tbuckley/cabot-search huggingface dataset:
Regulation of Inhibitor of Apoptosis Expression by Nitric Oxide and Cytokines
Authors: MARKUS MANDERSCHEID, UDO K. MEßMER, ROCHUS FRANZEN, JOSEF PFEILSCHIFTER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Mesangial cells and RAW 264.7 macrophages respond to different nitric oxide (NO) donors within 16 to 24 h or 6 to 8 h, respectively, with apoptotic cell death. RAW 264.7 macrophages also die in response to endogenous NO production. In contrast, endogenous NO production fails to significantly induce cell death in mesangial cells. It was hypothesized that differences in the expression of antiapoptotic proteins, in particular the inhibitor of apoptosis (IAP) protein family, might be responsible for this cell type-specific behavior. Therefore, IAP expression was investigated in relation to apoptosis induction in response to NO and cytokines in both cell types. In mesangial cells, interleukin-1β (IL-1β) and tumor necrosis factor-α induced cellular inhibitor of apoptosis 1 (cIAP1) mRNA expression within 3 h. In contrast, X chromosome-linked inhibitor of apoptosis (XIAP) mRNA levels remained unaffected by cytokines. Although coincubation of cells with IL-1β and tumor necrosis factor-α or IL-1β and basic fibroblast growth factor resulted in synergistic induction of inducible NO synthase, comparable potentiating effects on cIAP1 induction were absent. Exogenously released NO from NO donors promoted cIAP1 mRNA upregulation in mesangial cells, whereas XIAP mRNA was downregulated. However, the changes observed on the mRNA level were not adequately translated to the protein level, and corresponding values for cIAP1 and XIAP were only slightly affected. In contrast, in lipopolysaccharide/interferon-γ-stimulated RAW 264.7 macrophages, massive NO-dependent downregulation of cIAP1 and XIAP protein levels, which correlated temporally with the induction of apoptosis, was observed. This effect was at least partially reversed by NG-monomethyl-L-arginine, an inhibitor of NO synthase activity. In summary, a direct correlation between the downregulation of IAP protein levels and the induction of apoptosis by endogenous NO was observed in macrophages. In contrast, a stable level of IAP protein in mesangial cells might represent a mechanism for the resistance of the cells to endogenously produced NO.
Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens
Authors: Taruna Madan, Uday Kishore, Mamta Singh, Peter Strong, Howard Clark, Ejaj M. Hussain, Kenneth B.M. Reid, P. Usha Sarma
Journal: Journal of Clinical Investigation (2001)

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (Afu). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of Afu, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by Afu antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of Afu-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A–treated ABPA mice, and up to 16 days in the SP-D– or rSP-D–treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-γ was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions.
A20 protects endothelial cells from TNF-, Fas-, and NK-mediated cell death by inhibiting caspase 8 activation
Authors: Soizic Daniel, Maria B. Arvelo, Virendra I. Patel, Christopher R. Longo, Gautam Shrikhande, Tala Shukri, Jerome Mahiou, David W. Sun, Christina Mottley, Shane T. Grey, Christiane Ferran
Journal: Blood (2004)
Efficacy of daytime continuous positive airway pressure titration in severe obstructive sleep apnoea
Authors: J.C. Rudkowski, P. Verschelden, R.J. Kimoff
Journal: European Respiratory Journal (2001)

The aim of this study was to evaluate manual nasal continuous positive airway pressure (nCPAP) titration during daytime polysomnography compared with conventional overnight titration for patients with severe obstructive sleep apnoea. Thirty-two patients who underwent daytime titration were retrospectively matched (for age, sex, body mass index and apnoea/hypopnoea index (AHI)) to a group titrated overnight during the same period. Successful titration was defined as the identification of the nCPAP level (effective nCPAP ( P eff )) required to eliminate respiratory events during all sleep stages. After 3 months of therapy on nCPAP at P eff , nCPAP utilization history was obtained and a group of patients underwent a repeat polysomnogram (PSG) and completed a follow-up Epworth Sleepiness Scale (ESS) score. Initial titration was successful in 91% of daytime patients and 91% of overnight patients. The success of daytime titration was not related to diagnostic AHI or ESS score. Subjective nCPAP utilization was statistically similar in both groups. On the follow-up PSG, there were no significant differences between daytime (n=11) and overnight (n=11) patients in measures of sleep quality or respiratory disturbance. Both groups demonstrated similar and significant improvements in ESS score. These findings suggest that the effective nasal continuous positive airway pressure can be accurately established during daytime titration in a substantial proportion of severe, symptomatic obstructive sleep apnoea patients.
<i>KDR</i> Activating Mutations in Human Angiosarcomas Are Sensitive to Specific Kinase Inhibitors
Authors: Cristina R. Antonescu, Akihiko Yoshida, Tianhuo Guo, Ning-En Chang, Lei Zhang, Narasimhan P. Agaram, Li-Xuan Qin, Murray F. Brennan, Samuel Singer, Robert G. Maki
Journal: Cancer Research (2009)

Abstract Angiosarcomas (AS) represent a heterogeneous group of malignant vascular tumors occurring not only in different anatomic locations but also in distinct clinical settings, such as radiation or associated chronic lymphedema. Although representing only 1% to 2% of soft tissue sarcomas, vascular sarcomas provide unique insight into the general process of tumor angiogenesis. However, no molecular candidates have been identified to guide a specific therapeutic intervention. By expression profiling, AS show distinct up-regulation of vascular-specific receptor tyrosine kinases, including TIE1, KDR, SNRK, TEK, and FLT1. Full sequencing of these five candidate genes identified 10% of patients harboring KDR mutations. A KDR-positive genotype was associated with strong KDR protein expression and was restricted to the breast anatomic site with or without prior exposure to radiation. Transient transfection of KDR mutants into COS-7 cells showed ligand-independent activation of the kinase, which was inhibited by specific KDR inhibitors. These data provide a basis for the activity of vascular endothelial growth factor receptor–directed therapy in the treatment of primary and radiation-induced AS. [Cancer Res 2009;69(18):7175–9]
Quality of Life After Contralateral Prophylactic Mastectomy in Newly Diagnosed High-Risk Breast Cancer Patients Who Underwent <i>BRCA1</i>/<i>2</i> Gene Testing
Authors: Kenneth P. Tercyak, Beth N. Peshkin, Barbara M. Brogan, Tiffani DeMarco, Marie F. Pennanen, Shawna C. Willey, Colette M. Magnant, Sarah Rogers, Claudine Isaacs, Marc D. Schwartz
Journal: Journal of Clinical Oncology (2006)

Recent studies indicate that high-risk breast cancer patients (ie, women who carry mutations in BRCA1/2 genes) who opt for contralateral prophylactic mastectomy (CPM) have a substantially reduced risk of developing contralateral breast cancer. However, the immediate and long-term impact of this decision on women's quality of life and psychosocial functioning is largely unknown. In this study, we compared the impact of BRCA1/2 genetic test result and CPM on these outcomes among newly diagnosed breast cancer patients who opted for CPM at the time of their definitive surgical treatment versus patients who did not.Participants were 149 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. We measured self-reported quality of life, cancer-specific distress, and genetic testing-specific distress using standardized instruments before receipt of genetic test results and again 1 and 12 months later.Compared with patients who chose breast conservation or unilateral mastectomy, those who chose mastectomy of the affected breast and CPM of the unaffected breast did not report diminished quality of life or elevated distress.With respect to quality of life and distress, patients who choose CPM fare as well as those who do not in the first year after surgery.
Essential Role of Survivin, an Inhibitor of Apoptosis Protein, in T Cell Development, Maturation, and Homeostasis
Authors: Zheng Xing, Edward M. Conway, Chulho Kang, Astar Winoto
Journal: The Journal of Experimental Medicine (2003)

Survivin is an inhibitor of apoptosis protein that also functions during mitosis. It is expressed in all common tumors and tissues with proliferating cells, including thymus. To examine its role in apoptosis and proliferation, we generated two T cell-specific survivin-deficient mouse lines with deletion occurring at different developmental stages. Analysis of early deleting survivin mice showed arrest at the pre-T cell receptor proliferating checkpoint. Loss of survivin at a later stage resulted in normal thymic development, but peripheral T cells were immature and significantly reduced in number. In contrast to in vitro studies, loss of survivin does not lead to increased apoptosis. However, newborn thymocyte homeostatic and mitogen-induced proliferation of survivin-deficient T cells were greatly impaired. These data suggest that survivin is not essential for T cell apoptosis but is crucial for T cell maturation and proliferation, and survivin-mediated homeostatic expansion is an important physiological process of T cell development.
US task force recommends screening for depression
Authors: D. Josefson
Journal: BMJ (2002)

The US Preventive Services Task Force, an independent panel of healthcare experts that advises the federal government on health care, is urging that doctors routinely screen all adult patients for depression.

This is an upgrade of its 1996 recommendations, which found insufficient evidence to support or rule out routine screening. The panel still finds insufficient evidence to recommend for or against routine screening for depression in children and adolescents, despite a prevalence of the illness of up to 2% in children and 4.5% in adolescents. Clinicians should, however, continue to …
EXPERIMENTAL STUDIES ON DIABETES
Authors: Frederick M. Allen
Journal: The Journal of Experimental Medicine (1920)

1. The injurious effects of excessive carbohydrate diet are demonstrable in partially depancreatized dogs, in the same manner as in human patients. With severe diabetes there is rapid progress of emaciation and weakness and early death. 2. With milder diabetes, there is frequently a transitional state following operation, when the fate depends on the diet. If the tolerance is spared for a time, recovery sometimes occurs to such extent that diabetes cannot be produced by any kind or quantity of feeding, but only by removal of a small additional fragment of pancreatic tissue. The proper degree of carbohydrate overfeeding is important in this early period for producing the most useful type of diabetic animals; namely, those having good digestion and general health combined with a permanent lowering of assimilative power, like the condition of human patients. 3. In the early stage, glucose is more powerful than starch in producing diabetes, and animals which are progressing toward complete recovery on starch diet can be sent into hopeless diabetes by admixture of glucose. The difference seems to be merely of the rate of absorption, and indicates that a rapid flood of carbohydrate is more injurious to the pancreatic function than a slow absorption. Whenever permanent diabetes is present, so that complete recovery is impossible, starch brings on glycosuria more slowly than sugar, but just as surely. The difference in time in different cases amounts to days, weeks, or months. The clinical lesson from such experiments is that even if a patient becomes free from glycosuria on withdrawal of sugar only, nevertheless other foods should also be limited. 4. No significant differences were observed between the assimilation of different starches, or any extreme lowering of the carbohydrate tolerance by proteins, such as alleged by certain writers in connection with the "oatmeal cure". 5. Repair of traumatic inflammation and hypertrophy of the pancreas remnant have been mentioned incidentally as the basis of the early tendency to recovery, and also hydropic degeneration of Langerhans islands as an accompaniment of the lowering of tolerance by excessive diet. These are believed to have their parallels in human cases, and are to be described more fully hereafter.
Disorders of B cells and helper T cells in the pathogenesis of the immunoglobulin deficiency of patients with ataxia telangiectasia.
Authors: T A Waldmann, S Broder, C K Goldman, K Frost, S J Korsmeyer, M A Medici
Journal: Journal of Clinical Investigation (1983)

The pathogenesis of the immunoglobulin deficiency of 20 patients with ataxia telangiectasia was studied using an in vitro immunoglobulin biosynthesis system. 10 patients had no detectable IgA in their serum as assessed by radial diffusion in agar and 3 had a reduced serum IgA concentration. The peripheral blood mononuclear cells of 17 of the patients and 17 normal controls were cultured with pokeweed mitogen for 12 d and the immunoglobulin in the supernatants measured. The immunoglobulin synthesis was below the lower limit of the normal 95% confidence interval for IgM in 5 patients, for IgG in 8, and for IgA in 14. The mononuclear cells from 9 of the 10 patients with a serum IgA concentration less than 0.1 mg/ml failed to synthesize IgA in vitro. None of the patients manifested excessive suppressor cell activity. All patients had reduced but measurable helper T cell activity for immunoglobulin synthesis by co-cultured normal pokeweed mitogen-stimulated B cells (geometric mean 22% of normal). Furthermore, the addition of normal irradiated T cells to patient peripheral blood mononuclear cells led to an augmentation of IgM synthesis in 15 of 17 and to increased IgG synthesis in 9 of the 17 patients studied, including 9 of the 12 patients who had synthesized IgG before the addition of the irradiated T cells. In addition, IgA synthesis was increased in all eight patients examined that had serum IgA concentrations greater than 0.1 mg/ml. These studies suggest that a helper T cell defect contributes to the diminished immunoglobulin synthesis. However, a helper T cell defect does not appear to be the sole cause since there was no IgA synthesis by the peripheral blood mononuclear cells of 9 of the 10 patients with a profoundly reduced serum IgA even when co-cultured with normal T cells. Furthermore, the cells of the nine patients with profoundly reduced IgA levels examined also failed to produce IgA when stimulated with the relatively helper T cell-independent polyclonal activators, Nocardia water soluble mitogen or Epstein-Barr virus. Taken together these data support the view that the reduced immunoglobulin synthesis of these patients is due to defects of both B cells and helper T cells. Such a broad defect in lymphocyte maturation taken in conjunction with our demonstration of persistent alpha fetoprotein production by ataxia telangiectasia patients provides support for the proposal that these patients exhibit a generalized defect in tissue differentiation.
Acute ischemia-induced gap junctional uncoupling and arrhythmogenesis
Authors: J DEGROOT, R CORONEL
Journal: Cardiovascular Research (2004)

Sudden cardiac death forms a major cause of mortality. Myocardial ischemia-induced ventricular fibrillation (VF) is frequently the underlying mechanism. Ventricular arrhythmias arise in two distinct phases during the first hour of ischemia. The first, the 1A phase, has been extensively studied, and few studies relate to the 1B phase. The latter is associated with intercellular electrical uncoupling, mediated by decreased conductance of gap junction channels.
Pygopagus conjoined twins.
Authors: J. M. Gupta
Journal: BMJ (1966)

Congestive Heart Failure-Domenet et al.BirMMDI mild congestive phenomena.In such cases it appears justifiable to rely upon physiotherapeutic measures while in bed, and early ambulation, to prevent venous thromboembolism.In the case of older patients with severe congestive failure, however, oral anticoagulant drug therapy can be expected to prevent venous thromboembolism after the second week, and such prophylaxis is clearly indicated if its possible early thrombo- genic tendency can be overcome.Concurrent high-dosage intravenous heparin therapy during the first week or 10 days may surmount this difficulty, but, with the methods at present in use, would seriously interfere with the prothrombin estima- tions necessary for accurate adjustment of the dose of oral anticoagulant.Rapid attainment of therapeutically desirable prothrombin levels by means of heavier initial loading doses of a quicker acting oral anticoagulant such as ethyl biscoum- acetate (Weiner et ac., 1955), perhaps with heparin for the first day or two, may offer a preferable alternative. SummaryThe incidence of pulmonary embolism in 76 patients with congestive cardiac failure given prophylactic (oral) anticoagu- lant therapy was 8 %.The incidence in a similar control series of 80 such patients not given anticoagulants was 10%.Anticoagulant prophylaxis with phenindione, instituted at the time of admission, appears to afford protection against venous thromboembolic complications after the first 10 days, but this advantage is counterbalanced by an apparently increased tendency to such episodes during the first week or 10 days of administration of the drug.The risk of thromboembolism in patients with clinically mild degrees of failure is too small to warrant routine anticoagulant drug prophylaxis.We gratefully acknowledge the keen interest taken by the late Dr. 0. Brenner in the establishment of this trial and his kind permission to study patients under his care.Our thanks
Harmonisation of TB control in the WHO European region: the history of the Wolfheze Workshops
Authors: J Veen, G B Migliori, M Raviglione, H L Rieder, M Dara, D Falzon, J V Kuyvenhoven, V Schwoebel, R Zaleskis
Journal: European Respiratory Journal (2010)

In 1990 a workshop was organised in the village of Wolfheze (the Netherlands), where experts discussed the critical interventions that would foster elimination of TB in Europe. This event has been followed by several more over the following two decades to become known as the “Wolfheze Workshops”. This article provides a brief overview of the history and the impact the Wolfheze Workshops have had on the commitment of European governments to standardise definitions, recording and reporting systems and, thus, permitted comparison of interventions and improving TB control across borders. The Wolfheze Workshops have been and still are an essential platform for this exchange of experiences, promoting common approaches.
Regulation of airway neurogenic inflammation by neutral endopeptidase
Authors: GU Di Maria, S Bellofiore, P Geppetti
Journal: European Respiratory Journal (1998)

Airway neurogenic inflammation is caused by tachykinins released from peripheral nerve endings of sensory neurons within the airways, and is characterized by plasma protein extravasation, airway smooth muscle contraction and increased secretion of mucus. Tachykinins are degraded and inactivated by neutral endopeptidase (NEP), a membrane-bound metallopeptidase, which is located mainly at the surface of airway epithelial cells, but is also present in airway smooth muscle cells, submucosal gland cells and fibroblasts. The key role of NEP in limiting and regulating the neurogenic inflammation provoked by different stimuli has been demonstrated in a large series of studies published in recent years. It has also been shown that a variety of factors, which are relevant for airway diseases, including viral infections, allergen exposure, inhalation of cigarette smoke and other respiratory irritants, is able to reduce NEP activity, thus enhancing the effects of tachykinins within the airways. On the basis of these observations, the reduction of neutral endopeptidase activity may be regarded as a factor that switches neurogenic airway responses from their physiological and protective functions to a detrimental role that increases and perpetuates airway inflammation. However, further studies are needed to assess the role of neutral endopeptidase down regulation in the pathogenesis of asthma and other inflammatory airway diseases.
The positive impact of the new National Institute for Health and Care Excellence lipid guidelines on cardiovascular disease risk management in patients with psoriasis
Authors: S. Kaur, A.R. Shipman, K.E. Shipman
Journal: British Journal of Dermatology (2015)

Journal Article The positive impact of the new National Institute for Health and Care Excellence lipid guidelines on cardiovascular disease risk management in patients with psoriasis Get access S. Kaur, S. Kaur Heart of England NHS Foundation Trust Birmingham B9 5SS U.K Search for other works by this author on: Oxford Academic Google Scholar A.R. Shipman, A.R. Shipman University Hospitals Birmingham NHS Foundation Trust Birmingham U.K Search for other works by this author on: Oxford Academic Google Scholar K.E. Shipman K.E. Shipman Heart of England NHS Foundation Trust Birmingham B9 5SS U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 5, 1 November 2015, Pages 1327–1328, https://doi.org/10.1111/bjd.13950 Published: 01 November 2015