tbuckley/cabot-search huggingface dataset:
Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection.
Authors: H M Schrager, J G Rheinwald, M R Wessels
Journal: Journal of Clinical Investigation (1996)

It has been suggested that entry of pathogenic bacteria, including streptococci, into epithelial cells may represent an early stage of invasive infections. We found that poorly encapsulated wild-type strains and unencapsulated mutants of group A Streptococcus entered cultured human keratinocytes with high efficiency, while strains that produced large amounts of hyaluronic acid capsule did not, regardless of M-protein type or clinical source of the isolate. However, encapsulated streptococci produced extensive local necrosis and systemic infection in a mouse model of skin infection, while an isogenic acapsular strain did not. The results implicate the hyaluronic acid capsule as a virulence factor in soft tissue infection. Entry of poorly encapsulated group A Streptococcus into human epithelial cells does not appear to represent an initial step in invasive disease; rather, the capacity of encapsulated strains to avoid uptake by epithelial cells is associated with enhanced virulence in skin and soft tissue infection.
Inhibition of Human Airway Sensitization by a Novel Monoclonal Anti-IgE Antibody, 17-9
Authors: KLAUS F. RABE, NIKKI WATSON, GORDON DENT, BENITA E. MORTON, KATHRIN WAGNER, HELGO MAGNUSSEN, CHRISTOPH H. HEUSSER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We investigated the effect of a novel mouse IgG2b nonanaphylactogenic anti-human IgE antibody, 17-9, on allergen and histamine responses in passively sensitized human airways in vitro to determine the specific contribution of IgE to the sensitization process. Bronchial rings were sensitized with serum containing high levels of allergen-specific IgE (Dermatophagoides farinae), or with a hapten-specific chimeric humanized IgE (JW8). There was a concentration-dependent contraction of serum-sensitized bronchial rings to D. farinae (517 +/- 188 mg tension at 10 U/ml, n = 8) that was not observed in nonsensitized controls. This response was practically abolished when tissues were sensitized in the presence of 100 microg/ml anti-IgE antibody 17-9 (54 +/- 20 mg). In tissues sensitized with the anti-NIP IgE, JW8, there was a concentration-dependent contraction to the specific antigen NIP-BSA (560 +/- 154 mg at 0.3 microg/ml, n = 5) that was not observed in nonsensitized control subjects and that was substantially inhibited when 17-9 was present in the sensitization buffer (124 +/- 109 mg). The inhibition with 17-9 was specific, as pretreatment with a non-IgE-specific IgG2b antibody did not affect allergen responses. Potency and maximal contractions to histamine in serum-sensitized tissues were significantly elevated compared with nonsensitized controls; this was not affected by the presence of 17-9 during sensitization (pEC50 = 5.1 +/- 0.2 versus 5.0 +/- 0.3 in tissues sensitized in the absence of 17-9). In tissues sensitized with JW8 there was no significant increase in responsiveness to histamine. We conclude that allergen responses in sensitized human airways are dependent on IgE levels in the sensitizing serum while nonspecific (hyper)responsiveness depends on serum factors other than IgE. Nonanaphylactogenic anti-human IgE antibodies effectively inhibit allergen responses of human airways in vitro but may not affect other factors inducing hyperresponsiveness.
Pivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseases
Authors: Gobardhan Das, Jyoti Das, Paul Eynott, Yingyu Zhang, Alfred L.M. Bothwell, Luc Van Kaer, Yufang Shi
Journal: The Journal of Experimental Medicine (2006)

Unlike T cells restricted by major histocompatibility complex (MHC) class Ia or class II molecules, T cells restricted by MHC class I-like molecules demonstrate properties of both innate and adaptive immunity and are therefore considered innate-like lymphocytes (ILLs). ILLs are believed to have immunoregulatory functions, but their roles in autoimmunity and defense against infections remain elusive. To study the properties of ILLs, we generated mice expressing only MHC class I-like molecules by crossing CIITA-/- with Kb-/-Db-/- mice. Surprisingly, these mice developed a lymphoproliferative syndrome and autoimmunity, most notably inflammatory bowel disease (IBD) and insulitis. The CD8+ ILLs in these mice exhibit a constitutively activated phenotype, and depletion of these cells abolished the autoimmune disorders. In addition, adoptive transfer of CD8+ ILLs from Kb-/-Db-/-CIITA-/- mice to Rag-1-/-pfn-/- mice also resulted in IBD and insulitis. These findings provide direct evidence that CD8+ ILLs are sufficient to initiate and mediate autoimmune diseases.
The Call of Service: A Witness to Idealism
Authors: Burton C. Einspruch
Journal: JAMA (1994)

The 1960s were an interesting but troubled time in which to complete the rites of passage leading to physician-hood. The Vietnam War quickly brought to the surface many barely slumbering American conflicts. Robert Coles, an early and articulate element of the social conscience of that era, has recently authored<i>The Call of Service: A Witness to Idealism</i>. Recognized as a participant in the "activist movement" in America, especially as it was associated with civil rights, he has not surprisingly extended his advocacy to the study of children. Perhaps his best-known works are a series,<i>Children of Crisis</i>, but his writings include volumes of poetry, biographical works, and collaborative efforts in other arenas—writings that reflect his capacity to handle issues of substantial complexity with a probing simplicity, rather than obscurantism, and which reveal an ingenious and creative mind fueled by intense scholarship and its practicality. It may be trite to state
Serum Levels of Hepatitis B Surface Antigen Predict Severity of Fibrosis in Patients With E Antigen-Positive Chronic Hepatitis B
Authors: Patrick Marcellin, Michelle Martinot-Peignoux, Tarik Asselah, Richard Batrla, Diethelm Messinger, Vivien Rothe, George Lau, Yun-Fan Liaw
Journal: Clinical Gastroenterology and Hepatology (2014)

Noninvasive techniques are needed to assess hepatic fibrosis in patients with chronic hepatitis B. We developed a scoring system to determine the degree of fibrosis in patients with genotype B or genotype C hepatitis B virus (HBV) infection and positive for the hepatitis B e antigen.We performed a retrospective study to identify baseline variables associated with the severity of fibrosis (METAVIR scores, F0-F4) in a large phase 3 clinical trial of predominantly Asian patients (n = 710), using multivariate logistic regression analyses. Significant variables were used to construct predictive models using optimal cut-off values. The final model was validated in similar patients from a large phase 4 clinical trial (n = 465).We developed 2 prediction scoring systems (PSs). PS1 analyzed data on HBV genotype (B vs. C), patient age (<30 vs. ≥30 y), level of hepatitis B surface antigen (≤17,500 vs. >17,500 IU/mL), and level of alanine aminotransferase (≤3-fold vs. >3-fold the upper limit of normal). PS2 analyzed data on only age and level of hepatitis B surface antigen. PS1 identified patients with F0 to F1 vs. F2 to F4 fibrosis with more than 87% specificity and a positive predictive value greater than 75; it identified patients with F0 to F2 vs. F2 to F4 fibrosis with approximately 95% specificity and a positive predictive value (PPV) of approximately 97%. PS2 identified patients with F0 to F1 fibrosis with less accuracy than PS1, but identified patients with F0 to F2 fibrosis with an almost identical level of sensitivity and PPV.We developed a simple scoring system to determine the severity of fibrosis in patients with genotypes B or C HBV infection who are hepatitis B e antigen positive. Our system differentiated patients with no or mild fibrosis (F0-F1) from those with marked or severe (F2-F4) fibrosis with a high PPV. The high level of specificity for the identification of nonsevere fibrosis (F0-F2) limits the risk of overlooking patients with severe fibrosis (F3-F4).
Stuck Aortic Poppet
Authors: Marco G. Arrigoni
Journal: JAMA (1972)

Thirty-seven patients survived two days or longer after aortic valve replacement with a close-clearance Starr-Edwards cloth-covered prosthesis, model A2310; 16 patients subsequently died. In seven, the only pathologic finding at autopsy was an aortic poppet held at the apex of the cage by fibrin deposits. A stuck poppet was found at autopsy in another patient who also had an extensive subendocardial infarction dating to the time of operation. Three additional patients died suddenly in a manner suggesting an entrapped aortic poppet, but autopsies were not performed. Two other patients who received the diagnosis of intermittent entrapment of the ball valve were successfully operated upon a second time, and the aortic valve was replaced with another model of the prosthesis. In all, 35% of patients were known to have or were suspected of having a stuck valve poppet.
Orbofiban: An orally active GPIIb/IIIa platelet receptor antagonist
Authors: Nancy S. Nicholson, Norman A. Abood, Susan G. Panzer‐Knodle, Leo G. Frederick, Jimmy D. Page, Anita K. Salyers, Osman D. Suleymanov, James A. Szalony, Beatrice B. Taite, Robert J. Anders
Journal: Medicinal Research Reviews (2001)

Abstract A key role has been established for platelet activation and thrombus formation in the pathogenesis of acute coronary syndromes, and restenosis after percutaneous interventions. Antiplatelet agents that have a wider spectrum of activity than aspirin, and clopidogrel would be expected to provide improved antithrombotic protection. Preclinical studies were used to predict clinical efficacy of orally active GPIIb/IIIa antagonists such as xemilofiban, sibrafiban, lefradafiban, and orbofiban. While clinical trials have shown potent and sustained platelet inhibition, outcomes of trials with these first generation GPIIb/IIIa compounds have been disappointing. The active moiety of orbofiban is a potent and specific inhibitor of fibrinogen binding to GPIIb/IIIa, leading to inhibition of platelet aggregation to a wide variety of agonists. Studies comparing inhibition of aggregation and bleeding suggest that chronic inhibition of platelet aggregation can be achieved without major bleeding side effects. Thrombus formation is prevented in canine models of thrombosis. Orbofiban is approximately 28% bioavailable with a t 1/2 of 18 hr. The high bioavailability, long half‐life, and potential safety suggest orbofiban would be suitable for chronic oral administration. Clinical data demonstrate that orally administered orbofiban has the desired pharmacodynamic effect of inhibiting platelet aggregation but does not demonstrate clinical benefit when examined in large‐scale trials. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 3, 211–226, 2001
THE TREATMENT OF ACNE VULGARIS WITH TOLBUTAMIDE.
Authors: F. RAY BETTLEY
Journal: British Journal of Dermatology (1961)

Journal Article THE TREATMENT OF ACNE VULGARIS WITH TOLBUTAMIDE. Get access F. RAY BETTLEY, M.D., F.R.C.P. F. RAY BETTLEY, M.D., F.R.C.P. Physician for Diseases of the Skin, Middlesex Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 4, 1 April 1961, Pages 149–151, https://doi.org/10.1111/j.1365-2133.1961.tb14423.x Published: 01 April 1961
p47phox-Dependent NADPH Oxidase Regulates Flow-Induced Vascular Remodeling
Authors: Yves Castier, Ralf P. Brandes, Guy Leseche, Alain Tedgui, Stéphanie Lehoux
Journal: Circulation Research (2005)

Chronic alterations in blood flow elicit an adaptive response that tends to normalize shear stress, involving nitric oxide (NO) and matrix metalloproteinases (MMPs). To evaluate the role of NADPH oxidase in this process, we developed a new model of mouse arteriovenous fistula (AVF) connecting the right common carotid artery (RCCA) with the jugular vein, which does not affect blood pressure. Mice deficient for gp91phox and p47phox subunits of NADPH and wild-type controls were used. AVF greatly increased RCCA blood flow (0.78+/-0.12 to 4.71+/-0.78 mL/min; P<0.01), producing an abrupt rise in shear stress (35+/-1 to 261+/-17 dynes/cm2; P<0.01) within 24 hours. RCCA diameter (460+/-14 microm) gradually enlarged 1 and 3 weeks after AVF (534+/-14 microm and 627+/-19 microm; P<0.01), reducing shear stress (173+/-13 and 106+/-10 dynes/cm2, respectively). In gp91phox(-/-) mice, changes in RCCA caliber and shear stress matched controls. However, p47phox(-/-) mouse RCCAs enlarged only marginally, such that shear stress remained high (199+/-8 dynes/cm2 at 3 weeks). Likewise, remodeling was minimal in endothelial NO synthase (eNOS)(-/-) mice. In both control and gp91phox(-/-) animals, reactive oxygen species (ROS) production and MMP induction was enhanced by AVF, whereas in p47phox(-/-) and eNOS(-/-) mice such response was negligible. Similarly, nitrotyrosine staining, indicating peroxynitrite formation, was more pronounced in control and gp91phox(-/-) mice than in p47phox(-/-) and eNOS(-/-) mice. Hence, shear stress induces vascular NADPH oxidase comprising p47phox but not gp91phox. Generated ROS interact with NO to produce peroxynitrite, which in turn activates MMPs, facilitating vessel remodeling. Our study provides the first evidence that ROS play a fundamental role in flow-induced vascular enlargement.
Wallace's Line in serum sickness and Kawasaki disease
Authors: J.D. Bernhard, A.R. Rhodes, J.W. Melski
Journal: British Journal of Dermatology (1986)

Journal Article Wallace's Line in serum sickness and Kawasaki disease Get access J.D. Bernhard, J.D. Bernhard Division of Dermatology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A.R. Rhodes, A.R. Rhodes Division of Dermatology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J.W. Melski J.W. Melski Division of Dermatology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 5, 1 November 1986, Page 640, https://doi.org/10.1111/j.1365-2133.1986.tb05781.x Published: 01 November 1986
Mechanisms responsible for thirst and polyuria associated with primary hyperaldosteronism.
Authors: C J Thompson, P H Baylis
Journal: BMJ (1987)

disorder were excluded the same significant differences remained.Thus sexual dysfunction and the irritable bowel syndrome are specifically related, but the mechanism remains speculative.A particular feature was that sexual intercourse often induced abdominal pain, which often had a delayed onset.This may reflect secondary colonic spasm, although it may have originated within the genitourinary tract.More subtle psychological mechanisms must also be considered.The women in our study probably represent the severe end of the range of the irritable bowel syndrome.Thus extrapolation of these results to the syndrome as a whole is not justified.Our findings suggest, however, that sexual dysfunction in the irritable bowel syndrome is a hitherto completely unrecognised aspect of this condition that needs to be addressed.
Abstract 2662: Radiosensitizing potential of the PI3K inhibitor, BKM-120 and the HSP 90 inhibitor, HSP990, is dependent on PTEN status of glioblastoma cells
Authors: Phyllis Rachelle Wachsberger, Richard Y. Lawrence, Nick Feo, Yi Liu, Barbara Andersen, Adam P. Dicker
Journal: Cancer Research (2011)

Abstract Introduction: Radiation therapy plays an essential role in the treatment of Glioblastoma Multiforme (GBM), the most common primary adult brain tumor. GBMs frequently contain mutations in the tumor suppressor gene, PTEN, a down regulator of the pro-survival phosphatidylinositide-3-kinase (PI3K) pathway. PTEN loss causes overactivation of the pathway inducing radioresistance. Heat-shock protein (HSP) 90 is overexpressed in GBM; it is a chaperone for many oncogenic proteins and plays a key role in assisting tumor cell survival, proliferation, invasion, metastasis and tumor angiogenesis. The purpose of this study was to investigate the radiosensitizing potential of an HSP 90 inhibitor, (HSP990) and a PI3K inhibitor, (BKM-120) in U87 GBM cells expressing PTEN or null for PTEN. Methods: Two isogenic U87 cell lines, stably transfected with wildtype PTEN (U87 wtPTEN) or lacking PTEN (U87PTEN null) were used. Radiosensitivity was determined by clonogenic and apoptotic assays (Annexin V kit). DNA damage and repair was assessed by quantifying gamma Histone 2AX (γH2AX) foci. Immunoblots were performed to assess pAkt levels. HSP990 and BKM -120 were provided by Novartis Pharmaceuticals. Results: Neither HSP990 or BKM -120, alone or in combination, potentiated radiation-induced DNA damage in either cell line, as assessed by γH2AX foci. Radiation alone (6 Gy) activated AKT phosphorylation, with maximum activity occurring one hour post-radiation in both cell lines. Radiation-induced Akt phosphorylation was strongly inhibited by BKM -120 alone or in combination with HSP990 but not by HSP990 alone in both cell lines. In clonogenic assays, both drugs (alone or in combination), sensitized PTEN positive and PTEN null cells to radiation. Whereas the two drugs had similar efficacy in PTEN null cells, HSP990 was a better radiosensitizer than BKM -120 in U87 wtPTEN cells. Apoptosis assays revealed very little cell death 1 hr or 24 hr following drug and RT treatments. After 5 days, the percentage of apoptotic/necrotic cells increased &amp;gt;30% over control following treatment with BKM -120 alone or in combination with HSP 990 in PTEN null cells. In contrast, PTEN positive cells were more resistant to cell death following BKM -120. Conclusions: The results suggest that PI3K inhibition with BKM -120 will enhance radiotherapy for GBM lacking PTEN activity. HSP 90 inhibition by HSP990 may be of benefit in enhancing radiotherapy for GBM expressing functional PTEN. Thus, it appears that the optimal choice of radiosensitizer depends upon PTEN status. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2011-2662
Polypectomy at colonoscopy and sigmoidoscopy in England: a review of national data between 1997 and 2007
Authors: A. M. Almoudaris, S. Gupta, A. Bottle, P. Aylin, J. E. East, S. Thoms-Gibson, O. D. Faiz
Journal: Gut (2011)

<h3>Introduction</h3> Currently, there is no national endoscopic database in England. Information regarding the volume of therapeutic endoscopic procedures such as polypectomy is obtained mainly from small prospective studies. This article examines the Hospital Episode Statistics (HES) database to assess the number of patients that have undergone a therapeutic polypectomy for a diagnosis of a benign colorectal polyp over a 10-year period. We also analyse 28-day re-admission and 30-day mortality rates post procedure across 174 English National Health Service (NHS) units. <h3>Methods</h3> All elective patients having undergone a therapeutic polypectomy for a benign colorectal polyp between 1 Jan 1997 and 31 December 2007 in English NHS units were identified from HES after cleaning and formatting the dataset. Trends in rates of colonoscopies and flexible sigmoidoscopies were evaluated as well as 28-day re-admission and mortality rates over time. The reliability of HES data has previously been demonstrated in general surgical and medical patient cohorts <h3>Results</h3> The HES dataset reports that, 334,753 polypectomy procedures were performed on 286,204 patients in English NHS Trusts over the 10-year period. Of these, 233,119 (69.6%) were colonoscopicand 101,634 (30.4%) were via flexible sigmoidoscopy. Over this period a 55.2% increase in the total number of endoscopic polypectomy procedures were performed (from 20,289 in 1997 to 31,503 in 2007). Over the study years, the unadjusted average readmission (range-2.08% &gt; 2.47%) and mortality rates (range −0.33% &gt; 0.63%) overall were not significantly different (p = 0.440, both). <h3>Conclusion</h3> This analysis is the first to report national lower GI polypectomy numbers. It appears to demonstrates that patients undergoing endoscopic polypectomy rose by 55% from 1997 to 2007. Improved coding and a genuine increase in polypectomy workload may underlie these findings. Given the volumes of polypectomies being undertaken, and that polypectomy accounts for most of the procedure related risk with lower GI endoscopy, this may strengthen the case for improved training and accreditation in polypectomy.
FAS engagement drives apoptosis of enterocytes of coeliac patients
Authors: L Maiuri, C Ciacci, V Raia, L Vacca, I Ricciardelli, F Raimondi, S Auricchio, S Quaratino, M Londei
Journal: Gut (2001)

<h3>BACKGROUND</h3> Villus atrophy is the most distinctive sign of untreated coeliac disease (CD) and epithelial apoptosis is considered to be involved in this stage of the coeliac lesion. The extent of villus atrophy is, however, not homogeneous and patients with patchy or mild lesions have been described. <h3>AIMS</h3> To address: (a) the degree of "patchiness" in untreated CD patients; and (b) to clarify if apoptosis, and eventually which trigger drives it, causes epithelial damage. <h3>PATIENTS</h3> Twenty of 40 untreated, 14 treated coeliac patients, and 15 controls received five or more multiple duodenal biopsies; the remaining 20 untreated CD patients had no more than three biopsies. <h3>METHODS</h3> All biopsies were analysed to monitor the presence of a "flat" mucosa. Biopsies of 14 untreated, 10 treated coeliacs, and seven controls were cultured with or without gliadin. DNA fragmentation was studied by terminal deoxynucleotidyl transferase (TdT) mediated dUTP digoxigenin nick end labelling (TUNEL), and FAS and Ki67 expression by immunohistochemistry. Antiendomysium antibodies (EMA) were surveyed in biopsy culture supernatants. <h3>RESULTS</h3> A pattern of patchy duodenal lesions was observed in all untreated CD patients biopsied up to five times. High enterocyte FAS expression, and a high number of TUNEL+ and Ki67+ enterocytes were detected in areas with villus atrophy but not in those with a normal morphology (p&lt;0.001). Conversely, EMA in culture supernatants and signs of immunological activation were present in all untreated CD biopsies. In vitro gliadin challenge increased the number of TUNEL+ and Ki67+ enterocytes (p&lt;0.001 <i>v</i> cultures with medium alone) only in "flat" biopsies. Neutralising anti-FAS monoclonal antibodies were found to control gliadin induced enterocyte apoptosis (p&gt;0.01) while agonist anti-FAS monoclonal antibody increased it (p&lt;0.001). <h3>CONCLUSIONS</h3> Patchy lesions are observed in untreated CD mucosa and epithelial FAS engagement is a key trigger in driving villus atrophy in CD.
The Effect of Alexithymia on Morbidity in Hypertensives
Authors: Bruce C. Gage, Kelly J. Egan
Journal: Psychotherapy and Psychosomatics (1984)

Alexithymic and nonalexithymic hypertensives were assessed for severity of hypertension using a weighting system based on diastolic blood pressure, optic fundi, ECG, chest X ray, renal studies, and patient history. Outpatient hypertensives (diastolic blood pressure greater than 95 mm Hg) were selected as subjects because they are largely asymptomatic; thus, focusing on somatic ills to the exclusion of thoughts about emotions is not likely to be due to their hypertensive pathology but rather reflects psychological constitution. Controlling for age differences, it was found that alexithymics manifested more severe hypertensive sequelae than did nonalexithymics ; there was, however, no difference in severity of atherosclerosis. The results suggest that alexithymia is not only correlated with hypertension but may also play a role in its etiology.