tbuckley/cabot-search huggingface dataset:
A Simple Meal Plan Emphasizing Healthy Food Choices Is as Effective as an Exchange-Based Meal Plan for Urban African Americans With Type 2 Diabetes
Authors: David C. Ziemer, Kathy J. Berkowitz, Rita M. Panayioto, Imad M. El-Kebbi, Victoria C. Musey, Lynda A. Anderson, Nancy S. Wanko, Margaret L. Fowke, Carol W. Brazier, Virginia G. Dunbar, Wrenn Slocum, Gael M. Bacha, Daniel L. Gallina, Curtiss B. Cook, Lawrence S. Phillips
Journal: Diabetes Care (2003)

OBJECTIVE—To compare a simple meal plan emphasizing healthy food choices with a traditional exchange-based meal plan in reducing HbA1c levels in urban African Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 648 patients with type 2 diabetes were randomized to receive instruction in either a healthy food choices meal plan (HFC) or an exchange-based meal plan (EXCH) to compare the impact on glycemic control, weight loss, serum lipids, and blood pressure at 6 months of follow-up. Dietary practices were assessed with food frequency questionnaires. RESULTS—At presentation, the HFC and EXCH groups were comparable in age (52 years), sex (65% women), weight (94 kg), BMI (33.5), duration of diabetes (4.8 years), fasting plasma glucose (10.5 mmol/l), and HbA1c (9.4%). Improvements in glycemic control over 6 months were significant (P &amp;lt; 0.0001) but similar in both groups: HbA1c decreased from 9.7 to 7.8% with the HFC and from 9.6 to 7.7% with the EXCH. Improvements in HDL cholesterol and triglycerides were comparable in both groups, whereas other lipids and blood pressure were not altered. The HFC and EXCH groups exhibited similar improvement in dietary practices with respect to intake of fats and sugar sweetened foods. Among obese patients, average weight change, the percentage of patients losing weight, and the distribution of weight lost were comparable with the two approaches. CONCLUSIONS—Medical nutrition therapy is effective in urban African Americans with type 2 diabetes. Either a meal plan emphasizing guidelines for healthy food choices or a low literacy exchange method is equally effective as a meal planning approach. Because the HFC meal plan may be easier to teach and easier for patients to understand, it may be preferable for low-literacy patient populations.
Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall
Authors: Ravi M. Rao, Lin Yang, Guillermo Garcia-Cardena, Francis W. Luscinskas
Journal: Circulation Research (2007)

Inflammation is a fundamental process that protects organisms by removing or neutralizing injurious agents. A key event in the inflammatory response is the localized recruitment of various leukocyte subsets. Here we address the cellular and regulatory mechanisms of leukocyte recruitment to the vessel wall in cardiovascular disease and discuss our evolving understanding of the role of the vascular endothelium in this process. The vascular endothelium is the continuous single-cell lining of the cardiovascular system that forms a critical interface between the blood and its components on one side and the tissues and organs on the other. It is heterogeneous and has many synthetic and metabolic functions including secretion of platelet-derived growth factor, von Willebrand factor, prostacyclin, NO, endothelin-1, and chemokines and the expression of adhesion molecules. It also acts as a nonthrombogenic and selective permeable barrier. Endothelial cells also interact closely with the extracellular matrix and with adjacent cells including pericytes and smooth muscle cells within the vessel wall. A central question in vascular biology is the role of the endothelium in the initiation of inflammatory response, the extent of its “molecular conversations” with recruited leukocytes, and its influence on the extent and/or outcome of this response.
Nitric Oxide Accelerates Interleukin-13 Cytotoxin-Mediated Regression in Head and Neck Cancer Animal Model
Authors: Koji Kawakami, Mariko Kawakami, Raj K. Puri
Journal: Clinical Cancer Research (2004)

Receptors for interleukin-13 (IL-13R) are overexpressed on several types of solid cancers including gliobastoma, renal cell carcinoma, AIDS Kaposi's sarcoma, and head and neck cancer. Recombinant fusion proteins IL-13 cytotoxin (IL13-PE38QQR or IL13-PE38) have been developed to directly target IL-13R-expressing cancer cells. Although it has been found that IL-13 cytotoxin has a direct potent antitumor activity in vivo in nude mice models of human cancers, the involvement of indirect antitumor effecter molecules such as nitric oxide (NO) is unknown. To address this issue, we assessed the effect of NO inhibiter N(omega)-monomethyl-l-arginine on IL-13 cytotoxin-mediated cytotoxicity and NO2/NO3 production in HN12 head and neck cancer cells. In addition, antitumor effects and NO levels in HN12 and KCCT873 head and neck tumors xenografted s.c. in nude mice when treated with IL-13 cytotoxin were evaluated by tumor measurement, Western blot, and immunohistochemistry analyses. Pretreatment of animals with N(omega)-monomethyl-l-arginine significantly decreased the NO levels and IL-13 cytotoxin-mediated antitumor effects. In addition, depletion of macrophages, known to produce NO, also decreased antitumor activity of IL-13 cytotoxin. Based on these studies, we concluded that NO accelerates antitumor effect of IL-13 cytotoxin on head and neck tumor cells. Because IL-13 cytotoxin is currently being tested in the clinic for the treatment of patients with recurrent glioblastoma maltiforme, our current findings suggest maintaining macrophage and NO-producing cellular function for optimal therapeutic effect of this targeted agent.
Targeting PBK/TOPK decreases growth and survival of glioma initiating cells in vitro and attenuates tumor growth in vivo
Authors: Mrinal Joel, Awais A. Mughal, Zanina Grieg, Wayne Murrell, Sheryl Palmero, Birthe Mikkelsen, Hege B. Fjerdingstad, Cecilie J. Sandberg, Jinan Behnan, Joel C. Glover, Iver A. Langmoen, Biljana Stangeland
Journal: Molecular Cancer (2015)

Glioblastomas are invasive therapy resistant brain tumors with extremely poor prognosis. The Glioma initiating cell (GIC) population contributes to therapeutic resistance and tumor recurrence. Targeting GIC-associated gene candidates could significantly impact GBM tumorigenicity. Here, we investigate a protein kinase, PBK/TOPK as a candidate for regulating growth, survival and in vivo tumorigenicity of GICs. PBK is highly upregulated in GICs and GBM tissues as shown by RNA and protein analyses. We knocked down PBK using shRNA vectors and inhibited the function of PBK protein with a pharmacological PBK inhibitor, HITOPK-032. We assessed viability, tumorsphere formation and apoptosis in three patient derived GIC cultures. Gene knockdown of PBK led to decreased viability and sphere formation and in one culture an increase in apoptosis. Treatment of cells with inhibitor HITOPK-032 (5 μM and 10 μM) almost completely abolished growth and elicited a large increase in apoptosis in all three cultures. HI-TOPK-032 treatment (5 mg/kg and 10 mg/kg bodyweight) in vivo resulted in diminished growth of experimentally induced subcutaneous GBM tumors in mice. We also carried out multi-culture assays of cell survival to investigate the relative effects on GICs compared with the normal neural stem cells (NSCs) and their differentiated counterparts. Normal NSCs seemed to withstand treatment slightly better than the GICs. Our study of identification and functional validation of PBK suggests that this candidate can be a promising molecular target for GBM treatment.
Misdiagnosis of Myocardial Infarction Related to Limitations of the Current Regulatory Approach to Define Clinical Decision Values for Cardiac Troponin
Authors: Karin Wildi, Maria Rubini Gimenez, Raphael Twerenbold, Tobias Reichlin, Cedric Jaeger, Amely Heinzelmann, Christiane Arnold, Berit Nelles, Sophie Druey, Philip Haaf, Petra Hillinger, Nicolas Schaerli, Philipp Kreutzinger, Yunus Tanglay, Thomas Herrmann, Zoraida Moreno Weidmann, Lian Krivoshei, Michael Freese, Claudia Stelzig, Christian Puelacher, Katharina Rentsch, Stefan Osswald, Christian Mueller
Journal: Circulation (2015)

Background— Misdiagnosis of acute myocardial infarction (AMI) may significantly harm patients and may result from inappropriate clinical decision values (CDVs) for cardiac troponin (cTn) owing to limitations in the current regulatory process. Methods and Results— In an international, prospective, multicenter study, we quantified the incidence of inconsistencies in the diagnosis of AMI using fully characterized and clinically available high-sensitivity (hs) cTn assays (hs-cTnI, Abbott; hs-cTnT, Roche) among 2300 consecutive patients with suspected AMI. We hypothesized that the approved CDVs for the 2 assays are not biologically equivalent and might therefore contribute to inconsistencies in the diagnosis of AMI. Findings were validated by use of sex-specific CDVs and parallel measurements of other hs-cTnI assays. AMI was the adjudicated diagnosis in 473 patients (21%). Among these, 86 patients (18.2%) had inconsistent diagnoses when the approved uniform CDV was used. When sex-specific CDVs were used, 14.1% of female and 22.7% of male AMI patients had inconsistent diagnoses. Using biologically equivalent CDV reduced inconsistencies to 10% ( P &lt;0.001). These findings were confirmed with parallel measurements of other hs-cTn assays. The incidence of inconsistencies was only 7.0% for assays with CDVs that were nearly biologically equivalent. Patients with inconsistent AMI had long-term mortality comparable to that of patients with consistent diagnoses ( P =NS) and a trend toward higher long-term mortality than patients diagnosed with unstable angina ( P =0.05). Conclusions— Currently approved CDVs are not biologically equivalent and contribute to major inconsistencies in the diagnosis of AMI. One of 5 AMI patients will receive a diagnosis other than AMI if managed with the alternative hs-cTn assay. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00470587.
Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin.
Authors: H Wilke, P Preusser, U Fink, U Gunzer, H J Meyer, J Meyer, J R Siewert, W Achterrath, L Lenaz, H Knipp
Journal: Journal of Clinical Oncology (1989)

Thirty-four patients with locally advanced, nonresectable gastric cancer (staged by laparotomy) received etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). Thirty-three patients were evaluable for response and toxicity. Second-look surgery with removal of residual tumor by gastrectomy and lymphadenectomy was performed in case of complete/partial remission (CR/PR) after EAP. After successful resection (R0- and R1-resection), two cycles of EAP were administered for consolidation therapy. Patients refusing reoperation received up to six cycles of EAP. The response rate (CR/PR) after EAP was 70% (23/33), including a 21% (7/33) rate of clinical CRs (CCRs). Two patients had minor remission (MR)/no change and seven had progressive disease. There was one early death. Nineteen of 23 responders (5 CCRs, 14 clinical PRs [CPRs]) and one patient with MR underwent second-look surgery. Five CCRs were pathologically confirmed; 10 patients with CPR were without evidence of disease (NED) after resection. In three patients (CPR), R1-resections (microscopically tumor-cell positive proximal margin) were performed; two patients are disease-free, 22+ and 33+ months after consolidation chemotherapy. In two patients, the tumor was again considered nonresectable. Twenty patients were disease-free after EAP +/- surgery +/- consolidation chemotherapy. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of World Health Organization (WHO) grade 3 occurred in 30% and 9%, respectively and grade 4 in 18% and 9% of the patients, respectively. There was no increased peri- or postoperative morbidity. After a median follow-up of 20 months for disease-free patients, the relapse rate is 60% (12/20). The median survival time for all patients is 18 months and for disease-free patients 24 months. EAP is highly effective in locally advanced gastric cancer, and offers a chance for surgery with curative intention in patients with an otherwise fatal prognosis.
VCAP-AMP-VECP Compared With Biweekly CHOP for Adult T-Cell Leukemia-Lymphoma: Japan Clinical Oncology Group Study JCOG9801
Authors: Kunihiro Tsukasaki, Atae Utsunomiya, Haruhiko Fukuda, Taro Shibata, Takuya Fukushima, Yoshifusa Takatsuka, Shuichi Ikeda, Masato Masuda, Haruhisa Nagoshi, Ryuzo Ueda, Kazuo Tamura, Masayuki Sano, Saburo Momita, Kazunari Yamaguchi, Fumio Kawano, Shuichi Hanada, Kensei Tobinai, Masanori Shimoyama, Tomomitsu Hotta, Masao Tomonaga
Journal: Journal of Clinical Oncology (2007)

Our previous phase II trial for treating human T-lymphotropic virus type I-associated adult T-cell leukemia-lymphoma (ATLL) with vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP), doxorubicin, ranimustine, and prednisone (AMP), and vindesine, etoposide, carboplatin, and prednisone (VECP) showed promising results. To test the superiority of VCAP-AMP-VECP over biweekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), we conducted a randomized controlled trial exclusively for ATLL.Previously untreated patients with aggressive ATLL were assigned to receive either six courses of VCAP-AMP-VECP every 4 weeks or eight courses of biweekly CHOP. Both treatments were supported with granulocyte colony-stimulating factor and intrathecal prophylaxis.A total of 118 patients were enrolled. The complete response (CR) rate was higher in the VCAP-AMP-VECP arm than in biweekly CHOP arm (40% v 25%, respectively; P = .020). Progression-free survival rate at 1 year was 28% in the VCAP-AMP-VECP arm compared with 16% in the CHOP arm (P = .100, two-sided P = .200). Overall survival (OS) at 3 years was 24% in the VCAP-AMP-VECP arm and 13% in the CHOP arm (P = .085, two-sided P = .169). For VCAP-AMP-VECP versus biweekly CHOP, grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 or 4 infection rates were 98% v 83%, 74% v 17%, and 32% v 15%, respectively. There were three toxic deaths in the VCAP-AMP-VECP arm.The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
Molecular markers in pediatric neuro-oncology
Authors: K. Ichimura, R. Nishikawa, M. Matsutani
Journal: Neuro-Oncology (2012)

Pediatric molecular neuro-oncology is a fast developing field. A multitude of molecular profiling studies in recent years has unveiled a number of genetic abnormalities unique to pediatric brain tumors. It has now become clear that brain tumors that arise in children have distinct pathogenesis and biology, compared with their adult counterparts, even for those with indistinguishable histopathology. Some of the molecular features are so specific to a particular type of tumors, such as the presence of the KIAA1549-BRAF fusion gene for pilocytic astrocytomas or SMARCB1 mutations for atypical teratoid/rhabdoid tumors, that they could practically serve as a diagnostic marker on their own. Expression profiling has resolved the existence of 4 molecular subgroups in medulloblastomas, which positively translated into improved prognostication for the patients. The currently available molecular markers, however, do not cover all tumors even within a single tumor entity. The molecular pathogenesis of a large number of pediatric brain tumors is still unaccounted for, and the hierarchy of tumors is likely to be more complex and intricate than currently acknowledged. One of the main tasks of future molecular analyses in pediatric neuro-oncology, including the ongoing genome sequencing efforts, is to elucidate the biological basis of those orphan tumors. The ultimate goal of molecular diagnostics is to accurately predict the clinical and biological behavior of any tumor by means of their molecular characteristics, which is hoped to eventually pave the way for individualized treatment.
Extralobar lung sequestration associated with fatal neonatal respiratory distress
Authors: A. J. Bliek, D. J. Mulholland
Journal: Thorax (1971)

The radiological and pathological findings of lung sequestration in a premature infant are described. There was a left-sided variant of the extralobar type with double systemic arterial blood supply, single systemic venous drainage, and an incomplete bronchial tree for the remainder of the left lung.
Purifying Selection Can Obscure the Ancient Age of Viral Lineages
Authors: Joel O. Wertheim, Sergei L. Kosakovsky Pond
Journal: Molecular Biology and Evolution (2011)

Statistical methods for molecular dating of viral origins have been used extensively to infer the time of most common recent ancestor for many rapidly evolving pathogens.However, there are a number of cases, in which epidemiological, historical, or genomic evidence suggests much older viral origins than those obtained via molecular dating.We demonstrate how pervasive purifying selection can mask the ancient origins of recently sampled pathogens, in part due to the inability of nucleotide-based substitution models to properly account for complex patterns of spatial and temporal variability in selective pressures.We use codon-based substitution models to infer the length of branches in viral phylogenies; these models produce estimates that are often considerably longer than those obtained with traditional nucleotide-based substitution models.Correcting the apparent underestimation of branch lengths suggests substantially older origins for measles, Ebola, and avian influenza viruses.This work helps to reconcile some of the inconsistencies between molecular dating and other types of evidence concerning the age of viral lineages.
Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers
Authors: Jennifer L. Matsuda, Olga V. Naidenko, Laurent Gapin, Toshinori Nakayama, Masaru Taniguchi, Chyung-Ru Wang, Yasuhiko Koezuka, Mitchell Kronenberg
Journal: The Journal of Experimental Medicine (2000)

A major group of natural killer (NK) T cells express an invariant Vα14+ T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14+ NK T cells. Using these tetramers, we find that α-GalCer–specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1− but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of α-GalCer leads to the production of both interferon γ and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that α-GalCer–specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.
Sideroblastic anaemia in adult coeliac disease
Authors: A. M. Dawson, C. D. Holdsworth, C. S. Pitcher
Journal: Gut (1964)

Anaemia due to pyridoxine deficiency has not previously been described in adult coeliac disease. The patient described here had a sideroblastic bone marrow showing the characteristic perinuclear rings of iron-containing granules and biochemical evidence of pyridoxine deficiency. These changes disappeared completely when the patient was put on a gluten-free diet.
Biomarkers in melanoma
Authors: H. Gogas, A.M.M. Eggermont, A. Hauschild, P. Hersey, P. Mohr, D. Schadendorf, A. Spatz, R. Dummer
Journal: Annals of Oncology (2009)

Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques--DNA and RNA microarrays--have identified numerous possible biomarkers, but their relevance to melanoma progression, clinical outcome and the selection of optimal treatment strategies still needs to be established. The review discusses a possible molecular basis for predictive tissue biomarkers such as melanoma thickness, ulceration and mitotic activity, and provides a list of promising new biomarkers identified from tissue microarrays that needs confirmation by independent, prospectively collected clinical data sets. In addition, common predictive serum biomarkers--lactate dehydrogenase, S100B and melanoma-inhibiting activity--as well as selected investigational serum biomarkers such as TA90IC and YKL-40 are also reviewed. A more accurate, therapeutically predictive classification of human melanomas and selection of patient populations that would profit from therapeutic interventions are among the major challenges expected to be addressed in the future.
Constitutive and cytokine induced expression of HLA molecules, secretory component, and intercellular adhesion molecule-1 is modulated by butyrate in the colonic epithelial cell line HT-29.
Authors: D Kvale, P Brandtzaeg
Journal: Gut (1995)

Normal colonic epithelial cells play an important part in the mucosal immune system and use butyrate, a bacterial fermentation product, as an important energy source. Butyrate deficiency has been associated with inflammatory bowel disease, diversion colitis, and pseudomembranous colitis. Butyrate effects on important molecules for epithelial immune functions were studied in a colonic epithelial cell line (HT-29): the constitutive and cytokine regulated expression of secretory component (poly-Ig receptor), HLA class I and II molecules, and intercellular adhesion molecule-1 (ICAM-1). Butyrate facilitated the constitutive expression of secretory component and HLA class I. Butyrate furthermore tended to enhance cytokine mediated stimulation of protein expression, although tumour necrosis factor alpha (TNF) and interleukin 4 (IL 4) responses on HLA class I and secretory component, respectively, were relatively inhibited by butyrate. Cytokine mediated accumulation in the various mRNAs usually increased even more in the presence of butyrate, with the exception of TNF response on HLA class I and secretory component mRNA concentrations. In conclusion, butyrate may substantially influence constitutive and cytokine mediated expression of molecules with immune functions in a complex and differentiated manner, and butyrate deficiencies, as seen in various clinical conditions, might influence mucosal immune responses.