tbuckley/cabot-search huggingface dataset:
Genome-scale evidence of the nematode-arthropod clade.
Authors: Hernán Dopazo, Joaquín Dopazo
Journal: Genome biology (2005)

The issue of whether coelomates form a single clade, the Coelomata, or whether all animals that moult an exoskeleton (such as the coelomate arthropods and the pseudocoelomate nematodes) form a distinct clade, the Ecdysozoa, is the most puzzling issue in animal systematics and a major open-ended subject in evolutionary biology. Previous single-gene and genome-scale analyses designed to resolve the issue have produced contradictory results. Here we present the first genome-scale phylogenetic evidence that strongly supports the Ecdysozoa hypothesis.Through the most extensive phylogenetic analysis carried out to date, the complete genomes of 11 eukaryotic species have been analyzed in order to find homologous sequences derived from 18 human chromosomes. Phylogenetic analysis of datasets showing an increased adjustment to equal evolutionary rates between nematode and arthropod sequences produced a gradual change from support for Coelomata to support for Ecdysozoa. Transition between topologies occurred when fast-evolving sequences of Caenorhabditis elegans were removed. When chordate, nematode and arthropod sequences were constrained to fit equal evolutionary rates, the Ecdysozoa topology was statistically accepted whereas Coelomata was rejected.The reliability of a monophyletic group clustering arthropods and nematodes was unequivocally accepted in datasets where traces of the long-branch attraction effect were removed. This is the first phylogenomic evidence to strongly support the 'moulting clade' hypothesis.
CD4+CD25-Foxp3+ T cells are increased in systemic lupus erythematosus patients with active glomerulonephritis
Authors: M. Bonelli, L. Goschl, S. Bluml, E. Rath, J. S. Smolen, C. Scheinecker
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Regulatory T cells are critically involved in the pathogenesis of autoimmune diseases. Recently, a novel subset of regulatory T cells has been described in systemic lupus erythematosus (SLE), However, the role of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells in the pathogenesis of SLE is not known. The authors therefore performed comparative analyses of proportions of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells in SLE patients with different organ manifestations. <h3>Methods</h3> Phenotypic analysis of peripheral blood CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells was performed by flow cytometry (FACS) in SLE patients with different organ manifestations and healthy controls (HC). CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> as well as conventional regulatory T cells were analysed for the expression of the recently identified marker Helios and Icos and for their cytokine expression profile and correlated with clinical data, the daily cortisone dose and the SLE disease activity index (SLEDAI). <h3>Results</h3> The authors report that the proportions of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells are increased in patients with SLE as compared to HC. Expression of Helios and ICOS in CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells was similar to conventional Tregs, indicating that CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells are bona fide Tregs. Strikingly analysis of patients with different organ manifestations revealed increased proportions of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells in SLE patients with renal involvement, especially with active glomerulonephritis. Furthermore roportions of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells correlated with the extent of proteinuria. Ongoing experiments are performed in order to analyse the origin of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells. Therefore cells are stained for interleukin-4, interleukin-17 and IFN-γ and the transcription factor Foxp3, RORγt and GATA3. <h3>Conclusions</h3> In summary the authors found increased proportions of CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells in patients with SLE who suffer from glomerulonephritis suggesting their involvement in kidney pathology. CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>+</sup> T cells might therefore be a useful tool to recognise and monitor patients with renal involvement. Kidney biopsies and a further characterisation of this cell population have been designed to unravel their role in the development of glomerulonephritis in SLE patients.
Vitamin D3 and cardiovascular function in rats.
Authors: R E Weishaar, R U Simpson
Journal: Journal of Clinical Investigation (1987)

We have previously identified a receptor for 1,25-dihydroxyvitamin D3 in myocardial cells (Simpson, R.U. 1983. Circulation. 68:239.). To establish the relevance of this observation, we evaluated the role of the prohormone vitamin D3 in regulating cardiovascular function. In rats maintained on a vitamin D3-deficient diet for nine weeks, increases in systolic blood pressure (BP) and serum creatine phosphokinase (CPK) were observed. These increases coincided with a reduction of serum calcium from 10.3 to 5.6 mg/dl. However, while serum calcium remained depressed throughout the study, increases in BP and serum CPK were transient. After nine weeks of vitamin D3-depletion, but not after six weeks, ventricular and vascular muscle contractile function were also markedly enhanced. The increase in ventricular contractile function could not be prevented by maintaining serum calcium at 9.0 mg/dl during the period of D3-depletion. These observations suggest a primary role for the vitamin D3-endocrine system in regulating cardiovascular function.
Interaction between angiotensin II and the baroreceptor reflex in the control of adrenocorticotropic hormone secretion and heart rate in conscious dogs.
Authors: V L Brooks, I A Reid
Journal: Circulation Research (1986)

The present studies were designed to examine the effect of angiotensin II on baroreflex control of adrenocorticotropic hormone secretion and heart rate in conscious dogs. Baroreflex function was assessed by examining the relationship between blood pressure and plasma corticosteroid concentration (used as an index of adrenocorticotropic hormone secretion) and between blood pressure and pulse interval (the inverse of heart rate). Blood pressure was varied by intravenous infusion of four doses (0.3, 0.6, 1.5, and 3.0 micrograms/kg per min) of the vasodilator nitroprusside. Nitroprusside infusion produced an increase in plasma corticosteroid concentration and a decrease in pulse interval, both of which were linearly related to the fall in arterial blood pressure. During infusion of angiotensin II (10 ng/kg per min), however, the lines relating blood pressure to plasma corticosteroid concentration or blood pressure to pulse interval were shifted to a higher pressure level, suggesting that angiotensin II resets the baroreceptor reflex. Angiotensin II blockade with saralasin, an angiotensin II antagonist, or with captopril, a converting enzyme inhibitor, in sodium-depleted dogs with elevated plasma angiotensin II levels produced a shift in the opposite direction in these relationships. Because baroreflex function in sodium-depleted dogs before angiotensin II blockade was similar to that in sodium-replete dogs, despite the increased plasma angiotensin II levels, and because treatment of sodium-replete dogs with saralasin did not affect baroreflex function, these results suggest that endogenous angiotensin II is necessary for the maintenance of normal baroreflex control of adrenocorticotropic hormone secretion and heart rate during sodium depletion. Previous studies designed to evaluate the physiological significance of angiotensin II in the control of adrenocorticotropic hormone secretion showed that high, perhaps supraphysiological, levels of exogenous angiotensin II are required to increase adrenocorticotropic hormone secretion. An additional finding of the present study was that exogenous angiotensin II produces a larger increase in adrenocorticotropic hormone secretion when the pressor effect of angiotensin II was eliminated with simultaneous infusion of the vasodilators nitroprusside or hydralazine. This result suggests that experiments that evaluate the physiological role of angiotensin II in the control of adrenocorticotropic hormone secretion with infusions of exogenous AII may underestimate the importance of endogenously produced angiotensin II, which is normally released without an increase in pressure.
Results of Methonium Treatment of Hypertensive Patients
Authors: F. H. Smirk
Journal: BMJ (1954)

Except in malignant hypertension, the outlook of the individual hypertensive patient treated only by rest, sedation, and the amelioration of complications is difficult to assess unless the prognosis has evidently deteriorated because of substantial cardiac failure or renal impairment.Individual prognosis is hazardous, especially in milder cases, but the expectation of survival among large groups of hypertensive patients has been well worked out in terms of their presenting clinical features.Among such groups of patients the ex- pectation of survival is related to the extent of hyper- tensive changes in the retina, the presence or absence of heart failure, cardiac asthma, breathlessness, sub- stantial electrocardiographic changes and, in a general way, with the height of the blood pressure, especially the diastolic pressure.The age at which the patient begins to show such abnormal manifestations, and the sex, have a strong bearing on outlook.While different views are expressed, a scrutiny of the manner in which
Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain
Authors: Jessica O'Neill, Christina Brock, Anne Estrup Olesen, Trine Andresen, Matias Nilsson, Anthony H. Dickenson
Journal: Pharmacological Reviews (2012)

A large number of pharmacological studies have used capsaicin as a tool to activate many physiological systems, with an emphasis on pain research but also including functions such as the cardiovascular system, the respiratory system, and the urinary tract. Understanding the actions of capsaicin led to the discovery its receptor, transient receptor potential (TRP) vanilloid subfamily member 1 (TRPV1), part of the superfamily of TRP receptors, sensing external events. This receptor is found on key fine sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been exploited in animal studies, human psychophysics, and imaging studies. Its effects depend on the dose and route of administration and may include sensitization, desensitization, withdrawal of afferent nerve terminals, or even overt death of afferent fibers. The ability of capsaicin to generate central hypersensitivity has been valuable in understanding the consequences and mechanisms behind enhanced central processing of pain. In addition, capsaicin has been used as a therapeutic agent when applied topically, and antagonists of the TRPV1 receptor have been developed. Overall, the numerous uses for capsaicin are clear; hence, the rationale of this review is to bring together and discuss the different types of studies that exploit these actions to shed light upon capsaicin working both as a tool to understand pain but also as a treatment for chronic pain. This review will discuss the various actions of capsaicin and how it lends itself to these different purposes.
Is BRAF the Achilles' Heel of Thyroid Cancer?
Authors: Antonio Chiloeches, Richard Marais
Journal: Clinical Cancer Research (2006)

In this issue of Clinical Cancer Research , Ouyang et al. ([1][1]) present evidence suggesting that BRAF is a therapeutic target in thyroid cancer. Previous studies have shown that BRAF is mutated in a high proportion of thyroid cancers, but the therapeutic implications of this have not been
A Cold and its Cure
Authors: W. J. H. Wood
Journal: BMJ (1876)

second operation.The cough was very troublesome again, with con- siderable expectoration.The urine presented the same condition as before, and the addition of acetic acid did not show the presence of cystine.The saliva, sputa, and sweat were examined for cystine, in each case by adding acetic acid, but no evidence of its presence could be found.Au-ust Ist.From this date, the bronchitic symptoms gradually in- creased in severity, becoming of a more acute character and attended with a sense of great weakness.Along with these symptoms, there was no increased irritability or pain about the bladder.Signs of adynamia and deficient aeration of the blood set in, followed by coma, and the patient, gradually sinking, died on August 8th.Post PMortern Examination.-Bothlungs were much congested; the bronchi were dilated and filled with mucus.On the left side, there were some old pleuritic adhesions.The aortic valves allowed regurgi- tation, and had calcareous plates at their bases ; the other valves were healthy.The kidneys were surrounded by a large quantity of fat, which was abnormally adherent to their capsules; both contained nu- merous abscesses, the lining membrane of the pelves being, too, in- flamed and suppurating.The capsules were thickened and adherent.The ureters were thickened and dilated.The bladder was thickened and fasciculated.
Piero della Francesca's coral pendants: the hidden bronchial anatomy
Authors: Vincenzo Ambrogi
Journal: Thorax (2014)

During the Renaissance, painters frequently used to hide human anatomies inside their artworks. Piero della Francesca (1415–1492) in two paintings represents the infant Jesus with a necklace of coral beads, symbol of beauty and tool for protection against illness or sudden death. Interestingly, the shape of both coral pendants follows a scheme similar to the primary and secondary divisions of the lower respiratory system with the trachea, the main and the lobar bronchi. The numerous and surprising analogies between the coral and …
How large are the productivity losses in contemporary patients with RA, and how soon in relation to diagnosis do they develop?
Authors: Martin Neovius, Julia F Simard, Johan Askling
Journal: Annals of the Rheumatic Diseases (2011)

To estimate the sick leave and disability pension trajectory in patients diagnosed with early rheumatoid arthritis (RA) 1999-2007, and in prevalent patients in 2007.Individuals aged 19-59 years diagnosed with early RA were identified in the Swedish Rheumatology Quality Register (1999-2007; n=3029; 47 years; 73% women). Additionally, prevalent patients in 2007 were identified in the National Patient Register (n=25,922; 52 years; 73% women). For each patient, five age-, sex-, education- and county-matched general population comparators were sampled. Sick leave and disability pension days were retrieved from national registers.Sick leave and disability pension increased from a mean 43 to 77 days/year from 2 to 1 years before RA diagnosis. A further increase to 147 days/year was observed the next year, followed by a rebound to 116 days/year 4 years after diagnosis. During the 4 years following diagnosis, sick leave decreased from a mean 118 to 35 and disability pension increased from 29 to 81 days/year. In the prevalent RA population, patients had a mean 158 annual days of sick leave and disability pension compared to 71 in comparators. Large variations existed across age, sex and education level, but RA patients had consistently higher levels. In 2007, the costs associated with sick leave and disability pension were €16,000 per patient with €9,000 attributable to RA.Despite better drugs and improved treatment strategies, data from contemporary patients with early and established RA continue to indicate large unmet needs.
Management of hepatic coma complicating viral hepatitis
Authors: R. C. Pirola, J. M. Ham, R. G. Elmslie
Journal: Gut (1969)

The treatment is described of 17 patients with presumed viral hepatitis who developed hepatic coma unresponsive to standard conservative measures. Five patients were considered for treatment by exchange transfusion. Four were treated, with transient improvement in two, but all died. Nine patients were considered for treatment by heterologous liver perfusion. Six were treated, with transient improvement in two and complete recovery in one. The last patient remains well 12 months later. Dialysis in four patients had no effect on the coma; the addition of albumin to the dialysate did not increase the extraction of bilirubin. The clinical course in most cases was irregular. Complications were common, the most important being cerebral oedema with medullary coning, bleeding, bacterial infection, hypoglycaemia, and pancreatitis. Heterologous liver perfusion was the most efficient method of removing bilirubin. However, it is not yet clear whether it is more effective than exchange transfusion in the treatment of the patient.
Therapeutic control of anticoagulant treatment.
Authors: B M Duxbury
Journal: BMJ (1982)

Control of anticoagulant treatment was studied in 250 patients. One hundred and fifty patients receiving long-term anticoagulant treatment (group 1) were studied for 52 weeks and the remaining 100 (group 2) for 12 weeks after discharge from hospital. The desired British correlated ratio range was 2.5-3.3, and a range of 2.3-3.5 was classified as satisfactory. In group 1 a satisfactory ratio was obtained for 70% of the study period and 120 of the 150 patients were maintained within this range for over 60% of the time. In group 2 only half of the patients were maintained within the satisfactory range and for 50% of the study period or less. The time and effort expended in therapeutic control were more than most clinics could afford, and the results for group 2 were disappointing. The standard of long-term anticoagulant treatment should be improved by continuous review of control and by "therapeutic quality control."
Treatment of breast cancer during pregnancy: an observational study
Authors: Sibylle Loibl, Sileny N Han, Gunter von Minckwitz, Marijke Bontenbal, Alistair Ring, Jerzy Giermek, Tanja Fehm, Kristel Van Calsteren, Sabine C Linn, Bettina Schlehe, Mina Mhallem Gziri, Pieter J Westenend, Volkmar Müller, Liesbeth Heyns, Brigitte Rack, Ben Van Calster, Nadia Harbeck, Miriam Lenhard, Michael J Halaska, Manfred Kaufmann, Valentina Nekljudova, Frederic Amant
Journal: The Lancet Oncology (2012)
Hepatitis B Virus Reactivation in Lymphoma Patients With Prior Resolved Hepatitis B Undergoing Anticancer Therapy With or Without Rituximab
Authors: Winnie Yeo, Tung C. Chan, Nancy W.Y. Leung, Wai Y. Lam, Frankie K.F. Mo, Miu Ting Chu, Henry L.Y. Chan, Edwin P. Hui, Kenny I.K. Lei, Tony S.K. Mok, Paul K.S. Chan
Journal: Journal of Clinical Oncology (2008)

Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] +/- antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc-positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab.Between January 2003 and December 2006, all patients diagnosed with CD20(+) diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy.Among 104 CD20(+) DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation.Among HBsAg-negative/anti-HBc-positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.
* 8-year experience of enterocutaneous fistulae at a national intestinal failure centre
Authors: G. Rahbour, J. Warusavitarne, S. M. Gabe, A. L. Hart, P. Tozer, N. Daulatzai, C. J. Vaizey
Journal: Gut (2011)

<h3>Introduction</h3> Currently there are two national intestinal failure (IF) centres in England. The treatment of enterocutaneous fistulae (ECF) is complex and challenging. They primarily occur following surgery. Our study examines healing and mortality in ECF patients, with an evaluation of current management practice and outcome. <h3>Methods</h3> A retrospective review of ECF in 177 consecutive patients with mean age of 48.7 years (median 49 years) treated over an 8 year period (January 2003–June 2010) in a major tertiary referral centre has been completed. Results have been compared to a previously reported series from this unit of an 11-year experience of 277 patients.1 <h3>Results</h3> Fistulae resulted from surgery in 166 of the 177 patients (93.7%). 85 of the 177 patients (48.0%) had a medical history including inflammatory bowel disease (69 Crohn9s disease and 16 ulcerative colitis). 150 of the 177 patients underwent definitive surgery (84.7%). The overall healing rate following surgery in the current series was 94.6% compared with 82% in the previous series. Mean delay from previous surgery to current operation was 1 year in the current series compared with 8 months in the previous series. 30 day post fistulae resection mortality was 0% in this current series compared with 3.5% in the previous series. 27 of the 177 patients (15.3%) underwent medical management alone. The overall healing rate following medical management was 46.4% compared to 19.9% in the previous series. In addition to surgical or medical management, Infliximab was used in 5 patients and resulted in fistulae healing in 3. <h3>Conclusion</h3> By far the greatest aetiology for ECF formation was surgery performed in patients with a background of inflammatory bowel disease, and more specifically Crohn9s disease. Surgical management of ECF is safe and improving when performed in a dedicated unit and when time is allowed for patient optimisation. Factors contributing to the improved outcome may include an improved cohesion of our dedicated multidisciplinary team with increasing experience, an increase in mean delay time to surgery, insistence that the patient is discharged home prior to surgery wherever possible and improved medical management of Crohn9s disease with immunosuppressive and biological drugs.