tbuckley/cabot-search huggingface dataset:
Fas Ligand–Positive Membranous Vesicles Isolated from Sera of Patients with Oral Cancer Induce Apoptosis of Activated T Lymphocytes
Authors: Jeong Whun Kim, Eva Wieckowski, Douglas D. Taylor, Torsten E. Reichert, Simon Watkins, Theresa L. Whiteside
Journal: Clinical Cancer Research (2005)

In patients with oral squamous cell carcinoma, a high proportion of T cells in the tumor undergo apoptosis, which correlates with Fas ligand (FasL) expression on tumor cells. The present study was done to identify mechanisms responsible for apoptosis of T cells seen in the peripheral circulation of these patients.Sera of 27 patients, normal donor sera, and supernatants of cultured normal or tumor cells were fractionated by size exclusion chromatography and ultracentrifugation to isolate microvesicles. The presence of microvesicle-associated FasL was studied by Western blots, blocking with anti-Fas reagents, and immunoelectron microscopy. Biological activities of microvesicles were tested including the ability to induce apoptosis of Jurkat and T-cell blasts. Semiquantitative analysis of FasL in microvesicles was correlated with caspase-3 activity, DNA fragmentation, cytochrome c release, loss of mitochondrial membrane potential, and TCR-zeta chain expression in lymphocytes.FasL-positive (FasL+) microvesicles were detected in sera of 21 of 27 patients. Microvesicles contained 42 kDa FasL. These microvesicles induced caspase-3 cleavage, cytochrome c release, loss of mitochondrial membrane potential, and reduced TCR-zeta chain expression in target lymphocytes. Biological activity of the FasL+ microvesicles was partially blocked by ZB4 anti-Fas monoclonal antibody. Microvesicle-associated FasL levels correlated with the patients' tumor burden and nodal involvement.Sera of patients with active oral squamous cell carcinoma contain FasL+ microvesicles, which induce the receptor and mitochondrial apoptotic pathways in Jurkat and activated T cells.
Liver Diseases in the Hemochromatosis and Iron Overload Screening Study
Authors: Paul C. Adams, Leah Passmore, Subrata Chakrabarti, David M. Reboussin, Ronald T. Acton, James C. Barton, Gordon D. McLaren, John H. Eckfeldt, Fitzroy W. Dawkins, Victor R. Gordeuk, Emily L. Harris, Catherine Leiendecker–Foster, Elaine Gossman, Phyliss Sholinsky
Journal: Clinical Gastroenterology and Hepatology (2006)
Antibody recognition of the type 14 pneumococcal capsule. Evidence for a conformational epitope in a neutral polysaccharide.
Authors: M R Wessels, D L Kasper
Journal: The Journal of Experimental Medicine (1989)

Oligosaccharides consisting of one or more tetrasaccharide repeating units were derived from the capsular polysaccharide of type 14 pneumococcus (Pn14) by endo-beta-galactosidase digestion. The relative affinity of anticapsular antibody binding to derivative oligosaccharides of different chain lengths was measured in a Pn 14 ELISA inhibition assay. The concentration of inhibiting antigen required to achieve 50% inhibition of IgG binding increased progressively from 5.6 x 10(-4) M to 7.0 x 10(-11) M as the inhibiting saccharide chain length increased from 1 tetrasaccharide repeating unit to 2,500 repeating units. These data indicate that antibodies directed against the Pn14 polysaccharide recognize a conformational epitope fully expressed only in high molecular weight forms of the antigen. Similar results were found for inhibition of Fab fragment binding, suggesting that recognition of the conformational epitope is largely dependent on the intrinsic affinity of the Fab combining region. Unlike previously reported polysaccharides for which conformational epitopes have been described, the Pn14 polysaccharide does not contain negatively charged residues, indicating that expression of conformational determinants is not limited to acidic polysaccharides. Antibody recognition of conformational epitopes may be a common mechanism by which the host immune response discriminates between bacterial polysaccharides and host oligosaccharides of similar structure.
Clinical Comparison of the Newer Anti-Inflammatory Corticosteroids
Authors: Edward W. Boland
Journal: Annals of the Rheumatic Diseases (1962)

diseases responsive to steroids, the need for drugs with higher therapeutic indices has long been evident.Among the deficiencies inherent in the natural hormones are their suppressive rather than curative effect, the ephemeral nature of their benefits, their failure to halt the natural progression of rheu- matoid arthritis even while adequate degrees of improvement and functional rehabilitation are being maintained, and their inhibiting effect on endogenous adrenocortical function.Moreover, their usefulness, even as suppressive agents, is severely limited by their multiple physiological properties.In addition to their anti- inflammatory effect, they have many other actions, some of which produce unwanted signs of hormonal excess.The intrusion of these often prohibits the administration of doses of sufficient strength to maintain satisfactory improvement.The common undesirable reactions are now well known.They include heightened appetite coupled with excessive weight gain and abnormal deposits of adipose tissue; disturbances of electrolyte metabolism- particularly sodium and water retention and potassium loss, increased capillary fragility, cutaneous ecchymoses, thinning of the skin, striae, acne, and hypertrichiasis in women, negative calcium balance, and osteoporosis; retardation of fibrosis and delayed healing; elevation of blood pressure; nervous irritability; masking of infections; and other effects.And, in the course of treatment, unwanted physiological actions may promote such complications as peptic ulcer, pathological fractures, phlebitis, thrombo-embolic phenomena, emotional psychotic disturbances, necrotizing vasculitis, and peripheral neuropathy-or they may aggravate certain disease states, such as arterial hypertension, peptic ulcer, diabetes, osteoporosis, and tuberculosis, that may co-exist with rheumatoid arthritis.Were it possible to modify the chemical structures
Anatomical Observations on the Course of the Azygos Vein (Vena Azygos Major)
Authors: H. Nathan
Journal: Thorax (1960)

In man, the azygos vein is described as ascending on the right side of the vertebral column until it curves anteriorly over the right bronchus to end in the superior vena cava.However, it has been observed that frequently the azygos vein is found to run part of its course on the left side of the midline.No description of this course has been found in current anatomical textbooks or other literature dealing with the subject (Morison, 1879; Butler and
Fluctuation of blood and skin plasmacytoid dendritic cells in drug-induced hypersensitivity syndrome
Authors: Kazunari Sugita, Mikiko Tohyama, Hideaki Watanabe, Atsushi Otsuka, Saeko Nakajima, Masafumi Iijima, Koji Hashimoto, Yoshiki Tokura, Yoshiki Miyachi, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2010)
Persistent Depressive Symptoms after Acute Coronary Syndrome Are Associated with Compromised White Matter Integrity in the Anterior Cingulate: A Pilot Study
Authors: Michael A. Rapp, Nina Rieckmann, David A. Lessman, Cheuk Y. Tang, Robert Paulino, Matthew M. Burg, Karina W. Davidson
Journal: Psychotherapy and Psychosomatics (2010)

&lt;i&gt;Background:&lt;/i&gt; Persistent depressive symptoms after acute coronary syndrome (ACS) are common and increase the risk of recurrent cardiac events and mortality. However, the neurobiological correlates of post-ACS depressive symptoms have not yet been studied. &lt;i&gt;Methods:&lt;/i&gt; Three months after ACS, 22 patients were scanned for the presence of cerebral deep white matter changes and microstructural abnormalities in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex. We used the Coffey Rating Scale of deep white matter changes and measures of fractional anisotropy derived from diffusion tensor imaging. Patients also completed the Beck Depression Inventory, and the number of cardiovascular comorbidities as well as modifiable cardiovascular risk factors were assessed. &lt;i&gt;Results:&lt;/i&gt; Controlling for cardiovascular comorbidity, depressive symptom severity at 3 months was negatively related to fractional anisotropy in the ACC (r = –0.72, p &lt; 0.001), but this association disappeared when controlling for cardiovascular risk factors (p = 0.21). In comparison to patients who were non-depressed at 3 months after hospitalization (n = 14), patients with persistent depressive symptoms (n = 8) exhibited more advanced deep white matter changes overall (p &lt; 0.02), but not when controlling for cardiovascular comorbidity. Persistently depressed patients also had lower fractional anisotropy in the ACC (p &lt; 0.05), but this effect disappeared when controlling for modifiable cardiovascular risk factors. &lt;i&gt;Conclusions:&lt;/i&gt; This study provides the first evidence that persistent depressive symptoms after ACS are associated with vascular brain changes. Longitudinal studies are needed to determine whether depressive symptoms precede these changes or vice versa.
Reply to the comment on “Effects of long term angiotensin II AT-1 receptor blockade on survival, hemodynamics and cardiac remodeling in chronic heart failure in rats”
Authors: C Richer
Journal: Cardiovascular Research (1999)

We read with interest the comments by Willenheimer [1] on our paper recently published in Cardiovascular Research [2].

Willenheimer states that (a) collagen density being the same in untreated MI rats and in irbesartan-treated MI rats, and (b) heart weight/body weight ratio being decreased in irbesartan-treated vs. untreated MI rats, the absolute myocardial collagen content is reduced in the irbesartan-treated animals. In our …
Synergistic Antitumor Effects of Combined Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor-2 Targeted Therapy
Authors: James R. Tonra, Dhanvanthri S. Deevi, Erik Corcoran, Huiling Li, Su Wang, Francine E. Carrick, Daniel J. Hicklin
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Combination therapies that target the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) pathways, are being actively tested for the treatment of cancer. In evaluating combination strategies, the ideal combination would be one in which the treatments interact in a way that is synergistic with regard to antitumor effects. Here, we have evaluated the interaction between anti-EGFR antibody Erbitux (cetuximab) and anti-VEGFR2 antibody, DC101, in preclinical models of pancreatic (BxPC-3) and colon (GEO) cancer. Experimental Design: Analysis of the interaction between cetuximab and DC101 in vivo used a novel method for establishing the upper 95% confidence limits for the combination index (CI) of isobologram analyses, where CI &amp;lt; 1 indicates synergy. Assessment of tumor cell proliferation, apoptosis, VEGF production, and hypoxia, as well as tumor vascularization, was performed to gain insights into the mechanistic basis for synergy between agents targeting different tumor compartments. Results: Monotherapy ED50 values for tumor growth inhibition ranged from 1.8 to 2.3 mg/kg and 10.5 to 16.6 mg/kg for cetuximab and DC101, respectively. From the dose response of the combination treatment, it was determined that cetuximab and DC101 are synergistic in the BxPC-3 (CI = 0.1, P &amp;lt; 0.01) and GEO (CI = 0.1, P &amp;lt; 0.01) models. Overlapping effects on the tumor cell and vascular compartments form a basis for the interaction, with VEGF production and hypoxia-inducible factor 1α potentially acting as molecular links between EGFR and VEGFR2 inhibition. Conclusions: Results show antitumor synergy for combined EGFR and VEGFR2 targeted therapy, supporting the significant therapeutic potential of this combination strategy.
Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients
Authors: J.L. Westra, H. Hollema, M. Schaapveld, I. Platteel, K.A. Oien, W.N. Keith, R. Mauritz, G.J. Peters, C.H.C.M. Buys, R.M.W. Hofstra, J.Th.M. Plukker
Journal: Annals of Oncology (2005)
Changing Area Socioeconomic Patterns in U.S. Cancer Mortality, 1950-1998: Part I--All Cancers Among Men
Authors: G. K. Singh
Journal: JNCI Journal of the National Cancer Institute (2002)

Area socioeconomic deprivation indices are widely used to monitor health disparities in Europe. However, such indices have not been used in cancer surveillance in the United States. We developed an area socioeconomic index to examine area socioeconomic patterns in all-cancer mortality among U.S. men between 1950 and 1998.Principal components analysis on 11 census variables was used to develop an area socioeconomic index that was then used to stratify all U.S. counties into one of five socioeconomic categories. The index was linked to 1950-1998 county mortality data to generate annual mortality rates for each area socioeconomic group. Joinpoint regression analysis was used to model mortality trends, and Poisson regression analysis was used to estimate socioeconomic gradients in mortality over time.Area socioeconomic patterns in U.S. male cancer mortality changed dramatically between 1950 and 1998. Throughout the 1950s and 1960s, there was a positive socioeconomic gradient, with higher cancer mortality rates in high area socioeconomic groups than in low area socioeconomic groups. For example, in 1950-1952, cancer mortality was 49% (95% confidence interval [CI] = 41% to 59%) greater in the highest area socioeconomic group than in the lowest. The positive gradient narrowed in the 1970s, and by the late 1980s, socioeconomic differences in cancer mortality began to reverse and widen. In 1997-1998, cancer mortality was 19% (95% CI = 11% to 28%) higher in the lowest area socioeconomic group than in the highest. Gradients were steeper for men aged 25-64 years than for men aged 65 years or older.Socioeconomic patterns in male cancer mortality have reversed over time in the United States. Area socioeconomic indices could serve as a powerful surveillance tool for monitoring health disparities in cancer outcomes.
Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway
Authors: F M Ruemmele
Journal: Gut (2002)

Background: During the process of tumorigenesis most colon cancer cells acquire resistance to apoptosis. The short chain fatty acid butyrate is well established as an antitumour agent which selectively induces apoptosis in colon cancer cells but not in normal intestinal epithelial cells. Aims: To analyse the signalling pathway of butyrate induced apoptosis. Methods: Using Caco-2 cells we focused on the bcl family of proteins, mitochondrial pathway, and caspase signalling cascade involved in butyrate induced apoptosis. Techniques employed included western blots, immunofluorescence, as well as experiments with peptide inhibitors of specific caspases. Results: Butyrate induced a clear shift of the mitochondrial bcl rheostat towards a proapoptotic constellation, as demonstrated by upregulation of proapoptotic bak accompanied by reduced antiapoptotic bcl-xL levels. This was associated with translocation of cytochrome-c from the mitochondria to the cytosol, resulting in activation of the caspase cascade via caspase-9. Key executioner enzymes were caspases-3 and -1. No effect of butyrate on regulatory proteins of the inhibitor of apoptosis family was observed. Conclusions: Butyrate induced Caco-2 cell apoptosis via the mitochondrial pathway. Upregulation of bak and translocation of cytochrome-c were upstream of the caspase cascade. Subsequently, this cascade was activated via the formation of an apoptosome.
Infertility and coeliac disease.
Authors: P Collin, S Vilska, P K Heinonen, O Hallstrom, P Pikkarainen
Journal: Gut (1996)

BACKGROUND: Coeliac women may suffer from gynaecological and obstetric complications. It is possible that these complications are the first symptom of coeliac disease. AIMS: To investigate the occurrence of subclinical coeliac disease in patients with infertility or recurrent miscarriages. SUBJECTS: Women of reproductive age who were attending the hospital because of either primary or secondary infertility, or two or more miscarriages. Women undergoing sterilisation served as control subjects. METHODS: The diagnostic investigation for infertility included the endocrine status, diagnostic laparoscopy, investigation of tubal patency, postcoital test, and semen analysis of the partner. Circulating antibodies against IgA class reticulin and gliadin were used in screening for coeliac disease. In positive cases, the diagnosis was confirmed by small bowel biopsy specimens. RESULTS: Four (2.7%) of 150 women in the infertility group, and none of the 150 control subjects were found to have coeliac disease (p = 0.06). All four women with coeliac disease suffered from infertility of unexplained origin. Altogether 98 women had no discoverable reason for infertility. Thus, in this subgroup the frequency of coeliac disease was 4.1% (four of 98), the difference from the control group being statistically significant (p = 0.02). None of the coeliac women had extensive malabsorption, but two had iron deficiency anaemia. One women with coeliac disease has had a normal delivery. None of the 50 women with miscarriage had coeliac disease. CONCLUSION: Patients having fertility problems may have subclinical coeliac disease, which can be detected by serological screening tests. Silent coeliac disease should be considered in the case of women with unexplained infertility.
Dermatoses in five related female carriers of X-linked chronic granulomatous disease
Authors: JENNIFER J. GARIOCH, J.R. SAMPSON, MORAG SEYWRIGHT, J. THOMSON
Journal: British Journal of Dermatology (1989)

Eight female members of a family with X-linked chronic granulomatous disease were identified. Five were shown to be carriers of the disease gene. Each of these female carriers of the gene had a history of skin eruptions. The identification of the carrier state is important as genetic counselling should be offered and the prenatal diagnosis of this disorder is possible.
Deciding Against Resuscitation: Encouraging Signs and Potential Dangers
Authors: Robert M. Veatch
Journal: JAMA (1985)

One of the most important developments in medical ethics of the last decade has been the increasing recognition that there are times when it is unnecessary, even wrong, to resuscitate seriously ill patients. The American Medical Association's Judicial Council makes clear that this is its view when it says that "with informed consent a physician may do what is medically necessary to alleviate severe pain, or cease or omit treatment to let a terminally ill patient die, but he should not intentionally cause death."<sup>1(p9)</sup>The lay population seems to agree. Both secular philosophers and spokespersons for most of the major religious traditions now agree with the recent report of the President's Commission on Ethical Problems in Medicine that states that "a competent and informed patient or an incompetent patient's surrogate is entitled to decide with the attending physician that an order against resuscitation should be written in the chart."
Protective effect of respiratory devices in farmers with occupational asthma
Authors: D Muller-Wening, M Neuhauss
Journal: European Respiratory Journal (1998)

To the authors' knowledge there have been no previous reports on the protection afforded by powered filtering respirators in farmers with occupational asthma attributed to the inhalation of organic dust. In order to investigate this question, 26 farmers with occupational asthma were challenged with an exposure to work-related dusts for up to 60 min. This resulted in highly significant increases in airway resistance (Raw), thoracic gas volume (TGV) and specific airway resistance (sRaw) compared to baseline values. After a mean period of 21 weeks the farmers were subjected to a second challenge, this time wearing a protective respiratory device (RD) with a P2 filter. Significant increases in Raw, TGV and sRaw were again observed, but on average these were 50-80% smaller than the increases seen when RDs were not worn. These differences were found to be statistically significant. This shows that the use of a respiratory device in farmers suffering from occupational asthma reduces the development of bronchial obstruction but does not prevent it. The use of this kind of respiratory device cannot substitute for the proper management of asthma since the devices do not offer complete protection.
IκB kinases increase Myc protein stability and enhance progression of breast cancer cells
Authors: Pei-Yen Yeh, Yen-Shen Lu, Da-Liang Ou, Ann-Lii Cheng
Journal: Molecular Cancer (2011)

Abstract Background Both IκB kinase (IKK) complex and oncgenic protein Myc play important roles in cancer progression, including cancer cell invasiveness and metastasis. The levels of Myc is regulated by the phosphorylation of Myc at Thr58 and Ser62. Results In this study, we show that the expression of Myc is associated with IKKα and IKKβ in breast cancers and that Myc is an IKKs substrate. Suppression of IKK activity by either chemical inhibitor or transfection of kinase-dead mutants decreases the phosphorylation of Myc at Ser62 and enhances the degradation of Myc. Consequently, these treatments decrease the tumorigenic and invasive ability of breast cancer cells. Furthermore, doxorubicin, a frequently used anticancer drug in breast cancer, activates IKKs and Myc, thereby increasing invasiveness and tumorigenesis of breast carcinoma MCF7 cells. Inhibition of IKKs prevents these doxorubicin-induced effects. Conclusions Our study indicates that IKKs tightly regulate Myc expression through prolonging protein stability, and suggests that IKKs are potentially therapeutic targets and that suppression of IKKs may be used following chemotherapy to reduce the risk of treatment-induced tumor progression.
miRNA-34b Inhibits Prostate Cancer through Demethylation, Active Chromatin Modifications, and AKT Pathways
Authors: Shahana Majid, Altaf A. Dar, Sharanjot Saini, Varahram Shahryari, Sumit Arora, Mohd Saif Zaman, Inik Chang, Soichiro Yamamura, Yuichiro Tanaka, Takeshi Chiyomaru, Guoren Deng, Rajvir Dahiya
Journal: Clinical Cancer Research (2012)

miRNAs can act as oncomirs or tumor-suppressor miRs in cancer. This study was undertaken to investigate the status and role of miR-34b in prostate cancer.Profiling of miR-34b was carried out in human prostate cancer cell lines and clinical samples by quantitative real-time PCR and in situ hybridization. Statistical analyses were done to assess diagnostic/prognostic potential. Biological significance was elucidated by carrying out a series of experiments in vitro and in vivo.We report that miR-34b is silenced in human prostate cancer and the mechanism is through CpG hypermethylation. miR-34b directly targeted methyltransferases and deacetylases resulting in a positive feedback loop inducing partial demethylation and active chromatin modifications. miR-34b expression could predict overall and recurrence-free survival such that patients with high miR-34b levels had longer survival. Functionally, miR-34b inhibited cell proliferation, colony formation, migration/invasion, and triggered G(0)/G(1) cell-cycle arrest and apoptosis by directly targeting the Akt and its downstream proliferative genes. miR-34b caused a decline in the mesenchymal markers vimentin, ZO1, N-cadherin, and Snail with an increase in E-cadherin expression, thus inhibiting epithelial-to-mesenchymal transition. Finally we showed the antitumor effect of miR-34b in vivo. MiR-34b caused a dramatic decrease in tumor growth in nude mice compared with cont-miR.These findings offer new insight into the role of miR-34b in the inhibition of prostate cancer through demethylation, active chromatin modification, and Akt pathways and may provide a rationale for the development of new strategies targeting epigenetic regulation of miRNAs for the treatment of prostate cancer.