tbuckley/cabot-search huggingface dataset:
Sarcoidosis Presenting as Multiple Pulmonary Nodules
Authors: Raj B. Dhakhwa
Journal: JAMA (1976)

CHEST roentgenograms of patients with sarcoidosis vary from hilar adenopathy to diffuse parenchymal involvement of the lung. We report an unusual pulmonary nodular form of sarcoidosis that was confirmed histologically by transbronchial lung biopsy specimens. <h3>Report of a Case</h3> A 26-year-old woman was admitted to Saint Michael's Medical Center because of weight loss, fatigue, and night sweats of three months' duration. Four weeks prior to admission, she complained of a productive cough accompanied by chest pain. She also noticed pain in her ankles associated with transient nodules on the anterior surfaces of her legs. A purified protein derivative (PPD) (five tuberculin units) three months prior to her admission was reportedly negative. Because of the persistence of weight loss and fever, she was admitted for evaluation. On physical examination, she was found to have a pulse of 90 beats per minute at rest and a temperature of 38 C. No serious
Realities of medicine in South Africa lie behind its brain drain
Authors: T. van Rensburg
Journal: BMJ (2012)

The often stated claims about the huge amounts of money that sub-Saharan countries spend on training doctors only to lose them to “poachers” from developed countries is misleading at best and dishonest at worst.1

Tertiary education in South Africa is extremely expensive for students, and medicine is one of the most expensive courses. In most cases the only option …
MARCKS Regulates Growth and Radiation Sensitivity and Is a Novel Prognostic Factor for Glioma
Authors: John S. Jarboe, Joshua C. Anderson, Christine W. Duarte, Tapan Mehta, Somaira Nowsheen, Patricia H. Hicks, Alexander C. Whitley, Timothy D. Rohrbach, Raymond O. McCubrey, Sherard Chiu, Tamara M. Burleson, James A. Bonner, G. Yancey Gillespie, Eddy S. Yang, Christopher D. Willey
Journal: Clinical Cancer Research (2012)

Abstract Purpose: This study assessed whether myristoylated alanine-rich C-kinase substrate (MARCKS) can regulate glioblastoma multiforme (GBM) growth, radiation sensitivity, and clinical outcome. Experimental Design: MARCKS protein levels were analyzed in five GBM explant cell lines and eight patient-derived xenograft tumors by immunoblot, and these levels were correlated to proliferation rates and intracranial growth rates, respectively. Manipulation of MARCKS protein levels was assessed by lentiviral-mediated short hairpin RNA knockdown in the U251 cell line and MARCKS overexpression in the U87 cell line. The effect of manipulation of MARCKS on proliferation, radiation sensitivity, and senescence was assessed. MARCKS gene expression was correlated with survival outcomes in the Repository of Molecular Brain Neoplasia Data (REMBRANDT) Database and The Cancer Genome Atlas (TCGA). Results: MARCKS protein expression was inversely correlated with GBM proliferation and intracranial xenograft growth rates. Genetic silencing of MARCKS promoted GBM proliferation and radiation resistance, whereas MARCKS overexpression greatly reduced GBM growth potential and induced senescence. We found MARCKS gene expression to be directly correlated with survival in both the REMBRANDT and TCGA databases. Specifically, patients with high MARCKS expressing tumors of the proneural molecular subtype had significantly increased survival rates. This effect was most pronounced in tumors with unmethylated O6-methylguanine DNA methyltransferase (MGMT) promoters, a traditionally poor prognostic factor. Conclusions: MARCKS levels impact GBM growth and radiation sensitivity. High MARCKS expressing GBM tumors are associated with improved survival, particularly with unmethylated MGMT promoters. These findings suggest the use of MARCKS as a novel target and biomarker for prognosis in the proneural subtype of GBM. Clin Cancer Res; 18(11); 3030–41. ©2012 AACR.
A SEX-LINKED DEFECT IN THE CROSS-LINKING OF COLLAGEN AND ELASTIN ASSOCIATED WITH THE MOTTLED LOCUS IN MICE
Authors: David W. Rowe, Ermona B. McGoodwin, George R. Martin, Michael D. Sussman, Douglas Grahn, Barbara Faris, Carl Franzblau
Journal: The Journal of Experimental Medicine (1974)

A genetic abnormality in collagen and elastin cross-linking resembling experimental lathyrism has been identified in mice. The defect is an X-linked trait, attributed to the mottled locus which also influences coat color. The affected mice have aneurysms of the aorta and its branches, weak skin, and bone deformities in a spectrum of severity varying with the alleles at the mottled locus. A defect in the cross-linking of collagen was demonstrated in the skin of the affected animals by a marked increase in collagen extractability and a reduced proportion of cross-linked components in the extracted collagen. A decrease in lysine-derived aldehyde levels was found in both skin collagen and aortic elastin similar to that found in lathyritic tissue. Furthermore the in vitro formation of lysine-derived aldehyde was reduced. Thus the cause of the connective tissue abnormalities in these mice appears to be a defect in cross-link formation due to an impairment in aldehyde formation.
Tropical bacterial diseases
Authors: Jashin J Wu, Katie R. Pang, Omar Lupi, Stephen K. Tyring
Journal: Journal of the American Academy of Dermatology (2004)

Bacterial tropical infections are the cause of multiple illnesses such as bartonellosis, tropical ulcers, and tropical pyomyositis. Such sexually transmitted bacterial diseases such as granuloma inguinale and lymphogranuloma venereum are important diseases in some countries of the world. Other important groups of bacterial diseases are the non-venereal treponematosis such as pinta and yaws. Mycobacteriosis, caused by acid-fast, weakly gram-positive, nonsporulating rods have, however, a special impact on the tropical countries. It has been estimated that the genus Mycobacterium causes more suffering for humans than all the other bacterial genera combined. Leprosy is still a major challenge in most tropical countries, as is tuberculosis. In addition, the so-called atypical mycobacteria are increasingly recognized as human pathogens and may be the cause of skin disease more frequently than M. tuberculosis, especially Buruli ulcer. This poster will briefly discuss these disease entities and their treatment options.
Oppression of Left Main Trunk Due to Pseudoaneurysm With Graft Detachment in Patients With Behcet Disease Previously Treated by Bentall Procedure
Authors: Yu Kataoka, Takeshi Tsutsumi, Kouhei Ishibashi, Masahiro Higashi, Isao Morii, Atsushi Kawamura, Hatsue Ishibashi-Ueda, Kenji Minatoya, Hitoshi Ogino, Yoritaka Otsuka
Journal: Circulation (2009)
Elevated hexokinase increases cardiac glycolysis in transgenic mice
Authors: Q Liang
Journal: Cardiovascular Research (2002)

Objective: Cardiac glucose metabolism is critical to normal and pathological function. The significance of the first committed metabolic step, glucose phosphorylation, has not been established. In this study a new transgenic model was developed in order to investigate the importance of this enzymatic step in cardiac glycolysis. Methods: Transgenic mice were produced that overexpress yeast hexokinase B under the control of a cardiac specific promoter. Yeast hexokinase B is a high affinity enzyme that is not inhibited by glucose-6-phosphate. Hexokinase enzyme activity was measured by a modified radiometric procedure. Cardiac glucose metabolism and contractility were measured in the Langendorff mode. Cardiac glycogen content and glucose-6-phosphate independent glycogen synthase activity were also determined. Results: In transgenic hearts hexokinase activity was significantly elevated and increased glucose metabolism, particularly in the presence of insulin and during cardiac reperfusion. However during ischemic perfusion the effect of the transgene on glycolysis was minimal. Under all conditions tested there was no effect of hexokinase on contractility. Glycogen content of transgenic hearts was elevated 2-fold and glucose-6-phosphate independent glycogen synthase was also increased. Conclusion: These results demonstrate that glucose phosphorylation is a key step in determining cardiac glucose metabolism under oxidative conditions.
Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex.
Authors: J Sprent
Journal: The Journal of Experimental Medicine (1978)

F1 leads to parent bone marrow chimeras were prepared by transferring F1 hybrid marrow cells into heavily irradiated parental strain mice. When unprimed, donor-derived F1 T cells from the chimeras were activated to sheep erythrocytes (SRC) for 5 days in irradiated normal F1 mice, high IgM and IgG anti-SRC responses were observed with F1 B cells, and with B cells H-2-compatible with the strain in which the T cells were raised from stem cells. Significantly, however, responses with B cells of the opposite parental strain were either absent or very low. The restriction in T-helper function mapped to the K-end of the H-2 complex and could not be attributed to active suppression.
Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis
Authors: Adriano Boasso, Caroline M. Royle, Spyridon Doumazos, Veronica N. Aquino, Mara Biasin, Luca Piacentini, Barbara Tavano, Dietmar Fuchs, Francesco Mazzotta, Sergio Lo Caputo, Gene M. Shearer, Mario Clerici, David R. Graham
Journal: Blood (2011)
Metabolic Syndrome Accompanied by Hypercholesterolemia Is Strongly Associated With Proinflammatory State and Impairment of Fibrinolysis in Patients With Type 2 Diabetes
Authors: Yoshimasa Aso, Sadao Wakabayashi, Ruriko Yamamoto, Rika Matsutomo, Kohzo Takebayashi, Toshihiko Inukai
Journal: Diabetes Care (2005)

To determine whether plasma concentrations of thrombin-activatable fibrinolysis inhibitor (TAFI) in patients with type 2 diabetes were associated with components of metabolic syndrome (MS), including high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI)-1, and LDL cholesterol.We studied 136 consecutive patients with type 2 diabetes. Diagnosis of MS was diagnosed by current criteria. Hypercholesterolemia (HC) was defined as serum LDL cholesterol >140 mg/dl (3.6 mmol/l) or treatment with a statin. For comparisons, diabetic patients were divided into four groups: those with no MS and no HC (n = 38), with MS but not HC (n = 39), with no MS but with HC (n = 26), and with both MS and HC (n = 33).Considering all patients with type 2 diabetes, plasma PAI-1 was strongly associated with MS components such as BMI, triglyceride, alanine aminotransferase, a homeostasis model assessment of insulin resistance, and hs-CRP. Plasma TAFI only correlated positively and independently with LDL cholesterol. Plasma concentrations of plasmin-alpha2-antiplasmin complex (PAP), a measure of fibrinolytic activity in blood, showed a significant negative correlation with plasma PAI-1 but not TAFI. Diabetic patients with both MS and HC had the highest serum hs-CRP concentrations and the lowest plasma PAP concentrations.LDL cholesterol is a main determinant of plasma TAFI in patients with type 2 diabetes. Coexistence of MS and HC synergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of both TAFI and PAI-1, which inhibit fibrinolysis.
Genetic variability in the multidrug resistance associated protein-1 (ABCC1/MRP1) predicts hematological toxicity in breast cancer patients receiving (neo-)adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC)
Authors: C. Vulsteke, D. Lambrechts, A. Dieudonné, S. Hatse, B. Brouwers, T. van Brussel, P. Neven, A. Belmans, P. Schöffski, R. Paridaens, H. Wildiers
Journal: Annals of Oncology (2013)
Local anesthetics and the role of sodium in the force development by canine ventricular muscle and purkinje fibers.
Authors: M Vassalle, M Bhattacharyya
Journal: Circulation Research (1980)

We studied the effects of the local anesthetics, procaine and benzocaine, on the action potential and force of canine ventricular muscle and Purkinje fibers. In ventricular muscle, procaine often shifted the plateau to a more positive value and increased the force of contraction, whereas benzocaine shortened the action potential and decreased contractile force. In Purkinje fibers, both local anesthetics reduced contractile force and decreased the duration of the action potential markedly. In ventricular muscle fibers norepinephrine potentiated the positive inotropic effect of procaine and changed the effects of benzocaine from a negative to a positive inotropic effect. The potentiating effect of procaine on contraction was eliminated by propranolol. In the presence of norepinephrine (and the absence of propranolol), in Purkinje fibers both anesthetics decreased force but less than in the absence of norepinephrine. In the presence of tetrodotoxin (TTX) and norepinephrine, procaine and benzocaine increased contractile force of muscle fibers. Under the same conditions in Purkinje fibers, procaine increased contractile force and benzocaine decreased it (but less than in the absence of TTX). Administration of veratridine increased contractile force in both ventricular muscle and Purkinje fibers: under these conditions, both local anesthetics decreased contractile force in both tissues. We conclude that: (1) the positive inotropic effects of procaine and benzocaine are mediated through an adrenergic mechanism; (2) the negative inotropic effect is at least in part mediated through a reduction of sodium influx; and (3) the negative inotropic effect is more pronounced in Purkinje fibers because of a larger steady state sodium influx during the plateau.
Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons
Authors: Rui Liu, Sridhar Hannenhalli, Maja Bucan
Journal: Genome biology (2009)

Hundreds of proteins modulate neurotransmitter release and synaptic plasticity during neuronal development and in response to synaptic activity. The expression of genes in the pre- and post-synaptic neurons is under stringent spatio-temporal control, but the mechanism underlying the neuronal expression of these genes remains largely unknown.Using unbiased in vivo and in vitro screens, we characterized the cis elements regulating the Rab3A gene, which is expressed abundantly in presynaptic neurons. A set of identified regulatory elements of the Rab3A gene corresponded to the defined Rab3A multi-species conserved elements. In order to identify clusters of enriched transcription factor binding sites, for example, cis-regulatory modules, we analyzed intergenic multi-species conserved elements in the vicinity of nine presynaptic genes, including Rab3A, that are highly and specifically expressed in brain regions. Sixteen transcription factor binding motifs were over-represented in these multi-species conserved elements. Based on a combined occurrence for these enriched motifs, multi-species conserved elements in the vicinity of 107 previously identified presynaptic genes were scored and ranked. We then experimentally validated the scoring strategy by showing that 12 of 16 (75%) high-scoring multi-species conserved elements functioned as neuronal enhancers in a cell-based assay.This work introduces an integrative strategy of comparative genomics, experimental, and computational approaches to reveal aspects of a regulatory network controlling neuronal-specific expression of genes in presynaptic neurons.
Early Diagnosis and Monitoring of Transplanted Human Malignant Mesothelioma by Serum Hyaluronic Acid
Authors: J. Roboz, A. P. Chahinian, J. F. Holland, D. Silides, L. Szrajer
Journal: JNCI Journal of the National Cancer Institute (1989)

Serum concentrations of unhydrolyzed hyalnronic acid (HA) in nude mice bearing human malignant mesothelioma xenografts were determined by size-exclusion chromatog-raphy. HA rose to 8–16 μg/mL (controls: <1 μg/L) by the fourth to fifth day after tumor (epithelial) transplantation, 3 to 5 days before palpability. Decreases in HA during late tumor growth are probably attributed to tumor necrosis, based on the observation that HA was 2.5 times less in necrotic than in viable tumor tissues. This serum biomarker, recognizable before physical detectabihty of xenografted tumors, should have applicability to monitoring experimental chemotherapy in mice and to early diagnosis and monitoring of human malignant mesothelioma. [J Natl Cancer Inst 81:924-928, 1989]
Neuropsychological Impairment and Its Neurological Correlates in Adult Offspring With Heightened Risk for Schizophrenia and Affective Psychosis
Authors: Erland W. Schubert, Thomas F. McNeil
Journal: American Journal of Psychiatry (2005)

Schizophrenia is generally considered to be a neurodevelopmental disorder reflected in findings of neuropsychological impairments and neurological abnormality in patients and their relatives. The authors investigated whether neuropsychological impairments are related to neurological abnormality and whether such deficits also characterize risk for affective psychosis.In a longitudinal study with a 93% rate of effective follow-up, the authors investigated neuropsychological impairment and its relation to neurological abnormality at a mean age of 22.3 years in 74 offspring of mothers with a history of psychotic disorders (38 offspring with heightened risk for schizophrenia and 36 with risk for affective psychosis) and 88 normal-risk offspring born to mothers with no history of psychosis.Offspring with genetically heightened risk for schizophrenia showed significantly impaired verbal memory, selective attention, and grammatical reasoning, compared with normal-risk offspring. Having impaired verbal memory, attention, and grammatical reasoning functions identified a significantly larger subgroup (16%) among offspring with heightened risk for schizophrenia than among offspring with heightened risk for affective psychosis (0%) and among normal-risk offspring (3%). Multiple neuropsychological functions were significantly related to neurological abnormality in offspring with heightened risk for schizophrenia and in normal-risk offspring but not among offspring with heightened risk for affective psychosis. The extension of schizophrenia and affective psychosis risk groups to include additional offspring of mothers with psychosis-spectrum disorders yielded results similar to those for the core risk groups.The neurocognitive dysfunction attending heightened risk for schizophrenia is likely based on genetically mediated neurodevelopmental factors, with schizophrenia and affective psychosis belonging to different biological spheres.
Elastase activity of bronchoalveolar cells in advanced pulmonary sarcoidosis
Authors: M Mordelet-Dambrine, C Lafuma, G Stanislas-Leguern, L Robert, J Chretien, W Hornebeck
Journal: European Respiratory Journal (1988)

Elastase activities were investigated in bronchoalveolar lavage (BAL) cells from healthy controls (C, n = 8) and patients with untreated mediastinopulmonary sarcoidosis at different stages: I (n = 5), II (n = 7), IIIA (n = 3), IIIB (n = 4). Elastase activities (EA and ELA) were measured against a synthetic substrate, succinyl-trialanine-paranitroanilide (SLAPN) and radiolabelled ligamentum nuchae 3H insoluble elastin (specific radioactivity 3.7 MBq.mg-1). A significant increase of ELA of BAL cells was observed in patients (S III), in particular those exhibiting fibrotic roentgenographic patterns and a higher number of polymorphonuclear cells. On the contrary, EA of BAL cells showed no variation between different stages of sarcoidosis. ELA was never detected in the macrophage culture medium and appeared to be mainly associated with non-adherent macrophages, whereas EA appeared to be preferentially associated with adherent macrophages. The inhibitory profiles of ELA and EA were investigated using general proteinase inhibitors and also compounds interacting specifically with leucocyte elastase. ELA was mainly due to a serine protease, which has a sensitivity to inhibitors similar to leucocyte elastase and is increased in advanced stages of sarcoidosis. EA appears to be only slightly modified, if at all, in sarcoidosis and is probably related to the action of both a serine protease and a metalloenzyme. Thus, only ELA yields diagnostic information concerning stage III of sarcoidosis associated with a fibrotic or bullous roentgenographic pattern.
Widespread transcription of a Qa region gene in adult mice.
Authors: M J Palmer, J A Frelinger
Journal: The Journal of Experimental Medicine (1987)

The mouse MHC class I family includes genes encoded in four regions: H-2K, H-2D, Qa and Tla. While K/D genes are well characterized, relatively little is known about Qa or Tla genes. We have studied the transcription of a B10.P Qa region gene. DNA sequence comparisons of the transmembrane region, supported by Southern blot analysis of cosmid and genomic DNAs from BALB/c and C57BL/10, demonstrate the lambda 3a gene corresponds to Q4p. In both Northern blots and RNA protection experiments using probes derived from the 3' noncoding region, we found that Q4, like the H-2K and H-2D genes, is widely transcribed in B10.P tissues. These data demonstrate for the first time widespread transcription of a Qa gene.
Postgenomic up-regulation of CCL3L1 expression in HTLV-2–infected persons curtails HIV-1 replication
Authors: Elisabetta Pilotti, Lisa Elviri, Elisa Vicenzi, Umberto Bertazzoni, Maria Carla Re, Sonia Allibardi, Guido Poli, Claudio Casoli
Journal: Blood (2006)
Mucosal immune defence mechanisms in enterocolitis complicating Hirschsprung's disease.
Authors: A Imamura, P Puri, D S O'Briain, D J Reen
Journal: Gut (1992)

Enterocolitis remains an important cause of morbidity and mortality in Hirschsprung9s disease. The aetiology of enterocolitis is uncertain-ischaemic and bacterial causes and recently, rotavirus infections, have been suggested. Bowel tissue from 12 patients with Hirschsprung9s disease who underwent Swenson9s operation (five of whom had clinical evidence of enterocolitis) and colon from six controls subjects were examined to investigate possible immunopathological mechanisms associated with the disease. IgA, IgM, and J chain (but not IgG) containing plasma cells were significantly increased in the lamina propria along the entire length of resected bowel in enterocolitis patients, compared with non-enterocolitis patients and controls (p less than 0.01). Luminal secretory component staining of the anganglionic segment of colon from enterocolitis patients was considerably reduced. Lamina propria CD68 positive monocyte/macrophages and CD45RO positive leukocytes were increased in enterocolitis patients compared with non-enterocolitis patients (p less than 0.01). CD57 positive natural killer (NK) cells showed a unique distribution pattern compared with other cell types. Patients with enterocolitis showed a significant increase in CD57 positive NK cells in the lamina propria of ganglionic bowel only (p less than 0.05). NK cell values in ganglionic bowel of non-enterocolitis patients and in aganglionic bowel in all patients were similar to controls. The diversity of altered local immune response seen in this study may reflect a multifactorial microbial aetiology in enterocolitis associated with Hirschsprung9s disease.