tbuckley/cabot-search huggingface dataset:
Abstract 5159: Investigation of local vitamin D metabolism in breast cancer using an <i>ex vivo</i> tissue explant system
Authors: Rachel J. Suetani, Kristen Ho, Shalini Jindal, Paul M. Neilsen, Grantley Gill, Howard A. Morris, David F. Callen
Journal: Cancer Research (2012)

Abstract Vitamin D is an essential molecule obtained either by UV irradiation of the skin, or ingested through diet or supplementation. Sequential hydroxylations of vitamin D are required to generate the inactive precursor 25-hydroxyvitamin D (25D), and the active metabolite 1,25-dihydroxyvitamin D (1,25D) which activates the vitamin D receptor to alter transcription of target genes. In addition to its role in calcium homeostasis, vitamin D has been shown to have anti-proliferative, apoptotic and immunomodulating effects. Furthermore, many epidemiological studies have shown a link between a low vitamin D status and an increased risk of breast cancer. However, the mechanistic basis of this link remains unknown. We have utilized a breast explant system whereby fresh tumour and matched non-malignant breast tissues are obtained from women undergoing mastectomies. These tissues are placed on gelatin sponges in tissue culture media supplemented with either 25D or 1,25D. Tissues are then collected and analysed for alterations in gene expression and biological response. This system allows for the analysis of dynamic changes in viable tissue in response to exogenously applied compounds, and can easily be used to examine other compounds of interest. Explanted non-malignant and tumour tissue both displayed an increase in expression of the vitamin D metabolizing enzyme CYP24A1 when directly treated with 1,25D. In response to the precursor molecule 25D, non-malignant breast tissue showed a similar pattern of enzyme induction, indicating an intact and competent vitamin D metabolic pathway in these tissues. Metabolism in breast tumour tissue however was somewhat disrupted, with some cases showing little potential in converting 25D to the active metabolite 1,25D. Proliferation markers have also been examined in the non-malignant and tumour breast samples. Interestingly, some tumour specimens did not show any change in proliferation despite favourable changes in gene expression, indicating further dysregulation of vitamin D metabolism in these samples. These data will have implications for any future clinical studies of vitamin D supplementation to complement current chemopreventative therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5159. doi:1538-7445.AM2012-5159
Extracellular <scp>DNA</scp> traps in allergic, infectious, and autoimmune diseases
Authors: D. Simon, H.‐U. Simon, S. Yousefi
Journal: Allergy (2013)

Extracellular DNA traps are part of the innate immune response and are seen with many infectious, allergic, and autoimmune diseases. They can be generated by several different leukocytes, including neutrophils, eosinophils, and monocytes, as well as mast cells. Here, we review the composition of these extracellular DNA-containing structures as well as potential mechanisms for their production and function. In general, extracellular DNA traps have been described as binding to and killing pathogens, particularly bacteria, fungi, but also parasites. On the other hand, it is possible that DNA traps contribute to immunopathology in chronic inflammatory diseases, such as bronchial asthma. In addition, it has been demonstrated that they can initiate and/or potentiate autoimmune diseases. Extracellular DNA traps represent a frequently observed phenomenon in inflammatory diseases, and they appear to participate in the cross-talk between different immune cells. These new insights into the pathogenesis of inflammatory diseases may open new avenues for targeted therapies.
A Clinical Guide to Pediatric Sleep: Diagnosis and Management of Sleep Problems
Authors: Dennis Rosen
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Angiotensin-Converting Enzyme Inhibition Preserves Endothelium-Dependent Coronary Microvascular Responses During Short-term Ischemia-Reperfusion
Authors: Robert N. Piana, Steven Y. Wang, Menachem Friedman, Frank W. Sellke
Journal: Circulation (1996)

Background Chronic angiotensin-converting enzyme (ACE) inhibition initiated days to weeks after acute myocardial infarction can reduce ventricular dilatation and improve patient survival. However, the effects on coronary vascular and myocardial function of very early ACE inhibitor therapy for acute myocardial infarction remain unresolved. Methods and Results Hemodynamics, segmental shortening, coronary blood flow, and in vitro coronary microvascular relaxation responses were studied in noninstrumented control pigs (n=8) and pigs subjected to 30 minutes of left anterior descending ischemia followed by administration of 30 mL IV normal saline (IR-saline, n=8), 5 mg/kg IV captopril (IR-captopril, n=6), or 1.5 mg/kg IV enalaprilat (IR-enalaprilat, n=6) before 1 hour of reperfusion. Hemodynamics were similar at baseline, end of ischemia, and end of reperfusion. However, coronary blood flow immediately on reperfusion was significantly enhanced in the IR-enalaprilat cohort (59±10 mL/min) compared with the IR-saline group (32±3 mL/min, P &lt;.05). Segmental shortening in the dyskinetic ischemic region improved only minimally at the end of reperfusion to 1±2%, −7±3%, and −2±6% for the IR-saline, IR-captopril, and IR-enalaprilat groups, respectively ( P &lt;.05, IR-captopril versus IR-saline). Arteriolar microvascular endothelium-dependent responses to ADP ( P &lt;.01) and calcium ionophore A23187 ( P &lt;.01) were impaired after ischemia-reperfusion, whereas bradykinin responses were preserved ( P =.95). Endothelium-dependent venular responses to ADP and serotonin were maintained despite ischemia-reperfusion. Endothelium-independent responses to sodium nitroprusside were unaltered in arterioles and venules. Either captopril or enalaprilat restored ADP and A23187 arteriolar responses to control levels and increased bradykinin responses above control levels. Conclusions Brief ischemia followed by reperfusion induces arteriolar microvascular endothelial dysfunction, while venular endothelial function is preserved in this porcine model. ACE inhibition enhances coronary blood flow at the time of reperfusion and can prevent impairment of endothelium-dependent arteriolar responses. However, ACE inhibition does not enhance ventricular segmental shortening acutely despite improved microvascular endothelial function and augmented postischemic coronary blood flow in this model of ischemia-reperfusion.
Antineoplastons: the controversy continues
Authors: S. Burzynski
Journal: JAMA (1993)

To the Editor.  —As a paid consultant to those formerly in litigation against me, Dr Green1can scarcely be considered impartial. Not surprisingly, Green gravely misrepresents more than 20 years of research. Due to space constraints, I can address only a few of Green's misstatements, and therefore am unable to counter one of the most serious problems of the article, Green's omission of dozens of publications.  Green disputes my claim to a PhD degree in biochemistry and asserts that my bibliography does not identify a dissertation. The sworn affidavit of Professor Zdzislaw Kleinrok, president of the Medical Academy of Lublin, Poland, confirms that my PhD in biochemistry was awarded on October 16,1968. My doctoral dissertation2is always listed in my bibliography.  Green refers to tests done by the National Cancer Institute (NCI) as compelling evidence of the lack of efficacy of antineoplastons against experimental cancer. Green fails to
Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes?
Authors: Steven M. Haffner, Michael P. Stern, Helen P. Hazuda, Braxton D. Mitchell, Judith K. Patterson
Journal: JAMA (1990)

Although type II diabetes is associated with both microvascular and macrovascular complications, duration of diabetes and severity of glycemia are strongly associated only with the former. Since prediabetic individuals are hyperinsulinemia, and since hyperinsulinemia may be a cardiovascular risk factor, we hypothesized that prediabetic individuals might have an atherogenic pattern of risk factors even before the onset of clinical diabetes, thereby explaining the relative lack of an association of macrovascular complications with either glycemic severity or disease duration. We documented the cardiovascular risk factor status of 614 initially nondiabetic Mexican Americans who later participated in an 8-year follow-up of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Individuals who were nondiabetic at the time of baseline examination, but who subsequently developed type II diabetes (ie, confirmed prediabetic subjects, n = 43), had higher levels of total and low-density lipoprotein cholesterol, triglyceride, fasting glucose and insulin, 2-hour glucose, body mass index, and blood pressure, and lower levels of high-density lipoprotein cholesterol than subjects who remained nondiabetic (n = 571). Most of these differences persisted after adjustment for obesity and/or level of glycemia, but were abolished after adjustment for fasting insulin concentration. When subjects with impaired glucose tolerance at baseline (n = 106) were eliminated, the more atherogenic pattern of cardiovascular risk factors was still evident (and statistically significant) among initially normoglycemic prediabetic subjects. These results indicate that prediabetic subjects have an atherogenic pattern of risk factors (possibly caused by obesity, hyperglycemia, and especially hyperinsulinemia), which may be present for many years and may contribute to the risk of macrovascular disease as much as the duration of clinical diabetes itself.
Carbenicillin Therapy of Pseudomonas and Other Gram-Negative Bacillary Infections
Authors: THOMAS A. HOFFMAN
Journal: Annals of Internal Medicine (1970)

The activity of carbenicillin against Pseudomonas aeruginosa in vitro and its clinical effectiveness when used as the sole antibiotic treatment of serious infections were evaluated. Seventeen patients with serious pseudomonas infections and three patients with other Gram-negative bacillary infections were treated with carbenicillin. Although most patients showed improvement, only six were cured. The initial pathogenic species was not eradicated from 13 patients, and 5 relapsed due to P. aeruginosa with marked resistance to carbenicillin. The majority of P. aeruginosa isolated from patients after therapy were markedly resistant to carbenicillin (minimum inhibitory concentration, 125 to >500 µg/ml). Superinfections were noted in six patients and were usually caused by Klebsiella-Enterobacter-Serratia or Candida species. Manifestations of hypersensitivity to carbenicillin included drug fever and eosinophilia. Seizures were induced in two azotemic patients on 4 g carbenicillin per day, and pulmonary edema developed in one patient who was receiving 24 g/day.
Emergence of Large Treatment Effects From Small Trials—Reply
Authors: John P. A. Ioannidis, Tiago V. Pereira, Ralph I. Horwitz
Journal: JAMA (2013)

In Reply: We agree with Drs Batterham and Hopkins that small studies are not necessarily inherently flawed. However, probabilistically speaking, even in the absence of biases, small-sized trials are more prone to provide overestimates (or underestimates) compared with larger trials.
Abstract PR3: Considering alternate signaling mechanisms models in extrinsic apoptosis using programmatic modeling approaches
Authors: Carlos F. Lopez, Jeremy L. Muhlich, John J. Bachman, Peter K. Sorger
Journal: Cancer Research (2012)

Abstract Experiments often result in observations that suggest conflicting biochemical mechanisms in signaling networks. Mathematical modeling of biological systems is a method used to probe such experimental observations and provide a consensus among seemingly discordant observations. However, probing multiple mechanistic hypotheses in biological modeling often involves the instantiation of complex systems of equations, which despite their usefulness, makes model revision, extension, and sharing extremely challenging. To address these modeling barriers, we have developed a modeling framework that brings a process-based approach to biological modeling. In our approach, biological models are written as programs that encode biological functions as needed. Our modeling framework, developed in the Python language, offers access to a large set of existing numerical and programming methods to biological systems modeling. Given our choice of programming language, the resulting models are easier to share, distribute, extend, and revise, adding transparency to the model-creation and execution process. We demonstrate our approach by exploring three competing mechanisms that describe the interactions among the Bcl-2 family of proteins and their contributions to mitochondrial outer membrane permeabilization in extrinsic apoptosis. We used our modeling framework to systematically explore these three proposed mechanisms resulting in the instantiation of sixteen biochemical model topologies for numerical exploration. Our preliminary results, based on simulations calibrated to experimental data, suggest that the so-called indirect mechanism does not accurately reproduce experimental observations. Results from simulations suggest that the so-called embedded model more seems to better align with existing experimental data. Despite these observations, further topology- and numerical-based characterization of the model topology and parameter-space is being carried out to more accurately understand the role of these Bcl-2 proteins in apoptosis. We aim to formulate hypotheses, testable through experiments, about the interaction among these proteins and their role in Bcl-2 cancer biology. This proffered talk is also presented as Poster A9. Citation Format: Carlos F. Lopez, Jeremy L. Muhlich, John J. Bachman, Peter K. Sorger. Considering alternate signaling mechanisms models in extrinsic apoptosis using programmatic modeling approaches [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr PR3.
Community care and the fundholder.
Authors: R Morris
Journal: BMJ (1993)

According to the government, clearly agreed local arrangements should enable individual general practitioners to make their full contribution to the new system of community care without getting involved in extra bureaucracy. From 1 April the main part of that contribution will be to refer to social services those patients who seem to need social care. Many general practitioners are worried that such referrals will be complex and time consuming and will generate too much extra work. Moreover, general practitioners may also be asked to see patients specifically to help social workers' assessment procedures, and many fear that such consultations will overwork and underpay them. General practitioner fundholders already use contracts to spell out what they expect from hospital services. From 1 April they will be able to set up contracts for community health services such as district nursing and chiropody, and possibly this might be extended to social aspects of community care. Over the past 14 months Dr Rhidian Morris and his partners in a fundholding practice in Devon have piloted contracts for all aspects of community care. In this article Dr Morris explains how the most radical part of the pilot project--the contract for social care--was set up. He argues that the lessons on communication that came from what was essentially a fundholding project could apply also to non-fundholding practices.
858 IN VITRO RESISTANCE ANALYSIS OF HCV NS5A INHIBITOR: MK-8742 DEMONSTRATES INCREASED POTENCY AGAINST CLINICAL RESISTANCE VARIANTS AND HIGHER RESISITANCE BARRIER
Authors: R. Liu, R. Kong, P. Mann, P. Ingravallo, Y. Zhai, E. Xia, S. Ludmerer, J. Kozlowski, C. Coburn
Journal: Journal of Hepatology (2012)
Immunosuppressive treatment in stroke and renal failure.
Authors: I B Squire, D G Grosset, K R Lees
Journal: Annals of the Rheumatic Diseases (1993)

Rheumatic disease foliowing immunotherapySir: Arthralgias and exacerbation of pre- existing arthritis are well known side effects of treatment with interferons and interleukin-2 (IL-2).'-3We report here, however, on two patients with malignant melanoma receiving
Parathyroid Adenoma Imaged by Gallium-67 Citrate A Case Report
Authors: MAKOTO KATAGIRI, TANEKAZU HARADA, RYO KAWANO, YASUHIKO OKAMURA, KAZUMASA MIYAKE, NOBUAKI OTSUKA, MASAO FUKUNAGA, RIKUSHI MORITA
Journal: Clinical Nuclear Medicine (1987)

A parathyroid adenoma imaged by Ga-67 citrate in a 17- year-old man with primary hyperparathyroidism and a palpable solid tumor in the neck is presented. Although preoperative examination and intraoperative findings suggested a parathyroid carcinoma, histologic studies showed a parathyroid adenoma with predominant chief cell type.
Obstructed Labour due to Conjoined Twins
Authors: E. Ridehalgh
Journal: BMJ (1942)

Scottish Order, 1936-i.e., fewer than 200,000 viable bacteria per c.cm. and no B. coli in 0.01 c.cm.3. Methylene-blue Reductase Test.-The modified test described Wilson (1935) was adopted.To 10 c.cm. of milk in a standard sterile test-tube, 1 c.cm. of methylene-blue solution was added.The tube was fitted with a rubber bung, placed in a water bath at 37°C., and inverted at intervals of 30 minutes.The standard upon which the quality of the milk was judged was that demanded of " accredited milk " under the English Order, 1936-i.e., the milk must not decolorize methylene-blue within 4 hours if the sample is taken at any time from May 31 to Oct. 31; or within 51 hours if taken at any time from Nov. 1 to April 30.4. Examination for Tubercle Bacilli.-100c.cm. of each sample was centrifuged for 30 minutes at 3,000 r.p.m.The resulting deposit was then resuspended in 5 c.cm. of the supernatant fluid, and the entire bulk injected without further treatment into the inguinal region of a guinea-pig.
Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension
Authors: Qing Yu, Rong Shao, Hu Sheng Qian, Samuel E. George, Don C. Rockey
Journal: Journal of Clinical Investigation (2000)

Reduced production of nitric oxide (NO) in the cirrhotic liver results from a defect in hepatic endothelial cell nitric oxide synthase (ecNOS) and appears to contribute to the high intrahepatic resistance and portal hypertension typical of cirrhosis. Therefore, we postulated that targeting a heterologous NOS isoform to sinusoidal endothelial cells or other perisinusoidal cells, such as hepatic stellate cells, would counter the defect in NO production and reduce resistance to blood flow. Recombinant adenovirus (Ad) carrying the neuronal NOS gene (nNOS) targeted liver sinusoidal endothelial cells, stellate cells, and hepatocytes more efficiently than the corresponding cells in cirrhotic livers, but transduction rates were substantial even in cirrhotic animals. Expression of nNOS in each liver cell type, whether from normal or injured liver, caused increased NO production and inhibited endothelin-1–induced contractility of perisinusoidal stellate cells. Finally, in 2 different in vivo models of cirrhosis and portal hypertension, transduction of livers with recombinant Ad.nNOS significantly reduced intrahepatic resistance and portal pressure. The data highlight the feasibility of gene transfer to diseased liver and hepatic cells and demonstrate the potential of a novel therapy for portal hypertension caused by cirrhosis.
The mechanism of the REM state is more than a sum of its parts
Authors: Mark Solms
Journal: Behavioral and Brain Sciences (2000)

Nielsen has not demonstrated that NREM dreams are regularly accompanied by fragments of the REM state. However, even if this hypothetical correlation could be demonstrated, its physiological basis would be indeterminate. The REM state is a configuration of physiological variables, the basis of which is a control mechanism that recruits and coordinates multiple sub-mechanisms into a stereotyped pattern. The diverse sub-mechanisms underlying each individual component of the REM state do not have an intrinsic relationship with the REM state itself. [Nielsen]
The Burden of the M.R.C.P
Authors: D. S. Spero
Journal: BMJ (1946)

<h3>Background</h3> The interscalene brachial plexus block has been used effectively for intraoperative and postoperative analgesia in patients undergoing shoulder surgery, but it is associated with high rates of diaphragmatic dysfunction. Performing the block more distally, at the level of the superior trunk, may reduce the incidence of phrenic nerve palsy. We hypothesized that superior trunk block would result in diaphragmatic paralysis rate of less than 20%. <h3>Methods</h3> 30 patients undergoing arthroscopic shoulder surgery received superior trunk block under ultrasound guidance. Measurements of diaphragm excursion were determined with ultrasound prior to the block, 15 min after the block, and postoperatively in phase II of postanesthesia care unit, in conjunction with clinical parameters of respiratory function. <h3>Results</h3> 10 patients (33.3%, 95% CI 17.3% to 52.8%) developed complete hemidiaphragmatic paralysis at the postoperative assessment. An additional eight patients (26.7%) developed paresis without paralysis. Of the 18 patients with diaphragm effects, seven (38.9%) reported dyspnea. 83.3% of patients with abnormal diaphragm motion (56.7% of the total sample) had audibly reduced breath sounds on auscultation. Oxygen saturation measurements did not correlate with diaphragm effect and were not significantly reduced by the postoperative assessment. <h3>Conclusion</h3> Although injection of local anesthetic at the superior trunk level is associated with less diaphragmatic paralysis compared with traditional interscalene block, a significant portion of patients will continue to have ultrasonographic and clinical evidence of diaphragmatic weakness or paralysis.
Cardiac Magnetic Resonance Monitors Reversible and Irreversible Myocardial Injury in Myocarditis
Authors: Anja Zagrosek, Hassan Abdel-Aty, Philipp Boyé, Ralf Wassmuth, Daniel Messroghli, Wolfgang Utz, Andre Rudolph, Steffen Bohl, Rainer Dietz, Jeanette Schulz-Menger
Journal: JACC. Cardiovascular imaging (2009)