tbuckley/cabot-search huggingface dataset:
Abstract IA15: Role of PD-1 and LAG-3 in cancer immunotherapy.
Authors: Charles G. Drake
Journal: Cancer Research (2013)

Abstract PD-1 and LAG-3 are negative regulatory molecules expressed on the cell surface of “exhausted” or non-functional CD8 T cells in both cancer and in infectious disease. In several cancer models, blocking both molecules shows a synergistic anti-tumor effect, without overt signs of autoimmunity. In more recent studies, we have examined the role of LAG-3 and/or PD-1 blockade on memory induction in vivo. Interestingly, we found that a short course (1 week) of combined antibody blockade results in a significant increase in the frequency of memory T cells over 30 weeks later. Augmented CD8 T cell responses were not apparent in the secondary lymphoid organs, but rather manifested as an increase in tissue resident responses. Responding cells in the combined blockade group also showed an increase in polyfunctional cytokine production, confirming the potential for increased effector function. Taken together, these data support our previous studies implying that simultaneous blockade of multiple immune checkpoints may be required for optimal anti-tumor immunity. Citation Format: Charles G. Drake. Role of PD-1 and LAG-3 in cancer immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA15.
Postgraduate training in Italy
Authors: P. Albertazzi, G. Ghersi
Journal: BMJ (1995)

EDITOR,--We wish to add to the discussion about specialisation in Europe. In the past few years both the undergraduate and the postgraduate Italian medical curriculums have been reformed. Previously, no examinations had to be taken for entry to undergraduate courses and there were fairly relaxed entry examinations for the postgraduate curriculum; admissions have now been greatly restricted. In particular, postgraduate training changed dramatically with a reform in 1991 that was meant to bring Italian specialist training up to European standards. On …
Granulocytic spongiotic papulovesiculosis. A new entity?
Authors: S. Sayami, H. Tagami
Journal: British Journal of Dermatology (1984)

Journal Article Granulocytic spongiotic papulovesiculosis. A new entity? Get access S. Sayami, S. Sayami Department of Dermatology, Hamamatsu University School of Medicine, Sendai 980, Japan Search for other works by this author on: Oxford Academic Google Scholar H. Tagami H. Tagami Department of Dermatology, Tohoku University School of Medicine, Sendai 980, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 4, 1 April 1984, Pages 504–506, https://doi.org/10.1111/j.1365-2133.1984.tb04668.x Published: 01 April 1984
GATA-1 Is Essential in EGF-Mediated Induction of Nucleotide Excision Repair Activity and ERCC1 Expression through ERK2 in Human Hepatoma Cells
Authors: Lise O. Andrieux, Alain Fautrel, Anne Bessard, André Guillouzo, Georges Baffet, Sophie Langouët
Journal: Cancer Research (2007)

Abstract The nucleotide excision repair (NER) pathway and its leading gene excision-repair cross-complementary 1 (ERCC1) have been shown to be up-regulated in hepatocellular carcinomas even in the absence of treatment with chemotherapeutics. The aim of this study was to determine the mechanism involved in NER regulation during the liver cell growth observed in hepatocellular carcinoma. Both NER activity and ERCC1 expression were increased after exposure to the epidermal growth factor (EGF) in cultured normal and tumoral human hepatocytes. These increases correlated with the activation of the kinase signaling pathway mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK that is known to be a key regulator in the G1 phase of the hepatocyte cell cycle. Moreover, EGF-mediated activation of ERCC1 was specifically inhibited by either the addition of U0126, a MEK/ERK inhibitor or small interfering RNA-mediated knockdown of ERK2. Basal expression of ERCC1 was decreased in the presence of the phosphoinositide-3-kinase (PI3K) inhibitor and small hairpin RNA (shRNA) against the PI3K pathway kinase FKBP12-rapamycin-associated protein or mammalian target of rapamycin. Transient transfection of human hepatocytes with constructs containing different sizes of the 5′-flanking region of the ERCC1 gene upstream of the luciferase reporter gene showed an increase in luciferase activity in EGF-treated cells, which correlated with the presence of the nuclear transcription factor GATA-1 recognition sequence. The recruitment of GATA-1 was confirmed by chromatin immunoprecipitation assay. In conclusion, these results represent the first demonstration of an up-regulation of NER and ERCC1 in EGF-stimulated proliferating hepatocytes. The transcription factor GATA-1 plays an essential role in the induction of ERCC1 through the mitogen-activated protein kinase (MAPK) pathway, whereas the PI3K signaling pathway contributes to ERCC1 basal expression. [Cancer Res 2007;67(5):2114–23]
Letter: Gentamicin nephrotoxicity in patients with renal allografts.
Authors: J M Wellwood, A E Thompson, J R Tighe
Journal: BMJ (1975)

but the effect on glucose metabolismn of severe intoxication has not been reported.In rodents glucose appears to enhance the toxic effects of fenfluramine, which suggests that it is unlikely to have a therapeutic role in severe intoxication in humans.Although appetite suppressants cost the NHS over £2m in 1973, their efficacy in the long term remains somewhat dubious.Their dangers, however, even when in- dividually wrapped, continue to be demon- strated.
Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial
Authors: P. Gisondi, M. Del Giglio, C. Cotena, G. Girolomoni
Journal: British Journal of Dermatology (2008)

Background Combination treatments may increase efficacy while reducing dosages and side-effects of individual agents. No randomized controlled trials have been published combining biologics with conventional agents for psoriasis. Objectives To investigate the efficacy and safety of the association of acitretin and etanercept in the treatment of moderate to severe chronic plaque psoriasis. Methods A 24-week, randomized, controlled, investigator-blinded pilot trial was conducted. Sixty adult patients with moderate to severe chronic plaque psoriasis were randomized into three groups to receive etanercept 25 mg twice weekly subcutaneously, oral acitretin 0·4 mg kg−1 daily or etanercept 25 mg once weekly plus acitretin 0·4 mg kg−1 daily. The primary end point was a 75% or greater improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 24. Results At week 24, PASI 75 response was achieved by 10 of 22 patients in the etanercept group (45%), six of 20 in the acitretin group (30%) and eight of 18 (44%) in the group treated with etanercept plus acitretin (P = 0·001 for both etanercept groups compared with acitretin alone). A 50% or greater improvement from baseline in PASI was achieved by 15 of 22 (68%), 10 of 20 (50%) and 12 of 18 (67%) patients, respectively (P = 0·001). The safety profiles of the three groups were similar. Conclusions A combined therapeutic regimen with etanercept 25 mg once weekly and acitretin 0·4 mg kg−1 daily is as effective as etanercept 25 mg twice weekly, and more effective than acitretin alone. Although larger studies are needed to confirm these results, the etanercept/acitretin association could offer several advantages in the therapy of moderate to severe chronic plaque psoriasis.
Public Health Effects of Occupational and Environmental Radiation Exposure
Authors: J. M. Gould
Journal: JAMA (1991)

<h3>To the Editor.</h3> —We have completed a detailed examination of the National Cancer Institute (NCI) cancer mortality data summarized by Jablon et al<sup>1</sup>for each of the 50 civilian power reactors before and after start-up as shown in the Table for the Millstone reactor site in New London, Conn. In two thirds of these reactor sites we found significant increases in the aggregated standardized cancer mortality ratios, as in the case of Millstone, and no significant change in the other sites. This is in direct conflict with their conclusion that "if nuclear facilities posed a risk to neighboring populations, that risk was too small to be detected...." Most of the 50 civilian power reactors began operations in the 1970s and their pre-start-up periods should<i>not</i>include the 1950s. According to recent estimates of the Natural Resources Defense Council, fission products equivalent to 40 000 Hiroshima bombs were released into
An Olfactory Sensory Map Develops in the Absence of Normal Projection Neurons or GABAergic Interneurons
Authors: Alessandro Bulfone, Fan Wang, Robert Hevner, Stewart Anderson, Tyler Cutforth, Sandy Chen, Juanito Meneses, Roger Pedersen, Richard Axel, John L.R Rubenstein
Journal: Neuron (1998)

Olfactory sensory neurons expressing a given odorant receptor project to two topographically fixed glomeruli in the olfactory bulb. We have examined the contribution of different cell types in the olfactory bulb to the establishment of this topographic map. Mice with a homozygous deficiency in Tbr-1 lack most projection neurons, whereas mice with a homozygous deficiency in Dlx-1 and Dlx-2 lack most GABAergic interneurons. Mice bearing a P2-IRES-tau-lacZ allele and deficient in either Tbr-1 or Dlx-1/Dlx-2 reveal the convergence of axons to one medial and one lateral site at positions analogous to those observed in wild-type mice. These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb.
Clonally related follicular lymphomas and histiocytic/dendritic cell sarcomas: evidence for transdifferentiation of the follicular lymphoma clone
Authors: Andrew L. Feldman, Daniel A. Arber, Stefania Pittaluga, Antonio Martinez, Jerome S. Burke, Mark Raffeld, Mireia Camos, Roger Warnke, Elaine S. Jaffe
Journal: Blood (2008)
Possible New Drug for Inflammatory Bowel Disease?
Authors: Peter L. Sosnow
Journal: JAMA (1982)

To the Editor.—  Recent studies 1-3 have suggested that aminosalicylic acid may be as effective as sulfasalazine in the treatment of inflammatory bowel disease. These findings are promising and suggest a new avenue for drug design.  Aminosalicylic acid and sulfapyridine are metabolites of sulfasalazine that are liberated in the colon by bacterial action. Most toxic effects of sulfasalazine appear related to either the parent compound, or even more likely, the sulfapyridine metabolite. 4 Therefore, it would be desirable to use aminosalicylic acid alone. Toxic effects would be reduced, and the drug might be used in higher doses, allowing even greater therapeutic efficacy. However, when aminosalicylic acid is administered orally, most of the drug is absorbed in the proximal intestine and eventually excreted in urine. 5 The drug, therefore, may not reach the colon in the manner made possible by oral administration of sulfasalazine. The studies cited previously in fact used
Abstract 3298: Structure-based computer-aided drug design to discover novel small molecules that target brain tumor stem cells
Authors: Chunyu Gu, Kiran V. Mahasenan, Tyler Auvil, Kaushal Joshi, Snehalata Gupta, Anita Mattson, Cheng Li, Ichiro Nakano
Journal: Cancer Research (2011)

Abstract INTRODUCTION. Malignant glioma is one of the most lethal diseases in adulthood and remains refractory to the current therapies including chemoradiotherapies. The cancer stem cell theory dictates that brain tumor stem-like cells (BTSC) account for such intractability of malignant glioma. Recently, several molecularly-targeted therapies have demonstrated a varying degree of success in treatment of cancers including leukemia and breast cancer. In this study, we sought to determine the key kinases that regulate survival, self-renewal, and proliferation of BTSC, and to design novel small molecules by using the structure-based computantional modeling system. RESULTS. With the neurosphere cultures derived from our glioma patients, we identified 3 kinases that play vital roles in survival and/or proliferation of BTSC in vitro; Fibroblast Growth Factor Receptor 1, Aurora kinase B, and Maternal Embryonic Leucine-zipper Kinase. Structure-based computational modeling allowed us to perform in silico docking of various small molecule candidates to these kinases. As a result, four novel small molecules demonstrated highly specific targeting of the key structural elements of these kinases. We then synthesized these identified candidate compounds and confirmed their in vitro inhibition of the targeting kinase activities. Finally, we will also present our data about the treatment effect with these compounds on the in vitro BTSC growth and the in vivo tumor growth. CONCLUSION. Structure-based drug design will likely open up a new avenue to discover novel anti-cancer stem cell agents that can selectively target the key kinases in BTSC, leading to the growth arrest of malignant glioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3298. doi:10.1158/1538-7445.AM2011-3298
HIV Infection in Women in the United States
Authors: Shannon L. Hader, Dawn K. Smith, Janet S. Moore, Scott D. Holmberg
Journal: JAMA (2001)

During the past decade, knowledge of human immunodeficiency virus (HIV) infection in women has expanded considerably but may not be easily accessible for use in understanding and prioritizing the clinical needs of HIV-infected women.To perform a comprehensive review of epidemiologic, clinical, psychosocial, and behavioral information about HIV in women, and to recommend an agenda for future activities.A computerized search, using MEDLINE and AIDSline, of published literature was conducted; journal articles from January 1981 through July 2000 and scientific conference presentations from January 1999 through July 2000 were retrieved and reviewed for content; article reference lists were used to identify additional articles and presentations of interest.Data from surveillance and prospective cohort studies with at least 20 HIV-infected women and appropriate comparison groups were preferentially included.Included studies of historical importance and subsequent refined analyses of topics covered therein; these and studies with more current data were given preference. Four studies involving fewer than 20 women were included; 2 studies were of men only.Women account for an increasing percentage of all acquired immunodeficiency syndrome (AIDS) cases, from 6.7% (1819/27 140 cases) in 1986 to 18% (119 810/724 656 cases) in 1999. By the end of 1998, of all newly reported AIDS cases among women, proportionally more were in the South (41%), among black women (61%), and from heterosexual transmission (38%). Of note, increasingly more women have no identified or reported risk, about half or more of whom are estimated to be infected heterosexually. It is estimated that a total of at least 54% of women newly reported with AIDS in 1998 acquired HIV through heterosexual sex, including women in the no identified or reported risk category estimated to have been infected heterosexually, meeting the surveillance heterosexual risk definition. Natural history, progression, survival, and HIV-associated illnesses-except for those of the reproductive tract-thus far appear to be similar in HIV-infected women and men. Although antiretroviral therapy has proven to be highly effective in improving HIV-related morbidity and mortality rates, women may be less likely than men to use these therapies. Drug use, high-risk sex behaviors, depression, and unmet social needs interfere with women's use of available HIV prevention and treatment resources.Continued research on HIV pathogenesis and treatment is needed; however, emphasis should also be placed on using existing knowledge to improve the clinical care of women by enhancing use of available services and including greater use of antiretroviral therapy options, treating depression and drug use, facilitating educational efforts, and providing social support for HIV-infected women.
Pulmonary Mycobacterium tuberculosis in acquired immune deficiency syndrome.
Authors: N Doble, P Hykin, R Shaw, E E Keal
Journal: BMJ (1985)

A case of pulmonary infection with Mycobacterium tuberculosis in a patient with the acquired immune deficiency syndrome (AIDS) was studied. Diagnosis of AIDS was confirmed by the finding of pulmonary M tuberculosis with oral and oesophageal candidiasis accompanied by characteristic immunological changes with evidence of infection with human T cell lymphotropic virus III. Treatment of this patient was complicated by an unusual drug interaction between rifampicin and ketoconazole, leading to subtherapeutic serum concentrations and poor clinical response to treatment. Intravenous treatment was more effective than oral treatment. This drug interaction should be studied in greater detail as ketoconazole and rifampicin may be used together to treat patients with candidiasis and infection with M tuberculosis.
Hypertension Experts Recommend New Focus on the Systolic Reading
Authors: Mike Mitka
Journal: JAMA (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
(55) Persistent vaccination granuloma due to aluminium hypersensitivity
Authors: H.A. Fawcett, D. McGibbon, E. Cronin
Journal: British Journal of Dermatology (1985)

Journal Article (55) Persistent vaccination granuloma due to aluminium hypersensitivity Get access H.A. Fawcett, H.A. Fawcett St Thomas's Hospital, London SE1 and St John's Hospital for Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar D. McGibbon, D. McGibbon St Thomas's Hospital, London SE1 and St John's Hospital for Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar E. Cronin E. Cronin St Thomas's Hospital, London SE1 and St John's Hospital for Diseases of the Skin, London WC2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 101–102, https://doi.org/10.1111/j.1365-2133.1985.tb13070.x Published: 01 July 1985
Palestinian man shackled in Jerusalem hospital
Authors: J. Siegel-Itzkovich
Journal: BMJ (1997)

A Palestinian man belonging to the radical organisation Hamas and awaiting trial for acts of terrorism has been shackled to his hospital bed while receiving treatment. The incident has been criticised by human rights organisations and the Israel Medical Association.

Managers at the Hadassah University Hospital in Jerusalem said that, although they were against shackling patients, it had not jeopardised the man's treatment in any way. The 23 year old man, Bassem Ali, from …
Genetic modulation of the cellular antioxidant defense capacity.
Authors: P Amstad, P Cerutti
Journal: Environmental Health Perspectives (1990)

Oxidants are ubiquitous in our aerobic environment. While they are always toxic, they can also exert pathophysiological effects at low concentrations and play an etiological role in human disease. For example, oxidants can stimulate cell growth and act as tumor promoters. The cellular antioxidant defense system attenuates the effect of oxidants and consists of low molecular weight components and several enzymes. Most important are catalase (CAT), superoxide dismutases (SOD), and glutathione peroxidase. We are attempting to elucidate the role of CAT and Cu,Zn-SOD in oxidant tumor promotion of mouse epidermal cells JB6. We have found that the promotable clone 41 possesses 2- to 3-fold higher levels of activity, protein, and stationary mRNA of CAT and Cu,Zn-SOD than does the nonpromotable clone 30. We propose that the growth-stimulatory effect of oxidants is more pronounced in promotable clone 41 because it is better protected from oxidant toxicity. In order to corroborate this model, we have constructed JB6 cells with higher levels of Cu,Zn-SOD and CAT by transfection with expression vectors containing cDNA for these genes. On the other hand, cells with decreased amounts of Cu,Zn-SOD have been obtained by their stable transfection with a vector containing SOD-cDNA in the antisense orientation. These cell clones with modified antioxidant enzyme complements are being characterized. In particular, their promotability by oxidants and their sensitivity to killing and oxidative macromolecular damage are being measured. Certain tumor promoters that lack oxidizing properties may generate a cellular prooxidant state by a variety of mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy and toxicity of a rituximab and methotrexate based regimen (GMALL B‐ALL/NHL 2002 protocol) in Burkitt's and primary mediastinal large B‐cell lymphoma
Authors: Michele Pohlen, Hans U. Gerth, Ruediger Liersch, Steffen Koschmieder, Rolf M. Mesters, Torsten Kessler, Iris Appelmann, Carsten Müller‐Tidow, Wolfgang E. Berdel
Journal: American Journal of Hematology (2011)

There have been several attempts to improve treatment and outcome of patients with primary mediastinal B-cell lymphoma (PMBL) and Burkitt's lymphoma (BL). In recent years, chemotherapy dose intensification and the addition of rituximab have led to a remarkable progress and have developed into integral parts of treatment for both entities of lymphoma [1–4]. Here, we report our monocenter results of a high-dose methotrexate based alternating regimen with rituximab (B-ALL/NHL 2002 protocol) in 15 patients with PMBL and 28 patients with sporadic BL. Since the early 1980s, protocols of GMALL have been continuously adapted and in the meantime they have become reference treatment for BL and B-ALL in Germany. The latest changes comprised the additional use of rituximab, standardized G-CSF support,implementation of high-dose cytarabine, intrathecal triple therapy,and age-adjusted stratification. Furthermore, we additionally amended supportive care with palifermin as it reduced severity and prevalence of mucositis [5].