tbuckley/cabot-search huggingface dataset:
Comparison of Lysine-Rich Histones in Various Normal and Neoplastic Mouse Tissues&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Philip Hohmann, R. David Cole, Howard A. Bern
Journal: JNCI Journal of the National Cancer Institute (1971)

Lysine-rich histones from several normal and neoplastic mouse tissues were fractionated by chromatography and the subfractions in neoplastic tissues shown to match the normal ones. Individually, lysine-rich histone subfractions varied quantitatively from one tissue to another and possessed different specific activities after labeling in vivo.
Multicompartmental Analysis of Cholesterol Metabolism in Man
Authors: Charles C. Schwartz, Mones Berman, Z. R. Vlahcevic, L. Gregg Halloran, Daniel H. Gregory, Leon Swell
Journal: Journal of Clinical Investigation (1978)

The present report has presented the first clear evidence in man for the existence of specific hepatic cholesterol precursor sites associated with the formation and secretion of bile acids and biliary cholesterol. These hepatic compartments derive virtually all their cholesterol from newly synthesized and lipoprotein free cholesterol. The model which is presented was formulated on current concepts of cholesterol metabolism in man and is concerned, at this initial stage, with the elucidation of the bile acid and biliary cholesterol compartments. The complexity of cholesterol metabolism in man necessitated an initial approach that would minimize the number of inputs of cholesterol into the system, allow for the sampling of several cholesterol compartments, and permit the simultaneous labeling of newly synthesized cholesterol and preformed cholesterol. To achieve these objectives, we studied the patient with a total bile fistula. Six patients were administered simultaneously pulse injections of labeled mevalonic acid and [14C]cholesterol. The qualitative features of the specific activity time course curves after labeled mevalonic acid revealed no precursor-product relationship between bile acid, biliary cholesterol, and plasma free cholesterol. The peak specific activity of the bile acids was reached in approximately 100 min and was higher than the biliary cholesterol, which was higher than the plasma free cholesterol. The plasma free cholesterol specific activity became higher than the other lipids after 12 h and remained higher throughout the period of study. Similar related observations were made with [14C]cholesterol. The data were then subjected to simulation analysis and modeling using the SAAM-27 computer program. Computer least-square fits of the data were obtained after the model was evolved. During the model development, the least number of compartments and transport pathways were introduced consistent with a good fit of the data. Of particular importance was the constraint that the model fit the data obtained from both [14C]cholesterol and labeled mevalonic acid. The same parameter values were used to fit the data from both tracers. The fluxes arrived at in the model indicate that 31% and 20%, respectively, of the cholesterol input into the bile acid and biliary cholesterol precursor sites were derived directly from the newly synthesized hepatic cholesterol. The remainder had its origin predominantly from lipoprotein free cholesterol. Plasma esterified cholesterol (as free) made a small contribution (11%) to the bile acid compartment. Similarly, 10% of the biliary cholesterol arose from an unknown hepatic site.
Cyclophosphamide Plus Topotecan in Children With Recurrent or Refractory Solid Tumors: A Pediatric Oncology Group Phase II Study
Authors: Robert L. Saylors, Kimo C. Stine, Jim Sullivan, James L. Kepner, Donna A. Wall, Mark L. Bernstein, Michael B. Harris, Robert Hayashi, Teresa J. Vietti for the Pediatric Oncology Group
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the response rate of the combination of cyclophosphamide and topotecan in pediatric patients with recurrent or refractory malignant solid tumors. PATIENTS AND METHODS: A total of 91 pediatric patients, 83 of whom were fully assessable for response and toxicity, received cyclophosphamide (250 mg/m 2 /dose) followed by topotecan (0.75 mg/m 2 /dose), each given as a 30-minute infusion daily for 5 days. All patients received filgrastim (5 mcg/kg) daily until the absolute neutrophil count (ANC) was ≥ 1,500 μL after the time of the expected ANC nadir. RESULTS: A total of 307 treatment courses were given to the 83 fully assessable patients. Responses (complete response plus partial response) were seen in rhabdomyosarcoma (10 of 15 patients), Ewing’s sarcoma (six of 17 patients), and neuroblastoma (six of 13 patients). Partial responses were seen in two of 18 patients with osteosarcoma and in one patient with a Sertoli-Leydig cell tumor. Twenty-three patients had either minor responses (n = 6) or stable disease (n = 17); the median number of courses administered to patients with partial or complete response was six (range, two to 13 courses), and the median administered to those with stable disease was three (range, one to 11 courses). The toxicity of the combination was limited principally to the hematopoietic system. Of 307 courses, 163 (53%) were associated with grade 3 or 4 neutropenia, 84 (27%) with grade 3 or 4 anemia, and 136 (44%) with grade 3 or 4 thrombocytopenia. Despite the severe myelosuppression, only 34 (11%) of 307 courses were associated with grade 3 or 4 infection. Nonhematopoietic toxicity of grades ≥ 3 was rare and consisted of nausea and vomiting (two courses), perirectal mucositis (one course), transaminase elevation (one course), and hematuria (two courses). CONCLUSION: The combination of cyclophosphamide and topotecan is active in rhabdomyosarcoma, neuroblastoma, and Ewing’s sarcoma. Stabilization of disease was seen in osteosarcoma, although objective responses were rare in this disease. The therapy can be given with acceptable hematopoietic toxicity with the use of filgrastim support.
Filaggrin mutations are associated with recurrent skin infection in Singaporean Chinese patients with atopic dermatitis
Authors: S.C.S. Cai, H. Chen, W.-P. Koh, J.E.A. Common, H.P. van Bever, W.H.I. McLean, E.B. Lane, Y.C. Giam, M.B.Y. Tang
Journal: British Journal of Dermatology (2011)

Journal Article Filaggrin mutations are associated with recurrent skin infection in Singaporean Chinese patients with atopic dermatitis Get access S.C.S. Cai, S.C.S. Cai Institute of Medical Biology, A*STAR, 8A Biomedical Grove, 138648 Singapore, SingaporeEpithelial Genetics Group, Division of Molecular Medicine, Colleges of Life Sciences, Medicine, Dentistry and Nursing, Medical Sciences Institute, Dundee, U.K Search for other works by this author on: Oxford Academic Google Scholar H. Chen, H. Chen Institute of Medical Biology, A*STAR, 8A Biomedical Grove, 138648 Singapore, SingaporeEpithelial Genetics Group, Division of Molecular Medicine, Colleges of Life Sciences, Medicine, Dentistry and Nursing, Medical Sciences Institute, Dundee, U.K Search for other works by this author on: Oxford Academic Google Scholar W.‐P. Koh, W.‐P. Koh Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore Search for other works by this author on: Oxford Academic Google Scholar J.E.A. Common, J.E.A. Common Institute of Medical Biology, A*STAR, 8A Biomedical Grove, 138648 Singapore, Singapore Search for other works by this author on: Oxford Academic Google Scholar H.P. van Bever, H.P. van Bever Department of Paediatrics, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore Search for other works by this author on: Oxford Academic Google Scholar W.H.I. McLean, W.H.I. McLean Department of Paediatrics, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore Search for other works by this author on: Oxford Academic Google Scholar E.B. Lane, E.B. Lane Institute of Medical Biology, A*STAR, 8A Biomedical Grove, 138648 Singapore, Singapore Search for other works by this author on: Oxford Academic Google Scholar Y.C. Giam, Y.C. Giam National Skin Centre, 1 Mandalay Road, Singapore 308205, Singapore Search for other works by this author on: Oxford Academic Google Scholar M.B.Y. Tang M.B.Y. Tang National Skin Centre, 1 Mandalay Road, Singapore 308205, Singapore Mark B.Y. Tang. E‐mail: marktang@nsc.gov.sg Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 1, 1 January 2012, Pages 200–203, https://doi.org/10.1111/j.1365-2133.2011.10541.x Published: 01 January 2012 Article history Accepted: 19 July 2011 Published: 01 January 2012
Defining response of ovarian carcinoma to initial chemotherapy according to serum CA 125.
Authors: G J Rustin, A E Nelstrop, P McClean, M F Brady, W P McGuire, W J Hoskins, H Mitchell, H E Lambert
Journal: Journal of Clinical Oncology (1996)

To produce definitions based on serial CA 125 levels to measure response of ovarian carcinoma in patients receiving first-line chemotherapy.Definitions were derived from analysis of 277 patients in North Thames Ovary Trial 3. Patient data were then incorporated into a computer program and tested against 254 patients in North Thames Ovary Trial 4 and 458 patients in Gynecologic Oncology Group (GOG) protocol 97. For optimum detection of response, three response definitions have been combined into a computer program. The precise definitions use mathematic logic and take account of factors such as intervening samples. Response to a specific treatment has occurred if after two samples there has been a 50% decrease, confirmed by a fourth sample (50% response), or a serial decrease over three samples of greater than 75% (75% response). The final sample has to be at least 28 days after the previous sample.Six hundred twenty of 989 patients were considered assessable for response according to CA 125 level. Only two patients (0.3%) had a CA 125 response at the time of clinical progression. The CA 125 response rate was 62% and 54% in the North Thames trials. In the GOG trial, it was 66% in all 317 patients assessable for CA 125 and 67% in 221 patients whose CA 125 level was not measurable according to GOG criteria, compared with a GOG-defined response rate of 62%. The sensitivity for detecting GOG-defined response was at least 68%.Definitions based on a 50% or 75% decrease of CA 125 levels have been shown reliably to define partial response of ovarian cancer in patients receiving first-line chemotherapy. These definitions should be used in addition to or instead of standard response criteria.
Selective Treg reconstitution during lymphopenia normalizes DC costimulation and prevents graft-versus-host disease
Authors: Holly A. Bolton, Erhua Zhu, Alexandra M. Terry, Thomas V. Guy, Woon-Puay Koh, Sioh-Yang Tan, Carl A. Power, Patrick Bertolino, Katharina Lahl, Tim Sparwasser, Elena Shklovskaya, Barbara Fazekas de St. Groth
Journal: Journal of Clinical Investigation (2015)

Regulatory T cells (Tregs) have been shown to enhance immune reconstitution and prevent graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation; however, it is unclear how Tregs mediate these effects. Here, we developed a model to examine the mechanism of Treg-dependent regulation of immune reconstitution. Lymphopenic mice were selectively reconstituted with Tregs prior to transfer of conventional CD4+ T cells. Full Treg reconstitution prevented the rapid oligoclonal proliferation that gives rise to pathogenic CD4 effector T cells, while preserving the slow homeostatic form of lymphopenia-induced peripheral expansion that repopulates a diverse peripheral T cell pool. Treg-mediated CTLA-4-dependent downregulation of CD80/CD86 on DCs was critical for inhibition of rapid proliferation and was a function of the Treg/DC ratio achieved by reconstitution. In an allogeneic BM transplant model, selective Treg reconstitution before T cell transfer also normalized DC costimulation and provided complete protection against GVHD. In contrast, cotransfer of Tregs was not protective. Our results indicate that achieving optimal recovery from lymphopenia should aim to improve early Treg reconstitution in order to increase the relative number of Tregs to DCs and thereby inhibit spontaneous oligoclonal T cell proliferation.
Blood-Group Isoantigens in Leukemic Cells: Reversibility of Isoantigenic Changes by Neuraminidase&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. T. Kassulke, O. Stutman, E. J. Yunis
Journal: JNCI Journal of the National Cancer Institute (1971)
Protection of Human Neutrophils by Endogenous Catalase
Authors: Dirk Roos, Ron S. Weening, Sonja R. Wyss, Hugo E. Aebi
Journal: Journal of Clinical Investigation (1980)

To investigate the importance of catalase as a protecting enzyme against oxidative damage in phagocytic leukocytes, we have tested the functional capacity of neutrophils from two individuals homozygous for Swiss-type acatalasemia and from two individuals heterozygous for this deficiency. In the former cells, 25-30% of residual activity of catalase was present. In the latter cells, the values were close to normal. Chemotaxis towards casein, release of lysosomal enzymes and hydrogen peroxide during phagocytosis of zymosan, and intracellular killing of Staphylococcus aureus were normal in all cells tested. Inhibition of heme enzymes with azide (2 mM) enhanced the respiration and hexose monophosphate shunt activity of normal, but not of homozygous acatalasemic, neutrophils. This indicates that the enhancement in normal cells is, at least in part, due to catalase inhibition. After 15 min preincubation with an H(2)O(2)-generating system (glucose plus glucose oxidase), the respiratory response to zymosan phagocytosis was strongly depressed in the homozygous acatalasemic and in normal, azide-treated neutrophils, but not in normal, untreated cells. Under these conditions, the release of lysosomal enzymes was depressed and that of lactate dehydrogenase enhanced, in catalase-deficient and in catalase-inhibited, but not in normal, neutrophils. During prolonged incubation with the H(2)O(2)-generating system (30-60 min), the reduction level of intracellular glutathione remained high and the hexose monophosphate shunt continued to operate normally in all cells tested. Thus, although the function of neutrophils without catalase activity was depressed by extracellular hydrogen peroxide, the H(2)O(2) degradation via the glutathione redox system remained operative. The results indicate that the glutathione redox system by itself efficiently protects phagocytosing neutrophils against their own oxidative products. During heavy external oxidative stress, however, both catalase and the glutathione redox system are needed for adequate protection.
Morphogenesis and Growth Potentiality of Mammary Glands in Mice. I. Transplantability and Growth Potentiality of Mammary Tissue of Virgin Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;3&lt;/xref&gt;
Authors: Kazumasa Hoshino
Journal: JNCI Journal of the National Cancer Institute (1962)

Separation of mammary ducts from the nipple or the primary lactiferous duct, and resection of the mammary glands, except the portion proximal to the nipple, did not interfere with the growth of the remaining portion of the mammary gland. One hundred and fifty-one segments of the upper four pairs of mammary glands of virgin mice were transplanted into either male or female isologous hosts at four different sites—the pararenal fat pad, the dorsal subcutaneous area, the retroauricular fat-pad area, and the fourth mammary-gland-free fat pad. Female donors and both male and female hosts of the CBA and C57BL strains and their reciprocal CC hybrid groups were used. The transplanted mammary tissue grew equally well in all isologous combinations and parental to hybrid combinations. Transplantability, except for the size attained by the grafts, was not affected by the age or sex of donors and hosts, or the site of transplantation. Successfully transplanted mammary glands responded to either endogenous or exogenous hormones in a manner similar to the controls. They developed fully and lactated at all sites after parturition of the host, regardless of the extent of growth. The transplants at the four sites were similar histologically. The extent of growth was controlled by 1) the amount of adipose tissue at the transplantation site available for growth of the transplants, 2) the period of transplantation, and 3) the hormonal environment. The first factor was the essential one. The adipose tissue transplanted with the mammary parenchyma did not grow, but often diminished in size and was replaced by differing amounts of connective tissue of the host.
Clinical assessment of a portable FEV1/FEV6 meter for the detection of airway obstruction
Authors: Jan Vandevoorde, Rosalie Buysschaert, Sylvia Verbanck, Daniel Schuermans
Journal: European Respiratory Journal (2012)

Objectives  To evaluate the accuracy of the portable Vitalograph-COPD-6 device in the detection of airway obstruction.  Methodology  All participants underwent a measurement of FEV 1 , FEV 6  and FEV 1 /FEV 6  using the COPD-6 meter, and a conventional spirometry measuring FEV 1 , FVC and FEV 1 /FVC. Conventional spirometry was performed by highly trained lung function staff, whereas the COPD-6 meter was used by final-year medical students, according to the manufacturer9s instructions. Subjects were randomized to determine which measurement was performed first. The FEV 1 /FEV 6  ratio that corresponded to the optimal combination of sensitivity and specificity was determined from a ROC curve. Agreement was analyzed by calculating sensitivity, specificity, positive and negative predictive values (PPV and NPV), and the kappa-index.  Results  Test results of 147 subjects were analyzed. The prevalence of obstruction was 42%. The area under the ROC-curve was 0.946. The FEV 1 /FEV 6  ratio that corresponded to the optimal combination of sensitivity and specificity was 73%. For this cutoff value sensitivity, specificity, PPV and NPV were 82%, 93%, 90% and 88%, respectively. The kappa-index was 0.76. Lowering the cutoff point to 70% resulted in sensitivity, specificity, PPV and NPV of 65%, 98%, 95% and 79%, respectively. For a FEV 1 /FEV 6  cutoff point of 80%, they were 95%, 69%, 69% and 95%, respectively.  Conclusions  The portable Vitalograph-copd-6 device is an accurate device for detection of airway obstruction. Best sensitivity/specificity for FEV 1 /FEV 6  was obtained with a fixed cutoff point of 73%. For screening purposes, high sensitivity (95%) can be reached when using an 80% threshold for FEV 1 /FEV 6 .
Cost-effectiveness of a specialized nursing smoking-cessation unit in a tertiary hospital
Authors: Belen Ruiz Antorán, Trinidad Muñoz, Isabel Millán, Concepción Payares, Lucía Serrano, Myriam Aguilar Pérez, Rosa Malo de Molina Ruiz, Cristina Avendaño-Solá, Piedad Ussetti Gil
Journal: European Respiratory Journal (2014)

Introduction   There are different therapeutic approaches to support smoking cessation and long-term smoking abstinence that have shown to be cost-effective.   Objective :To analyse the cost-effectiveness of the Specialized Nursing Smoking Cessation Unit in a tertiary hospital.   Methods :In 2010,the nursing Specialized Smoking Cessation Unit was established,after specific training and medical support to the nursing staff.A retrospective descriptive study has been performed to assess the results of the visits from 2010 to 2013.Smoking cessation success was defined as subjects who remained abstinent after 6 months of follow-up.Regarding the cost estimation,direct healthcare cost estimates have been applied,excluding drug cost,indirect healthcare costs and non-healthcare costs.   Results :322 smokers were included(53±12 age;52% females),Fagerstrom test of 7,22 cigarettes/day,85% had previous unsuccessful attempts and 63% had co-morbidities.After follow-up,33.5% of patients remained abstinent.The average cost per abstinent included smoker at the follow-up visit was 212 euros.The most cost-effective intervention was observed in subjects l30 years of age versus ≥30 years old,with a total cost of 146 vs 212 euros.The overall cost of the specialized intervention in comparison with the “classical”approach was reduced by 60%(212 vs 537 euros).   Conclusion :The Specialized Nursing Unit has obtained similar results to those observed for more complex and higher cost Units, even though the majority of subjects included were prior relapsers and showed a high degree of nicotine dependence.  To promote the implementation of Specialized Nursing Smoking-cessation Units seems a highly cost-effective smoking-cessation strategy.
P-115 Transarterial Chemo-Embolization (TACE) and Radio-Embolization (TARE) in the combined modality treatment of advanced biliary tract cancer (aBTC): evaluation of feasibility and activity
Authors: V. Marsico, E. Vasile, G. Brandi, F. Leone, D. Santini, G. Aprile, S. Cereda, N. Silvestris, M. Milella, F. Bergamo, L. Fornaro, M. Bolshinsky, I. Paladina, S. Lonardi, C. Aliberti
Journal: Annals of Oncology (2015)
Selective Inhibition of Growth and Respiration of Melanomas by Tyrosinase Inhibitors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Harry B. Demopoulos, Martha A. Gerving, Helen Bagdoyan
Journal: JNCI Journal of the National Cancer Institute (1965)

A segment of respiration in pigmented human melanomas can be depressed in vitro by phenyl lactate, a tyrosinase inhibitor. Amelanotic human and nonpigmented S91 melanomas do not have a portion of respiration sensitive to this agent. The phenyl lactate-sensitive segment may be vital to pigmented melanoma melanocytes because the Pasteur effect is released when this segment is depressed. B16 mouse melanomas, which are very fast growing, heavily pigmented tumors, are resistant to phenyl lactate alone, but when treated very briefly with chilling or transient anaerobiosis become susceptible to it. This segment of respiration fn the human and mouse melanomas may represent tyrosinase activity, which furthermore may be vital to melanoma melanocyte respiration in vitro. Tissue culture growth studies revealed that phenyl lactate could also selectively prevent pigmented melanoma growth. The correlations between the Warburg and tissue culture studies suggest that tyrosinase may be necessary for the growth in vitro of melanoma melanocytes.
Textbook of Psychoanalysis, 2nd Editionedited by GabbardGlen O., M.D., LitowitzBonnie E., Ph.D., and WilliamsPaul, Ph.D. Washington, DC, American Psychiatric Publishing, 2012, 636 pp., $125.00.
Authors: Rosemary H. Balsam
Journal: American Journal of Psychiatry (2012)