tbuckley/cabot-search huggingface dataset:
DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer's disease
Authors: Jianmin Chen, Mark L Cohen, Alan J Lerner, Yan Yang, Karl Herrup
Journal: Molecular Neurodegeneration (2010)

Although the cerebellum is considered to be predominantly involved in fine motor control, emerging evidence documents its participation in language, impulsive behavior and higher cognitive functions. While the specific connections of the cerebellar deep nuclei (CDN) that are responsible for these functions are still being worked out, their deficiency has been termed "cerebellar cognitive affective syndrome" - a syndrome that bears a striking similarity to many of the symptoms of Alzheimer's disease (AD). Using ectopic cell cycle events and DNA damage markers as indexes of cellular distress, we have explored the neuropathological involvement of the CDN in human AD.We examined the human cerebellar dentate nucleus in 22 AD cases and 19 controls for the presence of neuronal cell cycle events and DNA damage using immunohistochemistry and fluorescence in situ hybridization. Both techniques revealed several instances of highly significant correlations. By contrast, neither amyloid plaque nor neurofibrillary tangle pathology was detected in this region, consistent with previous reports of human cerebellar pathology. Five cases of early stage AD were examined and while cell cycle and DNA damage markers were well advanced in the hippocampus of all five, few indicators of either cell cycle events (1 case) or a DNA damage response (1 case) were found in CDN. This implies that CDN neurons are most likely affected later in the course of AD. Clinical-pathological correlations revealed that cases with moderate to high levels of cell cycle activity in their CDN are highly likely to show deficits in unorthodox cerebellar functions including speech, language and motor planning.Our results reveal that the CDN neurons are under cellular stress in AD and suggest that some of the non-motor symptoms found in patients with AD may be partly cerebellar in origin.
Impaired Clearance of Enzymes in Mice Infected With the Lactic Dehydrogenase Agent
Authors: Abner Louis Notkins, M.D., Christina Scheele
Journal: JNCI Journal of the National Cancer Institute (1964)

Mice infected with the lactic dehydrogenase (LDH) agent cleared intravenously administered lactic dehydrogenase and isocitric dehydrogenase from the peripheral circulation at a slower rate than normal mice. No difference was found between normal and infected animals in the rate of clearance of alkaline phosphatase. Carbon tetrachloride, which liberates endogenous enzymes into the circulation by damaging cells, resulted in a more prolonged elevation of lactic dehydrogenase, isocitric dehydrogenase, and malic dehydrogenase in the plasma of infected animals than in normal animals. The onset of impaired enzyme clearance occurred within 13 hours after injection of the LDH agent and persisted for months. The clearance of colloidal carbon particles was also impaired early in the course of infection but returned to normal within 1 week. Evidence is discussed which suggests that impaired clearance of normally released endogenous enzymes might be responsible for the increase in plasma enzyme activity following infection with the LDH agent.
High Phosphoantigen Levels in Bisphosphonate-Treated Human Breast Tumors Promote Vγ9Vδ2 T-Cell Chemotaxis and Cytotoxicity <i>In Vivo</i>
Authors: Ismahène Benzaïd, Hannu Mönkkönen, Verena Stresing, Edith Bonnelye, Jonathan Green, Jukka Mönkkönen, Jean-Louis Touraine, Philippe Clézardin
Journal: Cancer Research (2011)

Abstract The nitrogen-containing bisphosphonate zoledronic acid (ZOL), a potent inhibitor of farnesyl pyrophosphate synthase, blocks the mevalonate pathway, leading to intracellular accumulation of isopentenyl pyrophosphate/triphosphoric acid I-adenosin-5′-yl ester 3-(3-methylbut-3-enyl) ester (IPP/ApppI) mevalonate metabolites. IPP/ApppI accumulation in ZOL-treated cancer cells may be recognized by Vγ9Vδ2 T cells as tumor phosphoantigens in vitro. However, the significance of these findings in vivo remains largely unknown. In this study, we investigated the correlation between the anticancer activities of Vγ9Vδ2 T cells and the intracellular IPP/ApppI levels in ZOL-treated breast cancer cells in vitro and in vivo. We found marked differences in IPP/ApppI production among different human breast cancer cell lines post-ZOL treatment. Coculture with purified human Vγ9Vδ2 T cells led to IPP/ApppI-dependent near-complete killing of ZOL-treated breast cancer cells. In ZOL-treated mice bearing subcutaneous breast cancer xenografts, Vγ9Vδ2 T cells infiltrated and inhibited growth of tumors that produced high IPP/ApppI levels, but not those expressing low IPP/ApppI levels. Moreover, IPP/ApppI not only accumulated in cancer cells but it was also secreted, promoting Vγ9Vδ2 T-cell chemotaxis to the tumor. Without Vγ9Vδ2 T-cell expansion, ZOL did not inhibit tumor growth. These findings suggest that cancers-producing high IPP/ApppI levels after ZOL treatment are most likely to benefit from Vγ9Vδ2 T-cell–mediated immunotherapy. Cancer Res; 71(13); 4562–72. ©2011 AACR.
Role of Mononuclear Cells and Inflammatory Cytokines in Pancreatic Cancer-Related Cachexia
Authors: Marc E. Martignoni, Phillipp Kunze, Wulf Hildebrandt, Beat Künzli, Pascal Berberat, Thomas Giese, Oliver Klöters, Jürgen Hammer, Markus W. Büchler, Nathalia A. Giese, Helmut Friess
Journal: Clinical Cancer Research (2005)

Abstract Background and Purpose: The mechanism behind aggressive development of cachexia in patients suffering from pancreatic cancer is not well understood. In this study, we investigated which factors are associated with the cachectic status of the patients and evaluated cachexia-promoting capacity of cancer and inflammatory cells. Experimental Design: DNA microarray analysis and quantitative reverse transcription-PCR were used to screen for cachexia-associated factors in pancreatic specimens obtained from noncachectic and cachetic patients diagnosed with pancreatic ductal adenocarcinoma. The expression pattern of the most prominently altered cachexia-associated factor, interleukin-6 (IL-6), was further analyzed in patients sera by ELISA, in pancreatic specimens by immunohistochemistry, and in a coculture system by quantitative reverse transcription-PCR using pancreatic cancer cell lines T3M4 (IL-6 positive) and Panc-1 (IL-6 negative) and peripheral blood mononuclear cells (PBMC) obtained from donors and noncachectic and cachectic patients. Results: Among numerous analyzed factors, IL-6 was significantly overexpressed in pancreatic specimens and elevated in serum of cachectic patients. The coculture system revealed that pancreatic cancer T3M4 cells but not Panc-1 cells were able to stimulate IL-6 exclusively in cachectic PBMC (by 14-fold) and this triggering was reduced by half in the presence of IL-6-neutralizing antibodies. Conclusion: IL-6 represents a prominent cachexia-associated factor in pancreatic cancer. IL-6 overexpression in cachectic patients is related to the ability of certain tumors to sensitize PBMC and induce cytokine expression in cachectic PBMC.
New Approaches in the Therapy of Cardiomyopathy in Muscular Dystrophy
Authors: Elizabeth M. McNally
Journal: Annual Review of Medicine (2007)

Cardiomyopathy is a frequent occurrence in muscular dystrophy, and heart disease in muscular dystrophy can contribute to both morbidity and mortality. A number of novel therapies are being developed for muscular dystrophy, and the efficacy of these therapies for heart disease is unknown. The most common X-linked recessive disease is Duchenne muscular dystrophy (DMD), which arises from defects in the dystrophin gene. Therapy specifically aimed at DMD is reviewed in the context of its projected effect on cardiomyopathy associated with DMD. Additionally, novel therapies are being pursued to treat specifically the cardiomyopathy of DMD. There is substantial genetic heterogeneity underlying the muscular dystrophies, and not all muscular dystrophy patients develop cardiomyopathy. A subset of muscular dystrophies may place patients at significantly greater risk of developing cardiomyopathy and cardiac rhythm disturbances. These disorders are discussed, highlighting recent studies and recommendations for therapy.
The Pathology and Treatment of Spasmodic Asthma
Authors: C. T. Williams
Journal: BMJ (1874)

any extra virus incapable of being admitted.In this pstance, it might be said that the patient carried into hospital the virus which was capable of producing these inoculations.Such a possibility as this I, however, disposed of by another observation, wvhich I made thus, as proof of the inoculative power of the vaginal discharge, and of its giving origin to a pustular sore, capable of reproduction in its kind.M. White, aged 20, with tumid labium, patches, vaginal discharge, no sore to be seen, indurated inguinal glands, alopecia, pains, and ca- chexia-admitted June Ist.The following inoculations were per- formed: June 22nd.With M. Burke's discharge; failed.June 23rd.With Conroy's discharge failed
Propylthiouracil and thiamazole do not alter in vitro neutrophil oxidative burst
Authors: Elisa Maria de Sousa Russo-Carbolante, Ana Elisa Caleiro Seixas Azzolini, Ana Christina Morseli Polizello, Ana Isabel de Assis-Pandochi, Yara Maria Lucisano-Valim
Journal: Metabolism (2005)
STUDIES IN THE SEROLOGY OF SYPHILIS
Authors: Harry Eagle
Journal: The Journal of Experimental Medicine (1931)

Serum, in concentrations greater than 1:25, causes a marked inhibition of complement fixation in general and of the Wassermann reaction in particular. The serum protein is probably adsorbed by the colloidally dispersed lipoid-reagin complexes, forming a protective film which prevents the fixation (adsorption) of complement. This inhibition explains the zone phenomenon in complement fixation: a weakly positive serum may give a completely positive reaction in e.g., 1:5 dilution, and yet, because of this serum inhibition, may appear completely negative when tested as whole serum. The greater sensitivity of the ice box test is due (1) to the fact that the serum inhibition just described is less marked at lower temperature; (2) to the prolonged incubation time, making for greater specific fixation; (3) to a more marked non-specific destruction of complement by antigen; and (4) a spontaneous deterioration in the longer ice box test. Because of the inhibition by serum protein in high concentration, a quantitative Wassermann technique involving the use of graded quantities of serum is worthless when carried out at 37°C. Even the ice box test, which is less susceptible to this inhibiting effect, will yield a positive reaction with whole serum only when the circulating reagin exceeds a surprisingly high threshold (six to ten times the quantity which could be detected in dilute serum). It is well known that a negative Wassermann, even by a very sensitive test, does not exclude syphilis: it now appears that a negative Wassermann does not exclude circulating reagin.
The expression of antimicrobial peptides is significantly altered in cutaneous squamous cell carcinoma and precursor lesions
Authors: N. Scola, T. Gambichler, H. Saklaoui, F.G. Bechara, D. Georgas, M. Stücker, R. Gläser, A. Kreuter
Journal: British Journal of Dermatology (2012)

Antimicrobial peptides and proteins are not only effectors of the immune system but are also attributed important roles in tumour progression or tumour suppression in several malignancies such as oral squamous cell carcinoma (SCC).These reports encouraged us to systematically investigate the expression of different classes of antimicrobial peptides and proteins in tissue samples of cutaneous SCC and its precursor lesions.The protein expression of human beta-defensin (hBD)-1, -2, and -3, ribonuclease (RNase)-7 and the S100 protein psoriasin were analysed in 25 patients with actinic keratosis (AK), 30 with SCC in situ (SCCis), 23 with SCC, nine healthy skin controls and 10 healthy, chronically ultraviolet (UV)-exposed controls, by means of immunohistochemistry.Expression of hBD-1 was significantly reduced in SCC compared with UV-exposed healthy skin, AK and SCCis. RNase-7 expression was reduced gradually parallel to every step of malignant transformation, with the highest expression in healthy skin and the lowest expression in SCC. hBD-2 and psoriasin were significantly overexpressed in SCC and SCCis, compared with healthy controls. hBD-3 showed significantly more frequent expression in AK than in healthy controls, and in patients with SCCis and SCC.It is tempting to speculate that hBD-1 and RNase-7 might act as tumour suppressors while hBD-2 and psoriasin might act in the opposite way as promoters of tumour progression. Further investigations should clarify whether hBD-2 and hBD-3 could be potential targets for the development of pharmacological therapy.
Fixed drug eruption due to phenylpropanolamine hydrochloride
Authors: H. Heikkilä, A-L. Kariniemi, S. Stubb
Journal: British Journal of Dermatology (2000)

Journal Article Fixed drug eruption due to phenylpropanolamine hydrochloride Get access H. Heikkilä, H. Heikkilä Department of Dermatology and Venereology, Helsinki University Central Hospital, Meilahdentie 2, 00250 Helsinki 25, Finland E‐mail: hannele.heikkila@pp.inet.fi Search for other works by this author on: Oxford Academic Google Scholar A‐L. Kariniemi, A‐L. Kariniemi Department of Dermatology and Venereology, Helsinki University Central Hospital, Meilahdentie 2, 00250 Helsinki 25, Finland E‐mail: hannele.heikkila@pp.inet.fi Search for other works by this author on: Oxford Academic Google Scholar S. Stubb S. Stubb Department of Dermatology and Venereology, Helsinki University Central Hospital, Meilahdentie 2, 00250 Helsinki 25, Finland E‐mail: hannele.heikkila@pp.inet.fi Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 4, 1 April 2000, Pages 845–847, https://doi.org/10.1046/j.1365-2133.2000.03458.x Published: 01 April 2000
Effect of bee venom on experimental arthritis.
Authors: R B Zurier, H Mitnick, D Bloomgarden, G Weissmann
Journal: Annals of the Rheumatic Diseases (1973)

theincreased biosynthesis of prostaglandins (RamwellandShaw, 1970). It hasbeensuggestedthatonesuchstimulus is inflammation, in the course of whichphospholipases are freed from the lysosomes ofphagocytes. Theseenzymescancleavephospholipidsofthecell membranetoyieldarachidonicacid, whichis in turn converted to prostaglandins by freelyavailable tissue enzymes (Anderson, Brocklehurst,andWillis, 1971). Phospholipasesarealsoamongthemost active components of a number of animalvenoms(Eliasson, 1959),suchasbeevenomandsnakevenom, which both contain phospholipase A andappear to release prostaglandins fromtissues (Vogt,Meyer,Kunze,Lufft, andBabilli, 1969). Since it hasbeenobservedthatprostaglandinE1
TCT-146 Comparison Of Peri-Procedural Platelet Inhibition With Prasugrel Versus Adjunctive Cilostazol To Dual Anti-platelet Therapy In Patients With ST Segment Elevation Myocardial Infarction
Authors: Keun-Ho Park, Youngkeun Ahn, Young Joon Hong, Myung Ho Jeong, Young Wook Jeong, Hae Chang Jeong, Sung Soo Kim, Ju Han Kim, Si Hyun Rhew, Doo Sun Sim
Journal: Journal of the American College of Cardiology (2013)
Late-breaking abstract: A novel method to detect infection in COPD exacerbations: The electronic nose
Authors: Hanaa Shafiek, Jose Merino, Federico Fiorentino, Carla López, Oriol Sibila, Bernat Togores, Ivan de Paul, Jaume Segura, Antonio Oliver, Borja Cosío
Journal: European Respiratory Journal (2014)

Background: Electronic nose (e-nose) is a novel technique based on the detection of volatile organic compounds (VOCs) breath prints in exhaled air. We hypothesized that e-nose could identify specific VOCs breath pattern for infection in acute exacerbation of COPD (AECOPD) and distinguish it from the stable state.

Objectives: To determine the validity of e-nose in detecting infection of AECOPD.

Methods: The study enrolled 53 AECOPD patients, 18 COPD with pneumonia and 29 stable COPD. Sputum sample was collected for microbiological evaluation. Exhaled air was collected with a Tedlar bag which was processed by a Cynarose320 e-nose. Breath-prints were analyzed by Linear Discriminant Analysis with One Out technique.

Results: Pathogenic microorganisms were detected in 37% of AECOPD, 43.7% of COPD with pneumonia and 17% of stable COPD. Thirty percent of sputum samples were invalid for microbiologic analysis. Breath-prints from AECOPD were significantly distinguishable from stable COPD in the presence of microorganism (p=0.036; 84.4% sensitivity;70% specificity), but better in absence of infection (p=0.014; 90.6% sensitivity; 80% specificity). However, breath-prints from COPD with pneumonia failed to show significant difference from AECOPD in the presence of microorganism (p=0.097); but they were significantly distinguishable in absence of infection (p=0.013; 87.5% sensitivity;77.8% specificity) and from stable COPD (specificity 90%; p<0.05).

Conclusion: Different breath-prints related to infection can be detected by the e-nose. AECOPD with/without pneumonia showed distinguishable breath-prints compared to stable COPD even if microorganism is not cultured.
Low blood pressure predicts increased mortality in very old age even without heart failure: the Leiden 85‐plus Study
Authors: Rosalinde K.E. Poortvliet, Jeanet W. Blom, Anton J.M. de Craen, Simon P. Mooijaart, Rudi G.J. Westendorp, Willem J.J. Assendelft, Jacobijn Gussekloo, Wouter de Ruijter
Journal: European Journal of Heart Failure (2012)
THE INFLUENCE OF LATENT SYPHILITIC INFECTION ON THE REACTION OF THE RABBIT TO THE BROWN-PEARCE TUMOR
Authors: Paul D. Rosahn
Journal: The Journal of Experimental Medicine (1935)

The reaction of the latent syphilitic rabbit to inoculation with the Brown-Pearce tumor was studied in 50 standard bred rabbits representing five breeds. The mean tumor mortality rate in the combined group was found to be significantly lower than a weighted control value for normal non-syphilitic animals, and the mean tumor mortality rate for each of the five breeds studied was lower in the syphilitic group than the corresponding breed mean value for normal animals. Moreover, the relative resistance of different breeds to the Brown-Pearce tumor was not altered by the latent syphilitic infection. Certain factors which might have contributed to the development of a tumor resistant state in the syphilitic group were discussed, and evidence was presented which demonstrates that as regards the breeds under consideration, there exists a high correlation between breed resistance to Tr. pallidum infection and breed resistance to the Brown-Pearce tumor.
A Comparison of the Distribution of Potassium and Exchangeable Rubidium in the Organs of the Dog, Using Rubidium <sup>86</sup>
Authors: W. D. LOVE, R. B. ROMNEY, G. E. BURCH
Journal: Circulation Research (1954)

From determinations of radioactivity and potassium content at intervals after the injection of Rb 86 , it was inferred that most organs of the dog contained exchangeable rubidium in a concentration paralleling but exceeding that of potassium, as compared with their relative concentrations in the plasma. A "lag phenomenon" resulting in higher rubidium specific activity in the myocardium than plasma was present. Analysis indicated that this was dependent on the relationship of myocardial rubidium exchange rate and the rate of decline of plasma rubidium specific activity. In experiments requiring prolonged observation, Rb 86 (half life, 19.5 days) is a useful tracer of potassium.
Mast cell regulation of airway smooth muscle function in asthma
Authors: P. Bradding
Journal: European Respiratory Journal (2007)

Asthma is a common disease affecting ≤10% of the adult Western population 1, 2. It is characterised by the presence of variable and potentially reversible airflow obstruction, which occurs as the result of bronchoconstriction, airway mucus plugging and airway oedema. Pathologically there is evidence of airway inflammation and remodelling 3–7. The mucosal inflammatory infiltrate commonly comprises activated T-cells, eosinophils and mast cells, while the accompanying structural changes include subepithelial collagen deposition, goblet cell- and mucous gland-hyperplasia, airway smooth muscle (ASM) hypertrophy and ASM hyperplasia.

An important physiological feature of asthma is the presence of bronchial hyperresponsiveness (BHR) 8. This means there is an exaggerated bronchoconstrictor response of the ASM to direct and indirect stimuli such as histamine and exercise, respectively. While BHR is aggravated in the presence of classic allergic eosinophilic airway inflammation, it persists once this inflammation is controlled and is not present in patients with eosinophilic bronchitis 8, 9. This suggests that there is either a fundamental abnormality of ASM behaviour in asthmatic subjects or that there are interacting factors that have not been previously recognised. In support of the former, several phenotypic differences are evident in ASM cells cultured from the airways of asthmatic subjects. For example, when compared with normal ASM cells, cultured asthmatic ASM cells proliferate faster due to an altered pattern of matrix protein deposition 10, 11, secrete greater amounts of connective tissue-derived growth factor in response to transforming growth factor-β stimulation 12, and secrete markedly increased amounts of the chemokine CXCL10 in response to activation by cytokines 13. There is decreased expression of prostaglandin (PG)E2 by the asthmatic ASM 14, and proliferation of asthmatic ASM is not inhibited by corticosteroids due to impaired expression of the transcription factor CCAAT/enhancer …
Computerised cognitive assessment of athletes with sports related head injury
Authors: A Collie, D Darby, P Maruff
Journal: British Journal of Sports Medicine (2001)

Professional and amateur participants in many sports are at risk of brain injury caused by impact with other players or objects. In many cases, mild cognitive deficits may persist after the common neurological signs of brain injury have passed. In recent years, the athlete's cognitive status after concussion has been measured with conventional "paper and pencil" neuropsychological tests. However, such tests are not ideal for sporting settings, as they are designed for the detection of gross cognitive impairments at a single assessment, not for the identification of mild cognitive deficits on repeated assessment. A number of computerised cognitive assessment tests and test batteries have been developed over the past two decades. These batteries offer major scientific and practical advantages over conventional neuropsychological tests which make them ideal for the assessment of cognitive function in sportspeople. This review first describes the problems associated with cognitive assessment of people with sports related cognitive deficits, and then critically examines the utility of conventional neuropsychological and computerised cognitive tests in sporting settings.