tbuckley/cabot-search huggingface dataset:
Defects in the precore region of the HBV genome in patients with chronic hepatitis B after sustained seroconversion from HBeAg to anti-HBe induced spontaneously or with interferon therapy
Authors: Kiyoshi Takeda, Yoshihiro Akahane, Hiroshi Suzuki, Hiroaki Okamoto, Fumio Tsuda, Yuzo Miyakawa, Makoto Mayumi
Journal: Hepatology (1990)

Hepatitis B virus DNA clones were propagated from sera of six patients with chronic hepatitis B who seroconverted from HBeAg to antibody to HBeAg either spontaneously or after administration of alpha-interferon. Defects in the precore region blocking synthesis and secretion of HBeAg were detected in all 46 hepatitis B virus DNA clones from three patients who remained positive for antibody to HBeAg and in whom hepatitis resolved. Defective clones had point mutations from guanine to adenine at nucleotide 83 in the precore region, converting codon 28 from tryptophan (TGG) to a stop codon (TAG). In contrast, this defect was not found in any of 39 hepatitis B virus DNA clones from three patients who seroconverted to antibody to HBeAg but then redeveloped HBeAg with reactivation of hepatitis. Using these results, the G-to-A point mutation at nucleotide 83 in the precore region would predict sustained positivity for antibody to HBeAg and remission of hepatitis in patients who have seroconverted either spontaneously or with interferon therapy.
Ventral/dorsal, predicate/argument: The transformation from perception to meaning
Authors: James R. Hurford
Journal: Behavioral and Brain Sciences (2003)

It is necessary to distinguish among representations caused directly by perception, representations of past perceptions in long-term memory, the representations underlying linguistic utterances, and the surface phonological and grammatical structures of sentences. The target article dealt essentially with predicate-argument structure at the first of these levels of representation. Discussion of the commentaries mainly involves distinguishing among various applications of the term “predicate”; clarifying the assumed relationship between classical FOPL and language; clarifying the status of unique individuals as conceived by humans; and addressing the issues of motion-perception, binding between object-percepts and predicate-percepts, and target-driven versus stimulus-driven attention.
TIMING OF ANGIOGRAPHY AND CLINICAL OUTCOMES AFTER FIBRINOLYSIS: A PATIENT-LEVEL ANALYSIS OF RANDOMIZED EARLY INVASIVE CLINICAL TRIALS
Authors: Mina Madan, Mary Tan, Sigrun Halvorsen, Cynthia M. Westernout, Warren Cantor, Michel R. Le May, Francesco Borgia, Federico Piscione, Carlo Di Mario, Bruno Scheller, Paul Armstrong, Francisco Fernandez-Aviles, Pedro L. Sanchez, John Graham, Andrew Yan, Shaun Goodman
Journal: Journal of the American College of Cardiology (2012)
Sulfotransferases and sulfated oligosaccharides
Authors: Koichi Honke, Naoyuki Taniguchi
Journal: Medicinal Research Reviews (2002)

Abstract Structural diversity of the sugar chains attached to proteins and lipids that arises from the variety of combinations of different monosaccharides, different types of linkages, branch formation and secondary modifications, such as sulfation, possesses a large amount of biological information. A number of proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates. Their sulfate groups provide a negative charge and play a role in a specific molecular recognition process. The sulfation of oligosaccharides is catalyzed by the Golgi‐associated sulfotransferases. Recent success in molecular cloning of these sulfotransferases has brought a breakthrough in the understanding of biological function of sulfated oligosaccharides in a variety of contexts. Investigations on the relationship of sulfated oligosaccharides to human diseases including hereditary deficiency, cancer, inflammation, and infection may provide hints for curing disastrous diseases. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 6, 637–654, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/med.10020
Noncanonical Wnt11 Signaling Is Sufficient to Induce Cardiomyogenic Differentiation in Unfractionated Bone Marrow Mononuclear Cells
Authors: Michael P. Flaherty, Ahmed Abdel-Latif, Qianhong Li, Greg Hunt, Smita Ranjan, Qinghu Ou, Xian-Liang Tang, Robin K. Johnson, Roberto Bolli, Buddhadeb Dawn
Journal: Circulation (2008)

Despite the frequent clinical use of adult unfractionated bone marrow mononuclear cells (BMMNCs) for cardiac repair, whether these cells are capable of undergoing cardiomyogenic differentiation in vitro remains uncertain. In addition, the role of Wnt signaling in cardiomyogenic differentiation of adult cells is unclear.Unfractionated BMMNCs were isolated from adult mice via Ficoll-Paque density-gradient centrifugation and cultured in the presence of Wnt3a or Wnt11. In control BMMNCs, Wnt11 was not expressed, whereas the expression of markers of pluripotency (Oct-4 and Nanog), as well as that of Wnt3a and beta-catenin, decreased progressively during culture. Exposure to Wnt3a rescued beta-catenin expression and markedly increased the expression of Oct-4 and Nanog, concomitant with increased cell proliferation and CD45 expression. In contrast, exposure to ectopically expressed noncanonical Wnt11 markedly decreased the expression of Oct-4 and Nanog and induced mRNA expression (quantitative real-time reverse-transcription polymerase chain reaction) of cardiac-specific genes (Nkx2.5, GATA-4, atrial natriuretic peptide, alpha- and beta-myosin heavy chain, and cardiac troponin T) by day 3 with subsequent progression to a pattern characteristic of the cardiac fetal gene program. After 21 days, 27.6+/-0.6% and 29.6+/-1.4% of BMMNCs expressed the cardiac-specific antigens cardiac myosin heavy chain and cardiac troponin T, respectively (immunocytochemistry), indicating cardiomyogenic lineage commitment. Wnt11-induced cardiac-specific expression was completely abolished by the protein kinase C inhibitor bisindolylmaleimide I, partially abolished by the c-Jun-N-terminal kinase inhibitor SP600125, and attenuated by the Wnt inhibitor Dickkopf-1.In adult density-gradient separated BMMNCs, canonical Wnt3a promotes stemness, proliferation, and hematopoietic commitment, whereas noncanonical signaling via Wnt11 induces robust cardiomyogenic differentiation in a protein kinase C- and c-Jun-N-terminal kinase-dependent manner.
Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications
Authors: M.B. Suraokar, M.I. Nunez, L. Diao, C.W. Chow, D. Kim, C. Behrens, H. Lin, S. Lee, G. Raso, C. Moran, D. Rice, R. Mehran, J.J. Lee, H.I. Pass, J. Wang, A.A. Momin, B.P. James, A. Corvalan, K. Coombes, A. Tsao, I.I. Wistuba
Journal: Annals of Oncology (2014)
Laparoscopic Nissen fundoplication--200 consecutive cases.
Authors: D C Gotley, B M Smithers, M Rhodes, B Menzies, F J Branicki, L Nathanson
Journal: Gut (1996)

PATIENTS--Laparoscopic Nissen fundoplication was undertaken in 200 patients between 1991 and 1994. METHODS--Pre-operative assessment included symptom score, endoscopy, manometry, and 24 hour pH monitoring of the oesophagus. Patients were evaluated at three and 12 months after surgery with symptom scoring and 96 patients also underwent 24 hour pH studies at three to six months postoperatively. RESULTS--In the first 100 patients median duration of operation was 155 minutes (range: 70-330), conversion rate to laparotomy was 7%, median hospital stay was three days (range: 2-57), and total morbidity was 16%. This compared with a median operation time of 120 minutes (60-240) (p = 0.0003, 95% CI 10, 40), a conversion rate of 2% (p = 0.2), a hospital stay of three days (1-18) (p = 0.0016, 95% CI 0, 1), and total morbidity of 7% (p = 0.15) in the second 100 patients. Median total symptom scores fell from 5/9 to 0/9 after fundoplication (&lt; 0.0001) while median 24 hour oesophageal acid exposure in 96 patients was reduced from 10% to 1% (p &lt; 0.001). CONCLUSIONS--Laparoscopic Nissen fundoplication is a safe and effective procedure for gastro-oesophageal reflux disease. With experience, the duration of operation falls and the hospital stay is shorter. Shortterm symptomatic and pH results are consistently improved by surgery.
Methylated RASSF1A in malignant peripheral nerve sheath tumors identifies neurofibromatosis type 1 patients with inferior prognosis
Authors: Stine A. Danielsen, Guro E. Lind, Matthias Kolberg, Maren Høland, Bodil Bjerkehagen, Kirsten Sundby Hall, Eva van den Berg, Fredrik Mertens, Sigbjørn Smeland, Piero Picci, Ragnhild A. Lothe
Journal: Neuro-Oncology (2014)

Malignant peripheral nerve sheath tumor (MPNST) is a rare and highly aggressive disease with no evidence of effect from adjuvant therapy. It is further associated with the hereditary syndrome neurofibromatosis type 1 (NF1). Silencing of the tumor suppressor gene RASSF1A through DNA promoter hypermethylation is known to be involved in cancer development, but its impact in MPNSTs remains unsettled.The RASSF1A promoter was analyzed by methylation-specific PCR in 113 specimens, including 44 NF1-associated MPNSTs, 47 sporadic MPNSTs, 21 benign neurofibromas, and 1 nonneoplastic nerve sheath control.RASSF1A methylation was found only in the malignant samples (60%) and identified a subgroup among patients with NF1-associated MPNST with a poor prognosis. These patients had a mean 5-year disease-specific survival of 27.3 months (95% CI: 17.2-37.4) versus 47.4 months (95% CI: 37.5-57.2) for NF1 patients with unmethylated promoters, P = 0.014. In multivariate Cox regression analysis, methylated RASSF1A remained an adverse prognostic factor independent of clinical risk factors, P = .013 (hazard ratio: 5.2; 95% CI: 1.4-19.4).A considerable number of MPNST samples display hypermethylation of the RASSF1A gene promoter, and for these tumors, this is the first molecular marker that if validated can characterize a subgroup of patients with inferior prognosis, restricted to individuals with NF1.
Nitric oxide biosynthesis by primary ciliary dyskinesia respiratory epithelial cells is similar to non-PCD patients
Authors: Woolf Walker, Claire Jackson, Peter Lackie, Jane Lucas
Journal: European Respiratory Journal (2012)

Introduction   The mechanism for the extremely low levels of nasal nitric oxide (NO) seen in patients with primary ciliary dyskinesia (PCD) has not been elucidated. A hypothesis has been that the respiratory epithelial cells in these patients do not biosynthesise normal levels of NO. NO is rapidly metabolised to nitrite, which is considered to be a surrogate marker of NO.   Aims   To compare the total nitrite concentrations of differentiated ciliated respiratory epithelial cells from PCD and non-PCD patients at baseline and following stimulation.   Methods   Airway epithelium from PCD and non-PCD patients was obtained by nasal brushing and cultured at air liquid interface (ALI) until differentiated and ciliated. PBS was incubated for 30 minutes on the apical surface of the ALI cultures and total nitrite detected by kit assay (Enzo Life Sciences). Basolateral incubation with 10 mg/ml IL-1β/IFNγ/TNFα for 18 hours stimulated NO biosynthesis via nitric oxide synthase (NOS) activity.   Results   Total nitrite concentration in differentiated PCD (n=5) and non-PCD (n=7) cultured epithelium was similar both at baseline, 16.1±1.1 mmol/l and 17.8±3.2 mmol/l respectively (mean±SD, p=0.14) and after stimulation; PCD (n=4) 32.0±12.7 mmol/l and non-PCD (n=4) 33.2±11.0 mmol/l respectively (p=0.46).   Conclusion   NO biosynthesis in differentiated ciliated airway epithelium from PCD patients is similar to non-PCD patients at baseline and following NOS stimulation. As nasal NO is increasingly used for screening of PCD, further work assessing the upper airway9s role in the low levels of nasal NO seen is warranted. Data collection continues.
Emotion Modulation in PTSD: Clinical and Neurobiological Evidence for a Dissociative Subtype
Authors: Ruth A. Lanius, Eric Vermetten, Richard J. Loewenstein, Bethany Brand, Christian Schmahl, J. Douglas Bremner, David Spiegel
Journal: American Journal of Psychiatry (2010)

In this article, the authors present evidence regarding a dissociative subtype of PTSD, with clinical and neurobiological features that can be distinguished from nondissociative PTSD. The dissociative subtype is characterized by overmodulation of affect, while the more common undermodulated type involves the predominance of reexperiencing and hyperarousal symptoms. This article focuses on the neural manifestations of the dissociative subtype in PTSD and compares it to those underlying the reexperiencing/hyperaroused subtype. A model that includes these two types of emotion dysregulation in PTSD is described. In this model, reexperiencing/hyperarousal reactivity is viewed as a form of emotion dysregulation that involves emotional undermodulation, mediated by failure of prefrontal inhibition of limbic regions. In contrast, the dissociative subtype of PTSD is described as a form of emotion dysregulation that involves emotional overmodulation mediated by midline prefrontal inhibition of the same limbic regions. Both types of modulation are involved in a dynamic interplay and lead to alternating symptom profiles in PTSD. These findings have important implications for treatment of PTSD, including the need to assess patients with PTSD for dissociative symptoms and to incorporate the treatment of dissociative symptoms into stage-oriented trauma treatment.
On-target JAK2/STAT3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells
Authors: Owen D. Stechishin, H. Artee Luchman, Yibing Ruan, Michael D. Blough, Stephanie A. Nguyen, John J. Kelly, J. Gregory Cairncross, Samuel Weiss
Journal: Neuro-Oncology (2012)

Glioblastoma multiforme (GBM) is characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity. GBM-derived brain tumor stem cells (BTSCs) closely model this molecular heterogeneity and likely have a key role in tumor recurrence and therapeutic resistance. Emerging evidence indicates that Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 is an important mediator of tumor cell survival, growth, and invasion in a large group of GBM. Here, we used a large set of molecularly heterogeneous BTSCs to evaluate the translational potential of JAK2/STAT3 therapeutics. BTSCs were cultured from GBM patients and MGMT promoter methylation, and the mutation statuses of EGFR, PTEN, and TP53 were determined. Endogenous JAK2/STAT3 activity was assessed in human GBM tissue, BTSCs, and orthotopic xenografts by immunohistochemistry and Western blotting. STAT3 short hairpin (sh)RNA, cucurbitacin-I, and WP1066 were used to inhibit JAK2/STAT3 activity in vitro and in vivo. The JAK2/STAT3 pathway was demonstrated to be highly activated in human GBM, molecularly heterogeneous BTSCs derived from these tumors, and BTSC xenografts. STAT3 shRNA knockdown or cucurbitacin-I and WP1066 administration resulted in on-target JAK2/STAT3 inhibition and dramatically reduced BTSC survival regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. BTSC orthotopic xenografts maintained the high levels of activated JAK2/STAT3 seen in their parent human tumors. Intraperitoneal WP1066 reduced intratumoral JAK2/STAT3 activity and prolonged animal survival. Our study demonstrates the in vitro and in vivo efficacy of on-target JAK2/STAT3 inhibition in heterogeneous BTSC lines that closely emulate the genomic and tumorigenic characteristics of human GBM.
Pityriasis rubra pilaris: epidermal cell kinetics
Authors: I.G. RALFS, R.P.R. DAWBER, T.J. RYAN, N.A. WRIGHT
Journal: British Journal of Dermatology (1981)

Journal Article Pityriasis rubra pilaris: epidermal cell kinetics Get access I.G. RALFS, I.G. RALFS Department of Dermatology, University of Oxford, Slade Hospital, Oxford W12 oHS Search for other works by this author on: Oxford Academic Google Scholar R.P.R. DAWBER, R.P.R. DAWBER Department of Dermatology, University of Oxford, Slade Hospital, Oxford W12 oHS Search for other works by this author on: Oxford Academic Google Scholar T.J. RYAN, T.J. RYAN Department of Dermatology, University of Oxford, Slade Hospital, Oxford W12 oHS Search for other works by this author on: Oxford Academic Google Scholar N.A. WRIGHT N.A. WRIGHT Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 oHS Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 3, 1 March 1981, Pages 249–252, https://doi.org/10.1111/j.1365-2133.1981.tb00945.x Published: 01 March 1981 Article history Accepted: 29 May 1980 Published: 01 March 1981
The Congenital Short Oesophagus
Authors: P. M. Peters
Journal: Thorax (1958)

There are two closely related developmental abnormalities which are rare predisposing causes of the common digestion oesophagitis.These are (a) congenital shortness of the squamous oesophagus, and (b) congenital enlargement of the oesophageal hiatus of the diaphragm.This paper presents an account of the pathology of 25 cases.
Five-year effects of nasal continuous positive airway pressure in obstructive sleep apnoea syndrome
Authors: A Chaouat, E Weitzenblum, R Kessler, M Oswald, E Sforza, MN Liegeon, J Krieger
Journal: European Respiratory Journal (1997)

There have been very few studies assessing the long-term physiological effects of nasal continuous positive airway pressure (CPAP) for the obstructive sleep apnoea syndrome. We therefore investigated prospectively the evolution of lung function, arterial blood gases and pulmonary haemodynamics in patients with this syndrome treated with CPAP. Sixty five patients were included. The mean duration of home treatment with nasal CPAP was 64+/-6 months. Most of the patients (77%) were smokers at the baseline assessment. We observed a small, but significant, decrease in forced expiratory volume in one second (FEV1) from 80+/-21% at baseline (t0) to 76+/-21% of the predicted value at the follow-up evaluation (t5) (p<0.01). Arterial oxygen tension (P[a,O2]) for the group as a whole remained stable (9.4+/-1.5 kPa (71+/-11 mmHg) versus 9.4+/-1.2 kPa (71+/-9 mmHg)). However, P(a,O2) increased in the subgroup of patients with hypoxaemia at t0 (n=23), from 7.8+/-0.7 kPa (59+/-5 mmHg) to 8.9+/-1.2 kPa (67+/-9 mmHg). Arterial carbon dioxide tension (P[a,CO2]) for the group as a whole increased slightly, but significantly, from 5.2+/-0.7 kPa (39+/-5 mmHg) to 5.4+/-0.5 kPa (41+/-4 mmHg) (p<0.05). Mean pulmonary artery pressure (Ppa) at rest did not change (16+/-5 mmHg versus 17+/-5 mmHg; NS) nor did exercising Ppa. In the 11 patients with pulmonary hypertension at t0, Ppa was 24+/-5 mmHg at t0 versus 20+/-7 mmHg at t5 (NS). We conclude that the significant decrease of forced expiratory volume in one second after 5 yr follow-up was related to a high percentage of smokers and exsmokers in the study population. Daytime arterial oxygen tension and pulmonary artery pressure remained stable in an unselected series of 65 obstructive sleep apnoea syndrome patients treated for 5 yrs with nasal continuous positive airway pressure, unlike arterial carbon dioxide tension, which increased by a small, but significant, amount.
Sorbitol malabsorption in normal volunteers and in patients with coeliac disease.
Authors: G R Corazza, A Strocchi, R Rossi, D Sirola, G Gasbarrini
Journal: Gut (1988)

Sorbitol is a hexahydroxy alcohol used as a sugar substitute in many dietetic foods and as a drug vehicle. Previous studies have suggested that sorbitol ingestion may be an additional cause of non-specific gastrointestinal distress. We evaluated sorbitol malabsorption in 30 healthy volunteers, seven patients with untreated coeliac disease and nine patients with coeliac disease on a gluten free diet, using a four hour H2 breath test. After ingestion of test solutions containing sorbitol 10 and 20 g and of four sweets (6.8 g sorbitol), 90%, 100%, and 62% of healthy volunteers, respectively had significantly raised H2 excretion, indicating malabsorption of sorbitol. Of all healthy subjects tested, 45% after 10 g, 100% after 20 g, and 50% after four sweets complained of symptoms of carbohydrate intolerance during the eight hours after sorbitol. After a 5 g dose given at concentrations of 2%, 4%, 8%, 16%, malabsorption was shown in 10%, 12%, 22%, and 43% of the healthy volunteers. Symptoms of intolerance at 5 g were experienced only at concentrations of 8% and 16%. Unlike healthy volunteers and coeliac patients on a gluten free diet, 100% of untreated coeliacs malabsorbed a 2% solution of 5 g sorbitol. These results show that malabsorption and intolerance of sorbitol may result from ingestion of doses and/or concentrations usually found in many foods and drugs; they underline the need to consider this as a possible and hitherto underestimated cause of gastrointestinal symptoms.
Whole Grain, Bran, and Germ Intake and Risk of Type 2 Diabetes: A Prospective Cohort Study and Systematic Review
Authors: Jeroen S. L de Munter, Frank B Hu, Donna Spiegelman, Mary Franz, Rob M van Dam
Journal: PLoS Medicine (2007)

Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes, but the role of specific dietary factors in the etiology of type 2 diabetes is less well established. We evaluated intakes of whole grain, bran, and germ in relation to risk of type 2 diabetes in prospective cohort studies.
Decreased noradrenaline (norepinephrine) synthesis in familial dysautonomia
Authors: McC. Goodall, S. E. Gitlow, H. Alton
Journal: Journal of Clinical Investigation (1971)

Noradrenaline synthesis and metabolism of dopamine was evaluated in three patients with familial dysautonomia and compared with that of six normal subjects. Each patient and subject was infused with 104.8 muCi of dopamine-2-(14)C dissolved in 1000 ml of physiological saline. The urine was collected during the infusion period and at intervals thereafter. Using a specially designed flow monitor system, the various biosynthetic and metabolic products of dopamine were separated, identified, and their radioactivity measured. The results indicate that in familial dysautonomia the synthesis of noradrenaline is significantly decreased; this is reflected by a decrease in recovery of radioactive noradrenaline as well as various metabolic products of noradrenaline, i.e. 3-methoxy-4-hydroxymandelic acid (MOMA), normetadrenaline, and normetadrenaline conjugate. Concomitant with this decrease in noradrenaline synthesis, there was a shift towards dopamine metabolism as reflected by an increase in the recovery of primary and secondary dopamine metabolites; 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylacetic acid (HVA), 3-methoxytyrosine, and respective conjugates, etc. Whereas all dysautonomic patients showed the same general metabolic pattern as was expected, they varied in degree.