tbuckley/cabot-search huggingface dataset:
Obstetrical Anesthesia in Myocardial Infarction and Complete Heart Block
Authors: Joseph G. Giuffrida
Journal: JAMA (1968)

To our knowledge, no case of pregnancy complicated by complete heart block and old myocardial infarction has been reported. In this communication, we shall describe the obstetrical course and anesthetic management of a pregnant patient with these unusual complications. <h3>Report of a Case</h3> A 35-year-old woman was admitted to Metropolitan Hospital in December 1960 with an acute myocardial infarction of the anterior wall, complete heart block, and syphilitic aortitis. Before this admission, she had delivered four children uneventfully, the last child having been born in May 1960. After treatment of the acute episode, she was followed up by the Home Care Service as a class 3-C cardiac (as defined by the New York Heart Association). She received pentaerythritol tetranitrate, 10 mg four times a day, and her physical activities were restricted because of easy fatiguability and angina pectoris. At age 40, the patient again became pregnant. Her expected date of
Abstract 5576: Pharmacologic targeting of CtBP by established and newly designed inhibitors.
Authors: Jung S. Byun, Kevin L. Gardner
Journal: Cancer Research (2013)

Abstract Breast cancer is not one single entity but a collection of multiple diseases that affect different populations with varying incidence, morbidity and mortality. Thus finding a unified marker and associated biological processes that provide an overall indication of prognosis with clear insights into therapy opportunities is critically needed. Previous our studies showed that CtBP drives invasion and metastasis by governing a mode of gene regulation that is not only reversible and strongly influenced by environmental factors, like metabolic status, but can be stably passed on to expanding clones of tumor cells. Recent studies indicate that this form of “epigenetic regulation” plays a critical role in tumor progression. Our most recent finding that CtBP expression can function as a single predictor of overall poor survival from breast cancer, independent of current criteria such as hormone receptor status, suggests that inhibiting CtBP and the pathways it controls may provide a unifying concept for improving breast cancer diagnosis and treatment. Using Computer Assisted Drug Design (CADD), we have identified multiple potential CtBP inhibitors from a panel of library of commercially available compounds. To validate the efficacy of these inhibitors, we have used targeted assessment by quantitative gene expression and ChIP analysis of established CtBP targets. We then scored compounds that disrupt CtBP controlled processes including EMT and genome instability at a low micromolar range. We found that some compounds were able to displace CtBP from endogenous genes and reactivate repressed gene expression. A smaller subset of these was able to inhibit cellular reprogramming associated with EMT and the wound healing response. These findings suggest that CtBP may be an effective target of pharmacological inhibition to impair tumor invasion and metastasis, and offers a proof-of-principle that will provide a foundation for more effective treatment strategies against aggressive forms of breast cancer. Citation Format: Jung S. Byun, Kevin L. Gardner. Pharmacologic targeting of CtBP by established and newly designed inhibitors. [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 5576. doi:10.1158/1538-7445.AM2013-5576
The potential of extrachromosomal replicating vectors for gene therapy
Authors: Michelle P. Calos
Journal: Trends in Genetics (1996)

Persistence of DNA vectors in target cells is advantageous in most applications of gene therapy. Particularly when target cells are undergoing proliferation, vector longevity will depend on either the integration of the vector into the chromosomes or the ability of the vector to replicate and be retained extrachromosomally. Vectors that efficiently integrate in a nonrandom fashion are currently unavailable, and those that can replicate extrachromosomally provide a major alternative strategy. Several classes of such vectors are under development, carrying mechanisms for prolonging DNA retention in mammalian nuclei that extend vector lifetime in non-proliferating cells as well. The vectors utilize either chromosomal or viral elements to mediate replication and retention, and have a large size capacity for insertion of genes of interest. I discuss the state of the art for these vectors, including the assets and limitations of their future use in gene therapy.
Optic Disc Topography and Peripapillary Retinal Nerve Fiber Layer Thickness in Nonarteritic Ischemic Optic Neuropathy and Open-Angle Glaucoma
Authors: Hitomi Saito, Atsuo Tomidokoro, Eiichiro Sugimoto, Makoto Aihara, Goji Tomita, Kazutaka Fujie, Masato Wakakura, Makoto Araie
Journal: Ophthalmology (2006)
Resurgent Heterophil-Antibody Reaction after Mononucleosis
Authors: Robert J. Hoagland
Journal: New England Journal of Medicine (1963)

IN 1958 Bender1 presented the first report of anamnestic resurgence of the heterophil-antibody reaction after recovery from infectious mononucleosis. His observation has heretofore been unconfirmed. The purpose of this communication is to confirm his observations and briefly to discuss some of its implications. "Anamnestic resurgence" means return of characteristic heterophil antibodies after a patient has recovered from mononucleosis, unaccompanied by clinical features of the disease.In Bender's first case, a patient who had had mononucleosis eighty-five days previously became ill with "atypical pneumonia." Six days before the onset of pneumonia, the heterophil-antibody titer (which had been positive in a dilution . . .
Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscopic study
Authors: Frank Parker, John D. Bagdade, George F. Odland, Edwin L. Bierman
Journal: Journal of Clinical Investigation (1970)

Plasma lipoprotein alterations in nine insulin-dependent diabetics with hyperlipemia have been related to the lipid accumulating in eruptive xanthomas evolving in these patients. Histochemical and electron microscopic examination of xanthomas have been correlated with the lipid analyses in order to obtain additional evidence regarding the lipoprotein origin of lipids accumulating in the lesions. Both analytical and morphologic evidence suggested that circulating chylomicrons significantly contribute to the xanthoma lipids. All the patients had large quantities of circulating triglyceriderich chylomicrons which carried approximately 70% of the triglyceride found in the plasma. The fatty acid pattern of chylomicron and xanthoma triglycerides were similar. Triglyceride constituted the major lipid found in the xanthomas when they were sampled during their eruption. These findings, take in conjunction with histochemical and electron microscopic evidence of chylomicron particles in the dermal capillary walls, support the theory that blood lipoproteins, and particularly chylomicrons, permeated the vascular walls and the triglycerides carried by these lipoproteins apparently accumulated in tissue macrophages and perithelial cells which evolved into foam cells. Initiation of appropriate therapy resulted in clearance of the chylomicronemia and a concomitant resolution of the xanthomas as reflected by a decrease in total xanthoma lipid. Sequential studies of resolving xanthomas in five patients revealed that xanthoma triglyceride was mobilized more rapidly than cholesterol, resulting in a redistribution of the xanthoma lipids, so that the resolving lesions were cholesterol rich. Consistent with this change in lipid composition, correlative electron microscopy revealed loss of amorphous material from many of the foam cell vacuoles.
SIMULTANEOUSLY DERIVED CIRCUMFERENTIAL AND LONGITUDINAL RIGHT VENTRICULAR STRAINS FROM 4D ULTRASOUND USING A NEW METHOD FOR 4D CARDIAC MECHANICS: VALIDATION BY SONOMICROMETRY
Authors: David J. Sahn, Sheetal Krishnakumar, Anugraha Rajendran, Sarah K. Yang, Shahryar Ashraf, Nicole Chang, Galyna Kovch, Weihui Shentu, Zhiwen Zhou, Bill Kenny, Berkley Cameron, Muhammad Ashraf
Journal: Journal of the American College of Cardiology (2011)
Upregulation of Flt3 Expression within the Bone Marrow Lin−Sca1+c-kit+ Stem Cell Compartment Is Accompanied by Loss of Self-Renewal Capacity
Authors: Jörgen Adolfsson, Ole Johan Borge, David Bryder, Kim Theilgaard-Mönch, Ingbritt Åstrand-Grundström, Ewa Sitnicka, Yutaka Sasaki, Sten E.W Jacobsen
Journal: Immunity (2001)
Hypertension for the Clinician
Authors: R D S Watson
Journal: BMJ (1995)

J Ian S Robertson, Stephen G Ball W B Saunders, pounds sterling30, pp320 ISBN 0 7020 1812 0

It is clearly in the publishers' interest to promote a textbook of hypertension to the widest possible readership, but the authors may have set themselves an overambitious task in aiming to “provide, in succinct form, severally for the primary care physician, the postgraduate student, and the hospital specialist.”

One has to ask whether a book of 320 pages could reasonably cover the disparate problems encountered in general practice and hospital. The primary care team will ask numerous practical questions. At what age is …
Making room for T cells
Authors: Gabriel N. Maine, James J. Mulé
Journal: Journal of Clinical Investigation (2002)

Under conditions of lymphopenia, transferred naive T cells can undergo marked proliferation (1, 2) as a result of both T cell–receptor engagement and cytokine stimulation. Naive T cells that undergo this homeostatic proliferation also acquire characteristics of memory and effector cells as measured by phenotype, by hypersensitivity to antigen stimulation, and by increased production of IFN-γ. This phenomenon has been observed following the adoptive transfer of either naive, transgenic T cells or of polyclonal, wild-type T cells. Recent studies using recombination-activating gene-deficient (Rag–/–) mice, CD3e-deficient mice, and irradiated normal mice as recipients have shown that memory T cells do not revert to naive T cells under these conditions to fill the peripheral naive T cell pool, as originally postulated. Rather, after lymphopenia, homeostasis-driven proliferation restores only the memory T cell compartment, whereas thymopoiesis is required to reconstitute the naive T cell compartment (3, 4).
Hypernatremic (Hypertonic) Dehydration in Infants
Authors: Laurence Finberg
Journal: New England Journal of Medicine (1973)

THE emergence of hypernatremic dehydration as a recognized and rather common clinical entity in pediatrics has occurred over the past 20 years. These two decades of clinical observation and clinical therapeutic trial have increased the known scope of the problem and have slowly produced advances in therapy.The entity defines a physiologic disturbance of two important parts, one of which (dehydration) denotes a loss of body water. The other part of the disturbance denotes a maldistribution of body water between its major compartments; the cells give up water to the extracellular space. Sodium salts, particularly chloride, because of the relative . . .
CLINICAL ASPECTS OF JAUNDICE
Authors: CHARLES S. McVICAR
Journal: JAMA (1927)

When a patient with jaundice presents himself, the clinician is confronted with the necessity of speedy diagnosis, and he will remember that operation on jaundiced patients carries the extra hazard of increased liability to hemorrhage. The need for prompt relief of obstruction in the extrabiliary passages has been illustrated by the work of Counseller and Mclndoe, who have shown in necropsy specimens the enormous dilatation of the intrahepatic biliary vessels which occurs in obstructive jaundice. When obstruction occurs rapidly, as in pancreatic carcinoma, this dilatation may quickly induce pressure atrophy of the parenchymal and vascular tissues of the liver. When obstruction occurs more slowly, dilatation of the bile passages is in part opposed by concomitant thickening of the walls of the ducts and proliferation of the interstitial or supporting tissue of the liver, a compensatory mechanism which may express itself later as biliary cirrhosis. But while surgical intervention should be
Needle aspiration of breast cysts.
Authors: A P Forrest, J R Kirkpatrick, M M Roberts
Journal: BMJ (1975)

A total of 149 breast cysts have been treated with primary aspiration. Findings were abnormal in 36 patients, 30 of whom underwent excision of the breast cyst with cancer being found in four. Careful examination of the breast after aspiration and follow-up are necessary, but, provided these precautions are observed, this type of treatment is simple, safe, and cheap besides often giving the patient relief at the first consultation.
AMPUTATION AT THE HIP JOINT, WITH A REVIEW OF THE VARIOUS METHODS OF CONTROLLING HÆMORRHAGE.
Authors: C. A. WHEATON
Journal: JAMA (1884)

Read in the Section of Surgery and Anatomy of the American Medical Association, May, 1884. Mr. Chairman and Gentlemen of the Surgical Section: You may perhaps think I display more of temerity than good judgment, in offering for your consideration an essay on this time-honored and much discussed subject, but my recent experience with two cases of Coxo-femoral amputation where the hæmorrhage was effectually controlled after the simple method recently described by Mr. Loyd in the<i>Lancet</i>of May 26, 1883, has led me to review the literature at my command of the operation since its first performance by Lacroix, of Orleans, in the year 1748. From the time of the first formal disarticulation at this joint to the middle of the present century, the hæmorrhage was controlled or sought to be, by digital compression against the pubic ramus at Poupart's ligament; by securing the crural vessels at that point,
Estimating Bed Needs by Means of Queuing Theory
Authors: James K. Cooper, Timothy M. Corcoran
Journal: New England Journal of Medicine (1974)

RECENTLY, a major urban hospital planned to increase and improve its cardiac-care services. The hospital desired an increase in the number of acute coronary-care-unit beds; it also planned to establish an intermediate-care facility so that patients with infarction could be discharged into a unit that provided less care than the acute unit, but more care than the general-hospital beds. Planning required an estimate of the number of beds necessary for both acute and intermediate coronary care.Since the admission of a patient with a suspected acute myocardial infarction is an event that cannot be expected to occur at regularly spaced . . .
Aggressiveness of breast cancers detected by screening.
Authors: S. W. Duffy
Journal: BMJ (1992)

hypofractionated radiotherapy may be offered, providing equivalent local control with acceptable late effects.Compared with more protracted regimens, the fewer hospital attendances required not only are cost effective but -may be more psychologically acceptable for elderly patients.A single hospital visit once a week for six weeks (3900 cGy in six fractions over six weeks) may be more acceptable than daily treatments for six weeks (6000 cGy in 30 fractions over six weeks).Further studies should address the issue of acceptability to patients in this regard.In contrast to Dixon, we believe that tamoxifen should not be given routinely to the elderly popula- tion unless there are specific indications such as involved axillary nodes or metastases.Although the trial of the Novadex Adjuvant Trial Organisa- tion and the meta-analysis by the Early Breast Cancer Trialists' Collaborative Group suggest an overall benefit, the probability of benefit to a given patient may depend more on specific prognostic factors.Determinants that may preclude the routine admuinistration of tamoxifen include practical issues such as compliance, potential interactions with other drugs, cost, and potential side effects such as nausea, flushing, and increased risk of thromboembolism and endometrial carcinoma.The potential advantages and disadvantages should be discussed with the patient non-dogmatically.For locally inoperable disease combined radio- therapy and tamoxifen may be appropriate if oestrogen receptor concentrations are raised, but age should not automatically contraindicate chemotherapy in elderly patients.Judicious appraisal ofa patient's medical status and biological age with appropriately tailored treatment is essential.
The Proposed Constitution and By-Laws for County Societies—A Suggestion.
Authors: William W. Golden
Journal: JAMA (1902)

Elkins, W. Va., Aug. 10, 1902. <h3>To the Editor:</h3> —As with the model of a constitution and by-laws for the reorganized state societies, so with the one now proposed for county societies, the committee has done its work well and deserves the thanks of the profession. Apart from the fact that it has contributed much toward a more uniform manner of organization of the different state associations, it has materially hastened their reorganization and has enabled many of them to materialize the suggestions of the American Medical Association even before one year has transpired from the time they were first made. Speaking for my own state, I can say that it is, at least in part, owing to the work of that committee that it is able to boast to-day of having been the first one to reorganize on the lines raid down by the American Medical Association at its
Cardiovascular regulation by central adrenergic mechanisms and its alteration by hypotensive drugs.
Authors: G Haeusler
Journal: Circulation Research (1975)

Electrical stimulation of the posterior hypothalamus is followed by an immediate increase in sympathetic nerve activity and rise in blood pressure. Destruction of hypothalamic adrenergic structures by local unilateral injection of 6-hydroxydopamine into the posterior hypothalamus reduced the blood pressure rise in response to stimulation of the lesioned side. This and numerous other findings indicate an involvement of central adrenergic neurons in the mediation of an increase of sympathetic nerve activity caused by hypothalamic stimulation. However, central adrenergic neurons do not seem to be an integral part of the sympathoexcitatory pathways originating in the posterior hypothalamus but rather facilitate their activation: after almost complete norepinephrine depletion produced by combined treatment with reserpine and alpha-methl-p-tyrosine, hypothalamic stimulation was still followed by an increase in spontaneous sympathetic nerve activity. Stimulation of an alpha-adrenoceptive site, probably located in the lower brain stem, mimics an activation of the baroreceptor reflex. The hypotensive drug, clonidine, stimulates this alpha-adrenoceptive site. In low doses clonidine facilitates the activation of the reflex, and in high doses this drug induces a state which closely resembles a pronounced activation of the reflex. Experiments following depletion of norepinephrine suggest that the central part of the baroreceptor reflex arc does not contain adrenergic neurons. However, these findings are compatible with the view that some neurons within the reflex arc are supplied with alpha-adrenoceptors. For the present it cannot be stated with certainty whether these alpha-adrenoceptors possess an innervation by adrenergic neurons projecting onto the reflex arc. In favor of such an innervation are the obsevations that alpha-methyldopa has its site of action in the lower brain stem and that the integrity of central adrenergic neurons is essential for its hypotensive effect. It seems that two central adrenergic systems exist with opposing effects on cardiovascular control. These are an excitatory hypothalamic and an inhibitory bulbar adrenergic system. Partial destruction of central adrenergic neurons by intraventricularly injected 6-hydroxydopamine prevents the development of DOCA/NaCl, renal, and neurogenic hypertension and alters the pattern of blood pressure rise in spontaneously hypertensive rats. Impairment of central adrenergic function or imbalance of the two central adrenergic mechanisms may represent a trigger mechanism for the initiation of hypertension.
Thymus-Derived Rosette-Forming Cells
Authors: Joseph Wybran, H. Hugh Fudenberg
Journal: New England Journal of Medicine (1973)

Modern immunology has defined the heterogeneity of the lymphocyte response triggered by antigen. Antigen can stimulate both humoral immunity and cellular immunity, and both B and T cells can co-operate in the immune response. Antibodies, effectors of the humoral response, are synthesized by B lymphocytes and plasma cells. The bursa of Fabricius is responsible for the competence of B lymphocytes in birds; the bursa equivalent remains ill defined in mammals. Cellular immunity is the responsibility of T lymphocytes. These T cells are derived, processed or influenced in some way by the thymus in animals and human beings.B and T . . .
Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog
Authors: Maisa Seppala, Michael J. Depew, David C. Martinelli, Chen-Ming Fan, Paul T. Sharpe, Martyn T. Cobourne
Journal: Journal of Clinical Investigation (2007)

Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly affecting the CNS and face, in which the embryonic forebrain fails to divide into distinct halves. Numerous genetic loci and environmental factors are implicated in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in both humans and mice. As growth arrest-specific 1 (Gas1) encodes a membrane glycoprotein previously identified as a Shh antagonist in the somite, we analyzed the craniofacial phenotype of mice harboring a targeted Gas1 deletion. Gas1(-/-) mice exhibited microform HPE, including midfacial hypoplasia, premaxillary incisor fusion, and cleft palate, in addition to severe ear defects; however, gross integrity of the forebrain remained intact. These defects were associated with partial loss of Shh signaling in cells at a distance from the source of transcription, suggesting that Gas1 can potentiate hedgehog signaling in the early face. Loss of a single Shh allele in a Gas1(-/-) background significantly exacerbated the midline craniofacial phenotype, providing genetic evidence that Shh and Gas1 interact. As human GAS1 maps to chromosome 9q21.3-q22, a region previously associated with nonsyndromic cleft palate and congenital deafness, our results establish GAS1 as a potential locus for several human craniofacial malformations.