tbuckley/cabot-search huggingface dataset:
Verrucous carcinoma of the tracheobronchial tree: an underdiagnosed entity?
Authors: Claus Steppert, Joseph Alhanna, Juergen Schubert, Jens Krugmann, Michael Vieth
Journal: European Respiratory Journal (2014)

To the Editor: 

Verrucous carcinomas, first described by Ackermann [1] in 1948, are rare, well-differentiated squamous cell carcinomas in the oropharynx [2], larynx [2–4] and oesophagus [5], and seem to be associated with Human papilloma virus (HPV) infections [6]. Macroscopically, they have a warty appearance and may easily be mistaken for papillomas [4]. Surprisingly, although found in the larynx, there are no descriptions of this tumour in the tracheobronchial tree.

A 74-year-old male with a history of chronic obstructive pulmonary disease and former smoking was admitted for increasing shortness of breath. On clinical investigation he had a subfebrile temperature (38.2°C) and dry rales. Chest radiography showed discrete infiltrates in the right lower lobe. Lung function testing revealed an obstructive flow–volume loop with a forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of 32% and a FEV1 of 1.1 L (37% predicted).

Although anti-obstructive treatment was intensified using inhaled β-adrenergics, steroids and antibiotic treatment (ampicillin/sulbactam), the dyspnoea did not improve. On bronchoscopy, the distal trachea was shown to be infiltrated by a wart-like tumour obstructing ∼70% of the cross sectional area (fig. 1). The tumour was partly removed during rigid bronchoscopy and partly …
Navigation skill impairment: Another dimension of the driving difficulties in minimal hepatic encephalopathy
Authors: Jasmohan S. Bajaj, Muhammad Hafeezullah, Raymond G. Hoffmann, Rajiv R. Varma, Jose Franco, David G. Binion, Thomas A. Hammeke, Kia Saeian
Journal: Hepatology (2007)

Patients with minimal hepatic encephalopathy (MHE) have attention, response inhibition, and working memory difficulties that are associated with driving impairment and high motor vehicle accident risk. Navigation is a complex system needed for safe driving that requires functioning working memory and other domains adversely affected by MHE. The aim of this study was to determine the effect of MHE on navigation skills and correlate them with psychometric impairment. Forty-nine nonalcoholic patients with cirrhosis (34 MHE+, 15 MHE−; divided on the basis of a battery of block design, digit symbol, and number connection test A) and 48 age/education-matched controls were included. All patients underwent the psychometric battery and inhibitory control test (ICT) (a test of response inhibition) and driving simulation. Driving simulation consisted of 4 parts: (1) training; (2) driving (outcome being accidents); (3) divided attention (outcome being missed tasks); and (4) navigation, driving along a marked path on a map in a “virtual city” (outcome being illegal turns). Illegal turns were significantly higher in MHE+ (median 1; P = 0.007) compared with MHE−/controls (median 0). Patients who were MHE+ missed more divided attention tasks compared with others (median MHE+ 1, MHE−/controls 0; P = 0.001). Similarly, accidents were higher in patients who were MHE+ (median 2.5; P = 0.004) compared with MHE− (median 1) or controls (median 2). Accidents and illegal turns were significantly correlated ( P = 0.001, r = 0.51). ICT impairment was the test most correlated with illegal turns ( r = 0.6) and accidents ( r = 0.44), although impairment on the other tests were also correlated with illegal turns. Conclusion: Patients positive for MHE have impaired navigation skills on a driving simulator, which is correlated with impairment in response inhibition (ICT) and attention. This navigation difficulty may pose additional driving problems, compounding the pre-existing deleterious effect of attention deficits. (Hepatology 2008.)
Calmodulin in normal and cystic fibrosis human intestine at different developmental stages.
Authors: C Rochette-Egly, B Lacroix, H Pflieger, M Doffoel, M Kedinger, K Haffen
Journal: Gut (1988)

Calmodulin concentrations and localisation have been analysed as a function of development in human intestinal epithelial cells from normal and cystic fibrosis individuals. In normal fetuses up to eight weeks of gestation intestinal epithelial cells which were still undifferentiated were not immunoreactive and their calmodulin content was low. From eight weeks onwards there was a significant overall increase in calmodulin content concomitant with its segregation to the apical side of epithelial cells. At 14 weeks of gestation calmodulin concentrations and localisation closely resembled those of adults. The developmental pattern of calmodulin appeared to parallel the morphological and functional maturation of brush borders which occurs during the first trimester of pregnancy. In the intestinal epithelial cells from a 19 weeks cystic fibrosis fetus and a cystic fibrosis newborn infant neither calmodulin concentration, nor its localisation were affected. Similarly, brush border calmodulin binding proteins and enzymatic activities were similar in normal subjects and the cystic fibrosis intestine.
Cyclin-Dependent Kinase 2/Cyclin E Complex Is Involved in p120 Catenin (p120ctn)–Dependent Cell Growth Control: A New Role for p120ctn in Cancer
Authors: Nicolas T. Chartier, Christiane I. Oddou, Michèle G. Lainé, Benjamin Ducarouge, Christiane A. Marie, Marc R. Block, Muriel R. Jacquier-Sarlin
Journal: Cancer Research (2007)

Abstract Depending on its cellular localization, p120 catenin (p120ctn) can participate in various processes, such as cadherin-dependent cell-cell adhesion, actin cytoskeleton remodeling, and intracellular trafficking. Recent studies also indicate that p120ctn could regulate cell proliferation and contact inhibition. This report describes a new function of p120ctn in the regulation of cell cycle progression. Overexpression of the p120ctn isoform 3A in human colon adenocarcinoma cells (HT-29) results in cytoplasmic accumulation of the protein, as observed in many tumors. This cytoplasmic increase is correlated with a reduction in proliferation and inhibition of DNA synthesis. Under these conditions, experiments on synchronized cells revealed a prolonged S phase associated with cyclin E stabilization. Both confocal microscopy and biochemical analysis showed that cyclin E and cyclin-dependent kinase 2 colocalized with p120ctn in centrosomes during mitosis. These proteins are associated in a functional complex evidenced by coimmunoprecipitation experiments and the emergence of Thr199-phosphorylated nucleophosmin/B23. Such post-translational modification of this centrosomal target has been shown to trigger the initiation of centrosome duplication. Therefore, p120ctn-mediated accumulation of cyclin E in centrosomes may participate in abnormal amplification of centrosomes and the inhibition of DNA replication, thus leading to aberrant mitosis and polyploidy. Because these modifications are often observed in cancer, p120ctn may represent a new therapeutic target for future therapy. [Cancer Res 2007;67(20):9781–90]
Phosphorylation of the ribosomal protein S6, a marker of mTOR (mammalian target of rapamycin) pathway activation, is strongly increased in hypertrophic scars and keloids
Authors: A. Andreoli, M.T. Ruf, P. Itin, G. Pluschke, P. Schmid
Journal: British Journal of Dermatology (2014)

Journal Article Phosphorylation of the ribosomal protein S6, a marker of mTOR (mammalian target of rapamycin) pathway activation, is strongly increased in hypertrophic scars and keloids Get access A. Andreoli, A. Andreoli Swiss Tropical and Public Health Institute Socinstr. 57 Basel SwitzerlandUniversity of Basel Petersplatz 1 Basel Switzerland Search for other works by this author on: Oxford Academic Google Scholar M.T. Ruf, M.T. Ruf Swiss Tropical and Public Health Institute Socinstr. 57 Basel SwitzerlandUniversity of Basel Petersplatz 1 Basel Switzerland Correspondence: Peter Schmid and Marie‐Therese Ruf. E‐mails: peschmid@aol.com and therese.ruf@unibas.ch Search for other works by this author on: Oxford Academic Google Scholar P. Itin, P. Itin Department of Dermatology University Hospital Basel Switzerland Search for other works by this author on: Oxford Academic Google Scholar G. Pluschke, G. Pluschke Swiss Tropical and Public Health Institute Socinstr. 57 Basel SwitzerlandUniversity of Basel Petersplatz 1 Basel Switzerland Search for other works by this author on: Oxford Academic Google Scholar P. Schmid P. Schmid Swiss Tropical and Public Health Institute Socinstr. 57 Basel SwitzerlandUniversity of Basel Petersplatz 1 Basel Switzerland Correspondence: Peter Schmid and Marie‐Therese Ruf. E‐mails: peschmid@aol.com and therese.ruf@unibas.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 5, 1 May 2015, Pages 1415–1417, https://doi.org/10.1111/bjd.13523 Published: 01 May 2015
Local inflammatory reactions in patients with diabetes and periodontitis
Authors: Sarah K. Sonnenschein, Joerg Meyle
Journal: Periodontology 2000 (2015)

The impact of diabetes mellitus on the prevalence, severity and progression of periodontal disease has been known for many years and intense efforts have been made to elucidate the underlying mechanisms. It is widely reported that hyperglycemia causes numerous systemic changes, including altered innate immune-cell function and metabolic changes. The aim of this review was to summarize and discuss the evidence for mechanisms that probably play a role in the altered local inflammatory reactions in the periodontium of patients with diabetes, focusing on local changes in cytokine levels, matrix metalloproteinases, reactive oxygen species, advanced glycation end-products, immune-cell functions, the RANKL/osteoprotegerin axis and toll-like receptors. Apart from the systemic effects of diabetes, recent evidence suggests that local changes in the periodontal tissues are characterized by enhanced interactions between leukocytes and endothelial cells and by altered leukocyte functions [resulting in increased levels of reactive oxygen species and of proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α)]. These local changes are amplified by the enhanced accumulation of advanced glycation end-products and their interaction with receptors for advanced glycation end-products. Furthermore, the increased levels of proinflammatory cytokines lead to an up-regulation of RANKL in periodontal tissues, stimulating further periodontal tissue breakdown.
High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Support Compared With Standard-Dose Chemotherapy in Breast Cancer Patients With 10 or More Positive Lymph Nodes: First Results of a Randomized Trial
Authors: A.R. Zander, N. Kröger, C. Schmoor, W. Krüger, V. Möbus, N. Frickhofen, B. Metzner, W. Schultze, W.E. Berdel, M. Koenigsmann, E. Thiel, H. Wandt, K. Possinger, L. Trümper, R. Kreienberg, M. Carstensen, E.H. Schmidt, F. Jänicke, M. Schumacher, W. Jonat
Journal: Journal of Clinical Oncology (2004)

Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes.Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), intravenously every 21 days) either HD-CT of cyclophosphamide 1500 mg/m(2), thiotepa 150 mg/m(2), and mitoxantrone 10 mg/m(2), intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival.After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P =.095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths).There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.
Mechanism of rhinovirus-induced changes in airway smooth muscle responsiveness.
Authors: H Hakonarson, N Maskeri, C Carter, R L Hodinka, D Campbell, M M Grunstein
Journal: Journal of Clinical Investigation (1998)

An important interplay exists between specific viral respiratory infections and altered airway responsiveness in the development and exacerbations of asthma. However, the mechanistic basis of this interplay remains to be identified. This study addressed the hypothesis that rhinovirus (RV), the most common viral respiratory pathogen associated with acute asthma attacks, directly affects airway smooth muscle (ASM) to produce proasthmatic changes in receptor-coupled ASM responsiveness. Isolated rabbit and human ASM tissue and cultured ASM cells were inoculated with human RV (serotype 16) or adenovirus, each for 6 or 24 h. In contrast to adenovirus, which had no effect, inoculation of ASM tissue with RV induced heightened ASM tissue constrictor responsiveness to acetylcholine and attenuated the dose-dependent relaxation of ASM to beta-adrenoceptor stimulation with isoproterenol. These RV-induced changes in ASM responsiveness were largely prevented by pretreating the tissues with pertussis toxin or with a monoclonal blocking antibody to intercellular adhesion molecule-1 (ICAM-1), the principal endogenous receptor for most RVs. In extended studies, we found that the RV-induced changes in ASM responsiveness were associated with diminished cAMP accumulation in response to dose-dependent administration of isoproterenol, and this effect was accompanied by autologously upregulated expression of the Gi protein subtype, Gialpha3, in the ASM. Finally, in separate experiments, we found that the RV-induced effects on ASM responsiveness were also accompanied by autologously induced upregulated mRNA and cell surface protein expression of ICAM-1. Taken together, these findings provide new evidence that RV directly induces proasthmatic phenotypic changes in ASM responsiveness, that this effect is triggered by binding of RV to its ICAM-1 receptor in ASM, and that this binding is associated with the induced endogenously upregulated expression of ICAM-1 and enhanced expression and activation of Gi protein in the RV-infected ASM.
Potential of Nasopharynx-associated Lymphoid Tissue for Vaccine Responses in the Airways
Authors: Per Brandtzaeg
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Section:ChooseTop of pageAbstract <<NAIVE B CELLS ENTER TONSI...B CELLS ARE ACTIVATED IN ...VARYING ISOTYPE AND J-CHA...DISSEMINATION OF ACTIVATE...EFFECT OF ADENOTONSILLECT...DISEASE- AND AGE-RELATED ...VACCINATION AGAINST PATHO...CONCLUSIONSReferencesCITING ARTICLES
Mechanical Forces in Diabetic Kidney Disease
Authors: Luigi Gnudi, Stephen M. Thomas, Giancarlo Viberti
Journal: Journal of the American Society of Nephrology (2007)

Nephropathy is one of the major microvascular complications of diabetes, and both hemodynamic and metabolic stimuli participate in its development and progression toward ESRD. There is now a greater understanding of the molecular pathways that are activated by high glomerular capillary pressure and hyperglycemia and how they interplay to produce kidney pathology. The observation that overexpression of glucose transporter 1 (GLUT-1) in mesangial cells could induce a "diabetic cellular phenotype" has led to the postulation that the expression of GLUT-1 could be upregulated in glomeruli that are exposed to high pressure. This review suggests a mechanism by which mechanical forces may aggravate a metabolic insult by stimulating excessive cellular glucose uptake. Proposed is the existence of a self-maintaining cycle whereby a hemodynamic stimulus on glomerular cells induces GLUT-1 overexpression followed by greater glucose uptake and activation of intracellular glucose metabolic pathways, resulting in excess TGF-beta1 production. TGF-beta1 in turn, maintains overexpression of GLUT-1, perpetuating a signaling sequence that has, as its ultimate effect, increased extracellular matrix synthesis. This mechanical and metabolic coupling suggests a novel pathophysiologic mechanism of injury in the kidney in diabetes and possibly other glomerular diseases.
Treatment of Hormone-Refractory Prostate Cancer with Docetaxel or Mitoxantrone: Relationships between Prostate-Specific Antigen, Pain, and Quality of Life Response and Survival in the TAX-327 Study
Authors: Dominik R. Berthold, Gregory R. Pond, Martin Roessner, Ronald de Wit, Mario Eisenberger, and Ian F. Tannock
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The TAX-327 study randomized 1,006 men with metastatic hormone-refractory prostate cancer to receive 3-weekly docetaxel, weekly docetaxel, or mitoxantrone, each with prednisone. Experimental Design: We used the TAX-327 database to address (a) the relationship between quality of life (QoL) and pain; (b) whether minimally symptomatic patients benefit from treatment or have treatment-related decline in QoL; (c) the relationships between prostate-specific antigen (PSA) response, pain response, and QoL response; (d) the times at which these responses are first observed; and (e) whether PSA, pain, and/or QoL response predict for overall survival. Results: At baseline, 374 of 815 men assessed for QoL had major pain; of these, 92% had substantial impairment of QoL compared with 75% without major pain (P &amp;lt; 0.001). Men with minimal symptoms had prolonged survival (median, 25.6 months) compared with symptomatic patients (median, 17.1 months; P = 0.009); they were more likely to have initial deterioration of QoL if treated with weekly docetaxel. PSA response and pain response, but not QoL response, were independently associated with survival in landmark analysis. Median times to PSA and pain response were 44 and 27 days, respectively; some men had initial increase in serum PSA before subsequent decline. Conclusions: Symptoms other than pain contribute to impaired QoL in men with hormone-refractory prostate cancer. Those with minimal symptoms have prolonged survival. Both pain and PSA response are associated with survival but are not adequate to use as surrogate end points in phase 3 studies. Early increases in serum PSA (up to 12 weeks) should be ignored when determining response or progression.
REFLECTIONS AFTER TWENTY-ONE YEARS OF GENERAL PRACTICE
Authors: F. W. Jollye
Journal: BMJ (1912)

A lonigitudlinal incision about 4 in.long was made over the tumour.On cutting through the integument and deep fascia, dark clots and about a pint of dark fluid blood were turned out.On exposing the femoral veii, it was seen that a sharp spicule of bone broken away from the pubic crest had penetrated the vessel just as it came under Poupart's ligament.The tear in the vein was longitudinal and about i in. in length.Fgrther haemorrhace was controlled by digital pressure below the laceration.The vein was repaired by lateral phleborrhaphy, a Lembert stuture of fine thread being inserted with a domestic needle.The spicule of bone was removed and a tube with gauze packed tightly round inserted into the cavity.Towards the end of the operation the patient's condition became critical, and about 4 pints of normal saline were infuLsed into the median hasitie -vein.After--History.The-tube and gauze were removed on the third day after operation, and the patient lay between sandbags with a tight binder over the pelvis for a month.He was then discharged, and was able to walk from the ward.There was never throughout the convalescence any swelling or oedema of the limb, which remained quite painless.It is therefore most probable that at no time was there any venous thrombosis of any extent.Al x-ray photograph taken a week after operation showed a flake of bone torn away from the pubic crest to about *-in.from tihe ptubic spine.The diagram shows the condition.Arrow denotes point of fracture and spicule of bone.(Drawn from actual skiagram.)Althouglh laceration of the femoral vessels is a well recognized complication of fractured pelvis there are few, if any, cases on record; certainly none treated in this manner with success.The interesting physical signs in this case liaking it possible to differentiate the venous haemor- rhage from arterial were very striking, as also the complete absence of venous complications after vein suture.Lejars states that there have been several successful cases-of suture of vein trunks reported.Out of six of the inferior vena cava there were four successes and two deaths.Jacobsthal has collected 53 cases of suture of large veins; in two only of these did lateral suture fail.It is thus evident that a large vein such as the femoral shiould always be given a chance by suture rather than resorting at once to ligature, as the results of femoral vein thrombosis are so often unfortunate, to say the least.In cases in which lateral ligature (partial) can be carried out suturing can in nearly all cases replace it, and the chances of secondary haemorrhage are said to be less than in lateral ligature.In infected wounds or veins injured by sepsis suture is useless.Lejars recommends round needles as used in the above case, and sutures of sterilized thread soaked in aseptic vaseline.He is against a Lembert suture being inserted, and always does a tlirough-and-through suture.It is quite evident that if a Lembert stuture is possible it is preferable.
Endogenous Axon Guiding Chemorepulsant Semaphorin-3F Inhibits the Growth and Metastasis of Colorectal Carcinoma
Authors: Feng Wu, Qi Zhou, Jing Yang, Guang-jie Duan, Juan-juan Ou, Rong Zhang, Feng Pan, Qiu-ping Peng, Hong Tan, Yi-fang Ping, You-hong Cui, Cheng Qian, Xiao-chu Yan, Xiu-wu Bian
Journal: Clinical Cancer Research (2011)

To elucidate the role of Semaphorin-3F (SEMA3F), originally described as an axon guiding chemorepulsant implicated in nerve development, in the progression of colorectal carcinoma.SEMA3F and its receptor NRP2 were examined in 72 cases of human colorectal carcinoma specimens and cell lines LoVo, SW480, and SW620 with immunohistochemistry and Western blotting. SEMA3F mRNA expression in the frozen tissue specimens and cell lines was examined with quantitative reverse transcriptase-PCR. Confocal laser scanning microscopy was used for detection of cellular localization of the proteins by immunofluorescent staining. MTT assay, flow cytometry, cell adhesion and migration, and xenografts were used to evaluate biological significance of SEMA3F.SEMA3F was significantly reduced in colorectal carcinoma tissues and cell lines. Overexpression of SEMA3F resulted in reduced proliferation, adhesion to fibronectin, and migratory capability as well as reduced S-phase population and integrin αvβ3 expression of SW480 colon cancer cells. In addition, SEMA3F-overexpressing cells exhibited diminished tumorigenesis when transplanted orthotopically in nude mice and reduced liver metastases. Moreover, transfection of siRNA targeting SEMA3F in colon cancer cells increased their tumorigenicity in vivo.Endogenous SEMA3F acts as a suppressor of the growth and metastasis of human colorectal cancer cells.