tbuckley/cabot-search huggingface dataset:
Perceived barriers to walking in the neighbourhood environment and change in physical activity levels over 12 months
Authors: Jill Dawson, Melvyn Hillsdon, Irene Boller, Charlie Foster
Journal: British Journal of Sports Medicine (2007)

To investigate whether, and to what extent, perceived barriers to neighbourhood walking (BTNW) may be associated with physical activity levels.Prospective survey with 12-month follow-up.750 people attending walking schemes throughout England and Scotland; 551 completed the follow-up. independent variables were demographic characteristics, examples of possible "external" barriers to walking-for example, "worries about personal safety", and one item concerning ill health. The main outcome measures were "metabolic equivalent" (MET) hours' walking and overall physical activity in the preceding week.Baseline and follow-up demographic characteristics were similar and physical activity levels generally high. Leisure walking changed little over 12 months, while total physical activity levels reduced significantly from a mean (SD) of 71.26 (78.14) MET hours per week at baseline to 59.57 (181.40) at the 12-month follow-up (p<0.001). External BTNW cited between baseline and 12 months increased significantly from a mean (SD) of 1.24 (1.61) at baseline to 1.43 (1.72) at the 12-month follow-up (p<0.001); only "worries about personal safety" reduced. A significant association was found between citing a health-related BTNW and the total number of external BTNW that were reported at baseline. The strength of this association increased over 12 months. Neither changes in reporting external BTNW that occurred over 12 months (increased vs decreased, vs unchanged) nor changes in the presence of a health-related BTNW were significantly related to levels of leisure walking and overall physical activity (MET hours in the preceding week) over the same period.Among older people who attended walking schemes, having a health problem that restricted walking had a detrimental influence on people's perceptions about external BTNW, which increased over time. Actual levels of walking and overall physical activity levels did not appear to be significantly affected by this.
VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek myeloma study group
Authors: K Zervas, D Mihou, E Katodritou, A Pouli, C.H. Mitsouli, A Anagnostopoulos, S Delibasi, M.C. Kyrtsonis, N Anagnostopoulos, E Terpos, P Zikos, A Maniatis, M.A. Dimopoulos
Journal: Annals of Oncology (2007)
Pendrin Modulates ENaC Function by Changing Luminal HCO3 −
Authors: Vladimir Pech, Truyen D. Pham, Seongun Hong, Alan M. Weinstein, Kathryn B. Spencer, Billy Jean Duke, Eric Walp, Young Hee Kim, Roy L. Sutliff, Hui-Fang Bao, Douglas C. Eaton, Susan M. Wall
Journal: Journal of the American Society of Nephrology (2010)

The epithelial Na(+) channel, ENaC, and the Cl(-)/HCO(3)(-) exchanger, pendrin, mediate NaCl absorption within the cortical collecting duct and the connecting tubule. Although pendrin and ENaC localize to different cell types, ENaC subunit abundance and activity are lower in aldosterone-treated pendrin-null mice relative to wild-type mice. Because pendrin mediates HCO(3)(-) secretion, we asked if increasing distal delivery of HCO(3)(-) through a pendrin-independent mechanism "rescues" ENaC function in pendrin-null mice. We gave aldosterone and NaHCO(3) to increase pendrin-dependent HCO(3)(-) secretion within the connecting tubule and cortical collecting duct, or gave aldosterone and NaHCO(3) plus acetazolamide to increase luminal HCO(3)(-) concentration, [HCO(3)(-)], independent of pendrin. Following treatment with aldosterone and NaHCO(3), pendrin-null mice had lower urinary pH and [HCO(3)(-)] as well as lower renal ENaC abundance and function than wild-type mice. With the addition of acetazolamide, however, acid-base balance as well as ENaC subunit abundance and function was similar in pendrin-null and wild-type mice. We explored whether [HCO(3)(-)] directly alters ENaC abundance and function in cultured mouse principal cells (mpkCCD). Amiloride-sensitive current and ENaC abundance rose with increased [HCO(3)(-)] on the apical or the basolateral side, independent of the substituting anion. However, ENaC was more sensitive to changes in [HCO(3)(-)] on the basolateral side of the monolayer. Moreover, increasing [HCO(3)(-)] on the apical and basolateral side of Xenopus kidney cells increased both ENaC channel density and channel activity. We conclude that pendrin modulates ENaC abundance and function, at least in part by increasing luminal [HCO(3)(-)] and/or pH.
Immunology of Experimental Tumors
Authors: L J Old, E A Boyse
Journal: Annual Review of Medicine (1964)

One of the most important advances in cancer biology of recent years is the conclusive demonstration that a variety of experimental tumors possess antigenicity capable of eliciting specific immune responses. This review will be restricted largely to those experimental systems in which the antigenic differences between tumor and host have been most clearly defined. In prac­ tice, this limits the field of discussion, with certain exceptions, to studies per­ formed with tumors of recent origin from inbred rodent stocks. A discussion of immunological studies with human tumors is not possible within the com­ pass of this review; this area has recently been reviewed by Southam (1). However, consideration will be given to those aspects of experimental tumor immunology that have direct implications for the study of tumors in man. Other topics of interest which cannot be dealt with here include the use of immunological techniques to identify the products of plasma cell and other neoplasms (2, 3), the immunological aspects of choriocarcinoma in man (4), and immunological evidence concerning the loss of normal cell constituents during the malignant transformation [see Gorer (5»).
Inhibition of T Cell Receptor Signal Transduction by Tyrosine Kinase–interacting Protein of Herpesvirus saimiri
Authors: Nam-Hyuk Cho, Pinghui Feng, Sun-Hwa Lee, Bok-Soo Lee, Xiaozhen Liang, Heesoon Chang, Jae U. Jung
Journal: The Journal of Experimental Medicine (2004)

T cells play a central role in orchestrating immunity against pathogens, particularly viruses. Thus, impairing T cell activation is an important strategy employed by viruses to escape host immune control. The tyrosine kinase–interacting protein (Tip) of the T lymphotropic Herpesvirus saimiri (HVS) is constitutively present in lipid rafts and interacts with cellular Lck tyrosine kinase and p80 endosomal protein. Here we demonstrate that, due to the sequestration of Lck by HVS Tip, T cell receptor (TCR) stimulation fails to activate ZAP70 tyrosine kinase and to initiate downstream signaling events. TCR ζ chains in Tip-expressing T cells were initially phosphorylated to recruit ZAP70 molecule upon TCR stimulation, but the recruited ZAP70 kinase was not subsequently phosphorylated, resulting in TCR complexes that were stably associated with inactive ZAP70 kinase. Consequently, Tip expression not only markedly inhibited TCR-mediated intracellular signal transduction but also blocked TCR engagement with major histocompatibility complexes on the antigen-presenting cells and immunological synapse formation. These results demonstrate that a lymphotropic herpesvirus has evolved a novel mechanism to deregulate T cell activation to disarm host immune surveillance. This process contributes to the establishment and maintenance of viral latency.
SEVERE SEPSIS AND SEPTIC SHOCK: The Role of Gram-Negative Bacteremia
Authors: Robert S. Munford
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Although Gram-negative bacteria have often been implicated in the pathogenesis of severe sepsis and septic shock, how they trigger these often lethal syndromes is uncertain. In particular, the role played by blood-borne bacteria is controversial. This review considers two alternatives. In the first, circulating Gram-negative bacteria induce toxic reactions directly within the vasculature; in the second, the major inflammatory stimulus occurs in local extravascular sites of infection and circulating bacteria contribute little to inducing toxic responses. Evidence for each alternative is found in the literature. Bacteremia and severe sepsis are not so closely linked that the most striking cases can be a model for the rest. Intravascular and extravascular triggers may warrant different approaches to prevention and therapy.
Factors influencing T-cell turnover in HIV-1–seropositive patients
Authors: Joseph M. McCune, Mary Beth Hanley, Denise Cesar, Robert Halvorsen, Rebecca Hoh, Diane Schmidt, Eric Wieder, Steven Deeks, Scott Siler, Richard Neese, Marc Hellerstein
Journal: Journal of Clinical Investigation (2000)

HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.
Activation of Toll-like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth
Authors: Zhenyu Cai, Amir Sanchez, Zhongcheng Shi, Tingting Zhang, Mingyao Liu, Dekai Zhang
Journal: Cancer Research (2011)

Abstract Increasing evidence showed that Toll-like receptors (TLR), key receptors in innate immunity, play a role in cancer progression and development but activation of different TLRs might exhibit the exact opposite outcome, antitumor or protumor effects. TLR function has been extensively studied in innate immune cells, so we investigated the role of TLR signaling in breast cancer epithelial cells. We found that TLR5 was highly expressed in breast carcinomas and that TLR5 signaling pathway is overly responsive in breast cancer cells. Interestingly, flagellin/TLR5 signaling in breast cancer cells inhibits cell proliferation and an anchorage-independent growth, a hallmark of tumorigenic transformation. In addition, the secretion of soluble factors induced by flagellin contributed to the growth-inhibitory activity in an autocrine fashion. The inhibitory activity was further confirmed in mouse xenografts of human breast cancer cells. These findings indicate that TLR5 activation by flagellin mediates innate immune response to elicit potent antitumor activity in breast cancer cells themselves, which may serve as a novel therapeutic target for human breast cancer therapy. Cancer Res; 71(7); 2466–75. ©2011 AACR.
Oral immunization with bacterial extracts for protection against acute bronchitis in elderly institutionalized patients with chronic bronchitis
Authors: B Orcel, B Delclaux, M Baud, J P Derenne
Journal: European Respiratory Journal (1994)

Acute bronchitis is a major source of morbidity in elderly patients. The purpose of this study was to assess the preventive effects of oral immunisation with a bacterial extract. Three hundred and fifty four patients with chronic bronchitis, living in institutions for the elderly (aged &gt; 65 yrs), were included in a randomized, placebo-controlled, double-blind study. The purpose of the study was to assess preventive effects of OM-85 BV (an immunostimulating agent consisting of lyophilized fractions of eight of the most common pathogens isolated in respiratory tract infections) against acute lower respiratory tract infections. Two hundred and ninety patients completed the study (143 taking placebo and 147 taking OM-85 BV). There was a 28% reduction in the number of lower respiratory tract infections in the patients treated with OM-85 BV; this was entirely due to 40% reduction in the number of episodes of acute bronchitis (p &lt; 0.01), with no difference in the number of episodes of pneumonia and bronchopneumonia. A larger number of patients in the OM-85 BV group were free of acute bronchitis throughout the 6 month study period (96 vs 69) and there was a 28% reduction in the number of antibiotic prescriptions in the OM-85 BV treated group. These results suggest that OM-85 BV has a protective effect against acute bronchitis in elderly patients living in institutions.
Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive analysis using interphase fluorescence in situ hybridisation
Authors: S. Nakamura, H. Ye, C. M Bacon, A. Goatly, H. Liu, A. H Banham, R. Ventura, T. Matsumoto, M. Iida, Y. Ohji, T. Yao, M. Tsuneyoshi, M.-Q. Du
Journal: Gut (2007)

<b>Background and aims:</b> There is a need for genetic biomarkers to guide prognosis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphomas. We assessed the incidence and clinical significance of the MALT lymphoma-associated genetic abnormalities t(11;18)/<i>API2-MALT1</i>, t(1;14)/<i>BCL10-IGH</i>, t(14;18)/<i>IGH-MALT1</i>, t(3;14)/<i>FOXP1-IGH</i>, and extra copies of <i>MALT1</i> and <i>FOXP1</i> in gastric MALT lymphomas from Japan. <b>Methods:</b> The presence of translocations and copy number changes involving <i>MALT1</i>, <i>IGH</i> and <i>FOXP1</i> were assessed in 90 cases of gastric MALT lymphoma using interphase fluorescence <i>in situ</i> hybridisation (FISH). In cases carrying a <i>MALT1</i> translocation, FISH for <i>API2-MALT1</i> was performed, whereas in those carrying an <i>IGH</i> translocation, FISH was performed for <i>BCL10</i>, <i>BCL6</i>, <i>BCL2</i>, <i>c-MYC</i> and/or <i>CCND1</i>. <b>Results:</b> t(11;18)/<i>API2-MALT1</i> was detected in 18 of 87 (21%) cases and was significantly associated with <i>Helicobacter pylori</i>-negativity, resistance to <i>H pylori</i> eradication and Bcl10 nuclear expression. Four of 68 (6%) cases carried a translocation involving <i>IGH</i> and <i>FOXP1</i> (n = 1), <i>BCL2</i> (n = 1) or an unknown partner (n = 2). Neither t(1;14)/<i>BCL10-IGH</i> nor t(14;18)/<i>IGH-MALT1</i> was detected. Extra copies of <i>MALT1</i> and <i>FOXP1</i> were detected in 18 of 71 (25%) cases and 10 of 59 (17%) cases, respectively. The presence of extra copies of <i>MALT1</i> was significantly associated with progression or relapse of lymphoma, and was an independent adverse prognostic factor for event-free survival as determined by multivariate analysis. <b>Conclusions:</b> t(11;18)/<i>API2-MALT1</i> is frequent, whereas <i>IGH</i>-involved translocations are rare in gastric MALT lymphoma in Japan. The presence of extra copies of <i>MALT1</i>, often suggestive of partial or complete trisomy 18, is a frequent genetic aberration in gastric MALT lymphoma, which appears to predict adverse clinical behaviour.
Degenerative joint disease in Praomys (Mastomys) natalensis.
Authors: L Sokoloff, K C Snell, H L Stewart
Journal: Annals of the Rheumatic Diseases (1967)

Innate lymphoid cells are abundant in uterine endometrium and their number dramatically increases during pregnancy. In addition to conventional NK (cNK) cells, unique uterine-specific NK cells populate the uterus. These, tissue-resident NK (trNK) cells are characterized by CD49a expression. A2v-ATPase is a proton pump molecule that acidifies intracellular vesicles and is critical in processing of Notch receptors. A knockout of a2v- ATPase in VAV-1 expressing cells (cells of hematopoietic origin) leads to dramatic reduction of NK cells in blood and spleen of the genetically modified animal (a2vKO mouse). Uterine tissues of a2VKO mice were analyzed for NK cell presence based on their reactivity with the lectin DBA. DBA-reactive cells were readily observed in uterine stroma of pregnant a2vKO mice. Although the number of DBA+ cells in a2vKO mice was lower than in wild type (WT) controls, the difference was not statistically significant. Flow cytometry analysis of uterine tissues from virgin a2vKO mice revealed a dramatic decrease of cNK cells (NK1.1<sup>+</sup>NKp46<sup>+</sup>CD11b<sup>−/low</sup>Dx5<sup>+</sup>CD49a<sup>−</sup>). However, the frequency of trNK cells, that possess phenotype NK1.1<sup>+</sup>NKp46<sup>+</sup>CD11b<sup>−</sup>Dx5<sup>−/+</sup>CD49a<sup>+</sup>, was comparable with what was found in WT. Similar findings were observed in pregnant a2vKO mice. Despite the absence of cNK cells that compose a significant proportion of lymphocytes in pregnant uterine tissue, mice fertility was not critically affected and this suggested a role for trNK cells in supporting pregnancy. In conclusion, the development of NK cells that takes place in endometrium appears to be different from NK cells originated in bone marrow, namely it is not dependent on a2vATPase; this can explain uniqueness of trNK cells.
<i>In vivo</i> Imaging of Inflammation- and Tumor-Induced Lymph Node Lymphangiogenesis by Immuno–Positron Emission Tomography
Authors: Viviane Mumprecht, Michael Honer, Benjamin Vigl, Steven T. Proulx, Eveline Trachsel, Manuela Kaspar, Nadja E. Banziger-Tobler, Roger Schibli, Dario Neri, Michael Detmar
Journal: Cancer Research (2010)

Metastasis to regional lymph nodes (LN) is a prognostic indicator for cancer progression. There is a great demand for sensitive and noninvasive methods to detect metastasis to LNs. Whereas conventional in vivo imaging approaches have focused on the detection of cancer cells, lymphangiogenesis within tumor-draining LNs might be the earliest sign of metastasis. In mouse models of LN lymphangiogenesis, we found that systemically injected antibodies to lymphatic epitopes accumulated in the lymphatic vasculature in tissues and LNs. Using a (124)I-labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), we imaged, for the first time, inflammation- and tumor-draining LNs with expanded lymphatic networks in vivo by positron emission tomography (PET). Anti-LYVE-1 immuno-PET enabled visualization of lymphatic vessel expansion in LNs bearing metastases that were not detected by [(18)F]fluorodeoxyglucose-PET, which is clinically applied to detect cancer metastases. Immuno-PET with lymphatic-specific antibodies may open up new avenues for the early detection of metastasis, and the images obtained might be used as biomarkers for the progression of diseases associated with lymphangiogenesis.
Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action
Authors: B. Pollock, D. Turner, M.R. Stringer, R.A. Bojar, V. Goulden, G.I. Stables, W.J. Cunliffe
Journal: British Journal of Dermatology (2004)

Background Acne affects 83–95% of 16‐year‐olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne. Objectives To study the efficacy of aminolaevulinic acid‐photodynamic therapy (ALA‐PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P. acnes and on sebum excretion. Methods Ten patients (nine men and one woman, age range 16–40 years) with mild to moderate acne on their backs were recruited. Each patient's back was marked with four 30‐cm2 areas of equal acne severity. Each site was then randomly allocated to either ALA‐PDT treatment, light alone, ALA alone or an untreated control site. At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P. acnes swabs performed. ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA‐PDT and ALA alone sites for 3 h. Red light from a diode laser was then delivered to the ALA‐PDT and light alone sites (635 nm, 25 mW cm−2, 15 J cm−2). Each patient was treated weekly for 3 weeks. At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P. acnes swabs were repeated. Results There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA‐PDT site but not at any of the other sites. No statistically significant reduction in P. acnes numbers or sebum excretion was demonstrated at any sites including the ALA‐PDT site. Conclusions ALA‐PDT is capable of clinically improving acne. An alternative mode of action for ALA‐PDT other than direct damage to sebaceous glands or photodynamic killing of P. acnes is suggested from the results of this study.
Cortisol Activity and Cognitive Changes in Psychotic Major Depression
Authors: Joseph K. Belanoff, Michelle Kalehzan, Brenda Sund, Shelley K. Fleming Ficek, Alan F. Schatzberg
Journal: American Journal of Psychiatry (2001)

The theory that psychotic major depression is a distinct syndrome is supported by reports of statistically significant differences between psychotic and nonpsychotic major depression in presenting features, biological measures, familial transmission, course and outcome, and response to treatment. This study examined differences in performance on a verbal memory test and in cortisol levels between patients with psychotic and nonpsychotic major depression and healthy volunteers.Ten patients with psychotic major depression, 17 patients with nonpsychotic major depression, and 10 healthy volunteers were administered the Wallach Memory Recognition Test and had blood drawn at half-hour intervals over the course of an afternoon to assay cortisol levels.Subjects with psychotic major depression had a higher rate of errors of commission on the verbal memory test (incorrectly identified distracters as targets) than did subjects with nonpsychotic major depression or healthy volunteers; errors of omission were similar among the three groups. Subjects with psychotic major depression had higher cortisol levels throughout the afternoon than subjects with nonpsychotic major depression or healthy volunteers. This effect became even more pronounced later in the afternoon.Psychotic major depression is endocrinologically different from nonpsychotic major depression and produces cognitive changes distinct from those seen in nonpsychotic major depression.