tbuckley/cabot-search huggingface dataset:
Decreased cutaneous expression of stem cell factor and of the p75NGF receptor in urticaria
Authors: B. Hermes, T. Zuberbier, N. Haas, B.M. Henz
Journal: British Journal of Dermatology (2003)

Summary Background Mast cells, the main effector cells in urticaria, have been reported to be increased in number in lesional and nonlesional skin of urticaria patients, but the underlying mechanisms have so far not been studied. Serum NGF has however, been reported to be increased in urticaria. Objectives We have therefore explored the potential involvement of known mast cell growth modulating factors in urticaria. Methods Tissue sections from patients with different types of urticaria and healthy controls were studied for the immunohistochemical expression of known mast cell growth factors (stem cell factor, SCF; nerve growth factor, NGF), of the inhibitory granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and of the corresponding receptors, using the alkaline phosphatase–antialkaline phosphatase technique. Results Compared to skin of normal controls, staining for SCF, but not for NGF and GM‐CSF, was significantly decreased in epidermis, endothelium and perivascular cells in lesional and nonlesional skin of all urticarias. On separate analysis of urticaria subtypes, decreased expression reached significance only in delayed pressure urticaria. Expression of the p75NGF receptor (p75NGFR) was also significantly decreased on endothelium and on perivascular cells of lesional and nonlesional skin in all urticarias. On evaluation of serial sections, p75NGFR expression was also decreased on c‐Kit positive dermal mast cells. In contrast, expression of the NGF receptor tyrosine kinase and of the SCF and GM‐CSF receptors was unchanged. Conclusions These findings show that SCF and p75NGFR are selectively and systemically down‐regulated in the skin of urticaria patients and may represent a negative feedback to increased mast cell reactivity and proliferation.
Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia.
Authors: O S Platt, S H Orkin, G Dover, G P Beardsley, B Miller, D G Nathan
Journal: Journal of Clinical Investigation (1984)

Hydroxyurea, a widely used cytotoxic/cytostatic agent that does not influence methylation of DNA bases, increases fetal hemoglobin production in anemic monkeys. To determine its effect in sickle cell anemia, we treated two patients with a total of four, 5-d courses (50 mg/kg per d, divided into three oral doses). With each course, fetal reticulocytes increased within 48-72 h, peaked in 7-11 d, and fell by 18-21 d. In patient I, fetal reticulocytes increased from 16.0 +/- 2.0% to peaks of 37.7 +/- 1.2, 40.0 +/- 2.0, and 32.0 +/- 1.4% in three successive courses. In patient II the increase was from 8.7 +/- 1.2 to 50.0 +/- 2.0%. Fetal hemoglobin increased from 7.9 to 12.3% in patient I and from 5.3 to 7.4% in patient II. Hemoglobin of patient I increased from 9.0 to 10.5 g/dl and in patient II from 6.7 to 9.9 g/dl. Additional single-day courses of hydroxyurea every 7-20 d maintained the fetal hemoglobin of patient I t 10.8-14.4%, and the total hemoglobin at 8.7-10.8 g/dl for an additional 60 d. The lowest absolute granulocyte count was 1,600/mm3; the lowest platelet count was 390,000/mm3. The amount of fetal hemoglobin per erythroid burst colony-forming unit (BFU-E)-derived colony cell was unchanged, but the number of cells per BFU-E-derived colony increased. Although examination of DNA synthesis in erythroid marrow cells in vitro revealed no decreased methylcytidine incorporation, Eco RI + Hpa II digestion of DNA revealed that hypomethylation of gamma-genes had taken place in vivo after treatment. This observation suggests that hydroxyurea is a potentially useful agent for the treatment of sickle cell anemia and that demethylation of the gamma-globin genes accompanies increased gamma-globin gene activity.
Histamine and insulin dose-response studies of gastric secretion in Indian control subjects and patients with duodenal ulcer in the Ganges delta
Authors: K. N. Jalan, D. Mahalanabis, T. K. Maitra, S. K. Agarwal
Journal: Gut (1978)

The gastric secretory responses to various doses of histamine and insulin have been studied in 11 control and 12 duodenal ulcer subjects belonging to the Ganges delta of India where the incidence of duodenal ulcer disease is known to be high. A dose of 0.04 mg/kg body weight of histamine acid phosphate was sufficient to produce peak gastric acid output both in the control and duodenal ulcer subjects. However, a dose as low as 0.025 U insulin/kg body weight was enough to produce peak rates of gastric acid output in duodenal ulcer subjects, whereas in the controls a minimum dose of 0.05 U insulin/kg body weight was sufficient. A greater proportion of the duodenal ulcer patients also showed a peak acid secretory response in the first hour after administration of insulin. Furthermore, increasing doses of insulin in this population did not produce lower levels of blood glucose but did produce increasingly high acid output as subjects do in the West. K values derived from the intravenous glucose tolerance test showed that 75% of duodenal ulcer patients and 54% of the controls had variable degrees of intolerance to glucose. Gastric acid secretion in response to a bolus of 50 ml 50% intravenous glucose was also studied in a separate group of 16 duodenal ulcer and 13 control subjects. A sharp rise in the volume, titratable acidity, and total acid output was observed in the early part of the fourth hour in the control and duodenal ulcer subjects. In a separate group of controls a bolus of intravenous hypertonic saline produced no such increase in gastric acid secretion.
Di Bella's cure declared ineffective
Authors: K. Abbasi
Journal: BMJ (1998)

A panel of international cancer experts has stated that the “miracle cure”for cancer prescribed by retired Italian physiologist Luigi Di Bella is ineffective and has a surprisingly high incidence of side effects.

The panel, convened by the Italian ministry of health to oversee trials of his treatment, includes Professor Gordon McVie of the Cancer Research Campaign and Professor Karol Sikora of the World Health Organisation.

Reporting on four of the 10 trials under way, the panel found that: “There were no signs of tumours shrinking or responding to treatment in any of the …
The expression of nectin-1alpha in normal human skin and various skin tumours
Authors: H. Matsushima, A. Utani, H. Endo, H. Matsuura, M. Kakuta, Y. Nakamura, N. Matsuyoshi, C. Matsui, H. Nakanishi, Y. Takai, H. Shinkai
Journal: British Journal of Dermatology (2003)

A novel cell-cell adhesion system that consists of nectin and afadin has been identified at cadherin-based cell-cell adherens junctions. Nectin is a Ca2+-independent homophilic and heterophilic cell adhesion molecule that belongs to the immunoglobulin superfamily. Nectin has recently been shown to serve as an alpha-herpesvirus entry and cell-cell spread mediator. In spite of the ubiquitous expression of nectin-1alpha, its detailed localization in human skin has not been examined so far.To investigate the localization of nectin-1alpha in normal human skin and the alteration of its expression in malignant skin tumours.Immunohistochemistry was employed to determine the expression of nectin-1alpha and other adhesion molecules.We detected nectin-1alpha in normal human epidermis, follicles and eccrine ducts. Nectin-1alpha was colocalized with E-cadherin at cell-cell adherens junctions of the epidermis. The concentration of the nectin-afadin system at cell-cell adherens junctions was reduced in the early stage of malignant transformation of keratinocytes, such as in basal cell carcinomas and squamous cell carcinomas, where the cadherin-catenin system was preserved. Nectin-1alpha at cell-cell adherens junctions was reduced in human epithelial cancer cells located at the advancing border of the tumour.Our results showed that nectin-1alpha is located at cell-cell adherens junctions in human skin and that reduction of nectin-1alpha at cell-cell adherens junctions may be involved in the invasion of squamous cell tumours.
Extrarenal Azotemia
Authors: Charles F. Appel, James H. Townsend
Journal: New England Journal of Medicine (1949)

AS FAR back as 1912 Froin and Marie1 reported the occurrence of prerenal azotemia in choleriform enteritis. Similar observations of prerenal azotemia were made by Nobécourt, Bidot and Maillet2 in gastrointestinal disturbances in infancy in 1912 and by Tileston and Comfort3 in intestinal obstruction with vomiting in 1914. Only in recent years, however, has this condition been more completely understood.The characteristic picture of extrarenal azotemia is that of renal failure without actual renal disease or of renal disease not sufficient to explain the signs of renal failure present. The more important signs of extrarenal azotemia include an elevation of . . .
Abstract P4-07-13: High microRNA-621 level predicts a better response to neoadjuvant chemotherapy in breast cancer patients
Authors: J Xue, Y Chen, Y Chi, X Ye, Z Wu, J Wu
Journal: Cancer Research (2013)

Abstract Purpose: Weekly paclitaxel plus carboplatin (PCb) regimen is an effective neoadjuvant chemotherapy for breast cancer. However, some patients respond to this regimen poorly and suffer from side effects. In this study, we aimed to define the microRNA (miRNA) biomarker for predicting sensitivity to PCb chemotherapy in breast cancer patients, and to explore the potential molecular mechanisms. Experimental Design: 81 patients with stages II and III breast cancer, who received four cycles of weekly PCb regimen preoperative chemotherapy, were included. Gene expression profiles from 31 patients was used as training set to determine differentially expressed genes (DEGs) and to predict miRNAs that may be associated with chemotherapeutic sensitivity. The other 50 patients were analyzed as validation set to test the accuracy of DEG identification and miRNAs prediction by quantitative real-time PCR. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of miRNA-dependent drug sensitivity. Results: Gene profiling analyses in the training set revealed significant correlation between high expression level of miR-345 and miR-621 and pathologic complete response (pCR) in breast cancer patients. We further validated that the expression level of miR-621 was significantly higher in tumor tissues of pCR patients than that in non-pCR patients (P = 0.01). In breast cancer cell lines, ectopic overexpression of miR-621 promoted apoptosis and increased chemosensitivity to paclitaxel and carboplatin both in vitro and in vivo. The potential miR-621-target genes were determined by TargetScan and miRNA CLIP-seq database, which were further confirmed as DEGs reversely-correlated to miR-621 in breast cancer patient samples. Among those, FBXO11 was verified as one of the direct targets of miR-621 in breast cancer cells, whose expression level negatively associated with chemosensitivity in breast cancer patients. The molecular mechanisms by which miR-621/FBXO11 axis regulates chemosensitivity may involve regulation of p53 transcriptional activity and epithelial-mesenchymal transition (EMT) in breast cancer cells. Conclusions: Our study revealed a strong correlation between miR-621 expression and chemosensitivity in breast cancers. High level of miR-621 predicts sensitivity to PCb regimen neoadjuvant chemotherapy in breast cancer patients who tend to achieve pCR. The increased chemosensitivity may be mediated by down-regulation of FBXO11 gene, which leads to enhanced p53 transactivity and reduced EMT in breast cancer cells. Therefore, miR-621 may be used as predictive biomarker and the potential therapeutic target in breast cancer treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-13.
A Simple Bedside Test To Identify Ulnar Collateral Flow
Authors: Karen O'Mara
Journal: Annals of Internal Medicine (1995)

Letters15 October 1995A Simple Bedside Test To Identify Ulnar Collateral FlowKaren O'Mara, DO and Brian Sullivan, MDKaren O'Mara, DOResurrection Medical Center; Chicago, IL 60631 and Brian Sullivan, MDResurrection Medical Center; Chicago, IL 60631Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-8-199510150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We report the use of a simple bedside test for identifying ulnar collateral flow that can be done before placement of arterial monitoring lines or removal of arterial blood from the radial artery. This procedure is recommended as a replacement of the Allen test or Doppler identification of ulnar flow, both of which often present results that are difficult to interpret in hypotensive patients. We have successfully applied this technique in hypotensive and normotensive patients and have occasionally noted asymmetrical collateral flow between two extremities in a single patient.The procedure involves placement of a bedside oximeter ... Author, Article, and Disclosure InformationAffiliations: Resurrection Medical Center; Chicago, IL 60631 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPulse oximetry: a new tool to assess patients with leg ulcersPulse oximetry: Principles and limitationsPulse Oximetry in the Evaluation of Peripheral Vascular Disease 15 October 1995Volume 123, Issue 8Page: 637KeywordsArteriesFemoral arteriesHeart rateHematologic testsOxygen Issue Published: 15 October 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Macrovascular Pulmonary Arteriovenous Malformations Demonstrated by Radionuclide Method
Authors: CRAIG TRENT, RICHARD H. TUPLER, PHILIP WILDENHAIN, ELLIOTT H. TURBINER
Journal: Clinical Nuclear Medicine (1993)

Pulmonary arteriovenous malformations (AVMs) are abnormal vascular communications that allow unoxygenated blood to pass from the venous to the arterial circulation. Usually congenital in origin and twice as likely in women, hemoptysis, dyspnea, and chest pain are the common presenting complaints in AVM. A case of pulmonary AVMs that were demonstrated on a radionuclide angiogram is presented. Pulmonary AVMs were suspected after finding radioactivity in both kidneys on a perfusion lung scan.
All members of primary care team are aware of importance of evidence based medicine
Authors: N. Hagdrup, M. Falshaw, R. W Gray, Y. Carter
Journal: BMJ (1998)

EDITOR—McColl et al present findings about the attitudes towards evidence based medicine of general practitioners in Wessex, but they lack information from other members of the primary care team.1Comprehensive evidence based practice will require the involvement of all members of staff. As part of a baseline needs assessment before the implementation of a computer network project we carried out a postal survey of general practices that participated in undergraduate medical education in …
Severe esophagitis in a patient with gastrointestinal stromal tumor treated with imatinib
Authors: M. Saponara, M. Di Battista, C. Lolli, M. Pantaleo, F. Azzaroli, D. Santini, V. Di Scioscio, F. Catena, M. Astorino, A. Maleddu, G. Biasco
Journal: Endoscopy (2009)

Imatinib is a specific inhibitor of tyrosine kinase and represents the standard treatment for metastatic and unresectable gastrointestinal stromal tumor (GIST) [1] [2]. Imatinib is orally administered and generally well tolerated; cases of severe toxicity have rarely been described [3]. We report the first case of severe esophagitis occurring during imatinib administration.
Immunologic and Nonimmunologic Generation of Superoxide from Mast Cells and Basophils
Authors: William R. Henderson, Michael Kaliner
Journal: Journal of Clinical Investigation (1978)

Mediator release from rat peritoneal and human lung mast cells as well as human leukemic basophils was examined to determine whether super-oxide (O−2) was concomitantly generated. Immunologic or nonimmunologic stimulation of each preparation induced parallel release of histamine and O−2 within 2 min. O−2 production was quantitated by superoxide dismutase (SOD)-inhibitable chemiluminescence and cytochrome c reduction. SOD was detected in basophil and mast cell lysates and was also released by rat mast cells stimulated by anti-IgE. Secretory granules isolated from purified rat mast cells released histamine, O−2, and SOD upon exposure to cations. Thus, both superoxide radicals and SOD may play a role in host defenses involved in immediate hypersensitivity reactions.
The Mechanical Rigidity of the Extracellular Matrix Regulates the Structure, Motility, and Proliferation of Glioma Cells
Authors: Theresa A. Ulrich, Elena M. de Juan Pardo, Sanjay Kumar
Journal: Cancer Research (2009)

Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here, we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. We cultured a series of glioma cell lines (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM substrates of defined mechanical rigidity and investigated the role of ECM rigidity in regulating tumor cell structure, migration, and proliferation. On highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to values comparable with normal brain tissue, tumor cells appear rounded and fail to productively migrate. Remarkably, cell proliferation is also strongly regulated by ECM rigidity, with cells dividing much more rapidly on rigid than on compliant ECMs. Pharmacologic inhibition of nonmuscle myosin II-based contractility blunts this rigidity-sensitivity and rescues cell motility on highly compliant substrates. Collectively, our results provide support for a novel model in which ECM rigidity provides a transformative, microenvironmental cue that acts through actomyosin contractility to regulate the invasive properties of GBM tumor cells.
Acute myeloblastic leukaemia--a model for assessing value for money for new treatment programmes.
Authors: P J Lobo, R L Powles, A Hanrahan, D K Reynold
Journal: BMJ (1991)

OBJECTIVE--To measure the effects of changes in treatment of acute myeloblastic leukaemia that may give better value for money. DESIGN--Retrospective analysis of patients9 notes to identify items of management costing money; prospective costing of these items. The Medical Research Council acute myeloblastic leukaemia 9 trial was used to identify the amount and distribution of these costs when either one or two courses of induction treatment were required to obtain complete remission. These findings were then extrapolated to four published international controlled trials using similarly intense treatment and in which the number of courses of treatment required for complete remission was stated, to compare British costs for treatment with idarubicin and daunorubicin, both in combination with cytarabine. SETTING--Leukaemia unit, Royal Marsden Hospital, London. SUBJECTS--Data on 10 patients receiving intensive induction treatment for acute myeloblastic leukaemia were used to identify 160 items of cost in four broad groups: general (including accommodation), diagnostic, supportive treatment, and cytotoxic chemotherapy. One newly treated patient was prospectively assessed over one month, including a time and motion study, to cost these items; then costs for 268 patients from the MRC trial receiving moderate induction chemotherapy including daunorubicin were assessed, and costs for treatment of 522 patients in the four international studies comparing daunorubicin with idarubicin were analysed. MAIN OUTCOME MEASURES--Cost effectiveness was measured as the overall cost to obtain complete remission in untreated patients with acute myeloblastic leukaemia after treatment with idarubicin or daunorubicin. RESULTS--The 160 costed items were measured for their sensitivity in varying the total cost of treatment, this being assessed within Britain in other district general and private hospitals to measure the extremes of cost of these items. Overall, idarubicin, although more expensive, showed a substantial saving (1477 pounds per patient) in total hospital costs, more than offsetting the increased cost (607 pounds) of the new treatment, an overall savings of 870 pounds per patient (5%). CONCLUSION--Approaches modelling cost effectiveness may be an essential part of planning new programmes of treatment in the future. This method can be used to estimate the cost effectiveness of the treatments in different environments and countries where costs may vary widely.
PLANNED INITIAL TRANSAPICAL APPROACH VERSUS ANTEGRADE TRANSSEPTAL OR RETROGRADE TRANSAORTIC APPROACHES FOR SEPTAL AND POSTERIORLY-LOCATED MITRAL PARAVALVULAR LEAK CLOSURE
Authors: Chad Kliger, Bryce Einhorn, Yuriy Dudiy, Vladimir Jelnin, Carmen Medina-Palomo, Gila Perk, Howard Cohen, Itzhak Kronzon, Carlos Ruiz
Journal: Journal of the American College of Cardiology (2012)
Natural Evolution and Pathological Alterations of Lymphocyte Proteins.
Authors: Mohamed A. Mobarak
Journal: Annals of Internal Medicine (1968)

s1 May 1968Natural Evolution and Pathological Alterations of Lymphocyte Proteins.Mohamed A. Mobarak, M.D., Jerome I. Brody, M.D., F.A.C.P.Mohamed A. Mobarak, M.D.Search for more papers by this author, Jerome I. Brody, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1171_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis investigation defines the immunochemical features of intralymphocyte antibody proteins as they relate to cell origin, and the age and the state of health of the lymphocyte donor. Tissues used as lymphocyte source were peripheral blood, thymus gland, lymph node, and tonsil, obtained as biopsy or autopsy specimens from healthy individuals and those with lymphoid neoplasms in the following age groups; neonatal, infancy, childhood, pre- and postadolescence, adult maturity, and senescence. Lymphocytes were separated from supporting, mesenchymal, and other extraneous materials and the water-soluble cellular proteins extracted by disrupting thoroughly washed cells with ultrasonic vibration. The clear derivatives were reacted... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Mohamed A. Mobarak, M.D.; Jerome I. Brody, M.D., F.A.C.P.Affiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1171-1171KeywordsAgingAutopsyBiopsyBloodChild healthLymph nodesLymphocytesProteinsThymusTonsils ePublished: 1 December 2008 Issue Published: 1 May 1968 PDF downloadLoading ...