tbuckley/cabot-search huggingface dataset:
The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction.
Authors: W Mourad, P Scholl, A Diaz, R Geha, T Chatila
Journal: The Journal of Experimental Medicine (1989)

The Staphylococcus aureus exotoxin toxic shock syndrome toxin 1 (TSST-1) is a potent activator of T cells and monocytes. We have recently demonstrated that TSST-1 is a superantigen that binds monomorphic determinants on MHC class II molecules. In the present study, we have examined the effect of TSST-1 on the activation and differentiation of high density human tonsillar B cells. TSST-1 bound to tonsilar B cells with high affinity and saturation kinetics. This binding was effectively inhibited by a combination of anti-HLA-DR and anti-HLA-DQ mAbs. Treatment of purified B cells with TSST-1 failed to induce B cell proliferation or Ig production. However, in the presence of irradiated T cells, TSST-1 induced resting B cells to proliferate and differentiate into Ig secretory cells. TSST-1 mimicked nominal antigen in that its induction of B cell responses was strictly dependent on physical contact between T and B cells, and was profoundly inhibited by anti-MHC class II mAbs, anti-CD3 mAbs, and, to a lesser extent, by anti-CD18 mAbs. However, unlike nominal antigen, TSST-1-mediated T/B cell interactions were MHC unrestricted. These results suggest that TSST-1 induces T cell-dependent B cell proliferation and differentiation by virtue of its ability to mediate MHC-unrestricted cognate T/B cell interaction via the TCR/CD3 complex and MHC class II antigens.
SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications
Authors: Christa Nilsson, Brianda Barrios-Lopez, Annukka Kallinen, Pasi Laurinmäki, Sarah J. Butcher, Mari Raki, Janne Weisell, Kim Bergström, Susan Weng Larsen, Jesper Østergaard, Claus Larsen, Arto Urtti, Anu J. Airaksinen, Anan Yaghmur
Journal: Biomaterials (2013)
A Mouse Cytomegalovirus Glycoprotein Retains MHC Class I Complexes in the ERGIC/cis-Golgi Compartments
Authors: Heike Ziegler, Regine Thäle, Pero Lucin, Walter Muranyi, Thomas Flohr, Hartmut Hengel, Helen Farrell, William Rawlinson, Ulrich H. Koszinowski
Journal: Immunity (1997)
Ligation of TLR9 induced on human IL-10–secreting Tregs by 1α,25-dihydroxyvitamin D3 abrogates regulatory function
Authors: Zoë Urry, Emmanuel Xystrakis, David F. Richards, Joanne McDonald, Zahid Sattar, David J. Cousins, Christopher J. Corrigan, Emma Hickman, Zarin Brown, Catherine M. Hawrylowicz
Journal: Journal of Clinical Investigation (2009)

Signaling through the TLR family of molecular pattern recognition receptors has been implicated in the induction of innate and adaptive immune responses. A role for TLR signaling in the maintenance and/or regulation of Treg function has been proposed, however its functional relevance remains unclear. Here we have shown that TLR9 is highly expressed by human Treg secreting the antiinflammatory cytokine IL-10 induced following stimulation of blood and tissue CD3+ T cells in the presence of 1α,25-dihydroxyvitamin D3 (1α25VitD3), the active form of Vitamin D, with or without the glucocorticoid dexamethasone. By contrast, TLR9 was not highly expressed by naturally occurring CD4+CD25+ Treg or by Th1 and Th2 effector cells. Induction of TLR9, but not other TLRs, was IL-10 dependent and primarily regulated by 1α25VitD3 in vitro. Furthermore, ingestion of calcitriol (1α25VitD3) by human volunteers led to an increase of both IL-10 and TLR9 expression by CD3+CD4+ T cells analyzed directly ex vivo. Stimulation of 1α25VitD3-induced IL-10–secreting Treg with TLR9 agonists, CpG oligonucleotides, resulted in decreased IL-10 and IFN-γ synthesis and a concurrent loss of regulatory function, but, unexpectedly, increased IL-4 synthesis. We therefore suggest that TLR9 could be used to monitor and potentially modulate the function of 1α25VitD3-induced IL-10–secreting Treg in vivo, and that this has implications in cancer therapy and vaccine design.
ET-42 * DEVELOPMENT OF A NOVEL, FUNCTION-BLOCKING ANTI-FIBULIN-3 ANTIBODY AS TARGETED REAGENT FOR GLIOBLASTOMA
Authors: M. Nandhu, P. Behera, E. A. Chiocca, M. Viapiano
Journal: Neuro-Oncology (2014)

Fibulin-3 is a protein secreted by glioblastoma (GBM) cells that is virtually absent in normal brain. This protein promotes tumor invasion and, more unusually, apoptotic resistance, by paracrine activation of Notch and NFkB pathways (see companion abstract). Conditional knockdown of fibulin-3 reduces GBM growth, invasion and vascularization, and prolongs survival. Here we report initial validation of biologics generated against this unique target in GBM. We first identified the sequence of fibulin-3 that activates Notch signaling (aa25-47) and developed an immunizing peptide maintaining a required Cys-loop within this sequence. An IgG1k monoclonal antibody generated against this peptide (mAb428.2) showed high affinity for fibulin-3 (Kd 5 nM) and no cross-reactivity against highly homologous fibulin-4 or -5. mAb428.2 detected fibulin-3 in the stroma and capillaries of human GBM without cross-reactivity against normal brain. The antibody (50-250 µg/ml) blocked the activation of Notch and NFkB reporters induced by fibulin-3, and caused significant GBM cell cytotoxicity but had no effects on astrocytes or HEK293 cells, which do not express fibulin-3. IV injection of mAb428.2 (range: 0.1-30 mg/kg, evaluation: 15min to 14 days) did not cause adverse effects and showed no histological findings. Using Alexa750-labeled mAb428.2 (IV) we observed rapid elimination through urine and slow accumulation in liver and lungs. Therefore, we performed initial efficacy tests with a GBM stem cell model implanted subcutaneously. mAb428.2 (4 x 10 mg/kg) or control IgG1 were administered intratumorally and animals sacrificed at 1 days. Results indicated 45% median volume reduction in mAb428.2-injected tumors, with significant tumor necrosis. To further develop targeted reagents against fibulin-3 we have subcloned the Vh and Vl sequences of mAb428.2 and already generated a single-chain variable fragment (scFv) that recognizes fibulin-3. Our overall encouraging results suggest that fibulin-3 is a novel target with high potential for developing targeted agents against GBM.
High Red Cell Distribution Width in Alcoholics: Not due to Liver Disease
Authors: Pekka Sillanaukee
Journal: JAMA (1992)

<h3>To the Editor.</h3> —In their reply to our letter, Drs Bessman and McClure<sup>1</sup>suggest that the high red cell distribution width (RDW) in alcoholics might be due to liver disease, since liver disease has been found to be a common cause of isolated increased RDW.<sup>2</sup>Consequently, they state that the challenge would now be to distinguish alcohol abuse per se from the liver disease that commonly results from alcohol abuse. Our previous results<sup>3</sup>provide a basis for considering this problem. Among the alcoholic men studied, 41% had a high RDW (&gt;14.1%). None of the alcoholics (n=106), however, showed signs or symptoms of alcoholic liver disease. To investigate further the possibility that alcoholic liver disease explained the elevated RDW values among alcoholics, we have now reexamined results in these subjects of several tests that might indicate liver disease. No statistically significant differences in any of the tested parameters
Role of Endoscopy in Upper Gastrointestinal Bleeding in Patients with Malignancy
Authors: A. Padmanabhan, H.O. Douglass, Jr., H.R. Nava
Journal: Endoscopy (1980)

A retrospective review of upper gastrointestinal bleeding in 55 patients with malignant disease is presented here. Major causative factors seem to be superficial gastritis and gastric erosions. With aggressive endoscopy, a diagnostic accuracy of 90 percent has been achieved. However, having the exact diagnosis too often has little significance on the final outcome of these critically ill patients, unless therapy directed against bleeding can provide time for effective antineoplastic treatment. With the better understanding of the pathology of the superficial gastric erosions, a better program of management can be evolved.
Disseminated Intravascular Coagulation and Head Trauma
Authors: Burton P. Drayer
Journal: JAMA (1975)

Disseminated intravascular coagulation (DIC) developed in two patients following head trauma. Brain parenchyma and highly vascular connective tissue of the choroid plexus and meninges are important pools of systemic coagulation components. This is an important consideration in the treatment of head injury.
Blood Pressure and the Brain
Authors: Tracy Hampton
Journal: JAMA (2007)

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
RANDOMIZED TRIAL TO INVESTIGATE THE IMPACT OF CILOSTAZOL ON THE ANGIOGRAPHIC OUTCOME OF DRUG-ELUTING CORONARY STENT: AN ANGIOGRAPHIC ANALYSIS OF CILON-T TRIAL
Authors: Jung-Won Suh, Seung-Pyo Lee, Il-Young Oh, Kyung Woo Park, Hyun-Jae Kang, Bon Kwon Koo, Young-Seok Cho, Tae-Jin Youn, In-Ho Chae, Dong-Ju Choi, Taek Geun Kwon, Jang-Ho Bae, Seung-Woon Rha, Jang-Whan Bae, Myeong Chan Cho, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2012)
Risk of second primary cancers after Hodgkin's disease by type of treatment: analysis of 2846 patients in the British National Lymphoma Investigation.
Authors: A. J. Swerdlow, A. J. Douglas, G. V. Hudson, B. V. Hudson, M. H. Bennett, K. A. MacLennan
Journal: BMJ (1992)

OBJECTIVE--To analyse the risk of second primary cancers during long term follow up of patients with Hodgkin9s disease. DESIGN--Cohort study. SETTING--The British National Lymphoma Investigation (a collaborative group of over 60 participating centres in Britain treating lymphomas). PATIENTS--2846 patients first treated for Hodgkin9s disease during 1970-87, for whom follow up was complete in 99.8%. MAIN OUTCOME MEASURES--Second primary cancers; uniform pathology reviews confirmed the diagnosis of Hodgkin9s disease and of second primary non-Hodgkin9s lymphomas. RESULTS--113 second primary cancers occurred. Relative risk of cancer other than Hodgkin9s disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non-Hodgkin9s lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to 6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1 to 33.9)). Absolute excess risk associated with treatment was greater for solid tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased soon after treatment, reaching a peak after five to nine years. It was increased substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of courses of chemotherapy but was not significantly increased after radiotherapy (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin9s lymphoma increased in the first five years after treatment and remained high but showed no clear relation with type or extent of treatment. Relative risk of solid tumours was less raised initially but increased throughout follow up and for lung cancer 10 years or more after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after treatments including radiotherapy and after chemotherapy alone. The risk after chemotherapy increased significantly with time since first treatment. CONCLUSION--The risk of solid cancer, not of leukaemia, is the major long term hazard of treatment for Hodgkin9s disease, and this seemed to apply after chemotherapy as well as after radiotherapy. These risks of second cancers are important in choice of treatment and in follow up of patients, but they are small compared with the great improvements in survival which have been brought about by modern therapeutic methods for Hodgkin9s disease.
ABC of brain stem death. Pitfalls and safeguards.
Authors: C Pallis
Journal: BMJ (1982)

Pitfalls in diagnosisCriteria of brain stem death can be judged fairly only when they are correctly applied.The basic truth that we all make mistakes should not be allowed to blur the difference between fallible physicians and fallacious criteria.Recent controversies have, if anything, re-emphasised the soundness of the criteria used in the UK code.The adoption of similar criteria in other countries points in the same direction.Nevertheless, it is necessary to be aware of potential pitfalls.These fall into three broad categories: failure to ensure that preconditions and exclusions have been met; technical errors in testing; and mistakes in interpreting observed signs.Failure to fulfil the preconditions ' I Failure to fulfil the preconditions is the commonest pitfall.To recommend that "it is almost (sic) always desirable to have an aetiologic basis for the diagnosis"' is asking for trouble.Testing for brain stem death should not be undertaken unless the cause of the coma has been established beyond all doubt.The UK code restricts the range of acceptable causes (by specifying which conditions should be excluded).It also emphasises the importance of timing. Eliciting and interpreting signsThe pupils-Despite the requirements of several earlier codes, it is not necessary for the pupils to be dilated.Mydriasis is not a feature of a dead brain-as can readily be ascertained in any morgue.2When the brain stem is dead the pupils are usually in the mid-position.The important point is that they should show no response to light.A really bright light is needed: household torches or ophthalmoscopes should not be used as sources of light.It is also advisable to darken the room.Widely dilated, unresponsive pupils may be caused by atropine, administered in the course of cardiac resuscitation.The effects may persist for several hours.Errors may also arise when topical mydriatics are instilled (to facilitate examination of the fundi) and the fact not recorded in the notes.Pre-existing ocular or neurological disease may account for the pupils failing to respond to light, as may local damage to the globe or nerves to the eye due to craniofacial injury.Corneal reflexes-Testing corneal reflexes in patients with suspected brain stem death requires much firmer pressure than is used in conscious patients.Delicate dabbing with a wisp of cotton does not really provide an adequate stimulus.A sterile throat swab is more suitable.* Meeting preonditions and exclusions * Techrique of eliciting signs.* Interpretation of signs elicited .,-I Is there: * A comotose patient on a ventiator ?* An unequivocally established cause for the coma ?* Irremediable, structural brain damage"?* Is te stimulus adequate ?* Have anticholinergic drugs been given by injection ?
Relation of Education to Sudden Death after Myocardial Infarction
Authors: Eve Weinblatt, William Ruberman, Judith D. Goldberg, Charles W. Frank, Sam Shapiro, Banvir S. Chaudhary
Journal: New England Journal of Medicine (1978)

We studied the influence of social and personal characteristics on prognosis among 1739 male survivors of myocardial infarction who had been monitored for one hour at a standard examination and subsequently followed for mortality. Over a three-year period men with little education (eight years of schooling or less) who had complex ventricular premature beats in the monitoring hour had over three times the risk of sudden coronary death found among better educated men with the same arrhythmia (cumulative mortality of 33 per cent and 9 per cent, respectively). No such differential appeared in the absence of complex ventricular premature beats. Neither risk factors for incidence of coronary heart disease nor clinical characteristics affecting prognosis accounted for the differences observed. There was no relation between education level and risk of recurrent infarction. (N Engl J Med 299:60–65, 1978)
Human osteoblasts in vitro secrete tissue inhibitor of metalloproteinases and gelatinase but not interstitial collagenase as major cellular products.
Authors: L Rifas, L R Halstead, W A Peck, L V Avioli, H G Welgus
Journal: Journal of Clinical Investigation (1989)

Human osteoblast cultures (hOB) were examined for the production of interstitial collagenase, tissue inhibitor of metalloproteinases (TIMP), and gelatinolytic enzymes. Cells were isolated by bacterial collagenase digestion of trabecular bone (vertebra, rib, tibia, and femur) from 11 subjects (neonatal to adult). Confluent cultures were exposed to phorbol 12-myristate 13-acetate, PTH, PGE2, epidermal growth factor, 1,25(OH)2 vitamin D3, recombinant human IL-1 beta, and dexamethasone. Collagenase and TIMP were assayed immunologically and also by measurements of functional activity. Collagenase was not secreted in significant quantities by human bone cells under any tested condition. Furthermore, collagenase mRNA could not be detected in hOB. However, hOB spontaneously secreted large amounts of TIMP for at least 72 h in culture. hOB TIMP was found to be identical to human fibroblast TIMP by double immunodiffusion, metabolic labeling and immunoprecipitation, Northern blot analysis, and stoichiometry of collagenase inhibition. SDS-substrate gel electrophoresis of hOB-conditioned media revealed a prominent band of gelatinolytic activity at 68 kD, and specific polyclonal antisera established its identity with the major gelatinolytic protease of human fibroblasts. Abundant secretion of gelatinolytic, but not collagenolytic, enzymes by hOB may indicate that human osteoblasts do not initiate and direct the cleavage of osteoid collagen on the bone surface, but may participate in the preparation of the bone surface for osteoclast attachment by removal of denatured collagen peptides. The constitutive secretion of TIMP may function to regulate metalloproteinase activity.
Food, Nutrition, and Nuclear War
Authors: Nevin S. Scrimshaw
Journal: New England Journal of Medicine (1984)

Some will consider the analysis of the specific effects of thermonuclear war on food and nutrition to be a meaningless exercise for a society whose populations would be decimated, and its social fabric destroyed, by such a war. However, consideration of these topics can add another dimension to the professional and public understanding of the horror of the threat. Most aware persons are aghast at the public utterances of those who emphasize the possible number of survivors after nuclear war in ways that seem to imply that there would be enough people left to pick up the pieces and go . . .
Talking about death is not outrageous--reducing it to a tickbox exercise is
Authors: M. McCartney
Journal: BMJ (2014)

The Daily Telegraph was outraged. The headline read, “Elderly patients asked during home visits by nurses: would you want to be resuscitated?”1 The offending question is part of the direct enhanced service for unplanned admissions. 

Essentially, GPs are being paid to try not to send people to hospital. On the basis of recent attendance patterns we are meant to identify patients at high risk of being admitted and work out a plan, as the NHS specification puts it, to “identify factors which could have avoided the admission or future A&E [accident and emergency] attendance with a view to taking appropriate action to prevent future episodes.” …
New equities of information in an electronic age
Authors: R. Manning
Journal: BMJ (1995)

EDITOR,--Christopher Zielinski's editorial “New equities of information in an electronic age,” is an excellent summary of the many problems faced by developing countries in receiving and supplying health information. Since 1977 the Appropriate Health Resources and Technologies Action Group (AHRTAG) has worked with partners in developing countries to disseminate relevant and accurate information on health and to develop information systems to meet local needs. The group is an independent non-government organisation and has no corporate links with commercial providers of information.

AHRTAG publishes …
Indian government outlines plans to tighten tobacco control laws
Authors: C. Travasso
Journal: BMJ (2015)

<h3>Objectives</h3> It is unknown if prenatal exposure to antiepileptic drugs (AEDs) increases the risk of low Apgar score in offspring. <h3>Setting</h3> Population-based study using health registers in Denmark. <h3>Participants</h3> We identified all 677 021 singletons born in Denmark from 1997 to 2008 and linked the Apgar score from the Medical Birth Register with information on the women9s prescriptions for AEDs during pregnancy from the Danish Register of Medicinal Product Statistics. We used the Danish National Hospital Registry to identify mothers diagnosed with epilepsy before birth of the child. Results were adjusted for smoking and maternal age. <h3>Results</h3> Among 2906 children exposed to AEDs, 55 (1.9%) were born with an Apgar score ≤7 as compared with 8797 (1.3%) children among 674 115 pregnancies unexposed to AEDs (adjusted relative risk (aRR)=1.41 (95% CI 1.07 to 1.85). When analyses were restricted to the 2215 children born of mothers with epilepsy, the aRR of having a low Apgar score associated with AED exposure was 1.34 (95% CI 0.90 to 2.01) When assessing individual AEDs, we found increased, unadjusted RR for exposure to carbamazepine (RR=1.86 (95% CI 1.01 to 3.42)), valproic acid (RR=1.85 (95% CI 1.04 to 3.30)) and topiramate (RR=2.97 (95% CI 1.26 to 7.01)) when compared to unexposed children. <h3>Conclusions</h3> Prenatal exposure to AEDs was associated with increased risk of being born with a low Apgar score, but the absolute risk of a low Apgar score was &lt;2%. Risk associated with individual AEDs indicate that the increased risk is not a class effect, but that there may be particularly high risks of a low Apgar score associated with certain AEDs.