tbuckley/cabot-search huggingface dataset:
EVIDENCE FOR A BLOOD-THYMUS BARRIER USING ELECTRON-OPAQUE TRACERS
Authors: Elio Raviola, Morris J. Karnovsky
Journal: The Journal of Experimental Medicine (1972)

In order to verify the existence of a blood-thymus barrier to circulating macromolecules, the permeability of the vessels of the thymus was analyzed in young adult mice using electron opaque tracers of different molecular dimensions (horseradish peroxidase, cytochrome c, catalase, ferritin, colloidal lanthanum). Results show that although blood-borne macromolecules do penetrate the thymus, their parenchyma] distribution is limited to the medulla of the lobe by several factors: (a) the differential permeability of the various segments of the vascular tree; (b) the spatial segregation of these segments within the lobe; (c) the strategic location of parenchymal macrophages along the vessels. The cortex is exclusively supplied by capillaries, which have impermeable endothelial junctions. Although a small amount of tracer is transported by plasmalemmal vesicles through the capillary endothelium, this tracer is promptly sequestrated by macrophages stretched out in a continuous row along the cortical capillaries and it does not reach the intercellular clefts between cortical lymphocytes and reticular cells. The medulla contains all the leaky vessels, namely postcapillary venules and arterioles. Across the walls of the venules, large quantities of all injected tracers escape through the clefts between migrating lymphocytes and endothelial cells; also the arterioles have a small number of endothelial junctions which are permeable to peroxidase, but do not allow passage of tracers of higher molecular weight. The tracers released by the leaky vessels penetrate the intercellular clefts of the medulla, but they never reach the cortical parenchyma, even at long time intervals after the injection. Therefore, a blood-thymus barrier to circulating macromolecules does exist, but is limited to the cortex. Medullary lymphocytes are freely exposed to blood-borne substances.
2 FARNESOID-X RECEPTOR AGONISTS: A NEW CLASS OF DRUGS FOR THE TREATMENT OF PBC? AN INTERNATIONAL STUDY EVALUATING THE ADDITION OF INT-747 TO URSODEOXYCHOLIC ACID
Authors: A. Mason, V. Luketic, K. Lindor, G. Hirschfield, S. Gordon, M. Mayo, K. Kowdley, A. Parés, M. Trauner, E. Castelloe, C. Sciacca, T.B. Jones, O. Böhm, D. Shapiro
Journal: Journal of Hepatology (2010)
Abstract 4696: Identification of driver mutations and gene amplifications in resected asophageal adenocarcinoma: Impact on clinical care
Authors: Haiyu Zhou, Luis Tapias Vargas, Justin Elliot, Douglas J. Mathisen, Michael Lanuti
Journal: Cancer Research (2014)

Abstract BACKGROUND: Adenocarcinoma of the distal esophagus and esophagogastric junction (EGJ) have received much attention because of increasing frequency and poor outcome despite multimodality therapy. Driver mutations and gene amplifications in resected esophageal adenocarcinoma are not widely investigated. Opportunity exists to discover actionable mutations in resected esophageal adenocarcinoma. METHODS: We analyzed driver mutations harbored in coding regions of 25 selected genes (∼95 point mutations) using a multiplex PCR-based assay. EGFR, HER2, MET, and PI3K amplifications were tested using fluorescent in situ hybridization in patients who underwent esophagectomy for distal esophagus and EGJ adenocarcinoma from 2009 to 2013. Disease free survival (DFS) and overall survival (OS) were compared between patients with TP53, KRAS, PI3K, BRAF, APC mutant and wild-type tumors using Kaplan-Meier methods and Cox regression models. The impact of HER2 expression and outcomes were also analyzed. RESULTS: Of 54 distal esophagus and EGJ adenocarcinoma patients, 5 different driver mutations were observed in 39 patients, including TP53 (11/39, 28.2%), KRAS (6/39,15.4%), PI3K (2/11,5.1%), BRAF(1/39, 2.6%) and APC (2/39,5.1%). Double driver mutations (3/39, 7.9%) were shared in 3 patients with TP53 and KRAS (1/39, 2.6%), TP53 and PI3K (1/39, 2.6%), KRAS and PI3K (1/39, 2.6%), respectively. Amplifications in HER2 (10/45, 22.2%), MET (1/34, 2.9%) and EGFR (2/17, 11.8%) were observed where directed therapy was altered in 5 patients (1 patient received induction herceptin and 4 patients received adjuvant herceptin). In the targeted patients with HER2 amplification who received herceptin, mean progression-free survival was 18.8 (range 7-41 months) vs. 8.9 (1-28 months) [p=0.089] and OS was 35.7 (range 26-46 months) vs. 24.2 (range 20-29 months) [p=0.053], compared to herceptin naive patients. We did not identify any significant difference in DFS and OS (inclusive of all stages) between TP53, KRAS or any mutation compared to wild type patients. DISCUSSION: Oncogenic driver mutations are under-investigated in resected distal esophageal and EGJ adenocarcinoma. Different therapeutic opportunities may become available if routine tumor genotyping is employed in the treatment of esophageal adenocarcinoma. We recommend the routine use of driver mutation and gene amplification analysis for esophageal cancer. Citation Format: Haiyu Zhou, Luis Tapias Vargas, Justin Elliot, Douglas J. Mathisen, Michael Lanuti. Identification of driver mutations and gene amplifications in resected asophageal adenocarcinoma: Impact on clinical care. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4696. doi:10.1158/1538-7445.AM2014-4696
New ways to harm doctors
Authors: R.-E. Goetze-Pelka
Journal: BMJ (2010)

Ruta has not thought about the consequences of his suggestions.1 Beerstecher has started to imagine the consequences,2 but they would be far worse.

In Germany all outpatient clinics are managed by self employed physicians, GPs, and consultants, who are paid according to how many patients they treat (with a maximum per patient). Doctors who …
Spontaneous remission of polycythemia vera: Clinical and cell culture characteristics
Authors: D. H. Cowan, H. A. Messner, N. Jamal, M. T. Aye, R. K. Smiley
Journal: American Journal of Hematology (1994)

Abstract A 20‐year‐old woman presented with polycythemia vera and was treated with phlebotomy alone for eleven years, following which all clinical manifestations of the disease disappeared. The clinical remission with normal physical findings and normal peripheral blood counts has persisted for a further 11 years. Erythroid colony culture results have paralleled the clinical state. Initial bone marrow cultures revealed spontaneous growth of erythroid burst‐forming units (BFU‐E). Subsequent cultures of peripheral blood cells throughout most of the period of spontaneous clinical remission have revealed little or no spontaneous growth of BFU‐E. This suggests a suppression of the abnormal stem cell clone during the period of remission. © 1994 Wiley‐Liss, Inc.
Difficult choice of treatment for poorly controlled maturity onset diabetes: tablets or insulin.
Authors: J I Mann, S Lousley, D Peterson
Journal: BMJ (1984)

munity based coronary heart disease prevention programme in the world is a unique develop- ment and the Health Education Council deserves much praise for it.At the outset it was never intended that the council should underwrite the total cost of the programme but rather that it should provide the core funding to which health authorities, the Welsh Office,
Safety and efficacy of intravenous pulse cyclophosphamide in acute steroid refractory inflammatory bowel disease
Authors: A Stallmach
Journal: Gut (2003)

<b>Background and aims:</b> One major problem in the management of steroid refractory attacks of patients with inflammatory bowel disease (IBD) is the establishment of a rapidly acting immunosuppressive regimen. Based on its well known efficacy in systemic vasculitis, intravenous cyclophosphamide pulse therapy was used in refractory IBD patients to evaluate both its efficacy and safety. <b>Methods:</b> Between December 1998 and May 2001, seven patients (Crohn's disease, n=5; indeterminate colitis, n=1) with severe steroid refractory IBD (Crohn's disease activity index (CDAI) 264–479 points) received 4–6 cycles of monthly treatment with intravenous cyclophosphamide (750 mg) in a prospective uncontrolled pilot study. <b>Results:</b> All patients improved after two intravenous pulses of cyclophosphamide and six of seven patients achieved complete remission (CDAI &lt;150 points). One patient with Crohn's disease of the small and large bowel showed an impressive clinical response but did not enter into remission. Tapering to low dose steroids was possible in all responders. Remission was maintained in all patients for 18 months (median) but required a second course of intravenous pulse cyclophosphamide in one patient. The drug was well tolerated except for two episodes of candida oesophagitis. <b>Conclusions:</b> Intravenous pulse cyclophosphamide may be a safe and effective treatment in patients with severe IBD unresponsive to steroid treatment and merits evaluation in a controlled trial.
Insulin Assay Standardization
Authors: Myrlene A. Staten, Michael P. Stern, W. Greg Miller, Michael W. Steffes, Scott E. Campbell
Journal: Diabetes Care (2009)

Diabetes, primarily type 2 diabetes, has increased in prevalence throughout the world and current projections suggest a continued rise worldwide for at least the next quarter century. Insulin resistance, which frequently accompanies obesity, is known to be a key factor in the pathogenic development of type 2 diabetes (1–6). Type 2 diabetes occurs when insulin secretion is no longer sufficient to compensate for the resistance to the actions of insulin.

Measurements of insulin sensitivity and secretion are currently done only for research purposes and are only comparable in individual studies. There are no clinical applications for these measures. In fact, there are no criteria by which an individual could be classified as being insulin sensitive or resistant or as having mild, moderate, or severe impairment of insulin secretion. In theory, one could envision that knowledge of an individual's response to insulin or the ability to secrete insulin might be useful for selecting patients for intensified prevention efforts, in the choice of initial therapy upon onset of overt hyperglycemia, or in evaluating the response to therapy beyond glycemia. For example, if a person newly diagnosed with diabetes could be determined to be very insulin resistant, the choice of initial therapy could be a drug that primarily improves insulin sensitivity. On the other hand, if the person was only moderately insulin resistant but had more of a defect in insulin secretion, a drug that improves insulin secretion might …
Value of adenosine deaminase in the diagnosis of tuberculous pleural effusions in young patients in a region of high prevalence of tuberculosis.
Authors: L Valdes, D Alvarez, E San Jose, J R Juanatey, A Pose, J M Valle, M Salgueiro, J R Suarez
Journal: Thorax (1995)

BACKGROUND--Pleural biopsy is usually considered important for the diagnosis of pleural effusions, especially for distinguishing between tuberculosis and neoplasia, even though tuberculous pleural fluid contains sensitive biochemical markers. In regions with a high prevalence of tuberculosis, and in patient groups with a low risk of other causes of pleurisy, the positive predictive value of these markers is increased. The criteria for performing a pleural biopsy under these circumstances have been investigated, using adenosine deaminase (ADA) as a pleural fluid marker for tuberculosis. METHODS--One hundred and twenty nine patients with a pleural effusion aged &lt; or = 35 years (mean (SD) 25.2 (4.9) years) were studied. Seventy three were men. Eighty one effusions (62.8%) were tuberculous, 12 (9.3%) parapneumonic, and 10 (7.7%) neoplastic, five were caused by pulmonary thromboembolism, four by systemic lupus erythematosus, seven by empyema, three following surgery, one was the result of asbestosis, and one of nephrotic syndrome. In five cases no definitive diagnosis was reached. ADA levels were determined by the method of Galanti and Giusti. RESULTS--The diagnostic yield of procedures not involving biopsy was 94.5% (122/129). Pleural biopsy provided a diagnosis in a further two cases, but not in the remaining five. All tuberculous cases had pleural fluid levels of ADA of &gt; 47 U/l (mean (SD) 111.1 (36.6) U/l). The only other cases in which ADA exceeded this level were six of the seven patients with empyema. Cytological examination of the pleural fluid diagnosed eight of the 10 neoplastic cases, compared with six diagnosed by pleural biopsy. CONCLUSIONS--In a region with a high prevalence of tuberculosis procedures not involving pleural biopsy have a very high diagnostic yield in patients with a pleural effusion aged &lt; or = 35 years, making biopsy necessary only in cases in which pleural levels of ADA are below 47 U/l, pleural fluid cytology is negative and, in the absence of a positive basis for some other diagnosis, neoplasia is suspected.
In praise of clouds
Authors: L. S. King
Journal: JAMA (1970)

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
Viperin restricts chikungunya virus replication and pathology
Authors: Terk-Shin Teng, Suan-Sin Foo, Diane Simamarta, Fok-Moon Lum, Teck-Hui Teo, Aleksei Lulla, Nicholas K.W. Yeo, Esther G.L. Koh, Angela Chow, Yee-Sin Leo, Andres Merits, Keh-Chuang Chin, Lisa F.P. Ng
Journal: Journal of Clinical Investigation (2012)

Chikungunya virus (CHIKV) is a mosquito-borne arthralgia arbovirus that is reemergent in sub-Saharan Africa and Southeast Asia. CHIKV infection has been shown to be self-limiting, but the molecular mechanisms of the innate immune response that control CHIKV replication remain undefined. Here, longitudinal transcriptional analyses of PBMCs from a cohort of CHIKV-infected patients revealed that type I IFNs controlled CHIKV infection via RSAD2 (which encodes viperin), an enigmatic multifunctional IFN-stimulated gene (ISG). Viperin was highly induced in monocytes, the major target cell of CHIKV in blood. Anti-CHIKV functions of viperin were dependent on its localization in the ER, and the N-terminal amphipathic α-helical domain was crucial for its antiviral activity in controlling CHIKV replication. Furthermore, mice lacking Rsad2 had higher viremia and severe joint inflammation compared with wild-type mice. Our data demonstrate that viperin is a critical antiviral host protein that controls CHIKV infection and provide a preclinical basis for the design of effective control strategies against CHIKV and other reemerging arthrogenic alphaviruses.
Irrigation of Renal Pelvis-Reply
Authors: Donald B. Jenny
Journal: JAMA (1979)

An aggressive surgical approach to remove calculi in the kidney and ureter is, in most cases, the usual means by which to manage this problem. Dr Olsson's comments reflect proper present-day urologic protocol, with which we are in total agreement. All aspects of the patient's care, however, could not be discussed because of the space limitation of a case report. In fact, surgery had already been carried out in our patient and had failed, with recurrence of stones and infection. Furthermore, this patient was and is in the final stages of his disease, for which no appropriate therapy has yet been defined. Irrigation of the renal pelvis to attempt stone dissolution was initiated for the following reasons: First, as noted in the case report, bilateral renal disease was present, and further surgery with the possible consequence of a total nephrectomy would have been a hazard to the patient's
Renal Transplants From Cadaver Donors
Authors: Hugh H. Hussey
Journal: JAMA (1975)

An editorial in an earlier issue ofThe Journal(226: 1226, 1973) stated that, in contrast to other organ transplantation procedures, renal transplantation has passed the experimental and entered the therapeutic stage. That same issue carried "The 11th Report of the Human Renal Transplant Registry" (226:1197-1204, 1973) in which cadaver donors had come to comprise 63.4% of renal grafts reported to the registry. That percentage is misleading unless the reader understands that the registry is international. In the United States, cadaver donors provided only 52.6% of grafts whereas in Europe 78.8% and in Australasia 98.3% of renal grafts came from cadavers. In this issue ofThe Journal(p 882), Chatterjee et al describe their experience with efforts to obtain postmortem donor kidneys. During the period April 1973 to April 1974, eight-six patients were referred to the Los Angeles County—University of Southern California Medical Center as potential postmortem kidney donors under
Alternative Strategies for Controlling Rising Cesarean Section Rates
Authors: Randall S. Stafford
Journal: JAMA (1990)

Cesarean section rates in the United States have increased from 5.5% in 1970 to 24.4% in 1987. This dramatic increase has generated considerable concern, leading to a variety of proposals to control rising use of cesarean section. Six strategies have been adopted or proposed to reduce cesarean section use: (1) education and peer evaluation, (2) external review, (3) public dissemination of cesarean section rates, (4) changes in physician payment, (5) changes in hospital payment, and (6) medical malpractice reform. These strategies differ in their specific assumptions regarding the process of clinical decision making, implications for physician autonomy, and methods of implementation. Educational efforts have been the most widely promoted. Of these, formal programs aimed at modifying practices within individual hospitals appear to be the most successful. However, insufficient research has been conducted to compare conclusively the impact and feasibility of these six strategies, pointing to the need for further study. (<i>JAMA</i>. 1990;263:683-687)
Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia
Authors: Majed J. Dasouki, Syed K. Rafi, Adam J. Olm-Shipman, Nathan R. Wilson, Sunil Abhyankar, Brigitte Ganter, L. Mike Furness, Jianwen Fang, Rodrigo T. Calado, Irfan Saadi
Journal: Blood (2013)
DCVax®- DIRECT: autologous activated dendritic cells for image guided intra-tumoral vaccination in patients with solid tumors - a phase I/II clinical trial in progress
Authors: Vivek Subbiah, Ravi Murthy, Chitra Hosing, Indresh Kaur, Gerald Falchook, Marnix Bosch
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Dendritic cells (DC) are acknowledged to be quintessential in the armamentarium to mount anti-tumor immune responses and have been utilized in varying capacities for cancer immunotherapy. Recent advancements & lessons leant from prior DC therapies have revealed that major barriers
Clinical Variations in the Diagnosis of Psittacosis
Authors: Richard H. Seibert, William S. Jordan, John H. Dingle
Journal: New England Journal of Medicine (1956)

SINCE the relaxation of regulations governing the transportation and sale of psittacine birds in December, 1951, there has been a dramatic increase in the number of human infections with psittacosis virus.1 2 3 4 5 Recognition of these infections requires an awareness of the importance of avian contact and knowledge of the clinical characteristics of psittacosis. Excellent summaries of the clinical and epidemiologic features of psittacosis are available in a number of textbooks and articles,6 7 8 so that an extensive review of the disease is unnecessary. Certain problems in diagnosis and treatment, however, deserve continued emphasis.The clinical manifestations of psittacosis are extremely variable. Infection . . .
Pathologic findings related to the lead system and repeated defibrillations in patients with the automatic implantable cardioverter-defibrillator
Authors: Igor Singer, Grover M. Hutchins, M. Mirowski, Morton M. Mower, Enrico P. Veltri, Thomas Guarnieri, Juan Juanteguy, Sara Fisher, Philip R. Reid, Myron L. Weisfeldt
Journal: Journal of the American College of Cardiology (1987)
Transplantation Resistance to a Rous Sarcoma Virus-Induced Tumor in Mice Immunized With v-src Protein1
Authors: N. Kuzumaki, H. Fujita, H. Dosaka, M. Katabami, A. D. Levinson
Journal: JNCI Journal of the National Cancer Institute (1988)

It is of great interest in tumor immunology to know whether oncogene products could be used not only as tumor markers for cancer diagnosis, but also as immunogens for cancer therapy. BALB/c mice immunized with syngeneic fibroblasts, Escherichia coli cells producing p60v-src, or the purified p60v-src protein extracted from the E. coli producer cells showed transplantation resistance to a Rous sarcoma virus-induced tumor but not a Kirsten sarcoma virus-induced tumor. In contrast, mice immunized with cells not producing p60v-src or their derived proteins or with chicken ovalbumin did not show any significant resistance. These findings suggest that p60v-src can act as a specific transplantation rejection antigen in mice. [J Natl Cancer Inst 1988;80:959–962]
The methylenetetrahydrofolate reductase (MTHFR) variant c.677C&gt;T (A222V) influences overall survival of patients with glioblastoma multiforme
Authors: Michael Linnebank, Alexander Semmler, Susanna Moskau, Yvo Smulders, Henk Blom, Matthias Simon
Journal: Neuro-Oncology (2008)

Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults. Prognosis is poor. Using a series of 214 GBM patients, we observed an effect of the variant 5,10-methylenetetrahydrofolate reductase (MTHFR) c.677C>T on overall survival. This effect was strongest in patients younger than 60 years at diagnosis (overall survival, median +/- SE: genotype CC, 13 +/- 1 months; CT, 11 +/- 2 months; TT, 7 +/- 3 months; multivariate Cox regression analysis, Wald = 8.58, p = 0.007). In addition, the MTHFR genotype significantly influenced the overall survival of patients with a postoperative Karnofsky score >70 (CC, 12 +/- 2 months; CT, 11 +/- 1 months; TT, 10 +/- 4 months; Wald = 5.89, p = 0.015). These data suggest the MTHFR c.677C>T variant is a risk factor for survival in GBM patients.