tbuckley/cabot-search huggingface dataset:
Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the gamma-secretase inhibitor LY-411575
Authors: Monica Garcia-Alloza, Meenakshi Subramanian, Diana Thyssen, Laura A Borrelli, Abdul Fauq, Pritam Das, Todd E Golde, Bradley T Hyman, Brian J Bacskai
Journal: Molecular Neurodegeneration (2009)

Abstract The γ-secretase complex is a major therapeutic target for the prevention and treatment of Alzheimer's disease. Previous studies have shown that treatment of young APP mice with specific inhibitors of γ-secretase prevented formation of new plaques. It has not yet been shown directly whether existing plaques would be affected by γ-secretase inhibitor treatment. Similarly, alterations in neuronal morphology in the immediate vicinity of plaques represent a plaque-specific neurotoxic effect. Reversal of these alterations is an important endpoint of successful therapy whether or not a treatment affects plaque size. In the present study we used longitudinal imaging in vivo with multiphoton microscopy to study the effects of the orally active γ-secretase inhibitor LY-411575 in 10–11 month old APP:PS1 mice with established amyloid pathology and neuritic abnormalities. Neurons expressed YFP allowing fluorescent detection of morphology whereas plaques were labelled with methoxy-XO4. The same identified neurites and plaques were followed in weekly imaging sessions in living mice treated daily (5 mg/kg) for 3 weeks with the compound. Although LY-411575 reduced Aβ levels in plasma and brain, it did not have an effect on the size of existing plaques. There was also no effect on the abnormal neuritic curvature near plaques, or the dystrophies in very close proximity to senile plaques. Our results suggest that therapeutics aimed at inhibition of Aβ generation are less effective for reversal of existing plaques than for prevention of new plaque formation and have no effect on the plaque-mediated neuritic abnormalities, at least under these conditions where Aβ production is suppressed but not completely blocked. Therefore, a combination therapy of Aβ suppression with agents that increase clearance of amyloid and/or prevent neurotoxicity might be needed for a more effective treatment in patients with pre-existing pathology.
Coassociation of Estrogen Receptor and p160 Proteins Predicts Resistance to Endocrine Treatment; SRC-1 is an Independent Predictor of Breast Cancer Recurrence
Authors: Aisling M. Redmond, Fiona T. Bane, Anthony T. Stafford, Marie McIlroy, Mary F. Dillon, Thomas B. Crotty, Arnold D. Hill, Leonie S. Young
Journal: Clinical Cancer Research (2009)

This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments.The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients.Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with human epidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively).SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.
Retrospective Analysis of Intravascular Large B-Cell Lymphoma Treated With Rituximab-Containing Chemotherapy As Reported by the IVL Study Group in Japan
Authors: Kazuyuki Shimada, Kosei Matsue, Kazuhito Yamamoto, Takuhei Murase, Naoaki Ichikawa, Masataka Okamoto, Nozomi Niitsu, Hiroshi Kosugi, Norifumi Tsukamoto, Hiroshi Miwa, Hideki Asaoku, Ako Kikuchi, Morio Matsumoto, Yoshio Saburi, Yasufumi Masaki, Motoko Yamaguchi, Shigeo Nakamura, Tomoki Naoe, Tomohiro Kinoshita
Journal: Journal of Clinical Oncology (2008)

To evaluate the safety and efficacy of rituximab-containing chemotherapies for intravascular large B-cell lymphoma (IVLBCL).We retrospectively analyzed 106 patients (59 men, 47 women) with IVLBCL who received chemotherapy either with rituximab (R-chemotherapy, n = 49) or without rituximab (chemotherapy, n = 57) between 1994 and 2007 in Japan. The median patient age was 67 years (range, 34 to 84 years). The International Prognostic Index was high-intermediate/high in 97% of patients.The complete response rate was higher for patients in the R-chemotherapy group (82%) than for those in the chemotherapy group (51%; P = .001). The median duration of follow-up for surviving patients was 18 months (range, 1 to 95 months). Progression-free survival (PFS) and overall survival (OS) rates at 2 years after diagnosis were significantly higher for patients in the R-chemotherapy group (PFS, 56%; OS, 66%) than for patients in the chemotherapy group (PFS, 27% with P = .001; OS, 46% with P = 0.01). Multivariate analysis revealed that the use of rituximab was favorably associated with PFS (hazard ratio [HR], 0.45; 95% CI, 0.25 to 0.80; P = .006) and OS (HR, 0.42; 95% CI, 0.21 to 0.85; P = .016). Treatment-related death was observed in three patients (6%) who received R-chemotherapy and in five patients (9%) who received chemotherapy.Our data suggest improved clinical outcomes for patients with IVLBCL in the rituximab era. Future prospective studies of rituximab-containing chemotherapies are warranted.
Cardiovascular Disease in Non-Western Countries
Authors: K. Srinath Reddy
Journal: New England Journal of Medicine (2004)

Concern about increasing rates of death and disability due to cardiovascular disease in non-Western countries is often met with skepticism: Do they really constitute a serious public health problem? With justifiable alarm about the spread of human immunodeficiency virus and AIDS and with old foes such as malaria and tuberculosis still posing formidable challenges in many developing countries, it is understandable that epidemics of cardiovascular disease have insidiously established themselves without attracting global attention or local action. The fact that 80 percent of deaths from cardiovascular disease worldwide and 87 percent of related disability currently occur in low-income and middle-income . . .
Effect of diameter on force generation and responsiveness of bronchial segments and rings
Authors: PR Gray, HW Mitchell
Journal: European Respiratory Journal (1996)

In this study, isovolumic bronchial segments and bronchial rings were used to investigate the influence of airway diameter on smooth muscle force generation and acetylcholine responsiveness. Segments with internal diameters ranging from 1.0-6.0 mm were obtained from the mainstem bronchus of eight pigs. Responses to increasing acetylcholine concentrations were quantified in segments by intralumenal pressure (cmH2O), and in rings by tension (g.cm-1). The negative log of the concentration producing half the maximal effect (EC50) (i.e. pD2) to acetylcholine was calculated for each segment and ring. Ring tension was used to calculate a theoretical lumen pressure for each ring, and this, along with the pD2, was compared with values obtained from segments of the same diameter. Intermediate-sized segments produced significantly greater intralumenal pressures than did large or small segments. Small segments were 160 times more sensitive to acetylcholine than large segments. In contrast to the segments, bronchial rings showed no effect of size on acetylcholine sensitivity. Theoretical ring lumen pressures matched those measured for large and intermediate segments, but not for small segments. The different behaviour of bronchial segments and rings obtained from the same sized airway suggests that the three-dimensional architecture of the airway is an important factor in determining behaviour, particularly in small airways.
Abuse-Deterrent Opioid Formulations
Authors: Hillary V. Kunins
Journal: JAMA Internal Medicine (2015)

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
Ampullary Neuro-Endocrine Tumour: Clinicopathological Features, Treatment and Prognosis
Authors: Singh Rakesh, Singh Rajneesh, Prakash Anand, Behari Anu, Kumar Ashok, V.K. Kapoor, Saxena Rajan, Kripalani Narendra, Neeraj Dr
Journal: Annals of Oncology (2014)
Alveolar antioxidant status in patients with acute respiratory distress syndrome
Authors: R. Schmidt
Journal: European Respiratory Journal (2004)

In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20). Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), α-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas–liquid chromatography), and F<sub>2</sub>-isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF. GSSG (ARDS: 0.13±0.02 µM; control: 0.03±0.01 µM; mean±sem) and F<sub>2</sub>-isoprostanes (ARDS: 78±10 pM; control: 26±5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77±15 nM; control: 26±3 nM) and uric acid (ARDS: 11.8±2.2 µM; control: 0.7±0.0 µM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of ∼3 in patients, but plasmalogens showed a significant decrease. In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding.
History, Memory, and Profession: A View of American Psychiatry Through APA Presidential Addresses, 1883–2003
Authors: Laura D. Hirshbein
Journal: American Journal of Psychiatry (2004)

The address of the retiring president of the American Psychiatric Association has been a traditional part of the annual meeting of the association since 1883. The presidential address, which has explicitly been exempted from general discussion or criticism, has become an opportunity for the elected leader of the association to reflect on the state of the profession. Over the last 120 years, the presidents of the association have themselves engaged with the history of psychiatry in ways that reflect the changes in psychiatry of the time. In the process, memory has served a professionalizing purpose, as some aspects of psychiatry's history have been remembered while others have not. In the presidential addresses, history is not just a story about the past but also a story about psychiatry's self-definition and its future.
The Role of the Number of Uninvolved Lymph Nodes in Predicting Locoregional Recurrence in Breast Cancer
Authors: Per Karlsson, Bernard F. Cole, Karen N. Price, Alan S. Coates, Monica Castiglione-Gertsch, Barry A. Gusterson, Elizabeth Murray, Jurij Lindtner, John P. Collins, Stig B. Holmberg, Martin F. Fey, Beat Thürlimann, Diana Crivellari, John F. Forbes, Richard D. Gelber, Aron Goldhirsch, Arne Wallgren
Journal: Journal of Clinical Oncology (2007)

To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT).Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected. All patients were treated with mastectomy without RT.No group with 10-year LRF risk exceeding 20% was found among patients with node-negative disease. Among patients with node-positive breast cancer, increasing numbers of uninvolved nodes were significantly associated with decreased risk of LRF, even after adjustment for other prognostic factors. The highest quartile of uninvolved nodes was compared with the lowest quartile. Among premenopausal patients, LRF risk was decreased by 35% (P = .0010); among postmenopausal patients, LRF risk was decreased by 46% (P < .0001). The 10-year cumulative incidence of LRF was 20% among patients with one to three involved lymph nodes and fewer than 10 uninvolved nodes. Age younger than 40 years and vessel invasion were also associated significantly with increased risk. Among patients with node-positive disease, overall survival was significantly greater in those with higher numbers of uninvolved nodes examined (P < .0001).Patients with one to three involved nodes and a low number of uninvolved nodes, vessel invasion, or young age have an increased risk of LRF and may be candidates for a similar treatment as those with at least four lymph node metastases.
Production and characterization of an Mls-1-specific monoclonal antibody.
Authors: N Mohan, D Mottershead, M Subramanyam, U Beutner, B T Huber
Journal: The Journal of Experimental Medicine (1993)

Superantigens (SAGs) represent a new class of antigens, characterized as T cell receptor (TCR) V beta-reactive elements. Bacterial toxins constitute the major group of exogenous SAGs, while the mouse mammary tumor virus (MMTV)-encoded Mls molecules represent the endogenous SAGs. Mls-1 is the prototype of the latter SAGs, because it elicits a very potent T cell stimulatory response in vitro in unprimed T cells expressing the TCR V beta 6 or 8.1 chains. In vivo, Mls-1 causes deletion of immature T cells bearing the V beta 6, 7, 8.1, or 9 chains. Although Mls-1 was functionally discovered &amp;gt; 20 yr ago, it has not been possible to raise antibodies against this molecule. We have previously cloned and sequenced the Mtv-7 sag gene, which encodes Mls-1. Sequence comparisons with other MMTV sag genes suggested that the polymorphic 3' end encodes the TCR V beta specificity of these SAGs. We have, therefore, immunized hamsters with a 14-amino acid peptide from the deduced COOH-terminal sequence of the Mtv-7 sag gene. We describe here the production of a monoclonal antibody (mAb), 3B12, which is peptide specific and reacts with a recombinant baculovirus product of Mtv-7 sag. This mAb blocks Mls-1-specific T cell recognition and detects the Mls-1 protein on the surface of the B cell hybridoma LBB.A, but not on LBB.11, which is an Mtv-7 loss variant of LBB.A. Transfection of the Mtv-7 sag gene into LBB.11 renders this cell functionally Mls-1+ as well as positive for 3B12 binding, confirming the specificity of this mAb. It is well documented that B cells and CD8+ T cells express T cell stimulatory Mls-1 determinants, and we show here that this functional profile correlates with the expression of MMTV-specific mRNA. However, primary lymphocytes derived from Mls-1+ mice do not stain with 3B12, even after in vitro activation with mitogens or phorbol ester.
Anticancer Drug Discovery
Authors: B. I. Sikic
Journal: JNCI Journal of the National Cancer Institute (1991)

The National Cancer Institute's (NCI's) human tumor cell line panel for screening potential new anticancer drugs is now operational (/). Its implementation and the demonstration of its feasibility represent a technical and organizational tour de force. The rationale for the change in the primary screen from leukemias in mice to the array of 60 human cancer cell lines was earlier debated in contrasting editorials in this journal (2,3). The new screening panel occupies a central position in the NCI's continued commitment to anticancer drug development (Fig. 1). A major implicit assumption in this schema is the presence of novel, highly active agents among the thousands funnelled into the system. The acquisition of candidate compounds is therefore the initial limiting factor. How did our current complement of 40 or so active anticancer drugs arrive at the first stage of development, and where can we expect future agents to originate? Sources of New Agents
Liver growth factor (LGF) reverts experimental lung emphysema induced by tobacco smoke in mice
Authors: Alvaro Giron-Martinez, Terron-Exposito Raul, Sandra Perez-Rial, Nicolas Gonzalez-Mangado, Peces-Barba German
Journal: European Respiratory Journal (2012)

The liver growth factor (LGF) is a hepatic mitogen able to modulate the remodeling induced in several diseases, as hypertension in the arteries or cirrhosis in the liver. Considering the therapeutic effect of the LGF on the experimental COPD model induced by CdCl2 (Arch. Bronconeumol. 2010; 46 (1:20-26), we aimed to study the regenerative effects of this factor over the experimental COPD tobacco induced model.

15 mice C57BL/6j were exposed to cigarette smoke or sham smoke during 6 month, twice a day and five days a week. After last exposition the treated group received 1.7 µg of LGF i.p. in two administrations (1/wk).Variables of lung morphometry (mean linear intercept –LM-), lung function (maximal volume at 30 cmH2O –Vmax-) and in vivo fluorescence molecular imaging (FMI) with the MMPsense680 probe that detects activation of matrix metalloproteases (MMPs-4-3-9-13) were analyzed in this study.

The tobacco smoke group developed lung emphysema as estimated by the LM value (41.88±0.64 µ vs 32.46±0.46 µ in the control group. p<0.01) and the Vmax (1.391±0.15 ml vs 1.287±0.149 ml. p<0.05). The LGF treated group significantly improved both values reaching the control values (LM 32.04±0.35 µ. p<0.01; Vmax 1.308±0.149 ml. p<0.05). In vivo FMI of MMPs activation showed a significative increasing in the tobacco smoke group (1.83±0.1 AU from respective control. P<0.01). After LGF treatment, in vivo FMI was significantly reduced also reaching the control level (p<0.01).

In conclusion, experimental lung emphysema developed by chronic exposition to cigarette smoke in C57BL/6j was reverted by LGF treatment, as estimated by MMPs activity, lung morphometry and lung function.
Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal
Authors: P. Valent, K. Sotlar, W.R. Sperr, L. Escribano, S. Yavuz, A. Reiter, T.I. George, H.C. Kluin-Nelemans, O. Hermine, J.H. Butterfield, H. Hägglund, C. Ustun, J.L. Hornick, M. Triggiani, D. Radia, C. Akin, K. Hartmann, J. Gotlib, L.B. Schwartz, S. Verstovsek, A. Orfao, D.D. Metcalfe, M. Arock, H.-P. Horny
Journal: Annals of Oncology (2014)
<i>Helicobacter pylori</i> Caga Protein Can Be Tyrosine Phosphorylated in Gastric Epithelial Cells
Authors: Momoyo Asahi, Takeshi Azuma, Shigeji Ito, Yoshiyuki Ito, Hiroyuki Suto, Yukifumi Nagai, Misao Tsubokawa, Yumi Tohyama, Shin Maeda, Masao Omata, Toshihiko Suzuki, Chihiro Sasakawa
Journal: The Journal of Experimental Medicine (2000)

Attachment of Helicobacter pylori to gastric epithelial cells induces various cellular responses, including the tyrosine phosphorylation of an unknown 145-kD protein and interleukin 8 production. Here we show that this 145-kD protein is the cagA product of H. pylori, an immunodominant, cytotoxin-associated antigen. Epithelial cells infected with various H. pylori clinical isolates resulted in generation of tyrosine-phosphorylated proteins ranging from 130 to 145 kD in size that were also induced in vitro by mixing host cell lysate with bacterial lysate. When epithelial cells were infected with [35S]methionine-labeled H. pylori, a radioactive 145-kD protein was detected in the immunoprecipitates with antiphosphotyrosine antibody or anti-CagA (cytotoxin-associated gene A) antibody. Consistently, the 145-kD protein recognized by the anti-CagA and antiphosphotyrosine antibodies was induced in epithelial cells after infection of wild-type H. pylori but not the cagA::Km mutant. Furthermore, the amino acid sequence of the phosphorylated 145-kD protein induced by H. pylori infection was identical to the H. pylori CagA sequence. These results reveal that the tyrosine-phosphorylated 145-kD protein is H. pylori CagA protein, which may be delivered from attached bacteria into the host cytoplasm. The identification of the tyrosine-phosphorylated protein will thus provide further insights into understanding the precise roles of CagA protein in H. pylori pathogenesis.
Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone
Authors: S. Novello, P. Bruzzi, C. Barone, R. Buosi, A. Masotti, G. Michetti, M. Fioretti, S. Barbera, M. Spatafora, L. Garetto, P. Mazzanti, V. Dongiovanni, G. Selvaggi, L. Crinò, G.V. Scagliotti
Journal: Annals of Oncology (2007)
Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis.
Authors: F Mion, B Napoleon, F Berger, M Chevallier, S Bonvoisin, L Descos
Journal: Gut (1991)

Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present.