tbuckley/cabot-search huggingface dataset:
A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation
Authors: Howard M. Shulman, Pankaj Sharma, Deborah Amos, L. Frederick Fenster, George B. McDonald
Journal: Hepatology (1988)

We tested the hypothesis that liver histology from patients with graft-versus-host disease could be distinguished from other common liver diseases. Liver biopsies from 33 allogeneic marrow transplant recipients with acute and chronic graft-versus-host disease and 37 nontransplant liver disease patients without graft-versus-host disease were recut, restained and coded for blind review. Analysis of individual histologic features showed significantly more cytologic aberration of bile duct epithelium and more cholestasis among biopsies with graft-versus-host disease when compared to biopsies without graft-versus-host disease (p ≤ 0.05). The duration of graft-versus-host preceding the biopsy influenced the histologic features. Biopsies before Day 35 showed frequent acidophilic bodies but infrequent bile duct changes. Biopsies from Days 35 to 90 posttransplant had more frequent bile duct exocytosis and disruption, and biopsies from patients with chronic graft-versus-host disease (beyond Day 90) showed more frequent portal fibrosis and bile duct dropout. Pattern assessment of coded biopsies showed that a histologic diagnosis of graft-versus-host disease had a positive predictive value of 86%, a sensitivity of 66% and a specificity of 91%. False-negative diagnoses occurred most frequently in biopsies obtained less than 4 weeks posttransplant, usually because bile duct abnormalities were not present. False-positive diagnoses of graft-versus-host disease occurred in nongraft-versus-host disease biopsies with periportal inflammation and proliferated bile ducts. However, biopsies of chronic graft-versus-host disease had more frequent dropout and disruption of bile duct epithelium than did biopsies of acute or chronic hepatitis. We conclude that a histologic diagnosis of hepatic graft-versus-host disease is likely to be correct if histology shows abnormal bile duct epithelium and cholestasis. While distinction between chronic graft-versus-host disease and non-A, non-B viral hepatitis is imprecise, cytologically atypical and destructive bile duct features favor chronic graft-versus-host disease. The histologic appearance of graft-versus-host disease is similar to that of primary biliary cirrhosis.
South Africa needs doctors
Authors: D Roberts
Journal: BMJ (1994)

EDITOR, - While in Britain recently I was saddened by the apparent malaise in the NHS and doctors' unhappiness with their lot. A survey conducted by the Royal College of General Practitioners is quoted as having found that 25% of general practitioners had positively considered leaving general practice and 45% wished to retire at age 55 because of disillusionment with general practice.1 In contrast, although South Africa is going through a period of rapid change and uncertainty, there is no such medical malaise. I have found my work here to be …
P2-286: Clinical experience with single agent oral vinorelbine in first-line advanced non-small-cell lung cancer (NSCLC) treatment of elderly patients (p)
Authors: Miguel Mendez, Jesus Andrade, Gaspar Esquerdo, Serafin Morales, Ramon Garcia-Gomez, Jose M. Garcia-Bueno, Isabel Blancas, Rafael Trujillo, Jose I. Juarez, Javier Gayo
Journal: Journal of Thoracic Oncology (2007)
THE ETIOLOGY OF MONGOLISM; With a Case of Mongol Twin
Authors: H. Armstrong
Journal: BMJ (1928)

a few cases.The tongue was nearly always coated at the dorsum and red at tlle nmairgins.Tonisillitis and pharyngitis were fairly commiiion.No parotitis was met with.'Nausea and vomitinlg were usual at the commencement, but rarely persisted t'lroughout the disease.Cconstipation -was the rule, and was followed by diarrhoea at the termiinal clisis.Dysenteiic syinptoms were preseint iii a few canses thlrougliout the malady.No changes were observed in liver or spleen that couild be attributed to dengue.U rina ry Systetnm.-Albumiu1uria'was comllmoni but transient.One case of acuite neplhritis was reported.Chlonic kidney disease is likely to end by uraciinia as the result of an attack of dengue.Diabetic )atielnts whien attacked sometimes developed a fatal coma, eveni during con- valescence.Epididymitis, orehitis, cystitis, etc., 'were not iiiet with.Corn plicatiotis.-Thesewere rare.Those met with were: pharyngitis, r
An α1A-Adrenergic–Extracellular Signal-Regulated Kinase Survival Signaling Pathway in Cardiac Myocytes
Authors: Yuan Huang, Casey D. Wright, Chastity L. Merkwan, Nichole L. Baye, Qiangrong Liang, Paul C. Simpson, Timothy D. O’Connell
Journal: Circulation (2007)

Background— In α1-AR knockout (α1ABKO) mice that lacked cardiac myocyte α1-adrenergic receptor (α1-AR) binding, aortic constriction induced apoptosis, dilated cardiomyopathy, and death. However, it was unclear whether these effects were attributable to a lack of cardiac myocyte α1-ARs and whether the α1A, α1B, or both subtypes mediated protection. Therefore, we investigated α1A and α1B subtype–specific survival signaling in cultured cardiac myocytes to test for a direct protective effect of α1-ARs in cardiac myocytes. Methods and Results— We cultured α1ABKO myocytes and reconstituted α1-AR signaling with adenoviruses expressing α1-GFP fusion proteins. Myocyte death was induced by norepinephrine, doxorubicin, or H 2 O 2 and was measured by annexin V/propidium iodide staining. In α1ABKO myocytes, all 3 stimuli significantly increased apoptosis and necrosis. Reconstitution of the α1A subtype, but not the α1B, rescued α1ABKO myocytes from cell death induced by each stimulus. To address the mechanism, we examined α1-AR activation of extracellular signal-regulated kinase (ERK). In α1ABKO hearts, aortic constriction failed to activate ERK, and in α1ABKO myocytes, expression of a constitutively active MEK1 rescued α1ABKO myocytes from norepinephrine-induced death. In addition, only the α1A-AR activated ERK in α1ABKO myocytes, and expression of a dominant-negative MEK1 completely blocked α1A survival signaling in α1ABKO myocytes. Conclusions— Our results demonstrate a direct protective effect of the α1A subtype in cardiac myocytes and define an α1A-ERK signaling pathway that is required for myocyte survival. Absence of the α1A-ERK pathway can explain the failure to activate ERK after aortic constriction in α1ABKO mice and can contribute to the development of apoptosis, dilated cardiomyopathy, and death.
Children's Hospitals Say About Health Care Reform, `One Size Won't Fit All'
Authors: Andrew A. Skolnick
Journal: JAMA (1993)

WHILE APPLAUDING President Clinton's efforts to reform the nation's health care system, representatives of children's hospitals say that the president's plan needs special tailoring to fit the needs of children. "At a time when one in every three children in the United States depends either on Medicaid or on charity to pay for health care, we commend the president's efforts to move the nation toward comprehensive health care reform," says Lawrence A. McAndrews, president and chief executive officer of the National Association of Children's Hospitals and Related Institutions Inc (NACHRI), Alexandria, Va. Speaking at the NACHRI's first international conference on child health, held in Atlanta, Ga, McAndrews said that reform is needed to "enhance both medical security for the nation's 65 million children and peace of mind for their parents." However, "NACHRI neither endorses nor rejects the Clinton plan in full," he says. "It is a good plan to work
Myoglobin facilitated oxygen diffusion maintains mechanical function of mammalian cardiac muscle
Authors: E. A BRAUNLIN, G. M WAHLER, C. R SWAYZE, R. V LUCAS, I. J FOX
Journal: Cardiovascular Research (1986)

Myoglobin, an intracellular iron containing protein that binds oxygen reversibly, has been shown in model systems to facilitate the diffusion of oxygen and thereby maintain the mechanical function of exercising canine skeletal muscle and of hypoxic benthic fish hearts. Since no such role has yet been established for mammalian cardiac muscle small diameter (less than or equal to 0.70 mm) isolated kitten papillary muscles were stimulated at 24 X min-1 under isometric conditions in a physiological bath maintained at 30 degrees C with an oxygen tension of approximately equal to 450 mm Hg (59.8 kPa) to obtain a level of oxygenation just adequate to meet the metabolic needs of the muscles, as confirmed experimentally. Myoglobin was inactivated by adding 2 X 10(-3) mol X litre-1 sodium nitrite to the bath to abolish the facilitated diffusion of oxygen in the presence or absence of glycolytic blockade by 10(-4) mol X litre-1 sodium iodoacetate. This resulted in a 22(8)% (with blockade) or 10(3)% (without blockade) decrease (p less than 0.05) in the maximal rate of relaxation (-dT/dtmax) of the papillary muscles. Since the depression in mechanical function was reversible by increasing the bath oxygen tension to approximately equal to 600 mm Hg (79.8 kPa) it is concluded that the myoglobin facilitated diffusion of oxygen plays a role in maintaining the mechanical function of mammalian cardiac muscle under normal conditions. Furthermore, the maximal rate of relaxation of cardiac muscle is a sensitive indicator of the presence of hypoxia.
Abstract 1029: Involvement of endocytic pathway in vorinostat-induced EGFR degradation.
Authors: Asmaa E. Elkenawi, John K. Cowell
Journal: Cancer Research (2013)

Abstract Epidermal growth factor receptor (EGFR) is frequently overexpressed or aberrantly activated in various malignancies. As a result, EGFR is considered an important target in cancer therapeutics. Strategies of EGFR targeting include blockade of its activation, inhibition of downstream signaling or induction of EGFR downregulation and/or degradation. Histone deacetylases (HDACs) inhibitors were previously shown to deplete EGFR through numerous mechanisms varying from suppression of EGFR transcription, attenuation of its mRNA stability and disruption of chaperone activity of HSP90. In this work, we are studying alteration of EGFR vesicular trafficking as another mechanism that may be involved in HDAC inhibitors-induced EGFR depletion. Cytotoxic and EGFR-degrading effects of vorinostat, a pan-HDAC inhibitor, were investigated in the EGFR-overexpressing cell lines, DU-145 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). Using different experimental designs, dose- and time- effects of vorinostat were studied in both cell lines. Proliferation assay, annexin V staining, PARP and caspase 7 cleavage were used to evaluate overall cellular toxicity. Effects on total EGFR protein level and relevant ERK phosphorylation were also investigated by immunoblotting. Moreover, accumulation of acetyl-α-tubulin was verified through immunoblotting and immunofluorescence imaging. Finally, serum-starved vorinostat-treated cells were stimulated with EGF in order to elucidate effect of vorinostat on EGF-induced EGFR degradation, an endocytic trafficking-dependent process. As presented in this study, vorinostat exerted potent cytotoxic effects on DU-145 and MDA-MB-231 cells manifested by a dose-dependent decrease in proliferation and increase in percentage of apoptotic cells. In addition, vorinostat caused a dose-dependent cleavage of both PARP and caspase 7, two markers of apoptotic cascade activation. Furthermore, vorinostat elicited a dose- and a time-dependent depletion of EGFR total protein in both cell lines with a corresponding decrease in ERK activation. Add to that, vorinostat caused accumulation of acetyl-α-tubulin and promoted EGFR degradation upon EGF stimulation denoting accelerated endocytic trafficking. In conclusion, vorinostat demonstrated a potent anti-tumor activity against EGFR-overexpressing cell lines. Such activity was accompanied by EGFR depletion that may be contributed in part by vorinostat-induced deregulated vesicular trafficking. Citation Format: Asmaa E. Elkenawi, John K. Cowell. Involvement of endocytic pathway in vorinostat-induced EGFR degradation. [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 1029. doi:10.1158/1538-7445.AM2013-1029
Diphenylhydantoin and Blood Dyscrasias
Authors: Samuel Livingston
Journal: JAMA (1974)

<h3>To the Editor.—</h3> We are writing in regard to the article entitled "Pure RBC Aplasia and Diphenylhydantoin" by Jeong et al (229:314, 1974). We are not convinced that the authors presented sufficient evidence to incriminate diphenylhydantoin as the causative agent in their two cases of erythroid aplasia, and agree with their statement that such factors as viral hepatitis, genetic susceptibility, other drugs, and undetermined factors may have been responsible for the development of this blood dyscrasia. Complete recovery of their patients following the withdrawal of diphenylhydantoin cannot be considered a valid basis for assigning a causative role to this drug, because treatment with steroids was initiated either before or concomitant with the cessation of diphenylhydantoin therapy. Moreover, since so far as we know there had been previously only one reported instance of erythroid aplasia due to diphenylhydantoin,<sup>1</sup>we think it quite remarkable that Jeong and associates observed two such
Relationships between Circulating and Intracellular Thyroid Hormones: Physiological and Clinical Implications*
Authors: P. REED LARSEN, J. ENRIQUE SILVA, MICHAEL M. KAPLAN
Journal: Endocrine Reviews (1981)

THYROXINE (T4), measured as protein-bound iodine, was the first hormone to be quantitated in human serum. As a consequence, it was possible to demonstrate clear relationships between circulating T4 concentrations and many of the physiological manifestations of thyroid hormone excess or deficiency. In 1952, 3,5,3′-triiodothyronine (T3) was identified in human plasma and metabolic studies in man soon led to the realization that this hormone was 3–4 times as potent metabolically as T4 (1–4). At that time, the question was first raised as to whether T4 or T3 was the "active" thyroid hormone (3). This question became even more pertinent when it was suggested first in 1955 (5) and shown conclusively in 1970 that T4 could be converted to T3 by peripheral human tissues (6, 7). These studies were made possible by the development of methods for quantitating T3 in human serum, initially by competitive protein binding techniques, followed soon thereafter by specific and sensitive RIAs.
The Medical College of Virginia.
Authors: J. N. Upshur
Journal: JAMA (1889)

[The recent Editor ofThe Journalhas not now, and never has had the slightest disposition to do injustice to the Medical College of Virginia. All that he has permitted to be said editorally has been founded on the published statistics of the State Board of Examiners and the published statements of what took place before the Legislature or its Committees. Whether 8 rejections out of 57 is 12¼ or 14 per cent., or whether 8 rejections out of 57 is a better showing than 1 rejection out of 33, any of our readers can figure for themselves. Hence we cheerfully close the subject by giving the following letter from the Faculty, N. S. D.] <h3>Mr. Editor:</h3> —In the number ofThe Journalfor December 15, 1888, in the editorial on the " Medical College of Virginia," is a statement referring to Dr. Geo. Ben. Johnston and myself, namely, that " the
Chronic Lung Function Decline in Cotton Textile Workers: Roles of Historical and Recent Exposures to Endotoxin
Authors: Jing Shi, Amar J. Mehta, Jing-qing Hang, Hongxi Zhang, Helian Dai, Li Su, Ellen A. Eisen, David C. Christiani
Journal: Environmental Health Perspectives (2010)

Long-term occupational exposure to cotton dust that contains endotoxin is associated with chronic respiratory symptoms and excessive decline in forced expiratory volume in 1 sec (FEV1), but the mechanisms of endotoxin-related chronic airflow obstruction remain unclear.In the current study, we examined temporal aspects of the exposure-response relationship between airborne endotoxin exposure, longitudinal change in FEV1, and respiratory symptoms in a cohort of Chinese cotton textile workers.This prospective cohort study followed 447 cotton textile workers from 1981 to 2006. at approximately 5-year intervals. We used a generalized estimating equations approach to model FEV1 level and respiratory symptoms as a function of past exposure (cumulative exposure up to the start of the most recent 5-year survey interval) and cumulative exposure (within the most recent interval) to endotoxins, after adjusting for other covariates. Models were stratified by active versus retired work status and by years employed before the baseline survey (< 5 and > or = 5 years).Past exposure to endotoxin was associated with reduced FEV1 level among retired cotton workers. Among all cotton workers, past exposure was more strongly associated with reduced FEV1 for those hired < 5 years before baseline than for those who were hired > or = 5 years after baseline. Recent endotoxin exposure was significantly associated with byssinosis, chronic bronchitis, and chronic cough.
P33. NK-92 cellular immunotherapy as an alternative to donor derived peripheral blood NK cells
Authors: H Klingemann
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Infusions with cytokine-activated NK cells obtained from blood of MHC mismatched donors have shown some promising results especially in patients with myeloid leukaemia. There is also indirect evidence that infusions of NK cells as part of a stem cell transplant result in lower
APPARATUS FOR HANDLING COMATOSE PATIENTS.
Authors: CHARLES S. WHITE
Journal: JAMA (1904)

In every hospital doing emergency work the problem of moving unconscious patients through dark, narrow halls and down flights of uncertain stairs confronts the surgeon almost daily, and to facilitate the handling of such cases I have had made a simple belt or sling. This is made of heavy canvas, 30 inches long and 10 inches wide. Each extremity is sewed securely about an iron rod three-eighths of an inch in diameter. The iron pieces have their ends bent squarely in a rectangular form, leaving sufficient space to fasten leather straps 11 inches long, each pair of which join at a metal ring about 2 inches in diameter. The sling is completed by a strap riveted in one ring, a buckle in the center, and connected with the other ring by a snaffle. The illustration shows the manner of using it. By rolling a patient first to one side, then to the
Humoral and cellular responses to cow milk proteins in patients with milk‐induced IgE‐mediated and non‐IgE‐mediated disorders
Authors: L. P. C. Shek, L. Bardina, R. Castro, H. A. Sampson, K. Beyer
Journal: Allergy (2005)

Cow milk allergy (CMA) is one of the most common food allergies in childhood. Patients with CMA present with a wide range of immunoglobulin (Ig)E- and non-IgE-mediated clinical syndromes. Limited information is known about the specific humoral and cellular responses to cow milk proteins in these various forms of CMA.The aim of the study was to determine IgE, IgA, IgG1 and IgG4 antibody levels and lymphocyte proliferative responses to the major cow milk allergens in patients with IgE- and non-IgE-mediated CMA.One hundred and forty cow milk allergic patients, 6 months to 22 years of age, were included in the study. One hundred and thirteen patients had IgE-mediated CMA, 11 had milk protein-induced enterocolitis syndrome and 16 had allergic eosinophilic gastroenteritis. Twenty-one patients without food allergy, 8 months to 18 years of age, served as controls. Serum IgE, IgA, IgG1 and IgG4 antibodies to alpha-, beta-, and kappa-casein, alpha-lactalbumin and beta-lactoglobulin were measured using enzyme-linked immunosorbent assays. For a subset of these patients, we performed lymphocyte proliferation assays to the various milk allergens.Patients with IgE-mediated CMA had higher specific IgE concentrations to casein compared with whey proteins (P < 0.001). In this group of patients, there was a positive correlation between IgE levels and levels of the other isotypes for all four milk proteins (P < 0.001). In general, the caseins were the more allergenic and antigenic proteins in all groups of patients. Patients with enterocolitis syndrome produced less milk protein-specific IgG4 (P < 0.05) and had a trend for higher IgA antibody levels when compared to the control group. Lymphocyte proliferative responses in all groups with CMA were significantly higher than controls (P < 0.05), although this response was similar in patients with IgE- and non-IgE-mediated CMA.There is a distinct pattern of humoral antibody response in the different forms of CMA. Patients with IgE-mediated CMA have an elevated polyisotypic response to cow milk protein. The relative lack of specific IgG4 production in patients with enterocolitis syndrome may be involved in the pathogenesis of the disease. In general, caseins appear to be the predominant allergen in patients with CMA.
Congenital Extra-abdominal Herniation of Bowel
Authors: G. M. Lurie
Journal: BMJ (1955)

~~~~~~~~~~~~~~~~~~~~~~~MEDICAL JOURNAL occur in any greater frequency than that expected in a normal population group.In a further investigation of families where the person with situs inversus was a twin, he concluded that the familial incidence of twinning was probably increased in this rare type of case.These findings are in conflict with my admittedly small series.However, the history of twinning in ascendants and collaterals in the families I have investigated is so striking that I suggest that this fact may be of importance genetically in some cases of situs inversus and is not mere coincidence.
Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo
Authors: Sarah E. Townsend, Christopher C. Goodnow
Journal: The Journal of Experimental Medicine (1998)

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.