tbuckley/cabot-search huggingface dataset:
Evaluation of Five Radiation Schedules and Prognostic Factors for Metastatic Spinal Cord Compression
Authors: Dirk Rades, Lukas J.A. Stalpers, Theo Veninga, Rainer Schulte, Peter J. Hoskin, Nermina Obralic, Amira Bajrovic, Volker Rudat, Rudolf Schwarz, Maarten C. Hulshof, Philip Poortmans, Steven E. Schild
Journal: Journal of Clinical Oncology (2005)

Purpose To study five radiotherapy (RT) schedules and potential prognostic factors for functional outcome in metastatic spinal cord compression (MSCC). Patients and Methods One thousand three hundred four patients who were irradiated from January 1992 to December 2003 were included in this retrospective review. The schedules of 1 × 8 Gy in 1 day (n = 261), 5 × 4 Gy in 1 week (n = 279), 10 × 3 Gy in 2 weeks (n = 274), 15 × 2.5 Gy in 3 weeks (n = 233), and 20 × 2 Gy in 4 weeks (n = 257) were compared for motor function, ambulatory status, and in-field recurrences. The following potential prognostic factors were investigated: age, sex, performance status, histology, number of involved vertebra, interval from cancer diagnosis to MSCC, pretreatment ambulatory status, and time of developing motor deficits before RT. A multivariate analysis was performed with the ordered logit model. Results Motor function improved in 26% (1 × 8 Gy), 28% (5 × 4 Gy), 27% (10 × 3 Gy), 31% (15 × 2.5 Gy), and 28% (20 × 2 Gy); and posttreatment ambulatory rates were 69%, 68%, 63%, 66%, and 74% (P = .578), respectively. On multivariate analysis, age, performance status, primary tumor, involved vertebra, interval from cancer diagnosis to MSCC, pretreatment ambulatory status, and time of developing motor deficits were significantly associated with functional outcome, whereas the RT schedule was not. Acute toxicity was mild, and late toxicity was not observed. In-field recurrence rates at 2 years were 24% (1 × 8 Gy), 26% (5 × 4 Gy), 14% (10 × 3 Gy), 9% (15 × 2.5 Gy), and 7% (20 × 2 Gy) (P &lt; .001). Neither the difference between 1 × 8 Gy and 5 × 4 Gy (P = .44) nor between 10 × 3 Gy, 15 × 2.5 Gy, and 20 × 2 Gy (P = .71) was significant. Conclusion The five RT schedules provided similar functional outcome. The three more protracted schedules seemed to result in fewer in-field recurrences. To minimize treatment time, the following two schedules are recommended: 1 × 8 Gy for patients with poor predicted survival and 10 × 3 Gy for other patients. Results should be confirmed in a prospective randomized trial.
King Tutankhamun’s Family and Demise
Authors: Brenda J. Baker
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 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
Why Rudolph's nose is red: observational study
Authors: C. Ince, A.-M. van Kuijen, D. M. J. Milstein, K. Yuruk, L. P. Folkow, W. J. Fokkens, A. S. Blix
Journal: BMJ (2012)

<b>Objective</b> To characterise the functional morphology of the nasal microcirculation in humans in comparison with reindeer as a means of testing the hypothesis that the luminous red nose of Rudolph, one of the most well known reindeer pulling Santa Claus’s sleigh, is due to the presence of a highly dense and rich nasal microcirculation. <b>Design</b> Observational study. <b>Setting</b> Tromsø, Norway (near the North Pole), and Amsterdam, the Netherlands. <b>Participants</b> Five healthy human volunteers, two adult reindeer, and a patient with grade 3 nasal polyposis. <b>Main outcome measures</b> Architecture of the microvasculature of the nasal septal mucosa and head of the inferior turbinates, kinetics of red blood cells, and real time reactivity of the microcirculation to topical medicines. <b>Results</b> Similarities between human and reindeer nasal microcirculation were uncovered. Hairpin-like capillaries in the reindeers’ nasal septal mucosa were rich in red blood cells, with a perfused vessel density of 20 (SD 0.7) mm/mm<sup>2</sup>. Scattered crypt or gland-like structures surrounded by capillaries containing flowing red blood cells were found in human and reindeer noses. In a healthy volunteer, nasal microvascular reactivity was demonstrated by the application of a local anaesthetic with vasoconstrictor activity, which resulted in direct cessation of capillary blood flow. Abnormal microvasculature was observed in the patient with nasal polyposis. <b>Conclusions</b> The nasal microcirculation of reindeer is richly vascularised, with a vascular density 25% higher than that in humans. These results highlight the intrinsic physiological properties of Rudolph’s legendary luminous red nose, which help to protect it from freezing during sleigh rides and to regulate the temperature of the reindeer’s brain, factors essential for flying reindeer pulling Santa Claus’s sleigh under extreme temperatures.
Yersiniosis as an Internal Disease
Authors: R. LEINO
Journal: Annals of Internal Medicine (1974)

In 1971-1973, 60 patients were hospitalized for an infectious disease caused by Yersinia enterocolitica serotypes III and IX or Yersinia pseudotuberculosis serotype I. At that time 65 patients with similar symptoms were treated as outpatients. Diagnosis was mainly based on elevated antibody titers against these microorganisms. Forty-three cases of infection were caused by Y. enterocolitica III, 13 by Y. enterocolitica IX and 4 by Y. pseudotuberculosis I. Fever, diarrhea, abdominal pains, erythema nodosum, and arthritis were the most prominent symptoms. One patient was first operated on for suspected acute appendicitis; another developed a severe, ulcerative, colitistype disease. Four patients showed electrocardiographic signs of myocarditis, but no murmurs could be heard. Hematuria and proteinuria were detected in one patient; needle biopsy of the kidney showed glomerulonephritic changes. One patient with yersiniosis had mild hepatitis. The data suggest that some patients previously diagnosed with rheumatic fever actually had yersiniosis.
Spider Toxins: Recent Applications in Neurobiology
Authors: Hunter Jackson, Thomas N. Parks
Journal: Annual Review of Neuroscience (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
The Koniocellular Pathway in Primate Vision
Authors: Stewart H. C. Hendry, R. Clay Reid
Journal: Annual Review of Neuroscience (2000)

A neurochemically distinct population of koniocellular (K) neurons makes up a third functional channel in primate lateral geniculate nucleus. As part of a general pattern, K neurons form robust layers through the full representation of the visual hemifield. Similar in physiology and connectivity to W cells in cat lateral geniculate nucleus, K cells form three pairs of layers in macaques. The middle pair relays input from short-wavelength cones to the cytochrome-oxidase blobs of primay visual cortex (V1), the dorsal-most pair relays low-acuity visual information to layer I of V1, and the ventral-most pair appears closely tied to the function of the superior colliculus. Throughout each K layer are neurons that innervate extrastriate cortex and that are likely to sustain some visual behaviors in the absence of V1. These data show that several pathways exist from retina to V1 that are likely to process different aspects of the visual scene along lines that may remain parallel well into V1.
Protective Effect of Thrombomodulin in a Murine Model of Allergen-Induced Asthma
Authors: T. Takagi, M. Onishi, M. Urawa, M. Naito, A. Fujiwara, T. Kobayashi, H. Kobayashi, M. Toda, D. Boveda, P. Gil-Bernabe
Journal: Journal of Allergy and Clinical Immunology (2011)
Heat-shock protein peptide complex–96 vaccination for recurrent glioblastoma: a phase II, single-arm trial
Authors: Orin Bloch, Courtney A. Crane, Yelena Fuks, Rajwant Kaur, Manish K. Aghi, Mitchel S. Berger, Nicholas A. Butowski, Susan M. Chang, Jennifer L. Clarke, Michael W. McDermott, Michael D. Prados, Andrew E. Sloan, Jeffrey N. Bruce, Andrew T. Parsa
Journal: Neuro-Oncology (2013)

Outcomes for patients with recurrent glioblastoma multiforme (GBM) are poor and may be improved by immunotherapy. We investigated the safety and efficacy of an autologous heat-shock protein peptide complex-96 (HSPPC-96) vaccine for patients with recurrent GBM.In this open-label, single-arm, phase II study, adult patients with surgically resectable recurrent GBM were given vaccine after gross total resection. The primary endpoint was overall survival at 6 months. Secondary endpoints included overall survival, progression-free survival, safety, and immune profiling. Outcome analyses were performed in the intention-to-treat and efficacy populations.Between October 3, 2007 and October 24, 2011, 41 patients underwent gross total resection of recurrent GBM and received a median of 6 doses of HSPPC-96 vaccine. Following treatment, 90.2% of patients were alive at 6 months (95% confidence interval [CI]: 75.9-96.8) and 29.3% were alive at 12 months (95% CI: 16.6-45.7). Median overall survival was 42.6 weeks (95% CI: 34.7-50.5). Twenty-seven (66%) patients were lymphopenic prior to therapy, and patients with lymphocyte counts below the cohort median demonstrated decreased overall survival (hazard ratio: 4.0; 95% CI: 1.4-11.8; P = .012). There were no treatment-related deaths. There were 37 serious (grades 3-5) adverse events reported, with 17 attributable to surgical resection and a single grade 3 constitutional event related to the vaccine.The HSPPC-96 vaccine is safe and warrants further study of efficacy for the treatment of recurrent GBM. Significant pretreatment lymphopenia may impact the outcomes of immunotherapy and deserves additional investigation.
Phorbol dibutyrate stimulates the release of diffusible endothelium-derived vasoconstrictor factor(s) from canine femoral arteries.
Authors: G M Rubanyi, A Luisi, A Johns
Journal: Circulation Research (1991)

The purpose of this study was to analyze the effect of the tumor-promoting phorbol ester 12,13-dibutyrate (PDBu) on the synthesis/release of nonprostanoid endothelium-derived vasoactive factors. In bioassay experiments (in the presence of 10(-5) M indomethacin), infusion of PDBu (10(-9)-10(-7) M) through a femoral artery (donor) segment with endothelium evoked further, concentration-dependent contraction of superfused canine coronary artery bioassay rings without endothelium (already contracted with 10(-7) M PDBu). Removal of the endothelium from the donor segment abolished further contractions of the bioassay ring to 10(-9) M PDBu and significantly depressed the contractile responses to 10(-9) and 10(-7) M PDBu infused through the donor segment. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate had no effect on vascular preparations mounted in the bioassay system. Selective exposure of the bioassay tissue to 10(-7) M PDBu completely inhibited its responsiveness to basally released endothelium-derived relaxing factor. These data indicate that PDBu stimulates the release of a diffusible and bioassayable vasoconstrictor mediator(s) from the endothelium of canine femoral arteries.
Theophylline for COPD
Authors: P J Barnes
Journal: Thorax (2006)

Reinstatement in the light of new evidence?

Theophylline has been used as a bronchodilator in the treatment of COPD for over 70 years, but has lost popularity as better tolerated and more effective bronchodilators have been introduced. However, new insights into the molecular action of theophylline have raised the possibility that this old drug may come back into favour as an anti-inflammatory treatment and may even reverse steroid resistance in COPD.1 A paper by Hirano et al in this issue of Thorax provides further support for the anti-inflammatory effects of theophylline in patients with COPD.2

In the major guidelines for the treatment of COPD, theophylline is relegated to a third line bronchodilator after inhaled anticholinergics and β2 agonists. Nevertheless, it is recognised that theophylline is a useful treatment in patients with severe COPD as its withdrawal leads to significant clinical worsening of the disease.3 Many older clinicians have been convinced by its clinical value in severe disease.

Traditionally, theophylline was used as a bronchodilator in the treatment of airway disease but, to achieve significant bronchodilatation comparable with that of a β2 agonist, relatively high plasma concentrations are needed (10–20 mg/l). Theophylline relaxes human airway smooth muscle in vitro through inhibition of phosphodiesterases (PDE), enzymes that break down cyclic nucleotides in the …
DNA-dependent protein kinase catalytic subunit modulates the stability of c-Myc oncoprotein
Authors: Jing An, Dong-Yan Yang, Qin-Zhi Xu, Shi-Meng Zhang, Yan-Ying Huo, Zeng-Fu Shang, Yu Wang, De-Chang Wu, Ping-Kun Zhou
Journal: Molecular Cancer (2008)

Abstract Background C-Myc is a short-lived oncoprotein that is destroyed by ubiquitin-mediated proteolysis. Dysregulated accumulation of c-Myc commonly occurs in human cancers. Some of those cases with the dysregulated c-Myc protein accumulation are attributed to gene amplification or increased mRNA expression. However, the abnormal accumulation of c-Myc protein is also a common finding in human cancers with normal copy number and transcription level of c-Myc gene. It seems that the mechanistic dysregulation in the control of c-Myc protein stabilization is another important hallmark associated with c-Myc accumulation in cancer cells. Here we report a novel mechanistic pathway through which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) modulates the stability of c-Myc protein. Results Firstly, siRNA-mediated silencing of DNA-PKcs strikingly downregulated c-Myc protein levels in HeLa and HepG2 cells, and simultaneously decreased cell proliferation. The c-Myc protein level in DNA-PKcs deficient human glioma M059J cells was also found much lower than that in DNA-PKcs efficient M059K cells. ATM deficiency does not affect c-Myc expression level. Silencing of DNA-PKcs in HeLa cells resulted in a decreased stability of c-Myc protein, which was associated the increasing of c-Myc phosphorylation on Thr58/Ser62 and ubiquitination level. Phosphorylation of Akt on Ser473, a substrate of DNA-PKcs was found decreased in DNA-PKcs deficient cells. As the consequence, the phosphorylation of GSK3 β on Ser9, a negatively regulated target of Akt, was also decreased, and which led to activation of GSK 3β and in turn phosphorylation of c-Myc on Thr58. Moreover, inhibition of GSK3 activity by LiCl or specific siRNA molecules rescued the downregulation of c-Myc mediated by silencing DNA-PKcs. Consistent with this depressed DNA-PKcs cell model, overexpressing DNA-PKcs in normal human liver L02 cells, by sub-chronically exposing to very low dose of carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), increased c-Myc protein level, the phosphorylation of Akt and GSK3 β, as well as cell proliferation. siRNA-mediated silencing of DNA-PKcs in this cell model reversed above alterations to the original levels of L02 cells. Conclusion A suitable DNA-PKcs level in cells is necessary for maintaining genomic stability, while abnormal overexpression of DNA-PKcs may contribute to cell proliferation and even oncogenic transformation by stabilizing the c-Myc oncoprotein via at least the Akt/GSK3 pathway. Our results suggest DNA-PKcs a novel biological role beyond its DNA repair function.
Expression Profiles Provide Insights into Early Malignant Potential and Skeletal Abnormalities in Multiple Endocrine Neoplasia Type 2B Syndrome Tumors
Authors: Sanjay Jain, Mark A. Watson, Mary K. DeBenedetti, Yuji Hiraki, Jeffrey F. Moley, Jeffrey Milbrandt
Journal: Cancer Research (2004)

Abstract Identifying the molecular basis for genotype-phenotype correlations in human diseases has direct implications for understanding the disease process and hence for the identification of potential therapeutic targets. To this end, we performed microarray expression analysis on benign (pheochromocytomas) and malignant (medullary thyroid carcinomas, MTCs) tumors from patients with multiple endocrine neoplasia (MEN) type 2A or 2B, related syndromes that result from distinctive mutations in the RET receptor tyrosine kinase. Comparisons of MEN 2B and MEN 2A MTCs revealed that genes involved in the process of epithelial to mesenchymal transition, many associated with the tumor growth factor β pathway, were up-regulated in MEN 2B MTCs. This MEN 2B MTC profile may explain the early onset of malignancy in MEN 2B compared with MEN 2A patients. Furthermore, chondromodulin-1, a known regulator of cartilage and bone growth, was expressed at high levels specifically in MEN 2B MTCs. Chondromodulin-1 mRNA and protein expression was localized to the malignant C cells, and its high expression was directly associated with the presence of skeletal abnormalities in MEN 2B patients. These findings provide molecular evidence that associate the previously unexplained skeletal abnormalities and early malignancy in MEN 2B compared with MEN 2A syndrome.
Recrudescence of Helicobacter pylori after apparently successful eradication: novel application of randomly amplified polymorphic DNA fingerprinting.
Authors: H X Xia, H J Windle, D G Marshall, C J Smyth, C T Keane, C A O'Morain
Journal: Gut (1995)

The aim of this study was to find out if reinfection or recrudescence accounted for the recurrence of Helicobacter pylori infections after apparent eradication of the bacterium. Three hundred and twenty patients were treated with colloidal bismuth subcitrate (120 mg four times daily for four weeks), metronidazole and tetracycline (400 mg and 500 mg, respectively, thrice daily for the first week). H pylori was eradicated four weeks after the end of treatment as assessed by the rapid urease test, histological examination, Gram staining, and culture. However, the infection recurred in 29 (9.1%) of the patients one year after apparent eradication. Pre and posteradication isolates from five patients were available. DNA was extracted and used for restriction endonuclease analysis with Hind III and Hae III, and for polymerase chain reaction (PCR) based randomly amplified polymorphic DNA fingerprinting with a combination of two 10 nucleotide primers. Sodium dodecyl sulphate polyacrylamide gel electrophoretic analysis was performed also. Randomly amplified polymorphic DNA fingerprinting was unique in that it yielded highly discriminatory fingerprints, which showed that the pretreatment and recurrent isolates obtained from each of the five patients were indistinguishable from one another. This shows that recurrence of H pylori infection is probably caused by recrudescence and that the discriminatory power of randomly amplified polymorphic DNA fingerprinting is a practicable and discriminatory typing scheme for H pylori.
Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element
Authors: Truyen Nguyen, Philip J. Sherratt, Cecil B. Pickett
Journal: The Annual Review of Pharmacology and Toxicology (2003)

The expression of genes encoding antioxidative and Phase II detoxification enzymes is induced in cells exposed to electrophilic compounds and phenolic antioxidants. Induction of these enzymes is regulated at the transcriptional level and is mediated by a specific enhancer, the antioxidant response element or ARE, found in the promoter of the enzyme's gene. The transcription factor Nrf2 has been implicated as the central protein that interacts with the ARE to activate gene transcription constitutively or in response to an oxidative stress signal. This review focuses on the molecular mechanisms whereby the trancriptional activation mediated by the interaction between the ARE and NF-E2-related factor 2 (Nrf2) is regulated. Recent studies suggest that the sequence context of the ARE, the nature of the chemical inducers, and the cell type are important for determining the activity of the enhancer in a particular gene.
Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis
Authors: Jerry A. Nick, Christopher D. Coldren, Mark W. Geraci, Katie R. Poch, Brian W. Fouty, James O'Brien, Michael Gruber, Simona Zarini, Robert C. Murphy, Katherine Kuhn, Don Richter, Kelly R. Kast, Edward Abraham
Journal: Blood (2004)
Anti-cyclic citrullinated peptide antibodies in hepatitis C virus associated rheumatological manifestations and Sjogren's syndrome
Authors: D Sene
Journal: Annals of the Rheumatic Diseases (2006)

<h3>Abstract</h3> Founder events play a critical role in shaping genetic diversity, impacting the fitness of a species and disease risk in humans. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods for characterizing founder events require large sample sizes or phased genomes. To learn about the frequency and evolutionary history of founder events, we introduce <i>ASCEND</i> (Allele Sharing Correlation for the Estimation of Non-equilibrium Demography), a flexible two-locus method to infer the age and strength of founder events. This method uses the correlation in allele sharing across the genome between pairs of individuals to recover signatures of past bottlenecks. By performing coalescent simulations, we show that <i>ASCEND</i> can reliably estimate the parameters of founder events under a range of demographic scenarios, with genotype or sequence data. We apply <i>ASCEND</i> to ~5,000 worldwide human samples (~3,500 present-day and ~1,500 ancient individuals), and ~1,000 domesticated dog samples. In both species, we find pervasive evidence of founder events in the recent past. In humans, over half of the populations surveyed in our study had evidence for a founder events in the past 10,000 years, associated with geographic isolation, modes of sustenance, and historical invasions and epidemics. We document that island populations have historically maintained lower population sizes than continental groups, ancient hunter-gatherers had stronger founder events than Neolithic Farmers or Steppe Pastoralists, and periods of epidemics such as smallpox were accompanied by major population crashes. Many present-day groups--including Central &amp; South Americans, Oceanians and South Asians--have experienced founder events stronger than estimated in Ashkenazi Jews who have high rates of recessive diseases due to their history of founder events. In dogs, we uncovered extreme founder events in most groups, more than ten times stronger than the median strength of founder events in humans. These founder events occurred during the last 25 generations and are likely related to the establishment of dog breeds during Victorian times. Our results highlight a widespread history of founder events in humans and dogs, and provide insights about the demographic and cultural processes underlying these events.