tbuckley/cabot-search huggingface dataset:
A Phylogenomic Investigation into the Origin of Metazoa
Authors: Iñaki Ruiz-Trillo, Andrew J. Roger, Gertraud Burger, Michael W. Gray, B. Franz Lang
Journal: Molecular Biology and Evolution (2008)

The evolution of multicellular animals (Metazoa) from their unicellular ancestors was a key transition that was accompanied by the emergence and diversification of gene families associated with multicellularity. To clarify the timing and order of specific events in this transition, we conducted expressed sequence tag surveys on 4 putative protistan relatives of Metazoa including the choanoflagellate Monosiga ovata, the ichthyosporeans Sphaeroforma arctica and Amoebidium parasiticum, and the amoeba Capsaspora owczarzaki, and 2 members of Amoebozoa, Acanthamoeba castellanii and Mastigamoeba balamuthi. We find that homologs of genes involved in metazoan multicellularity exist in several of these unicellular organisms, including 1 encoding a membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI) in Capsaspora. In Metazoa, MAGI regulates tight junctions involved in cell-cell communication. By phylogenomic analyses of genes encoded in nuclear and mitochondrial genomes, we show that the choanoflagellates are the closest relatives of the Metazoa, followed by the Capsaspora and Ichthyosporea lineages, although the branching order between the latter 2 groups remains unclear. Understanding the function of "metazoan-specific" proteins we have identified in these protists will clarify the evolutionary steps that led to the emergence of the Metazoa.
Staphylococcal Enterotoxins G and I, a Cause of Severe but Reversible Neonatal Enteropathy
Authors: Sandhia Naik, Fabienne Smith, John Ho, Nicholas M. Croft, Paola Domizio, Elisabeth Price, Ian R. Sanderson, Nigel J. Meadows
Journal: Clinical Gastroenterology and Hepatology (2007)
Audit study of next of kin's satisfaction with clinical necropsy service
Authors: R D Start, S J Sherwood, G Kent, C A Angel
Journal: BMJ (1996)

The public may have considerable appreciation of the nature and purposes of necropsy,1 but these attitudes could change when people are faced with requests for necropsies on members of their own family. We investigated the level of satisfaction of bereaved relatives with a clinical necropsy service.

We selected 206 consecutive requests for clinical necropsies for inclusion in our study. At least six months (range 6-14 months) after the requests had been made, a specially trained academic psychologist tried to contact the relatives whose consent had been requested. Sixty seven of the relatives were excluded because they could not be contacted, they gave incomplete information, or there were issues of confidentiality or litigation. Of the remaining 139 relatives, 75 participated in the study—31 by the preferred method of personal interview, 31 by postal …
Autonomic Control of Insulin Secretion and the Treatment of Heart Failure
Authors: P. A. Majid, C. Saxton, J. R. W. Dykes, M. C. Galvin, S. H. Taylor
Journal: BMJ (1970)

To investigate the role of the autonomic nervous system in controlling insulin secretion 13 normal subjects and 5 patients with heart failure underwent insulin secretion tests. Alpha-adrenergic stimulation and beta-receptor blockade significantly depressed the secretion of insulin in response to intravenous tolbutamide in normal subjects, while both alpha-blockade and beta-stimulation significantly increased the insulin secretion response in both normal subjects and patients in heart failure. Parasympathetic stimulation and blockade had no significant effect on the insulin secretion response. These findings suggest that drugs that block the alpha-adrenergic receptors or stimulate the beta-adrenergic receptors by their ability to counteract the insulin suppression resulting from increased sympathetic nervous activity may play a vital metabolic part in the deranged metabolism of the failing heart in addition to their direct haemodynamic benefits.
Abstract 1349: Chemosensitization of breast cancer cell lines by <i>Ell3</i>
Authors: Hee-Jin Ahn, Sun-Hee Heo, Gwangil Kim, Kyung-Soon Park
Journal: Cancer Research (2014)

Abstract Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven-nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis by the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. Contrary to our expectation, ectopic expression of Ell3 in MCF7 induces CDDP (cisplatin) susceptibility by enhancing p53 dependent apoptosis. CDDP treatments leads to the accumulation of p53 protein in the Ell3 overexpressing MCF7. We confirmed that Ell3 inhibits proteosomal degradation of p53 upon cisplatin treatment in MCF7. Ell3 also confer chemosensitivity to MCF7 to DNA damaging agent, camptothecin. The treatment of camptothecin to Ell3 overexpressing MCF7 results in the accumulation of cells at G2/M phase of cell cycle by the increases of p53 protein. Consistent with these results, Ell3 downregulates the expression of MDM2, which binds p53 and marks it for degradation using the proteasome. The underlying mechanism of Ell3 to regulate MDM2 expression is under investigation. Citation Format: Hee-Jin Ahn, Sun-Hee Heo, Gwangil Kim, Kyung-Soon Park. Chemosensitization of breast cancer cell lines by Ell3. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1349. doi:10.1158/1538-7445.AM2014-1349
A memorable patient: "There is nothing wrong with me"
Authors: M. Oliver
Journal: BMJ (1997)

“Next, please,” and in came a spry, fit looking, silver haired man. In answer to the usual question, “What can I do for you?” he replied, “I am not complaining of anything. There is nothing wrong with me.”

There was no letter from his general practitioner. Why not? “Because there was no point in troubling him, so I came straight to you because you are the consultant for outpatients.” There was open access in the general medical outpatients department in the Royal Infirmary of …
Abstract B76: Novel human 3D in vitro invasion model identifies tumor and stroma heterogeneity in squamous cell carcinoma
Authors: Manuel Berning, Petra Boukamp
Journal: Cancer Research (2015)

Abstract 3D in vitro skin models are valuable research tools to investigate normal keratinocyte as well as skin carcinoma cell interaction with dermal fibroblasts. Currently, the models lack either a structured vital human extracellular matrix or long-term stability and longevity. Therefore, we aimed at a new 3D in vitro skin model for normal human epidermis and tumorigenic stages of skin cancer. This model is based on dermal equivalents containing a highly structured cell-derived matrix (CDM) produced by human dermal fibroblasts. First, we show that the CDM dermal equivalent supports a high structural integrity of the skin model and maintains a vital epidermis for six months. The epidermis is well-stratifying and differentiates in a regular orthokeratotic pattern. Transmission electron microscopy reveals ultrastructural entities as basement membranes, hemidesmosomes, desmosomes, keratohyalin granulae and lamellar bodies. In line, the molecular differentiation markers are properly distributed. Second, five non-tumorigenic and tumorigenic HaCaT keratinocyte variants are tested for their proliferation, differentiation and invasion capacities. After four weeks of co-cultivation the tumorigenic HaCaT variants show hyperproliferative epithelia and lose the capability of an ordered stratification and differentiation. Furthermore, they destroy the basement membrane as well as the extracellular matrix and invade the dermal equivalent. Moreover, seven squamous cell carcinoma (SCC) cell lines were co-cultivated with the CDM dermal equivalent. All SCC cells form hyperproliferative epithelia that heavily invade the extracellular matrix. Remarkably, the epithelia are individually distinct for their invasion and differentiation capacity. Thus, the CDM-based skin cancer model is suitable for demonstrating the heterogeneity of SCC tumors and their interaction with the microenvironment. In conclusion, the CDM model for normal skin and tumorigenic keratinocytes provides a novel tool to investigate keratinocyte-fibroblast interactions and microenvironment modulations during SCC development. Therefore, this system will provide further insights into mechanistic processes and the interaction of SCCs with their tumor microenvironment. Citation Format: Manuel Berning, Petra Boukamp. Novel human 3D in vitro invasion model identifies tumor and stroma heterogeneity in squamous cell carcinoma. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B76. doi:10.1158/1538-7445.CHTME14-B76
MRI Study of Cavum Septi Pellucidi in Schizophrenia, Affective Disorder, and Schizotypal Personality Disorder
Authors: Jun Soo Kwon, Martha E. Shenton, Yoshio Hirayasu, Dean F. Salisbury, Iris A. Fischer, Chandlee C. Dickey, Deborah Yurgelun-Todd, Mauricio Tohen, Ron Kikinis, Ferenc A. Jolesz, Robert W. McCarley
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: A cavum between the septi pellucidi may reflect neurodevelopmental anomalies in midline structures of the brain. The authors examined cavum septi pellucidi in subjects with schizophrenia, affective disorder, and schizotypal personality disorder and in normal subjects. METHOD: Thirty schizophrenic patients (15 chronic, 15 first-episode), 16 patients with affective disorder (first-episode), 21 patients with schizotypal personality disorder, and 46 normal subjects were evaluated with magnetic resonance imaging. Cavum septi pellucidi was assessed by counting the number of 1.5-mm slices containing cavum septi pellucidi. RESULTS: The presence or absence of cavum septi pellucidi did not differentiate among groups. However, the prevalence of abnormal cavum septi pellucidi (i.e., cavum septi pellucidi contained on four or more slices) was 30.4% for schizophrenic patients (36.4% for chronic, 25.0% for first-episode), 20.0% for patients with affective disorder, 18.8% for patients with schizotypal personality disorder, and 10.3% for normal subjects. When the authors used the Nopoulos et al. criteria for rating cavum septi pellucidi, which omitted borderline cases with cavum septi pellucidi on three slices, the prevalence of abnormal cavum septi pellucidi increased to 35.0% for schizophrenia (40.0% for chronic, 30.0% for first-episode), 25.0% for affective disorder, 27.3% for schizotypal personality disorder, and 13.0% for normal subjects. There was a statistically significant difference in ratings between schizophrenic and normal subjects. CONCLUSIONS: The results suggest that alterations in midline structures during the course of neurodevelopment may play a role in the pathogenesis of schizophrenia.
Rhinoconjunctivitis and bronchial asthma due to monosensitization to Quercus pollen*1
Authors: J. Bartra, M.San Miguel-Moncin, M. Lombardero, R. Alonso, B. Fernández Parra, R. Tella, A. Cistero-Bahima
Journal: Journal of Allergy and Clinical Immunology (2004)
Unraveling how Giardia infections cause disease
Authors: Theodore E. Nash
Journal: Journal of Clinical Investigation (2013)

A 40-year-old NIH male scientist camped and fished in a remote lake in Alaska. On his return, he developed diarrhea, cramps, and loose stools without blood or mucus in the absence of fever and was diagnosed with giardiasis. A 3-year-old female living in the Florida Keys complained of intermittent stomachaches over a 2-month period. Her stools were variably loose. The patient was diagnosed with giardiasis, which led to examination of her mother, father, and brother, who were mildly symptomatic; all 3 were subsequently diagnosed with giardiasis. The child’s only exposure was from swimming in a local community pool. A 40-year-old male from Mexico, who resided in Virginia and worked as a cook in a fast food restaurant, was diagnosed with giardiasis. He denied any symptoms and was not allowed to prepare food. Treatment with metronidazole, nitazoxanide, and albendazole failed to eradicate the infection. He was successfully treated with the combination of paromomycin and metronidazole.
Learning Clinical Reasoning
Authors: Dennis Rosen
Journal: JAMA (2010)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Mechanism of compensatory hyperinsulinemia in normoglycemic insulin-resistant spontaneously hypertensive rats. Augmented enzymatic activity of glucokinase in beta-cells.
Authors: C Chen, H Hosokawa, L M Bumbalo, J L Leahy
Journal: Journal of Clinical Investigation (1994)

The cause of compensatory hyperinsulinemia in normoglycemic insulin-resistant states is unknown. Using spontaneously hypertensive rats (SHR), we tested the hypothesis that a lowered beta-cell set-point for glucose causes a hypersecretion of insulin at a normal glucose level. Islets isolated from normoglycemic hyperinsulinemic SHR were compared to age-matched (12 wk old) Wistar-Kyoto (WK) rats. The ED50 for glucose-induced insulin secretion was 6.6 +/- 1.0 mM glucose in SHR versus 9.6 +/- 0.5 mM glucose in WK (P < 0.02). Glucokinase enzymatic activity was increased 40% in SHR islets (P < 0.02) without any change in the glucokinase protein level by Western blot. The level of the beta-cell glucose transporter (GLUT-2) was increased 75% in SHR islets (P < 0.036). In summary, the beta-cell sensitivity for glucose was increased in these normoglycemic insulin resistant rats by an enhanced catalytic activity of glucokinase. We have identified a regulatory system for glucokinase in the beta-cell which entails variable catalytic activity of the enzyme, is modulated in response to variations in whole-body insulin sensitivity, and is not dependent on sustained changes in the plasma glucose level.
Presymptomatic testing for Huntington's disease in the United Kingdom. The United Kingdom Huntington's Disease Prediction Consortium.
Authors: A. Tyler, D. Ball, D. Craufurd
Journal: BMJ (1992)

To evaluate the United Kingdom Huntington's disease presymptomatic testing programme.Postal questionnaire survey to collect data on all tests performed by clinical genetics centres between 1987 and 1990.Genetic centres providing presymptomatic testing in the United Kingdom.248 subjects at risk of Huntington's disease who had presymptomatic testing at their request.Sex, age, prior risk, and risk after testing.The risk of carrying the Huntington disease gene was reduced for 151 (61%) of the applicants and raised for 97 (39%). 158 (64%) of the subjects were female and 90 (36%) male. The median age at which the results were given was 32.5 years.The demand for testing was lower than expected and may have reached its peak in 1990. The excess of low risk results was not fully explained by the age effect. All the genetics centres concerned have agreed a common service protocol which requires extensive pre-test counselling and post-test follow up. The worth of the procedure remains to be decided. The availability of a large body of pooled data from all the United Kingdom testing centres, which individually are likely to have only a few results, will form a valuable resource for monitoring the long term psychosocial impact of testing.
Prognostic Biomarkers in Head and Neck Cancer
Authors: Jennifer R. Grandis
Journal: Clinical Cancer Research (2006)

Most of the cancers that arise in the mucosa of the upper aerodigestive tract, including the oral cavity, pharynx, and larynx, are squamous cell carcinomas. To date, although there are no primary mutations that have been discovered to cause these cancers, aberrant expression of a variety of
Very severe thrombocytopenia and fragmentation hemolysis mimicking thrombotic thrombocytopenic purpura associated with a giant intracardiac vegetation infected with <i>Staphylococcus epidermidis</i>: Role of monocyte procoagulant activity induced by bacterial supernatant
Authors: Kathleen Selleng, Theodore E. Warkentin, Andreas Greinacher, Andrew M. Morris, Irwin R. Walker, H. Alexander Heggtveit, Petra Eichler, Irene J. Cybulsky
Journal: American Journal of Hematology (2006)

Abstract The pathogenesis of very severe thrombocytopenia in bacterial endocarditis is uncertain. We report a 50‐year‐old male with platelet counts &lt; 10 × 10 9 /l and fragmentation hemolysis complicating Staphyloccoccus epidermidis pacemaker endocarditis with a giant vegetation. Antibiotics, corticosteroids, high‐dose intravenous gammaglobulin, and plasmapheresis (for initially‐suspected thrombotic thrombocytopenic purpura) failed to produce significant platelet count increase. However, therapeutic‐dose heparin anticoagulation was associated with a platelet count increase from &lt;10 to ∼40 × 10 9 /l, with parallel reduction in thrombin‐antithrombin complexes (from 8.9 to 3.5 μg/l), facilitating surgical intervention. The thrombocytopenia promptly resolved following surgical removal of the vegetation. Culture supernatant from S. epidermidis isolated from the patient's blood induced monocytes to express procoagulant activity (assessed by factor Xa generation) equivalent to lipopolysaccharide (1 μg/ml), with half‐maximal activation seen with culture supernatant diluted to 1:12,800. These data are consistent with previous animal models of endocarditis demonstrating staphylococci‐induced procoagulant changes in monocytes. This case demonstrates that heparin anticoagulation can be therapeutic in infective endocarditis‐associated severe thrombocytopenia in a non‐bleeding patient, and that such therapy may ameliorate the platelet count enough to permit surgical intervention. Am. J. Hematol 2007. © 2006 Wiley‐Liss, Inc.
Phase II Study of Neoadjuvant Imatinib in Glioblastoma: Evaluation of Clinical and Molecular Effects of the Treatment
Authors: Evangelia Razis, Panayotis Selviaridis, Stephanos Labropoulos, Jeremy L. Norris, Mei-Jun Zhu, David D. Song, Thea Kalebic, Michael Torrens, Anna Kalogera-Fountzila, George Karkavelas, Sofia Karanastasi, Jonathan A. Fletcher, George Fountzilas
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Phase I-II studies indicate that imatinib is active in glioblastoma multiforme. To better understand the molecular and clinical effects of imatinib in glioblastoma multiforme, we conducted a neoadjuvant study of imatinib with pretreatment and posttreatment biopsies. Experimental Design: Patients underwent a computerized tomography-guided biopsy of their brain tumors. If diagnosed with glioblastoma multiforme, they were immediately treated with 7 days of imatinib 400 mg orally twice daily followed by either definitive surgery or re-biopsy. Pretreatment and posttreatment tissue specimens were tested by immunohistochemistry for Ki67 and microvessel destiny, and posttreatment specimens were analyzed for the presence of intact imatinib in tissue. Furthermore, pretreatment and posttreatment pairs were analyzed by Western blotting for activation of platelet-derived growth factor receptor, epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase/AKT, and mitogen-activated protein kinase signaling pathways. Pharmacokinetic studies were also done. Results: Twenty patients were enrolled. Median survival was 6.2 months. Intact imatinib was detected in the posttreatment tissue specimens using mass spectrometry. There was no evidence of a drug effect on proliferation, as evidenced by a change in Ki67 expression. Biochemical evidence of response, as shown by decreased activation of AKT and mitogen-activated protein kinase or increased p27 level, was detected in 4 of 11 patients with evaluable, matched pre- and post-imatinib biopsies. Two patients showed high-level EGFR activation and homozygous EGFR mutations, whereas one patient had high-level platelet-derived growth factor receptor-B activation. Conclusions: Intact imatinib was detected in glioblastoma multiforme tissue. However, the histologic and immunoblotting evaluations suggest that glioblastoma multiforme proliferation and survival mechanisms are not substantially reduced by imatinib therapy in most patients. (Clin Cancer Res 2009;15(19):6258–66)
Prenatal Care and HIV Screening
Authors: Andrew M. Kaunitz
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The most common risk factors for women with human immunodeficiency virus (HIV) infection in the United States are intravenous drug abuse and heterosexual contact with persons at risk.<sup>1</sup>Some women, however, are unaware that their sexual partners belong to a high-risk group. For these reasons, we offered screening for antibodies to HIV to all women presenting for prenatal care at our clinic for indigent patients from Dec 12, 1987, to March 12, 1987. <h3>Study.—</h3> A questionnaire asking for known HIV risk factors was administered. Women were considered seropositive if results of two enzyme immunoassays for antibodies to HIV and a confirmatory Western blot analysis were positive. After counseling and obtaining informed consent, 299 of 302 women were screened. Overall, two (6.7 per 1000) of these women were seropositive. Of 39 women reporting one or more risk factors, one (25.7 per 1000) was seropositive. Of the 250 women
Abnormalities in the Distribution of Serum Immunoglobulin Concentrations in Juvenile Rheumatoid Arthritis
Authors: James T. Cassidy, Ross E. Petty, Donita B. Sullivan
Journal: Journal of Clinical Investigation (1973)

Concentrations of serum IgG. IgA, and IgM were determined in 200 patients with juvenile rheumatoid arthritis. The relative frequency distribution of IgG and IgM approached that of a log-normal curve; however, there was marked skewing of the distribution of the serum concentrations of IgA. The prevalence of selective IgA deficiency was 4%. In order to permit further intragroup comparisons, the serum immunoglobulin concentrations were standardized by comparison to a sex-age matched control group. By this process it was found that there was concordance of the serum levels of IgG with IgA, and IgG with IgM. The standardized concentrations of IgA and IgM were less in females than males. The aberration in distribution of serum IgA concentrations found in this study, and the relative inability of females to respond to their disease by increasing specific serum immunoglobulin levels, add further data supporting the concept of immunodeficiency in the pathogenesis of juvenile rheumatoid arthritis.