tbuckley/cabot-search huggingface dataset:
11C-Meta-Hydroxyephedrine
Authors: Stefano Boschi, Filippo Lodi, Laura Boschi, Cristina Nanni, Sotirios Chondrogiannis, Patrick M. Colletti, Domenico Rubello, Stefano Fanti
Journal: Clinical Nuclear Medicine (2014)

Dysfunction of the sympathetic nervous system underlies many cardiac diseases and can be assessed by molecular imaging using SPECT tracers as I-metaiodobenzylguanidine (I-MIBG). The norepinephrine analog C-meta-hydroxyephedrine (HED) has been used with PET to map the regional distribution of cardiac sympathetic neurons. Hydroxyephedrine is rapidly transported into sympathetic neurons by the norepinephrine transporter and stored in vesicles. This review describes the mechanism of action, radiosynthesis, and application of HED in the assessment of the cardiac sympathetic nervous system in heart failure, myocardial infarction, and arrhythmias. Noncardiac applications of HED in the clinical setting of sympathetic nervous system tumors and other emerging research applications are described.
Abstract P3-12-07: Voyagers and their aids: The role of interactions between tumor and endothelial cells in brain metastasis
Authors: KN Shah, JS Faridi
Journal: Cancer Research (2012)

Abstract Clinically, brain metastases are most commonly observed in breast, lung, and melanoma cancers. When a tumor cell leaves its site of origin, it enters a nearby blood vessel on a voyage to find a new tissue to invade. These circulating tumor cells will act as voyagers and they interact with a endothelial cell. For example, in the case of brain metastasis, tumor cells need to adhere to brain endothelial cells before they can invade into the surrounding brain tissue. Thus, investigating the mechanisms of tumor and endothelial cell interactions can serve as a very powerful tool to inhibit the voyage of these tumor cells and prevent the formation of metastases. In this study, we performed trans-endothelial migration assay using HBMVEC cells to study tumor-endothelial interactions. In general, HBMVEC cells were seeded to BD-Falcon cell culture inserts at a density of 2 × 105 cells and allowed to grow for 24 hours to form a confluent monolayer and GFP expressing tumor cells (MCF-7, Akt3 overexpressing MCF7, MDA-MB-231 and MDA-MB-231-BR) were incubated at suitable interval at 37°C. At the end of incubation period, cells were fixed and number of tumor cells that will penetrate the monolayer of HBMEC were counted using Phase-contrast microscope in 12 different visual fields. Transmigrating tumor cells are thought to be able to overcome the endothelial barrier by inducing changes within endothelial cells. We identified the molecular changes responsible for such adhesion and invasion by cell sorting for gene expression analysis. After co-culturing the HBMEC (after transfecting with Mcherry protein) with GFP expressing tumor cells and Mcherry labeled HBMEC, we used cell sorting to separate tumor and HBMEC cells. After sorting the tumor cells and endothelial cells from co-culture, (MCF-7 monolayer vs MCF-7 co-cultured, MDA-MB-231 monolayer vs MDA-MB-231 co-cultured, HBMEC monolayer vs HBMEC co-cultured) gene expression analysis was performed using SABiosciences cell adhesion assay kit to accurately capture the genetic changes that occured in the tumor and endothelial cells upon co-culture. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-07.
New Data Suggest Fewer Mammograms For Younger, Older Women
Authors: Kara Smigel
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article New Data Suggest Fewer Mammograms For Younger, Older Women Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 24, 16 December 1992, Pages 1860–1862, https://doi.org/10.1093/jnci/84.24.1860 Published: 16 December 1992
The Role of Lung Scintigraphy in the Diagnosis of Nephrotic Syndrome With Pulmonary Embolism
Authors: S C Cherng, W S Huang, Y F Wang, S P Yang, Y F Lin
Journal: Clinical Nuclear Medicine (2000)

Purpose: Patients with nephrotic syndrome (NS) have an increased tendency to develop thrombosis and even to progress to pulmonary embolism (PE). This study was performed to determine the incidence of PE in NS with severe hypoalbuminemia and to investigate the possible role of ventilation–perfusion (V/Q) lung scans to evaluate these patients. Methods: Eighty-nine patients with NS (serum albumin concentration < 2 g/dl) and risk factors for PE were studied. In all patients, the probability that PE would develop was assessed based on the results of V/Q lung scans (Xe-133 for ventilation and Tc-99m MAA for perfusion imaging). The lung scans were judged using the modified Prospective Investigation of Pulmonary Embolism Diagnosis criteria. In 25 (28%) patients whose lung scans showed an intermediate or low probability, but for whom there was a strong clinical indication of PE, pulmonary angiography was performed. The patients’ clinical symptoms and signs on initial examination were observed. Additional examinations included electrocardiograms, chest radiography, and hematochemical tests such as albumin, blood urea nitrogen, creatinine, cholesterol, triglycerides, fibrinogen, antithrombin III, prothrombin time, and activated partial thromboplastin time. Results: Based on the findings of lung scans, 19 (21%) of the patients were categorized as having a high probability of PE. However, pulmonary angiography found that 10 (11%) other patients had PE despite having lung scan findings categorized as intermediate or low probability of PE. Except for plasma fibrinogen and antithrombin III levels, neither the clinical symptoms and signs, electrocardiogram findings, chest radiograph results, nor values of hematochemical testing were consistent with the occurrence of PE in these 29 patients. Conclusion: The results of this study suggest that PE is not a rare complication in patients with NS, and is usually clinically silent. In this series, the occurrence of PE did not appear to be always correlated with the clinical or hematochemical severity of NS, except for the association with elevated levels of fibrinogen and antithrombin III. When treating the clinical symptoms of patients with NS, physicians should be alert to the possible complication of PE. Serial V/Q lung scans may provide valuable clues in the evaluation of these patients.
Localized Changes in Properties of the Blood and Effects of Anticoagulant Drugs in Experimental Cerebral Infarction
Authors: John S. Meyer, Robert C. Struzziero
Journal: New England Journal of Medicine (1958)

RECENT clinical reports have stressed beneficial effects resulting from the use of anticoagulant drugs in thrombosis of the basilar and carotid arteries1 2 3 4 and in thromboembolic cerebrovascular disease.5 , 6 It was concluded that this type of treatment improves transient symptoms due to intermittent ischemia, decreases the occurrence of cerebral embolism and thrombosis but does not alter the course of cerebral infarction once established.7 How anticoagulant drugs cause benefit in cerebrovascular disease is not fully understood. Clinical and experimental evidence indicates that after a delay such treatment may result in recanalization of a thrombosed vessel. More rapid improvement occurring within the first week . . .
Multiple Colorectal Carcinomas, Polyposis coli, and Neurofibromatosis
Authors: C. B. PRATT, D. M. PRAHAM, B. N. RAO, I. D. FLEMING, R. DILAWARI
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Multiple Colorectal Carcinomas, Polyposis coli, and Neurofibromatosis Get access CHARLES B. PRATT, CHARLES B. PRATT 2Departments of Hematology/Oncology, St. Jude Children's Research HospitalP.O.Box 318, Memphis, TN 381013Departments of Pediatrics, University of Tennessee College of MedicineMemphis Search for other works by this author on: Oxford Academic PubMed Google Scholar DAVID M. PRAHAM, DAVID M. PRAHAM 4Pathology and Laboratory Medicine, St. Jude Children's Research HospitalP.O.Box 318, Memphis, TN 381016Pathology, University of Tennessee College of MedicineMemphis Search for other works by this author on: Oxford Academic PubMed Google Scholar BHASKAR N. RAO, BHASKAR N. RAO 5Surgery, St. Jude Children's Research HospitalP.O.Box 318, Memphis, TN 381017Surgery, University of Tennessee College of MedicineMemphis Search for other works by this author on: Oxford Academic PubMed Google Scholar IRVIN D. FLEMING, IRVIN D. FLEMING 5Surgery, St. Jude Children's Research HospitalP.O.Box 318, Memphis, TN 381017Surgery, University of Tennessee College of MedicineMemphis Search for other works by this author on: Oxford Academic PubMed Google Scholar RAZA DILAWARI RAZA DILAWARI 5Surgery, St. Jude Children's Research HospitalP.O.Box 318, Memphis, TN 381017Surgery, University of Tennessee College of MedicineMemphis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 14, 21 September 1988, Pages 1170–1172, https://doi.org/10.1093/jnci/80.14.1170 Published: 21 September 1988
Abstract 2352: Critical structural determinants of maspin necessary for maspin's subcellular localization, biological, and biochemical functions
Authors: Sijana Dzinic, Yonghong Meng, Shijie Sheng
Journal: Cancer Research (2010)

Abstract Maspin (serpin B5), is the sole member of the serine protease inhibitor superfamily whose homozygous deletion results in embryonic lethality. Furthermore, maspin stands alone as the only non-inhibitory clade B serpin, despite the accumulating evidence for maspin's tumor suppressive effects in the progression of many types of cancer including breast, prostate, and lung. In addition, maspin is exclusively an epithelial-specific serpin with distinctive functions in the nucleus, cytosol, and the extracellular space. Our previous research discovered a novel maspin partnership with serine protease-like molecules such as the zymogen form of urokinase type plasminogen activator (pro-uPA) and histone deacetylase 1 (HDAC1). Structural analyses revealed several distinctive maspin motifs and domains that may be important for partnership of maspin with its target proteins as well as subcellular localization during tumor progression. In this study we aimed to determine if these structural motifs/domains of maspin, in addition to the earlier identified reactive center loop (RCL), are indeed important for maspin complex molecular interactions and biological activities. We utilized the prostate cancer cell line DU145, expressing low endogenous levels of maspin, to deliver wild type maspin and five rational maspin mutants by adenovirus. Different maspin mutants exhibited different affinities for the pro-uPA/uPAR complex on the cell surface and different affinities for intracellular HDAC1 and cytosolic heat shock protein 90 (HSP 90). Based on our biophysical evidence, a unique KDEL motif located downstream of the RCL domain, seems to play a critical role in dictating the subcellular localization and secretion of maspin. It has been shown that the majority of proteins that have a KDEL motif at the extreme C-terminus are endoplasmic reticulum resident proteins. Our study with maspin provides the first evidence that an internal KDEL motif may suffice to direct protein subcellular localization. This finding sheds a new light into the aberrant maspin subcellular localization during tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2352.
Utility of Bone Imaging in Differentiation of Pulmonary Metastatic Calcification From Cystine Crystal Deposition in Cystinosis
Authors: CHARLES J. CHUNG, TRACEY O'CONNELL, LYNN A. FORDHAM, BARBARA SPECTER, PIERRE BARKER
Journal: Clinical Nuclear Medicine (1998)

A child with cystinosis was known to have cystine crystals in the thyroid and kidneys. While she was being evaluated for a pulmonary infiltrate, a bone scan was performed that showed uptake in the lungs, but not in the thyroid. These findings confirmed that the lung uptake was due to metastatic calcification and not due to cystine crystal deposition in the lungs.
Reviving the FDA
Authors: Susan Okie
Journal: New England Journal of Medicine (2010)

Approaching the end of her first year as commissioner of the Food and Drug Administration (FDA), Dr. Margaret Hamburg remarked that, despite past experience with government bureaucracies, she is struck by how hard it is to make her agency act quickly. “You feel it differently at the FDA — how long it takes to move things through the system,” she told an audience at the Institute of Medicine (IOM) in February. “The process of regulation does not allow you to respond in a timely way to emerging science or to other important emerging concerns.” The FDA's principal deputy commissioner, Dr. . . .
Munchausen's Syndrome Presenting as Baroreflex Failure
Authors: Tahir Tellioglu, John A. Oates, Italo Biaggioni
Journal: New England Journal of Medicine (2000)

To the Editor: In their study of the histochemical detection of metastases from breast cancer to bone marrow, Braun et al. (Feb.24 issue) 1 found that multivariate analysis identified the presence of cytokeratin-positive cells in the bone marrow as an independent predictor of survival.What do the authors think about the use of flow cytometry after cytokeratin staining?Their results clearly demonstrate that the presence of cytokeratin-positive cells in the bone marrow of patients with breast carcinoma is associated with shorter survival.However, because cytokeratin-positive cells were detected in control patients with nonmalignant disease and stage I tumors had fewer than 5 cytokeratin-positive cells per 2¬10 6 bone marrow cells, the authors should also clarify the threshold of positivity needed to avoid false positive results.Braun et al. found a median of 3 cytokeratin-positive cells per 2¬10 6 bone marrow cells, but the exclusion of patients with fewer than 3 cytokeratin-positive cells per 2¬10 6 bone marrow cells would not be enough, because the confidence interval for each stage is not mentioned.
Abstract 4281: Nedd4 controls cell migration by regulating PDGF receptor signaling.
Authors: Nobuyuki Tanaka, Kyoko Oyama, Keiichi Tamai
Journal: Cancer Research (2013)

Abstract The ubiquitin ligase Nedd4 is an ubuiquitin ligase (E3) which belongs to the HECT family. Like other member of this family members, such as Itch and Smurf, Nedd4 has been proposed to regulate a number of signaling pathways, as well as the traffic of several cell surface molecules, however, its physiological role in mammals has not been well characterized. Former reports identified reduction in the mitogenic activity and increase of the adaptor protein Grb10, aberrant IGF-1, VEGF and FGF receptor localization and / or signaling. In the present study, we performed an analysis of Nedd4-null murine embryonal fibroblastoid cells (MEFs) to show that loss of Nedd4 may affect any additional growth factor signaling. Surface expression of PDGF receptor was significantly increased in homozygous mutant mouse embryonic fibroblasts. Accordingly, PDGF-BB stimulation induced enhanced signaling as judged by MAP kinase p42/44 and Akt phosphorylation. Knockdown of Nedd4 in cell lines also induced similar phenotype. Nedd4, when transiently expressed, ubiquitinated PDGF receptor, which lead to degradation. Under the presence of lysosome inhibitors, PDGF receptor down regulation was at least partially blocked, suggesting its lysosome-dependent degradation. Subcellular localization of the PDGF receptor was also analyzed, but apparent difference was not observed. In the scratch assay, Nedd4 knockout cells showed enhanced migration activity, suggesting their active movement. Thus, Nedd4 appears to negatively control PDGF signaling partly through the regulation of its lysosome dependent degradation. Citation Format: Nobuyuki Tanaka, Kyoko Oyama, Keiichi Tamai. Nedd4 controls cell migration by regulating PDGF receptor signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4281. doi:10.1158/1538-7445.AM2013-4281
P230 Do we need a "two week rule" referral pathway for lung cancer?
Authors: M. H. Ali, A. Berry, J. Van Griethuysen, H. Peters, A. Jameel, G. Haji, F. Shora, M. P. Berry, E. F. Bowen
Journal: Thorax (2011)

<h3>Introduction</h3> The introduction of the two week rule (TWR) cancer referral system aimed to expedite the diagnosis and treatment of patients with lung cancer. There have been concerns that the system may even lead to delays and there remains little evidence to support its use. We therefore used prospective data to assess the effectiveness of this system. <h3>Methods</h3> We prospectively collected data on patients referred in 2010 with suspected lung cancer to a large West London lung cancer centre. We evaluated final diagnosis, performance status, lung cancer staging, time until seen in specialist clinic and time until first treatment for patients referred under the TWR compared with patients referred via our in-house abnormal radiology referral service. <h3>Results</h3> In total 249 patients were included in the study (181 from radiology reporting and 68 from GP referrals via the 2 week wait). 83 (33%) cancers were diagnosed from a total of 249 referrals. Patients referred from the radiology department were significantly more likely to have a diagnosis of lung cancer (73/181, 40%) than patients referred under the TWR (10/68, 15%; p&lt;0.001). The mean time from date of referral to seeing a specialist was similar in both groups. All patients diagnosed with lung cancer referred through the TWR had an abnormal chest radiograph. More patients with a performance status 0–1 and earlier stage disease were referred from radiology than through the TWR. <h3>Conclusions</h3> A robust radiology referral system is an effective alternative method to diagnosing lung cancer than the TWR. Patients referred from radiology are significantly more likely to have lung cancer. We propose that out-patient clinic slots are reserved for urgent radiology referrals rather than all being allocated to TWR appointments amenable to direct GP bookings. More work is needed to develop this referral pathway further.
Identification of a Gene Responsible for Familial Wolff–Parkinson–White Syndrome
Authors: Michael H. Gollob, Martin S. Green, Anthony S.-L. Tang, Tanya Gollob, Akihiko Karibe, Al-Sayegh Hassan, Ferhaan Ahmad, Ryan Lozado, Gopi Shah, Lameh Fananapazir, Linda L. Bachinski, Terry Tapscott, Oscar Gonzales, David Begley, Saidi Mohiddin, Robert Roberts
Journal: New England Journal of Medicine (2001)

The Wolff-Parkinson-White syndrome, with a prevalence in Western countries of 1.5 to 3.1 per 1000 persons, causes considerable morbidity and may cause sudden death. We identified two families in which the Wolff-Parkinson-White syndrome segregated as an autosomal dominant disorder.We studied 70 members of the two families (57 in Family 1 and 13 in Family 2). The subjects underwent 12-lead electrocardiography and two-dimensional echocardiography. Genotyping mapped the gene responsible to 7q34-q36, a locus previously identified to be responsible for an inherited form of Wolff-Parkinson-White syndrome. Candidate genes were identified, sequenced, and analyzed in normal and affected family members to identify the disease-causing gene.A total of 31 members (23 from Family 1 and 8 from Family 2) had the Wolff-Parkinson-White syndrome. Affected members of both families had ventricular preexcitation with conduction abnormalities and cardiac hypertrophy. The maximal combined two-point lod score was 9.82 at a distance of 5 cM from marker D7S636, which confirmed the linkage of the gene in both families to 7q34-q36. Haplotype analysis indicated that there were no alleles in common in the two families at this locus, suggesting that the two families do not have a common founder. We identified a missense mutation in the gene that encodes the gamma2 regulatory subunit of AMP-activated protein kinase (PRKAG2). The mutation results in the substitution of glutamine for arginine at residue 302 in the protein.The identification of this genetic defect has important implications for elucidating the pathogenesis of ventricular preexcitation. Further understanding of how this molecular defect leads to supraventricular arrhythmias could influence the development of specific therapies for other forms of supraventricular arrhythmia.
The Prognostic Importance of Clinical and Histologic Features in Asymptomatic and Symptomatic Primary Biliary Cirrhosis
Authors: Joseph Roll, James L. Boyer, Daniel Barry, Gerald Klatskin
Journal: New England Journal of Medicine (1983)

To determine the life expectancy of patients with primary biliary cirrhosis, we analyzed survival data from 280 patients with either symptomatic (243) or asymptomatic (37) disease. Patients were followed for up to 19 years (mean, 6.9 years). The average length of survival was 11.9 years--nearly twice that reported in other studies. In contrast, over a 12-year period the survival of the asymptomatic patients after diagnosis did not differ from that of a control population matched for age and sex. Jaundice, weight loss, hepatomegaly, splenomegaly, and ascites were each associated with a poor prognosis. Prognosis also correlated with the histologic stages of hepatic fibrosis, cholestasis, and periportal-cell necrosis. A multivariate analysis of clinical features revealed that at the onset of disease, age, hepatomegaly, and elevated levels of serum bilirubin were independent discriminators of a poor prognosis. A histologic finding of fibrosis limited to portal areas improved this discrimination, correlating with prolonged survival. No other factors enchanced the prediction of risk.
Nail Injury to the Skull
Authors: W X Shandera, A Hayman
Journal: New England Journal of Medicine (2001)

Figure 1. A 58-year-old carpenter was working at a home-construction site while a colleague working above him fired nails into a board with a nail gun. The board broke during one of the firings, accidentally propelling a galvanized nail into the patient's left medial orbit and across the sinuses and soft tissues below the base of the skull. He presented without any evident neurologic damage. An arteriogram documented the absence of vascular damage. The nail was removed, and the patient remains well with no sequelae.