tbuckley/cabot-search huggingface dataset:
Clinical Implications of p53 Autoantibodies in the Sera of Patients With Non-Small-Cell Lung Cancer
Authors: T. Mitsudomi, S. Hatooka, M. Shinoda, M. Suyama, Y. Yatabe, M. Kuwabara, M. Nishio, K. Gotoh, M. Ogawa, T. Takahashi, T. Takahashi, S. Suzuki, Y. Ariyoshi
Journal: JNCI Journal of the National Cancer Institute (1998)

The presence of autoantibodies to p53 protein has been associated with the presence of p53 (also known as TP53) gene mutations in primary tumors and with poor prognosis. This study was undertaken to determine the clinical significance of p53 autoantibodies in patients with non-small-cell lung cancer (NSCLC).We studied 188 consecutive patients with NSCLC who underwent pulmonary resection and for whom preoperative serum was available. The presence of p53 autoantibodies, detected by use of two amino-terminal and two carboxy-terminal peptides (20-30 mers) as antigens and an enzyme-linked immunosorbent assay, was related to various clinicopathologic parameters and to overexpression of p53 protein in the primary tumor. For 22 patients who had p53 autoantibodies before surgery, we also examined sera taken during postoperative follow-up. Reported P values are two-sided.Autoantibodies to p53 protein were detected in 38 patients. Patients with squamous cell carcinoma, those with more advanced disease (stage III-IV), and those with tumors that overexpressed p53 had a significantly higher incidence of p53 autoantibodies (P = .05,.0079, and .02, respectively). In all but one of the patients with postoperative serum samples, the antibody titer declined after surgery; however, there was no relationship between clinical course and this change in antibody titer. In addition, there was no relationship between the presence of p53 autoantibodies and overall survival in 171 patients who underwent potentially curative resection (P = .28); however, 13 patients with autoantibodies to amino-terminal peptides had a worse overall survival (P = .02).In NSCLC, the incidence of p53 autoantibodies is associated with histologic type, stage, and p53 overexpression--but not with patient survival. Our data do not support the clinical utility of p53 autoantibodies as diagnostic or prognostic markers in patients with NSCLC.
The p53 Gene in Breast Cancer: Prognostic Value of Complementary DNA Sequencing Versus Immunohistochemistry
Authors: S. Sjogren, M. Inganas, T. Norberg, A. Lindgren, H. Nordgren, L. Holmberg, J. Bergh
Journal: JNCI Journal of the National Cancer Institute (1996)

Mutations in the p53 tumor suppressor gene (also known as TP53) have been detected in a wide variety of human cancers. In breast cancer, the presence of p53 gene alterations has been associated with worse prognosis. We compared a complementary DNA (cDNA)-based sequencing method and an immunohistochemical (IHC) method for their abilities to detect p53 mutations in breast cancer specimens. In addition, we determined the prognostic value of information obtained when these two methods were used. Specimens from 316 primary breast tumors were evaluated for the presence of mutant p53 protein by use of the mouse monoclonal antibody Pab 1801 (that recognizes both wild-type and mutant forms of p53) and standard IHC methods. In addition, the entire coding region of p53 genes expressed in these tumors was screened for mutations by combining reverse transcription, the polymerase chain reaction, and DNA sequencing. Probabilities for overall survival (OS), breast cancer-corrected survival (BCCS; death from breast cancer is the considered event), and relapse-free survival (RFS) were estimated by use of the Kaplan—Meier method, and survival curves for different patient subgroups were compared by use of the logrank method. All reported P values are from two-sided tests. Sixty-nine (22%) of 316 tumors had p53 gene mutations detected by the cDNA-based sequencing method; only 31 (45%) of these mutations were located in evolutionarily conserved portions of the p53 coding region. Sixty-four tumors (20% of the total) had elevated levels of p53 protein as detected by IHC, suggesting the presence of mutations. Of the sequencing-positive tumors (i.e., p53 mutant), 23 exhibited negative IHC reactions, indicating that IHC failed to detect 33% of the mutations. Furthermore, 19 of the IHC-positive tumors were sequencing negative (i.e., p53 wild-type), suggesting a 30% false-positive frequency with IHC. Four tumors (1.3% of the total) could not be analyzed by the cDNA-based sequencing method, and three tumors (1% of the total) could not be analyzed by IHC. The 5-year estimates for RFS, BCCS, and OS were significantly shorter for patients with p53 sequencing-positive tumors than for patients with sequencing-negative tumors ( P = .001, P = .01, and P = .0003, respectively). Patients with IHC-positive tumors showed reduced survival in all three categories when compared with those with IHC-negative tumors, but the differences were not statistically significant. Use of a cDNA-based sequencing method to determine the status of the p53 gene in primary breast cancers yielded better prognostic information than IHC performed with the Pab 1801 monoclonal antibody. [J Natl Cancer Inst 1996;88:173–82]
Therapeutic Effectiveness of Recombinant Cancer Vaccines Is Associated with a Prevalent T-Cell Receptor α Usage by Melanoma-specific CD8+ T Lymphocytes
Authors: Raffaele De Palma, Ilaria Marigo, Francesco Del Galdo, Carmela De Santo, Paolo Serafini, Sara Cingarlini, Thomas Tüting, Julia Lenz, Giuseppe Basso, Gabriella Milan, Paola Zanovello, Vincenzo Bronte
Journal: Cancer Research (2004)

Abstract Definition of immune variables that correlate with the antitumor activity of cancer vaccines is critical for monitoring immunotherapy protocols. To define surrogate end points predictive of the therapeutic efficacy of recombinant vaccines based on melanoma antigen tyrosinase-related protein (TRP)-2, we evaluated several properties of antigen-specific CD8+ T lymphocytes in single mice undergoing either prophylactic or therapeutic immunization. Predictive markers for the efficacy of genetic vaccination were identified in the prophylactic model used. Interestingly, the number of tetramer+ CD8+ T lymphocytes expanded in vitro after a single cycle of stimulation with the immunodominant TRP-2 peptide was of the highest predictive value. In the therapeutic model, no variable examined at a single mouse level predicted the long-term therapeutic effect. Mice that survived did not show the highest expansion of antigen-specific lymphocytes or the more functionally active effectors, ex vivo or after in vitro culture with the peptide antigen. Successful therapy correlated strictly with the skewing of the T-cell receptor repertoire of tetramer-sorted, TRP-2–specific CD8+ T lymphocytes, which showed a preferential α chain usage with a common CDR3 region.
Natural history of recurrent Crohn's disease at the ileocolonic anastomosis after curative surgery.
Authors: P Rutgeerts, K Geboes, G Vantrappen, R Kerremans, J L Coenegrachts, G Coremans
Journal: Gut (1984)

An endoscopical and histological study was carried out in 114 patients, treated by 9curative9 resection of the terminal ileum and part of the colon for Crohn9s disease, in order to study the natural history of recurrent Crohn9s disease. The recurrence rate of Crohn9s disease in patients examined within one year of the operation was 72%. This figure did not differ significantly from that in patients examined one to three years or three to 10 years after surgery (79% and 77% respectively). Recurrence was located in the neoterminal ileum and at the anastomosis in 88% of the patients. Early endoscopic signs of recurrence were small aphthous ulcers in the neoterminal ileum. Ileal biopsies at this stage showed an important inflammatory cell infiltrate of the lamina propria with numerous eosinophils and fusion and blunting of the villi. More advanced lesions observed in patients examined one to three years after surgery, consisted of larger, often serpiginous ulcerations and nodular thickening of folds. In patients examined three to 10 years after the operation, the anastomosis was frequently stenosed and rigid, with large ulcers extending from the stenosis into the colon. Mucosal granulomas may be found in normal appearing mucosa as well as in the obviously inflamed mucosa surrounding the ulcers. These studies suggest that recurrence of Crohn9s disease almost always develops in the first year after the operation. Significant endoscopic lesions may be present without clinical symptoms, particularly in the earlier stages of the disease.
Function of carbonic anhydrase IX in glioblastoma multiforme
Authors: M. A. Proescholdt, M. J. Merrill, E.-M. Stoerr, A. Lohmeier, F. Pohl, A. Brawanski
Journal: Neuro-Oncology (2012)

Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma.
Distribution of Size and Shape in Populations of Normal Human Red Cells
Authors: P. B. CANHAM, ALAN C. BURTON
Journal: Circulation Research (1968)

The diameter, area, and volume of individual human erythrocytes (of 8 subjects, newborn to age 71) were determined by photographing the cells hanging on edge. Measurements from high magnification prints were processed by computer. The distributions of diameter, area, and volume are described statistically, with the unexpectedly linear regression equations for their interrelations. The plot of area vs. volume for the 1016 normal cells from seven subjects (newborn excluded) was remarkably linear with a "straight-line" boundary restricting the distribution. Shape was characterized by a dimensionless "sphericity index" (4.84.volume 2/3 /area). Cells of larger volume tended to be thinner than the smaller cells. The red cell can easily be deformed at constant volume, but an increase in membrane area results in hemolysis. A theoretical geometric parameter, the "minimum cylindrical diameter" (MCDiam), in microns, the thinnest cylindrical channel through which each individual cell could pass, predicts the linear boundary of the plot of area vs. volume. The MCDiam value of 3.66 µ ± 0.04 SEM accurately represents the thinnest channel through which 95% of the cells can pass. In two splenectomized patients with hereditary spherocytosis the MCDiam was increased to approximately 4.0 µ, suggesting that the severest restriction is located in the spleen.
Endobronchial versus intravenous application of the vasopressin derivative glypressin during diagnostic bronchoscopy
Authors: HW Breuer, S Charchut, H Worth, HJ Trampisch, K Glanzer
Journal: European Respiratory Journal (1989)

Glypressin is a vasopressin derivative which is used in the present study to stop pulmonary bleeding. The effects of endobronchially versus intravenously applied glypressin were examined during diagnostic fibreoptic bronchoscopy in 27 patients. Transcutaneously measured blood gases and haemodynamics were analysed after 1 mg glypressin was given. The glypressin plasma level was 251 fold higher after the intravenous than after the endobronchial administration. After endobronchial application no significant changes were observed for blood pressure, heart rate or blood gases. Following the intravenous glypressin application there was a significant increase in diastolic blood pressure. The bronchial mucosa pallor appeared earlier after topical than after systemic glypressin application. The haemostyptic effect was similar for both routes of application.
Phase I Study of Recombinant Human Interleukin-7 Administration in Subjects with Refractory Malignancy
Authors: Claude Sportès, Rebecca R. Babb, Michael C. Krumlauf, Frances T. Hakim, Seth M. Steinberg, Catherine K. Chow, Margaret R. Brown, Thomas A. Fleisher, Pierre Noel, Irina Maric, Maryalice Stetler-Stevenson, Julie Engel, Renaud Buffet, Michel Morre, Robert J. Amato, Andrew Pecora, Crystal L. Mackall, Ronald E. Gress
Journal: Clinical Cancer Research (2010)

Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant), and may have roles in immune reconstitution or enhancement of immunotherapy. We report here on the toxicity and biological activity of recombinant human IL-7 (rhIL-7) in humans.Subjects with incurable malignancy received rhIL-7 subcutaneously every other day for 2 weeks in a phase I interpatient dose escalation study (3, 10, 30, and 60 microg/kg/dose). The objectives were safety and dose-limiting toxicity determination, identification of a range of biologically active doses, and characterization of biological and, possibly, antitumor effects.Mild to moderate constitutional symptoms, reversible spleen and lymph node enlargement, and marked increase in peripheral CD3(+), CD4(+), and CD8(+) lymphocytes were seen in a dose-dependent and age-independent manner in all subjects receiving >or=10 microg/kg/dose, resulting in a rejuvenated circulating T-cell profile, resembling that seen earlier in life. In some subjects, rhIL-7 induced in the bone marrow a marked, transient polyclonal proliferation of pre-B cells showing a spectrum of maturation as well as an increase in circulating transitional B cells.This study shows the potent biological activity of rhIL-7 in humans over a well-tolerated dose range and allows further exploration of its possible therapeutic applications.
Streptokinase versus alteplase and other treatments for acute and delayed thrombolysis of blood stains in clothing
Authors: C K Pager
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To assess the usefulness of heparin, alteplase, and streptokinase in removing blood stains. <b>Design:</b> Randomised controlled trial. <b>Setting:</b> Hospital laundry. <b>Interventions:</b> Blood stains were allocated to treatment with alteplase, streptokinase, heparin, a commercial enzymatic stain remover, or no treatment at all after three or seven hours and then washed in hot or cold water two hours later. <b>Results:</b> Both hot water and early treatment were strongly associated with improved stain removal. All four treatments were associated with a worse outcome than no treatment at all, although for streptokinase this trend did not reach significance. The commercial stain remover gave the worst results of all treatments tested. <b>Conclusions:</b> Contrary to popular wisdom, hot water is much more effective than cold in removing blood stains. Methodologically rigorous research and evidence based principles are needed within the laundry industry, and the role of thrombolytic drugs should be assessed further.
Exploration of the Patient-Therapist Relationship in Psychotherapy
Authors: Per Høglend
Journal: American Journal of Psychiatry (2014)

Research from several domains indicates that genetic factors, childhood environment, and later interpersonal experiences are important sources of how patients relate to their therapists (transference). Transference work, a core specific technique in psychodynamic psychotherapy, focuses on exploring the patient-therapist relationship, with the idea that this may lead to improvement of the patients' relationships outside therapy. Many psychotherapy researchers hold the position that specific techniques do not contribute much to the outcome of psychotherapy. However, more than 30 studies have reported significant associations between transference work and outcome. These findings indicate that transference work interventions are indeed active ingredients (for better or worse). Naturalistic studies suggest that a high frequency of transference interventions may have negative effects. Randomized clinical trials indicate that transference-based treatments and alternative treatments work equally well with regard to symptom improvement. However, transference-based treatments appear to be much more effective with regard to interpersonal relations and other measures of personality functioning. The average between-groups effect size for the experimental studies listed in this article was large. Contrary to common clinical wisdom, transference interventions seem to be most important for (mainly female) patients with difficult interpersonal relationships and more severe personality pathology. Gain of insight may be a specific mechanism of change in dynamic psychotherapy, but only one treatment component study has linked transference work directly to gains in insight and subsequent improvement in interpersonal functioning. Research that examines how transference phenomena may be responded to in nondynamic therapies is scarce.
Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes
Authors: M.K. Purokivi, M-R. Hirvonen, J.T. Randell, M.H. Roponen, T.M. Meklin, A.I. Nevalainen, T.M. Husman, H.O. Tukiainen
Journal: European Respiratory Journal (2001)

Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood. In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-α (TNF-α) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday. The authors found a significant elevation of IL-1, TNF-α and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings. The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways.
Effects of Barium on Mature and Embryonic Heart Cells
Authors: Morris Kleinfeld, Edward Stein, Clem Tionaytis
Journal: Circulation Research (1966)

Barium chloride was administered to isolated preparations of dog heart and rat atrium and to trypsinized embryonic chick heart cells cultured in vitro. Transmembrane action potentials recorded from pacemaker, specialized conductive and contractile fibers of the dog heart, and atrial fibers of rat heart showed a slowing in the rising and falling phases of the action potential and a prominent negative after-potential. The action potential of the Purkinje fiber of the dog heart showed in addition a depolarization during diastole. A decrease in resting potential was observed later. The isometric tension developed by the rat atrium showed a significant increase which was greater at the higher concentractions (greater than 3.5 x 10 -4 M) of barium chloride. The cultured embryonic heart cells were appreciably more sensitive to barium than the mature heart cells. An increase in rate of beat of the embryonic heart cells was observed at concentrations of 10 -6 M whereas a change in heart rate was first observed in the adult heart at concentrations above 10 -4 M. The induction of beating in cell communities previously quiescent is due to a local automatic activity rather than to a propagated activity from an adjacent cell community. The slowing in rise time of the action potential can be attributed to a depression of the sodium-carrying system. The slowing of repolarization can be ascribed to a decrease in potassium conductance. The pronounced negative after-potential can be explained on the basis of sustained impermeability of the membrane to potassium. The mechanism by which barium produces a positive inotropic effect in the rat atrium is open to conjecture. It cannot be attributed solely to a prolongation of the duration of the action potential nor can a direct effect on the contractile proteins be excluded. The presence of extracellular calcium is essential in order to obtain a positive inotropic effect in the rat atrium when barium is added.
Dendritic Peptide Release Mediates Interpopulation Crosstalk between Neurosecretory and Preautonomic Networks
Authors: Sook Jin Son, Jessica A. Filosa, Evgeniy S. Potapenko, Vinicia C. Biancardi, Hong Zheng, Kaushik P. Patel, Vicky A. Tobin, Mike Ludwig, Javier E. Stern
Journal: Neuron (2013)
Multiwalled Carbon Nanotubes Interact with Macrophages and Influence Tumor Progression and Metastasis
Authors: Man Yang, Jie Meng, Xuelian Cheng, Jing Lei, Hua Guo, Weiqi Zhang, Hua Kong, Haiyan Xu
Journal: Theranostics (2012)

Macrophages are one of the most important types of immune effector cells and are closely associated with tumor progression and metastasis. In this work, we investigated the influences of oxidized multiwalled carbon nanotubes (o-MWCNT) on macrophages that are resting in the normal subcutis tissue or in the tumor microenvironment in vivo as well as on the macrophage cell line of RAW 264.7 treated with combination of IL4, IL10 and IL13 in vitro. The o-MWCNT were characterized with SEM, DLS, FTIR, TGA, and UV-vis-NIR spectroscopy, and their effects on the RWA 264.7 cell line and breast cancer tumor-bearing mice were analyzed using the MTS assay, flow cytometry analysis, and histological and immunohistochemical observations. Our experimental results showed that subcutaneously injected o-MWCNT not only induced phagocytosis of the local resident macrophages, but also competitively recruited macrophages from other tissues. These interactions resulted in macrophage reduction and decreased vessel density around the tumor mass, which together inhibited tumor progression and metastasis in the lung. In the cell line model, the o-MWCNT inhibited the ability of the interleukin treated RAW macrophages to promote tumor cell migration as well as decreased their proliferation rate.