tbuckley/cabot-search huggingface dataset:
Reform of GMSC not needed
Authors: J D. Watts
Journal: BMJ (1995)

EDITOR,—I believe that David Roberts is wrong in his assertion that morale in general practice is related to the method of election of the General Medical Services Committee and in his conclusion that the committee is undemocratic.1 I have been a member of the GMSC since 1980 and have served on the agenda committee for the annual representative meeting for several years. I carried out the detailed work on the section of the agenda that included the motion about the …
CT and MRI Improve Detection of Hepatocellular Carcinoma, Compared With Ultrasound Alone, in Patients With Cirrhosis
Authors: Nam C. Yu, Vinika Chaudhari, Steven S. Raman, Charles Lassman, Myron J. Tong, Ronald W. Busuttil, David S.K. Lu
Journal: Clinical Gastroenterology and Hepatology (2010)
Immune Responses to Insulin Aspart and Biphasic Insulin Aspart in People With Type 1 and Type 2 Diabetes
Authors: Anders Lindholm, Lisbeth B. Jensen, Philip D. Home, Philip Raskin, Bernhard O. Boehm, Jacob Råstam
Journal: Diabetes Care (2002)

OBJECTIVE—The antibody responses to a novel rapid-acting insulin analog, insulin aspart (IAsp), and their potential clinical correlates were studied with a specifically developed method in 2,420 people with diabetes treated for up to 1 year with preprandial subcutaneous injections of IAsp. RESEARCH DESIGN AND METHODS—Circulating insulin antibodies were analyzed by radioimmunoassay with 125I insulin or IAsp tracers and polyethylene glycol precipitation. Four multinational, open, parallel group studies were conducted in Europe and North America, with a total of 1,534 people with diabetes exposed to IAsp and 886 people exposed to human insulin (HI) as meal-related insulin for 6–12 months. RESULTS—Insulin antibodies specific to HI or IAsp were absent in a majority of patients throughout the 6- to 12-month study periods. A majority of the patients (64–68%) had antibodies cross-reacting between HI and IAsp when entering the studies, with baseline levels (means ± SD of percent bound/total) of 16.6 ± 16.3% in study 1 and 10.3 ± 14.0% in study 4. In all four studies, cross-reactive antibodies increased in patients exposed to IAsp, with a maximum at 3 months, and thereafter there was a decline toward baseline levels at 9–12 months (levels at 3 and 12 months: 22.3 ± 19.7 and 16.8 ± 16.5% in study 1 and 21.5 ± 21.9 and 16.9 ± 17.4% in study 4). Antibody levels showed similar changes in people with type 1 and type 2 diabetes, and there was no consistent relationship between antibody formation and glycemic control or between antibody formation and safety in terms of adverse events. CONCLUSIONS—Treatment with IAsp is associated with an increase in cross-reactive insulin antibodies, with a subsequent fall toward baseline values, without any indication of clinical relevance because no effect on efficacy or safety could be identified.
BMA's annual report for 1993-4
Authors: A Khanna, M Bown
Journal: BMJ (1994)

EDITOR, - I was interested to see in the annual report of the British Medical Association for 1993-4 that the association generated a surplus of pounds sterling 3.6m, is expecting a similar surplus for 1994, and has an overall surplus of pounds sterling 40.12m - the market value of its investments (pp 62-3).1 There seems to be a lack of a clear strategy on the use of these funds, except perhaps for speculation on the stock markets (p 41). In the absence of a coherent strategy I suggest, among other things, a policy of increasing the membership of the BMA by subsidising subscription fees rather than increasing them (p 41). A membership campaign emphasising the services offered and the reduction of fees would, with increased membership, give more political leverage to the BMA and in the long run might generate a further surplus - if that is indeed a strategy of …
Effect of gel-forming gums on the intestinal unstirred layer and sugar transport in vitro.
Authors: I T Johnson, J M Gee
Journal: Gut (1981)

The effect of two gel-forming polysaccharide gums, guar gum and Na-carboxymethyl-cellulose (CMC), on glucose transport in vitro was investigated using everted sacs of rat jejunum. The gums were added to the mucosal bathing media to give apparent viscosities in the range of 1-110 Pascal seconds X 10(-3), mPa.s(cP). Serosal glucose transport fell steeply by about 60% as the viscosities of the mucosal media rose to 20mPa.s, and levelled off thereafter. A similar effect was observed in sacs preincubated with guar gum (15 minutes) and exposed to glucose in a subsequent guar-free incubation. Glucose transport with and without the addition of guar gum was found to be sensitive to mucosal stirring, so that, when shaken at 130 oscillations per minute, sacs exposed to guar gum (0.25 %, viscosity c.a. 16 mPa.s (cP) transported glucose at a similar rate to sacs incubated without guar at 80 oscillations per minute. By measuring the time course for the establishment of osmotic induced potentials, it was shown that incubation with guar or CMC led to an increase in the apparent thickness of the unstirred fluid layer overlying the mucosa (guar-free thickness = 317 +/- 15 mu, guar treated thickness = 468 +/- 25 mu). It is suggested that the presence of a polysaccharide gum in the fluid film surrounding the villi increases its viscosity, and thus gives rise to a thickening of the rate-limiting unstirred layer. If such an effect occurs in vivo, this could contribute to the diminished post-prandial glycaemia observed in human subjects fed guar gum.
GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.
Authors: M H Davies, E Elias, S Acharya, W Cotton, G C Faulder, A A Fryer, R C Strange
Journal: Gut (1993)

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype.
CX3CL1 (fractalkine) and its receptor CX3CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin
Authors: Delphine Staumont-Sallé, Sébastien Fleury, Anne Lazzari, Olivier Molendi-Coste, Nicolas Hornez, Céline Lavogiez, Akira Kanda, Julien Wartelle, Anissa Fries, Davide Pennino, Cyrille Mionnet, Janne Prawitt, Emmanuel Bouchaert, Emmanuel Delaporte, Nicolas Glaichenhaus, Bart Staels, Valérie Julia, David Dombrowicz
Journal: The Journal of Experimental Medicine (2014)

Atopic dermatitis (AD) is a chronic allergic dermatosis characterized by epidermal thickening and dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the chronic stage. Among chemokines and chemokine receptors associated with inflammation, increased levels of CX3CL1 (fractalkine) and its unique receptor, CX3CR1, have been observed in human AD. We have thus investigated their role and mechanism of action in experimental models of AD and psoriasis. AD pathology and immune responses, but not psoriasis, were profoundly decreased in CX3CR1-deficient mice and upon blocking CX3CL1–CX3CR1 interactions in wild-type mice. CX3CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX3CR1 expression by both Th2 and Th1 cells was required to induce AD. Surprisingly, unlike in allergic asthma, where CX3CL1 and CX3CR1 regulate the pathology by controlling effector CD4+ T cell survival within inflamed tissues, adoptive transfer experiments established CX3CR1 as a key regulator of CD4+ T cell retention in inflamed skin, indicating a new function for this chemokine receptor. Therefore, although CX3CR1 and CX3CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases.
THE PATHOLOGY AND SYMPTOMS OF DUODENAL ULCER
Authors: H. T. Gray
Journal: BMJ (1924)

tiesue than are x rays, wvhilst its effect on the 7aterine niusele is greater.Taussig states that "radiuim is less likely to produce vomiting, cramps, and catarhlial stools," and that it will iUndce amenorrhoen when x iays have failed.In the use of radium we ha"e a better conception of dosage than when r rays are employed.My own experience with the use of radium in the treat- ment of liaemorrhage has been in chronic metritis, and the results have been so favourable that I shall be tempted to extend its application to the treatment of haemorrhage in eases of small unconmplicated uterine fibroids at the time of the climacteric-in other words, for this group of cases I regard it as legitimate to consider the use of radium as an alternative to hysterec-tomy.In conclusion, if asked " In what cases do uterine fibroids still require operative removal?" my ansver would be, In 55 per cent. of all fibroids no treatment whatever is needed.In the remaining 45 per cent., 35 per cent.require removal, leaving 10 per cent.to be dealt with by radium.This is equivalent to stating that the field for operation is from three to four times as great as that for radiotherapy.In the treatment of uterine fibroids s;urgery and radio- therapy may be run tandem-but to radiotherapy we assign a very subsidiary status.
Bone Marrow–generated Dendritic Cells Pulsed with Tumor Extracts or Tumor RNA Induce Antitumor Immunity against Central Nervous System Tumors
Authors: David M. Ashley, Brenda Faiola, Smita Nair, Laura P. Hale, Darell D. Bigner, Eli Gilboa
Journal: The Journal of Experimental Medicine (1997)

Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the central nervous system (CNS): dendritic cell (DC)-based vaccines pulsed with either tumor extract or tumor RNA, and cytokine gene–modified tumor vaccines. Using the B16/F10 murine melanoma (B16) as a model for CNS tumor, we show that vaccination with bone marrow–generated DCs, pulsed with either B16 cell extract or B16 total RNA, can induce specific cytotoxic T lymphocytes against B16 tumor cells. Both types of DC vaccines were able to protect animals from tumors located in the CNS. DC-based vaccines also led to prolonged survival in mice with tumors placed before the initiation of vaccine therapy. The DC-based vaccines were at least as effective, if not more so, as vaccines containing B16 tumor cells in which the granulocytic macrophage colony-stimulating factor gene had been modified. These data support the use of DC-based vaccines for the treatment of patients with CNS tumors.
Toxicological Aspects of Alterations of Pulmonary Macrophage Function
Authors: J D Brain
Journal: The Annual Review of Pharmacology and Toxicology (1986)

Pulmonary macrophages are similar to mononuclear phagocytes throughout the body, such as those found in the peritoneal cavity or liver. Yet, pulmonary macrophages face unique challenges. Found on the inner surfaces of the respiratory tract, they come in direct contact with toxic particles and gases as well as pathogens contained in the inspired air. Their mobility, phagocytic capacity, and bactericidal properties are essential to the maintenance of clean and sterile alveoli. Since these cells are accessible by bronchopulmonary lavage, they have been studied extensively in vitro. Our knowledge of the cell biology and toxicology of phagocytic cells has been extended by experiments with isolated pulmonary macrophages. These cells are of interest since their migratory patterns, phagocytic behavior, and secretory potential are pivotal events in the pathogenesis of pulmonary disease. Even though macrophages are an essential line of defense for airway and alveolar surfaces, they can also injure the host. For these reasons, the toxicology of pulmonary macrophages is an essential aspect of how toxic agents injure the lung (I). Under certain conditions, macrophages are damaged as a consequence of particle ingestion, and the nature of that damage is relevant to pUlmonary disease. In response to phagocytic stimuli, macrophages secrete lysosomal hydrolases, proteases, and antiproteases, chemotactic factors, interferon, and other mediators (2). Excessive or prolonged secretion, or secretion in an inappropriate site, can cause tissue damage. An imbalance between protease and antiprotease levels in thehmgs can lead to emphysema [reviewed by P. J.
Regulation of Ca2+ signaling in rat bile duct epithelia by inositol 1,4,5-trisphosphate receptor isoforms
Authors: Keiji Hirata, Jean-François Dufour, Kazunori Shibao, Roy Knickelbein, Allison F. O’Neill, Hans-Peter Bode, Doris Cassio, Marie V. St-Pierre, Nicholas F. LaRusso, Fatima M. Leite, Michael H. Nathanson
Journal: Hepatology (2002)

Cytosolic Ca 2+ (Ca i 2+ ) regulates secretion of bicarbonate and other ions in the cholangiocyte. In other cell types, this second messenger acts through Ca 2+ waves, Ca 2+ oscillations, and other subcellular Ca 2+ signaling patterns, but little is known about the subcellular organization of Ca 2+ signaling in cholangiocytes. Therefore, we examined Ca 2+ signaling and the subcellular distribution of Ca 2+ release channels in cholangiocytes and in a model cholangiocyte cell line. The expression and subcellular distribution of inositol 1,4,5-trisphosphate (InsP 3 ) receptor (InsP 3 R) isoforms and the ryanodine receptor (RyR) were determined in cholangiocytes from normal rat liver and in the normal rat cholangiocyte (NRC) polarized bile duct cell line. Subcellular Ca 2+ signaling in cholangiocytes was examined by confocal microscopy. All 3 InsP 3 R isoforms were expressed in cholangiocytes, whereas RyR was not expressed. The type III InsP 3 R was the most heavily expressed isoform at the protein level and was concentrated apically, whereas the type I and type II isoforms were expressed more uniformly. The type III InsP 3 R was expressed even more heavily in NRC cells but was concentrated apically in these cells as well. Adenosine triphosphate (ATP), which increases Ca 2+ via InsP 3 in cholangiocytes, induced Ca 2+ oscillations in both cholangiocytes and NRC cells. Acetylcholine (ACh) induced apical-to-basal Ca 2+ waves. In conclusion, Ca 2+ signaling in cholangiocytes occurs as polarized Ca 2+ waves that begin in the region of the type III InsP 3 R. Differential subcellular localization of InsP 3 R isoforms may be an important molecular mechanism for the formation of Ca 2+ waves and oscillations in cholangiocytes. Because Ca i 2+ is in part responsible for regulating ductular secretion, these findings also may have implications for the molecular basis of cholestatic disorders.
Human Dignity and Transhumanism: Do Anthro-Technological Devices Have Moral Status?
Authors: Fabrice Jotterand
Journal: The American Journal of Bioethics (2010)

In this paper, I focus on the concept of human dignity and critically assess whether such a concept, as used in the Universal Declaration on Bioethics and Human Rights, is indeed a useful tool for bioethical debates. However, I consider this concept within the context of the development of emerging technologies, that is, with a particular focus on transhumanism. The question I address is not whether attaching artificial limbs or enhancing particular traits or capacities would dehumanize or undignify persons but whether nonbiological entities introduced into or attached to the human body contribute to the “augmentation” of human dignity. First, I outline briefly how the Universal Declaration on Bioethics and Human Rights uses the concept of dignity. Second, I look at the possibility of a universal bioethics in relation to the concept of human dignity. Third, I examine the concept of posthuman dignity and whether the concept of human dignity as construed in the declaration has any relevance to posthuman dignity.
Clinicopathologic Features of Osteosarcoma in Patients With Rothmund-Thomson Syndrome
Authors: M. John Hicks, Jill R. Roth, Claudia A. Kozinetz, Lisa L. Wang
Journal: Journal of Clinical Oncology (2007)

Purpose Patients with Rothmund-Thomson syndrome (RTS) and RECQL4 gene mutations have an increased risk of developing osteosarcoma (OS). Because RTS is considered a genomic instability syndrome, patients may experience increased toxicity with chemotherapy. The purpose of this study was to summarize the clinical features and response to therapy of OS in patients with RTS. The results of this analysis will help to define treatment guidelines for this complex and rare condition. Patients and Methods An international cohort of patients with RTS and OS was enrolled in an institutional review board–approved study at Baylor College of Medicine (Houston, TX). Medical records were reviewed, and the following information was extracted: clinical features, treatment, pathologic findings, and clinical outcome. Results The median age at diagnosis of OS for the 12 patients was 10 years. The most common primary tumor sites were the long bones (femur, tibia); the most frequent histologic subtype was conventional OS. Histologic response to chemotherapy and outcome were similar to other published large series of sporadic OS. Eight patients are alive and disease free; four died as a result of cancer. Five patients required chemotherapy dose modifications, most commonly due to mucositis from doxorubicin. Conclusion Our results indicate that patients with RTS and OS are younger, but that their clinical behavior is similar to patients with sporadic OS. Our report suggests that these patients should initially be treated with conventional doses of chemotherapy as prescribed by current protocols; however, cautious and careful clinical observation is warranted to monitor for enhanced doxorubicin sensitivity in patients with RTS.
Monoexponential Extrapolation of Tracer Clearance Curves in Kinetic Analysis
Authors: Niels A. Lassen, Per Sejrsen
Journal: Circulation Research (1971)

Kinetic analysis of inert tracers shows that some of the most important parameters such as the average turnover rate and the total volume of distribution can he calculated only if the entire time course of the tracer clearance is known. This means that extrapolation beyond the observation period (to infinity) must necessarily be accomplished. This paper presents arguments to support the monoexponential extrapolating function which often is used without justification. The arguments show that one cannot in the general case assign any clearcut physical value to the intercept or exponential coefficient of the extrapolating function. Theoretically, a monoexponential tail of a tracer clearance curve obtained from a system in a steady state is reached when the slope of the curve is proportional to the curve. Under certain conditions this slope can be measured as an independent observation, and hence the monoexponentiality can be put to a fairly rigorous experimental test. This concept is illustrated by clearance studies of 51 Cr-EDTA and 181 I-thalamate from the isolated cat gastrocnemius muscle. Furthermore, it is demonstrated that monoexponential extrapolation as made before the appearance of the final exponential part of the outflow curve can cause considerable error in determination of the mean transit time and hence of the volume of distribution for the tracer. Even with an apparent recovery of the tracer of about 99.7%, the mean transit time was underestimated by 20%.
Durability of Transgene Expression and Vector Integration: Recombinant SV40-Derived Gene Therapy Vectors
Authors: David S Strayer, Francisco Branco, Mark A Zern, Priscilla Yam, Sandra A Calarota, Carmen N Nichols, John A Zaia, John Rossi, Haiting Li, Bhupesh Parashar, Siddhartha Ghosh, J.Roy Chowdhury
Journal: Molecular Therapy (2002)
MONOCLONAL PRODUCTION OF BOTH IgM AND IgG1 ANTIHAPTEN ANTIBODY
Authors: Joan L. Press, Norman R. Klinman
Journal: The Journal of Experimental Medicine (1973)

The anti-DNP antibodies produced by primary and secondary splenic foci were analyzed for heavy chain class by a radioimmunoassay, using iodinated, purified goat antimouse micro-chain antibody and goat antimouse gamma1 chain antibody. The frequency of primary and secondary foci producing both IgM and IgG1 anti-DNP antibody (16% and 14%, respectively) was considerably higher than that which would be predicted by a random distribution. It would thus appear that IgM and IgG1 antibody can be made by the clonal progeny of a single precursor cell.
Towards host-directed therapies for tuberculosis
Authors: Alimuddin Zumla, Jeremiah Chakaya, Michael Hoelscher, Francine Ntoumi, Roxana Rustomjee, Cristina Vilaplana, Dorothy Yeboah-Manu, Voahangy Rasolofo, Paula Munderi, Nalini Singh, Eleni Aklillu, Nesri Padayatchi, Eusebio Macete, Nathan Kapata, Modest Mulenga, Gibson Kibiki, Sayoki Mfinanga, Thomas Nyirenda, Leonard Maboko, Alberto Garcia-Basteiro, Niaina Rakotosamimanana, Matthew Bates, Peter Mwaba, Klaus Reither, Sebastien Gagneux, Sarah Edwards, Elirehema Mfinanga, Salim Abdulla, Pere-Joan Cardona, James B.W. Russell, Vanya Gant, Mahdad Noursadeghi, Paul Elkington, Maryline Bonnet, Clara Menendez, Tandakha N. Dieye, Bassirou Diarra, Almoustapha Maiga, Abraham Aseffa, Shreemanta Parida, Christian Wejse, Eskild Petersen, Pontiano Kaleebu, Matt Oliver, Gill Craig, Tumena Corrah, Leopold Tientcheu, Martin Antonio, Martin Rao, Timothy D. McHugh, Aziz Sheikh, Giuseppe Ippolito, Gita Ramjee, Stefan H. E. Kaufmann, Gavin Churchyard, Andrie Steyn, Martin Grobusch, Ian Sanne, Neil Martinson, Rajhmun Madansein, Robert J. Wilkinson, Bongani Mayosi, Marco Schito, Robert S. Wallis, Markus Maeurer
Journal: Nature Reviews Drug Discovery (2015)