tbuckley/cabot-search huggingface dataset:
Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes.
Authors: M R Alderson, T W Tough, S F Ziegler, K H Grabstein
Journal: The Journal of Experimental Medicine (1991)

Peripheral blood monocytes can be induced by stimuli such as bacterial lipopolysaccharide (LPS) to secrete an array of cytokines. We have studied the effects of interleukin 7 (IL-7) on human peripheral blood mononuclear cells (PBMC) and found that IL-7 is a relatively potent inducer of IL-6 secretion IL-6 protein levels were determined either by the B9 hybridoma growth factor assay or by enzyme-linked immunosorbent assay, and mRNA for IL-6 was analyzed by Northern hybridization. Detailed examination revealed that, among PBMC, monocytes, rather than lymphocytes, were secreting IL-6 in response to IL-7. In contrast to the low concentrations of IL-7 required to stimulate T cell growth and differentiation (as low as 0.1 ng/ml), relatively high concentrations of IL-7 were necessary to induce IL-6 secretion by monocytes (at least 10 ng/ml). An optimal concentration of IL-7 (100 ng/ml) induced monocytes to secrete 10-fold more IL-6 than an optimal concentration of IL-1 beta (10 ng/ml), and almost as much as LPS. However, significantly more IL-7 than IL-1 beta was required to induce detectable levels of IL-6. The kinetics of IL-6 secretion by monocytes were identical in response to IL-7, IL-1 beta, or LPS, with IL-6 protein detectable in culture supernatants as early as 2 h after the initiation of culture. IL-4 was found to markedly inhibit the ability of IL-7 or LPS to induce IL-6 mRNA and IL-6 secretion. In addition to promoting IL-6 production, IL-7 induced the secretion of immunoreactive IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by monocytes. IL-7 also induced monocyte/macrophage tumoricidal activity against a human melanoma cell target, an activity that may be related to the secretion of IL-1 alpha, IL-1 beta, and TNF-alpha. Finally, we used a whole blood culture system as a bridge to in vivo analysis to demonstrate that IL-7 induces cytokine secretion in the absence of culture medium, fetal calf serum, and adherence to plastic. Our data suggest that IL-7, in addition to regulating lymphocyte growth and differentiation, has potent effects on cells of the monocytic lineage. Thus, IL-7 may be an important mediator in inflammation and in the macrophage immune response to tumors.
Abstract P6-10-05: First-line chemotherapy versus first-line endocrine therapy in hormone receptor positive HER2 negative patients with metastatic breast cancer in China: Results of the study of breast cancer group of the Chinese Society of Clinical Oncology (CSCO)
Authors: T Wang, TT Yang, LJ Yang, HY Song, CQ Ouyang, JX Wang, CX Hu, JG Zhang, HB Xu, FJ Feng, SZ Tong, FZ Jiang
Journal: Cancer Research (2013)

Abstract Background: The primary objective for metastatic breast cancer is to prolong the patients survival. So the appropriate choice of the first-line therapy strategy is very important. For the HR-positive metastatic breast cancer, we haven't strong data to head-to-head compare the chemotherapy with endocrine therapy as the first-line treatment. Methods: Two hundreds patients with HR-positive metastatic breast cancer were enrolled at 47 cancer centers in China from 2009 to 2012. Investigators decided to give chemotherapy or endocrine therapy according to their clinical judgements. Chemotherapy and endocrine therapy regimens followed the NCCN guildline. All the patiens haven't take any treatment after relapse or metastasis. All the patients were estrogen- receptor positive and/or progesterone-receptor positive,HER2 negative. Chemotherapy or endocrine therapy was continued in the progressive disease(PD) or unacceptable toxicity. Primary endpoint was progression-free survival(PFS), second endpoints were time to failure(TTF), response rate. Results: According to the investigator judgements, one hundred patient took chemotherapy(CT arm), another one hundreds patients took endocrine therapy(ET arm). Pt characteristics were balanced between the two arms: median age 49y/50y, median disease-free survival(DFS) 40m/30m, visceral/non-visceral metastatic 52%/40%. There was more patients with ≥2 metastatic sites in CT arm than ET arm (50% vs 32%). Following up to Dec 2012, reasons for early treatment discontinuation were : PD 25 pts, toxicity 38 pts in CT arm, PD 82 pts, toxicity 2 pts in ET ram. The median PFS was 52 weeks(95% CI 23.2-80.8 weeks) and 48 weeks(95% CI 38.9-57.0 weeks) for CT arm and ET arm(P = 0.589),respectively. The median TTF was 20 weeks and 48 weeks for CT arm and ET arm,respectively(P = 0.025). Response rate was 63% and 22% for CT arm and ET arm,respectively(P&amp;lt;0.001). But clinical benefit rate(CR+PR+SD≥6months) was 67% and 69% for CT arm and ET arm,respectively(P = 0.333). Subgroup analysis showed TTF were 48 weeks in ET arm and 15 weeks in CT arm(p = 0.038) for patients who had more than 2 years DFS. TTF results also indicated significant difference in single metastatic site pts and non-visceral metastatic pts between two arms. ET arm was superior to CT arm. Conclusions: Our results indicate first-line chemotherapy has higher response rate than first-line endocrine therapy for HR-positive meatstatic breast cancer, but chemotherapy has shorter maintaining therapy time. First-line endocrine therapy was more suitable than first-line chemotherapy for pts with DFS≥2y, single metastatic site and non-visceral metastatic. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-10-05.
Post-Bronchodilator Spirometry Reference Values in Adults and Implications for Disease Management
Authors: Ane Johannessen, Sverre Lehmann, Ernst R. Omenaas, Geir Egil Eide, Per S. Bakke, Amund Gulsvik
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: International guidelines promote the use of post-bronchodilator spirometry values in the definition and severity classification of chronic obstructive pulmonary disease. However, post-bronchodilator reference values have not yet been developed.Objectives: To derive reference values for post-bronchodilator forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and to compare these reference values with locally derived and existing pre-bronchodilator reference values.Methods: Based on a random sample of a general adult population, 2,235 subjects (70% of invited subjects) performed spirometry with reversibility testing. A reference population of healthy never-smokers constituted 23% of the study population (n = 515). Reference values for median and lower-limit-of-normal pre- and post-bronchodilator lung function and bronchodilator response were modeled using quantile regression analyses.Main Results: The reference population had equal proportions of men and women in the age range 26–82 yr. Both FEV1 and FVC decreased with age and increased with height. FEV1/FVC decreased with age, although this trend was not statistically significant for men after bronchodilatation. Linear models gave the best overall fit. Lower-limit-of-normal post-bronchodilator FEV1/FVC exceeded 0.7 for both sexes. Post-bronchodilator prediction equations gave higher predicted FEV1 and FEV1/FVC than both locally derived and existing pre-bronchodilator equations. The bronchodilator response decreased with age.Conclusions: The present study is the first to develop reference values for post-bronchodilator lung function. Post-bronchodilator prediction equations can facilitate better management of patients with chronic obstructive pulmonary disease by avoiding falsely high FEV1% predicted with a subsequent underestimation of disease severity.
Intravascular ultrasound assessment of patterns of arterial remodeling in the absence of significant reference segment plaque burden in patients with coronary artery disease
Authors: Myeong-Ki Hong, Gary S Mintz, Cheol Whan Lee, Young-Hak Kim, Jae-Whan Lee, Jong-Min Song, Ki-Hoon Han, Duk-Hyun Kang, Jae-Kwan Song, Jae-Joong Kim, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2003)
Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding.
Authors: J Aramburu, L Azzoni, A Rao, B Perussia
Journal: The Journal of Experimental Medicine (1995)

The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer (NK) cells have not been elucidated. We report here that the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of several cytokines, mediates CD16-induced activation of cytokine genes in human NK cells. CD16 (Fc gamma RIIIA)-induced expression of cytokine mRNA in NK cells occurs via a CsA-sensitive and Ca(2+)-dependent mechanism. Stimulation of NK cells with CD16 ligands induces NFAT-like DNA binding activity in the nuclear extracts from these cells, as detected in electrophoretic mobility shift assays. This occurs with fast kinetics after stimulation, via a CsA-sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis. NK cell NFAT is present in the cytosol of nonstimulated cells, migrates to the nucleus upon stimulation, and can associate with AP-1. Two distinct molecules, NFATp and NFATc, have been reported to mediate NFAT activity. The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily, if not exclusively, NFATp, and Western blot analysis shows that this has the same electrophoretic mobility (approximately 120 kD) as that of T lymphocytes. NK cells do not express NFATc constitutively, but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands. However, supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester-stimulated cells at any time tested, up to 4 h. These results provide the first direct evidence that both CsA-sensitive transcription factors, NFATp and NFATc, are expressed in human NK cells, and that their activation and/or expression can be regulated in primary cells by a single stimulus, that, in the case of CD16 in NK cells, results in early activation of NFATp and subsequently induced expression of NFATc mRNA.
Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen.
Authors: A A Scalzo, N A Fitzgerald, A Simmons, A B La Vista, G R Shellam
Journal: The Journal of Experimental Medicine (1990)

The genetic basis of the control of acute splenic MCMV infection was studied after intraperitoneal inoculation of the virus. Classical Mendelian analyses using C57BL/6 (resistant) and BALB/c (susceptible) parental strains disclosed an autosomal dominant non-H-2 gene that regulates splenic virus replication. The probable location of this gene, to which we have assigned the symbol Cmv-1, is on chromosome 6 as defined by the strain distribution pattern of splenic MCMV replication in CXB recombinant inbred mice. Although there is a similar hierarchy of resistance to MCMV and HSV-1 with respect to the C57BL and BALB genetic backgrounds, the strain distribution pattern of HSV-1 replication in recombinant inbred mice suggests that Cmv-1 is not involved in restricting the spread of this virus. This is the first clear identification of a non-H-2 gene regulating the magnitude of MCMV infection. Elucidation of the function of this gene may be a fundamental step towards understanding the control of systemic CMV infection.
Evidence suggesting a role for hydroxyl radical in gentamicin-induced acute renal failure in rats.
Authors: P D Walker, S V Shah
Journal: Journal of Clinical Investigation (1988)

The protective effect of hydroxyl radical scavengers and iron chelators has strongly implicated the hydroxyl radical in several models of tissue injury. Based on in vitro studies showing gentamicin-enhanced generation of reactive oxygen metabolites in renal cortical mitochondria, we examined the effect of hydroxyl radical scavengers and iron chelators in gentamicin-induced acute renal failure. Rats treated with gentamicin (G) alone (100 mg/kg, s.c. x 8 d) developed advanced renal failure (BUN 215 +/- 30 mg/dl) compared to saline-treated controls (BUN 16 +/- 1 mg/dl, P less than 0.001). In contrast, rats treated with gentamicin and either dimethylthiourea (DMTU, an hydroxyl radical scavenger, 125 mg/kg, i.p. twice a day) or deferoxamine (DFO, an iron chelator, 20 mg/day by osmotic pump) had significantly lower BUN (G + DMTU 48.8 +/- 8 mg/dl, P less than 0.001, n = 8; G + DFO 30 +/- 7 mg/dl, P less than 0.001, n = 8). In separate experiments, treatment with two other hydroxyl radical scavengers (dimethyl sulfoxide or sodium benzoate) and a second iron chelator (2,3,dihydroxybenzoic acid) had a similar protective effect on renal function (as measured by both BUN and creatinine). In addition, histological evidence of damage was markedly reduced by the interventional agents. Finally, concurrent treatment with DMTU prevented the gentamicin induced increase in renal cortical malondialdehyde content (G: 4.4 +/- 0.2 nmol/mg; G + DMTU: 3.1 +/- 0.2 nmol/mg, P less than 0.0001, n = 8) suggesting that the protective effect of DMTU was related to free radical mechanisms rather than to some other effect. Taken together, these data strongly support a role for hydroxyl radical or a similar oxidant in gentamicin-induced acute renal failure.
Electrophysiological Effects of Remodeling Cardiac Gap Junctions and Cell Size
Authors: Madison S. Spach, J. Francis Heidlage, Paul C. Dolber, Roger C. Barr
Journal: Circulation Research (2000)

Abstract —The increased incidence of arrhythmias in structural heart disease is accompanied by remodeling of the cellular distribution of gap junctions to a diffuse pattern like that of neonatal cardiomyocytes. Accordingly, it has become important to know how remodeling of gap junctions due to normal growth hypertrophy alters anisotropic propagation at a cellular level (V̇ max ) in relation to conduction velocities measured at a macroscopic level. To this end, morphological studies of gap junctions (connexin43) and in vitro electrical measurements were performed in neonatal and adult canine ventricular muscle. When cells enlarged, gap junctions shifted from the sides to the ends of ventricular myocytes. Electrically, normal growth produced different patterns of change at a macroscopic and microscopic level. Although the longitudinal and transverse conduction velocities were greater in adult than neonatal muscle, the anisotropic velocity ratios were the same. In the neonate, mean V̇ max was not different during longitudinal (LP) and transverse (TP) propagation. However, growth hypertrophy produced a selective increase in mean TP V̇ max ( P &lt;0.001), with no significant change in mean LP V̇ max . Two-dimensional neonatal and adult cellular computational models show that the observed increases in cell size and changes in the distribution of gap junctions are sufficient to account for the experimental results. Unexpectedly, the results show that cellular scaling (cell size) is as important (or more so) as changes in gap junction distribution in determining TP properties. As the cells enlarged, both mean TP V̇ max and lateral cell-to-cell delay increased. V̇ max increased because increases in cell-to-cell delay reduced the electric current flowing downstream up to the time of V̇ max , thus enhancing V̇ max . The results suggest that in pathological substrates that are arrhythmogenic, maintaining cell size during remodeling of gap junctions is important in sustaining a maximum rate of depolarization.
Stimulation of P2Y receptors activates c-fos gene expression and inhibits DNA synthesis in cultured cardiac fibroblasts
Authors: Jing-Sheng Zheng, Lydia O'Neill, Xilin Long, Tania E Webb, Eric A Barnard, Edward G Lakatta, Marvin O Boluyt
Journal: Cardiovascular Research (1998)

Objectives: The aims of this study were to determine (1) whether neonatal rat cardiac fibroblasts (CAFB) express P2Y receptors; (2) whether CAFB respond to extracellular ATP by inducing expression of c-fos mRNA; and (3) whether extracellular ATP modulates norepinephrine (NE)-stimulated cell growth in CAFB. Methods: Expression of P2Y1 and P2Y2 receptors and induction of c-fos were examined by Northern blot analysis. CAFB growth was assessed by measuring [3H]thymidine incorporation and DNA content. P2Y receptor pharmacology was studied using various ATP analogues. Results: Northern blot analysis of polyA enriched RNA confirmed that at least 2 subtypes of P2Y receptors (P2Y1 and P2Y2) are expressed in cultured CAFB. Extracellular ATP induced the expression of c-fos mRNA through a pathway that was sensitive to inhibitors of protein kinase C (PKC), but not to inhibitors of intracellular Ca2+ signaling. Extracellular ATP inhibited the NE-stimulated increases in DNA content and in [3H]thymidine incorporation into DNA. Whereas the potency order for stimulation of c-fos expression was ATP = UTP > ADP > adenosine, the potency order to inhibit the NE-induced increase of [3H]thymidine incorporation into DNA was ATP > ADP > UTP > adenosine. Conclusions: These data demonstrate that CAFB express both P2Y1 and P2Y2 receptor mRNA and that CAFB respond to P2Y receptor stimulation by induction of c-fos and inhibition of DNA synthesis. These findings suggest that the effects of ATP on [3H]thymidine incorporation into DNA and on expression of c-fos mRNA are exerted via distinct P2Y receptor subtypes.
Spinal Manipulation for Low-Back Pain
Authors: Paul G. Shekelle, Alan H. Adams, Mark R. Chassin, Eric L. Hurwitz, Robert H. Brook
Journal: Annals of Internal Medicine (1992)

Purpose: To review the use, complications, and efficacy of spinal manipulation as a treatment for low-back pain. Data Identification: Articles were identified through a MEDLINE search, review of articles' bibliographies, and advice from expert orthopedists and chiropractors. Study Selection: All studies reporting use and complications of spinal manipulation and all controlled trials of the efficacy of spinal manipulation were analyzed. Fifty-eight articles, including 25 controlled trials, were retrieved. Data Analysis: Data on the use and complications of spinal manipulation were summarized. Controlled trials of efficacy were critically appraised for study quality. Data from nine studies were combined using the confidence profile method of meta-analysis to estimate the effect of spinal manipulation on patients' pain and functional outcomes. Results of Data Synthesis: Chiropractors provide most of the manipulative therapy used in the United States for patients with low-back pain. Serious complications of lumbar manipulation, including paraplegia and death, have been reported. Although the occurrence rate of these complications is unknown, it is probably low. For patients with uncomplicated, acute low-back pain, the difference in probability of recovery at 3 weeks favoring treatment with spinal manipulation is 0.17 (for example, increase in recovery from 50% to 67%; 95% probability limits of estimate, 0.07 to 0.28). For patients with low-back pain and sciatic nerve irritation, the difference in probabilities of recovery at 4 weeks is 0.098 (probability limits, — 0.016 to 0.209). Conclusions: Spinal manipulation is of short-term benefit in some patients, particularly those with uncomplicated, acute low-back pain. Data are insufficient concerning the efficacy of spinal manipulation for chronic low-back pain.
Thrombolysis With Tissue-Type Plasminogen Activator in Acute Myocardial Infarction
Authors: Allan S. Jaffe, Burton E. Sobel
Journal: JAMA (1986)

RAPID dissemination of preliminary results of research may predispose the medical profession and the public to premature, ill-advised, or indiscriminate acceptance of allegedly therapeutic modalities before efficacy has been established. Objective evaluation of an intervention such as coronary thrombolysis may be obscured by excessive enthusiasm of advocates, undue cynicism of critics, media hype, and real or imagined competitive pressures impinging on the modern practitioner of medicine. In this article we shall consider, in this context, findings pertinent to coronary thrombolysis with conventional activators or tissue-type plasminogen activator (t-PA) in the treatment of acute myocardial infarction. The concept that acute coronary thrombosis is responsible for myocardial infarction is not new. Initial attempts in 1959 by Sherry and associates were made to activate the fibrinolytic system in pilot studies of patients with acute infarction. Subsequently, 13 large-scale trials with intravenous streptokinase were performed in Europe and Scandinavia. Conflicting results ensued, in part
Comparison of Recommendations by Urologists and Radiation Oncologists for Treatment of Clinically Localized Prostate Cancer
Authors: Floyd J. Fowler, Jr
Journal: JAMA (2000)

Multiple treatment options are available for men with prostate cancer, but therapeutic recommendations may differ depending on the type of specialist they consult.To define and contrast the distribution of management recommendations by urologists and radiation oncologists for a spectrum of men with prostate cancer.Mail survey sent in 1998 to a random sample of physicians in the United States, who were listed as urologists (response rate 64%, n=504) and radiation oncologists (response rate 76%, n=559) in the American Medical Association Registry of Physicians and practicing at least 20 hours per week.Questionnaire addressing beliefs and practices regarding prostate cancer management.Forty-three percent of radiation oncologists vs 16% of urologists would recommend routine prostate-specific antigen testing for men aged 80 years and older. For men with moderately differentiated, clinically localized cancers, and a more than 10-year life expectancy, 93% of urologists chose radical prostatectomy as the preferred treatment option, while 72% of radiation oncologists believed surgery and external beam radiotherapy were equivalent treatments. For most tumor grades and prostate-specific antigen levels, both specialty groups were significantly more likely to recommend the treatment in their specialty than the other treatment. Both groups reported giving patients similar estimates of the risks of complications due to surgery and radiation. Neither group favored watchful waiting in their treatment management except for a subset of men with life expectancies of less than 10 years and cancers with very favorable prognoses (Gleason score of 3 or 4 and prostate-specific antigen level </=5 ng/mL).Based on this study, while urologists and radiation oncologists do agree on a variety of issues regarding detection and treatment of prostate cancer, specialists overwhelmingly recommend the therapy that they themselves deliver. JAMA. 2000;283:3217-3222
Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations.
Authors: J Teres, J M Bordas, C Bru, F Diaz, M Bruguera, J Rodes
Journal: Gut (1976)

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.