tbuckley/cabot-search huggingface dataset:
Activation of phospholipase D is tightly coupled to the phagocytosis of Mycobacterium tuberculosis or opsonized zymosan by human macrophages.
Authors: D J Kusner, C F Hall, L S Schlesinger
Journal: The Journal of Experimental Medicine (1996)

Phagocytosis of Mycobacterium tuberculosis by human mononuclear phagocytes is mediated primarily by complement receptors (CRs) but the transmembrane signaling mechanisms that regulate phagocytosis of the bacterium are unknown. We have analyzed the activation of phospholipase D (PLD) during phagocytosis of the virulent Erdman and attenuated H37Ra strains of M. tuberculosis by human monocyte-derived macrophages (MDMs), radiolabeled with [3H]-lyso-phosphatidylcholine. Phagocytosis of either Erdman or H37Ra M. tuberculosis in the presence of autologous non-immune serum was associated with a 2.5-3-fold increase in phosphatidic acid (PA). Definitive evidence for activation of PLD by M. tuberculosis was provided by markedly increased generation of the PLD-specific product phosphatidylethanol (PEt) (9.9-fold increases in [3H]-PEt for both Erdman and H37Ra strains compared to control, P &amp;lt; 0.001, n = 12), in the presence of 0.5% ethanol. Phagocytosis of opsonized zymosan (OZ), which is also mediated by CRs, was similarly associated with activation of PLD (12.2-fold increase in PEt, P &amp;lt; 0.001, n = 12). The competitive PLD inhibitor 2,3-diphosphoglycerate (2,3-DPG) produced concentration-dependent inhibition of PLD activity stimulated by either M. tuberculosis (-78 +/- 8%) or OZ (-73 +/- 6%). Inhibition of PLD by 2,3-DPG was associated with concentration-dependent reductions in phagocytosis of M. tuberculosis (-74 +/- 4%) and OZ (-68 +/- 5%). Addition of purified PLD from Streptomyces chromofuscus to 2,3-DPG-treated macrophages restored phagocytosis of M. tuberculosis to control levels. Inhibition of M. tuberculosis- or OZ-stimulated PA generation by ethanol was associated with concentration-dependent reductions in phagocytosis of both particles. Incubation of MDMs with either Erdman or H37Ra M. tuberculosis, or OZ, resulted in rapid (onset 1 min) and sustained (60 min) increases in the tyrosine phosphorylation (Tyr-P) of multiple MDM proteins. Prominent Tyr-P was noted in proteins of 150, 95, 72, 56, and 42 kD. The protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A reduced M. tuberculosis-stimulated PLD activity by 66-84%. Inhibition of PLD activity by genistein or herbimycin A was associated with inhibition of phagocytosis of M. tuberculosis and OZ. These data demonstrate that PLD is activated during macrophage phagocytosis of M. tuberculosis or OZ, that PTKs are involved in this stimulation of PLD, and that the extent of phagocytosis of these particles is tightly coupled to activation of PLD.
Hypogonadism in chronic liver disease: impaired release of luteinising hormone.
Authors: P Bannister, T Handley, C Chapman, M S Losowsky
Journal: BMJ (1986)

Alcohol abuse leads to impotence, infertility, and feminisation. Patients with chronic alcoholism may have impaired hypothalamic-pituitary function. The release of luteinising hormone was investigated in men with alcoholic cirrhosis with and without hypogonadism and controls. Blood was sampled every 15 minutes for six or eight hours and luteinising hormone concentrations measured by radioimmunoassay. Data were analysed by iterative computerised analysis and spectral analysis to assess pulsatile release and the length of the cycle, respectively. Pulsatile release of luteinising hormone was shown in all the control subjects; in the men with alcoholic liver disease it was normal in those with subclinical primary testicular failure but absent or grossly attenuated in those with overt combined central and primary gonadal failure. The impaired release of luteinising hormone in the men with overt gonadal failure might be due to a hypothalamic defect.
Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.
Authors: H Gavras, H R Brunner, J H Laragh, E D Vaughan, M Koss, L J Cote, I Gavras
Journal: Circulation Research (1975)

The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.
Absence of a Direct Effect of Phosphate or 5'-AMP on the Contractile Proteins of Hog Carotid Arteries
Authors: JEREMIAH T. HERLIHY, RICHARD A. MURPHY
Journal: Circulation Research (1971)

Two to 4 m M 5'-adenosine monophosphate (AMP) caused a 28% inhibition of the ATPase activity of a crude "fibrillar" contractile protein preparation isolated from porcine vascular smooth muscle. This effect was absent in highly purified Ca 2+ -insensitive actomyosin extracted from carotid arteries as well as a Ca 2+ -dependent actomyosin preparation. Inorganic phosphate (P 1 ) caused no inhibition of ATPase activity in either actomyosin preparation, but 4 m M P 1 produced a slight depression in ATP hydrolysis of the crude fibrillar proteins. Superprecipitation of actomyosin remains unaffected by additions of either 4 m M P 1 or 4 m M AMP to the purified protein solutions. The effects of P 1 and AMP in combination were additive in the fibrillar system. However, the combination of the two agents had no effect on the ATPase activity of the two actomyosin preparations. These results indicate that concentrations of P 1 and AMP which might be produced under physiological conditions have no direct inhibitory action on the vascular smooth muscle actin-myosin interaction.
Early Depressive Symptoms in Cancer Patients Receiving Interleukin 2 and/or Interferon Alfa-2b Therapy
Authors: Lucile Capuron, Alain Ravaud, Robert Dantzer
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Depressive symptomatology is frequently associated with interleukin (IL)-2 and interferon alfa-2b (INFα-2b) therapy in cancer patients. The objective of the present study was to evaluate the depressive and anxiety symptoms induced by IL-2 and/or INFα-2b in cancer patients during the first days of cytokine immunotherapy. PATIENTS AND METHODS: The study included 48 patients with renal cell carcinoma or melanoma. Patients were treated either with subcutaneous IL-2, alone (n = 20) or in combination with INFα-2b (n = 6); or with INFα-2b alone, administered subcutaneously at a low dose (n = 8) or intravenously at a high dose (n = 14). Depressive symptoms were evaluated using the Montgomery and Asberg Depression Rating Scale (MADRS), and anxiety symptoms were evaluated using the Covi scale. Evaluations were performed just before initiation of treatment (day 1) and on days 3 and 5 of treatment. RESULTS: Patients treated with IL-2 alone or in association with INFα-2b had significantly higher MADRS scores after 5 days of cytokine therapy, and patients who received both cytokines had increased scores on day 3. In contrast, patients treated with INFα-2b alone did not have varying MADRS scores during the course of treatment. Cytokine therapy had no effect on anxiety, except in patients treated with IL-2 in combination with INFα-2b. In these patients, the enhancement in anxiety scores that was observed on day 5 was mainly attributable to increased somatic complaints. CONCLUSION: IL-2 and INFα-2b have differential effects on mood, and IL-2 therapy induces depressive symptoms early in treatment.
Functional Roles of Ca <sub>v</sub> 1.3(α <sub>1D</sub> ) Calcium Channels in Atria
Authors: Zhao Zhang, Yuxia He, Dipika Tuteja, Danyan Xu, Valeriy Timofeyev, Qian Zhang, Kathryn A. Glatter, Yanfang Xu, Hee-Sup Shin, Reginald Low, Nipavan Chiamvimonvat
Journal: Circulation (2005)

Background— Previous data suggest that L-type Ca 2+ channels containing the Ca v 1.3(α 1D ) subunit are expressed mainly in neurons and neuroendocrine cells, whereas those containing the Ca v 1.2(α 1C ) subunit are found in the brain, vascular smooth muscle, and cardiac tissue. However, our previous report as well as others have shown that Ca v 1.3 Ca 2+ channel–deficient mice ( Ca v 1.3 −/− ) demonstrate sinus bradycardia with a prolonged PR interval. In the present study, we extended our study to examine the role of the Ca v 1.3(α 1D ) Ca 2+ channel in the atria of Ca v 1.3 −/− mice. Methods and Results— We obtained new evidence to demonstrate that there is significant expression of Ca v 1.3 Ca 2+ channels predominantly in the atria compared with ventricular tissues. Whole-cell L-type Ca 2+ currents ( I Ca,L ) recorded from single, isolated atrial myocytes from Ca v 1.3 −/− mice showed a significant depolarizing shift in voltage-dependent activation. In contrast, there were no significant differences in the I Ca,L recorded from ventricular myocytes from wild-type and null mutant mice. We previously documented the hyperpolarizing shift in the voltage-dependent activation of Ca v 1.3 compared with Ca v 1.2 Ca 2+ channel subunits in a heterologous expression system. The lack of Ca v 1.3 Ca 2+ channels in null mutant mice would result in a depolarizing shift in the voltage-dependent activation of I Ca,L in atrial myocytes. In addition, the Ca v 1.3 -null mutant mice showed evidence of atrial arrhythmias, with inducible atrial flutter and fibrillation. We further confirmed the isoform-specific differential expression of Ca v 1.3 versus Ca v 1.2 by in situ hybridization and immunofluorescence confocal microscopy. Conclusions— Using gene-targeted deletion of the Ca v 1.3 Ca 2+ channel, we established the differential distribution of Ca v 1.3 Ca 2+ channels in atrial myocytes compared with ventricles. Our data represent the first report demonstrating important functional roles for Ca v 1.3 Ca 2+ channel in atrial tissues.
Correct Evaluation of the 7th Edition of the TNM Classification for Gastric Cancer?
Authors: Jingyu Deng, Han Liang
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: We read with great interest the article by Warneke et al, which reported that the seventh edition of the International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification for gastric cancer has not improved the assessment of patient prognosis compared with the fifth and sixth editions of the UICC/AJCC TNM classification. In contrast, other investigators demonstrated that the seventh edition of the TNM classification for gastric cancer was more suitable for predicting the prognosis of patients after surgery than the previous editions. After a careful analysis of this article’s results, we found several obvious defects which could give rise to bias in the conclusions and which should be addressed in detail. In comparison with patients with gastric cancer, patients with esophagogastric junction tumors could have a more distinctive prognosis, given that these patients were classified as having esophageal cancer according to the seventh edition of the UICC/AJCC TNM classification. In addition, the authors did not provide detailed information to show the number of dissected lymph nodes, which is considered a requirement for curative resection of gastric cancer and radical lymphadenectomy. Actually, 15 or more lymph nodes should be required to determine the accurate pN stage and inhibit stage migration. Lastly, we found that some patients described in this article as having advanced stage cancer only underwent palliative resection and had distant metastasis. These patients must have had a poorer prognosis and could not be evaluated precisely for TNM classification. Strictly speaking, patients with distant metastasis should be excluded from the study.
Management of Adults With Traumatic Brain Injuryedited by David B. Arciniegas, M.D., Nathan D. Zasler, M.D., Rodney D. Vanderploeg, Ph.D., and Michael S. Jaffee, M.D. Washington, DC, American Psychiatric Publishing, 2013, 587 pp., $79.00 (paper).
Authors: Brian S. Appleby
Journal: American Journal of Psychiatry (2013)
Inhibition of respiratory syncytial virus infection with intranasal siRNA nanoparticles targeting the viral NS1 gene
Authors: Weidong Zhang, Hong Yang, Xiaoyuan Kong, Subhra Mohapatra, Homero San Juan-Vergara, Gary Hellermann, Sumita Behera, Rajeswari Singam, Richard F Lockey, Shyam S Mohapatra
Journal: Nature Medicine (2004)
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Authors: Julie R. Brahmer, Scott S. Tykodi, Laura Q.M. Chow, Wen-Jen Hwu, Suzanne L. Topalian, Patrick Hwu, Charles G. Drake, Luis H. Camacho, John Kauh, Kunle Odunsi, Henry C. Pitot, Omid Hamid, Shailender Bhatia, Renato Martins, Keith Eaton, Shuming Chen, Theresa M. Salay, Suresh Alaparthy, Joseph F. Grosso, Alan J. Korman, Susan M. Parker, Shruti Agrawal, Stacie M. Goldberg, Drew M. Pardoll, Ashok Gupta, Jon M. Wigginton
Journal: New England Journal of Medicine (2012)

Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models.
In Memoriam
Authors: Claus Brun, Hugh E. deWardener, Priscilla S. Kincaid-Smith, George E. Schreiner, Gabriel Richet, Donald W. Seldin, Klaus Thurau, J. Stewart Cameron, Robert W. Schrier, Kiyoshi Kurokawa, Thomas E. Andreoli, Robert C. Atkins, Jan J. Weening
Journal: Journal of the American Society of Nephrology (2004)

<h3>Abstract</h3> Lipid-based carriers of the hydrophobic drug paclitaxel (PTX) are used in clinical trials as next-generation agents for cancer chemotherapy. Improving the loading capacity of these carriers requires enhanced PTX solubilization. We compared the solubility of PTX in cationic liposomes (CLs) with lipid tails containing one (oleoyl; C18:1 Δ<sup>9</sup>; DOTAP/DOPC) or two (linoleoyl; C18:2 Δ<sup>9</sup>; DLinTAP/DLinPC) <i>cis</i> double bonds with newly synthesized cationic DLinTAP (2,3-dilinoleoyloxypropyltrimethylammonium methylsufate). We used differential-interference-contrast microscopy to directly observe PTX crystal formation and generate kinetic phase diagrams representing the time-dependence of PTX solubility as a function of PTX content in the membrane. Replacing tails bearing one <i>cis</i> double bond (DO lipids) with those bearing two (DLin lipids) significantly increased PTX membrane solubility in CLs. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the membrane solubility limit which has been the focus of most previous fundamental studies and clinical trials) in DOTAP/DOPC CLs. The large increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX upon replacement of oleoyl by linoleoyl tails, rather than by the transition in membrane structure from lipid bilayers to inverse cylindrical micelles observed in small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against human prostate cancer (PC3) cells from measurements of the IC50 of PTX cytotoxicity was unaffected by changing the lipid tails, and toxicity of the CL carrier alone was negligible. Moreover, efficacy was approximately doubled against human melanoma (M21) cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. The findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading well over the typically used 3 mol% while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.
Immunohistochemical differences between hyaluronan- and non-hyaluronan-producing malignant mesothelioma
Authors: A Thylen, AM Levin-Jacobsen, A Hjerpe, G Martensson
Journal: European Respiratory Journal (1997)

In many but not all cases, malignant mesothelioma is associated with an elevated content of hyaluronan in pleural fluid. The hyaluronan-producing mesothelioma has not yet been immunohistochemically characterized; therefore, the purpose of this study was to compare the immunohistochemical reactivity patterns in relation to the ability of this tumour to produce hyaluronan. Pleural fluid samples from 33 patients with malignant mesothelioma were analysed for content hyaluronan using a quantitative high performance liquid chromatographic method. Biopsy specimens from the patients were studied immunohistochemically, using monoclonal antibodies against carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), a low molecular weight cytokeratin antigen (CAM 5.2) and vimentin. An elevated hyaluronan content, i.e. &gt; 100 mg.L-1, was noted in 23 patients (70%). There was no reactivity to the monoclonal antibody raised against CEA in any case. There was a significantly higher reactivity to EMA (p = 0.026), a higher reactivity to CAM 5.2 (p = 0.053) and a lower reactivity to vimentin (p = 0.057) in the hyaluronan-producing mesotheliomas as compared to those with normal levels of hyaluronan. Mesotheliomas that produced hyaluronan differed immunohistochemically from those that did not. The connection between the ability to produce different antigens and hyaluronan may relate to the degree of differentiation of the tumour. Both of these characteristics (immunophenotype and ability to produce hyaluronan) may, therefore, be of importance in studies concerning the prognosis and treatment of the malignant mesothelioma.
Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD Mice
Authors: Ł Krych, DS Nielsen, AK Hansen, CHF Hansen
Journal: Gut Microbes (2015)

Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3+ regulatory T cells, CD11b+ dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24–7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.
Immune recognition of self in immunity against cancer
Authors: Alan N. Houghton, José A. Guevara-Patiño
Journal: Journal of Clinical Investigation (2004)

Most antigens expressed by human cancer cells and recognized by host T cells and antibodies are nonmutated self antigens — molecules also expressed on the surface of normal cells. These self antigens are ineffective at triggering immune responses against cancer cells, which provides one explanation for the difficulties in trying to immunize against human cancer. A new study describes how tumors can avoid recognition by the immune system and how enhancing the affinity of the interaction between a self antigen and the MHC-I molecule may lead to cancer immunity.
Nicoumalone and Nalidixic Acid Interaction
Authors: ISRAEL POTASMAN
Journal: Annals of Internal Medicine (1980)

Letters1 April 1980Nicoumalone and Nalidixic Acid InteractionISRAEL POTASMAN, M.D., HARRY BASSAN, M.D.ISRAEL POTASMAN, M.D., HARRY BASSAN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-92-4-571_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A 65-year-old woman suffering from hypothyroidism and ischemic heart disease was admitted with hemoptysis and breathlessness found to be due to pulmonary embolism. Treatment was commenced with heparin and nicoumalone (a warfarin derivative). Within the first 4 days she received a total of 32 mg of nicoumalone, and satisfactory levels of prothrombin time were achieved. On the fifth day the prothrombin time was 26 s (control, 9.7 s). On the following day, proven urinary tract infection necessitated the administration of nalidixic acid. The drug was given in a daily dose of 1 g.Quite unexpectedly a further...References1. HOFFBRAND B. Interaction of nalidixic acid and warfarin. Br Med J. 1974;2:666. Letter. CrossrefMedlineGoogle Scholar2. SELLERS E and KOCH-WESER J. Displacement of warfarin from human albumin by diazoxide and ethacrynic, mefenamic, and nalidixic acids. Clin Pharmacol Ther. 1970;11:524-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ISRAEL POTASMAN, M.D.; HARRY BASSAN, M.D.Affiliations: Department of Internal Medicine B Rothschild University Hospital Haifa, Israel. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byINTERACTIONS OF WARFARINInteraction Between Nalidixic Acid and WarfarinJONATHAN LEOR, M.D., DAVID LEVARTOWSKY, M.D., CHARLOTTE SHARON, M.D.Absence of interaction between ofloxacin and phenprocoumonAntimicrobials and Haemostasis 1 April 1980Volume 92, Issue 4Page: 571-571KeywordsCardiovascular therapyDrugsDyspneaHeparinHypothyroidismProthrombin timePulmonary embolism ePublished: 1 December 2008 Issue Published: 1 April 1980 PDF downloadLoading ...