tbuckley/cabot-search huggingface dataset:
CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection.
Authors: R Manetti, F Annunziato, R Biagiotti, M G Giudizi, M P Piccinni, L Giannarini, S Sampognaro, P Parronchi, F Vinante, G Pizzolo, E Maggi, S Romagnani
Journal: The Journal of Experimental Medicine (1994)

A large panel of CD8+ T cell clones generated from peripheral blood lymphocytes (PBL) of healthy donors or human immunodeficiency virus (HIV)-infected individuals were assessed for both cytokine secretion profile and CD30 expression and release. The great majority of CD8+ T cell clones generated from healthy individuals showed the ability to produce interferon gamma (IFN-gamma), but not interleukin 4 (IL-4), and none of them either expressed membrane CD30 or released substantial amounts of soluble CD30 (sCD30) in their supernatant. In contrast, high numbers of CD8+ T cell clones generated from HIV-infected individuals, which produced IL-4 (and IL-5) in addition to IFN-gamma or IL-4 (and IL-5) alone, expressed membrane CD30 and released detectable amounts of sCD30 in their supernatants. Indeed, CD30 expression appeared to be positively correlated with the ability of CD8+ T cell clones to produce IL-4 and IL-5 and inversely correlated with their ability to produce IFN-gamma, whereas no correlation between CD30 expression and production of IL-10 was observed. These data suggest that CD30 is a marker for CD8+ T cells that have switched to the production of type 2 helper cytokines.
1049 AD-MMP8 ADMINISTRATION IN SKELETAL MUSCLE DECREASED THE FIBROSIS PERCENTAGE, TGF-B, COL-1 AND CTGF IN EXPERIMENTAL LIVER FIBROSIS
Authors: E. Oceguera-Contreras, D. Gordillo-Bastidas, A.S. Sandoval-Rodriguez, J.J. Garcia-Bañuelos, J. Armendáriz-Borunda
Journal: Journal of Hepatology (2011)
A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)
Authors: Clive Ballard, Marisa Margallo Lana, Megan Theodoulou, Simon Douglas, Rupert McShane, Robin Jacoby, Katja Kossakowski, Ly-Mee Yu, Edmund Juszczak
Journal: PLoS Medicine (2008)

Background There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease. Methods and Findings Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial. Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom. Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo. Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo. Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI). Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment. Conclusions For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy. Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).
INDUCTION OF B CELL TOLERANCE IN VITRO TO 2,4-DINITROPHENYL COUPLED TO A COPOLYMER OF <scp>D</scp>-GLUTAMIC ACID AND <scp>D</scp>-LYSINE (DNP-<scp>D</scp>-GL)
Authors: G. J. V. Nossal, Beverley L. Pike, David H. Katz
Journal: The Journal of Experimental Medicine (1973)

Spleen cells from CBA or congenitally athymic ("nude") mice were pretreated with various concentrations of DNP coupled to a copolymer of D-glutamic acid and D-lysine (DNP(37)-D-GL), under various conditions of time and temperature. After washing, they were then cultured for 3 days with the direct B cell immunogen, DNP coupled to Salmonella adelaide flagella (DNP-FLA). Under all circumstances tried, exposure of cells to 1 microg/ml DNP-D-GL caused a 70-100% depression in the subsequent DNP-specific PFC response, and 100 ng/ml caused a lesser but still substantial effect. At the concentrations used, DNP-D-GL did not affect irrelevant antibody responses. Though cells from nude mice responded somewhat less well to DNP-FLA than those from CBA mice, no significant difference in the reaction of the two populations to the tolerogen was noted. This demonstrates that DNP-D-GL can, as previously suspected, directly cause unresponsiveness in B lymphocytes.
CUTIS VERTICIS GYRATA.*
Authors: M. G. HANNAY
Journal: British Journal of Dermatology (1923)

Journal Article CUTIS VERTICIS GYRATA. Get access M. G. HANNAY, M.D., M.R.C.P. M. G. HANNAY, M.D., M.R.C.P. Physician, St. John's Hospital for Diseases of the Skin Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 35, Issue 12, 1 December 1923, Pages 451–454, https://doi.org/10.1111/j.1365-2133.1923.tb09076.x Published: 01 December 1923
Metabolic effect of 3,3',5'-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells. Evidence for a unique mechanism of thyroid hormone action.
Authors: D L St Germain
Journal: Journal of Clinical Investigation (1985)

Physiologic levels of 3,3',5'-triiodothyronine (rT3) are generally believed to have minimal metabolic effects in the pituitary gland and other tissues. In the present studies, the regulatory role of rT3 and other thyroid hormones on iodothyronine 5'-deiodinase (I5'D) activity was studied in a growth hormone-producing rat pituitary tumor cell line (GH3 cells). I5'D activity was thiol-dependent and displayed nonlinear reaction kinetics suggesting the presence of two enzymatic processes, one having a low Michaelis constant (Km for thyroxine [T4] of 2 nM) and a second with a high Km value (0.9 microM). Growth of cells in hormone-depleted medium resulted in a two- to 3.5-fold increase in low Km I5'D activity (P less than 0.001). The addition of thyroid hormones to the culture medium resulted in a rapid, dose-dependent inhibition of low Km I5'D activity with the following order of analogue potency: rT3 greater than or equal to T4 greater than 3,5,3'-triiodothyronine (T3). Using serum-free culture conditions, rT3 was approximately 50 times more active than T3. These inhibitory effects were noted within 15 min of hormone addition and could not be attributed to substrate competition with T4. These findings suggest that the control of T4 to T3 conversion by thyroid hormones in the anterior pituitary gland is mediated by a unique cellular mechanism that is independent of the nuclear T3 receptor; and under some circumstances, rT3 may play a regulatory role in controlling this enzymatic process.
Heat Shock Protein 27 Protects L929 Cells from Cisplatin-Induced Apoptosis by Enhancing Akt Activation and Abating Suppression of Thioredoxin Reductase Activity
Authors: Yong Zhang, Xun Shen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Heat shock protein 27 (Hsp27) is up-regulated in multiple malignancies and implicated in cisplatin resistance. It is attempted to know how Hsp27 endues cell with cisplatin resistance by interfering with upstream of both apoptosis signal–regulating kinase 1 (ASK1)/p38 mitogen-activated protein kinase–activated apoptotic signaling and serine/threonine kinase Akt-dependent survival signaling. Experimental Design: The mouse L929 cells stably transfected with human Hsp27 or its dominant-negative mutant and the human cervical cancer HeLa cells transfected with Hsp27 siRNA were used. The cisplatin-induced apoptosis and activation of ASK1, p38, and Akt were compared in control cells, cells overexpressing Hsp27, and cells with their endogenous Hsp27 knocked down. Results: Hsp27 effectively protected the cells from cisplatin-induced DNA fragmentation. The p38 inhibitors obviously decreased whereas Akt inhibitors markedly increased the apoptotic fraction in cisplatin-treated cells. Overexpression of Hsp27 doubly enhanced the drug-induced Akt activation while substantially depressing the drug-induced activation of ASK1 and p38. Knockdown of the endogenous Hsp27 in HeLa cells resulted in the effects opposite to that observed in the Hsp27-overexpressing cells. Enhancement of Akt activation is associated with complex formation between Akt and Hsp27, whereas depression of ASK1/p38 activation is attributed to a reversion of the drug-induced inhibition of thioredoxin reductase activity and subsequent oxidation of thioredoxin. Conclusions: Hsp27 endues cells with cisplatin resistance via depression of the drug-induced ASK1/p38 activation and enhancement of the drug-induced Akt activation. This study revealed the intervention of Hsp27 in upstream of both ASK1/p38 apoptotic signaling and phosphatidylinositol 3-kinase/Akt survival signaling. Therefore, the inhibition of Hsp27 may be a novel strategy of cancer chemotherapy.
TCT-50 Influence of Age on Clinical Outcomes in Patients with NSTEMI Undergoing Treatment with Abciximab plus Unfractionated Heparin vs. Bivalirudin: Analysis of the ISAR React 4 Study
Authors: Lamin King, Lamin King, Oltjon Albajrami, Robert Byrne, Salvatore Cassese, Tomohisa Tada, Julinda Mehilli, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2012)
In vitro generation of procoagulant activity by leukemic promyelocytes in reponse to cytotoxic drugs
Authors: Eitan Fibach, Aliza Treves, Avraham Korenberg, Eliezer A. Rachmilewitz
Journal: American Journal of Hematology (1985)

Disseminated intravascular coagulation (DIC) is a frequent occurrence in acute promyelocytic leukemia (APL), especially after onset of chemotherapy. We have used a human promyelocytic leukemic established cell line (HL-60) and various other human leukemic cells to investigate the effect of cytotoxic drugs on generation of procoagulant activity (PCA). The results indicate that, unlike normal human peripheral blood monocytes and certain other cell types where PCA induction requires active mRNA and protein synthesis, in HL-60 cells, compounds such as actinomycin D, puromycin, and cytosine arabinoside and a variety of other cytotoxic agents, induced generation of a potent PCA. Although different in its mechanism of induction, this HL-60 cell PCA was similar, and may be identical, to mononuclear cell tissue factor. The PCA induction was rapid and preceded the lytic effect of the drugs. It was first detected on the outer cell surface but, following prolonged exposure to the drugs, upon lysis of the cells, it was also found in the extracellular medium. This in vitro effect mimics the development of DIC in patients with APL. The system may, therefore, serve as a model for the study of the cellular and molecular events associated with PCA generation by malignant promyelocytes and DIC occurrence in patients with APL and other malignancies.
Updated Data on Clinical and Molecular Profile of Surgically Resected Small Cell Lung Cancer: Intergroup Study with Fight002 and Hot1301
Authors: Y. Fujita, H. Yokouchi, H. Nishihara, T. Ishida, H. Suzuki, H. Uramoto, S. Yamazaki, H. Kikuchi, K. Akie, F. Sugaya, K. Takamura, M. Harada, T. Harada, M. Higuchi, M. Maemondo, O. Honjo, H. Akita, H. Isobe, M. Nishimura, M. Munakata
Journal: Annals of Oncology (2014)
The Dorset Get-Fit Campaign--community fitness testing programme.
Authors: D Nutbeam, J Catford
Journal: British Journal of Sports Medicine (1985)

A pilot programme promoting fitness and exercise was launched through the local media in the Bournemouth area. The aim was to study the feasibility and effectiveness of a fitness testing programme as a trigger to increase exercise participation. Three hundred and eighty adult volunteers (male and female, all ages) undertook a sub-maximal fitness test and were given advice on exercise and diet by trained counsellors. Two hundred and eighty-five (75%) completed a second, follow-up fitness test, four months later. The results were very encouraging. Almost all of those classified as being unfit at the first test had exercised more frequently and made great improvements in physical fitness by the second test (p less than 0.01). Similarly, most of those who were overweight made substantial weight reductions during the course of the campaign (p less than 0.01). The majority of the group also made important changes in their diet. There appears to be sufficient interest in the general population to recruit people of all ages and fitness levels to join in fitness promotion programmes, but drop-out rates may be appreciative. On the basis of these findings it is proposed that fitness testing is an acceptable and helpful trigger to increased physical activity for both males and females of all ages. Such an increase in exercise appears to result in important improvements in fitness and, in combination with dietary modification, favourable reductions in weight. Further work should now be conducted in the form of controlled trials to compare the costs and effectiveness of fitness testing programmes with other methods of raising exercise levels in the community.
The Drosophila Alcohol Dehydrogenase Gene May Have Evolved Independently of the Functionally Homologous Medfly, Olive Fly, and Flesh Fly Genes
Authors: Saverio Brogna, Panayiotis V. Benos, Giuliano Gasperi, Charalambos Savakis
Journal: Molecular Biology and Evolution (2001)

cDNAs for alcohol dehydrogenase (ADH) isozymes were cloned and sequenced from two tephritid fruit flies, the medfly Ceratitis capitata and the olive fly Bactrocera oleae. Because of the high sequence divergence compared with the Drosophila sequences, the medfly cDNAs were cloned using sequence information from the purified proteins, and the olive fly cDNAs were cloned by functional complementation in yeast. The medfly peptide sequences are about 83% identical to each other, and the corresponding mRNAs have the tissue distribution shown by the corresponding isozymes, ADH-1 and ADH-2. The olive fly peptide sequence is more closely related to medfly ADH-2. The tephritid ADHs share less than 40% sequence identity with Drosophila ADH and ADH-related genes but are >57% identical to the ADH of the flesh fly Sarcophaga peregrina, a more distantly related species. To explain this unexpected finding, it is proposed that the ADH: genes of the family Drosophilidae may not be orthologous to the ADH: genes of the other two families, Tephritidae and Sarcophagidae.
Phase I Pharmacokinetic-Pharmacodynamic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (17AAG, NSC 330507), a Novel Inhibitor of Heat Shock Protein 90, in Patients with Refractory Advanced Cancers
Authors: Ramesh K. Ramanathan, Donald L. Trump, Julie L. Eiseman, Chandra P. Belani, Sanjiv S. Agarwala, Eleanor G. Zuhowski, Jing Lan, Douglas M. Potter, S. Percy Ivy, Sakkaraiappan Ramalingam, Adam M. Brufsky, Michael K.K. Wong, Susan Tutchko, Merrill J. Egorin
Journal: Clinical Cancer Research (2005)

17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a benzoquinone antibiotic, down-regulates oncoproteins by binding specifically to heat shock protein 90 (HSP90). We did a phase I study of 17AAG to establish the dose-limiting toxicity and maximum tolerated dose and to characterize 17AAG pharmacokinetics and pharmacodynamics.Escalating doses of 17AAG were given i.v. over 1 or 2 hours on a weekly x 3 schedule every 4 weeks to cohorts of three to six patients. Plasma pharmacokinetics of 17AAG and 17-(amino)-17-demethoxygeldanamycin (17AG) were assessed by high-performance liquid chromatography. Expression of HSP70 and HSP90 in peripheral blood mononuclear cells was measured by Western blot.Forty-five patients were enrolled to 11 dose levels between 10 and 395 mg/m2. The maximum tolerated dose was 295 mg/m2. Dose-limiting toxicity occurred in both patients (grade 3 pancreatitis and grade 3 fatigue) treated with 395 mg/m2. Common drug-related toxicities (grade 1 and 2) were fatigue, anorexia, diarrhea, nausea, and vomiting. Reversible elevations of liver enzymes occurred in 29.5% of patients. Hematologic toxicity was minimal. No objective responses were observed. 17AAG pharmacokinetics was linear. Peak plasma concentration and area under the curve of 17AG, the active major metabolite of 17AAG, increased with 17AAG dose, but the relationships were more variable than with 17AAG. 17AAG and 17AG in plasma were >90% protein bound. There were no consistent changes in peripheral blood mononuclear cell HSP90 or HSP70 content.17AAG doses between 10 and 295 mg/m2 are well tolerated. 17AAG pharmacokinetics is linear. Peripheral blood mononuclear cell HSP90 and HSP70 are uninformative pharmacodynamic markers. The dose recommended for future studies is 295 mg/m2 weekly x 3, repeated every 4 weeks.
Pulmonary hypertension in chronic obstructive pulmonary disease: current theories of pathogenesis and their implications for treatment
Authors: J L Wright
Journal: Thorax (2005)

The development of pulmonary hypertension is a poor prognostic sign in patients with chronic obstructive pulmonary disease (COPD), affecting both mortality and quality of life. Although pulmonary hypertension in COPD is traditionally viewed as a result of emphysematous destruction of the vascular bed and/or hypoxia, recent studies indicate that neither of these factors correlates very well with pulmonary artery pressures. New human and animal experimental data are beginning to show that pulmonary hypertension in this setting is probably a result of the direct effect of tobacco smoke on the intrapulmonary vessels with abnormal production of mediators that control vasoconstriction, vasodilatation, and vascular cell proliferation, ultimately leading to aberrant vascular remodelling and aberrant vascular physiology. These changes are in many ways similar to those seen in other forms of pulmonary hypertension and suggest that the treatments used for primary pulmonary hypertension may be beneficial in patients with COPD.
ARTIFICIAL KIDNEY FUNCTION: KINETICS OF HEMODIALYSIS 1
Authors: A. V. Wolf, Donald G. Remp, John E. Kiley, Gordon D. Currie
Journal: Journal of Clinical Investigation (1951)

Y: velocity constant of excretion for natural kidneys; equal to C/b for no-threshold substances D: dialysance, equal to uU/(A-U) d: relative dialysance, equal to Dx
Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis.
Authors: B L McRae, C L Vanderlugt, M C Dal Canto, S D Miller
Journal: The Journal of Experimental Medicine (1995)

The role of epitope spreading in the pathology of relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) was examined. Using peripherally induced immunologic tolerance as a probe to analyze the neuropathologic T cell repertoire, we show that the majority of the immunopathologic reactivity during the acute phase of R-EAE in SJL/J mice induced by active immunization with the intact proteolipid (PLP) molecule is directed at the PLP139-151 epitope and that responses to secondary encephalitogenic PLP epitopes may contribute to the later relapsing phases of disease. Intermolecular epitope spreading was demonstrated by showing the development of T cell responses to PLP139-151 after acute disease in mice in which R-EAE was initiated by the transfer of T cells specific for the non-cross-reactive MBP84-104 determinant. Intramolecular epitope spreading was demonstrated by showing that endogenous host T cells specific for a secondary encephalitogenic PLP epitope (PLP178-191) are demonstrable by both splenic T cell proliferative and in vivo delayed-type hypersensitivity responses in mice in which acute central nervous system damage was initiated by T cells reactive with the immunodominant, non-cross-reactive PLP139-151 sequence. The PLP178-191-specific responses are activated as a result of and correlate with the degree of acute tissue damage, since they do not develop in mice tolerized to the initiating epitope before expression of acute disease. Most importantly, we show that the PLP178-191-specific responses are capable of mediating R-EAE upon adoptive secondary transfer to naive recipient mice. Furthermore, induction of tolerance to intact PLP (which inhibits responses to both the initiating PLP139-151 epitope and to the PLP178-191 epitope) after the acute disease episode is sufficient to prevent relapsing disease. These results strongly support a contributory role of T cell responses to epitopes released as a result of acute tissue damage to the immunopathogenesis of relapsing clinical episodes and have important implications for the design of antigen-specific immunotherapies for the treatment of chronic autoimmune disorders in humans.
Research and its governance in health research institutions in sub-Saharan African countries: results of a questionnaire-based survey
Authors: Derege Kebede, Chris Zielinski, Peter Ebongue Mbondji, Issa Sanou, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

Summary Objective: To describe governance and stewardship of research in health research institutions in the World Health Organization (WHO) African Region. Design: A structured questionnaire was used to solicit information on governance and stewardship from health research institutions. Setting: Forty-two Member States of the WHO African Region. Participants: Key informants from the respondent health research institutions in the respondent sub-Saharan African countries. Main outcome measures: Institutions’ participation in setting the national health research agenda. Institutional research priorities, scientific reviews and governance structure. Results: During the previous 12 months, the heads of 49% of respondent health research institutions participated in the setting or coordination of national research priorities. The most frequently cited priorities for contributing to or performing research were improving health programmes, producing new knowledge, influencing health policies and conducting operational research. For 78% of respondent institutions, scientific review was required for research funded directly by the institution, and for 73% of respondent institutions, scientific review was required for research not funded by the institution. However, most respondent institutions did not have written policies or guidelines, either for the scientific review of proposals (70%) or regarding conflict of interest on scientific review committees (80%). Conclusions: Some health research institutions demonstrate good practice in terms of the establishment of structures and processes for governance and stewardship, many others do not. There is a need for the strengthening of the stewardship capacity of research institutions in the Region.