tbuckley/cabot-search huggingface dataset:
Plasma aldosterone and cortisol levels in psoriasis and atopic dermatitis
Authors: P.C.M. KERKHOF
Journal: British Journal of Dermatology (1982)

The levels of plasma aldosterone were significantly raised in groups of patients with psoriasis and atopic dermatitis compared with a control group of patients with other skin diseases. Simultaneous assay of plasma cortisol indicated that these changes were not the effects of prior corticosteroid therapy. The reasons for the increased aldosterone levels are not clear, but our findings are compatible with a "permissive" role for this hormone in psoriasis and atopic dermatitis.
hTERT Overexpression Alleviates Intracellular ROS Production, Improves Mitochondrial Function, and Inhibits ROS-Mediated Apoptosis in Cancer Cells
Authors: Inthrani R. Indran, Manoor P. Hande, Shazib Pervaiz
Journal: Cancer Research (2010)

The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase holoenzyme. Evidence is accumulating to link hTERT to activities other than telomere maintenance and immortalization. Here, we show that hTERT overexpression not only reduces the basal cellular reactive oxygen species (ROS) levels but also inhibits endogenous ROS production in response to stimuli that induce intracellular ROS generation. Conversely, siRNA-mediated gene silencing of hTERT potentiated the increase in cellular ROS levels following exposure to oxidative stress. This antioxidant effect of hTERT is mediated via a significant increase in the ratio of reduced to oxidized glutathione (GSH:GSSG) as well as efficient recovery of the oxidized peroxiredoxin to its nonoxidized form. Our data also provide evidence for mitochondrial localization of hTERT, and a significantly higher activity of cytochrome C oxidase, the rate-limiting enzyme in the mitochondrial electron transport chain, in hTERT overexpressing cells. To ascertain whether the improved mitochondrial function and antioxidant effect of hTERT could provide cancer cells with a survival advantage, the effect of oxidative stress on mitochondrial apoptosis was evaluated. Indeed, hTERT overexpressing cells inhibited cytosolic acidification, translocation of Bax, the drop in mitochondrial transmembrane potential, the release of cytochrome C to the cytosol, and cell death. Taken together, these data demonstrate a hitherto undefined role of hTERT in alleviating cellular ROS levels by way of potentiating the cellular antioxidant defense systems, and in doing so endowing cancer cells with the ability to evade death stimuli.
Antibiotic resistance in Serratia marcescens.
Authors: J D Sleigh
Journal: BMJ (1983)

that high molecular weight neutrophil chemotactic activity is derived from mast cells, and increases in plasma histamine with exercise may originate from circulating basophils.6 12Furthermore, sodium cromoglycate has several pharmacological effects other than mast cell stabilisation which may be relevant to its protective effect in exercise induced asthma.13Several factors should be taken into account when assessing and treating patients, and especially children, with exercise induced bronchoconstriction.'4 Asthmatics are often in poor physical condition and even small amounts of exercise may produce disproportionate hyperventilation and therefore bronchoconstriction.Nevertheless, they need regular physical activities to maintain their fitness and help them through difficult periods.Children with asthma are commonly ex- empted from physical exercise at school and they may avoid sports or exercise in their leisure time.'5These attitudes need to be reversed, and local activity groups are being or have been set up to encourage physical training and group activities.At least 70 such groups are operating in Britain and have proved a great success.As well as encouraging asthmatic children to be more competitive and sociable they promote the prophylactic use of drugs and the gradual build up of muscle strength.The groups' physical activities include a warming up period followed by games and organised physical training programmes.Several studies have shown definite psychological and social benefit from such programmes.'5The gains include an increase in aerobic fitness; an improvement in breathing mechanics, posture, body mass, cardiac output, muscle strength, and endurance; and also reductions in the frequency and severity of asthma attacks, absenteeism from school, and requirements for medication.Most training pro- grammes are designed to require submaximal exercise, falling short of inducing exercise induced bronchoconstriction.'6One recent study, however, has shown that a distance running programme can be safely undertaken by asthmatic children- but with benefit only in relation to physical fitness and not in resting pulmonary function, exercise induced broncho- constriction, or ventilatory muscle strength.'7Plainly the image of bronchial asthma is now changing-a fact reflected in the large number of asthmatic people who have achieved outstanding successes in a variety of international sports.How gratifying it is that these sporting celebrities have been so ready to allow their condition to be widely publicised for the benefit of others.
Dual-Agent Molecular Targeting of the Epidermal Growth Factor Receptor (EGFR)
Authors: Shyhmin Huang, Eric A. Armstrong, Sergio Benavente, Prakash Chinnaiyan, Paul M. Harari
Journal: Cancer Research (2004)

Abstract Molecular inhibition of epidermal growth factor receptor (EGFR/HER1) signaling is under active investigation as a promising cancer treatment strategy. We examined the potency of EGFR inhibition achieved by combining anti-EGFR monoclonal antibody and tyrosine kinase inhibitor, which target extracellular and intracellular domains of the receptor, respectively. We specifically studied the combination of cetuximab (Erbitux, C225; ImClone Systems, New York, NY) with either gefitinib (Iressa, ZD1839; AstraZeneca, Macclesfield, UK) or erlotinib (Tarceva, OSI-774; Genentech, South San Francisco, CA) across a variety of human cancer cells. The combination of cetuximab plus gefitinib or erlotinib enhanced growth inhibition over that observed with either agent alone. As measured by immunostaining, inhibition of EGFR phosphorylation with the combination of cetuximab plus gefitinib or erlotinib was augmented over that obtained with single-agent therapy in head and neck (H&amp;N) cancer cell lines. Phosphorylation inhibition of downstream effector molecules [mitogen-activated protein kinase (MAPK) and AKT] also was enhanced in tumor cells treated with the combination of cetuximab plus gefitinib or erlotinib. Flow cytometry and immunoblot analysis demonstrated that treatment of H&amp;N tumor cells with cetuximab in combination with either gefitinib or erlotinib amplified the induction of apoptosis. Following establishment of cetuximab-resistant cell lines, we observed that gefitinib or erlotinib retained the capacity to inhibit growth of lung and H&amp;N tumor cells that were highly resistant to cetuximab. Treatment with gefitinib or erlotinib, but not cetuximab, also could further inhibit the activation of downstream effectors of EGFR signaling in cetuximab-resistant cells, including MAPK and AKT. These data suggest that tyrosine kinase inhibitors may further modulate intracellular signaling that is not fully blocked by extracellular anti-EGFR antibody treatment. Finally, animal studies confirmed that single EGFR inhibitor treatment resulted in partial and transient tumor regression in human lung cancer xenografts. In contrast, more profound tumor regression and regrowth delay were observed in mice treated with the combination of cetuximab and gefitinib or erlotinib. Immunohistochemical staining, which demonstrated significant reduction of the proliferative marker proliferating cell nuclear antigen in mice treated with dual EGFR inhibitors, further supported this in vivo observation. Together, these data suggest that combined treatment with distinct EGFR inhibitory agents can augment the potency of EGFR signaling inhibition. This approach suggests potential new strategies to maximize effective target inhibition, which may improve the therapeutic ratio for anti-EGFR-targeted therapies in developing clinical trials.
Perinatal Outcome of Fetal Atrioventricular Block
Authors: Lilian M. Lopes, Gláucia Maria Penha Tavares, Ana Paula Damiano, Marco Antônio Borges Lopes, Vera Demarchi Aiello, Regina Schultz, Marcelo Zugaib
Journal: Circulation (2008)

Background— Fetal atrioventricular (AV) block is an uncommon lesion with significant mortality. Because of the rarity of this disorder, the natural course, extensive evaluation of untreated fetuses, and late follow-up remain unclear. Methods and Results— Of the 116 consecutive cases of fetal AV block studied from 1988 to 2006, only 1 was terminated, and 75% were live births. Fifty-nine cases of AV block were associated with major structural heart disease, mainly left atrial isomerism (n=40), with only 26% of neonatal survivors. Of the 57 fetuses with normal cardiac anatomy, 41 (72%) were positive for maternal antinuclear antibodies, and 32 of these seropositive mothers did not receive any treatment. This untreated group had live-birth and 1-year infant survival rates of 93% and 90%, respectively. Five fetuses from seronegative mothers showed regression to sinus rhythm during pregnancy. The presence of major structural heart disease, hydrops, an atrial rate ≤120 bpm, and a ventricular rate ≤55 bpm were identified as risk factors for mortality. Logistic regression analysis of the whole group showed that the presence of structural heart disease was the only independent predictor of death ( P &lt;0.001). Conclusions— This long-term study confirms that fetal AV block has a poor outcome when associated with structural heart disease and that spontaneous regression of AV block is possible in seronegative forms. The survival rate of &gt;90% of our untreated patients with isolated forms of AV block raises concerns about any decision to intervene with immunosuppressive agents.
Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda
Authors: Philippe J Guerin, Piero Olliaro, Shyam Sundar, Marleen Boelaert, Simon L Croft, Philippe Desjeux, Monique K Wasunna, Anthony DM Bryceson
Journal: The Lancet Infectious Diseases (2002)
Detection of Ki-ras gene point mutations in bile specimens for the differential diagnosis of malignant and benign biliary strictures
Authors: J-C Saurin
Journal: Gut (2000)

The present study was undertaken to determine if detection of Ki-ras gene point mutations in bile specimens could differentiate between benign and malignant biliary strictures.Bile specimens were obtained from 117 patients exhibiting a stricture of the main bile duct, the nature of which was assessed by cholangiography, histology, and follow up.DNA from frozen bile specimens was extracted, amplified, and tested for codon 12 point mutations of Ki-ras gene using sequence specific oligonucleotide hybridisation and mutant allele specific amplification.DNA amplification was successful in 110/117 bile specimens (94%). Detection of Ki-ras gene mutations in bile specimens was positive in 24.4% (22/90) of patients with malignant strictures, in 31.4% (22/70) when only primary malignant tumours were considered, and in 4% (1/25) of patients with benign strictures. Of the 49 patients with histological specimens obtained before surgery, the sensitivity of histology, Ki-ras mutation analysis, and combined methods was 59.2%, 28.6%, and 73.5% respectively.Our study showed that Ki-ras mutations may be detected in about one third of bile specimens from patients with primary tumours invading the main bile duct. Detection of such mutations appears to be specific and may help to differentiate between benign and malignant biliary strictures.
Patellofemoral pain: consensus statement from the 3rd International Patellofemoral Pain Research Retreat held in Vancouver, September 2013
Authors: Erik Witvrouw, Michael J Callaghan, Joshua J Stefanik, Brian Noehren, David M Bazett-Jones, John D Willson, Jennifer E Earl-Boehm, Irene S Davis, Christopher M Powers, Jenny McConnell, Kay M Crossley
Journal: British Journal of Sports Medicine (2014)

Patellofemoral pain (PFP) is often seen in physically active individuals and may account for 25–40% of all knee problems seen in a sports injury clinic.1 ,2 Patellofemoral-related problems occur more frequently in women than in men.3 PFP is characterised by diffuse pain over the anterior aspect of the knee and aggravated by activities that increase patellofemoral joint (PFJ) compressive forces, such as squatting, ascending and descending stairs and prolonged sitting, as well as repetitive activities such as running. It, therefore, has a debilitating effect on sufferers’ daily lives by reducing their ability to perform sporting and work-related activities pain free. Dye has described PFP as an orthopaedic enigma, and it is one of the most challenging pathologies to manage.4 Alarmingly, a high number of individuals with PFP have recurrent or chronic pain.5 While physiotherapy interventions for PFP have proven effective compared with sham treatments, treatment results can be disappointing in a proportion of patients. This variability in treatment results may be due to the fact that the underlying factors that contribute to the development of PFP are not being addressed, or are not the same for all patients with PFP. The mission of the 3rd International Patellofemoral Research Retreat was to improve our understanding concerning the factors that contribute to the development and consequently to the treatment of PFP.

The 3rd International Patellofemoral Research Retreat was held in Vancouver, Canada, in September 2013, for 3 days: from 18 September to 21 September. After peer-review for scientific merit and relevance to the retreat, 58 abstracts were accepted for the retreat (39 podiums, 8 posters and 11 thematic posters). The podium and poster presentations were grouped into three categories: (1) natural history of PFP and local factors that influence PFP, (2) trunk and distal factors that influence PFP and …
Gab1, SHP2, and Protein Kinase A Are Crucial for the Activation of the Endothelial NO Synthase by Fluid Shear Stress
Authors: Madhulika Dixit, Annemarieke E. Loot, Annisuddin Mohamed, Beate Fisslthaler, Chantal M. Boulanger, Bogdan Ceacareanu, Aviv Hassid, Rudi Busse, Ingrid Fleming
Journal: Circulation Research (2005)

Fluid shear stress enhances NO production in endothelial cells by a mechanism involving the activation of the phosphatidylinositol 3-kinase and the phosphorylation of the endothelial NO synthase (eNOS). We investigated the role of the scaffolding protein Gab1 and the tyrosine phosphatase SHP2 in this signal transduction cascade in cultured and native endothelial cells. Fluid shear stress elicited the phosphorylation and activation of Akt and eNOS as well as the tyrosine phosphorylation of Gab1 and its association with the p85 subunit of phosphatidylinositol 3-kinase and SHP2. Overexpression of a Gab1 mutant lacking the pleckstrin homology domain abrogated the shear stress–induced phosphorylation of Akt but failed to affect the phosphorylation or activity of eNOS. The latter response, however, was sensitive to a protein kinase A (PKA) inhibitor. Mutation of Gab1 Tyr627 to phenylalanine (YF-Gab1) to prevent the binding of SHP2 completely prevented the shear stress–induced phosphorylation of eNOS, leaving the Akt response intact. A dominant-negative SHP2 mutant prevented the activation of PKA and phosphorylation of eNOS without affecting that of Akt. Moreover, shear stress elicited the formation of a signalosome complex including eNOS, Gab1, SHP2 and the catalytic subunit of PKA. In isolated murine carotid arteries, flow-induced vasodilatation was prevented by a PKA inhibitor as well as by overexpression of either the YF-Gab1 or the dominant-negative SHP2 mutant. Thus, the shear stress–induced activation of eNOS depends on Gab1 and SHP2, which, in turn, regulate the phosphorylation and activity of eNOS by a PKA-dependent but Akt-independent mechanism.
Phase II Trial of Stereotactic Body Radiation Therapy Combined With Erlotinib for Patients With Limited but Progressive Metastatic Non–Small-Cell Lung Cancer
Authors: Puneeth Iyengar, Brian D. Kavanagh, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, Paul A. Bunn, Hak Choy, Robert Timmerman
Journal: Journal of Clinical Oncology (2014)

Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse.Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated.Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated. Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field. Two grade 3 toxicities were radiation related. Zero of 13 patients tested were positive for an EGFR mutation.Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high PFS and OS, substantially greater than historical values for patients who only received systemic agents.
A preliminary study of the effects of Tai Chi and Qigong medical exercise on indicators of metabolic syndrome, glycaemic control, health-related quality of life, and psychological health in adults with elevated blood glucose
Authors: X Liu, Y D Miller, N W Burton, W J Brown
Journal: British Journal of Sports Medicine (2008)

To evaluate the feasibility, acceptability and effects of a Tai Chi and Qigong exercise programme in adults with elevated blood glucose.A single group pre-post feasibility trial with 11 participants (3 male and 8 female; aged 42-65 years) with elevated blood glucose.Participants attended Tai Chi and Qigong exercise training for 1 to 1.5 h, 3 times per week for 12 weeks, and were encouraged to practise the exercises at home.Indicators of metabolic syndrome (body mass index (BMI), waist circumference, blood pressure, fasting blood glucose, triglycerides, HDL-cholesterol); glucose control (HbA1c, fasting insulin and insulin resistance (HOMA)); health-related quality of life; stress and depressive symptoms.There was good adherence and high acceptability. There were significant improvements in four of the seven indicators of metabolic syndrome including BMI (mean difference -1.05, p<0.001), waist circumference (-2.80 cm, p<0.05), and systolic (-11.64 mm Hg, p<0.01) and diastolic blood pressure (-9.73 mm Hg, p<0.001), as well as in HbA1c (-0.32%, p<0.01), insulin resistance (-0.53, p<0.05), stress (-2.27, p<0.05), depressive symptoms (-3.60, p<0.05), and the SF-36 mental health summary score (5.13, p<0.05) and subscales for general health (19.00, p<0.01), mental health (10.55, p<0.01) and vitality (23.18, p<0.05).The programme was feasible and acceptable and participants showed improvements in metabolic and psychological variables. A larger controlled trial is now needed to confirm these promising preliminary results.
Psychiatric morbidity and the menopause: clinical features.
Authors: C B Ballinger
Journal: BMJ (1976)

A sample of 114 women from the general population aged 40-55 years were identified as possible psychiatric cases and subjected to a standardised psychiatric interview. Mean ratings for reported symptoms and observed abnormalities were assessed in relation to menopausal status. There was no evidence of any specific combination of symptoms and signs associated with the cessation of menstrual periods, though after the menopause insomnia and hypochondriacal preoccupations were more common. In comparison with matched normal controls have been previous psychiatric illness, and contact with general practitioners was more frequent. Many women developing psychiatric symptoms at the time of the menopause appear to belong to a vulnerable population who are likely to develop symptoms in relation to stress.
Autocrine stimulation by erythropoietin and autonomous growth of human erythroid leukemic cells in vitro.
Authors: M T Mitjavila, J P Le Couedic, N Casadevall, S Navarro, J L Villeval, A Dubart, W Vainchenker
Journal: Journal of Clinical Investigation (1991)

Autonomous colony formation is a frequent event in erythroleukemia. In 13 cases of early erythroid leukemias, we investigated whether erythropoietin (Epo) autocrine stimulation was responsible for the growth factor autonomy. Epo transcripts were detected by Northern blotting in cells from one patient. These cells also expressed an Epo receptor (1,000 receptors per cell) with a 420-pM affinity and Epo was detected in the supernatant of cultured cells. In 8 of the 13 cases, Epo transcripts were revealed by the polymerase chain reaction ranging from 0.5 to 500 copies per cell. In situ hybridization proved that these Epo transcripts were present in the blast cells. No Epo gene abnormalities were detected by Southern blotting. In two cases, leukemic cells were grown in the presence of Epo-neutralizing antibodies or Epo antisense oligomers. In one case, the antibody significantly reduced autonomous growth. In contrast, the antibody had no effect in the second case in which blast cells transcribed the Epo gene at a low level. However, Epo antisense oligomers partially inhibited autonomous growth. This inhibition was reversed by addition of exogenous Epo. Overall, these results suggest that an extracellular or intracellular autocrine Epo stimulation occurs in some cases of erythroid malignancies.
IgE binding to pepsin‐digested water soluble and insoluble wheat proteins
Authors: M. Mesa‐del‐Castillo, C. Martínez‐Cócera, M. L. Caballero, L. Vazquez, I. Moneo
Journal: Allergy (2004)

Background: Positive skin prick tests to wheat are a common finding among atopic patients, but only a minor fraction of these patients show immediate clinical symptoms after wheat ingestion. The aim of this study was to evaluate the allergenicity of wheat proteins after pepsin treatments. Methods: Six patients with positive specific IgE and/or skin prick test to soluble wheat proteins and to gluten were studied. Five of them had no symptoms after wheat ingestion and showed a negative oral challenge test. All sera were analysed with extracts obtained after pepsin hydrolysis during different time periods of water‐soluble and insoluble wheat proteins by IgE immunoblotting. Results: A pepsin‐sensitive allergen of around 35 kDa was recognized by the five atopic negative wheat oral challenge patients in the undigested water‐insoluble extract. A patient showing immediate urticaria after wheat ingestion detected a pepsin‐resistant allergen with similar molecular weight. Finally, an inhalation‐induced asthma patient recognized water‐soluble proteins (of around 14 kDa) that could correspond to the α ‐amylase inhibitors. Conclusions: Our immunoblotting method shows better correlation with the clinical symptoms than skin prick test and CAP results. Pepsin resistance of the acetic acid‐soluble wheat proteins may be responsible for the immediate symptoms of the patient who presented immediate urticaria.