37 research outputs found
Glucagon-Like Peptide-1 Modulates Neurally-Evoked Mucosal Chloride Secretion in Guinea Pig Small Intestine In Vitro.
Glucagon-like peptide-1 (GLP-1)
acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion
of insulin and to inhibit secretion of glucagon and gastric acid.
Involvement in mucosal secretory physiology has received negligible
attention. We aimed to study involvement of GLP-1 in mucosal
chloride secretion in the small intestine. Ussing chamber methods, in
concert with transmural electrical field stimulation (EFS), were used
to study actions on neurogenic chloride secretion. ELISA was used to
study GLP-1R effects on neural release of acetylcholine (ACh).
Intramural localization of GLP-1R was assessed with immunohistochemistry.
Application of GLP-1 to serosal or mucosal sides of
flat-sheet preparations in Ussing chambers did not change baseline
short-circuit current (Isc), which served as a marker for chloride
secretion. Transmural EFS evoked neurally mediated biphasic increases
in Isc that had an initial spike-like rising phase followed by a
sustained plateau-like phase. Blockade of the EFS-evoked responses
by tetrodotoxin indicated that the responses were neurally mediated.
Application of GLP-1 reduced the EFS-evoked biphasic responses in
a concentration-dependent manner. The GLP-1 receptor antagonist
exendin-(9 –39) suppressed this action of GLP-1. The GLP-1 inhibitory
action on EFS-evoked responses persisted in the presence of
nicotinic or vasoactive intestinal peptide receptor antagonists but not
in the presence of a muscarinic receptor antagonist. GLP-1 significantly
reduced EFS-evoked ACh release. In the submucosal plexus,
GLP-1R immunoreactivity (IR) was expressed by choline acetyltransferase-
IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons,
and vasoactive intestinal peptide-IR neurons. Our results suggest
that GLP-1R is expressed in guinea pig submucosal neurons and that
its activation leads to a decrease in neurally evoked chloride secretion
by suppressing release of ACh at neuroepithelial junctions in the
enteric neural networks that control secretomotor functions
Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro
Glucagon-like peptide-2 (GLP-2) is
an important neuroendocrine peptide in intestinal physiology. It influences
digestion, absorption, epithelial growth, motility, and blood
flow. We studied involvement of GLP-2 in intestinal mucosal secretory
behavior. Submucosal-mucosal preparations from guinea pig
ileum were mounted in Ussing chambers for measurement of shortcircuit
current (Isc) as a surrogate for chloride secretion. GLP-2 action
on neuronal release of acetylcholine was determined with ELISA.
Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was
studied with immunohistochemical methods. Application of GLP-2
(0.1–100 nM) to the serosal or mucosal side of the preparations
evoked no change in baseline Isc and did not alter transepithelial ionic
conductance. Transmural electrical field stimulation (EFS) evoked
characteristic biphasic increases in Isc, with an initially rapid rising
phase followed by a sustained phase. Application of GLP-2 reduced
the EFS-evoked biphasic responses in a concentration-dependent
manner. The GLP-2R antagonist GLP-2-(3-33) significantly reversed
suppression of the EFS-evoked responses by GLP-2. Tetrodotoxin,
scopolamine, and hexamethonium, but not vasoactive intestinal peptide
type 1 receptor (VPAC1) antagonist abolished or reduced to near
zero the EFS-evoked responses. GLP-2 suppressed EFS-evoked acetylcholine
release as measured by ELISA. Pretreatment with GLP-2-
(3-33) offset this action of GLP-2. In the submucosal plexus, GLP-2R
immunoreactivity (-IR) was expressed in choline acetyltransferase-IR
neurons, somatostatin-IR neurons, neuropeptide Y-IR neurons, and
vasoactive intestinal peptide-IR neurons. We conclude that submucosal
neurons in the guinea pig ileum express GLP-2R. Activation of
GLP-2R decreases neuronally evoked epithelial chloride secretion by
suppressing acetylcholine release from secretomotor neurons
Activation of T lymphocytes for the adoptive immunotherapy of cancer
Background: Adoptive immunotherapy of malignancy involves the passive transfer of antitumor-reactive cells into a host in order to mediate tumor regression. Based on animal models, the transfer of immune lymphoid cells can eradicate widely disseminated tumors and establish long-term systemic immunity. Critical for successful adoptive immunotherapy is the ability to isolate large numbers of immune cells. For clinical therapy, it will require the development of in vitro methods to promote the sensitization and propagation of tumor-reactive cells. However, this is formidable task since human cancers are postulated to be poorly immunogenic because of their spontaneous origins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41399/1/10434_2006_Article_BF02303568.pd
Ventricular dyssynchrony assessment with equilibrium radionuclide angiography phase analysis predicts outcome after cardiac resynchronization therapy
The value of hepatobiliary phase in EOB-MRI in predicting hypervascularization outcome of non-hypervascular hypointense lesions in high-risk patients for hepatocellular carcinoma
Immunological weapons against acute myeloid leukaemia
A better understanding of the biology of malignant cells and of the host immune system together with dramatic advances in technology have led to the design of innovative immune-mediated approaches to control neoplastic clones, including various haematological malignancies. One of the major problems with conventional cancer therapies is their inability to eradicate residual cancer cells that are resistant to therapy, hence immune intervention might improve the clinical outcome of patients. This mini-review will focus mainly on immunological approaches to the therapy of acute myeloid leukaemia (AML), a subset of a much larger family of leukaemias. Immune-mediated approaches ranging from allogeneic lymphocyte transplants to cytokine therapy, immune-gene therapy and vaccination by dendritic-cell-based vaccines will be discussed
Differential expression of cytokine transcripts in human epithelial ovarian carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour, tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour cell lines
T cell lines derived in low concentrations of recombinant IL-2 (rIL-2) from TIL of patients with epithelial ovarian carcinoma (EOC) often exhibit specific cytotoxicity against autologous tumour cells. However, the ability of T cells at the tumour site to respond to ovarian carcinoma cells may be affected by the production of cytokines by the various cell types present. Using reverse transcriptase-polymerase chain reaction (RT-PCR) we investigated cytokine transcripts in: (i) established EOC tumour cell lines; (ii) solid tumour specimens or peritoneal exudate cells (PEC) from ascites or peritoneal washings of patients with EOC; and (iii) CD4+ TCRαβ+ and CD8+ TCRαβ+ TIL-derived T cell lines developed in rIL-2. We have found that (i) established EOC tumour cell lines expressed transcripts for transforming growth factor-beta 2 (TGF-β2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-γ) (0/7) and rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13), and TGF-β2 (12/13), and less often, IFN-γ (3/13), whereas solid tumour specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF-β2 (4/8), and IL-10 (5/8), but not for IFN-γ (0/8); (iii) CD4+ TCRαβ+ T cell lines expressed transcripts for IFN-γ (4/4), IL-2 (4/4) and IL-10 (3/4), whereas CD8+ TCRαβ+ T cell lines expressed transcripts for IFN-γ (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines expressed TGF-β2 transcripts. The frequency of IL-2 and TGF-β2 transcripts in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4+ or CD8+ T cell lines expressing IFN-γ, IL-2 and IL-10 transcripts were derived in culture with rIL-2 from the TIL of specimens that did not necessarily express these cytokines in the absence of rIL-2. The frequency of cytokine transcripts in T cell lines compared with these same transcripts in the PEC was significantly higher for IFN-γ (P = 0.0005) and lower for TGF-β2 (P = 0.0001). An association was observed between the expression of cytokine transcripts in vivo or by TIL-derived cell lines and functions exhibited by either production of cytokines or in vitro cytotoxicity