tbuckley/cabot-search huggingface dataset:
Characterization of humoral immune responses against p16 in HPV-associated and non HPV-associated disease
Authors: Miriam Reuschenbach, Tim Waterboer, Jens Einenkel, Keng-Ling Wallin, Joakim Dillner, Bernhard Heilig, Eva Hamsikova, Michael Pawlita, Magnus von Knebel Doeberitz, Nicolas Wentzensen
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2126 

Introduction: The cellular tumor suppressor p16INK4a is strongly and constantly overexpressed in cervical cancers and their precursor lesions, while in normal tissue, barely any p16INK4a expression is detected. The aberrant p16INK4a expression results from the HPV E7 mediated disruption of pRb binding to E2F. We have previously demonstrated that infiltrating T lymphozytes reactive against p16INK4a can be found in cervical cancer patients and that T cells from healthy donors can be stimulated with p16INK4a peptides and are able to lyse cervical cancer cell lines. Based on these findings, we hypothesized that p16INK4a might induce humoral immune responses in cervical cancer patients.    Methods: In this study, sera of 360 cervical cancer patients, 64 colorectal cancer patients, 35 patients with HPV related head and neck cancer, 92 patients with autoimmune diseases and 236 healthy controls were analyzed using Western blot, peptide ELISA and a Luminex based assay with recombinant GST-tagged p16INK4a. In addition sera were analyzed for antibodies against p53 and the viral antigens HPV16-E6 and HPV16-E7.    Results: In all series only low p16INK4a antibody reactivity was observed.    No significant difference in p16INK4a antibody frequency could be found between patients and healthy controls in the cervical cancer case control study (OR=0.86; CI 0.56, 1.31). Anti-p53 reactivity was found in all series at slightly higher levels than anti-p16. Antibodies against the HPV oncoproteins E6 and E7 were detected at much higher frequency and titer in HPV related diseases (E6 OR=27.78, E7 OR=2.36).    Conclusion: This is the first study evaluating humoral immune responses against p16INK4a. Only weak antibody responses against the strongly overexpressed p16INK4a in HPV related tumors were observed. The slightly higher percentage of responses in healthy controls might be related to a protective effect of p16INK4a autoantibodies but needs to be analyzed in a series of women with regressing dysplastic cervical lesions.
Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1
Authors: Gunther G. Pendl, Caroline Robert, Meike Steinert, Renate Thanos, Ruth Eytner, Eric Borges, Martin K. Wild, John B. Lowe, Robert C. Fuhlbrigge, Thomas S. Kupper, Dietmar Vestweber, Stephan Grabbe
Journal: Blood (2002)
Modulation of fibrin clot formation by human serum amyloid P component (SAP) and heparin.
Authors: C S Ku, B A Fiedel
Journal: The Journal of Experimental Medicine (1983)

Serum amyloid P-component (SAP) is a normal plasma constituent in man with a circulating concentration of approximately 40 micrograms/ml. Supraphysiological amounts of SAP (150-300 micrograms/ml) have been reported to affect coagulation. We have investigated this further by studying the effect of SAP upon clot times in both the absence and presence of heparin, a suggested ligand for SAP and itself a modulator of coagulation processes. In the absence of heparin, SAP (5-125 micrograms/ml) had no effect on clot times generated by Activated Thrombofax Reagent, brain thromboplastin, Russell's Viper Venom or thrombin when assessed in normal citrated plasma. However, in the presence of amounts of heparin that had only a minor effect upon clot times, SAP (5-40 micrograms/ml) greatly prolonged clot formation, with the thrombin time the most sensitive to SAP. This suggested that the primary effect of SAP was at this distal level of the coagulation pathway. Evaluation by radioimmunoassay revealed that supraphysiological concentrations of SAP (150-300 micrograms/ml) alone reduced by approximately 25% the release of fibrinopeptide A (FPA) from fibrinogen. In the presence of heparin, substantial synergism was observed with maximal reductions of approximately 70% in FPA production requiring only 25-50 micrograms/ml SAP. This inhibition correlated with increased thrombin clot time but was unrelated to any direct modulation in either the activities of anti-thrombin III or activated Factor XIII, and was independent of an alteration in the rate of fibrinolysis. Further, while SAP itself did not interfere with the process of spontaneous fibrin polymerization, in the presence of heparin a prolonged polymerization time (greater than 145%) was observed. We believe that these data reflect the primary mechanisms by which serum amyloid P component influences blood coagulation.
Inhibition of c-kit tyrosine kinase by imatinib mesylate induces apoptosis in mast cells in rheumatoid synovia: a potential approach to the treatment of arthritis
Authors: A Juurikivi
Journal: Annals of the Rheumatic Diseases (2005)

Mast cells have been implicated in the pathogenesis of arthritis, but elucidation of their precise role has been hampered by a lack of efficient and selective inhibitors of their function.To elucidate the role of mast cells in the pathogenesis of rheumatoid arthritis (RA) and to assess whether apoptosis of cultured and synovial tissue mast cells can be induced by inhibiting mast cell growth factor receptor, c-kit tyrosine kinase.Double staining with tumour necrosis factor (TNF) alpha and tryptase antibodies showed the presence of TNFalpha positive mast cells in human rheumatoid synovial tissue. Selective activation of mast cells by anti-IgE resulted in production of TNFalpha in synovial tissue cultures. Inhibition of the c-kit tyrosine kinase with imatinib mesylate (1.0-10 micromol/l) induced profound apoptosis in cultured mast cells as judged by typical apoptotic morphology, increased number of apoptotic nucleosomes, and activation of caspases 8 and 9. Importantly, imatinib also induced apoptosis of mast cells in explant cultures of synovial tissue obtained from patients with RA as judged by a TUNEL assay. Inhibition of c-kit tyrosine kinase was accompanied by significant reduction of TNFalpha production in synovial tissue cultures.Mast cells may have a role in the pathogenesis of RA, and inhibition of c-kit may be a new means of inhibiting mast cell activity and of abrogating the contribution of mast cells to synovial inflammation in RA.
Loss of IFNγ Receptor Is an Independent Prognostic Factor in Ovarian Cancer
Authors: Timothy J. Duncan, Phil Rolland, Suha Deen, Ian V. Scott, David T.Y. Liu, Ian Spendlove, Lindy G. Durrant
Journal: Clinical Cancer Research (2007)

Abstract Purpose: There is evidence that IFNγ plays an important role in ovarian cancer development. IFNγ produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFNγ receptor, thus leading to altered tumor biology and patient prognosis. This hypothesis would support the theory of immunoediting in ovarian cancer. Experimental Design: Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFNγ receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied. Results: Tumors expressing high levels of IFNγ receptor had significantly improved survival (P = 0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (P = 0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. The level of IFNγ receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. There was no correlation between receptor status and any of the standard clinicopathologic variables. Conclusions: Loss of IFNγ receptor independently predicts poor prognosis in ovarian cancer. Loss of receptor expression may be responsible for the limited success in the therapeutic use of IFNγ in ovarian cancer trials and highlights a subgroup of high expressing IFNγ receptor tumors which are more likely to be susceptible to such treatments.
The Hormonal Regulation of Food Intake, Digestion, and Absorption
Authors: C G Nicholl, J M Polak, S R Bloom
Journal: Annual Review of Nutrition (1985)

INTRODUCTION . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 REG ULATORY PEPTIDES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214 FOO D INTAKE . . . . . ... . . . . . . . . . . . ... . . . .. . . . . . . . . . . . . . . . .. . ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 DIGESTION AND ABSORPT ION . . . . . . . . . . . . ...... ..... . . . . . . . . . . . .. . ...... . . . . . . . . . .... .. . . . . . . 222 Mouth . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . 222 Esophagus . . . . . . .. . . . . . . . . . . . ...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . ...... . . . . . . . . . . 223 Stomach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 Small Intestine . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ....... . .. . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . ... . . 229 Pancreas . . . . . ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . .. ........ . . . . . . . . . . . . .. ....... . . . . . . . . .. . . . . . . . . . . . . . . 230 Biliary Tract . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . ........ . . . . . . . . . . . . . . . ...... . . . . . . . . .. . . . . . . . . . . . . . . . . 231 Colon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   . . . . . . . . . . . . . ....... . . . . . . . . . . ...... . . . . . . .. . . . . 232 CONCLUS ION . . . . . . . . . . . ... ........ . . . . . . . . . . . . . . .. . . .. . .. ... . . . . . . . . . . . . .. . . . .. . . . . . .. . . . . . . . . . .. . . . 232
A public health context for residual risk assessment and risk management under the clean air act.
Authors: G Charnley, B D Goldstein
Journal: Environmental Health Perspectives (1998)

The 1990 amendments to the Clean Air Act required the EPA to institute new pollution control technology requirements for industrial sources of air pollution. In part because agreement could not be reached on the best way for the EPA to determine whether any significant risks to human health will remain after the technology controls are in place, the amendments also created a Commission on Risk Assessment and Risk Management and gave the commission a broad mandate to review and make recommendations concerning risk assessment and risk management in federal regulatory programs. In its March 1997 final report to Congress and the administration, the commission recommended a tiered approach to assessing such residual risks. That approach included the idea that when decisions about managing residual risks are made, emissions should be evaluated in the context of other sources of air pollution. Evaluating risks in their larger contexts is consistent with what the commission called a public health approach to environmental risk management. This paper describes the public health approach and how it applies to evaluating residual risks under the Clean Air Act.
Quality of Life in Long-Term Breast Cancer Survivors
Authors: Tina Hsu, Marguerite Ennis, Nicky Hood, Margaret Graham, Pamela J. Goodwin
Journal: Journal of Clinical Oncology (2013)

There is considerable interest in the quality of life (QOL) of long-term breast cancer (BC) survivors. We studied changes in QOL from time of BC diagnosis to long-term survivorship and compared QOL in long-term survivors to that of age-matched women with no history of BC.In all, 535 women with localized BC (T1-3N0-1M0) were recruited from 1989 to 1996 and followed prospectively, completing QOL questionnaires at diagnosis and 1 year postdiagnosis. Between 2005 and 2007, those alive without distant recurrence were recontacted to participate in a long-term follow-up (LTFU) study. A control group was recruited from women presenting for screening mammograms, and both groups completed LTFU QOL questionnaires. Longitudinal change in BC survivors and differences between BC survivors and controls were assessed in eight broad categories with clinically significant differences set at 5% and 10% of the breadth of each QOL scale.A total of 285 patients with BC were included in the study, on average 12.5 years postdiagnosis. Longitudinally, clinically significant improvements were observed in overall QOL by 1 year postdiagnosis with further improvements by LTFU. Some clinically significant improvements over time were seen in all categories. A total of 167 controls were recruited. Deficits were observed in self-reported cognitive functioning (5.3% difference) and financial impact (6.3% difference) in BC survivors at LTFU compared with controls.Long-term BC survivors show improvement in many domains of QOL over time, and they appear to have similar QOL in most respects to age-matched noncancer controls, although small deficits in cognition and finances were identified.
Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure
Authors: Bertram Pitt, Harvey White, Jose Nicolau, Felipe Martinez, Mihai Gheorghiade, Michael Aschermann, Dirk J. van Veldhuisen, Faiez Zannad, Henry Krum, Robin Mukherjee, John Vincent
Journal: Journal of the American College of Cardiology (2005)
TREATMENT OF IDIOPATHIC HYPERHIDROSIS WITH IONTOPHORESIS OF TAP WATER AND POLDINE METHOSULPHATE
Authors: KATHKRINE GRICE, H. SATTAR, HARVEY BAKER
Journal: British Journal of Dermatology (1972)

SUMMARY.— Iontophoresis of tap water or of an anticholincrgic compound (poldine methosulphate) was simple and useful in the treatment of idiopathic hyperhidrosis of the palms and soles. Axillary hyperhidrosis was not so easily controlled. Poldine was more effective than tap water; with increasing doses, systemic effects were produced. Treatment was arranged easily in the Physical Medicine Department, It was suggested that, before resorting to surgery, iontophoresis is worth a trial in idiopathic hyperhidrosis.
Local expression of antiinflammatory cytokines in cancer.
Authors: M Yamamura, R L Modlin, J D Ohmen, R L Moy
Journal: Journal of Clinical Investigation (1993)

To characterize the nature of the local cytokine response to cancer, we chose to investigate cytokine patterns in biopsy specimens of basal cell carcinoma (BCC). We hypothesized that a distinct pattern of local cytokine production may be characteristic of BCC, a neoplasia of epidermis, in comparison to the pattern of seborrheic keratosis (SK), a benign growth of epidermis. We analyzed cytokine mRNAs in BCC versus SK by performing polymerase chain reaction on mRNA derived from biopsy specimens. The mRNAs encoding cytokines for IL-4, IL-5, IL-10, and granulocyte macrophage colony-stimulating factor were strongly expressed in BCC lesions and weakly expressed in SK lesions. Conversely, IL-2, IFN-gamma, and lymphotoxin mRNAs were strongly expressed in SK lesions and weakly expressed in BCC lesions. The response to malignancy, BCC, was typified by cytokines characteristic of murine TH2 cells. This cytokine pattern favors humoral immunity with concomitant immunosuppression of cell-mediated immune responses. In comparison, the response to the benign growth, SK, was typified by cytokines characteristic of murine TH1 cells that favor cell-mediated immune reactions. The findings of a distinct cytokine pattern in skin cancer provide a framework to develop strategies for immunologic intervention.
Grand Rounds: Asbestos-Related Pericarditis in a Boiler Operator
Authors: Belayneh A. Abejie, Eugene H. Chung, Richard W. Nesto, Stefanos N. Kales
Journal: Environmental Health Perspectives (2007)

Occupational and environmental exposures to asbestos remain a public health problem even in developed countries. Because of the long latency in asbestos-related pathology, past asbestos exposure continues to contribute to incident disease. Asbestos most commonly produces pulmonary pathology, with asbestos-related pleural disease as the most common manifestation. Although the pleurae and pericardium share certain histologic characteristics, asbestos-related pericarditis is rarely reported.We present a 59-year-old man who worked around boilers for almost 30 years and was eventually determined to have calcific, constrictive pericarditis. He initially presented with an infectious exacerbation of chronic bronchitis. Chest radiographs demonstrated pleural and pericardial calcifications. Further evaluation with cardiac catheterization showed a hemodynamic picture consistent with constrictive pericarditis. A high-resolution computerized tomography scan of the chest demonstrated dense calcification in the pericardium, right pleural thickening and nodularity, right pleural plaque without calcification, and density in the right middle lobe. Pulmonary function testing showed mild obstruction and borderline low diffusing capacity.Based on the patient's occupational history, the presence of pleural pathology consistent with asbestos, previous evidence that asbestos can affect the pericardium, and absence of other likely explanations, we concluded that his pericarditis was asbestos-related.Similar to pleural thickening and plaque formation, asbestos may cause progressive fibrosis of the pericardium.
BRD4-NUT Fusion Oncogene: A Novel Mechanism in Aggressive Carcinoma
Authors: Christopher A. French, Isao Miyoshi, Ichiro Kubonishi, Holcombe E. Grier, Antonio R. Perez-Atayde, Jonathan A. Fletcher
Journal: Cancer Research (2003)

The poorly differentiated carcinoma with t(15;19)(q13, p13.1) is characterized by its highly aggressive, invariably lethal clinical course. The chromosome 19 translocation breakpoint targets the BRD4 double bromodomain-containing gene, which functions in regulation of cell cycle progression. Herein we demonstrate that BRD4 is fused with nearly the entire transcript of the novel 15q13 gene, NUT (nuclear protein in testis), forming a 6.4-kb fusion oncogene, BRD4-NUT. NUT, like BRD4, is predicted to encode a nuclear protein but, unlike the ubiquitous BRD4 transcript, is expressed only in testis. These findings establish a model to elucidate the oncogenic consequences of unscheduled NUT expression and altered BRD4 function. Very few fusion oncogenes have been identified in epithelial tumors, and BRD4-NUT is the first fusion oncogene mechanism identified in a highly lethal form of carcinoma.
Cartilage morphogenetic proteins: role in joint development, homoeostasis, and regeneration
Authors: A H Reddi
Journal: Annals of the Rheumatic Diseases (2003)

Articular cartilage homoeostasis is critical for joint function. The steady state homoeostasis of articular cartilage is a balance between anabolic morphogens such as cartilage derived morphogenetic proteins (CDMPs) and bone morphogenetic proteins (BMPs) of the BMP family and catabolic cytokines such as interleukin (IL)1, IL17, and tumour necrosis factor alpha. Although bone and articular cartilage are adjacent tissues, there is a profound difference in their regeneration potential. Bone has the highest potential for regeneration. On the other hand, articular cartilage is recalcitrant to repair.To examine the hypothesis that the feeble innate regeneration ability of cartilage is due to the preponderance of catabolic cytokines such as IL1 and IL17.During a systematic investigation of CDMPs and cytokines IL17B (chondroleukin) was found in bovine articular cartilage.BMP-7 and IL17B are present in articular cartilage and synthesised in chondrocytes as shown by northern blots and real-time reverse transcription-polymerase chain reaction. The coexistence of anabolic morphogens and catabolic cytokines in articular cartilage has important implications for cartilage homoeostasis and regeneration. The networks of signalling systems of morphogens and cytokines determine the net capacity for regenerative morphogenesis of articular cartilage. Finally, the feeble innate capacity for articular cartilage may be improved by targeted therapy by soluble receptors to block catabolic cytokines.
Delusions of parasitosis. A psychiatric disorder to be treated by dermatologists? An analysis of 33 patients
Authors: None Zomer, None DE Wit, None Van Bronswijk, None Nabarro, None Van Vloten
Journal: British Journal of Dermatology (1998)

Delusions of parasitosis is a rare disorder in which patients have the false and fixed belief that they are infested by parasites. It is a psychiatric disorder, but patients usually present to a dermatologist and referral to a psychiatrist is almost always rejected. Treating a patient with delusions of parasitosis requires patience and tact. The neuroleptic pimozide is the treatment of choice, but a significant problem is convincing the patient to take the drug. We report a study of 33 patients (13 men and 20 women) with delusions of parasitosis. The mean age at onset was 56.9 years and the mean duration of symptoms before attending the department of dermatology was 1.3 years. Pimozide (Orap) was prescribed for 24 patients, but only 18 patients took it. Follow-up information was available for 18 patients: five had full remission, four were less symptomatic, five were unchanged and four had died of unrelated causes.