tbuckley/cabot-search huggingface dataset:
Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.
Authors: H J Aanstoot, S M Kang, J Kim, L A Lindsay, U Roll, M Knip, M Atkinson, P Mose-Larsen, S Fey, J Ludvigsson
Journal: Journal of Clinical Investigation (1996)

Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. Removal of N-linked carbohydrates results in a protein of 22,000 M(r). Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several years before clinical onset. The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes.
Getting urgent information to doctors
Authors: M. E Black
Journal: BMJ (1996)

EDITOR,—Using electronic mail and the Internet to ensure rapid and systematic communication of urgent material from the Department of Health to general practitioners, as Rank Sullivan reports,1 seems an obvious and long overdue move. An efficient “electronic cascade” could link many parts and functions of the health service, including departments of public health, hospitals, and colleagues in other countries. It could even make sound business …
Dr. Hammond Replies to His Critics.
Authors: William A. Hammond
Journal: JAMA (1893)

<h3>Dear Sir:</h3> —In the last number of theJournal of the American Medical Associationthere is a communication from Dr. D. R. Brower transmitting the details of an analysis made of cerebrine and medulline, said to have been prepared by my formulas. Of course I have no assurance that the specimens examined were really what they purported to be, neither does Professor Delafontaine, who made the analysis; so assert. He examined what was given him and I have no disposition to question his honesty in the matter. I have only to say: 1. That the cerebrine as prepared by my process is a solution obtained by macerating the brain of the ox and the contained blood for from six months to a year in a mixture of equal parts of absolute alcohol, glycerin, and a saturated solution of boric acid in water, with frequent agitation and the application of strong
Ebstein's Anomaly
Authors: Aiden J. O'Loughlin, Chris Hayward
Journal: New England Journal of Medicine (2005)

A 44-year-old woman presented with increasing dyspnea. The patient had Ebstein's anomaly, which had first been diagnosed when she was in her early 20s. She had declined heart transplantation three years before her admission to our hospital. The findings on physical examination included atrial fibrillation, a diffuse anterior chest heave and friction rub, and severe right heart failure. The electrocardiogram showed atrial fibrillation and right bundle-branch block. Her chest x-ray films (Panels A and B) showed a cardiothoracic ratio of 1, splaying of the carina, and cardiac enlargement posterior to the vertebral bodies. On transthoracic echocardiography (Panel C and Video . . .
Abstract LB-265: ONO-AE3-208 inhibits myeloid derived suppressor cells and glioma growth
Authors: Kohanbash Gary, Erin Straw, Amram Averick, Brian Ahn, Matthew Smith-Cohn, Takayuki Ohkuri, Akemi Kosaka, Hideho Okada
Journal: Cancer Research (2014)

Abstract Myeloid Derived Suppressor Cells (MDSCs) are up-regulated in all known solid tumors and suppress anti-tumor T-cell activity. Our recent studies have demonstrated the ability of monocytic, Ly6C+ MDSCs to promote glioma growth through the activation of cyclooxygenase (COX)-2 pathway, which is responsible for plostaglandin-synthesis. ONO-AE3-208 is an antagonist of the prostaglandin E (EP)-4 receptor, which is an important positive feedback regulator of the COX-2 pathway. We thus examined the ability of ONO-AE3-208 to suppress MDSC activity in gliomas. ONO-AE3-208 treatment in mice bearing established GL261-quad glioma in the brain resulted in complete and persistent rejection of the tumors (n=4). Flow cytometric analysis revealed that gliomas in the ONO-AE3-208-treated mice were infiltrated by fewer numbers of Ly6C+ MDSCs compared with non-treated animals. We subsequently isolated glioma-infiltrating Ly6C+ MDSCs by flow-sorting to address their functions. RT-PCR analysis revealed that the Ly6C+ MDSCs derived from ONO-AE3-208 treated mice expressed lower levels of the Arg1 and Cox2 expression compared to control animals. Consistently, brain infiltrating leukocytes in ONO-AE3-208 treated tumor-bearing mice demonstrated enhanced Ifng expression compared with control mice, suggestive of enhanced T-cell activity. Our data demonstrate that ONO-AE3-208 may be useful in the treatment of glioma patients to suppress Ly6C+ MDSCs and promote anti-tumor immunity. Citation Format: Kohanbash Gary, Erin Straw, Amram Averick, Brian Ahn, Matthew Smith-Cohn, Takayuki Ohkuri, Akemi Kosaka, Hideho Okada. ONO-AE3-208 inhibits myeloid derived suppressor cells and glioma growth. [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 LB-265. doi:10.1158/1538-7445.AM2014-LB-265
Hepatic- and Celiac-Artery Aneurysms
Authors: William R. Sweetman
Journal: JAMA (1966)

ANEURYSMS of the hepatic and celiac arteries are both unusual and lethal. The total number of reports in the United States and European literature is 143 and 38, respectively.<sup>1-20</sup>Of the 37 cases treated surgically, excision of the aneurysm was successful in only a dozen. At the present time there is no doubt as to the necessity of surgical intervention in hepatic and celiac aneurysms. Eighty percent or more will rupture into the peritoneal cavity, bile ducts,<sup>11</sup>gallbladder, duodenum, or stomach.<sup>17</sup>One case has been reported in which the aneurysm ruptured into the portal veins, producing esophageal varices and death due to hemorrhage.<sup>6</sup>Few incidental aneurysms have been reported at autopsy, and we have found only one case in which an arteriosclerotic hepatic aneurysm noted at surgery has been followed for four years and has remained asymptomatic.<sup>19</sup>The lethal nature of the celiac-artery aneurysm is obvious,
Cough Caused by Exposed Endobronchial Sutures
Authors: ROBERT E. ALBERTINI
Journal: Annals of Internal Medicine (1981)

Five patients with histories of resectional lung surgery presented with recurrent or persistent cough. Lobectomy or pneumonectomy had been done for carcinoma (three patients), bronchial adenoma (one patient), and bronchiectasis (one patient). The cough in each case was first interpreted as being due to recurrence of the original disease. Bronchoscopy excluded recurrent disease and led to the discovery of exposed endobronchial sutures. Elimination of the sutures spontaneously in one patient and removal by bronchoscopy in four patients alleviated the cough. Exposed sutures apparently cause cough by producing local irritation, granuloma formation, and infection. This cause should be considered in the differential diagnosis of cough in the post-thoracotomy patient.
Developmental changes in the rat atriopeptin hormonal system.
Authors: Y F Wei, C P Rodi, M L Day, R C Wiegand, L D Needleman, B R Cole, P Needleman
Journal: Journal of Clinical Investigation (1987)

We undertook a study of fetal synthesis, storage, and release of atriopeptin (AP). Plasma levels of both atriopeptin immunoreactivity (APir) and the NH2-terminal fragment of the prohormone immunoreactivity (NTFir) were very high in the fetus (4 and 20 times the maternal plasma, respectively). However, the atrial content of the AP was low, but surprisingly, ventricular content of AP was quite high (relative to the adult) in the fetus and fell postnatally. Atrial AP messenger RNA (mRNA) increased with postnatal age, whereas ventricular mRNA was extremely high in the fetus and fell rapidly after birth. High fetal plasma peptide levels may derive from the mother since infusion of exogenous atriopeptin 24 into the mother resulted in parallel increases in fetal and maternal peptide levels. Fetal plasma APir and NTFir levels partially reflect the markedly reduced total renal metabolic capacity compared with that of the adult. Plasma levels fell progressively after birth; whereas neonatal atrial content rose substantially. Plasma AP and NTF were simultaneously elevated in both the maternal and fetal circulation after vasopressin injection of the mother. The fetus can also respond to exogenous stimuli (vasopressin or indomethacin--presumably via ductal closure) and promptly release substantial amounts of peptide into its circulation. Thus, it appears that the AP hormonal system is functional during fetal life and responds avidly to increases in intracardiac pressure as does the mature animal.
Coronary angioplasty of chronic total occlusions with bridging collateral vessels: immediate and follow-up outcome from a large single-center experience
Authors: Isao Kinoshita, Osamu Katoh, Jin Nariyama, Satoru Otsuji, Hitone Tateyama, Tohru Kobayashi, Nobuhiko Shibata, Tadashi Ishihara, Nakaaki Ohsawa
Journal: Journal of the American College of Cardiology (1995)
Relationship Between Alternate-Day Corticosteroid Therapy and Behavioral Abnormalities
Authors: Steven S. Sharfstein, David S. Sack, Anthony S. Fauci
Journal: JAMA (1982)

Three patients with inflammatory or immunologically mediated disease manifested striking behavioral abnormalities in association with long-term alternate-day prednisone regimens. Of particular note was the fact that differences in the abnormalities depended on the day that the patients received their drug: the symptoms that appeared on a treatment day were opposite those present on a day of no therapy. These symptoms were reminiscent of rapid mood cycling in some patients with manic-depressive affective disorder. The phenomenon was dose related and markedly diminished in two patients as the dosage of corticosteroid was decreased, despite the fact that the alternate-day regimen was continued.
Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios as Prognostic Factors after Stereotactic Radiation Therapy for Early-Stage Non–Small-Cell Lung Cancer
Authors: Nathan A. Cannon, Jeffrey Meyer, Puneeth Iyengar, Chul Ahn, Kenneth D. Westover, Hak Choy, Robert Timmerman
Journal: Journal of Thoracic Oncology (2014)
CANCER OF SKIN AND OCCUPATIONAL TRAUMA
Authors: John Godwin Downing
Journal: JAMA (1952)

Occupational cancer is an injury arising out of and in the course of employment. Such an injury has been recognized in Europe for centuries, and its occurrence has been duly reported and recorded. In the United States, however, apparently it is rarely recorded. At least in Massachusetts it is almost impossible to find a record of this type of injury in the various departments which should be interested in it. Perhaps such cancers in the United States are rare. After 25 years of experience in reviewing many thousands of claims for compensation, I have been able to find only a few claims for compensation for occupational cancer. In the first 2,000 cases reviewed by me, only six patients made such claim, and not one presented sufficient evidence to substantiate it.<sup>1</sup>However, the fact that only rarely does a worker make such a claim suggests that he may have good
Complaints against the NHS in England reached 3000 a week last year
Authors: G. Iacobucci
Journal: BMJ (2013)

Complaints against NHS hospitals in England rose by 2% last year, with NHS organisations in total receiving more than 3000 written grievances a week, new figures show.

Latest annual figures from the Health and Social Care Information Centre show that there were 162 000 written complaints about NHS organisations in England during 2012-13.1

The majority of these (109 000) were made against NHS hospitals and community health services in England, with 2057 more complaints against hospitals than in 2011-12.

A further 52 700 complaints were recorded …
Treatment and Prognosis of Medulloblastoma
Authors: G. M. Tice
Journal: JAMA (1962)

In the 27-year period from 1932 to 1959, 22 patients were treated for cerebellar medulloblastoma, the diagnosis being verified in 19. Seven typical case histories are given. Five patients were living 7 or more years later without evidence that either brain or spinal cord had been damaged by the radiation applied. The results showed that a patient treated with a depth dose of 5,000 roentgens may be cured without damage to the normal brain tissue surrounding the tumor and that a dose of 1,500 to 2,000 roentgens to the cord sometimes prevents recurrence without damage to the cord. Since these experiences do not justify the hopeless attitude of the past towards this admittedly serious disease, it is believed that a word of encouragement should be given to the child's relatives.
Postprandial antral hypomotility in patients with idiopathic nausea and vomiting.
Authors: P Kerlin
Journal: Gut (1989)

The pathogenesis of idiopathic nausea and vomiting is poorly understood and could involve disorders of gut motility. The contractile activity of the stomach and small bowel was studied in 20 patients (seven men) with nausea and vomiting for longer than six months. None had previous gastric surgery, mechanical obstruction and metabolic causes were excluded. Fasting (four hours) and fed (up to two hours) contractile activity was recorded by a low compliance infusion system from the gastric antrum (four sites), the duodenum and the jejunum. Normal criteria were established in seven healthy controls. During fasting, from one to three (median 2) migrating motor complexes (MMC's) were present in patients and controls. Only two patients had contractile abnormalities during fasting. After a solid-liquid test meal, the contractility of the gastric antrum (quantified electronically as a cumulative motility index for 60 minutes) was significantly impaired in patients (p = 0.012). Six patients had normal qualitative and quantitative antral activity but two of them had 'phrase III-like fasting activity' in the small bowel after the test meal. Postprandial antral hypomotility was identified as a major abnormality in patients with unexplained nausea and vomiting.
Meeting the challenges of providing universal health coverage
Authors: A. Mulley, T. Evans, A. Binagwaho
Journal: BMJ (2013)

New approaches to service delivery must produce greater value for patients

Momentum is gathering around efforts to achieve universal health coverage—defined by the World Health Organization as universal access to needed health services without the patient experiencing financial hardship to pay for them.1 2 In December 2012, the United Nations General Assembly unanimously adopted a resolution endorsing universal health coverage and urging governments to provide all people with access to affordable healthcare.3 There is also strong support for making such provision a priority in the post-2015 global development framework that will succeed the millennium development goals.4 These developments are timely, for the health inequalities that leave more than a billion people without access to health services are increasingly recognized as an infringement of human rights and a constraint on the economic growth and social development of nations.5

The risk, however, is that a welcome global endeavor to ensure that more people can realize their right to health may default to a vast global investment in the replication of past mistakes.

The improvement in people’s health cannot be achieved by merely expanding and scaling up the healthcare delivery models of today. The 2010 world health report estimated that 20-40% …
Significance of Isolated Antibody to Hepatitis B Core Antigen Determined by Immune Response to Hepatitis B Vaccination
Authors: Michael Draelos
Journal: JAMA (1987)

The immune response to hepatitis B vaccine was studied in 14 individuals with isolated, high-titer antibody to hepatitis B core antigen (anti-HBc) and examined as an indicator of this serologic pattern's significance. Four subjects demonstrated a low-titer antibody to hepatitis B surface antigen (anti-HBs) on repeated testing, and three in this subgroup had anamnestic responses (anti-HBs, 82 to 140 ratio units) after vaccination. Compared with 22 seronegative controls, the remaining ten had significantly higher anti-HBs response rates (78% vs 22%, P = .003) and median anti-HBs titers (4 vs 0 ratio units, P = .008) two weeks after vaccination. One of ten subjects had an anamnestic response, while another exhibited no response. The general pattern of anti-HBs responsiveness observed in those subjects with isolated, high-titer anti-HBc was intermediate between seronegative and anti-HBs-positive groups and may indicate a state of waning immunity after natural infection. Hepatitis B vaccination with follow-up anti-HBs testing should be done for those patients with isolated, high-titer anti-HBc to help exclude chronic infection and boost protective immunity.
Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial
Authors: E Tavernier, J-M Boiron, F Huguet, K Bradstock, N Vey, T Kovacsovics, A Delannoy, N Fegueux, P Fenaux, A Stamatoullas, O Tournilhac, A Buzyn, O Reman, C Charrin, C Boucheix, J Gabert, V Lhéritier, J-P Vernant, H Dombret, X Thomas
Journal: Leukemia (2007)
Differential expression and regulation of nucleoside transport systems in rat liver parenchymal and hepatoma cells
Authors: Belén del Santo, Raquel Valdés, João Mata, Antonio Felipe, Javier F. Casado, Marçal Pastor-Anglada
Journal: Hepatology (1998)

Primary cultures of rat–liver parenchymal cells show carrier–mediated nucleoside uptake by a mechanism that mainly involves concentrative, Na + –dependent transport activity. In contrast, the hepatoma cell line FAO shows high nucleoside transport activity, although it is mostly accounted for by Na + –independent transport processes. This is associated with a low amount of sodium purine nucleoside transporter (SPNT) mRNA. SPNT encodes a purine–preferring transporter expressed in liver parenchymal cells. To analyze whether SPNT expression is modulated during cell proliferation, SPNT mRNA levels were determined in the early phase of liver growth after partial hepatectomy and in synchronized FAO cells that had been induced to proliferate. SPNT mRNA amounts increased as early as 2 hours after partial hepatectomy. FAO cells induced to proliferate after serum refeeding show an increase in SPNT mRNA levels, which is followed by an increase in Na + –dependent nucleoside uptake and occurs before the peak of 3 H–thymidine incorporation into DNA. FAO cells also express significant equilibrative nucleoside transport activity, which may be accounted for by the expression of the nitrobenzylthioinosine (NBTI)–sensitive and –insensitive isoforms, rat equilibrative nucleoside transporter 1 (rENT1) and rENT2, respectively. Interestingly, rENT2 mRNA levels follow a similar pattern to that described for SPNT when FAO cells are induced to proliferate, whereas rENT1 appears to be constitutively expressed. Liver parenchymal cells show low and negligible mRNA levels for rENT1 and rENT2 transporters, respectively, although most of the equilibrative transport activity found in hepatocytes is NBTI–resistant. It is concluded that: 1) SPNT expression is regulated both in vivo and in vitro in a way that appears to be dependent on cell cycle progression; 2) SPNT expression may be a feature of differentiated hepatocytes; and 3) equilibrative transporters are differentially regulated, rENT2 expression being cell cycle-dependent. This is consistent with its putative role as a growth factor-induced delayed early response gene.
IκBβ is an essential co-activator for LPS-induced IL-1β transcription in vivo
Authors: Melanie Scheibel, Bettina Klein, Heidrun Merkle, Manon Schulz, Ralph Fritsch, Florian R. Greten, Melek C. Arkan, Günter Schneider, Roland M. Schmid
Journal: The Journal of Experimental Medicine (2010)

Inhibitor of κB (IκB) β (IκBβ) represents one of the major primary regulators of NF-κB in mammals. In contrast to the defined regulatory interplay between NF-κB and IκBα, much less is known about the biological function of IκBβ. To elucidate the physiological role of IκBβ in NF-κB signaling in vivo, we generated IκBβ-deficient mice. These animals proved to be highly refractory to LPS-induced lethality, accompanied by a strong reduction in sepsis-associated cytokine production. In response to LPS, IκBβ is recruited to the IL-1β promoter forming a complex with the NF-κB subunits RelA/c-Rel required for IL-1β transcription. Further transcriptome analysis of LPS-stimulated wild-type and IκBβ-deficient BM-derived macrophages revealed several other genes with known regulatory functions in innate immunity arguing that a subset of NF-κB target genes is under control of IκBβ. Collectively, these findings provide an essential proinflammatory role for IκBβ in vivo, and establish a critical function for IκBβ as a transcriptional coactivator under inflammatory conditions.
Cholera toxin inhibits signal transduction by several mitogens and the in vitro growth of human small-cell lung cancer.
Authors: J Viallet, Y Sharoni, H Frucht, R T Jensen, J D Minna, E A Sausville
Journal: Journal of Clinical Investigation (1990)

Cholera toxin (CT) inhibited the in vitro growth of three of four human small-cell lung carcinoma (SCLC) cell lines with a 50% inhibitory concentration of 27-242 ng/ml. Loss of surface membrane ruffling and the capacity of [Tyr4]-bombesin, vasopressin, and fetal calf serum to stimulate increases in intracellular free calcium clearly preceded effects on cellular metabolic activity and cell growth. 125I-[Tyr4]-bombesin binding was unaffected by CT treatment but [Tyr4]-bombesin stimulated phospholipase C activity was decreased in membranes from CT-treated SCLC cells. CT stimulated a rapid but transient increase in intracellular cyclic AMP ([cAMP]i) in SCLC. The effects of CT on susceptible SCLC were not reproduced by elevations of [cAMP]i induced by forskolin or cyclic AMP analogues. GM1 ganglioside, the cellular binding site for CT, was highly expressed in the CT-sensitive but not the CT-resistant SCLC cell lines. In contrast, expression of guanine nucleotide binding protein substrates for ADP-ribosylation by CT was similar. These data demonstrate the existence of a CT-sensitive growth inhibitory pathway in SCLC-bearing GM1 ganglioside. Addition of CT results in decreased responsiveness to several mitogenic stimuli. These results suggest novel therapeutic approaches to human SCLC.