tbuckley/cabot-search huggingface dataset:
NI-43 * GROWTH KINETICS OF CONTRAST ENHANCING GLIOMAS ASSOCIATE INVASIVE GROWTH WITH SEIZURE PRESENTATION
Authors: J. Juliano, R. Rockne, A. Hawkins-Daarud, P. Jackson, J. Jacobs, E. Kokkinos, A. Rosenberg, J. Crisman, C. Peters, D. Sharfman, S. Johnston, M. Sondag, S. Badhe, M. Lester, T. Gallagher, P. Kumthekar, K. Swanson
Journal: Neuro-Oncology (2014)

PURPOSE: Epileptic seizure is a common presentation for patients with malignant glioma. Although the biological mechanisms which produce tumor-associated seizures are unclear, seizures are more prevalent in grade II gliomas. We hypothesized that an invasive growth kinetic would be associated with seizure incidence at presentation, and this association may explain why non-grade IV gliomas are more likely to present with seizures. METHODS: A total of 354 patients with contrast enhancing gliomas WHO grade II (N = 13), III (N = 28), and IV (N = 313) were studied. We incorporated diagnostic T1 + contrast and T2/FLAIR MRIs into a mathematical growth model to calculate a ratio of migration (D, mm2/yr) and proliferation (P, 1/yr) rates of tumor growth. We examined the association between the relative invasiveness ratio (D/P, mm2) and seizure presentation. RESULTS: When stratifying patients by histologic grade, grade III seizure presenting (SP) patients exhibited higher average D/P (p = 0.012, t-test) than non-seizure presenting (NSP) patients. Within grade III patients, SP patients with little to no mass effect similarly exhibited higher average D/P than NSP patients (p = 0.035 t-test). Broadening our scope, we observed that among all grade II-IV contrast enhancing gliomas, SP patients had higher D/P (p = 0.025, Mann-Whitney) than NSP patients. CONCLUSIONS: The association of high D/P with SP suggests that patients with an invasive growth pattern (high D/P) may be more likely to present with seizures than nodular tumors (low D/P). We interpret this association to imply that more infiltrative tumor growth is more likely to produce a seizure due to tumor cell invasion along white matter tracts, disrupting functional connectivity. In contrast, nodular growth may predominately push against, rather than invade along white matter tracts, leading to less disruption of functional connectivity and decreased seizure incidence.
Treatment with inhaled steroids in patients with symptoms suggestive of asthma but with normal lung function
Authors: P. Rytilä, L. Ghaly, S. Varghese, W. Chung, O. Selroos, T. Haahtela
Journal: European Respiratory Journal (2008)

A total of 144 patients with lower airway symptoms suggestive of asthma, but who did not fulfil the functional criteria of asthma, were included in a randomised, double-blind, placebo-controlled 8-week “proof-of-concept” study with mometasone furoate (MF), 400 µg once daily. The primary efficacy variable was the mean change from baseline in six morning and evening weekly symptom scores: cough, sputum production, wheeze, shortness of breath, chest tightness and exercise-induced cough/wheeze. Total symptom scores were calculated after treatment for 4 and 8 weeks. Compared with placebo, MF improved total morning symptom score at 8 weeks. Changes in total evening symptom scores did not differ between treatments. MF improved all individual symptom scores more than placebo, although the differences in changes between treatments were not always statistically significant. Morning and evening peak expiratory flow rates increased with MF compared with placebo. MF reduced eosinophils and the levels of eosinophilic cationic protein in induced sputum. The results show that symptoms suggestive of asthma exist in patients without significant β 2 -agonist reversibility or diurnal variability in peak flow. Once-daily MF may benefit some of these patients and a short course with inhaled corticosteroids may be tried. Responders should be better identified in further studies.
Resistance to an Irreversible Epidermal Growth Factor Receptor (EGFR) Inhibitor in EGFR-Mutant Lung Cancer Reveals Novel Treatment Strategies
Authors: Zhiwei Yu, Titus J. Boggon, Susumu Kobayashi, Cheng Jin, Patrick C. Ma, Afshin Dowlati, Jeffrey A. Kern, Daniel G. Tenen, Balázs Halmos
Journal: Cancer Research (2007)

Abstract Patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer derive significant clinical benefit from treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Secondary EGFR mutations such as EGFR T790M commonly lead to resistance to these agents, limiting their long-term efficacy. Irreversible EGFR inhibitors such as CL-387,785 can overcome resistance and are in clinical development, yet acquired resistance against these agents is anticipated. We carried out a cell-based, in vitro random mutagenesis screen to identify EGFR mutations that confer resistance to CL-387,785 using T790M-mutant H1975 lung adenocarcinoma cells. Mutations at several residues occurred repeatedly leading to functional resistance to CL-387,785. These variants showed uninhibited cell growth, reduced apoptosis, and persistent EGFR activation in the presence of CL-387,785 as compared with parental H1975 cells, thus confirming their role in resistance. A screen of alternative agents showed that both an alternative EGFR inhibitor and a cyclin-dependent kinase 4 inhibitor led to significant inhibition of cell growth of the resistant mutants, suggestive of potential alternative treatment strategies. These results identify novel mutations mediating resistance to irreversible EGFR inhibitors and reveal alternative strategies to overcome or prevent the development of resistance in EGFR-mutant non–small cell lung cancers. [Cancer Res 2007;67(21):10417–27]
Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal allograft rejection in rats
Authors: Qing Pan, Qingguo Xu, Nicholas J. Boylan, Nicholas W. Lamb, David G. Emmert, Jeh-Chang Yang, Li Tang, Tom Heflin, Saeed Alwadani, Charles G. Eberhart, Walter J. Stark, Justin Hanes
Journal: Journal of Controlled Release (2015)
The pathobiochemistry of uremia and hyperargininemia further demonstrates a metabolic relationship between urea and guanidinosuccinic acid
Authors: Bart Marescau, Peter P. De Deyn, Ijaz A. Qureshi, Marc E. De Broe, Italo Antonozzi, Stephen D. Cederbaum, Roberto Cerone, Nestor Chamoles, Rosa Gatti, Soo-Sang Kang, Marie Lambert, Ilse Possemiers, Selma E. Snyderman, Makoto Yoshino
Journal: Metabolism (1992)
25 Years of Endoscopic Sphincterotomy in Erlangen: Assessment of the Experience in 3498 Patients
Authors: T. Rabenstein, H. T. Schneider, E. G. Hahn, C. Ell
Journal: Endoscopy (1998)

Background and Study Aims: The aim of the study was to investigate the evolution of endoscopic sphincterotomy (EST) over a period of 25 years at its birthplace in Erlangen, Germany.
Genome-wide search followed by replication reveals genetic interaction of<i>CD80</i>and<i>ALOX5AP</i>associated with systemic lupus erythematosus in Asian populations
Authors: Yan Zhang, Jing Yang, Jing Zhang, Liangdan Sun, Nattiya Hirankarn, Hai-Feng Pan, Chak Sing Lau, Tak Mao Chan, Tsz Leung Lee, Alexander Moon Ho Leung, Chi Chiu Mok, Lu Zhang, Yongfei Wang, Jiangshan Jane Shen, Sik Nin Wong, Ka Wing Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Brian Hon-Yin Chung, Chun Yin Chong, Raymond Woon Sing Wong, Mo Yin Mok, Wilfred Hing Sang Wong, Kwok Lung Tong, Niko Kei Chiu Tse, Xiang-Pei Li, Yingyos Avihingsanon, Pornpimol Rianthavorn, Thavatchai Deekajorndej, Kanya Suphapeetiporn, Vorasuk Shotelersuk, Shirley King Yee Ying, Samuel Ka Shun Fung, Wai Ming Lai, Chun-Ming Wong, Irene Oi Lin Ng, Maria-Merce Garcia-Barcelo, Stacey S Cherny, Yong Cui, Pak Chung Sham, Sen Yang, Dong-Qing Ye, Xue-Jun Zhang, Yu Lung Lau, Wanling Yang
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility. <h3>Methods</h3> The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction. <h3>Results</h3> Interaction of <i>CD80</i> (rs2222631) and <i>ALOX5AP</i> (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, <i>P_int_all</i>=7.7E-04 at false discovery rate&lt;0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (<i>P_all</i>=4.5E-08, OR=0.86) and is independent of rs6804441 in <i>CD80,</i> whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between <i>BLK</i> (rs13277113) and <i>DDX6</i> (rs4639966), and between <i>TNFSF4</i> (rs844648) and <i>PXK</i> (rs6445975) were also observed in both GWAS data sets. <h3>Conclusions</h3> Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.
Roentgenology of Intracranial Meningiomas
Authors: Daniel Ruge
Journal: JAMA (1961)

This book presents not only an interesting roentgenographic study of intracranial meningiomas, but a very excellent study of meningiomas in their entirety. The author had available to him a large series of 220 meningiomas which had been operated upon at the Montreal Neurological Institute. He has reviewed the literature of meningiomas rather thoroughly and has presented a historical review interestingly. The chapter on clinical observations is very complete. The various pathological classifications are also presented. On the whole, the roentgenograms are of excellent quality, and a large variety of films are shown. These include plain skull roentgenograms as well as contrast studies, such as angiography and the various air studies. There are a number of drawings which are also of excellent quality and aid in elucidating the text. I think this is a very fine book, concisely written, and it should be of interest to both neurosurgeon and radiologist.
Direct Retrograde Femoral Aortography
Authors: John A. Waldhausen, Eugene C. Klatte
Journal: New England Journal of Medicine (1962)

OWING to the advances in vascular surgery corrective operative procedures for arterial disease are now commonly performed. Accurate preoperative information is helpful to evaluate the type and extent of the surgery. The use of femoral arteriography is well established as a safe and practical method. For the demonstration of the abdominal portion of the aortic tree several technics have been developed.Translumbar aortography is an effective method of contrast visualization of the aorta. This method has been largely replaced by other technics because of the hazards of dissection of the aorta, or inadvertent placement of the needle into a branch . . .
Point mutation in a leucine-rich repeat of platelet glycoprotein Ib alpha resulting in the Bernard-Soulier syndrome.
Authors: J Ware, S R Russell, P Marchese, M Murata, M Mazzucato, L De Marco, Z M Ruggeri
Journal: Journal of Clinical Investigation (1993)

Leucine-rich repeats are a conserved structural motif, of yet undefined significance, found in a group of proteins from different species. Among these are the four components of the human platelet glycoprotein Ib-IX-V complex, a membrane receptor that performs an essential role in the thrombogenic function of platelets by interacting with the adhesive protein, von Willebrand factor. We have found that a single amino acid substitution (Ala156-->Val) within one of the six leucine-rich repeats in the alpha-subunit of glycoprotein Ib results in a variant form of the congenital bleeding disorder, Bernard-Soulier syndrome, characterized by giant dysfunctional platelets. Genetic studies of the propositus and his family members were complemented by immunological and functional analysis of expressed recombinant GP Ib alpha fragments to demonstrate that the observed mutation is the cause of defective von Willebrand factor binding. These studies define the molecular basis of the Bernard-Soulier syndrome within this family and demonstrate that structural integrity of a leucine-rich repeat is necessary for normal function of the glycoprotein Ib-IX-V receptor complex and, possibly, for normal platelet morphology.
Shipman inquiry calls for major changes in death certification
Authors: C. Dyer
Journal: BMJ (2002)

Sweeping changes are needed to plug loopholes in the systems of death and cremation certification that allowed the English GP Harold Shipman to murder more than 200 patients, the Shipman inquiry says in a discussion paper this week.

Shipman, from Hyde, Greater Manchester, who became Britain's most prolific serial killer, killed 215 patients, according to the inquiry's findings. Many of the victims, mainly middle aged and elderly women, died unexpectedly, without any history of terminal or life threatening illness.

Shipman avoided referrals to the coroner by claiming that he was in a position to certify the …
Predicting Gross Motor Function in Cerebral Palsy
Authors: Stephen L. Kinsman
Journal: JAMA (2002)

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
Gal-Gal pili vaccines prevent pyelonephritis by piliated Escherichia coli in a murine model. Single-component Gal-Gal pili vaccines prevent pyelonephritis by homologous and heterologous piliated E. coli strains.
Authors: B Pecha, D Low, P O'Hanley
Journal: Journal of Clinical Investigation (1989)

The initial pathogenic step in nonobstructive Escherichia coli pyelonephritis usually involves the binding of a bacterial adhesin with host uroepithelial glycoprotein receptors containing the D-Gal p alpha 1----4 D-Gal p beta 1 (Gal-Gal) moiety. In this study, groups of mice were immunized with Gal-Gal pili and challenged 2 wk later intravesicularly with E. coli strains expressing homologous or heterologous pili. 63 of 129 pili-immunized mice (49%) were protected from subsequent E. coli renal colonization compared with 5 of 85 control mice (6%). Among mice that had E. coli cultured from their right kidney, control mice had greater bacterial colony counts than pili-immunized animals (P less than 0.05). Light microscopic examination of kidneys demonstrated less histopathology among pili immunized mice than among control mice (P less than 0.05). Protection correlated with the presence of specific IgG antibodies in the urine and serum that bind to the major pilin structural polypeptide and not to the Gal-Gal pili tip adhesin per se. These results support the concept that immunization with a bacterial surface-coat constituent can prevent mucosal infection by interfering with colonization. Also Gal-Gal pili of E. coli represent a suitable candidate for immunoprophylaxis against pyelonephritis.
Outpatient treatment of falciparum malaria is possible
Authors: Mark Melzer
Journal: BMJ (2006)

G-protein βγ subunits (Gβγ) interact with presynaptic proteins and regulate neurotransmitter release downstream of Ca<sup>2+</sup> influx. To accomplish their roles in sensory signaling, photoreceptor synapses employ specialized presynaptic proteins that support neurotransmission at active zone structures known as ribbons. While several G-protein coupled receptors (GPCRs) influence synaptic transmission at ribbon synapses of cones and other retinal neurons, it is unknown whether Gβγ contributes to these effects. We tested whether activation of one particular GPCR, a metabotropic glutamate receptor (mGluR), can reduce cone synaptic transmission via Gβγ in tiger salamander retinas. In recordings from horizontal cells (HCs), we found that an mGluR agonist (L-AP4) reduced cone-driven light responses and mEPSC frequency. In paired recordings of cones and HCs, L-AP4 slightly reduced cone I<sub>Ca</sub> (∼10%) and caused a larger reduction in cone-driven EPSCs (∼30%). Proximity ligation assay revealed direct interactions between SNAP-25 and Gβγ subunits in retinal synaptic layers. Pre-treatment with the SNAP-25 cleaving protease BoNT/A inhibited L-AP4 effects on synaptic transmission, as did introduction of a peptide derived from the SNAP-25 C-terminus. Introducing Gβγ subunits directly into cones reduced EPSC amplitude. This effect was inhibited by BoNT/A, supporting a role for Gβγ/SNAP-25 interactions. However, the mGluR-dependent reduction in I<sub>Ca</sub> was not mimicked by Gβγ, indicating this effect was independent of Gβγ. The finding that synaptic transmission at cone ribbon synapses is regulated by Gβγ/SNAP-25 interactions indicates that these mechanisms are shared by conventional and ribbon-type synapses. Gβγ liberated from other photoreceptor GPCRs is also likely to regulate synaptic transmission. <b>SIGNIFICANCE STATEMENT</b> Dynamic regulation of synaptic transmission by presynaptic G-protein coupled receptors shapes information flow through neural circuits. At the first synapse in the visual system, presynaptic metabotropic glutamate receptors (mGluRs) regulate cone photoreceptor synaptic transmission, although the mechanisms and functional impact of this are unclear. We show that mGluRs regulate light response encoding across the cone synapse, accomplished in part by triggering G-protein βγ subunits (Gβγ) interactions with SNAP-25, a core component of the synaptic vesicle fusion machinery. In addition to revealing a role in visual processing, this provides the first demonstration that Gβγ/SNAP-25 interactions regulate synaptic function at a ribbon-type synapse, contributing to an emerging picture of the ubiquity of Gβγ/SNARE interactions in regulating synaptic transmission throughout the nervous system.
Hereditary Pulmonary Alveolar Proteinosis
Authors: Takuji Suzuki, Takuro Sakagami, Lisa R. Young, Brenna C. Carey, Robert E. Wood, Maurizio Luisetti, Susan E. Wert, Bruce K. Rubin, Katharine Kevill, Claudia Chalk, Jeffrey A. Whitsett, Carrie Stevens, Lawrence M. Nogee, Ilaria Campo, Bruce C. Trapnell
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: We identified a 6-year-old girl with pulmonary alveolar proteinosis (PAP), impaired granulocyte-macrophage colony–stimulating factor (GM-CSF) receptor function, and increased GM-CSF.Objectives: Increased serum GM-CSF may be useful to identify individuals with PAP caused by GM-CSF receptor dysfunction.Methods: We screened 187 patients referred to us for measurement of GM-CSF autoantibodies to diagnose autoimmune PAP. Five were children with PAP and increased serum GM-CSF but without GM-CSF autoantibodies or any disease causing secondary PAP; all were studied with family members, subsequently identified patients, and controls.Measurement and Main Results: Eight children (seven female, one male) were identified with PAP caused by recessive CSF2RA mutations. Six presented with progressive dyspnea of insidious onset at 4.8 ± 1.6 years and two were asymptomatic at ages 5 and 8 years. Radiologic and histopathologic manifestations were similar to those of autoimmune PAP. Molecular analysis demonstrated that GM-CSF signaling was absent in six and severely reduced in two patients. The GM-CSF receptor β chain was detected in all patients, whereas the α chain was absent in six and abnormal in two, paralleling the GM-CSF signaling defects. Genetic analysis revealed multiple distinct CSF2RA abnormalities, including missense, duplication, frameshift, and nonsense mutations; exon and gene deletion; and cryptic alternative splicing. All symptomatic patients responded well to whole-lung lavage therapy.Conclusions: CSF2RA mutations cause a genetic form of PAP presenting as insidious, progressive dyspnea in children that can be diagnosed by a combination of characteristic radiologic findings and blood tests and treated successfully by whole-lung lavage.
Timed-Disintegration Capsules (Tymcaps) — A Further Study
Authors: Theodore M. Feinblatt, Edgar A. Ferguson
Journal: New England Journal of Medicine (1957)

WE have continued our study of timed-disintegration capsules to amplify the description of the disintegration pattern and to compare the x-ray visualization of the breakdown of the capsules with blood-level determinations by pentaerythritol tetranitrate.LiteratureBefore publication of the in vivo roentgenographic study1 little could be found in the literature relating to timed-disintegration capsules. According to a study by the Pharmaceutical Chemical, Vitamin and Nutrition Sections of the Canadian Department of National Health and Welfare,2 a nonmetabolite (sodium para-aminosalicylate) is less available the longer the in vivo disintegration time. The original work by the same group had been criticized by . . .
A COMPARISON OF VIRUS-INDUCED RABBIT TUMORS WITH THE TUMORS OF UNKNOWN CAUSE ELICITED BY TARRING
Authors: Peyton Rous, John G. Kidd
Journal: The Journal of Experimental Medicine (1939)

Tarring the ears of rabbits of one sort with a single kind of tar evoked epidermal tumors of a few sharply defined types, namely ordinary papillomas, carcinoids, carcinomas, and "frill horns." These last, relatively infrequent, are now recognized for the first time. The carcinoids have proved to be the expression of a spurious malignancy of papillomas, resulting from intercurrent influences, and they were wholly dependent upon these for their threatening aspect and behavior. Chief amongst such influences was continued tarring. It had the effect of establishing the papillomas, stimulated their proliferation, complicated their morphology, and rendered some of them disorderly, aggressive, and anaplastic. It brought all of the tissues of the ears into an excitable state, and often this state endured long after the skin had apparently returned to normal. The characters of the papilloma-carcinoids and of the frill horns were so different and distinctive as to imply the action of differing, specific causes. The papillomas were very like those induced with the Shope virus, and hence a point-to-point comparison was made of their manifestations, including the derivation of carcinomas from them. This comparison demonstrated that the unknown cause of the tar papillomas provoked neoplastic phenomena which were identical in all essential respects with those due to the virus. To suppose, for experimental purposes, that the papillomas which tarring elicits are caused by a virus rendered pathogenic by this procedure, is to demand least of the unknown. Yet it does not follow that they must be due to a virus.