tbuckley/cabot-search huggingface dataset:
ESOPHAGEAL APERISTALSIS AND ACHALASIA PRODUCED IN DOGS BY PROLONGED CHOLINESTERASE INHIBITION*
Authors: Lauran D. Harris, W. D. Ashworth, Franz J. Ingelfinger
Journal: Journal of Clinical Investigation (1960)

Considerable evidence suggests that cardio- spasm, or achalasia of the esophagus, is a disease of the intrinsic innervation of that organ (1-6).If so, a neurotoxic agent might produce a similar picture in experimental animals.This possibility is enhanced by the report of Koelle and Gilman (7) who, while studying the effects of prolonged administration to dogs of the anticholinesterase agent di-isopropylfluorophosphate (DFP), noted the appearance of objective evidences of dysphagia, esophageal stasis, and "cardiospasm."However, not all motor dysfunctions causing dysphagia and esophageal stasis in man are manifestations of cardiospasm, and no studies have been performed to show that DFP-induced canine "cardiospasm" is indeed analogous to the condition seen in man.Consequently, we undertook to see if 1) prolonged DFP administration does regularly produce an esophageal motor disorder in dogs, and 2), if so, to determine its nature and its similarity to hu- man cardiospasm. METHODSSix adult mongrel dogs, 2 male and 4 female, weighing 15 to 18 kg, were prepared with permanent cervical esophageal fistulas by the method of Ware and Howe (8).This preparation allows natural feeding with only minimal leakage, yet permits ready insertion of recording balloons, tubes and barium with no discomfort to the unanesthetized animal.Special care was taken during preparation of the fistula to identify and avoid injury to the vagi.All dogs ate and drank normally and main- tained their weight before and after the fistulas were pre- pared.Weights were recorded weekly throughout the control and experimental periods.The dogs were easily trained to lie quietly for as long as 4 hours, unrestrained, while studies were done.
Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis
Authors: Shaun A. Summers, Betty S. van der Veen, Kim M. O'Sullivan, Poh-Yi Gan, Joshua D. Ooi, Peter Heeringa, Simon C. Satchell, Peter W. Mathieson, Moin A. Saleem, Kumar Visvanathan, Stephen R. Holdsworth, A. Richard Kitching
Journal: Kidney International (2010)
Rituximab and Intravenous Immune Globulin for Desensitization during Renal Transplantation
Authors: Ashley A. Vo, Marina Lukovsky, Mieko Toyoda, Jennifer Wang, Nancy L. Reinsmoen, Chih-Hung Lai, Alice Peng, Rafael Villicana, Stanley C. Jordan
Journal: New England Journal of Medicine (2008)

Few options for transplantation currently exist for patients highly sensitized to HLA. This exploratory, open-label, phase 1-2, single-center study examined whether intravenous immune globulin plus rituximab could reduce anti-HLA antibody levels and improve transplantation rates.Between September 2005 and May 2007, a total of 20 highly sensitized patients (with a mean [+/-SD] T-cell panel-reactive antibody level, determined by use of the complement-dependent cytotoxicity assay, of 77+/-19% or with donor-specific antibodies) were enrolled and received treatment with intravenous immune globulin and rituximab. We recorded rates of transplantation, panel-reactive antibody levels, cross-matching results at the time of transplantation, survival of patients and grafts, acute rejection episodes, serum creatinine values, adverse events and serious adverse events, and immunologic factors.The mean panel-reactive antibody level was 44+/-30% after the second infusion of intravenous immune globulin (P<0.001 for the comparison with the pretreatment level). At study entry, the mean time on dialysis among recipients of a transplant from a deceased donor was 144+/-89 months (range, 60 to 324). However, the time to transplantation after desensitization was 5+/-6 months (range, 2 to 18). Sixteen of the 20 patients (80%) received a transplant. At 12 months, the mean serum creatinine level was 1.5+/-1.1 mg per deciliter (133+/-97 micromol per liter), and the mean survival rates of patients and grafts were 100% and 94%, respectively. There were no infusion-related adverse events or serious adverse events during the study. Long-term monitoring for infectious complications and neurologic problems revealed no unanticipated events.These findings suggest that the combination of intravenous immune globulin and rituximab may prove effective as a desensitization regimen for patients awaiting a transplant from either a living donor or a deceased donor. Larger and longer trials are needed to evaluate the clinical efficacy and safety of this approach. (ClinicalTrials.gov number, NCT00642655.)
Second round robin for plasma hepcidin methods: First steps toward harmonization
Authors: Joyce J.C. Kroot, Antonius E. van Herwaarden, Harold Tjalsma, Rob T.P. Jansen, Jan C.M. Hendriks, Dorine W. Swinkels
Journal: American Journal of Hematology (2012)

Measurements of the iron regulatory hormone hepcidin by various methodologies and laboratories are not harmonized. As a result different numeric results are obtained for the same clinical sample. We investigated whether better agreement between plasma hepcidin methods can be achieved by harmonization. Native plasma pools (n = 11) of a variety of hepcidin concentrations and blank plasma spiked with three different quantities of synthetic hepcidin-25 purchased from two different commercial sources (n = 6), were distributed in duplicate among 21 methods worldwide. We assessed commutability by comparing results from synthetic hepcidin with those from native samples in various method couples by Bland-Altman plots. Methods differed substantially in absolute values and reproducibility. For the majority of methods we found that samples with synthetic hepcidin-25 were noncommutable with the native samples. In an attempt to harmonize by using native hepcidin results, we selected two methods that showed good mutual agreement of native results and calculated consensus values as the medians for the 11 duplicate native samples obtained by these two methods. Finally, we constructed algorithms enabling the laboratories to calculate the hepcidin consensus (HEPCON) value using their own native hepcidin results. We found that the use of these algorithms substantially reduced the between-method CV. Until commutable materials are defined, hepcidin harmonization can be achieved by exploiting specific algorithms, allowing each lab to report their native hepcidin concentrations in HEPCON values. This study represents the first step toward harmonization of plasma hepcidin methods and facilitates aggregation of hepcidin data from different research investigations.
A Contribution of Mouse Dendritic Cell–Derived IL-2 for NK Cell Activation
Authors: Francesca Granucci, Ivan Zanoni, Norman Pavelka, Serani L.H. van Dommelen, Christopher E. Andoniou, Filippo Belardelli, Mariapia A. Degli Esposti, Paola Ricciardi-Castagnoli
Journal: The Journal of Experimental Medicine (2004)

Dendritic cells (DCs) play a predominant role in activation of natural killer (NK) cells that exert their functions against pathogen-infected and tumor cells. Here, we used a murine model to investigate the molecular mechanisms responsible for this process. Two soluble molecules produced by bacterially activated myeloid DCs are required for optimal priming of NK cells. Type I interferons (IFNs) promote the cytotoxic functions of NK cells. IL-2 is necessary both in vitro and in vivo for the efficient production of IFNγ, which has an important antimetastatic and antibacterial function. These findings provide new information about the mechanisms that mediate DC–NK cell interactions and define a novel and fundamental role for IL-2 in innate immunity.
Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma
Authors: Beatriz Somovilla-Crespo, Manuel Alfonso-Pérez, Carlos Cuesta-Mateos, Cristina Carballo-de Dios, Amada E Beltrán, Fernando Terrón, Juan J Pérez-Villar, Carlos Gamallo-Amat, Gema Pérez-Chacón, Elena Fernández-Ruiz, Juan M Zapata, Cecilia Muñoz-Calleja
Journal: Journal of Hematology & Oncology (2013)

Abstract Background The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model. Methods NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 × 200 μg) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively. Results The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated. Conclusions The anti-CCR7 mAb exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies.
Comparative study of dose escalation versus interval reduction to obtain dose-intensification of epirubicin and cyclophosphamide with granulocyte colony-stimulating factor in advanced breast cancer.
Authors: R I Lalisang, J A Wils, H W Nortier, J T Burghouts, P S Hupperets, F L Erdkamp, H C Schouten, G H Blijham
Journal: Journal of Clinical Oncology (1997)

PURPOSE A potential application of hematopoietic growth factors is to obtain an increased dose-intensity. This can be achieved by either higher doses of chemotherapy with standard intervals, or by standard doses with shorter intervals. The potential of these approaches has not been investigated systematically. PATIENTS AND METHODS In a randomized, multicenter study, 49 advanced breast cancer patients were treated with granulocyte colony-stimulating factor (G-CSF) and either increasing doses of epirubicin and cyclophosphamide with fixed intervals (arm one) or progressively shorter intervals with fixed doses of epirubicin and cyclophosphamide (arm two). A cohort of at least six patients was studied at each interval/dose. A more intensified interval/dose was given if less than 50% of patients encountered a dose-intensity limiting criterium (DILC) in the first three courses. RESULTS In arm one, epirubicin 140 mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic. Subsequently, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10 patients encountering a DILC. All initial DILCs consisted of febrile neutropenia. In arm two, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely with 14- and 12-day intervals. In the 10-day interval, eight of 12 patients completed the first three cycles without a DILC. In the 8-day interval, seven of eight patients encountered a DILC. Incomplete neutrophil recovery, and to a lesser extent stomatitis, were dose-limiting. CONCLUSION In combination with G-CSF, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every 21 days was feasible (projected dose-intensity, 40 mg/m2/wk and 233 mg/m2/wk, respectively). Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely every 10 days, allowing a projected dose-intensity of 52.5 mg/m2/wk and 350 mg/m2/wk, respectively.
13C carbohydrate breath tests
Authors: R J Vonk, F Stellaard, H Hoekstra, H A Koetse
Journal: Gut (1998)

In paediatric practice proper digestion of carbohydrates is of major importance for adequate growth and development and for prevention of intestinal complaints. Several carbohydrates can be considered in this respect: (a) lactose: the main carbohydrate in the nutrition of early life and also in later life for many white people; (b) starch: the main energy supplier in our food; (c) fructose: a constituent of fruit juices and increasingly used as a sweetener; and (d) galactose: a component of lactose. The fate of this sugar will be considered in more detail in section five, dealing with the measurement of liver function.

Lactose maldigestion due to hypolactasia can be diagnosed in several ways. The non-invasive test most commonly used is the breath hydrogen test after lactose provocation. The reliability of this test, however, is disputed owing to non-H2 producing flora,1 2 or extra intestinal influences that can disturb the test. Moreover, this test has to be done with unphysiological high doses of substrate to get a measurable hydrogen response in breath.3 4 This prompted investigators to develop diagnostic tools which permit the analysis of lactase enzyme activity non-invasively in a more direct way and therefore hopefully also in a more accurate and quantitative way. Hiele et al used naturally enriched 13C lactose and measured the13CO2 excretion in breath to diagnose adult hypolactasia patients.5 

In the BIOMED programme SIGN this principle has also been used by Koetse et al (abstract 1) in paediatric patients. In 27 patients, lactase activity in jejunal biopsy specimens were compared with H2 and 13CO2 breath tests after administration of 13C lactose. Combination of the H2 /13CO2 test results produced a higher sensitivity (85%) and a lower specificity (65%) than the outcome of …
CD4+ T helper cells use CD154–CD40 interactions to counteract T reg cell–mediated suppression of CD8+ T cell responses to influenza
Authors: André Ballesteros-Tato, Beatriz León, Frances E. Lund, Troy D. Randall
Journal: The Journal of Experimental Medicine (2013)

CD4+ T cells promote CD8+ T cell priming by licensing dendritic cells (DCs) via CD40–CD154 interactions. However, the initial requirement for CD40 signaling may be replaced by the direct activation of DCs by pathogen-derived signals. Nevertheless, CD40–CD154 interactions are often required for optimal CD8+ T cell responses to pathogens for unknown reasons. Here we show that CD40 signaling is required to prevent the premature contraction of the influenza-specific CD8+ T cell response. CD40 is required on DCs but not on B cells or T cells, whereas CD154 is required on CD4+ T cells but not CD8+ T cells, NKT cells, or DCs. Paradoxically, even though CD154-expressing CD4+ T cells are required for robust CD8+ T cell responses, primary CD8+ T cell responses are apparently normal in the absence of CD4+ T cells. We resolved this paradox by showing that the interaction of CD40-bearing DCs with CD154-expressing CD4+ T cells precludes regulatory T cell (T reg cell)–mediated suppression and prevents premature contraction of the influenza-specific CD8+ T cell response. Thus, CD4+ T helper cells are not required for robust CD8+ T cell responses to influenza when T reg cells are absent.
Epidermolysis bullosa acquisita
Authors: C. NIEBOER, D. M. BOORSMA, M. J. WOERDEMAN, G. L. KALSBEEK
Journal: British Journal of Dermatology (1980)

SUMMARY Four patients with the clinical picture of epidermolysis bullosa acquisita were investigated. Biopsies were taken from the involved and uninvolved areas of the skin and the immunohistochemical and microscopic changes were studied. Direct immunofluorescence showed deposition of IgG and C3/4 in a linear or notched pattern along the epidermal basement membrane in both the involved and the uninvolved skin. In addition IgA (3/4), IgM (1/4), C4 (3/4) and properdin (3/4) could be detected. Indirect immunofluorescence revealed the presence of circulating antibodies against inter alia the epithelial basement membrane zone in one patient. Routine electron microscopy showed that the blister was situated in the dermis leaving the basal lamina in the roof of the blister. With immunoelectron microscopy using peroxidase-labelled antibody the in vivo deposition of IgG was observed just beneath the basal lamina in the dermis of both the perilesional and the uninvolved skin. These observations show that epidermolysis bullosa acquisita is a distinct entity, in which autoimmune mechanisms might possibly play a role.
Immunosuppression by pulmonary surfactant: mechanisms of action.
Authors: M L Wilsher, D J Parker, P L Haslam
Journal: Thorax (1990)

Pulmonary surfactant has been shown by this group to suppress peripheral blood lymphocyte responses to mitogens and alloantigens in a dose dependent manner, though the mechanism of action of the suppressive effect is not clearly understood. To try to clarify this, attempts were made to reverse the effects of preincubation with surfactant, obtained by bronchoalveolar lavage from pigs, on lymphocytes and accessory monocytes obtained from the blood of normal volunteers, by washing and incubating the cells in medium alone for various periods up to 24 hours. Immunosuppression, measured as the reduction in thymidine incorporation in response to the mitogen phytohaemagglutinin, could not be reversed by these methods. The addition of indomethacin (up to 100 micrograms/ml for 72 hours) also had no effect, indicating that the immunosuppression was not related to synthesis of prostaglandins. Incubation with surfactant for as little as two hours before addition of mitogen suppressed in vitro lymphoproliferative responses by half, but surfactant added two hours after mitogen had no observed effect. Preincubation of purified lymphocytes in surfactant, before they were cultured with accessory monocytes and mitogen, caused significant suppression of response, but preincubation of purified monocytes had no suppressive effect. There was no change in the intensity of HLA-DR expression on monocytes. These results support the hypothesis that surfactant exerts its effects on the resting uncommitted lymphocyte rather than on antigen presenting monocytes.
Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study
Authors: Karim Fizazi, Michael Carducci, Matthew Smith, Ronaldo Damião, Janet Brown, Lawrence Karsh, Piotr Milecki, Neal Shore, Michael Rader, Huei Wang, Qi Jiang, Sylvia Tadros, Roger Dansey, Carsten Goessl
Journal: The Lancet (2011)
Detection of human papillomavirus ( <scp>HPV</scp> ) in patients with squamous cell carcinoma and the clinical characteristics of <scp>HPV</scp> ‐positive cases
Authors: A. Shimizu, M. Kato, Y. Takeuchi, T. Sano, K. Kaira, H. Uezato, O. Ishikawa
Journal: British Journal of Dermatology (2014)

The association between human papillomavirus (HPV) and squamous cell carcinoma (SCC) has been reported; however, the prevalence of HPV infection varies, and the clinical characteristics of HPV-positive cases remain unknown.To elucidate the frequency of HPV infection in a series of Japanese patients with SCC and to identify the characteristics of HPV-positive cases.We evaluated 38 patients with SCC treated at our department. HPV typing was performed using SCC samples from different body sites. Immunohistochemical staining for HPV proteins and p16(INK) (4a) was performed, in addition to polymerase chain reaction and in situ hybridization. The clinical characteristics of the HPV-positive cases were clarified.Two genital lesions were positive for HPV type 16. Both cases showed basaloid features histopathologically, and were considered to have SCC that had arisen from bowenoid papulosis. p16(INK) (4a) expression was observed in 11 cases, including the two HPV-positive cases.The present study indicates that the prevalence of HPV is not high and that bowenoid papulosis is an HPV-associated precancerous lesion. Further investigation is necessary to assess the relationship between HPV infection and SCC.
Association between low functional health literacy and mortality in older adults: longitudinal cohort study
Authors: S. Bostock, A. Steptoe
Journal: BMJ (2012)

To investigate the association between low functional health literacy (ability to read and understand basic health related information) and mortality in older adults.Population based longitudinal cohort study based on a stratified random sample of households.England.7857 adults aged 52 or more who participated in the second wave (2004-5) of the English Longitudinal Study of Ageing and survived more than 12 months after interview. Participants completed a brief four item test of functional health literacy, which assessed understanding of written instructions for taking an aspirin tablet.Time to death, based on all cause mortality through October 2009.Health literacy was categorised as high (maximum score, 67.2%), medium (one error, 20.3%), or low (more than one error, 12.5%). During follow-up (mean 5.3 years) 621 deaths occurred: 321 (6.1%) in the high health literacy category, 143 (9.0%) in the medium category, and 157 (16.0%) in the low category. After adjusting for personal characteristics, socioeconomic position, baseline health, and health behaviours, the hazard ratio for all cause mortality for participants with low health literacy was 1.40 (95% confidence interval 1.15 to 1.72) and with medium health literacy was 1.15 (0.94 to 1.41) compared with participants with high health literacy. Further adjustment for cognitive ability reduced the hazard ratio for low health literacy to 1.26 (1.02 to 1.55).A third of older adults in England have difficulties reading and understanding basic health related written information. Poorer understanding is associated with higher mortality. The limited health literacy capabilities within this population have implications for the design and delivery of health related services for older adults in England.
Prematurity, atopy, and childhood asthma in Puerto Ricans
Authors: Christian Rosas-Salazar, Sima K. Ramratnam, John M. Brehm, Yueh-Ying Han, Nadia Boutaoui, Erick Forno, Edna Acosta-Pérez, María Alvarez, Angel Colón-Semidey, Glorisa Canino, Juan C. Celedón
Journal: Journal of Allergy and Clinical Immunology (2013)