tbuckley/cabot-search huggingface dataset:
MicroRNA Networks Alter to Conform to Transcription Factor Networks Adding Redundancy and Reducing the Repertoire of Target Genes for Coordinated Regulation
Authors: H. Iwama, K. Murao, H. Imachi, T. Ishida
Journal: Molecular Biology and Evolution (2010)

Transcription factors (TFs) and microRNAs (miRNAs) comprise two major layers of gene regulatory networks (GRNs). TFs and miRNAs function coordinately, but they have distinct molecular mechanisms and evolutionary backgrounds. Therefore, we aimed to systematically reveal the difference in contribution between TF and miRNA networks to the evolution of their coordinated regulations by focusing on composite feedforward circuits (cFFCs) that each comprises a TF and an miRNA. We compiled 124,736 human–mouse conserved TF regulatory connections and 34,298 conserved miRNA regulatory connections into two distinct connection matrices. To differentially assess the contributions to cFFC formation of TFs and miRNAs, we randomized one matrix and kept the other unchanged and subsequently examined the number of cFFCs, the number of cFFC-targeted genes, and the redundancy formed by cFFCs in comparison with those of the real GRNs. Because the matrices represent selectively constrained networks, if selection has been operating on the networks for or against cFFC formation, the values of cFFC network properties would deviate significantly from the expectation of the randomized networks. As the cFFC includes both TF and miRNA connections, the partial randomizations indicate the extent of influence of selection on cFFC formation differentially between TF and miRNA networks. Thus, we adopted the deviation of each cFFC network property value as a measure to estimate the extent of influence of selection on cFFCs and to compare the contribution between TF and miRNA networks. We found that miRNA regulatory networks changed their configuration such that they conformed to the stable TF regulatory networks with an increased circuit redundancy and a marked reduction in the repertoire of cFFC-targeted genes. We also revealed that this redundancy-adding role is preferentially attributable to miRNA network alterations. The results indicate that the redundancy-adding role might serve as a niche for many miRNA connections to survive, avoiding conflicts with the stable TF regulatory networks.
The Road Not Taken
Authors: Lawrence Steinman
Journal: JAMA Neurology (2013)

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 Neurology 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 Neurology journal
Role of macrophages and colony-stimulating factor-1 in murine antiglomerular basement membrane glomerulonephritis.
Authors: J Neugarten, G W Feith, K J Assmann, Z Shan, E R Stanley, D Schlondorff
Journal: Journal of the American Society of Nephrology (1995)

Macrophages have been shown to mediate glomerular injury in antiglomerular basement membrane (anti-GBM) glomerulonephritis in rats and rabbits. To evaluate the role of macrophages and the macrophage-related cytokines, colony stimulating factor-1 (CSF-1), monocyte chemoattractant protein-1 (MCP-1) and RANTES, accelerated anti-GBM nephritis was studied in op/op mutant mice, which lack CSF-1 and are severely macrophage deficient, and in heterozygous op/+ control mice. Observations were made 24 h and 3 days after the injection of rabbit anti-mouse GBM antibody in mice preimmunized with rabbit immunoglobulin G. Proteinuria rose progressively in both groups but did not differ between them (urine protein/creatinine ratio at 3 days: 1.01 +/- 0.38 in op/op versus 1.45 +/- 0.43 in op/+; P, not significant). In both op/op and op/+ mice, anti-GBM nephritis was associated with renal expression of mRNA for RANTES and MCP-1 and barely detectable levels of mRNA for CSF-1. In contrast, these cytokines were not expressed in sham-injected mice. Morphologic lesions appeared earlier in op/op mice but were comparable by Day 3. Glomerular injury consisted of capillary thrombosis and endothelial cell damage associated with mild to moderate leukocyte infiltration. Despite enhanced expression of mRNA for RANTES and MCP-1, glomerular macrophage infiltration was not increased in op/+ mice. It was concluded that, in mice, in contrast to rats and rabbits, accelerated anti-GBM nephritis may develop in the absence of both CSF-1 and macrophage infiltration.
Anthrax as a Biological Weapon, 2002
Authors: Thomas V. Inglesby, Tara O'Toole, Donald A. Henderson, John G. Bartlett, Michael S. Ascher, Edward Eitzen, Arthur M. Friedlander, Julie Gerberding, Jerome Hauer, James Hughes, Joseph McDade, Michael T. Osterholm, Gerald Parker, Trish M. Perl, Philip K. Russell, Kevin Tonat, None for the Working Group on Civilian Biodefense
Journal: JAMA (2002)

To review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population.The working group included 23 experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies.MEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources.The first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations.Specific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.
Evaluation of a Panel of Tumor Markers for Molecular Detection of Circulating Cancer Cells in Women with Suspected Breast Cancer
Authors: Monica M. Reinholz, Andrea Nibbe, Leslie M. Jonart, Kathleen Kitzmann, Vera J. Suman, James N. Ingle, Raymond Houghton, Barbara Zehentner, Patrick C. Roche, Wilma L. Lingle
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We examined the feasibility of using molecular characterization of circulating tumor cells as a method for early detection of breast cancer. Research Design: Women without a prior history of cancer who had a breast abnormality detected on imaging followed by a breast biopsy were enrolled in this study. Density gradient centrifugation and immunomagnetic capture were used to enrich for epithelial cells from ∼20 mL of blood. Real-time reverse transcription-PCR was used to quantitate the expression levels of the highly breast-specific genes, mammaglobin, γ-aminobutyric acid type A receptor π subunit (GABA Aπ), B305D-C, and B726P in the epithelial cell–enriched samples. Results: The assay was technically feasible in 154 of 199 accrued patients. From their clinical assessment, 100 patients had benign breast disease, 10 patients had ductal carcinoma in situ, and 44 patients had invasive breast cancer. We constructed a diagnostic test that classified patients with mammaglobin levels of at least 32.2 copies/pg β-actin (units) in their circulating epithelial cells as positive for invasive breast cancer. This resulted in a sensitivity and specificity of 63.3% and 75.0%, respectively. A diagnostic test that classified patients as positive for invasive breast cancer when either mammaglobin levels were &amp;gt;46.3 units or B305D-C levels were &amp;gt;11.6 units increased the sensitivity and specificity to 70.5% and 81.0%, respectively. In the latter test, 12 of the 14 node-positive breast cancer patients were correctly identified. Including GABA Aπ and B726P in the test did not increase its diagnostic potential. Conclusions: These results suggest that molecular characterization of circulating epithelial cells using mammaglobin and B305D-C offers potential for early detection of invasive breast cancer.
Protein Kinase A Phosphorylates Titin’s Cardiac-Specific N2B Domain and Reduces Passive Tension in Rat Cardiac Myocytes
Authors: R. Yamasaki, Y. Wu, M. McNabb, M. Greaser, S. Labeit, H. Granzier
Journal: Circulation Research (2002)

β-Adrenergic stimulation of cardiac muscle activates protein kinase A (PKA), which is known to phosphorylate proteins on the thin and thick filaments of the sarcomere. Cardiac muscle sarcomeres contain a third filament system composed of titin, and here we demonstrate that titin is also phosphorylated by the β-adrenergic pathway. Titin phosphorylation was observed after β-receptor stimulation of intact cardiac myocytes and incubation of skinned cardiac myocytes with PKA. Mechanical experiments with isolated myocytes revealed that PKA significantly reduces passive tension. In vitro phosphorylation of recombinant titin fragments and immunoelectron microscopy suggest that PKA targets a subdomain of the elastic segment of titin, referred to as the N2B spring element. The N2B spring element is expressed only in cardiac titins, in which it plays an important role in determining the level of passive tension. Because titin-based passive tension is a determinant of diastolic function, these results suggest that titin phosphorylation may modulate cardiac function in vivo.
Effects of intravenously infused histamine on canine forelimb transvascular protein efflux following adrenergic receptor blockade.
Authors: G J Grega, D L Marciniak, B S Jandhyala, R M Raymond
Journal: Circulation Research (1980)

The intravenous infusion of high doses of histamine (400 micrograms base/min) produced only small increases in weight (approximately equal to +30 g) and lymph total protein concentration (+ 0.9 g/100 ml) in canine forelimbs perfused at constant inflow. The weight gain was associated with profound decreases in aortic pressure (112 to 30 mm Hg) and in forelimb perfusion pressure (105 to 75 mm Hg) and marked increases in forelimb skin small-vein pressure (from 12 to 25 mm Hg). After treatment with phentolamine, the intravenous infusion of these doses of histamine under the same conditions produced marked decreases in forelimb perfusion pressure (120 to 60 mm Hg) and failed to increase forelimb skin small-vein pressure, yet still produced only minimal increases in weight (+ 12 g) and lymph total protein concentration (+ 0.8 g/100 ml). Following treatment with both phentolamine and propranolol, the intravenous infusion of histamine caused very marked increases in forelimb weight (approximately equal to +75 g) and lymph total protein concentration (+ 2.9 g/100 ml). These marked increases in forelimb weight and lymph formation were associated with profound decreases in perfusion pressure (112 to 60 mm Hg) but no change in skin small-vein pressure relative to control. These same increases in weight and lymph total protein concentration were observed after treatment with propranolol alone. Thus, treatment with propranolol markedly increased net fluid filtration and protein efflux during intravenous infusions of massive doses of histamine, idicating that this edemogenic agent causes an endogenous release of catecholamines which tend to antagonize the direct actions of histamine on the microvascular membrane via stimulation of beta-adrenergic receptors.
Fourteenth Biannual Report of the Cochrane Haematological Malignancies Group--Focus on Autologous Stem Cell Transplantation in Hematological Malignancies
Authors: M. Rancea, N. Skoetz, I. Monsef, K. Hubel, A. Engert, K. Bauer
Journal: JNCI Journal of the National Cancer Institute (2012)
A new variant of Glanzmann's thrombasthenia (Strasbourg I). Platelets with functionally defective glycoprotein IIb-IIIa complexes and a glycoprotein IIIa 214Arg----214Trp mutation.
Authors: F Lanza, A Stierlé, D Fournier, M Morales, G André, A T Nurden, J P Cazenave
Journal: Journal of Clinical Investigation (1992)

We describe a new variant of Glanzmann's thrombasthenia (variant Strasbourg I). The patient (M.S.) showed an absence of platelet aggregation to ADP, thrombin, and collagen, and a decreased clot retraction. Platelet fibrinogen was approximately 20% of normal levels. ADP-stimulated platelets bound markedly reduced amounts of soluble fibrinogen and platelet adhesion to surface-bound fibrinogen was defective. Normal to subnormal amounts of glycoprotein (GP) IIb-IIIa (alpha IIb beta 3) complexes, the platelet fibrinogen receptor, were revealed by SDS-PAGE, crossed immunoelectrophoresis, and antibody binding. However, the complexes were unusually sensitive to dissociation with EDTA at room temperature. Furthermore, flow cytometry showed that the platelets failed to bind the activation-dependent monoclonal antibody, PAC-1, after stimulation. In contrast, an RGDS-containing peptide induced significant binding of the anti-ligand-induced binding site antibody, D3GP3, suggesting the presence of a functional RGD binding domain on the patient's GPIIb-IIIa complex. Sequence analysis was performed after polymerase chain reaction amplification of selected patient's GPIIIa exons, and of the patient's platelet GPIIb and GPIIIa mRNAs. A point mutation (C to T) was localized in exon D (iv) of GPIIIa that resulted in an 214Arg to 214Trp amino acid substitution. The defect has been inherited from the parents who are heterozygous for the same mutation. This substitution points to an essential amino acid in a region of GPIIIa involved in the binding of fibrinogen and influencing the Ca(2+)-dependent stability of the GPIIb-IIIa complex.
DETECTION OF THE VIRUS OF POLIOMYELITIS IN THE NOSE AND THROAT AND GASTRO-INTESTINAL TRACT OF HUMAN BEINGS AND MONKEYS
Authors: S. D. Kramer, B. Hoskwith, L. H. Grossman
Journal: The Journal of Experimental Medicine (1939)

Five strains of virus were recovered from nasal washings and feces. Four strains were of human origin, the fifth strain came from a monkey sacrificed at the height of the disease. Of the four human strains the first was isolated from the feces of a 14 year old child 7 days after the onset of illness. The second strain was from the nasal washings of a 6(1/2) year old child, 5 days after the onset of illness. The third and fourth strains were recovered from the same patient, a 2(1/2) year old child, 9 days after the onset of illness. One of these strains was obtained from nasopharyngeal washings and the other from the feces. The single monkey strain was isolated from the upper intestinal segment and appears to be the only instance of its isolation from this source in the literature. We believe that the detection of the virus in the nasal washings of two additional patients during convalescence lends further support to the belief that the virus of poliomyelitis is spread by human contact. Furthermore, the recovery of the virus from the gastro-intestinal tract with as great or greater frequency as from the upper respiratory tract, need not, it appears to us, alter our concept of the mode of entrance of the virus into the body, namely, by way of the upper respiratory tract. If the presence of the virus is conceded, then a consideration of the physiologic passage of nasal and oral secretions into the gastro-intestinal tract by reflex swallowing would serve to explain adequately the presence of the virus in those organs. It might even be further predicated that since the gastro-intestinal tract functions as a temporary reservoir for secretions from the upper respiratory tract, the gut should, after a time, contain the virus in higher concentration than any single sample of secretion obtained from the upper respiratory tract by nasal washing. It appears to us that failures to detect the virus in the gastro-intestinal tract are perhaps more indicative of inadequate procedures for its detection than of its absence. The recovery of the virus from the feces 7 and 9 days after the onset of illness takes on added significance. It indicates first, that the virus withstands the gastric acidity which under normal physiological conditions tends to keep gastric contents relatively free of bacteria. It further suggests that improper disposal of feces from patients with poliomyelitis may have serious public health consequences, particularly in smaller communities where inadequate sewage disposal may result in contamination of surrounding beaches or even local water systems.
Intrarenal Distribution of Blood Flow in the Transplanted Dog Kidney: Effect of Denervation and Rejection*
Authors: Stanley M. Rosen, Bruno P. Truniger, Hans R. Kriek, Joseph E. Murray, John P. Merrill
Journal: Journal of Clinical Investigation (1967)

Serial measurements of intrarenal distribution of blood flow have been recorded in anesthetized dogs with the (133)xenon "washout" technique. The results showed that normal kidneys redistributed their blood flow after laparotomy and mobilization of the kidney. This alteration consisted of a diminution in percentage of total renal blood flow supplied to the fastest flowing component, and a diminution of renal mass supplied by that component. This effect lasted for as long as 7 days. Thereafter, the blood flow distribution remained stable. Autotransplanted kidneys had a stable distribution of blood flow between 0 and 77 days after operation, the values being identical with the stable normal kidney. Homotransplanted kidneys had the same intrarenal distribution of blood flow after operation as the autotransplanted kidneys. Whereas the intrarenal distribution of blood flow of the autotransplanted kidneys remained stable, a redistribution occurred in the homotransplanted kidneys as rejection progressed. This phenomenon occurred before marked elevation of blood urea nitrogen. The redistribution was due to a decrease in percentage of blood flow supplied to the fastest flowing component, and a relative reduction of tissue mass perfused by this component. Radioautography of the kidneys before rejection demonstrated that the cortex was homogeneously perfused by the fastest flowing component of blood flow. As rejection progressed, a reduced area of cortex was perfused by this component. Terminally, the fastest flowing component was located in the outer medulla. It is suggested that the reduction in cortical blood flow produced by immunological mechanisms may play a prominent role in the ensuing renal failure.
Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression
Authors: A Rocco, R Caruso, S Toracchio, L Rigoli, F Verginelli, T Catalano, M Neri, M C Curia, L Ottini, V Agnese, V Bazan, A Russo, G Pantuso, G Colucci, R Mariani-Costantini, G Nardone
Journal: Annals of Oncology (2006)
Importance of an Increased Gamma Globulin Level in the Determination of Gm Groups in Collagen Diseases
Authors: H. Julkunen, Anja Tiilikainen
Journal: Annals of the Rheumatic Diseases (1959)

<h3>Purpose</h3> In the last few decades, there has been an increase in the reports of nutritional rickets due to deficient intake of vitamin D in the United States and other developed countries, particularly among vulnerable population of children. We call the attention over the reemergence of a nutritional problem that should have been eradicated. <h3>Methods and Results</h3> We have seen in the last 10 years several patients with nutritional rickets and have selected 4 representative cases from our clinics that presented with tetany, bony deformities such as bowed legs, widening of wrists and ankles, and rachitic rosary, ages 0.3 to 3.3 years, three African American and one Arabic. They all had been breast-fed with no vitamin D supplementation and after weaning from breast milk had negligible intake of vitamin D-fortified milk or dairy products, with very limited exposure to UV solar radiation. All had low serum total calcium between 6.1 and 7.8 mg/dL (8.7-10.3 mg/dL) and ionized calcium between 2.2 and 4.3 mg/dL (4.3-5.9 mg/dL), relatively low normal serum phosphorus between 4.3 and 6.1 mg/dL (4.0-9.5 mg/dL), and elevated alkaline phosphatase between 391 and 1,158 U/L (70-250 U/L). All had low serum 25(OH) vitamin D between 5.0 and 21 ng/mL (20-60 ng/mL) and high PTH between 25 and 454 pg/mL (10-60 pg/mL) and relatively high 1,25(OH)2 vitamin D between 93 and 195 pg/mL (15-90 pg/mL). Renal and liver functions were normal. All had complete or near-complete resolution of their medical problems with appropriate therapeutic doses of calcium, ergocalciferol, or calcitriol. <h3>Conclusions</h3> Nutritional rickets due to vitamin D deficiency and not associated with other organic or metabolic problem resolves easily with the administration of intravenous calcium followed by oral calcium supplementation and therapeutic doses of ergocalciferol or calcitriol. The risk factors for vitamin D deficiency in these children were not timely anticipated. Recommendations from the Committee on Nutrition of the American Academy of Pediatrics 2003 (adequate UV light solar exposure and supplementation of 200 IU vitamin D if taking fortified formula or 400 IU vitamin D if breast-fed exclusively) had not been followed. Health care providers should be aware that nutritional rickets due to vitamin D deficiency is still prevalent and is preventable.
International evidence-based recommendations for point-of-care lung ultrasound
Authors: Giovanni Volpicelli, Mahmoud Elbarbary, Michael Blaivas, Daniel A. Lichtenstein, Gebhard Mathis, Andrew W. Kirkpatrick, Lawrence Melniker, Luna Gargani, Vicki E. Noble, Gabriele Via, Anthony Dean, James W. Tsung, Gino Soldati, Roberto Copetti, Belaid Bouhemad, Angelika Reissig, Eustachio Agricola, Jean-Jacques Rouby, Charlotte Arbelot, Andrew Liteplo, Ashot Sargsyan, Fernando Silva, Richard Hoppmann, Raoul Breitkreutz, Armin Seibel, Luca Neri, Enrico Storti, Tomislav Petrovic
Journal: Intensive Care Medicine (2012)
Treatment Patterns in Prepaid Psychiatric Care
Authors: OTTO H. SPOERL
Journal: American Journal of Psychiatry (1974)

The author describes the evolution and current functioning of a menial health service in an HMO that serves more than 175,000 members in the Seattle metropolitan area. A cohort of 159 patients was followed for 18 months to investigate referral patterns, categories of presenting problems, diagnostic impressions, treatment modalities, and patterns of utilization. The advantages and problems of the prepayment system vis-à-vis psychiatric care are discussed.