tbuckley/cabot-search huggingface dataset:
Lymphocytic colitis: clinical presentation and long term course
Authors: B Mullhaupt, U Güller, M Anabitarte, R Güller, M Fried
Journal: Gut (1998)

Lymphocytic colitis is characterised by chronic watery diarrhoea with normal endoscopic or radiological findings and microscopic evidence of pronounced infiltration of the colonic mucosa with lymphocytes.To investigate the long term clinical and histological evolution of the disease in a large group of patients with well characterised lymphocytic colitis.Between 1986 and 1995 the histological diagnosis of lymphocytic colitis was obtained in 35 patients; 27 of these agreed to a follow up examination. All clinical, endoscopic, and histopathological records were reviewed at that time and the patients had a second endoscopic examination with follow up biopsies.The patients initially presented with the typical findings of lymphocytic colitis. After a mean (SD) follow up of 37.8 (27.5) months, diarrhoea subsided in 25 (93%) and histological normalisation was observed in 22 (82%) of the 27 patients. Progression from lymphocytic colitis to collagenous colitis was not observed.Lymphocytic colitis is characterised by a benign course with resolution of diarrhoea and normalisation of histology in over 80% of patients within 38 months. Considering the benign course of the disease, the potential benefit of any drug treatment should be carefully weighed against its potential side effects.
Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy
Authors: S. Magina, J. Santos, A. Coroas, J.G. Oliveira, P. Serrao, P. Soares-Da-Silva, C. Resende, M. Pestana
Journal: British Journal of Dermatology (2005)

Journal Article Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy Get access S. Magina, S. Magina Departments of DermatologyInstitute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal Search for other works by this author on: Oxford Academic Google Scholar J. Santos, J. Santos Nephrology, Hospital S. João Search for other works by this author on: Oxford Academic Google Scholar A. Coroas, A. Coroas Nephrology, Hospital S. João Search for other works by this author on: Oxford Academic Google Scholar J.G. Oliveira, J.G. Oliveira Nephrology, Hospital S. João Search for other works by this author on: Oxford Academic Google Scholar P. Serrão, P. Serrão Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal Search for other works by this author on: Oxford Academic Google Scholar P. Soares‐Da‐Silva, P. Soares‐Da‐Silva Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200 Porto, Portugal Search for other works by this author on: Oxford Academic Google Scholar C. Resende, C. Resende Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar M. Pestana M. Pestana Nephrology, Hospital S. João M. Pestana. E‐mail: mvasconcelos@hsjoao.min‐saude.pt Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 4, 1 April 2005, Pages 773–776, https://doi.org/10.1111/j.1365-2133.2005.06518.x Published: 01 April 2005 Article history Accepted: 27 October 2004 Published: 01 April 2005
Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2
Authors: Esther Lopez-Rivera, Padmini Jayaraman, Falguni Parikh, Michael A. Davies, Suhendan Ekmekcioglu, Sudeh Izadmehr, Denái R. Milton, Jerry E. Chipuk, Elizabeth A. Grimm, Yeriel Estrada, Julio Aguirre-Ghiso, Andrew G. Sikora
Journal: Cancer Research (2014)

Melanoma is one of the cancers of fastest-rising incidence in the world. Inducible nitric oxide synthase (iNOS) is overexpressed in melanoma and other cancers, and previous data suggest that iNOS and nitric oxide (NO) drive survival and proliferation of human melanoma cells. However, specific mechanisms through which this occurs are poorly defined. One candidate is the PI3K-AKT-mTOR pathway, which plays a major role in proliferation, angiogenesis, and metastasis of melanoma and other cancers. We used the chick embryo chorioallantoic membrane (CAM) assay to test the hypothesis that melanoma growth is regulated by iNOS-dependent mTOR pathway activation. Both pharmacologic inhibition and siRNA-mediated gene silencing of iNOS suppressed melanoma proliferation and in vivo growth on the CAM in human melanoma models. This was associated with strong downregulation of mTOR pathway activation by Western blot analysis of p-mTOR, p70 ribosomal S6 kinase (p-P70S6K), p-S6RP, and p-4EBP1. iNOS expression and NO were associated with reversible nitrosylation of tuberous sclerosis complex (TSC) 2, and inhibited dimerization of TSC2 with its inhibitory partner TSC1, enhancing GTPase activity of its target Ras homolog enriched in brain (Rheb), a critical activator of mTOR signaling. Immunohistochemical analysis of tumor specimens from stage III melanoma patients showed a significant correlation between iNOS expression levels and expression of the mTOR pathway members. Exogenously supplied NO was also sufficient to reverse the mTOR pathway inhibition by the B-Raf inhibitor vemurafenib. In summary, covalent modification of TSC2 by iNOS-derived NO is associated with impaired TSC2/TSC1 dimerization, mTOR pathway activation, and proliferation of human melanoma. This model is consistent with the known association of iNOS overexpression and poor prognosis in melanoma and other cancers.
Expression of Complement Components Differs Between Kidney Allografts from Living and Deceased Donors
Authors: Maarten Naesens, Li Li, Lihua Ying, Poonam Sansanwal, Tara K. Sigdel, Szu-Chuan Hsieh, Neeraja Kambham, Evelyne Lerut, Oscar Salvatierra, Atul J. Butte, Minnie M. Sarwal
Journal: Journal of the American Society of Nephrology (2009)

A disparity remains between graft survival of renal allografts from deceased donors and from living donors. A better understanding of the molecular mechanisms that underlie this disparity may allow the development of targeted therapies to enhance graft survival. Here, we used microarrays to examine whole genome expression profiles using tissue from 53 human renal allograft protocol biopsies obtained both at implantation and after transplantation. The gene expression profiles of living-donor kidneys and pristine deceased-donor kidneys (normal histology, young age) were significantly different before reperfusion at implantation. Deceased-donor kidneys exhibited a significant increase in renal expression of complement genes; posttransplantation biopsies from well-functioning, nonrejecting kidneys, regardless of donor source, also demonstrated a significant increase in complement expression. Peritransplantation phenomena, such as donor death and possibly cold ischemia time, contributed to differences in complement pathway gene expression. In addition, complement gene expression at the time of implantation was associated with both early and late graft function. These data suggest that complement-modulating therapy may improve graft outcomes in renal transplantation.
Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial hypertension
Authors: G.A. Heresi, W.H.W. Tang, M. Aytekin, J. Hammel, S.L. Hazen, R.A. Dweik
Journal: European Respiratory Journal (2011)

Circulating cardiac troponins are markers of myocardial injury. We sought to determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is associated with disease severity and prognosis in pulmonary arterial hypertension (PAH). cTnI was measured in 68 patients with PAH diagnostic category 1 in a research-based sensitive immunoanalyser with a lower limit of detection of 0.008 ng·mL −1 . The associations between cTnI and PAH severity and clinical outcomes were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan–Meier analysis and Cox regression models. cTnI was detected in 25% of patients. Patients with detectable cTnI had more advanced functional class symptoms, a shorter 6-min walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels. 36-month transplant-free survival was 44% in patients with detectable cTnI versus 85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold increased risk of death related to right ventricular failure or transplant (hazard ratio 4.74, 95% CI 1.89–11.89; p&lt;0.001), even when adjusted individually for known parameters of PAH severity. Elevated plasma cTnI, even at subclinically detectable levels, is associated with more severe disease and worse outcomes in patients with PAH.
Terence Reginald Wilson
Authors: Peter Wilson
Journal: BMJ (2004)

Forde Cayley went from medical school straight into service in wartime France and then to Singapore.Captured by the Japanese, he was taken to the infamous River Kwai.The horrors he had witnessed never left him, but he believed in reconciliation, not hatred.As a postwar pioneer of drug treatment for tuberculosis, he took up the respiratory medicine post that he held until retirement.His spare time was divided between BMA activities, his work as a lay reader, and in his prolific vegetable plot.Predeceased by his wife, Eileen, he leaves two sons and three grandsons.
Pneumococcal serotypes and their clinical relevance
Authors: M. KALIN
Journal: Thorax (1998)

Pneumococcal disease is endemic all over the world. Epidemics may occur, most often in closed institutional settings such as schools and military camps,1-3 but account for only a minority of all the cases. The total incidence of pneumococcal pneumonia in Western populations is 1–5 per 1000 person-years, and several times higher in the very young and the elderly. In developing countries it is estimated that at least one million children below the age of five die each year from pneumococcal pneumonia.4 Streptococcus pneumoniae is also the most important pathogen in bacterial meningitis, otitis media, and sinusitis. The annual incidence of pneumococcal bacteraemia in North America and Europe is at least 10–20 per 100 000 individuals, the majority of cases being due to pneumonia. However, the most common host-parasite interrelationship is the asymptomatic carriage of one (or occasionally two or more) pneumococcal strains in the nasopharynx.5 6 

As in other Gram positive bacteria, the pneumococcal cell wall is composed of peptidoglycan and teichoic acid (fig 1). A predominant component of teichoic acid is the C-polysaccharide which is covalently bound to the peptidoglycan layer and distributed both on its inner and outer side.7 The exact chemical structure of the C-polysaccharide has been established as a ribitol teichoic acid containing glucose, 2-acetamido-2,4,6-trideoxygalactose, galactosamine, ribitol phosphate, and phosphorylcholine.8 Interestingly, each of these components has been identified as constituents of different capsular polysaccharides, possibly pointing to an evolutionary origin of the capsular substances from the C-polysaccharide.



Figure 1 
Schematic illustration of the arrangement of the pneumococcal cell wall.



All wild strains of Streptococcus pneumoniae are provided with a polysaccharide capsule. To date, 90 distinct capsular types have been described, six of them very recently.9Some of the types are antigenically related to each other and such related types are included together in …
Increased matrix metalloproteinase-9 concentration and activity after stimulation with interleukin-17 in mouse airways
Authors: O Prause
Journal: Thorax (2004)

<b>Background:</b> The proteolytic enzyme matrix metalloproteinase (MMP)-9 can degrade structural compounds such as the extracellular matrix and the basement membrane in the airways and lungs. MMP-9 has therefore been implicated in remodelling of the airways and lungs during severe asthma and chronic obstructive pulmonary disease (COPD). <b>Methods:</b> The effect of the T lymphocyte derived proinflammatory cytokine interleukin (IL)-17 on MMP-9 protein release and activity in the airways was studied in vivo and in vitro. <b>Results:</b> In vivo, intranasal stimulation of mice with IL-17 induced the release of the precursor molecule proMMP-9 in bronchoalveolar lavage (BAL) fluid, associated with a pronounced local accumulation of neutrophils that stained positive for MMP-9. Stimulation with IL-17 also increased the concentration of free soluble MMP-9 that was proteolytically active as determined by a gelatinase substrate assay. The concentration of MMP-9 in BAL fluid had a strong positive correlation with the number of neutrophils; the amount of MMP-9 per neutrophil was not increased by IL-17 stimulation. In vitro, stimulation of mouse neutrophils with IL-17 did not increase the concentration of proMMP-9 in the conditioned medium. <b>Conclusion:</b> Local stimulation with IL-17 increases the concentration of biologically active MMP-9 as well as its precursor molecule in mouse airways in vivo. This increase in proteolytic load is probably mainly due to an increased number of neutrophils and not to an increase in the release of MMP-9 from each neutrophil. These findings indicate a link between the T lymphocyte cytokine IL-17 and increased proteolytic load in the airways which may be relevant for chronic inflammatory airway diseases such as severe asthma and COPD.
Normal and Pathological Remodeling of Human Trabecular Bone: Three Dimensional Reconstruction of the Remodeling Sequence in Normals and in Metabolic Bone Disease*
Authors: E. F. ERIKSEN
Journal: Endocrine Reviews (1986)

THE INTRODUCTION of the quantum concept for bone remodeling and in vivo tetracycline labeling by Frost in 1964 (1–3) has had a profound impact on histological studies of metabolic bone diseases over the last two decades. The quantum concept implies that changes in bone mass result from an imbalance between the amount of bone resorbed and formed, leading to either loss or gain of bone during the continuous remodeling of adult bone (1–3). Recently, a new dimension to the theories on bone loss emphasizing the importance of trabecular perforations in the development of osteopenia has been introduced by Parfitt (4). This theory explains the profound disintegration of the trabecular network occurring in certain disease states characterized by high bone turnover and increased resorptive activity (e.g. postmenopausal osteoporotic women with spontaneous vertebral fractures) and may also explain part of the bone loss that occurs with increasing age.
The contribution of transforming growth factor- and epidermal growth factor signalling to airway remodelling in chronic asthma
Authors: C. Boxall, S. T. Holgate, D. E. Davies
Journal: European Respiratory Journal (2005)

Asthma is increasing in prevalence in the developing world, affecting ∼10% of the world’s population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time. Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-β is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma. This review highlights the role of transforming growth factor-β in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo , however, it is the balance between transforming growth factor-β and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways. A fuller comprehension of the actions of transforming growth factor-β, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.
Weekly Rifapentine/Isoniazid or Daily Rifampin/Pyrazinamide for Latent Tuberculosis in Household Contacts
Authors: Mauro Schechter, Roberto Zajdenverg, Gisely Falco, Grace Link Barnes, José Cláudio Faulhaber, Jacqueline S. Coberly, Richard D. Moore, Richard E. Chaisson
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies.To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil.Contacts of patients with TB were randomized to rifapentine 900 mg/isoniazid 900 mg once weekly for 12 wk or rifampin 450-600 mg/pyrazinamide 750-1,500 mg daily for 8 wk and followed for at least 2 yr.TB rates, adverse events, and adherence to therapy.A total of 399 household contacts were enrolled, 206 in the rifapentine/isoniazid arm and 193 in the rifampin/pyrazinamide arm. The median age was 34 yr, median weight was 63 kg, 60% of participants were female, and only one patient was HIV infected. Rifapentine/isoniazid was well tolerated, but the trial was halted by the investigators before completion because of unanticipated hepatotoxicity in the rifampin/pyrazinamide arm. Twenty of 193 participants (10%) receiving rifampin/pyrazinamide experienced grade 3 or 4 hepatotoxicity, compared with 2 of 206 participants (1%) on rifapentine/isoniazid (p<0.001). There were no hospitalizations or deaths due to hepatotoxicity, and all participants' liver enzyme levels returned to normal during follow-up. During follow-up, four cases of active TB developed, three in the rifapentine/isoniazid group and one in the rifampin/pyrazinamide group (1.46 vs. 0.52%; difference, 0.94%; 95% confidence interval, -1.6 to 3.7%).Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.
Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
Authors: Robert J Motzer, Bernard Escudier, Stéphane Oudard, Thomas E Hutson, Camillo Porta, Sergio Bracarda, Viktor Grünwald, John A Thompson, Robert A Figlin, Norbert Hollaender, Gladys Urbanowitz, William J Berg, Andrea Kay, David Lebwohl, Alain Ravaud
Journal: The Lancet (2008)
Outcomes of Patients Hospitalized With Community-Acquired, Health Care–Associated, and Hospital-Acquired Pneumonia
Authors: Mario Venditti
Journal: Annals of Internal Medicine (2009)

Traditionally, pneumonia has been classified as either community- or hospital-acquired. Although only limited data are available, health care-associated pneumonia has been recently proposed as a new category of respiratory infection. "Health care-associated pneumonia" refers to pneumonia in patients who have recently been hospitalized, had hemodialysis, or received intravenous chemotherapy or reside in a nursing home or long-term care facility.To ascertain the epidemiology and outcome of community-acquired, health care-associated, and hospital-acquired pneumonia in adults hospitalized in internal medicine wards.Multicenter, prospective observational study.55 hospitals in Italy comprising 1941 beds.362 patients hospitalized with pneumonia during two 1-week surveillance periods.Cases of radiologically and clinically assessed pneumonia were classified as community-acquired, health care-associated, or hospital-acquired and rates were compared.Of the 362 patients, 61.6% had community-acquired pneumonia, 24.9% had health care-associated pneumonia, and 13.5% had hospital-acquired pneumonia. Patients with health care-associated pneumonia had higher mean Sequential Organ Failure Assessment scores than did those with community-acquired pneumonia (3.0 vs. 2.0), were more frequently malnourished (11.1% vs. 4.5%, and had more frequent bilateral (34.4% vs. 19.7%) and multilobar (27.8% vs. 21.5%) involvement on a chest radiograph. Patients with health care-associated pneumonia also had higher fatality rates (17.8% [CI, 10.6% to 24.9%] vs. 6.7% [CI, 2.9% to 10.5%]) and longer mean hospital stay (18.7 days [CI, 15.9 to 21.5 days] vs. 14.7 days [CI, 13.4 to 15.9 days]). Logistic regression analysis revealed that depression of consciousness (odds ratio [OR], 3.2 [CI, 1.06 to 9.8]), leukopenia (OR, 6.2 [CI, 1.01 to 37.6]), and receipt of empirical antibiotic therapy not recommended by international guidelines (OR, 6.4 [CI, 2.3 to 17.6]) were independently associated with increased intrahospital mortality.The number of patients with health care-associated pneumonia was relatively small. Microbiological investigations were not always homogeneous. The study included only patients with pneumonia that required hospitalization; results may not apply to patients treated as outpatients.Health care-associated pneumonia should be considered a distinct subset of pneumonia associated with more severe disease, longer hospital stay, and higher mortality rates. Physicians should differentiate between patients with health care-associated pneumonia and those with community-acquired pneumonia and provide more appropriate initial antibiotic therapy.
Immunoelectron microscopic observation of intrahepatic HBeAg in patients with chronic hepatitis B
Authors: Gotaro Yamada, Kouichi Takaguchi, Kazuhiro Matsueda, Hiroshi Nishimoto, Michiko Takahashi, Shigeatsu Fujiki, Motowo Mizuno, Shingo Kinoyama, Takao Tsuji
Journal: Hepatology (1990)

Immune light and electron microscopic studies using monoclonal antibodies have been applied to localize HBeAg in liver biopsy specimens of 19 patients with chronic hepatitis B. Under the light microscope, HBeAg was demonstrated in nuclei, cytoplasm and on the cell surface of hepatocytes. The number of HBeAg-positive hepatocytes correlated well with the serum levels of HBeAg (enzyme immunoassay) and DNA-polymerase. Of 11 patients in whom high numbers of HBeAg-positive hepatocytes were found at the light microscopic level, HBeAg was also studied in hepatocytes at the electron microscopic level. The HBeAg in nuclei was either found as aggregates or dispersed diffusely. In the aggregates of HBeAg, the 27-nm core particles were frequently found. In addition, the antigen was found in the cytosol of some hepatocytes as amorphous mass and in some hepatocytes in the cisternae of perinuclear space, endoplasmic reticulum and Golgi saccules. Occasionally the antigen was found on the membranes of the cell organelles and on the plasma membranes that faced the intercellular and the Disse spaces. These findings suggest that cytoplasmic HBeAg in hepatocytes may be ultrastructurally classified into two different patterns by its distribution, mainly in endoplasmic reticulum or in cytosol. The ratio varied between hepatocytes with these two types of patterns. The titer of serum HBeAg tended to be higher when the corresponding liver biopsy specimens contained more hepatocytes with HBeAg in endoplasmic reticulum than those with HBeAg in the cytosol.
Interpretation of arteriography.
Authors: J Bull
Journal: BMJ (1971)

47sarcoma, the histological appearances were those of a "hard fibroma," and the long history and complete lack of metastases do not suggest a malignant neoplasm.In retro- spect this was almost certainly the first account of the disease described some 10 years later by Riedel, and incidentally, of its association (and contiguity) with idio- pathic mediastinal fibrosis.Perhaps this tantalizing group of diseases, with its cumbersome and variable nomenclature, should be called "Bowlby's disease".-I am, etc.