tbuckley/cabot-search huggingface dataset:
The contribution of Alu exons to the human proteome
Authors: Lan Lin, Peng Jiang, Juw Won Park, Jinkai Wang, Zhi-xiang Lu, Maggie P. Y. Lam, Peipei Ping, Yi Xing
Journal: Genome biology (2016)

Alu elements are major contributors to lineage-specific new exons in primate and human genomes. Recent studies indicate that some Alu exons have high transcript inclusion levels or tissue-specific splicing profiles, and may play important regulatory roles in modulating mRNA degradation or translational efficiency. However, the contribution of Alu exons to the human proteome remains unclear and controversial. The prevailing view is that exons derived from young repetitive elements, such as Alu elements, are restricted to regulatory functions and have not had adequate evolutionary time to be incorporated into stable, functional proteins. We adopt a proteotranscriptomics approach to systematically assess the contribution of Alu exons to the human proteome. Using RNA sequencing, ribosome profiling, and proteomics data from human tissues and cell lines, we provide evidence for the translational activities of Alu exons and the presence of Alu exon derived peptides in human proteins. These Alu exon peptides represent species-specific protein differences between primates and other mammals, and in certain instances between humans and closely related primates. In the case of the RNA editing enzyme ADARB1, which contains an Alu exon peptide in its catalytic domain, RNA sequencing analyses of A-to-I editing demonstrate that both the Alu exon skipping and inclusion isoforms encode active enzymes. The Alu exon derived peptide may fine tune the overall editing activity and, in limited cases, the site selectivity of ADARB1 protein products. Our data indicate that Alu elements have contributed to the acquisition of novel protein sequences during primate and human evolution.
Abstract 2455: Differences in dynamic modulation of CoQ10 redox status and intracellular localization between non-disease and cancer cell lines
Authors: Katerina Krumova, Sumit Garg, Sirisha Dhavala, Vivek K. Vishnudas, Michael A. Kiebish, Rangaprasad Sarangarajan, Niven R. Narain
Journal: Cancer Research (2015)

Abstract Although it is well recognized that Coenzyme Q10 (CoQ10) is present in all cellular membrane structures, its effects on cellular functions other than mitochondrial regulation is poorly understood. The present study was aimed at gleaning insights into effect on CoQ10 on sub-cellular metabolism, regulation of the redox status, as well as gene regulation. A series of fluorescent probes were developed with the ability to report on the consequence of specific biological events in which CoQ10 was involved. The probes constituted fluorescently labeled CoQ10 analogues designed to track the distribution, biochemical and redox behaviour of CoQ10 in a non-invasive manner providing real time information in live cells. Compartmentalization of fluorescent labeled CoQ10 probe incorporated within BPM 31510 liposomal formulation was characterized in human derived primary non-disease and cancer cell lines. Cellular distribution of the fluorescent CoQ10 varied depending upon cell type. The fluorescent CoQ10 probes were designed and utility to provide a time resolved assessment on the redox state of CoQ10 in whole cells and organelles as a measure of the cell's overall and intracellular location specific metabolic micro-environments. The ratio of reduced and oxidized form of fluorescent CoQ10 was also examined in relation to ROS production in cancer cells. The overall results describes the presence of a constant redox flux influencing the redox state of CoQ10 within cancer and normal cells with significant variation depending on cell type and disease status. Citation Format: Katerina Krumova, Sumit Garg, Sirisha Dhavala, Vivek K. Vishnudas, Michael A. Kiebish, Rangaprasad Sarangarajan, Niven R. Narain. Differences in dynamic modulation of CoQ10 redox status and intracellular localization between non-disease and cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2455. doi:10.1158/1538-7445.AM2015-2455
The diagnostic yield of sampling techniques used in the diagnosis of tuberculous lymphadenitis
Authors: Laura-Jane Smith, Yasser Madani, Akeel Jubber, Angela Hauser, Bridget Hall
Journal: European Respiratory Journal (2013)

Introduction:  Lymphadenitis is the commonest manifestation of extrapulmonary tuberculosis (TB). It remains a diagnostic challenge and requires a high degree of clinical suspicion as it mimics other conditions and can yield inconsistent investigation findings.  Objective:  To evaluate the yield of various sampling techniques used in diagnosing tuberculous lymphadenitis.  Methods:  Medical records of 97 patients diagnosed with tuberculous lymphadenitis between 2009 and 2011 in a district general hospital in Essex, UK, identified from the TB database, were retrospectively reviewed.  Results:  26% had intrathoracic and extrathoracic nodes, 60% extrathoracic and 14% intrathoracic only. Most commonly affected nodes were supraclavicular (33%), cervical (32%) and inferior mediastinal (24%). Fine needle aspiration (FNA) was undertaken in 24 cases and was positive for microbiology in 15 (63%, microscopy 7, culture 10) and for cytology in 5 (21%). Trucut biopsy was undertaken in 9 cases and was positive for microbiology in 3 (33%, microscopy 0, culture 3) and for histology in 8 (89%). Excision biopsy was undertaken in 49 cases and was positive for microbiology in 21 (43%, microscopy 2, culture 19) and histology in 43 (88%).  Conclusion:  Contrary to previously published data, FNA provided the highest yield for both microscopy and culture. The literature has traditionally advocated excisional biopsy as the diagnostic procedure of choice given its high sensitivity. FNA has emerged as a safer, quicker, simpler and less invasive alternative. If FNA is negative and clinical suspicion remains high, trucut or excisional biopsy should be pursued. Definitive diagnosis is by culture which remains the gold standard.
Biomarkers of Fluorouracil Toxicity
Authors: Steven M. Offer, Robert B. Diasio
Journal: JAMA Oncology (2016)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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 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 Oncology journal
Correlation of quantitative p95HER2 and HER2 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant (NEO) trastuzumab-containing therapy.
Authors: Jose Caetano Villasboas, Judith Hurley, Jodi Marie Weidler, Agnes Paquet, Carmen Gomez Fernandez, Maureen Cioffi Lavina, Jeff Sperinde, Ahmed Chenna, Mojgan Haddad, Yolanda Lie, John William Winslow, Weidong Huang, Christos J. Petropoulos, Mark D. Pegram
Journal: Journal of Clinical Oncology (2012)

608 Background: Elevated p95 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p110 or p95HER2] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data have been presented on the correlation between p95 and pCR to T in the NEO setting, where p95 was measured by immunohistochemistry. In the current study, we sought to determine whether quantitative p95 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: HER2 expression (H2T) was quantified by HERmark in 47 breast tumors using formalin-fixed, paraffin-embedded sections. Tissue remained in 40 cases to measure p95 by VeraTag and compare to a previously published cutoff (Clin Cancer Res 16:4226, 2010). pCR data were available for 45 cases. pCR was defined as the absence of invasive disease in the breast. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; Wilcoxon rank p&lt;0.0001) and was significantly associated with higher H2T levels (p=0.02). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups [median H2T=111.5 (IQR 63.4-162.2) vs 150.5 (IQR 43 – 226.2), respectively; p=0.721]. However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group [median H2T=254 (IQR 181.5-584.5) vs 37.3 (IQR 16.4-89); p=0.024]. Using multivariate logistic regression, increasing log(H2T) (p = 0.011), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T expression in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. A trend towards pCR was seen in tumors that had low p95. These data suggest that quantitative H2T and p95 may provide additional information on response to T-based regimens in breast cancer, particularly ER+ breast cancer. Additional investigation into the possible relationship between quantitative levels of HER2 and p95 expression and T response in the NEO setting in larger cohorts is warranted.
IP10 as a diagnostic marker for childhood tuberculosis in a Tanzanian population
Authors: Line Lindebo Holm, Michala Vaaben Rose, Thomas Nørlykke, Pernille Ravn, Morten Ruhwald
Journal: European Respiratory Journal (2012)

Intro

A main challenge in childhood TB management is the lack of good diagnostic tools. IP-10 is a novel marker for latent tuberculosis (TB), but very few studies have examined the use of IP-10 in childhood TB.

Aims

To compare the performance of the Quantiferon test (QFT) and IP-10 for the diagnosis of TB in Tanzanian children

Methods

207 TB suspected children (0-15 years) and 102 adults with confirmed TB were included. QFT tests were analyzed locally and IP-10 was measured using ELISA. The children were divided in to three risk groups using clinical parameters, CXR, microscopy and culture: Confirmed/highly probable TB (probTB, n=33), possible TB (possTB, n=84) and Not TB (notTB, n=90).

Results

In children the positivity rate was low in all groups for both tests.

View this table:

Table 1





IP-10 positivity rate was associated with TB risk groups (p=0.02), QFT was not (p= 0.12). The agreement between IP-10 and QFT was 70%, discordance was mainly found in the possTB and notTB groups, combining tests did not increase test sens. For both tests indet. outcome was not associated with HIV status, young age or malnutrition.

In adults the sens. was 80% for both tests; and the indet. rate was 11% for IP-10 and 6% for the QFT (agree. 83%, k=0.5, p<0.0001).

Discussion

In the children both tests had poor performance with low positivity rate and high indeterminate rate; this was not explained by risk factors for poor test performance. In adults the QFT and IP-10 test performance was in line with other studies. Our findings could be explained by group heterogeneity and severity of illness.
Relationship of Urinary Excretion of Modified Nucleosides to Disease Status in Childhood Acute Lymphoblastic Leukemia<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: D A Heldman, M R Grever, J S Miser, R W Trewyn
Journal: JNCI Journal of the National Cancer Institute (1983)

The levels of urinary excretion of five modified nucleosides were quantitated by high-performance liquid chromatography for 15 normal children and 24 children with acute lymphoblastic leukemia (ALL). Excretion of each nucleoside decreased linearly with age when quantitation was based on urine creatinine content. Patients with childhood ALL at initial diagnosis or in relapse had significantly higher concentrations of 1-methylinosine, N2,N2-dimethylguanosine, 1-methylguanosine, and pseudouridine in their urine when compared to the concentrations in either patients in remission (P less than 0.001, P less than 0.001, P less than 0.01, and P less than 0.05, respectively) or normal controls (P less than 0.001, P less than 0.02, P less than 0.01, and P less than 0.001, respectively). Excretion of 2-pyridone-5-carboxamide-N'-ribofuranoside did not show significant differences. Urinary excretion of 1-methylinosine demonstrated a positive linear relationship with the percentage of blast cells in the bone marrow [correlation coefficient (r) = 0.90]; the other nucleosides had lower degrees of correlation. In comparison, the absolute blast cell count in the peripheral blood showed less correlation to the percentage of blast cells in the bone marrow (r = 0.47) than did four of the five nucleosides. The data demonstrate that excretion of modified nucleosides reflects disease activity in childhood ALL and that the urinary nucleosides could be useful clinical markers for this disease.
Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in pleural mesothelioma
Authors: A.S.T. Planting, M.E.L. van der Burg, S.H. Goey, J.H.M. ScheUens, M.J. van den Bent, M. de Boer-Dennert, G. Stoter, J. Verweij
Journal: Annals of Oncology (1995)
Psychiatry and the criminal justice system: testing the myths
Authors: M R Phillips, A S Wolf, D J Coons
Journal: American Journal of Psychiatry (1988)

Several states are changing legislation and treatment programs for mentally ill offenders without knowing how current laws and programs operate. To address this problem the authors linked data from police records, court reports, and clinical files for 2,735 psychiatric referrals from the criminal justice system of Alaska from 1977 through 1981. They found that only 0.2%-2.0% of all schizophrenic persons in the community were arrested for violent crimes each year, accounting for 1.1%-2.3% of all arrests for violent crimes; that psychiatrists agreed about competency and responsibility in 79% of the cases evaluated by more than one clinician; and that a successful insanity defense occurred in 0.1% or less of all criminal cases.
Abstract P102: Circulating Adipocytokines and Risk of Chronic Kidney Disease
Authors: Katherine T Mills, L Lee Hamm, Brent Alper, Chad Miller, Alhakam Hudaihed, Saravanan Balamuthusamy, Chung-Shiuan Chen, Yanxi Liu, Joseph Tarsia, Nader Rifai, Myra Kleinpeter, Jing Chen
Journal: Circulation (2012)

Recent studies have found a link between obesity and chronic kidney disease (CKD). However, the mechanism for this association is not well understood. Obesity-related CKD may be partially mediated by adipocytokines, including leptin, resistin, and adiponectin. In this study we investigated the association of plasma leptin, resistin and adiponectin with risk of CKD in 201 cases with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m2 or presence of albuminuria. Median levels of adipocytokines and odds ratios of CKD were estimated and adjusted for age, gender, race, smoking, drinking, education, physical activity, systolic blood pressure, glucose, low-density lipoprotein cholesterol, and body mass index. Compared to controls, adjusted median plasma leptin (38,385 vs. 17,303 ng/mL, p&lt;0.0001) and resistin (15.0 vs. 8.0 ng/mL, p&lt;0.0001) were significantly higher in CKD cases. The median ratio of high molecular weight adiponectin to total adiponectin was lower in cases than in controls (0.38 vs. 0.43, p=0.0001). The odds ratios (OR) for CKD comparing the highest third to the lowest two thirds of leptin was 4.7 (95% CI, 2.2, 9.8) and of resistin was 17.0 (95% CI, 8.4, 34.2). A non-significant weak inverse effect was seen when comparing the highest third to the lowest two thirds of the adiponectin ratio with an OR of 0.8 (95% CI, 0.4, 1.3). The results did not change substantially after further adjustment for history of cardiovascular disease. Our study found that increased leptin and resistin are associated with an increased risk of CKD. In conclusion, these findings suggest that adipocytokines may play a role in the etiology of CKD. Longitudinal studies are warranted to further evaluate the causal relationship of these adipocytokines with development of CKD.
Management for Doctors: Getting started as a medical manager
Authors: J F Riordan, J. Simpson
Journal: BMJ (1994)

Three years after his appointment as a consultant physician, Dr B was persuaded by his colleagues to become chairman of the cogwheel division of medicine, all the other physicians having taken their turn. He coped easily with running the monthly divisional meeting, found some satisfaction in juggling the junior medical rotas, and saw his most challenging role as resisting the attempts of the surgeons to “protect” their beds.

After a year in post a keen new general manager was appointed to take the hospital into trust status; he selected Dr B with several other consultants, not all of whom were divisional chairs, to form a management board. Dr B became the first clinical director of medicine. Initially he found this difficult as his colleagues continued to run the old divisional structure in parallel with the new arrangements. Also the senior nurses in medicine were suspicious of medical involvement in their management.

After some months of regular meetings with the nurse manager, along with several training and team building sessions, Dr B found that by working as part of a team he could influence the functioning of the medical service and achieved a number of successes. These included improving the process of case note retrieval; rearranging the appointments procedure; and developing a number of enthusiastic teams to take on specific projects within the directorate. After a few months the atmosphere and communication within the directorate had improved considerably, with staff of all grades beginning to contribute their ideas and support for the new systems. On the strength of this, Dr B managed to persuade his consultant colleagues to disband the cogwheel division and set up a full directorate structure with a number of subdirectorates. To his surprise he found that he enjoyed working with some of the newly recruited, bright, and …
The effect of the PI3K/AKT pathway inhibition on leiomyosarcoma cells
Authors: G. Z. D'Amato, S. Mohapatra, R. Jove, T. C. Windham, A. C. Burns, D. Sullivan, C. Muro-Cacho, G. D. Letson, W. J. Pledger
Journal: Journal of Clinical Oncology (2004)

9002 Background: Leiomyosarcomas (LMS) are one of the most common histological types of soft tissue sarcomas and are usually resistant to standard chemotherapy. Novel agents that can cause apoptosis must be explored. The PI3K/AKT pathway is an important survival pathway and is upregulated in many tumor cells. Recent publications have shown that the AKT pathway is an important survival pathway for a uterine LMS cell line, SKLMS-1. In this study we examined the effects of LY294002, a specific PI 3-kinase inhibitor on the survival of the SKLMS-1 cell line. Methods: Various doses of LY294002 were added to growing SKLMS-1 cells for 24, 48 and 72 hours. Cells were harvested at these time points and counted. Cell cycle distribution was analyzed by propidium iodide staining. Apoptosis was analyzed by both TUNEL assay and cleavage of PARP by western blotting. Cell lysates were analyzed for cyclin D3, cyclin A, and p27 by western blot. Results: At all doses (10, 20 and 50 μM) LY294002 caused G0/G1 growth arrest at 24hours in a dose-dependent manner. Cells that were treated for 48 and 72 hours were killed as demonstrated by decreased cell counts, TUNEL assay and PARP cleavage. Apoptosis occurred in both a time and dose dependent manner. At a dose of 10 μM, a 5-fold and 14-fold decrease in cell number was found at 48 and 72 hours respectively, compared to cells treated with the control DMSO. At a dose of 50 μM, cell count revealed more than a 12-fold decrease in cell numbers for both 48 and 72 hours. Analysis of the cell cycle distribution correlated with the cell counts. Results showed that LY294002 arrested the cells early in G0/G1 allowing them to transverse through one cell cycle, and then become trapped in G0 and ultimately die through apoptosis. Expression of cyclin A and cyclin D3 was reduced in the treated cells. Interestingly, p27 levels did not increase with treatment. Conclusions: The PI3K inhibitor, LY294002 caused apoptosis in a both dose and time dependent manner. At 24 hours cells were arrested in G0/G1. At higher doses and at 48 and 72 hours, cells were killed by apoptosis. These preclinical data may provide an opportunity for the development of novel therapies that target the P13K/AKT pathway No significant financial relationships to disclose.
Cytotoxicity of Antibody-Directed Liposomes That Recognize Two Receptors on K562 Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Keith S. Bragman, Timothy D. Heath
 6, Demetrios Papahadjopoulos
Journal: JNCI Journal of the National Cancer Institute (1984)

Encapsulation of methotrexate-γ-aspartate in antibody-conjugated liposomes increased its toxicity for K562 cells, a human leukemia cell line that expresses Fc receptors and human glycophorin A. The liposomes were conjugated with either nonspecific mouse IgG, which interacts with an Fc receptor, or with monoclonal anti-human glycophorin, which interacts simultaneously with an Fc receptor and human glycophorin in the cell membrane. The drug in antibody-directed liposomes was up to 20 times more effective than the free drug, and it was 55 times more effective than the drug in liposomes bearing no surface ligand. The efficacy of drug delivery with liposomes directed only to an Fc receptor was reduced ninefold in the presence of soluble human IgG. Efficacy of drug delivery with liposomes directed both to the Fc receptor and to glycophorin A was not reduced by human IgG or soluble antiglycophorin A, but it was reduced twofold in the presence of both soluble ligands. These results were qualitatively consistent with previous studies on the binding of targeted liposomes to K562 cells.