tbuckley/cabot-search huggingface dataset:
Factors that affect the occurrence of fumonisin.
Authors: J D Miller
Journal: Environmental Health Perspectives (2001)

The two important Fusarium ear rots of corn, Gibberella ear rot (Fusarium graminearum, formally F. moniliforme and allied species) and Fusarium ear rot (F. verticillioides and allied species) grow under different environmental conditions. F. graminearum grows well only between 26 and 28 degrees C and requires rain both at silking and during disease progression. F. verticillioides grows well at higher temperatures, and ear rot and fumonisin accumulation are associated with drought and insect stress and growing hybrids outside their areas of adaptation. In southern Transkei, where esophageal cancer has been associated with the consumption of F. verticillioides and fumonisin-contaminated corn, environmental conditions favor this fungus in most years. In the nearby areas where the soils, crops, food consumption, and populations are the same and where esophageal cancer is low, temperatures are cooler and F. graminearum is favored. Although F. verticillioides is associated with a disease of corn, it may be that this fungus is a mutualistic endophyte of the plant. Perhaps because of this, breeding for resistance to Fusarium ear rot has produced inconclusive results to date. The best available strategies for reducing the risk of fumonisin contents of maize are to ensure that hybrids are adapted to the environment and to limit drought stress and insect herbivory. It may also be necessary to make use of alternative strategies such as producing hybrids that contain enzymes to degrade fumonisin as it is produced.
Rheumatology at the general practitioner/hospital interface: a study of prevalence and access to specialist care.
Authors: F M Sullivan, J H Barber, R D Sturrock
Journal: Annals of the Rheumatic Diseases (1990)

Four general practices with a combined population of 23,300 in the west of Scotland participated in a record research and questionnaire assessment of 551 patients with rheumatic diseases. The study describes the prevalence, levels of disability found, and the types of service used. Even with this number of patients it was not possible to detect any significant differences in disability levels, use of second line drugs, or aids/appliances when comparing practices with adequate or inadequate access to rheumatological facilities (general practitioner perception). General practice is an appropriate setting in which to investigate the effect of service provision, but larger studies will be needed to reach more definite conclusions.
Identification of HLA-A2- or HLA-A24-Restricted CTL Epitopes Possibly Useful for Glypican-3-Specific Immunotherapy of Hepatocellular Carcinoma
Authors: Hiroyuki Komori, Tetsuya Nakatsura, Satoru Senju, Yoshihiro Yoshitake, Yutaka Motomura, Yoshiaki Ikuta, Daiki Fukuma, Kazunori Yokomine, Michiko Harao, Toru Beppu, Masanori Matsui, Toshihiko Torigoe, Noriyuki Sato, Hideo Baba, Yasuharu Nishimura
Journal: Clinical Cancer Research (2006)

Abstract Purpose and Experimental Design: We previously reported that glypican-3 (GPC3) was overexpressed, specifically in hepatocellular carcinoma (HCC) and melanoma in humans, and it was useful as a novel tumor marker. We also reported that the preimmunization of BALB/c mice with dendritic cells pulsed with the H-2Kd-restricted mouse GPC3298-306 (EYILSLEEL) peptide prevented the growth of tumor-expressing mouse GPC3. Because of similarities in the peptide binding motifs between H-2Kd and HLA-A24 (A*2402), the GPC3298-306 peptide therefore seemed to be useful for the immunotherapy of HLA-A24+ patients with HCC and melanoma. In this report, we investigated whether the GPC3298-306 peptide could induce GPC3-reactive CTLs from the peripheral blood mononuclear cells (PBMC) of HLA-A24 (A*2402)+ HCC patients. In addition, we used HLA-A2.1 (HHD) transgenic mice to identify the HLA-A2 (A*0201)–restricted GPC3 epitopes to expand the applications of GPC3-based immunotherapy to the HLA-A2+ HCC patients. Results: We found that the GPC3144-152 (FVGEFFTDV) peptide could induce peptide-reactive CTLs in HLA-A2.1 (HHD) transgenic mice without inducing autoimmunity. In five out of eight HLA-A2+ GPC3+ HCC patients, the GPC3144-152 peptide-reactive CTLs were generated from PBMCs by in vitro stimulation with the peptide and the GPC3298-306 peptide-reactive CTLs were also generated from PBMCs in four of six HLA-A24+ GPC3+ HCC patients. The inoculation of these CTLs reduced the human HCC tumor mass implanted into nonobese diabetic/severe combined immunodeficiency mice. Conclusion: Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for a large number of HCC patients.
Transfer to Sulphonylurea Therapy in Adult Subjects With Permanent Neonatal Diabetes Due to <i>KCNJ11</i>-Activating Mutations
Authors: Maciej T. Malecki, Jan Skupien, Tomasz Klupa, Krzysztof Wanic, Wojciech Mlynarski, Agnieszka Gach, Iwona Solecka, Jacek Sieradzki
Journal: Diabetes Care (2006)

Activating mutations in the KCJN11 gene encoding in the ATP-sensitive K+ channel (KATP channel) subunit Kir6.2 were reported (1) as the most common cause of permanent neonatal diabetes (PND). Recently, it has been shown that most subjects with Kir6.2 mutations could be switched from insulin to sulfonylurea and that such treatment is both safe and highly effective, at least in the short term (2,3). Notably, the majority of reported successfully transferred patients were children. Data on adults are very scarce, and there are few mutation carriers transferred off insulin (2,4). Moreover, some adult subjects are unable to switch from insulin to sulfonylurea (2).

We have recently identified four adult carriers of a Kir6.2 mutation and provided evidence that they, before the sulfonylurea exposure, were characterized by decreased insulin sensitivity (5). Here, we report their successful transfer to sulfonylurea.

To dissect the genetic background of PND in Poland, the Nationwide Registry has recently been established. Four adult subjects with Kir6.2-activating mutations were identified by the end of 2005. Three subjects carried the R210H mutation, while one individual had the K170N substitution. They were included in the current project, which aimed to switch from insulin to sulfonylurea and to assess, by hyperinsulinemic-euglycemic clamp, whether the alteration in insulin action occurs after this transfer. The study protocol and informed-consent procedures were approved by the ethics committee of Jagiellonian University. The project was conducted according to the …
No Plateau for HIV/AIDS Epidemic in US Women
Authors: Pat Phillips
Journal: JAMA (1997)

TWO MAJOR messages emerged from the third National Conference on Women and HIV, held last month in Pasadena, Calif: Women have become the fastest-increasing new group of AIDS patients in the United States, and they as a group are being overlooked. The acquired immunodeficiency syndrome has become the third leading cause of death among women in the 25- to 44-year-old age group, and the disease ranks first as cause of death among African-American women in that group. See also p 1752. According to the Centers for Disease Control and Prevention (CDC), Atlanta, Ga, in the first 2 quarters of 1996, the estimated number of AIDS deaths was 13% lower than the estimated number of AIDS deaths in 1995. Deaths declined in men by 15% but increased among women by 3%. Earlier in the US epidemic, in 1985, women accounted for only 7% of cases; while in 1996, the percentage of
<i>EDNRB</i> and <i>DCC</i> Salivary Rinse Hypermethylation Has a Similar Performance as Expert Clinical Examination in Discrimination of Oral Cancer/Dysplasia versus Benign Lesions
Authors: Juliana Schussel, Xian Chong Zhou, Zhe Zhang, Kavita Pattani, Francisco Bermudez, Germain Jean-Charles, Thomas McCaffrey, Tapan Padhya, Joan Phelan, Silvia Spivakovsky, Mariana Brait, Ryan Li, Helen Yoo Bowne, Judith D. Goldberg, Linda Rolnitzky, Miriam Robbins, A. Ross Kerr, David Sirois, Joseph A. Califano
Journal: Clinical Cancer Research (2013)

Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy.Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR.HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95% CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76).EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.
A simple method for assessing intestinal inflammation in Crohn's disease
Authors: J Tibble
Journal: Gut (2000)

<h3>BACKGROUND AND AIMS</h3> Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn9s disease and those with irritable bowel syndrome. <h3>METHODS</h3> The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn9s disease (35 studies) by comparing faecal excretions and concentrations using four day faecal excretion of<sup>111</sup>indium white cells. A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn9s disease (n=116). A prospective study assessed the value of faecal calprotectin in discriminating between patients with Crohn9s disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic. <h3>RESULTS</h3> Four day faecal excretion of <sup>111</sup>indium (median 8.7%; 95% confidence interval (CI) 7–17%; normal &lt;1.0%) correlated significantly (p&lt;0.0001) with daily (median ranged from 39 to 47 mg; normal &lt;3 mg; <i>r</i>=0.76–0.82) and four day faecal calprotectin excretion (median 101 mg; 95% CI 45–168 mg; normal &lt;11 mg; <i>r</i>=0.80) and single stool calprotectin concentrations (median 118 mg/l; 95% CI 36–175 mg/l; normal &lt;10 mg/l; <i>r</i>=0.70) in patients with Crohn9s disease. The cross sectional study showed a sensitivity of 96% for calprotectin in discriminating between normal subjects (2 mg/l; 95% CI 2–3 mg/l) and those with Crohn9s disease (91 mg/l; 95% CI 59–105 mg/l). With a cut off point of 30 mg/l faecal calprotectin has 100% sensitivity and 97% specificity in discriminating between active Crohn9s disease and irritable bowel syndrome. <h3>CONCLUSION</h3> The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn9s disease and irritable bowel syndrome.
Prioritizing causal disease genes using unbiased genomic features
Authors: Rahul C Deo, Gabriel Musso, Murat Tasan, Paul Tang, Annie Poon, Christiana Yuan, Janine F Felix, Ramachandran S Vasan, Rameen Beroukhim, Teresa De Marco, Pui-Yan Kwok, Calum A MacRae, Frederick P Roth
Journal: Genome biology (2014)

Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits.
A Phase I Trial and Pharmacokinetic Study of Sorafenib in Children with Refractory Solid Tumors or Leukemias: A Children's Oncology Group Phase I Consortium Report
Authors: Brigitte C. Widemann, AeRang Kim, Elizabeth Fox, Sylvain Baruchel, Peter C. Adamson, Ashish M. Ingle, Julia Glade Bender, Michael Burke, Brenda Weigel, Diana Stempak, Frank M. Balis, Susan M. Blaney
Journal: Clinical Cancer Research (2012)

To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with refractory extracranial solid tumors and evaluate the tolerability of the solid tumor MTD in children with refractory leukemias.Sorafenib was administered orally every 12 hours for consecutive 28-day cycles. Pharmacokinetics (day 1 and steady-state) and pharmacodynamics were conducted during cycle 1.Of 65 patients enrolled, 60 were eligible. In the solid tumor cohort (n = 49), 4 of 6 patients experienced a DLT [hypertension, pain, rash/urticaria, thrombocytopenia, alanine aminotransferase (ALT)/aspartate aminotransferase (AST)] at the starting dose (150 mg/m(2)/dose) which resulted in de-escalation to 105 mg/m(2)/dose. After eligibility criteria modification and dose re-escalation, the MTD was 200 mg/m(2)/dose for solid tumors and 150 mg/m(2)/dose for leukemias. Sorafenib exposure was highly variable between patients but was within the ranges reported in adults. The apparent sorafenib clearance increased with patient age. Diarrhea, rash, fatigue, and increased ALT/AST were the most common sorafenib-related toxicities. Stable disease for 4 or more cycles was observed in 14 solid tumor patients, and 2 patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (FLT3ITD) experienced a decrease in bone marrow blasts to less than 5%.The recommended phase II dose of sorafenib administered every 12 hours continuously for children with solid tumors is 200 mg/m(2)/dose and 150 mg/m(2)/dose for children with leukemias. Sorafenib toxicities and distribution in children are similar to adults. The activity of sorafenib in children with AML and FLT3ITD is currently being evaluated, and a phase II study for select solid tumors is ongoing.
European League Against Rheumatism recommendations for monitoring patients with systemic lupus erythematosus in clinical practice and in observational studies
Authors: M. Mosca, C. Tani, M. Aringer, S. Bombardieri, D. Boumpas, R. Brey, R. Cervera, A. Doria, D. Jayne, M. A. Khamashta, A. Kuhn, C. Gordon, M. Petri, O. P. Rekvig, M. Schneider, Y. Sherer, Y. Shoenfeld, J. S. Smolen, R. Talarico, A. Tincani, R. F. van Vollenhoven, M. M. Ward, V. P. Werth, L. Carmona
Journal: Annals of the Rheumatic Diseases (2009)

Objectives To develop recommendations for monitoring patients with systemic lupus erythematosus (SLE) in clinical practice and observational studies and to develop a standardised core set of variables to monitor SLE. Methods We followed the European League Against Rheumatism (EULAR) standardised procedures for guideline development. The following techniques were applied: nominal groups, Delphi surveys for prioritisation, small group discussion, systematic literature review and two Delphi rounds to obtain agreement. The panel included rheumatologists, internists, dermatologists, a nephrologist and an expert related to national research agencies. The level of evidence and grading of recommendations were determined according to the Levels of Evidence and Grades of Recommendations of the Oxford Centre for Evidence-Based Medicine. Results A total of 10 recommendations have been developed, covering the following aspects: patient assessment, cardiovascular risk factors, other risk factors (osteoporosis, cancer), infection risk (screening, vaccination, monitoring), frequency of assessments, laboratory tests, mucocutaneous involvement, kidney monitoring, neuropsychological manifestations and ophthalmology assessment. A 'core set' of minimal variables for the assessment and monitoring of patients with SLE in clinical practice was developed that included some of the recommendations. In addition to the recommendations, indications for specific organ assessments that were viewed as part of good clinical practice were discussed and included in the flow chart. Conclusions A set of recommendations for monitoring patients with SLE in routine clinical practice has been developed. The use of a standardised core set to monitor patients with SLE should facilitate clinical practice, as well as the quality control of care for patients with SLE, and the collection and comparison of data in observational studies.
Confusion in equal measure
Authors: Michael Barrie
Journal: Journal of the Royal Society of Medicine (2008)

Sir,

With successive ocular oscillations I was able to visually partake in your scripted correspondence which you had consensually contributed to the JRSM.1 It was only by this due process, and not, I hasten to add, by any other assimilated or subjunctive discursions [sic], that I am both rendered and obligated (here and now, that is, in this present moment of time) to concur and unconditionally agree with your stated and assumed viewpoint. Your avowed, declared and affirmed stance is admirable – and I am minded to assume a positive, and thus non-negative, psyche which is in turn positive (and thus non-negative) in both willpower and essence. That said, one must remember, that I should not publicly nor openly state these assertions. We know that overt is superior to covert, but equally it then surely is by the same token akin to the pouch of Douglas in your own profession: what lurks therein should by definition lurk. To be seen to be not lurking implies a measure of dissimilitude, and this leads to a lack of perspective.

Elaboration evaporates to a greater sense of overdoing. And the result? Well, failure of course. Just as the sun should never set on a breech, then too much exaggeration leads to the greater folly. The folly of Lord Darzi's attempt at evidence-based medicine. To gain a foothold in such arguments is to clutch at random ideas which float, ballpark-figure-like, in an imaginary delusional ether.

My point is thus: it is to realize that this letter will be of greater worth but, surely, lesser by dint of its certain context. My approach in such matters is but surely akin to that of your own.

In shared and mutual confusion,

Yours etc,
Mobility of model proteins in hydrogels composed of oppositely charged dextran microspheres studied by protein release and fluorescence recovery after photobleaching
Authors: Sophie R. Van Tomme, Bruno G. De Geest, Kevin Braeckmans, Stefaan C. De Smedt, Florence Siepmann, Juergen Siepmann, Cornelus F. van Nostrum, Wim E. Hennink
Journal: Journal of Controlled Release (2005)
A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen
Authors: Gianluca Matteoli, Pedro J Gomez-Pinilla, Andrea Nemethova, Martina Di Giovangiulio, Cathy Cailotto, Sjoerd H van Bree, Klaus Michel, Kevin J Tracey, Michael Schemann, Werend Boesmans, Pieter Vanden Berghe, Guy E Boeckxstaens
Journal: Gut (2013)

The cholinergic anti-inflammatory pathway (CAIP) has been proposed as a key mechanism by which the brain, through the vagus nerve, modulates the immune system in the spleen. Vagus nerve stimulation (VNS) reduces intestinal inflammation and improves postoperative ileus. We investigated the neural pathway involved and the cells mediating the anti-inflammatory effect of VNS in the gut. The effect of VNS on intestinal inflammation and transit was investigated in wild-type, splenic denervated and Rag-1 knockout mice. To define the possible role of α7 nicotinic acetylcholine receptor (α7nAChR), we used knockout and bone marrow chimaera mice. Anterograde tracing of vagal efferents, cell sorting and Ca<sup>2+</sup> imaging were used to reveal the intestinal cells targeted by the vagus nerve. VNS attenuates surgery-induced intestinal inflammation and improves postoperative intestinal transit in wild-type, splenic denervated and T-cell-deficient mice. In contrast, VNS is ineffective in α7nAChR knockout mice and α7nAChR-deficient bone marrow chimaera mice. Anterograde labelling fails to detect vagal efferents contacting resident macrophages, but shows close contacts between cholinergic myenteric neurons and resident macrophages expressing α7nAChR. Finally, α7nAChR activation modulates ATP-induced Ca<sup>2+</sup> response in small intestine resident macrophages. We show that the anti-inflammatory effect of the VNS in the intestine is independent of the spleen and T cells. Instead, the vagus nerve interacts with cholinergic myenteric neurons in close contact with the muscularis macrophages. Our data suggest that intestinal muscularis resident macrophages expressing α7nAChR are most likely the ultimate target of the gastrointestinal CAIP.
Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment
Authors: Yiming Huang, Francine Rezzoug, Paula M. Chilton, H. Leighton Grimes, Daniel E. Cramer, Suzanne T. Ildstad
Journal: Blood (2004)
BRCA1-Associated Protein 1 Interferes with BRCA1/BARD1 RING Heterodimer Activity
Authors: Hiroyuki Nishikawa, Wenwen Wu, Ayaka Koike, Ryoko Kojima, Hiromichi Gomi, Mamoru Fukuda, Tomohiko Ohta
Journal: Cancer Research (2008)

Abstract The breast and ovarian tumor suppressor BRCA1 constitutes a RING heterodimer E3 ligase with BARD1. BRCA1-associated protein 1 (BAP1) is a ubiquitin COOH-terminal hydrolase that was initially identified as a protein that bound to the RING finger domain of BRCA1. However, how BAP1 contributes to the E3 activity of BRCA1/BARD1 is unclear. Here, we report that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of BRCA1/BARD1. Domains comprised by residues 182-365 of BAP1 interact with the RING finger domain of BARD1, and surface plasmon resonance spectroscopy (BIAcore) analyses showed that BAP1 interferes with the BRCA1/BARD1 association. The perturbation resulted in inhibition of BRCA1 autoubiquitination and NPM1/B23 ubiquitination by BRCA1/BARD1. Although BAP1 was capable of deubiquitinating the polyubiquitin chains mediated by BRCA1/BARD1 in vitro, a catalytically inactive mutant of BAP1, C91S, still inhibited the ubiquitination in vitro and in vivo, implicating a second mechanism of action. Importantly, inhibition of BAP1 expression by short hairpin RNA resulted in hypersensitivity of the cells to ionizing irradiation and in retardation of S-phase progression. Together, these results suggest that BAP1 and BRCA1/BARD1 coordinately regulate ubiquitination during the DNA damage response and the cell cycle. [Cancer Res 2009;69(1):111–9]
Predisposing Factors for Adrenal Insufficiency
Authors: Stefan R. Bornstein
Journal: New England Journal of Medicine (2009)

Clinicians must be aware of the growing list of causes and predisposing factors that may lead to the life-threatening disorder of acute adrenal insufficiency. This review provides a guide to the recognition and treatment of adrenal insufficiency, whether it is primary or secondary to disease, hereditary disorders, medication use, or critical illness.