tbuckley/cabot-search huggingface dataset:
Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease. A placebo-controlled randomized trial.
Authors: A M Schols, P B Soeters, R Mostert, R J Pluymers, E F Wouters
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Nutritional depletion commonly occurs in patients with COPD, causing muscle wasting and impaired physiologic function. Two hundred seventeen patients with COPD participated in a placebo-controlled, randomized trial investigating the physiologic effects of nutritional intervention alone (N) for 8 wk or combined with the anabolic steroid nandrolone decanoate (N + A). Nandrolone decanoate or placebo (P) was injected intramuscularly (women, 25 mg; men, 50 mg) in a double-blind fashion on Days 1, 15, 29, and 43. Nutritional intervention consisted of a daily high caloric supplement (420 kcal; 200 ml). Also, all patients participated in an exercise program. In the depleted patients, both treatment regimens induced a similar significant body weight gain (2.6 kg) but different body compositional changes. Particularly in the last 4 wk of treatment, weight gain in the N group was predominantly due to an expansion of fat mass (p < 0.03 versus P and N + A), whereas the relative changes in fat-free mass (FFM) and other measures of muscle mass were more favorable in the N + A group (p < 0.03 versus P). Maximal inspiratory mouth pressure improved within both treatment groups in the first 4 wk of treatment, but after 8 wk only N + A was significantly different from P (p < 0.03). Nutritional supplementation in combination with a short course of anabolic steroids may enhance the gain in FFM and respiratory muscle function in depleted patients with COPD without causing adverse side effects.
Midkine Is Involved in Kidney Development and in Its Regulation by Retinoids
Authors: José Vilar, Claude Lalou, Jean-Paul Duong Van Huyen, Stéphanie Charrin, Sylvie Hardouin, Daniel Raulais, Claudie Merlet-Bénichou, Martine Leliévre-Pégorier
Journal: Journal of the American Society of Nephrology (2002)

In the kidney, in which development depends on epithelial-mesenchymal interactions, it has been shown that retinoids modulate nephrogenesis in a dose-dependent manner in vivo and in vitro. Midkine (MK) is a retinoic acid responsive gene for a heparin-binding growth factor. The aim of the present study was therefore to quantify the expression of MK mRNA during renal development in the rat, to analyze the regulation of MK expression by retinoids in vivo and in vitro, and, finally, to study the role of MK in rat metanephric organ cultures. The spatiotemporal expression of MK in fetal kidney was studied. In control rats, MK expression is ubiquitous at gestational day 14, i.e., at the onset of nephrogenesis. On day 16, MK is expressed in the condensed mesenchyme and in early epithelialized mesenchymal derivatives. On gestational day 21, MK is rather localized in the nonmature glomeruli of the renal cortex. In utero exposure to vitamin A deficiency did not modify the specific spatial and temporal expression pattern of MK gene in the metanephros, although a decrease in mRNA expression occurred. In metanephroi explanted from 14-d-old fetuses and cultured in a defined medium, expression of MK mRNA was found to be stimulated when retinoic acid (100 nM) was added in the culture medium. Finally, in vitro nephrogenesis was strongly inhibited in the presence of neutralizing antibodies for MK: the number of nephrons formed in vitro was reduced by approximately 50% without changes in ureteric bud branching morphogenesis. These results indicated that MK is implicated in the regulation of kidney development by retinoids. These results also suggested that MK plays an important role in the molecular cascade of the epithelial conversion of the metanephric blastema.
RHEUMATOID FACTOR PROPERTIES OF HYPERIMMUNE RABBIT SERA
Authors: Charles L. Christian
Journal: The Journal of Experimental Medicine (1963)

The rheumatoid factor-like substance (RFLS) induced by hyperimmunization of rabbits with bacteria was consistently and exclusively associated with the macroglobulin fraction of the sera studied. The RFLS is separable from the bulk of serum proteins by zone centrifugation, DEAE cellulose chromatography, and gel filtration. Partially purified preparations of the RFLS were studied by immunoelectrophoretic analysis and analytical ultracentrifugation. Certain RFLS sera demonstrated selective reactivity with one or more rabbit isohemagglutinin antibodies. Pepsin treatment of rabbit gamma-globulin removed or greatly diminishes its capacity to react with the RFLS.
Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46).
Authors: T Seya, T Hara, M Matsumoto, Y Sugita, H Akedo
Journal: The Journal of Experimental Medicine (1990)

We have developed polyclonal and monoclonal antibodies against human membrane cofactor protein (MCP) to use as tools to investigate the functions of MCP on intact nucleated cells. Two human T cell lines, CEM and TALL, are CR1- and DAF-. Pretreatment of these cell lines with M177 and polyclonal anti-MCP, which inhibit cofactor activity almost completely, resulted in effective C3 deposition immediately following addition of these cells to Mg2+/EGTA/human sera. The deposited C3 remained expressed partly on the cell surface and most of them were gradually converted to C3bi. Some of the deposited C3 were complexed with membrane proteins, since 140- and 250-kD bands became significantly accumulated on SDS-PAGE by treatment with the antibodies. We next tested whether these C3-coated cells were damaged by complement-mediated cytolysis. p18, an inhibitor of membrane attack complex (MAC) formation, was negative in TALL but positive in CEM. TALL was lysed efficiently only by treatment with the polyclonal anti-MCP, while CEM showed only slight lysis with the same treatment. Monoclonal antibodies to MCP, including M177, caused only minimal cell destruction. Based on these results, together with the fact that decay-accelerating factor (DAF) serves as a factor for preventing C3 attack on human cells, we conclude that MCP and DAF cooperatively protect host cells from C3 targeting and, in these T cell lines, MCP is sufficient for preventing C3 deposition even without DAF. After all, human cells undergo almost no autologous complement-mediated cytolysis if they express at least one of the functionally active inhibitors, MCP, DAF, or p18.
Different training patterns and bone mineral density of the femoral shaft in elite, female athletes.
Authors: R L Wolman, L Faulmann, P Clark, R Hesp, M G Harries
Journal: Annals of the Rheumatic Diseases (1991)

The effects of sporting activity and of menstrual status on the bone mineral content of the femoral mid-shaft were investigated. The cohort consisted of 67 elite, female athletes comprising 21 runners, 36 rowers, and 10 dancers. Twenty five of these athletes were amenorrhoeic, 27 eumenorrhoeic, and 15 were taking the oral contraceptive. The bone mineral content was also measured in 13 eumenorrhoeic, sedentary women. The mean (95% confidence interval) bone mineral content in the runners was 1.51 (1.47 to 1.55) g/cm2, which was significantly higher than in the rowers, dancers, and sedentary controls whose values were 1.43 (1.40 to 1.47), 1.39 (1.33 to 1.45), and 1.40 (1.34 to 1.45) g/cm2 respectively. There was no significant difference in the bone mineral content between the amenorrhoeic, eumenorrhoeic, and oral contraceptive taking athletes. These results may have implications for devising exercise strategies to reduce the possibility of fractures in later life.
Low Molecular Weight Cyclin E Overexpression Shortens Mitosis, Leading to Chromosome Missegregation and Centrosome Amplification
Authors: Rozita Bagheri-Yarmand, Anna Biernacka, Kelly K. Hunt, Khandan Keyomarsi
Journal: Cancer Research (2010)

Abstract Overexpression of the low molecular weight isoforms (LMW-E) of cyclin E induces chromosome instability; however, the degree to which these tumor-specific forms cause genomic instability differs from that of full-length cyclin E (EL), and the underlying mechanism(s) has yet to be elucidated. Here, we show that EL and LMW-E overexpression impairs the G2-M transition differently and leads to different degrees of chromosome instability in a breast cancer model system. First, the most significant difference is that EL overexpression prolongs cell cycle arrest in prometaphase, whereas LMW-E overexpression reduces the length of mitosis and accelerates mitotic exit. Second, LMW-E–overexpressing cells are binucleated or multinucleated with amplified centrosomes, whereas EL-overexpressing cells have the normal complement of centrosomes. Third, LMW-E overexpression causes mitotic defects, chromosome missegregation during metaphase, and anaphase bridges during anaphase, most of which are not detected on EL induction. LMW-E induces additional mitotic defects in cooperation with p53 loss in both normal and tumor cells. Fourth, LMW-E–overexpressing cells fail to arrest in the presence of nocodazole. Collectively, the mitotic defects mediated by LMW-E induction led to failed cytokinesis and polyploidy, suggesting that LMW-E expression primes cells to accrue chromosomal instability by shortening the length of mitosis. Lastly, LMW-E expression in human breast cancer tissues correlates with centrosome amplification and higher nuclear grade. These results suggest that LMW-E overexpression leads to higher centrosome numbers in breast cancer, which is a prerequisite for genomic instability. Cancer Res; 70(12); 5074–84. ©2010 AACR.
MyD88-adaptor protein acts as a preventive mechanism for memory deficits in a mouse model of Alzheimer's disease
Authors: Jean-Philippe Michaud, Karine L Richard, Serge Rivest
Journal: Molecular Neurodegeneration (2011)

Abstract Background Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with brain innate immune activation mainly mediated by microglia. These cells are known to be activated in the brain of AD patients and to produce inflammatory cytokines and neurotoxic molecules in response to Amyloid beta (Aβ). Activation of microglia can also promote Aβ clearance via Toll-like receptors (TLRs). Myeloid differentiation factor 88 (MyD88) is the adaptor molecule for most of these innate immune receptors, transducing the intracellular signal from TLRs to nucleus. Results Here, we report that more than 50% reduction in MyD88 expression in a mouse model of AD accelerated spatial learning and memory deficits. Brain of APP swe /PS1-MyD88 +/- mice was characterized by a delay in accumulation of Aβ plaques and increased soluble levels of Aβ oligomers. Furthermore, inflammatory monocyte subset and brain IL-1β gene expression were significantly reduced in APP swe /PS1 mice with impaired MyD88 signaling. Conclusions These data indicate that activation of MyD88 intracellular signaling pathway, likely by TLRs, acts as a natural innate immune mechanism to restrict disease progression of APP swe /PS1 mice.
Unexpected Detection of Nodular Melanoma of the Skin on the Scalp by I-123 IBZM Brain SPECT
Authors: Jan Booij, Erik Boot, Susanne van Eeden, Thérèse van Amelsvoort
Journal: Clinical Nuclear Medicine (2011)

Melanocytes and dopaminergic neurons share the same ectodermal origin and can both produce melanin. Indeed, in vivo studies have shown that the radiopharmaceutical iodine-123-iodobenzamide (I-123 IBZM), which binds in vivo to dopamine D(2/3) receptors, is also able to detect melanoma, and particularly melanotic melanoma. We report a case of intense IBZM uptake in nodular melanoma of the skin on the scalp. The presence of unexpected focal IBZM uptake of the skin justified histologic examination, which revealed nodular melanoma. Melanoma should be considered when one is confronted with atypical focal uptake of benzamide derivatives like IBZM, in or outside the brain.
EXPERIMENTAL STUDY OF DIPHTHERITIC POLYNEURITIS IN THE RABBIT AND GUINEA PIG
Authors: Byron H. Waksman, Raymond D. Adams, Herbert C. Mansmann
Journal: The Journal of Experimental Medicine (1957)

Diphtheritic neuritis was produced in rabbits and guinea pigs by injection of underneutralized toxin-antitoxin mixtures. The disease is a progressive, ataxic paresis related in severity to the dose of injected toxin-antitoxin. Cerebrospinal fluids of rabbits with this disease showed "albuminocytologic dissociation" similar to that found in the same disease in man. Histologically the disease is a progressive demyelination of the peripheral nervous system, un-accompanied by axis cylinder damage or inflammation. It involves the spinal roots and sensory ganglia in the rabbit, the peripheral nerves in the guinea pig. Diphtheritic neuritis can be distinguished from experimental allergic neuritis in the rabbit and guinea pig on both clinical and histological grounds. The rabbit disease is however an excellent model of diphtheritic neuritis in man. In the animals with diphtheritic neuritis, studied in the present work, there was vigorous production of circulating antitoxin and infrequently complement-fixing antibody to horse serum proteins. No antibody against rabbit spinal cord or sciatic nerve was demonstrated. Skin reactivity to both rabbit nerve suspension and diphtheria toxoid was present at 1 to 2 weeks following inoculation and reached a maximum well before the peak of antitoxin response. These reactions did not seem to be typical delayed reactions. No correlation existed between the development of diphtheritic polyneuritis and any of these immunologic events or the circulating complement level, either in time or in degree. Treatment of rabbits with 400 r whole body irradiation 48 hours before inoculation resulted in severe leukopenia lasting about 3 weeks, delay of antitoxin formation with considerable reduction of peak titers, and some decreased skin reactivity to toxoid. It had no effect on the disease process. It is concluded that diphtheritic polyneuritis is produced by a non-immunologic mechanism, e.g., direct toxicity.
Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa
Authors: C Jeulin
Journal: Human Reproduction Update (1996)

Spermatozoa are produced in the testis and undergo post-gonadal modifications in the epididymis to acquire fertilizing ability. In epididymal plasms, high-molecular-weight proteins and such small molecules as free-L carnitine convert the gametes into 'competent' and functional cells. This review summarizes the knowledge pertaining to L-carnitine and the significance of free L-carnitine uptake into the mature spermatozoa of mammals. We provide an overview of the function of free L-carnitine and carnitine esters in the metabolism of eukaryotic cells and review the role of the specific carnitine acyltransferases in mitochondrial transport of fatty acids and in modulating the acyl-coenzyme A (CoA) pools in cellular organelles. In mammals, including man, free L-carnitine is taken from blood plasma and concentrated in the epididymal lumen. This epididymal secretion is beneficial for spermatozoa and is not merely an excretory waste. The uptake of free L-carnitine into the spermatozoa and its metabolic outcome are discussed first in in-vivo and then in in-vitro situations. Free L-carnitine goes through the sperm plasma membrane by passive diffusion. Free L-carnitine is acetylated in mature spermatozoa only. The excess acetyl-CoA from the mitochondria is probably stored as acetyl-L-carnitine and modulates the reserves of free CoA essential to the function of the tricarboxylic acid cycle. These properties of L-carnitine of buffering CoA in the mitochondrial matrix are known in somatic cells but are accentuated in this study of the male germinal cells. In the future, a precise measurement of the in-vivo and in-vitro concentrations of free CoA and acetyl-CoA in the cellular compartments of immature and mature spermatozoa might complete these data. The relationship between the endogenous pools of free and acetylated L-carnitine and the percentage of progressive sperm motility indicates a more important metabolic function related to flagellar movement. In conclusion, the potential to initiate sperm motility, which takes place in the epididymis, is probably independent of the carnitine system, while the energy properties of acetyl-L-carnitine can only be relevant in situations of 'energy crisis'. The uptake of 'cytoplasmic' free L-carnitine in mature spermatozoa must be a protective form of mitochondrial metabolism useful to the survival of this isolated cell.
TCT-467 The SYNTAX Score And Risk Of Stent Thrombosis In Patients Undergoing PCI For NSTE-ACS: An ACUITY Trial PCI Cohort Analysis
Authors: Mayank Yadav, Philippe Genereux, Tullio Palmerini, Adriano Caixeta, Mahesh V. Madhavan, Ke Xu, Ajay J. Kirtane, Sorin Brener, Roxana Mehran, Gregg Stone
Journal: Journal of the American College of Cardiology (2013)
Glycemic Response and Attainment of A1C Goals Following Newly Initiated Insulin Therapy for Type 2 Diabetes
Authors: Gregory A. Nichols, Teresa M. Kimes, Joyce B. Harp, Tzuyung Doug Kou, Kimberly G. Brodovicz
Journal: Diabetes Care (2012)

To identify the characteristics associated with glycemic response to newly initiated insulin therapy.We identified 1,139 type 2 diabetic patients who initiated insulin therapy between 1 January 2009 and 30 June 2010. Outcomes of interest were the proportion of patients achieving A1C <7% and mean change in A1C within 3-9 months.Mean A1C at insulin initiation was 8.2 vs. 9.2% among those who did and did not attain A1C <7% (P < 0.001). Within a mean of 5 months, 464 (40.7%) patients attained A1C <7%. In multivariable analyses controlling for insulin regimen, dose, and oral agent use, preinsulin A1C was responsible for nearly all the explained variance in A1C change. Each one percentage point of preinsulin A1C reduced the probability of attaining <7% by 26% (odds ratio 0.74 [95% CI 0.68-0.80]).Insulin initiation at lower levels of A1C improves goal attainment and independently increases glycemic response.
Optical Coherence Tomography Angiography of Optic Disc Perfusion in Glaucoma
Authors: Yali Jia, Eric Wei, Xiaogang Wang, Xinbo Zhang, John C. Morrison, Mansi Parikh, Lori H. Lombardi, Devin M. Gattey, Rebecca L. Armour, Beth Edmunds, Martin F. Kraus, James G. Fujimoto, David Huang
Journal: Ophthalmology (2014)
Lupus anticoagulant in children with thrombosis
Authors: Marilyn J. Manco‐Johnson, Rachelle Nuss
Journal: American Journal of Hematology (1995)

Nineteen children who presented with thromboses over a 7-year period were found to have a lupus anticoagulant (LA). The initial thrombosis was proximal deep vein thrombosis (DVT) in six children, central nervous system (CNS) in five, primary pulmonary in four, distal DVT in two, central venous in one, and proximal arterial in one. Five children were diagnosed with systemic lupus erythematosus (SLE), including two children for whom thrombosis was the presenting sign of SLE. The remaining 14 children were diagnosed with the antiphospholipid antibody (APA) syndrome. The APA syndrome was manifest by venous or arterial thrombosis in association with a positive LA; positive anticardiolipin antibodies and a fine, speckled antinuclear antibody (ANA) pattern were additionally found in the majority of children. Approximately one-half of the children with SLE or the APA syndrome had a pulmonary embolus, and one-half developed recurrent thrombosis. Oral anticoagulation with coumadin to achieve an INR of > 2.0 prevented thrombosis recurrence. The recognition of a LA in children with thrombosis necessitates evaluation for SLE, APA, and other autoantibodies.
TRANSENDOTHELIAL TRANSPORT OF RECEPTOR-TARGETED NANOBUBBLES INDUCED BY RECEPTOR-MEDIATED ENDOCYTOSIS IN VITRO AND IN VIVO
Authors: Jian-Ping Bin, Ying Li, yunbin xiao, Zonglei Zhao, Zhonghua Teng, Juefei Wu, Wangjun Liao, Yulin Liao
Journal: Journal of the American College of Cardiology (2012)
Systemic lupus erythematosus, eosinophilia and Löffler′s endocarditis. An unusual association
Authors: M. Thomeer, PH. Moerman, R Westhovens, A. Van den Eeckhout, J Dequeker, M. Demedts
Journal: European Respiratory Journal (1999)

A 24-yr-old male, known since the age of 11 to have a nonerosive arthritis and later diagnosed as having systemic lupus erythematosus (SLE), developed subacute heart failure with diffuse lung infiltrates and died suddenly after having presented a moderate hypereosinophilia for 6 months for which no other causes besides the SLE were found. A post mortem examination revealed Löffler's endocarditis (endocarditis parietalis fibroplastica) with acute pulmonary capillaritis. This represents Löffler's endocarditis in the setting of SLE. To the best of the authors' knowledge, this association has not been reported before.
Development of Systemic and Local Tumors Induced by Avian Reticuloendotheliosis Virus After Thymectomy or Bursectomy2
Authors: T. J. Linna, Cheng-po Hu, Kenneth D. Thompson
Journal: JNCI Journal of the National Cancer Institute (1974)

We studied the effects of thymectomy and surgical and chemical (cyclophosphamide) bursectomy on tumor development and mortality after systemic or local administration of avian reticuloendotheliosis virus, strain T. Significantly more thymectomized and bursectomized chickens died from reticuloendothelial tumors than did their sham-operated controls. Locally induced tumors regressed frequently in normal animals, but mostthymectomized or bursectomized birds developed progressively growing, ultimately fatal tumors. These studies showed that not only thymus-dependent, cell-mediated immunity but also the bursa-dependent, antibody-producing system had a host-protective influence—a "surveillance" function. The results were not compatible with a tumorprotective role for the antibody-producing system in vivo.
Inhibition of the Mitochondrial Protease ClpP as a Therapeutic Strategy for Human Acute Myeloid Leukemia
Authors: Alicia Cole, Zezhou Wang, Etienne Coyaud, Veronique Voisin, Marcela Gronda, Yulia Jitkova, Rachel Mattson, Rose Hurren, Sonja Babovic, Neil Maclean, Ian Restall, Xiaoming Wang, Danny V. Jeyaraju, Mahadeo A. Sukhai, Swayam Prabha, Shaheena Bashir, Ashwin Ramakrishnan, Elisa Leung, Yi Hua Qia, Nianxian Zhang, Kevin R. Combes, Troy Ketela, Fengshu Lin, Walid A. Houry, Ahmed Aman, Rima Al-awar, Wei Zheng, Erno Wienholds, Chang Jiang Xu, John Dick, Jean C.Y. Wang, Jason Moffat, Mark D. Minden, Connie J. Eaves, Gary D. Bader, Zhenyue Hao, Steven M. Kornblau, Brian Raught, Aaron D. Schimmer
Journal: Cancer Cell (2015)
Activation of Dendritic Cells through the Interleukin 1 Receptor 1 Is Critical for the Induction of Autoimmune Myocarditis
Authors: Urs Eriksson, Michael O. Kurrer, Ivo Sonderegger, Giandomenica Iezzi, Anna Tafuri, Lukas Hunziker, Shinobu Suzuki, Kurt Bachmaier, Roland M. Bingisser, Josef M. Penninger, Manfred Kopf
Journal: The Journal of Experimental Medicine (2003)

Dilated cardiomyopathy, resulting from myocarditis, is the most common cause of heart failure in young patients. We here show that interleukin (IL)-1 receptor type 1-deficient (IL-1R1(-/-)) mice are protected from development of autoimmune myocarditis after immunization with alpha-myosin-peptide(614-629). CD4(+) T cells from immunized IL-1R1(-/-) mice proliferated poorly and failed to transfer disease after injection into naive severe combined immunodeficiency (SCID) mice. In vitro stimulation experiments suggested that the function of IL-1R1(-/-)CD4(+) T cells was not intrinsically defect, but their activation by dendritic cells was impaired in IL-1R1(-/-) mice. Accordingly, production of tumor necrosis factor (TNF)-alpha, IL-1, IL-6, and IL-12p70 was reduced in dendritic cells lacking the IL-1 receptor type 1. In fact, injection of immature, antigen-loaded IL-1R1(+/+) but not IL-1R1(-/-) dendritic cells into IL-1R1(-/-) mice fully restored disease susceptibility by rendering IL-1R1(-/-) CD4(+) T cells pathogenic. Thus, IL-1R1 triggering is required for efficient activation of dendritic cells, which is in turn a prerequisite for induction of autoreactive CD4(+) T cells and autoimmunity.