tbuckley/cabot-search huggingface dataset:
Nuclear NF-κB p65 Phosphorylation at Serine 276 by Protein Kinase A Contributes to the Malignant Phenotype of Head and Neck Cancer
Authors: Pattatheyil Arun, Matthew S. Brown, Reza Ehsanian, Zhong Chen, Carter Van Waes
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Aberrant nuclear activation and phosphorylation of the canonical NF-κB subunit RELA/p65 at Serine-536 by inhibitor κB kinase is prevalent in head and neck squamous cell carcinoma (HNSCC), but the role of other kinases in NF-κB activation has not been well defined. Here, we investigated the prevalence and function of p65-Ser276 phosphorylation by protein kinase A (PKA) in the malignant phenotype and gene transactivation, and studied p65-Ser276 as a potential target for therapy. Experimental Design: Phospho and total p65 protein expression and localization were determined in HNSCC tissue array and in cell lines. The effects of the PKA inhibitor H-89 on NF-κB activation, downstream gene expression, cell proliferation and cell cycle were examined. Knockdown of PKA by specific siRNA confirmed the specificity. Results: NF-κB p65 phosphorylated at Ser276 was prevalent in HNSCC and adjacent dysplastic mucosa, but localized to the cytoplasm in normal mucosa. In HNSCC lines, tumor necrosis factor-α (TNF-α) significantly increased, whereas H-89 inhibited constitutive and TNF-α–induced nuclear p65 (Ser276) phosphorylation, and significantly suppressed NF-κB and target gene IL-8 reporter activity. Knockdown of PKA by small interfering RNA inhibited NF-κB, IL-8, and BCL-XL reporter gene activities. H-89 suppressed cell proliferation, induced cell death, and blocked the cell cycle in G1-S phase. Consistent with its biological effects, H-89 down-modulated expression of NF-κB–related genes Cyclin D1, BCL2, BCL-XL, COX2, IL-8, and VEGF, as well as induced cell cycle inhibitor p21CIP1/WAF1, while suppressing proliferative marker Ki67. Conclusions: NF-κB p65 (Ser276) phosphorylation by PKA promotes the malignant phenotype and holds potential as a therapeutic target in HNSCC. (Clin Cancer Res 2009;15(19):5974–84)
Pulmonary tuberculosis with acute respiratory failure
Authors: Y. J. Kim, K. M. Pack, E. Jeong, J. O. Na, Y-M. Oh, S. D. Lee, W. S. Kim, D. S. Kim, W. D. Kim, T. S. Shim
Journal: European Respiratory Journal (2008)

The aim of the present study was to evaluate the clinical characteristics, prognoses and predictors of mortality of patients with pulmonary tuberculosis (TB) with acute respiratory failure (ARF), and to investigate the adjunctive use of corticosteroids in such cases. TB patients with ARF requiring mechanical ventilation (n = 90) were enrolled retrospectively during 1989-2006. The patients were divided into two groups: tuberculous pneumonia (TBP; n = 66), and miliary TB (MTB; n = 24). The TBP patients were older than the MTB patients (mean age 68.0 versus 54.5 yrs), and the mean+/-SD interval from hospital admission to start of anti-TB treatment was longer for the TBP than for the MTB group (5.0+/-7.0 versus 2.8+/-2.5 days). However, there was no difference in in-hospital mortality rate between the two groups (68.2 versus 58.3%). In the TBP patients, multivariate analysis showed that advanced age and shock unrelated to sepsis were associated with poor outcomes. Even though corticosteroid use was a predictor of survival in TBP patients, it was difficult to conclusively determine the efficacy of corticosteroids in TBP with ARF because of the retrospective study design. The present study reveals the need for randomised controlled trials to clarify the role of corticosteroids as adjunctive therapy in the management of tuberculous pneumonia with acute respiratory failure.
DELUSIONS OF PARASITOSIS.
Authors: G. L. TULLETT
Journal: British Journal of Dermatology (1965)

Journal Article DELUSIONS OF PARASITOSIS. Get access G. L. TULLETT, B.Sc., M.B., M.R.C.P., D.P.M. G. L. TULLETT, B.Sc., M.B., M.R.C.P., D.P.M. Rupert Hallam Institute of Dermatology, Sheffield Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 8-9, 1 August 1965, Pages 448–455, https://doi.org/10.1111/j.1365-2133.1965.tb14676.x Published: 01 August 1965
The lung and carbon dioxide: implications for permissive and therapeutic hypercapnia
Authors: D.A. Kregenow, E.R. Swenson
Journal: European Respiratory Journal (2002)

Although acute respiratory acidosis may be a sign of impending respiratory failure in spontaneously breathing patients, it is commonly encountered in intubated patients with acute lung injury (ALI). This is especially the case now that limiting tidal volumes and airway pressures have been proven to reduce mortality in ALI, presumably by reducing additional lung injury caused by mechanical ventilation itself 1. A respiratory acidosis arising from lung-protective ventilation strategies has been termed permissive hypercapnia 2–5. As the name indicates, permissive hypercapnia has been regarded as an inconvenient side-effect that must be tolerated in order to realise the mortality benefits of a low lung-stretch strategy.

There is growing evidence that hypercapnic acidosis may itself minimise or reduce lung injury as a result of suppressing inflammatory events. The mechanism(s) for this effect is (are) not entirely known. Nonetheless, there was sufficient suggestive data from cell culture and isolated organ studies over the past two decades for Laffey and Kavanagh 6 not only to support the use of permissive hypercapnia but also to advocate the use of “therapeutic hypercapnia” through the addition of carbon dioxide (CO2) to the inspired gas. In addition to the possibility of improved outcomes due to anti-inflammatory effects, hypercapnic acidosis has effects on ventilation-perfusion matching that improve gas exchange. Therapeutic hypercapnia has previously been shown to increase arterial oxygenation by this mechanism in normal animals 7, 8 and in a sheep model of Klebsiella pneumonia 9. The only study of changes in gas exchange with permissive hypercapnia in humans with ALI showed an increase in shunt 10. This was most likely due to a reduction in tidal volume used to produce a hypercapnic acidosis than to permissive hypercapnia itself. Thus, the effects of hypercapnic acidosis on ventilation, perfusion, and their regional …
Superior vena cava syndrome caused by encapsulated pleural effusion
Authors: CL Lai, TT Tsai, SC Ko, KY Yang, RP Perng, YM Chen
Journal: European Respiratory Journal (1997)

Pleural effusion is often a manifestation of the superior vena cava (SVC) syndrome. However, pleural effusion has never been reported to be a cause of the SVC syndrome. We report the case of a 68 yr old male patient who presented with SVC syndrome and respiratory failure, both attributable to an encapsulated pleural effusion over the right upper mediastinum. Simple drainage was performed as a diagnostic and therapeutic procedure. The pleural effusion was confirmed to be a tuberculous empyema. Chest computed tomography (CT) scan is the most appropriate initial diagnostic procedure for superior vena cava syndrome.
Activating <i>FGFR2–RAS–BRAF</i> Mutations in Ameloblastoma
Authors: Noah A. Brown, Delphine Rolland, Jonathan B. McHugh, Helmut C. Weigelin, Lili Zhao, Megan S. Lim, Kojo S.J. Elenitoba-Johnson, Bryan L. Betz
Journal: Clinical Cancer Research (2014)

Ameloblastoma is an odontogenic neoplasm whose overall mutational landscape has not been well characterized. We sought to characterize pathogenic mutations in ameloblastoma and their clinical and functional significance with an emphasis on the mitogen-activated protein kinase (MAPK) pathway.A total of 84 ameloblastomas and 40 non-ameloblastoma odontogenic tumors were evaluated with a combination of BRAF V600E allele-specific PCR, VE1 immunohistochemistry, the Ion AmpliSeq Cancer Hotspot Panel, and Sanger sequencing. Efficacy of a BRAF inhibitor was evaluated in an ameloblastoma-derived cell line.Somatic, activating, and mutually exclusive RAS-BRAF and FGFR2 mutations were identified in 88% of cases. Somatic mutations in SMO, CTNNB1, PIK3CA, and SMARCB1 were also identified. BRAF V600E was the most common mutation, found in 62% of ameloblastomas and in ameloblastic fibromas/fibrodentinomas but not in other odontogenic tumors. This mutation was associated with a younger age of onset, whereas BRAF wild-type cases arose more frequently in the maxilla and showed earlier recurrences. One hundred percent concordance was observed between VE1 immunohistochemistry and molecular detection of BRAF V600E mutations. Ameloblastoma cells demonstrated constitutive MAPK pathway activation in vitro. Proliferation and MAPK activation were potently inhibited by the BRAF inhibitor vemurafenib.Our findings suggest that activating FGFR2-RAS-BRAF mutations play a critical role in the pathogenesis of most cases of ameloblastoma. Somatic mutations in SMO, CTNNB1, PIK3CA, and SMARCB1 may function as secondary mutations. BRAF V600E mutations have both diagnostic and prognostic implications. In vitro response of ameloblastoma to a BRAF inhibitor suggests a potential role for targeted therapy.
Acute mountain sickness.
Authors: J S Milledge
Journal: Thorax (1983)

Acute mountain sicknessThe lure of the mountains draws more and more people to the Himalayas and Andes each year.Climbing expeditions proliferate but it is the trek- king industry that has seen a veritable explosion of numbers in the last 12 years, especially in Nepal.Most find the experience of hiking through the grandest mountain scenery in the world rewarding, both mentally and physically.Unfortunately, some have their holidays blighted by illnesses, the most common of which are intestinal infections.But acute mountain sickness accounts for an appreciable mor- bidity amongst trekkers and in this issue the paper by Dickinson and others (p 646) reminds us of the potentially fatal nature of this condition.Acute mountain sickness is also a problem for residents of high altitude areas returning home, especially in South America, where residents of Cerro de Pasco (4300 m), for instance, can return from Lima (sea level) by road in a few hours.It is also a problem for construction and mining companies undertaking projects at high altitude and needing to send work- men up rapidly after periods of leave.The common, mild form of acute mountain sickness, sometimes called simple or, better, benign acute mountain sickness,' is well known and occurs in almost half of those undertaking the popular trek to Everest Base Camp.2It was very well described by Ravenhill in 1913.3It consists of some or all of the following symptoms: headache, nausea, anorexia, vomiting, insomnia, poor climbing performance.As the epithet benign implies, provided that the hypoxic stress is not increased by climbing to a higher altitude the condition is self limiting, usually lasting two to three days.These symptoms are, however, to be regarded as a warning sign that further ascent is ill advised because of the possible development of one of the malignant forms of acute mountain sickness-that is, pulmonary (acute pulmonary oedema of high altitude) or cerebral (cerebral oedema of high altitude), or a mixture of the two.The onset of pulmonary acute mountain sick- ness is indicated by the development of breathless-
Transmission of &lt;EMPH TYPE="ITAL"&gt;Mycobacterium tuberculosis&lt;/EMPH&gt; From Medical Waste
Authors: K R Johnson, C R Braden, K L Cairns, K W Field, A C Colombel, Z Yang, C L Woodley, G P Morlock, A M Weber, A Y Boudreau, T A Bell, I M Onorato, S E Valway, P A Stehr-Green
Journal: JAMA (2000)

ContextWashington State has a relatively low incidence rate of tuberculosis (TB) infection. However, from May to September 1997, 3 cases of pulmonary TB were reported among medical waste treatment workers at 1 facility in Washington. There is no previous documentation of Mycobacterium tuberculosis transmission as a result of processing medical waste.ObjectiveTo identify the source(s) of these 3 TB infections.Design, Setting, and ParticipantsInterviews of the 3 infected patient-workers and their contacts, review of patient-worker medical records and the state TB registry, and collection of all multidrug-resistant TB (MDR-TB) isolates identified after January 1, 1995, from the facility's catchment area; DNA fingerprinting of all isolates; polymerase chain reaction and automated DNA sequencing to determine genetic mutations associated with drug resistance; and occupational safety and environmental evaluations of the facility.Main Outcome MeasuresPrevious exposures of patient-workers to TB; verification of patient-worker tuberculin skin test histories; identification of other cases of TB in the community and at the facility; drug susceptibility of patient-worker isolates; and potential for worker exposure to live M tuberculosis cultures.ResultsAll 3 patient-workers were younger than 55 years, were born in the United States, and reported no known exposures to TB. We did not identify other TB cases. The 3 patient-workers' isolates had different DNA fingerprints. One of 10 MDR-TB catchment-area isolates matched an MDR-TB patient-worker isolate by DNA fingerprint pattern. DNA sequencing demonstrated the same rare mutation in these isolates. There was no evidence of personal contact between these 2 individuals. The laboratory that initially processed the matching isolate sent contaminated waste to the treatment facility. The facility accepted contaminated medical waste where it was shredded, blown, compacted, and finally deactivated. Equipment failures, insufficient employee training, and respiratory protective equipment inadequacies were identified at the facility.ConclusionProcessing contaminated medical waste resulted in transmission of M tuberculosis to at least 1 medical waste treatment facility worker.
Proteinases of Pseudomonas aeruginosa evoke mucin release by tracheal epithelium.
Authors: J D Klinger, B Tandler, C M Liedtke, T F Boat
Journal: Journal of Clinical Investigation (1984)

We have determined the potential of exoproducts from pathogenic bacteria to stimulate the release of high molecular weight mucins from goblet cells of airway epithelium in a rabbit tracheal explant system. Culture supernatants from proteolytic strains of Pseudomonas aeruginosa and Serratia marcescens, but not supernatants from a number of non-proteolytic strains, released mucins from goblet cells. Highly purified elastase and alkaline proteinase from P. aeruginosa stimulated goblet cell mucin release in a dose-dependent fashion. Lipopolysaccharide, exotoxin A, and alginate of P. aeruginosa did not possess mucin release properties. Proteolytic activity was required for mucin release by P. aeruginosa elastase, but such release in goblet cells was not mediated by cyclic AMP. Morphologic studies suggested rapid release of mucins from goblet cells was response to elastase by a process resembling apocrine secretion. Several nonbacterial proteinases mimicked the effect of Pseudomonas proteases. These studies provide support for the hypothesis that bacterial and other play a role in the pathogenesis of mucus hypersecretion in acute and chronic lung infections.
Pneumococcal antibody levels after pneumovax in patients with rheumatoid arthritis on methotrexate
Authors: E. Coulson, V. Saravanan, J. Hamilton, K. S. Long, L. Morgan, C. Heycock, M. Rynne, C. Kelly
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Introduction</h3> Immunisation against pneumococcus has been shown to reduce pneumonia in rheumatoid arthritis (RA). There is concern that methotrexate may reduce its efficacy. There are very few objective data on the effect of methotrexate on the efficacy of pneumococcal vaccination with pneumovax, and no objective evidence on whether revaccination is necessary in RA patients on methotrexate. <h3>Methods</h3> The authors collected information from 180 RA patients on methotrexate relating to their vaccination status and assayed their pneumococcal antibody levels. Data on pulmonary infection were retrieved in the same patients over the preceding decade. <h3>Results</h3> Full data were available for 152 patients, of whom 28 had never been vaccinated against pneumococcus. Median levels were significantly higher in those who had been vaccinated. Unvaccinated patients and those taking oral prednisone were more likely to have had pneumonia in the previous 10 years. The RR for developing pneumonia among non-vaccinated patients was 9.7 (p=0.005) and among steroid-treated patients was 6.5 (p=0.001), after adjusting for age, gender, disease duration and comorbidity. No significant correlation was found between pneumococcal antibody levels and time since vaccination. <h3>Conclusions</h3> This study suggests that a single administration of pneumovax early in RA offers up to 10 years protection against the development of pneumococcal pneumonia in RA patients on methotrexate.
Hitchhiking nanoparticles: Reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes
Authors: Laura Wayteck, Heleen Dewitte, Lynn De Backer, Karine Breckpot, Jo Demeester, Stefaan C. De Smedt, Koen Raemdonck
Journal: Biomaterials (2015)
The effect of high parathyroid hormone levels on the development of aluminum-induced osteomalacia in the rat.
Authors: A J Felsenfeld, L Machado, M Rodriguez
Journal: Journal of the American Society of Nephrology (1991)

A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat.
Missed Opportunities: Racial Disparities in Adjuvant Breast Cancer Treatment
Authors: Nina A. Bickell, Jason J. Wang, Soji Oluwole, Deborah Schrag, Henry Godfrey, Karen Hiotis, Jane Mendez, Amber A. Guth
Journal: Journal of Clinical Oncology (2006)

Purpose Underuse of adjuvant therapy is a potentially important and remediable explanation for the inferior survival of minority women with breast cancer. We sought to measure a racial disparity in the underuse of adjuvant treatments for early-stage breast cancer and to identify associated factors. Methods Cross-sectional study with review of all inpatient and outpatient medical records of 677 women treated surgically for a primary American Joint Committee on Cancer stage I or II breast cancer in 1999 to 2000. Underuse was defined as omissions of radiation therapy after breast-conserving surgery, adjuvant chemotherapy after resection of hormone-receptor-negative tumors ≥ 1 cm, or hormonal therapy for receptor-positive tumors ≥ 1 cm. Results One hundred forty-five (21%) of 677 women experienced underuse of appropriate adjuvant therapy: 16% in whites, 34% in blacks, and 23% in Hispanics (P &lt; .001). Women referred to medical oncologists were less likely to experience underuse of necessary adjuvant treatments (relative risk [RR] for underuse = 0.2; 95% CI, 0.1 to 0.3). Women who were minorities (RR = 2.0; 95% CI, 1.3 to 3.1), had higher levels of comorbidity (RR = 1.4; 95% CI, 1.1 to 1.8) and lacked insurance (RR = 1.9; 95% CI, 0.9 to 4.0) were at greater risk for underuse. Conclusion Minority women with early-stage breast cancer have double the risk of white women for failing to receive necessary adjuvant treatments despite rates of oncologic consultation similar to those for white women. Oncology referrals are necessary to reduce treatment disparities but are not sufficient to ensure patients' receipt of efficacious adjuvant treatment.
Lens Epithelium-Derived Growth Factor Is an Hsp70-2 Regulated Guardian of Lysosomal Stability in Human Cancer
Authors: Mads Daugaard, Thomas Kirkegaard-Sørensen, Marie Stampe Ostenfeld, Mads Aaboe, Maria Høyer-Hansen, Torben Falck Ørntoft, Mikkel Rohde, Marja Jäättelä
Journal: Cancer Research (2007)

Abstract Heat shock protein 70-2 (Hsp70-2) is a chaperone protein essential for the growth of spermatocytes and cancer cells. Here, we show that Hsp70-2 depletion triggers lysosomal membrane permeabilization and cathepsin-dependent cell death and identify lens epithelium-derived growth factor (LEDGF) as an Hsp70-2–regulated guardian of lysosomal stability in human cancer. Knockdown of LEDGF in cancer cells induces destabilization of lysosomal membranes followed by caspase-independent and Bcl-2–resistant cell death. Accordingly, ectopic LEDGF stabilizes lysosomes and protects cancer cells against cytotoxicity induced by anticancer agents that trigger the lysosomal cell death pathway. Remarkably, ectopic LEDGF also increases the tumorigenic potential of human cancer cells in immunodeficient mice, and LEDGF expression is increased in human breast and bladder carcinomas correlating with that of Hsp70-2 in invasive bladder cancer. Taken together, these data reveal LEDGF as an oncogenic protein that controls a caspase-independent lysosomal cell death pathway. [Cancer Res 2007;67(6):2559–67]
Case of Congenital Multilocular Cyst of the Abdominal Wall
Authors: A. M. Anderson
Journal: BMJ (1879)

15~~~~~~~ their colour and distinctness, the position of some being marked only by a purple discoloration of the skin.A shows the general appearance of the affected limbs.B represents the fully developed spot on the inside of the left thigh; and is of life-size.C and D, also of life-size, exhibit the earliest and the half-formed stage of the eruption respectively.