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Journal Article 2007; 28(4): 401-405 PubMed PMID: 17693965 Citation  Keywords:  Animals, Cattle, Exons, Genotype, Liver:metabolism, Male, Polymorphism, Single Nucleotide:genetics, Protein Binding:genetics, Receptors, Somatotropin:genetics, Signal Transduction,.   

OBJECTIVES: Nucleotide sequence polymorphisms in the coding gene regions may influence the biological properties of proteins encoded by a gene. The A/T substitution in exon 8 of the growth hormone receptor (GHR) gene results in changed amino acid sequence 279 (Phe/Tyr) in the transmembrane domain of the receptor protein and therefore could influence its functional parameters. We searched for the relationship between the A/T nucleotide polymorphism in the GHR gene the receptor binding capacity and dissociation constant.

METHODS: Nucleotide sequence variations in the exon 8 (coding for the transmembrane domain of the receptor) of the bovine GHR gene and in fragments of adjacent introns were analysed using PCR-SSCP and sequencing techniques. GH receptor binding capacity (Bmax) and dissociation constant (Kd) for GHR were determined by the Scatchard analysis in livers of ten bulls carrying the AA or AT GHR genotypes.

RESULTS: Two single nucleotide polymorphisms (SNPs) were identified--the C/T transition in intron 8 at position 863+32 and the A/T transversion in exon 8 at position 836, the latter resulting in Phe/Tyr amino acid substitution in the receptor protein. The results showed significant differences in the GHR binding capacity between these genotypes. Bmax was significantly greater (p< or =0.01) in bulls carrying TT genotype of GHR in comparison to those with the AT genotype. No significant differences in the dissociation constants (Kd) were found.

CONCLUSION: Our results demonstrated that single base substitution in the transmembrane domain encoding region of GH receptor gene may influence the physiological properties of the receptor....

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Journal Article 2007; 28(3): 267-273 PubMed PMID: 17627260 Citation  Keywords:  Acetamides:pharmacology, Animals, Autoradiography, Binding Sites, Brain:metabolism, Circadian Rhythm, Female, Melatonin:metabolism, Memory, Receptors, Melatonin:analysis, Stress, Psychological:physiopathology, Suprachiasmatic Nucleus:chemistry, Tupaiidae,.   

OBJECTIVE: In this study we investigated the distribution of melatonergic receptors in the tree shrew brain. The psychosocial stress in the tree shrew is a validated model of depression with disturbance of circadian rhythms.

METHODS: Given the role of melatonin in the modulation of circadian rhythms, we determined by autoradiography the distribution of binding sites of 2-[125I]-MLT, a ligand for the two melatonergic receptors MT1 and MT2, in the tree shrew brain focusing mostly on the suprachiasmatic nucleus (SCN), the biological clock involved in resynchronization of circadian rhythms. We also analyzed the distribution of 2-[125I]-MLT in other brain areas involved in regulation of mood.

RESULTS: Specific binding of 2-[125I]-MLT was found in the SCN. In addition, several structures in the tree shrew brain were labeled, among them the pars tuberalis, the cerebellum, structures of the hippocampal formation and dopaminergic areas such as the caudate putamen and nucleus accumbens, providing other potential targets of psychosocial stress in the tree shrew, in addition to the SCN.

CONCLUSIONS: The demonstration of melatonergic receptors in these brain areas supports their probable involvement in the behavioural, neuroendocrine and circadian rhythms disturbances observed in the psychosocial stress model of depression in the tree shrew....

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Letter 2007; 28(3): 250-251 PubMed PMID: 17627256 Citation  Keywords:  Adult, Brain Stem Neoplasms:diagnostic imaging, Female, Glioma:diagnostic imaging, Humans, Indium Radioisotopes, Receptors, Somatostatin:analysis, Somatostatin:analogs & derivatives, Tomography, Emission-Computed, Single-Photon,.   

: In diffuse brainstem gliomas often surgical biopsies cannot be obtained. The diagnosis relies upon imaging criteria, first line being MRI. Gliomas generally express somatostatin receptors (SSTR), which might enable receptor imaging. We present the case of a female adolescent with acute onset of hallucinations, dysphagia and diplopia. MRI detected a suggestive large pontine glioma. This lesion presented with marked In-111-pentreotide tracer uptake. SSTR-scan provided information about SSTR-expression, tumour viability and extension. Radiopeptide therapy for selected patients might be discussed....

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Journal Article 2007; 28(3): 221-229 PubMed PMID: 17627253 Citation  Keywords:  Carcinoma, Papillary:genetics, Gene Rearrangement, Genotype, Humans, Neoplasms, Radiation-Induced:genetics, Phenotype, Proto-Oncogenes, Receptor, trkA:genetics, Thyroid Neoplasms:genetics,.   

: Papillary thyroid carcinoma (PTC) represents an example of tumour with high incidence of oncogenic sequences, such as RET/PTC and Trk. Both of them arise from the fusion of 3' terminal sequences of TK domain of RET or NTRK1 gene, respectively, with 5' terminal sequences of their activating genes. In case of NTRK1 oncogene, several rearrangement types are observed, characteristic for PTC: Trk (TMP3), Trk-T1, Trk-T2, Trk-T3 and Trk-2h, observed in human breast cancer cell line. Studies from different geographical regions, revealed significant population differences in the incidence of Trk rearrangements (0-50%), while within the same population, the frequency of Trk in spontaneous and radiation-associated PTCs is similar. The results of studies, focused on the correlation between tumour genotype and the histopathological type of tumour, involving cases of both RET/PTC and Trk rearrangements in PTC, are not unequivocal. In many studies, no correlation was observed between the presence of RET and/or NTRK1 rearrangement and such parameters, as patient's age at diagnosis, gender, histopathological type of tumour or clinical stage (TNM stage grouping), although the earliest clinical symptoms and the worst disease outcomes were observed for RET/NTRK1 rearrangement positive tumours. Differences in the rearrangement incidence between male and female patients were associated with the latency period of radiation-associated tumours, being significantly lower in women. In general, it is assumed that oncogenic Trk sequences are typical for the spontaneous type of PTC....

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Journal Article 2007; 28(2): 77-105 PubMed PMID: 17435680 Citation  Keywords:  Carcinoma:etiology, Cell Transformation, Neoplastic:genetics, Chromosomes, Human, Pair 3, GTP-Binding Proteins:genetics, Genes, Suppressor, Genetic Predisposition to Disease, Humans, Models, Biological, Proto-Oncogene Proteins:genetics, Receptors, Thyrotr.   

: The process of carcinogenesis is permanently one of the most interesting and significant issues for researchers in different fields of medicine. Therefore, we attempted to bring closer the problem of neoplastic transformation in the thyroid gland. This article covers the latest data about genetic factors, involved in thyroid carcinogenesis. We have presented results of the most recent studies referred to molecular biology of thyroid neoplasms. We have demonstrated not only the genetic background of cancers, derived from the thyroid follicular cell, but also genetic aspects related to medullary thyroid carcinoma and some benign thyroid lesions. The review describes DNA methylation disturbances and the mutations in thyrotropin receptor and G protein genes. Furthermore, we introduce the results of studies performed at our laboratory, concerning mutations in the following protooncogenes: RAS, RET, Trk, MET, and BRAF. Also, we present our data, regarding the loss of heterozygosity (LOH) in the short arm of chromosome 3. Additionally, we discuss overexpression of cyclin D1 gene in benign and malignant thyroid lesions. Previous studies performed at our laboratory indicate the role of IGF-I in the pathogenesis and invasiveness of thyroid cancers. The review indicates that progress in genetics of the thyroid cancer is extremely rapid....

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Journal Article 2006; 27(6): 703-710 PubMed PMID: 17187025 Citation  Keywords:  Agonistic Behavior:drug effects, Animals, Arachidonic Acids:pharmacology, Behavior, Animal:drug effects, Cannabinoid Receptor Agonists, Cannabinoid Receptor Antagonists, Central Nervous System Stimulants:administration & dosage, Drug Administration Schedu.   

OBJECTIVES: Psychostimulants and cannabinoids can elicit so called behavioural sensitization after repeated administration, a gradually increased behavioural response to a drug. This phenomenon if conditioned by previous pre-treatment with different drug is termed cross-sensitization. The present study was focused on a possible sensitisation to antiaggressive effect of methamphetamine and cross-sensitization to this effect after repeated pre-treatment with cannabinoid CB1 and CB2 receptor ligands with different intrinsic activity (CB1 agonist methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM 251).

METHODS: Behavioural interactions of singly-housed mice with non-aggressive group-housed partners were video-taped and behavioural elements of agonistic behaviour of isolates were recorded in four categories: sociable, timid, aggressive and locomotor.

RESULTS: Repeated administration of methamphetamine elicited a significant sensitization to its antiaggressive effects. Methanandamide pre-treatment provoked cross-sensitization to this methamphetamine effect, whereas pre-treatment with JWH 015 did not. Combined pre-treatment with methamphetamine+AM 251 suppressed the sensitization to antiaggressive effects of methamphetamine.

CONCLUSIONS: Our findings have shown that it is possible to provoke sensitization not only to the stimulatory effects as stated widespread in the literature but also to inhibitory antiaggressive effects of methamphetamine. Furthermore, we confirmed our working hypothesis that it is possible to elicit either cross-sensitization to inhibitory effects of methamphetamine conditioned by repeated pre-treatment with cannabinoid CB1 receptor agonist methanandamide, or suppression of methamphetamine sensitizing influence by co-administration of CB1 receptor antagonist....

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Journal Article 2006; 27(Suppl 1): 46-48 PubMed PMID: 16804511 Citation  Keywords:  Antigens, CD:metabolism, Antigens, CD28:metabolism, Antigens, Differentiation, T-Lymphocyte:metabolism, Antigens, Surface:metabolism, Cadmium:pharmacology, Cell Culture Techniques, Humans, Lectins, C-Type, Lymphocyte Activation:drug effects, Receptors, Ig.   

OBJECTIVES: Metals have different effects on the immune functions. Through the experimental in vitro model, we studied the changes in the activation and co-stimulatory surface markers in human lymphocytes cultivated with selected metal salts.

METHODS: Whole human blood was cultivated with cadmium (Cd) or zinc (Zn) sulfate for 18 hours. The number of lymphocytes positive for activation and co-stimulatory markers was evaluated by flow cytometry.

RESULTS: Elevation of the CD69 and CD23 markers as well as higher expression of CD28 was found in cultures of lymphocytes incubated with Cd. In cultures incubated with Zn, minor elevation of the HLA-DR antigen expression was observed in comparison to Cd-treated cell cultures. Decrease of CD3 expression was observed after cultivation with both Cd and Zn salts.

CONCLUSION: Cd and Zn exhibit different effects on the expression of human surface activation antigens and co-stimulatory molecules. Cd in non-toxic concentrations stimulated expression of early activation molecules and therefore could change the early phase of immune response. This was not the case for Zn, where the results were similar to untreated cell cultures....

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Journal Article 2006; 27(5): 601-608 PubMed PMID: 17186997 Citation  Keywords:  Animals, Azo Compounds:pharmacology, Dose-Response Relationship, Drug, Fibroblasts:drug effects, Lipid Metabolism:drug effects, Melatonin:pharmacology, Mice, NIH 3T3 Cells, Oleic Acid:pharmacology, Receptors, Melatonin:antagonists & inhibitors, Tryptamine.   

: The current study was undertaken to uncover the role of melatonin in lipid metabolism in the murine fibroblasts. The results show melatonin in vitro enhances lipid accumulation and lipid droplet formation in this cell line. Using oil red O staining, it was found that when oleic acid was present in the culture media, melatonin at doses of 0.1-2mM, significantly increased the lipid concentrations in the cells. However, low levels of melatonin, with or without oleic acid, did not influence lipid metabolism in the cultured fibroblasts. When a non-specific melatonin receptor antagonist, luzindole 10 microM was co-incubated with 1mM melatonin, the stimulatory effects of melatonin on lipid accumulation in these cells was significantly reduced. It appears that the effects of melatonin on lipid metabolism in murine fibroblasts is mediated by melatonin membrane receptors....

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