tbuckley/cabot-search huggingface dataset:
Lipid rafts are essential for peroxisome biogenesis in HepG2 cells
Authors: Jannes Woudenberg, Krzysztof P. Rembacz, Mark Hoekstra, Antonella Pellicoro, Fiona A. J. van den Heuvel, Janette Heegsma, Sven C. D. van IJzendoorn, Andreas Holzinger, Tsuneo Imanaka, Han Moshage, Klaas Nico Faber
Journal: Hepatology (2010)

Peroxisomes are particularly abundant in the liver and are involved in bile salt synthesis and fatty acid metabolism. Peroxisomal membrane proteins (PMPs) are required for peroxisome biogenesis [e.g., the interacting peroxisomal biogenesis factors Pex13p and Pex14p] and its metabolic function [e.g., the adenosine triphosphate–binding cassette transporters adrenoleukodystrophy protein (ALDP) and PMP70]. Impaired function of PMPs is the underlying cause of Zellweger syndrome and X-linked adrenoleukodystrophy. Here we studied for the first time the putative association of PMPs with cholesterol-enriched lipid rafts and their function in peroxisome biogenesis. Lipid rafts were isolated from Triton X-100–lysed or Lubrol WX–lysed HepG2 cells and analyzed for the presence of various PMPs by western blotting. Lovastatin and methyl-β-cyclodextrin were used to deplete cholesterol and disrupt lipid rafts in HepG2 cells, and this was followed by immunofluorescence microscopy to determine the subcellular location of catalase and PMPs. Cycloheximide was used to inhibit protein synthesis. Green fluorescent protein–tagged fragments of PMP70 and ALDP were analyzed for their lipid raft association. PMP70 and Pex14p were associated with Triton X-100–resistant rafts, ALDP was associated with Lubrol WX–resistant rafts, and Pex13p was not lipid raft–associated in HepG2 cells. The minimal peroxisomal targeting signals in ALDP and PMP70 were not sufficient for lipid raft association. Cholesterol depletion led to dissociation of PMPs from lipid rafts and impaired sorting of newly synthesized catalase and ALDP but not Pex14p and PMP70. Repletion of cholesterol to these cells efficiently reestablished the peroxisomal sorting of catalase but not ALDP. Conclusion: Human PMPs are differentially associated with lipid rafts independently of the protein homology and/or their functional interaction. Cholesterol is required for peroxisomal lipid raft assembly and peroxisome biogenesis. HEPATOLOGY 2010
Epstein-Barr virus infection-associated renal disease
Authors: T Nadasdy, C S Park, S C Peiper, J E Wenzl, J Oates, F G Silva
Journal: Journal of the American Society of Nephrology (1992)

There are only a few reports of renal disease associated with Epstein-Barr virus (EBV) infection. The diagnosis of EBV infection in these previously reported patients was based primarily on positive serology. Two patients with renal disease who, despite repeatedly negative serologies, were shown by molecular hybridization techniques--in situ hybridization (ISH) and polymerase chain reaction (PCR)--to have EBV infection are reported here. Site-specific molecular probes directed against specific, tandemly repeated EBV genomic regions were used. A synthetic 23-mer terminally biotin-labeled oligonucleotide probe selected from the EBV NotI region was used for ISH. For PCR, oligonucleotide primers were designed from sequences of the highly conserved, long internal direct repeat region of EBV to specifically amplify a 110-base-pair segment. The first patient, a 3-yr-old girl with a 1-yr history of fatigue, fever, splenomegaly, and lymphadenopathy developed hematuria. A renal biopsy revealed widespread glomerular mesangiolysis admixed with segmental mesangial sclerosis; no immune deposits were noted by electron microscopy or immunofluorescence. ISH on paraffin sections of the resected spleen and lymph nodes was positive for EBV. The second patient, a 28-yr-old male renal allograft recipient, received a double dose of OKT3. Seven weeks after transplantation, a renal biopsy revealed a lymphoproliferative disorder. Paraffin sections of the nephrectomy specimen were positive for EBV by both ISH and PCR. It was concluded that (1) EBV cannot be excluded on the basis of multiple negative serologies in some patients, and (2) ISH and PCR may lead to the detection of viral genomic information in renal and nonrenal tissues.
Bone marrow as an alternative site for islet transplantation
Authors: Elisa Cantarelli, Raffaella Melzi, Alessia Mercalli, Valeria Sordi, Giuliana Ferrari, Carsten Werner Lederer, Emanuela Mrak, Alessandro Rubinacci, Maurilio Ponzoni, Giovanni Sitia, Luca G. Guidotti, Ezio Bonifacio, Lorenzo Piemonti
Journal: Blood (2009)
ST-Segment Elevation Followed by Progressive Widening of the QRS Complex
Authors: Daniel Czuriga, Judit Barta, Ildiko Rácz, Istvan Edes, Ferenc Györy, Istvan Czuriga, Zoltan Csanádi
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine 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 Internal Medicine journal
Transient PI3K Inhibition Induces Apoptosis and Overcomes HGF-Mediated Resistance to EGFR-TKIs in<i>EGFR</i>Mutant Lung Cancer
Authors: Ivan S. Donev, Wei Wang, Tadaaki Yamada, Qi Li, Shinji Takeuchi, Kunio Matsumoto, Takao Yamori, Yasuhiko Nishioka, Saburo Sone, Seiji Yano
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib, show favorable response to EGFR mutant lung cancer. However, the responders acquire resistance almost without exception. We recently reported that hepatocyte growth factor (HGF) induces EGFR-TKI resistance by activating MET that restores downstream mitogen activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K)/Akt signaling. The purpose of this study was to determine whether inhibition of PI3K, a downstream molecule of both EGFR and MET, could overcome HGF-mediated EGFR-TKI resistance in EGFR mutant lung cancer cells PC-9 and HCC827. Experimental Design: We explored therapeutic effect of a class I PI3K inhibitor PI-103 on HGF-induced EGFR-TKI resistance in vitro and in vivo. Results: Unlike gefitinib or erlotinib, continuous exposure with PI-103 inhibited proliferation of PC-9 and HCC827 cells, even in the presence of HGF. On the other hand, in gefitinib-resistant xenograft model by using PC-9 cells mixed with HGF high producing fibroblasts, PI-103 monotherapy did not inhibit tumor growth. However, PI-103 combined with gefitinib successfully regressed gefitinib-resistant tumor. In vitro experiments by considering short half-life of PI-103 reveal that transient exposure of PI-103 combined with gefitinib caused sustained inhibition of Akt phosphorylation, but not ERK1/2 phosphorylation, resulting in induction of tumor cell apoptosis even in the presence of HGF. Conclusions: These results indicate that transient blockade of PI3K/Akt pathway by PI-103 and gefitinib could overcome HGF-mediated resistance to EGFR-TKIs by inducing apoptosis in EGFR mutant lung cancer. Clin Cancer Res; 17(8); 2260–9. ©2011 AACR.
The Resurgence of Measles in the United States, 1989-1990
Authors: William L. Atkinson, Walter A. Orenstein, Saul Krugman
Journal: Annual Review of Medicine (1992)

After almost a decade of relatively few reported cases, a major resurgence of measles occurred in the United States in 1989-1990. The increase primarily involved unvaccinated racial and ethnic minority children less than five years of age residing in inner-city areas. Outbreaks of measles among vaccinated school-aged children continued to occur but had less impact than outbreaks among preschool-aged children. Efforts to prevent measles must be aimed at improving age-specific measles vaccination coverage among preschool-aged children, and implementation of a two-dose measles strategy among school-aged children.
MPs condemn UK clinical trials system for its "invisible" results
Authors: A. O'Dowd
Journal: BMJ (2013)

MPs have called on the government to act urgently to improve the current clinical trials system in the United Kingdom, which they say allows the results of much research never to see the light of day.

The UK has an “unacceptable” approach to clinical trials that allows the results of too many studies to remain unseen by clinicians, scientists, and the public, said MPs on the House of Commons Science and Technology Committee.

In their report on clinical trials published on 17 September, MPs said that action was essential to tackle the country’s lack of clinical trial transparency, a problem that the government’s efforts had so far failed to solve.1

The committee’s chairman, …
Change of Antigenic Expression on Rat Tumor Cells After Their Transplantation
Authors: Eiki Gotohda, Fujiro Sendo, Masayuki Nakayama, Masuo Hosokawa, Tsugumichi Kawamura, Takao Kodama, Hiroshi Kobayashi
Journal: JNCI Journal of the National Cancer Institute (1975)

Antigenic expression of 3-methylcholanthrene-induced transplantable fibrosarcoma KMT-17 cells was investigated in relation to days after ip transplantation. Cytotoxicity tests with antiserum against tumor-associated surface antigen of KMT-17 cells revealed that cytotoxic sensitivity and absorbing capacity decreased after transplantation, but they increased when other normal rats were given transplants of tumor cells. A decrease in the sensitivity was observed when immunosuppressively irradiated rats were given tumor transplants. Tumor cell density in the abdominal cavities of rats directly and absorbing capacity of KMT-17 cells to antiserum against the histocompatibility antigen did not change after transplantation. The possible mechanisms of antigenic change of KMT-17 cells were discussed.
Progressive case of recurrent respiratory papillomatosis successfully treated with gefitinib
Authors: Vitezslav Kolek, Marian Hajduch, Juraj Kultan, Lucie Fajkosova
Journal: European Respiratory Journal (2012)

Recurrent respiratory papillomatosis (RRP) or juvenile laryngeal papillomatosis is a rare disease, caused by human papilloma virus (HPV). It is characterized by epithelial neoplastic polyps in larynx, trachea (2 - 5%) and lungs (1%). Typical symptoms are hoarseness, chronic cough and dyspnea. Diagnosis is based on laryngo/bronchoscopy, chest x-ray, biopsy and HPV testing.  We describe a case of woman with progressive laryngeal papillomatosis from the age of 1 year. Disease slowly progressed to trachea, although patient underwent about 80 endoscopic laser procedures. In the age of 37 y, chest X ray showed multiple nodules and cysts filled with fluid. VATS biopsy proved parenchymal papillomatosis. Patient was treated unsuccessfully with interferon, antiviral vaccine and Cidofovir. In the age of 41 y, therapy with gefitinib 250 mg bid was started. Bronchoscopy revealed regression of papillomas after 2 months and normal laryngeal and tracheal mucosa after 6 months. Chest X-ray was normal and CT showed tiny cysts without fluid. Patient felt well without dyspnea and tolerated treatment without problems.  Gefitinib - tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) was chosen according to knowledge of EGFR overexpression in papillomas and sporadic information about treatment of children with laryngeal papillomatosis. To our knowledge, this is the first report of successful gefitinib treatment of RRP in adult patient. The role of HPV in tumor forming tissue reaction is not known. Frequent HPV detection in gefitinib-responsive lung adenocarcinomas gives another support for gefitinib indication in RPP and a new hope for patients, too.
HLA class II regulation and structure. Analysis with HLA-DR3 and HLA-DP point mutants.
Authors: D Pious, L Dixon, F Levine, T Cotner, R Johnson
Journal: The Journal of Experimental Medicine (1985)

Point mutations that affect HLA-DR structure or expression have not previously been described. In the present study, we isolated such mutants by immunoselection of an ethyl methanesulfonate-mutagenized HLA-DR3 cell line with an anti-HLA-DR3 monoclonal antibody, 16.23. To facilitate analysis, we used a parent cell line with a preexisting deletion of one haplotype encompassing DR and DQ alpha and beta. The selection yielded two sets of mutants, one with defects in DR3 structure, the other with defects in different steps leading to DR expression. Of the expression-defective mutants, one had undergone a second deletion removing the remaining DR alpha gene but no other class II genes. It had a normal abundance of DR beta mRNA but had lost binding of DR monomorphic antibodies, indicating that DR beta chains do not form noncognate dimers. A second mutant had an abnormally large DR alpha mRNA, probably resulting from a splice site mutation. Several mutants had marked reductions in DR beta mRNA levels; in two of these, the lesion appeared to be transcriptional because the reduction in DR beta mRNA was paralleled by an altered methylation pattern of one of the DR beta genes. Other expression-defective mutants had different posttranscriptional defects. Some of the mutations were similar to those that have been found in mouse strains defective in I-E expression, whereas others have no known natural counterpart. The matrix of reactivities of anti-HLA class II monomorphic antibodies with these and similar mutants allowed us to define the gene products recognized by these antibodies. A set of seven mutants were "epitope defective," that is, they expressed normal or near normal levels of HLA-DR3 but no longer bound 16.23. Unexpectedly, each of the epitope mutants had decreased DR dimer stability. These mutants should be useful in localizing the DR3 alloepitope and in elucidating its contribution as a restriction element in the presentation of soluble antigen to immune T cells.
Competitive nature of the intestinal transport mechanism for cobalt and iron in the rat
Authors: A. B. R. Thomson, L. S. Valberg, D. G. Sinclair
Journal: Journal of Clinical Investigation (1971)

Dose- and time-response studies were performed in iron-loaded and iron-deficient rats in order to define, (a) the kinetics of absorption of cobalt and iron, (b) the nature of the inhibitory effect of one metal on the absorption of the other, and (c) the effect of variations in body iron stores on these processes. The duodenum was perfused for 5-90 min with labeled solutions containing 5.0 mM iron or 5.0 mM cobalt. In iron-loaded rats, the rate of cobalt absorption was constant for 90 min whereas the rate of iron absorption fell after 30 min. In comparison to these results, the rate of absorption of both metals was increased in iron deficiency, and was more rapid in the first 30 min than in the 30-90 min period.
Subclinical Hypercortisolism among Outpatients Referred for Osteoporosis
Authors: Iacopo Chiodini, Maria Lucia Mascia, Silvana Muscarella, Claudia Battista, Salvatore Minisola, Maura Arosio, Stefano Angelo Santini, Giuseppe Guglielmi, Vincenzo Carnevale, Alfredo Scillitani
Journal: Annals of Internal Medicine (2007)

Background: Hypercortisolism is known to cause osteoporosis. Objective: To evaluate the prevalence of subclinical hypercortisolism in participants referred for evaluation of osteoporosis. Design: Cross-sectional study. Setting: Two community hospitals and research institutes in Italy. Patients: 219 patients without clinically overt hypercortisolism or other secondary causes of osteoporosis who were referred for evaluation of osteoporosis between January 2005 and December 2005. Measurements: Bone mineral density was measured by using dual-energy x-ray absorptiometry, and hypercortisolism was assessed with serum cortisol levels after a dexamethasone suppression test. Also measured were 24-hour urinary free cortisol levels and midnight plasma cortisol levels. Results: Seven of 65 patients with T-scores of 2.5 or less and vertebral fractures had subclinical hypercortisolism (prevalence, 10.8% [95% CI, 3.23% to 18.31%]). This prevalence was 4.8% (CI, 1.32% to 8.20%) among patients with osteoporosis. In multivariable analyses adjusted for age, sex, and body mass index, a positive dexamethasone suppression test result was associated with the presence of osteoporosis (odds ratio, 3.37 [CI, 1.78 to 6.43]; P < 0.001) and vertebral fractures (odds ratio, 1.70 [CI, 1.04 to 2.79]; P = 0.035). Limitations: The study was conducted in a referral setting; its findings may not apply to the general population. Conclusions: Subclinical hypercortisolism may be more common than is generally recognized in patients with osteoporosis in whom secondary causes of osteoporosis have been excluded.
86 SAFETY AND ANTIVIRAL ACTIVITY OF SCH 900518 ADMINISTERED AS MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2B TO NAIVE AND TREATMENT-EXPERIENCED HCV-1 INFECTED PATIENTS
Authors: H. Reesink, J. Bergmann, J. de Bruijne, C. Weegink, J. van Lier, A. van Vliet, A. Keung, J. Li, E. O'Mara, M. Treitel, E. Hughes, H. Janssen, R. de Knegt
Journal: Journal of Hepatology (2009)
Chemoimmunotherapy With Low-Dose Fludarabine and Cyclophosphamide and High Dose Rituximab in Previously Untreated Patients With Chronic Lymphocytic Leukemia
Authors: Kenneth A. Foon, Michael Boyiadzis, Stephanie R. Land, Stanley Marks, Anastasios Raptis, Louis Pietragallo, Dennis Meisner, Andrew Laman, Mathew Sulecki, Allyson Butchko, Patricia Schaefer, Diana Lenzer, Ahmad Tarhini
Journal: Journal of Clinical Oncology (2008)

Chemoimmunotherapy combining fludarabine, cyclophosphamide, and rituximab (FCR) is an active regimen for untreated patients with chronic lymphocytic leukemia (CLL) with 70% complete responses (CRs) and 95% overall responses (ORs). However, grade 3/4 neutropenia was reported in 52% of cycles of treatment. The purpose of this trial was to maintain the high responses but reduce the toxicity of FCR by decreasing the fludarabine and cyclophosphamide (FCR-Lite).We conducted a single arm study of FCR-Lite which includes maintenance rituximab in 50 untreated CLL patients. Patients were evaluated for response using both the 1996 National Cancer Institute Working Group (NCIWG) guidelines and the 2008 guidelines. Two thirds of patients were treated by community physicians.The median age was 58 years (range, 36 to 85 years); 20 patients had Rai stage 1, 22 had Rai stage 2, and eight had Rai stage 3 and 4. The OR and CR rates were 100% and 79%, respectively, using the 1996 NCIWG guidelines and 100% and 77% using the 2008 guidelines. Median duration of complete response was 22.3 months (range, 5.2 to 42.5 months) and none of the complete responders have relapsed. Grade 3/4 neutropenia was noted in 13% of the cycles of therapy.FCR-Lite is highly effective in previously untreated CLL patients. Grade 3/4 neutropenia was dramatically reduced compared to standard FCR and our data demonstrated FCR-Lite can be safely administered in the community setting.
Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks
Authors: Michaël Chopin, Cyril Seillet, Stéphane Chevrier, Li Wu, Hongsheng Wang, Herbert C. Morse, Gabrielle T. Belz, Stephen L. Nutt
Journal: The Journal of Experimental Medicine (2013)

Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation remain sparse. We addressed the function of a group of key DC transcription factors—PU.1, ID2, IRF4, and IRF8—in the establishment of the LC network. We show that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow–derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-β responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements in a TGF-β–dependent manner, whereas ectopic expression of RUNX3 rescued LC differentiation in the absence of PU.1 and promoted LC differentiation from PU.1-sufficient progenitors. These findings highlight the dual molecular network underlying LC differentiation, and show the central role of PU.1 in these processes.
Early effective drainage in the treatment of loculated tuberculous pleurisy
Authors: C-L. Chung, C-H. Chen, C-Y. Yeh, J-R. Sheu, S-C. Chang
Journal: European Respiratory Journal (2008)

The role of early effective drainage in loculated tuberculous (TB) pleurisy treatment remains unclear. Consecutive patients with TB pleurisy subjected to anti-TB treatment and pigtail drainage (n = 64) were divided into three groups: 1) patients with free-flowing effusions irrigated with saline (free-flowing group; n = 20); 2) patients with loculated effusions irrigated with streptokinase (streptokinase group; n = 22); and 3) patients with loculated effusions irrigated with saline (saline group; n = 22). Pleural irrigation was performed for 3 days consecutively and the effusion drained as completely as possible. Outcomes were assessed for 12 months by clinical symptoms, effusion removed, radiological scores for effusion amount, lung function and occurrence of residual pleural thickening. The total effusion volumes removed were significantly greater in the free-flowing (2.36±1.62 L) and streptokinase groups (2.59±1.77 L) than in the saline group (1.28±1.21 L). Compared with the saline group, the free-flowing and streptokinase groups showed significant improvement in radiological scores and forced vital capacity at different time-points during follow-up, and a significantly lower occurrence of residual pleural thickening. All outcome variables were comparable between the streptokinase and free-flowing groups. In summary, early effective drainage and complete anti-tuberculosis treatment may hasten clearance of pleural effusion, reduce residual pleural thickening occurrence and accelerate pulmonary function recovery in patients with symptomatic loculated tuberculous pleurisy.
Downregulation of cell-surface CD4 expression by simian immunodeficiency virus Nef prevents viral super infection.
Authors: R E Benson, A Sanfridson, J S Ottinger, C Doyle, B R Cullen
Journal: The Journal of Experimental Medicine (1993)

The nef gene product encoded by the mac239 proviral clone of simian immunodeficiency virus (SIV) markedly enhances viral replication and pathogenesis in vivo. We have used this biologically active nef isolate to examine the phenotype of Nef in retrovirally transduced human T cells in culture. SIV Nef is shown to dramatically inhibit cell-surface expression of the CD4 glycoprotein without significantly affecting the total steady-state level of cellular CD4. This downregulation of the cell-surface CD4 receptor for human immunodeficiency virus type 1 (HIV-1) infection correlated with the acquisition of resistance to superinfection by HIV-1. However, SIV Nef did not affect the level of gene expression directed by the HIV-1 long terminal repeat. It is hypothesized that downregulation of cell-surface CD4 by Nef facilitates the efficient release of infectious progeny virions and, hence, viral spread in vivo.