tbuckley/cabot-search huggingface dataset:
B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen-specific tolerance.
Authors: V A Boussiotis, G J Freeman, G Gray, J Gribben, L M Nadler
Journal: The Journal of Experimental Medicine (1993)

Presentation of antigen by the major histocompatibility complex to T lymphocytes without the requisite costimulatory signals does not induce an immune response but rather results in a state of antigen-specific unresponsiveness, termed anergy. To determine which costimulatory signals are critical for the T cell commitment to activation or anergy, we developed an in vitro model system that isolated the contributions of alloantigen and each candidate costimulatory molecule. Here, we show that transfectants expressing HLA-DR7 and either B7 or intercellular adhesion molecule 1 (ICAM-1) deliver independent costimulatory signals resulting in alloantigen-induced proliferation of CD4-positive T lymphocytes. Although equivalent in their ability to costimulate maximal proliferation of alloreactive T cells, B7 but not ICAM-1 induced detectable interleukin 2 secretion and prevented the induction of alloantigen-specific anergy. These results are consistent with the hypothesis that blockade of the ICAM-1:lymphocyte function-associated 1 pathway results in immunosuppression, whereas blockade of the B7:CD28/CTLA4 pathway results in alloantigen-specific anergy. This approach, using this model system, should facilitate the identification of critical costimulatory pathways which must be inhibited in order to induce alloantigen-specific tolerance before human organ transplantation.
ABC of intensive care: Cutting edge
Authors: M. Singer, R. Little
Journal: BMJ (1999)

Few areas of clinical medicine are changing as rapidly as intensive care. Greater understanding of the pathophysiology of disease processes, technological innovations, targeted pharmaceutical and “nutriceutical” interventions, and the use of specialised audit and scoring methods to improve patient classification and monitor disease progression have all contributed to changes in practice in the past decade. This article considers developments that may affect patient management in the next 10 years.
Superficial Depressed-Type Cancer Monitored by Colonoscopy through the Early Phase of Invasion
Authors: Y. Baba, Y. Suzuki, M. Kobayashi, M. Azumaya, M. Takeuchi, K. Shioji, T. Honma, R. Narisawa, Y. Ajioka, H. Asakura
Journal: Endoscopy (2002)

Although previous retrospective reports have demonstrated the developmental course of several colorectal tumors, the natural history and progression of depressed carcinoma, especially in the early stage, remains obscure. We report a case of superficial depressed tumor in the transverse colon in a 71-year-old man, which did not change in size and gross configuration through prospective colonoscopic observation over a period of 19 months but which was finally diagnosed as early-stage submucosal invasive cancer. Most depressed cancers have been supposed to arise de novo and grow rapidly, showing aggressive behavior when 10 mm or less in size. However, this case report may suggest that even a depressed tumor may grow to approximately 10 mm within the mucosal layer over a few years and that the growth of colorectal tumors, whether they are polypoid or depressed in configuration, might be fairly slow.
AB0584 Safety and efficacy of etanercept in patients with active psoriatic arthritis with peripheral involvement in belgium: 66 months follow-up.
Authors: K. de Vlam, C. Boone
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> to describe the long-term efficacy and types of adverse events (AEs) in psoriatic arthritis (PsA) patients treated with etanercept in a daily clinical setting in Belgium. <h3>Methods</h3> This is a prospective, multi-center, open-label, observational study in patients with active PsA, who have previously failed DMARD therapy. Patients were treated with etanercept 25 mg subcutaneously twice a week or 50 mg OW. Health Assessment Questionnaire (HAQ-DI) was completed, swollen joint count was made, and adverse events (AEs) occurring during the treatment period were registered. Patients were followed up for 5.5 years. <h3>Results</h3> 303 patients were treated with etanercept, representing a total of 1184 patient-years. 114 patients discontinued treatment, and 33 patients were lost to follow-up. Reasons for discontinuation included non-responder (primary and secondary, n =54) and safety (n = 31). 204 (67,77%) patients reported adverse events of which 177(58,8%) events were related to the treatment. 65(21,59%) patients reported a serious adverse event of which 53 (17,61%) events are considered to be related to the treatment. Infections were the most frequent AE’s. 13 cases were considered as serious adverse events. No cases of tuberculosis were reported. 6 cases of herpes zoster were noticed. Injection site reactions were uncommon (n=6). Efficacy was evaluated by measuring number of joints with active synovitis and HAQ-DI. At baseline, the mean number of joints with active synovitis was 11,81±6,77. At month 6, the mean number of joints with active synovitis decreased to 2,1 ± 3,36. At month 66, the mean number of joints with synovitis further decreased to 0,73 ± 2,00. This represents a statistically significant decrease at both time points from baseline. 118 out of 152 (77,63%) patients with presented with no swollen joints at month 66. At baseline, the mean HAQ-DI-score (/60) was 26,99±8,94. At month 6, the mean HAQ- DI score decreased to 9,72± 9,37. At month 66, the HAQ-DI-score was 7,70± 9,09. This represents a statistically significant decrease at both time points from baseline. <h3>Conclusions</h3> These results confirm the safety and efficacy profile of Enbrel in psoriatic arthritis when used in daily clinical practice in Belgium. No new safety signals were detected. <h3>Disclosure of Interest</h3> K. de Vlam Consultant for: Pfizer, Speakers bureau: Pfizer, C. Boone Employee of: Pfizer
Patients who discharge themselves need further thought
Authors: David R Warriner
Journal: BMJ (2011)

<h3>Summary</h3> MicroRNAs (miRNAs) are short non-coding RNAs that mediate the repression of target transcripts in plants and animals. Although miRNAs are required throughout plant development, relatively little is known regarding their embryonic functions. To systematically characterize embryonic miRNAs in <i>Arabidopsis thaliana</i>, we developed or applied high-throughput sequencing based methods to profile hundreds of miRNAs and associated targets throughout embryogenesis. We discovered dozens of miRNAs that dynamically cleave and repress target transcripts including 30 that encode transcription factors. Transcriptome analyses indicated that these miRNA:target interactions have a profound impact on embryonic gene expression programs, and we further demonstrated that the miRNA-mediated repression of six transcription factors were individually required for embryo morphogenesis. These data indicate that the miRNA-directed repression of multiple transcription factors is critically important for the establishment of the plant body plan, and provide a foundation to further investigate how miRNAs contribute to these initial cellular differentiation events.
Diverticulosis of the colon and diet.
Authors: M. N. Morgan, H. Ellis
Journal: BMJ (1969)

JORA 53 intense loneliness, having never been without a dog before.I am now hopeful she may now change her mind, at least to* the extent of a Siamese cat, and that this may eventually permit corticosteroids to be tailed-off without relapse of her arteritis in one of its more unpleasant guises.This happened to a patient from the same practice only a few months back who stopped taking her prednisone, prescribed for her temporal arteritis, because the doctor emigrated.Her cardiac infarction, at first thought unremarkable, was followed by pericarditis and mental confusion, both of which, like her previous temporal arteritis, responded at once to prednisone.It seems likely that further studies on deprivation by death or other means of close relatives or pets will show significant results, not only-in mortality in the aged from cardiac infarction but also in morbidity and mortality from the other protean manifesta- tions of giant cell arteritis.-Iam, etc.,
In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type.
Authors: P Matzinger, G Mirkwood
Journal: The Journal of Experimental Medicine (1978)

Fully H-2 incompatible radiation chimeras were prepared using BALB congenic mice. Such chimeric mice were immunized in vivo against histocompatibility antigens of the C57BL/10Sn (B10) background in association with either of the parental H-2 haplotypes, and their spleen cells subsequently boosted in vitro with the same minor antigens. Strong H-2-restricted cytotoxic activity against minor antigens was detected, and the specificity of the restriction could be to the H-2 haplotype of the donor or the host depending on the cells used for priming or boosting. Cross priming could also be demonstrated in these mice. The results show that fully allogenic radiation chimeras can produce H-2-restricted T-cell responses to minor histocompatibility (H) antigens, and are discussed in relation to contrasting results recently obtained against viral antigens.
Cost-effectiveness of and satisfaction with a Helicobacter pylori "test and treat" strategy compared with prompt endoscopy in young Asians with dyspepsia
Authors: S Mahadeva, Y-C Chia, A Vinothini, M Mohazmi, K-L Goh
Journal: Gut (2008)

<h3>Objective:</h3> To compare a <i>Helicobacter pylori</i> “test and treat” strategy with prompt endoscopy in young Asians with dyspepsia. <h3>Methods:</h3> A randomised, prospective study was carried out on uninvestigated dyspeptics aged &lt;45 years in a single (academic) primary care centre. Patients were randomised to either a [<sup>13</sup>C]urea breath test (UBT) or prompt endoscopy (oesophagogastroduodenoscopy (OGD) and followed-up for 12 months. <h3>Results:</h3> 432 patients (mean (SD) age 30 (8) years, male 46%, ethnicity: Malays 33.3%, Chinese 30.6%, Indians 34.7%) were randomised to UBT (n = 222) or OGD (n = 210). 387 (89.6%) patients completed the study. At 12 months, there was no difference in symptom change (measured by the Leeds Dyspepsia Questionnaire) between the two groups, but more patients were very satisfied (40.0% vs 21.6%, p&lt;0.0001) in the OGD group. More additional endoscopy was performed in the UBT group (25 vs 10, p = 0.03), but medication consumption was higher in the OGD group (proton pump inhibitor 3.6 (8.8) vs 2.0 (7.5) weeks, p&lt;0.001; H2 receptor antagonist 5.3 (9.7) vs 3.9 (9.2) weeks, p = 0.017; prokinetics 1.4 (4.7) vs 0.4 (2.5) weeks, p&lt;0.001) and no differences in medical consultation were noted. The median cost of the initial prompt endoscopy approach at 12 months was significantly higher than a “test and treat” strategy (US$179.05 vs US$87.10, p&lt;0.0001). <h3>Conclusion:</h3> A <i>H pylori</i> “test and treat” strategy is more cost-effective but less satisfying than prompt endoscopy in the management of young Asian patients with uncomplicated dyspepsia.
Notch signaling and new therapeutic options in liver disease
Authors: Carola Maria Morell, Mario Strazzabosco
Journal: Journal of Hepatology (2013)

Notch signaling is a crucial determinant of cell fate decision during development and disease in several organs. Notch effects are strictly dependent on the cellular context in which it is activated. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis. Recent advances have shed light on Notch as a critical player in liver regeneration and repair, as well as in liver metabolism and inflammation and cancer. Notch signaling is finely regulated at several levels. The complexity of the pathway provides several possible targets for development of therapeutic agents able to inhibit Notch. Recent reports have shown that persistent activation of Notch signaling is associated with liver malignancies, particularly hepatocellular with stem cell features and cholangiocarcinoma. These novel findings suggest that interfering with the aberrant activation of the Notch pathway may have therapeutic relevance. However, further studies are needed to clarify the mechanisms regulating physiologic and pathologic Notch activation in the adult liver, to better understand the mechanistic role(s) of Notch in liver diseases and to develop safe and specific therapeutic agents.
III. Improving Local Health Services
Authors: George James
Journal: JAMA (1962)

MYPURPOSE is to discuss the mission of the National Advisory Committee on Local Health Departments. I should like to ask that 3 general principles be kept in mind: Local health services should be designed solely to meet specific local health needs effectively and efficiently. The rapid change in health needs requires extreme flexibility in the development of local health services. Flexibility is aided by: (a) research efforts to create new resources and package them for greater acceptability to the population; (b) demonstrations to develop and adapt the new resources for practical programs for specific populations; (c) a chronic feeling of dissatisfaction with all results in order that we be constantly forced to evaluate them and improve their shortcomings; and (d) over-all administrative guidance by one or more public health generalists. Our cherished traditions, charters, and manuals of procedure are greatly disturbed when we leave our sheltered nooks in the
Metallothionein Gene Therapy for Chemical-Induced Liver Fibrosis in Mice
Authors: Youchun Jiang, Y. James Kang
Journal: Molecular Therapy (2004)

Liver fibrogenesis resulting from a diversity of pathological changes involves a disturbance in mineral, in particular zinc, homeostasis. The present study was undertaken to determine whether gene therapy with metallothionein (MT), a small protein critically involved in the regulation of zinc homeostasis, can improve the recovery of liver fibrosis in a mouse model. Wild-type (WT) mice treated with carbon tetrachloride in corn oil twice a week at 1 ml/kg for 4 weeks developed a reversible liver fibrosis upon removal of the chemical, correlating with a high level of hepatic MT; but those treated for 8 weeks developed an irreversible liver fibrosis along with low levels of hepatic MT. The same carbon tetrachloride treatment for 4 weeks resulted in an irreversible liver fibrosis in MT-knockout (MT-KO) mice. Adenoviral delivery of the human MT-II gene (approved symbol MT2A) through intravenous injection reversed the fibrosis along with increased hepatocyte regeneration within 3 days in both WT and MT-KO mice with irreversible fibrosis. The MT elevation was associated with increased activities of collagenases in the liver. This study indicates that MT makes a critical contribution to the reversal of chemical-induced hepatic fibrosis and has therapeutic potential for patients with certain liver fibrosis.
Tc-99m DTPA Diffuse Pulmonary Uptake in Patients with Coronary Artery Disease and Renal Insufficiency
Authors: CHARLES M. INTENZO, CHAN H. PARK, SUNG M. KIM
Journal: Clinical Nuclear Medicine (1992)

Diffuse bilateral lung uptake was observed in 10 patients undergoing Tc-99m DTPA renal scanning, referred for the evaluation of rising serum creatinine levels. All 10 patients demonstrated renal insufficiency (RI) as shown by both decreased bilateral renal tracer concentration and elevated background activity. Nine of the patients were known to have coronary artery disease (CAD) and six of these nine patients were in congestive heart failure (CHF), at or around the time of scanning. However, Tc-99m DTPA lung uptake was not observed in five other patients whose scans demonstrated RI, in whom there was no CAD or other cardiac disease. Diffuse lung uptake of Tc-99m DTPA in patients with RI therefore is highly suggestive of cardiac dysfunction (i.e. CAD and/or CHF).
Marijuana as Medicine
Authors: Elizabeth A. Lowenthal
Journal: JAMA (1995)

<h3>To the Editor.</h3> —As an oncologist I am continually astounded by government policy surrounding the medicinal use of marijuana. The recent Commentary by Dr Grinspoon and Mr Bakalar<sup>1</sup>stated the problem with eloquence and sensitivity. In addition, I would point out that in contrast to marijuana, cigarette tobacco has no proven medicinal effect whatsoever, is as addictive as cocaine and heroin,<sup>2</sup>is subsidized with tax dollars, and costs the United States an estimated $100 billion in health care expenditures and lost productivity.<sup>3</sup> It is ironic to inform cancer patients that they cannot partake of marijuana to relieve their metastatic lung cancer— associated anorexia and cachexia acquired from years of partaking in "the only consumer product sold legally in the United States that is unequivocally carcinogenic when used as directed."<sup>3</sup>In addition, with the cost of other effective appetite stimulants and antiemetics in excess of $200 per
Tissue transglutaminase as the autoantigen of coeliac disease
Authors: MARKKU MÄKI
Journal: Gut (1997)

Dieterich et al show that immunoprecipitation of human fibrosarcoma cell lysates (cell line HT1080) using the IgA fraction from serum samples of patients with coeliac disease results in a single protein band with a molecular weight of 85 kDa. Immunoprecipitation occurred exclusively with 25 coeliac disease serum samples, but with none of the 25 control samples. The 85 kDa antigen was cleaved with endoproteinase Asp-N, and after amino-terminal sequence analysis, the three cleavage products tested all yielded sequences that could be assigned to tissue transglutaminase (EC 2.3.2.13; tTG). In order to prove that tTG obtained from the fibrosarcoma cells binds to the endomysial antibody fraction of coeliac serum IgA, the authors performed indirect immunofluorescence with high titre coeliac disease serum samples on monkey oesophagus with or without prior incubation of those samples with a commercially available tTG extract (Sigma, Deisenhofer, Germany). Pretreatment with tTG almost completely abolished endomysial antibody labelling. Also, when the Sigma tTG was used as antigen in an enzyme linked immunosorbent assay (ELISA), 12 coeliac disease patient samples but none of the seven control serum samples displayed increased IgA immunoreactivity. Dieterich et al conclude they have identified tTG as the unknown endomysial autoantigen.
A PATHOLOGICAL STUDY OF SYPHILITIC AORTITIS AND ITS SEROLOGY
Authors: John H. Larkin, I. J. Levy
Journal: The Journal of Experimental Medicine (1916)

1. Syphilitic aortitis is a productive inflammatory process, the earliest and most constant feature of which is a perivascular round cell infiltration in the adventitia. 2. The typical gross picture of luetic aortitis is often obscured by a superimposed, diffuse atherosclerosis. In the early cases the aorta appears fairly normal, presenting only the characteristic histological changes. 3. A pure aortic insufficient valve, with the exception of an infectious endocarditis, is always luetic. 4. Cardiac hypertrophy is not a complication of luetic aortitis. When present it is usually associated with a nephritis. 5. The demonstration of Spirochoeta pallida, even in advanced specimens of syphilitic aortas, is doubtful. 6. An antigen prepared from alcoholic extract of guinea pig heart with the original Wassermann technique should be preferred in diagnosing luetic aortitis. 7. Positive complement fixations in patients suffering with syphilis for a period of about fifteen years or longer suggest the probability, at least, of histological luetic changes in the aorta in 80 to 90 per cent of the cases. 60 per cent of these die from aortitis. 8. About 94 per cent of patients suffering with aortitis give positive Wassermann reactions.
Successful treatment of digital vasospasm.
Authors: J L Smith
Journal: BMJ (1971)

ceptives have been more widely publicized.Equally disturbing is the increased ra-e of venereal disease among the young.If the British Medical Association can spend time in warning the public of the health hazards of smoking, why does it consistently neglect its duty in warning young people of the health hazards of sexual promiscuity?-Iam, etc.,
Bacterial toxin cripples dendritic cells
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

A mycobacterium that causes skin ulcers protects itself from the immune system by suppressing dendritic cell (DC) activity, according Coutanceau et al. (page 1395).

In the initial stages of Mycobacterium ulcerans infection, the skin puckers up into nodules that brim with bacteria and inflammatory cells. But this primary immune response gradually loses steam. As disease progresses, the inflammatory cells disappear and the nodules transform into festering ulcers. The bug seems to enforce immune suppression even outside the lesions as patients with ulcers have poor systemic cellular responses.

Coutanceau et al. found several structural similarities between mycolactone—a lipid toxin produced by the bug—and known immune-suppressive drugs, and postulated that the toxin might function as an immune modulator. They now find that mycolactone hinders the DCs that drive T cell activation. The toxin prevented skin-derived DCs from migrating to the draining lymph nodes and blood-derived DCs from acquiring their usual antigen-presenting and chemokine-secreting functions. But why the toxin initially allows the primary immune response to occur and how it hobbles DCs after ulcers form are still unclear.

Other mycobacteria, such as the bug that causes tuberculosis, secrete related biologically active lipids. Some of them target macrophages and inhibit the production of inflammatory cytokines, not chemokines. The team is now investigating the structural and molecular basis of this difference in toxin function.