tbuckley/cabot-search huggingface dataset:
Induction of Anti-Glioma Natural Killer Cell Response following Multiple Low-Dose Intracerebral CpG Therapy
Authors: Darya Alizadeh, Leying Zhang, Christine E. Brown, Omar Farrukh, Michael C. Jensen, Behnam Badie
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Stimulation of toll-like receptor-9 by CpG oligodeoxynucleotides (CpG-ODN) has been shown to counteract the immunosuppressive microenvironment and to inhibit tumor growth in glioma models. These studies, however, have used high doses of CpG-ODN, which can induce toxicity in a clinical setting. The goal of this study was to evaluate the antitumor efficacy of multiple low-dose intratumoral CpG-ODN in a glioma model. Experimental Design: Mice bearing 4-day-old intracranial GL261 gliomas received a single or multiple (two or four) intratumoral injections of CpG-ODN (3 μg) every 4 days. Tumor growth was measured by bioluminescent imaging, brain histology, and animal survival. Flow cytometry and cytotoxicity assays were used to assess anti-glioma immune response. Results: Two and four intracranial injections of low-dose CpG-ODN, but not a single injection, eradicated gliomas in 70% of mice. Moreover, surviving animals exhibited durable tumor-free remission (&amp;gt; 3 months) and were protected from intracranial rechallenge with GL261 gliomas, showing the capacity for long-term antitumor immunity. Although most inflammatory cells seemed to increase, activated natural killer (NK) cells (i.e., NK+CD107a+) were more frequent than CD8+CD107a+ in the brains of rechallenged CpG-ODN–treated animals and showed a stronger in vitro cytotoxicity against GL261 target cells. Leukocyte depletion studies confirmed that NK cells played an important role in the initial CpG-ODN antitumor response, but both CD8 and NK cells were equally important in long-term immunity against gliomas. Conclusions: These findings suggest that multiple low-dose intratumoral injections of CpG-ODN can eradicate intracranial gliomas possibly through mechanisms involving NK-mediated effector function. Clin Cancer Res; 16(13); 3399–408. ©2010 AACR.
Step-up therapy remains an appropriate option
Authors: Duncan R Porter
Journal: Annals of the Rheumatic Diseases (2013)

I congratulate the research team from Rotterdam for the high-quality study design of the treatment in the Rotterdam Early Arthritis Cohort (tREACH) study, but their conclusions are overstated.1 Their quotation of the literature is incomplete, referring to some studies of initial combination disease-modifying antirheumatic drugs (DMARDs) plus corticosteroid (BeSt, FinRACo, COBRA trial) but excluding some other studies that do not support their conclusions. There have been two previously published randomised controlled trials comparing the step-up and initial combination triple DMARD therapy, which show no sustained benefit of the initial …
Derivation of Transplantable 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Chicken Fibrosarcoma Lines: Differences in Metastasizing Properties and Organ Specificity&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J E Galton, B Xue, G M Hochwald, G J Thorbecke
Journal: JNCI Journal of the National Cancer Institute (1982)

Several transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. Striking similarities as well as differences were found between tumor lines' ability to grow in various organs. Artificial metastases were seen primarily in the stomach, pancreas, lungs, heart, and muscle, and occasionally also in the kidneys and in the liver. Agammaglobulinemic recipients showed more extensive organ involvement than normal recipients of the same age. Whole-body γ-irradiation also enhanced the incidence of artificial metastases, particularly in lungs. Antibody from the serum of a primary tumor-bearing host reduced the growth of the corresponding tumor in many organs. The metastatic pattern of line CHCT-NYU4 was a relatively stable property, since there was little difference in the internal localization of these tumor cells studied before and after 15 serial subcutaneous transplants. However, intravenous transplantation of tumor cells from line CHCT-NYU4 taken from the liver, lungs, and pancreas of a single recipient established sublines with changes in organ specificity. After a few such serial transplants of liver-derived tumor, a line was derived that grew virtually in the liver alone. A subline with preference for growth in lungs was also obtained, but its ability to grow in the pancreas persisted. A pancreas-derived tumor line also grew in the liver and lungs. Subcutaneous transplants of tissue fragments of the lung-derived tumor line caused the appearance of spontaneous metastases in lungs. The incidence of spontaneous metastases with the lung-derived line was much greater than that with the liver-derived line or with the original CHCT-NYU4 line.
Streptococcus milleri pulmonary disease: a review and clinical description of 25 patients.
Authors: C A Wong, F Donald, J T Macfarlane
Journal: Thorax (1995)

BACKGROUND--Streptococcus milleri is increasingly being recognised as an important pulmonary pathogen which may lead to the development of empyema or lung abscess. Although several small series have been reported, the clinical and laboratory features have yet to be fully characterised. METHODS--Twenty five cases were identified and the clinical and laboratory data from case records were analysed. RESULTS--There were 16 empyemas, five lung abscesses, and four with both lung abscess and empyema. The mean age of the patients was 61 years (range 36-89) and 84% were men. The most common symptoms at presentation were shortness of breath, chest pain, cough, and weight loss; only 36% had a fever. Four of the nine patients with lung abscess required a diagnostic lobectomy because of suspected malignancy. Predisposing factors were present in 80% of patients and included the following: pneumonia, periodontal disease, excess alcohol intake, previous thoracic surgical procedures, and malignancy. Laboratory features of S milleri infection were leucocytosis, neutrophilia, anaemia, abnormal liver function tests, and hypoalbuminaemia. In the group with empyema five patients had a pneumothorax on initial presentation and pleural loculation occurred in 10 of these patients. The median stay in hospital was 34 days (range 11-88). Six patients died, five of whom had significant underlying illnesses. CONCLUSIONS--Pulmonary infection with S milleri may result in considerable morbidity and mortality, and is characterised by a strong male predominance, non-specific symptoms (often without toxicity), the presence of predisposing factors, pleural loculation, pneumothorax, and a protracted stay in hospital.
The Generalist Role of Specialty Physicians
Authors: Roger A. Rosenblatt, L. Gary Hart, Laura-Mae Baldwin, Leighton Chan, Ronald Schneeweiss
Journal: JAMA (1998)

Context.-Despite increased emphasis on primary care in the United States, most care continues to be provided by specialists.The extent to which specialists incorporate elements of primary care in their approach to ambulatory patients is unknown.Objectives.-To examine the extent to which selected medical and surgical subspecialties provide generalist care to Medicare patients, and to compare patterns of care between specialists and generalists.Design.-A cross-sectional study of all ambulatory care recorded in Part B of the Washington State Medicare Claims Database in 1994 and 1995.Setting.-Ambulatory practices in Washington State.Patients.-Medicarebeneficiaries 65 years or older who made office visits to the study physicians.Main Outcome Measures.-Theextent to which individual specialties accounted for the majority of visits made by patients to physicians (a measure of continuity), provided care outside the traditional domain of their specialty (a measure of comprehensiveness), and provided influenza immunization.Results.-A total of 373 505 patients constituted the sample.Patients had an average of 7.48 outpatient visits per year; 9.6% saw only generalists, while 14.7% saw only specialists.The practices of general internists and family physicians differ systematically from the practices of most specialists.Approximately half (49.8%) of all ambulatory visits to general internists and family physicians are made by patients for whom they provide the majority of outpatient care, compared with 21.0% of medical specialist and 11.7% of surgical specialist visits.The rate of influenza immunization was 55.4% for patients who received the majority of their care from generalists, 47.7% from medical specialists, and 39.6% from surgical specialists.Pulmonologists, general surgeons, and gynecologists were more likely than other specialists to provide services outside their specialty.Conclusions.-Mostspecialists do not assume the principal care responsibility for elderly patients, although a substantial proportion of patients see only specialists for their care.Selected specialties assume the generalist role more often, particularly when they provide the majority of outpatient care for an individual patient.
CREB regulation of nucleus accumbens excitability mediates social isolation–induced behavioral deficits
Authors: Deanna L Wallace, Ming-Hu Han, Danielle L Graham, Thomas A Green, Vincent Vialou, Sergio D Iñiguez, Jun-Li Cao, Anne Kirk, Sumana Chakravarty, Arvind Kumar, Vaishnav Krishnan, Rachael L Neve, Don C Cooper, Carlos A Bolaños, Michel Barrot, Colleen A McClung, Eric J Nestler
Journal: Nature Neuroscience (2009)
Baum's Textbook of Pulmonary Diseases
Authors: S. Alam
Journal: JAMA (2004)

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
Molecular Basis of Asbestos-Induced Lung Disease
Authors: Gang Liu, Paul Cheresh, David W. Kamp
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking.
Hyperimmune serum from healthy vaccinated individuals for Ebola virus disease?
Authors: Raquel Almansa, Jose Maria Eiros, David Fedson, Jesus F Bermejo-Martin
Journal: The Lancet Global Health (2014)

As highlighted by Rajesh Gupta (October issue),1Gupta R Rethinking the development of Ebola treatments.Lancet Glob Health. 2014; 2: e563-e564Summary Full Text Full Text PDF Scopus (9) Google Scholar strategies for developing treatments for Ebola virus disease (EVD) need to be rethought. New treatments have to be safe and effective, and in this sense testing already-approved drugs for a new indication is a good approach. With the same philosophy in mind, there are old approaches that could be saving lives in the current outbreak of EVD. Hyperimmune serum from convalescent patients is regarded by WHO as a potential treatment for EVD.2WHO Blood Regulators NetworkPosition paper on collection and use of convalescent plasma or serum as an element in filovirus outbreak response.http://www.who.int/bloodproducts/brn/brn_positionpaperconvplasmafiloviruses_finalweb14august2014.pdfGoogle Scholar The rationale for convalescent serum treatment is provided by limited experiences during the Ebola outbreak in the Democratic Republic of Congo in 19953Mupapa K Massamba M Kibadi K et al.Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients.J Infect Dis. 1999; 179: S18-S23Crossref PubMed Scopus (366) Google Scholar and also from tests in non-human primates.4Dye JM Herbert AS Kuehne AI et al.Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease.Proc Natl Acad Sci USA. 2012; 109: 5034-5039Crossref PubMed Scopus (231) Google Scholar Additionally, convalescent serum has been used in Spain and other countries to treat patients with EVD during the current outbreak. Nonetheless, obtaining convalescent serum is a difficult task and not free of risk. The logistics of identifying survivors is not easy. Also, blood from survivors needs to be tested to rule out presence of virus. Vaccinated individuals might represent a safer source of hyperimmune serum. Two vaccine candidates will be tested soon in west Africa.5Cohen J Ebola vaccines racing forward at record pace.Science. 2014; 345: 1228-1229Crossref PubMed Scopus (17) Google Scholar If serum from vaccinated individuals has neutralising activity against the virus in cell models, this serum could be used as adjuvant therapy for EVD. In parallel, animal models could be developed to compare hyperimmune serum against a placebo. In the current scenario, this strategy could offer some hope to patients with this devastating disease. We declare no competing interests.
Acute hepatitis C infection after sexual exposure.
Authors: C J Healey, D B Smith, J L Walker, E C Holmes, K A Fleming, R W Chapman, P Simmonds
Journal: Gut (1995)

A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two.
Endovascular Treatment for Acute Ischemic Stroke
Authors: Alfonso Ciccone, Luca Valvassori, Michele Nichelatti, Annalisa Sgoifo, Michela Ponzio, Roberto Sterzi, Edoardo Boccardi
Journal: New England Journal of Medicine (2013)

In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed.
Genome Evolution of Wolbachia Strain wPip from the Culex pipiens Group
Authors: L. Klasson, T. Walker, M. Sebaihia, M. J. Sanders, M. A. Quail, A. Lord, S. Sanders, J. Earl, S. L. O'Neill, N. Thomson, S. P. Sinkins, J. Parkhill
Journal: Molecular Biology and Evolution (2008)

The obligate intracellular bacterium Wolbachia pipientis strain wPip induces cytoplasmic incompatibility (CI), patterns of crossing sterility, in the Culex pipiens group of mosquitoes. The complete sequence is presented of the 1.48-Mbp genome of wPip which encodes 1386 coding sequences (CDSs), representing the first genome sequence of a B-supergroup Wolbachia. Comparisons were made with the smaller genomes of Wolbachia strains wMel of Drosophila melanogaster, an A-supergroup Wolbachia that is also a CI inducer, and wBm, a mutualist of Brugia malayi nematodes that belongs to the D-supergroup of Wolbachia. Despite extensive gene order rearrangement, a core set of Wolbachia genes shared between the 3 genomes can be identified and contrasts with a flexible gene pool where rapid evolution has taken place. There are much more extensive prophage and ankyrin repeat encoding (ANK) gene components of the wPip genome compared with wMel and wBm, and both are likely to be of considerable importance in wPip biology. Five WO-B–like prophage regions are present and contain some genes that are identical or highly similar in multiple prophage copies, whereas other genes are unique, and it is likely that extensive recombination, duplication, and insertion have occurred between copies. A much larger number of genes encode ankyrin repeat (ANK) proteins in wPip, with 60 present compared with 23 in wMel, many of which are within or close to the prophage regions. It is likely that this pattern is partly a result of expansions in the wPip lineage, due for example to gene duplication, but their presence is in some cases more ancient. The wPip genome underlines the considerable evolutionary flexibility of Wolbachia, providing clear evidence for the rapid evolution of ANK-encoding genes and of prophage regions. This host–Wolbachia system, with its complex patterns of sterility induced between populations, now provides an excellent model for unraveling the molecular systems underlying host reproductive manipulation.
The Role of Physician Specialty Board Certification Status in the Quality Movement
Authors: Troyen A. Brennan, Ralph I. Horwitz, F. Daniel Duffy, Christine K. Cassel, Leslie D. Goode, Rebecca S. Lipner
Journal: JAMA (2004)

The Institute of Medicine's reports and discussions on quality of medical care have focused on a systems-based approach to quality improvement. Our objective is to summarize evidence and theory about the role of a physician's current board certification status in quality improvement. The first body of evidence includes the validity of board certification demonstrated by the testing process, the relationship of examination scores with other measures of physician competence, and the relationship between certification status and clinical outcomes. The second body of evidence involves the adaptation of error prevention theory to medical care. Patient safety is enhanced when problem-solving uses readily accessed habits of behavior, the same behavior necessary to achieve board certification. The third body of evidence, obtained through a Gallup poll, demonstrates that certification and maintenance of certification are highly valued by the public. The majority of respondents thought it important for physicians to be reevaluated on their qualifications every few years and that physicians should do more to demonstrate ongoing competence than is currently required by the profession. We conclude that a physician's current certification status should be among the evidence-based measures used in the quality movement.
BluepRINT for Moderate-to-Low Penetrance Cancer Susceptibility Genes Needed: Breast Cancer and Beyond
Authors: Joanne Ngeow, Charis Eng
Journal: Cancer Discovery (2014)

Abstract Summary:RINT1 is a novel moderately penetrant cancer susceptibility gene seen in breast cancer as well as possibly in Lynch syndrome–related cancers. Cancer Discov; 4(7); 762–3. ©2014 AACR. See related article by Park et al., p. 804
The Differential Staurosporine-Mediated G1 Arrest in Normal versus Tumor Cells Is Dependent on the Retinoblastoma Protein
Authors: Mollianne McGahren-Murray, Nicholas H.A. Terry, Khandan Keyomarsi
Journal: Cancer Research (2006)

Abstract Previously, we reported that breast cancer cells with retinoblastoma (pRb) pathway–defective checkpoints can be specifically targeted with chemotherapeutic agents, following staurosporine-mediated reversible growth inhibition in normal cells. Here we set out to determine if the kinetics of staurosporine-mediated growth inhibition is specifically targeted to the G1 phase of cells, and if such G1 arrest requires the activity of wild-type pRb. Normal human mammary epithelial and immortalized cells with intact pRb treated with low concentrations of staurosporine arrested in the G1 phase of the cell cycle, whereas pRb-defective cells showed no response. The duration of G1 and transition from G1 to S phase entry were modulated by staurosporine in Rb-intact cells. In pRb+ cells, but not in Rb− cells, low concentrations of staurosporine also resulted in a significant decrease in cyclin-dependent kinase 4 (CDK4) expression and activity. To directly assess the role of pRb in staurosporine-mediated G1 arrest, we subjected wild-type (Rb+/+) and pRb−/− mouse embryo fibroblasts (MEFs) to staurosporine treatments. Our results show that whereas Rb+/+ MEFs were particularly sensitive to G1 arrest mediated by staurosporine, pRb−/− cells were refractory to such treatment. Additionally, CDK4 expression was also inhibited in response to staurosporine only in Rb+/+ MEFs. These results were recapitulated in breast cancer cells treated with siRNA to pRb to down-regulate the pRb expression. Collectively, our data suggest that treatment of cells with nanomolar concentrations of staurosporine resulted in down-regulation of CDK4, which ultimately leads to G1 arrest in normal human mammary epithelial and immortalized cells with an intact pRb pathway, but not in pRb-null/defective cells. (Cancer Res 2006; 66(19): 9744-53)
Surrogate End Points, Health Outcomes, and the Drug-Approval Process for the Treatment of Risk Factors for Cardiovascular Disease
Authors: Bruce M. Psaty
Journal: JAMA (1999)

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