tbuckley/cabot-search huggingface dataset:
CX3CR1/CX3CL1 axis negatively controls glioma cell invasion and is modulated by transforming growth factor-beta1
Authors: Giuseppe Sciumè, Alessandra Soriani, Mario Piccoli, Luigi Frati, Angela Santoni, Giovanni Bernardini
Journal: Neuro-Oncology (2010)

The chemokine CX3CL1 is constitutively expressed in the central nervous system by neurons and astrocytes controlling neuronal survival and neurotransmission. In this work, we analyzed the expression and function of the chemokine CX3CL1 and its receptor, CX3CR1, by human glioma cells. We show that both molecules are expressed on the tumor cell plasma membrane and that soluble CX3CL1 accumulates in the culture supernatants, indicating that the chemokine is constitutively released. We found that CX3CR1 is functional, as all the cell lines adhered to immobilized recombinant CX3CL1 and migrated in response to the soluble form of this chemokine. In addition, the blockade of endogenous CX3CL1 function by means of a neutralizing monoclonal antibody markedly delayed tumor cell aggregation and increased their invasiveness. We also show that CX3CL1 expression is potently modulated by the transforming growth factor-beta1 (TGF-beta1), a key regulator of glioma cell invasiveness. Indeed, both the treatment of glioma cells with recombinant TGF-beta1 and the inhibition of its endogenous expression by siRNA showed that TGF-beta1 decreases CX3CL1 mRNA and protein expression. Overall, our results indicate that endogenously expressed CX3CL1 negatively regulates glioma invasion likely by promoting tumor cell aggregation, and that TGF-beta1 inhibition of CX3CL1 expression might contribute to glioma cell invasive properties.
Increased Leukotriene B<sub>4</sub> and Interleukin-6 in Exhaled Breath Condensate in Cystic Fibrosis
Authors: Giovanna E. Carpagnano, Peter J. Barnes, Duncan M. Geddes, Margaret E. Hodson, Sergei A. Kharitonov
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Chronic neutrophilic airway inflammation is an important feature of cystic fibrosis (CF). Noninvasive inflammatory markers may be useful in monitoring CF. Leukotriene B4 (LTB4) and interleukin (IL)-6 are inflammatory mediators that are increased in chronic neutrophilic inflammation. The aim of this study was to assess whether LTB4 and IL-6 were increased in exhaled breath condensate of CF patients and whether they could be used to monitor inflammation. Twenty patients with CF (13 males, age of 28 ± 9 years) were recruited together with 15 age-matched healthy subjects (8 males, age 35 ± 7 years). LTB4 and IL-6 levels were markedly elevated in patients with acute exacerbations (28.8 ± 4.3 and 8.7 ± 0.4 pg/ml) compared with control subjects (6.8 ± 0.7 and 2.6 ± 0.1 pg/ml, p < 0.0001). We also observed a decrease of exhaled LTB4 and IL-6 concentrations after antibiotic treatment in six patients who were followed until clinically stable (31.1 ± 4.4 and 9.5 ± 0.4 pg/ml vs. 18.8 ± 0.8 and 6.4 ± 0.2 pg/ml, respectively) and an increase in 15 CF patients infected with Pseudomonas aeruginosa (34.3 ± 5.0 and 9.3 ± 0.3 pg/m) compared with those infected with other bacteria (18.3 ± 0.7 and 6.9 ± 0.5 pg/ml). These findings suggest that LTB4 and IL-6 levels are increased in exhaled breath condensate of patients with CF during exacerbation and could be used to monitor airway inflammation in these patients.
Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.
Authors: A P Harris, R C Koehler, C A Gleason, M D Jones, R J Traystman
Journal: Circulation Research (1989)

Fetal head compression during normal labor can increase intracranial pressure (ICP). We studied the cerebral and peripheral blood flow responses to ICP elevation in utero in chronically catheterized fetal sheep using the radiolabeled microsphere technique. ICP was elevated, stepwise, in increments of 6 +/- 1 mm Hg by infusion of artificial cerebrospinal fluid into a lateral ventricle. When ICP was raised to within 28 mm Hg of baseline mean arterial blood pressure (i.e., ICP above 22 mm Hg), arterial pressure began to increase. Above this ICP level, up to 41 mm Hg, mean cerebral perfusion pressure was maintained by equivalent increases in arterial pressure. Cerebral blood flow and O2 uptake at the highest ICP levels were not different from baseline values. Changes in peripheral organ blood flow were graded according to the level of ICP. At the highest level (ICP = 41 mm Hg), renal, gastrointestinal, and skin blood flow decreased by 68%, 69%, and 65%, respectively. Myocardial and adrenal blood flow doubled, whereas heart rate and cardiac output were unchanged. Placental blood flow increased in proportion to arterial pressure. Arterial plasma epinephrine, norepinephrine and arginine vasopressin increased by nearly two orders of magnitude. Therefore, as ICP approaches baseline mean arterial pressure, fetal lambs are capable of sustaining cerebral perfusion by initiating profound visceral vasoconstriction without curtailing placental blood flow. Since cerebral O2 uptake was maintained, there is no evidence that stimulation of the peripheral response requires pronounced cerebral ischemia. This highly developed Cushing response may be important for ensuring cerebral viability when the fetal head is compressed during parturition.
Hemodynamic effects of exogenous and endogenous vasopressin at low plasma concentrations in conscious dogs.
Authors: J P Montani, J F Liard, J Schoun, J Möhring
Journal: Circulation Research (1980)

The possibility that vasopressin plays a role in cardiovascular control arouses increasing interest. We studied in unanesthetized dogs the hemodynamic consequences of 1-hour vasopressin infusions that modified plasma concentrations over a range similar to that found in physiological situations. We also examined the cardiovascular events following the stimulation of endogenous vasopressin release by an increase in plasma osmolality. In dogs with baroreceptor reflexes intact, vasopressin infusions which increased plasma vasopressin concentration by 2-20 fmol/ml did not affect mean arterial pressure. However, they significantly decreased cardiac ouput (measured by an electromagnetic flowmeter) and increased total peripheral resistance. After baroreceptor denervation, vasopressin infusion rates as low as 40 fmol/kg per min (0.017 microU/kg per min) led to an increase in mean arterial pressure. Cardiac output was unaffected until much higher infusion rates were used. Changes in total peripheral resistance were very similar to those calculated in dogs with intact baroreceptors. The release of vasopressin following infusions of hypertonic solutions either intravenously or into a carotid artery induced detectable hemodynamic changes which appeared in many respects similar to those following low infusion rates of vasopressin. We conclude that physiological plasma concentrations of vasopressin have hemodynamic effects even though they do not normally modify arterial pressure, presumably because of some particular interaction of vasopressin with the baroreceptor reflex.
The presence of neutrophils in human cutaneous ultraviolet-B inflammation
Authors: J.L.M. HAWK, G.M. MURPHY, C.A. HOLDEN
Journal: British Journal of Dermatology (1988)

Journal Article The presence of neutrophils in human cutaneous ultraviolet‐B inflammation Get access J.L.M. HAWK, J.L.M. HAWK Department of Photobiology, Institute of Dermatology, St. Thomas'Hospital, London SE1 7EH, U.K. Dr J.L.M.Hawk. Search for other works by this author on: Oxford Academic Google Scholar G.M. MURPHY, G.M. MURPHY Department of Photobiology, Institute of Dermatology, St. Thomas'Hospital, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.A. HOLDEN C.A. HOLDEN Department of Photobiology, Institute of Dermatology, St. Thomas'Hospital, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 1, 1 January 1988, Pages 27–30, https://doi.org/10.1111/j.1365-2133.1988.tb01746.x Published: 01 January 1988
Overexpression of tumour necrosis factor-alpha-converting enzyme in psoriasis
Authors: M. Kawaguchi, Y. Mitsuhashi, S. Kondo
Journal: British Journal of Dermatology (2005)

Journal Article Overexpression of tumour necrosis factor‐α‐converting enzyme in psoriasis Get access M. Kawaguchi, M. Kawaguchi Department of Dermatology, Yamagata University School of Medicine, 2‐2‐2 Iida‐Nishi, Yamagata 990‐9585, Japan Masakazu Kawaguchi. E‐mail: kawaguch@med.id.yamagata‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Mitsuhashi, Y. Mitsuhashi Department of Dermatology, Yamagata University School of Medicine, 2‐2‐2 Iida‐Nishi, Yamagata 990‐9585, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Kondo S. Kondo Department of Dermatology, Yamagata University School of Medicine, 2‐2‐2 Iida‐Nishi, Yamagata 990‐9585, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 5, 1 May 2005, Pages 915–919, https://doi.org/10.1111/j.1365-2133.2005.06440.x Published: 01 May 2005 Article history Accepted: 05 August 2004 Published: 01 May 2005
United airways: the impact of chronic rhinosinusitis and nasal polyps in bronchiectasic patient’s quality of life
Authors: J. M. Guilemany, J. Angrill, I. Alobid, S. Centellas, E. Prades, J. Roca, L. Pujols, M. Bernal‐Sprekelsen, C. Picado, J. Mullol
Journal: Allergy (2009)

Background: The nose and the bronchi belong, in anatomical and physiopathological terms, to the concept of united airways. Associations between upper and lower airways diseases have been demonstrated in allergic rhinitis and asthma, nasal polyposis (NP) and asthma, chronic rhinosinusitis (CRS) and chronic obstructive pulmonary disease, and more recently CRS/NP and bronchiectasis (BQ). Objective: To evaluate the impact of CRS on quality of life (QoL) of patients with BQ, and to correlate these findings with the pulmonary status, nasal symptoms, and general health status. Methods: In a prospective study, patients with BQ ( n = 80) were evaluated for CRS and NP using EP 3 OS criteria, and severity of BQ using chest high resolution computed tomography (HRCT)‐scan. Quality of life was assessed in all patients by using specific [Sinonasal Outcome Test‐20 (SNOT‐20), St George Respiratory Questionnaire (SGRQ)], and generic (Short Form‐36; SF‐36) questionnaires. Results: Using SNOT‐20, patients with CRS had worse QoL (2.1 ± 0.1; P &lt; 0.001) than patients without CRS (0.4 ± 0.06). Using SGRQ total score, patients with CRS had worse QoL (43.7 ± 2.2; P &lt; 0.001) than patients without CRS (24.7 ± 2.5). Using SF‐36, patients with CRS had worse QoL, both in the physical summary (64 ± 3.4; P &lt; 0.05) and the mental summary (65.5 ± 4.7; P &lt; 0.05), than patients without CRS (physical summary [PS]: 76.2 ± 3.3; mental summary [MS]: 78.3 ± 5.3, respectively). Sinonasal Outcome Test‐20 was correlated with SGRQ total score ( r = 0.72; P &lt; 0.01), and SF‐36 physical summary ( r = −0.63; P &lt; 0.01). St George Respiratory Questionnaire was correlated with SF‐36 on physical summary ( r = −0.58; P &lt; 0.05) and with forced expiratory volume in 1 s ( r = −0.41; P &lt; 0.05). Conclusion: These results suggested that CRS, measured by both specific and generic questionnaires, has a considerable impact on the QoL of patients with BQ.
Phase I and Pharmacokinetic Study of Bortezomib in Combination with Idarubicin and Cytarabine in Patients with Acute Myelogenous Leukemia
Authors: Eyal C. Attar, Daniel J. DeAngelo, Jeffrey G. Supko, Ferdinando D'Amato, David Zahrieh, Andres Sirulnik, Martha Wadleigh, Karen K. Ballen, Steve McAfee, Kenneth B. Miller, James Levine, Ilene Galinsky, Elizabeth G. Trehu, David Schenkein, Donna Neuberg, Richard M. Stone, Philip C. Amrein
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Proteasome inhibition results in cytotoxicity to the leukemia stem cell in vitro. We conducted this phase I study to determine if the proteasome inhibitor bortezomib could be safely added to induction chemotherapy in patients with acute myelogenous leukemia (AML). Experimental Design: Bortezomib was given on days 1, 4, 8, and 11 at doses of 0.7, 1.0, 1.3, or 1.5 mg/m2 with idarubicin 12 mg/m2 on days 1 to 3 and cytarabine 100 mg/m2/day on days 1 to 7. Results: A total of 31 patients were enrolled. The median age was 62 years, and 16 patients were male. Nine patients had relapsed AML (ages, 18-59 years, n = 4 and ≥60 years, n = 5). There were 22 patients of ≥60 years with previously untreated AML (eight with prior myelodysplasia/myeloproliferative disorder or cytotoxic therapy). All doses of bortezomib, up to and including 1.5 mg/m2, were tolerable. Nonhematologic grade 3 or greater toxicities included 12 hypoxia (38%; 11 were grade 3), 4 hyperbilirubinemia (13%), and 6 elevated aspartate aminotransferase (19%). Overall, 19 patients (61%) achieved complete remission (CR) and three had CR with incomplete platelet recovery. Pharmacokinetic studies revealed that the total body clearance of bortezomib decreased significantly (P &amp;lt; 0.01, N = 26) between the first (mean ± SD, 41.9 ± 17.1 L/h/m2) and third (18.4 ± 7.0 L/h/m2) doses. Increased bone marrow expression of CD74 was associated with CR. Conclusions: The combination of bortezomib, idarubicin, and cytarabine showed a good safety profile. The recommended dose of bortezomib for phase II studies with idarubicin and cytarabine is 1.5 mg/m2.
Docetaxel and cisplatin combination chemotherapy in advanced carcinoma of the urothelium: A multicenter phase II study of the Hellenic Cooperative Oncology Group
Authors: M.A. Dimopoulos, C. Bakoyannis, V. Georgoulias, C. Papadimitriou, L.A. Moulopoulos, C. Deliveliotis, A. Karayannis, I. Varkarakis, G. Aravantinos, A. Zervas, D. Pantazopoulos, G. Fountzilas, A. Bamias, Z. Kyriakakis, A. Anagnostopoulos, A. Giannopoulos, P. Kosmidis
Journal: Annals of Oncology (1999)
Right atrial pressure-volume relationships in tricuspid regurgitation.
Authors: M J Miller, R G McKay, J J Ferguson, P Sahagian, S Nakao, P C Come, W Grossman
Journal: Circulation (1986)

Pressure-volume relationships in the right atrium were examined before and after the creation of acute experimental tricuspid regurgitation in pigs. A 1.3 kHz multielectrode impedance catheter with a measuring current of 4 mA was used to determine instantaneous right atrial pressure and relative blood volume; right atrial dimension was assessed simultaneously with ultrasonic crystals attached to the atrial walls. Impedance volume waveforms and ultrasonic crystal dimensions closely paralleled each other at baseline and after the induction of tricuspid regurgitation. The normal right atrial pressure-volume plot exhibited a figure-of-eight configuration, with an "a-loop" and a "v-loop" corresponding to the a-wave and v-wave of the right atrial pressure tracing. With severe tricuspid regurgitation, atrial pump function was abolished, and the pressure-volume plot exhibited a single clockwise loop, consistent with complete ventricularization of the right atrium. Intermediate degrees of tricuspid regurgitation preserved the figure-of-eight loop, but the size of both the a-loop and the v-loop were increased, consistent with a Starling-type load imposed on the atrium by the regurgitant blood volume. Increased right ventricular afterload mediated by constriction of the pulmonary artery and infusion of methoxamine reversibly converted the right atrial pressure-volume loop from that of mild to that of severe tricuspid regurgitation. Alternatively, constriction of the inferior vena cava and infusion of nitroprusside changed the right atrial pressure-volume loop from that of a severe pattern of tricuspid regurgitation to a less severe type of pattern. Infusion of dobutamine increased the size of the a-loop relative to the v-loop both at baseline and after induction of tricuspid regurgitation. We conclude that tricuspid regurgitation induces changes in right atrial mechanics that can be detected and quantified with an impedance catheter.
Dominant-Negative Activator Protein 1 (TAM67) Targets Cyclooxygenase-2 and Osteopontin under Conditions in which It Specifically Inhibits Tumorigenesis
Authors: Connie P. Matthews, Alysia M. Birkholz, Alyson R. Baker, Christine M. Perella, George R. Beck, Matthew R. Young, Nancy H. Colburn
Journal: Cancer Research (2007)

Abstract Activation of activator protein 1 (AP-1) and nuclear factor κB (NFκB)–dependent transcription is required for tumor promotion in cell culture models and transgenic mice. Dominant-negative c-Jun (TAM67) blocks AP-1 activation by dimerizing with Jun or Fos family proteins and blocks NFκB activation by interacting with NFκB p65. Two-stage [7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)] skin carcinogenesis experiments in a model relevant to human cancer risk, transgenic mice expressing human papillomavirus 16 E7 oncogene (K14-HPV16-E7), show E7-enhanced tumor promotion. A cross to K14-TAM67–expressing mice results in dramatic inhibition of tumor promoter–induced AP-1 luciferase reporter activation and papillomagenesis. Epithelial specific TAM67 expression inhibits tumorigenesis without affecting TPA- or E7-induced hyperproliferation of the skin. Thus, the mouse model enriches for TAM67 targets relevant to tumorigenesis rather than to general cell proliferation or hyperplasia, implicating a subset of AP-1– and/or NFκB-dependent genes. The aim of the present study was to identify target genes responsible for TAM67 inhibition of DMBA-TPA–induced tumorigenesis. Microarray expression analysis of epidermal tissues revealed small sets of genes in which expression is both up-regulated by tumor promoter and down-regulated by TAM67. Among these, cyclooxygenase-2 (Cox-2/Ptgs2) and osteopontin (Opn/Spp1) are known to be functionally significant in driving carcinogenesis. Results identify both Cox-2 and Opn as transcriptional targets of TAM67 with CRE, but not NFκB sites important in the Cox-2 promoter and an AP-1 site important in the Opn promoter. [Cancer Res 2007;67(6):2430–8]
A common idiotype on SJL and C57BL/6 anti-(4-hydroxy-3-nitrophenyl) acetyl antibodies and its relationship with lambda chain production.
Authors: S T Ju, K Karjalainen, M E Dorf
Journal: The Journal of Experimental Medicine (1981)

Hybridoma cell lines secreting antibodies specific to (3-nitro-4-hydroxyphenyl) acetyl (NP) were generated by fusion of NP-immunized SJL spleen cells with the SP2/0 cell line. One hybridoma (N-hybridoma) anti-NP antibody (mu, lambda2) was found to partially inhibit (35-40%) the binding of the predominant idiotype in primary C57BL/6 anti-NP antibodies (NPb). Iodinated hybridoma antibody could be completely bound with anti-idiotypic antiserum made against either specifically purified C57BL/6 anti-NP antibodies, SJL anti-NP antibodies, or N-hybridoma antibody. The idiotypic specificities defined with anti-idiotypic antiserum made against N-hybridoma antibody were termed NP-1 idiotype. Strain distribution and genetic mapping studies indicate that the gene(s) controlling the production of NP-1 idiotype is closely associated with Igh-1b and Igh-1e alleles and mapped within the same chromosomal segment that controls the synthesis of NPb idiotype. However, unlike NPb idiotype, the expression of NP-1 idiotype is not influenced by the gene(s) that control lambda1 chain synthesis. Thus, SJL mice that produce low or undetectable levels of NPb idiotype due to a defect in lambda1 chain production express high levels of NP-1 idiotype. Specifically purified C57BL/6 and SJL anti-NP antibodies fully express NP-1 idiotype, the level of which correlates with the level of lambda2 chain-bearing molecules. Nonetheless, further experiments indicate that lambda1-bearing anti-NP antibodies can express extremely weak NP-1 idiotypic cross-reactivity.
SYNERGY DURING IN VITRO CYTOTOXIC ALLOGRAFT RESPONSES
Authors: Hermann Wagner
Journal: The Journal of Experimental Medicine (1973)

A mouse in vitro allograft system was used to evaluate the concept of T-T interaction in T cell-mediated cellular immunity. In analyzing the responsiveness of thymus-processed lymphocytes as obtained from different tissues, a heretogeneity within T cells was found in regard to their capacity to be immunized in vitro against transplantation antigens. Recirculating T cells were 10-20-fold superior to thymocytes, splenic T cells being intermediate. When few (1.5 x 10(6)) peripheral T cells, in numbers too small to yield good cytotoxic responses, were mixed with 14 x 10(6) thymocytes and the cell mixture immunized in vitro against cell-bound alloantigens, cytotoxic activity was generated exceeding about 10-20-fold the values that could be explained by a pure additive effect. Synergy occurred also in a mixture of responder T cells derived from CBA (H-2(k)) and AKR (H-2(k)) mice. Thus AKR anti-phi C3H serum could be used for discriminating between thymus-derived and peripheral T cell-derived cytotoxic lymphocytes (CL). Cytotoxic activity produced during the synergistic interaction between thymocytes and peripheral T cells was about 70% T cell derived, the remainder being thymus derived. The synoptic interpretation of this finding and "limiting dilution" experiments of the responder cells suggested strongly that peripheral T cells provide the major source for precursor cells of CL, thymocytes acting mainly as helper (amplifier) cells.
Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension.
Authors: B I Levy, J B Michel, J L Salzmann, M Azizi, P Poitevin, M Safar, J P Camilleri
Journal: Circulation Research (1988)

The effect of hypertension and of therapy by converting enzyme inhibitor (S 9490-3, perindopril) on the function and structure of large arteries has been studied in two-kidney, one-clip Goldblatt hypertensive rats. After one month without treatment, clipped hypertensive rats (n = 24) and sham-operated rats (n = 24) were randomly allocated to treatment by S 9490, 1 mg/kg once a day (n = 24) or to placebo (n = 24) and pursued for 4 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity measured by Döppler, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were recorded in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Morphological parameters of the aortic media, including medial thickness, nucleus density, and cross sectional area and relative density in proteins of interstitial matrix, were recorded by an automated morphometrical system. Hypertension was associated with an increase in characteristic impedance of the aorta and a decrease in compliance of the arterial system. Treatment with converting enzyme inhibitors completely reversed these in vivo markers of the rigidity of large arteries. Hypertension was associated with a shift of the passive pressure-volume relation in the carotid. Treatment with converting enzyme inhibitors normalized the carotid pressure-volume relation, whereas poisoning smooth muscle cells induced a disappearance of the curve differences between hypertensive and normotensive animals. Morphometric analysis of aortic walls permits us to report this functional change to structural modification of the arterial wall. Aortic media thickness was increased by hypertension; this phenomenon was reversed by treatment. Modification of aortic thickness was due to hypertrophy of smooth muscle cells with parallel modifications of absolute amount of collagen, whereas absolute amount of elastin did not change in this early phase of renovascular hypertension in young rats. Treatment with converting enzyme inhibitors reversed the thickness of aortic media without regression of the increase in absolute amount of collagen content whereas absolute amount of elastin content did not change.