tbuckley/cabot-search huggingface dataset:
PAX5 Expression in Acute Leukemias
Authors: Enrico Tiacci, Stefano Pileri, Annette Orleth, Roberta Pacini, Alessia Tabarrini, Federica Frenguelli, Arcangelo Liso, Daniela Diverio, Francesco Lo-Coco, Brunangelo Falini
Journal: Cancer Research (2004)

Abstract The transcription factor PAX5 plays a key role in the commitment of hematopoietic precursors to the B-cell lineage, but its expression in acute leukemias has not been thoroughly investigated. Hereby, we analyzed routine biopsies from 360 acute leukemias of lymphoid (ALLs) and myeloid (AMLs) origin with a specific anti-PAX5 monoclonal antibody. Blasts from 150 B-cell ALLs showed strong PAX5 nuclear expression, paralleling that of CD79a in the cytoplasm. Conversely, PAX5 was not detected in 50 T-cell ALLs, including 20 cases aberrantly coexpressing CD79a. Among 160 cytogenetically/molecularly characterized AMLs, PAX5 was selectively detected in 15 of 42 cases bearing the t(8;21)/AML1-ETO rearrangement. Real-time reverse transcription-PCR studies in t(8;21)-AML showed a similar up-regulation of PAX5 transcript in all of the 8 tested samples (including 4 cases that were negative at anti-PAX5 immunostaining), suggesting that PAX5 is expressed in t(8;21)-AML more widely than shown by immunohistochemistry. Interestingly, PAX5+ t(8;21)-AML also expressed CD79a and/or CD19 (major transcriptional targets of PAX5 in B-cells) in 10 of 12 evaluable cases. Our results indicate that PAX5 is a more specific marker than CD79a for B-cell ALL diagnosis. Moreover, among AMLs, PAX5 expression selectively clusters with t(8;21), allowing its immunohistochemical recognition in a proportion of cases, and likely explaining a peculiar biological feature of this subset of myeloid leukemias, i.e. the aberrant expression of B-cell genes.
Dying of lung cancer or cardiac failure: prospective qualitative interview study of patients and their carers in the community
Authors: S. A Murray
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To compare the illness trajectories, needs, and service use of patients with cancer and those with advanced non-malignant disease. <b>Design:</b> Qualitative interviews every three months for up to one year with patients, their carers, and key professional carers. Two multidisciplinary focus groups. <b>Setting:</b> Community based. <b>Participants:</b> 20 patients with inoperable lung cancer and 20 patients with advanced cardiac failure and their main informal and professional carers. <b>Main outcome measures:</b> Perspectives of patients and carers about their needs and available services. <b>Results:</b> 219 qualitative interviews were carried out. Patients with cardiac failure had a different illness trajectory from the more linear and predictable course of patients with lung cancer. Patients with cardiac failure also had less information about and poorer understanding of their condition and prognosis and were less involved in decision making. The prime concern of patients with lung cancer and their carers was facing death. Frustration, progressive losses, social isolation, and the stress of balancing and monitoring a complex medication regimen dominated the lives of patients with cardiac failure. More health and social services including financial benefits were available to those with lung cancer, although they were not always used effectively. Cardiac patients received less health, social, and palliative care services, and care was often poorly coordinated. <b>Conclusions:</b> Care for people with advanced progressive illnesses is currently prioritised by diagnosis rather than need. End of life care for patients with advanced cardiac failure and other non-malignant diseases should be proactive and designed to meet their specific needs.
Identification of a Forskolin-Like Molecule in Human Renal Cysts
Authors: William C. Putnam, Sarah M. Swenson, Gail A. Reif, Darren P. Wallace, George M. Helmkamp, Jared J. Grantham
Journal: Journal of the American Society of Nephrology (2007)

Renal cyst enlargement is increased by adenosine cAMP, which is produced within mural epithelial cells. In a search for modulators of cAMP synthesis cyst fluids from 18 patients with autosomal dominant or recessive polycystic kidney disease (PKD) were analyzed, and in 15 of them, a stable lipophilic molecule that increased cAMP levels, stimulated transepithelial chloride and fluid secretion, and promoted the proliferation of human cyst epithelial cells was characterized. With the use of HPLC-mass spectrometry, a bioactive lipid with the same mass spectral fingerprint, the same chromatographic retention time, and the same biologic properties as forskolin, a widely known, potent adenylyl cyclase agonist, has been isolated and identified within the cyst fluid. Forskolin is synthesized by the plant Coleus forskohlii, but its appearance or compounds like it have not been reported in animals. The origin of forskolin in patients with PKD was not revealed by this study. Synthesis by mural cyst epithelial cells or an exogenous source are the most likely possibilities. Forskolin is sold for weight management and as a cardiovascular tonic in health stores and through the Worldwide Web. It is concluded that forskolin may have a role in promoting the enlargement of cysts in autosomal dominant PKD and recommended that patients avoid oral and parenteral preparations that contain this compound.
Antibiotic-resistant Propionibacteria acnes may not be the major issue clinically or microbiologically in acne
Authors: C.N. Burkhart, C.G. Burkhart
Journal: British Journal of Dermatology (2003)

Journal Article Antibiotic‐resistant Propionibacteria acnes may not be the major issue clinically or microbiologically in acne Get access C.N. Burkhart, C.N. Burkhart Departments of Microbiology and Immunology, and E‐mail: cburkhart@mco.edu Search for other works by this author on: Oxford Academic Google Scholar C.G. Burkhart C.G. Burkhart Medicine (Dermatology), Medical College of Ohio, 5600 Monroe Street, Suite 106B Sylvania, OH 43623 US.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 2, 1 February 2003, Pages 365–366, https://doi.org/10.1046/j.1365-2133.2003.05097_3.x Published: 01 February 2003
Eradication of Helicobacter pylori After Endoscopic Resection of Gastric Tumors Does Not Reduce Incidence of Metachronous Gastric Carcinoma
Authors: Jeongmin Choi, Sang Gyun Kim, Hyuk Yoon, Jong Pil Im, Joo Sung Kim, Woo Ho Kim, Hyun Chae Jung
Journal: Clinical Gastroenterology and Hepatology (2013)
Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials
Authors: K. Chen, J.C. Craig, S. Shumack
Journal: British Journal of Dermatology (2005)

Background The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest. Objectives The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population. Methods Three electronic databases were searched for relevant trials: MEDLINE (1966–October 2003), EMBASE (1980–week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review. Results Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up. Conclusions The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk–benefit ratio.
Factors influencing the occurrence of airway hyperreactivity in the general population: the importance of atopy and airway calibre
Authors: J Britton, I Pavord, K Richards, A Knox, A Wisniewski, I Wahedna, W Kinnear, A Tattersfield, S Weiss
Journal: European Respiratory Journal (1994)

The factors that determine the occurrence of airway hyperreactivity in the general population are not clearly understood. This study was designed to assess the independent effects of age, atopy, smoking and airway calibre. In a random sample of 2,415 adults aged 18-70 yrs we measured reactivity to methacholine as the dose provoking a 20% fall (PD20) in one-second forced expiratory volume (FEV1), atopy as the mean skin wheal response to three common environmental allergens, and airway calibre as the baseline FEV1 in absolute terms, as percent predicted (FEV1 % predicted) and as percent forced vital capacity (FEV1 % FVC). Hyperreactivity, defined as a PD20 < or = 12.25 mumol, was present in 314 (13%) of the sample, and before adjustment for FEV1 was more common in females (independent odds ratio (OR) = 2.05 (95% confidence interval 1.6-2.7)), current smokers (OR = 1.89 (1.3-2.6)), atopics (OR = 1.39 (1.3-1.5) per mm skin wheal), and in older age groups (OR for age 60-70 yrs relative to 18-29 yrs = 2.70 (1.7-4.3)). However, the odds of hyperreactivity were also strongly and independently related to absolute FEV1 (OR = 0.46 (0.27-0.77) per litre), FEV1 % predicted (OR = 0.96 (0.94-0.98) per percent), and FEV1 % FVC (OR = 0.92 (0.90-0.94) per percent; combined chi-square on 3 df = 312, p << 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing
Authors: Harikrishnan K N, Maggie Z Chow, Emma K Baker, Sharmistha Pal, Sahar Bassal, Daniella Brasacchio, Li Wang, Jeff M Craig, Peter L Jones, Saïd Sif, Assam El-Osta
Journal: Nature Genetics (2005)
Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides.
Authors: M R Bennett, S Anglin, J R McEwan, R Jagoe, A C Newby, G I Evan
Journal: Journal of Clinical Investigation (1994)

Restenosis after angioplasty is due predominantly to accumulation of vascular smooth muscle cells (VSMCs). The resistance of restenosis to pharmacological treatment has prompted investigation of genes involved in VSMC proliferation. We have examined the effect on VSMC proliferation of blocking expression of the c-myc proto-oncogene with antisense oligodeoxynucleotides, both in vitro and in a rat carotid artery injury model of angioplasty restenosis. Antisense c-myc oligodeoxynucleotides reduced average cell levels of c-myc mRNA and protein by 50-55% and inhibited proliferation of VSMCs when mitogenically stimulated from quiescence or when proliferating logarithmically (IC50 = 10 micrograms/ml). Corresponding sense c-myc, two-base-pair mismatch antisense c-myc, antisense alpha-actin or glyceraldehyde phosphate dehydrogenase oligodeoxynucleotides did not suppress c-myc expression or inhibit VSMC proliferation. Antisense c-myc inhibition was relieved by overexpression of an exogenous c-myc gene. After balloon catheter injury, peak c-myc mRNA expression occurred at 2 h. Antisense c-myc applied in a pluronic gel to the arterial adventitia reduced peak c-myc expression by 75% and significantly reduced neointimal formation at 14 d, compared with sense c-myc and gel application alone. We conclude that c-myc expression is required for VSMC proliferation in vitro and in the vessel wall. C-myc is a therefore a potential target for adjunctive therapy to reduce angioplasty restenosis.
Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome
Authors: Joost P.H. Drenth, Laurence Cuisset, Gilles Grateau, Christian Vasseur, Saskia D. van de Velde-Visser, Jan G.N. de Jong, Jacques S. Beckmann, Jos W.M. van der Meer, Marc Delpech & contributing members of t
Journal: Nature Genetics (1999)
The gastric secretory response to insulin: an `all-or-none' phenomenon?
Authors: J. Spencer, M. I. Grossman
Journal: Gut (1971)

Dogs were prepared with Pavlov pouches which could be perfused with saline so as to detect rapidly changes occurring in acid secretion. Dose-response studies were performed by the intravenous injection of insulin (0·06, 0·12, 0·25, 0·5, or 1·0 unit/kg). Both the magnitude of peak response and the duration of response were dose-related and both were related to the magnitude of fall in plasma glucose. These results are not consistent with an `all-or-none9 hypothesis for insulin-stimulated gastric acid secretion, but favour the alternative hypothesis that insulin provides a graded glycopenic stimulus producing a graded secretory response.
Increased osteoclast formation and activity by peripheral blood mononuclear cells in chronic liver disease patients with osteopenia
Authors: Brenda J. Olivier, Ton Schoenmaker, Reina E. Mebius, Vincent Everts, Chris J. Mulder, Karin M. J. van Nieuwkerk, Teun J. de Vries, Schalk W. van der Merwe
Journal: Hepatology (2007)

Osteoporosis is a common complication of chronic liver disease, and the underlying mechanisms are not understood. We aimed to determine if osteoclasts develop from osteoclast precursors in peripheral blood mononuclear cells (PBMCs) of chronic liver disease patients with osteopenia compared with controls. PBMCs were isolated and fluorescence-activated cell sorting was performed to quantify the activated T lymphocyte population and receptor activator of nuclear factor κβ ligand (RANKL) expression. The activated T lymphocyte populations were comparable for all 3 groups, and RANKL was not detectable. The percentage of CD14+CD11b+ cells containing osteoclast precursors was comparable between the 3 groups. To assess the formation and functional activity of osteoclasts formed from circulating mononuclear cells, PBMCs were cultured (1) without addition of cytokines, (2) with macrophage colony-stimulating factor (M-CSF), (3) with M-CSF and osteoprotegerin, and (4) with M-CSF and RANKL. The number of tartrate-resistant acid phosphatase-positive multinucleated cells and bone resorption was assessed. PBMCs from chronic liver disease patients with osteopenia formed more osteoclast-like cells, which, when cultured in the presence of M-CSF and RANKL resorbed more bone than controls. The number of osteoclast-like cells and the amount of bone resorption correlated with lumbar bone densities. Addition of M-CSF increased numbers of osteoclast-like cells formed in healthy controls; however, this was not observed in either of the chronic liver disease groups. Plasma levels of M-CSF were elevated in both patient groups compared with healthy controls. Conclusion: Circulating mononuclear cells from chronic liver disease patients with osteopenia have a higher capacity to become osteoclasts than healthy controls or chronic liver disease patients without osteopenia. This could partially be due to priming with higher levels of M-CSF in the circulation. (Hepatology 2007.)
Effect of Cyclin D1 Overexpression on Drug Sensitivity in a Human Fibrosarcoma Cell Line
Authors: D. Hochhauser, B. Schnieders, E. Ercikan-Abali, R. Gorlick, R. Muise-Helmericks, W.-W. Li, J. Fan, D. Banerjee, J. R. Bertino
Journal: JNCI Journal of the National Cancer Institute (1996)

Background Alterations in the expression of genes that control the cell cycle may be of critical importance in determining the sensitivity of cells and tumors to drugs (chemosensitivity) and radiation. Mutations and deletions of the p53 tumor suppressor gene in cell lines and tumors are associated with resistance to a variety of DNA-damaging agents. The effects of alterations in the cyclin genes and their products on drug action have not been studied. One of these genes, cyclin D1, is expressed in early G 1 phase, and its protein product, together with the cyclin-dependent kinases CDK4 and CDK6, mediates the phosphorylation and functional inactivation of the retinoblastoma protein (pRb). Elevated levels of expression of cyclin D1 protein have been found in a variety of cancers, including breast cancer, head and neck cancer, non-small-cell lung cancer, and mantle cell lymphomas.
A functional role of Stat3 in in vivo megakaryopoiesis
Authors: Keita Kirito, Masatake Osawa, Haruhiko Morita, Ritsuko Shimizu, Masayuki Yamamoto, Atsushi Oda, Hiroyoshi Fujita, Masaru Tanaka, Koichi Nakajima, Yasusada Miura, Keiya Ozawa, Norio Komatsu
Journal: Blood (2002)
Differential Inhibition of HSP72 and HSP25 Produces Profound Impairment of Cellular Integrity
Authors: Michael Riordan, Vivek Garg, Gunilla Thulin, Michael Kashgarian, Norman J. Siegel
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. To test a putative cause and effect relationship between heat-shock protein (HSP) expression and response to renal cell injury, HSP72 and HSP25 were differentially inhibited in LLC-PK1 cells by means of transcription factor decoy and short interference RNA (siRNA). Cellular injury was assessed by solubilization of NaK ATPase (S-NaK). An exonuclease-resistant, ethylene glycol–bridged, circular oligonucleotide decoy for heat-shock transcription factor (HSF)-1, based on the sequence of the porcine heat-shock element, was constructed and validated. It was found that under all experimental conditions, cells had comparable ATP levels; that decoy of unligated or scrambled sequence was ineffective; that HSP72 mRNA and HSP72/HSP25 proteins were significantly reduced in decoy-treated cells; and that the dampened response to HSF activation in decoy-treated, injured cells was accompanied by a substantially amplified loss of cellular integrity (S-NaK was 85% compared with baseline levels). Specific inhibition of HSP72 that used siRNA directed against an inducible porcine HSP72 gene resulted in complete ablation of injury-induced HSP72. Isolated inhibition of HSP72 was also associated with marked NaK ATPase detachment from the cytoskeleton (S-NaK was 135% compared with baseline levels). These studies suggest that an HSF-1 decoy effectively dampens the HSP72/HSP25 response to injury in renal cells; that HSP72 siRNA ablates injury-induced induction of HSP72; and that dampening of the HSP72/HSP25 response and ablation of the HSP72 response are both associated with impaired restitution of cellular polarity.
Valproic acid causes dose- and time-dependent changes in nuclear structure in prostate cancer cells in vitro and in vivo
Authors: Madeleine Kortenhorst, Sumit Isharwal, Paul van Diest, Wasim Chowdhury, Cameron Marlow, Michael Carducci, Ronald Rodriguez, Robert Veltri
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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INTRODUCTION Histone deacetylase inhibitors such as valproic acid (VPA) are promising anti-cancer agents that change the acetylation status of histone tails and loosen the chromatin structure by virtue of their ionic charge. Recent literature has shown that quantitative analysis of nuclear morphometric descriptors (NMDs) can be of additive value in staging occult pathologic disease and predicting recurrence. The aim of this study was to investigate whether VPA treatment in prostate cancer results in measurable chromosomal rearrangements that can be assessed with NMDs and used as a biomarker for treatment.    METHODS AND RESULTS To study nuclear morphometric changes of prostate cancer in response to VPA, (PCa) cell lines LNCaP, CWR22R, DU145 and PC3, in vitro and in vivo tissue microarrays (TMAs) were constructed. The in vitro TMA consisted of formalin fixed paraffin embedded (FFPE) PCa cell plugs treated for 3, 7 and 14 days with 0, 0.6 and 1.2 mM VPA; the in vivo TMA consisted of cores from FFPE PCa xenografts from nude mice treated for 30 days with 0.2% or 0.4% VPA in drinking water. In addition, liver and kidney tissue of these mice were included in the TMA. DNA was labeled with Feulgen stain prior to measurement of the 40 NMDs using the Nikon CoolScope Virtual Slide pathology suite. Using logistic regression analysis of at least 200 nuclei per treatment arm; two sets of 7 NMDs were chosen to compare the NMD data of control and treated in vitro and in vivo nuclei. Both sets included descriptors of size and shape, texture, and DNA content.    Depending on type of PCa cell line, the area under the ROC curves (treatment vs controls) ranged between 0.6-0.9 and was dose-dependent both in vitro and in vivo. Analysis of in vitro cells showed that the differences were also time-dependent. Analysis of the liver and kidney tissue showed that HDACI treatment also marginally affects nuclear morphometry in these (drug) filtering organs.    CONCLUSION In vitro and in vivo treatment of PCa cell lines with HDACI VPA results in significant changes in nuclear structure that are time-and dose dependent. The in vitro and in vivo NMD sets are not identical, likely reflecting differences in the tissue local microenvironment. HDACI VPA also affects nuclear morphometry in mouse liver and kidney tissue which likely reflects a normal physiological response.
Clinical trials in ovarian carcinoma: requirements for standard approaches and regimens
Authors: T. Thigpen, G. Stuart, A. du Bois, M. Friedlander, K. Fujiwara, J.P. Guastalla, S. Kaye, H. Kitchener, G. Kristensen, R. Mannel, W. Meier, B. Miller, A. Poveda, D. Provencher, F. Stehman, I. Vergote
Journal: Annals of Oncology (2005)