tbuckley/cabot-search huggingface dataset:
Mechanisms and Physiological Significance of the Cholinergic Control of Pancreatic β-Cell Function
Authors: Patrick Gilon, Jean-Claude Henquin
Journal: Endocrine Reviews (2001)

Acetylcholine (ACh), the major parasympathetic neurotransmitter, is released by intrapancreatic nerve endings during the preabsorptive and absorptive phases of feeding. In beta-cells, ACh binds to muscarinic M(3) receptors and exerts complex effects, which culminate in an increase of glucose (nutrient)-induced insulin secretion. Activation of PLC generates diacylglycerol. Activation of PLA(2) produces arachidonic acid and lysophosphatidylcholine. These phospholipid-derived messengers, particularly diacylglycerol, activate PKC, thereby increasing the efficiency of free cytosolic Ca(2+) concentration ([Ca(2+)](c)) on exocytosis of insulin granules. IP3, also produced by PLC, causes a rapid elevation of [Ca(2+)](c) by mobilizing Ca(2+) from the endoplasmic reticulum; the resulting fall in Ca(2+) in the organelle produces a small capacitative Ca(2+) entry. ACh also depolarizes the plasma membrane of beta-cells by a Na(+)- dependent mechanism. When the plasma membrane is already depolarized by secretagogues such as glucose, this additional depolarization induces a sustained increase in [Ca(2+)](c). Surprisingly, ACh can also inhibit voltage-dependent Ca(2+) channels and stimulate Ca(2+) efflux when [Ca(2+)](c) is elevated. However, under physiological conditions, the net effect of ACh on [Ca(2+)](c) is always positive. The insulinotropic effect of ACh results from two mechanisms: one involves a rise in [Ca(2+)](c) and the other involves a marked, PKC-mediated increase in the efficiency of Ca(2+) on exocytosis. The paper also discusses the mechanisms explaining the glucose dependence of the effects of ACh on insulin release.
A PLEOMORPHIC BACILLUS FROM PNEUMONIC LUNGS OF CALVES SIMULATING ACTINOMYCES
Authors: Theobald Smith
Journal: The Journal of Experimental Medicine (1918)

A bacillus was found associated in pure culture with an extensive lobar bronchopneumonia in calves. It occurs in the exudate as a minute bacillus in small groups. In cultures it appears in three forms: as a bacillus, as a coccus-like endospore or arthrospore, and as a conglomerate Actinomyces-like flake or colony with peripheral clubs. The bacillar and coccoid forms occur on agar, the Actinomyces form in the condensation water of coagulated serum (horse). The coccoid form is probably a spore state, the minute refringent spore being contained in a roundish, unstainable mass representing either the remnants of bacillar substance or some capsular material. The somewhat striking similarities between this organism and Actinomyces are expressed by the massed growth with terminal clubs, the bacillar and coccoid stages, all of which are characteristic of Actinomyces. Sealing the tubes is essential for multiplication. Cultures must be renewed within a few days, otherwise multiplication fails. The substance which forms the bulk of the radiate flocculi is probably of capsular nature, greatly overproduced in serum tubes and scarce or absent on agar. Its nature is unknown. The organism is not appreciably pathogenic when injected into certain small laboratory animals.
Evidence that the type I adenylyl cyclase may be important for neuroplasticity: Mutant mice deficient in the gene for type I adenylyl cyclase show altered behavior and LTP
Authors: Zhengui Xia, Daniel R. Storm
Journal: Behavioral and Brain Sciences (1995)

Abstract The regulatory properties of the neurospecific, type I adenylyl cyclase and its distribution within brain have suggested that this enzyme may be important for neuroplasticity. To address this issue, the murine, Ca 2+ -stimulated adenylyl cyclase (type I), was inactivated by targeted mutagenesis. Ca 2+ -stimulated adenylyl cyclase activity was reduced 40% to 60% in the hippocampus, neocortex, and cerebellum. Long term potentiation in the CA1 region of the hippocampus from mutants was perturbed relative to controls. Both the initial slope and maxim um extent of changes in synaptic response were reduced. Although mutant mice learned to find a hidden platform normally in the Morris water task, they did not display a preference for the region where the platform had been when it was removed. The behavioral phenotype of these mice is very similar to that exhibited by mice which have been surgically lesioned in the hippocampus. These results indicate that disruption of the gene for the type I adenylyl cyclase produces changes in spatial memory and indicate that the cAMP signal transduction pathway may play an important role for synaptic plasticity.
Pyogenic osteomyelitis presenting as an acute sterile arthropathy.
Authors: P N Platt, I D Griffiths
Journal: Annals of the Rheumatic Diseases (1984)

We report two cases of osteomyelitis secondary to staphylococcal septicaemia, presenting with large sterile effusions in adjacent joints. In both cases the clinical features were suggestive of septic arthritis. Multiple joints were involved in each patient. Initial radiographs showed no abnormalities.
Immunoparesis and monoclonal gammopathy of undetermined significance are disassociated in advanced age
Authors: Benjamin M. Cherry, Rene Costello, Adriana Zingone, Jason Burris, Neha Korde, Elisabet Manasanch, Mary Kwok, Christina Annunziata, Mark J. Roschewski, Eric A. Engels, Ola Landgren
Journal: American Journal of Hematology (2012)

Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of immune dysfunction predictive of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have reported increased prevalence of MGUS by age, but no study has examined the relationship between immunoparesis and abnormal FLC ratios in the elderly. We screened 453 older adults (median age, 80 years; range, 65-96) to characterize the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001), respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the youngest and oldest groups. Our observed disassociation between MGUS prevalence and impaired immunoglobulin production suggests that separate mechanisms are involved in the development of MGUS and immunoparesis in advanced age. These findings emphasize the need for molecularly defined methods to characterize myeloma precursor states and better predict progression to MM.
Efficient Inhibition of Intra-Peritoneal Tumor Growth and Dissemination of Human Ovarian Carcinoma Cells in Nude Mice by Anti-L1-Cell Adhesion Molecule Monoclonal Antibody Treatment
Authors: Matthias J.E. Arlt, Ilse Novak-Hofer, Daniela Gast, Verena Gschwend, Gerhard Moldenhauer, Jürgen Grünberg, Michael Honer, P. August Schubiger, Peter Altevogt, Achim Krüger
Journal: Cancer Research (2006)

Abstract The L1 cell adhesion molecule is implicated in the control of proliferation, migration, and invasion of several tumor cell types in vitro. Recently, L1 overexpression was found to correlate with tumor progression of ovarian carcinoma, one of the most common causes of cancer-related deaths in gynecologic malignant diseases. To evaluate L1 as a potential target for ovarian cancer therapy, we investigated the effects of anti-L1 monoclonal antibodies (chCE7 and L1-11A) on proliferation and migration of L1-positive human SKOV3ip ovarian carcinoma cells in vitro and the therapeutic efficacy of L1-11A against i.p. SKOV3ip tumor growth in nude mice. In vitro, both anti-L1 antibodies efficiently inhibited the proliferation of SKOV3ip cells as well as other L1-expressing tumor cell lines (renal carcinoma, neuroblastoma, and colon carcinoma). On two cell lines, hyper-cross-linking of L1-11A with a secondary antibody was necessary for significant inhibition of proliferation, indicating that cross-linking of L1 is required for the antiproliferative effect. L1-negative prostate carcinoma cells were not influenced by antibody treatment. Biweekly treatment of ovarian carcinoma-bearing mice with L1-11A led to a dose-dependent and significant reduction of tumor burden (up to −63.5%) and ascites formation (up to −75%). This effect was associated with reduced proliferation within the tumors. L1-directed antibody-based inhibition of peritoneal growth and dissemination of human ovarian carcinoma cells represents important proof-of-principle for the development of a new therapy against one of the leading gynecologic malignant diseases. (Cancer Res 2006; 66(2): 936-43)
NK and K cell activity of human blood: differences according to sex, age, and disease.
Authors: J Penschow, I R Mackay
Journal: Annals of the Rheumatic Diseases (1980)

We report a study on the activity of NK cells ('natural' killer cells) and K cells (antibody-dependent killer cells) in human peripheral blood in health and disease. The 'targets' used were cells of the Chang cell-line, sensitised with rabbit anti-Chang cell antibody for K cell activity, and killing was assessed by release of radiochromium at effector: target ratios of 50:1 and 100:1. The positive findings were that NK cell activity, but not K cell activity, was greater in males and in youth, that NK cell activity was reduced in systemic lupus erythematosus, that neither NK nor K cell activity was altered in rheumatoid arthritis, and that K cell activity was reduced in chronic active hepatitis.
Constitutive production of macrophage colony-stimulating factor by human ovarian and breast cancer cell lines.
Authors: S Ramakrishnan, F J Xu, S J Brandt, J E Niedel, R C Bast, E L Brown
Journal: Journal of Clinical Investigation (1989)

Many nonhematologic tumors produce growth factors that may influence cellular proliferation either by autocrine or by paracrine mechanisms. In the current study, human tumor cell lines were investigated for the constitutive production of macrophage colony-stimulating factor (M-CSF). Culture supernatants obtained from cell lines were analyzed using a radioimmunoassay and a radioreceptor assay specific for M-CSF. Among the various cell types analyzed, all the ovarian cell lines and a majority of the breast cancer cell lines secreted significant amount of an M-CSF-like factor. Treatment of mouse bone marrow cultures with culture supernatants from ovarian cancer cells stimulated the production of macrophage colonies. Analysis of total cellular RNA obtained from the ovarian cell lines by Northern blot showed multiple sizes of M-CSF transcripts with an abundance of a 4.2-kb message. The relative amount of M-CSF transcripts correlated with the level of immunoreactive material seen in the culture supernatants.
<i>CHFR</i> Promoter Methylation Indicates Poor Prognosis in Stage II Microsatellite Stable Colorectal Cancer
Authors: Arjen H.G. Cleven, Sarah Derks, Muriel X.G. Draht, Kim M. Smits, Veerle Melotte, Leander Van Neste, Benjamin Tournier, Valerie Jooste, Caroline Chapusot, Matty P. Weijenberg, James G. Herman, Adriaan P. de Bruïne, Manon van Engeland
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Data on the prognostic significance of promoter CpG island methylation in colorectal cancer (CRC) are conflicting, possibly due to associations between methylation and other factors affecting survival such as genetic alterations and use of adjuvant therapy. Here, we examine the prognostic impact of promoter methylation in patients with CRC treated with surgery alone in the context of microsatellite instability (MSI), BRAF and KRAS mutations. Experimental Methods: One hundred and seventy-three CRCs were analyzed for promoter methylation of 19 tumor suppressor and DNA repair genes, the CpG island methylator phenotype (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations. Results: Unsupervised hierarchical clustering based on methylation status of 19 genes revealed three subgroups: cluster 1 [CL1, 57% (98/173) of CRCs], cluster 2 [CL2, 25% (43/173) of CRCs], and cluster 3 [CL3, 18% (32/173) of CRCs]. CL3 had the highest methylation index (0.25, 0.49, and 0.69, respectively, P = &amp;lt;0.01) and was strongly associated with CIMP (P &amp;lt; 0.01). Subgroup analysis for tumor stage, MSI, and BRAF status showed no statistically significant differences in survival between CL1, CL2, and CL3 nor between CIMP and non-CIMP CRCs. Analyzing genes separately revealed that CHFR promoter methylation was associated with a poor prognosis in stage II, microsatellite stability (MSS), BRAF wild-type (WT) CRCs: multivariate Cox proportional HR = 3.89 [95% confidence interval (CI), 1.58–9.60, P &amp;lt; 0.01; n = 66] and HR = 2.11 (95% CI, 0.95–4.69, P = 0.068, n = 136) in a second independent population-based study. Conclusions: CHFR promoter CpG island methylation, which is associated with MSI, also occurs frequently in MSS CRCs and is a promising prognostic marker in stage II, MSS, BRAF WT CRCs. Clin Cancer Res; 20(12); 3261–71. ©2014 AACR.
The Esophageal Propulsive Force: Esophageal Response to Acute Obstruction*
Authors: Daniel H. Winship, F. Frank Zboralske
Journal: Journal of Clinical Investigation (1967)

The response of the normal human esophagus to an obstructing intraluminal bolus was investigated and compared to the response evoked by transient intraluminal distention. A balloon, immobilized within the esophagus by external attachment to a force transducer, was inflated with from 3 to 25 ml of air for from 3 to 210 sec. Pressure phenomena occurring in the esophagus were simultaneously recorded from the body of the esophagus above and below the balloon. Transient distention (5 sec or less) with small volumes (5 ml or less) often evoked a secondary peristaltic wave in the esophagus distal to the balloon, but infrequently resulted in the registration of any force exerted upon the balloon to drive it downward. Conversely, distentions of longer duration and with greater volume elicited an esophageal propulsive force exerted upon the balloon oriented to propel it aborally, and much less often evoked a propagated wave of secondary peristalsis. The propulsive force, obviously resulting from esophageal muscular contraction, occurred promptly, and once initiated, was sustained until deflation of the balloon. It varied widely in magnitude, from 4 to 200 g, and was associated with no motor phenomena recorded from the body of the esophagus proximal or distal to the balloon which could account for its presence, onset, magnitude, or duration. The force was inhibited by deglutition, but arrival of the primary peristaltic wave at the bolus resulted in augmentation of the force. When the obstructing balloon was freed from its attachment, the persistent, stationary force was converted to a propagated one that propelled the balloon before it. It the balloon was arrested before entering the stomach, the moving contraction was also arrested and the persistent propulsive force acting upon the balloon was maintained. The velocity of the moving contraction wave was determined in great part by the resistance offered by the bolus. Unrestrained, the balloon was propelled aborally at 4-8 cm/sec by the esophageal propulsive force; when restrained by 50 g, the rate of passage was reduced to 0.2-0.8 cm/sec. The esophageal response to intraluminal distention is thus not limited to the uninterrupted wave of secondary peristalsis but is versatile and is determined by the nature of the distending bolus. Transient distention by a mobile or collapsible bolus elicits the propagated secondary peristaltic wave.
Absence of Pulmonary Embolism
Authors: Alan. A. Jones
Journal: BMJ (1964)

accident-prone at the time when they have already been inoculated with tetanus.Only the future will show how adequate antibiotics are as a prophylactic against tetanus.Active immunization of the whole population remains the ideal prophylaxis.In spite of the great difficulties of such a cam- paign this ought to be considered if surgical excision and antibiotics do not substantially reduce the incidence of tetanus.-Weare, etc.,
Prognostic Implications of Nonobstructive Coronary Plaques in Patients With Non–ST-Segment Elevation Myocardial Infarction
Authors: Thomas S. Kristensen, Klaus F. Kofoed, Jørgen T. Kühl, Walter B. Nielsen, Michael B. Nielsen, Henning Kelbæk
Journal: Journal of the American College of Cardiology (2011)
TCT-617 Impact Of Gender In The Relationship Between Intravascular Ultrasound And Fractional Flow Reserve
Authors: Alfazir Omar, Rebecca Torguson, Philippe Genereux, James Blankenship, Jose M. De la Torre Hernandez, Farrel Hellig, Jacek Legutko, Gary S. Mintz, Tom McAndrew, Jasvindar Singh, Akiko Maehara, Gregg Stone, Ron Waksman
Journal: Journal of the American College of Cardiology (2013)
Dantrolene in Amyotrophic Lateral Sclerosis
Authors: Victor M. Rivera
Journal: JAMA (1975)

<h3>To the Editor.—</h3> In relation to the article by Dr. Michael H. M. Dykes (231:862, 1975), our experience using the muscle relaxant dantrolene sodium (Dantrium) in patients with amyotrophic lateral sclerosis (ALS) may provide additional information on side effects and precautions. Dantrolene has been used in controlling spasticity resulting from disorders such as spinal cord injury, brain damage secondary to birth trauma, multiple sclerosis, and stroke. Although the spastic syndromes associated with motor neuron manifestations in ALS are not mentioned in the literature<sup>1-3</sup>or in the package insert by the company producing the drug, it would seem justifiable to use this muscle relaxant because this syndrome affects the corticospinal pathways, producing spasticity that interferes with motor function and rehabilitation. Amyotrophic lateral sclerosis comprises a group of progressive diseases in which variable degrees of atrophy of motor neurons and degeneration of the corticospinal tracts are the common pathological results: Progressive
Standards of Medical Care in Diabetes
Authors: Vivian Fonseca, Nathaniel G. Clark
Journal: Diabetes Care (2006)

We would like to thank Dr. Power for his letter (1) and allowing us to comment on the appropriateness of the title for our clinical practice guidelines, the evidence levels used in our guidelines, and specifically our recommendation regarding screening for type 2 diabetes (2). The title “Standards of Medical Care in Diabetes” was chosen because in the view of the American Diabetes Association (ADA), the recommendations represent what we consider the “standards” for the care of patients with diabetes. We see a need to define these so that providers have a guide …
The Prevalence of Confirmed Maltreatment Among US Children, 2004 to 2011
Authors: Christopher Wildeman, Natalia Emanuel, John M. Leventhal, Emily Putnam-Hornstein, Jane Waldfogel, Hedwig Lee
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> Child maltreatment is a risk factor for poor health throughout the life course. Existing estimates of the proportion of the US population maltreated during childhood are based on retrospective self-reports. Records of officially confirmed maltreatment have been used to produce annual rather than cumulative counts of maltreated individuals. <h3>Objective</h3> To estimate the proportion of US children with a report of maltreatment (abuse or neglect) that was indicated or substantiated by Child Protective Services (referred to as confirmed maltreatment) by 18 years of age. <h3>Design, Setting, and Participants</h3> The National Child Abuse and Neglect Data System (NCANDS) Child File includes information on all US children with a confirmed report of maltreatment, totaling 5 689 900 children (2004-2011). We developed synthetic cohort life tables to estimate the cumulative prevalence of confirmed childhood maltreatment by 18 years of age. <h3>Main Outcomes and Measures</h3> The cumulative prevalence of confirmed child maltreatment by race/ethnicity, sex, and year. <h3>Results</h3> At 2011 rates, 12.5% (95% CI, 12.5%-12.6%) of US children will experience a confirmed case of maltreatment by 18 years of age. Girls have a higher cumulative prevalence (13.0% [95% CI, 12.9%-13.0%]) than boys (12.0% [12.0%-12.1%]). Black (20.9% [95% CI, 20.8%-21.1%]), Native American (14.5% [14.2%-14.9%]), and Hispanic (13.0% [12.9%-13.1%]) children have higher prevalences than white (10.7% [10.6%-10.8%]) or Asian/Pacific Islander (3.8% [3.7%-3.8%]) children. The risk for maltreatment is highest in the first few years of life; 2.1% (95% CI, 2.1%-2.1%) of children have confirmed maltreatment by 1 year of age, and 5.8% (5.8%-5.9%), by 5 years of age. Estimates from 2011 were consistent with those from 2004 through 2010. <h3>Conclusions and Relevance</h3> Annual rates of confirmed child maltreatment dramatically understate the cumulative number of children confirmed to be maltreated during childhood. Our findings indicate that maltreatment will be confirmed for 1 in 8 US children by 18 years of age, far greater than the 1 in 100 children whose maltreatment is confirmed annually. For black children, the cumulative prevalence is 1 in 5; for Native American children, 1 in 7.
Photopatterning of Multifunctional Hydrogels to Direct Adult Neural Precursor Cells
Authors: Mikhail V. Tsurkan, Richard Wetzel, Heidi R. Pérez‐Hernández, Karolina Chwalek, Anna Kozlova, Uwe Freudenberg, Gerd Kempermann, Yixin Zhang, Andrés F. Lasagni, Carsten Werner
Journal: Advanced Healthcare Materials (2014)

Matrix-metalloproteinase and photosensitive peptide units are combined with heparin and poly(ethylene glycol) into a light-sensitive multicomponent hydrogel material. Localized degradation of the hydrogel matrix allows the creation of defined spatial constraints and adhesive patterning for cells grown in culture. Using this matrix system, it is demonstrated that the degree of confinement determines the fate of neural precursor cells in vitro.
Laser-opened coronary arteries close again within months—
Authors: John Henahan
Journal: JAMA (1985)

In an update of work reported a few months ago (<i>JAMA</i>[MEDICAL NEWS] 1983;250:3135-3141), Daniel S. J. Choy, MD, St Luke's-Roosevelt Hospital Center, New York City, has told a Milan, Italy, conference that the argon laser has successfully opened occluded arteries—in a matter of a few minutes—in another three patients. However, as with five other patients who underwent the laser angioplasty procedure earlier, all of the arteries closed up again within three months. All of the laser angioplasties were carried out at the Centre de Chirurgie Cardio-Vasculaire, Centre Hospitalier Universitaire de Purpan (Center for Cardiovascular Surgery, Central University Hospital, University of Purpan) near Toulouse, in southern France. The team consisted of Choy, Simon H. Stertzer, MD, research director, and Richard K. Myler, MD, medical director, San Francisco Heart Institute of Seton Medical Center, Daly City, Calif; Jean Marcos, MD, professor of medicine, of the Toulouse III Faculté de Médecin (Faculty