanisms by which the two fibres exert their effects are likely to be different.