tbuckley/cabot-search huggingface dataset:
Evidence for differential effects of hepcidin in macrophages and intestinal epithelial cells
Authors: T Chaston, B Chung, M Mascarenhas, J Marks, B Patel, S K Srai, P Sharp
Journal: Gut (2007)

Reticulo-endothelial macrophages together with duodenal enterocytes coordinate body iron homeostasis. The aim of this study was to investigate the regulatory actions of the hormone hepcidin on ferroportin expression in these two cell types.We investigated the in vitro effects of hepcidin in well-characterised human cell culture models of macrophages (differentiated THP-1 cells) and intestinal epithelial cells (Caco-2 cells). The in vivo effects of hepcidin were also investigated in mice injected with a synthetic hepcidin peptide.Exposure to hepcidin (presented either as conditioned medium from interleukin-6-stimulated HuH7 cells or as a synthetic peptide) resulted in a rapid (within 4 h) decrease in ferroportin expression in THP-1 macrophages but had no effect on ferroportin levels in Caco-2 cells. To determine whether these rapid effects of hepcidin were also evident in vivo we injected mice with a synthetic hepcidin peptide. Four hours post-injection, ferroportin levels in the macrophage-rich red pulp of the spleen were decreased significantly and the hepcidin-treated mice developed hypoferraemia. Interestingly, in the same mice there was no effect of hepcidin on duodenal ferroportin protein expression or duodenal iron transport.These data suggests that the rapid response to hepcidin is cell type and tissue specific. Upon its release, hepcidin initially targets macrophage iron recycling. The duodenum appears to be less sensitive to this initial rise in hepcidin levels. We believe the fact that macrophages respond more acutely to a hepcidin challenge is fully consistent with their central role in maintaining body iron homeostasis.
Lipoprotein(a) in cirrhosis.
Authors: H. Schmidt, S. Wagner, R. Kolm, M. Manns
Journal: BMJ (1992)

Volunteers (or families) might, however, have a role in maintaining benefit, and indeed the aim of all rehabilitation should be to involve families in longer term support.To this extent we failed, and further studies are needed to confirm our results and investigate ways of maintaining mobility.
Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma
Authors: Robert Chen, Joycelynne M. Palmer, Sandra H. Thomas, Ni-Chun Tsai, Len Farol, Auayporn Nademanee, Stephen J. Forman, Ajay K. Gopal
Journal: Blood (2012)
The Premedication of Children for Tonsillectomy
Authors: C. M. Rendell
Journal: BMJ (1954)

MEDICALJSHRNAL 1397 in McKhann's cases is not known, but in those of Greenberg et al. it was 5 ml., and in those of Karelitz et al. 10 to 20 ml.How far the dose of the placental extract influences the reaction rate is to be investigated. SummaryResults from the injection of placental globulin to 32 patients in the diphtheria ward of the Medical College Hospitals, Calcutta, who came in contact with measles are discussed.The protection rate of 96.6% which was obtained may have been due partly to the prompt and effective isola- tion of the patients who developed measles, together with the immediate immunization of all contacts.There was no reaction with 2 ml. of placental globu- lin, but with 4 ml.two out of three developed a reaction.It is suggested that the high reaction rate of the previous observers might have been due to the use of larger doses of the antiserum.Grateful thanks are extended to Professors J. C.
Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs
Authors: W. L. Blalock, C. Weinstein-Oppenheimer, F. Chang, P. E. Hoyle, X. Y. Wang, P. A. Algate, R. A. Franklin, S. M. Oberhaus, L. S. Steelman, J. A. McCubrey
Journal: Leukemia (1999)
Effect of Pregnancy and Parturition on Phthisis
Authors: R. C. Cohen
Journal: BMJ (1943)

MEDi ItURNA 7 patient to believe that his recovery will be rapid and complete, as there is a considerable tendency for a minor degree of pain or weakness to persist as a hysterical condition after the organic cause has been removed.This is especially likely to occur in patients who have already been disappointed at the failure to gain relief from prolonged treatment by rest, physiotherapy, and perhaps-injections of one kind or another.
A New Index for Quantitative Ballistocardiography: The Velocity of Body Displacement
Authors: VINCENZO MASINI, PAOLO ROSSI
Journal: Circulation (1953)

Calculation of the velocity of body displacement and of the momentum of the body from 100 normal ballistic tracings shows that the values of the velocity of body displacement present a small scatter (mean value 68.3 ± 13.9 mm. per second) and are independent of body weight and surface area. For uniformity of values and simplicity of calculation, which can be effected also on many abnormal tracings, it is suggested that the velocity of body displacement be used as an index of quantitative ballistocardiography.
IMPACT OF MULTIPLE RISK FACTOR INTERVENTION ON PROGRESSION OF CORONARY ATHEROSCLEROSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Yu Kataoka, Mingyuan Shao, Kathy Wolski, Kiyoko Uno, E. Murat Tuzcu, Steven E. Nissen, Stephen J. Nicholls
Journal: Journal of the American College of Cardiology (2011)
Hodgkin’s disease inHIV-infected patients: report of eight cases usefully treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus granulocyte colony- stimulating factor
Authors: R. Gastaldi, P. Martino, G. Gentile, V. Picardi, M.S. De Propris, M.F. Pirillo, A. De Vellis, F. Mandelli
Journal: Annals of Oncology (2002)
Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma
Authors: Julie A. Price, Stephen J. Kovach, Timothy Johnson, Leonidas G. Koniaris, Paul A. Cahill, James V. Sitzmann, Iain H. McKillop
Journal: Hepatology (2002)

Hepatocyte growth factor-scatter factor (HGF-SF) is a potent hepatic mitogen yet inhibits hepatocellular carcinoma (HCC) cell growth in vitro . Insulin-like growth factor I (IGF-I) is a pleiotropic growth factor shown to be important in cell growth and differentiation in other tumors. We hypothesized that IGF-I may play a role in regulating HGF-SF activity and HCC progression. Using an in vivo model of HCC, we showed elevated IGF-I messenger RNA (mRNA) expression in normal liver from tumor-burdened animals in the absence of changes in circulating IGF-I levels. Analysis of IGF-I receptor (IGF-IR) and HGF-SF (c-met) receptor expression showed significantly higher expression of both receptors in normal liver compared with an HCC specimen. Using cultured HCC cells from this model, we next showed that treatment with IGF-I led to significant increases in mitogen-activated protein kinase (MAPK) activity. Furthermore, we observed significant time-dependent increases in the expression of the c-fos and c-jun proto-oncogenes after addition of IGF-I (n = 5 per group, P &lt; .05). Despite activation of a MAPK pathway and increased proto-oncogene expression, IGF-I failed to significantly affect cell mitogenesis. In contrast, HGF significantly inhibited cell mitogenesis in HCC lines (68.4% ± 9.4% vs. control, n = 4, P &lt; .05). Pretreatment of HCC cells with IGF-I (60 minutes) led to significant HGF-SF stimulation of total cell mitogenesis dependent on both IGF-I and HGF-SF dose (194% ± 8% increase vs. control, n = 4, P &lt; .05). In conclusion, tumor burden is important in altering intrahepatic growth factor synthesis. Signal cooperation between multiple cytokine pathways is an important factor in the progression of HCC.
Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism.
Authors: G A Arreaza, M J Cameron, A Jaramillo, B M Gill, D Hardy, K B Laupland, M J Rapoport, P Zucker, S Chakrabarti, S W Chensue, H Y Qin, B Singh, T L Delovitch
Journal: Journal of Clinical Investigation (1997)

Optimal T cell responsiveness requires signaling through the T cell receptor (TCR) and CD28 costimulatory receptors. Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). Here, we demonstrate that anti-CD28 mAb stimulation restores complete NOD T cell proliferative responsiveness by augmentation of IL-4 production. Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. Simultaneous anti-IL-4 treatment abrogates the preventative effect of anti-CD28 treatment. Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM.
The Empathic Practitioner: Empathy, Gender, and Medicine
Authors: Richard E. Peschel
Journal: JAMA (1995)

Empathy in medicine has become an important topic in the medical literature. In a recent commentary in Medical<i>Humanities Review</i>, David Barnard found 1158 titles listed under "empathy" in the last decade.<sup>1</sup>Several diverse and scholarly books devoted to empathy in medicine have been recently published, for instance,<i>Empathy and the Practice of Medicine</i>(Yale University Press).<sup>2</sup> <h3>The Empathic Practitioner</h3> :<i>Empathy, Gender, and Medicine</i>is a unique contribution to the growing literature on empathy in medicine because, as the editors state in their introduction, the book "represents our attempt to broach the relationship between empathy and gender in the culture of modern medicine." Because of its unique perspective on the subject combined with numerous scholarly and well-written essays, this book is an unqualified success. The volume is divided into four major sections, and my favorite was the last, "Empathy and the Politics of Difference." For example, in this
Fifteen-Year Survival With Prostate Cancer in Sweden-Reply
Authors: Johansson Jan-Erik
Journal: JAMA (1997)

<h3>In Reply.</h3> —Drs Aus and Hugosson claim that we have underascertained deaths due to prostate cancer in our study. Their concern is based on a rather cavalier approach to epidemiological methods; they attempt to validate the mortality data we reported in a closed cohort study by means of cross-sectional data from the entire population. It is well established,<sup>1</sup>and further demonstrated in our article that patients with prostate cancer have excess mortality during many years. Hence, mortality rates during the 18-year period 1977 through 1994 are generated by 3 distinguishable cohorts of patients, namely, those who developed prostate cancer (1) during a number of years prior to 1977; (2) between 1977 and 1983 (those who were clinically diagnosed are included in our study cohort); and (3) between 1984 and 1994. Aus and Hugosson apparently overlook the need to separate mortality generated by our incidence cohort from that among prevalent cases in
Screening and surveillance for asymptomatic colorectal cancer in IBD
Authors: A Forbes
Journal: Gut (2003)

We would like to voice our concerns about some of the recommendations in the guidelines recently published by the British Society of Gastroenterology and Association of Coloproctology for screening and surveillance for asymptomatic colorectal cancer in patients with inflammatory bowel disease ( Gut 2002; 51 (suppl V):v10–12).

(1) In the present medicolegal environment, failure to comply with guidelines which carry the imprimatur of respected national bodies will require vigorous defence should mishap occur. We do not believe the evidence is strong enough to justify the recommendation that every patient with extensive colitis of duration greater than 8–10 years should undergo regular colonoscopy. Firstly, it must be determined at each hospital whether it is possible and considered sufficiently cost effective to offer such a service within the constraint of local resources available. Secondly, if regular colonoscopy can be offered, then each patient should decide whether or not to accept regular colonoscopy after full discussion of its possible advantages and limitations.

(2) The success of colonoscopic surveillance programmes is disputed. Although some centres (including our own) have been protagonists for this approach, others have argued that it is not only labour intensive but also ineffective. Before imposing global national guidelines we should have firm evidence of a scheme’s efficacy or, failing this, we should have multicentre consensus. The guidelines, as published, appear to be the sincerely held opinions of a single consultant team based on their own research and assessment of the literature, followed by approval of a committee, but no indication is given of widespread consultation.

(3) The recommendations for patients with extensive colitis of a colonoscopy every third year during the second decade of disease, every second year during the third decade, and annual colonoscopies thereafter are complex. The evidence for an increasing risk of cancer in the second, third, and …
The Uncertain Consequences of Formaldehyde Toxicity
Authors: Ralph E. Yodaiken
Journal: JAMA (1981)

FOR MANY years, pathologists and their assistants have been crying over formaldehyde in much the same way as cooks cry over onions. Itchy eyes, a running nose, browning or blistering of the fingers,<sup>1</sup>and coughing and respiratory distress (even to the point of acute pulmonary congestion with edema)<sup>2</sup>has been the lot of pathologists, their residents, and their assistants. Formaldehyde toxic reactions have been an accepted part of the profession, whether one hovers over the cutting board with biopsy specimens or takes "pickled" organs out of the earthenware containers for student demonstrations. Fume-filled anatomy rooms and pathology museums have been a part of the medical student's heritage. Now all that may be rapidly on its way out. Why the sudden concern to put specimens under hoods, to find ways of flushing out preparation rooms to rid them of the formaldehyde residues, to ventilate storage rooms, and to use
Compartmentalization of T lymphocytes to the site of disease: intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C.
Authors: M A Minutello, P Pileri, D Unutmaz, S Censini, G Kuo, M Houghton, M R Brunetto, F Bonino, S Abrignani
Journal: The Journal of Experimental Medicine (1993)

The adult liver is an organ without constitutive lymphoid components. Therefore, any intrahepatic T cell found in chronic hepatitis should have migrated to the liver after infection and inflammation. Because of the little information available on the differences between intrahepatic and peripheral T cells, we used recombinant proteins of the hepatitis C virus (HCV) to establish specific T cell lines and clones from liver biopsies of patients with chronic hepatitis C and compared them with those present in peripheral blood mononuclear cells (PBMC). We found that the protein nonstructural 4 (NS4) was able to stimulate CD4+ T cells isolated from liver biopsies, whereas with all the other HCV proteins we consistently failed to establish liver-derived T cell lines from 16 biopsies. We then compared NS4-specific T cell clones obtained on the same day from PBMC and liver of the same patient. We found that the 22 PBMC-derived T cell clones represent, at least, six distinct clonal populations that differ in major histocompatibility complex restriction and response to superantigens, whereas the 27 liver-derived T cell clones appear all identical, as further confirmed by cloning and sequencing of the T cell receptor (TCR) variable and hypervariable regions. Remarkably, none of the PBMC-derived clones has a TCR identical to the liver-derived clone, and even with polymerase chain reaction oligotyping we did not find the liver-derived clonotypic TCR transcript in the PBMC, indicating a preferential intrahepatic localization of these T cells. Functionally, the liver-derived T cells provided help for polyclonal immunoglobulin (Ig)A production by B cells in vitro that is 10-fold more effective than that provided by the PBMC-derived clones, whereas there is no difference in the help provided for IgM and IgG production. Altogether these results demonstrate that the protein NS4 is highly immunogenic for intrahepatic CD4+ T cells primed by HCV in vivo, and that there can be compartmentalization of some NS4-specific CD4+ T cells to the liver of patients with chronic hepatitis C.
Doctoring: The Nature of Primary Care
Authors: Donald L. Madison
Journal: JAMA (1997)

Eric Cassell's name is well known to the students at my medical school, who early in their first year read—to good effect—a portion of The Nature of Suffering . His earlier book, The Healer's Art , and the more recent Talking With Patients have also enjoyed appreciative audiences; and so the appearance of a new Cassell book is of more than passing interest.  The title Doctoring calls on a term that carries several different meanings. Lord Dawson of Penn first used   to advance the concept of the health center, an institution he believed should form the base of an idealized, hierarchical medical  system for post-World War I Britain. Dawson's scheme was never implemented, but his original, organizational use of primary care reappeared several times after 1920. It was not until the 1960s, after the general practitioner (in the United States) had been minimized, that the term took on
487. Liver-Targeted Gene Therapy in Glycogen Storage Disease Type Ia (GSD-Ia) Requires Widespread, Regulated Glucose-6-phosphatase
Authors: Dwight D. Koeberl, Lopamudra Banerjee, Andrew Bird, Baodong Sun, Y.T. Chen
Journal: Molecular Therapy (2006)

The glucose-6-phosphatase (G6Pase) deficiency of GSD-Ia prevents the conversion of glycogen to glucose in the liver. G6Pase overexpression was associated with blood glucose elevations; therefore, unregulated G6Pase expression should be avoided when considering strategies for gene therapy for GSD-Ia. A minimal G6Pase promoter containing insulin-responsive sequence elements was placed upstream of the human G6Pase cDNA in AAV-GRPhG6PpA. This vector was pseudotyped as AAV2/8 and administered to two week-old affected GSD-Ia mice (3 × 1011 DNase-resistant vector particles; 6 × 1013 particles/kg). An AAV2/8 vector containing the universally active CB promoter, AAV-CBcG6PpA, was also administered to affected GSD-Ia mice; however, the CB promoter is NOT glucose-responsive. Importantly, G6Pase expression with the glucose-responsive promoter (GRP) was as effective as the CB promoter/enhancer at correcting hypoglycemia. AAV-GRPhG6PpA significantly corrected hypoglycemia in fasting, affected GSD-Ia mice at 4 weeks of age. Pseudotyping AAV-GRPhG6PpA as AAV2/8 or AAV2/1 corrected hypoglycemia equivalently in GSD-Ia mice. Resolution of hypoglycemia was associated with the correction of other biochemical abnormalities, including hypercholesterolemia and G6Pase deficiency/glycogen storage in the liver. Furthermore, AAV- GRPhG6pA promoted normal growth and prolonged the survival of GSD-Ia mice by greater than 6 months, in comparison to untreated, affected mice which failed to grow and did not survive weaning. AAV-GRPhG6PpA was modified by deleting the D sequence from the terminal repeat to package scAAV-GRPhG6PpA, thereby increasing the efficiency of liver transduction. When scAAV- GRPhG6PpA, pseudotyped as AAV2/8, was administered to 2 week- old affected G6Pase-KO mice (3 × 1011 vector particles), blood glucose was significantly increased (90 +/- 16 mg/dl versus 31 +/- 19 mg/dL for untreated, affected mice; p<0.005). Furthermore, the number of scAAV vector particles administered could be reduced 10-fold compared to the analogous non-scAAV vector, while still correcting hypoglycemia and prolonging survival. An AAV vector encoding a liver-specific promoter (AAV-LSPhG6PpA) to drive unregulated G6Pase expression was administered to unaffected (wild-type) G6Pase-KO mice at 2 weeks of age and a glucose tolerance test was performed at 1 month old. The glucose tolerance test detected elevated glucose, in comparison to untreated wild-type mice, which reflected glucose intolerance related to unregulated G6Pase expression driven by the LSP. In contrast, AAV-GRPhG6PpA administration did not cause glucose intolerance in affected or wild-type mice. Hence, an scAAV vector efficaciously delivered a regulated transgene to liver without causing glucose intolerance in GSD-Ia.
Pre-emptive hypoxia-regulated HO-1 gene therapy improves post-ischaemic limb perfusion and tissue regeneration in mice
Authors: Agnieszka Jazwa, Jacek Stepniewski, Martin Zamykal, Jolanta Jagodzinska, Marco Meloni, Costanza Emanueli, Alicja Jozkowicz, Jozef Dulak
Journal: Cardiovascular Research (2012)

AimsHaem oxygenase-1 (HO-1) is a haem-degrading enzyme that generates carbon monoxide, bilirubin, and iron ions. Through these compounds, HO-1 mitigates cellular injury by exerting antioxidant, anti-apoptotic, and anti-inflammatory effects. Here, we examined the influence of HO-1 deficiency and transient hypoxia/ischaemia-induced HO-1 overexpression on post-injury hindlimb recovery.
Diet First, Then Medication for Hypercholesterolemia
Authors: James W. Anderson
Journal: JAMA (2003)

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