tbuckley/cabot-search huggingface dataset:
Cardioprotective effects of platelets against ischaemia-reperfusion injury are related in part to platelet glutathione redox cycle
Authors: B C Yang, A Mehta, J L Mehta
Journal: Cardiovascular Research (1994)

Objective: Washed platelets have been shown to protect isolated buffer perfused rat hearts from injury and dysfunction following ischaemia-reperfusion. This study was designed to investigate whether platelet glutathione redox cycle contributes to the protective effect of platelets. Methods: Isolated rat hearts were perfused with Krebs-Henseleit buffer alone, buffer containing platelets, or buffer containing platelets pretreated with inhibitors of glutathione redox cycle. All hearts were subjected to 40 min of global ischaemia followed by 30 min of reperfusion. Results: Following ischaemia and reperfusion, hearts perfused with buffer alone showed a marked reduction in force of cardiac contraction and heart rate, an increase in coronary perfusion pressure and diastolic tone, and a release of creatine kinase in the coronary effluent. Myocardial creatine kinase, superoxide dismutase activity, and glutathione content all fell. Perfusion of hearts with washed platelets provided significant protection from ischaemia-reperfusion related myocardial injury and dysfunction. The cardioprotective effects of platelets were attenuated when they were preincubated with the glutathione redox cycle inhibitors dehydroepiandros-terone, 1,3-bis (2-chloroethyl)-l-nitrosurea, or l-chloro-2,4-dinitrobenzene. Pretreatment of platelets with glutathione redox cycle inhibitors did not affect the platelet mediated preservation of myocardial superoxide dismutase activity. Conclusions: Platelet glutathione redox cycle contributes in part to the cardioprotective effects of platelets against ischaemia-reperfusion injury and dysfunction in the isolated rat heart. Cardiovascular Research 1994;28:1586-1593
Abstract 4990: Epidermal growth factor-induced expression of PTX3 regulates metastasis of head and neck squamous cell carcinoma
Authors: Ben-Kuen Chen, Shuo-Lun Wu, Jhih-Peng Tsai
Journal: Cancer Research (2014)

Abstract Overexpression of epidermal growth factor receptor (EGFR) and production of proinflammatroy cytokines are common in head and neck squamous cell carcinoma (HNSCC) and correlates with enhanced invasion and metastasis. However, molecular mechanisms associated with activation of EGFR and productions of cytokines in regulating metastasis of HNSCC remain poorly understood. Here, we identified PTX3 as a metastasis-promoting factor in HNSCC to regulate EGF-induced metastasis. We found that EGF induced the expression of PTX3, and was mediated through transcriptional activation, but not through mRNA stability. The involvement of Akt/NF-κB and AP-1 signaling pathways in the EGF-induced PTX3 gene expression was confirmed by knockdown of RelA and c-Jun, respectively. The expression of dominant negative IκB also repressed the activation of NF-κB and inhibited EGF-induced PTX3 expression. Furthermore, EGF increased the binding of NF-κB and c-Jun to the AP-1 binding site of the PTX3 promoter through the activation of the Akt/NF-κB pathway, which resulted in activating PTX3 promoter activity. In addition, EGF stimulated the secretion of PTX3 from cancer cells, resulting in enhancing cancer metastasis and the interaction between cancer cells and endothelial cells. EGF-enhanced metastasis-related molecules, such as fibronectin and MMP-9, and reduction of E-cadherin were reversed in PTX3 knockdown cells. These findings suggest that autocrine production of EGF-induced PTX3 regulates metastasis of HNSCC by mediating the expression levels of metastatic molecules fibronectin, MMP-9 and E-cadherin. The EGF-induced PTX3 could be a potential diagnostic marker and target for metastasis in the cancer therapy. Citation Format: Ben-Kuen Chen, Shuo-Lun Wu, Jhih-Peng Tsai. Epidermal growth factor-induced expression of PTX3 regulates metastasis of head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4990. doi:10.1158/1538-7445.AM2014-4990
Tuberculosis skin test, but not interferon-γ-releasing assays is affected by BCG vaccination in HIV patients
Authors: T. Wolf, U. Goetsch, G. Oremek, M. Bickel, P. Khaykin, A. Haberl, O. Bellinger, R. Gottschalk, H.R. Brodt, C. Stephan
Journal: Journal of Infection (2012)
Viral hepatitis and the E.S.R.
Authors: J Vahrman
Journal: BMJ (1971)

Background: Claudin-4, a component of the tight junction, plays an important role in tumorigenesis and metastasis of ovarian cancer, but its role in platinum resistance has not been elucidated. Materials and Methods: Claudin-4 expression in ovarian cancer cells was inhibited and the changes in cisplatin sensitivity were examined. Fluorescence-labeled cisplatin was used to examine whether inhibition of claudin-4 changed the cellular accumulation of cisplatin. Claudin-4 expression in ovarian cancer tissue resected from the patients surgically was evaluated immunohistochemically. Results: Suppression of claudin-4 resulted in a significant increase of cisplatin sensitivity and cellular accumulation of fluorescence-labeled cisplatin. Claudin-4 expression was significantly greater in ovarian cancer tissue from chemoresistant patients compared to chemosensitive patients. The overall survival was significantly shorter for claudin-4-positive than claudin-4-negative cases. Conclusion: These data suggest that claudin-4 contributes to platinum resistance in ovarian cancer and may be a potential target in the treatment of platinum-resistant tumors.
Carcinogenicity of chloroform.
Authors: M D Reuber
Journal: Environmental Health Perspectives (1979)

Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats.
Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab
Authors: Kimio Yonesaka, Kreshnik Zejnullahu, Isamu Okamoto, Taroh Satoh, Federico Cappuzzo, John Souglakos, Dalia Ercan, Andrew Rogers, Massimo Roncalli, Masayuki Takeda, Yasuhito Fujisaka, Juliet Philips, Toshio Shimizu, Osamu Maenishi, Yonggon Cho, Jason Sun, Annarita Destro, Koichi Taira, Koji Takeda, Takafumi Okabe, Jeffrey Swanson, Hiroyuki Itoh, Minoru Takada, Eugene Lifshits, Kiyotaka Okuno, Jeffrey A. Engelman, Ramesh A. Shivdasani, Kazuto Nishio, Masahiro Fukuoka, Marileila Varella-Garcia, Kazuhiko Nakagawa, Pasi A. Jänne
Journal: Science Translational Medicine (2011)

Cetuximab, an antibody directed against the epidermal growth factor receptor, is an effective clinical therapy for patients with colorectal, head and neck, and non-small cell lung cancer, particularly for those with KRAS and BRAF wild-type cancers. Treatment in all patients is limited eventually by the development of acquired resistance, but little is known about the underlying mechanism. Here, we show that activation of ERBB2 signaling in cell lines, either through ERBB2 amplification or through heregulin up-regulation, leads to persistent extracellular signal-regulated kinase 1/2 signaling and consequently to cetuximab resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal cancer patients who exhibit either de novo or acquired resistance to cetuximab-based therapy has ERBB2 amplification or high levels of circulating heregulin. Collectively, these findings identify two distinct resistance mechanisms, both of which promote aberrant ERBB2 signaling, that mediate cetuximab resistance. Moreover, these results suggest that ERBB2 inhibitors, in combination with cetuximab, represent a rational therapeutic strategy that should be assessed in patients with cetuximab-resistant cancers.
Abstract 5363: Aggregation rather than monoclonal expansion explains ovarian cancer spheroid formation
Authors: Zhiqing Huang, William J. Lowery, Andrew Berchuck, Susan K. Murphy
Journal: Cancer Research (2012)

Abstract Purpose: It is thought that a subpopulation of ovarian cancer cells possess stem cell like properties and are responsible for both the emergence of cancer and for subsequent chemoresistance and recurrence. A common approach used to enrich for cancer stems cells in vitro involves culture in selective media on low attachment plates resulting in non-attached multicellular spheres. Spheroids are present in ascites fluid of women with ovarian cancer, and may contain stem cells responsible for metastasis and recurrence. Our objective was to address whether spheroids are truly monoclonal in origin and arise from expansion of a single common progenitor cell. Procedures: We cultivated 5 ovarian cancer cell lines (DOV13, HEYC2, OVCAR2, OVCAR3, and PEO4) to confluence in monolayer cultures. The cell lines were chosen for their ability to form spheroids as well as variation in expression of the stem cell marker CD133 (OVCAR2, OVCAR3 CD133+, others negative). The cells were trypsinized to form single cell suspensions and plated at densities ranging from 100 to 5000 cells per plate in stem cell-selective media in ultra-low attachment culture dishes. A Zeiss Axio Observer microscope was used for time-lapse photography of the plated cells at 5-minute intervals over a 24-hour period. In addition, single cell suspensions were subjected to flow activated cell sorting to plate one cell in each well of 96-well Costar ultra-low cluster plates to monitor clonal formation of spheroids. Results: Cells were dissociated and plated under stem cell-selective conditions and 288 images of each cell line were recorded over 24 hours. The cells were found to begin to aggregate within two to four hours, regardless of cell numbers plated. By 24 hours post-plating, there was pronounced aggregation in 5/5 (100%) cell lines with formation of tightly compacted spheroid structures in 4/5 (80%) cell lines. Single cells in the 96-well plates showed no evidence of spheroid formation over a 14-day observation period. Conclusion: We observed spheroid formation in both CD133 positive and negative ovarian cancer cell lines. Formation occured due to cellular aggregation rather than clonal expansion from a single progenitor with stem cell properties. Although cellular aggregation may be relevant to ovarian cancer biology, these data suggest that spheroid formation should be viewed with caution if used as a proxy for monoclonal expansion of ovarian cancer stem cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5363. doi:1538-7445.AM2012-5363
Transient Postpartum Hypothyroidism: Fourteen Cases with Autoimmune Thyroiditis
Authors: NOBUYUKI AMINO
Journal: Annals of Internal Medicine (1977)

Twenty-five episodes of postpartum primary hypothyroidism were observed in 23 patients without thyroid hormone treatment: three were cases of irreversible hypothyroidism and the others were of transient hypothyroidism. The characteristics of transient postpartum hypothyroidism deduced by serial observations on 14 patients were [1] a high incidence of previous goiter; [2] thyroid enlargement at ½ to 4 months postpartum; [3] hypothyroidism at 3 to 5 months postpartum; [4] spontaneous recovery at 5 to 10 months postpartum; [5] high titers of antithyroid microsomal antibodies; and [6] persistence of small goiter. Transient postpartum hyperthyroidism before the occurrence of hypothyroidism and the recurrence of transient postpartum hypothyroidism were observed during two consecutive postpartum periods in two patients. Transient hypothyroidism was also observed in two patients after abortion. Fourteen of the 23 patients first noticed thyroid abnormality after delivery. These changes seem to be induced during the course of autoimmune thyroiditis by the immunologic changes occurring after delivery.
Culture and drug biotransformation capacity of adult human keratinocytes from post-mortem skin
Authors: B. HIREL, E. WATIER, C. CHESNE, M. PATOUX-PiBOUIN, A. GUILLODZO
Journal: British Journal of Dermatology (1996)

The aim of this study was to analyse viability, growth, differentiation and drug metabolic capacity of cultured human keratinocytes obtained from post-mortem skin. Epidermal cells were prepared from 1-day post-mortem paired sun-exposed (outer) and sun-protected (inner) sites of the upper arm, of donors aged 47-80 years. The percentage of viable cells obtained from post-mortem skin was only slightly lower than that usually obtained for keratinocytes isolated from fresh skin, and no alterations of epidermal markers were noted. Keratinocytes isolated post-mortem from non-exposed skin had a higher viability (78 versus 73%), and a more active proliferation, while their attachment rate, keratin composition, lipid synthesis capacity and transglutaminase activity levels were similar to those of epidermal cells obtained from the sun-exposed skin. Keratinocytes isolated from post-mortem skin expressed various phase I and II activities at levels similar to those obtained with keratinocytes isolated from fresh skin while drug metabolizing enzyme activities were consistently higher in sun-exposed compared to sun-protected cells. The results support the conclusion that skin collected post-mortem can represent an alternative source of viable and functional epidermal cells, and that the functional changes that occur in adult keratinocytes habitually exposed to the sun, affect much more strongly the drug metabolism capacity than the expression of differentiation markers.
A rectocolic hemangioma as the cause of rectal bleeding and treated with rubber-band ligation and sclerotherapy
Authors: S. Alberto, A. Martins, S. Pires, A. Figueiredo, J. de Deus
Journal: Endoscopy (2008)

We read with great interest the article by Zurakowski et al. [1] about the treatment of cavernous hemangiomas.
Methotrexate and triamterene---a potentially fatal combination?
Authors: R. RICHMOND, E. R MCRORIE, D. A OGDEN, C M. LAMBERT
Journal: Annals of the Rheumatic Diseases (1997)

A 57 year old woman had been treated for several years with diclofenac 150 mg/day, atenolol 50 mg/day, and triamterene/ hydrochlorthiazide 50/25 mg/day for rheumatoid arthritis (RA) and hypertension. Her doctor started treatment with methotrexate 5 mg/week for active RA. At the start of methotrexate treatment her full blood count was normal except for a haemoglobin of 10.1 g/dl. Renal and liver function were not checked. She weighed 68.5 kg. After one month her haemoglobin had fallen to 8.0 g/dl and her white cell count to 3.6 × 109/l and she developed mouth ulcers, dyspnoea, and easy bruising. She continued taking methotrexate, but after a month of these symptoms was admitted to hospital as an emergency.

On examination she was pale, tachypnoeic, and dehydrated with extensive mucosal ulceration. Investigations …
Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women.
Authors: H Burger, J Hailes, J Nelson, M Menelaus
Journal: BMJ (1987)

Infrared television pupillometry was performed on 34 insulin-treated diabetic patients and 55 healthy subjects. Sixteen of the diabetic patients had pupils that failed to dilate normally in darkness. The occurrence of a small pupil was associated with cardiac vagal dysfunction and somatic sensory loss. The small pupil was found to be supersensitive to the mydriatic effect of topical 2% phenylephrine but normally sensitive to 0.5% hydroxyamphetamine eyedrops. It is concluded that the failure of the pupil to dilate in darkness in some diabetic patients is due to neuropathy of the sympathetic innervation.
Endoscopic Hydrogen Peroxide Spray May Facilitate Localization of the Bleeding Site in Acute Upper Gastrointestinal Bleeding
Authors: D. C. Wu, C. Y. Lu, C. H. Lu, Y. C. Su, D. S. Perng, W. M. Wang, C. S. Liu, C. M. Jan
Journal: Endoscopy (1999)

A major problem encountered in the emergency endoscopic management of acute upper gastrointestinal (UGI) bleeding is poor localization of the bleeding site, which can be obscured by blood or clots. Traditional attempts to overcome this problem have been by physical methods, which have usually proved unsatisfactory. The aim of this prospective study was to show that hydrogen peroxide can be used as a dissolution agent, resulting in an alteration of the characteristics of blood clots and allowing a clearer visual field.Twenty patients with acute UGI bleeding (13 male, seven female) were included in the study. The suspected site of bleeding was initially sprayed with 200 ml of saline and then with 25-175 ml of 3 % H2O2. Pictures of the visual field were taken before and after irrigation with both saline and H2O2. These pictures were evaluated by three gastroenterologists and scored using the following visual clearance scoring system: -3, marked worsening of visual field; -2, moderate worsening; -1, slight worsening; 0, no change; +1, slight improvement; +2, moderate improvement; + 3, marked improvement. In cases of active oozing or spurting, after initial hemostasis was achieved the bleeding point was injected with pure ethanol or cauterized with a heater probe. In order to assess the safety of 3 % H2O2 endoscopic biopsies of the antrum and the duodenal bulb were performed before and 30 minutes after its use and examined by a pathologist.There was a significant improvement in the mean visual clearance score after irrigation with H2O2 compared to irrigation with saline alone (2.13 vs. 0.43, P<0.001). During endoscopic examination there were 19 patients with active oozing from the ulcer base covered by an adherent blood clot; 12 of these (63.1%) achieved initial hemostasis after H2O2 spraying. Eleven of 18 (61.1 %) patients complained of a mild epigastric burning sensation during H2O2 irrigation. There was no clinically significant change in the histology of the antrum and the duodenal bulb after H2O2 therapy.We concluded that H2O2 is a safe and effective way to clear the visual field, facilitating the localization of the bleeding site during emergency endoscopy for acute UGI bleeding, with only mild side effects. In some cases H2O2 therapy can also induce temporary hemostasis. We recommended the use of hydrogen peroxide to improve endoscopic visualization, especially in cases where an adherent blood clot covers the suspected bleeding site.
HLA-DR4 in ankylosing spondylitis with different patterns of joint involvement.
Authors: W Miehle, M Schattenkirchner, D Albert, M Bunge
Journal: Annals of the Rheumatic Diseases (1985)

Fifty patients with ankylosing spondylitis (AS) confined to the spine and sacroiliac joints were compared with 50 cases of AS complicated by various patterns of non-axial joint involvement. Radiological and clinical features were evaluated and HLA-DR4 typing was carried out. This antigen was found in 16% of 200 normal individuals in 18% of patients suffering from exclusively axial AS, and in 54% of patients with additional purely peripheral joint involvement (wrist, finger, ankle, toe). The possibility that HLA-DR4 represents a non-specific marker for peripheral arthritis in patients with ankylosing spondylitis is discussed.
Scintigraphic detection of carotid atherosclerosis with indium-111-labeled autologous platelets.
Authors: H H Davis, B A Siegel, L A Sherman, W A Heaton, T P Naidich, J H Joist, M J Welch
Journal: Circulation (1980)

Using autologous platelets labeled with indium-111-oxine, we studied the localization of platelets on arterial lesions by radionuclide scintigraphy in 34 patients with suspected cerebrovascular disease. The imaging results were compared with the findings of contrast angiography in 23 patients, 16 of whom were receiving antiplatelet and/or anticoagulant drugs during the platelet imaging study. Angiography demonstrated atherosclerotic lesions at 33 sites in the extracranial arteries of 16 of these patients. There was accumulation of 111In-platelets at 20 of these sites (61%) and at three other sites without definite angiographic abnormalities. Lesions with stenoses less than 50% were slightly more frequent than those with greater stenosis (68% vs 45%). The frequency of true-positive scintigraphic results was slightly higher in patients not treated with antithrombotic agents than in those on such drugs (70% vs 57%). Our results suggest that imaging with 111In-labeled autologous platelets may be useful for evaluating the pathophysiologic characteristics of atherosclerotic lesions in patients with cerebrovascular disease.
Endogenous Adenosine Is an Antiarrhythmic Agent
Authors: Jamie Beth Conti, Luiz Belardinelli, David B. Utterback, Anne B. Curtis
Journal: Circulation (1995)

Background Adenosine administered intravenously terminates supraventricular tachycardias (SVT) involving the AV node as part of the reentrant circuit. Dipyridamole increases interstitial myocardial levels of this nucleoside. This study was designed to determine whether intravenous dipyridamole increases coronary sinus plasma adenosine concentrations ([Ado]cs) in humans to levels sufficient to alter electrophysiological parameters and terminate SVT. Methods and Results A custom-designed catheter and syringe for sampling blood for measurement of [Ado]cs was placed in the coronary sinuses of 7 patients. [Ado]cs and refractory periods and conduction characteristics of the atrium and AV node were determined after autonomic blockade and dipyridamole infusion (5 μg · kg −1 · min −1 after a loading dose of 0.56 mg/kg). The atrial effective and functional refractory periods remained unchanged after dipyridamole infusion. In contrast, the AV nodal functional refractory period increased from 350±32 to 381±41 milliseconds ( P =.03); the Wenckebach cycle length also increased from 309±47 to 350±57 milliseconds ( P &lt;.0001). Coincident with these changes, [ADO]cs increased from 0.18±0.11 to 0.31±0.12 μmol/L ( P =.02). In another 10 patients with AV or AV nodal reentrant tachycardia, SVT was induced, and coronary sinus blood samples were drawn. Dipyridamole was infused, and coronary sinus blood samples were obtained after 15 minutes or coincident with termination of SVT. Mean [ADO]cs increased from 0.17±0.06 μmol/L during SVT to 0.38±0.21 μmol/L after dipyridamole ( P =.02). Mean tachycardia cycle length increased from 334±132 to 375±139 milliseconds ( P =.02); this effect was confined to the AV node, as demonstrated by an increase in AH interval from 171±144 to 214±140 milliseconds ( P =.003). SVT terminated with the infusion of dipyridamole in 4 of the 10 patients. Conclusions Administration of dipyridamole is associated with elevation of [ADO]cs, with coincident prolongation of the mean Wenckebach cycle length and AV nodal functional refractory period. During SVT, dipyridamole leads to prolongation of the AH interval and tachycardia cycle length and to an increase in [ADO]cs, with termination of SVT in four patients. These results support the hypothesis that adenosine may function as an endogenous antiarrhythmic metabolite.