tbuckley/cabot-search huggingface dataset:
Regulation of macrophage alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein by lipopolysaccharide and interferon-gamma.
Authors: J LaMarre, B B Wolf, E L Kittler, P J Quesenberry, S L Gonias
Journal: Journal of Clinical Investigation (1993)

alpha 2-Macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2M-R/LRP) is a broad specificity receptor that may function in lipoprotein metabolism, proteinase regulation, and growth factor regulation. In this study, we demonstrated that alpha 2M-R/LRP expression in macrophages can be markedly decreased by LPS and by IFN-gamma. Regulation of alpha 2M-R/LRP in RAW 264.7 cells was demonstrated at the mRNA, antigen, and receptor-function levels. In receptor-function studies, the decrease in alpha 2M-R/LRP expression was detected as a 90% decrease in the Bmax or maximum receptor binding capacity for activated alpha 2M after treatment with LPS or IFN-gamma. Western blot analysis of whole cell lysates demonstrated significant loss of alpha 2M-R/LRP heavy-chain. Northern blot analysis of poly(A)+ RNA revealed a marked decrease in alpha 2M-R/LRP mRNA after treatment with LPS (79% decrease) or IFN-gamma (70% decrease). Other cytokines, including tumor necrosis factor-alpha, transforming growth factor-beta-1, and interleukin-6 did not regulate alpha 2M-R/LRP. The ability of LPS and IFN-gamma to regulate alpha 2M-R/LRP was confirmed in experiments with primary cultures of murine bone marrow macrophages. These studies demonstrate that macrophage alpha 2M-R/LRP is subject to significant downregulation by physiologically significant cytokines and signaling macromolecules.
Potential Efficiency Benefits of Nonmydriatic Ultrawide Field Retinal Imaging in an Ocular Telehealth Diabetic Retinopathy Program
Authors: Paolo S. Silva, Jerry D. Cavallerano, Dorothy Tolls, Ahmed Omar, Komal Thakore, Bina Patel, Mina Sehizadeh, Ann M. Tolson, Jennifer K. Sun, Lloyd M. Aiello, Lloyd Paul Aiello
Journal: Diabetes Care (2013)

OBJECTIVE To compare efficiency of nonmydriatic ultrawide field retinal imaging (UWFI) and nonmydriatic fundus photography (NMFP) in a diabetic retinopathy (DR) ocular telehealth program. RESEARCH DESIGN AND METHODS Patients in this retrospective, comparative cohort study underwent NMFP and UWFI between 1 November 2011 and 1 November 2012. Images were evaluated for DR and diabetic macular edema (DME) by certified graders using a standard protocol at a centralized reading center. Identification of DR, image evaluation time, and rate of ungradable eyes were compared. RESULTS NMFP and UWFI were performed in 1,633 and 2,170 consecutive patients, respectively. No statistically significant differences were found between groups regarding age, diabetes duration, sex, ethnicity, or insulin use. The ungradable rate per patient for DR (2.9 vs. 9.9%, P &amp;lt; 0.0001) and DME (3.8 vs. 8.8%, P &amp;lt; 0.0001) was lower with UWFI than with NMFP. With UWFI, the median image evaluation time per patient was reduced from 12.8 to 9.2 min (P &amp;lt; 0.0001). The identification of patients with DR (38.4 vs. 33.8%) and vision-threatening DR (14.5 vs. 11.9%) was increased with UWFI versus NMFP. In a consecutive subgroup of 502 eyes of 301 patients with DR, the distribution of peripheral retinal lesions outside Early Treatment Diabetic Retinopathy Study fields suggested a more severe DR level in 9.0% (45 eyes). CONCLUSIONS In a standardized DR ocular telehealth program, nonmydriatic UWFI reduced the ungradable rate by 71% (to &amp;lt;3%) and reduced image evaluation time by 28%. DR was identified 17% more frequently after UWFI, and DR peripheral lesions suggested a more severe DR level in 9%. These data suggest that UWFI may improve efficiency of ocular telehealth programs evaluating DR and DME.
The role of “prespecification” in an embodied cognition
Authors: J. Scott Jordan
Journal: Behavioral and Brain Sciences (2004)

Grush makes extensive use of von Holst and Mittelstaedt's (1950) efference copy hypothesis. Although his embellishment of the model is admirably more sophisticated than that of its progenitors, I argue that it still suffers from the same conceptual limitations as entailed in its original formulation.
SPECIFICITY OF THE INFLAMMATORY RESPONSE IN VIRAL ENCEPHALITIS
Authors: Henry F. McFarland, Diane E. Griffin, Richard T. Johnson
Journal: The Journal of Experimental Medicine (1972)

The viral-induced perivascular inflammatory response in Sindbis virus encephalitis of mice was shown to be immunologically specific. Mice were inoculated intracerebrally with Sindbis virus, and 24 hr later a single dose of cyclophosphamide was given which ablated the inflammatory response. 3 days after virus inoculation, cells and/or sera from specifically and nonspecifically sensitized donor mice were given, and the inflammatory reactions, virus content, and antibody response of recipients were examined 5 days later. Reconstitution of the viral inflammatory response required virus-specific sensitized lymph node cells and was enhanced when these lymph node cells were combined with bone marrow cells. Reconstitution was not achieved with Sindbis virus immune serum even when combined with nonspecifically sensitized cells. Combination of immune serum with Sindbis virus-sensitized cells did not produce an accentuation of the reaction. In distinction, reconstitution of the inflammatory reaction surrounding the stab wound was reconstituted with bone marrow cells from mice inoculated with Sindbis virus or control antigens. Reconstitution of the perivascular reaction was associated with a reduction in brain virus content. Although the transfer of Sindbis virus-sensitized lymph node cells and bone marrow cells resulted in the limited production of neutralizing antibody in the immunosuppressed recipient, the reduction in virus was significantly greater with the transfers of Sindbis virus-sensitized lymph node cells than with the passive transfer of immune serum alone.
Functional Proteomic Analysis of Advanced Serous Ovarian Cancer Using Reverse Phase Protein Array: TGF-β Pathway Signaling Indicates Response to Primary Chemotherapy
Authors: Mark S. Carey, Roshan Agarwal, Blake Gilks, Kenneth Swenerton, Steve Kalloger, Jennifer Santos, Zhenlin Ju, Yiling Lu, Fan Zhang, Kevin R. Coombes, Dianne Miller, David Huntsman, Gordon B. Mills, Bryan T. Hennessy
Journal: Clinical Cancer Research (2010)

Using reverse phase protein array, we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage, high-grade serous ovarian cancer.Tumor samples were obtained from 45 patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples, and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by reverse phase protein array. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization and Cox regression to test for the association between protein expression and progression-free survival. A significance level of P<or=0.05 was used.The mean age at diagnosis was 56.8 years. epidermal growth factor receptor, YKL-40, and several transforming growth factor beta (TGF-beta) pathway proteins [c-jun-NH2-kinase (JNK), JNK phosphorylated at residues 183 and 185, plasminogen activator inhibitor 1, Smad3, TAZ] showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, epidermal growth factor receptor (P<0.02), JNK (P<0.01), and Smad3 (P<0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGF-beta pathway proteins was unlikely because of false discovery (P<0.007; Bonferroni adjusted).TGF-beta pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted.
Effect of thromboxane A2/endoperoxide antagonist SQ29548 on the contractile response to acetylcholine in newborn piglet cerebral arteries.
Authors: L C Wagerle, D W Busija
Journal: Circulation Research (1990)

Previous studies have shown that cholinergic stimulation results in a prostanoid-dependent cerebral vasoconstriction in piglets. The present study specifically investigated the contribution of thromboxane A2 (TXA2)/prostaglandin endoperoxide and prostaglandin F2 alpha (PGF2 alpha) to the cerebral vascular response to exogenous acetylcholine (ACh). Effects of TXA2/prostaglandin endoperoxide-receptor antagonist SQ29548 on responsiveness of pial arterioles to ACh (10(-7) and 10(-4) M), PGF2 alpha (10(-7)-10(-5) M), TXA2 mimetic 9,11-methanoepoxy prostaglandin H2 (U46619, 5 and 10 ng/ml), and norepinephrine (10(-6)-10(-4) M) were studied by use of a closed cranial window in 37 anesthetized mechanically ventilated newborn piglets. Pial arteriolar diameter was measured by intravital microscopy. Topical application of exogenous PGF2 alpha and U46619 resulted in dose-dependent cerebral vasoconstriction, and the dose-response curve for each agonist was shifted to the right by the increasing concentrations of SQ29548 (10(-6)-10(-8) M). Topical application of high concentration of ACh (10(-4) M) caused a transient 34 +/- 4% decrease in pial arteriolar diameter from 98 +/- 6 to 65 +/- 5 microns (p less than 0.05). This constriction was attenuated (16 +/- 3%) in the presence of 10(-8) M SQ29548 and abolished with 10(-6) or 10(-4) M SQ29548. SQ29548 (10(-6) M) was without effect on the vasoconstrictor response to exogenous norepinephrine. Low concentration of ACh (10(-7) M) had no consistent effect on pial arterioles in the absence or presence of TXA2/prostaglandin endoperoxide-receptor blockade. The data suggest that vascular prostaglandin/endoperoxide receptors mediate cerebral vasoconstriction upon muscarinic-receptor stimulation.
What size parapneumonic effusions should be sampled?
Authors: V Skouras, A Awdankiewicz, R W Light
Journal: Thorax (2009)

The indications for operative intervention in parapneumonic effusions (PPEs) are currently based on their anatomical, bacteriological and biochemical features. Because PPEs  10 mm on the lateral decubitus radiograph, ultrasound or CT scan should be sampled.1 2 3 However, Espana et al used a PFT cut-off point of 20 mm on the lateral decubitus radiograph for admitting patients with PPE and reported a significantly low outpatient mortality (0.5%).4

We examined the association between PFT and the development of pleural …
Modulation of extracellular matrix proteins in rat liver during development
Authors: Shimon Reif, Victor P. Terranova, Mamdouh El-Bendary, Emanuel Lebenthal, James K. Petell
Journal: Hepatology (1990)

The expression and localization of extracellular matrix proteins in rat liver was investigated as a function of liver development. Levels of extracellular matrix proteins were measured by dot-blot or immunoblot protocols using monospecific antibodies prepared against collagen types I, III and IV; laminin; fibronectin; and fibronectin receptor. Proline and hydroxyproline levels from extracted liver collagen were quantitated by Pico Tag analysis. It was observed that the content of type IV collagen and fibronectin in the rat liver increased two to four times during the perinatal period. In contrast, levels of laminin and collagen types I and III decreased up to twofold in developing rat livers. The content of fibronectin receptor during ontogeny was decreased four times in an inverse relationship to fibronectin molecules. Fibronectin receptor and extracellular matrix proteins displayed no difference in apparent molecular weight as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots. Indirect immunofluorescence staining of frozen thin liver sections revealed that the pattern of localization of extracellular matrix proteins in the nonvascular regions of fetal liver was punctate rather than restricted to a specific region such as the perisinusoidal area of adult livers. Similarly, fibronectin receptor was also present, mainly in the sinusoidal area of adult livers, whereas fetal sections were diffusely stained. Our findings suggest that the differential modulation of extracellular matrix proteins and their localization in the developing rat livers undergo a dramatic alteration in the composition and structural organization of matrix material, which may act to modulate proliferation and to promote the differentiation of liver cells during development. (Hepatology 1990;12:519-525).
Cumulative Live-Birth Rates after In Vitro Fertilization
Authors: Beth A. Malizia, Michele R. Hacker, Alan S. Penzias
Journal: New England Journal of Medicine (2009)

Outcomes of in vitro fertilization (IVF) treatment are traditionally reported as pregnancies per IVF cycle. However, a couple's primary concern is the chance of a live birth over an entire treatment course.We estimated cumulative live-birth rates among patients undergoing their first fresh-embryo, nondonor IVF cycle between 2000 and 2005 at one large center. Couples were followed until either discontinuation of treatment or delivery of a live-born infant. Analyses were stratified according to maternal age and performed with the use of both optimistic and conservative methods. Optimistic methods assumed that patients who did not return for subsequent IVF cycles would have the same chance of a pregnancy resulting in a live birth as patients who continued treatment; conservative methods assumed no live births among patients who did not return.Among 6164 patients undergoing 14,248 cycles, the cumulative live-birth rate after 6 cycles was 72% (95% confidence interval [CI], 70 to 74) with the optimistic analysis and 51% (95% CI, 49 to 52) with the conservative analysis. Among patients who were younger than 35 years of age, the corresponding rates after six cycles were 86% (95% CI, 83 to 88) and 65% (95% CI, 64 to 67). Among patients who were 40 years of age or older, the corresponding rates were 42% (95% CI, 37 to 47) and 23% (95% CI, 21 to 25). The cumulative live-birth rate decreased with increasing age, and the age-stratified curves (< 35 vs. > or = 40 years) were significantly different from one another (P<0.001).Our results indicate that IVF may largely overcome infertility in younger women, but it does not reverse the age-dependent decline in fertility.
Synovial immunopathology in haemochromatosis arthropathy
Authors: Gisela Ruiz Heiland, Elmar Aigner, Tomáš Dallos, Enijad Sahinbegovic, Veit Krenn, Christoph Thaler, Günter Weiss, Jörg H Distler, Christian Datz, Georg Schett, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2009)

Background Hereditary haemochromatosis (HH) is a common autosomal recessive inherited disorder that frequently causes arthritis. The pathophysiology of musculoskeletal involvement is, however, unclear. Objective To analyse synovial tissue obtained at surgery from patients with HH arthropathy and compare it qualitatively and quantitatively with specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods Synovial tissue from 15 patients with HH, 20 with RA and 39 with OA was obtained during surgery. A synovitis grading system was used to determine the severity of synovial inflammation. Using immunohistochemistry, synovial neovascularisation and infiltration of macrophages, neutrophils and lymphocytes were quantitatively assessed. Results Synovitis in HH arthropathy largely resembles OA with mild infiltration of mononuclear cells and lymphocytes, formation of synovial microvessels and a low degree of synovial hyperplasia. While many features of HH arthropathy are reminiscent of OA, macrophage and especially neutrophil invasion is clearly more prominent in HH arthropathy than in primary OA and mimics features of RA. This finding was observed particularly in synovial tissue of HH samples with marked haemosiderin deposition. Discussion The histological picture of the synovium in HH arthropathy largely resembles a process reminiscent of OA. Neutrophil invasion is, however, markedly increased in HH arthropathy, especially in joints with iron deposition. Accumulation of neutrophils may be crucial for the production of matrix enzymes, which enables cartilage degradation and more rapidly progressive articular damage.
Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
Authors: Philippe Moreau, Halyna Pylypenko, Sebastian Grosicki, Ievgenii Karamanesht, Xavier Leleu, Maria Grishunina, Grigoriy Rekhtman, Zvenyslava Masliak, Tadeusz Robak, Anna Shubina, Bertrand Arnulf, Martin Kropff, James Cavet, Dixie-Lee Esseltine, Huaibao Feng, Suzette Girgis, Helgi van de Velde, William Deraedt, Jean-Luc Harousseau
Journal: The Lancet Oncology (2011)
Phase III Trial of Doxorubicin Plus Cisplatin With or Without Paclitaxel Plus Filgrastim in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study
Authors: Gini F. Fleming, Virginia L. Brunetto, David Cella, Katherine Y. Look, Gary C. Reid, Adnan R. Munkarah, Richard Kline, Robert A. Burger, Annekathryn Goodman, R. Tucker Burks
Journal: Journal of Clinical Oncology (2004)

To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities.Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle.Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median, 8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy.TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.
ELECTROENCEPHALOGRAPHY IN BEHAVIOUR PROBLEM CHILDREN
Authors: CHARLES I. SOLOMON, WARREN T. BROWN, MAX DEUTSCHER
Journal: American Journal of Psychiatry (1944)

The EEGs of the 20 best behaved boys in a junior high school class of 131 boys were compared with the tracings of the 20 most troublesome boys in the class. These represented extremes from the point of view of behaviour and adjustment in a given situation. The age range of the two groups was the same (13-16½ years). Choice of boys over 13 years of age made comparison easier because adult patterns are then already established and consideration of normal year to year variations of tracings in children below this age was thus made unnecessary. Social, economic and cultural background was similar in the two groups, thus eliminating an important variable found in the groups compared in all previous studies by other authors. The boys in the most troublesome group were behaviour problems at home and in the neighborhood, as well as in the school situation. The boys in the so-called normal group presented no difficulties of behaviour in school, home or neighborhood. There were 12 abnormal tracings in the first group and 11 in the second. Intelligence level did not in itself have any influence on the nature of the tracings. The EEGs of the 10 best behaved and least delinquent boys in an institution for delinquent boys and the 10 most chronic delinquents with the most severe and chronic types of behaviour disorder were similarly compared. Four of the former and 9 of the latter 10 boys showed abnormal tracings. Results of comparison between intelligence, efficiency of performance and personality with type of EEG were also similarly contradictory, confusing and difficult to interpret. Individual case studies illustrated these contradictions and discrepancies over and over again. The most consistent incidence of abnormal EEGs was found in the most poorly behaved institution group, in the group with the severest and most chronic disorders of behaviour. This would suggest that the finding of an abnormal cortical electrical pattern may be indicative of a physiological disturbance which influences behaviour adversely. However, the very frequent presence of abnormal rhythms and patterns of the same kind found by us and by other observers in children without behaviour disorders and of normal and abnormal tracings in apparently similar types of behaviour problem children makes it difficult to interpret the significance of the findings in the individual case. The EEG is of course Valuable in the detection of hidden focal lesions and of cryptic epilepsy. The most that can be said at present for the value of other findings of dysrhythmia in behaviour problem children is that they may be regarded as a probable additional unfavorable personal factor, among many other factors, adversely influencing behaviour. Studies and results to date do not warrant further interpretation or clinical application in diagnosis, therapy or prognosis.
The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein–induced bone formation
Authors: Mikihiko Morinobu, Tetsuya Nakamoto, Kazunori Hino, Kunikazu Tsuji, Zhong-Jian Shen, Kazuhisa Nakashima, Akira Nifuji, Haruyasu Yamamoto, Hisamaru Hirai, Masaki Noda
Journal: The Journal of Experimental Medicine (2005)

Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)–induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2–induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.