tbuckley/cabot-search huggingface dataset:
Inhibition by noradrenaline and adrenaline of the increase in glucose and lactate output and decrease in flow after sympathetic nerve stimulation in perfused rat liver: Possible involvement of protein kinase C
Authors: Hisayuki Miura, Andreas Gardemann, Josip Rosa, Kurt Jungermann
Journal: Hepatology (1992)

In perfused rat liver stimulation of the hepatic nerve plexuses increased via α 1 -receptors glucose and lactate output decreased flow and caused an overflow of noradrenaline into the hepatic vein. Infusion of noradrenaline and adrenaline also elicited similar metabolic and hemodynamic alterations via α 1 -receptors, whereas infusion of isoproterenol via β 2 -receptors enhanced glucose output and slightly reduced lactate release without affecting flow. The influence of circulating catecholamines on the nerve stimulationdependent changes was investigated. Noradrenaline (100 nmol/L) or adrenaline (40 nmol/L) but not isoproterenol (1 μmol/L), which themselves caused about half-maximal alterations, strongly inhibited the nerve stimulation-induced increase in glucose and lactate output and decrease in flow but had no effect on noradrenaline overflow. The protein kinase C activator (4β)phorbol 12-myristate, 13-acetate (100 nmol/L) but not its analog (4α)phorbol 12,13-didecanoate (100 nmol/L) strongly inhibited the metabolic and hemodynamic changes caused by nerve stimulation or noradrenaline infusion. The protein kinase C inhibitor H7 (20 μmol/L) partially prevented the inhibition of the nerve actions by noradrenaline. The results lead us to conclude that noradrenaline and adrenaline inhibited the metabolic and hemodynamic nerve actions by means of a mechanism involving protein kinase C rather than presynaptic α-receptors or β-receptors. The catecholamines apparently increased via α 1 -receptors inositol 1,4,5-trisphosphate, which in turn enhanced cytosolic Ca 2+ and thus altered metabolism and in part hemodynamics, and diacylglycerol, which in turn activated protein kinase C and thus feedback inhibited the signal chain from α 1 -receptors via G proteins to phospholipase C. (Hepatology 1992;15:477-484).
Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1 /Fas) Mediated apoptosis
Authors: Susanne Strand, Walter J. Hofmann, Annette Grambihler, Hubert Hug, Martin Volkmann, Gerd Otto, Horst Wesch, Sara M. Mariani, Volker Hack, Wolfgang Stremmel, Peter H. Krammer, Peter R. Galle
Journal: Nature Medicine (1998)
Rim and "Doughnut" Signs, and Variants: Review and Reappraisal
Authors: WILFRIDO M. SY, REZA KHATIB, ROBERT BAY
Journal: Clinical Nuclear Medicine (1976)

The “rim” and doughnut” signs on brain imaging are reappraised. The two signs are distinct, distinguishable and imply diagnostic significance above what is generally realized. The “rim” sign is more commonly associated with subdural and epidural collections, while the “doughnut” sign is indicative of more spherical intracerebral lesions such as tumors, hematomas, abscesses or infarcts. Twelve additional cases resulting from various cerebral disease manifesting either of the two signs or their variants are presented. Examples of the variants of each sign are given and discussed.
Comparing bacterial infections in portacaval and distal splenorenal shunts
Authors: Ousama E. Moussa, Harold O. Conn
Journal: Hepatology (1987)

Since 1976, we have compared the end-to-side portacaval shunt (PCS) with the distal splenorenal shunt (DSRS) in patients with alcoholic liver disease and recurrent variceal bleeding. Fifty-four patients were randomly assigned to receive either shunt procedure. There were 27 patients in each group and both groups were highly comparable in clinical and laboratory characteristics. Median follow-up was 31 mo in each group. Postoperative complications and operative mortality (7% after PCS, 12% after DSRS) were comparable. Spontaneous portasystemic encephalopathy developed in 32% of the patients at risk after PCS and in 39% after DSRS. Rebleeding from varices occurred in 4% of the patients after PCS and in 27% after DSRS. Cumulative survival was not significantly different between groups (5-yr survival: 31% after PCS, 43% after DSRS). We have failed to demonstrate superiority of DSRS in our patients with alcoholic liver disease with respect to postoperative encephalopathy or survival, and have experienced an unusually high rate of variceal rebleeding after DSRS.
Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects.
Authors: A. J. Cowley, R. D. Wynne, K. Stainer, L. Fullwood, J. M. Rowley, J. R. Hampton
Journal: BMJ (1988)

There is no single, simple test with which to evaluate new treatments for heart failure. Various methods need to be used, and a study of both the acute haemodynamic and longer term symptomatic effects of flosequinan, a new direct acting arteriolar and venous vasodilator, was therefore carried out in patients with heart failure. In one group of patients flosequinan increased cardiac output and caused a fall in pulmonary capillary wedge pressure, both effects lasting for 24 hours. In a double blind, placebo controlled study in another group flosequinan improved mean exercise tolerance from 9.9 to 12.7 minutes after four weeks of treatment. The drug also reduced perceived exertion during submaximal exercise and increased calf and therefore skeletal muscle blood flow. It reduced plasma renin activity and noradrenaline concentrations. Flosequinan possesses all the important properties of a drug likely to be of value in the treatment of heart failure.
THE USE OF HUMAN PLASMA IN SPINAL ANESTHESIA
Authors: E. M. PAPPER
Journal: JAMA (1942)

During the relatively short history of spinal anesthesia, attention has been focused on two problems in designing technic for placing drugs into the subarachnoid space. The first of these has been to produce the desired extent of anesthesia in a manner predictable and with minimal dangers; the second, to secure the required duration of anesthesia with doses of the agent that provide a wide margin of safety. The latter problem has been approached in several ways. Recently, nupercaine and pontocaine, drugs more toxic but more potent than procaine, have been given in relatively smaller amounts and act for longer periods of time. Retarding the absorption of anesthetic drugs has been attempted by dissolving them in various foreign substances of higher osmotic tension than spinal fluid. Finally, prolonged spinal anesthesia is being accomplished by the repeated administration of relatively small doses of the drug. The problem of obtaining predictable levels of
Abstract 341: Effects of immunosuppressive cyclosporin A on epidermal keratinocytes
Authors: Weinong Han, Mei Ming, Tong-Chuan He, Yu-Ying He
Journal: Cancer Research (2010)

Abstract Non-melanoma skin cancer, the most common neoplasia after solid organ transplantation, causes serious morbidity and mortality and is related to sun exposure. Cyclosporin A (CsA) has been used widely to prevent rejection in organ transplantation. The mechanism of CsA action in causing cancer was thought to be well understood via immunosuppression. Here, we show that CsA promotes primary skin tumor growth in immune-deficient mice. CsA treatment at therapeutic plasma concentrations promotes growth and survival from removal of extracellular matrix or UVB radiation. CsA treatment enhances AKT activation following serum treatment and UVB radiation. Furthermore we found that PTEN expression, the negative regulator of AKT activation, is reduced significantly upon CsA treatment in human HaCaT and A431 cells and in mouse skin in vivo. Accordingly, the enhanced AKT activation in CsA-treated cells upon UVB radiation is observed in PTEN knockdown keratinocytes. CsA-induced PTEN suppression is critical for increased AKT activation. Inhibition of AKT activation abolishes CsA-promoted growth and survival, indicating that AKT hyperactivation is essential for the enhanced growth and survival of CsA-treated cells. In addition, mTOR signaling as a known AKT downstream target is required for CsA-enhanced growth and survival. Taken together, we have identified PTEN/AKT pathway as new molecular targets of CsA in epidermal keratinocytes, suggesting a previously unknown mechanism in CsA-enhanced skin carcinogenesis. Our findings challenge assumptions about how CsA-associated tumors arise in skin. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 341.
Extracellular matrix and integrin-signaling in the regulation of cell growth
Authors: Richard K. Assoian
Journal: Kidney International (1999)

The extracellular matrix (ECM) and mitogenic growth factors are jointly required for cell cycle progression through G1 phase, and this combined requirement is manifest in the regulation of the G1-phase cyclins and cyclin dependent kinase (CDK) inhibitors. One of the G1-phase cell cycle events regulated by cell adhesion is the expression of the CDK inhibitor p21. p21 is induced in early G1 phase, and this induction may play a role in assembling cyclin-CDK complexes. Down-regulation of p21 then occurs in mid-late G1, coincident with the activation of G1-phase cyclin-CDKs. We have examined the relative contributions of both mitogens and the ECM in the regulation of p21. Our results show that p21 expression can be divided into two discrete phases: The rapid up-regulation is strongly dependent on mitogens, whereas the subsequent down-regulation is strongly dependent on cell anchorage. Comparative studies with wild-type and p21-null fibroblasts confirm that this ECM-dependent repression of p21 is important for proper control of cyclin E-CDK2. We also find that the growth factor-dependent induction of p21 contributes to the timing of pRb phosphorylation and expression of cyclin A. Finally, we find that mitogen-activated protein (MAP) kinase is responsible for the growth factor-stimulated expression of p21, but we also find that this induction does not require the sustained activation of MAP kinase. To our knowledge, this is the first report of a functionally significant cell cycle effect that is mediated by the transient induction of MAP kinase.
UK aims to increase its organ donor rate by 50% over next eight years
Authors: N. Hawkes
Journal: BMJ (2013)

Ambitious new targets have been set for increasing the UK rate of organ transplantation by 2020. The strategy contains no radical changes or headline grabbing initiatives, seeking rather to build on the success of the past five years, which have seen a 50% rise in organ donation.1

When this target was set in 2008 there was some scepticism that it could be achieved, but it was: the number of donors rose from 809 in 2007-08 to 1212 in 2012-13.

Sally Johnson, director of organ donation and transplantation at NHS Blood and Transplant, introducing the new strategy at a London press conference, said, “There has been tremendous progress over the last five years, and more lives have been saved, but there is a limit to what the NHS can do without a change in attitude in the UK, because the overall percentage of people consenting to donate their organs has not increased.”

Overall, just 57% of families agreed to donate the organs of deceased relatives when they were asked. Among black and other ethnic minority communities …
Book Review Through the Patient's Eyes: Understanding and Promoting Patient-Centered Care Edited by Margaret Gerteis, Susan Edgman-Levitan, Jennifer Daley, and Thomas L. Delbanco. 317 pp. San Francisco, Jossey-Bass, 1993. $29.95. 0-1-55542-544-5
Authors: Anthony L. Suchman
Journal: New England Journal of Medicine (1994)
VISUALIZATION OF ACUTE AND SUBACUTE EP LESIONS IN PATIENTS AFTER ATRIAL FLUTTER ABLATION
Authors: Peter Nordbeck, Karl-Heinz Hiller, Florian Fidler, Marcus Warmuth, Matthias Nahrendorf, Peter M. Jakob, Georg Ertl, Wolfgang R. Bauer, Oliver Ritter
Journal: Journal of the American College of Cardiology (2011)
Selective Expression of a Stable Cell Surface Molecule on Type 2 but Not Type 1 Helper T Cells
Authors: Damo Xu, Woon Ling Chan, Bernard P. Leung, Fang-ping Huang, Rachel Wheeler, David Piedrafita, John H. Robinson, Foo Y. Liew
Journal: The Journal of Experimental Medicine (1998)

T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4+ cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor–α/β transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-γ. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-γ production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention.
Do we really know the law about students and patient consent?
Authors: Alexander S J Shaw
Journal: BMJ (2005)

It is difficult to understand medical law without an appreciation and full understanding of the scale and importance of consent. Through spending time on the wards and in the theatres, medical students learn the necessity and legal importance of consent. However, I wonder whether we truly know the laws of consent, and I go as far as to ask whether all doctors themselves do. It seems to me that the true breadth of the term consent is not fully appreciated and has become yet another automatism in the profession.

Many situations arise where doctors and medical students are required to obtain consent. In clerking and performing procedures on conscious patients, it is obvious that we need to get informed consent. But at other times consent is neglected. We learn and seem to appreciate that without consent any procedure or examination is deemed as battery and assault—a prosecutable offence. Consent therefore legitimises an otherwise unlawful act. However, we …
Gene Expression Profiling Does Not Identify Molecular Subgroup Among Nodal Peripheral T-Cell Lymphomas
Authors: Vincenzo Pitini, Carmela Arrigo, Giuseppe Altavilla
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: In the August 1, 2007, issue of the Journal of Clinical Oncology, Cuadros et al report on the microarray study of 35 nodal peripheral T-cell lymphomas (PTCLs; 23 PTCLs unspecified and 12 angioimmunoblastic T-cell lymphomas [AITLs]) using two different microarray platforms. Although the authors found a proliferation signature in the tumors associated with a shorter survival for patients, they did not observe any association between gene clusters and the histologic subtypes of PTCLs. Furthermore, given the clinical significance of the proliferation signature, which is associated with a high expression of topoisomerase II , they suggest that inhibitors of topoisomerase II , such as doxorubicin are likely to play an important role in this setting. In our opinion there are two key issues that can be underlined. First, WHO classification of PTCLs recognizes three major categories, two of which are studied by Cuadros et al. AITLs show a distinct morphological and phenotypic pattern whereas unspecified PTCLs are more heterogeneous. So far, microarray analysis has served to refine lymphoma classification by recognizing well-defined lymphoma categories as well as by discovering new entities (eg, activated v germinal center in diffuse large B-cell lymphoma or different geneexpression profiles in mantle-cell lymphomas). In their study, Cuadros et al, using an unsupervised hierarchical clustering analysis, failed to separate unspecified PTCLs from AITLs, so one should assume that currently accepted classification of T-cell lymphoma is wrong and should be deeply revised, even if Ballester et al, in a similar microarray study, was been able to discriminate AITLs from PTCLs. The second consideration is that doxorubin-based chemotherapy has been the mainstay of therapy for PTCLs, but with the notable exception of anaplastic lymphoma kinase–positive anaplastic large-cell lymphomas, the outcome has been uniformly disappointing, so novel treatment approaches are urgently needed.
Ulcerative colitis: one disease or two? (Quantitative histological differences between distal and extensive disease).
Authors: D Jenkins, A Goodall, B B Scott
Journal: Gut (1990)

Cell counts and measurements of mucosal architecture were made on rectal biopsies from nine patients with total colitis, eight with left sided colitis, 15 with distal colitis, and 11 with proctitis. The mean total lamina propria cell count in proctitis and distal colitis approached twice that of extensive left sided and total colitis (p less than 0.001) and in distal proctocolitis the cell numbers are further increased in the chronic over the acute phase. This difference was not explained by age, duration, activity, or treatment. The predominantly increased lymphoid and mononuclear cell infiltrate in distal proctocolitis indicates a different pattern of immune response, suggesting a separate process from extensive colitis or a more intense reaction resulting in localisation of disease.
An Opposite Pattern of Selection of a Single T Cell Antigen Receptor in the Thymus and among Intraepithelial Lymphocytes
Authors: Daniel Cruz, Beate C. Sydora, Kristine Hetzel, Gian Yakoub, Mitchell Kronenberg, Hilde Cheroutre
Journal: The Journal of Experimental Medicine (1998)

The differentiation of intestinal intraepithelial lymphocytes (IEL) remains controversial, which may be due in part to the phenotypic complexity of these T cells. We have investigated here the development of IEL in mice on the recombination activating gene (RAG)-2−/− background which express a T cell antigen receptor (TCR) transgene specific for an H-Y peptide presented by Db (H-Y/Db × RAG-2− mice). In contrast to the thymus, the small intestine in female H-Y/Db × RAG-2− mice is severely deficient in the number of IEL; TCR transgene+ CD8αα and CD8αβ are virtually absent. This is similar to the number and phenotype of IEL in transgenic mice that do not express the Db class I molecule, and which therefore fail positive selection. Paradoxically, in male mice, the small intestine contains large numbers of TCR+ IEL that express high levels of CD8αα homodimers. The IEL isolated from male mice are functional, as they respond upon TCR cross-linking, although they are not autoreactive to stimulator cells from male mice. We hypothesize that the H-Y/Db TCR fails to undergo selection in IEL of female mice due to the reduced avidity of the TCR for major histocompatibility complex peptide in conjunction with the CD8αα homodimers expressed by many cells in this lineage. By contrast, this reduced TCR/CD8αα avidity may permit positive rather than negative selection of this TCR in male mice. Therefore, the data presented provide conclusive evidence that a TCR which is positively selected in the thymus will not necessarily be selected in IEL, and furthermore, that the expression of a distinct CD8 isoform by IEL may be a critical determinant of the differential pattern of selection of these T cells.
Abstract 1765: Potent antitumor BO-1922, derivative of indolizino[6,7-<i>b</i>]indole, against human colon, lung, and pancreatic cancers in xenograft model
Authors: Tsann-Long Su, Satishkumar Tala, Ravi Chaniyara, Chi-Wei Chen, Te-Chang Lee, Ting-Chao Chou
Journal: Cancer Research (2012)

Abstract Our previously studies demonstrated that bis(hydroxymethyl)cyclopenta[a]indenes, which bear a bis(hydroxymethyl)pyrrolidine pharmacophore, exhibited potent antitumor activity in inhibiting various human tumor xenografts. We also demonstrated that these agents showed strong synergistic therapeutic efficacy in combination with arsenic trioxide (ATO) against acquire or inherited MDR human tumors in xenograft model (human lung H460 or bladder cancer resistant to cisplatin NTUB1/P). Based on these findings, we have recently synthesized a series of 1,2-bis(hydroxymethyl)indolizino[6,7-b]indols and their bis(alkylcarbomate) derivatives for antitumor evaluation. These new agents were easily prepared starting from L-tryptophane in 5 steps. The in vitro cytotoxicity studies showed that the newly synthesized derivatives possessed a broad spectrum of anticancer activity against human lymphoblastic leukemia and various solid tumor cell growth in vitro. Of these analogues, 1,2-bis(hydroxymethyl)-3,6-dimethylindolizino[6,7-b]indole (BO-1922) was selected for further antitumor studies. We found that this agent displayed potent therapeutic efficacy against human colon cancer HT-29, lung adenocarcinoma lung A549, and primary pancreatic adenocarcinoma BX-PC3 xenografts. The antitumor activity of BO-1922 was compared with Irinotecan (CPT-11) in animal xenograft model. It revealed that BO-1922 is more potent than CPT-11 against human colon cancer HT-29 xenograft; complete tumor suppression on day 20 after mice treated with BO-1922 (25 mg/kg, QD×4, intravenous injection), while, tumor relapsed on day 9 after mice treated with CPT-11 (60 mg/kg, Q2D×3, iv. inj.). Under the same drug administration conditions (dosage and schedule), BO-1922 is as potent as CPT-11 against lung cancer A549 and pancreatic cancer BX-PC3 xenografts. Although the bodyweight of all drug treated mice recovered after ceasing of treatment, it was found that BO-1922 is less toxic to the host based on the average body-weight loss. The alkaline agarose gel shifting assay showed that this agent is able to induce DNA double strand cross-linking. Flow cytomeric assay revealed that BO-1922 induced cell cycle arrest at G1/S phase in non-small cell lung carcinomas H1299. These results suggest that BO-1922 is a promising candidate for clinical application and is currently undergoing preclinical studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1765. doi:1538-7445.AM2012-1765
Hydrocortisone Tertiary-Butylacetate for Intra-Articular Therapy in Rheumatic Diseases
Authors: J. Zuckner, O. Machek, A. M. Ahern
Journal: Annals of the Rheumatic Diseases (1956)

In arthritic individuals who have only one or two peripheral joints causing difficulty, it would seem advisable to treat these joints locally by direct intra- articular injection of medication in an effort to decrease the incidence and severity of toxicity associated with systemic therapy.The first very effective anti-rheumatic preparation for intra- articular injection was hydrocortisone acetate (hereafter referred to as hydrocortisone).Hollander, Brown, Jessar, and Brown (1951), Stevenson, Zuckner, andFreyberg (1952), and Kersley and Desmarais (1952) demonstrated a beneficial response in approximately 70 to 80 per cent. of joints so treated with an average duration of improvement 2 to 3 weeks.Recently, Hollander, Brown, Jessar, Udell, Smukler, and Bowie (1955) reported superior results with a derivative of hydro- cortisone, hydrocortisone tertiary-butylacetate* (hereafter referred to as TBA).The purpose of this article is to report our experiences with the intra- articular administration of TBA in 38 patients, eighteen with rheumatoid arthritis, and twenty with osteo-arthritis.