Search results for "TYR"
showing 10 items of 2017 documents
VIP-containing deep short-axon cells of the olfactory bulb innervate interneurons different from granule cells
2003
This study investigates the targets of the population of vasoactive intestinal polypeptide (VIP)-containing deep short-axon cells of the rat olfactory bulb (OB), combining single- and double-immunocytochemical approaches under light and electron microscopy. It has been assumed that deep short-axon cells innervate granule cells in the mammalian OB, but their synaptic connectivity has not been demonstrated to date. Our results indicate that, instead of the accepted scheme of the bulbar circuitry, VIP-containing deep short-axon cells are gamma-aminobutyric acid (GABA)ergic interneurons specialized in the selective innervation of other GABAergic deep short-axon cells. Their axons contact with t…
Dibutyryl cyclic AMP and adrenaline increase contractile force and 45Ca uptake in mammalian cardiac muscle
1973
The effects of dibutyryl cyclic AMP (DB-AMP; 10−3M) and adrenaline (2.2×10−6 M) on contractile force, 45Ca uptake, and total myocardial Ca concentration were investigated in electrically driven left auricles isolated from rat hearts. The experiments were performed at an extracellular Ca concentration of 0.45 mM and at low frequency of stimulation (15 beats/min). 45Ca exposure was 5 min. Under the conditions used, both drugs increased contractile force and enhanced 45Ca uptake (expressed as relative specific activity) by about 30% (DB-AMP) and 40% (adrenaline), respectively. Thus, the results provide evidence that the effects of adrenaline on 45Ca uptake in mammalian cardiac muscle can be mi…
Calcium/calmodulin-dependent protein kinases in the carotid body: an immunohistochemical study
2012
We determined the presence of Ca(2+)/calmodulin-dependent protein kinases (CaMKs), a family of multifunctional proteins engaged in Ca(2+)-linked signaling, in carotid body chemoreceptor cells which are critical for the hypoxia-sensing. Carotid bodies were dissected from anesthetized normoxic adult Wistar rats and were double stained for individual CaMKs and for tyrosine hydroxylase (TH), a marker of chemoreceptor cells. Immunofluorescence was examined by confocal laser scanning microscopy. We found that CaMKI and CaMKII were expressed in chemoreceptor cells, but their distribution and intensity varied. CaMKI immunoreactivity was distributed throughout the cytoplasm, whereas that of CaMKII w…
Purification and characterization of the ?-β-hydroxybutyrate dehydrogenase from dromedary liver mitochondria
2001
Abstract d -β-Hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a membrane enzyme, has been purified to homogeneity from dromedary ( Camelus dromedarius ) liver mitochondria. Our new purification method consisted of the solubilization of mitochondrial membranes by Triton X 100 and purification of BDH by two steps: DEAE-Sephacel and Phenyl-Sepharose. The molecular mass of the enzyme subunit size was 67 kDa. The purified enzyme is recognized by anti rat liver mitochondrial BDH antibodies. Furthermore, BDH activity was absolutely dependent upon phospholipids. BDH is also characterized by specific enzymatic parameters: an optimum pH of approximately 8 for the oxidation reaction, and approximat…
Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological c…
2022
Abstract Background The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. Patients and methods The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates…
Isoprenylhydroquinone glucoside: a new non-antioxidant inhibitor of peroxynitrite-mediated tyrosine nitration
2004
Abstract Three hydroquinone glucosides and four caffeoylquinic esters were examined for their effect on tyrosine nitration, as well as on the oxidation of dihydrorhodamine (DHR) 123 and cytochrome c 2+ induced by peroxynitrite. All these phenolics, which had previously been characterized as the active principles of the plant Phagnalon rupestre , were fairly active in preventing the oxidation of DHR 123, though inefficient in the cytochrome c test. While their antioxidant potency is associated with the presence of a caffeoyl moiety, not so an obvious chemical character was correlated to a greater activity against nitration of tyrosine. Here, the highest potency corresponded to 2-isoprenylhyd…
Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by …
2013
The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in…
Heterogeneous response to differentiation induction with different polar compounds in a clonal rat rhabdomyosarcoma cell line (BA-HAN-1C)
1989
The clonal rat rhabdomyosarcoma cell line BA-HAN-1C was tested for its susceptibility to differentiation induction with different polar compounds. This cell line is composed of proliferating mononuclear tumour cells, some of which spontaneously fuse to form terminally differentiated postmitotic myotube-like giant cells. Exposure of BA-HAN-1C cells to dimethylsulphoxide (DMSO), hexamethylene bisacetamide (HMBA), sodium butyrate (NaBut) and N-monomethylformamide (NMF) resulted in a significant inhibition of proliferation (P less than 0.001) and in a simultaneous increase in differentiation. The response was most pronounced after exposure to NMF as evidenced by a marked increase in the creatin…
STAT5 and STAT5 Inhibitors in Hematological Malignancies
2019
The JAK-STAT pathway is an important physiologic regulator of different cellular functions including proliferation, apoptosis, differentiation, and immunological responses. Out of six different STAT proteins, STAT5 plays its main role in hematopoiesis and constitutive STAT5 activation seems to be a key event in the pathogenesis of several hematological malignancies. This has led many researchers to develop compounds capable of inhibiting STAT5 activation or interfering with its functions. Several anti-STAT5 molecules have shown potent STAT5 inhibitory activity in vitro. However, compared to the large amount of clinical studies with JAK inhibitors that are currently widely used in the clini…
Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia
2009
Imatinib mesylate (Gleevec) is a drug unique for the treatment of certain forms of cancer. It works by targeting, and turning off, specific tyrosine kinase proteins that cause the uncontrolled cell growth and the inhibition of apoptosis in cancer cells. Imatinib was designed on the basis of the structure of the ATP binding site of the Abl protein kinase with the aim to stabilizes the inactive form of Bcr-Abl, an oncoprotein involved in malignant transformation in chronic myelogenous leukemia (CML). However, imatinib can also target other tyrosine kinase proteins different from Bcr-Abl such as Kit, that is the suspected cause of gastrointestinal stromal tumor (GIST). Despite successful clini…