tbuckley/cabot-search huggingface dataset:
Intestinal Microbial Diversity during Early-Life Colonization Shapes Long-Term IgE Levels
Authors: Julia Cahenzli, Yasmin Köller, Madeleine Wyss, Markus B. Geuking, Kathy D. McCoy
Journal: Cell Host & Microbe (2013)

Microbial exposure following birth profoundly impacts mammalian immune system development. Microbiota alterations are associated with increased incidence of allergic and autoimmune disorders with elevated serum IgE as a hallmark. The previously reported abnormally high serum IgE levels in germ-free mice suggests that immunoregulatory signals from microbiota are required to control basal IgE levels. We report that germ-free mice and those with low-diversity microbiota develop elevated serum IgE levels in early life. B cells in neonatal germ-free mice undergo isotype switching to IgE at mucosal sites in a CD4 T-cell- and IL-4-dependent manner. A critical level of microbial diversity following birth is required in order to inhibit IgE induction. Elevated IgE levels in germ-free mice lead to increased mast-cell-surface-bound IgE and exaggerated oral-induced systemic anaphylaxis. Thus, appropriate intestinal microbial stimuli during early life are critical for inducing an immunoregulatory network that protects from induction of IgE at mucosal sites.
Breast abscess due to <i>Corynebacterium striatum</i>
Authors: N. STONE, P. GILLETT, S. BURGE
Journal: British Journal of Dermatology (1997)

Corynebacterium striatum, a normal constituent of the skin flora, is rarely pathogenic. Previous reports of infection are few, and are mainly confined to immunosuppressed patients or those with indwelling prosthetic devices. We report a case in which the organism caused a recurrent breast abscess in a woman with normal immune function. The only previous reports of Corynebacterium striatum mastitis have been in cows.
Ursodeoxycholic acid in chronic hepatitis C
Authors: R. Poupon, L. Serfaty
Journal: Gut (2007)

short courses of steroids to prevent long-term disease complications.N Does treatment prevent the develop- ment of organ dysfunction?It appears that progression to pancreatic atrophy occurs in 30-50% of AIP patients.We have seen progression to cirrhosis in patients with biliary disease.It is unclear whether steroid treatment prevents or decreases the likelihood of disease progression.N Do different manifestations of IgG4- related systemic disease have different disease courses?IgG4-related systemic disease can involve multiple organs (pancreas, bile duct, retroperitoneum, kidneys, lungs, salivary glands).It is unclear if relapse rates and long-term prognosis differ with various manifestations of the disease.If so, then mode and duration of treatment may need to be tailored based on the involved organ.N What is the significance of isolated serological relapse?Serological relapse is a common clinical scenario.Patients present with elevated IgG4 after treatment but no recurrent disease on imaging.The significance of this finding and whether these patients eventually progress to clinical relapse is unknown.If so, then this would support the early treatment of serological relapses.
Pulmonary Function at Follow-up of Very Preterm Infants from the United Kingdom Oscillation Study
Authors: Mark R. Thomas, Gerrard F. Rafferty, Elizabeth S. Limb, Janet L. Peacock, Sandra A. Calvert, Neil Marlow, Anthony D. Milner, Anne Greenough
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Prematurely born infants supported by conventional ventilation (CV) frequently have abnormal pulmonary function when assessed in childhood. The aim of this study was to test the hypothesis that infants who were randomly assigned to high-frequency oscillatory ventilation would have superior pulmonary function at follow-up compared with those who received CV (UK Oscillation Study). Infants from 12 trial centers were recruited for pulmonary function testing at a single center. Seventy-six infants, of a mean gestational age 26.4 weeks, were studied after sedation with chloral hydrate at between 11 and 14 months of age, corrected for prematurity. Infants assigned to CV had similar pulmonary function compared with those assigned to high-frequency oscillatory ventilation, with mean (SD) results as follows: functional residual capacity measured by whole-body plethysmography, 26.9 (6.3) versus 26.5 (6.4) ml/kg; functional residual capacity measured by helium dilution, 24.1 (5.4) versus 23.5 (5.7) ml/kg; inspiratory airway resistance, 3.3 (1.3) versus 3.4 (1.6) kPa. second. L; expiratory airway resistance, 4.4 (2.8) versus 4.1 (2.5) kPa. second. L; respiratory rate, 31.2 (6.0) versus 33.9 (8.0) breaths/minute. We conclude that early use of high-frequency oscillatory ventilation in very preterm infants appears to offer no advantage over CV in terms of pulmonary function at follow-up.
Improved or fatal acute disseminated intravascular coagulation in systemic lupus erythematosus
Authors: Yoshinori Shimamoto, Akihide Ohta, Masayuki Sano, Kenji Suga, Masaya Yamaguchi
Journal: American Journal of Hematology (1993)

Abstract To analyze the outcome of systemic lupus erythematosus (SLE) associated with acute disseminated intravascular coagulation (DIC) and also to clarify the clinical factor(s) contributing to the outcome, we retrospectively investigated 120 SLE patients treated between 1981 and 1991. Eight of these patients (6.7%) developed acute DIC; four recovered and the other four died within 2 weeks of onset. Infection preceded acute DIC in all these patients. Acute DIC associated with atypical pneumonia was always fatal, while the patients with pharyngitis or urinary tract infection survived when they were treated adequately. Comparison of the dead and surviving groups revealed that the activity of SLE before the onset of DIC, the severity of DIC, and the treatment given for DIC and the coexistent infection were not significantly related to a fatal outcome. However, severe infection such as atypical pneumonia in patients with secondary immunodeficiency was likely to be fatal irrespective of the presence of DIC. © 1993 Wiley‐Liss, Inc.
Breast Cancer Risk in Female Survivors of Hodgkin's Lymphoma: Lower Risk After Smaller Radiation Volumes
Authors: Marie L. De Bruin, Judith Sparidans, Mars B. van't Veer, Evert M. Noordijk, Marieke W.J. Louwman, Josée M. Zijlstra, Hendrik van den Berg, Nicola S. Russell, Annegien Broeks, Margreet H.A. Baaijens, Berthe M.P. Aleman, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2009)

Purpose We assessed the long-term risk of breast cancer (BC) after treatment for Hodgkin's lymphoma (HL). We focused on the volume of breast tissue exposed to radiation and the influence of gonadotoxic chemotherapy (CT). Patients and Methods We performed a cohort study among 1,122 female 5-year survivors treated for HL before the age of 51 years between 1965 and 1995. We compared the incidence of BC with that in the general population. To assess the risk according to radiation volume and hormone factors, we performed multivariate Cox regression analyses. Results After a median follow-up of 17.8 years, 120 women developed BC (standardized incidence ratio [SIR], 5.6; 95% CI, 4.6 to 6.8), absolute excess risk 57 per 10,000 patients per year. The overall cumulative incidence 30 years after treatment was 19% (95% CI, 16% to 23%); for those treated before age 21 years, it was 26% (95% CI, 19% to 33%). The relative risk remained high after prolonged follow-up (&gt; 30 years after treatment: SIR, 9.5; 95% CI, 4.9 to 16.6). Mantle field irradiation (involving the axillary, mediastinal, and neck nodes) was associated with a 2.7-fold increased risk (95% CI, 1.1 to 6.9) compared with similarly dosed (36 to 44 Gy) mediastinal irradiation alone. Women with ≥ 20 years of intact ovarian function after radiotherapy at young ages (&lt; 31 years) experienced significantly higher risks for BC than those with fewer than 10 years of intact ovarian function. Conclusion Reduction of radiation volume appears to decrease the risk for BC after HL. In addition, shorter duration of intact ovarian function after irradiation is associated with a significant reduction of the risk for BC.
Metabolic coupling of glutathione between mouse and quail cardiac myocytes and its protective role against oxidative stress.
Authors: T Y Nakamura, I Yamamoto, Y Kanno, Y Shiba, K Goshima
Journal: Circulation Research (1994)

Cultured quail myocytes were much more resistant to H2O2 toxicity than cultured mouse myocytes. The intracellular concentration of glutathione ([GSH]i) and the activity of gamma-glutamylcysteine synthetase (gamma-GCS) in quail heart cells were about five and three times higher, respectively, than in mouse heart cells, although catalase and glutathione peroxidase (GSHpx) activity was similar in both. Preloading of gamma-glutamylcysteine monoethyl ester (gamma-GCE), a membrane-permeating GSH precursor, increased the H2O2 resistance of cultured mouse myocytes. These observations suggest that the high [GSH]i and the high activity of gamma-GCS in quail myocytes are responsible for their high resistance to H2O2. Both H2O2 sensitivity and [GSH]i of mosaic sheets composed of equal amounts of mouse and quail myocytes approximated those of sheets composed entirely of quail myocytes. From these observations, it is hypothesized that GSH was transferred from quail myocytes to mouse myocytes, probably through gap junctions between them, and that quail myocytes resynthesized GSH by a feedback mechanism, thus maintaining their intracellular GSH levels. When the fluorescent dye lucifer yellow was injected into a beating quail myocyte in a mosaic sheet, it spread to neighboring mouse myocytes but not to neighboring L cells (a cell line derived from mouse connective tissue). These observations indicate that existence of gap junctions in the region of cell contact between mouse and quail myocytes but not between quail myocytes and L cells. When quail myocytes preloaded with [3H]gamma-GCE were cocultured with mouse myocytes and L cells, the radioactivity was transmitted to neighboring mouse myocytes but not L cells. These observations show that GSH and/or its precursors can be transmitted from quail myocytes to mouse myocytes through gap junctions and that this can protect mouse myocytes from H2O2 toxicity. Mouse myocyte sheets composed of 10(4) cells or more showed higher resistance to H2O2 toxicity than single isolated mouse myocytes. Metabolic coupling of GSH between myocytes may contribute at least in part to this high resistance of the cell sheets.
Micropuncture Study of Inorganic Phosphate Excretion in the Rat *
Authors: James C. Strickler, David D. Thompson, Ruth M. Klose, Gerhard Giebisch, Judith N. Gluck, Judith B. Vaughan
Journal: Journal of Clinical Investigation (1964)

The mechanism by which the mammalian kidney excretes inorganic phosphate has not been fully elucidated.The only micropuncture data avail- able are those of Walker and Hudson (1), and they deal with the mode of phosphate excretion in two amphibian species.These investigators reported that the inorganic phosphate concentration rises progressively along the proximal and distal neph- ron of the frog and Necturus.In the frog this rise can be accounted for by tubular fluid reab- sorption, but in the Necturus the secretion of phosphate could not always be excluded.Evi- dence obtained by clearance experiments in verte- brates indicates significant species differences.Thus, renal tubular phosphate secretion has been conclusively demonstrated in certain fish (2-4), the alligator (5), and the chicken (6).The mechanism of phosphate excretion in the mam- malian kidney, on the other hand, has remained, to some extent, controversial.According to Pitts and Alexander, in the dog (7) there is a maximal tubular reabsorptive capacity for phosphate, the renal transfer of phosphate being achieved by a combination of glomerular filtration and subse- *
Pulmonary Vascular Endothelial Growth Factor and Flt-1 in Fetuses, in Acute and Chronic Lung Disease, and in Persistent Pulmonary Hypertension of the Newborn
Authors: PATRIK LASSUS, MAILA TURANLAHTI, PÄIVI HEIKKILÄ, LEIF C. ANDERSSON, IRMELI NUPPONEN, ANNIKKI SARNESTO, STURE ANDERSSON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<PATIENTSMETHODSRESULTSDISCUSSIONReferencesCITING ARTICLES
Measurement of lung volumes in humans: review and recommendations from an ATS/ERS workshop
Authors: JL Clausen, AL Coates, PH Quanjer
Journal: European Respiratory Journal (1997)

Neutrophils are essential players in innate immune responses to bacterial infection. Despite the striking resistance of <i>Legionella pneumophila</i> (<i>Lpn</i>) to bactericidal neutrophil function, neutrophil granulocytes are important effectors in the resolution of legionellosis. Indeed, mice depleted of neutrophils were unable to clear <i>Lpn</i> due to a lack of the critical cytokine IFN-γ, which is produced by NK cells. We demonstrate that this can be ascribed to a previously unappreciated role of neutrophils as major NK cell activators. In response to <i>Lpn</i> infection, neutrophils activate caspase-1 and produce mature IL-18, which is indispensable for the activation of NK cells. Furthermore, we show that the IL-12p70 response in <i>Lpn</i>-infected neutropenic mice is also severely reduced and that the <i>Lpn</i>-induced IFN-γ production by NK cells is strictly dependent on IL-12. However, since dendritic cells, and not neutrophils, are the source of <i>Lpn</i>-induced IL-12, its paucity is a consequence of the absence of IFN-γ produced by NK cells rather than the absence of neutrophils per se. Therefore, neutrophil-derived IL-18, in combination with dendritic cell-produced IL-12, triggers IFN-γ synthesis in NK cells in <i>Lpn</i>-infected mice. We propose a novel central role for neutrophils as essential IL-18 producers and hence NK cell “helpers” in bacterial infection.
Prospective Evaluation of a Follow-Up Schedule in Cutaneous Melanoma Patients: Recommendations for an Effective Follow-Up Strategy
Authors: Claus Garbe, Andrena Paul, Hanna Kohler-Späth, Ulf Ellwanger, Waltraud Stroebel, Monika Schwarz, Bettina Schlagenhauff, Friedegund Meier, Birgit Schittek, Hans-Juergen Blaheta, Andreas Blum, Gernot Rassner
Journal: Journal of Clinical Oncology (2003)

To prospectively examine and evaluate the results of follow-up procedures in a large cohort of cutaneous melanoma patients.This was a prospective study in 2,008 consecutive patients with stage I to IV cutaneous melanoma from 1996 to 1998 on the yield of stage-appropriate follow-up examinations according to the German guidelines. Documentation of patient and follow-up data comprised patient demography, primary tumor specifics, and any clinical and technical examinations performed. The detection of metastasis was classified as early or late, and the means of their detection and the resulting overall survival probabilities were examined.A total of 3,800 clinical examinations and 12,398 imaging techniques were documented. Sixty-two second primary melanomas in 46 patients and 233 disease recurrences in 112 patients were detected during this time. In stage I to III disease, physical examination was responsible for the discovery of 50% of all recurrences. In the primary tumor stages, 21% of all recurrences were discovered by lymph node sonography, with the majority being classified as early detection. Forty-eight percent of the recurrences were classified as early detection, and these patients had a significant benefit of overall survival probability.The results of our study suggest that an elaborated follow-up schedule in cutaneous melanoma is suitable for the early detection of second primary melanomas and early recurrences. The intensity of clinical and technical examinations can be reduced during follow-up of patients in the primary tumor stages and may be intensified in locoregional disease. Recommendations for an effective follow-up strategy are outlined.
Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension
Authors: S. C. Mathai, R. E. Girgis, M. R. Fisher, H. C. Champion, T. Housten-Harris, A. Zaiman, P. M. Hassoun
Journal: European Respiratory Journal (2006)

Combination therapy has been recommended for the treatment of pulmonary arterial hypertension (PAH). However, there is scant information on combination therapy after failure of monotherapy, particularly in patients with scleroderma-associated PAH (PAH-SSD). From a group of 82 consecutive patients with PAH who received initial bosentan monotherapy, a total of 13 idiopathic PAH (IPAH) and 12 PAH-SSD patients requiring additional therapy with sildenafil were studied. Sildenafil was added for clinical deterioration based upon symptoms, New York Heart Association (NYHA) classification or 6-min walk distance (6MWD). Clinical data and haemodynamics were collected at baseline. Assessments were made at 1–3-month intervals. At baseline, there were no differences in demographics, NYHA classification, haemodynamics or 6MWD between the two groups. After initiation of bosentan, both groups experienced clinical improvement but ultimately deteriorated (median time to monotherapy failure 792 versus 458 days for IPAH and PAH-SSD patients, respectively). After addition of sildenafil, more IPAH patients tended to improve in NYHA class (five out of 13 versus two out of 12) and walked further (mean difference in 6MWD 47±77 m versus -7±40 m) compared with PAH-SSD patients. In conclusion, addition of sildenafil after bosentan monotherapy failure improved New York Heart Association class and 6-min walk distance in idiopathic pulmonary arterial hypertension patients but failed to improve either parameter in scleroderma-associated pulmonary arterial hypertension patients. Additional studies are needed to assess the tolerability and efficacy of this combination in patients with scleroderma-associated pulmonary arterial hypertension.
Activation and Tolerance in CD4+ T Cells Reactive to an Immunoglobulin Variable Region
Authors: Christopher M. Snyder, Katja Aviszus, Ryan A. Heiser, Daniel R. Tonkin, Amanda M. Guth, Lawrence J. Wysocki
Journal: The Journal of Experimental Medicine (2004)

Antibody diversity creates an immunoregulatory challenge for T cells that must cooperate with B cells, yet discriminate between self and nonself. To examine the consequences of T cell reactions to the B cell receptor (BCR), we generated a transgenic (Tg) line of mice expressing a T cell receptor (TCR) specific for a κ variable region peptide in monoclonal antibody (mAb) 36-71. The κ epitope was originally generated by a pair of somatic mutations that arose naturally during an immune response. By crossing this TCR Tg mouse with mice expressing the κ chain of mAb 36-71, we found that κ-specific T cells were centrally deleted in thymi of progeny that inherited the κTg. Maternally derived κTg antibody also induced central deletion. In marked contrast, adoptive transfer of TCR Tg T cells into κTg recipients resulted in T and B cell activation, lymphadenopathy, splenomegaly, and the production of IgG antichromatin antibodies by day 14. In most recipients, autoantibody levels increased with time, Tg T cells persisted for months, and a state of lupus nephritis developed. Despite this, Tg T cells appeared to be tolerant as assessed by severely diminished proliferative responses to the Vκ peptide. These results reveal the importance of attaining central and peripheral T cell tolerance to BCR V regions. They suggest that nondeletional forms of T tolerance in BCR-reactive T cells may be insufficient to preclude helper activity for chromatin-reactive B cells.
Computational Design and Application of Endogenous Promoters for Transcriptionally Targeted Gene Therapy for Rheumatoid Arthritis
Authors: Jeroen Geurts, Leo AB Joosten, Nozomi Takahashi, Onno J Arntz, Anton Glück, Miranda B Bennink, Wim B van den Berg, Fons AJ van de Loo
Journal: Molecular Therapy (2009)

The promoter regions of genes that are differentially regulated in the synovial membrane during the course of rheumatoid arthritis (RA) represent attractive candidates for application in transcriptionally targeted gene therapy. In this study, we applied an unbiased computational approach to define proximal-promoters from a gene expression profiling study of murine experimental arthritis. Synovium expression profiles from progressing stages of collagen-induced arthritis (CIA) were classified into six distinct groups using k-means clustering. Using an algorithm based on local over-representation and comparative genomics, we identified putatively functional transcription factor-binding sites (TFBS) in TATA-dependent proximal-promoters. Applying a filter based on spacing between TATA box and transcription start site (TSS) combined with the presence of over-represented nuclear factor kappaB (NFkappaB), AP-1, or CCAAT/enhancer-binding protein beta (C/EBPbeta) sites, 382 candidate murine and human promoters were reduced to 66, corresponding to 45 genes. In vitro, 9 out of 10 computationally defined promoter regions conferred cytokine-inducible expression in murine cells and human synovial fibroblasts. Under these conditions, the serum amyloid A3 (Saa3) promoter showed the strongest transcriptional induction and strength. We applied this promoter for driving therapeutically efficacious levels of the interleukin-1 receptor antagonist (Il1rn) in a disease-regulated fashion. These results demonstrate the value of bioinformatics for guiding the selection of endogenous promoters for transcriptionally targeted gene therapy.
Doctors' leaders call for public health to remain part of the NHS
Authors: A. O'Dowd
Journal: BMJ (2011)

Public health should remain part of the NHS under the control of a single public health agency or the health service could be dangerously fragmented and damaged, claims the BMA.

In its official response to the government’s white paper Healthy Lives, Healthy People on public health, the BMA said the proposed reforms have caused great anxiety among the public health community and the government should reconsider its proposals.

The government intends to restructure public health services in England, so directors of public health will move to local authorities, which will have responsibility for public health, and to create a new division within the Department of Health, which will be called Public …