tbuckley/cabot-search huggingface dataset:
Pathogenesis of steatorrhea in primary biliary cirrhosis
Authors: Stephen J. Lanspa, Albert T.H. Chan, Sumner J. Bell, Vay Liang W. Go, Rolland E. Dickson, Eugene P. Dimagno
Journal: Hepatology (1985)

To investigate the pathophysiology of steatorrhea in primary biliary cirrhosis, the severity of steatorrhea, small bowel histology and function, cholestasis, exocrine pancreatic secretion and liver histology were studied. Twenty-four primary biliary cirrhotic patients had a quantitative stool fat collection, serum bilirubin and alkaline phosphatase and liver biopsies. From this group, ten had further studies: a small bowel biopsy (n = 7); a D-xylose test (n = 9); measurement of pancreatiobiliary concentrations and outputs after intravenous cholecystokinin (n = 10); essential amino acid perfusion of the duodenum (n = 9), and eating a test meal (n = 7). D-xylose absorption was normal, and only one patient had a minimal small bowel mucosal abnormality. Pancreatic lipase outputs in response to cholecystokinin were low in two primary biliary cirrhotic patients, but were greater than 10% of normal. Postprandial lipase outputs were normal except in one patient who had abnormal duodenal acidification. Mean enzyme outputs in primary biliary cirrhotic patients were normal in response to essential amino acid perfusion; but 6 had low lipase and 5 had low trypsin outputs which were associated with decreased bile acid outputs (p less than 0.03). Severity of steatorrhea was associated with reduced bile acid outputs and concentrations (r = 0.82; p less than 0.0001), degree of cholestasis (serum bilirubin; r = 0.88; p less than 0.001) and advanced histologic stages (p less than 0.005). Severe intraluminal bile acid deficiency combined with a submaximal intraluminal stimulus (essential amino acids) may be associated with decreased exocrine pancreatic secretion in primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
DNA Damage–Specific Control of Cell Death by Cryptochrome in p53-Mutant Ras–Transformed Cells
Authors: Jin Hyup Lee, Shobhan Gaddameedhi, Nuri Ozturk, Rui Ye, Aziz Sancar
Journal: Cancer Research (2012)

The main feedback loop driving circadian rhythm in mice is controlled, in part, by the genes encoding the cryptochromes Cry1 and Cry2. Targeted mutation of both Cry1 and Cry2 delay the early onset of tumor formation in p53-null mutant mice. Furthermore, Ras-transformed p53- and Cry-null mouse skin fibroblasts are more sensitive than p53 mutants to apoptotic cell death initiated by agents that activate either the intrinsic or the extrinsic apoptosis pathways. Here, we investigated the effect of Cry1 and Cry2 mutations on cell death by other genotoxic agents that generate alkylated bases, interstrand crosslinks, DNA-protein crosslinks, and double-strand breaks. Both ultraviolet (UV) and the UV mimetic compound oxaliplatin and the radiomimetic compound doxorubicin promoted apoptosis by upregulating the tumor suppressor p73. However, only the UV and oxaliplatin-induced upregulation of p73 mediated by the transcription factor Egr1, but not the doxorubicin-induced upregulation mediated by the transcription factor E2F1, was enhanced by Cry1/Cry2 double mutation. Accordingly, Egr1 downregulation reduced oxaliplatin-induced apoptosis, whereas E2F1 downregulation reduced doxorubicin-induced apoptosis. Our findings establish distinct roles for cryptochromes in intrinsic apoptosis induced by UV mimetic and radiomimetic agents.
Lack of Collagen XVIII/Endostatin Exacerbates Immune-Mediated Glomerulonephritis
Authors: Yuki Hamano, Takashi Okude, Ryota Shirai, Ikumi Sato, Ryota Kimura, Makoto Ogawa, Yoshihiko Ueda, Osamu Yokosuka, Raghu Kalluri, Shiro Ueda
Journal: Journal of the American Society of Nephrology (2010)

Collagen XVIII is a component of the highly specialized extracellular matrix associated with basement membranes of epithelia and endothelia. In the normal kidney, collagen XVIII is distributed throughout glomerular and tubular basement membranes, mesangial matrix, and Bowman's capsule. Proteolytic cleavage within its C-terminal domain releases the fragment endostatin, which has antiangiogenic properties. Because damage to the glomerular basement membrane (GBM) accompanies immune-mediated renal injury, we investigated the role of collagen XVIII/endostatin in this disorder. We induced anti-GBM glomerulonephritis in collagen XVIII α1-null and wild-type mice and compared the resulting matrix accumulation, inflammation, and capillary rarefaction. Anti-GBM disease upregulated collagen XVIII/endostatin expression within the GBM and Bowman's capsule of wild-type mice. Collagen XVIII/endostatin-deficient mice developed more severe glomerular and tubulointerstitial injury than wild-type mice. Collagen XVIII/endostatin deficiency altered matrix remodeling, enhanced the inflammatory response, and promoted capillary rarefaction and vascular endothelial cell damage, but did not affect endothelial proliferation. Supplementing collagen XVIII-deficient mice with exogenous endostatin did not affect the progression of anti-GBM disease. Taken together, these results suggest that collagen XVIII/endostatin preserves the integrity of the extracellular matrix and capillaries in the kidney, protecting against progressive glomerulonephritis.
Antihypertensive Treatment Based on Blood Pressure Measurement at Home or in the Physician's Office&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Jan A. Staessen
Journal: JAMA (2004)

ContextSelf-measurement of blood pressure is increasingly used in clinical practice, but how it affects the treatment of hypertension requires further study.ObjectiveTo compare use of blood pressure (BP) measurements taken in physicians' offices and at home in the treatment of patients with hypertension.Design, Setting, and ParticipantsBlinded randomized controlled trial conducted from March 1997 to April 2002 at 56 primary care practices and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured at physicians' offices were enrolled and followed up for 1 year.InterventionsAntihypertensive drug treatment was adjusted in a stepwise fashion based on either the self-measured DBP at home (average of 6 measurements per day during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's office (n = 197). If the DBP guiding treatment was above (&gt;89 mm Hg), at (80-89 mm Hg), or below (&lt;80 mm Hg) target, a physician blinded to randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively.Mean Outcome MeasuresOffice and home BP levels, 24-hour ambulatory BP, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and costs of treatment.ResultsAt the end of the study (median follow-up, 350 days; interquartile range, 326-409 days), more home BP than office BP patients had stopped antihypertensive drug treatment (25.6% vs 11.3%; P&lt;.001) with no significant difference in the proportions of patients progressing to multiple-drug treatment (38.7% vs 45.1%; P = .14). The final office, home, and 24-hour ambulatory BP measurements were higher (P&lt;.001) in the home BP group than in the office BP group. The mean baseline-adjusted systolic/diastolic differences between the home and office BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively. Left ventricular mass and reported symptoms were similar in the 2 groups. Costs per 100 patients followed up for 1 month were only slightly lower in the home BP group (€3875 vs €3522 [$4921 vs $4473]; P = .04).ConclusionsAdjustment of antihypertensive treatment based on home BP instead of office BP led to less intensive drug treatment and marginally lower costs but also to less BP control, with no differences in general well-being or left ventricular mass. Self-measurement allowed identification of patients with white-coat hypertension. Our findings support a stepwise strategy for the evaluation of BP in which self-measurement and ambulatory monitoring are complementary to conventional office measurement and highlight the need for prospective outcome studies to establish the normal range of home-measured BP.
Neuron-derived orphan receptor 1 mediated human pulmonary arterial smooth muscle cells proliferation via cyclin D1
Authors: Da-Xiong Zeng, Chang-Guo Wang, Wei Lei, Jian-An Huang
Journal: European Respiratory Journal (2014)

Our previous studies demonstrated the role of cyclin D1 in pulmonary arterial smooth muscle cells (PASMCs) proliferation. In this study, we observed the role of neuron-derived orphan receptor 1 (NOR1) in the regulation of cyclin D1 and PASMCs proliferation.

Fetal bovine serum (FBS) induced the proliferation of human PASMCs in a dose-dependent way (figure 1A, * P <0.05 as compared with control). 10% FBS induced a maxima NOR1 expression at 2h (figure 1B and 1C, * P <0.01). Transfection of an over-expressed plasmid induced NOR1 up-regulation (figure 1D and 1E, * P <0.01) and cells proliferation (figure 1F, * P <0.05).

![Figure][1] 



NOR1 over-expression significantly induced cyclin D1 up-regulation (figure 2A and 2B, * P  0.05 as compared with FBS group).

![Figure][1] 



So, we concluded that NOR1 mediated human PASMCs proliferation at least partly via cyclin D1.

 [1]: pending:yes
Microsatellite evolution--a reciprocal study of repeat lengths at homologous loci in cattle and sheep
Authors: H. Ellegren, S. Moore, N. Robinson, K. Byrne, W. Ward, B. C. Sheldon
Journal: Molecular Biology and Evolution (1997)

The application of microsatellites in evolutionary studies requires an understanding of the patterns governing their evolution in different species. The finding that homologous microsatellite loci are longer, i.e., containing more repeat units, in human and in other primates has been taken as evidence for directional microsatellite evolution and for a difference in the rate of evolution between species. However, it has been argued that this finding is an inevitable consequence of biased selection of longer-than-average microsatellites in human, because cloning procedures are adopted to generate polymorphic and, hence, long markers. As a test of this hypothesis, we conducted a reciprocal comparison of the lengths of microsatellite loci in cattle and sheep using markers derived from the bovine genome as well as the ovine genome. In both cases, amplification products were longer in the focal species, and loci were also more polymorphic in the species from which they were originally cloned. The crossing pattern that we found suggests that interspecific length differences detected at homologous microsatellite loci are the result of biased selection of loci associated with cloning procedures. Hence, comparisons of microsatellite evolution between species are flawed unless they are based on reciprocal analyses or on genuinely random selection of loci with respect to repeat length.
Effects of nedocromil sodium (Tilade®) on the activation of human eosinophils and neutrophils and the release of histamine from mast cells
Authors: R. Moqbel, O. Cromwell, G. M. Walsh, A. J. Wardlaw, L. Kurlak, A. B. Kay
Journal: Allergy (1988)

The ability of nedocromil sodium, a new anti-inflammatory agent for the treatment of asthma, to inhibit activation of human eosinophils and neutrophils in vitro, has been studied using an adherence reaction (the "rosette" technique) as well as a cytotoxicity assay. We have also investigated the capacity of nedocromil sodium to inhibit IgE-dependent histamine release from human lung mast cells. The drug was a potent inhibitor (IC50 approx 5 x 10(-9)M) of fMLP-induced enhancement of eosinophil and neutrophil complement (C3b) and IgG (Fc) rosettes. There was also a comparable inhibition of enhancement, by fMLP, of eosinophil and neutrophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Although nedocromil sodium also inhibited histamine release from human lung mast cells in a dose-dependent fashion its activity was relatively weak (IC30 5 x 10(-6)M) compared to its effect on granulocytes. These experiments support the view that the principal mode of action of nedocromil sodium is its capacity to inhibit the activation of inflammatory cells.
<b> <i>FGFR3</i> </b> and <b> <i>P53</i> </b> Characterize Alternative Genetic Pathways in the Pathogenesis of Urothelial Cell Carcinoma
Authors: Bas W. G. van Rhijn, Theo H. van der Kwast, André N. Vis, Wim J. Kirkels, Egbert R. Boevé, Adriaan C. Jöbsis, Ellen C. Zwarthoff
Journal: Cancer Research (2004)

Fibroblast growth factor receptor 3 (FGFR3) and P53 mutations are frequently observed in bladder cancer. We here describe the distribution of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell carcinomas. FGFR3 mutations were observed in 59% and P53 overexpression in 25%. Interestingly, FGFR3 and P53 alterations were mutually exclusive, because they coincided in only 5.7% of tumors. Consequently, we propose that they characterize two alternative genetic pathways in urothelial cell carcinoma pathogenesis. The genetic alterations were reflected in the pathology and the clinical outcome, i.e., FGFR3 mutations were found in low-stage/-grade tumors and were associated with a favorable disease course, whereas P53 alterations were tied to adverse disease parameters.
Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis
Authors: Armando E. Giuliano
Journal: JAMA (2011)

<h3>Context</h3>Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival.<h3>Objective</h3>To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.<h3>Design, Setting, and Patients</h3>The American College of Surgeons Oncology Group Z0011 trial, a phase 3 noninferiority trial conducted at 115 sites and enrolling patients from May 1999 to December 2004. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and 1 to 2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin-eosin staining on permanent section. Targeted enrollment was 1900 women with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected.<h3>Interventions</h3>All patients underwent lumpectomy and tangential whole-breast irradiation. Those with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Systemic therapy was at the discretion of the treating physician.<h3>Main Outcome Measures</h3>Overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND. Disease-free survival was a secondary end point.<h3>Results</h3>Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up, March 4, 2010), 5-year overall survival was 91.8% (95% confidence interval [CI], 89.1%-94.5%) with ALND and 92.5% (95% CI, 90.0%-95.1%) with SLND alone; 5-year disease-free survival was 82.2% (95% CI, 78.3%-86.3%) with ALND and 83.9% (95% CI, 80.2%-87.9%) with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 (90% CI, 0.56-1.11) without adjustment and 0.87 (90% CI, 0.62-1.23) after adjusting for age and adjuvant therapy.<h3>Conclusion</h3>Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00003855
Novel D761Y and Common Secondary T790M Mutations in Epidermal Growth Factor Receptor–Mutant Lung Adenocarcinomas with Acquired Resistance to Kinase Inhibitors
Authors: Marissa N. Balak, Yixuan Gong, Gregory J. Riely, Romel Somwar, Allan R. Li, Maureen F. Zakowski, Anne Chiang, Guangli Yang, Ouathek Ouerfelli, Mark G. Kris, Marc Ladanyi, Vincent A. Miller, William Pao
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In patients whose lung adenocarcinomas harbor epidermal growth factor receptor (EGFR) tyrosine kinase domain mutations, acquired resistance to the tyrosine kinase inhibitors (TKI) gefitinib (Iressa) and erlotinib (Tarceva) has been associated with a second-site EGFR mutation, which leads to substitution of methionine for threonine at position 790 (T790M). We aimed to elucidate the frequency and nature of secondary EGFR mutations in patients with acquired resistance to TKI monotherapy. Experimental Design: Tumor cells from patients with acquired resistance were examined for secondary EGFR kinase domain mutations by molecular analyses. Results: Eight of 16 patients (50% observed rate; 95% confidence interval, 25-75%) had tumor cells with second-site EGFR mutations. Seven mutations were T790M and one was a novel D761Y mutation found in a brain metastasis. When combined with a drug-sensitive L858R mutation, the D761Y mutation modestly reduced the sensitivity of mutant EGFR to TKIs in both surrogate kinase and cell viability assays. In an autopsy case, the T790M mutation was found in multiple visceral metastases but not in a brain lesion. Conclusions: The T790M mutation is common in patients with acquired resistance. The limited spectrum of TKI-resistant mutations in EGFR, which binds to erlotinib in the active conformation, contrasts with a wider range of second-site mutations seen with acquired resistance to imatinib, which binds to ABL and KIT, respectively, in closed conformations. Collectively, our data suggest that the type and nature of kinase inhibitor resistance mutations may be influenced by both anatomic site and mode of binding to the kinase target.
Gastrointestinal hormones in short bowel syndrome. Peptide YY may be the 'colonic brake' to gastric emptying.
Authors: J M Nightingale, M A Kamm, J R van der Sijp, M A Ghatei, S R Bloom, J E Lennard-Jones
Journal: Gut (1996)

BACKGROUND: Short bowel patients with a jejunostomy have large volume stomal outputs, which may in part be due to rapid gastric emptying of liquid. Short bowel patients with a preserved colon do not have such a high stool output and gastric emptying of liquid is normal. AIMS: To determine if differences in the gastric emptying rate between short bowel patients with and without a colon can be related to gastrointestinal hormone changes after a meal. SUBJECTS: Seven short bowel patients with no remaining colon (jejunal length 30-160 cm) and six with jejunum in continuity with a colon (jejunal length 25-75 cm), and 12 normal subjects. METHODS: The subjects all consumed a 640 kcal meal; blood samples were taken for 180 minutes for measurement of gastrointestinal hormones. RESULTS: Patients with a colon had high fasting peptide YY values (median 71 pmol/l with a colon; 11 pmol/l normal subjects, p &lt; 0.005) with a normal postprandial rise, but those without a colon had a low fasting (median 7 pmol/l, p = 0.076) and a reduced postprandial peptide YY response (p &lt; 0.050). Motilin values were high in some patients without a colon. In both patient groups fasting and postprandial gastrin and cholecystokinin values were high while neurotensin values were low. There were no differences between patient groups and normal subjects in enteroglucagon, pancreatic polypeptide, or somatostatin values. CONCLUSIONS: Low peptide YY values in short bowel patients without a colon may cause rapid gastric emptying of liquid. High values of peptide YY in short bowel patients with a retained colon may slow gastric emptying of liquid and contribute to the "colonic brake9.
Bronchial hyperreactivity to leucotriene D4 and histamine in exogenous asthma.
Authors: H Bisgaard, S Groth, F Madsen
Journal: BMJ (1985)

Reactivity of the small and large airways to inhaled leucotriene D4, one of the leucotrienes that constitute slow reacting substance of anaphylaxis, was studied in eight patients with exogenous asthma and nine healthy subjects with no history of atopy. Non-cumulative dose response relations were constructed for leucotriene D4 in a randomised, double blind set up. Reactivity to the leucotriene was compared with reactivity to histamine in the two groups. Both groups reacted to leucotriene D4 with significant airway obstruction evident in forced expiratory volume in one second (FEV1), peak expiratory flow rate, maximal expiratory flow rate at 30% of forced vital capacity estimated from a partial flow volume curve initiated at 50% of vital capacity (V30), and an increase in volume of trapped gas. The airways of the patients were significantly (p less than 0.01) more reactive to leucotriene D4 than those of the controls. The differences were in order of magnitude, 10(2)-10(3) for FEV1 but only about 15 for V30 (p less than 0.05). The hyperreactivity of the airways of the asthmatic subjects to leucotriene D4 was comparable to that to histamine. Inhalation of leucotriene D4 caused pronounced dyspnoea only among the patients. The findings suggest a role for leucotriene D4 in human bronchial asthma.
In vitro evaluation of the bioadhesive properties of hydrophobic polybasic gels containing N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate
Authors: D. Quintanar-Guerrero, R. Villalobos-Garcı́a, E. Alvarez-Colı́n, J.M. Cornejo-Bravo
Journal: Biomaterials (2001)
Human cardiac and bone marrow stromal cells exhibit distinctive properties related to their origin
Authors: Alessandra Rossini, Caterina Frati, Costanza Lagrasta, Gallia Graiani, Alessandro Scopece, Stefano Cavalli, Ezio Musso, Marco Baccarin, Marina Di Segni, Francesco Fagnoni, Antonia Germani, Eugenio Quaini, Manuel Mayr, Qingbo Xu, Andrea Barbuti, Dario DiFrancesco, Giulio Pompilio, Federico Quaini, Carlo Gaetano, Maurizio C. Capogrossi
Journal: Cardiovascular Research (2010)

Bone marrow mesenchymal stromal cell (BMStC) transplantation into the infarcted heart improves left ventricular function and cardiac remodelling. However, it has been suggested that tissue-specific cells may be better for cardiac repair than cells from other sources. The objective of the present work has been the comparison of in vitro and in vivo properties of adult human cardiac stromal cells (CStC) to those of syngeneic BMStC.Although CStC and BMStC exhibited a similar immunophenotype, their gene, microRNA, and protein expression profiles were remarkably different. Biologically, CStC, compared with BMStC, were less competent in acquiring the adipogenic and osteogenic phenotype but more efficiently expressed cardiovascular markers. When injected into the heart, in rat a model of chronic myocardial infarction, CStC persisted longer within the tissue, migrated into the scar, and differentiated into adult cardiomyocytes better than BMStC.Our findings demonstrate that although CStC and BMStC share a common stromal phenotype, CStC present cardiovascular-associated features and may represent an important cell source for more efficient cardiac repair.