tbuckley/cabot-search huggingface dataset:
Hyperosmolality In Vivo Upregulates Aquaporin 2 Water Channel and Na-K-2Cl Co-Transporter in Brattleboro Rats
Authors: Chunling Li, Weidong Wang, Sandra N. Summer, Melissa A. Cadnapaphornchai, Sandor Falk, Fuminori Umenishi, Robert W. Schrier
Journal: Journal of the American Society of Nephrology (2006)

There are considerable experimental results that indicate that arginine vasopressin (AVP)-independent factors are involved in urinary concentration. This study examined the role of hyperosmolality in vivo to modulate aquaporin 2 (AQP2) and Na-K-2Cl co-transporter (NKCC2), pivotal factors in urinary concentration, in AVP-deficient Brattleboro (BB) rats. Hyperglycemia with associated hyperosmolality occurred in diabetic BB rats (BBDM). Protein abundance of AQP2 increased and was reversed by insulin in the inner medulla (IM; control 100+/-5%; BBDM 146+/-8%; BBDM+Ins 122+/-9%; P<0.001) and inner stripe of outer medulla (ISOM; control 100+/-4%; BBDM 123+/-8%; BBDM+Ins 93+/-6%; P<0.05). These results were confirmed by immunohistochemistry studies. NKCC2 rose in the ISOM but was not reversed with insulin treatment. For investigation of the role of hyperosmolality in the absence of hyperglycemia on the regulation of the expression of renal AQP and NKCC2, studies were performed with hyperosmolality that was induced by 0.5% NaCl in drinking water in BB rats. Hyperosmolality that was induced by NaCl increased significantly the protein abundance of IM AQP2 (121+/-2 versus 100+/-5%; P<0.01), ISOM AQP2 (135+/-6 versus 100+/-5%; P<0.001), cortex plus outer stripe of outer medulla AQP2 (121+/-4 versus 100+/-1%; P<0.001), ISOM NKCC2 (133+/-1 versus 100+/-4%; P<0.05), and cortex plus outer stripe of outer medulla NKCC2 (142+/-16 versus 100+/-9%; P<0.05). In conclusion, hyperosmolality, secondary to either glucose or NaCl, upregulated renal AQP2 and NKCC2 in vivo in BB rats.
T-Lymphocyte precursors. I. Synergy between precursor and mature T lymphocytes in the response to concanavalin A.
Authors: J J Cohen, S S Fairchild
Journal: The Journal of Experimental Medicine (1976)

When mouse bone marrow cells are mixed with cortisol-resistant thymocytes and stimulated in vitro with concanavalin A, the mitogenic response observed is much greater than additive, that is, it is synergistic. Between 94 and 96% of responding cells could be identified as T cells (Thy-1 positive) and of these, 79-100% derived from the cortisol-resistant thymocyte population, not from the bone marrow. Purified macrophages could not replace bone marrow; and marrow depleted of mature T or B cells worked as well as normal marrow. Thus, T and B cells and macrophages were ruled out as the synergizing cell of bone marrow. Nude spleen contained 10 times as many precursors of T cells as did nude marrow and was 10 times better at synergy with cortisol-resistant thymocytes. This implication of the pre-T cell as synergizer was supported by the finding that the synergistic activity of marrow was lost on preincubation, but maintained if the preincubation medium contained thymosin or cyclic AMP. Thus, the ability to enhance the response of relatively mature T cells to Con A is a property of pre-T cells. It is anticipated that this property will allow more detailed studies of T-cell precursor development in mice, and possibly in man.
A prognostic computer model to predict individual outcome in interventional cardiology—The INTERVENT project
Authors: Michael Haude, Thomas Budde, Hans W. Hoepp, Sebastian Kerber, Guido Caspari, Guido Faßbender, Maria Fingerhuth, Erland Erdmann, Günter Breithardt, Raimund Erbel, Manfred B. Wischnewski
Journal: Journal of the American College of Cardiology (1996)
Complications of single-balloon enteroscopy: a prospective evaluation of 166 procedures
Authors: H. Aktas, L. de Ridder, J. Haringsma, E. Kuipers, P. Mensink
Journal: Endoscopy (2010)

See also: Commentaire de travail de H. Aktas et al., pp. 365Endoscopy 2010; 42(05): 433-433DOI: 10.1055/s-0031-1291854
Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia
Authors: Chamira Rodrigo, Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Tricia M. Mckeever, Caroline L. Trotter, Mary Slack, Robert George, Wei Shen Lim
Journal: European Respiratory Journal (2015)

Infant 13-valent pneumococcal conjugate vaccination (PCV13) was introduced to the UK in 2010. Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known. Beginning in 2008, a 5-year prospective cohort study of adults admitted to hospital with community-acquired pneumonia (CAP) was conducted. Pneumococcal serotype was established using a validated multiplex immunoassay (Bio-Plex; Bio-Rad, Hercules, CA, USA). The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 (95% CI 76.6–83.3) and 23.4 (95% CI 21.6–25.3) per 100 000 population, respectively. A decline in CAP (incidence rate ratio (IRR) per year 0.96, 95% CI 0.94–0.99; p=0.016) and pneumococcal CAP (IRR per year 0.84, 95% CI 0.80–0.89; p&lt;0.001) was observed over the 5-year period of the study. Between the pre- and post-PCV13 periods of the study, the incidence of CAP due to serotypes included in the PCV7 declined by 88% (IRR 0.12, 95% CI 0.08–0.20; p&lt;0.001), and CAP due to the additional 6 serotypes in PCV13 declined by 30% (IRR 0.70, 95% CI 0.51–0.96; p=0.024). Incidence of adult pneumococcal pneumonia declined over the last 5 years, with serotypes included in PCV13 declining post-PCV13 introduction, indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease. These effects may accrue over the coming years with implications for national pneumococcal vaccination policies in adults.
Mast cells promote lung vascular remodelling in pulmonary hypertension
Authors: J. Hoffmann, J. Yin, M. Kukucka, N. Yin, I. Saarikko, A. Sterner-Kock, H. Fujii, H. Leong-Poi, H. Kuppe, R.T. Schermuly, W.M. Kuebler
Journal: European Respiratory Journal (2010)

Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws / Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.
FRI0299 Fast Infusion of TOCILIZUMAB in Rheumatoid Arthritis is Well Tolerated:
Authors: H.M. Lindegaard, P.B. Johansen, G. Gröndal, E.C.N. Jensen, L. Juul, A.M. Schlemmer, B.M. Agular, I.M.J. Hansen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tocilizumab (TCZ) is administered by IV infusions over 1 hour. Reduction of infusion time will optimize the utilization of hospital resources and be of benefit for patients. However, the treatment bears a risk of infusion reactions. Optimizing administration has been shown for other biological DMARDs [1,2]. <h3>Objectives</h3> The purpose of this study was to investigate whether an infusion time of TCZ IV in RA patients can be halved without impact on infusion reactions, overall safety concerning administration of TCZ and efficacy. Primary objective was incidence of infusion reactions defined as any reaction that occurred during infusion with TCZ, or in the following 24 hours. Additional safety, immunogenicity and clinical efficacy assessments were evaluated as secondary outcomes. <h3>Methods</h3> This was a 24 week multi-center, open-label, randomized parallel group study to compare infusion reactions to TCZ IV 8 mg/kg every 4 week. Patients with moderate to severe RA, who had an inadequate clinical response to DMARDs and/or a TNF a-inhibitor were randomized to one of two arms: Control group: 1 hour infusion for 6 infusions. Fast infusion group: Infusion over 1 hour at the first infusion followed by infusion over 31 minutes (remaining five infusions). <h3>Results</h3> 47 patients were included in the study. Incidences of infusion reactions were similar between the two groups, none of them leading to withdrawal. There was no difference in the incidence of AE9s. Two serious AE9s were reported, both in the control group (infective tenosynovitis and lymphoma cutis). Four patients withdrew due to adverse events, 2 from each arm. Efficacy at Week 24 was comparable between the two groups. <h3>Conclusions</h3> Administration of TCZ in 31 minutes did not show any differences compared to the current recommended administration time (1 hour) regarding adverse events or infusion reactions. The safety profile of a faster infusion was consistent with the results of clinical studies where a 60 minutes administration was recommended and furthermore with results seen in similar fast infusion trials [3,4]. <h3>References</h3> van Vollenhoven RF, et al. Ann Rheum Dis. 2005;64(4):654. Buch MH, et al. Rheumatology 2006;45(4):485-6. G. Bukh et al EULAR 2011 AB1013-HP. M. Alperi et al. EULAR 2012 FRI0195. <h3>Acknowledgements</h3> The study was sponsored by Roche a/s <h3>Disclosure of Interest</h3> H. Lindegaard: None declared, P. Johansen: None declared, G. Gröndal: None declared, E. Jensen: None declared, L. Juul: None declared, A. Schlemmer: None declared, B. Agular Employee of: Roche A/S, I. Hansen: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2089
Activation and negative selection of functionally distinct subsets of antibody-secreting cells by influenza hemagglutinin as a viral and a neo-self antigen.
Authors: A J Caton, J R Swartzentruber, A L Kuhl, S R Carding, S E Stark
Journal: The Journal of Experimental Medicine (1996)

We have compared transgenic mice that express the influenza virus PR8 hemagglutinin (PR8 HA) as a membrane-bound neo-self antigen (HA104 mice) with nontransgenic (non-Tg) mice for their ability to generate HA-specific B cell responses after primary immunization with PR8 virus. HA-specific, IgM-secreting B cells were induced with similar frequencies in HA104 and non-Tg mice. In addition, a B cell clonotype (C4) that is characteristic of anti-HA immune responses of BALB/c mice was identified among HA-specific IgM hybridomas from HA104 mice. A subset of HA-specific, IgG-secreting B cells that arises rapidly after primary virus immunization in non-Tg mice, however, was substantially reduced in HA104 mice. Likewise, a B cell clonotype (C12) that dominates HA-specific IgG hybridomas generated after primary immunization of non-Tg mice was present at greatly reduced frequencies among hybridomas from HA104 mice. Because HA-specific, IgG-secreting B cells were generated by HA104 mice in response to a mutant HA containing an amino acid interchange in a B cell antigenic site, we conclude that these PR8 HA-specific, IgG-secreting B cells are negatively selected in HA104 mice as a result of their specificity for the neo-self PR8 HA. The findings demonstrate that HA-specific B cells that display distinct phenotypic potentials in non-Tg mice also differ in their susceptibility to negative selection from the primary B cell repertoire of HA104 mice: a subset of B cells that undergo rapid differentiation to become HA-specific IgG antibody-secreting cells (ASC) after activation in non-Tg mice is negatively selected in HA104 mice. By contrast, a subset that gives rise to HA-specific, IgM-secreting ASC persists in the primary repertoire of HA104 mice and can be activated by virus immunization.
Theophylline improves steroid sensitivity in acute alcoholic hepatitis
Authors: Stuart F. W. Kendrick, Elsbeth Henderson, Jeremy Palmer, David E. J. Jones, Chris P. Day
Journal: Hepatology (2010)

Corticosteroid therapy has shown some benefit in severe acute alcoholic hepatitis (AAH); however, this is limited by uncertainty in patient selection and variable clinical response. Theophylline has been shown to ameliorate impaired steroid sensitivity in chronic obstructive pulmonary disease by facilitating corticosteroid-induced silencing of proinflammatory genes. We aimed to explore the mechanistic basis of the variable response to corticosteroid therapy seen in patients with AAH and to address the extent to which theophylline can improve this response. The ability of dexamethasone to inhibit phytohemagglutinin-induced lymphocyte proliferation was assessed by 3H-thymidine incorporation in 12 severe AAH patients and age-matched and sex-matched controls. Steroid sensitivity was measured in terms of Imax, the maximum inhibition of proliferation. The effect of 10−5 M theophylline and, in survivors, change in Imax during recovery were observed. Lymphocyte steroid sensitivity was found to be significantly reduced in AAH compared with controls (Imax 67[±4.5]% versus 95[±2.3]%, P = 0.0002) and correlated with clinical markers of steroid responsiveness. In survivors, Imax increased in recovery. Theophylline 10−5 M significantly increased lymphocyte steroid sensitivity (Imax 86[±6.6]% versus 67[±5.0]%, P = 0.027). Conclusion: Acute alcoholic hepatitis is associated with significant lymphocyte steroid insensitivity, which improves in recovery and can be ameliorated ex vivo by theophylline. This offers potential to rationalize corticosteroid prescribing in AAH and, furthermore, justifies investigation of this novel role for an existing pharmacological agent in this common and frequently fatal condition. (Hepatology 2010;)
Amino acid metabolism during starvation in human pregnancy
Authors: Philip Felig, Young Jin Kim, Vincent Lynch, Rosa Hendler
Journal: Journal of Clinical Investigation (1972)

To evaluate the factors regulating gluconeogenesis in pregnancy, plasma amino acid levels were determined during the course of an 84-90 hr fast in physically healthy women studied during wk 16-22 of gestation (before undergoing therapeutic abortion), and in nonpregnant controls. The effect of pregnancy on the glycemic response to exogenous alanine administration during starvation was also investigated.
Pericardial Effusion Complicating Breast Cancer
Authors: Penella J Woll, R K Knight, R D Rubens
Journal: Journal of the Royal Society of Medicine (1987)

Thirty-five patients with metastatic breast cancer and pericardial effusions are described. They were treated with specific endocrine or chemotherapy. Twenty-two (63%) had presented in cardiac tamponade and were rapidly relieved by pericardiocentesis. Eighteen (82%) of these required no further local treatment, 2 obtained relief from a second aspiration and 2 needed additional treatment (intrapericardial bleomycin instillation and surgical pleuropericardial window). The median survival was 13.2 months. No patient relapsed again in the pericardium, suggesting that their prognosis was that of the underlying disease. Cardiac tamponade should be considered in any breathless patient with malignancy. In breast cancer, periocardiocentesis is lifesaving and systemic treatment can usefully prolong life.
Hepatitis C virus genotypes: An investigation of type-specific differences in geographic origin and disease
Authors: Geoffrey Dusheiko, Hemda Schmilovitz-Weiss, David Brown, Fiona McOmish, Pong-Lee Yap, Sheila Sherlock, Neil McIntyre, Peter Simmonds
Journal: Hepatology (1994)

Because of the nucleotide sequence diversity of different isolates of hepatitis C virus, it has become important to clarify whether distinct genotypes of hepatitis C virus vary with respect to pathogenicity, infectivity, response to antiviral therapy and geographic clustering. We assessed nucleotide sequence variability in the 5' noncoding region of hepatitis C virus, using restriction enzymes to analyze the distribution of hepatitis C virus genotypes, in 80 patients with chronic hepatitis C virus infection. Genotypes were correlated with demographic, clinical and histological features. Thirty-seven patients were infected with type 1, 10 had type 2 and 8 had type 3, and another 23 were infected with a new distinct hepatitis C virus type now classified as type 4. Two were infected with variants whose classification are uncertain. Types 1, 2 and 3 were found in patients from the United Kingdom, southern Europe, Asia, Africa and South America. Nineteen of 23 type 4 genotype isolates were from Middle Eastern patients, compared with 0 of 37 type 1 isolates (p < 0.001). Of 21 Middle Eastern patients, 19 (90.4%) had type 4 hepatitis C virus (p = 0.001, odds ratio = 9). We found no significant difference between the mean ages or mean serum aminotransferase concentrations between the various types. Types 1, 2, 3 and 4 were found in patients with mild-to-moderate disease or severe disease. However, 21 of 29 (72.4%) patients with type 1 who underwent liver biopsy had severe chronic hepatitis, cirrhosis or hepatocellular carcinoma histologically; 8 had mild or moderate chronic hepatitis without cirrhosis (p = 0.03, odds ratio = 2.6).(ABSTRACT TRUNCATED AT 250 WORDS)
DIET AND TISSUE GROWTH
Authors: Arthur H. Smith, T. S. Moise
Journal: The Journal of Experimental Medicine (1927)

The rate of compensatory enlargement of the remaining kidney after unilateral nephrectomy has been studied in adult rats fed diets containing various concentrations of protein. A curve of enlargement on "standard" food (18 per cent casein) shows a rapid initial increase with subsequent slower rise to the 120th day. There is no significant difference between the value at 120 days (44 per cent) and that at 150 days (48 per cent). A similar series with diets containing increasing concentrations of protein but with a constant time interval (21 days) after nephrectomy shows an increase in the degree of enlargement directly proportional to the protein content of the food. The values vary from 24 per cent with the 18 per cent casein ration to 77 per cent with the 90 per cent casein diet. A third series shows the enlargement on "high protein" food (85 per cent casein). The values vary from 49 per cent at 3 days to 121 per cent at 150 days. There is no significant difference between the value at 120 days (123 per cent) and that at 150 days (121 per cent). Determinations of total solids on the experimental kidneys show that the recorded enlargement involves mainly an actual tissue increase.
Editors and their priorities about libel and fraud: Everyone in science must be active in its process
Authors: J. H Lange
Journal: BMJ (2004)

Diagnosis of autism Adequate funding is needed for assessment services2][3] One important additional reason for such provision, which their review does not emphasise, is that well coordinated, multiagency assessment teams for autism spectrum disorders have a better chance of accurately not giving a diagnosis of it.Our multiagency assessment service for autism spectrum disorders has seen 57 patients in the past two years.We request baseline speech and language therapy and (where applicable) educational psychology assessments on the likelihood of autism spectrum disorder in all cases before patients are seen by our team, so as to ensure best use of clinical resources.Despite this approach only 26 patients (46%) deemed to be likely cases of autism spectrum disorder received a positive diagnosis.This is not due to overzealous interpretation of ICD-10 diagnostic criteria (which are increasingly recognised as being in urgent need of review), as we tend, if anything, to err in favour of diagnosis, even if ICD-10 (or DSM-IV) criteria, are not strictly fulfilled.Relevant agencies must receive adequate funding for implementing the national autism plan for children. 3This is to benefit not only the children and their families who are struggling with the often devastating impact of this disorder but also the depressingly high number of children whom, we suspect, will be wrongly, or inaccurately, given diagnoses, if assessment services for autism spectrum disorders do not improve.
Gene Expression Signature in Organized and Growth-Arrested Mammary Acini Predicts Good Outcome in Breast Cancer
Authors: Marcia V. Fournier, Katherine J. Martin, Paraic A. Kenny, Kris Xhaja, Irene Bosch, Paul Yaswen, Mina J. Bissell
Journal: Cancer Research (2006)

Abstract Nonmalignant human mammary epithelial cells (HMEC) seeded in laminin-rich extracellular matrix (lrECM) form polarized acini and, in doing so, transit from a disorganized proliferating state to an organized growth-arrested state. We hypothesized that the gene expression pattern of organized and growth-arrested HMECs would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in 184 (finite life span) and HMT3522 S1 (immortal nonmalignant) HMECs on successive days after seeding in a lrECM assay. Both HMECs underwent growth arrest in G0-G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines and examined the expression of these genes in a previously published panel of microarray data for 295 breast cancer samples. We show that genes that are significantly lower in the organized, growth-arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically. (Cancer Res 2006; 66(14): 7095-102)