tbuckley/cabot-search huggingface dataset:
Use of anti-HLA antibodies to mask major histocompatibility complex gene products on tumor cells can enhance susceptibility of these cells to lysis by natural killer cells.
Authors: P I Lobo, C E Spencer
Journal: Journal of Clinical Investigation (1989)

The role of major histocompatibility gene products (i.e., HLA molecules) in rendering tumor cells resistant to natural killer (NK) cell-mediated lysis was investigated by using mouse monoclonal antibodies to bind and mask HLA or non-HLA gene products on the cell membrane of human allogeneic tumor targets. Enhanced lysis of resistant lymphoid and certain other solid tumor cell lines was observed only when monoclonals used reacted to class I and II HLA molecules but not non-HLA molecules on tumor targets. Enhanced lysis was not due to antibody dependent cellular cytotoxicity or due to an effect of antibody on NK effectors. Of importance, normal autologous and allogeneic human lymphocytes could not be lysed by NK cells despite blast transformation with mitogens or masking of HLA membrane determinants on blasts with monoclonal antibodies. Enhanced lysis, in the presence of antibody to HLA antigens, was not due to increased NK cell binding to tumor targets, but a consequence of enhanced postbinding lysis. Studies using granules obtained from NK cells indicated that masking of HLA antigens did not enhance the susceptibility of tumor targets to cytolysins. Such observations would suggest that HLA antigens on tumor targets inhibit the triggering of effector cells (and release of cytolysins) after recognition and binding of NK cells to target cells.
Abstract 3836: Identification of PTPsigma as an autophagic phosphatase
Authors: Katie R. Martin, Yong Xu, Brendan D. Looyenga, Ryan J. Davis, Chia-Lun Wu, Michel L. Tremblay, H Eric Xu, Jeffrey P. Mackeigan
Journal: Cancer Research (2011)

Abstract Macroautophagy is a dynamic process whereby portions of the cytosol are encapsulated in double-membrane vesicles and delivered to the lysosome for degradation. Phosphatidylinositol-3-phosphate (PI(3)P) is concentrated on autophagic vesicles and recruits effector proteins critical for this process. The production of PI(3)P by the class III phosphatidylinositol 3-kinase (PI3K), Vps34, has been well established; however, protein phosphatases which antagonize this early step in autophagy remain to be identified. To identify such enzymes, we screened human phosphatase genes by RNA interference (RNAi) and found that loss of PTPsigma, a dual-domain protein tyrosine phosphatase (PTP), increases cellular PI(3)P. The abundant PI(3)P-positive vesicles conferred by PTPsigma loss strikingly phenocopied those observed in amino acid-starved cells. Accordingly, we discovered that loss of PTPsigma hyperactivates both constitutive and induced autophagy. Finally, we found that PTPsigma localizes to PI(3)P-positive membranes in cells and this vesicular localization is enhanced during autophagy. Our findings propose a novel role for PTPsigma and provide insight into the regulation of autophagy. Mechanistic knowledge of this process is critical for understanding and targeting therapies for several human diseases, including cancer and Alzheimer's disease, in which abnormal autophagy may be pathological. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3836. doi:10.1158/1538-7445.AM2011-3836
A postscript to Circulation of the blood: men and ideas.
Authors: R L Riley
Journal: Circulation (1982)

Since 1964, when Fishman and Richards published Circulation of the Blood: Men and Ideas, Guyton's model of the circulation, in which mean circulatory pressure serves as the upstream pressure for venous return, has been extended, and the concept of vascular smooth muscle tone acting like the pressure surrounding a Starling resistor has been postulated. According to this scheme, the positive zero flow intercepts of rapidly determined arterial pressure-flow curves are the effective downstream pressures for arterial flow to different tissues. The arterioles, like Starling resistors, determine the downstream pressures and are followed by abrupt pressure drops, or "waterfalls." Capillary pressures are closely linked to those of the venules into which they flow. Capillary-venular pressures are the upstream pressures for venous return. In exercising muscles, reduced arteriolar tone lowers arteriolar pressure and increases arterial flow. This, in turn, raises capillary-venular pressure and increases venous flow. The arteriolar-capillary waterfall is decreased or eliminated. Total blood flow is increased by diversion of blood from tissues with slow venous drainage to muscles with fast venous drainage (low resistance X compliance). The heart pumps away the increased venous return by shifting to a new ventricular function curve.
TRAK/Milton Motor-Adaptor Proteins Steer Mitochondrial Trafficking to Axons and Dendrites
Authors: Myrrhe van Spronsen, Marina Mikhaylova, Joanna Lipka, Max A. Schlager, Dave J. van den Heuvel, Marijn Kuijpers, Phebe S. Wulf, Nanda Keijzer, Jeroen Demmers, Lukas C. Kapitein, Dick Jaarsma, Hans C. Gerritsen, Anna Akhmanova, Casper C. Hoogenraad
Journal: Neuron (2013)
The Chromogranin–Secretogranin Family
Authors: Laurent Taupenot, Kimberly L. Harper, Daniel T. O'Connor
Journal: New England Journal of Medicine (2003)

The members of the chromogranin–secretogranin family of peptide hormones, biogenic amines, and neurotransmitters are enclosed within vesicles in the neuroendocrine system and a variety of neurons. These granins, the chief of which is chromogranin A, participate in sympathoadrenal activity and serve as markers of neuroendocrine tumors, especially pheochromocytoma.
Notch signaling is a critical regulator of allogeneic CD4+ T-cell responses mediating graft-versus-host disease
Authors: Yi Zhang, Ashley R. Sandy, Jina Wang, Vedran Radojcic, Gloria T. Shan, Ivy T. Tran, Ann Friedman, Koji Kato, Shan He, Shuaiying Cui, Elizabeth Hexner, Dale M. Frank, Stephen G. Emerson, Warren S. Pear, Ivan Maillard
Journal: Blood (2010)
The ??Yarmulke?? Sign of Paget??s Disease
Authors: JEFFREY R. KUNIN, PETER J. STROUSE
Journal: Clinical Nuclear Medicine (1991)

A 78-year-old man with a history of Paget's disease and right hip pain was evaluated by whole body Tc-99m MDP bone scintigraphy. The activity of Paget's disease can be assessed by bone scanning. Quiescent portions may appear normal while active areas of osteolysis or osteoblastosis show increased uptake, ft has been shown previously that the peripheral margins of osteoporosis circumscripta demonstrate increased uptake relative to surrounding bone or even to its central portion. We describe the bone scan findings in a case of mixed osteolytic and osteosclerotic Paget's disease of the skull, resulting in the appearance of a “yarmulke” sign.
REPORT OF COMMITTEE ON COMPENSATION TABLES FOR EYE INJURIES
Authors: Harry S. Gradle
Journal: JAMA (1933)

Your committee has continued its activities during the last year and is pleased to report increasing use of the method advocated by it for determining the visual efficiency of an individual following industrial injury or occupational disease of the eyes. In reply to a letter of inquiry directed to the International Association of Industrial Accident Boards and Commissions of the U. S. A., as to the uniformity of methods for evaluating visual efficiency following ocular injuries or occupational diseases, and as to how many boards and commissions utilized the American Medical Association committee's methods, the secretary replied (in part): "Except in states where compensation for specific injuries is written into the statutes, I think all the states compute partial permanent (disability) on a percentage of total permanent (disability), and this would apply to eye injuries as far as I know. "Economic blindness is construed as total permanent disability by a
A labile transcriptional repressor modulates endotoxin tolerance.
Authors: K E LaRue, C E McCall
Journal: The Journal of Experimental Medicine (1994)

Tolerance to bacterial lipopolysaccharide (LPS, endotoxin) is an adaptive cellular process whereby exposure to endotoxin induces a subsequent hyporesponsive state characterized by decreased levels of LPS-induced cytokine mRNA and protein. We demonstrate, in a human promonocytic cell line, THP-1, that endotoxin tolerance is manifested by decreased LPS-induced interleukin 1 beta (IL-1 beta) transcription. Inhibition of protein synthesis reverses the tolerant phenotype by inducing transcription of IL-1 beta in the absence of a second stimulus. These results indicate that a labile protein contributes to the endotoxin-tolerant phenotype, and that this factor acts in a dominant repressive manner to inhibit the activity of existing transcription factors. We provide further data that cellular expression of I kappa B-alpha correlates with downregulated IL-1 beta gene expression during endotoxin tolerance, implicating I kappa B-alpha as a potential candidate for the labile repressor identified herein.
The Specialties in General Practice
Authors: Jerome T. Nolan
Journal: JAMA (1964)

This volume, since its first appearance in 1951, has remained an almost standard reference for the generalist's bookshelf. In its present edition, the third, it has lost none of its usefulness and gained by the addition of three new chapters on the clinical laboratory, neurology, and industrial medicine. The only other significant alteration has been the enlargement of "Minor Surgery" to the broader "Surgery" which now contains detailed discussions of presurgical management and postoperative care. "Fractures," "Dislocations," and "Orthopedic Surgery" have been combined into "Orthopedic Trauma," but suffer somewhat from the amalgamation, which imparts less specific detail than many of the other sections. Notable are several chapters. The diseases of the anus, rectum, and colon are exhaustively treated with literate good humor. Urology contains useful tables as diagnostic and differential aids. In the section, "Obstetrics and Gynecology," the portions dealing with infertility and contraception are up to date and exceptional.
Doctor suspended as high death rate in emergency department is investigated
Authors: Claire Wallerstein
Journal: BMJ (2005)

Obesity in children in England continues to rise 334 More than one in four children in England are overweight or obese, said a government report published last week which showed that obesity in young people is continuing to rise.The report said that the prevalence of obesity in children aged 2 to 10 increased from 9.9% in 1995 to 13.7% in 2003.The total number of overweight and obese children rose from 22.7% to 27.7% in this period.Obesity increased most in older children aged 8 to 10, rising from 11.2% in 1995 to 16.5% in 2003.Levels of obesity were similar for both sexes, increasing from 9.6% in 1995 to 14.9% in 2003 for boys and from 10.3% to 12.5% for girls.Children living in households with the lowest incomes had higher rates of obesity than those from households with the highest incomes (15.8% v 13.3%).
Do calcium channel blockers and antimuscarinics protect against perforated colonic diverticular disease? A case control study
Authors: C R Morris, I M Harvey, W S L Stebbings, C T M Speakman, H J Kennedy, A R Hart
Journal: Gut (2003)

<b>Background:</b> The aetiology of perforated colonic diverticular disease (PCDD) remains largely unknown. Perforation may result from a combination of high intracolonic pressures, secondary to excessive colonic segmentation, and impairment of the mucosal barrier. Calcium channel blockers and antimuscarinic drugs, which reduce colonic contractility and tone, could potentially protect against perforation. The aim of this study was to test this hypothesis using a case control design. <b>Methods:</b> All cases of acute PCDD were identified over a five year period in two hospitals in Norfolk, UK. Each case was matched for age, sex, and date of admission to two controls groups: (1) patients undergoing cataract surgery and (2) patients with basal cell carcinoma. Data on drug use prior to hospital admission were obtained from medical and nursing records and compared between cases and controls. <b>Results:</b> A total of 120 cases of PCDD were identified and matched to 240 controls in each group. A statistically significant protective association was seen between calcium channel blocker use and PCDD using both control groups. The odds ratios were 0.41 (95% confidence interval (CI) 0.18–0.93) using the ophthalmology control group and 0.36 (95% CI 0.16–0.82) using the dermatology control group. <b>Conclusions:</b> This study has shown for the first time that a protective association exists between calcium channel blockers and PCDD. The validity of this association is supported by the consistent finding in both control groups and the plausible biological mechanisms. Further studies are required to confirm this association but calcium channel blockers may represent a potential preventive therapy in PCDD.
PHF6 mutations in T-cell acute lymphoblastic leukemia
Authors: Pieter Van Vlierberghe, Teresa Palomero, Hossein Khiabanian, Joni Van der Meulen, Mireia Castillo, Nadine Van Roy, Barbara De Moerloose, Jan Philippé, Sara González-García, María L Toribio, Tom Taghon, Linda Zuurbier, Barbara Cauwelier, Christine J Harrison, Claire Schwab, Markus Pisecker, Sabine Strehl, Anton W Langerak, Jozef Gecz, Edwin Sonneveld, Rob Pieters, Elisabeth Paietta, Jacob M Rowe, Peter H Wiernik, Yves Benoit, Jean Soulier, Bruce Poppe, Xiaopan Yao, Carlos Cordon-Cardo, Jules Meijerink, Raul Rabadan, Frank Speleman, Adolfo Ferrando
Journal: Nature Genetics (2010)
UK government sues Servier for 220m over alleged blocking of generic substitute
Authors: C. Dyer
Journal: BMJ (2011)

The UK government is suing the French drug company Servier for £220m (€246m; $360m) for allegedly blocking generic versions of its angiotensin converting enzyme inhibitor perindopril entering the UK market between 2001 and 2007.

The Department of Health, along with all the strategic health authorities and primary care trusts in England, has launched a High Court action to reclaim the money they say that the NHS in England was forced to pay for more expensive drugs.

Servier’s patent on the drug, used to treat hypertension and heart disease, ran out in 2001, after which, the …
On Amputation at the Ankle-Joint
Authors: G. H. B. Macleod
Journal: BMJ (1869)

Association would assist, in the most effectual way, the great objects of its foundation.I cannot for a moment suppose that the Council of this Association, if urged by you to do so, would resist such an appeal; and it is to me certain, that, in this manner, real advantage to the profession, and a sure advance in our knowledge, might be annually effected without encroach- ing upon any other useful objects.Should you agree with me, I would urge that a very strong representation to that effect be sent from this Section to the Council.At any rate, 1 trust you will forgive my bringing this matter before you, feeling, as I do, that, in the present condition of medicine, what we require is not brilliant hypothesis, or ingenious speculation, but that solid genuine work to which we may look for furnishing us with truthful data.Let us resolve, by means of renewed experiments and careful observations with our modern appliances, to overcome the difficulties which surround us, and there can be little doubt we shall render the practice of our art worthy of the advanced state of science which now prevails.
Burkitt's Lymphoma
Authors: John L. Ziegler
Journal: New England Journal of Medicine (1981)

TWO decades have passed since Denis Burkitt, a British surgeon working in Uganda, originally described the tumor that now bears his name.1 The discovery that this tumor has distinctive clinical and histologic features among the malignant lymphomas2 , 3 was soon followed by the observation of its dramatic response to chemotherapy.4 5 6 The occurrence of spontaneous regressions and long-term remissions after treatment led Burkitt and others to postulate a tumor-directed host immune response.4 , 7 Burkitt was also intrigued by the apparent geographic limitation of this lymphoma. His renowned "tumor safaris" defined a "lymphoma belt" with distinct topographic and climatic features that originally suggested a . . .
Metoclopramide for Gastroparesis Diabeticorum
Authors: D Braverman, A Bogoch
Journal: Diabetes Care (1978)

Three patients with uncontrolled diabetes mellitus and with symptoms due to gastric retention proved to have gastroparesis diabeticorum. The diagnosis was established by the beefsteak-barium meal. After the administration of metoclopramide, gastric emptying improved and the diabetes was easily controlled. Gastroparesis diabeticorum is one cause of uncontrolled diabetes mellitus and may be helped by the administration of metoclopramide.
LEGAL AND THERAPEUTIC ASPECTS OF SYPHILIS AND PREGNANCY
Authors: CHARLES H. PECKHAM
Journal: JAMA (1941)

More than twenty-five years have elapsed since the first legal attempt was made to control the transmission of venereal disease from one partner in marriage to the other. This early legislation was faulty and failed to produce the desired result, since it did not apply to both sexes and did not require microscopic or serologic tests as aids in diagnosis. In the last five years the public has been made violently conscious of the venereal disease problem (and particularly so with regard to syphilis) both from the standpoint of the individual and from that of the community, the state and the nation as a whole. Partly because of this and partly because public health authorities have instituted an active anti-venereal disease campaign, many state legislatures have enacted statutes to forbid the issue of marriage licenses to persons suffering from such diseases unless it was felt that the condition is not
Immunisation and eczema.
Authors: S Lingham, R S Wells
Journal: BMJ (1978)

1 in 10 (or greater) chance of diagnosing a brain tumour is not to be missed, then referral of all stroke patients with the appropriate evolution would completely swamp the available CAT scanning resources.Stroke evolution is only one factor determining the attitude of a general physician towards the management of a stroke patient.Considering the scarcity and the costliness of the new diagnostic machinery, information is required concerning the incidence of tumour or subdural haematoma in stroke patients as they present on the general medical ward.
The onset and autonomic regulation of cardiac pacemaker activity: relevance of the f current
Authors: D. DiFrancesco
Journal: Cardiovascular Research (1995)

Journal Article The onset and autonomic regulation of cardiac pacemaker activity: relevance of the f current Get access Dario DiFrancesco Dario DiFrancesco Dipartimento di Fisiologia e Biochimica Generali, Elettrofisiologia, University of Milan, via Celoria 26, 20133 Milan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 4, April 1995, Pages 449–456, https://doi.org/10.1016/S0008-6363(96)88518-X Published: 01 April 1995 Article history Received: 28 June 1994 Accepted: 31 October 1994 Published: 01 April 1995
PROGNOSIS IN IDIOPATHIC HEMOPTYSIS
Authors: Bruce E. Douglass
Journal: JAMA (1952)

Expectoration of blood may be caused by many disorders. In some instances thorough investigation fails to disclose the cause of this symptom and the patient may be said to have idiopathic hemoptysis. Several authors<sup>1</sup>have suggested that hemoptysis in the absence of demonstrable causative disease may be due to ulceration of the mucosa of small bronchi. Other possibilities have been suggested: namely, small pulmonary infarctions; vicarious menstruation; blood dyscrasias; and systemic and pulmonary hypertension. The frequency of idiopathic hemoptysis as reported in the literature varies considerably, depending on the method of selection of cases and the thoroughness of their study. Chaves<sup>2</sup>studied a group of 325 patients who had had hemoptysis less than three months before they were examined in a New York City chest clinic; 189, or 58.1%, of these had no objective evidence of thoracic disease at the time of examination. Jackson and Diamond<sup>1a</sup>reported
RUPTURED GASTRIC ULCER IN INFANCY: REPORT OF CASE
Authors: H. E. Butka
Journal: JAMA (1927)

Although the literature abounds in reports of duodenal ulcers, the occurrence of gastric ulcer in infants is exceedingly rare. A careful search has revealed only three cases of ruptured gastric ulcer in infants under 2 months of age. In 7,219 autopsies reported by Sturtevant and Shapiro<sup>1</sup>from Bellevue Hospital, there were five cases of gastric ulcer in children. Adler<sup>2</sup>reports twenty-six fatal cases of gastric ulcer in children, nine of which had perforated. Proctor,<sup>3</sup>reporting from the Mayo Clinic for the years 1906-1924, describes only two cases of typical gastric ulcer in children. Thiele<sup>4</sup>states that gastric ulcer in children under 16 years of age is comparaively rare, and reports 119 cases. Cackovic<sup>5</sup>found that 2.3 per cent of gastric ulcer in his clinic was in children under 10 years of age. Carteaux<sup>6</sup>reports the first recorded fatal case of ulcer of the stomach in a new-born infant, in
Propanthelene as an agent for medical vagotomy.
Authors: R G Checketts, I E Gillespie, A W Kay
Journal: Gut (1966)

EDITORIAL SYNOPSIS This well-designed, briefly and clearly presented study of the use of Proban- thine as a blocking agent, in an attempt to predict the effect of surgical vagotomy on gastric acid responses, has produced potentially important results.Computer analysis has provided a formula with which to predict the post-operative responses more accurately than a comparison of absolute values.
Adeno-associated virus capsid antigen presentation is dependent on endosomal escape
Authors: Chengwen Li, Yi He, Sarah Nicolson, Matt Hirsch, Marc S. Weinberg, Ping Zhang, Tal Kafri, R. Jude Samulski
Journal: Journal of Clinical Investigation (2013)

Adeno-associated virus (AAV) vectors are attractive for gene delivery-based therapeutics, but data from recent clinical trials have indicated that AAV capsids induce a cytotoxic T lymphocyte (CTL) response that eliminates transduced cells. In this study, we used traditional pharmacological agents and AAV mutants to elucidate the pathway of capsid cross-presentation in AAV-permissive cells. Endosomal acidification inhibitors blocked AAV2 antigen presentation by over 90%, while proteasome inhibitors completely abrogated antigen presentation. Using mutant viruses that are defective for nuclear entry, we observed a 90% decrease in capsid antigen presentation. Different antigen presentation efficiencies were achieved by selectively mutating virion nuclear localization signals. Low antigen presentation was demonstrated with basic region 1 (BR1) mutants, despite relatively high transduction efficiency, whereas there was no difference in antigen presentation between BR2 and BR3 mutants defective for transduction, as compared with wild-type AAV2. These results suggest that effective AAV2 capsid antigen presentation is dependent on AAV virion escape from the endosome/lysosome for antigen degradation by proteasomes, but is independent of nuclear uncoating. These results should facilitate the design of effective strategies to evade capsid-specific CTL-mediated elimination of AAV-transduced target cells in future clinical trials.