tbuckley/cabot-search huggingface dataset:
Challenges Facing JAK Inhibitor Therapy for Myeloproliferative Neoplasms
Authors: Ayalew Tefferi
Journal: New England Journal of Medicine (2012)

William Vainchenker discovered the gain-of-function mutation in the gene encoding Janus kinase (JAK) 2 (JAK2 V617F) in early 2004 (reported in 2005)1 and subsequently described its association with BCR-ABL1–negative myeloproliferative neoplasms and its ability to induce erythrocytosis in mice. At that time, many researchers hoped that a specific targeted agent would be developed for these neoplasms, similar to imatinib for chronic myeloid leukemia. This particular prospect was bolstered by the detection of other activating mutations that are relevant to JAK–signal transducer and activator of transcription (STAT) (e.g., MPL W515L and JAK2 K539L) in patients with JAK2 V617F–negative disease. . . .
TREATMENT OF PELLAGRA
Authors: Marvin Sandorf
Journal: JAMA (1935)

<h3>To the Editor:—</h3> InThe Journal, April 20, 1935, page 1377, was an article by Dr. Tom D. Spies on the treatment of pellagra. It is surprising that Dr. Spies made no mention of the achlorhydria or hypochlorhydria that all pellagrins show. In a series of fifty patients from Tennessee and the Carolinas that I have studied it was found that the use of dilute hydrochloric acid in the treatment of pellagra immediately improved the stomatitis and diarrhea that these patients generally show. It has been my opinion that the achlorhydria has a definite pathologic significance and that one must take cognizance of this fact. Dermatitis, diarrhea, stomatitis and nervous symptoms are late manifestations of the disease but an achlorhydric anemia is an early manifestation.
Thyrotoxicosis Presenting As Choreoathetosis
Authors: WARREN HEFFRON
Journal: Annals of Internal Medicine (1970)

Two thyrotoxic patients presented with choreoathetosis. The choreoathetotis was resolved with antithyroid drugs, and one patient rapidly improved with beta blockade. Only one previous case of this association has been reported in the English literature. Our observations suggest that chorea in hyperthyroidism represents a thyroxin-potentiated hyperadrenergic state. The clinical importance of beta blockade in the treatment of thyrotoxicosis is exemplified by these observations.
Through the Vanishing Point: Space in Poetry and Painting
Authors: Charles G. Roland
Journal: JAMA (1969)

It is impossible to assess Marshall McLuhan "correctly." No one, including the swami himself (by his own admission) is sure what he means. Some of his opinions suggest medical implications. If overexposure to TV does numb some of the senses, does this effect have a clinical component? If automobiles<i>are</i>extensions of our limbs, does this sensory reaction relate to the epidemic of highway deaths? In<i>Through the Vanishing Point</i>McLuhan and Parker attempt to describe and illustrate how space is viewed in poetry and painting. Unfortunately the authors choose not to define space, and accept no standard definition. They pair the word with at least a dozen adjectives; we read of "festive space," "single-line space," "Oriental space," and "legally constituted space." The structure of<i>Vanishing Point</i>is simple enough. The authors divide the book into more than 40 sections, each containing a poem, a painting or drawing, and comments
Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas.
Authors: F V Cromme, J Airey, M T Heemels, H L Ploegh, P J Keating, P L Stern, C J Meijer, J M Walboomers
Journal: The Journal of Experimental Medicine (1994)

Malignant tumor cells can escape CD8+ cytotoxic T cell killing by downregulating class I major histocompatibility complex (MHC) expression. Stable class I MHC surface expression requires loading of the heavy chain/light chain dimer with antigenic peptide, which is delivered to class I MHC molecules in the endoplasmic reticulum by the presumed peptide transporter, encoded by the transporter associated with antigen presentation (TAP) 1 and 2 genes. We have investigated whether loss of class I MHC expression frequently observed in different cancers could result from interference with TAP function. A polyclonal antiserum, raised against a bacterial glutathione S-transferase/human TAP-1 fusion protein, was used for the immunohistochemical analysis of TAP-1 expression in 76 cervical carcinomas. Results showed loss of TAP-1 expression in neoplastic cells in 37 out of 76 carcinomas. Immunohistochemical double staining procedures in combination with HLA-specific antibodies revealed congruent loss at the single cell level of TAP-1 and HLA-A/B expression in 28 out of 37 carcinomas. The remaining samples expressed HLA(-A) in the absence of TAP-1 (n = 6) or showed loss of HLA(-A/B) while TAP-1 was expressed (n = 3). These data strongly indicate that inhibition of peptide transport by downregulation of TAP-1 is a potential strategy of malignant cells to evade immune surveillance.
Searching published reports.
Authors: S. Henshaw
Journal: BMJ (1992)

situation.The consumer is reasonably happy with it, it is politically acceptable, and it is probably more equitable.It does, however, mean that we must accept the inevitability of waiting lists as a method of rationing.Well managed waiting lists, for all their prob- lems, are a good method of rationing.They are explicit and can be regulated to ensure that they are equitable.Furthermore, they are reasonably acceptable to the public: far better to be on a waiting list than to be told that an operation on the NHS will never be done under any circumstances.Our view is that economic dogma has held sway for too long in health care.Yet when the hard decisions are being made in health authorities and health boards the dogmatists are nowhere to be seen.We should now formalise the social model of resource allocation along lines that have been suggested previously.'With this method economic appraisal is but one of the four variables-with government priorities, consumer opinion, and formal needs assessment -that determine resource allocation.We would thus ensure that the NHS was, as Smyth puts it, "an element of the national apparatus of justice."
TCTAP C-082 Large Interventricular Septal Hematoma After Retrograde Intervention via the Ipsilateral Intraseptal Collateral for a Chronic Total Occlusion of a Left Anterior Descending Coronary Artery
Authors: Mei-Ling Chen, Sing-Kai Chuo, Ji-Hung Wang
Journal: Journal of the American College of Cardiology (2014)
Depicting second-order isomorphism and “depictive” representations
Authors: Hedy Amiri, Chad J. Marsolek
Journal: Behavioral and Brain Sciences (2002)

According to Pylyshyn, depictive representations can be explanatory only if a certain kind of first-order isomorphism exists between the mental representations and real-world displays. What about a system with second-order isomorphism (similarities between different mental representations corresponding with similarities between different real-world displays)? Such a system may help to address whether “depictive” representations contribute to the visual nature of imagery.
Clinton's plan will cost more, not less, says Congress
Authors: J Roberts
Journal: BMJ (1994)

President Clinton's promise to provide health care for all Americans but still trim $59bn ( £39bn) from the federal budget deficit by 2000 cannot be done, said Congress auditors last week. The health care plan would actually add $74bn ( £49bn) to the budget, said the report from the congressional budget office.

Republicans were keen to go on …
Mutations in <i>HFM1</i> in Recessive Primary Ovarian Insufficiency
Authors: Jian Wang, Wenxiang Zhang, Hong Jiang, Bai-Lin Wu
Journal: New England Journal of Medicine (2014)

To the Editor: Nonsyndromic primary ovarian insufficiency, which is characterized by amenorrhea with elevated gonadotropin levels, is observed in 1% of otherwise healthy women under the age of 40 years. It is a heterogeneous disease, and most cases appear to be sporadic, yet familial cases are observed in approximately 12% of patients. The disorder is believed to have a strong genetic component, but the underlying cause remains unknown in the majority of patients.1,2 Although there is no direct evidence that meiotic gene expression is involved in this disorder, several meiotic-gene knockout mice have had phenotypes resembling human primary ovarian . . .
USE OF WARFARIN THERAPY AND RISK STRATIFICATION TOOLS FOR ATRIAL FIBRILLATION PATIENTS
Authors: Julia Winfield, Geoffrey D. Barnes, Scott Kaatz, Xiaokui Gu, Eva Kline-Rogers, Jay Kozlowski, Leaden Hickman, Thomas Leyden, Dennis Besley, Brian Haymart, Adam Leidal, Allison Theurer, James B. Froehlich
Journal: Journal of the American College of Cardiology (2011)
Book Review Cholera, Chloroform, and the Science of Medicine: A Life of John Snow By Peter Vinten-Johansen, Howard Brody, Nigel Paneth, Stephen Rachman, and Michael Rip, with the assistance of David Zuck. 437 pp., illustrated. New York, Oxford University Press, 2003. $49.95. 0-19-513544-X
Authors: Stephanie J. Snow
Journal: New England Journal of Medicine (2003)
Correlations Between Fasting Plasma C-Peptide, Glucagon-Stimulated Plasma C-Peptide, and Urinary C-Peptide in Insulin-Treated Diabetics
Authors: Hans J Gjessing, Lars E Matzen, Anders Frøland, Ole K Faber
Journal: Diabetes Care (1987)

This study correlated fasting plasma C-peptide (CP), plasma CP 6 min after stimulation with 1 mg glucagon i.v., and the mean of three 24-h urinary excretions of C-peptide (UCP)/creatinine in 132 insulin-treated diabetics. Patients were divided into three groups: group 1, stimulated CP &amp;lt; 0.06 nM (n = 51); group 2, stimulated CP 0.067−0.60 nM (n = 48); and group 3, stimulated CP &amp;gt; 0.60 nM (n = 33). In all patients fasting CP was closely correlated to stimulated CP (r = .988, P &amp;lt; .001), whereas the correlations between UCP and both fasting CP (r = .904, P &amp;lt; .001) and stimulated CP r = .902, P &amp;lt; .001) were slightly less pronounced. The associations between UCP and both fasting CP (r = .716, P &amp;lt; .001) and stimulated CP (r = .731, P &amp;lt; .001) were modest in group 2, and even more so in group 3 (r = .557, P &amp;lt; .001 and r = .641, P &amp;lt; .001, respectively). In conclusion, fasting CP is closely correlated to glucagon-stimulated CP in insulin-treated diabetics and can probably be used equally well in the assessment of β-cell function. The associations between UCP and both fasting and glucagon-stimulated CP are less pronounced, especially in patients with well-preserved β-cell function.
A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia.
Authors: E J Brown, S W Hosea, C H Hammer, C G Burch, M M Frank
Journal: Journal of Clinical Investigation (1982)

The mechanism of protection of type-specific antipneumococcal antibody and complement in bacteremia was investigated with purified rabbit antibody and a guinea pig model of pneumococcal bacteremia. IgG and IgM were isolated from the sera of rabbits immunized with type 7 pneumococci (Pn), and their binding to Pn was quantitated. The number of antibody-binding sites on the pnuemococcal capsule was also determined. Pn were incubated with various amounts of the immunoglobulin preparations before intravenous injection into nonimmune guinea pigs. Whereas 120 molecules of IgM per Pn were sufficient to enhance bloodstream clearance of Pn, 1,400 molecules of IgG per bacterium were required to produce this effect. As the amount of either IgG or IgM added to the Pn was increased, the rate of bloodstream clearance accelerated. In striking contrast, greater than 1,000 molecules of IgM had no effect on the rate of clearance in C4-deficient guinea pigs, which cannot activate complement via the classic pathway. Similarly, 5,000 molecules of IgG had only minimal effect in C4-deficient guinea pigs, and 24,000 molecules of IgG had no effect in guinea pigs depleted of complement by cobra venom factor. Thus, the in vivo opsonic effects of both IgG and IgM anticapsular antibody are mediated via their ability to activate complement. IgG anti-pneumococcal cell wall antibody, raised by intravenous injection of rabbits with unencapsulated Pn, had no effect on the rate of bloodstream clearance of Pn or on the polymorphonuclear leukocyte killing of type 7 Pn in an in vitro bacterial assay. Because the opsonic effects of anticapsular antibody required complement activation, the ability of anticell wall IgG to activate complement was compared with the two classes of anticapsular antibody. As judged by depletion of C3 and C4 from guinea pig serum, as well as by the fixation of radiolabeled C3 to Pn, IgM anticapsular antibody was the best complement activator. However, anticell wall IgG was somewhat more active than anticapsular IgG in each of these tests of complement activation and fixation. When equivalent amounts of C3 were fixed to Pn by each of the three antibodies, Pn sensitized with IgG and IgM anticapsular antibodies caused immune adherence, whereas Pn sensitized with anticell wall IgG did not. This may explain the failure of anticell wall antibody of mediate complement-dependent phagocytosis of Pn in vivo or in vitro. Although anticell wall IgG is capable of activating complement and fixing C3 to Pn, it is not opsonic; the most likely reason is that the nonopsonic antibody mediates C3 deposition in sites on the Pn that cannot interact efficiently with phagocytic cell C3 receptors.
Where does perception end and when does action start?
Authors: Dennis J. McFarland
Journal: Behavioral and Brain Sciences (2002)

Currently there is considerable interest in the notion that dorsal and ventral visual systems might differ in their specializations for thought and action. Behavior invariably involves multiple processes such as perception, judgment, and response execution. It is not clear that characteristics of the dorsal and ventral processing streams, as described by Norman, are entirely of a perceptual nature.
Abstract P3-10-24: Fibroblast Growth Factor Receptor 1 Amplification and Overexpression in Breast Cancer Tissue Microarrays Using Chromogenic In Situ Hybridization and Immunohistochemistry
Authors: P Nuciforo, T Burzykowski, C Lambertini, H Gardner, WH Liu, B Lee, P Barzaghi-Rinaudo, J Rheinhardt, C Barrett, R Linnartz, M Dugan, W Hackl, W Eiermann, T Pienkowski, J Crown, N Robert, M Pawlicki, M Martin, R Finn, M-A Lindsay, D Slamon, M Press
Journal: Cancer Research (2010)

Abstract Fibroblast growth factor receptors 1 (FGFR1) belongs to a subfamily of receptor tyrosine kinases (RTKs), which are involved in proliferation and apoptosis. FGFR1 amplification and mRNA overexpression occurs in ∼10% of breast cancers and has been associated with poor outcome. However, studies assessing FGFR1 amplification and protein overexpression in a large collection of breast tumors are lacking. In this prospective, we examined a series of primary breast cancers samples derived from the BCIRG trials assembled into 15 tissue microarrays. FGFR1 gene amplification was studied using chromogenic in situ hybridization (CISH) and evaluated with respect to association with level of protein expression and clinicopathological parameters. FGFR1 gene amplification was significantly associated with high protein levels as determined by immunohistochemistry (P&amp;lt;0.0001, 3294 pts with available matched CISH and IHC records). Overall, the incidence of FGFR1 amplification found was 9.7% (160 out of 1646 pts. with available clinicopathological records) without a statistically significant difference between Her2- (78 out 720 pts., 11%) and Her2+ (82 out of 926 pts., 9%) cancers. In both cohorts, the hormone receptor-positive (ER+/PR+) cancers showed statistically significant higher levels of FGFR1 amplification compared to hormone receptor-negative tumors. In the analysis of the association of FGFR1 and the presence of PIK3CA mutations, the incidence of FGFR1 amplificationwas greatly reduced in mutant vs. wt PI3KCA tumors. In these cohorts, a clear relationship between FGFR1 amplification status and clinical outcome was not detected. Data from this large study confirms recently reported incidences of FGFR1 amplification in breast cancer and shows for the first time an association between FGFR1 gene amplification and protein overexpression. Moreover, the lower incidence of FGFR1 amplification in PIK3CA mutated cancers suggests that these are largely exclusive molecular events that could benefit from different targeted therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-24.
Benign rheumatoid nodules in a woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy.
Authors: P R Cohen, R Kurzrock
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To report benign rheumatoid nodules in a woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy and to summarise the features of the patients with adult onset benign rheumatoid nodules. METHODS--A 66 year old woman with chronic lymphocytic leukaemia and borderline lepromatous leprosy who presented with subcutaneous elbow nodules, which were at first suspected to represent either progression of her haematological disease or leprosy, is described. The clinical characteristics of our patient and previous reports of another 24 subjects with adult onset benign rheumatoid nodules are reviewed. RESULTS--Biopsy of the patient9s subcutaneous lesion disclosed the histopathology of a rheumatoid nodule; serological and clinical evaluations for rheumatoid arthritis and other rheumatoid nodule associated systemic diseases were negative. Adult onset benign rheumatoid nodules are clinically and histologically identical to those found in patients with rheumatoid arthritis. They often appeared in women during their 20s, frequently resolved spontaneously or were adequately treated by excision, and recurred in about one third of patients. The lesions were located in the ocular adnexa in 60% of patients. The most common lesional sites in patients with non-ocular benign rheumatoid nodules were the elbows, feet, and knees. None of these patients subsequently developed rheumatoid arthritis or other rheumatoid nodule associated diseases during follow up periods of as long as 20 years. CONCLUSION--The appearance of subcutaneous nodules is often the harbinger of an associated systemic disorder. Although benign rheumatoid nodules occur infrequently in adults, they should be considered in the differential diagnosis of new nodular lesions.
Three-Dimensional Reconstruction of the Color Doppler–Imaged Vena Contracta for Quantifying Aortic Regurgitation
Authors: Yoshiki Mori, Takahiro Shiota, Michael Jones, Suthep Wanitkun, Timothy Irvine, Xiaokui Li, Alain Delabays, Natesa G. Pandian, David J. Sahn
Journal: Circulation (1999)

The purpose of this study was to investigate the use of 3-dimensional (3D) reconstruction of color Doppler flow maps to image and extract the vena contracta cross-sectional area to determine the severity of aortic regurgitation (AR) in an animal model. Evaluation of the vena contracta with 2-dimensional imaging systems may not be sufficiently robust to fully characterize this region, which may be asymmetrically shaped.In 6 sheep with surgically induced chronic AR, 18 hemodynamically different states were studied. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary electromagnetic flowmeters (EMFs) as reference standards, and aortic regurgitant effective orifice areas (EOAs) were determined from EMF regurgitant flow rates divided by continuous-wave (CW) Doppler velocities. Composite video data for color Doppler imaging of the aortic regurgitant flows were transferred into a TomTec computer after computer-controlled 180 degrees rotational acquisition. After the 3D data transverse to the flow jet were sectioned, the smallest proximal jet cross section was identified for direct measurement of the vena contracta area. Peak regurgitant flow rates and regurgitant stroke volumes were calculated as the product of these areas and the CW Doppler peak velocities and velocity-time integrals, respectively. There was an excellent correlation between the 3D-derived vena contracta areas and reference EOAs (r=0.99, SEE=0.01 cm2) and between 3D and reference peak regurgitant flow rates and regurgitant stroke volumes (r=0.99, difference=0.11 L/min; r=0.99, difference=1.5 mL/beat, respectively).3D-based determination of the vena contracta cross-sectional area can provide accurate quantification of the severity of AR.
Chronic Kidney Disease—A Challenge for All Ages
Authors: Ian H. de Boer
Journal: JAMA (2012)

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
Standardization of House Dust Mite Extracts Liberation of Allergenic and Antigenic Components in Relation to Extraction Conditions
Authors: H. F. Kauffman, S. van der Heide, H. Hovenga, K. de Vries
Journal: Allergy (1985)

The spontaneous release of house dust mite components from cultures of Dermatophagoides pteronyssinus into slightly buffered water was studied against time, using both continuous and discontinuous extraction procedures. It was shown that proteins, carbohydrates, IgE binding components and precipitating antigenic components were rapidly released from the house dust mite cultures, reaching a maximal liberation within 1 h of extraction. Repeated extractions of house dust mite cultures (discontinuous extraction) showed an additional release of IgE components but the IgE binding potency declined after successive extractions, while showing increasing release of immunological inactive components. IgE binding to antigens immobilized to polystyrene surfaces (IgE-ELISA) appeared to be less sensitive compared with cyanogen-bromide activated discs (IgE-RAST). It was concluded that extraction procedures of house dust mite cultures with short incubation time of 1 h or less are to be preferred.