ABSTRACT
Deletion in the 22.9 -Mb chromosomal (chr.) 8p21.3-23 region has been shown to be necessary for the development of breast carcinoma (CaBr). In this study, we have attempted to detect the minimal deleted region(s) in the chr.8p21.3-23 region in 62 primary breast lesions having 56 CaBr tumors and six other breast lesions of Indian patients using 15 microsatellite markers. The loss of heterozygosity (LOH) was observed for at least one marker in 96.4% (54/56) of the CaBr samples. Three discrete minimal deleted regions with high frequencies of LOH (39-65%) were identified in the chromosomal 8p23.1-23.2 (D1), 8p23.1 (D2) and 8p 21.3-22 (D3) regions within 2.03, 0.41, 2.47 Mb, respectively. No significant correlation was observed with the high deleted regions and the different clinicopathological parameters. Interestingly, 51.8% (29/56) CaBr samples showed either loss of chr.8p or interstitial deletions in this arm, indicating the importance of chr.8p in the development of CaBr. The pattern of allelic loss in the bilateral lesions had indicated that the lesions were clonal in origin and probably the deletion in the D3 region was the early event among the D1-D3 regions. Thus, our data have indicated that the D1-D3 regions could harbor candidate tumor suppressor gene(s) (TSGs) associated with the development of CaBr.
Subject(s)
Breast Neoplasms/genetics , Chromosomes, Human, Pair 8/genetics , Fibroadenoma/genetics , Adult , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , DNA, Neoplasm/genetics , Female , Fibroadenoma/epidemiology , Fibroadenoma/pathology , Genes, Tumor Suppressor , Humans , India/epidemiology , Loss of Heterozygosity , Microsatellite RepeatsABSTRACT
OBJECTIVE: Dopamine, a catecholamine neurotransmitter, influences growth and proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is available on the effect of physiological concentrations of circulating dopamine on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in humans during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppression of T cell functions during stress is not yet clear. In the present investigation, we evaluated the effect of the dopamine level attained in the plasma of individuals with uncoping stress on the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. METHODS: T cell subpopulations were separated by panning. The effect of dopamine on IL-2-induced cell proliferation in vitro was evaluated by [3H]thymidine incorporation and cytotoxicity by 51Cr release, receptors by radioligand binding, cAMP by an assay kit and apoptosis by DNA fragmentation. RESULTS: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediated inhibition of proliferation was more marked on CD8+ T cells than on CD4+ T cells. The underlying mechanism was found to be D1 class of dopamine-receptor-mediated stimulation of intracellular cAMP. CONCLUSION: Results may be of significance to understand the role of peripheral dopamine in human neuroimmune communication in terms of physiological homeostasis in health and disease.
Subject(s)
Adenine/analogs & derivatives , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Dopamine/pharmacology , Immunity, Cellular/drug effects , Mouth Neoplasms/immunology , Neuroimmunomodulation/physiology , Receptors, Dopamine/physiology , Stress, Psychological/immunology , 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Adenine/pharmacology , Adenylyl Cyclase Inhibitors , Adult , Bucladesine/pharmacology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Division/drug effects , Cells, Cultured/drug effects , Cyclic AMP/agonists , Cyclic AMP/physiology , Cytotoxicity, Immunologic/drug effects , Dopamine/administration & dosage , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Female , Humans , Interferon-gamma/metabolism , Interleukin-2/metabolism , Lymphocyte Activation/drug effects , Male , Middle Aged , Mouth Neoplasms/blood , Mouth Neoplasms/complications , Mouth Neoplasms/psychology , Psychoneuroimmunology , Receptors, Dopamine/drug effects , Second Messenger Systems/drug effects , Stress, Psychological/blood , Stress, Psychological/etiology , Theophylline/pharmacologyABSTRACT
Oral tumor specimens (n = 50) from eastern Indian population were studied for the presence of mutations in the H-, K- and N-ras genes using selective oligodeoxynucleotide hybridization and restriction fragment length polymorphism analysis of polymerase chain reaction-amplified products. Mutations in H- and K-ras genes were observed at a frequency of 28 and 33%, respectively, whereas no N-ras mutation was noticed.
Subject(s)
Genes, ras/genetics , Mouth Neoplasms/genetics , Mutation/genetics , Female , Humans , India , Male , Polymorphism, Restriction Fragment LengthABSTRACT
In 1984 capripox entered Bangladesh developing into a severe epidemic causing high mortality in the indigenous goat population. Although at present mainly confined to the western districts the disease has spread to some central and northern districts and unless controlled could spread further. Clinically and biochemically the strain is closely related to a strain previously isolated in central India. It has been shown that restriction endonuclease analysis of the genome of field isolates of capripoxvirus can provide a useful epidemiological technique in investigating outbreaks of capripox.
