tbuckley/cabot-search huggingface dataset:
CD40 Activation Induces Apoptosis in Cultured Human Hepatocytes via Induction of Cell Surface Fas Ligand Expression and Amplifies Fas-mediated Hepatocyte Death during Allograft Rejection
Authors: Simon C. Afford, Satinder Randhawa, Aristides G. Eliopoulos, Stefan G. Hubscher, Lawrence S. Young, David H. Adams
Journal: The Journal of Experimental Medicine (1999)

We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68(+) macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the HepG2 cell line in both of which apoptosis was induced, not only by cross-linking Fas directly but also via CD40 activation. Our data suggest that CD40 activation induces apoptosis via Fas because (a) ligation of CD40 upregulated hepatocyte FasL expression, and (b) apoptosis induced via activation of CD40 was prevented by a neutralizing monoclonal antibody to FasL. Thus, CD40 engagement triggers apoptosis of human hepatocytes and might amplify Fas-dependent hepatocyte apoptosis in chronic rejection and other inflammatory liver diseases in which Fas-mediated apoptosis is involved.
The Role of the Government in the Provision of Health Services
Authors: STUART BONDURANT
Journal: Annals of Internal Medicine (1968)

It appears that the government has assumed responsibility for developing a system to assure a standard of comprehensive health care for all citizens. This system will involve payment through a mechanism that spreads the financial burden of health care in time and among individuals. The agencies responsible for collecting, holding, and dispersing funds will, for the foreseeable future, include both governmental and private groups; but from the point of both the consumer and the provider the distinction between the two will be reduced by government regulation of private insurers. Government will, by intent or by default, be a major determinant of the priority of health care among national goals and of the priority of the various components of the health care system. Government will be the organ for matching the needs of the consumers with the needs and potential of the providers of health care within the limits of the resources that are available.
PHARMACOINVASIVE STRATEGY VERSUS FIBRINOLYTIC THERAPY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: A PROPENSITY SCORE MATCHED ANALYSIS FROM THE NATIONWIDE INPATIENT SAMPLE
Authors: Nileshkumar Patel, Nish Patel, Badal Thakkar, Nilay Patel, Shilpkumar Arora, Ankit Chothani, Sidakpal Panaich, Vikas Singh, Sunny Jhamnani, Abhishek Deshmukh, Apurva Badheka, Carlos Alfonso, Mauricio Cohen
Journal: Journal of the American College of Cardiology (2015)
Radiation Oncology: Rationale, Technique, Results
Authors: Walter G. Gunn
Journal: JAMA (1989)

Beginning in 1959 and revised and updated about every five years thereafter, the text by Moss, with and without various coauthors, has been used by trainees and by physicians practicing therapeutic radiology from that day to this. Ten years have elapsed since the last edition, the fifth, was printed, and now we have a new one, largely rewritten. Professor Moss has been joined by Dr Cox as coeditor and has confined his own writing efforts to part or all of seven chapters. It should be pointed out immediately, however, that one of the great strengths of the previous editions was an introductory section in each chapter detailing the response of the specific organ in question to irradiation. These were usually four- or five-page, succinct, well-illustrated discussions of the pathophysiology of irradiation, and they were, to my knowledge, unique to this particular text and vital to the understanding and analysis of
Two Centuries of Medicine: A History of the School of Medicine, University of Pennsylvania
Authors: Lester S. King
Journal: JAMA (1965)

The title is apt. Dr. Comer not only gives us a history of the oldest medical school in this country but, through its windows, shows us the panorama of American medicine during two centuries. The great figures of early American medicine, such as Morgan, Shippen, Rush, Kuhn, pass before us as the new medical school took shape and struggled through its early years. With the dislocations of the Revolutionary War and the postwar period, new physicians came into prominence and assumed leadership.  Dr. Corner, as he traces the fortunes and events of the school, lays constant stress on the problems that beset medicine as a whole. In brief compass we perceive how the social and scientific climate changed, and how medical practice altered. We see the problems of medical education—the limitations of the lecture system, the lack of practical training, the difficulties in securing suitable hospital facilities, the conflict between
Use of differentiation inducing agents in the myelodysplastic syndrome and acute non‐lymphocytic leukemia
Authors: Stephen J. Hoffman, William A. Robinson
Journal: American Journal of Hematology (1988)

Abstract The use of chemical agents that induce differentiation of malignant cells to normal cells has held great promise as an adjunct to standard chemotherapy. In vitro data has shown that 13‐ cis ‐retinoic acid can differentiate certain leukemia cell lines (e.g., HL‐60) into stable granulocyte cells. In this study, oral 13‐ cis ‐retinoic acid was administered to four patients with the myelodysplastic syndrome (MDS) and to four patients with acute nonlymphocytic leukemia (ANLL). None of the MDS patients showed an hematologic response to the drug, while three of four ANLL patients responded with normalized peripheral blood counts. The side effects of the drug at 80‐120 mg/d (dry skin, cheilitis, epistaxis) were self limiting.
Left Axis Deviation: Prevalence, Associated Conditions, and Prognosis
Authors: LEON D. OSTRANDER
Journal: Annals of Internal Medicine (1971)

In Tecumseh, Michigan, 4,678 persons past 20 years of age participated in a series of comprehensive examinations in 1959 and 1960. The electrocardiograms of 248 participants showed a mean QRS axis of -30 deg or beyond in the frontal plane. Men had a higher prevalence of left axis deviation than women, and the frequency increased with age among both sexes. Fifty-nine percent of the persons with left axis deviation had other findings that suggested heart disease. Forty-one percent were free of such abnormalities (isolated left axis deviation). Those with isolated left axis deviation had no excess incidence of heart disease morbidity or mortality during an average observation period of 4 years. Their frequency of coronary heart risk factors was similar to that observed in the entire study population. Isolated left axis deviation appears to be a common electrocardiographic finding without unfavorable prognostic implications.
Pollutant Particles Produce Vasoconstriction and Enhance MAPK Signaling via Angiotensin Type I Receptor
Authors: Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Yuh-Chin T. Huang
Journal: Environmental Health Perspectives (2005)

Exposure to particulate matter (PM) is associated with acute cardiovascular mortality and morbidity, but the mechanisms are not entirely clear. In this study, we hypothesized that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor that regulates inflammation and vascular function. We investigated the acute effects of St. Louis, Missouri, urban particles (UPs; Standard Reference Material 1648) on the constriction of isolated rat pulmonary artery rings and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) in human pulmonary artery endothelial cells with or without losartan, an antagonist of AT1R. UPs at 1–100 μg/mL induced acute vaso-constriction in pulmonary artery. UPs also produced a time- and dose-dependent increase in phosphorylation of ERK1/2 and p38 MAPK. Losartan pretreatment inhibited both the vasoconstriction and the activation of ERK1/2 and p38. The water-soluble fraction of UPs was sufficient for inducing ERK1/2 and p38 phosphorylation, which was also losartan inhibitable. Copper and vanadium, two soluble transition metals contained in UPs, induced pulmonary vasoconstriction and phosphorylation of ERK1/2 and p38, but only the phosphorylation of p38 was inhibited by losartan. The UP-induced activation of ERK1/2 and p38 was attenuated by captopril, an angiotensin-converting enzyme inhibitor. These results indicate that activation of the local renin–angiotensin system may play an important role in cardiovascular effects induced by PM.
Control of the corpus luteum: a model system for toxicology research.
Authors: M E Freeman
Journal: Environmental Health Perspectives (1981)

The rodent corpus luteum is an ephemeral structure releasing progesterone for only a few hours rather than several days. However, in response to the mating stimulus, sufficient prolactin is released from the pituitary gland in a unique pattern to activate the corpus luteum and maintain it in a secretory state for several days. Progesterone, secreted from the corpus luteum, prolongs the secretion of prolactin, while the uterus may secrete a substance which terminates the functional life of the corpus luteum directly and also acts upon he prolactin secretory apparatus within the hypothalamopituitary axis to terminate prolactin secretion.
Double Early Epidermoid Carcinoma of the Esophagus in Columnar Epithelium
Authors: C.H. Resano, N. Cabrera, D. Gonzalez Cueto, A.E. Sanchez Basso, H.H. Rubio
Journal: Endoscopy (1985)

Two epidermoid, identical but independent tumors of the middle esophagus, arising in columnar lined esophagus (Barrett's esophagus or endobrachyesophagus) are reported. Both were diagnosed endoscopically and resected. The upper tumor involved only the mucosa, the aboral one the mucosa and submucosa.
PREVENTION OF CONTRACTURES FOLLOWING INFECTIONS OF THE HAND
Authors: SUMNER L. KOCH
Journal: JAMA (1927)

The many crippling deformities resulting from infections of the hand that have come to my attention during recent years emphasize the fact that, if serious disabilities are to be avoided, attention must be concentrated on the preservation of function as well as on the control of infection. The old adage as to the ounce of prevention and pound of cure may well be applied to contractures of the hand, for the prevention of contractures is much simpler than their successful treatment once they are developed. The rapid and diffuse swelling of the hand and forearm associated with acute lymphatic infections is generally recognized as a danger signal which indicates absolute rest, hot dressings and abstention from any operative treatment. If exploratory incisions are made in such cases in the hope of finding pus (fig. 1), the patient may quickly succumb to a systemic infection; or in the process of a
A8.15 ProS and Gas6 - two structurally related proteins with therapeutic effects in experimental arthritis, but via two different mechanisms
Authors: S Beermann, CEJ Waterborg, BT van den Brand, MB Bennink, MI Koenders, M de Vries, CV Rothlin, FAJ van de Loo
Journal: Annals of the Rheumatic Diseases (2015)

<h3></h3> Protein S (ProS) and growth-arrest-specific protein 6 (Gas6) are both ligands for TAM receptors, a family of receptor tyrosin kinases consisting of Axl, Mertk and Tyro3. Activation of these receptors induces a negative feedback loop by inhibiting TLR- and cytokine receptor signalling. ProS, next to its function as a TAM receptor ligand, plays a role in coagulation where it acts as a cofactor of the anticoagulant Protein C. Due to the anti-inflammatory effects of Gas6 and ProS, they could be a promising treatment for different autoimmune disease such as rheumatoid arthritis (RA). In RA joints, activation of non-immunological pathways also takes place, like the coagulation cascade and factors of the coagulation cascade are described to cleave and activate complement factors. In this way the anti-coagulative function of ProS could positively affect RA pathology. We therefore investigated the therapeutic effect of Gas6 and ProS in experimental arthritis. Adenoviruses for overexpressing <i>Gas6</i> or <i>Pros1</i> genes were injected locally into the knee joints of mice in two different RA models: one day after the booster injection in the T-cell dependent collagen-induced arthritis (CIA) model or one day before the second injection of serum in the anti-GPI autoantibody driven KRN serum transfer model. Mice were sacrificed at day 31 or day 14, respectively and knee joints were taken for histology and synovial biopsies for cytokine profiling. In the CIA model, mice receiving adenoviruses encoding for either <i>Pros1</i> or <i>Gas6</i> showed reduced joint inflammation, bone and cartilage erosion in which the effect of <i>Gas6</i> was more prominent than that of <i>Pros1</i>. Furthermore, levels of pro-inflammatory cytokines in the synovium such as IL-6 and IL-1b and also MMP-9 and MMP-13 were reduced whereas expression of SOCS1 and protein levels of SOCS3, downstream molecules of TAM receptor signalling, were increased indicating a TAM receptor mediated mechanism. In KRN arthritis, inflammation, bone and cartilage erosion and osteophyte formation was strongly reduced in <i>Pros1</i> treated mice, whereas <i>Gas6</i> was completely ineffective in this model. Expression of cytokines like TNFa, IL-1b and MMP-13 in the synovium were decreased in mice receiving <i>Pros1</i> whereas SOCS1 and SOCS3 expression remains unchanged, indicating a TAM receptor independent effect. In conclusion, Gas6 and ProS appear to interfere with the pathology of arthritis on two different levels. In CIA, both of them can induce anti-inflammatory TAM receptor signalling whereas in the KRN model, ProS presumably blocks the coagulation cascade and thereby prevents complement C5 activation.
Manpower in Medicine
Authors: OSLER L. PETERSON
Journal: Annals of Internal Medicine (1979)

Letters1 September 1979Manpower in MedicineOSLER L. PETERSON, M.D., BERNARD S. BLOOM, PH.D.OSLER L. PETERSON, M.D.Search for more papers by this author, BERNARD S. BLOOM, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-3-490_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In a recent review of manpower studies in Annals of Internal Medicine (1), we strongly criticized the poor, irrelevant data and inappropriate criteria that have been commonly used for manpower planning. The study by Girard and colleaques (2) is an example of how physician manpower should be studied. The collection of data on physicians' workdays using self-reported log diaries provides relevant manpower statistics for physician-manpower decisions. Their application to a large number of specialties represents a singular achievement.We raise two issues about the study, the first being the mean workweek length of 50 to 55 h...References1. BLOOM B and PETERSON O. Physician manpower expansionism: a policy review. Ann Intern Med. 1979;90:249-56. LinkGoogle Scholar2. GIRARD R, MENDENHALL R, TARLOV A, RADECKI S, and ABRAHAMSON S. A national study of internal medicine and its specialties: I. An overview of the practice of internal medicine. Ann Intern Med. 1979; 90:965-75. LinkGoogle Scholar3. HAUCK W, BLOOM B, MCPHERSON C, NICKERSON R, COLTON T, and PETERSON O. Surgeons in the United States: activities, output, and income. JAMA. 1976;236:1864-71. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: OSLER L. PETERSON, M.D.; BERNARD S. BLOOM, PH.D.Affiliations: University of Pennsylvania School of Medicine Philadelphia, PA. 19104 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1979Volume 91, Issue 3Page: 490-490KeywordsStatistical data ePublished: 1 December 2008 Issue Published: 1 September 1979 PDF downloadLoading ...
143 MODIFIED ORIENTATION-LOG (MO-LOG) IS AN OBJECTIVE METHOD TO PREDICT OUTCOMES IN PATIENTS ADMITTED WITH HEPATIC ENCEPHALOPATHY
Authors: J. Bajaj, M. Salam, R.T. Stravitz, I.S. Farooq, D.M. Heuman, R.K. Sterling, A.J. Sanyal
Journal: Journal of Hepatology (2011)
Deadly Deceit: Low-Level Radiation, High-Level Cover-up
Authors: Glyn G. Caldwell
Journal: JAMA (1991)

This small book is another in the genre of less is more, and there is an enormous conspiracy to cover up that fact. The authors clearly abhor all things nuclear and have collected and searched through a huge databank seeking any and all variations in disease occurrence, which are then causally attributed to low-level ionizing radiation. In fact, they have attributed so many diseases and infections that it appears to be a situation in which some radiation event occurred and they searched until they found a disease, any disease, that increased during that time. Claims that the first identification of or increases in occurrence of specific diseases must be the result of low-level radiation seem to me to be examples of the "wish bias."<sup>1</sup>Diseases such as acquired immunodeficiency syndrome (AIDS), allergies, Lyme disease, chronic Epstein-Barr virus infection, toxic shock syndrome,<i>Candida albicans</i>infection, herpes, and pelvic inflammatory disease
Abstract 4694: Nuclear expression of IL23p19 shows indolent tumor features and favorable outcome in patients with colorectal cancer.
Authors: Inti Zlobec, Melina Helbling, Eva Diamantis-Karamitopoulou, Viktor H. Koelzer, Heather Dawson, Alessandro Lugli
Journal: Cancer Research (2013)

Abstract Background: The IL23 signaling pathway is involved in chronic inflammation and autoimmune disorders but its role in cancer progression is not fully elucidated. The aim of this study was to characterize the expression of IL23 subunits p40 and p19 as well as IL23R in the normal-adenoma-carcinoma-metastasis cascade of colorectal cancers and investigate the relationship between these proteins and clinicopathological, molecular and clinical outcome data in colorectal cancer patients. Methods: Immunohistochemistry for IL12p40 (p40 subunit shared between IL12 and IL23), IL23 (polyclonal), IL23p19 (monoclonal) and IL23R was performed on a multiple-punch tissue microarray of 213 colorectal cancers from patients with full clinicopathological and follow-up information. Normal tissues, matched adenomas and lymph node metastases were assessed as well as microsatellite instability (MSI), KRAS and BRAF mutations. Results: IL12p40, IL23, IL23p19 and IL23R expression were significantly increased in colorectal cancers in comparison to all other tissue types (p&amp;lt;0.001; all). Cytoplasmic and/or membranous expression of all proteins was unrelated to clinicopathological or molecular features. Unexpectedly, 45 cases (23.1%) showed distinct nuclear IL23p19+ expression associated with smaller tumor diameter (p=0.0333), early TNM stage (p=0.0186), absence of venous (p=0.0124) and lymphatic invasion (p=0.0493), lymph node negativity (p=0.0621) and MSI (p=0.0032). IL23p19+ patients had more favorable overall survival (p=0.0634); none had distant metastatic disease (p=0.0146). No relationship with KRAS or BRAF was observed. Conclusion: Our results of a more indolent, less aggressive cancer expressing nuclear IL23p19 support a more “protective” role of this protein in colorectal cancer progression. These findings add to the current controversy regarding the pro- or anti-tumor effects of IL23 signaling in cancer. Citation Format: Inti Zlobec, Melina Helbling, Eva Diamantis-Karamitopoulou, Viktor H. Koelzer, Heather Dawson, Alessandro Lugli. Nuclear expression of IL23p19 shows indolent tumor features and favorable outcome in patients with colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4694. doi:10.1158/1538-7445.AM2013-4694
Further Observations on the Medical Aspects of Amateur Boxing
Authors: J. L. Blonstein, E. Clarke
Journal: BMJ (1957)

Case 19.-A heavyweight aged 31 was knocked out "through the ropes" in 1945 and was dazed for the next 24 hours.The right leg was found to be weak immediately after his fight and continued so.Within the day or two following this same fight his right hand began to shake: the left hand started to tremble some six months later.He was hospitalized seven years later, a typical severe punch-drunk.Case 20.-A delinquent mild punch-drunk, interviewed in prison, gave up boxing at the age of 20 because he was not feeling himself.He felt drunk although he had taken nothing in the way of alcohol: his head would be in a swim after each fight.Case 21.-A Royal Navy welterweight, aged 22, matched against a tougher opponent, was struck heavily over the heart in the second round, causing him to feel dizzy or groggy.Shortly after he got a severe blow to the side of the head, flooring him for a count of nine, when he rose and resumed the fight.He could remember vividly every incident up till then; but after that his memory was a blank.Apparently he finished the second round, and in the third round he received heavy punishment, being knocked down 10 times, striking his head on the floor more than once.His next recollection is being on the deck of his ship about an hour later, feeling dizzy and sore about the stomach.Two weeks later he became ill with headaches, vertigo, and vomiting, and was hospitalized.Investigation showed old blood-staining of the C.S.F. Conclusions There is much in boxing to interest a practising neuro- logist, and special attention should be focused upon (1) the phenomenon of groggy states as occurring during or after a contest, and (2) the condition known as traumatic progressive encephalopathy (or punch- drunkenness).Owing to the extreme paucity of pathological data, it is highly desirable that opportunity should be afforded neuropathologists of studying the appearances in the brain of punch-drunk patients.There is a scope for further study of boxers by electroencephalographic as well as clinical techniques, at all stages: that is, early as well as late in their careers; and before and immediately after a contest, especially if a knock-out has occurred.For permission to quote the naval cases