tbuckley/cabot-search huggingface dataset:
Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrahepatic tumors in athymic mice
Authors: Ruth Adler, Esther Hurwitz, Jack R. Wands, Michael Sela, Daniel Shouval
Journal: Hepatology (1995)

Doxorubicin (adriamycin), once considered the treatment of choice for hepatocellular carcinoma (HCC), is known to cause cardiotoxicity and myelotoxicity. To reduce the systemic toxicity of adriamycin by direct delivery of the drug to the tumor site, we established a panel of monoclonal antibodies (MAbs) to hepatoma associated antigens that were conjugated to adriamycin by a dextran bridge. Initially, the efficacy of these conjugates in suppressing tumor growth was assessed using a model of subcutaneous HCC tumors injected in athymic mice. In the second stage of the study, we tested these conjugates in an experimental model in which human HCC was transplanted intrahepatically by intrasplenic injection, thus providing the tumor cells with growth factors and an adequate cellular matrix, similar to the natural microenvironment of HCC. Anti-tumoral therapy resulted in lower serum alpha-fetoprotein (AFP) levels in two of three experimental groups treated with different specific conjugates as compared with control mice treated with the individual components. Efficacy of targeting was enhanced using the intrahepatic model system for propagation of HCC and was demonstrated by fluorescence of adriamycin and MAb in tumor tissue and absence of this fluorescence in healthy liver tissue surrounding the tumor. Reduction of systemic toxicity was shown by the absence of adriamycin fluorescence in myocardial tissue in conjugate-treated mice, whereas in all other treatment groups, including mice treated with a mixture of adriamycin and specific MAb, there was strong myocardial fluorescence of adriamycin.
Vertebrate Rhodopsin Adaptation to Dim Light via Rapid Meta-II Intermediate Formation
Authors: T. Sugawara, H. Imai, M. Nikaido, Y. Imamoto, N. Okada
Journal: Molecular Biology and Evolution (2009)

Rhodopsin is a photoreceptive protein present in vertebrate rod photoreceptor cells, which are responsible for scotopic vision. Recent molecular studies have shown that several aquatic vertebrate species have independently acquired rhodopsin containing Asp83Asn, Glu122Gln, and Ala292Ser substitutions, causing a blue shift in the rhodopsin absorption spectra for adaptation to the blue-green photic environment in deep water. Here, we provide new evidence for the evolutionary and functional relevance of the Asp83Asn substitution. Spectroscopic and kinetic analyses of rhodopsins in six cichlid fishes from the East African Great Lakes using charge-coupled device spectrophotometer revealed that the Asp83Asn substitution accelerated the formation of meta-II, a rhodopsin intermediate crucial for activation of the G-protein transducin. Because rapid formation of meta-II likely results in effective transduction of photic signals, it is reasonable to assume that deep-water cichlid species have acquired rhodopsin containing Asn83 to adapt to dim lighting. Remarkably, rhodopsin containing Asn83 has been identified in terrestrial vertebrates such as bats, and these rhodopsin variants also exhibit accelerated meta-II formation. Our results indicated that the Asp83Asn substitution observed in a variety of animal species was acquired independently in many different lineages during vertebrate evolution for adaptation to dimly lit environments.
Gonadectomy and hormonal replacement changes systolic blood pressure and ventricular myosin isoenzyme pattern of spontaneously hypertensive rats.
Authors: M Lengsfeld, I Morano, U Ganten, D Ganten, J C Rüegg
Journal: Circulation Research (1988)

We investigated the influence of testosterone on systolic blood pressure, heart weight, body weight, and ventricular myosin isoenzyme pattern of male spontaneously hypertensive stroke-prone rats (SHRSP). In two different study series (study 1, postpubertal; study 2, prepubertal), SHRSP were gonadectomized (HG), gonadectomized and replaced with dihydrotestosterone (HG-T), and sham-operated (H). Blood pressure was significantly higher in HG-T animals in both study series. Only prepubertal gonadectomy (study 2, HG group) led to a significantly decreased blood pressure. Heart weight and body weight were significantly diminished in the HG group when compared to the H group in study 2. Dihydrotestosterone (HG-T group) reversed this effect. In both study series gonadectomy shifted the myosin isoenzyme pattern to the V3 form while testosterone replacement led to a myosin isoenzyme pattern in favor of the V1 form. We conclude that the ventricular myosin isoenzyme pattern is under the dominant control of androgens and dissociates the expression of myosin isoenzyme from both blood pressure and cardiac hypertrophy in spontaneously hypertensive rats.
The pattern recognition receptor Nod1 activates CCAAT/enhancer binding protein signalling in lung epithelial cells
Authors: J. L. Barton, T. Berg, L. Didon, M. Nord
Journal: European Respiratory Journal (2007)

The innate immune receptor nucleotide-binding oligomerisation domain protein 1 (Nod1) recognises peptidoglycan containing meso -diaminopimelic acid found in all Gram-negative and some Gram-positive bacteria. Nod1 has been shown to activate nuclear factor (NF)-κB. The aim of the present study was to examine the expression of Nod1 in the lung, particularly in lung epithelial cells, and to investigate the activation of CCAAT/enhancer binding protein (C/EBP) transcription factors downstream of the Nod1 receptor in these cells. The expression of Nod1 in mouse lung was examined using immunohistochemistry. A tissue array was used to determine the expression pattern in the human lung. Signalling downstream of Nod1 was examined in the human lung epithelial cell type, BEAS-2B, by electrophoretic mobility shift assay and reporter gene activation. Nod1 expression was seen in various cell types in the lung, including epithelial cells. Activation of Nod1 in these cells resulted in modest activation of NF-κB, together with strong activation of the C/EBP transcription factors, particularly C/EBPβ. This activation appears to be independent of de novo protein synthesis. The present study showed that nucleotide-binding oligomerisation domain protein 1 is expressed in lung epithelial cells. The results demonstrate a novel pathway downstream of the nucleotide-binding oligomerisation domain protein 1 receptor in these cells and suggest that C/EBPβ may play a role in immune responses to meso -diaminopimelic acid-containing bacteria in the lung.
Curcumin Suppresses Growth of Head and Neck Squamous Cell Carcinoma
Authors: Maria M. LoTempio, Mysore S. Veena, Helen L. Steele, Bharathi Ramamurthy, Tirunelveli S. Ramalingam, Alen N. Cohen, Rita Chakrabarti, Eri S. Srivatsan, Marilene B. Wang
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The purpose of this study was to determine whether curcumin would trigger cell death in the head and neck squamous cell carcinoma (HNSCC) cell lines CCL 23, CAL 27, and UM-SCC1 in a dose-dependent fashion. Experimental Design: HNSCC cells were treated with curcumin and assayed for in vitro growth suppression using 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide and fluorescence-activated cell sorting analyses. Expression of p16, cyclin D1, phospho-Iκβ, and nuclear factor-κβ (NF-κβ) were measured by Western blotting, gel shift, and immunofluorescence. Results: Addition of curcumin resulted in a dose-dependent growth inhibition of all three cell lines. Curcumin treatment resulted in reduced nuclear expression of NF-κβ. This effect on NF-κβ was further reflected in the decreased expression of phospho-Iκβ-α. Whereas the expression of cyclin D1, an NF-κβ–activated protein, was also reduced, there was no difference in the expression of p16 at the initial times after curcumin treatment. In vivo growth studies were done using nude mice xenograft tumors. Curcumin was applied as a noninvasive topical paste to the tumors and inhibition of tumor growth was observed in xenografts from the CAL27 cell line. Conclusions: Curcumin treatment resulted in suppression of HNSCC growth both in vitro and in vivo. Our data support further investigation into the potential use for curcumin as an adjuvant or chemopreventive agent in head and neck cancer.
Novel Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor–Secreting Tumor Vaccine for Pancreatic Cancer: A Phase I Trial of Safety and Immune Activation
Authors: Elizabeth M. Jaffee, Ralph H. Hruban, Barbara Biedrzycki, Daniel Laheru, Karen Schepers, Patricia R. Sauter, Marti Goemann, Joanne Coleman, Louise Grochow, Ross C. Donehower, Keith D. Lillemoe, Seamus O’Reilly, Ross A. Abrams, Drew M. Pardoll, John L. Cameron, Charles J. Yeo
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF–secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 × 10 7 vaccine cells, three patients received 5 × 10 7 vaccine cells, three patients received 10 × 10 7 vaccine cells, and five patients received 50 × 10 7 vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received ≥ 10 × 10 7 vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF–secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.
Hormonal Treatment Duration in Elderly Patients: An Open Question
Authors: Diana Crivellari, Aron Goldhirsch, Alan Coates
Journal: Journal of Clinical Oncology (2004)

disease previously treated with chemotherapy.We targeted patients for whom there was no established curative therapy, as was appropriate for an exploratory trial.In their editorial that accompanied our paper, Connell and Weichselbaum [6] commented that some of the patients could have received chemoradiotherapy [7].Indeed, our eligibility criteria did not exclude prior radiotherapy, nor were patients discouraged from receiving radiotherapy after gene therapy.We also recognized that bulky tumors, although more amenable to biopsy, were less likely to show clinical benefit from gene therapy than were low-volume tumors.Accordingly, our eligibility criteria required that there be at least one measurable lesion in the bladder, which could be as little as a "patch" of erythema in a bladder with carcinoma in situ.Understandably, however, there were also patients with deeply invasive tumors that would not be fully penetrated by an adenoviral vector.Our study demonstrates that success in this and other phase I clinical trials, for gene therapy and otherwise, does not depend on a "home run" in terms of efficacy but does require careful analysis of biologic end points and the clinical experience to learn from unanticipated outcomes.
Associations of obesity with modifiable risk factors for the development of cardiovascular disease in patients with rheumatoid arthritis
Authors: A Stavropoulos-Kalinoglou, G S Metsios, V F Panoulas, K M J Douglas, A M Nevill, A Z Jamurtas, M Kita, Y Koutedakis, G D Kitas
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). Methods: BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted thresholds in ⩾3 CVD risk factors were classified as having the metabolic syndrome (MetS). Results: BMI independently associated with hypertension (OR = 1.28 (95% CI = 1.22 to 1.34); p = 0.001), high-density lipoprotein (OR = 1.10 (95% CI = 1.06 to 1.15); p = 0.025), insulin resistance (OR = 1.13 (95% CI = 1.08 to 1.18); p = 0.000) and MetS (OR = 1.15 (95% CI = 1.08 to 1.21); p = 0.000). In multivariable analyses, BMI had the strongest associations with CVD risk factors (F 1–354 = 8.663, p = 0.000), and this was followed by lipid-lowering treatment (F 1–354 = 7.651, p = 0.000), age (F 1–354 = 7.541, p = 0.000), antihypertensive treatment (F 1–354 = 4.997, p = 0.000) and gender (F 1–354 = 4.707, p = 0.000). Prevalence of hypertension (p = 0.004), insulin resistance (p = 0.005) and MetS (p = 0.000) was significantly different between patients with RA who were normal, overweight and obese, and BMI differed significantly according to the number of risk factors present (p = 0.000). Conclusions: Increasing BMI associates with increased CVD risk independently of many confounders. RA-specific BMI cut-off points better identify patients with RA at increased CVD risk. Weight-loss regimens should be developed and applied in order to reduce CVD in patients with RA.
Caries Patterns in the Primary Dentition: Cluster Analysis of a Sample of 5,169 Arizona Children 5–59 Months of Age
Authors: Walter J Psoter, David G Pendrys, Douglas E Morse, He‐ping Zhang, Susan T Mayne
Journal: International Journal of Oral Science (2009)

Cluster analysis was conducted on data from 5,169 United States (U.S.) Arizona children, age's 5‐59‐months with the goal of delineating patterns of caries in the primary dentition of pre‐school children without a priori pattern definitions. Cluster analyses were conducted using all data for children ages 0–4 years in aggregate: 1) for all subjects, and 2) for subjects without crowned restored teeth. Each of these two sets of analyses consisted of 8 differently specified cluster analyses as a validation procedure. The caries patterns identified from the clustering analysis are: 1) smooth surfaces (other than the maxillary incisor), 2) maxillary incisor, 3) occlusal surfaces of first molars, and 4) pit and fissure surfaces of second molars. The cluster analysis findings were consistent with results produced by multidimensional scaling. These cross‐validated patterns may represent resulting disease conditions from different risks or the timing of various risk factor exposures. As such, the patterns may be useful case definitions for caries risk factor investigations in children under 60 months of age.
A T Helper Cell 2 (Th2) Immune Response against Non-self Antigens Modifies the Cytokine Profile of Autoimmune T Cells and Protects against Experimental Allergic Encephalomyelitis
Authors: Marika Falcone, Barry R. Bloom
Journal: The Journal of Experimental Medicine (1997)

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS), and the most commonly used experimental model for multiple sclerosis. It is mediated by autoreactive T cell clones exhibiting a T helper cell (Th) 1 cytokine profile. Nonencephalitogenic T lymphocytes specific for self or exogenous antigens have been found to suppress encephalitogenic T cell responses and to protect against autoimmune disease. The mechanisms by which exogenous antigens modulate autoimmunity are not fully understood. In this study, we tested the hypothesis that a Th2-type immune response against an exogenous, nonself antigen, keyhole limpet hemocyanin (KLH), by releasing IL-4 in the microenvironment, could shift the cytokine profile of encephalitogenic T cells from an inflammatory Th1 to a protective Th2 type. SJL/J mice were preimmunized with the KLH in incomplete Freund's adjuvant to induce a population of Th2 memory cells that would be expected to release Th2 cytokines when activated by the specific antigen at the time of EAE induction. Four weeks later, mice received an encephalitogenic challenge containing guinea pig myelin in complete Freund's adjuvant with or without KLH. All KLH primed animals not receiving the exogenous antigen at the time of EAE induction developed a severe clinical disease indistinguishable from control mice not KLH primed. In contrast, animals preimmunized and challenged with the encephalitogenic inoculum containing KLH showed either no, or markedly reduced, clinical signs. Enzyme-linked immunospot analysis demonstrated that KLH-specific T cells in the primed mice were producing IL-4 characteristic of Th2 cells. In the KLH-primed and restimulated mice, the cytokine profile of the autoreactive, myelin basic protein–specific T cells was shifted from an inflammatory Th1 towards a protective Th2 type. We infer that the presence of IL-4 secreted by KLH-specific memory Th2 cells in the lymphoid system microenvironment in which the autoreactive T cells were engaged by the encephalitogenic stimulus were able to bias their cytokine profile towards a protective Th2 phenotype. This interpretation is supported by the observation that the protective effect of preimmunization with KLH was overcome by rm– IL-12, which inhibited the production of IL-4 by the Th1 cells and biased the autoimmune response to a predominantly Th1 type. Since IL-4 mRNA could not be detected by reverse transcriptase PCR in the CNS, the protective effect was inferred to be mediated by Th2 cells in the lymphoid system, and not the target organ. We conclude that exogenous, nonself antigens that can induce Th2 responses, can modify the cytokine environment sufficiently to alter the cytokine phenotype of inflammatory, autoreactive T cell clones, and ultimately, to provide significant protection against EAE and possibly other T cell–mediated autoimmune diseases.
Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients
Authors: Roberto N. Miranda, Tariq N. Aladily, H. Miles Prince, Rashmi Kanagal-Shamanna, Daphne de Jong, Luis E. Fayad, Mitual B. Amin, Nisreen Haideri, Govind Bhagat, Glen S. Brooks, David A. Shifrin, Dennis P. O'Malley, Chan Y. Cheah, Carlos E. Bacchi, Gabriela Gualco, Shiyong Li, John A. Keech, Ephram P. Hochberg, Matthew J. Carty, Summer E. Hanson, Eid Mustafa, Steven Sanchez, John T. Manning, Zijun Y. Xu-Monette, Alonso R. Miranda, Patricia Fox, Roland L. Bassett, Jorge J. Castillo, Brady E. Beltran, Jan Paul de Boer, Zaher Chakhachiro, Dongjiu Ye, Douglas Clark, Ken H. Young, L. Jeffrey Medeiros
Journal: Journal of Clinical Oncology (2013)

Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown.We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up.The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively).Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.
Ultrasound biomicroscopy of sclerotomy sites: Author’s reply
Authors: Muna Bhende, Satish G Agraharam, Lingam Gopal, Kallakuri Sumasri, Balusamy Sukumar, Joshua George, Tarun Sharma, Mahesh P Shanmugam, Pramod S Bhende, Nitin S Shetty, Rajat N Agrawal, Dhanashree A Deshpande
Journal: Ophthalmology (2001)
Deferring of patients with restenotic coronary lesions based on the concept of fractional flow reserve measurement
Authors: Johannes Rieber, Isabelle Erhard, Tobias Segmiller, Andreas Koenig, Thomas M. Schiele, Hagen Gross, Silke Ebel, Karl Theisen, Volker Klauss
Journal: Journal of the American College of Cardiology (2003)
A global survey identifies novel upstream components of the Ath5 neurogenic network
Authors: Marcel Souren, Juan Martinez-Morales, Panagiota Makri, Beate Wittbrodt, Joachim Wittbrodt
Journal: Genome biology (2009)

Investigating the architecture of gene regulatory networks (GRNs) is essential to decipher the logic of developmental programs during embryogenesis. In this study we present an upstream survey approach, termed trans-regulation screen, to comprehensively identify the regulatory input converging on endogenous regulatory sequences. Our dual luciferase-based screen queries transcriptome-scale collections of cDNAs. Using this approach we study the regulation of Ath5, the central node in the GRN controlling retinal ganglion cell (RGC) specification in vertebrates. The Ath5 promoter integrates the input of upstream regulators to enable the transient activation of the gene, which is an essential step for RGC differentiation. We efficiently identified potential Ath5 regulators that were further filtered for true positives by an in situ hybridization screen. Their regulatory activity was validated in vivo by functional assays in medakafish embryos. Our analysis establishes functional groups of genes controlling different regulatory phases, including the onset of Ath5 expression at cell-cycle exit and its down-regulation prior to terminal RGC differentiation. These results extent the current model of the GRN controlling retinal neurogenesis in vertebrates.
Supported home-care schemes: the key to increasing outpatient care?
Authors: A.M. Collins, S. Wilks, D. Wootton, S.B. Gordon
Journal: European Respiratory Journal (2012)

To the Editors:

We agree with Choudhury et al. [1] that more patients (18–20%) could be managed at home by family practitioners with the application of current guidelines, but we would like to comment that a greater number of patients (approximately 60%) could be managed at home with additional supported home-based care.

As described by the authors, factors other than disease severity often prompt hospital admission. These include substance abuse, inability to cope alone at home, inability to take oral antibiotics, comorbidities and homelessness [2, 3]. The case for outpatient care based on severity markers is clear, but there is an urgent need for …