tbuckley/cabot-search huggingface dataset:
Abstract 2183: Determining the functional roles of the specific isoforms of ARID3B from cellular localizations
Authors: Victoria E. Deneke
Journal: Cancer Research (2012)

Abstract Ovarian cancer is the leading cause of death from a gynecological malignancy in the United States, yet the genetic mechanisms that contribute to ovarian cancer progression are poorly understood. We have determined that ARID3B, a member of the AT-rich interaction domain (ARID) family of proteins, is overexpressed in ovarian cancer. Therefore, we want to assess if ARID3B plays an important role in ovarian cancer progression. We have demonstrated that there are two ARID3B isoforms: the long form (ARID3BFL at 61kDa) and the short form (ARID3Bsh at 28kDa). We show that the ARID3BFL is mostly found in the nucleus and some is found in the membrane of cells. Furthermore, the short isoform of ARID3B (when overexpressed) is primarily found in cytoplasmic and membrane/mitochondria fractions. Therefore, we hypothesize that by virtue of these unique cellular distributions that ARID3B isoforms elicit different cellular responses. ARID3BFL binds DNA and induces apoptosis in ovarian cancer cell lines while ARID3Bsh does not induce cell death. Further elucidation of the roles of the two ARID3B isoforms will help us understand ovarian cancer progression, cellular response to chemotherapy, and develop prognostic markers and targeted therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2183. doi:1538-7445.AM2012-2183
First trimester DNA-based exclusion of recessive dystrophic epidermolysis bullosa from chorionic villus sampling
Authors: J.A. McGRATH, M.G.S. DUNNILL, A.M. CHRISTIANO, B.D. LAKE, D.J. ATHERTON, C.H. RODECK, P.M. POPE, R.A.J. EADY, J. UITTO
Journal: British Journal of Dermatology (1996)

Summary A 28-year-old woman, who previously had had a child affected with the hereditary blistering skin disorder, recessive dystrophic epidermolysis bullosa, presented at 7 weeks' gestation for prenatal diagnosis. Genomic DNA obtained from her. her husband (who is a first cousin), their unaffected child, and their previously affected child, was used to screen all 118 exons of the type VII collagen gene (C0L7A1) by polymerase chain reaction (PCR) amplification followed by hierodule analysis of the PCR products. Established common polymorphisms within the NC-1 region of C0L7A1 were informative for both the normal maternal and paternal alleles. In addition, a putative homozygous mutation, a G to C transfusion at nucleotide position 7708 was identified in the affected child. This substitution converts a glycine residue (GGT) within the Gly-X-Y region of the type VII collagen triple helix into an arginine residue (CGT) and leads to the creation of a new MM/I restriction site. Both parents and the healthy sibling were shown to be clinically normal heterozygous carriers of this mutation. A chorionic villus biopsy was performed at 10 weeks' gestation and DNA was extracted from the villi. Assessment of informative intragenic markers, and the putative mutation, revealed that the fetus had inherited both the normal maternal and paternal C0L7A1 alleles. Thus, first trimester DNA-based prenatal diagnosis predicts that this child is neither affected with recessive dystrophic epidermolysis bullosa, nor is an unaffected carrier of this genodermatosis.
Value of Culdocentesis
Authors: A. Robson
Journal: BMJ (1970)

<h3>Background</h3> Community pharmacists are well positioned to support patients’ minor ailments. The objective was to evaluate the clinical and humanistic impact of a minor ailment service (MAS) in community pharmacy compared with usual pharmacist care (UC). <h3>Methods</h3> A cluster randomised controlled trial was conducted. Intervention patients received MAS, which included a consultation with the pharmacist. MAS pharmacists were trained in clinical pathways and communication systems mutually agreed with general practitioners and received monthly support. Control patients received UC. All patients were followed up by telephone at 14 days. Clinical and humanistic impact were defined by primary (appropriate referral rate and appropriate non-prescription medicine rate) and secondary outcomes (clinical product-based intervention rate, referral adherence, symptom resolution, reconsultation and EuroQol EQ-5D visual analogue scale (VAS)). <h3>Results</h3> Patients (n=894) were recruited from 30 pharmacies and 82% (n=732) responded to follow-up. Patients receiving MAS were 1.5 times more likely to receive an appropriate referral (relative rate (RR)=1.51; 95% CI 1.07 to 2.11; p=0.018) and were five times more likely to adhere to referral, compared with UC (RR=5.08; 95%CI 2.02 to 12.79; p=0.001). MAS patients (94%) achieved symptom resolution or relief at follow-up, while this was 88% with UC (RR=1.06; 95% CI 1 to 1.13; p=0.035). MAS pharmacists were 1.2 times more likely to recommend an appropriate medicine (RR 1.20, 95% CI 1.1 to 1.3; p=0.000) and were 2.6 times more likely to perform a clinical product-based intervention (RR=2.62, 95% CI 1.28 to 5.38; p=0.009), compared with UC. MAS patients had a greater mean difference in VAS at follow-up (4.08; 95% CI 1.23 to 6.87; p=0.004). No difference in reconsultation was observed (RR=0.98; 95% CI 0.75 to 1.28; p=0.89). <h3>Conclusion</h3> The study demonstrates improved clinical and humanistic outcomes with MAS. National implementation is a means to manage minor ailments more effectively in the Australian health system. <h3>Trial registration number</h3> ACTRN12618000286246.
Synergistic combinations of recombinant human tissue-type plasminogen activator and human single-chain urokinase-type plasminogen activator. Effect on thrombolysis and reocclusion in a canine coronary artery thrombosis model with high-grade stenosis.
Authors: A A Ziskind, H K Gold, T Yasuda, M Kanke, J L Guerrero, J T Fallon, T Saito, D Collen
Journal: Circulation (1989)

The synergistic effects of recombinant human tissue-type plasminogen activator (rt-PA) and single-chain urokinase-type plasminogen activator (scu-PA) on coronary arterial thrombolysis were investigated in open-chest dogs with thrombosis of the left anterior descending coronary artery and a superimposed high-grade stenosis. A 90% stenosis was generated by external constriction, reducing blood flow to 40 +/- 10% of baseline. Localized thrombosis was produced by endothelial cell injury and instillation of thrombin and fresh blood. Intravenous infusion for 60 minutes of either 30 micrograms/kg/min rt-PA alone or 10 micrograms/kg/min scu-PA alone consistently produced coronary artery recanalization (six of eight dogs and five of five dogs, respectively) but was almost always associated with reocclusion during or shortly after the end of the infusion (four of six dogs and five of five dogs, respectively). Infusion of either 15 micrograms/kg/min rt-PA or 5 micrograms/kg/min scu-PA for 60 minutes did not cause coronary artery recanalization (none of four dogs in each group). Combined infusion of 7.5 micrograms/kg/min rt-PA and 2.5 micrograms/kg/min scu-PA for 60 minutes (one fourth of the minimum thrombolytic dose of each agent) induced coronary artery recanalization (six of six dogs) but was also associated with early reocclusion (six of six dogs). Combined infusion of 3.75 micrograms/kg/min rt-PA and 1.25 micrograms/kg/min scu-PA for 60 minutes did not consistently cause recanalization (one of four dogs). Combined infusion of 15 micrograms/kg/min rt-PA and 5 micrograms/kg/min scu-PA for 60 minutes caused recanalization in all of six dogs but was associated with reocclusion in all six.(ABSTRACT TRUNCATED AT 250 WORDS)
Presented antigen from damaged pancreatic β cells activates autoreactive T cells in virus-mediated autoimmune diabetes
Authors: Marc S. Horwitz, Alex Ilic, Cody Fine, Enrique Rodriguez, Nora Sarvetnick
Journal: Journal of Clinical Investigation (2002)

The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM. However, the molecular pathway between viral infection and the subsequent activation of T cells specific for islet antigen has not been elucidated. These T cells could become activated through exposure to sequestered antigens released by damaged beta cells, or they could have responded to factors secreted by the inflammatory response itself. To distinguish between these possibilities, we treated mice harboring a diabetogenic T cell repertoire with either the islet-damaging agent streptozotocin (STZ) or poly I:C, which nonspecifically activates T cells. Significantly, only treatment of mice with STZ resulted in IDDM and mimicked the effects observed following CB4 infection. Furthermore, antigen-presenting cells from STZ-treated mice were shown to directly activate autoreactive T cells and induce diabetes. Therefore, the primary role of CB4 in the precipitation of IDDM is to damage tissue, causing release and presentation of sequestered islet antigen. These events stimulate autoreactive T cells and thereby initiate disease.
Struggles With Clinical Translation of Immune Intervention Trials
Authors: Jay S. Skyler
Journal: Diabetes Care (2014)

Immune intervention trials in type 1 diabetes have shown very mixed, and often surprising, results. Despite suggestions of benefit from GAD-Alum vaccine in a phase 2 study (1), further studies, including two large phase 3 trials, showed no effect (2–4). Phase 3 trials with Anti-CD3 monoclonal antibodies failed to achieve their primary outcome (5–7), despite very promising results from multiple phase 2 trials (8–13). The conflicting Anti-CD3 data may be explained by unfortunate changes in design (5) or dose (6,7) in phase 3 (14). Many immunologic strategies have been tested in phase 2 trials, some with signs of benefit, such as rituximab (15) and abatacept (16); others without benefit, such as mycophenolate mofetil with or without daclizumab (17) or anti-interleukin 1 blockade with either canakinumab or anakinra (18); and others with ambiguous effects, such as thymoglobulin (19) or alefacept (20). In this issue, there are two articles describing results from the phase 3 Efficacy Study of DiaPep277 in Newly Diagnosed Type 1 Diabetes Patients (DIA-AID 1) trial evaluating the safety and efficacy of a 24 amino acid peptide derived from heat shock protein 60, called DiaPep277 (21,22). According to Raz et al. (21) and Pozzilli et al. (22), it appears as if the study demonstrated a beneficial effect, and if so, that would be a very exciting finding. Yet, as outlined below, there are several aspects of the study that make that conclusion less certain. This commentary examines the studies and explores some clinically relevant issues readers may want to consider when interpreting the data from the trial.

The principal measure of efficacy in immune intervention trials in type 1 diabetes is preservation of C-peptide as an index of β-cell …
The liver in systemic amyloidosis: insights from <sup>123</sup>I serum amyloid P component scintigraphy in 484 patients
Authors: L B Lovat, M R Persey, S Madhoo, M B Pepys, P N Hawkins
Journal: Gut (1998)

Background and aims —The liver is frequently involved in amyloidosis but the significance of hepatic amyloid has not been systematically studied. We have previously developed scintigraphy with 123 I serum amyloid P component ( 123 I-SAP) to identify and monitor amyloid deposits quantitatively in vivo and we report here our findings in hepatic amyloidosis. Methods —Between 1988 and 1995, 805 patients with clinically suspected or biopsy proven systemic amyloidosis were evaluated. One hundred and thirty eight patients had AA amyloidosis, 180 had AL amyloidosis, 99 had hereditary amyloid syndromes, and 67 had dialysis related (β 2 microglobulin) amyloid. One hundred and ninety two patients with amyloidosis were followed for six months to eight years. Results —Hepatic amyloid was found in 98/180 (54%) AL and 25/138 (18%) AA patients but in only 1/53 patients with familial transthyretin amyloid polyneuropathy and in none with dialysis related amyloidosis. There was complete concordance between hepatic SAP scintigraphy and the presence or absence of parenchymal amyloid deposits on liver histology. Amyloidosis was never confined to the liver. Mortality was rarely due to hepatic failure, although hepatic involvement with AA amyloid carried a poor prognosis. Successful therapy to reduce the supply of amyloid fibril protein precursors was followed by substantial regression of all types of amyloid. Conclusions —SAP scintigraphy is a specific and sensitive method for detecting and monitoring hepatic amyloid. Liver involvement is always associated with major amyloid in other organ systems and carries a poor prognosis in AA type. Appropriate therapy may substantially improve prognosis in many patients.
Myocardial and peripheral catecholamine responses to acute coronary artery constriction before and after propranolol treatment in the anaesthetised dog
Authors: B P McGRATH, S P LIM, L LEVERSHA, A SHANAHAN
Journal: Cardiovascular Research (1981)

Journal Article Myocardial and peripheral catecholamine responses to acute coronary artery constriction before and after propranolol treatment in the anaesthetised dog Get access B P McGRATH, B P McGRATH * From the Monash University Departments of Medicine and Surgery, Prince Henry's Hospital, Melbourne, Australia *Address for reprints: Dr B P McGrath, Monash University Dept of Medicine, Prince Henry's Hospital, St Kilda Road, Melbourne, 3004, Australia. Search for other works by this author on: Oxford Academic PubMed Google Scholar S P LIM, S P LIM From the Monash University Departments of Medicine and Surgery, Prince Henry's Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar L LEVERSHA, L LEVERSHA From the Monash University Departments of Medicine and Surgery, Prince Henry's Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar A SHANAHAN A SHANAHAN From the Monash University Departments of Medicine and Surgery, Prince Henry's Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 15, Issue 1, January 1981, Pages 28–34, https://doi.org/10.1093/cvr/15.1.28 Published: 01 January 1981
ADVICE TO THE PROSPECTIVE MOTHER ASSISTANCE DURING HER CONFINEMENT AND CARE FOR A FEW DAYS FOLLOWING.
Authors: J. O. MALSBERY
Journal: JAMA (1897)

Our advice to the prospective mother must necessarily be ineffective, owing to her inherent tendencies and conformity to custom. The advice to have been effective, should have been given and more or less closely observed by her progenitor mother. This advice not having been followed, if given. has led to a change in her anatomy and lessening of her vital and physical forces. Then does it look plausible that we can supplant those inherent defects, if such there be, by advice and rules of habit to be followed during gestation or just prior to confinement, and make her delivery as of yore? I answer, no. We can do much, however, by hints and suggestions suited to each patient, to lead the prospective mother up to her time of confinement in the best possible manner, considering her heritage, inborn customs and acquired habits of dress, providing, however, that our enjoinders be
Mastectomy or conservation: the patient's choice.
Authors: M. Baum, L. Fallowfield, A. Hall
Journal: BMJ (1988)

To determine whether, if given the choice, patients with breast cancer would prefer mastectomy or conservation treatment, neither treatment having been shown to be preferable.Non-randomised case series with 28 patients interviewed after two years and all followed up.Secondary care referral centre.153 women, aged less than 65, with T1, T2, N1, and N0 tumours of the breast given the choice of treatment (that is, all eligible patients from December 1979).Patients were asked, after information and counselling, which treatment they would prefer. The chosen treatment was given without further question. Mastectomy included node sampling and local radiotherapy if indicated. Conservation treatment comprised excision of the lump, external radiotherapy, and irridium wire implant to tumour bed.Conservation treatment was chosen by 54 women and mastectomy by 99. Reasons for preferring mastectomy included desire for rapid treatment for domestic or employment reasons and fear of possibility of future mastectomy. Only two of the sample interviewed regretted their choice. During limited follow up no advantages to either form of treatment were seen in terms of recurrence or survival.Patients with breast cancer are capable of choosing treatment and should play a part in deciding which treatment to have. They do not automatically choose to retain the breast.
More Cases of Multiple Phlebectasia
Authors: Melvin A. Shiffman
Journal: JAMA (1964)

<h3>To the Editor:—</h3> The paper by I. Rappaport and M. A. Shiffman, "Multiple Phlebectasia Involving Jejunum, Oral Cavity, and Scrotum" (<i>JAMA</i><b>185</b>:437 [Aug 10] 1963) described a group of lesions not previously noted to be associated. The occasional instance of bleeding from jejunal phlebectasia makes recognition of the concomitant mucocutaneous vascular malformations extremely important. Since that paper was published, three new cases of multiple phlebectasia have been noted at the Veterans Administration Hospital, Long Beach, Calif. The intestinal lesions were restricted to the jejunum in two cases, and an additional lesion was noted in the proximal ileum in another. Two patients had no history of peptic ulcer or upper gastrointestinal bleeding. The third patient had a diagnosis of peptic ulcer for nine years associated with intermittent hematemesis and melena. The ages ranged from 62 to 76. A total of six cases of multiple phlebectasia have now been noted. Careful
A8.17 Expression of the autoimmune regulator aire in human lymph node stromal cells
Authors: J Hähnlein, T H Ramwadhdoebe, J F Semmelink, K I Maijer, I. Y. Choi, N A M Smits, F H Berger, M Maas, D M Gerlag, T B Geijtenbeek, P P Tak, L G M van Baarsen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objective</h3> Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Immune activation in peripheral lymphoid tissues seems to precede synovial tissue inflammation. The stromal compartment of lymph nodes is crucial for the induction and adaption of immune responses. Recent murine studies have implicated a role of lymph node stromal cells (LNSCs) in tolerance due their expression of Aire. In the thymus the autoimmune regulator Aire is the main transcription factor regulating T cell central tolerance by driving expression of tissue-restricted antigens. Here we investigated the expression of Aire in human LNSCs obtained during the earliest phases of RA to assess their potential role in peripheral tolerance during autoimmunity. <h3>Materials and Methods</h3> We included autoantibody positive individuals with arthralgia without any evidence of arthritis who were positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies (n = 11; RA risk group). Furthermore, we included patients with undifferentiated arthritis (n = 2), RA patients (n = 4) and healthy controls (n = 4). All subjects underwent ultrasound-guided inguinal lymph node biopsy. LNSCs were cultured from freshly collected lymph node needle biopsies and passages 3-6 were used for experiments. LNSCs were characterised by CD45, gp38 and CD31 expression using flowcytometry (n = 12). Aire was measured on mRNA level by qPCR and on protein level by flowcytometry and immunofluorescence stainings on chamber slides under homeostatic conditions or after stimulation for 24h with TLR-3 ligand polyI:C. <h3>Results</h3> LNSCs in culture appeared to be a mixture of fibroblastic reticular cells (FRC: gp38+ , CD31-) and double negative (DN) cells. Expression of Aire could be detected at both mRNA and protein level. Aire protein expression did not correlate to gp38 expression and remained stable between homeostatic and inflammatory conditions. Immunofluorescence staining showed expected nuclear localization of Aire and was detected in the majority of cultured cells. Overall, Aire expression was highly variable between donors. <h3>Conclusions</h3> We developed a culture system for human LNSCs to facilitate research on the role of the lymph node microenvironment in the pathogenesis of RA. This is the first study showing that cultured human LNSCs express Aire and our data suggest that human FRCs as well as DN cells express it. This may indicate tissue-specific self-antigen expression by LNSCs pointing towards an important role for the lymph node stromal environment in peripheral tolerance and autoimmunity.
The Second Baby Doe Rule-Reply
Authors: David K. Stevenson
Journal: JAMA (1988)

<h3>In Reply.</h3> —In her Letter, Dr Kopelman accurately points out that while the Supreme Court has struck down the BDR-I, the BDR-II, which is based on the 1984 amendments to the Child Abuse Prevention and Treatment Act, remains in effect. This rule forbids the "withholding of medically indicated services." Exceptions to this rule are to be made only when "(1) the infant is chronically and irreversibly comatose; (2) the provision of such treatment would merely prolong dying or not be effective in ameliorating or correcting all the infant's life-threatening conditions or otherwise be futile in terms of the survival of the infant; or (3) the provision of such treatment would be virtually futile in terms of the survival of the infant and the treatment itself under such circumstances would be inhumane." The notion that these few directives are in some way capable of providing meaningful guidance in the vast array
Another pound of cure
Authors: T. J. Romano
Journal: JAMA (1992)

To the Editor.  —Senator Harkin 1 criticized JAMA for its  to substantively address health promotion and the prevention of disease and disability and that this failure was conspicuous.  What is conspicuous is Senator Harkin's total lack of understanding of what is going on in health care today.  Nowhere in his article is there any mention of tort reform, the tort system being one of the big impediments toward access in our country. Unfortunately, much of the resources of this country are spent on defensive medicine when they could otherwise be spent on medical care for those less fortunate or truly needy in our society.
Hairy‐cell leukemia with hybrid B‐T features: A study with a panel of monoclonal antibodies
Authors: R. J. Armitage, C. P. Worman, M. C. Galvin, J. C. Cawley
Journal: American Journal of Hematology (1985)

Abstract The peripheral blood of three patients with otherwise typical hairy‐cell leukemia (HCL), but with a substantial number of circulating cells expressing both light chain restricted surface immunoglobulin (SIg) and sheep erythrocyte (E) receptor, was studied with a panel of monoclonal antibodies. The presence of hybrid B‐T surface features was confirmed and, although as in previous studies of E + SIg + proliferations, the precise phenotypes varied at different times of study, E + non‐T SIg + and E + T + SIg + populations were at times present in all three patients together with typical B hairy‐cell (HC) and phenotypically normal T‐cell populations. In one patient an E − OKT11 + SIg + population was also observed. Extensive precautions were taken to exclude spurious explanations for these hybrid phenotypes. These results are discussed in relation to the recent demonstration that both HCs and normal B cells can express T‐cell features after appropriate in vitro stimulation.