tbuckley/cabot-search huggingface dataset:
Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphomas: an epidemiological observational multicentre study. The Spanish Working Group on Cutaneous Lymphoma
Authors: Y. Peñate, B. Hernández-Machín, L.I. Pérez-Méndez, F. Santiago, B. Rosales, O. Servitje, T. Estrach, M. Fernández-Guarino, L. Calzado, E. Acebo, F. Gallardo, A. Salar, R. Izu, P.L. Ortiz-Romero, R.M. Pujol, R. Fernández-de-Misa
Journal: British Journal of Dermatology (2012)

Intravenous rituximab is a safe and effective option for the treatment of systemic non-Hodgkin B-cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B-cell lymphomas (PCBL) has been described in a small number of patients.To evaluate the effectiveness, tolerance and adverse effects of ILR in patients with follicle centre (FCL) and marginal zone (MZL) PCBL.This was an epidemiological observational multicentre study of patients with PCBL treated with ILR.Seventeen patients with MZL and 18 with FCL PCBL were included. The median number of lesions treated was two per patient. The treatment regimen used in 74% of the patients was a course of three injections in a single week at 1-month intervals. The dose per lesion and day of treatment was 10 mg in 71% of the patients. The median cumulative dose of rituximab per lesion was 60 mg (range 13-270) and per patient was 150 mg (range 20-360 mg). Complete response (CR) and partial response were achieved in 71% and 23% of patients, respectively. The median time to CR in patients who received 10 mg of ILR per lesion was 8 weeks. Similar response rates were observed in MZL and FCL. Median disease-free survival was 114·1 weeks. No parameters that significantly predicted CR were identified. Adverse reactions were recorded in 19 patients; the most frequent was localized pain at the injection site. Median follow-up was 21 months.Intralesional rituximab is a well-tolerated and effective treatment for FCL and MZL PCBL. It should be considered a useful alternative in patients with recurrent lesions and in which the sequelae of radiotherapy or surgery would be significant.
The Increase in the Number of Subunits in Eukaryotic RNA Polymerase III Relative to RNA Polymerase II Is due to the Permanent Recruitment of General Transcription Factors
Authors: R. Carter, G. Drouin
Journal: Molecular Biology and Evolution (2009)

The number of subunits of RNA polymerases (RNAPs) increases during evolution from 5 in eubacteria to 12 in archaea. In eukaryotes, which have at least three RNAPs, the number of subunits has expanded from 12 in RNA polymerase II (RNAPII) to 14 in RNA polymerase I (RNAPI) and to 17 in RNA polymerase III (RNAPIII). It was recently demonstrated that the two additional subunits found in RNAPI relative to RNAPII are homologous to TFIIF, a dimeric general transcription factor of RNAPII. Here, we extend this finding by demonstrating that four of the five RNAPIII-specific subunits are also homologous to transcription factors of RNAPII. We use the available evidence to propose an evolutionary history of the eukaryotic RNAPs and argue that the increases in the number of subunits that occurred in RNAPs I and III are due to the permanent recruitment of preexisting transcription factors.
IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell–dependent antigen
Authors: Emilie Jacque, Edina Schweighoffer, Alexander Visekruna, Stamatia Papoutsopoulou, Julia Janzen, Rachel Zillwood, David M. Tarlinton, Victor L.J. Tybulewicz, Steven C. Ley
Journal: The Journal of Experimental Medicine (2014)

The importance of IκB kinase (IKK)-induced proteolysis of NF-κB1 p105 in B cells was investigated using Nfkb1(SSAA/SSAA) mice, in which this NF-κB signaling pathway is blocked. Nfkb1(SSAA) mutation had no effect on the development and homeostasis of follicular mature (FM) B cells. However, analysis of mixed bone marrow chimeras revealed that Nfkb1(SSAA/SSAA) FM B cells were completely unable to mediate T cell-dependent antibody responses. Nfkb1(SSAA) mutation decreased B cell antigen receptor (BCR) activation of NF-κB in FM B cells, which selectively blocked BCR stimulation of cell survival and antigen-induced differentiation into plasmablasts and germinal center B cells due to reduced expression of Bcl-2 family proteins and IRF4, respectively. In contrast, the antigen-presenting function of FM B cells and their BCR-induced migration to the follicle T cell zone border, as well as their growth and proliferation after BCR stimulation, were not affected. All of the inhibitory effects of Nfkb1(SSAA) mutation on B cell functions were rescued by normalizing NF-κB activation genetically. Our study identifies critical B cell-intrinsic functions for IKK-induced NF-κB1 p105 proteolysis in the antigen-induced survival and differentiation of FM B cells, which are essential for T-dependent antibody responses.
A New Series on Molecular Medicine for Clinicians
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1994)

When I was a first-year medical student at New York University in 1950, neither the biochemistry curriculum nor the 650-page textbook we used mentioned DNA or genes. For the entire year, I studied carbohydrates, fats, and proteins; the composition of milk and urine; and energy metabolism. Molecular biology as we know it today was only a dream. In my third year, on the wards of Bellevue Hospital, clinical medicine was just as primitive as biochemistry. I inserted subcutaneous stainless-steel Southey's tubes to drain fluid from the legs of patients with cirrhosis; collected urine from one patient to recover penicillin for . . .
Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis
Authors: M. Prinz
Journal: Journal of Clinical Investigation (2006)

Inflammatory diseases of the CNS, such as MS and its animal model EAE, are characterized by infiltration of activated lymphocytes and phagocytes into the CNS. Within the CNS, activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurologic deficit. TLRs recognize microbes and are pivotal mediators of innate immunity. Within the CNS, augmented TLR expression during EAE is observed, even in the absence of any apparent microbial involvement. To determine the functional relevance of this phenomenon during sterile autoimmunity, we studied the role of different TLRs as well as their common signaling adaptor MyD88 in the development of EAE. We found that MyD88–/– mice were completely EAE resistant. Surprisingly, this protection is partly due to engagement of the CpG receptor TLR9. Restricting the MyD88 or TLR9 mutation to host radio-resistant cells, including the cells within the CNS, revealed that engagement of radio-resistant cells modulated the disease course and histopathological changes. Our data clearly demonstrate that both TLR9 and MyD88 are essential modulators of the autoimmune process during the effector phase of disease and suggest that endogenous “danger signals” modulate the disease pathogenesis.
Mutation in a new H-2-associated histocompatibility gene closely linked to H-2D.
Authors: T H Hansen, S E Cullen, R Melvold, H Kohn, L Flaherty, D H Sachs
Journal: The Journal of Experimental Medicine (1977)

Sequential precipitations of soluble BALB/c antigen with antisera detecting private and public H-2 specificities indicated three distinct classes of molecules of 45,000 mol wt. However, only two of these classes of molecules were detectable in antigen from the loss mutant, BALB/c-H-2db. The class of molecules, detectable in the wild-type strain but missing in the mutant, does not bear private specificities but does react with an antiserum detecting H-2 public specificities. Absorption in mutant mice of the antiserum to public specificities, left antibodies specific for the antigen detectable in BALB/c but not BALB/c-H-2db. Genetic mapping studies using this specific antiserum indicated that the antigenic loss of this mutant is in a gene which maps in or close to the H-2D region, separable from the H-2K, S, G, Qa-2, and Tla regions.
Stromal EGF and IGF-I Together Modulate Plasticity of Disseminated Triple-Negative Breast Tumors
Authors: Zafira Castaño, Timothy Marsh, Ramya Tadipatri, Hanna S. Kuznetsov, Fatima Al-Shahrour, Mahnaz Paktinat, April Greene-Colozzi, Björn Nilsson, Andrea L. Richardson, Sandra S. McAllister
Journal: Cancer Discovery (2013)

Abstract The causes for malignant progression of disseminated tumors and the reasons recurrence rates differ in women with different breast cancer subtypes are unknown. Here, we report novel mechanisms of tumor plasticity that are mandated by microenvironmental factors and show that recurrence rates are not strictly due to cell-intrinsic properties. Specifically, outgrowth of the same population of incipient tumors is accelerated in mice with triple-negative breast cancer (TNBC) relative to those with luminal breast cancer. Systemic signals provided by overt TNBCs cause the formation of a tumor-supportive microenvironment enriched for EGF and insulin-like growth factor-I (IGF-I) at distant indolent tumor sites. Bioavailability of EGF and IGF-I enhances the expression of transcription factors associated with pluripotency, proliferation, and epithelial–mesenchymal transition. Combinatorial therapy with EGF receptor and IGF-I receptor inhibitors prevents malignant progression. These results suggest that plasticity and recurrence rates can be dictated by host systemic factors and offer novel therapeutic potential for patients with TNBC. Significance: Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which patients with cancer are likely to relapse. Our findings reveal novel mechanisms of tumor phenotypic and gene expression plasticity that are mandated by microenvironmental factors, identifying novel therapeutic targets for patients with TNBC. Cancer Discov; 3(8); 922–35. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 826
Overexpression of pRB in Human Pancreatic Carcinoma Cells: Function in Chemotherapy-Induced Apoptosis
Authors: T. Plath, M. Peters, K. Detjen, M. Welzel, Z. von Marschall, C. Radke, B. Wiedenmann, S. Rosewicz
Journal: JNCI Journal of the National Cancer Institute (2002)

Human pancreatic adenocarcinomas are highly resistant to chemotherapy. The p16 tumor-suppressor protein is inactivated in more than 90% of human pancreatic cancers. The p16 protein transcriptionally inhibits expression of retinoblastoma tumor-suppressor gene pRB. The pRB protein transcriptionally inhibits expression of the p16 gene. Because pRB normally prevents apoptosis, we investigated whether pRB is involved in resistance to chemotherapy-induced apoptosis in pancreatic cancer cells.pRB expression was examined by immunohistochemistry in 106 human pancreatic tissue specimens. The human pancreatic tumor cell line Capan-1 (pRB+/p16-) was stably transfected with p16 to functionally inactivate pRB. pRB gene expression was examined by western and northern blot analyses, and pRB function was assessed by electrophoretic mobility shift assays and promoter transactivation studies for the transcription factor E2F. Changes in cell sensitivity to chemotherapy were measured by assays for cytotoxicity and apoptosis.pRB was overexpressed in pancreatic ductal adenocarcinomas but was hardly detectable in other pancreatic malignancies, chronic pancreatitis, or nontransformed human pancreatic tissue. Expression of p16 in Capan-1 cells resulted in the loss of pRB gene and protein expression concomitant with increased activity of the transcription factor E2F, which was not detected in wild-type or control-transfected Capan-1 cells. Wild-type and control-transfected Capan-1 cells were resistant to chemotherapy-induced apoptosis, but pRB-depleted (i.e., p16-transfected) Capan-1 cells were highly sensitive. The effect was specific to pRB depletion because two other human pancreatic cancer cell lines that retained high pRB expression after p16 transfection were resistant to chemotherapy-induced apoptosis.Overexpression of pRB is associated with human pancreatic duct-cell cancer and may allow pancreatic cancer cells to evade chemotherapy-induced apoptosis.
A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region
Authors: R. Baran, M. Feuilhade, A. Datry, S. Goettmann, P. Pietrini, C. Viguie, G. Badillet, C. Larnier, J. Czernielewski
Journal: British Journal of Dermatology (2000)

Abstract In view of recent advances in the development of antifungal agents, this study examined the possible synergy of two new antifungal agents, terbinafine and amorolfine. The study compared two different courses of terbinafine treatment combined with amorolfine 5% solution nail lacquer. Terbinafine was given orally for 6 (AT6 group) or 12 weeks (AT12 group) and amorolfine nail lacquer applied weekly for 15 months. A control group received terbinafine alone for 12 weeks. This was a randomized, prospective, open study of severe dermatophyte toenail onychomycosis with matrix region involvement. Nail samples were taken before the start of the study, at inclusion and at the visits at 6 weeks, 3, 9, 15 and 18 months. To assess the value of such combined therapy we chose an early parameter as the principal outcome variable, which was the result of mycological examination, including direct microscopy and culture, at 3 months (allowing a margin of 15 days). The secondary parameters of success were the mycological results at the later visits, clinical evaluation and a combined mycological–clinical response. Safety and tolerance were also assessed. Adverse events were recorded and liver function tests were performed monthly during the terbinafine treatment. Of the 147 patients included in the trial, 121 attended the 3-month visit, within a time limit of 15 days of 3 months after the beginning of treatment: 40 in the AT6 group, 40 in the AT12 group and 41 in the control group. In all, 32 of 121 patients (26·4%) had negative mycological results on direct microscopy and culture: 14 of 40 (35·0%) in the AT6 group, 11 of 40 (27·5%) in the AT12 group and seven of 41 (17·1%) in the control group. The cure rate for the global (mycological and clinical cure) response measured at 18 months in 145 patients was 44·0% (22 patients) in the AT6 group, 72·3% (34 patients) in the AT12 group and 37·5% (18 patients) in the terbinafine group. These results suggest that the combination of amorolfine and terbinafine may be of value in the treatment of severe onychomycosis. At the same time a pilot pharmacoeconomic analysis was performed demonstrating a better cost per cure ratio for the patients receiving combination treatment.
An undetected burden of asthma in Italy: the relationship between clinical and epidemiological diagnosis of asthma
Authors: R de Marco, I Cerveri, M Bugiani, M Ferrari, G Verlato
Journal: European Respiratory Journal (1998)

This study aimed to compare questions and tests used in asthma epidemiology with clinical diagnosis of current asthma and to assess the extent of undiagnosed asthma in Italy. Thus, 811 attenders to the second stage of the European Community Respiratory Health Survey were classified by panels of respiratory physicians as current asthmatics or not. Among those with a clinical diagnosis of asthma (n=105), 69% reported current wheezing and 68% asthma in their lifetime (ever asthma), while asthma attacks in the previous year and/or current treatment for asthma (self-reported current asthma) were mentioned by only 37%. Thirty two per cent did not mention asthma at any time, but nevertheless presented a rate of hospitalization close to that of people with self-reported current asthma. On the other hand, almost no subjects labelled nonasthmatics by clinicians (n=706) presented self-reported current asthma (99.7%), while some reported ever asthma (5%) or current wheezing (9%). A model simulation showed that, in its usual range (0-15%), asthma prevalence is markedly overestimated by the question on wheezing and underestimated by the questions on self-reported current asthma, with respect to clinical judgement. Prevalence estimates close to those obtained by clinical judgement were achieved by combining asthma-like symptoms in the previous year with the results of lung function and allergological tests, but especially by using the single question on ever asthma. In conclusion, the present results suggest that the question on ever asthma gives prevalence estimates close to those obtained by clinical judgement and that asthma is greatly underdiagnosed in Italy.
DELAYED PRESSUKE URTICARIA
Authors: T. J. RYAN, N. SHIM-YOUNG, J. L. TURK
Journal: British Journal of Dermatology (1968)

SUMMARY. Delayed pressure urticaria in 15 patients has been investigated. It is characterized by the development of deep painful swelling 4–6 hours after pressure has been applied to the skin. It is sometitnes accompanied by systemic manifestations such as a leucocytosis and rigors. Delayed pressure urticaria is unaffected by antihistamines but it is controlled by steroids. The injection into the skin of saline and various pharmacological agents also causes delayed wealing. Prior treatment of the skin with 48/80 prevents the reaction. Immunofluorescent studies showed that the affected tissues contained no excess fibrinogen, immunoglobulins or complement. It is suggested that delayed pressure urticaria is related to delayed dermographism and may be due to a disorder of kinin activity. The timing and depth of the changes in vascular permeability characteristic of urticaria can be correlated. They are influenced by many mediators and by the pattern of the vasculature of the skin. A change in the timing or depth of the urticaria is the most that should be expected from the use of a single pharmacological agent in the treatment of urticaria.
Immunologic recovery following autologous stem-cell transplantation with pre- and posttransplantation rituximab for low-grade or mantle cell lymphoma
Authors: Y.L. Kasamon, R.J. Jones, R.A. Brodsky, E.J. Fuchs, W. Matsui, L. Luznik, J.D. Powell, A.L. Blackford, A. Goodrich, C.D. Gocke, R.A. Abrams, R.F. Ambinder, I.W. Flinn
Journal: Annals of Oncology (2009)
Annexin 1 Induced by Anti-Inflammatory Drugs Binds to NF-κB and Inhibits Its Activation: Anticancer Effects <i>In vitro</i> and <i>In vivo</i>
Authors: Zhiquan Zhang, Liqun Huang, Wenping Zhao, Basil Rigas
Journal: Cancer Research (2010)

Annexin A1 (ANXA1), a mediator of the anti-inflammatory action of glucocorticoids, is important in cancer development and progression, whereas NF-kappaB regulates multiple cellular phenomena, some of them associated with inflammation and cancer. We showed that glucocorticoids and chemopreventive modified nonsteroidal anti-inflammatory drugs, such as nitric oxide-donating aspirin (NO-ASA) and phospho-aspirin, induced ANXA1 in cultured human colon and pancreatic cancer cells. ANXA1 associated with NF-kappaB and suppressed its transcriptional activity by preventing NF-kappaB binding to DNA. The induction of ANXA1 by glucocorticoids was proportional to their anti-inflammatory potency, as was the suppression of NF-kappaB activity, which was accompanied by enhanced apoptosis and inhibition of cell growth mediated by changes in NF-kappaB-dependent cell signaling. The proposed novel mechanism was operational in the intestinal mucosa of mice treated with dexamethasone or NO-ASA. ANXA1-based oligopeptides displayed the same effects as ANXA1 on NF-kappaB. One such tripeptide (Gln-Ala-Trp) administered to nude mice inhibited the growth of SW480 human colon cancer xenografts by 58% compared with control (P < 0.01). Our findings reveal that ANXA1 is an inducible endogenous inhibitor of NF-kappaB in human cancer cells and mice, provide a novel molecular mechanism for the action of anti-inflammatory agents, and suggest the possibility of mechanism-driven drug development.
Guidelines on small bowel enteroscopy and capsule endoscopy in adults
Authors: R Sidhu, D S Sanders, A J Morris, M E McAlindon
Journal: Gut (2007)

1.0 Introduction

2.0 Formulation of guidelines

2.1 Grading of recommendations

2.2 Scheduled review

3.0 Summary of recommendations

4.0 Types of small bowel enteroscopy

4.1 Enteroscopy using a colonoscope

4.2 Sonde enteroscopy

4.3 Push enteroscopy

4.4 Intraoperative enteroscopy

4.5 Double balloon (push and pull) enteroscopy

5.0 Capsule endoscopy

5.1. Technique

5.2 Indications for capsule endoscopy

5.3 Complications of capsule endoscopy

5.4 Patency capsule

6.0 Service provision and training

References

The small bowel has historically been a difficult area to examine due to its anatomy, location and relative tortuosity. Examination beyond the duodenojejunal flexure is of importance in a number of small bowel disorders. Before the advent of enteroscopy or capsule endoscopy, radiographic studies had been the main investigative modality of the small bowel. Barium follow-through and enteroclysis permits indirect examination of the small bowel but has a low diagnostic yield particularly in the context of obscure gastrointestinal bleeding.1–3

Capsule endoscopy and enteroscopy are now the preferred methods to examine the small bowel in most situations. These guidelines are intended to provide an evidence based document describing endoscopic investigation of small bowel disorders.

These guidelines were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) and have been produced by the small bowel and endoscopy sections of the BSG. The guidelines have been produced to conform to the North of England evidence based guidelines development project.4 5 They have been drawn up from a Medline, Embase and Ovid literature search using terms “enteroscopy”, “push enteroscopy”, “intraoperative enteroscopy”, “double balloon enteroscopy” and “capsule endoscopy”. There have been 180 peer review studies, seven review articles, 58 case reports and letters, and one set of American guidelines on enteroscopy.6 The literature search for capsule endoscopy includes 100 peer review studies, 51 review articles, 74 …