tbuckley/cabot-search huggingface dataset:
Use of the Humanized Anti-Epidermal Growth Factor Receptor Monoclonal Antibody h-R3 in Combination With Radiotherapy in the Treatment of Locally Advanced Head and Neck Cancer Patients
Authors: Tania Crombet, Marta Osorio, Teresa Cruz, Carlos Roca, Ramón del Castillo, Rosa Mon, Normando Iznaga-Escobar, René Figueredo, James Koropatnick, Enrique Renginfo, Eduardo Fernández, Daniel Alvárez, Olga Torres, Mayra Ramos, Idrissa Leonard, Rolando Pérez, Agustín Lage
Journal: Journal of Clinical Oncology (2004)

To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built.Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response.The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity.h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.
Novel Proteasome Inhibitors to Overcome Bortezomib Resistance
Authors: Amy M. Ruschak, Malik Slassi, Lewis E. Kay, Aaron D. Schimmer
Journal: JNCI Journal of the National Cancer Institute (2011)

The proteasome is an intracellular enzyme complex that degrades ubiquitin-tagged proteins and thereby regulates protein levels within the cell. Given this important role in maintaining cellular homeostasis, it is perhaps somewhat surprising that proteasome inhibitors have a therapeutic window. Proteasome inhibitors have demonstrated clinical efficacy in the treatment of multiple myeloma and mantle cell lymphoma and are under evaluation for the treatment of other malignancies. Bortezomib is the first and only Food and Drug Administration-approved proteasome inhibitor that inhibits this enzyme complex in a reversible fashion. Although bortezomib improves clinical outcomes when used as a single agent, most patients do not respond to this drug and those who do respond almost uniformly relapse. As such, efforts are underway to develop proteasome inhibitors that act through mechanisms distinct from that of bortezomib. Specifically, inhibitors that bind the active site of the proteasome and inhibit the complex irreversibly have been developed and are in advanced clinical trials. Inhibitors that act on sites of the proteasome outside of the catalytic center have also been identified and are in preclinical development. In this review, we discuss the structure and function of the proteasome. We then focus on the molecular biology, chemistry, and the preclinical and clinical efficacy of novel proteasome inhibitors as strategies to inhibit this target and overcome some forms of bortezomib resistance.
Weight Gain Associated With Increased Food Intake and Low Habitual Activity Levels in Male Adolescent Schizophrenic Inpatients Treated With Olanzapine
Authors: Doron Gothelf, Bareket Falk, Pierre Singer, Michal Kairi, Moshe Phillip, Levana Zigel, Irit Poraz, Siegal Frishman, Naama Constantini, Gil Zalsman, Abraham Weizman, Alan Apter
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors studied weight gain mechanisms and energy balance in patients treated with olanzapine. METHOD: The body mass index of male schizophrenic adolescent inpatients treated with olanzapine (N=10) and of 10 matched patients treated with haloperidol (N=10) were measured at baseline and after 4 weeks of treatment. For the patients treated with olanzapine, caloric intake, resting energy expenditure, and physical activity (determined through accelerometry and heart rate monitoring) were assessed at baseline and after 4 weeks of treatment. RESULTS: Body mass index significantly increased in those treated with olanzapine but not in those given haloperidol. The increase in body mass index was due to an increase in caloric intake without change in diet composition. Olanzapine had no significant effect on resting energy expenditure. Daily energy expenditure was very low before and after treatment. CONCLUSIONS: Olanzapine-induced weight gain is associated with a general increase in caloric intake.
Current status of haploidentical stem cell transplantation for leukemia
Authors: Xiao-jun Huang
Journal: Journal of Hematology & Oncology (2008)

Haploidentical hematopoietic stem cell transplantation has made tremendous progress over the past 20 years and has become a feasible option for leukemia patients without a HLA identical sibling donor. The early complications of severe graft-versus-host disease (GVHD), graft failure and delayed engraftment, as well as disease recurrence have limited the use of this approach. Newer strategies have been applied and overcome some of the problems, including the use of T-cell depleted graft, "mega" dose of stem cells, intensive post-transplant immunosuppression and manipulation of the graft. These have decreased the transplant related mortality and GVHD associated with haploidentical transplantation, however, the major problems of disease relapse and infection, which related to late immune reconstitution, limit the development of haploidentical HSCT. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GVHD, while preserving graft-versus-leukemia effect to prevent the recurrence of underlying malignancy.
Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial
Authors: Kazumoto Iijima, Mayumi Sako, Kandai Nozu, Rintaro Mori, Nao Tuchida, Koichi Kamei, Kenichiro Miura, Kunihiko Aya, Koichi Nakanishi, Yoshiyuki Ohtomo, Shori Takahashi, Ryojiro Tanaka, Hiroshi Kaito, Hidefumi Nakamura, Kenji Ishikura, Shuichi Ito, Yasuo Ohashi
Journal: The Lancet (2014)
Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction
Authors: Kaare Harald Bønaa, Inger Njølstad, Per Magne Ueland, Henrik Schirmer, Aage Tverdal, Terje Steigen, Harald Wang, Jan Erik Nordrehaug, Egil Arnesen, Knut Rasmussen
Journal: New England Journal of Medicine (2006)

Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction.
Screening and Prevention of Venous Thromboembolism in Critically Ill Patients
Authors: Sachin Sud, Nicole Mittmann, Deborah J. Cook, William Geerts, Brian Chan, Peter Dodek, Michael K. Gould, Gordon Guyatt, Yaseen Arabi, Robert A. Fowler
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality.To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients.A Markov decision analytic model to compare weekly compression ultrasound screening (screening) plus investigation for clinically suspected deep vein thrombosis (DVT) (case finding) versus case finding alone; and a hypothetical program to increase adherence to DVT prevention. Probabilities were derived from a systematic review of venous thromboembolism in medical-surgical intensive care unit patients. Costs (in 2010 $US) were obtained from hospitals in Canada, Australia, and the United States, and the medical literature. Analyses were conducted from a societal perspective over a lifetime horizon. Outcomes included costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios.In the base case, the rate of proximal DVT was 85 per 1,000 patients. Screening resulted in three fewer pulmonary emboli than case-finding alone but also two additional bleeding episodes, and cost $223,801 per QALY gained. In sensitivity analyses, screening cost less than $50,000 per QALY only if the probability of proximal DVT increased from a baseline of 8.5-16%. By comparison, increasing adherence to appropriate pharmacologic thromboprophylaxis by 10% resulted in 16 fewer DVTs, one fewer pulmonary emboli, and one additional heparin-induced thrombocytopenia and bleeding event, and cost $27,953 per QALY gained. Programs achieving increased adherence to best-practice venous thromboembolism prevention were cost-effective over a wide range of program costs and were robust in probabilistic sensitivity analyses.Appropriate prophylaxis provides better value in terms of costs and health gains than routine screening for DVT. Resources should be targeted at optimizing thromboprophylaxis.
Lethal Outbreak of Hepatitis B in a Dental Practice
Authors: Frederic E. Shaw
Journal: JAMA (1986)

Between April 1, 1984, and Feb 1, 1985, nine cases of hepatitis B occurred in the patients of a dentist practicing in a rural Indiana county (population, 35,000). This was over 20 times the mean annual incidence for the county in the previous decade. All of the patients had been treated by the dentist two to five months before illness. Although the dentist had never had hepatitis symptoms, his serum was positive for hepatitis B surface antigen and hepatitis B e antigen and negative for anti-hepatitis B core IgM antibody, indicating that he was probably a hepatitis B carrier. Two patients (22%) died of fulminant hepatitis; the case-fatality ratio was over ten times the reported US mean for hepatitis B. Using a case definition based on anti-hepatitis B core IgM antibody positivity and exposure to the dentist during a defined time period, a serosurvey of the dentist's patients identified 15 asymptomatic cases (overall attack rate, 3.2%). Infection risk was related to the amount of trauma involved in the cases' dental procedures. No cause was found for the unusual lethality of the outbreak.
Implications of universal screening for HIV infection
Authors: J. Sugarman
Journal: BMJ (2013)

Ethical concerns must be considered and sound practices adopted 

Universal voluntary screening of all adolescents and adults for HIV infection is now recommended by the United States Preventive Services Task Force.1 This follows similar recommendations announced by the US Centers for Disease Control in 2006.2 Although there are good reasons for endorsing universal screening, the ethical and practical implications of this approach need to be considered.

Universal voluntary screening could help identify asymptomatic people who are infected with HIV but who might otherwise go undetected until late in the course of infection. It is essential to identify such people for their own personal health and the health of others to whom they may unwittingly transmit the virus. Because of advances in the care of HIV infection, early treatment is paramount, both for individual benefit and for decreasing the likelihood of transmission. Taken together, there is a clear public health imperative to screen for this infection.3

A crucial aspect of the task …
THoR: a tool for domain discovery and curation of multiple alignments.
Authors: Nicholas J Dickens, Chris P Ponting
Journal: Genome biology (2003)

We describe a tool, THoR, that automatically creates and curates multiple sequence alignments representing protein domains. This exploits both PSI-BLAST and HMMER algorithms and provides an accurate and comprehensive alignment for any domain family. The entire process is designed for use via a web-browser, with simple links and cross-references to relevant information, to assist the assessment of biological significance. THoR has been benchmarked for accuracy using the SMART and pufferfish genome databases.
Prevalence of Diabetes in New York City, 2002–2008
Authors: Leena S. Gupta, Charles C. Wu, Stephanie Young, Sharon E. Perlman
Journal: Diabetes Care (2011)

To describe diabetes prevalence in New York City by race/ethnicity and nativity.Data were from the New York City 2002-2008 Community Health Surveys. Respondents were categorized on the basis of self-reported race/ethnicity and birth country: foreign-born South Asian (Indian subcontinent), foreign-born other Asian, U.S.-born non-Hispanic black, U.S.-born non-Hispanic white, and U.S.-born Hispanic. Diabetes status was defined by self-reported provider diagnosis. Multivariable models examined diabetes prevalence by race/ethnicity and birth country.Prevalence among foreign-born South Asians was nearly twice that of foreign-born other Asians (13.6 vs. 7.4%, P = 0.001). In multivariable analyses, normal-BMI foreign-born South Asians had nearly five times the diabetes prevalence of comparable U.S.-born non-Hispanic whites (14.1 vs. 2.9%, P < 0.001) and 2.5 times higher prevalence than foreign-born other Asians (P < 0.001).Evaluating Asians as one group masks the higher diabetes burden among South Asians. Researchers and clinicians should be aware of differences in this population.
Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells
Authors: I D Iliev, I Spadoni, E Mileti, G Matteoli, A Sonzogni, G M Sampietro, D Foschi, F Caprioli, G Viale, M Rescigno
Journal: Gut (2009)

<h3>Objective:</h3> In mice, a subpopulation of gut dendritic cells (DCs) expressing CD103 drives the development of regulatory T (T<sub>reg</sub>) cells. Further, it was recently described that the cross-talk between human intestinal epithelial cells (IECs) and DCs helps in maintaining gut immune homeostasis via the induction of non-inflammatory DCs. In this study, an analysis was carried out to determine whether IECs could promote the differentiation of CD103<sup>+</sup> tolerogenic DCs, and the function of primary CD103<sup>+</sup> DCs isolated from human mesenteric lymph nodes (MLNs) was evaluated. <h3>Methods:</h3> Monocyte-derived DCs (MoDCs) and circulating CD1c<sup>+</sup> DCs were conditioned or not with supernatants from Caco-2 cells or IECs isolated from healthy donors or donors with Crohn's disease and analysed for their ability to induce T<sub>reg</sub> cell differentiation. In some cases, transforming growth factor β (TGFβ), retinoic acid (RA) or thymic stromal lymphopoietin (TSLP) were neutralised before conditioning. CD103<sup>+</sup> and CD103<sup>−</sup> DCs were sorted by fluorescence-activated cell sorting (FACS) from MLNs and used in T<sub>reg</sub> cell differentiation experiments. <h3>Results:</h3> It was found that human IECs promoted the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3<sup>+</sup> T<sub>reg</sub> cells. This control was lost in patients with Crohn's disease and paralleled a reduced expression of tolerogenic factors by primary IECs. MoDCs differentiated with RA or IEC supernatant upregulated the expression of CD103. Consistently, human primary CD103<sup>+</sup> DCs isolated from MLNs were endowed with the ability to drive T<sub>reg</sub> cell differentiation. This subset of DCs expressed CCR7 and probably represents a lamina propria-derived migratory population. <h3>Conclusions:</h3> A population of tolerogenic CD103<sup>+</sup> DCs was identified in the human gut that probably differentiate in response to IEC-derived factors and drive T<sub>reg</sub> cell development.
Severe pulmonary stenosis in infancy and early childhood
Authors: I. M. Anderson, S. Nouri-Moghaddam
Journal: Thorax (1969)

Twenty-six patients in infancy and early childhood with severe pulmonary valve stenosis and intact ventricular septum are reviewed. They were selected from a larger series of 112 patients with pulmonary stenosis of any degree, on account of early onset of symptoms and the severity of the stenosis proven by cardiac catheterization and angiocardiography, at operation or at necropsy. Our criteria for severity in this series were: presence of symptoms within the first two years of life; right ventricular and right atrial hypertrophy on electrocardiography; and right ventricular pressure equal to or higher than systemic blood pressure. The warning signs prompting valvotomy are deterioration of the following features: cyanosis and dyspnoea; congestive cardiac failure; tricuspid incompetence; cardiac enlargement and pulmonary oligaemia on radiograph; and right ventricular and right atrial hypertrophy on electrocardiography. The lives of 13 patients were saved by timely valvotomy. These patients are all well six months to six years after operation. Five patients died before any operation could be performed. Eight patients died within 48 hours of operation. Had some of these patients been operated on earlier the evidence indicates that they would have had a better prognosis. Therefore the importance of early recognition, prompt treatment, and emergency valvotomy, if necessary, is emphasized.
Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents
Authors: Stephen C. Benoit, Christopher J. Kemp, Carol F. Elias, William Abplanalp, James P. Herman, Stephanie Migrenne, Anne-Laure Lefevre, Céline Cruciani-Guglielmacci, Christophe Magnan, Fang Yu, Kevin Niswender, Boman G. Irani, William L. Holland, Deborah J. Clegg
Journal: Journal of Clinical Investigation (2009)

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.
Effect of Body Mass Index on Recurrences in Tamoxifen and Anastrozole Treated Women: An Exploratory Analysis From the ATAC Trial
Authors: Ivana Sestak, Wolfgang Distler, John F. Forbes, Mitch Dowsett, Anthony Howell, Jack Cuzick
Journal: Journal of Clinical Oncology (2010)

Third-generation aromatase inhibitors have been widely used in postmenopausal women for the adjuvant treatment of hormone receptor-positive breast cancer. As aromatase inhibitors work by inhibiting the conversion of androgens to estrogens in adipose tissue, we hypothesized that anastrozole may be more effective in women with a high body mass index (BMI).The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized clinical trial in which postmenopausal women with early-stage breast cancer were randomly assigned to receive oral daily anastrozole (1 mg) alone, tamoxifen (20 mg) alone, or the combination in a double-blind fashion. Analyses were based on the 100-month median follow-up for women with hormone receptor-positive breast cancers (estrogen [ER] and/or progesterone [PgR] positive). Here, we investigate the impact of BMI on recurrence and the relative benefit of anastrozole versus tamoxifen according to baseline BMI. Results Overall, women with a high BMI (BMI > 35 kg/m(2)) at baseline had more recurrences than those women with a low BMI (BMI < 23 kg/m(2); adjusted hazard ratio [HR], 1.39; 95% CI, 1.06 to 1.82; P(heterogeneity) = .03) and significantly more distant recurrences (adjusted HR, 1.46; 95% CI, 1.07 to 1.61; P(heterogeneity) = .01). Overall, the relative benefit of anastrozole versus tamoxifen was nonsignificantly better in thin women compared to overweight women.These results confirm the poorer prognosis of obese women with early-stage breast cancer. Recurrence rates were lower for anastrozole than tamoxifen for all BMI quintiles. Our results suggest that the relative efficacy of anastrozole compared to tamoxifen is greater in thin postmenopausal women and higher doses or more complete inhibitors might be more effective in overweight women, but this requires independent confirmation.
(59) Non-iatrogenic chronic arsenicism
Authors: M.E. Kesseler, D. Slater
Journal: British Journal of Dermatology (1986)

Journal Article (59) Non‐iatrogenic chronic arsenicism Get access M.E. Kesseler, Drs, M.E. Kesseler, Drs Rotherham District General Hospital Search for other works by this author on: Oxford Academic Google Scholar D. Slater D. Slater Rotherham District General Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue s30, 1 July 1986, Page 102, https://doi.org/10.1111/j.1365-2133.1986.tb07754.x Published: 01 July 1986
Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice.
Authors: K Rajkumar, M Krsek, S T Dheen, L J Murphy
Journal: Journal of Clinical Investigation (1996)

Transgenic mice that overexpressed IGFBP-1 are hyperinsulinemic in the first week of life and gradually develop fasting hyperglycemia. In adult transgenic mice, the hypoglycemic response to IGF-I but not insulin or des (1-3) IGF-I was attenuated (P < 0.05) compared with wild-type mice. Furthermore, in isolated adipocytes from transgenic mice, the stimulatory effect of IGF-I but not insulin on 2-deoxy-[3H]-glucose uptake was reduced (P < 0.02). In contrast, in isolated soleus muscle, the effects of both IGF-I and insulin on 2-deoxy-3H-glucose uptake and on [3H]-glucose incorporation into glycogen were significantly reduced compared to wild-type mice. The decline in specific activity of the 2-deoxy-3H-glucose, a measure of glucose appearance in the circulation, was more marked in transgenic animals (P < 0.05). In addition, tissue uptake of glucose was significantly higher in diaphragm, heart, intestine, liver, soleus muscle, and adipose tissue from fasting transgenic mice. Plasma concentrations of alanine, lysine, and methionine were also elevated in transgenic mice. These data suggest that overexpression of IGFBP-1 attenuates the hypoglycemic effect of endogenous IGF-I, which is initially compensated for by enhanced pancreatic insulin production. However, in adult mice pancreatic insulin content is reduced, insulin resistance is demonstrable in skeletal muscle and fasting hyperglycemia develops.