tbuckley/cabot-search huggingface dataset:
GROUP-SPECIFIC CARBOHYDRATE OF GROUP C-VARIANT HEMOLYTIC STREPTOCOCCI
Authors: Paulo Araujo, Richard M. Krause
Journal: The Journal of Experimental Medicine (1963)

The trypsinized cell walls of Group C hemolytic streptococci are composed of the specific carbohydrate antigen and a mucopeptide matrix. Certain phage resistant strains of Group C streptococci, isolated from organisms which survive exposure to Group C bacteriophage also possess carbohydrate and mucopeptide fractions, but the carbohydrate gives a precipitin reaction with Group A-variant antiserum and not with Group C antiserum. These strains have been termed Group C-variant. The C-variant carbohydrate contains 86 per cent rhamnose and only 2 per cent galactosamine, and is thus chemically and immunologically similar to Group A-variant carbohydrate. The evidence suggests that the antigenic determinants of Groups A-variant and C-variant carbohydrates are rhamnose-rhamnose linkages. These results strongly support the hypothesis that the carbohydrates of Groups A and C streptococci are composed of a similar rhamnose moiety but that the determinant amino sugar terminal to the rhamnose-rhamnose linkages in the case of Group A is N-acetylglucosamine whereas that of Group C is N-acetylgalactosamine.
Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors
Authors: Juliann Chmielecki, Aimee M Crago, Mara Rosenberg, Rachael O'Connor, Sarah R Walker, Lauren Ambrogio, Daniel Auclair, Aaron McKenna, Michael C Heinrich, David A Frank, Matthew Meyerson
Journal: Nature Genetics (2013)
Obesity and reproductive disorders in women
Authors: Renato Pasquali, Carla Pelusi, Silvia Genghini, Mauro Cacciari, Alessandra Gambineri
Journal: Human Reproduction Update (2003)

Obesity, particularly the abdominal phenotype, is associated with several reproductive disturbances. Whereas mechanisms by which obesity affect fertility are complex and still not completely understood, an important role appears to be played by the presence of a condition of functional hyperandrogenism and hyperinsulinaemia, which accompanies the insulin‐resistant state. In women with the polycystic ovary syndrome, abdominal obesity may be co‐responsible for the development of hyperandrogenism and associated chronic anovulation, through mechanisms primarily involving the insulin‐mediated overstimulation of ovarian steroidogenesis and decreased sex hormone‐binding globulin blood concentrations. By these mechanisms, obesity may also favour resistance to clomiphene and gonadotrophin‐induced ovulation and reduce outcomes of IVF/ICSI procedures. Due to the beneficial effects of weight loss, lifestyle intervention programmes should represent the first‐line approach in the treatment of infertile obese women. Insulin‐sensitizing agents may add further benefits, particularly if administered in combination with hypocaloric dieting. Therefore, individualized pharmacological support aimed at favouring weight loss and improving insulin resistance should be widely extended in clinical practice in obese infertile patients. This may be beneficial even during pregnancy, thereby permitting favourable physiological delivery and healthy babies.
C-Terminal Truncation of Cardiac Troponin I Causes Divergent Effects on ATPase and Force
Authors: D. Brian Foster, Teruo Noguchi, Peter VanBuren, Anne M. Murphy, Jennifer E. Van Eyk
Journal: Circulation Research (2003)

Myocardial stunning is a form of reversible myocardial ischemia/reperfusion injury associated with systolic and diastolic contractile dysfunction. In the isolated rat heart model, myocardial stunning is characterized by specific C-terminal proteolysis of the myofilament protein, troponin I (cTnI) that yields cTnI 1-193 . To determine the effect of this particular C-terminal truncation of cTnI, without the confounding factor of other stunning-induced protein modifications, a series of solution biochemical assays has been undertaken using the human homologue of mouse/rat cTnI 1-193 , cTnI 1-192 . Affinity chromatography and actin sedimentation experiments detected little, or no, difference between the binding of cTnI (cTnI 1-209 ) and cTnI 1-192 to actin-tropomyosin, troponin T, or troponin C. Both cTnI and cTnI 1-192 inhibit the actin-tropomyosin–activated ATPase activity of myosin subfragment 1 (S1), and this inhibition is released by troponin C in the presence of Ca 2+ . However, cTnI 1-192 , when reconstituted as part of the troponin complex (cTn 1-192 ), caused a 54±11% increase in the maximum Ca 2+ -activated actin-tropomyosin-S1 ATPase activity, compared with troponin reconstituted with cTnI (cTn). Furthermore, cTn 1-192 increased Ca 2+ sensitivity of both the actin-tropomyosin-activated S1 ATPase activity and the Ca 2+ -dependent sliding velocity of reconstituted thin filaments, in an in vitro motility assay, compared with cTn. In an in vitro force assay, the actin-tropomyosin filaments bearing cTn 1-192 developed only 76±4% ( P &lt;0.001) of the force obtained with filaments composed of reconstituted cTn. We suggest that cTnI proteolysis may contribute to the pathophysiology of myocardial stunning by altering the Ca 2+ -sensing and chemomechanical properties of the myofilaments.
Cancer Pharmacoethnicity: Ethnic Differences in Susceptibility to the Effects of Chemotherapy
Authors: Peter H. O'Donnell, M. Eileen Dolan
Journal: Clinical Cancer Research (2009)

A long-term goal of pharmacogenomics research is the design of individualized therapy based on the genomic sequence of the patient, in order to maximize response and minimize adverse drug reactions. Pharmacoethnicity, or ethnic diversity in drug response or toxicity, is becoming increasingly recognized as an important factor accounting for interindividual variation in anticancer drug responsiveness. Although pharmacoethnicity is determined by genetic and nongenetic factors, there is rapidly accumulating clinical evidence about ethnic differences in the frequencies of polymorphisms within many of the important cancer drug-related genes. This article reviews the current clinical evidence for ethnic differences in anticancer drug disposition and sensitivity while highlighting the challenges, and potential solutions, to acquiring such knowledge. The discovery of "ethnic-specific genetic signatures," representing unique sets of drug susceptibility-governing polymorphisms, may be the outcome of such work. Ultimately, such understanding will further the lofty goal of individualization of chemotherapy based on a person's unique genetic make-up to improve the tolerability and effectiveness of chemotherapy for all patients.
Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies
Authors: Holger Hebart, Claudia Bollinger, Paul Fisch, Jacqueline Sarfati, Christoph Meisner, Manuela Baur, Jürgen Loeffler, Michel Monod, Jean-Paul Latgé, Hermann Einsele
Journal: Blood (2002)
The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization: a cross-sectional study
Authors: K. Ross-Hansen, A. Linneberg, J.D. Johansen, L.-G. Hersoug, C. Brasch-Andersen, T. Menné, J.P. Thyssen
Journal: British Journal of Dermatology (2012)

Background Contact sensitization is frequent in the general population and arises from excessive or repeated skin exposure to chemicals and metals. However, little is known about its genetic susceptibility. Objectives To determine the role of polymorphisms of glutathione S‐transferase (GST) genes and the claudin‐1 gene (CLDN1) on the risk of contact sensitization, taking common filaggrin gene (FLG) mutations into account. Methods In total, 3471 adult Danes from the general population were standard patch tested and filled out a questionnaire on their general health. They were genotyped for the following polymorphisms: GSTM1 and GSTT1 deletion, GSTP1 single nucleotide polymorphism (SNP) rs1695, four CLDN1 SNPs (rs893051, rs9290927, rs9290929 and rs17501010) and the FLG null mutations R501X and 2282del4. Results In individuals without ear piercings, a higher prevalence of nickel sensitization was found in those with the minor allele of CLDN1 SNP rs9290927 (Ptrend = 0·013). For CLDN1 rs17501010, contact sensitization to organic compounds was associated with the major allele (Ptrend = 0·031). The risk pattern was also identified for self‐reported nickel dermatitis (Ptrend = 0·011). The fragrance sensitization prevalence differed in a pairwise comparison of the CLDN1 rs893051 SNP genotypes (P = 0·022), with the minor allele being associated with a higher prevalence. The associations were confirmed in logistic regression analyses. Conclusions The CLDN1 polymorphisms rs9290927, rs893051 and rs17501010 were associated, respectively, with nickel contact sensitization in individuals without ear piercings, contact sensitization to fragrances, and with both organic compounds and nickel contact dermatitis. We could not find associations between GST gene polymorphisms and contact sensitization. FLG mutations did not affect the observed associations.
Haematopoietic stem cell recruitment to injured murine liver sinusoids depends on 4 1 integrin/VCAM-1 interactions
Authors: D P J Kavanagh, L E Durant, H A Crosby, P F Lalor, J Frampton, D H Adams, N Kalia
Journal: Gut (2009)

Evidence suggests haematopoietic stem cells (HSCs) can migrate to injured liver and influence tissue repair. However, mechanisms governing HSC recruitment to injured hepatic microcirculation are poorly understood. These were investigated in vivo following hepatic ischaemia-reperfusion (IR) injury and in vitro using flow-based adhesion assays.Partial IR was induced in anaesthetised WT or PECAM-1(-/-) mice for 90 min. Recruitment of systemically administered HSCs was monitored and effects of function blocking antibodies against alpha(4)beta(1) integrin, CD18, CD44, PECAM-1 or VCAM-1 investigated. The kinetics and molecular events governing adhesion to murine cardiac endothelial cells in vitro were also determined. Effects of conditioned media from IR injured liver on HSC adhesion molecule expression was determined by FACS.Administered HSCs homed predominantly to lungs rather than liver, highlighting a potential therapeutic hurdle. Hepatic HSC recruitment following IR injury was inhibited by anti-alpha(4)beta(1) and anti-VCAM-1 antibodies. A role for alpha(4)beta(1) was also confirmed using flow-based adhesion assays. Incubating HSCs with conditioned media from IR injured liver increased alpha(4)beta(1) expression. CD18, CD44 and PECAM-1 were not involved in recruitment.This novel study demonstrates that the alpha(4)beta(1)/VCAM-1 pathway mediates HSC recruitment to injured liver. Manipulating this pathway may enhance delivery of HSCs to the liver.
Serious pulmonary toxicity in patients with Hodgkin’s lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcγRIIIa-158 V/F polymorphism
Authors: K.A. Blum, S.-H. Jung, J.L. Johnson, T.S. Lin, E.D. Hsi, D.M. Lucas, J.C. Byrd, B.D. Cheson, N.L. Bartlett
Journal: Annals of Oncology (2010)
Effect of antihistamines and antiallergic drugs on responses to allergen and histamine provocation tests in asthma.
Authors: M J Phillips, S Ollier, C Gould, R J Davies
Journal: Thorax (1984)

The inhibition of immediate allergen or histamine induced airflow obstruction by inhaled ketotifen, clemastine, sodium cromoglycate, and placebo was studied in two groups of asthmatic subjects. Single doses of ketotifen (0.5 mg), clemastine (0.5 mg), sodium cromoglycate (20 mg), or placebo were administered by inhalation 45 minutes before bronchial provocation testing at weekly intervals, double blind and in random order. Inhalation of ketotifen and clemastine, but not sodium cromoglycate, caused an increase in the amount of histamine which had to be administered to cause a 20% fall in FEV1 from control levels (PD20-FEV1) compared with placebo. The PD20-FEV1 for allergen increased significantly after inhalation of clemastine and sodium cromoglycate. Clemastine, primarily an H1 receptor antagonist, inhibited airflow obstruction after inhalation of both histamine and allergen. Its inhibitory effect on allergen induced asthma did not differ significantly from that of sodium cromoglycate. Ketotifen, when inhaled in a single dose of 0.5 mg before bronchial provocation testing, showed potent antihistamine activity, but there was no evidence of any additional "antianaphylactic" activity.
Chemokines in the vascular inflammatory response of atherosclerosis
Authors: A. Zernecke, C. Weber
Journal: Cardiovascular Research (2009)

Atherosclerosis is considered to be a chronic inflammatory disease of the vessel wall that encompasses the accumulation of lipids, and it is critically shaped by the recruitment of leucocytes during all phases of the disease. In addition, the progression of atherosclerosis is determined by a disturbed equilibrium of immune responses. Chemokines and their receptors are instrumental in orchestrating the influx of leucocytes to the vascular wall, but also seem to regulate immune functions. Recent work has shed light on the apparent redundancy and the robustness of the chemokine system and has also provided evidence for its specialized role in the regulation of specific functions and trafficking of leucocyte subpopulations. This review will give a comprehensive summary to highlight those chemokines addressed in different models of atherosclerosis and vascular injury to date. In addition, we will discuss recent developments scrutinizing heterophilic interactions of chemokines that have advanced our understanding of how chemokines control vascular inflammatory responses.
CB/CC diffuse lymphoma: A distinct subtype of non-Hodgkin's lymphoma?
Authors: L. Munksgaard, B.E. Christensen, H. Brincker, N.T. Pedersen
Journal: Annals of Oncology (1997)

Between 1983 and 1993, 3165 cases of non-Hodgkin's lymphoma (NHL) were reported to the West Danish Lymphoma Registry (LYFO). Out of these, 148 (4.7%) were of the CB/CC diffuse subtype according to the Kiel classification. However, in the new European American NHL consensus classification (REAL, 1994), CB/CC diffuse lymphoma was categorized as a provisional subtype only. In the LYFO material, death-probability curves show a significantly shorter survival in CB/CC diffuse than in CB/CC follicular. In order to detect further possible differences between CB/CC diffuse and other NHL subtypes, a number of clinical parameters at presentation were analyzed in a subset of five types of lymphoma. This subset included 148 cases of CB/CC diffuse, 435 cases of CB/CC follicular, 667 cases of CB diffuse, 202 cases of CC diffuse, and 131 cases of peripheral T-cell lymphoma. Using logistic regression analysis, significant differences could be demonstrated between CB/CC diffuse and the four other subtypes as regards sex ratio, age distribution, and sites of both nodal and extranodal involvement. These findings indicate that CB/CC diffuse has a distinct clinical phenotype and imply the existence of real biological differences between CB/CC diffuse and other subtypes of lymphoma.
Delayed anti-HCV antibody seroconversion in 41 heart transplanted patients with non A non B post transfusion hepatitis
Authors: F. Lunel, J.F. Cadranel, J. Moussalli, M. Perrin, J.J. Ghoussoub, M. Descuenne, P. Grippon, A. Cabrol, J.M. Huraux, P. Opolon
Journal: Journal of Hepatology (1991)
Hormonal contraceptives and asthma in women of reproductive age: analysis of data from serial national Scottish Health Surveys
Authors: Bright I Nwaru, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2015)

Objectives Sex steroid hormones may explain known gender-related variations in asthma prevalence and clinical manifestation. We investigated the relationship between use of hormonal contraceptives and asthma in women, and assessed evidence of biological interaction between use of hormonal contraceptives and body mass index in this relationship. Design Population-based analysis using data from serial (i.e. 2003, 2008 and 2010) Scottish Health Surveys. Setting Random samples of the Scottish general population. Participants A total of 3257 non-pregnant, 16–45-year-old women. Exposure Current use of hormonal contraceptives. Main outcome measures Self-reported current physician-diagnosed asthma, current wheezing symptoms, wheezing attacks and treatment for asthma or wheeze. Results Women comprising 30.9% (95% confidence interval 29.3–32.5) were currently using any hormonal contraceptive and current physician-diagnosed asthma was present in 6.5% (95% confidence interval 5.7–7.4). Use of any hormonal contraceptive was associated with reduced risk of current physician-diagnosed asthma (odds ratio 0.68; 95% confidence interval 0.47–0.98) and receiving ≥3 asthma care episodes (odds ratio 0.45; 95% confidence interval 0.25–0.82), but the evidence was equivocal for wheezing attacks. Use of hormonal contraceptives among overweight or obese women was non-statistically significantly associated with asthma, but there was 42–135% increased risk in overweight and obese non-contraceptive using women. Conclusions Use of hormonal contraceptives may reduce asthma exacerbations and number of care episodes. Overweight and obese non-contraceptive-using women may be at increased risk of asthma. Prospective studies are now needed to confirm these findings. Both oestrogen and progesterone may stimulate smooth airway muscle function and inhibit the activities of TH2 responses. Future studies should investigate these underlying mechanisms.
The bronchodilator response from increasing doses of terbutaline inhaled from a multi-dose powder inhaler (Turbuhaler)
Authors: G Persson, JE Wiren
Journal: European Respiratory Journal (1990)

Twelve adult asthmatics inhaled single doses of 0.5, 2.0 or 4.0 mg of terbutaline, respectively, via Turbuhaler, on three separate days. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate were measured 15, 30, 45 and 60 min after inhalation from the inhaler and then hourly up to 8 h. The results showed that a more rapid onset of action, a greater maximal response and a longer duration of action can be achieved by exceeding the standard dose of terbutaline of 0.5 mg. The incidence of adverse effects was very low even at the highest dose, 4 mg. This study emphasizes the need for individual dosing of inhaled bronchodilators.
Sustained Weight Loss Following 12-Month Pramlintide Treatment as an Adjunct to Lifestyle Intervention in Obesity
Authors: Steve R. Smith, Louis J. Aronne, Colleen M. Burns, Nicole C. Kesty, Amy E. Halseth, Christian Weyer
Journal: Diabetes Care (2008)

OBJECTIVE—To assess long-term weight loss efficacy and safety of pramlintide used at different dosing regimens and in conjunction with lifestyle intervention (LSI). RESEARCH DESIGN AND METHODS—In a 4-month, double-blind, placebo-controlled, dose-ranging study, 411 obese subjects were randomized to receive pramlintide (six arms: 120, 240, and 360 μg b.i.d. and t.i.d.) or placebo in conjunction with a structured LSI program geared toward weight loss. Of the 4-month evaluable subjects (n = 270), 77% opted to continue preexisting treatment during an 8-month single-blind extension (LSI geared toward weight maintenance). RESULTS—At month 4, mean weight loss from baseline in the pramlintide arms ranged from 3.8 ± 0.7 to 6.1 ± 0.8 kg (2.8 ± 0.8 kg with placebo). By month 12, initial 4-month weight loss was regained in the placebo group but was maintained in all but the 120-μg b.i.d. group. Placebo-corrected weight loss with 120 μg t.i.d. and 360 μg b.i.d. averaged 3.2 ± 1.2 kg (3.1 ± 1.1% body wt) and 3.3 ± 1.1 kg (3.1 ± 1.0% body wt), respectively, at month 4 (both P &amp;lt; 0.01; 4-month evaluable n = 270) and 6.1 ± 2.1 kg (5.6 ± 2.1% body wt) and 7.2 ± 2.3 kg (6.8 ± 2.3% body wt), respectively, at month 12 (both P &amp;lt; 0.01; 12-month evaluable n = 146). At month 12, 40 and 43% of subjects treated with 120 μg t.i.d. and 360 μg b.i.d., respectively, achieved ≥10% weight loss (vs. 12% for placebo). Nausea, the most common adverse event with pramlintide in the 4-month study (9–29% pramlintide vs. 2% placebo), was generally mild to moderate and occurred in &amp;lt;10% of subjects during the extension. CONCLUSIONS—When used over 12 months as an adjunct to LSI, pramlintide treatment, with low-dose three-times-daily or higher-dose two-times-daily regimens, helped obese subjects achieve greater initial weight loss and enhanced long-term maintenance of weight loss.
Influence of Preoperative and Postoperative Pelvic Floor Muscle Training (PFMT) Compared with Postoperative PFMT on Urinary Incontinence After Radical Prostatectomy: A Randomized Controlled Trial
Authors: Inge Geraerts, Hendrik Van Poppel, Nele Devoogdt, Steven Joniau, Ben Van Cleynenbreugel, An De Groef, Marijke Van Kampen
Journal: European Urology (2013)
Insulin Resistance and Preeclampsia in Gestational Diabetes Mellitus
Authors: Martin N. Montoro, Siri L. Kjos, Mary Chandler, Ruth K. Peters, Anny H. Xiang, Thomas A. Buchanan
Journal: Diabetes Care (2005)

To compare the degree of insulin resistance in women with gestational diabetes mellitus (GDM) who do and do not develop preeclampsia.We conducted a prospective cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and glucose clamp studies in the early third trimester (n = 150) and 15 months postpartum (n = 89). After delivery, the women were categorized as nonpreeclamptic or preeclamptic (systolic blood pressure [SBP] > or = 140 mmHg, diastolic blood pressure [DBP] > or = 90 mmHg, and at least >1+ proteinuria or >300 mg/24 h). Metabolic parameters between the groups were compared by chi2 or Fisher's exact tests and ANOVA with P < 0.05 as significant.A total of 29 women (19%) developed preeclampsia, which was mild in 21 and severe in 8 women. At entry, there were no differences in age, weight indexes, and glycemic measures between the nonpreeclamptic and preeclamptic groups. Those with preeclampsia were significantly taller (61.5 +/- 2.4 vs. 60.1 +/- 2.3 in, P = 0.003), were more often nulliparous (38 vs. 16%, P = 0.01), and had higher entry SBP (112 +/- 10 vs. 103 +/- 6.9 mmHg, P < 0.0001) and DBP (64 +/- 9 vs. 59 +/- 5 mmHg, P = 0.002). No significant differences between the groups were found in any measures of the OGTT glucose levels, insulin sensitivity index, glucose effectiveness, acute response to glucose, or disposition index, nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose, insulin, free fatty acid, hepatic glucose output, peripheral glucose clearance, C-peptide, or glucagon. At 15 months postpartum, blood pressure levels remained significantly higher in the preeclamptic group (n = 19) compared with the nonpreeclamptic group (n = 70). No differences in any glycemic or insulin resistance measures were found.Women with GDM were uniformly insulin resistant. Those who developed preeclampsia, when compared with those who remained nonpreeclamptic, were not more insulin resistant in either the third trimester or 15 months postpartum. However, women who developed preeclampsia had blood pressure levels that were significantly higher, although still in the normal range, than those of women who remained nonpreeclamptic.