tbuckley/cabot-search huggingface dataset:
Pericardial effusion and mitral valve involvement in systemic lupus erythematosus. Echocardiographic study.
Authors: U Elkayam, S Weiss, S Laniado
Journal: Annals of the Rheumatic Diseases (1977)

Echocardiography was used in 30 women and 2 men with systemic lupus erythematosus (SLE) in order to determine the incidence and severity of pericardial effusion and mitral valve involvement. 31 patients showed normal thickness of the mitral valve leaflets, only one patient showed irregular thickening of the leaflets suggesting the presence of vegetations. Mitral valve motions were normal in all patients. These results indicate that myocardial and valvular involvement in SLE is usually not severe enough to result in haemodynamic abnormalities. Pericardial effusion was found in 2 patients who were symptom free, whereas 4 of the patients with a past history suggestive of pericarditis showed no echocardiographic evidence of pericardial effusion. These suggest the transient nature of pericarditis in SLE, and the value of echocardiography as a diagnostic tool in detecting clinically inapparent lupus pericarditis.
Receptor-mediated Immunoglobulin G Transport Across Mucosal Barriers in Adult Life
Authors: Gerburg M. Spiekermann, Patricia W. Finn, E. Sally Ward, Jennifer Dumont, Bonny L. Dickinson, Richard S. Blumberg, Wayne I. Lencer
Journal: The Journal of Experimental Medicine (2002)

Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain the immunoglobulins (Ig)G and secretory IgA (sIgA) that function together in host defense. Exactly how IgG crosses epithelial barriers to function in mucosal immunity remains unknown. Here, we test the idea that the MHC class I–related Fc-receptor, FcRn, transports IgG across the mucosal surface of the human and mouse lung from lumen to serosa. We find that bronchial epithelial cells of the human, nonhuman primate, and mouse, express FcRn in adult-life, and demonstrate FcRn-dependent absorption of a bioactive Fc-fusion protein across the respiratory epithelium of the mouse in vivo. Thus, IgG, like dimeric IgA, can cross epithelial barriers by receptor-mediated transcytosis in adult animals. These data show that mucosal surfaces that express FcRn reabsorb IgG and explain a mechanism by which IgG may act in immune surveillance to retrieve lumenal antigens for processing in the lamina propria or systemically.
Physician desire for euthanasia and assisted suicide: would physicians practice what they preach?
Authors: O M Howard, D L Fairclough, E R Daniels, E J Emanuel
Journal: Journal of Clinical Oncology (1997)

PURPOSE Euthanasia is a pressing public issue. We sought to assess how frequently physicians could perceive of a desire for euthanasia themselves and whether they would be willing to provide patients the same interventions. METHODS We interviewed 355 randomly selected oncologists from the United States and interviewed them about their attitudes and practices related to euthanasia and assisted suicide. RESULTS Of the 355 oncologists, 48.1% could imagine a situation in which they might desire euthanasia or assisted suicide for themselves. Oncologists who were Catholic and more religious were significantly less likely to desire these interventions for themselves. Of those oncologists who could imagine a situation in which they might desire euthanasia or assisted suicide for themselves, 85.8% found euthanasia and/or assisted suicide acceptable for their patients. Of the oncologists who could not imagine a situation in which they might desire euthanasia or assisted suicide for themselves, 41.7% still found these interventions ethical for their patients. Only 6.8% of oncologists could imagine a situation in which they might desire euthanasia or assisted suicide for themselves but found these interventions unacceptable for their patients. CONCLUSION Almost half of surveyed oncologists could imagine a situation in which they would desire euthanasia or assisted suicide. However, in many cases, this was for nonterminal illness which would be prohibited by proposed laws. When physicians desire euthanasia or assisted suicide for themselves, they are willing to provide these interventions for their patients; therefore, most physicians would practice what they preach. Indeed, when they deviate, oncologists overwhelmingly respect patient autonomy rather than impose their own views on patients.
GROWTH AND SURVIVAL SIGNALS CONTROLLING SYMPATHETIC NERVOUS SYSTEM DEVELOPMENT
Authors: Natalia O. Glebova, David D. Ginty
Journal: Annual Review of Neuroscience (2005)

The precise coordination of the many events in nervous system development is absolutely critical for the correct establishment of functional circuits. The postganglionic sympathetic neuron has been an amenable model for studying peripheral nervous system formation. Factors that control several developmental events, including multiple stages of axon extension, neuron survival and death, dendritogenesis, synaptogenesis, and establishment of functional diversity, have been identified in this neuron type. This knowledge allows us to integrate the various intricate processes involved in the formation of a functional sympathetic nervous system and thereby create a paradigm for understanding neuronal development in general.
Summary Statement on Primary Central Nervous System Lymphomas From the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002
Authors: Andrés J.M. Ferreri, Lauren E. Abrey, Jean-Yves Blay, Bettina Borisch, Jacob Hochman, Edward A. Neuwelt, Joachim Yahalom, Emanuele Zucca, Franco Cavalli, James Armitage, Tracy Batchelor
Journal: Journal of Clinical Oncology (2003)

Under the sponsorship of the International Extranodal Lymphoma Study Group, a Multidisciplinary Workshop on primary CNS lymphoma (PCNSL) with over 50 participants from Europe, North America, Israel, and Australia was held as part of the Eighth International Conference on Malignant Lymphoma in Lugano, Switzerland (June 12 to 15, 2002). The main purposes of the Workshop were to exchange the latest scientific information, to analyze methodologic issues in the design of clinical trials, to reach a consensus on treatment recommendations and prognostic factors, to discuss clinical and molecular targets for future studies, and to establish an international collaborative group to conduct laboratory and clinical investigations in PCNSL. This article summarizes the contents of the Workshop, analyzes the current knowledge on the most relevant biologic and clinical issues in PCNSL, and focuses on fundamental challenges to be addressed in future studies.
INTRAMUSCULAR HUMAN INTERFERON-β INJECTIONS IN TREATMENT OF CONDYLOMATA ACUMINATA
Authors: Alexander Schonfeld, Amihai Schattner, Madeleine Crespi, Hanoch Levavi, Jacob Shoham, Schmuel Nitke, David Wallach, Talia Hahn, Ovadia Yarden, Thomas Doerner, Michet Revel
Journal: The Lancet (1984)
Postnatal Soluble FGFR3 Therapy Rescues Achondroplasia Symptoms and Restores Bone Growth in Mice
Authors: Stéphanie Garcia, Béatrice Dirat, Thomas Tognacci, Nathalie Rochet, Xavier Mouska, Stéphanie Bonnafous, Stéphanie Patouraux, Albert Tran, Philippe Gual, Yannick Le Marchand-Brustel, Isabelle Gennero, Elvire Gouze
Journal: Science Translational Medicine (2013)

Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3(ach/+) mice-the mouse model of achondroplasia-twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3(ach/+) mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.
Phase II Study of Enzastaurin, a Protein Kinase C Beta Inhibitor, in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Michael J. Robertson, Brad S. Kahl, Julie M. Vose, Sven de Vos, Mary Laughlin, Patrick J. Flynn, Kendrith Rowland, Jose C. Cruz, Stuart L. Goldberg, Luna Musib, Christelle Darstein, Nathan Enas, Jeffery L. Kutok, Jon C. Aster, Donna Neuberg, Kerry J. Savage, Ann LaCasce, Donald Thornton, Christopher A. Slapak, Margaret A. Shipp
Journal: Journal of Clinical Oncology (2007)

Purpose Protein kinase C beta (PKCβ) was identified by gene-expression profiling, preclinical evaluation, and independent immunohistochemical analysis as a rational therapeutic target in diffuse large B-cell lymphoma (DLBCL). We conducted a multicenter phase II study of a potent inhibitor of PKCβ, enzastaurin, in patients with relapsed or refractory DLBCL. Patients and Methods Enzastaurin was taken orally once daily until disease progression or unacceptable toxicity occurred. Study end points included freedom from progression (FFP) for ≥ two cycles (one cycle = 28 days), objective response, and toxicity. Results Fifty-five patients (median age, 68 years) were enrolled. Patients had received a median number of two prior therapies (range, one to five); six patients relapsed after high-dose therapy and autologous stem-cell transplantation. Only one grade 4 toxicity (hypomagnesemia) occurred. Grade 3 toxicities included fatigue (n = 2), edema (n = 1), headache (n = 1), motor neuropathy (n = 1), and thrombocytopenia (n = 1). No grade 3 or 4 neutropenia occurred. No deaths or discontinuations due to toxicity were reported. Fifteen patients completed less than one cycle of therapy. Twelve of 55 patients (22%; 95% CI, 13% to 46%) experienced FFP for ≥ two cycles, and eight patients remained free from progression for ≥ four cycles (15%; 95% CI, 6% to 27%). Four patients (7%; 95% CI, 2% to 18%), including three complete responders and one patient with stable disease, continue to experience FFP 20+ to 50+ months after study entry. Conclusion Treatment with enzastaurin was well-tolerated and associated with prolonged FFP in a small subset of patients with relapsed or refractory DLBCL. Further studies of enzastaurin in DLBCL are warranted.
Should we refer diminutive polyps to post-CTC polypectomy?
Authors: C Hassan, P J Pickhardt, A Laghi, D H Kim, A Zullo
Journal: Gut (2009)

We read with interest paper by Graser et al 1 comparing CT colonography (CTC) with optical colonoscopy (OC) and other screening tests in an average-risk population. In a series of 311 subjects, the authors described 13 cases of advanced neoplasia (high-grade dysplasia or a villous component) in <10 mm polyps. In detail, seven of these cases occurred in <5 mm adenomas, so that diminutive adenomas accounted for 16% of all of the advanced neoplasia detected in the study, also being more frequent than 6–9 mm advanced adenomas. Such a relatively high rate of advanced neoplasia in <5 …
Direct communication between the right pulmonary artery and the left atrium.
Authors: I Lekuona, A Cabrera, R Inguanzo, C Cid, J Agosti
Journal: Thorax (1986)

Direct communication between the pulmonary artery trunk or its branches and the left atrium is a rare finding and only 25 cases have been published."1-Thisanomaly has been classified into four types2 67 on the basis of two main features-the presence or absence of an aneurysm in the communication and the anatomy of the pulmonary venous drainage.We report a sixth case of the type II anomaly and discuss its embryological basis, as well as the surgical approach appropriate to each type. Case reportA 20 year old man was referred to our hospital for evaluation of fatigue, dyspnoea, and cyanosis that had started one year before admission.On physical examination the patient was well developed and well nourished.His blood pressure was 120/70 mm Hg and the pulse was regular at 75 beats/min.There was no chest deformity and no clubbing of the fingers.No haemangiomas of the skin or mucous membranes were present and no murmurs were found on careful auscultation.
Hemagglutinin-specific cytotoxic T-cell response during influenza infection.
Authors: F A Ennis, W J Martin, M W Verbonitz
Journal: The Journal of Experimental Medicine (1977)

Specific cytotoxic thymus-derived (T) lymphocytes were detected in the cervical lymph nodes and spleen during influenza infection of mice. The cytotoxic T cells can distinguish target cells infected with different influenza A subtypes. Infection with parent viruses and their recombinant progeny possessing the hemagglutinin of one parent and the neuraminidase of the other demonstrated that significant cytotoxicity occurred only when the hemagglutinin of the immunizing viruses was the same as that of the virus used to infect the target cell. In addition to this specific cytotoxic response to the major surface antigen, a cross-reactive response could be detected when the relatively nonpermissive L cell was used as the target cell. These results indicate there is a specific cytotoxic T-cell response to the surface hemagglutinin, and a cross-reactive cytotoxic response, not directed to the hemagglutinin, during influenza infection. The cytotoxic T-cell response specific for the hemagglutinin antigen may play an important role in in vivo immunity to influenza.
Profound Hypokalemia With Rhabdomyolysis in Bartter's Syndrome
Authors: Th. L. J. M. van der Loos
Journal: JAMA (1986)

To the Editor.—  Hypokalemia, hyperreninemia, hyperaldosteronism, decreased sensitivity to exogenous angiotensin II, and hyperplasia of juxtaglomerular apparatus on biopsy are the most characteristic findings in Bartter's syndrome. We describe a patient with Bartter's syndrome, rhabdomyolysis, and profound hypokalemia.  Report of a Case.—  A 26-year-old man presented at our hospital with paresis os his proximal muscles. He had no history of vomiting or diarrhea. He took no drugs or other substances known to cause hypokalemia. He had a normal blood pressure. Laboratory values were as follows: hemoglobin, 17.9 g/dL (179 g/L); erythrocytes, 5.25×10 6 / mm 3 (5.25×10 12 /L); potassium, 1.6 mEq/L (1.6 mmol/L); creatinine, 0.9 mg/dL (79.5 μmol/L); and creatine kinase, 15.390 U/L (reference range,  -1 ·s -1 ) (reference range, 2.6 to 3.6 ng/mL/h [0.7 to 1.0 ng·L -1 ·s -1 ]), and
Breast Cancer Subtype-Specific Interactions with the Microenvironment Dictate Mechanisms of Invasion
Authors: Tuyen T. Dang, Amanda M. Prechtl, Gray W. Pearson
Journal: Cancer Research (2011)

Most ductal breast carcinoma cells are weakly invasive in vitro and in vivo, suggesting that components of their microenvironment may facilitate a transition from in situ to invasive stages during progression. Here, we report that coculture of mammary fibroblasts specifically triggers invasive behavior in basal-type breast cancer cells through a ligand independent mechanism. When cultured alone in organotypic culture, both basal- and luminal-type breast cancer cells formed noninvasive spheroids with characteristics of ductal carcinoma in situ (DCIS). In contrast, when cocultured with mammary fibroblasts, basal-type spheroids exhibited invasive character whereas the luminal-type spheroids retained a benign and noninvasive duct-like architecture. Real-time imaging and functional studies revealed that the specificity of invasion was linked to a unique capacity of basal-type breast cancer cells to move within spheroids. Mammary fibroblasts induced invasion by triggering basal-type breast cancer cells to convert from a noninvasive program of mammary epithelial morphogenesis to an invasive program of sprouting endothelial angiogenesis. Contrary to the existing invasion models, soluble ligands produced by the fibroblasts were not sufficient to trigger invasion. Instead, basal-type invasion relied upon a Cdc42-dependent reorganization of collagen fibers in the extracellular matrix by fibroblasts. Inhibiting basal-type cell movement with clinically relevant drugs blocked invasion both in organotypic culture and in animals, suggesting a new treatment strategy for early-stage patients. Together our findings establish that fibroblast recruitment by basal-type breast cancer cells into early-stage tumors is sufficient to trigger their conversion from a benign, noninvasive DCIS-like stage to a malignant invasive stage. Furthermore, our findings suggest that different subtypes of breast cancer may require distinct types of contributions from the microenvironment to undergo malignant progression.
TWO KINDS OF ANTIGEN SUPPRESSION IN TUMOR CELLS REVEALED BY CELL FUSION
Authors: George Klein, Sten Friberg, Henry Harris
Journal: The Journal of Experimental Medicine (1972)

The Ehrlich ascites tumor, which has been subjected to prolonged selection for growth in allogeneic hosts, possesses powerful mechanisms for the suppression of antigens normally found on the cell surface. It has previously been shown (1, 2) that when cells in which surface antigens are fully expressed are fused with Ehrlich cells, the suppressive mechanisms of the latter continue to operate and the new surface antigens introduced into the hybrid cell by the other partner are also suppressed. In the present paper we describe the properties of hybrids in which one parent cell was the TA3 ascites carcinoma. There are two sublines of this carcinoma which originally arose as a spontaneous mammary carcinoma in a strain A mouse. The TA3/St line has a high concentration of H-2(a) antigens and shows a strain-specific transplantation behavior; the TA3/Ha subline has a drastically reduced antigen concentration and readily transgresses histoincompatibility barriers. The immunoresistant TA3/Ha subline arose spontaneously without having been subjected to any known immunological selection pressure. Hybridization of TA3/Ha cells with normal diploid ACA fibroblasts reestablished full expression of H-2(a) antigens in nine independently derived hybrid clones. Full reestablishment of both D- and K-end components of the H-2(a) complex could be demonstrated. In some hybrid clones the concentration of H-2(a) antigens was found to be comparable to that seen in (A x ACA)F(1) fibroblasts, whereas in others a higher concentration was observed, even exceeding, in some cases, the levels found in the TA3/St line. The H-2(f) complex, contributed by the ACA parent cell, was fully expressed in eight of the nine hybrid clones studied. Antigen suppression thus behaves as a recessive character in the TA3/Ha hybrids, whereas in the Ehrlich hybrids antigen suppression is dominant.
Islet Cell Antibody–Positive Versus –Negative Phenotypic Type 2 Diabetes in Youth
Authors: Hala Tfayli, Fida Bacha, Neslihan Gungor, Silva Arslanian
Journal: Diabetes Care (2009)

OBJECTIVE Using the clamp technique, youths with a clinical diagnosis of type 2 diabetes (CDx-type 2 diabetes) and positive pancreatic autoantibodies (Ab+) were shown to have severe impairment in insulin secretion and less insulin resistance than their peers with negative antibodies (Ab−). In this study, we investigated whether oral glucose tolerance test (OGTT)-derived indexes of insulin secretion and sensitivity could distinguish between these two groups. RESEARCH DESIGN AND METHODS A total of 25 Ab−, 11 Ab+ CDx-type 2 diabetic, and 21 obese control youths had an OGTT. Fasting and OGTT-derived indexes of insulin sensitivity (including the Matsuda index, homeostasis model assessment [HOMA] of insulin resistance, quantitative insulin sensitivity check index, and glucose-to-insulin ratio) and insulin secretion (HOMA of insulin secretion and 30-min insulogenic and C-peptide indexes) were used. Glucagon and glucagon-like peptide (GLP)-1 responses were assessed. RESULTS Fasting C-peptide and C-peptide–to–glucose ratio, and C-peptide area under the curve (AUC) were significantly lower in the Ab+ CDx-type 2 diabetic patients. Other OGTT-derived surrogate indexes of insulin sensitivity and secretion were not different between the Ab+ versus Ab− patients. GLP-1 during the OGTT was highest in the Ab+ youths compared with the other two groups, but this difference disappeared after adjusting for BMI. Ab+ and Ab− CDx-type 2 diabetes had relative hyperglucagonemia compared with control subjects. CONCLUSIONS The clinical measures of fasting and OGTT-derived surrogate indexes of insulin sensitivity and secretion, except for fasting C-peptide and C-peptide AUC, are less sensitive tools to distinguish metabolic/pathopysiological differences, detected by the clamp, between Ab+ and Ab− CDx-type 2 diabetic youths. This underscores the importance of using more sensitive methods and the importance of determining antibody status in obese youths with CDx-type 2 diabetes.
Contribution of Hepatic Cytochrome P450 3A4 Metabolic Activity to the Phenomenon of Clopidogrel Resistance
Authors: Wei C. Lau, Paul A. Gurbel, Paul B. Watkins, Charlene J. Neer, Amy S. Hopp, David G.M. Carville, Kirk E. Guyer, Alan R. Tait, Eric R. Bates
Journal: Circulation (2004)

Interindividual variability of platelet inhibition after aspirin or clopidogrel administration has been described. Additionally, aspirin resistance and clopidogrel resistance occur in some individuals. Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity.Platelet aggregation was measured before and after clopidogrel treatment in 32 patients undergoing coronary artery stent implantation and in 35 healthy volunteers. The erythromycin breath test was used to measure CYP3A4 activity in vivo in 25 of the healthy volunteers. Individual platelet aggregation was studied in 10 healthy volunteers after the coadministration of clopidogrel and rifampin (a CYP3A4 inducer). Clopidogrel nonresponders, low responders, and responders were defined by a relative inhibition of adenosine diphosphate (20 micromol/L)-induced platelet aggregation of <10%, 10% to 29%, and > or =30%, respectively. Among patients, 22% were clopidogrel nonresponders, 32% were low responders, and 47% were responders. Among volunteers, 16% were nonresponders, 12% were low responders, and 72% were responders. Percent platelet aggregation after clopidogrel inversely correlated with CYP3A4 activity (r=-0.6, P=0.003). Improved platelet inhibition in volunteers resistant to clopidogrel was observed with the coadministration of clopidogrel and rifampin.Clopidogrel administration results in interindividual variability in platelet inhibition, which correlates with CYP3A4 metabolic activity. Measurement of antiplatelet drug efficacy with a point-of-care device and alternative antithrombotic strategies for aspirin or clopidogrel nonresponders and low responders could reduce the incidence of thrombotic events that continue to occur despite oral antiplatelet therapy.
Histologic features of melanoma associated with CDKN2A genotype
Authors: Michael R. Sargen, Peter A. Kanetsky, Julia Newton-Bishop, Nicholas K. Hayward, Graham J. Mann, Nelleke A. Gruis, Margaret A. Tucker, Alisa M. Goldstein, Giovanna Bianchi-Scarra, Susana Puig, David E. Elder
Journal: Journal of the American Academy of Dermatology (2015)