tbuckley/cabot-search huggingface dataset:
Prospective evaluation of the treatment of solitary rectal ulcer syndrome with biofeedback
Authors: C J Vaizey, A J Roy, M A Kamm
Journal: Gut (1997)

Background —Solitary rectal ulcer syndrome (SRUS) is often resistant to medical and surgical treatment. Aim —To determine whether biofeedback retraining is a useful treatment for this condition. Patients —Thirteen consecutive patients with SRUS (three men, median age 34 years, median duration of symptoms three years) underwent treatment. Previous surgical treatment had failed in five. Methods —Patients were evaluated prospectively. Anorectal physiological studies were performed in 11 patients before treatment. A standardised questionnaire was used before and after treatment, and all but two patients were examined after treatment. Results —Median follow up was nine months (range 3–22 months). After treatment four patients were asymptomatic, and four felt improved. Symptom improvement or elimination occurred in: need to strain (7/13 patients), digitation (7/11), laxative use (5/9). Time in the toilet (median 30 v 10 minutes, before v after treatment) and number of visits to toilet (6 v 3/day) were also improved. Three patients were able to maintain employment before treatment compared with eight after treatment. The solitary ulcer did not heal completely in any of the nine patients examined after treatment, but improved in four. Previous surgery, the macroscopic appearance of the ulcer, the presence of pelvic floor paradox, and other physiological parameters did not predict outcome. Conclusion —Biofeedback retraining is a useful treatment for this condition. Long term studies are now required.
Copy Number Aberrations in Mouse Breast Tumors Reveal Loci and Genes Important in Tumorigenic Receptor Tyrosine Kinase Signaling
Authors: J. Graeme Hodgson, Tiffany Malek, Sophia Bornstein, Sujatmi Hariono, David G. Ginzinger, William J. Muller, Joe W. Gray
Journal: Cancer Research (2005)

Abstract Receptor tyrosine kinase (RTK) signaling plays a key role in the development of breast cancer. Defining the genes and pathways in the RTK signaling network that are important regulators of tumorigenesis in vivo will unveil potential candidates for targeted therapeutics. To this end, we used microarray comparative genomic hybridization to identify and compare copy number aberrations in five mouse models of breast cancer induced by wild-type and mutated forms of oncogenic ErbB2 or the polyomavirus middle T antigen (PyMT). We observed distinct genomic alterations among the various models, including recurrent chromosome 11 amplifications and chromosome 4 deletions, syntenic with human 17q21-25 and 1p35-36, respectively. Expression of oncogenic Erbb2 (NeuNT) under control of the endogenous Erbb2 promoter results in frequent (85%) amplification at the Erbb2 locus with striking structural similarity to the human amplicon, resulting in overexpression of at least two of the genes, Erbb2 and Grb7. Chromosome 11 amplicons distal to Erbb2 arise in a model (DB) overexpressing a mutant variant of PyMT (Y315/322F) unable to activate phosphatidylinositol 3-kinase. These amplicons are not observed in DB hyperplasias or in tumors overexpressing wild-type PyMT and result in overexpression of Grb2 and Itgb4. Distal chromosome 4 deletions occur in a significantly higher proportion of Erbb2 than PyMT tumors and encompass 14-3-3σ (Stratifin), which is expressed at low or undetectable levels in the majority of NeuNT tumors. Our studies highlight loci and genes important in the regulation of tumorigenic RTK signaling in mammary epithelial cells in vivo.
Increased thickness of pregnancy-associated melanoma
Authors: R.L. TRAVERS, A.J. SOBER, M. BERWICK, M.C. MIHM, R.L. HARNHILL, L. M. DUNCAN
Journal: British Journal of Dermatology (2010)

The effects of pregnancy on the pathophysiology of melanoma remain unclear. Although a gender‐specific advantage for women vs. men is seen for characteristics such as stage at presentation, site of primary tumour, and survival time, an adverse effect of pregnancy on melanoma development and progression has been reported. In a retrospective study, we investigated the tumour characteristics of women who developed pregnancy‐associated melanoma, and compared them with melanomas arising in non‐pregnant women of child‐bearing age. The patient records of the Massachusetts General Hospital Pigmented Lesion Clinic were reviewed, and 465 women of reproductive age (16–45 years) who developed melanoma were identified. Of these, in 45 women (age 21–42 years) there was a close temporal relationship between diagnosis of the tumour and pregnancy. Clinical and histological characteristics of the primary tumours were recorded. Differences in tumour thickness, site and histological type were analysed. The mean thickness of pregnancy‐associated melanomas was significantly greater than that of non‐pregnancy‐associated tumours (2.28 vs. 1.22 mm, respectively: P < 0.007). No differences in histological type (P = 0.64) or site (P = 0.74) of the primary tumours were found between the two patient groups. Not surprisingly, multivariate analysis revealed that tumour thickness was a statistically significant variable in determining prognosis (P = 0001). An unexpected finding, on multivariate analysis, was a possible pregnancy‐associated prognostic advantage (P = 008). Melanomas arising during pregnancy are thicker, but are not necessarily associated with a less favourable prognosis than tumours arising in non‐pregnant women of child‐bearing age. The mechanisms by which pregnancy may lead to increased thickness of melanoma have yet to be elucidated, and merit further study.
Loss of Hepatocyte Growth Factor/c-Met Signaling Pathway Accelerates Early Stages of <i>N</i>-nitrosodiethylamine–Induced Hepatocarcinogenesis
Authors: Taro Takami, Pal Kaposi-Novak, Koichi Uchida, Luis E. Gomez-Quiroz, Elizabeth A. Conner, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2007)

Abstract Hepatocyte growth factor (HGF) has been reported to have both positive and negative effects on carcinogenesis. Here, we show that the loss of c-Met signaling in hepatocytes enhanced rather than suppressed the early stages of chemical hepatocarcinogenesis. c-Met conditional knockout mice (c-metfl/fl, AlbCre+/−; MetLivKO) treated with N-nitrosodiethylamine developed significantly more and bigger tumors and with a shorter latency compared with control (w/w, AlbCre+/−; Cre-Ctrl) mice. Accelerated tumor development was associated with increased rate of cell proliferation and prolonged activation of epidermal growth factor receptor (EGFR) signaling. MetLivKO livers treated with N-nitrosodiethylamine also displayed elevated lipid peroxidation, decreased ratio of reduced glutathione to oxidized glutathione, and up-regulation of superoxide dismutase 1 and heat shock protein 70, all consistent with increased oxidative stress. Likewise, gene expression profiling done at 3 and 5 months after N-nitrosodiethylamine treatment revealed up-regulation of genes associated with cell proliferation and stress responses in c-Met mutant livers. The negative effects of c-Met deficiency were reversed by chronic p.o. administration of antioxidant N–acetyl–l-cysteine. N–acetyl–l-cysteine blocked the EGFR activation and reduced the N-nitrosodiethylamine–initiated hepatocarcinogenesis to the levels of Cre-Ctrl mice. These results argue that intact HGF/c-Met signaling is essential for maintaining normal redox homeostasis in the liver and has tumor suppressor effect(s) during the early stages of N-nitrosodiethylamine–induced hepatocarcinogenesis. [Cancer Res 2007;67(20):9844–51]
Erythrocyte membrane phosphorylation in untreated and in etretinate-treated psoriatic patients*
Authors: R. KUMAR, VIRGINIA C.WEISS, D.P. WEST, LAURA A.CHIERO
Journal: British Journal of Dermatology (1983)

Levels of phosphorylation were decreased in bands 2 to 2.1, 2.9 to 3 and 4-5 to 4-8 of erythrocyte membranes from psoriatic patients compared with control values. In addition, higher than control levels of 32P were incorporated into a new polypeptide hand (mol. wt. 18-20,000 daltons) of red cell membranes from patients. Uptake of 32P by these bands returned towards normal after the patients received oral etretmate treatment. These results suggest there is a gcneralixed plasma membrane defect in psoriasis and that ctretinate may affect the metabolism of red cell membrane proteins.
High-Power Handheld Blue Laser-Induced Maculopathy
Authors: Sulaiman M. Alsulaiman, Abdulaziz Adel Alrushood, Jluwi Almasaud, Sultan Alzaaidi, Yahya Alzahrani, J. Fernando Arevalo, Nicola G. Ghazi, Emad B. Abboud, Sawsan R. Nowilaty, Mohammad Al-Amry, Saba Al-Rashaed
Journal: Ophthalmology (2013)
Regulation of lysyl oxidase in vascular cells: lysyl oxidase as a new player in cardiovascular diseases
Authors: C. Rodriguez, J. Martinez-Gonzalez, B. Raposo, J. F. Alcudia, A. Guadall, L. Badimon
Journal: Cardiovascular Research (2008)

Lysyl oxidase (LOX) plays a crucial role in the maintenance of extracellular matrix stability and could participate in vascular remodelling associated with cardiovascular diseases. Evidence from in vitro and in vivo studies shows that LOX downregulation is associated with the endothelial dysfunction characteristic of earlier stages of the atherosclerotic process. Conversely, upregulation of this enzyme in vascular cells could induce neointimal thickening in atherosclerosis and restenosis. In fact, LOX is chemotactic for vascular smooth muscle cells and monocytes, is modulated by proliferative stimulus in these cells, and could control other cellular processes such as gene expression and cell transformation. Furthermore, it is conceivable that LOX downregulation could underlie plaque instability and contribute to the destructive remodelling that takes place during aneurysm development. Overall, LOX could play a key role in vascular homeostasis and, hence, it emerges as a new player in cardiovascular diseases. This review addresses the experimental evidence related to the role of LOX in vascular disorders and the potential benefits of controlling its expression and function.
Non–Small Cell Lung Cancer Exhibits Transcript Overexpression of Genes Associated with Homologous Recombination and DNA Replication Pathways
Authors: Silvia Saviozzi, Paolo Ceppi, Silvia Novello, Paolo Ghio, Marco Lo Iacono, Piero Borasio, Alberto Cambieri, Marco Volante, Mauro Papotti, Raffaele A. Calogero, Giorgio V. Scagliotti
Journal: Cancer Research (2009)

Genes involved in DNA repair and replication have been recently investigated as predictive markers of response to chemotherapy in non-small cell lung cancer (NSCLC). However, few data on the expression of these genes in tumor compared with corresponding normal lung are available. The aim of this study was to evaluate differential mRNA levels of 22 DNA repair genes of five different DNA repair pathways: direct, base excision, nucleotide excision (NER), double-strand break (DSBR), and postreplicative repair. In addition, six genes involved in DNA replication (REP) and three telomere maintenance genes were investigated. Total RNAs extracted from fresh-frozen tumors and corresponding normal tissues of 50 consecutive chemo-naïve resected NSCLC patients were analyzed. Transcript levels were quantified by real-time PCR. A significant overexpression was detected in 20 of 30 (67%) genes, mostly belonging to DSBR pathways, whereas others (XPA, XPC, and UBE2N; 10%) were significantly underexpressed. For 7 of 30 (23%) genes, mostly belonging to NER pathway, no significant difference between paired tumor and normal samples was observed. Transcript overexpression of DSBR and REP genes was significantly higher in poorly differentiated carcinomas and DSBR levels were higher in men compared with women. The transcriptional overexpression of four genes (XRCC5, TOP3B, TYMS, and UNG) showed significant correlation with a shorter patients' outcome at the univariate, whereas only stage of disease appeared as an independent factor affecting prognosis, as assessed by multivariate analysis. In conclusion, genes belonging to DNA repair/replication pathways are overexpressed in NSCLC and are associated with a more aggressive phenotype.
Paclitaxel-Coated Balloon Catheter Versus Paclitaxel-Coated Stent for the Treatment of Coronary In-Stent Restenosis
Authors: Martin Unverdorben, Christian Vallbracht, Bodo Cremers, Hubertus Heuer, Christian Hengstenberg, Christian Maikowski, Gerald S. Werner, Diethmar Antoni, Franz X. Kleber, Wolfgang Bocksch, Matthias Leschke, Hanns Ackermann, Michael Boxberger, Ulrich Speck, Ralf Degenhardt, Bruno Scheller
Journal: Circulation (2009)

Treatment of in-stent restenosis with paclitaxel-coated balloon catheter as compared with plain balloon angioplasty has shown surprisingly low late lumen loss at 6 months and fewer major adverse cardiac events up to 2 years. We compared the efficacy and safety of a paclitaxel-coated balloon with a paclitaxel-eluting stent as the current standard of care.One hundred thirty-one patients with coronary in-stent restenosis were randomly assigned to treatment by a paclitaxel-coated balloon (3 microg/mm2) or a paclitaxel-eluting stent. The main inclusion criteria encompassed diameter stenosis of > or =70% and < or =22 mm in length, with a vessel diameter of 2.5 to 3.5 mm. The primary end point was angiographic in-segment late lumen loss. Quantitative coronary angiography revealed no differences in baseline parameters. At 6 months follow-up, in-segment late lumen loss was 0.38+/-0.61 mm in the drug-eluting stent group versus 0.17+/-0.42 mm (P=0.03) in the drug-coated balloon group, resulting in a binary restenosis rate of 12 of 59 (20%) versus 4 of 57 (7%; P=0.06). At 12 months, the rate of major adverse cardiac events were 22% and 9%, respectively (P=0.08). This difference was primarily due to the need for target lesion revascularization in 4 patients (6%) in the coated-balloon group, compared with 10 patients (15%) in the stent group (P=0.15).Treatment of coronary in-stent restenosis with the paclitaxel-coated balloon was at least as efficacious and as well tolerated as the paclitaxel-eluting stent. For the treatment of in-stent restenosis, inhibition of re-restenosis does not require a second stent implantation.
Novel Temperature-Sensitive Liposomes with Prolonged Circulation Time
Authors: Lars H. Lindner, Martin E. Eichhorn, Hansjoerg Eibl, Nicole Teichert, Marcus Schmitt-Sody, Rolf D. Issels, Marc Dellian
Journal: Clinical Cancer Research (2004)

Hyperthermia increases the efficiency of various chemotherapeutic drugs and is administered as an adjunct to chemotherapy for the treatment of cancer patients. The temperature-dependent effect can be strongly increased by the use of temperature-sensitive liposomes in combination with regional hyperthermia, which specifically releases the entrapped drug in the heated tumor tissue. The novel lipid 1.2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPGOG), which is closely related to the naturally occurring 1.2-dipalmitoyl-sn-glycero-3-phosphoglycerol, in combination with 1.2-dipalmitoyl-sn-glycero-3-phosphocholine and 1.2-distearoyl-sn-glycero-3-phosphocholine provides long-circulating temperature-sensitive liposomes with favorable properties under mildly hyperthermic conditions (41-42 degrees C). DPPGOG facilitates temperature-triggered drug release from these liposomes (diameter, 175 nm) and leads to a substantially prolonged plasma half-life for the encapsulated drug with t(1/2) = 9.6 h in hamsters and t(1/2) = 5.0 h in rats. Quantitative fluorescence microscopy of amelanotic melanoma grown in the transparent dorsal skin fold chamber of hamsters demonstrated a favorable drug accumulation in heated tissue after i.v. application of these liposomes (42 degrees C for 1 h). The mean area under the curve for tissue drug concentration was increased by more than sixfold by application of the new liposomes compared with nonliposomal drug delivery. In summary, we present a new DPPGOG-based liposomal formulation enabling long circulation time combined with fast and efficient drug release under mild hyperthermia. This adds positively to the results with lipid-grafted polyethylenglycol used thus far in temperature sensitive liposomes and widens the possibilities for clinical applications.
Epithelium related deposition of activated complement in Helicobacter pylori associated gastritis.
Authors: A E Berstad, P Brandtzaeg, R Stave, T S Halstensen
Journal: Gut (1997)

BACKGROUND AND AIMS: It is unknown whether Helicobacter pylori infection activates complement in vivo. Mucosal deposition of various activation products of the complement system may contribute to the pathogenesis of chronic gastritis and was therefore studied by immunohistochemistry. PATIENTS AND METHODS: Ethanol fixed antrum or body gastric tissue sections from 24 patients infected with H pylori (determined by bacterial immunohistochemistry) and 22 uninfected patients were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and in the terminal complex (TCC). As a control group, biopsy samples from the gastric stump of 23 Billroth II operated patients were studied. RESULTS: Patchy, bright staining for TCC occurred below the surface epithelium and around the glands in H pylori positive and negative gastritis as well as in stump gastritis but seldom in normal mucosa. Activated C3 was present at the apical face of the surface epithelium, significantly more often in the antrum and body from patients with than without H pylori infection (p = 0.05 and p = 0.03 respectively), and particularly in samples with granulocyte infiltration (p = 0.04). Many bacteria were coated with activated C3 towards the pit openings but seldom within the foveolae. CONCLUSIONS: Local complement activation was shown to take place in simple chronic gastritis, associated as well as unassociated with H pylori infection, and also in stump gastritis. The fact that activated C3 was seldom seen on H pylori within the foveolae, suggested that the bacterium evades complement attack in this location.
Functional and neurophysiological aspects in patients with chronic obstructive pulmonary disease
Authors: Carolina Rocco, Luciana Malosá, Roberto Stirbulov, João Carlos Corrêa
Journal: European Respiratory Journal (2011)

The neurophysiological alterations found in patients with chronic obstructive pulmonary disease (COPD) in combination with impairment of peripheral muscle, may further compromise functional activity of these patients. The purpose was to assess functional (balance and sit-to-stand test) and neurophysiological aspects (latency time the patellar and achilles reflexes) relating these responses to the BODE Index. A cross-sectional study design was used to assess 22 patients with moderate to very severe COPD (> 60 years) and 16 healthy volunteers as the control group (CG), performed measures of static and dynamic balance (pressure plate and Tinetti scale), monosynaptic reflexes (surface EMG), peripheral muscle strength (load cell) and SST. The individuals with COPD had a reduced reflex response to patellar 36.77±3.23 and Achilles reflex 43.54±6.60. Achieved a lower number repetitions on the SST 19.27±3.88, lesser peripheral muscle strength on the femoral quadriceps muscle, 24.98±6.88 and exhibit deficits in functional balance on the Tinetti scale 26.86±1.69, compared to the CG, all with p <0.05. The BODE Index demonstrated correlations with Tinetti scale, r = 0.59 ( p <0.05) and the SST, r = 0.78 ( p <0.05). The individuals with COPD had functional and neurophysiological alterations in comparison with control group. The Bode Index was correlated with the Tinetti scale and SST. Both are functional tests, easy to administer, low cost and feasible, especially the SST. The results suggest a worse prognosis; however, more studies are needed to identify the causes of these changes and the repercussions that could result in their activities of daily living.
Proprioceptive neuromuscular facilitation training induced alterations in muscle fibre type and cross sectional area
Authors: N Kofotolis, I S Vrabas, E Vamvakoudis, A Papanikolaou, K Mandroukas
Journal: British Journal of Sports Medicine (2005)

To compare the effects of proprioceptive neuromuscular facilitation (PNF) and isokinetic training on fibre type distribution and cross sectional area of the vastus lateralis muscle.Twenty four male university students were divided into two equal groups: PNF training and isokinetic training (ISO). The training regimen for the PNF group consisted of three sets of 30 repetitions against maximal resistance, alternating two patterns of sequential movements of the right lower extremity: (a) toe flexion and ankle plantar flexion and eversion; (b) knee extension and hip extension, abduction, and internal rotation. The ISO group performed three sets of 30 repetitions alternating knee extension and flexion of the right leg at angular velocities of 180 and 90 degrees /s in an isokinetic dynamometer (Cybex). Both groups trained three times a week for a total of eight weeks. Muscle biopsy specimens were obtained from the right vastus lateralis muscle before and after training.The mean percentage area of type IIB fibre was significantly decreased (p<0.01) after eight weeks of PNF training, whereas that of type IIA fibre was significantly (p<0.05) increased. The mean percentage area of ISO trained type IIAB fibres exhibited an augmentative pattern (p<0.01) with a parallel reduction (p<0.05) in type IIA. Percentage fibre type distribution exhibited a similar pattern.Both PNF and ISO training alter fibre type distribution and mean cross sectional area. These changes occur in the type II fibre subgroup.
Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage
Authors: A N Kimmings
Journal: Gut (2000)

Obstructive jaundice is associated with postoperative complications related to increased endotoxaemia and the inflammatory response. In animals obstructive jaundice is associated with endotoxaemia and cytokine induction, which are reversed by internal biliary drainage.To study endotoxaemia and the subsequent inflammatory response in obstructive jaundiced patients and after endoscopic biliary drainage.In 15 patients with malignant distal obstructive jaundice, inflammatory and bacteriological parameters were assessed before endoscopic stent placement and after three weeks endoscopic drainage.Drainage reduced bilirubin from 252.5 to 45.1 micromol/l. At baseline low level endotoxaemia was detected (4.3 pg/ml) which was not affected after drainage (4.5 pg/ml). Serum interleukin 8 (IL-8) and endotoxin binding proteins were increased in jaundice and reduced after drainage (IL-8 113.6 to 20.7 pg/ml; lipopolysaccharide binding protein 24.2 to 16.5 microg/ml; sCD14 17.4 to 7.6 microg/ml; bactericidal/permeability increasing protein 2.9 to 1.8 ng/ml). Levels of other cytokines, augmented in animals, were only slightly increased and not changed after drainage (tumour necrosis factor (TNF): 21.7 and 18.4 pg/ml; sTNFr p55/75: 2.9/7.0 and 2.7/5.6 ng/ml; IL-6: 4.2 and 6.1 pg/ml; IL-10: 4.5 and 2.7 pg/ml). Elastase and lactoferrin tended towards reduction after drainage. All bile cultures were positive after stenting.The effects of obstructive jaundice in humans on endotoxin and cytokines are different from those in animal models. Obstructive jaundice causes alterations in circulating endotoxin binding proteins and IL-8. Concentrations of other mediators (TNF, previously suggested as being responsible for systemic endotoxaemia effects) are low and not affected by drainage.