tbuckley/cabot-search huggingface dataset:
HER2 signaling regulates different angiogenic factors through different pathways in breast cancer cells
Authors: Xianfeng Wen, Jinsong Liu, Robert Bast, Xiao-Feng Le
Journal: Cancer Research (2005)

2035  The HER family of receptors, including EGFR (HER1), HER2, HER3, and HER4 are important mediators of cell proliferation, survival, and angiogensis. HER2 overexpression occurs in about 20-30% of breast cancers and is associated with poor prognosis. HER2 signaling has been linked to expression of vascular endothelial growth factor (VEGF), an angiogenic factor. However, effects of HER2 signaling on other angiogenic factors such as interleukin-8 (IL-8) and basic fibroblast growth factor (bFGF) and antiangiogenic factor such as thrombspondin-1 (TSP-1) remain to be elucidated. In this study, we have investigated the effects of activation and inhibition of HER2 signaling on several breast cancer cell lines that overexpress HER2 exogenously and endogenously. Reexpression of the HER2 oncogene in MCF-7 and T47D cells that express low levels of HER2 resulted in elevated expression of VEGF and IL-8, decreased expression of TSP-1, and no significant change of bFGF levels on RT-PCR, ELISA, or Western blot analysis. Reexpression of HER2 was associated with elevated PI3K-AKT activity. Inhibition of HER2 function in BT474 cells that overexpress HER2 with its specific antibody trastuzumab (Herceptinâ) led to a decrease in VEGF and IL-8 expression and to an increase in TSP-1 expression. Inhibition of HER2 with a specific small interference RNA (SiRNA) resulted in similar effects to trastuzumab. Inhibition of HER2 with trastuzumab or HER2 SiRNA did not affect bFGF expression. To further elucidate the pathways by which HER2 signaling regulates the expression of VEGF, IL-8, and TSP-1, different signaling inhibitors were employed. Inhibition of the PI3K-AKT pathway with LY294002 downregulated IL-8 and VEGF expression. Inhibition of HER2 with trastuzumab and SiRNA inhibited PI3K-AKT activity. However, LY294002 had no effect on TSP-1 expression, suggesting TSP-1 production, unlike IL-8 and VEGF, did not depend on the PI3K-AKT pathway. Instead, the p38 MAPK specific inhibitor SB203580 inhibited the TSP-1 expression. On the other hand, overexpression of p38 MAPK increased TSP-1 expression. Trastuzumab transiently activated p38 MAPK and was able to reverse the TSP-1 inhibition induced by SB203580. Consequently, HER2 signaling is able to upregulate pro-angiogenic factors VEGF and IL-8 via the PI3K-AKT pathway and to downregulate anti-angiogenic factor TSP-1 via the p38 MAPK pathway. Anti-HER2 antibody trastuzumab is a potent inhibitor of angiogenesis in breast cancer by affecting different angiogenic factors simultaneously.
Rapid detection, differentiation and typing of methicillin-resistant Staphylococcus aureus harbouring either mecA or the new mecA homologue mecALGA251
Authors: M. Stegger, P.S. Andersen, A. Kearns, B. Pichon, M.A. Holmes, G. Edwards, F. Laurent, C. Teale, R. Skov, A.R. Larsen
Journal: Clinical Microbiology and Infection (2011)
Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice Commentary: Reporting of adverse events is worth the effort
Authors: R. D Mann
Journal: BMJ (2000)

To investigate the frequency with which sedation was reported in post-marketing surveillance studies of four second generation antihistamines: loratadine, cetirizine, fexofenadine, and acrivastine.Prescription-event monitoring studies.Prescriptions were obtained for each cohort in the immediate post-marketing period.Event data were obtained for a total of 43 363 patients.Reporting of sedation or drowsiness.The odds ratios (adjusted for age and sex) for the incidence of sedation were 0.63 (95% confidence interval 0.36 to 1.11; P=0.1) for fexofenadine; 2.79 (1.69 to 4.58; P<0.0001) for acrivastine, and 3.53 (2.07 to 5.42; P<0.0001) for cetirizine compared with loratadine. No increased risk of accident or injury was evident with any of the four drugs.Although the risk of sedation was low with all four drugs, fexofenadine and loratadine may be more appropriate for people working in safety critical jobs.
The role of p53 family members in regulation of mTOR function.
Authors: Hakan Cam, Peter Houghton
Journal: Cancer Research (2008)

2783   Background: The transcription factor and tumor suppressor p53 and its two homologues p63 and p73 form a protein family. The p53 family members are involved in sensing various types of cellular stress to coordinate cell fate decisions such as cell cycle arrest, senescence, differentiation or apoptosis. To ensure normal cell growth and proliferation, it is critical for cells to coordinate the stimulatory signals arising from nutrients and growth factors as well as the inhibitory signals arising from intracellular stresses. mTOR (Target Of Rapamycin) is an evolutionarily conserved Ser/Thr protein kinase that belongs to the PIKK [phosphoinositide 3-kinase (PI3K)-related kinase) family, and it too acts as a sensor being regulated by nutritional status, growth factors, hypoxia, and metabolic state (AMP). Therefore, the direct communication between the p53 family members and mTOR pathways might play an important role in ensuring normal cell growth and proliferation. However, how the p53 family members cooperate to regulate mTOR function remains unclear.  Methods: Wild type (WT) murine embryo fibroblasts (MEFs), or MEFs nullizygous for p53, p63, p73, ARF/LKB1, ARF/ATM, ARF/p21, human rhabdomyosarcoma cell lines Rh30, Rh41 and a human melanoma cell line G361 (LKB1-/-, p53 WT), were exposed for 24 hr to increasing concentrations of etoposide, topotecan or cisplatin, or hypoxia (0.2% O2) Furthermore, we used dominant-negative mini-proteins of p53 (p53DD) or p63/73 (p73DD), to characterize the specific function of either p53 or p73 in mTOR regulation. The activation state of mTOR was determined by western blot for phospho-S6 and 4EBP1.  Results: In MEFs complete abrogation of p-S6 and p-4EBP1 by etoposide, topotecan cisplatin and hypoxia is p53 but not p63 and p73 dependent. DNA damaging agents did not reduce p-S6 and p-4EBP1 in LKB1-/- and ATM-/- MEFs implicating LKB1 and ATM in the p53-mediated suppression of mTOR. Surprisingly, DNA damage decreased p-S6 and p-4EBP1 in G361 cells lacking LKB1, suggesting LKB1 independent signaling. Interestingly, for the suppression of mTOR activity in human G361 as well as rhabdomyosarcoma cell lines Rh30, Rh41, a cooperation of all p53 family members are necessary.  Conclusions: Here, we show that the tumor suppressor protein p53 regulates mTOR function via LKB1 dependent or independent pathways. Furthermore, under these conditions, the regulation of mTOR function is tightly regulated by ATM kinase activity. Surprisingly, in human cell lines, for the complete inhibition of mTOR activity all p53 family members are necessary. Since inhibition of mTOR function by DNA damage as well as hypoxia is likely to be important for tumor suppression, our findings establish a new activity of the tumor suppressor p53 protein and its family members in regulation of mTOR function.  Supported by USPHS grant CA77776.
436. Recombinant Adeno-Associated Virus Gene Therapy for Cob(I)Alamin Adenosyltransferase Deficiency
Authors: Kirsten Elizabeth Erger, Thomas James Conlon, Dietrich Matern, Thomas A. Bobik, Terence R. Flotte
Journal: Molecular Therapy (2004)

Metabolism of inactive cobalamins, both in the recycling and assimilation from dietary sources, into the B12 coenzymes is vital for various metabolic pathways. Disruption of vitamin B12 coenzyme synthesis has been linked to chronic liver disease, cancer, elevated serum homocysteine (possible risk factor for heart disease), increased rate of DNA damage and impaired cognitive function. Vitamin B12 (cyano-cobalamin, CNCbl) is a precursor of two B12 coenzymes, adenosyl-cobalamin (AdoCbl) and methyl-cobalamin (CH3Cbl), which are instable due to a labile upper ligand to the cobalt atom. The assimilation and recycling pathway consists of a multi-enzyme pathway, the last step being the conversion of cob(I)alamin to AdoCbl by the ATP dependent cob(I)alamin adenosyltransferase (ATR). In humans, methylmalonyl-CoA mutase (MCM), responsible for the conversion of propionyl-CoA to the TCA cycle intermediate succinyl-CoA, is dependent on AdoCbl. Propionyl-CoA is produced by the catabolism of the amino acids valine, isoleucine, methionine, and threonine, as well as thymine, cholesterol and odd-chain fatty acids. The impaired activity of MCM, resulting from the lack of coenzyme B12 (AdoCbl), leads to methylmalonic aciduria (MMA), a disease that is often fatal in the first years of life with a frequency of 1/50,000 births. MMA is diagnosed primarily by a buildup of methylmalonyl-CoA in the serum and in the urine. We have obtained human fibroblast cell lines from patients with known ATR deficiencies. Identification of mutations, generally seen to be a single nucleotide or missense mutation, have been performed on most. The human ATR cDNA is 753 bp, the appropriate length for use in rAAV gene therapy vector. It has been cloned into our rAAV vector driving expression of hATR from the hybrid CMV enhancer chicken-beta actin promoter and pseudotyped in AAV 2 and 8 capsids. Next, cell lines were stably transfected with an ATR-neo plasmid and selected for using G418. Levels of methylmalonic acid in the tissue culture medium is measured using tandem mass spectroscopy and an enzyme assay for the conversion of cob(I)alamin to AdoCbl with the ATR enzyme. RESULTS: Overexpression of hATR message from the pCB-hATR vector in patient and control cell lines was confirmed by semi-quantitative RT-PCR. Transgene expression in neomycin resistant clones was 3 to 7 times greater than endogenous expression. Correction of deficient patient cell lines will be assayed at varying doses of rAAV virus. Further experiments will include testing vector expressed ATR mRNA and increased enzyme acitivity in the muscle and liver tissues of C57Bl/6 mice.
Possible relationship of the estrogenic hormones, genetic susceptibility, and milk influence in the production of mammary cancer in mice.
Authors: John J. Bittner
Journal: Cancer Research (1942)

A review of the possible relationship of the estrogenic hormones genetic susceptibility and milk influence in the production of  cancer in mice is presented.  The role of hormones is discussed including the structure of the  glands and variations in the degree of estrogenic stimulation in the different inbred strains of mice.  The characteristics of the active milk influence is described.  Inherited susceptibility to spontaneous  carcinoma is mentioned.  Several experimental procedures performed on mice with a low incidence of spontaneous tumor are described with emphasis on a comparison of the C(57) black C and CBA stocks.  Experiments with high incidence mice are also reviewed and demonstrate that the incidence of tumor is due to an active milk influence from the mother.  Experiments involving the production of induced estrogenic  tumors in susceptible and nonsusceptible strains are discussed.  The incidence of  tumors in the progeny of cancerous and noncancerous mothers of inbred strains suggests that there are at least 2 types of these neoplasms in mice.  The influences underlying the development of  tumors in mice may each be considered as mammary tumor preparatory influence or inciter - milk influence genetic susceptibility and estrogen stimulation.
Providing spectacles in developing countries
Authors: A. R Potter
Journal: BMJ (1998)

Imagine the scenario. You are an indigenous teacher or civil servant stationed in a small rural community in a tropical country. Almost by definition you are over the age of 40 as your government has not recruited any public employees for several years on the advice of the World Bank and International Monetary Fund. You are a worried man. Your second daughter, always the intelligent one among your children, has begun to perform poorly in school. Her teacher says she makes too many mistakes when copying her lessons from the blackboard. Your wife is also distraught. Her mother, who recently underwent a cataract operation at great expense (your own), does not see well enough to return to her village. And worse, your own eyes seem to be failing and you can no longer study in the evenings for that professional diploma that would bring a promotion at work. Your distress is heightened by the knowledge that even if you travelled the 350 miles to the capital during your annual holiday the waiting list to see the ophthalmologist is over four months long and the price of the three pairs of glasses at the optician's shop well beyond …
Bush Announces Tax Credits
Authors: Brian Vastag
Journal: JAMA (2004)

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
Lung Screening Study to Test Popular CT Scans
Authors: Brian Vastag
Journal: JAMA (2002)

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
Synchrotron X-ray analyses demonstrate phosphate-bound gadolinium in skin in nephrogenic systemic fibrosis
Authors: Simon J. George, Samuel M. Webb, Jerrold L. Abraham, Stephen P. Cramer
Journal: British Journal of Dermatology (2010)

Background Nephrogenic systemic fibrosis (NSF) is an incurable, debilitating disease found exclusively in patients with decreased kidney function and comprises a fibrosing disorder of the skin and systemic tissues. The disease is associated with exposure to gadolinium (Gd)‐based contrast agents (GBCA) used in magnetic resonance imaging (MRI). Tissue samples from many patients with NSF contain micron‐sized insoluble Gd‐containing deposits. However, the precise composition and chemical nature of these particles is unclear. Objectives To clarify the precise chemical structure of the Gd‐containing deposits in NSF tissues. Methods Autopsy skin tissues from a patient with NSF were examined in situ using synchrotron X‐ray fluorescence (SXRF) microscopy and extended X‐ray absorption fine structure (EXAFS) spectroscopy and in correlation with light microscopy and the results of scanning electron microscopy/energy dispersive spectroscopy analyses. Results The insoluble Gd deposits were shown to contain Gd no longer coordinated by GBCA chelator molecules but rather in a sodium calcium phosphate material. SXRF microscopy shows a clear correlation between Gd, Ca and P. EXAFS spectroscopy shows a very different spectrum from the GBCAs, with Gd–P distances at 3·11 Å and 3·72 Å as well as Gd–Gd distances at an average of 4·05 Å, consistent with a GdPO4 structure. Conclusions This is the first direct evidence for the chemical release of Gd from GBCA in human tissue. This supports the physical–chemical, clinical and epidemiological data indicating a link between stability and dose of GBCA to the development of NSF.
A novel member of the F-box/WD40 gene family, encoding dactylin, is disrupted in the mouse dactylaplasia mutant
Authors: Arend Sidow, Monique S. Bulotsky, Anne W. Kerrebrock, Bruce W. Birren, David Altshuler, Rudolf Jaenisch, Kenneth R. Johnson, Eric S. Lander
Journal: Nature Genetics (1999)
Angiogenic growth factors augment K–Cl cotransporter expression in erythroid cells via hypoxia‐inducible factor‐1α
Authors: Caryn S. Gonsalves, Scott Crable, Sharat Chandra, Wei Li, Vijay K. Kalra, Clinton H. Joiner
Journal: American Journal of Hematology (2013)

The potassium chloride cotransporters (KCC) family of proteins are widely expressed and are involved in the transepithelial movement of potassium and chloride ions and the regulation of cell volume. KCC activity is high in reticulocytes, and contributes to the dehydration of sickle red blood cells. Because plasma levels of both vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are elevated in sickle cell individuals, and VEGF has been shown to increase KCC expression in other cells, we hypothesized that VEGF and PlGF influence KCC expression in erythroid cells. Both VEGF and PlGF treatment of human erythroid K562 cells increased both mRNA and protein levels of KCC1, KCC3b, and KCC4. VEGF- and PlGF-mediated cellular signaling involved VEGF-R1 and downstream effectors, specifically, PI-3 kinase, p38 MAP kinase, mTOR, NADPH-oxidase, JNK kinase, and HIF-1α. VEGF and PlGF-mediated transcription of KCC3b and KCC4 involved hypoxia response element (HRE) motifs in their promoters, as demonstrated by promoter analysis, EMSA and ChiP. These results were corroborated in vivo by adenoviral-mediated overexpression of PlGF in normal mice, which led to increased expression of mKCC3 and mKCC4 in erythroid precursors. Our studies show that VEGF and PlGF regulate transcription of KCC3b and KCC4 in erythroid cells via activation of HIF-1α, independent of hypoxia. These studies provide novel therapeutic targets for regulation of cell volume in RBC precursors, and thus, amelioration of dehydration in RBCs in sickle cell disease.
Social class and psychiatric practice: a revision of the Hollingshead and Redlich model
Authors: R F Mollica, M Milic
Journal: American Journal of Psychiatry (1986)

In 1958, Hollingshead and Redlich demonstrated that there were major differences in mental health care for lower-class patients: they primarily received low-intervention treatments from nonprofessional staff. The authors report a follow-up study initiated by F.C. Redlich that reveals new trends at the community mental health center (CMHC) serving the region studied by Hollingshead and Redlich. More than half of the lower-class patients who sought evaluation at this CMHC were discharged without a treatment assignment. Many lower-class patients, however, gained access to the CMHC's psychotherapy unit. Most of these patients were women, employed, and diagnosed as psychoneurotic. The authors conclude that the effect of social class on psychiatric care is less complete than Hollingshead and Redlich originally demonstrated.
Phase 1 Study Of Investigational Agent MLN8237 (Alisertib) + Rituximab ± Vincristine In Patients (Pts) With Relapsed/Refractory (Rel/Ref) Aggressive B-Cell Lymphomas
Authors: Kevin R. Kelly, Daniel O. Persky, Daruka Mahadevan, Thomas P. Miller, Soham D. Puvvada, Kevin McDonagh, John Hayslip, Steven I. Park, Jia Ruan, Peter J. Rosen, Swaminathan Padmanabhan Iyer, Alexandra Stefanovic, Bin Zhang, Xiaofei Zhou, Claudio Dansky Ullmann, E. Jane Leonard, Jonathan W. Friedberg
Journal: Blood (2013)
Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits
Authors: Christopher P. Larsen, Nidia C. Messias, Patrick D. Walker, Mary E. Fidler, Lynn D. Cornell, Loren H. Hernandez, Mariam P. Alexander, Sanjeev Sethi, Samih H. Nasr
Journal: Kidney International (2015)

The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. This change is due to the recognition that many of these cases are driven by abnormalities of the alternative complement cascade, resulting in the concept of C3 glomerulopathy. Here we reviewed our case files to identify those with an MPGN pattern that show false negative staining for monoclonal immunoglobulins by routine immunofluorescence. Monoclonal immunoglobulin deposits were unmasked by performing immunofluorescence on formalin-fixed paraffin embedded tissue after protease digestion. Clinico-pathological details of 16 such cases with a mean serum creatinine of 2.7 mg/dl and mean 24 h proteinuria of 7.1 g were then determined. Hypocomplementemia was present in two-thirds of patients. Fourteen patients had a paraprotein on serum immunofixation, all of which matched the biopsy immunofluorescence staining pattern. Bone marrow biopsy showed plasma cell dyscrasia or B-cell lymphoproliferative disorder in 13 patients. Ten of these patients had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed.
Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors
Authors: Richard O. Snyder, Carol Miao, Leonard Meuse, Julie Tubb, Brian A. Donahue, Hui-Feng Lin, Darrel W. Stafford, Salil Patel, Arthur R. Thompson, Timothy Nichols, Marjorie S. Read, Dwight A. Bellinger, Kenneth M. Brinkhous, Mark A. Kay
Journal: Nature Medicine (1999)
Mutations in the skeletal muscle α-actin gene in patients with actin myopathy and nemaline myopathy
Authors: Kristen J. Nowak, Duangrurdee Wattanasirichaigoon, Hans H. Goebel, Matthew Wilce, Katarina Pelin, Kati Donner, Rebecca L. Jacob, Christoph Hübner, Konrad Oexle, Janice R. Anderson, Christopher M. Verity, Kathryn N. North, Susan T. Iannaccone, Clemens R. Müller, Peter Nürnberg, Francesco Muntoni, Caroline Sewry, Imelda Hughes, Rebecca Sutphen, Atilano G. Lacson, Kathryn J. Swoboda, Jaqueline Vigneron, Carina Wallgren-Pettersson, Alan H. Beggs, Nigel G. Laing
Journal: Nature Genetics (1999)
Decrease in resting metabolic rate during abstinence from bulimic behavior
Authors: M Altemus, M M Hetherington, M Flood, J Licinio, M L Nelson, A S Bernat, P W Gold
Journal: American Journal of Psychiatry (1991)

Among eight normal-weight bulimic women studied during 1 week of binge eating and vomiting and 7 weeks of abstinence without weight loss, resting metabolic rate and T3 and T4 levels fell significantly during abstinence. These data suggest that a physiological consequence of binge eating and vomiting is an increase in metabolic rate, in part due to increased thyroid hormone activity.