tbuckley/cabot-search huggingface dataset:
Leukemic Cell-Surface CD13/Aminopeptidase N and Resistance to Apoptosis Mediated by Endothelial Cells
Authors: Y. Mishima
Journal: JNCI Journal of the National Cancer Institute (2002)

Attachment of leukemic cells to vascular endothelial cells induces the vascular endothelial cells to release endothelial cell-derived interleukin 8 (endothelial IL-8), which then induces leukemic cells to undergo apoptosis. NB4, a human promyelocytic leukemic cell line that expresses high levels of cell-surface CD13/aminopeptidase N, does not undergo endothelial IL-8-induced apoptosis. Consequently, we investigated the relationship between cell-surface aminopeptidase activity and endothelial IL-8 induction of apoptosis in various leukemic cell lines.CD13/aminopeptidase N activity and IL-8-induced apoptosis were examined in leukemic cell lines. Endothelial IL-8-induced apoptosis was examined further in NB4 cells, K562 cells (human chronic myelogenous leukemic cells expressing low levels of CD13/aminopeptidase N), CD13/aminopeptidase N-transfected K562 (K562/CD13) cells that overexpress aminopeptidase, and mock-transfected K562 cells (vector only). These cells were also cocultured with a vascular endothelial cell layer to investigate the association between aminopeptidase activity and apoptosis in this system. All statistical tests were two-sided.Endothelial IL-8 induced apoptosis in K562 cells but not in K562/CD13 cells. A combination of an aminopeptidase inhibitor (such as bestatin) and endothelial IL-8 induced apoptosis in NB4 cells and K562/CD13 cells (2.88-fold difference [95% confidence interval [CI] = 1.82-fold to 3.94-fold], P =.004 for bestatin-treated NB4 cells and 4.31-fold difference [95% CI = 3.52-fold to 5.10-fold], P<.001 for bestatin-treated K562/CD13 cells). When aminopeptidase activity in NB4 cells was modulated by aminopeptidase inhibitors, a statistically significant correlation was found between aminopeptidase activity and the proportion of apoptotic cells induced by endothelial IL-8 (r = -.837, P<.001 by Pearson's correlation coefficient; r = -.697, P =.013 by Spearman's correlation analysis by ranks). K562/CD13 cells cocultured with vascular endothelial cells did not undergo apoptosis, but the addition of bestatin resulted in the induction of apoptosis in K562/CD13 cells (2.70-fold difference [95% CI = 1.77-fold to 3.63-fold], P<.001). Bestatin treatment increased the level of IL-8 mRNA in and the amount of IL-8 secreted by vascular endothelial cells.High levels of cell-surface CD13/aminopeptidase N appear to allow leukemic cells to resist endothelial IL-8-induced apoptosis. The combination of endothelial IL-8 and bestatin induce leukemic cells expressing high levels of CD13/aminopeptidase N to undergo apoptosis. Bestatin may be useful for treating patients with leukemia.
Thrombosis in the Superior Longitudinal Sinus following Childbirth
Authors: J. P. Martin
Journal: BMJ (1941)

The details of pre-operative treatment, operation, and post-operative care are described, and subsequent injection treatment is outlined.The whole varicose circulation can be completely obliterated in from six to eight weeks from the time of operation, and the patient rendered fit even for heavy work.Patients with the severe type of varicosity should be reviewed at intervals of a year or so whenever possible.The factors governing prognosis are outlined.Of the controllable factors the most important is the completeness of the obliteration of the varicose circulation.
British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis
Authors: D. Gleeson, M. A. Heneghan
Journal: Gut (2011)

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease which, if untreated, often leads to cirrhosis, liver failure and death. Major advances were made in its management based on controlled trials performed in England and the USA in the 1970s and 1980s. Unfortunately, in recent decades there has been a dearth of controlled clinical trials and, thus, many questions regarding the optimal management of this disease remain unanswered. Many promising newer immunosuppressive therapies await formal comparison with standard therapies and also many important details in relation to the application of standard therapies remain unclear. These guidelines describe the optimal management strategies in adults based on available published evidence, including the American Association for the Study of Liver Diseases practice guidelines for the diagnosis and treatment of AIH published in 2002 and recently updated.
Phase I Study of Pazopanib in Patients with Advanced Solid Tumors and Hepatic Dysfunction: A National Cancer Institute Organ Dysfunction Working Group Study
Authors: Stephen I. Shibata, Vincent Chung, Timothy W. Synold, Jeffrey A. Longmate, A. Benjamin Suttle, Lone H. Ottesen, Heinz-Josef Lenz, Shivaani Kummar, R. Donald Harvey, Anne L. Hamilton, Bert H. O'Neil, John Sarantopoulos, Patricia LoRusso, Michelle A. Rudek, Afshin Dowlati, Daniel L. Mulkerin, Chandra P. Belani, Leena Gandhi, S. Cecilia Lau, S. Percy Ivy, Edward M. Newman
Journal: Clinical Cancer Research (2013)

Pazopanib is a potent, multitargeted receptor tyrosine kinase inhibitor; however, there is limited information regarding the effects of liver function on pazopanib metabolism and pharmacokinetics. The objective of this study was to establish the maximum-tolerated dose (MTD) and pharmacokinetic profile of pazopanib in patients with varying degrees of hepatic dysfunction.Patients with any solid tumors or lymphoma were stratified into four groups based on the degree of hepatic dysfunction according to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria. Pazopanib was given orally once a day on a 21-day cycle. A modified 3+3 design was used.Ninety-eight patients were enrolled. Patients in the mild group tolerated 800 mg per day. The moderate and severe groups tolerated 200 mg per day. Pharmacokinetic data in the mild group were similar to the data in the normal group. Comparison of the median Cmax and area under the curve [AUC(0-24)] in the moderate or severe groups at 200 mg per day to the values in the normal and mild groups at 800 mg per day indicated less than dose-proportional systemic exposures in patients with moderate and severe hepatic impairment. This suggests that the lower maximum-tolerated dose in the moderate and severe group is not due to a decrease in drug clearance or alteration in the proportion of metabolites.In patients with mild liver dysfunction, pazopanib is well tolerated at the Food and Drug Administration (FDA)-approved dose of 800 mg per day. Patients with moderate and severe liver dysfunction tolerated 200 mg per day.
Management of Sepsis
Authors: James A. Russell
Journal: New England Journal of Medicine (2006)

A better understanding of the inflammatory, procoagulant, and immunosuppressive aspects of sepsis has contributed to rational therapeutic plans. This review considers optimal management of sepsis from the point of early, goal-directed therapy, lung-protective ventilation, antibiotics, and additional therapies, such as activated protein C, as well as the use of corticosteroids, vasopressin, and intensive insulin.
Building or Extending a Hospital Department: Radiology a Path through the Planning Minefield (8)
Authors: E J Roebuck, D J Manton, G L Fordham
Journal: Journal of the Royal Society of Medicine (1987)

This is the eighth of a series of articles on the planning and building of a new radiology department or the extension of an old one. While the series focuses on a radiology department, it will be of interest to anyone who is planning any part of a hospital, particularly in the detailed information about the planning process and the part to be played by hospital staff during the subsequent building and commissioning. (The first article in the series appeared in the January issue, p 40.)
Ideas galore: Examining the moods of a modern caveman
Authors: Peter Totterdell
Journal: Behavioral and Brain Sciences (2004)

A self-experiment by Roberts found that watching faces on early morning television triggered a delayed rhythm in mood. This surprising result is compared with previous research on circadian rhythms in mood. I argue that Roberts' dual oscillator model and theory of Stone-Age living may not provide the explanation. I also discuss the implications of self-experiments for scientific practices.
A SURVEY OF METHODS USED TO PRODUCE "EXPERIMENTAL NEUROSIS."
Authors: Stuart W. Cook
Journal: American Journal of Psychiatry (1939)

When the experimental conditions which led to behavior disturbances in the various species are compared, we find the following similarities: 1. In all the successful experiments, with the exception of those involving the chimpanzee and the cat, the subjects were restrained from making any very considerable gross bodily movement either by mechanical devices or by previous training to remain quiet. 2. With the same exceptions plus that of the food-getting response in the pig experiment, the learned responses in all the experiments were set up after the Pavlovian pattern. 3. In all the species experimented upon, a situation requiring a discrimination between two similar stimuli which evoked antagonistic behavior proved adequate to produce behavior disturbances. 4. Likewise, in all the species where it has been tried, i. e., the dog, the human child and the sheep, requiring the inhibition (or delay) of a response in the presence of excitatory stimuli to that response has proved to constitute an adequate precipitating situation. Theoretical concepts have been advanced by various experimenters to account for the development of the behavior disturbances they observed. However, it is unlikely that any hypothesis thus far proposed will be comprehensive enough to account for all the facts we have described. While it is beyond the scope of this survey to evaluate and propose explanatory constructs, this has been attempted in a later paper. Even if it were possible at such an early stage in the study of "experimental neurosis" to draw comparisons with and inferences for adult human behavior, this would, in the opinion of the writer, be an unwise procedure. It is his conviction that the contributions to be made to psychiatry by the study of this problem will be realized only after the total picture of the appearance and disappearance of experimentally-produced behavior disturbances has been described and understood. From this comprehension of the total process and not from comparisons of specific details should come valuable suggestions for explanatory concepts and therapeutic devices.
Determinants on surface proteins of Plasmodium knowlesi merozoites common to Plasmodium falciparum schizonts.
Authors: L H Miller, J G Johnson, R Schmidt-Ullrich, J D Haynes, D F Wallach, R Carter
Journal: The Journal of Experimental Medicine (1980)

In this report and (R. Schmidt-Ullrich, L. H. Miller, and D. F. H. Wallach. Manuscript in preparation.), we have demonstrated that malaria proteins on the surface of merozoites and infected erythrocytes cross-react between at least two primate malarias, Plasmodium knowlesi and P. falciparum. Sera from five Gambian adults who were highly immune to P. falciparum were used as a reagent to study the cross-reactivity between P. falciparum schizonts and surface proteins on P. knowlesi merozoites. Although the sera bound to the surface of viable, intact P. knowlesi merozoites, the sera did not block invasion of rhesus erythrocytes. 125I-lactoperoxidase-labeled surface proteins on merozoites formed complexes with the antibody. All major protein bands seen in the electrophoresis of the original Triton extract were bound by the immune sera. Because Gambians have never been exposed to P. knowlesi malaria, the antibodies that reacted with P. knowlesi merozoites must be directed against antigens of another parasite such as P. falciparum. We tested this hypothesis by competition for antibody in a Gambian serum between Triton-extracted antigens from P. falciparum schizont-infected erythrocytes and from surface-labeled P. knowlesi merozoites. P. falciparum inhibited the reaction, thus indicating cross-reaction between antigens in P. falciparum schizonts and P. knowlesi merozoites.
LARGE enzyme activity deciphered: a new therapeutic target for muscular dystrophies
Authors: Jane E Hewitt
Journal: Genome Medicine (2012)

A significant proportion of severe, inherited congenital muscular dystrophies are due to aberrant glycosylation of the extracellular matrix receptor α-dystroglycan and a consequent lack of ligand-binding activity. A key member of this glycosylation pathway is the LARGE protein, which was originally identified through genome sequencing and genetic studies. Until recently, the biochemical activity of this enzyme proved frustratingly elusive, but a recent study shows that LARGE encodes a bifunctional glycosyltransferase that synthesizes a novel polysaccharide structure, which is required for functional dystroglycan. Identification of this structure should lead to development of new diagnostic tools and therapeutic strategies for these dystrophies.
Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors
Authors: Ping Yu, Youjin Lee, Wenhua Liu, Thomas Krausz, Anita Chong, Hans Schreiber, Yang-Xin Fu
Journal: The Journal of Experimental Medicine (2005)

Tumor environment can be critical for preventing the immunological destruction of antigenic tumors. We have observed a selective accumulation of CD4+CD25+ T cells inside tumors. In a murine fibrosarcoma Ld-expressing Ag104, these cells made up the majority of tumor-infiltrating lymphocytes at the late stage of tumor progression, and their depletion during the effector phase, rather than priming phase, successfully enhanced antitumor immunity. We show here that CD4+CD25+ T cells suppressed the proliferation and interferon-γ production of CD8+ T cells in vivo at the local tumor site. Blockade of the effects of IL-10 and TGF-β partially reversed the suppression imposed by the CD4+ cells. Furthermore, local depletion of CD4+ cells inside the tumor resulted in a change of cytokine milieu and led to the eradication of well-established highly aggressive tumors and the development of long-term antitumor memory. Therefore, CD4+CD25+ T cells maintained an environment in the tumor that concealed the immunogenicity of tumor cells to permit progressive growth of antigenic tumors. Our study illustrates that the suppression of antitumor immunity by regulatory T cells occurs predominantly at the tumor site, and that local reversal of suppression, even at a late stage of tumor development, can be an effective treatment for well-established cancers.
Expression of urokinase-type plasminogen activator receptor in hepatocellular carcinoma
Authors: Y Morita, Y Hayashi, Y Wang, T Kanamaru, S Suzuki, K Kawasaki, K Ohta, M Yamamoto, Y Saitoh, H Itoh, W F Doe
Journal: Hepatology (1997)

It is well known that a urokinase-type plasminogen activator receptor (uPAR) is a key protein in the plasminogen activation system, which plays a proteolytically important role in the invasion and metastasis of various cancer cells. To assess the expression of uPAR in hepatocellular carcinoma (HCC), we analyzed the expression of uPAR messenger RNA (mRNA) and the protein in 31 pair-samples of solitary HCC and nontumorous liver tissues from the same patients. Fifteen samples exhibited no histological potential of recurrence, such as portal involvement or intrahepatic metastasis (group A), and 16 samples exhibited such histological features (group B). Seventy-one percent of the cases showed uPAR signals, and these signals were mainly localized at the cytoplasm of the tumor cells and tended to be at the front of invasive foci. 87.5% of the cases in group B showed uPAR signals against 53.3% of the cases in group A (P < .05). The rate of recurrence in the uPAR positive/negative cases in group A was 75.0% and 14.3%, respectively (P < .05). In non-neoplastic cases, e.g., chronic active hepatitis and cirrhosis, weak uPAR mRNA and protein signals were detected in hepatocytes neighboring the portal tracts, suggesting that this protein plays some role in such cases. The present study indicates that uPAR plays an important role at least in its initial stage in invasion and metastasis of HCC, and that uPAR expression can be a candidate predictor of these factors.
Outcome of Ethnic Minorities With Acute or Chronic Leukemia Treated With Hematopoietic Stem-Cell Transplantation in the United States
Authors: K. Scott Baker, Fausto R. Loberiza, Hongmei Yu, Mitchell S. Cairo, Brian J. Bolwell, Willem A. Bujan-Boza, Bruce M. Camitta, Juan Jose Garcia, Winston G. Ho, Jane L. Liesveld, Dipnarine Maharaj, David I. Marks, Kirk R. Schultz, Peter Wiernik, Axel R. Zander, Mary M. Horowitz, Armand Keating, Daniel J. Weisdorf
Journal: Journal of Clinical Oncology (2005)

We previously reported a higher risk of mortality among Hispanics after allogeneic hematopoietic stem-cell transplantation (HSCT). However, it is not known how specific post-transplantation events (acute or chronic graft-versus-host disease [GVHD], treatment-related mortality [TRM], and relapse) may explain mortality differences. The purpose of this study was to examine the relationship between ethnicity and post-transplantation events and determine their net effect on survival.We identified 3,028 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myeloid leukemia reported to the International Bone Marrow Transplant Registry between 1990 and 2000 who received an HLA-identical sibling HSCT after a myeloablative conditioning regimen in the United States. There were 2,418 white patients (80%) and 610 ethnic minority patients (20%), of whom 251 were black (8%), 122 were Asian (4%), and 237 were Hispanic (8%). Cox proportional hazards regression was used to compare outcomes between whites and ethnic minorities while adjusting for other significant clinical factors.No statistically significant differences in the risk of acute or chronic GVHD, TRM, or relapse were found between whites and any ethnic minority group. However, Hispanics had higher risks of treatment failure (death or relapse; relative risk [RR] = 1.30; 95% CI, 1.08 to 1.54; P = .004) and overall mortality (RR = 1.23; 95% CI, 1.03 to 1.47; P = .02).The higher risks of treatment failure and mortality among Hispanics may be the net result of modest but not statistically significant increases in both relapse and TRM and cannot be accounted for by any single transplantation-related complication. Further studies should examine the role of social, economic, and cultural factors.
Poor Outcome With Front-Line Autologous Transplantation in t(4;14) Multiple Myeloma: Low Complete Remission Rate and Short Duration of Remission
Authors: Michele Cavo, Carolina Terragna, Matteo Renzulli, Elena Zamagni, Patrizia Tosi, Nicoletta Testoni, Chiara Nicci, Delia Cangini, Paola Tacchetti, Tiziana Grafone, Claudia Cellini, Michela Ceccolini, Giulia Perrone, Giovanni Martinelli, Michele Baccarani, Luciano Guardigni
Journal: Journal of Clinical Oncology (2006)
A T cell receptor beta chain variable region polymorphism associated with radiographic progression in rheumatoid arthritis.
Authors: N de Vries, C F Prinsen, E B Mensink, P L van Riel, M A van't Hof, L B van de Putte
Journal: Annals of the Rheumatic Diseases (1993)

In rheumatoid arthritis (RA) genetic factors influence susceptibility to disease and progression. Identifying these genetic factors may give more insight into the aetiology and pathogenesis of this disease. Furthermore, if these genetic markers can predict progression in an early stage of disease, timely institution of more aggressive treatment in patients with a bad prognosis may help to prevent joint damage. Several studies have shown that HLA-DRB1 alleles are associated with RA, whereas others have indicated that genes not linked to the HLA complex are also involved. Candidates for such genes are the T cell receptor (TCR) alpha/beta genes.The association of a polymorphism in a TCR beta chain variable region gene (TCR-V beta 8) with both risk for RA and radiographic progression of joint disease was analysed after a three year follow up. A cohort of 118 white patients with a duration of disease shorter than one year at entry, and 110 white controls were typed for this (BamHI) TCR-V beta 8 polymorphism.The distribution of the two alleles, 2.0 and 23.0 kb, was identical in patients and controls. Radiographic progression (modified Sharp method) after a three year follow up, studied in 111 patients, was significantly less in the group possessing the 2.0 kb allele (p = 0.03).This does not confirm the reported association of the (BamHI) TCR-V beta 8 2.0 kb allele with RA. By contrast with previous findings in smaller studies, in the present study this 2.0 kb allele was protective against radiographic progression. Because well known prognostic variables in RA were corrected for, the findings indicate that the TCR-V beta 8 polymorphism studied is a new prognostic marker for this disease.
Effect of proximal gastric vagotomy and anticholinergics on the acid and gastrin responses to sham feeding in duodenal ulcer patients.
Authors: B Stenquist, J F Rehfeld, L Olbe
Journal: Gut (1979)

Plasma gastrin concentrations and gastric acid output after modified sham feeding were determined in 20 duodenal ulcer patients. Sham feeding produced an acid response corresponding to 40-68% of the maximal acid output after pentagastrin stimulation, with no significant increase of plasma gastrin concentrations. In eight patients proximal gastric vagotomy almost abolished the acid responses to both insulin hypoglycaemia and sham feeding. Sham feeding in the vagotomised patients did not change the gastrin concentrations in plasma. After pretreatment with benzilonium, an anticholinergic with minimal central nervous effects, plasma gastrin concentrations increased after sham feeding. The study confirms that sham feeding is a poor stimulus for gastrin release in duodenal ulcer patients and supports a cholinergic inhibition of gastrin release. Intravenous injection of benzilonium bromide in a dose close to 70 micrograms/kg, and atropine in the low dose of 30 micrograms/kg inhibited the acid response to sham feeding by about 65%. Atropine in a dose of 50 micrograms/kg virtually abolished the acid sham feeding response, possibly owing to ganglionic or central nervous blockade. Vagal activation of the acid secretory glands does not seem to involve a purely cholinergic neurotransmission.