tbuckley/cabot-search huggingface dataset:
Nuclear Translocation of Lactosylated Poly-l-lysine/cDNA Complex in Cystic Fibrosis Airway Epithelial Cells
Authors: Daniel T. Klink, Simon Chao, Mary Catherine Glick, Thomas F. Scanlin
Journal: Molecular Therapy (2001)

<h2>Abstract</h2> Poly-l-lysine, with 40% of its amino groups substituted with lactose, is an effective vector to transfer the CFTR gene into CF airway epithelial cells and correct the chloride channel dysfunction. The intracellular fate of the lactosylated poly-l-lysine/cDNA complex was studied using confocal microscopy. In the presence of chloroquine the complex remained intact during internalization, intracellular transport, and, most importantly, transport into the nucleus. When cells were transfected in the presence of agents that enhance transfection efficiency such as E5CA peptide, a fusogenic peptide, or glycerol a similar fate of the lactosylated poly-l-lysine/cDNA complex was seen. However, when these agents were omitted from the transfection medium, the complex remained in the perinuclear region. Uncomplexed lactosylated poly-l-lysine reached the nucleus efficiently. In contrast mannosylated poly-l-lysine or unsubstituted poly-l-lysine complexed to plasmid did not. Therefore the nuclear accumulation of the complex may be attributed to the substitution of poly-l-lysine with lactose. It is hypothesized that the lactose residues provide for nuclear localization by means of targeting a potential lectin-like protein with galactose/lactose specificity. This mechanism may be responsible for the nuclear internalization of the complex.
Gastric Cancer Found on 3′-Deoxy-3′ F-18 Fluorothymidine Positron Emission Tomography
Authors: Mitsuru Koizumi, Tsuneo Saga, Kyosan Yoshikawa, Masayuki Baba
Journal: Clinical Nuclear Medicine (2008)

We report a case of gastric cancer that was incidentally found on 3′-deoxy-3′ F-18fluorothymidine (FLT) positron emission tomography (PET). FLT PET has the potential utility for noninvasively measuring cellular proliferation in vivo in many malignant tumors. A 68-year-old male with squamous cell carcinoma of the left upper lung was treated by carbon ion radiotherapy (CIRT; 52.8 GyE./4 fractions). To evaluate the response of the lung cancer to CIRT, an FLT PET/CT study was performed before and 3 months after CIRT. Very intense focal uptake of FLT in the gastric wall on PET images obtained 3 months after CIRT raised the suspicion of gastric malignancy. Endoscopic examination revealed an advanced gastric cancer (tubular adenocarcinoma, well to moderately differentiated) at the site of intense FLT uptake.
Clinical Significance of <i>EpCAM</i> mRNA-Positive Circulating Tumor Cells in Hepatocellular Carcinoma by an Optimized Negative Enrichment and qRT-PCR–Based Platform
Authors: Wei Guo, Xin-Rong Yang, Yun-Fan Sun, Min-Na Shen, Xiao-Lu Ma, Jiong Wu, Chun-Yan Zhang, Yan Zhou, Yang Xu, Bo Hu, Xin Zhang, Jian Zhou, Jia Fan
Journal: Clinical Cancer Research (2014)

This study aimed to construct a novel platform for the detection of circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC) and to investigate the clinical significance of epithelial cell adhesion molecule mRNA-positive (EpCAM(mRNA+)) CTCs using this platform.An optimized platform for CTC detection was constructed by evaluating different negative enrichment, mRNA isolation, and cDNA synthesis procedures and compared with the CellSearch system. A total of 299 patients with HCC were recruited into this prospective study; of these, 157 who received curative resection, 76 who received transcatheter arterial chemoembolization (TACE), and 66 who received radiotherapy were tested using our platform. The diagnostic value of EpCAM(mRNA+) CTCs was investigated in 122 patients with HCC who underwent resection and 120 control subjects.The optimized negative enrichment and quantitative real-time PCR (qRT-PCR)-based CTC detection platform had high sensitivity, specificity, and reproducibility and a low sample volume requirement. This platform showed a potential diagnostic value in patients with HCC and exhibited 76.7% consistency with the CellSearch system (r = 0.54, P < 0.050). Pretreatment CTC level showed prognostic significance in patients with HCC treated with resection, TACE, and radiotherapy (all P < 0.050). Most of the patients showed a decrease in CTC levels after treatment that reflected tumor response. In contrast, patients with an increased CTC level showed disease progression after treatment.We established an optimized platform based on negative enrichment and qRT-PCR for highly sensitive, specific, and reproducible CTC detection. This platform might be clinically useful in auxiliary diagnosis, treatment response assessment, and early decision-making to tailor the most effective antitumor strategies.
Pulmonary sarcoidosis and the acute respiratory distress syndrome (ARDS)
Authors: F Sabbagh
Journal: Thorax (2002)

A 50 year old man presented with 3 weeks of exertional dyspnoea. His chest radiograph on admission revealed diffuse bilateral interstitial infiltrates. He did not respond to antibiotics but subsequently improved on high dose corticosteroids. Bronchoscopic examination with transbronchial biopsy specimens revealed the presence of non-necrotising granulomas. This case demonstrates an unusual clinical presentation of life threatening pulmonary sarcoidosis characterised by the development of acute respiratory distress syndrome (ARDS) with acute respiratory failure.
Commentary: misinterpretation of the rules
Authors: C. Reeves
Journal: BMJ (1995)

Mr Adams has concluded from the particular experience of his department that NHS accounting rules create a disincentive to treating private patients in NHS hospitals as a means of income generation. This is simply not the case. The income generated from private patients is making an increasingly valuable contribution to the resources available to treat NHS patients, and the rules are framed to accommodate this.

Mr Adams states that resources have not followed patients. In fact, as is clear from his article, all the extra patients treated in his department have brought in …
Preimplantation genetic testing
Authors: P. R. Brezina, D. S. Brezina, W. G. Kearns
Journal: BMJ (2012)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Preimplantation genetic testing Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Methodologic approaches to studying environmental factors in childhood cancer.
Authors: S Grufferman
Journal: Environmental Health Perspectives (1998)

Little is known about environmental causes of childhood cancer. This is probably due to the relative rarity of cancer in children. In the United States, cancer incidence in adults is over 20 times greater than cancer incidence in children. The situation is compounded by the fact that two groups of cancers, leukemias and brain and spinal tumors, account for half of all childhood cancers. The rarity of childhood cancer renders the conduct of most cohort studies infeasible. The majority of studies assessing potential environmental risk factors for childhood cancers have been case-control studies, which are highly efficient for studying rare diseases. Case-control studies of childhood cancers have been greatly facilitated by using cooperative clinical trial groups for case identification. The national studies that have emerged utilize random-digit telephone dialing and telephone interviewing as feasible and economic means of identifying and interviewing controls. Other approaches such as descriptive epidemiology, ecologic studies, and studies of cancer clusters have proven to be disappointing in elucidating environmental causes of childhood cancer. Descriptive and ecologic studies provide no information on specific exposures of study subjects; rather, they use population levels as surrogates for individual exposure. Studies of cancer clusters have also proven to be disappointing. Although there are numerous difficulties in conducting research on the causes of childhood cancer, these difficulties can be remedied by using carefully designed and conducted studies. It should be remembered that the epidemiologic approach is probably the most likely research venue for uncovering environmental causes of childhood cancer.
SEPSIS OF THE NEWBORN.
Authors: HENRY E. TULEY
Journal: JAMA (1896)

lately a photograph of a child has been published, in which the outline gave also an idea of the density of the tissues.In my clinic we got good results in the examination of rickets.The bones made scarcely a shadow, giving ocular demonstration of the diagnosis already made of rickets.I don't think, Mr. President, there is any field in the practice of medicine in which the diagnosis can be, if the proper amount of patience is used, so easy, so thorough and so satisfactory.
Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines
Authors: Emanuela Romano, Michael Scordo, Stephen W. Dusza, Daniel G. Coit, Paul B. Chapman
Journal: Journal of Clinical Oncology (2010)

Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based.Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period.The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse.Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses.
Insig: a significant integrator of nutrient and hormonal signals
Authors: Alan D. Attie
Journal: Journal of Clinical Investigation (2004)

Lipogenesis is regulated by sterols and by insulin through the regulated expression and activation of the sterol regulatory element–binding proteins (SREBPs). A new study shows one way in which sterol and insulin regulation can be decoupled. In transgenic mice overexpressing a protein that regulates SREBP activation, lipogenesis is more sensitive to cholesterol and less sensitive to insulin.
Res Ipsa Loquitur
Authors: Howard Newcomb Morse
Journal: JAMA (1966)

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
FK506 inhibits antigen receptor-mediated induction of <i>c-rel</i> in B and T lymphoid cells.
Authors: L Venkataraman, S J Burakoff, R Sen
Journal: The Journal of Experimental Medicine (1995)

Stimulation of B and T cells via the antigen receptor, by phorbol ester or by phorbol ester and ionomycin, leads to nuclear translocation of the inducible transcription factor NF-kappa B, comprising the p50 and p65 rel-related polypeptides. In this report we show that c-rel is a component of the antigen receptor-induced kappa B binding proteins in both B and T cells. Whereas NF-kappa B can be induced by phorbol ester alone, optimal induction of c-rel requires stimulation by both phorbol ester and ionomycin, the dual signal that is necessary for proliferation of untransformed lymphocytes. Furthermore, c-rel induction is blocked by the immunosuppressive drug FK506 that is known to inhibit B and T cell activation. c-rel-dependent transactivation of the interleukin-2 receptor alpha chain (IL-2R alpha) promoter is augmented by coexpression of calcineurin, suggesting the involvement of a calcineurin-dependent intracellular pathway. Our results identify c-rel as a target of immunosuppressive agents and illustrate the similarity of activation pathways in both B and T cells.
Electroconvulsive therapy: Conflicting advice confuses prescribers
Authors: R. Evans
Journal: BMJ (2003)

Editor—Carney and Geddes highlight the conflicting advice on the use of electroconvulsive therapy by two influential bodies, the National Institute for Clinical Excellence (NICE) and the Royal College of Psychiatrists.1 The NICE guidelines restrict the use of electroconvulsive therapy while the royal college argues for wider inclusion criteria. The NICE guidelines also emphasise that no patient should be coerced into treatment.

So what is the reason for the disagreement between NICE and the royal college? NICE deliberately wants to curb the use of electroconvulsive therapy because of unresolved concerns about side effects, particularly memory loss.2 Studies into its long term effects on cognitive function are lacking, but in their systematic review Rose et al say that 29-55% of patients report persistent memory loss.3,4 However, the validity of this figure is questionable because of the poor methodological design of the studies included.

Faced with such a lack of convincing evidence NICE's approach has been to restrict the use of electroconvulsive therapy on the one hand while emphasising the need for fully informed consent on the other. How is the latter possible if we are still uncertain about the long term effects on memory?

Psychiatrists will now have to decide which expert opinion to accept. In the current medicolegal climate the implications of operating outside the NICE guidelines are likely to trump other considerations such as patient choice. We would advocate that the Royal College of Psychiatrists and NICE meet to resolve their differences and provide unified guidelines for patients and clinicians.
C-Reactive Protein Levels and the Expansion of Screen-Detected Abdominal Aortic Aneurysms in Men
Authors: Paul Norman, Carole A. Spencer, Michael M. Lawrence-Brown, Konrad Jamrozik
Journal: Circulation (2004)

Background— C-reactive protein (CRP) levels have been shown to predict a number of cardiovascular outcomes. CRP levels have also been found to be elevated in patients with abdominal aortic aneurysms (AAAs). The aim of this study was to assess the relation between CRP levels and rates of expansion of small AAAs. Methods and Results— A cohort of men with small aneurysms was identified in a trial of screening with ultrasound scanning. After initial screening, men were rescanned at 6- to 12-month intervals. CRP levels were measured at the first follow-up visit. Rates of expansion and risk factors for expansion were assessed with the use of data from 545 men who attended for at least 1 scan after CRP levels were measured. These men were followed for a median of 48 (range, 5 to 69) months. The mean annual rate of expansion was 1.6 mm. The median CRP level was 2.6 mg/L in men with the smaller AAAs (30 to 39 mm, n=433) compared with 3.5 mg/L in men with larger AAAs (40 to 54 mm, n=112) ( P =0.007). The multivariate age-adjusted logistic model confirmed initial aortic diameter to be the only factor associated with rapid expansion with an odds ratio of 7.2 (95% CI, 4.3,12.2) for an initial diameter of 40 to 54 mm relative to one of 30 to 39 mm. Conclusions— Most small aneurysms expand slowly. CRP levels are elevated in larger aneurysms but do not appear to be associated with rapid expansion. The most useful predictor of aneurysmal expansion in men is aortic diameter.
Abstract PR6: Widespread potential for growth factor-driven resistance to anti-cancer kinase inhibitors
Authors: Timothy R. Wilson, Jane Fridlyand, Antoni Ribas, Jiang Li, Hartmut Koeppen, Mark Merchant, Richard Neve, Jeff Settleman, Yibing Yan, Elicia Penuel, Luciana Burton, Emily Chan, Jing Peng, Eva Lin, Yulei Wang, Jeff Sosman
Journal: Clinical Cancer Research (2012)

Abstract Mutationally activated kinases, including EGFR, HER2, ALK, ABL, PDGFR, c-KIT, and BRAF, define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumors harbor such alleles is invariably limited by innate or acquired drug resistance. As molecular mechanisms of resistance have begun to be elucidated, a recurrent theme is the engagement of survival signals redundant to those transduced by the targeted oncogenic kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs), and many of these can potentially mediate signals that converge on common and critical downstream cell survival effectors - most notably, PI-3 kinase (PI3K) and MAP kinase (MAPK). Consequently, an increase in RTK ligand levels, via autocrine tumor cell production, paracrine contribution by tumor stroma, or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar downstream signaling output. Indeed, using a large panel of kinase-“addicted” cancer cell lines, we found that the vast majority of such cells can be “rescued” from drug sensitivity by simply exposing them to one or more RTK ligands that engage redundant survival effectors. Among the findings with immediate clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the HER2 kinase inhibitor lapatinib in HER2 amplified breast cancer cells, and to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF mutant melanoma cells. Analysis of systemic HGF levels from PLX4032-treated BRAF mutant metastatic melanoma patients who were enrolled on the BRIM2 study indicated that increased HGF levels were significantly associated with a worse clinical outcome. These observations highlight the extensive redundancy of RTK-transduced signaling in cancer cells and the potentially broad role of widely expressed RTK ligands in both innate and acquired resistance to drugs targeting oncogenic kinases. This proffered talk is also presented as Poster B38.
Effect of antihypertensive treatment on kidney function in diabetic nephropathy.
Authors: H H Parving, A R Andersen, U M Smidt, E Hommel, E R Mathiesen, P A Svendsen
Journal: BMJ (1987)

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.
Nail Changes after Chemotherapy
Authors: P H Slee
Journal: New England Journal of Medicine (1997)

Figure 1. A 50-year-old woman with metastatic breast cancer received seven courses of docetaxel at three-week intervals. After this treatment, the number and sizes of her lung metastases (the only known metastases) were unchanged. Total alopecia developed, but she experienced no nausea or loss of appetite.
Premature Extravasation
Authors: AYDA EL-SHIRBINY, RAFAEL FERNANDEZ, LIONEL S. ZUCKIER
Journal: Clinical Nuclear Medicine (1995)

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.