tbuckley/cabot-search huggingface dataset:
Clinical and Histologic Determinants of Renal Outcome in ANCA-Associated Vasculitis
Authors: Robert A.F. de Lind van Wijngaarden, Herbert A. Hauer, Ron Wolterbeek, David R.W. Jayne, Gill Gaskin, Niels Rasmussen, Laure-He[Combining Acute Accent]le[Combining Grave Accent]ne Noe[Combining Diaeresis]l, Franco Ferrario, Ru[Combining Diaeresis]diger Waldherr, E. Christiaan Hagen, Jan A. Bruijn, Ingeborg M. Bajema
Journal: Journal of the American Society of Nephrology (2006)

This study aimed to identify clinical and histologic prognostic indicators of renal outcome in patients with ANCA-associated vasculitis and severe renal involvement (serum creatinine >500 micromol/L). One hundred patients who were enrolled in an international, randomized, clinical trial to compare plasma exchange with intravenous methylprednisolone as an additional initial treatment were analyzed prospectively. Diagnostic renal biopsies were performed upon entry into the study. Thirty-nine histologic and nine clinical parameters were determined as candidate predictors of renal outcome. The end points were renal function at the time of diagnosis (GFR0) and 12 mo after diagnosis (GFR12), dialysis at entry and 12 mo after diagnosis, and death. Multivariate analyses were performed. Predictive of GFR0 were age (r = -0.40, P = 0.04), arteriosclerosis (r = -0.53, P = 0.01), segmental crescents (r = 0.35, P = 0.07), and eosinophilic infiltrate (r = -0.41, P = 0.04). Prognostic indicators for GFR12 were age (r = -0.32, P = 0.01), normal glomeruli (r = 0.24, P = 0.04), tubular atrophy (r = -0.28, P = 0.02), intraepithelial infiltrate (r = -0.26, P = 0.03), and GFR0 (r = 0.29, P = 0.01). Fibrous crescents (r = 0.22, P = 0.03) were predictive of dialysis at entry. Normal glomeruli (r = -0.30, P = 0.01) and treatment arm (r = -0.28, P = 0.02) were predictive of dialysis after 12 mo. No parameter predicted death. Both chronic and acute tubulointerstitial lesions predicted GFR12 in severe ANCA-associated glomerulonephritis, whereas plasma exchange was a positive predictor of dialysis independence after 12 mo for the entire patient group. Plasma exchange remained a positive predictor when patients who were dialysis dependent at presentation were analyzed separately (r = -0.36, P = 0.01). Normal glomeruli were a positive predictor of dialysis independence and improved renal function after 12 mo, indicating that the unaffected part of the kidney is vital in determining renal outcome.
DNA Damage Links Mitochondrial Dysfunction to Atherosclerosis and the Metabolic Syndrome
Authors: John R. Mercer, Kian-Kai Cheng, Nichola Figg, Isabelle Gorenne, Melli Mahmoudi, Julian Griffin, Antonio Vidal-Puig, Angela Logan, Michael P. Murphy, Martin Bennett
Journal: Circulation Research (2010)

DNA damage is present in both genomic and mitochondrial DNA in atherosclerosis. However, whether DNA damage itself promotes atherosclerosis, or is simply a byproduct of the risk factors that promote atherosclerosis, is unknown.To examine the effect of DNA damage on atherosclerosis, we studied apolipoprotein (Apo)E(-/-) mice that were haploinsufficient for the protein kinase ATM (ataxia telangiectasia mutated), which coordinates DNA repair.ATM(+/-)/ApoE(-/-) mice developed accelerated atherosclerosis and multiple features of the metabolic syndrome, including hypertension, hypercholesterolemia, obesity, steatohepatitis, and glucose intolerance. Transplantation with ATM(+/+) bone marrow attenuated atherosclerosis but not the metabolic syndrome. ATM(+/-) smooth muscle cells and macrophages showed increased nuclear DNA damage and defective DNA repair signaling, growth arrest, and apoptosis. Metabolomic screening of ATM(+/-)/ApoE(-/-) mouse tissues identified metabolic changes compatible with mitochondrial defects, with increased β-hydroxybutyrate but reduced lactate, reduced glucose, and alterations in multiple lipid species. ATM(+/-)/ApoE(-/-) mouse tissues showed an increased frequency of a mouse mitochondrial "common" deletion equivalent and reduced mitochondrial oxidative phosphorylation.We propose that failure of DNA repair generates defects in cell proliferation, apoptosis, and mitochondrial dysfunction. This in turn leads to ketosis, hyperlipidemia, and increased fat storage, promoting atherosclerosis and the metabolic syndrome. Prevention of mitochondrial dysfunction may represent a novel target in cardiovascular disease.
Dynamic regulation of gastric surface pH by luminal pH
Authors: Shaoyou Chu, Shin Tanaka, Jonathan D. Kaunitz, Marshall H. Montrose
Journal: Journal of Clinical Investigation (1999)

In vivo confocal imaging of the mucosal surface of rat stomach was used to measure pH noninvasively under the mucus gel layer while simultaneously imaging mucus gel thickness and tissue architecture. When tissue was superfused at pH 3, the 25 microm adjacent to the epithelial surface was relatively alkaline (pH 4.1 +/- 0.1), and surface alkalinity was enhanced by topical dimethyl prostaglandin E2 (pH 4.8 +/- 0.2). Luminal pH was changed from pH 3 to pH 5 to mimic the fasted-to-fed transition in intragastric pH in rats. Under pH 5 superfusion, surface pH was relatively acidic (pH 4.2 +/- 0.2). This surface acidity was enhanced by pentagastrin (pH 3.5 +/- 0.2) and eliminated by omeprazole, implicating parietal cell H,K-ATPase as the dominant regulator of surface pH under pH 5 superfusion. With either pH 5 or pH 3 superfusion (a) gastric pit lumens had the most divergent pH from luminal superfusates; (b) qualitatively similar results were observed with and without superfusion flow; (c) local mucus gel thickness was a poor predictor of surface pH values; and (d) no channels carrying primary gastric gland fluid through the mucus were observed. The model of gastric defense that includes an alkaline mucus gel and viscous fingering of secreted acid through the mucus may be appropriate at the intragastric pH of the fasted, but not fed, animal.
Vascular Targeted Therapy With Anti–Prostate-Specific Membrane Antigen Monoclonal Antibody J591 in Advanced Solid Tumors
Authors: Matthew I. Milowsky, David M. Nanus, Lale Kostakoglu, Christine E. Sheehan, Shankar Vallabhajosula, Stanley J. Goldsmith, Jeffrey S. Ross, Neil H. Bander
Journal: Journal of Clinical Oncology (2007)

Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response.Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues.Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment.Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.
Fifteen Months' Experience of Electric Illumination of the Bladder in the Diagnosis of Obscure Vesical Disease
Authors: E. H. Fenwick
Journal: BMJ (1889)

Royal Infirmary, Newcastle-upon-Tyne, March 3rd, 1888, suffering from what was supposed to be an ovarian tumour.She stated that ten years ago, while at school, she fell over a form and injured her right side.She was in consequence confined to bed for some weeks with an acute attack of illness, which she was told was an inflammation of the side.Nothing more definite could be learned of this illness.When able to get about again, it was noticed she had a swelling, about the size of an orange, a little below the short ribs on the right side.During the following three years her health was so delicate that she was unable to do much.The swelling in the -sid4 never disappeared, though it varied from time to time in size, but the patient could not state that its size varied with the amount of urine she passed.Five years after the accident, at the age of 16, she went out as a
Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study
Authors: Jed A Hartings, M Ross Bullock, David O Okonkwo, Lilian S Murray, Gordon D Murray, Martin Fabricius, Andrew IR Maas, Johannes Woitzik, Oliver Sakowitz, Bruce Mathern, Bob Roozenbeek, Hester Lingsma, Jens P Dreier, Ava M Puccio, Lori A Shutter, Clemens Pahl, Anthony J Strong
Journal: The Lancet Neurology (2011)
Sleep apnoea in patients with quadriplegia.
Authors: R D McEvoy, I Mykytyn, D Sajkov, H Flavell, R Marshall, R Antic, A T Thornton
Journal: Thorax (1995)

This study was undertaken to establish the prevalence of, and the factors contributing towards, sleep disordered breathing in patients with quadriplegia.Forty representative quadriplegic patients (time since injury > 6 months, injury level C8 and above, Frankel category A, B, or C; mean (SE) age 35.0 (1.7) years) had home sleep studies in which EEG, EOG, submental EMG, body movement, nasal airflow, respiratory effort, and pulse oximetry (SpO2) were measured. Patients reporting post traumatic amnesia of > 24 hours, drug or alcohol abuse or other major medical illness were excluded from the study. A questionnaire on medications and sleep was administered and supine blood pressure, awake SpO2, spirometric values, height, and neck circumference were measured.A pattern of sustained hypoventilation was not observed in any of the patients. Sleep apnoeas and hypopnoeas were, however, common. Eleven patients (27.5%) had a respiratory disturbance index (RDI, apnoeas plus hypopnoeas per hour of sleep) of > or = 15, with nadir SpO2 ranging from 49% to 95%. Twelve of the 40 (30%) had an apnoea index (AI) of > or = 5 and, of these, nine (75%) had predominantly obstructive apnoeas-that is, > 80% of apnoeas were obstructive or mixed. This represents a prevalence of sleep disordered breathing more than twice that observed in normal populations. For the study population RDI correlated with systolic and diastolic blood pressure and neck circumference. RDI was higher in patients who slept supine compared with those in other postures. Daytime sleepiness was a common complaint in the study population and sleep architecture was considerably disturbed with decreased REM sleep and increased stage 1 non-REM sleep.Sleep disordered breathing is common in quadriplegic patients and sleep disturbance is significant. The predominant type of apnoea is obstructive. As with non-quadriplegic patients with sleep apnoea, sleep disordered breathing in quadriplegics is associated with increased neck circumference and the supine sleep posture.
Moderate vs. high exercise intensity: Differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function
Authors: O KEMI, P HARAM, J LOENNECHEN, J OSNES, T SKOMEDAL, U WISLOFF, O ELLINGSEN
Journal: Cardiovascular Research (2005)

Objective: Current guidelines are controversial regarding exercise intensity in cardiovascular prevention and rehabilitation. Although high-intensity training induces larger increases in fitness and maximal oxygen uptake (VO2max), moderate intensity is often recommended as equally effective. Controlled preclinical studies and randomized clinical trials are required to determine whether regular exercise at moderate versus high intensity is more beneficial. We therefore assessed relative effectiveness of 10-week HIGH versus moderate (MOD) exercise intensity on integrative and cellular functions.
Race, Socioeconomic Status, and Breast Cancer Treatment and Survival
Authors: Cathy J Bradley, Charles W Given, Caralee Roberts
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Previous studies have found that African-American women are more likely than white women to have late-stage breast cancer at diagnosis and shortened survival. However, there is considerable controversy as to whether these differences in diagnosis and survival are attributable to race or socioeconomic status. Our goal was to disentangle the influence of race and socioeconomic status on breast cancer stage, treatment, and survival. Methods: We linked data from the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER)1 Editor's note: SEER is a set of geographically defined, population-based central cancer registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Registry data are submitted electronically without personal identifiers to the NCI on a biannual basis, and the NCI makes the data available to the public for scientific research.
Expression of lamins depends on epidermal differentiation and transformation
Authors: M. Oguchi, J. Sagara, K. Matsumoto, T. Saida, S. Taniguchi
Journal: British Journal of Dermatology (2002)

It has been suggested that A- and B-type lamins, proteins of the nuclear lamina, play important roles in the morphogenesis of the nucleus and cellular differentiation.To investigate the expression of these nuclear proteins in normal skin and some keratinocytic tumours of the skin.We examined by means of immunohistochemistry the expression of lamins in normal skin and some keratinocytic tumours of the skin, such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease, solar keratosis, keratoacanthoma and seborrhoeic keratosis.In normal skin, A-type lamin was expressed in all epidermal cells, but the expression level of B-type lamins diminished from basal cells to granular cells. In keratinocytic tumours, the expression of A-type lamin was reduced, especially in BCCs, Bowen's disease and poorly differentiated SCCs. B-type lamins were reduced and exhibited heterogeneous expression patterns in most well-differentiated SCCs and keratoacanthomas. Antibodies against B-type lamins stained only peripheral cells of the lobules in keratoacanthomas, while no regular staining patterns were seen in well-differentiated SCCs.Lamin expression depends on the differentiation and transformation of the human skin. This finding should be useful for the diagnosis of keratinocytic tumours.
Allogeneic Transplantation for Low-Grade Lymphoma: Long-Term Follow-Up
Authors: Koen van Besien, Issa Khouri Richard Champlin, Philip McCarthy
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.3.702 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10653889 Allogeneic Transplantation for Low-Grade Lymphoma: Long-Term Follow-Up Koen van BesienxKoen van BesienSearch for articles by this author , Issa Khouri Richard ChamplinxIssa Khouri Richard ChamplinSearch for articles by this author , Philip McCarthyxPhilip McCarthySearch for articles by this author Show More University of Illinois ChicagoILM.D. Anderson Cancer Center HoustonTXRoswell Park Cancer Institute BuffaloNY https://doi.org/10.1200/JCO.2000.18.3.702 Full Text PDF Figures and Tables "Allogeneic Transplantation for Low-Grade Lymphoma: Long-Term Follow-Up." Journal of Clinical Oncology, 18(3), p. 702© 2000 by American Society of Clinical Oncology
Maternal smoking rates and associated adverse birth outcomes in an Irish hospital over the ten year period 2000 - 2009
Authors: Vanessa Clarke, Zubair Kabir, Sheila Keogan, Pat Goodman, Luke Clancy
Journal: European Respiratory Journal (2013)

Maternal smoking in pregnancy is an important risk factor for low birth weight (LBW) (< 2,500g) and prematurity (<37 weeks gestation) [1]. The purpose of this study was to examine smoking rates and prevalence of associated adverse birth outcomes in The Coombe Women and Infants University Hospital, Dublin over a ten year period 2000 –2009.

A cross-sectional observational study was conducted using routinely collected data from the Euroking K2 maternity system from January 2000 – December 2009 (n= 77,533).

Smoking prevalence declined significantly from 29.6% to 17.4% over the period. Rates in teenage mothers remained very high (44.3% in 2009). Smoking prevalence was almost twice as high in mothers of LBW compared to normal birthweight babies, one and a half times higher in mothers of preterm babies compared to full term and more than twice as high in mothers of Small for gestational age (SGA) babies compared to non SGA. A statistically significant decline was seen in the prevalence of SGA babies in the period. No statistically significant change was seen in the prevalence of LBW or preterm babies.

Prevalence rates in pregnancy are high in Ireland compared with other developed countries. Increased focussed efforts are needed to reduce smoking rates.

References

1. Surgeon General: The Health Consequences of Smoking A Report of the Surgeon General. Washington: US Department of Health and Human Services; 2004.
Experts warn of disruption to NHS services caused by government reforms
Authors: A. O'Dowd
Journal: BMJ (2010)

<h3>Abstract</h3> The human pathogen <i>Pseudomonas aeruginosa</i> (Pa) is one of the most frequent and severe causes of nosocomial infection. This organism is also a major cause of airway infections in people with cystic fibrosis (CF). Pa is known to have a remarkable metabolic plasticity, allowing it to thrive in diverse environmental conditions and ecological niches, yet little is known about the central metabolic pathways which sustain its growth during infection, or precisely how these pathways operate. In this work, we used a combination of ‘omics approaches (transcriptomics, proteomics, metabolomics and <sup>13</sup>C-fluxomics) and reverse genetics to provide a systems-level insight into how the infection-relevant organic acids, succinate and propionate, are metabolized by Pa. Moreover, through structural and kinetic analysis of the 2-methylcitrate synthase (PrpC) and its paralogue, citrate synthase (GltA), we show how these two crucial enzymatic steps are interconnected in Pa organic acid assimilation. We found that Pa can rapidly adapt to the loss of GltA function by acquiring mutations in a transcriptional repressor, which then de-represses <i>prpC</i> expression. Our findings provide a clear example of how ‘underground metabolism’, facilitated by enzyme substrate promiscuity, “rewires” Pa metabolism, allowing it to overcome the loss of a crucial enzyme. This pathogen-specific knowledge is critical for the advancement of a model-driven framework to target bacterial central metabolism.
Challenges and perspectives for improved management of HIV/Mycobacterium tuberculosis co-infection
Authors: M. Sester, C. Giehl, R. McNerney, B. Kampmann, G. Walzl, P. Cuchí, C. Wingfield, C. Lange, G.B. Migliori, A.L. Kritski, A. Meyerhans
Journal: European Respiratory Journal (2010)

HIV and Mycobacterium tuberculosis (MTB) are two widespread and highly successful microbes whose synergy in pathogenesis has created a significant threat for human health globally. In acknowledgement of this fact, the European Union (EU) has funded a multinational support action, the European Network for global cooperation in the field of AIDS and TB (EUCO-Net), that brings together experts from Europe and those regions that bear the highest burden of HIV/MTB co-infection. Here, we summarise the main outcome of the EUCO-Net project derived from an expert group meeting that took place in Stellenbosch (South Africa) (AIDS/TB Workshop on Research Challenges and Opportunities for Future Collaboration) and the subsequent discussions, and propose priority areas for research and concerted actions that will have impact on future EU calls.
Is Single-Agent Chemotherapy Acceptable in Platinum-Sensitive Relapsed Ovarian Cancer?
Authors: Rony M. Abou-Jawde, Satinderjit S. Oberoi
Journal: Journal of Clinical Oncology (2008)

tissue available for each patient.This attitude is consistent with the perfect concordance of KRAS mutations that was observed between primary tumor and liver metastases in a series of 96 metastatic CRC patients, among whom 48 were analyzed both in liver metastases and matched primary tumors. 2n conclusion, there is a convergence of relevant results concerning the prognostic and predictive value of KRAS mutations on response to cetuximab in metastatic CRC.As it was specified in the conclusion of our article, these results require confirmation in a randomized trial comparing an experimental arm containing cetuximab with a control arm without this targeted therapy.
Heart Mitochondrial Function in Acute and in Chronic Hyperthyroidism in Rats
Authors: DOROTHY A. PIATNEK-LEUNISSEN, REINHARD L. LEUNISSEN
Journal: Circulation Research (1969)

The effects of acute versus chronic hyperthyroidism on rat heart mitochondria were explored. Acute, severe hyperthyroidism with an 18% loss of body weight was induced by injecting subcutaneously 10 µg/100g/day of triiodothyronine for 6 to 14 days, and chronic, anabolic, moderate hyperthyroidism was induced by placing triiodothyronine in the drinking water at a dose of 25 or 50 µg/100 ml for 15 to 60 days. Mitochondrial function was assessed polarographically using α-ketoglutarate as the oxidizing substrate, and mitochondrial structure was assessed indirectly from changes in rates of swelling in decimolar alkaline salt solutions in vitro. The P-O ratios of heart mitochondria isolated with Nagarse incubation from both types of hyperthyroid rats decreased slightly (15%) but significantly ( P = 0.05). Simple dilution of the hyperthyroid mitochondrial suspensions effected a 75% increase in the P-O ratio of the acutely treated rats but only a 19% increase in that of the chronically treated rats. Significantly increased susceptibility to swelling in vitro was exhibited only by the mitochondria of the chronically triiodothyronine-treated rats. On the other hand, only those of the acutely treated rats showed significant increases in the activity of Mg 2+ -stimulated mitochondrial ATPase. These data suggest that the mechanisms whereby excess thyroid hormone in vivo affects the function and structure of isolated rat heart mitochondria vary with the mode of induction and the duration of the hyperthyroid state.
EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2013
Authors: Marko Babjuk, Maximilian Burger, Richard Zigeuner, Shahrokh F. Shariat, Bas W.G. van Rhijn, Eva Compérat, Richard J. Sylvester, Eero Kaasinen, Andreas Böhle, Joan Palou Redorta, Morgan Rouprêt
Journal: European Urology (2013)