tbuckley/cabot-search huggingface dataset:
Dissection of the human CD2 intracellular domain. Identification of a segment required for signal transduction and interleukin 2 production.
Authors: H C Chang, P Moingeon, P Lopez, H Krasnow, C Stebbins, E L Reinherz
Journal: The Journal of Experimental Medicine (1989)

To evaluate those residues in the 117 amino acids of the CD2 cytoplasmic domain required for transduction of T lymphocyte activation signals, a full-length human CD2 cDNA and a series of deletion and substitution mutants were inserted into the ovalbumin-specific, I-Ad-restricted murine T cell hybridoma 3DO54.8 using a retroviral system. The resulting cells express surface CD2 protein and unlike the parental murine line, are reactive with murine anti-human CD2 antibodies. Anti-T11(2) plus anti-T11(3) antibody stimulation of cells expressing a full-length CD2 cDNA results in a characteristic rise in cytosolic-free calcium [( Ca2+]i), and subsequent IL-2 secretion that accompany CD2 stimulation in human T lymphocytes. Transfectants expressing CD2 delta C98 and CD2 delta C77, partially deleted CD2 molecules containing the entire extracellular and transmembrane CD2 segments but only 98 and 77 amino acids of the cytoplasmic domain, respectively, are also activated by anti-CD2 mAbs. In contrast, clones expressing more severely truncated CD2 structures, CD2 delta C43 and CD2 delta C18, are not stimulated. These data show that the cytoplasmic domain plays an essential role in transduction of activation signals via CD2, and that the segment between amino acid residues 253 and 278 is necessary for activation. This region contains two tandem repeats of the sequence PPPGHR, thought to form part of a putative cationic site. Disruption of the latter by site-directed mutagenesis does not affect IL-2 gene induction, suggesting that only one of the repeats is required for activating this function of the CD2 molecule.
Influence of Adenosine Triphosphate, Adenosine Monophosphate and Heparin in Experimental Arteriopathy
Authors: OSCAR F. DAVIS, Y. T. OESTER, BERNARD FRIEDMAN
Journal: Circulation Research (1955)

The effects, in rabbits, of heparin, AMP, and ATP against both experimental cholesterol-induced atherosclerosis and epinephrine-thyroxine medial arteriosclerosis, were studied. Heparin and AMP, in general, were ineffective. Marked, statistically significant inhibition of both experimental atherosclerosis and experimental medial arteriopathy was achieved with ATP.
Elf-pulsed magnetic fields modulate opioid peptide gene expression in myocardial cells
Authors: C Ventura
Journal: Cardiovascular Research (2000)

Objectives: Magnetic fields have been shown to affect cell proliferation and growth factor expression in cultured cells. Although the activation of endorphin systems is a recurring motif among the biological events elicited by magnetic fields, compelling evidence indicating that magnetic fields may modulate opioid gene expression is still lacking. We therefore investigated whether extremely low frequency (ELF) pulsed magnetic fields (PMF) may affect opioid peptide gene expression and the signaling pathways controlling opioid peptide gene transcription in the adult ventricular myocyte, a cell type behaving both as a target and as a source for opioid peptides. Methods: Prodynorphin gene expression was investigated in adult rat myocytes exposed to PMF by the aid of RNase protection and nuclear run-off transcription assays. In PMF-exposed nuclei, nuclear protein kinase C (PKC) activity was followed by measuring the phosphorylation rate of the acrylodan-labeled MARCKS peptide. The effect of PMF on the subcellular distribution of different PKC isozymes was assessed by immunoblotting. A radioimmunoassay procedure coupled to reversed-phase high performance liquid chromatography was used to monitor the expression of dynorphin B. Results: Here, we show that PMF enhanced myocardial opioid gene expression and that a direct exposure of isolated myocyte nuclei to PMF markedly enhanced prodynorphin gene transcription, as in the intact cell. The PMF action was mediated by nuclear PKC activation but occurred independently from changes in PKC isozyme expression and enzyme translocation. PMF also led to a marked increase in the synthesis and secretion of dynorphin B. Conclusions: The present findings demonstrate that an opioid gene is activated by myocyte exposure to PMF and that the cell nucleus and nuclear embedded PKC are a crucial target for the PMF action. Due to the wide ranging importance of opioid peptides in myocardial cell homeostasis, the current data may suggest consideration for potential biological effects of PMF in the cardiovascular system.
Impact of Renal Denervation on 24-Hour Ambulatory Blood Pressure
Authors: George L. Bakris, Raymond R. Townsend, Minglei Liu, Sidney A. Cohen, Ralph D’Agostino, John M. Flack, David E. Kandzari, Barry T. Katzen, Martin B. Leon, Laura Mauri, Manuela Negoita, William W. O’Neill, Suzanne Oparil, Krishna Rocha-Singh, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2014)
Deposition and clearance of inhaled 18FDG powder in patients with chronic obstructive pulmonary disease
Authors: M Yanai, J Hatazawa, F Ojima, H Sasaki, M Itoh, T Ido
Journal: European Respiratory Journal (1998)

As freon is limited in its use as a generator for aerosol inhalation, powder particles are used as an alternative for inhalation therapy. The pulmonary deposition and clearance of inhaled powder particles was studied by positron emission tomography (PET) in ten patients with chronic obstructive pulmonary disease (COPD) and in five normal controls. The powder, 5 microm in mean diameter, was water soluble and labelled with 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG). Powder inhalation was done with single deep inspiration from residual volume to total lung capacity. The initial deposition ratio in the right or left lung field to total inhaled dose, measured by an anteroposterior rectilinear scan, did not differ between normals and COPD patients. Ratios of radioactivity detected within the central and peripheral regions (the central to peripheral ratio) measured by the PET scan was not significantly different between COPD patients (4.8+/-2.6, mean+/-SD) and normals (2.6+/-0.8, mean+/-SD). However, the regional powder deposition in peripheral lung fields measured by the PET scan was significantly more uneven in COPD patients than in normal patients. The clearance rate of 18FDG, defined as the retention ratio of 18FDG activity to the initially deposited 18FDG at 60 and 120 min after inhalation, in the trachea, large bronchi or peripheral lung fields measured by tomographic scan showed a wider variation in COPD patients than in normals. To conclude, inhaled powder tended to be deposited more centrally and was distributed more unevenly in the peripheral lung in chronic obstructive pulmonary disease patients than in normals. This could be a limitation of powder inhalation used for therapy in chronic obstructive pulmonary disease patients.
Role of cAMP-Phosphodiesterase 1C Signaling in Regulating Growth Factor Receptor Stability, Vascular Smooth Muscle Cell Growth, Migration, and Neointimal Hyperplasia
Authors: Yujun Cai, David J. Nagel, Qian Zhou, Katherine D. Cygnar, Haiqing Zhao, Faqian Li, Xinchun Pi, Peter A. Knight, Chen Yan
Journal: Circulation Research (2015)

Neointimal hyperplasia characterized by abnormal accumulation of vascular smooth muscle cells (SMCs) is a hallmark of occlusive disorders such as atherosclerosis, postangioplasty restenosis, vein graft stenosis, and allograft vasculopathy. Cyclic nucleotides are vital in SMC proliferation and migration, which are regulated by cyclic nucleotide phosphodiesterases (PDEs).Our goal is to understand the regulation and function of PDEs in SMC pathogenesis of vascular diseases.We performed screening for genes differentially expressed in normal contractile versus proliferating synthetic SMCs. We observed that PDE1C expression was low in contractile SMCs but drastically elevated in synthetic SMCs in vitro and in various mouse vascular injury models in vivo. In addition, PDE1C was highly induced in neointimal SMCs of human coronary arteries. More importantly, injury-induced neointimal formation was significantly attenuated by PDE1C deficiency or PDE1 inhibition in vivo. PDE1 inhibition suppressed vascular remodeling of human saphenous vein explants ex vivo. In cultured SMCs, PDE1C deficiency or PDE1 inhibition attenuated SMC proliferation and migration. Mechanistic studies revealed that PDE1C plays a critical role in regulating the stability of growth factor receptors, such as PDGF receptor β (PDGFRβ) known to be important in pathological vascular remodeling. PDE1C interacts with low-density lipoprotein receptor-related protein-1 and PDGFRβ, thus regulating PDGFRβ endocytosis and lysosome-dependent degradation in an low-density lipoprotein receptor-related protein-1-dependent manner. A transmembrane adenylyl cyclase cAMP-dependent protein kinase cascade modulated by PDE1C is critical in regulating PDGFRβ degradation.These findings demonstrated that PDE1C is an important regulator of SMC proliferation, migration, and neointimal hyperplasia, in part through modulating endosome/lysosome-dependent PDGFRβ protein degradation via low-density lipoprotein receptor-related protein-1.
Presence of the Tn antigen on hematopoietic progenitors from patients with the Tn syndrome.
Authors: W Vainchenker, G Vinci, U Testa, A Henri, A Tabilio, M P Fache, H Rochant, J P Cartron
Journal: Journal of Clinical Investigation (1985)

The Tn syndrome is an acquired clonal disorder characterized by the exposure of a normally hidden determinant, the Tn antigen, on the surface of human erythrocytes, platelets, granulocytes, and lymphocytes. Two distinct populations, Tn positive (Tn+) and Tn negative (Tn-), of mature hemopoietic cells are present in Tn patients. To determine whether the Tn antigen is already expressed on erythroid, myeloid, and pluripotent progenitors, light-density mononuclear blood cells from two patients with this syndrome were separated by fluorescent-activated cell sorting and by affinity chromatography into Tn+ and Tn- fractions, using their binding properties to Helix pomatia agglutinin (HPA). Burst-forming-unit erythroid (BFU-E), colony-forming-unit granulocyte/macrophage (CFU-GM), cells were assayed in plasma clot cultures. After 12-14 d of culture, colonies were studied by a double fluorescent labeling procedure. First, a fluorescein-conjugated HPA permitted evaluation of the presence or absence of the Tn antigen at the surface of the cells composing each colony, and second, the binding of a murine monoclonal antibody against either glycophorin A (LICR-LON-R10) or against a myeloid antigen (80H5), revealed by an indirect fluorescent procedure, was used to establish the erythroid or myeloid origin of each cell. The Tn+ fraction obtained by cell sorting gave rise to nearly 100% Tn+ colonies composed exclusively of cells bearing this antigen. The reverse was observed for the Tn- cell fraction. These results demonstrate that in the Tn syndrome, BFU-E, CFU-GM, and CFU-GEMM of the Tn+ clone express the Tn antigen at this early stage of differentiation.
Ancient DNA from amber fossil bees?
Authors: K. K. Walden, H. M. Robertson
Journal: Molecular Biology and Evolution (1997)

Amber fossils of insects provide excellent preservation of several tissues (e.g., Poinar and Hess 1982), and two groups have published claims of amplification of ribosomal RNA gene sequences from four amber fossil insect specimens (Cano et al. 1992, 1993; DeSalle et al. 1992; DeSalle, Barcia, and Wray 1993; DeSalle 1994). Unlike amplifications of ancient DNA from thousand-year-old mammalian specimens (e.g., Taylor 1996), no independent replications and no extensions of this work have been reported. We initially attempted to extend this work to transposable elements of the mariner and Tel families likely to occur in insect genomes (Robertson 1993; Avancini, Walden, and Robertson 1996). These transposons commonly occur in high copy numbers (Robertson and Lampe 1995) and therefore provide an alternative target to the multicopy rRNA genes or mitochondrial genome. Calibrating the ages and molecular evolution of such transposons using amber fossil sequences would be particularly useful, because it is otherwise difficult to estimate the ages of transposons in host genomes. We focused on the Dominican amber fossil stingless bee Proplebeia dominicana, and began by obtaining partial sequences of mariner (Robertson et al. 1997) and Tel (Avancini, Walden, and Robertson 1996) family transposons from four extant relatives (see below). PCR primers designed to conserved sequences of elements shared between several of these extant relatives were thought likely to be able to amplify elements from P. dominicana; however, we were unable to obtain amplifications from ancient DNA extractions provided by R. J. Cano, nor was his laboratory able to obtain amplifications from fresh extractions (R. J. Cano and D. Da Silva, personal communication). We therefore attempted to replicate the claimed amplifications of 18s rRNA gene sequences from a single specimen of P. dominicana (Cano et al. 1992). We initially amplified, cloned, and sequenced in both directions the first third of the 18s rRNA gene (630 bp) from DNA extractions of four extant relatives of the fossil meliponine bee, Melipona panamica, Nogueirapis mirandula, Plebeia frontalis, and P. jatiformis (Michener 1990) (kindly supplied by R. J. Cano), and the honey bee Apis mellifera for comparison. The consensus sequences from multiple clones
An Evaluation of a New Anticoagulant, Acenocoumarin (Sintrom)
Authors: MURRAY WEINER, MARIANO JIMINEZ, IRWIN KATZKA
Journal: Circulation (1956)

A new coumarin anticoagulant, acenocoumarin (Sintrom) is compared with other hypoprothrombinemic agents in the same human subjects. Comparing doses which result in the same peak prothrombin time, both speed of onset and duration of effect are found to be a function of the rate of biotransformation. Rapid biotransformation results in fast onset and short duration of action and vice versa. Sintrom is intermediate between the slow, long-acting compounds (Dicumarol, Warfarin, Coumopyrin) and the fast, short-acting Tromexan. One 16 to 32 mg. dose of Sintrom rapidly results in a desirable hypoprothrombinemia which is maintained by a single daily dose of 2 to 10 mg.
Difficulties in diagnosing meningococcal meningitis.
Authors: L S Lewis
Journal: BMJ (1979)

treat local swelling with oral antihistamines.A patient with any systemic manifestations should be given a Medihaler-Epi as well as antihistamine tablets, although it is doubtful if any medication will be absorbed by the gastric mucosa after a sting.Although there may be few actual fatalities from insect stings, the number of nearfatalities and of incidents terrifying to patients and their relatives must, to judge by the number seen at our clinic, be high.Some attempt should therefore be made to protect acutely sensitive patients.The best method available at present is hyposensitisation and the pure venom extracts mentioned in your article should become available in a few weeks.
Decision Analysis of Prophylactic Surgery or Screening for <i>BRCA1</i> Mutation Carriers: A More Prominent Role For Oophorectomy
Authors: Mariëlle S. van Roosmalen, Lia C.G. Verhoef, Peep F.M. Stalmeier, Nicoline Hoogerbrugge, Willem A.J. van Daal
Journal: Journal of Clinical Oncology (2002)

BRCA1 mutation carriers have a high risk of developing breast and ovarian cancer. Carriers may opt for prophylactic surgery and screening. Recent data suggesting that prophylactic oophorectomy reduces breast cancer risk have been incorporated in a decision analysis.A Markov model was developed to compare LE and QALE following four strategies: (1) prophylactic mastectomy and prophylactic oophorectomy (PMPO), (2) screening for breast cancer and prophylactic oophorectomy (BSPO), (3) prophylactic mastectomy and screening for ovarian cancer (PMOS), and (4) screening for breast and ovarian cancer (BSOS). The analysis was performed for a high (85% breast cancer, 63% ovarian cancer) and medium (56% breast cancer, 16% ovarian cancer) risk level. Utilities for the health states after prophylactic surgery were obtained from mutation carriers. Other model parameter values were obtained from the literature. Sensitivity analyses were performed.When compared with BSOS, the average gain in LE for 30-year-old carriers in the high (medium) risk group was 11.7 (6.6) years for PMPO, 9.5 (5.3) years for BSPO, and 4.9 (4.4) years for PMOS. For 30-year-old carriers, BSPO had a QALE advantage when PO was performed before age 40. In the medium-risk group, there was a stronger advantage for BSPO when QALE was considered.PMPO is the most effective strategy to prolong life. However, if patient preferences were taken into account, BSPO tends to be a better strategy in most women at medium risk or in young women at high risk when PO was performed before age 40.
A Single Nucleotide Polymorphism in <i>KCNQ1</i> Is Associated With Susceptibility to Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes
Authors: Toshihiko Ohshige, Yasushi Tanaka, Shin-ichi Araki, Tetsuya Babazono, Masao Toyoda, Tomoya Umezono, Hirotaka Watada, Daisuke Suzuki, Yasuhiko Iwamoto, Ryuzo Kawamori, Yusuke Nakamura, Shiro Maeda
Journal: Diabetes Care (2010)

OBJECTIVE Genetic factors have been considered to contribute to the development and progression of diabetic nephropathy. The KCNQ1 gene (potassium voltage-gated channel, KQT-like subfamily, member 1) was originally identified as a strong susceptibility gene for type 2 diabetes in two Japanese genome-wide association studies. In this study, we examined the association of single nucleotide polymorphisms (SNPs) within KCNQ1 with diabetic nephropathy in Japanese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS We genotyped 33 SNPs in KCNQ1 using 754 type 2 diabetic patients with overt nephropathy and 558 control subjects (an initial study), and we further examined the association of a candidate SNP using three other independent Japanese populations (replications 1–3). RESULTS We found that five SNPs were nominally associated with diabetic nephropathy, and the association of rs2237897 was the strongest. We also found that the T allele frequencies of rs2237897 were consistently higher in the nephropathy groups than in the control groups for all study populations (initial study: 0.33 vs. 0.27; replication 1: 0.32 vs. 0.30; replication 2: 0.33 vs. 0.28; and replication 3: 0.32 vs. 0.28), although the individual associations did not reach statistically significant levels. Combined analysis by a meta-analysis revealed that the T allele of rs2237897 was significantly associated with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes (odds ratio 1.22 [95% CI 1.10–1.34], P = 3.1 × 10–4, corrected P = 0.01). CONCLUSIONS These results suggest that KCNQ1 is a new candidate gene for conferring susceptibility to diabetic nephropathy.
THE RENAL HANDLING OF HEMOGLOBIN
Authors: H. Franklin Bunn, James H. Jandl
Journal: The Journal of Experimental Medicine (1969)

The fate of small doses of isotopically labeled isologous hemoglobin was studied in the rat. When haptoglobin depleted animals were given 2.0 mg of (59)Fe hemoglobin intravenously, nearly half was trapped by the kidneys. Kidney (59)Fe activity disappeared slowly over several weeks. Whatever iron was lost from the kidneys was largely reutilized. In contrast, the porphyrin of hemoglobin absorbed by the kidneys appeared to be rapidly catabolized, since 5 hr after the injection of (14)C or (59)Fe heme-labeled hemoglobin only a small fraction was recovered as hematin. Likewise, after injection of globin-labeled hemoglobin, rapid disappearance of kidney protein activity indicated that the absorbed globin was readily catabolized in situ.
Essential role of Skp2-mediated p27 degradation in growth and adaptive expansion of pancreatic β cells
Authors: Lingwen Zhong, Senta Georgia, Shuen-ing Tschen, Keiko Nakayama, Keiichi Nakayama, Anil Bhushan
Journal: Journal of Clinical Investigation (2007)

Diabetes results from an inadequate mass of functional beta cells, due to either beta cell loss caused by immune assault or the lack of compensation to overcome insulin resistance. Elucidating the mechanisms that regulate beta cell mass has important ramifications for fostering beta cell regeneration and the treatment of diabetes. We report here that Skp2, a substrate recognition component of Skp1-Cul1-F-box (SCF) ubiquitin ligase, played an essential and specific role in regulating the cellular abundance of p27 and was a critical determinant of beta cell proliferation. In Skp2(-/-) mice, accumulation of p27 resulted in enlarged polyploid beta cells as a result of endoreduplication replacing proliferation. Despite beta cell hypertrophy, Skp2(-/-) mice exhibited diminished beta cell mass, hypoinsulinemia, and glucose intolerance. Increased insulin resistance resulting from diet-induced obesity caused Skp2(-/-) mice to become overtly diabetic, because beta cell growth in the absence of cell division was insufficient to compensate for increased metabolic demand. These results indicate that the Skp2-mediated degradation pathway regulating the cellular degradation of p27 is essential for establishing beta cell mass and to respond to increased metabolic demand associated with insulin resistance.
First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis
Authors: J Braun, J Davis, M Dougados, J Sieper, S van der Linden, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To update the international recommendations for use of anti-tumour necrosis factor (TNF) agents in the treatment of ankylosing spondylitis. <b>Methods:</b> The published recommendations on anti-TNF treatment in ankylosing spondylitis formed the basis of the update. A questionnaire was sent to the ASAS (assessment in ankylosing spondylitis) members before the final decisions were agreed upon at an international meeting of the ASAS working group. <b>Results:</b> Only minor changes to the original consensus statement were required. For the <i>initiation</i> of anti-TNF treatment, there should be: a diagnosis of definitive ankylosing spondylitis (normally based on modified New York criteria); active disease for at least four weeks, as defined by a sustained Bath ankylosing spondylitis disease activity index (BASDAI) of ⩾4 on a 0–10 scale and expert opinion based on clinical findings; refractory disease, defined by failure of at least two non-steroidal anti-inflammatory drugs during a three month period, failure of intra-articular steroids (if indicated), and failure of sulfasalazine in patients with predominantly peripheral arthritis; and application of the usual precautions and contraindications for biological treatment. For <i>monitoring</i> anti-TNF treatment: both the ASAS core set for clinical practice and the BASDAI should be followed after the initiation of treatment. <i>Discontinuation</i> of anti-TNF treatment in non-responders should be considered after 6–12 weeks. <i>Response</i> is defined by improvement of at least 50% <i>or</i> 2 units (on a 0–10 scale) of the BASDAI. <b>Conclusions:</b> This updated consensus statement is recommended in guiding clinical practice and as a basis for developing national guidelines. Evaluation and regular update of this consensus statement is subject to further research by the ASAS group.