tbuckley/cabot-search huggingface dataset:
Systemic Delivery of Fusogenic Membrane Glycoprotein-expressing Neural Stem Cells to Selectively Kill Tumor Cells
Authors: Detu Zhu, Dang Hoang Lam, Yovita Ida Purwanti, Sal Lee Goh, Chunxiao Wu, Jieming Zeng, Weimin Fan, Shu Wang
Journal: Molecular Therapy (2013)

Intravenously injected neural stem cells (NSCs) can infiltrate both primary and metastatic tumor sites; thus, they are attractive tumor-targeting vehicles for delivering anticancer agents. However, because the systemic distribution of the injected NSCs involves normal organs and might induce off-target actions leading to unintended side effects, clinical applications of this approach is impeded. Given that the vesicular stomatitis virus glycoprotein (VSV-G) can promote the formation of multinucleated syncytia to kill cells in a pH-dependent manner, we engineered a pH sensor of VSV-G and generated a novel VSV-G mutant that efficiently promotes syncytium formation at the tumor extracellular pH (pHe) but not at pH 7.4. Using transduced NSCs derived from induced pluripotent stem cells (iPSCs), the VSV-G mutant was delivered into mice with metastatic breast cancers in the lung through tail vein injection. Compared with the conventional stem cell-based gene therapy that uses the herpes simplex virus thymidine kinase (HSVtk) suicide gene, this treatment did not display toxicity to normal non-targeted organs while retaining therapeutic effects in tumor-bearing organs. Our findings demonstrate the effectiveness of a new approach for achieving tumor-selective killing effects following systemic stem cell administration. Its potential in stem cell-based gene therapy for metastatic cancer is worthy of further exploration. Intravenously injected neural stem cells (NSCs) can infiltrate both primary and metastatic tumor sites; thus, they are attractive tumor-targeting vehicles for delivering anticancer agents. However, because the systemic distribution of the injected NSCs involves normal organs and might induce off-target actions leading to unintended side effects, clinical applications of this approach is impeded. Given that the vesicular stomatitis virus glycoprotein (VSV-G) can promote the formation of multinucleated syncytia to kill cells in a pH-dependent manner, we engineered a pH sensor of VSV-G and generated a novel VSV-G mutant that efficiently promotes syncytium formation at the tumor extracellular pH (pHe) but not at pH 7.4. Using transduced NSCs derived from induced pluripotent stem cells (iPSCs), the VSV-G mutant was delivered into mice with metastatic breast cancers in the lung through tail vein injection. Compared with the conventional stem cell-based gene therapy that uses the herpes simplex virus thymidine kinase (HSVtk) suicide gene, this treatment did not display toxicity to normal non-targeted organs while retaining therapeutic effects in tumor-bearing organs. Our findings demonstrate the effectiveness of a new approach for achieving tumor-selective killing effects following systemic stem cell administration. Its potential in stem cell-based gene therapy for metastatic cancer is worthy of further exploration.
Acute generalized exanthematous pustulosis induced by ingestion of lacquer chicken
Authors: Y.M. Park, J.G. Park, H. Kang, D. Houh, D.G. Byun, J.W. Kim
Journal: British Journal of Dermatology (2000)

Journal Article Acute generalized exanthematous pustulosis induced by ingestion of lacquer chicken Get access Y.M. Park, Y.M. Park Department of Dermatology, College of Medicine, The Catholic University of Korea, 665 Bupyung‐dong, Bupyung‐gu, Inchon, 403–720, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar J.G. Park, J.G. Park Department of Dermatology, College of Medicine, The Catholic University of Korea, 665 Bupyung‐dong, Bupyung‐gu, Inchon, 403–720, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar H. Kang, H. Kang Department of Dermatology, College of Medicine, The Catholic University of Korea, 665 Bupyung‐dong, Bupyung‐gu, Inchon, 403–720, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar D. Houh, D. Houh Department of Dermatology, College of Medicine, The Catholic University of Korea, 665 Bupyung‐dong, Bupyung‐gu, Inchon, 403–720, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar D.G. Byun, D.G. Byun Department of Dermatology, College of Medicine, The Catholic University of Korea, 665 Bupyung‐dong, Bupyung‐gu, Inchon, 403–720, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar J.W. Kim J.W. Kim Department of Dermatology, College of Medicine, The Catholic University of Korea, 665 Bupyung‐dong, Bupyung‐gu, Inchon, 403–720, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 1, 1 July 2000, Pages 230–232, https://doi.org/10.1046/j.1365-2133.2000.03643.x Published: 01 July 2000
Notch pathway activation targets AML-initiating cell homeostasis and differentiation
Authors: Camille Lobry, Panagiotis Ntziachristos, Delphine Ndiaye-Lobry, Philmo Oh, Luisa Cimmino, Nan Zhu, Elisa Araldi, Wenhuo Hu, Jacquelyn Freund, Omar Abdel-Wahab, Sherif Ibrahim, Dimitris Skokos, Scott A. Armstrong, Ross L. Levine, Christopher Y. Park, Iannis Aifantis
Journal: The Journal of Experimental Medicine (2013)

Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia.
The Harveian Oration on Physiological Darkness before Harvey: Delivered before the Royal College of Physicians on October 18th
Authors: T. C. Allbutt
Journal: BMJ (1900)

Tne discovery of the circu- lation of the blood by William Harvey is commonly regarded among scientific discoveries as eminent if not unique, and this in the judgment not of Englishmen only.My purpose to-day is to show that at any rate it was made against enormous difficulties.To put this discovery in 'right perspective we must have some vision of the history of philosophy, science, and medi- .cine.Medicine, herein in contrast with theology and law, had its sources almost wholly in the Greeks; from them good or evil it took its first scheme of thought; and in schools of Hippocrates and of Alexandria it was based, more soundly, on natural history and anatomy.The noble figure Galen, the first physiologist and the last of the great physicians, pourtrayed for us by Dr. J. F. Payne in Harveian Oration of I896, stood eminent upon the brink of abyss when, as if by some convulsion of Nature, medicine overwhelmed for fifteen centuries.Galen practised the method of verific4tion by experiment, first introduced, perhaps, Archimedes, but after him it was lost till the time of Gilbert, Galileo, and Harvey.In the growth of societies small civilisations have sacrificed to the formation of larger aggregates, whereby stable equilibrium may be attained for the highest Perhaps because of her very freedom of thought Greece became a nation.Even the Roman peace, bought as at the cost of learningand the arts, was but a meebanical peace.In the wilder regions of the empire the bodies but not the wills of men were in subjugation, and even in Rome the sanction of patriotism was failing.Under the Frankish
Absorption of xylose, glucose, glycine, and folic (pteroylglutamic) acid in Zambian Africans with anaemia.
Authors: G C Cook
Journal: Gut (1976)

Rates of glucose, glycine, and folic (pteroylglutamic) acid absorption were determined for a 30 cm jejunal segment in vivo, with a double-lumen tube perfusion system, in 10 Zambian African women with a mean haemoglobin concentration of 5-1 (3-5-9-2) g/dl. In four the anaemia was megaloblastic (due to folate deficiency) and in six hypochromic. Perfusion solutions contained (1) glucose 200 mmol/1, (2) glycine 100 mmol/1, and (3) folic acid 250 mug/1. D-xylose absorption after a 25 g oral load was determined in them, and also in 18 additional patients (11 had megaloblastic and seven either hypochromic or haemolytic anaemia). Xylose absorption tests were significantly impaired in the patients with megaloblastic compared with hypochromic or haemolytic anaemia (P less than 0-001); those with untreated megaloblastic anaemia had a greater abnormality than those who had started treatment. Mean glucose, glycine, and folic acid absorption rates were similar to those in controls, and the rates in patients with megaloblastic and hypochromic anaemia were not significantly different. Correlation between glucose absorption rate and xylose excretion was, however, significantly (P less than 0-02). If more patients had been studied it seems likely therefore that a significant impairment of glucose absorption rate in the presence of megaloblastic anaemia would also have been demonstrated. In this investigation anaemia per se did not affect glucose, glycine, or folic acid absorption rates or xylose absorption, but xylose absorption was reduced in patients with megaloblastic anaemia. That abnormality was probably related to folate deficiency, and the underlying mechanism seems to be different from that causing impairment of monosaccharide absorption in patients with systemic bacterial infections. Mean glycine and folic acid absorption rates were not altered by megaloblastic anaemia, indicating that folate deficiency does not cause a general depression of absorption.
Syphilis presenting as acute multifocal retino-choroiditis
Authors: Shery Thomas, Martin Wiselka, Jyoti Dhar, Kim Bibby
Journal: Journal of the Royal Society of Medicine (2006)

Fusobacterium nucleatum is an anaerobic bacillus of oropharyngeal origin.We describe a case of two manifestations of fusobacterium-induced sepsis originating from an asymptomatic dental root abscess. CASE HISTORYA 63-year-old Caucasian man presented to the accident and emergency department with a 2-week history of night sweats, anorexia, 6 kg weight loss and lumbo-sacral back pain radiating to the right buttock and thigh.In addition, he had been intermittently confused and drowsy over the previous 48 hours.Other than gout and osteoarthritis there was no significant past medical history.On examination, he was apyrexial but tachycardic, with normal cardiac sounds and no peripheral stigmata of infective endocarditis.There was no focal spinal tenderness or nuchal rigidity and neurological examination was normal apart from significantly diminished straight leg raise on the right.Laboratory tests showed raised inflammatory markers (C-reactive protein [CRP] 402 mg/L, normal range [NR]510; erythrocyte sedimentation rate [ESR] 84 mm in first hour), leucocytosis, (total white cell count [WCC] 27.5 with neutrophils 23.1Â10 9 /L) and deranged liver function (alkaline phosphatase 282 IU/L, NR5125; AST 53 IU/L, NR540; LDH 225 IU/L, NR5180).Serial blood cultures, myeloma screen, tumour markers, X-ray of the chest and lumbo-sacral spine, abdominal ultrasound and electrocardiogram were negative or normal.Magnetic resonance imaging of the lumbar spine showed discitis of L4/L5.This disc was subsequently aspirated under computed tomography guidance prior to commencement of empirical antibiotic therapy with intravenous flucloxacillin and oral Fucidin (sodium fusidate).
Contributions of the Xg^a Blood Group System to Medicine.
Authors: Charles E. Jackson
Journal: Annals of Internal Medicine (1969)

s1 May 1969Contributions of the Xga Blood Group System to Medicine.Charles E. Jackson, M.D., F.A.C.P., Joseph D. Mann, M.D.Charles E. Jackson, M.D., F.A.C.P.Search for more papers by this author, Joseph D. Mann, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1107_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe 1962 report of the discovery of a sex-linked A blood group system, termed Xga, has been a recent stimulus to the study of X-linked inheritance in man. This presentation reviews the contributions of this system to medical science and discusses its proposed interaction with the male-to-female birth ratio.Family studies of Xgaby numerous investigators have permitted the mapping of the X chromosome for genes for muscular dystrophy, hemophilia, color blindness, and many other conditions in relationship to the Xgamarker gene. Xgastudies in Klinefelter's and Turner's syndromes have permitted the tracing of the parental origin of the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Charles E. Jackson, M.D., F.A.C.P.; Joseph D. Mann, M.D.Affiliations: Bluffton, Indiana; and Grand Rapids, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1107-1108KeywordsBirthBlindnessBlood groupsHemophiliaMuscular dystrophiesTurner syndromeX chromosomes ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...
Life With the Pneumococcus: Notes From the Bedside, Laboratory, and Library
Authors: Jerry D. Smilack
Journal: JAMA (1986)

ABSTRACT Despite the availability of antibiotics active against Streptococcus pneumoniae, death from pneumococcal infection is still an everyday occurrence. Pneumococcal pneumonia and meningitis remain life-threatening illnesses, even as we approach the 50th anniversary of the discovery of the penicillins. Perhaps no one alive has studied the microbe and its interaction with the human host more intensively than the author of this enjoyable little book. Dr Austrian has been a student of the pneumococcus for much of his professional life. In recent years, realizing the shortcomings of treatment of established pneumococcal disease, he has championed vaccination as a highly effective means of prevention.In this volume, the author assembles his previously published essays tracing the discovery of the organism in the 1880s and its importance as a cause of pneumonia. He vividly tells of the confusion over whether Klebsiella pneumoniae (Friedlander's bacillus) or the pneumococcus was the cause of most bacterial pneumonia.
Influence of treatment with pancreatic extracts on pancreatic enzyme secretion.
Authors: J Mossner, H P Wresky, W Kestel, J Zeeh, U Regner, W Fischbach
Journal: Gut (1989)

We have evaluated the effects of porcine pancreatic extracts on human pancreatic secretion. Ten male volunteers were intubated with a 4-lumen jejunal tube to collect gastric and duodenal secretions separately via the first and third tube, to infuse PEG 4000 distal the pylorus via the second tube and to apply porcine pancreatic extracts via the fourth tube distal the ligament of Treitz. Pancreatic extracts were given four times at 40 minute intervals; the first two as active enzymes and subsequently as heat denatured proportions. Secretin was continuously infused intravenously (0.5 E/kg bw/h) to achieve minimal pancreatic flow. Lipase, amylase, trypsin, chymotrypsin, volume, and bicarbonate were measured in duodenal contents in eight pooled 15 minute fractions. Three subjects who received HEPES-Ringer buffer instead of pancreatic enzymes served as controls. Plasma cholecystokinin (CCK) was measured using a sensitive bioassay. Both active and heat denatured pancreatic extracts caused a small but significant increase in amylase and chymotrypsin secretion. Basal plasma CCK values were 0.85 (0.05) pM. After intrajejunal instillation of either active or heat denatured pancreatic extracts plasma CCK rose to 3.25 (0.30) pM and to 3.28 (0.36) pM respectively. In a second group of five volunteers, plasma CCK concentrations were measured after a test meal. On day 1, volunteers received a liquid fat and protein rich meal and on day 2, the same test meal containing porcine pancreatic extracts. In both cases, a similar increase in plasma CCK was observed. We conclude that therapy with pancreatic extracts stimulate pancreatic enzyme secretion. This may be mediated through release of CCK.
Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195
Authors: E Feldman, M Kalaycio, G Weiner, S Frankel, P Schulman, L Schwartzberg, J Jurcic, E Velez-Garcia, K Seiter, D Scheinberg, D Levitt, N Wedel
Journal: Leukemia (2003)
An unusual case of severe iron deficiency anaemia
Authors: P Schnuelle
Journal: Gut (2006)

Abnormal iron absorption is a well recognised feature of subtle non-bleeding gastrointestinal conditions, such as coeliac disease or atrophic body gastritis, without otherwise gastrointestinal symptoms. We recently observed a patient with severe iron deficient anaemia mimicking impaired iron absorption in the absence of gastrointestinal pathology.

A 47 year old women was admitted to hospital in 2005 because a haemoglobin level of 6.4 g/dl had attracted attention when she was donating blood. She complained of fatigue and occasionally frontal headaches. On physical examination she appeared to have a normal nutritional condition but her skin was pale and she had brittle nails. Despite the severity of the anaemia she appeared well. Pulse frequency and blood pressure were normal. Blood smear showed a strikingly microcytotic hypochromic red blood cell …
Functional T lymphocyte immune deficiency in a population of homosexual men who do not exhibit symptoms of acquired immune deficiency syndrome.
Authors: G M Shearer, S M Payne, L J Joseph, W E Biddison
Journal: Journal of Clinical Investigation (1984)

To determine whether healthy homosexual men are immunologically impaired, peripheral blood leukocytes (PBL) from 20 male homosexuals were compared prospectively with PBL from 14 age-matched male heterosexual donors with respect to: (a) the capacity of their PBL to generate functional T cell immune responses in vitro; and (b) the content of total T cells and T cell subsets in their peripheral blood. The homosexual donors studied indicated moderate sexual life styles in that all but one of the donors had less than five current sexual partners. The percentages of OKT3+, OKT4+, and OKT8+ T cells were similar to those of heterosexual controls. T cell function was assessed by measuring cytotoxic T cell responses to influenza virus and to allogeneic cells. Approximately one-third of the homosexual donors consistently exhibited weak cytotoxic T lymphocyte (CTL) responses to influenza virus, whereas all of the heterosexual donors generated strong CTL responses to influenza. There was no correlation between the strength of CTL responsiveness to influenza virus and the strength of CTL responses to allogeneic cells. These results suggest that the influenza-specific CTL response may be a sensitive indicator of immunologic defects in asymptomatic homosexuals. If acquired immune deficiency syndrome results from an infectious agent, it remains to be seen if such immunosuppression predisposes to the infection, or if it reflects early consequences of infection.
Aspirin and Reye's syndrome
Authors: T. J. Halpin
Journal: JAMA (1983)

<h3>In Reply.—</h3> The Ohio Department of Health received only two reports of Reye's syndrome cases from the Cleveland Clinic during the study period (December 1978 through March 1980). The first of the two cases reported to us was not included in the study because our nurse coordinator could not get timely access to the child's record to verify fulfillment of the case definition. This child was reported by Dr Orlowski to have received aspirin. The other patient who was included in our study did not have a history of aspirin ingestion. Thirty-three hospitals reported cases to the Ohio Department of Health. With the exception of Dr Orlowski, there is no evidence of similar reporting problems at the other 32 hospitals. The vast majority of cases (85% ) of the 227 cases were reported from the state's six major pediatric referral centers. In Cleveland, this was Rainbow Babies and Children's Hospital (affiliated
Nonmyeloablative allogeneic bone marrow transplantation for treatment of myelodysplastic syndrome complicated by recent intracerebral hemorrhage
Authors: Korenori Ohtsubo, Ken Takase, Koji Nagafuji, Hideho Henzan, Tetsuya Tanimoto, Takahiro Fukuda, Toshihiro Miyamoto, Shoichi Inaba, Mine Harada
Journal: American Journal of Hematology (2004)

Abstract A patient with intracerebral hemorrhage is considered ineligible for hematopoietic stem cell transplantation (HSCT). We report a 49‐year‐old woman with myelodysplastic syndrome (MDS) complicated by refractoriness to platelet transfusion and intracerebral hemorrhage, who underwent allogeneic bone marrow transplantation from an HLA‐identical unrelated male donor. Nine days before the scheduled transplantation, she developed dysarthria and right hemiparesis; computed tomography (CT) of the brain disclosed an acute hematoma in the left parietal lobe exceeding 3 cm in diameter. She underwent conditioning with reduced‐intensity, including fludarabine (30 mg/m 2 /day on days −8 to −3), busulfan (4 mg/kg/day on days −6 and −5), and total body irradiation (4 Gy on day −2). Two weeks after transplantation, dysarthria and right hemiparesis began to resolve, and CT showed spontaneous resolution of the hematoma. Simultaneously, engraftment was confirmed. Thus, recent stroke may be not an absolute contraindication for HSCT. Am. J. Hematol. 77:400–404, 2004. © 2004 Wiley‐Liss, Inc.
Management of isolated thyroid swellings: a prospective six year study of fine needle aspiration cytology in diagnosis.
Authors: E L Cusick, C A MacIntosh, Z H Krukowski, V M Williams, S W Ewen, N A Matheson
Journal: BMJ (1990)

OBJECTIVE--To audit the accuracy and impact on the frequency of operation of fine needle aspiration cytology of isolated thyroid swellings. DESIGN--Prospective analysis over six years of cytological predictions compared with histological findings. SETTING--Thyroid clinic serving the Grampian region. PATIENTS--395 Consecutive patients presenting with an isolated thyroid swelling, 307 of whom underwent surgical excision. Analysis was confined to a subgroup of 283 patients with satisfactory aspirates who were operated on. RESULTS--The positive predictive value of aspiration cytology for detecting malignant disease was 100% and the sensitivity 83%. The sensitivity for the detection of neoplasia (frank malignancy together with follicular adenomas) was 76%. The specificity was 58% and the overall accuracy 69%. Recalculation of data in previous papers with strict criteria showed the accuracy of aspiration cytology to be variable and lower than is widely accepted. Since the introduction of aspiration cytology 21% fewer operations for isolated thyroid swellings have been performed. CONCLUSIONS--As a basis of selection for surgical excision of isolated thyroid swellings according to prediction of neoplasia fine needle aspiration cytology is less reliable than is widely accepted. It is an adjunct to management rather than a definitive test, and negative cytological results do not exclude neoplastic disease. Further study should take account of the implications of repeated clinic attendances for review and aspiration as these may culminate in delayed surgical treatment.