tbuckley/cabot-search huggingface dataset:
Differential distribution of protein kinases along the crypt-to-lumen regions of rat colonic epithelium.
Authors: B Schwartz, G M Fraser, J Levy, Y Sharoni, R Guberman, J Krawiec, S A Lamprecht
Journal: Gut (1988)

The activity of cAMP-dependent and cAMP-independent protein kinases, a class of enzymes involved in the regulation of cell proliferation was measured in rat colonic epithelium. Sequential cell populations harvested by a stepwise scraping technique from colonic crypt regions were identified by histology and incorporation of [3H]-thymidine into DNA. cAMP-independent phosphorylation of casein, in the presence of [gamma-32P]ATP, was markedly suppressed by quercetin, a bioflavonoid known to inhibit G-type casein kinase, protein kinase-C and tyrosine protein kinase. Conversely, the cyclic nucleotide regulatable form requiring histone as substrate was responsive to the action of the heat stable protein kinase inhibitor. The protein kinase species were characterised and partially purified by DEAE-cellulose chromatography. The activity of cAMP-dependent protein kinase in colonic cytosols (pmol 32P/min/mg protein, means (SE)) increased from 129.4 (15.9) in superficial cell populations to 238.5 (31.4) in lower crypt cell fractions (p less than 0.01). Colonic cAMP-independent protein kinase activity increased from 87.3 (15.6) in surface cell preparations to 178.1 (30.0) in lower crypt cell populations (p less than 0.02). A comparable activity gradient was observed in membrane fractions. The activity gradient persisted when the results were expressed as a function of cellular DNA. These findings indicate that protein kinases display a defined topological segregation along the colonic crypt regions and that during migration to the lumen colonic cells attenuate enzyme signals supposedly related to tissue growth.
Nocturnal Muscular Pains
Authors: Frederick H. von Hofe
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Relative to the question of nocturnal muscular pain, which appears in the Nov. 19 issue ofThe Journal, page 1656, I should like to state that, in my limited experience, these nocturnal pains occur quite regularly in the lower extremities, and not uncommonly they occur after a day of exercise beyond what is customary for the child. I have found that applying a snug spiral bandage to the lower extremity gives almost immediate relief in most cases. This method, used prophylactically in children who are having recurrent attacks, proves to be of real value.
The Use of Anthropometric Measures for Cardiometabolic Risk Identification in a Rural African Population
Authors: Georgina A.V. Murphy, Gershim Asiki, Rebecca N. Nsubuga, Elizabeth H. Young, Janet Seeley, Manjinder S. Sandhu, Anatoli Kamali
Journal: Diabetes Care (2014)

It has been suggested that the current definitions of obesity may not be appropriate for African populations (1–3). However, few studies of anthropometric indicators of cardiometabolic risk have been conducted within sub-Saharan Africa, where obesity is a rapidly growing problem (4,5). A better understanding of the relationship between adiposity and the risk of cardiometabolic disease in sub-Saharan African populations will be important for the design and implementation of public health care and prevention programs.

This cross-sectional study assessed the ability of anthropometric measures to identify risk of diabetes, hypertension, and dyslipidemia, and considered the optimal cutoff points for BMI and waist circumference (WC) in a rural Ugandan general population, using receiver operating characteristic (ROC) analysis. A total of 6,136 participants, aged ≥18 years, were surveyed, of which 5,518 (57% women) had complete data for analysis. Data were collected using standard procedures. Hypertension was defined as systolic …
Pneumoconiosis, Silicosis, and the Physics and Chemistry of Dust
Authors: C N Davies
Journal: Annual Review of Medicine (1957)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Neonatal death in Northern Ireland
Authors: M. J Scott, G. McClure, M. M. Reid, J W K. Ritchie, S. R Keilty
Journal: BMJ (1978)

A survey of neonatal deaths occurring over two years in Northern Ireland disclosed that many hospitals where babies could be born probably could not be staffed and equipped to deal effectively with major perinatal problems. The incidence of congenital malformations, especially neural tube defects, was high. A reduction in neonatal deaths from this cause might be expected if facilities for antenatal diagnosis and termination of pregnancy were made available, although this raises grave ethical problems. Many infants died of prematurity and the idiopathic respiratory distress syndrome. A considerable reduction in neonatal deaths might be expected with improved care at the place of delivery backed by a regional centre with facilities for transporting and treating severely ill infants needing intensive care.
Precursors of Hodgkin's Disease and B-Cell Lymphomas
Authors: John P Manis
Journal: New England Journal of Medicine (1999)

Nearly a century after Reed–Sternberg cells in Hodgkin's disease were first described, information about these unusual cells has begun to accumulate rapidly. Cytogenetic studies have clearly demonstrated that, in a given case, these cells arise from a single clone.13 Even so, the progenitor of this clone has for years eluded detection. In this issue of the Journal, Bräuninger and colleagues4 report their studies of two patients in whom both a B-cell lymphoma and Hodgkin's disease developed. From their molecular investigations of these rare “double” lymphomas, they conclude that a common B-cell precursor located in a germinal center gave rise . . .
Targeting Lymphatic Vessel Activation and CCL21 Production by Vascular Endothelial Growth Factor Receptor-3 Inhibition Has Novel Immunomodulatory and Antiarteriosclerotic Effects in Cardiac Allografts
Authors: Antti I. Nykänen, Henrik Sandelin, Rainer Krebs, Mikko A.I. Keränen, Raimo Tuuminen, Terhi Kärpänen, Yan Wu, Bronislaw Pytowski, Petri K. Koskinen, Seppo Ylä-Herttuala, Kari Alitalo, Karl B. Lemström
Journal: Circulation (2010)

Lymphatic network and chemokine-mediated signals are essential for leukocyte traffic during the proximal steps of alloimmune response. We aimed to determine the role of lymphatic vessels and their principal growth signaling pathway, vascular endothelial growth factor (VEGF)-C/D/VEGFR-3, during acute and chronic rejection in cardiac allografts.Analysis of heterotopically transplanted rat cardiac allografts showed that chronic rejection increased VEGF-C(+) inflammatory cell and hyaluronan receptor-1 (LYVE-1)(+) lymphatic vessel density. Allograft lymphatic vessels were VEGFR-3(+), contained antigen-presenting cells, and produced dendritic cell chemokine CCL21. Experiments with VEGFR-3/LacZ mice or mice with green fluorescent protein-positive bone marrow cells as cardiac allograft recipients showed that allograft lymphatic vessels originated almost exclusively from donor cells. Intraportal adenoviral VEGFR-3-Ig (Ad.VEGFR-3-Ig/VEGF-C/D-Trap) perfusion was used to inhibit VEGF-C/D/VEGFR-3 signaling. Recipient treatment with Ad.VEGFR-3-Ig prolonged rat cardiac allograft survival. Ad.VEGFR-3-Ig did not affect allograft lymphangiogenesis but was linked to reduced CCL21 production and CD8(+) effector cell entry in the allograft. Concomitantly, Ad.VEGFR-3-Ig reduced OX62(+) dendritic cell recruitment and increased transcription factor Foxp3 expression in the spleen. In separate experiments, treatment with a neutralizing monoclonal VEGFR-3 antibody reduced arteriosclerosis, the number of activated lymphatic vessels expressing VEGFR-3 and CCL21, and graft-infiltrating CD4(+) T cells in chronically rejecting mouse cardiac allografts.These results show that VEGFR-3 participates in immune cell traffic from peripheral tissues to secondary lymphoid organs by regulating allograft lymphatic vessel CCL21 production and suggest VEGFR-3 inhibition as a novel lymphatic vessel-targeted immunomodulatory therapy for cardiac allograft rejection and arteriosclerosis.
MEDICAL SCHOOL RECOGNIZED IN NEW YORK
Authors: None Dean
Journal: JAMA (1918)

<h3>To the Editor:</h3> —Table D, published inThe Journal, April 13, indicates that the University of Virginia Department of Medicine is not a registered medical school in New York and New Jersey. With regard to New Jersey, I wish to state that this board dropped the University of Virginia without consulting or even notifying me. The first intimation I had of its action was a letter received a week ago from one of our graduates informing me that this board had declined to allow a graduate of this school to take the licensure examination until he had spent an additional year of study in one of their registered schools. A letter from the secretary of the New Jersey board informs me that their list of acceptable schools is the New York list. With regard to New York, the University of Virginia was registered with the regents until the spring of
Precordial Area in Children.
Authors: A. L. Benedict
Journal: JAMA (1899)

Buffalo, N. Y., Jan. 4, 1899. <h3>To the Editor:</h3> —Although rather late, I would like to discuss the paper of Dr. H. B. Whitney on "Precordial Area in Children," published in theJournalof Nov. 5, 1898. Although my work does not include attendance on many children—for some reason, children remain in the hands of the general practitioner when adults would seek a specialist—yet it seems that such a peculiar variation with age as Dr. Whitney assigns to the precordial area would have attracted attention. While agreeing with Dr. Hall's remark that percussion should be made with the fingers—personally, I rarely use more than the one finger—and with Dr. Musser's observation as to the possibilities of palpation in the intercostal spaces, I should like to urge the more general use of auscultatory percussion. By this method, the mapping out of organs is rendered very simple and positive. It is rather
Changes in Bone Density With Lactation-Reply
Authors: Mary Fran Sowers
Journal: JAMA (1993)

<h3>In Reply.</h3> —In response to Dr Klahr's letter, we agree that our observation of bone loss during a period of high prolactin levels (lactation), coupled with a similar observation in women with prolactin-secreting adenomas, suggests the importance of further exploration of calcium metabolism in high prolactin states. Antipsychotic drugs are indeed a major cause of hyperprolactinemia that may cause galactorrhea and amenorrhea and, ultimately, bone loss. This is an important group for further study as available data are limited. However, based on our current data in lactating women, we cannot determine whether hyperprolactinemia is solely or partially responsible for bone demineralization. Naylor and Newman chastise us for providing what is, in their view, an insufficient explanation as to why bone mass might not have returned to baseline at 12 months in the group that breast-fed at least 6 months. They correctly point out that this group included some women who
Host granulomatous response in schistosomiasis mansoni. Antibody and cell-mediated damage of parasite eggs in vitro.
Authors: P A de Brito, J W Kazura, A A Mahmoud
Journal: Journal of Clinical Investigation (1984)

In chronic schistosomiasis mansoni the major pathologic lesions are granulomas surrounding eggs deposited in host tissues. Parasite ova release antigenic material that sensitize the host, resulting in the development of delayed-type hypersensitivity granulomas. The objectives of the present study were to assess the ability of components of the host granulomatous response to induce biochemical and biologic alterations in eggs in vitro, and to correlate these with the capacity of ova to induce granulomas in vivo. An assay of egg tricarboxylic acid cycle activity was developed by use of 2-[14C]acetate as substrate and measurement of accumulation of released 14CO2. Addition of human granulocytes (96% neutrophils, 4% eosinophils) to eggs (cell/egg ratio 1,000:1) and heat-inactivated normal human serum reduced predicted egg 14CO2 generation by 15.6 +/- 3.0%. This effect was greater in the presence of sera of subjects with schistosomiasis (25.6 +/- 2.8% reduction) or when complement was present (24.4 +/- 4.0%). Autologous eosinophils and neutrophils were equally effective in decreasing egg 2-[14C]acetate metabolism (25.6 and 21.4% reductions, respectively). Since the biological role of schistosome eggs relates to their ability to hatch and produce miracidia, we evaluated the effect of granulocytes and sera on this function. The hatching rate of eggs incubated with normal serum was 52.8 +/- 3.3 miracidia/100 eggs; this value decreased to 37.0 +/- 2.6 when granulocytes were added (P less than 0.01). Granulocytes plus antibody- or complement-containing sera led to hatching rates of 23 and 20 miracidia/100 eggs. When ova were pre-incubated with granulocytes and various sera and injected into mice, the areas of egg-induced pulmonary granulomas measured 8 d later were reduced 32 to 45% as compared with lesions elicited by parasite eggs not exposed to granulocytes. Exposure of antigen-coated Sepharose beads to granulocytes and immune serum before injection into mice also led to a reduction in granuloma formation as compared with beads pre-incubated with serum alone. These data indicate that granulocytes in conjunction with antibodies and complement inflict biologically relevant toxic effects on eggs that are manifest in vivo by a decreased ability to elicit granulomas.
Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization
Authors: Angel Porgador, Kari R. Irvine, Akiko Iwasaki, Brian H. Barber, Nicholas P. Restifo, Ronald N. Germain
Journal: The Journal of Experimental Medicine (1998)

Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8+ T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50–100 cells in an individual draining LN. However, over this same time period, the total number of CD11c+ DC increases more than twofold, by an average of 20,000–30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8+ T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming.
Anti‐allergic action of anti‐malarial drug artesunate in experimental mast cell‐mediated anaphylactic models
Authors: C. Cheng, D. S. W. Ng, T. K. Chan, S. P. Guan, W. E. Ho, A. H. M. Koh, J. S. Bian, H. Y. A. Lau, W. S. F. Wong
Journal: Allergy (2012)

Abstract Background Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross‐linking of allergen‐specific I g E ‐bound high‐affinity I g E receptors, leading to immediate mast cell degranulation. Artesunate is a semi‐synthetic derivative of artemisinin, an active component of the medicinal plant A rtemisia annua . Artesunate is a clinically effective anti‐malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti‐allergic effects of artesunate in animal models of I g E ‐dependent anaphylaxis. Methods Anti‐allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin‐induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell‐stabilizing effect of artesunate was examined in RBL ‐2 H 3 mast cell line and in mature human cultured mast cells. Anti‐allergic signaling mechanisms of action of artesunate in mast cells were also investigated. Results Artesunate prevented I g E ‐mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose‐dependent manner. In addition, artesunate suppressed ovalbumin‐mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration‐dependently blocked I g E ‐mediated degranulation of RBL ‐2 H 3 mast cells and human culture mast cells. Artesunate was found to inhibit I g E ‐induced S yk and PLC γ1 phosphorylation, production of IP 3 , and rise in cytosolic C a +2 level in mast cells. Conclusions We report here for the first time that artesunate possesses anti‐allergic activity by blocking I g E ‐induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell‐mediated allergic disorders.
Abstract A41: Inhibition of Lkb1 in cultured embryonic pancreas destabilizes tissue architecture to generate precancerous-like lesions
Authors: Bryan Lo, Manuel Viotti, Geraldine Strasser, Ira Mellman
Journal: Cancer Research (2013)

Abstract The tumor suppressor Lkb1 is a regulator of cellular energy, proliferation, and polarity, yet the mechanism by which it controls tissue morphogenesis or cancer remains poorly defined. By culturing embryonic tissues from mice harboring a mutant Lkb1 that can be rapidly inhibited, we have previously shown that acute loss of Lkb1 results in destabilized tissue architecture and the formation of highly dynamic pancreatic cysts (Lo et al, JCB 2012). Remarkably, the pancreatic cysts evolve within a few days into precancerous-like lesions that we now demonstrate to have a transcriptional profile that is strikingly similar to those reported for mouse and human PanINs (Pancreatic Intraepithelial Neoplasias). Utilizing fluorescence activated cell sorting, we have begun to track gene expression signatures associated with canonical signaling pathways in both single cells and subsets of cells from the embryonic explants. Since our experimental system offers precise temporal control and accessibility to manipulation within a tissue context, we are able to gain unprecedented insight into the earliest events in pancreatic oncogenesis. Citation Format: Bryan Lo, Manuel Viotti, Geraldine Strasser, Ira Mellman. Inhibition of Lkb1 in cultured embryonic pancreas destabilizes tissue architecture to generate precancerous-like lesions. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A41.
Eradicating child poverty
Authors: R. Smith
Journal: BMJ (1999)

Britain has more children living in poverty than any other country in the European Union. But, to its credit, the government is determined to eradicate child poverty, described by Gordon Brown, the Chancellor of the Exchequer, as “a scar on the soul of Britain.” The prime minister has set an ambitious target, even more ambitious perhaps than trying to achieve peace in Northern Ireland: “Our historic aim,” he says, “will be for ours to be the first generation to end child poverty.”

Last week the Chancellor and Alistair Darling, secretary of state for social security, called a meeting in Downing Street to discuss eradicating child poverty. “Many important meetings have been held in this room,” the Chancellor began, “but none more important than this.” Cynics might say that this was the Labour government trying to reassert some old Labour values after doing poorly in the European elections, but an academic at the meeting pointed out that in 25 years' studying child poverty this was the first time he had been invited to discuss the subject with the Chancellor. The recent BMA report on growing up in Britain reminded readers that “The Chancellor has a much greater impact on health than the secretary of state for health, a thought that may well not cross the minds of either.”1 It seems to have crossed the mind of this chancellor.

The task is huge. One in three …
Insulin pumps with a sensor and threshold-suspend reduced nocturnal hypoglycemia in type 1 diabetes
Authors: Rozalina McCoy, Steven Smith
Journal: Annals of Internal Medicine (2013)

ACP Journal ClubSeptember 17, 2013Insulin pumps with a sensor and threshold-suspend reduced nocturnal hypoglycemia in type 1 diabetesRozalina McCoy, MD, Steven Smith, MDRozalina McCoy, MDMayo Clinic, Rochester, Minnesota, USA (R.M., S.S.)Search for more papers by this author, Steven Smith, MDMayo Clinic, Rochester, Minnesota, USA (R.M., S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-159-6-201309170-02007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBergenstal RM, Klonoff DC, Garg SK, et al; ASPIRE In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med. 2013;369:224-32. https://pubmed.ncbi.nlm.nih.gov/23789889Clinical Impact RatingsGIM/FP/GP: Endocrinology: Reference1 Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36:1384-95. [PMID: 23589542] Google Scholar Author, Article, and Disclosure InformationAffiliations: Mayo Clinic, Rochester, Minnesota, USA (R.M., S.S.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics September 17, 2013Volume 159, Issue 6Page: JC7KeywordsAdolescentsEndocrinologyExerciseGlucoseGlycationHemoglobinHospitalizationsHyperglycemiaHypoglycemiaInsulinMorbidityRenal diseasesThyroidType 1 diabetes Issue Published: September 17, 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines
Authors: Thomas C. Wehler, Marion Nonn, Britta Brandt, Cedrik M. Britten, Mark Gröne, Mariya Todorova, Irina Link, Shamsul A. Khan, Ralf G. Meyer, Christoph Huber, Udo F. Hartwig, Wolfgang Herr
Journal: Blood (2006)
The Continuing Impact of Thyroid Scintigraphy on the Diagnosis of Thyroid Enlargement
Authors: HARRY R. MAXON, VICKI HERTZBERG, PRASAN VASAVADA, MOK YAO PU, DAVID VOLARICH
Journal: Clinical Nuclear Medicine (1986)

The impact of thyroid scintigraphy on the working diagnosis was evaluated in 204 consecutive patients referred for thyroid testing. The a priori and a posteriori diagnoses were discordant about one third of the time. The differences were highly significant (P less than 0.001) in the cases of uninodular and multinodular goiter.