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The matter in dispute is determined by ascertaining the eastern line of the lot which was conveyed by the plaintiff to George and Samuel Phelps, by his deed of May 4, 1850. Tyler vs. ...doi:10.2307/3301836 fatcat:5raf4svnzbeqdb4gqruacqr7my
Review & Expositor
The Immortal Seven: Judson and His Associates, Dr. and Mrs. Adoniram Judson, Samuel Newell, Harriet Newell, Gordon Hall, Samuel Nott, Luther Rice. By James L. ... Judson the Pioneer. By J. Mervin Hull. ...doi:10.1177/003463731401100238 fatcat:d4rdfx3b2rdndisxcyzmox5nbi
Notes and Queries
SAMUEL WOODFORD AND EDMUND SPENSER. ... JUDSON. Indiana University, Bloomington, Indiana. LADY PERFECT AND SIR JOHN LOVEALL.—The editors! ...doi:10.1093/nq/189.9.191b fatcat:bsylzt2y7vdu7ff7pd7xopmkuy
Annals of Surgery
., anp SAMUEL S. Scuarrer, M.D. Houston, Tex. AN ExostTosis of the scapula, with no similar lesions elsewhere, has been reported to be comparatively rare: Du Mortier and Halpert,! ...doi:10.1097/00000658-193712000-00017 fatcat:m5itwt4vgzgyveekejfdyaqch4
BACKGROUND-Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a propensity for local recurrence and metastasis despite an indolent course. To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease. METHODS- The clinical behavior and treatment responses of 87 patients with EMC who were seen at 2 institutions between 1975 and 2008 were examined. RESULTS- The median age of thedoi:10.1002/cncr.23978 pmid:18951519 pmcid:PMC2779719 fatcat:w2ib5fcvzjhixcw53r2nnyiyum
more »... age of the patients at the time of diagnosis was 49.5 years, with a maleto-female ratio of 2:1. For patients presenting without metastases, 37% developed local recurrence (median time of 3.3 years) and 26% developed distal recurrence (median time of 3.2 years). Approximately 13% of patients presented with metastases. The 5-year, 10-year, and 15-year overall survival rates were 82%, 65%, and 58%, respectively. Twenty-one patients received 32 evaluable courses of chemotherapy. No significant radiologic or clinical responses were noted. The median time to disease progression while receiving chemotherapy was 5.2 months. The best physicianassessed response to chemotherapy was stable disease for at least 6 months in 25% of patients, stable disease for <6 months in 41% of patients, and disease progression in 34% of patients. The estimated progression-free survival rates at 3 months, 4 months, 6 months, and 9 months were 69%, 65%, 40%, and 26%, respectively. CONCLUSIONS-This retrospective review highlights the poor response rate to chemotherapy and emphasizes aggressive control of localized disease as the primary approach to management. Although there are biases inherent in retrospective analyses, these data provide a benchmark for time to disease progression for the study of new agents for the treatment of patients with this diagnosis.
Delayed maturation of the adolescent prefrontal cortex (PFC) may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during post-natal days (PD) 28-42 on GABAergic neurotransmission in the prelimbic cortex (PrL-C). In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealeddoi:10.1111/adb.12353 pmid:26804056 pmcid:PMC4958607 fatcat:rlpsq5ovr5f6tinaj2hlqeorbm
more »... atal ages revealed a developmental increase in the GABA A receptor-mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE exposed rats, the amplitude of the tonic current was significantly reduced compared to controls when tested at PD 45, 60 and 90-120. This AIE-induced reduction in tonic current was found to reflect attenuation of currents mediated by δ-subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE exposed adult rats compared to control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by δ-GABA A receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of δ-GABA A subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in δ-GABA A tonic currents in the adult PrL-C that may contribute to deficits in decision-making and behavioral control in adulthood.
The use of microRNAs as biomarkers has been proposed for many diseases including the diagnosis of melanoma. Although hundreds of microRNAs have been identified as differentially expressed in melanomas as compared to benign melanocytic lesions, limited consensus has been achieved across studies, constraining the effective use of these potentially useful markers. In this study we quantified microRNAs by next-generation sequencing from melanomas and their adjacent benign precursor nevi. We applieddoi:10.1101/507400 fatcat:njvcve5etrahvbzwoi4ckrsc3q
more »... or nevi. We applied a machine learning-based pipeline to identify a microRNA signature that separated melanomas from nevi and was unaffected by confounding variables, such as patient age and tumor cell content. By employing the ratios of microRNAs that were either enriched or depleted in melanoma compared to nevi as a normalization strategy, the classifier performed similarly across multiple published microRNA datasets, obtained by microarray, small RNA sequencing, or RT-qPCR. Validation on separate cohorts of melanomas and nevi correctly classified lesions with 83% sensitivity and 71-83% specificity, independent of variation in tumor cell content of the sample or patient age.
The efficacy and toxicity of first line palliative chemotherapy for soft tissue sarcomas (STS) in the elderly is poorly described. Methods: Patients over the age of 65 years receiving first line chemotherapy for advanced non-GIST STS January 1998 -January 2012 at the Royal Marsden Hospital were identified. Data regarding survival and predictive factors were collected retrospectively. Results: 120 patients (52 females) with a median age of 72 (range 65-83) were treated. The most commondoi:10.1186/s13569-015-0026-y pmid:25922657 pmcid:PMC4411764 fatcat:yupwzox6wvesvexbdnhe7rszaq
more »... st common histological subtypes were undifferentiated sarcoma (30%), leiomyosarcoma (27%), angiosarcoma (14%). 42% of patients had high grade tumours. 70% of patients had metastatic disease at presentation; lung metastasis being the most common disease site (72%). 80% received single agent chemotherapy, mostly with doxorubicin (60%). The median number of cycles was 2 (IQR 3). A partial response was reported in 20% of patients with disease stabilisation in a further 20%. 38% of patients were hospitalised for chemotherapy related toxicity. The median overall survival (OS) was 6.5 months (95% CI 4.7-8.3). Anaemia, lymphopenia, hypoalbuminemia, sarcoma subtype and co-morbidities were predictive for overall survival. Conclusion: The overall survival for elderly patients with STS is poor but several predictive factors have been identified. Hospital admissions for chemotherapy related toxicity are common.
Background-The long-term consequences of adolescent alcohol abuse that persist into adulthood are poorly understood and have not been widely investigated. We have shown that intermittent exposure to alcohol during adolescence decreased the amplitude of GABA A receptormediated tonic currents in hippocampal dentate granule cells in adulthood. The aim of the present study was to investigate the enduring effects of chronic intermittent alcohol exposure during adolescence or adulthood on thedoi:10.1111/acer.12562 pmid:25421517 pmcid:PMC4244607 fatcat:xkcbvls7yffw3hteszkhoqsyom
more »... hood on the expression of hippocampal GABA A receptors (GABA A Rs). Methods-We used a previously characterized tissue fractionation method to isolate detergent resistant membranes and soluble fractions, followed by western blots to measure GABA A R protein expression. We also measured mRNA levels of GABA A R subunits using quantitative realtime PCR. Results-Although the protein levels of α1-, α4and δ-GABA A R subunits remained stable between postnatal day (PD) 30 (early adolescence) and PD71 (adulthood), the α5-GABA A R subunit was reduced across that period. In rats that were subjected to adolescent intermittent ethanol (AIE) exposure between PD30-46, there was a significant reduction in the protein levels of the δ-GABA A R, in the absence of any changes in mRNA levels, at 48 hours and 26 days after the last ethanol exposure. Protein levels of the α4-GABA A R subunit were significantly reduced, but mRNA levels were increased, 26 days (but not 48 hours) after the last AIE exposure. Protein levels of α5-GABA A R were not changed by AIE, but mRNA levels were reduced at 48hrs but normalized 26 days after AIE. In contrast to the effects of AIE, chronic intermittent exposure to ethanol during adulthood (CIE) had no effect on expression of any of the GABA A R subunits examined. Conclusions-AIE produced both short-and long-term alterations of GABA A R subunits mRNA and protein expression in the hippocampus, whereas CIE produced no long lasting effects on those measures. The observed reduction of protein levels of the δ-GABA A R, specifically, is consistent with previously reported altered hippocampal GABA A R-mediated electrophysiological responses after AIE. The absence of effects of CIE underscores the emerging view of adolescence as a time of distinctive vulnerability to the enduring effects of repeated ethanol exposure.
Repeated binge-like exposure to alcohol during adolescence has been reported to perturb prefrontal cortical development, yet the mechanisms underlying these effects are unknown. Here we report that adolescent intermittent ethanol exposure induces cellular and dopaminergic abnormalities in the adult prelimbic cortex (PrL-C). Exposing rats to alcohol during early-mid adolescence (PD28-42) increased the density of long/thin dendritic spines of layer 5 pyramidal neurons in the adult PrL-C.doi:10.1038/npp.2016.190 pmid:27620551 pmcid:PMC5506791 fatcat:yhclsnnlzjccxofon35qduiree
more »... ult PrL-C. Interestingly, although AIE exposure did not alter the expression of glutamatergic proteins in the adult PrL-C, there was a pronounced reduction in dopamine (DA) D 1 receptor modulation of both intrinsic firing and evoked NMDA currents in pyramidal cells, whereas D 2 receptor function was unaltered. Recordings from fast-spiking interneurons also revealed that AIE reduced intrinsic excitability, glutamatergic signaling, and D 1 receptor modulation of these cells. Analysis of PrL-C tissue of AIE-exposed rats further revealed persistent changes in the expression of DA-related proteins, including reductions in the expression of tyrosine hydroxylase and catechol-O-methyltransferase (COMT). AIE exposure was associated with hypermethylation of the COMT promoter at a conserved CpG site in exon II. Taken together, these findings demonstrate that AIE exposure disrupts DA and GABAergic transmission in the adult medial prefrontal cortex (mPFC). As DA and GABA work in concert to shape and synchronize neuronal ensembles in the PFC, these alterations could contribute to deficits in behavioral control and decisionmaking in adults who abused alcohol during adolescence.
Samuel J . C a s e l l a , V i c t o r K.M. Han. & . J o~g p h n '~r r n l~, M 2 r d w E. Svoboda, J u d s o n J . ... Samuel J . C a s e l l a , V i c t o r K.M. Han. & . J o~g p h n '~r r n l~, M 2 r d w E. Svoboda, J u d s o n J . ...doi:10.1203/00006450-198506000-00073 fatcat:zmcbfsejijhnjjakl7ctjcjkly
Judson A. ... Samuel A. Ball, Ph.D., is Professor of psychiatry at the Yale University School of Medicine and Director of Research for the APT Foundation in New Haven, Connecticut. ...doi:10.3109/10826084.2011.521069 pmid:21190403 pmcid:PMC3083447 fatcat:j6dlzoye2be2pbxi334s5sr7fe
Myeloid cells comprise a major component of the Tumor Microenvironment (TME) promoting tumor growth and immune evasion. By employing a novel small molecule inhibitor of glutamine metabolism not only were we able to inhibit tumor growth but we markedly inhibited the generation and recruitment of Myeloid Derived Suppressor Cells (MDSC). Targeting tumor glutamine metabolism led to a decrease in CSF-3 and hence recruitment of MDSC as well immunogenic cell death leading to an increase indoi:10.1101/656553 fatcat:5bpebyc7mnb3rjp3hy7oximnqm
more »... ease in inflammatory Tumor Associated Macrophages (TAMs). Alternatively, inhibiting glutamine metabolism of the MDSC themselves led to activation induced cell death and conversion of MDSC to inflammatory macrophages. Surprisingly, blocking glutamine metabolism also inhibited IDO expression of both the tumor and myeloid derived cells leading to a marked decrease in kynurenine levels. This in turn inhibited the development of metastasis and further enhanced anti-tumor immunity. Indeed, targeting glutamine metabolism rendered checkpoint blockade-resistant tumors susceptible to immunotherapy. Overall, our studies define an intimate interplay between the unique metabolism of tumors and the metabolism of suppressive immune cells.
Objective-To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results. Methods-Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had andoi:10.1016/j.ygyno.2012.11.034 pmid:23201592 pmcid:PMC3638213 fatcat:uqapbthsqvgdjjndxzqpclze5y
more »... who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2 cm from midline), midline, or lateral ambiguous (LA) if located within 2 cm., but not involving the midline. Results-Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors. Conclusion-The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN.
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