tbuckley/cabot-search huggingface dataset:
Interferon γ Is Required for Activation-induced Death of T Lymphocytes
Authors: Yosef Refaeli, Luk Van Parijs, Stephen I. Alexander, Abul K. Abbas
Journal: The Journal of Experimental Medicine (2002)

The effector cytokine interferon γ (IFN-γ) may play a role in T cell homeostasis. We have examined the requirement for IFN-γ in one mechanism that regulates T cell expansion and survival, activation-induced cell death (AICD). CD4+ T cells lacking IFN-γ or the Stat1 transcription factor are resistant to AICD. IFN-γ is required for the production of caspases, and retrovirus-mediated expression of caspase-8 restores the sensitivity of Stat1-deficient T cells to AICD. In vitro, IFN-γ limits the expansion of T cells that are stimulated through their antigen receptors. Thus, IFN-γ may function to control the expansion and persistence of T cells by promoting caspase-8–dependent apoptosis.
Tumor-Selective Replication of an Oncolytic Adenovirus Carrying Oct-3/4 Response Elements in Murine Metastatic Bladder Cancer Models
Authors: Chao-Liang Wu, Gia-Shing Shieh, Chao-Ching Chang, Yi-Te Yo, Chih-Hau Su, Meng-Ya Chang, Yin-Hui Huang, Pensee Wu, Ai-Li Shiau
Journal: Clinical Cancer Research (2008)

Oncolytic adenoviruses are attractive therapeutics for cancer because they selectively replicate in tumors. However, targeting tumor metastasis remains a major challenge for current virotherapy for cancer. Oct-3/4 is specifically expressed in embryonic stem cells and tumor cells. Oct-3/4 highly expressed in cancer cells may be a potential target for cancer therapy. We developed an E1B-55 kDa-deleted adenovirus, designated Ad.9OC, driven by nine copies of Oct-3/4 response element for treating Oct-3/4-expressing metastatic bladder cancer.We examined the expression of Oct-3/4 in human bladder tumor tissues and bladder cancer cell lines. We also evaluated the cytolytic and antitumor effects of Ad.9OC on bladder cancer cells in vitro and in vivo.Oct-3/4 expression was detected in bladder cancer cell lines, as well as in human bladder tumor tissues. Notably, Oct-3/4 expression was higher in metastatic compared with nonmetastatic bladder cancer cells. Ad.9OC induced higher cytolytic activity in metastatic bladder cancer cells than in their nonmetastatic counterparts, whereas it did not cause cytotoxicity in normal cells. Pharmacologic and short hairpin RNA-mediated Oct-3/4 inhibition rendered bladder cancer cells more resistant to Ad.9OC-induced cytolysis. Replication of Ad.9OC was detected in murine bladder cancer cells and bladder tumor tissues. We also showed the effectiveness of Ad.9OC for treating bladder cancer in subcutaneous, as well as metastatic, bladder tumor models.Ad.9OC may have therapeutic potential for treating Oct-3/4-expressing tumors. Especially, metastatic bladder tumors are good target for Ad.9OC treatment. Because Oct-3/4 is expressed in a broad spectrum of cancers, Ad.9OC may be broadly applicable.
Effect of Biliary Diversion on Rat Mesenteric Lymph Apolipoprotein-I and High Density Lipoprotein
Authors: H. Robert Bearnot, Robert M. Glickman, Lee Weinberg, Peter H. R. Green, Alan R. Tall
Journal: Journal of Clinical Investigation (1982)

The effect of biliary diversion on intestinal apolipoprotein (apoA)-I and high density lipoprotein formation was studied in mesenteric lymph fistula rats. Bile diversion was produced by an exteriorized catheter that allowed interruption and reconstitution of the enterohepatic circulation. Bile diversion reduced lymph cholesterol output from 0.47±0.05 μmol/h to 0.17±0.03 μmol/h (P < 0.025), and lymph triglyceride output from 3.6±0.3μmol/h to 0.6±0.05 μmol/h (P < 0.025) after 24 h. This was due to depletion of lymph chylomicrons and very low density lipoprotein (VLDL). Despite the reduced lipid outputs, lymph apoA-I output was maintained during biliary diversion (basal: 119±15 μg/h; diverted 140±20 μg/h, n = 12). During biliary diversion, high density lipoprotein (HDL) were maintained in mesenteric lymph as shown by lipoprotein and immunoelectrophoresis. Bile diversion altered the lipid composition of lymph HDL. Bile-diverted lymph HDL was depleted in total cholesterol and has a greater phospholipid/cholesterol ester ratio than basal lymph HDL. Lymph HDL contained discoidal particles when examined by negative stain electron microscopy. Bile diversion was associated with a reduction in the size of discoidal HDL particles (basal, nondiverted, 165±7Å (n = 112) compared with diverted 126±5Å (n = 98, P < 0.025). Experiments were then carried out to determine the source of the apoA-I and HDL found in lymph from bile-diverted animals. The transfer of HDL from plasma into lymph was determined by the intravenous infusion of 125I-apoA-I labeled HDL into lymph fistula rats. In both nonbile-diverted and diverted rats, the specific activity of apoA-I in the HDL fraction of lymph was 23% of the specific activity of apoA-I in plasma HDL, indicating that the major portion (75%) of mesenteric lymph apoA-I did not come from plasma filtration. In other experiments the intraduodenal infusion of [3H]leucine to bile fistula, lymph fistula rats resulted in relative fivefold increase in the specific activity in apoA-I in lymph HDL when compared with the specific activity of apoA-I in plasma HDL from the same animal. We conclude that intestinal apoA-I secretion is maintained during biliary diversion and that synthesis of this apoprotein occurs in the absence of chylomicron formation. We also conclude that discoidal HDL are present in mesenteric lymph despite reduced triglyceride absorption and secretion into lymph.
A Survey of the Humoral Immune Response of Cancer Patients to a Panel of Human Tumor Antigens
Authors: Elisabeth Stockert, Elke Jäger, Yao-Tseng Chen, Matthew J. Scanlan, Ivan Gout, Julia Karbach, Michael Arand, Alexander Knuth, Lloyd J. Old
Journal: The Journal of Experimental Medicine (1998)

Evidence is growing for both humoral and cellular immune recognition of human tumor antigens. Antibodies with specificity for antigens initially recognized by cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis (CT) antigen initially identified by autologous antibody, have recently been identified. To establish a screening system for the humoral response to autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1 patient. No reactivity to these antigens was found in sera from 70 normal individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and 12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY-ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients with NY-ESO-1+ antibody had NY-ESO-1+ tumors, and no patients with NY-ESO-1− tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO-1 is 20–40% and only patients with NY-ESO-1+ tumors have antibody, this would suggest that a high percentage of patients with NY-ESO-1+ tumors develop an antibody response to NY-ESO-1.
Complement factor H or a related protein is a marker for transitional cell cancer of the bladder.
Authors: R Kinders, T Jones, R Root, C Bruce, H Murchison, M Corey, L Williams, D Enfield, G M Hass
Journal: Clinical Cancer Research (1998)

The BTAstat and BTA TRAK tests are new immunoassays that detect and measure an antigen in the urine of individuals diagnosed with bladder cancer. As described in this report, the monoclonal antibodies used in these kits were developed by immunizing mice with partially purified protein preparations derived from the urine of patients with bladder cancer. The antigen that is recognized by the monoclonal antibodies was purified from the urine of bladder cancer patients by immunoaffinity chromatography and identified as being either complement factor H (FH) or a closely related protein (CFHrp) by partial amino acid sequence analysis. Like serum FH, the urine antigen was demonstrated to have a complement factor C3b binding site and to accelerate the degradation of C3b in the presence of complement factor I. The culture supernatants from several human bladder, cervical, and renal cancer cell lines contained antigen as determined by immunoassay, and antigen affinity-purified from HeLaS3 culture media was shown to have FH activity. Moreover, the cell lines were shown to make products of the expected sizes by reverse transcription-PCR using FH-specific primers. In contrast, normal human epithelial keratinocytes, a myeloid leukemia cell line, and the colon cancer line LS174T were negative for production of a FH-like protein (CFHrp). We propose that the expression of proteins with FH-like activities may confer a selective growth advantage to cancer cells in vivo by decreasing complement activity, thus aiding their escape from lysis by immune surveillance. Identification of these proteins as cancer products also suggests avenues of chemotherapy or immunotherapy of some cancers.
Paget cells express cytokeratins typical of glandular epithelia
Authors: A. -L. KARINIEMI, F. RAMAEKERS, V. -P. LEHTO, I. VIRTANEN
Journal: British Journal of Dermatology (1985)

Journal Article Paget cells express cytokeratins typical of glandular epithelia Get access A. ‐L. KARINIEMI, A. ‐L. KARINIEMI Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland A.‐L. Kariniemi, M.D., Department of Dermatology, Helsinki University Central Hospital, Snellmaninkatu 14, SF‐00170 Helsinki 17, Finland. Search for other works by this author on: Oxford Academic Google Scholar F. RAMAEKERS, F. RAMAEKERS Department of Pathology, Radboud Hospital, University of Nijmegen, Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar V. ‐P. LEHTO, V. ‐P. LEHTO Department of Pathology, University of Helsinki, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar I. VIRTANEN I. VIRTANEN Department of Pathology, University of Helsinki, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 2, 1 February 1985, Pages 179–183, https://doi.org/10.1111/j.1365-2133.1985.tb00081.x Published: 01 February 1985 Article history Accepted: 16 July 1984 Published: 01 February 1985
Lymphoma Recurrence 5 Years or Later Following Diffuse Large B-Cell Lymphoma: Clinical Characteristics and Outcome
Authors: Jean-François Larouche, Françoise Berger, Catherine Chassagne-Clément, Martine Ffrench, Evelyne Callet-Bauchu, Catherine Sebban, Hervé Ghesquières, Florence Broussais-Guillaumot, Gilles Salles, Bertrand Coiffier
Journal: Journal of Clinical Oncology (2010)

PURPOSE Patients with diffuse large B-cell lymphoma (DLBCL) usually relapse early following diagnosis but some relapses happen at 5 years or later. Few data exist regarding clinical characteristics and outcome of these patients. PATIENTS AND METHODS We performed a retrospective analysis of all patients from two centers in Lyon, France, between 1985 and 2003 who had a biopsy-proven relapse 5 years or later following diagnosis of DLBCL. All available biopsies were reviewed and immunohistochemistry was completed. Results Among 1,492 patients with DLBCL, 54 were eligible. At diagnosis, 63% of patients had stage I-II, 82% had low/low-intermediate International Prognostic Index (IPI) score, 65% had extranodal involvement, 24% had an indolent component associated with DLBCL, 57% had germinal center phenotype, and 43% had non-germinal center phenotype. Median time from diagnosis to relapse was 7.4 years (range, 5 to 20.5 years). At time of relapse, 83% had DLBCL histology, and 17% had indolent histology. Having an indolent component at diagnosis was associated with indolent histology at relapse (P = .028). Five-year event free-survival (EFS) was 17% for patients with DLBCL relapse and 61% for patients with indolent relapse (P = .027). Five-year overall survival was 27% for patients with DLBCL and 75% for patients with indolent relapse (P = .029). For DLBCL relapse, 3-year EFS was 56% versus 18% with autologous stem-cell transplantation or not, respectively (P = .0661). CONCLUSION Patients with DLBCL who had a late relapse usually had localized stage, favorable IPI score, and extranodal involvement at diagnosis. The outcome of patients with DLBCL at time of relapse remains poor, and aggressive treatment such as autologous stem-cell transplantation should be pursued whenever possible. Biopsy at relapse is essential because some patients relapse with indolent histology.
Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.
Authors: Y Kawakami, S Eliyahu, K Sakaguchi, P F Robbins, L Rivoltini, J R Yannelli, E Appella, S A Rosenberg
Journal: The Journal of Experimental Medicine (1994)

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein-1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.
Airway resistance variability and response to bronchodilator in children with asthma
Authors: C. A. Lall, N. Cheng, P. Hernandez, P. T. Pianosi, Z. Dali, A. Abouzied, G. N. Maksym
Journal: European Respiratory Journal (2007)

Variability of airway function is a feature of asthma, spanning timescales from months to seconds. Short-term variation in airway resistance (R(rs)) is elevated in asthma and is thought to be due to increased variation in the contractile activation of airway smooth muscle. If true, then variation in R(rs) should decrease in response to bronchodilators, but this has not been investigated. Using the forced oscillation technique, R(rs) and the variation in R(rs) from 4-34 Hz were measured in 39 children with well-controlled mild-to-moderate asthma and 31 healthy controls (7-13 yrs) before and after an inhaled bronchodilator (200 microg salbutamol) or placebo. In agreement with other findings, baseline R(rs) at all frequencies and the sd of R(rs) (R(rs) sd) below 14 Hz were found to be elevated in asthma while neither forced expiratory volume in one second nor the mean forced expiratory flow between 25 and 75% of forced vital capacity were different compared with controls. The present authors found that R(rs) sd changed the most of any measurement in asthma, and this was the only measurement that changed significantly more in children with asthma following bronchodilator administration. The present results show that like airway narrowing, short-term airway variability of resistance may be a characteristic feature of asthma that may be useful for monitoring response to therapy.
Direct labelling of ipratropium bromide aerosol and its deposition pattern in normal subjects and patients with chronic bronchitis.
Authors: S G Spiro, C A Singh, S E Tolfree, M R Partridge, M D Short
Journal: Thorax (1984)

A technique for the direct labelling of ipratropium bromide with bromine-77, with reconstitution of the drug in a metered dose inhaler so as to be identical to the commercial product, was used to study drug deposition patterns in seven normal subjects and seven patients with chronic bronchitis (mean FEV1 32% (SD 12.2%) predicted normal). The gamma camera image of the thorax was divided into a middle zone--the mediastinal zone--and the lung itself into a central zone comprising its medial third and a peripheal zone, the lateral two thirds. Measurements after 10 inhalations of labelled ipratropium bromide showed similar results for the two groups of subjects. The total lung dose inhaled was 11.2% of 203 micrograms and 11.7% of 186 micrograms in the normal subjects and the patients respectively. In contrast to the deposition patterns seen in aerosol studies using steady state inhalation methods, there was no difference in deposition pattern--that is, the distribution between the central and the peripheral lung zones--between the normal subjects and the patients with airways obstruction.
Artificial Insemination, Donor: An Issue of Ethical and Moral Values
Authors: Herbert W. Horne
Journal: New England Journal of Medicine (1975)

Unexplained human infertility is not a medical problem in the strictest sense. Just as cosmetic surgery (face lifting, nose straightening, or bosom enlarging) is a social problem to the patient, so is the relief of human infertility a social matter. In these conditions, whether or not an attempt to correct the problem is made, the patient's physical health is not involved.The question of artificial insemination by donor semen (Artificial Insemination, Donor or A.I.D.) should be considered in a similar light. The success or failure of "treatment" should not solely be measured by whether or not a pregnancy occurred and . . .
“Doctor, Will the Treatment You Are Recommending Cause Chemobrain?”
Authors: Patricia A. Ganz
Journal: Journal of Clinical Oncology (2011)

For more than a decade, patients and their oncologists have been sharing conversations about cognitive complaints after chemotherapy treatment. 1 Early on, only occasional patients complained of trouble with concentration and memory during treatment, with a minority noting persistence beyond the end of treatment. The oncologist, who rarely heard this complaint, could be dismissive, saying that the drugs the patient received did not cross the blood-brain barrier, and therefore, it was unlikely that the difficulties were related to the cancer treatment. Post-treatment cognitive complaints became much more evident during the late 1990s and early 21st century as adjuvant treatment regimens intensified and autologous bone marrow transplantation became more common in adults. 2,3 Often, cognitive complaints were associated with persistent fatigue and depressive symptoms, making it challenging to sort out whether or not the complaints of poor memory, attention, and difficulties with multitasking were related to brain dysfunction or were merely a manifestation of an uncontrolled mood disorder. 4-6 Many who complained were younger patients with breast cancer who had become menopausal prematurely with chemotherapy, and their experiences of vasomotor symptoms, nighttime awakening, and poor sleep might have explained some of their cognitive complaints. 7
Concanavalin A Receptors on the Surfaces of Human Breast Cancer Cells in Organ Culture
Authors: J. Matoška, J. Siracký
Journal: JNCI Journal of the National Cancer Institute (1977)

The binding of concanavalin A (Con A) at the free apical membranes of surface tumor cells in human breast cancer explants grown in organ culture was studied cytochemically with horseradish peroxidase (HRP) as a marker. On the cell membranes in aldehyde-fixed explants or explants exposed to Con A at 4 degrees C, a continuous label covered the entire free surface of the cell, which indicated the dispersed distribution of Con A binding sites. The binding of Con A at 20 degrees C resulted in discontinuous label of the cell surface, with gaps of unlabeleled membrane and partial endocytosis of the label. Incubation at 37 degrees C, following the binding of Con A and HRP at both temperatures, induced more extensive, incubation time-dependent discontinuities of the surface label that led to complete disappearance of the label from the surface and its eventual endocytosis. Con A was topically stablized on the surface only in those regions where two membranes or a different part of a folded membrane were in close contact. No differences were found in the binding, redistribution, and internalization of bound Con A among the various tumors studied.
Role of thrombolysis in haemodynamically stable patients with pulmonary embolism
Authors: A. Proudfoot, D. Melley, P. L Shah
Journal: Thorax (2008)

Pulmonary embolism (PE) is a common cardiopulmonary illness with an age and sex adjusted incidence of approximately 117 cases per 100 000 person years.1 Incidence rises sharply after the age of 60 years in both men and women. While mortality rates exceed 15% in the 3 months following diagnosis, they are reduced to 2–10% if PE is diagnosed and treated promptly.2 3 The majority of patients with PE are haemodynamically stable at presentation and receive anticoagulation with heparin. By contrast, thrombolysis (or embolectomy) is the accepted standard of care in those patients who present with haemodynamic compromise.4 Under such circumstances, mortality approaches 50% and although to date no study has been powered to show a mortality benefit, such treatment potentially outweighs the complication rate of 3%.2 5 Importantly, it is now recognised that there is another cohort of patients who, although haemodynamically stable, are nevertheless at an increased risk of death and who currently receive only standard anticoagulation regimens. To date, no consensus exists regarding the identification, appropriate risk stratification or indeed the further management of these patients. Those who favour thrombolysis for the treatment of PE argue that its use should be extended to the subgroup of patients with preserved systemic arterial pressure but evidence of right ventricular (RV) dysfunction.5 6 …
Progress in type II dehydroquinase inhibitors: From concept to practice
Authors: Concepción González‐Bello, Luis Castedo
Journal: Medicinal Research Reviews (2006)

Abstract Scientists are concerned by an ever‐increasing rise in bacterial resistance to antibiotics, particularly in diseases such as malaria, toxoplasmosis, tuberculosis, and pneumonia, where the currently used therapies become progressively less efficient. It is therefore necessary to develop new, safe, and more efficient antibiotics. Recently, the existence of the shikimic acid pathway has been demonstrated in certain parasites such as the malaria parasite. These types of parasites cause more than a million casualties per year, and their effects are particularly strong in people with a compromised immune system such as HIV patients. In such cases it is possible that inhibitors of this pathway could be active against a large variety of microorganisms responsible for the more opportunistic infections in HIV patients. Interest in this pathway has resulted in the development of a wide variety of inhibitors for the enzymes involved. This review covers recent progress made in the development of inhibitors of the third enzyme of this pathway, i.e., the type II dehydroquinase. The X‐ray crystal structures of several dehydroquinases ( Streptomyces coelicolor , Mycobacterium tuberculosis , etc.) with an inhibitor bound in the active site have recently been solved. These complexes identified a number of key interactions involved in inhibitor binding and have shed light on several aspects of the catalytic mechanism. These crystal structures have also proven to be a useful tool for the design of potent and selective enzyme inhibitors, a feature that will also be discussed. © 2006 Wiley Periodicals, Inc. Med Res Rev