tbuckley/cabot-search huggingface dataset:
Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy.
Authors: D L Longo, P L Duffey, E S Jaffe, M Raffeld, S M Hubbard, R I Fisher, R E Wittes, V T DeVita, R C Young
Journal: Journal of Clinical Oncology (1994)

PURPOSE To review the efficacy of cyclophosphamide, doxorubicin, etoposide, methotrexate with leucovorin, and prednisone (ProMACE)-based combination chemotherapy programs in the treatment of patients with diffuse small noncleaved-cell non-Burkitt's lymphoma. PATIENTS AND METHODS Thirty-three patients with diffuse small noncleaved-cell non-Burkitt's lymphoma were accrued: eight with localized disease were treated with modified ProMACE-mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus involved-field radiation therapy, and 25 with advanced-stage disease were treated with ProMACE/MOPP flexitherapy (n = 8), ProMACE-MOPP (n = 9), or ProMACE-cytarabine, bleomycin, vincristine, and methotrexate with leucovorin (CytaBOM) (n = 8). The median follow-up duration is 10 years. RESULTS All eight patients with localized disease achieved a complete response, none have relapsed, and one died of intercurrent illness. Among patients with advanced-stage disease, five of eight (63%) flexitherapy-treated patients, six of nine (67%) ProMACE-MOPP-treated patients, and eight of eight (100%) ProMACE-CytaBOM-treated patients achieved a complete response. If the two ProMACE-MOPP-based groups are considered together, disease-free and overall survival rates at 15 years are projected at 61% and 35%, respectively. In contrast, only one patient has relapsed from a ProMACE-CytaBOM-induced complete remission, and overall survival of ProMACE-CytaBOM-treated patients (88%) is significantly higher than that for flexitherapy and ProMACE-MOPP (P2 = .04). CONCLUSION Adult patients with diffuse small non-cleaved-cell non-Burkitt's lymphoma may be effectively treated with regimens that are effective in other aggressive lymphomas (eg, diffuse large-cell lymphoma).
IL-17A expression by mast cells in smokers
Authors: Yvonne Nussbaumer-Ochsner, Luiz F. Ferraz da Silva, Klaus F. Rabe, Annemarie M. van Schadewijk, Thais Mauad, Pieter S. Hiemstra
Journal: European Respiratory Journal (2011)

Background:  Mast cells are increasingly recognized as important contributors to smoking-induced inflammation. IL-17A is a cytokine produced by inflammatory cells which promotes neutrophilic inflammation. We evaluated whether IL-17A is expressed by mast cells in the airways of smokers.   Methods:  Immunohistochemical staining was performed in large (LA) and small (SA) airways from 12 (ex-) smokers undergoing lung cancer resection. In airways free of tumour a double staining protocol was used for the simultaneous visualization of mucosal (MC T , positive for the protease tryptase) and connective tissue (MC TC , positive for the proteases chymase and tryptase) mast cells as well as for IL-17A and MC T  resp. MC TC . Image analysis was performed using spectral microscopy. Values are expressed as cells/BM length for inner and outer layers.   Results:  See Table 1.   Conclusion:  A marked proportion of mast cells in LA and SA of smokers express IL-17A. High expression of IL-17A was observed in both MC T  and MC TC , and mast cells situated in the outer layer. These findings suggest that mast cells contribute to inflammation in LA and SA via IL-17A expression.
Antibodies to outer root sheath of hair
Authors: J. H. SAURAT, LILIANE DIDIERJEAN
Journal: British Journal of Dermatology (1980)

SUMMARY By screening 1500 sera obtained from patients undergoing a bone marrow graft, five sera have been selected which contained antibodies to the basal cell layer (B. C. L.) of the outer root sheath (O. R. S.) of hair follicles. It was demonstrated that these sera reacted with the B. C. L. of the O. R. S. but not with the B. C. L. of the adjacent epidermis. The change in antigenic properties was situated at the orifice of the sebaceous gland canal; thus basal cells below this orifice express an antigen distinct from those expressed by the epidermal basal cells. This is a novel example of tissue specific differentiation antigens that are linked to the type of keratinocyte differentiation.
The challenge of safer prescribing
Authors: Anne Spinewine
Journal: BMJ (2008)

Doctors should pay greater attention to managing the risk-benefit relationship to improve care of patients over 65, urge <b>Jerry Avorn</b> and <b>William Shrank</b> (doi: 10.1136/bmj.39520.671053.94). The challenge of safer prescribing, says <b>Anne Spinewine</b>, lies in shared decision making
Abstract 5131: The Healthy Habits Trials: Positive affect induction improves medication adherence in hypertensive African Americans
Authors: Gbenga O Ogedegbe, Carla Boutin-Foster, Martin T Wells, John P Allegrante, Jared B Jobe, Mary E Charlson
Journal: Circulation (2008)

Poor medication adherence is a significant problem in hypertensive African Americans and leads to disproportionately higher blood pressure (BP) and poor health outcomes. This randomized controlled ...
Antibody Response to Related Leukosis Viruses Induced in Chickens Tolerant to an Avian Leukosis Virus2
Authors: Paul Meyers
Journal: JNCI Journal of the National Cancer Institute (1976)

White Leghorn chickens congenitally infected with a subgroup A avian leukosis virus ALV-F42 were challenged at various ages with the serologically related subgroup A avian leukosis viruses (ALV) RAV-1, RAV-3, and RAV-5 and their antibody responses and viremic status determined. Birds given injections of RAV-1 failed to produce neutralizing antibody to any of the pseudotype sarcoma viruses of the various ALV, whereas many birds challenged with RAV-3 or RAV-5 produced neutralizing antibody directed against the heterologous RAV-1 as well as the homologous viruses, but not against the tolerated virus ALV-F42. Virtually all birds remained viremic despite the presence of neutralizing antibody. The results suggested that a phenomenon akin to circumvention or abrogation of tolerance to ALV-F42 was effected, and that there are multiple determinants of the viral envelope antigens of ALV as measured by neutralization.
ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines.
Authors: David A Weaver, Erin L Crawford, Kristy A Warner, Fadel Elkhairi, Sadik A Khuder, James C Willey
Journal: Molecular Cancer (2005)

Although 40-50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 beta-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.Following validation, single variable models best correlated with chemoresistance (p < 0.001), were ERCC2/XPC, ABCC5/GTF2H2, ERCC2/GTF2H2, XPA/XPC and XRCC1/XPC. All single variable models were examined hierarchically to achieve two variable models. The two variable model with the highest correlation was (ABCC5/GTF2H2, ERCC2/GTF2H2) with an R2 value of 0.96 (p < 0.001).These results provide markers suitable for assessment of small fine needle aspirate biopsies in an effort to prospectively identify cisplatin resistant tumors.
Activity of Carcinogens, Carcinogen Analogs, and Metabolic Inhibitors in the Lymphocyte Tritiated Thymidine Assay&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J R Warren, J W Summerville
Journal: JNCI Journal of the National Cancer Institute (1980)

Inhibition of tritiated thymidine ([3H]dThd) incorporation into replicating DNA of concanavalin A (Con A)-stimulated C57BL/6J splenic lymphocytes has been further evaluated as an end point for rapid in vitro discrimination between carcinogenic and noncarcinogenic chemicals. Results of this evaluation include: a) Inhibition of [3H]dThd incorporation into DNA of Con A-stimulated cells clearly discriminated between known DNA-damaging chemical carcinogens (N-methyl-N-nitrosourea, 4-nitroquinoline 1-oxide, 4-(hydroxyamino)quinoline 1-oxide, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and benz[a]anthracene) and non-DNA-damaging metabolic inhibitors of replication (dimethyl sulfoxide, ethanol, hydroxyurea, cycloheximide, potassium cyanide, and oligomycin). b) Inhibition of [3H]dThd incorporation also discriminated between carcinogens and noncarcinogens in the two pairs 4-nitroquinoline 1-oxide versus quinoline-N-oxide, and benzo[a]pyrene versus pyrene. c) Inhibition of [3H]dThd incorporation did not quantitatively discriminate between the structurally related strong carcinogen dimethylbenz[a]anthracene, the weak carcinogen benz[a]anthracene, and the equivocal carcinogens anthracene and phenanthrene. d) Inhibition of [3H]dThd incorporation was not a sensitive in vitro end point for the carcinogenic hypolipidemic drug 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14,643).
Randomized trial of observation versus adjuvant therapy with cyclophosphamide, fluorouracil, prednisone with or without tamoxifen following mastectomy in postmenopausal women with node-positive breast cancer.
Authors: J N Ingle, L K Everson, H S Wieand, J K Martin, H J Votava, L E Wold, J E Krook, S A Cullinan, J K Paulsen, D I Twito
Journal: Journal of Clinical Oncology (1988)

Following mastectomy for node-positive breast cancer, 261 postmenopausal women were randomized to observation or adjuvant treatment with cyclophosphamide, fluorouracil, prednisone (CFP) alone or combined with tamoxifen (T). Doses used were: C, 150 mg/m2 intravenously (IV) days 1 to 5; F, 300 mg/m2 IV days 1 to 5; P, 10 mg by mouth 3 times daily on days 1 to 7; and T, 10 mg by mouth 2 times daily. A total of ten courses of treatment, administered every 6 weeks, was planned and T was stopped 6 weeks after the last course of CFP. Two hundred thirty-four patients were fully eligible and evaluable. With a median observation time slightly in excess of 5 years, the proportion of recurrences on each arm were: CFP, 29 of 75 (39%); CFPT, 29 of 71 (41%); and observation, 50 of 88 (57%). Relapse-free survival distributions for both CFP and CFPT were superior to observation (both two-sided P = .01). Considering prognostic factors in covariate analysis revealed two-sided P = .0006 for CFP v observation and P = .0003 for CFPT v observation. No substantial difference was identified between CFP and CFPT. Survival data are not yet mature with 31% dead; and, although slight separations of the curves exist in favor of the treatment arms, no significant differences in survival have been seen. Both adjuvant therapy programs are well tolerated and there were no treatment-related deaths. Further maturation of the data is required to determine if the advantages in relapse-free survival will be translated into any overall survival benefit which must be considered the goal of primary interest.
Natural killer cells regulate T cell immune responses in primary biliary cirrhosis
Authors: Shinji Shimoda, Satomi Hisamoto, Kenichi Harada, Sho Iwasaka, Yong Chong, Minoru Nakamura, Yuki Bekki, Tomoharu Yoshizumi, Ken Shirabe, Toru Ikegami, Yoshihiko Maehara, Xiao‐Song He, M. Eric Gershwin, Koichi Akashi
Journal: Hepatology (2015)

The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T- and B-cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver-derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)-γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4(+) T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN-γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN-γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4(+) T cells to become cytopathic.NK cell-mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen-specific T cells, essential for progression of disease.
Protective effects of inhaled ipratropium bromide on bronchoconstriction induced by adenosine and methacholine in asthma
Authors: N Crimi, F Palermo, R Oliveri, R Polosa, I Settinieri, A Mistretta
Journal: European Respiratory Journal (1992)

Although adenosine-induced bronchoconstriction is mainly due to mast cell mediator release, vagal reflexes have also been implicated in this response. We have investigated the effect of a specific muscarinic-receptor antagonist, ipratropium bromide, on methacholine- and adenosine-induced bronchoconstriction in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Airway response was evaluated as forced expiratory volume in one second (FEV1). Inhaled ipratropium bromide (40 micrograms), administered 20 min prior to bronchoprovocation, increased the provocation dose of inhaled methacholine and adenosine required to reduce FEV1 by 20% from baseline (PD20) from 0.11 to 0.79 mg (p less than 0.01) and from 0.57 to 1.27 mg (p less than 0.01), respectively. The mean baseline FEV1 values after administration of ipratropium bromide were significantly higher than after placebo administration (p less than 0.05). However, there was no correlation between the degree of bronchodilatation and dose-ratios for methacholine and adenosine. The findings of the present study implicate vagal reflexes in the bronchospastic response induced by inhaled adenosine in asthma.
Effect of an allergy prevention programme on incidence of atopic symptoms in infancy
Authors: S. Halken, A. Høst, L.G. Hansen, O. Østerballe
Journal: Allergy (1992)

A total of 105 "high-risk" infants born in 1988 were studied prospectively from birth to 18 months of age. The infants were recommended breastfeeding and/or hypoallergenic formula (Nutramigen or Profylac) combined with avoidance of solid foods during the first 6 months of life. All mothers had unrestricted diet. Avoidance of daily exposure to tobacco smoke, furred pets and dust-collecting materials in the bedroom were advised. This prevention group was compared with a control group consisting of 54 identically defined "high-risk" infants born in 1985 in the same area. All infants had either severe single atopic predisposition combined with cord blood IgE > or = 0.5 KU/l or biparental atopic predisposition. The control group had unrestricted diet and was not advised about environmental factors. Apart from the prevention programme and year of birth the prevention group and the control group were comparable. The parents were highly motivated and compliance was good. The rate of participation was 97%, and 85% followed the dietary measures strictly. The cumulative prevalence of atopic symptoms was significantly lower at 18 months in the prevention group (32%), as compared with the control group (74%) (p < 0.01), due to reduced prevalence of recurrent wheezing (13% versus 37%; p < 0.01), atopic dermatitis (14% versus 31%; p < 0.01), vomiting/diarrhoea (5% versus 20%; p < 0.01) and infantile colic (9% versus 24%; p < 0.01). The cumulative prevalence of food allergy was significantly lower in the prevention group (6% versus 17%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Relationship between snoring with sleep behavioral and movement disturbance (SBMD) in children
Authors: Abolfazl Mozafari, Mohammad Vakil Aliabadi, Hossein Ghasemi
Journal: European Respiratory Journal (2012)

Background: sleep disturbance is one of the most important subjects in pediatric medicine which its prevalence is 5% in society and have many important effects on child social function and quality of life. Sleep disturbance is seen in different kind of sign and symptom such as night terror, leg movement, walking and go to bed lately. Snoring prevalence is 12% in children that is one of the important reasons of sleep disturbance.  Methods: We have chosen 100 children with snoring as study group and 100 healthy children as control group. Their parents fill the questions about snoring and 22 item of SBMD like sleep walking, sleep talking, night terror. Pearson correlation coefficient was used to measure the strength of association between continuous variables. For analysis of qualitative parameters, we use from chi-square and if it was required, checked by fisher9s exact test.  Result: The mean age of children was 6/8 years, mean height 116 cm, 41% were overweight or fatty and 52% were male. There were significant correlation among SBMD in case and control (8.54 vs 5.64 item, p  Conclusion: This study have showed the importance of sleep medicine in children we can prevent children from many sleep disturbance with on time diagnosis of snoring. It is important that we educated sleep subject to parents for helping to achieve better sleep in children.
The nitration mediated inhibition of Rac1 is involved in the endothelial barrier dysfunction induced by lipopolysaccharide
Authors: Christine Gross, Ruslan Rafikov, Saurabh Aggarwal, Yali Hou, Stephen Black
Journal: European Respiratory Journal (2011)

Lipopolysaccaharide (LPS) induced acute lung injury (ALI) is a respiratory condition characterized by alveolar epithelial and endothelial cell damage resulting in increased lung leak. Recent studies have shown that protein nitration plays a key role in the endothelial barrier dysfunction in LPS exposed mice. The molecular mechanisms involved in this process are not well understood. Immunoprecipitation analyses, using human lung microvascular endothelial cells, demonstrated that LPS mediates an increase in Rac1 nitration and a decrease in activity which were attenuated by the cell-permeant peroxynitrite scavenger, manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP). Utilizing mass spectroscopy, we found that LPS induces a single tyrosine nitration in human Rac1 located at amino acid 32 (Y32). The crystal structure analysis of Rac1 indicated that Y32 lies adjacent to the nucleotide-binding site within Switch I, a region known to modulate GTP/GDP binding. Molecular dynamic simulations predicted the nitration of Y32 of Rac1 would preferentially stabilize the closed conformation of Switch I. To test this prediction, we utilized stopped-flow analysis to measure changes in GDP and GTP binding and found that the nitration of Y32 did not alter GTP binding, but enhanced GDP binding to Rac1. LPS also induced Rac1 nitration and decreased Rac1 activity in the mouse lung. These changes were attenuated in mice pretreated with MnTMPyP. Lung permeability studies using Evans blue dye showed that peroxynitrite scavenging decreased LPS induced lung leak. We conclude that agents that prevent Rac1 nitration may have clinical importance in the management of ALI.
Thymidine Kinase as a Proliferative Marker: Clinical Relevance in 1,692 Primary Breast Cancer Patients
Authors: P. Broët, S. Romain, A. Daver, G. Ricolleau, V. Quillien, A. Rallet, B. Asselain, P.M. Martin, F. Spyratos
Journal: Journal of Clinical Oncology (2001)

To assess the prognostic value of thymidine kinase (TK), an enzyme involved in the DNA synthesis salvage pathway, relative to other prognostic factors in primary breast cancer.This retrospective study involved 1,692 patients with operable breast cancer treated in six institutions (median follow-up, 82 months). Among the 857 node-negative patients, 135 received adjuvant chemotherapy (fluorouracil, doxorubicin, cyclophosphamide [FAC] or fluorouracil, etoposide, and cisplatin [FEC]). TK was assayed in cytosol with a quantitative radioenzymatic technique. Disease-specific survival (DSS), local recurrence-free interval (LRI), and distant-relapse-free interval (DRI) were investigated.High TK levels were associated with large tumor size, high histologic grade, and steroid hormone receptor negativity. Univariate analysis of the entire data set showed that high TK levels were related to shorter DSS (P < 10(-5)), LRI (P < 10(-3)), and DRI (P < 10(-5)). In time-dependent Cox models, high TK levels remained an independent predictor of the three outcomes, both in the overall population and in node-negative patients, although its prognostic value decreased over time. In node-negative patients, the introduction of an interaction term in multivariate analysis suggested that chemotherapy was more efficacious for patients who had tumors with high TK contents. In node-positive patients, high TK levels were related only to an increased risk of LRI.High TK values are an important risk factor in node-negative patients and seem to be associated with a beneficial effect of adjuvant FAC or FEC in patients who received adjuvant chemotherapy. The rationale of chemotherapy for patients with slowly proliferating tumors has to be discussed from a risk-benefit point of view.