tbuckley/cabot-search huggingface dataset:
Protecting Human Subjects: First Biennial Report on the Adequacy and Uniformity of Federal Rules and Policies, and Their Implementation, for the Protection of Human Subjects in Biomedical and Behavioral Research
Authors: Herman S. Wigodsky
Journal: JAMA (1983)

In the first biennial report of the work of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, the commission presents a summary of their observations on the adequacy and uniformity of the federal rules and policies and their implementation for the protection of human subjects in biomedical and behavioral research. The commission identified 23 separate federal entities in 17 federal departments or agencies that conduct or support biomedical or behavioral research using human subjects and reviewed the rules or procedures in these various federal agencies regarding use of human research subjects. In addition, the commission reviewed the rules and procedures of the Food and Drug Administration relating to research on new drugs, biologicals, and medical devices that uses human research subjects. The regulations or policies of 17 of 22 of the federal entities that conduct or support research involving human subjects conform
Red Blood Cell Porphobilinogen Deaminase in the Evaluation of Acute Intermittent Porphyria
Authors: Claus A. Pierach, Mary K. Weimer, Ruth A. Cardinal, Irene C. Bossenmaier, Joseph R. Blommer
Journal: JAMA (1987)

We measured the activity of the enzyme porphobilinogen deaminase in red blood cells of 222 persons. Ninety-seven of 107 patients with acute intermittent porphyria had enzyme activity below the normal range, whereas 55 of 56 patients with other types of porphyria had normal activity. This underscores the utility of this test in confirming the diagnosis of acute intermittent porphyria. Measurement of enzyme activity in 41 families with acute intermittent porphyria demonstrated that deficient activity is inherited as an autosomal dominant trait. Many latent carriers of the genetic defect were identified by family studies, permitting appropriate precautions to avoid potentially lethal porphyric attacks.
Differential Diagnosis of the Abnormal Mean Corpuscular Volume (MCV).
Authors: P. McPhedran
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Differential Diagnosis of the Abnormal Mean Corpuscular Volume (MCV).P. McPhedran, M.D., M. G. Barnes, M.D., J. Weinstein, M.D.P. McPhedran, M.D.Search for more papers by this author, M. G. Barnes, M.D.Search for more papers by this author, J. Weinstein, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-869_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis study was made to furnish statistical information to aid in the interpretation of abnormal mean corpuscular volumes, detected by the Model S Coulter Counter. No systematic study of the meaning of an abnormal MCV has been made since accurate red cell sizing became routinely available. Although an abnormal MCV is known to be a useful clue to diagnosis in severely anemic patients, its usefulness in other patients has scarcely been studied. Patients with mean corpuscular volumes of 115 or greater and 75 or less, regardless of hematrocrit level, were selected for study. Patients with macrocytosis had plasma B12and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New Haven, Conn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCOMPREHENSIVE TESTING FOR THALASSEMIA TRAITHematologic Screening Tests 1 May 1972Volume 76, Issue 5Page: 869-870KeywordsBlood plasmaMean corpuscular volume Issue Published: 1 May 1972 PDF DownloadLoading ...
Evidence for Intracellular Endothelin-Converting Enzyme-2 Expression in Cultured Human Vascular Endothelial Cells
Authors: Fraser D. Russell, Anthony P. Davenport
Journal: Circulation Research (1999)

Abstract —We have previously reported the intracellular localization of the endothelin-converting enzyme-1 (ECE-1) in human umbilical vein endothelial cells. In the present study, we provide the first immunocytochemical and biochemical evidence for the presence of ECE-2 in human cells. ECE activity was determined by conversion of exogenously added big endothelin-1 (big ET-1) to ET-1 in subcellular fractions obtained by sucrose density gradient centrifugation of human umbilical vein endothelial cell homogenates. ECE-1 and ECE-2 can be differentiated by pH dependence for optimal activity and by sensitivity to phosphoramidon, which shows selectivity for ECE-2 over ECE-1 and PD159790, a novel ECE-1 selective inhibitor. Optimal ECE activity was measured at pH 6.0, a value intermediate between that reported for ECE-1 (pH 6.8) and ECE-2 (pH 5.5), indicating expression of both enzymes. At pH 6.9, conversion of big ET-1 was inhibited markedly by 30 μmol/L PD159790 and by 100 μmol/L phosphoramidon but not by 0.1 μmol/L phosphoramidon. In contrast, ECE activity was unaffected by 30 μmol/L PD159790 but was inhibited markedly by 0.1 and 100 μmol/L phosphoramidon at pH 5.4 (IC 50 1.5 nmol/L), consistent with ECE-2 activity. Confocal microscopy revealed a punctate pattern of ECE-2–like immunoreactive staining in the cell cytosol, suggesting localization to secretory vesicles with a possible role in processing big ET-1 while in transit to the cell surface via the constitutive secretory pathway.
Differences in Kidney Function and Incident Hypertension: The Multi-Ethnic Study of Atherosclerosis
Authors: Bryan Kestenbaum, Kyle D. Rudser, Ian H. de Boer, Carmen A. Peralta, Linda F. Fried, Michael G. Shlipak, Walter Palmas, Catherine Stehman-Breen, David S. Siscovick
Journal: Annals of Internal Medicine (2008)

Background: Kidney disease and hypertension commonly coexist, yet the direction of their association is still debated. Objective: To evaluate whether early kidney dysfunction, measured by serum cystatin C levels and urinary albumin excretion, predates hypertension in adults without clinically recognized kidney or cardiovascular disease. Design: Observational cohort study using data from 2000 to 2005. Setting: The MESA (Multi-Ethnic Study of Atherosclerosis), a community-based study of subclinical cardiovascular disease in adults age 45 to 84 years. Participants: 2767 MESA participants without prevalent hypertension, cardiovascular disease, or clinically recognized kidney disease (an estimated glomerular filtration rate <60 mL/min per 1.73 m2 or microalbuminuria). Measurements: Cystatin C was measured by using a nephelometer, and urinary albumin and creatinine were measured from a spot morning collection. The primary outcome was incident hypertension, defined as systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or use of an antihypertensive medication. Results: During a median follow-up of 3.1 years, 19.7% of the cohort (545 participants) developed hypertension. After adjustment for established hypertension risk factors, each 15-nmol/L increase in cystatin C was associated with a statistically significant 15% greater incidence of hypertension (P = 0.017). The highest sex-specific quartile of urinary albumin–creatinine ratio was associated with a statistically insignificant 16% greater incidence of hypertension (P = 0.192) compared with the lowest quartile. No statistical evidence suggested a multiplicative interaction. Limitations: Unmeasured characteristics may have confounded observed associations of kidney markers with hypertension. Follow-up was relatively short. Hypertension that may have occurred between study visits or hypertension that was not captured by standard cuff measurements may have been missed. Conclusion: Differences in kidney function, indicated by cystatin C levels, are associated with incident hypertension among individuals without clinical kidney or cardiovascular disease. These population-based findings complement experimental work implicating early kidney damage in the pathogenesis of essential hypertension.
EXPERIMENTAL IMMUNOLOGIC ADRENAL INJURY
Authors: Jan W. Steiner, B. Langer, D. L. Schatz, R. Volpe
Journal: The Journal of Experimental Medicine (1960)

Twenty-three unilaterally adrenalectomized guinea pigs were injected with autologous and homologous adrenal tissue homogenates respectively, in Freund's adjuvant. Widespread adrenal lesions were found in 10 of 12 animals receiving auto-antigen and to a lesser extent in 6 of 11 animals injected with homologous pooled antigen. Widespread systemic lesions were present in both these and in control animals receiving Freund's adjuvant alone. These latter animals showed no adrenal involvement. The early changes within the adrenal consisted of perisinusoidal cellular proliferations in the deeper layers of the cortex. Focal granulomata developing at a later stage tended to become confluent and to displace cortical cells. Some loss of these cells was attributable to ischemic injury. The localization in the deep fasciculata and reticularis was thought to depend (a) on the varying antigenicity of adrenal cortical components, (b) the possible inhibitory effect of antiphlogistic adrenal cortical hormones on the development of lesions in the outer cortex, and (c) the presence of littoral cells in the deep cortex. These cells are thought to be involved in the mediation of the stimulus initiating differentiation of primitive mesenchymal cells in response to a circulating auto-antigen. The medullary lesions may be related to the presence of ectopic reticularis cells in this location. It was suggested that the cellular response in the target organ to injections of adrenal homogenates may denote a specific "organ-self" recognition mechanism involving an immune (i.e. defensive) reaction. It was postulated that this may be an accentuation of the physiological function of immunologically competent cells. Their proliferation, under normal circumstances, would prevent by means of production of "binding" globulins, the escape and dissemination of endogenous freed adrenal antigens into the circulation. Although the experimental stimulus arose from without the gland, by virtue of the presence of a circulating adjuvant-bound antigen, the adrenal reaction followed the same pattern as would obtain if the antigen was liberated within the suprarenal cortex.
Skeletonized versus pedicled bilateral internal mammary artery grafting: Outcomes and concerns analyzed through a meta-analytical approach
Authors: Michel Pompeu Barros Oliveira Sá, Paulo Ernando Ferraz Cavalcanti, Henrique José de Andrade Costa Santos, Artur Freire Soares, Rodrigo Gusmão Albuquerque Miranda, Mayara Lopes Araújo, Ricardo Carvalho Lima
Journal: International Journal of Surgery (2014)
A National Strategy for Research in Chronic Obstructive Pulmonary Disease
Authors: Timothy F. Murphy
Journal: JAMA (1997)

<h3>To the Editor.</h3> —In the workshop summary on a proposed national strategy for research in chronic obstructive pulmonary disease (COPD), Drs Petty and Weinmann<sup>1</sup>recommend several important areas of research to pursue. Virtually absent from consideration in the workshop was the role of bacterial infection in the course and the pathogenesis of COPD. Lower respiratory tract infection in patients with COPD is responsible for enormous morbidity, mortality, and health care costs. Chronic obstructive pulmonary disease causes 165 000 deaths, 10 million office visits, and 2 million hospitalizations annually in the United States,<sup>2</sup>with a large proportion of these owing to exacerbations related to infection.<sup>3</sup>Infection was the single most common identifiable cause of death in 1 prospective study of patients with COPD.<sup>4</sup>Preventing such infections would reduce morbidity, improve quality of life, and reduce health care costs. Research into new ways to prevent infection in patients
A Method for Evaluating Computer Programs for Electrocardiographic Interpretation
Authors: JAMES J. BAILEY, SAMUEL B. ITSCOITZ, LEONARD E. GRAUER, JOHN W. HIRSHEFELD, MARTHA R. HORTON
Journal: Circulation (1974)

A previously described method for evaluating computer programs for electrocardiographic (ECG) interpretation was applied to Version D of the Public Health Service (PHS) program and to the Mayo Clinic program of 1968. Staff cardiologists found agreement with the results of the PHS program in 45.5% of 1150 unselected tracings. Clinically significant disagreements based strictly on application of different criteria occurred in 29%, while disagreements based on program errors were found in 25.5%. The corresponding results for the Mayo Clinic program are: agreement in 47%, disagreements due to criteria differences in 30.9%, and disagreements due to program errors in 22.1%. Both programs had serious deficiencies, particularly in the diagnostic categories of myocardial infarction and cardiac arrhythmias. PHS program errors resulted primarily from mismeasurements and deficient program logic, while Mayo Clinic program errors more frequently resulted from pattern recognition failures. Neither program appears suitable for routine clinical use at the present time.
Link between systolic and diastolic dysfunction in hypertensive subjects with inappropriate left ventricular hypertrophy: the hyperGEN study
Authors: Giovanni de Simone, Dalane W. Kitzman, Vittorio Palmieri, Jennifer E. Liu, Jonathan N. Bella, Albert Oberman, Paul N. Hopkins, D.C. Rao, Donna K. Arnett, Richard B. Devereux
Journal: Journal of the American College of Cardiology (2002)
Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies
Authors: Young Joo Jeon, Sihem Khelifa, Boris Ratnikov, David A. Scott, Yongmei Feng, Fabio Parisi, Chelsea Ruller, Eric Lau, Hyungsoo Kim, Laurence M. Brill, Tingting Jiang, David L. Rimm, Robert D. Cardiff, Gordon B. Mills, Jeffrey W. Smith, Andrei L. Osterman, Yuval Kluger, Ze’ev A. Ronai
Journal: Cancer Cell (2015)
Regulatory bodies can root out corruption
Authors: F. J Morrissey
Journal: BMJ (2003)

EDITOR—Wilmshurst described institutional corruption in medicine.1 In Queensland the Nursing Act enables the Queensland Nursing Council to appoint inspectors. Acts regulating other health professions, including medicine, also have similar powers. Inspectors can require the production of documents, etc, and can enter and search for evidence of breaches of the act. The inspectors can …
THE INTERACTION OF HUMAN MONOCYTES AND LYMPHOCYTES
Authors: Martin J. Cline, Virginia C. Swett
Journal: The Journal of Experimental Medicine (1968)

Monocytes isolated from the peripheral blood of tuberculin-positive and tuberculin-negative donors were exposed to PPD, extensively washed, and incubated with autologous or homologous lymphocytes. Lymphocyte transformation was measured morphologically and by incorporation of 14C-labeled thymidine. Monocytes from tuberculin-positive subjects induced transformation of autologous lymphocytes in 19 of 29 experiments. Studies to define the optimal conditions of exposure to monocytes to PPD and to autologous lymphocytes showed that viable, metabolically intact monocytes are required. A ratio of only 1 monocyte to 100 lymphocytes sufficed to induce transformation; neutrophils were inactive. In general, PPD-sensitized monocytes failed to induce transformation of homologous lymphocytes from either tuberculin-positive or tuberculin-negative subjects. Direct contact between monocytes and lymphocytes was required for consistent transformation, and islands of transforming lymphocytes were observed around a central core of monocytes.
HTLV-I infection of WE17/10 CD4+ cell line leads to progressive alteration of Ca2+ influx that eventually results in loss of CD7 expression and activation of an antiapoptotic pathway involving AKT and BAD which paves the way for malignant transformation
Authors: H Akl, B M Badran, N E Zein, F Bex, C Sotiriou, K E Willard-Gallo, A Burny, P Martiat
Journal: Leukemia (2007)
ON SOME POINTS IN REGARD TO STERILIZATION IN PRIVATE DWELLINGS, WITH THE DEMONSTRATION OF SOME NEW ASEPTIC APPLIANCES.
Authors: CARL BECK
Journal: JAMA (1895)

Since the experiments of Petri and Cleves-Symmer have demonstrated that by bacteriologic test, what long before appeared to be probable on the base of clinical observation, namely, that the atmosphere has practically no bearing upon infection, but that the human body is invaded by bacteria by contact; in other words, by the wounding instrument, by the hands of the surgeon, by clothing or by the skin of the patient, the question of operating inside the hospital has entered a new stage. As besides Lister, the father of modern wound treatment, there is still a considerable number of surgeons who maintain that the atmosphere has at least<i>some</i>bearing upon infection, I thought it to be well worth while to refer to the experiments alluded to from a strictly surgical standpoint. Petri fixed the special forms of microbes suspended in the atmosphere and ascertained at the same time the number of
Familial Recurrent Orogenital Ulceration
Authors: I. J. Forbes, H. N. Robson
Journal: BMJ (1960)

Recuirrent aphthous ulceration of the mouth is common, its aetiology is unknown, and treatment is unsatisfactory.A small proportion of persons with this complaint also suffer recurrent ulceration of the genitalia.A still smaller fraction of these persons develop serious ocular complications at some stage in the illness.Recurrent oral and genital ulceration together with hypopyon iritis constitute the " triple symptom complex " of Behcet.Several authors accept two of the three manifestations as criteria for the diagnosis of Behcet's syndrome (Berlin, 1944; Phillips and Scott, 1955; Curth, 1956; Wadia and Williams, 1957).
Jewish Medical Association UK
Authors: Jane Cassidy
Journal: BMJ (2011)

The immune system contains natural regulatory cells important in the maintenance of tolerance. Although this suppressive function is usually attributed to CD4 regulatory T cells, recent reports have revealed an immunoregulatory role for IL-10-producing B cells in the context of several autoimmune diseases including collagen-induced arthritis. In the present study, we attribute this suppressive function to a B cell subset expressing high levels of CD21, CD23, and IgM, previously identified as transitional 2-marginal zone precursor (T2-MZP) B cells. T2-MZP B cells are present in the spleens of naive mice and increase during the remission phase of arthritis. Following adoptive transfer to immunized DBA/1 mice, T2-MZP B cells significantly prevented new disease and ameliorated established disease. The suppressive effect on arthritis was paralleled by an inhibition of Ag-specific T cell activation and a reduction in cells exhibiting Th1-type functional responses. We also provide evidence that this regulatory subset mediates its suppression through the secretion of suppressive cytokines and not by cell-to-cell contact. The ability to regulate an established immune response by T2-MZP B cells endows this subset of B cells with a striking and previously unrecognized immunoregulatory potential.
Is ticlopidine a necessary component of antiplatelet regimens following coronary artery stenting
Authors: Christopher M. Goods, Khaled F. Al-Shalbi, Brian H. Negus, Ming W. Liu, Sanjay S. Yadav, Suresh P. Jain, Larry S. Dean, Sriram S. Iyer, J.Michael Parks, Gary S. Roubin
Journal: Journal of the American College of Cardiology (1996)
THE ANTIBODY RESPONSE OF RATS DEPLETED OF LYMPHOCYTES BY CHRONIC DRAINAGE FROM THE THORACIC DUCT
Authors: D. D. McGregor, J. L. Gowans
Journal: The Journal of Experimental Medicine (1963)

The chronic drainage of lymph and cells from a thoracic duct fistula in rats results in a reduction in the weight of all the lymph nodes and of their content of small lymphocytes. The primary immune response to tetanus toxoid or sheep erythrocytes is severely depressed or abolished in such animals. This unresponsive state is related to the loss of lymphocytes from the thoracic duct fistula and, not to stress factors ensuing from the trauma of operation and restraint; it can be reversed by injecting inocula which contain almost exclusively small lymphocytes. In contrast to the severe impairment of the primary immune response in lymphocyte-depleted rats, such animals show a normal response to a second injection of tetanus toxoid. The mechanism by which small lymphocytes mediate the primary immune response is discussed.
Perspectives on whole-organ assembly: moving toward transplantation on demand
Authors: Alejandro Soto-Gutierrez, Jason A. Wertheim, Harald C. Ott, Thomas W. Gilbert
Journal: Journal of Clinical Investigation (2012)

There is an ever-growing demand for transplantable organs to replace acute and chronically damaged tissues. This demand cannot be met by the currently available donor organs. Efforts to provide an alternative source have led to the development of organ engineering, a discipline that combines cell biology, tissue engineering, and cell/organ transplantation. Over the last several years, engineered organs have been implanted into rodent recipients and have shown modest function. In this article, we summarize the most recent advances in this field and provide a perspective on the challenges of translating this promising new technology into a proven regenerative therapy.
Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system
Authors: Ulf Schulze-Topphoff, Alexandre Prat, Timour Prozorovski, Volker Siffrin, Magdalena Paterka, Josephine Herz, Ivo Bendix, Igal Ifergan, Ines Schadock, Marcelo A Mori, Jack Van Horssen, Friederike Schröter, Alina Smorodchenko, May Htwe Han, Michael Bader, Lawrence Steinman, Orhan Aktas, Frauke Zipp
Journal: Nature Medicine (2009)
Variant Angina of Prinzmetal with Normal Coronary Arteriograms
Authors: TSUNG O. CHENG, TALI BASHOUR, GEORGE A. KELSER, LOWELL WEISS, JAMES BACOS
Journal: Circulation (1973)

Variant angina of Prinzmetal has been generally presumed to be caused by a significant focal obstruction in a single major coronary artery which should be an ideal lesion for aortocoronary saphenous vein bypass graft. Recognition of this clinical syndrome would then be of particular diagnostic and therapeutic importance if such a consistent association can be demonstrated. Of five patients with variant angina studied in our cardiac catheterization laboratories, four had normal coronary arteriograms. Two important conclusions may be derived from this study. First, identical ECG changes may be observed both in the presence and absence of pain and thus the incidence and severity of the variant angina could be underestimated. Second, until a larger series of patients with variant angina is studied by coronary arteriography, one must exercise reservation in assuming that all patients with the clinical syndrome are operative candidates for saphenous vein bypass surgery.
Isotope Demonstration of CSF Pathways
Authors: David C. McCullough
Journal: JAMA (1969)

Obstruction of the outlets of the fourth ventricle and high spinal subarachnoid block developed in a patient with Coccidioides immitis meningitis. Radioisotope visualization procedures demonstrated absence of communication between basal meningeal areas, cerebral ventricles, and spinal theca. Drugs instilled in the crebrospinal fluid could not be effectively delivered to the basal meninges because of the two blocks. Isotope ventriculography and cisternography may be particularly useful in evaluating routes of drug administration in chronic fungal meningitis.