tbuckley/cabot-search huggingface dataset:
Transcriptional Activation of the Mixed Lineage Leukemia–p27Kip1 Pathway by a Somatostatin Analogue
Authors: Kazuhiko Horiguchi, Masanobu Yamada, Tetsurou Satoh, Koshi Hashimoto, Junko Hirato, Masahiko Tosaka, Shozo Yamada, Masatomo Mori
Journal: Clinical Cancer Research (2009)

Mixed lineage leukemia (MLL) is a histone methyltransferase that activates gene transcription and associates with menin. In multiple endocrine neoplasia type 1 (Men1), a mutation of menin caused decreased expression of the p27(Kip1) and p18(Ink4C) genes and deregulated cell growth. We hypothesized that the same pathway might be involved in sporadic pituitary adenomas.mRNA levels for MLL, Men1, p27(Kip1), and p18(Ink4C) were measured in specimens of several sporadic pituitary adenomas, and a search for clinical parameters revealed that octreotide treatment affected the level of expression of some genes tested. To study molecular mechanisms, we cloned and characterized the MLL promoter region and used small interfering RNA for MLL and specific inhibitors for signal transduction pathways.A strong correlation between MLL and p27(Kip1) mRNA levels was observed in prolactinomas and growth hormone-secreting adenomas, and these levels were attenuated except in growth hormone-secreting adenomas treated with a somatostatin analogue, octreotide. Conversely, the patients treated with octreotide showed high levels of MLL-p27(Kip1) mRNA. Experiments in vitro showed that octreotide increased MLL and p27(Kip1) protein and mRNA levels, and overexpression of MLL induced a marked increase in p27(Kip1)promoter activity. Furthermore, octreotide stimulated the promoter activity of the MLL gene through phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. In addition, incubation with an inhibitor for methyltransferase, MTA, and knockdown of MLL completely inhibited the octreotide-induced expression of p27(Kip1).The MLL-p27(Kip1) pathway was down-regulated in the pituitary adenomas, and octreotide increased the p27(Kip1) level, at least in part, by sequential transcriptional stimulation of the MLL and p27(Kip1) genes through phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways.
Ectopic ACTH Production in Carcinoma of the Lung
Authors: George Gewirtz, Rosalyn S. Yalow
Journal: Journal of Clinical Investigation (1974)

Immunoreactive ACTH was found in almost all tissue extracts of lung carcinoma from patients without clinical evidence of Cushing's syndrome; i.e. 14 of 15 primary tumors, nine of nine metastatic lymph nodes, and four of four metastatic liver nodules contained immunoreactive ACTH. The incidence of ACTH in extracts of other tumor types was much lower. Comparable normal tissues contained no detectable ACTH. Immunoreactive growth hormone, parathyroid hormone, or gastrin was not found in the same carcinoma tissue. The predominant form of ACTH in the tumor extracts was big ACTH. In pituitary extracts little ACTH predominated.
An esophageal ulcer mimicking advanced esophageal cancer in a patient on alendronate sodium treatment for osteoporosis
Authors: T. Terashima, K. Hiramatsu, A. Shimatani, M. Matsuda, H. Ogino, Y. Satomura, Y. Noda
Journal: Endoscopy (2006)

We report a case of an esophageal ulcer that mimicked advanced esophageal cancer in a patient who was on alendronate sodium treatment.
Dietary calcium intakes of urban children at risk of lead poisoning.
Authors: K Bruening, F W Kemp, N Simone, Y Holding, D B Louria, J D Bogden
Journal: Environmental Health Perspectives (1999)

Dietary calcium is well known to decrease gastrointestinal lead absorption and thereby reduce the risk for lead poisoning. Because children in economically deprived urban centers are especially likely to have excessive lead exposure, we surveyed dietary calcium intakes of 314 children from the greater Newark, New Jersey, area. The areas of Newark and adjacent communities studied had been previously identified as containing significant sources of environmental lead by geographic information systems technology. An abbreviated National Cancer Institute Health Habits and History Questionnaire, modified to focus on foods high in calcium, was used to determine dietary calcium. Calcium intakes were then compared to the new Dietary Reference Intake (DRI) guidelines. The respondents were primarily the parents of African-American and Hispanic children ranging in age from 1 to 8 years, with a mean age of 3.5 years. The most recent blood lead concentration was 11.4 +/- 0.8 microg/dL (mean +/- standard error), and 48.6% had concentrations at or above the current guideline of 10 microg/dL. Quintiles of calcium intake were: 221 +/- 13; 488 +/- 9; 720 +/- 6; 885 +/- 6; and 1,389 +/- 49 mg/day. Fifty-five of 175 (31.4%) children aged 1-3 years had calcium intakes below the DRI, as did 82 of 139 (59.0%) children aged 4-8 years. The percentage of mothers reporting lactose intolerance in their children was 2.5%. The observation that the children in the highest quintile easily exceeded the DRIs for calcium suggests that urban parents who include dairy foods in their childrens' meals can provide a diet that meets the DRI guidelines. Children in the lowest quintiles are at risk of increased absorption of the environmental lead to which they are inevitably exposed, as well as other problems associated with a low intake of dietary calcium. The data suggest that both lead exposure and low dietary calcium continue to pose significant health risks to urban minority children.
BIORENERV-REGISTER: KIDNEY-INJURY-MOLECULE-1 (KIM-1) AS A BIOMARKER FOR DAMAGE IN PROXIMAL RENAL TUBULE SYSTEM AFTER RENAL DENERVATION
Authors: Oliver D&ouml;rr, Christoph Liebetrau, Helge M&ouml;llmann, Daniel Sedding, Christian Troidl, Stephan Achenbach, Christian Hamm, Holger Nef
Journal: Journal of the American College of Cardiology (2012)
CONDUCTION AND CONTRACTION OF CARDIAC MUSCULATURE IN WATER RIGOR
Authors: CLYDE BROOKS
Journal: JAMA (1926)

No problem in physiology is so small that it may not require a lifetime for its solution, nor so simple that it may not require unattained knowledge for its complete analysis. For we discover only the primary conditions that bear on the mechanism we seek to understand. Other secondary conditions which bear on the primary conditions, remain to be discovered and solved. And the complete and ultimate analysis lies continually beyond us. So it is with the long continued discussion of the origin of the heart beat and the essential nature of conduction and coordination in the heart, which discussion continues to excite interest and to enlist the effort of physiologists.  In a former paper I 1 attempted to solve an apparently simple point bearing on the problem of the mechanism of the heart beat; namely, Does skeletal muscle conduct the contractile impulse after it has been put into a
Innovations in services and the appliance of science
Authors: A. Haines, S. Iliffe
Journal: BMJ (1995)

Everyone now accepts that new drugs should be tested extensively before their introduction. A similar consensus is developing over health technology.1 2 Broadly defined, health technology includes methods of organising care,3 but currently innovations in how health services are organised and delivered often seem to be unregulated and unevaluated. Several factors drive innovation in services. These include perceptions of improved cost effectiveness on the part of policymakers or local purchasers and providers, perceptions of demand from the public and patients for changes in the delivery of care, and enthusiastic promotion of new technologies by commercial interests. Perceptions of usefulness are, however, all too often based on subjective impressions rather than established facts.

Many current innovations are concerned with the interface between primary and secondary care because of the (largely untested) belief that shifting care to the community will be more cost effective and more acceptable to the public than current patterns of provision of hospital services. Such innovations include hospitals at home, specialist outreach schemes, primary care emergency centres, and the development of discharge planning. Other innovations include changes in skill mix and professional roles, such as the introduction of practice counsellors, nurse practitioners, and health advocates for ethnic minority groups. Research on several of these topics is now being commissioned4 as part of the …
Significance of connective tissue proliferation in the breakdown of cartilage: a novel in vivo model.
Authors: F B De Brito, A R Moore, S Adhya, A Y Al-Duaij, D A Willoughby
Journal: Annals of the Rheumatic Diseases (1986)

The implantation of homologous femoral head cartilage in subcutaneous tissues of random bred Wistar rats results in both subchondral and articular surfaces becoming overlaid by an adherent granulation tissue comprising predominantly fibroblast-like cells. The response of the tissue to cartilage encapsulated with cotton fibres was also similar but erosions, mainly subchondral, were more evident and proteoglycan loss markedly greater. The connective tissue response to cotton was the progressive formation of a foreign body granuloma comprising mononuclear cells, multinucleated giant cells, and fibroblasts with very few polymorphonuclear leucocytes.
Abstract B17: Mechanisms of resistance of BRAF fusions to first generation selective BRAF inhibitors
Authors: Angela Jae Sievert, Shih-Shan Lang, Phillip B. Storm, Adam C. Resnick
Journal: Clinical Cancer Research (2012)

Abstract Astrocytomas are the most common type of central nervous system tumor in children. We and others have previously reported that activated BRAF mutations, via the KIAA1549-BRAF fusion gene, are a key feature of low-grade astrocytomas. We generated several different cell lines stably expressing various altered BRAF and BRAF-fusion constructs and evaluated first and second-generation BRAF inhibitors including PLX4720 and PLX-PB compounds. In vitro kinase assays demonstrated the KIAA1549-BRAF fusion kinase, like V600E BRAF, undergoes inhibition in the presence of both first and second-generation selective BRAF inhibitors. However, KIAA1549-BRAF fusion expressing cell lines were resistant to PLX4720 and displayed paradoxal activation to first-generation BRAF inhibitor suggesting distinct and cell-context dependent mechanisms for MAPK activation. In contrast, KIAA1549-BRAF-fusion-mediated MAPK activation was abrogated by PB-3, a second-generation, “paradox-breaking,” selective BRAF inhibitor. This suggests that pediatric low-grade astrocytomas harboring the KIAA1549-BRAF fusion may be responsive to second-generation BRAF inhibitors. Our current studies are focused on understanding how KIAA1549-BRAF fusion signaling is mechanistically different than canonical BRAF V600E mutant and how this impacts the differential responses to selective BRAF inhibition.
PTH-021 Nutrition Assessment In The Acute Medical Unit
Authors: A Doyle, J Abbott, P Chopra
Journal: Gut (2014)

<h3>Introduction</h3> Malnutrition can increase hospital mortality rates, worsen clinical outcomes and increase the length of hospital stays. Those at particular risk include patients with cancer, gastrointestinal and neurological disease. We wanted to review whether patients admitted to the Acute Medical Unit were adequately assessed for malnutrition and whether identified patients had been referred to or received specialist nutritional assessment and support in a prompt manner. <h3>Methods</h3> A prospective audit was performed on 77 acute medical admissions. Data was collected during the first 48 h of the patients’ stay and was compared to the current recommendations highlighted in the NICE Clinical Guideline 32 – ‘Nutrition support in adults’. Patients’ notes were then recalled following discharge to determine whether further nutritional interventions had taken place during their admission. <h3>Results</h3> We found that only 36% of patients were screened appropriately for malnutrition and through our analysis, we identified that at admission 51% were either malnourished or at risk of malnutrition. Only one patient was referred to a dietician and started on nutritional support during the acute admission period. <h3>Conclusion</h3> Nutrition assessment needs to be reinforced as a clinical priority and essential screening for patients admitted to hospital through the Acute Medical Unit. This should be jointly addressed by the medical and nursing teams and by ensuring early input from dieticians is available. <h3>Disclosure of Interest</h3> None Declared.
Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT)
Authors: Inder S. Anand, Lloyd D. Fisher, Yann-Tong Chiang, Roberto Latini, Serge Masson, Aldo P. Maggioni, Robert D. Glazer, Gianni Tognoni, Jay N. Cohn
Journal: Circulation (2003)

Neurohormones are considered markers of heart failure progression. We examined whether changes in brain natriuretic peptide (BNP) and norepinephrine (NE) over time are associated with corresponding changes in mortality and morbidity in the Valsartan Heart Failure Trial.Plasma BNP and NE were measured before randomization and during follow-up in approximately 4300 patients in the Valsartan Heart Failure Trial. The relation between baseline BNP and NE and all-cause mortality and first morbid event (M&M) was analyzed in subgroups, with values above and below the median, and by quartiles. The change and percent change from baseline to 4 and 12 months in BNP and NE were also analyzed by quartiles for subsequent M&M. Risk ratios for M&M were calculated using a Cox proportional hazard model. Risk ratio of M&M for patients with baseline BNP or NE above the median was significantly higher than that for patients with values below the median. Baseline BNP and NE in quartiles also showed a quartile-dependent increase in M&M. BNP had a stronger association with M&M than NE. Patients with the greatest percent decrease in BNP and NE from baseline to 4 and 12 months had the lowest whereas patients with greatest percent increase in BNP and NE had the highest M&M.Not only are plasma BNP and NE important predictors of heart failure M&M, but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials.
Counterimmunoelectrophoresis and Bacterial Meningitis
Authors: Ayser C. Hamoudi
Journal: JAMA (1978)

<h3>To the Editor.—</h3> We read with interest both letters concerning counterimmunoelectrophoresis (CIE) and bacterial meningitis by Denis et al (238:1248, 1977) and Eckfeldt et al (239:615, 1978). We thought it would be helpful to state our own findings. We believe that CIE is a useful, specific, rapid diagnostic test in a pediatric hospital. We would also like to emphasize the value of including serum and urine in CIE studies on meningitis to increase the sensitivity of the test. From August 1976 through May 1978, we ran CIE on 284 clinical specimens. Of these, 181 cases were negative on CIE and cultures and were subsequently found to have no bacterial infection or infections due to causes other than the antigens we were testing for, namely,<i>Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae</i>, or group B streptococci. In all of these specimens we ran across no crossreactions or false-positives. Table 1 summarizes our
Is tyrosine kinase activation involved in basophil histamine release in asthma due to western red cedar?
Authors: A. Frew, H. Chan, H. Salari, M. Chan‐Yeung
Journal: Allergy (1998)

Occupational asthma due to western red cedar is associated with histamine release from basophils and mast cells on exposure to plicatic acid (PA), but the machanisms underlying this response remain unclear. Specific kinase inhibitors were used to study the role of tyrosine kinase inhibitor methyl 2,5‐dihydroxy‐cinnamate (MDHC) attenuated histamine release from basophils triggered by anti‐IgE (29.8% inhibition; n=15; P&lt;0.01) or grass pollen (48% inhibition; n=6; P&lt;0.01). Inhibition was concentration‐dependent and could be reversed by washing the cells in buffer, while the inactive stereoisomer of MDHC did not affect histamine release. In contrast, the protein kinase C inhibitor staurosporin did not affect histamine release by either anti‐IgE or grass pollen. Pretreatment with MDHC partially inhibited PA‐induced histamine release from basophils of 6/9 patients with red cedar asthma (25.4% vs 33.8%; P=NS). Staurosporin gave a similar level of inhibition of PA‐induced histamine release (25.4% vs 33.8%; P=NS). Thus, signal trasduction of the human basophil Fc E RI appears to depend upon tyrosine kinase activation, but not on protein kinase C (serine/threonine kinase) activation. The lack of specific effect on plicatic acid‐induced histamine release in basophils obtained from patients with occupational asthma due to western red cedar suggests that tyrosine kinases are not as important in this disease as in atopic asthma, and is consistent with the view that histamine release in red cedar asthma is largely IgE‐independent.
Global Methylation in Exposure Biology and Translational Medical Science
Authors: Heather H. Nelson, Carmen J. Marsit, Karl T. Kelsey
Journal: Environmental Health Perspectives (2011)

Many groups are actively investigating how the epigenetic state relates to environmental exposures and development of disease, including cancer. There are myriad choices for capturing and measuring the epigenetic state of a tissue, ranging from assessing the total methyl-CpG content to array-based platforms that simultaneously probe hundreds of thousands of CpG loci. There is an emerging literature that uses CpG methylation at repetitive sequences, including LINE-1 (long interspersed nuclear element-1) elements, to capture the epigenomic state. We explored the complexity of using CpG methylation at repetitive sequences in epidemiology and translational medical research and suggest needed avenues of research to clarify its meaning and utility. Among the most urgent avenues of research is the need for prospective studies to eliminate the possibilities of reverse causality, and development of new LINE-1 assays that capture both class of LINE-1 element and copy number.
The Anrep Effect Reconsidered
Authors: R. G. Monroe, W. J. Gamble, C. G. Lafarge, A. E. Kumar, J. Stark, G. L. Sanders, C. Phornphutkul, M. Davis
Journal: Journal of Clinical Investigation (1972)

Evidence is presented supporting the hypothesis that the positive inotropic effect after an abrupt increase in systolic pressure (Anrep effect) is the recovery from subendocardial ischemia induced by the increase and subsequently corrected by vascular autoregulation of the coronary bed. Major evidence consists of data obtained from an isolated heart preparation showing that the Anrep effect can be abolished with coronary vasodilation, and that with an abrupt increase in systolic pressure there is a significant reduction in the distribution of coronary flow to subendocardial layers of the ventricle. Furthermore, the intracardiac electrocardiogram shows S-T segment and T wave changes after an abrupt increase in ventricular pressure similar to that noted after coronary constriction. Major implications are that normally there may be ischemia of the subendocardial layers tending to reduce myocardial contractility which may account, in part, for the positive inotropic effect of various coronary vasodilators; that with an abrupt increase in ventricular pressure the subendocardium is rendered temporarily ischemic, placing the heart in jeopardy from arrhythmias until this is corrected; and that end-diastolic pressure and the intracardiac electrocardiogram may provide a means of evaluating the adequacy of circulation to subendocardial layers in diseased ventricles when systolic pressure is abruptly increased.
Diclofenac shouldn't be prescribed to people with heart problems, drug agency says
Authors: J. Wise
Journal: BMJ (2013)

<h3>Background</h3> Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes. <h3>Case presentation</h3> We report 3 patients who developed granulomatous/sarcoid-like lesions while being treated with immune checkpoint therapy for advanced-stage melanoma, and we provide a comprehensive review of the literature in which similar cases are described. To date, 26 patients (including the 3 from this report) have been described with a median age of 57&nbsp;years who developed granulomatous/sarcoid-like lesions associated with CPIs (median onset 6&nbsp;months), of which 77% of patients had melanoma as primary tumor. To manage this adverse side effect, therapy was withheld in 38% of patients and 44% of the patients were treated with systemic steroids and 8% patients with localized therapy (one patient with intralesional triamcinolone). 96% of patients demonstrated either resolution or improvement of granulomatous/sarcoid-like lesions associated with CPIs irrespective of medical intervention. Therapeutic response, stable disease, or remission of primary malignancy was observed in 71% of reported patients who developed granulomatous/sarcoid-like lesions associated with CPIs over a median follow-up of 11.5&nbsp;months since initiation of treatment. <h3>Conclusions</h3> The development of granulomatous/sarcoid-like lesions associated with CPIs is a recognized manifestation with the current class of immune checkpoint therapy that may clinically and radiographically mimic disease recurrence. Awareness of this type of toxicity is important for appropriate management and possible measurement of therapeutic response in a subset of patients who manifest this type of immune-mediated reaction.
Rapid-Death Abreaction
Authors: Oscar W. Haffke
Journal: JAMA (1965)

To the Editor:—  To my knowledge there is nothing in the medical literature that specifically relates itself to this phenomenon. I have been exposed to it so often that it now has become predictable in my practice.  In brief, almost invariably following a rapid death in a family, the wife, husband, mother, or father will be depressed and not up to his normal behavior pattern. Perhaps a few days, weeks, or even months later he will approach the doctor by phone or office visit with some rather trivial question or symptom. If the physician is alert to this situation and quietly alludes to the death of the loved one, almost immediately he is forced into a listening position that may last as long as an hour. The bereaved individual will recount every detail and movement of the deceased in a chronological order from a few days to perhaps one week
"Aphasia of the Hand."
Authors: F. W. Higgins
Journal: JAMA (1896)

Cortland, N. Y., Dec. 1, 1896. <h3>To the Editor:</h3> —In reference to your very interesting editorial in the last number of theJournalon "Aphasia of the Hand" will you allow me to call your attention to the opinion of Max Knies, as to the location of the lesion. You will find it at the bottom of page 92 of the German edition of "Die Beziehungen des Sehorgans und seiner Erkrankungen zu den übrigen Krankheiten des Körpers und seiner Organe." It is, as you will notice, that for writing, the important special center for the right hand lies about in the middle of the posterior central convolution. Yours sincerely,