Cytogenetic variability in radiation induced mouse leukaemia.

C57BL mice and certain of their hybrids have a high incidence of radiation induced leukaemia. The incidence is greater than 70 % in (C57BL x CBA.T6T6)F1 hybrids aged between 30 and 40 days receiving 4 fractions of 200 rads gamma radiation at 4-day intervals (Ilbery, 1967). The great majority of primary reticular neoplasms arising in irradiated mice show a variation in chromosome number in the range 41 to 45 and distinctive new marker chromosomes are often present (Ford, Hamerton and Mole, 1958). It has been suggested that karyotypic alterations are of primary significance in the onset of neoplasia (Winge, 1930) but more probably there is an association for such changes with tumour progression (Hauschka, 1961). Nevertheless from cytogenetic studies of the thymus in the preleukaemic phase it seems that observable variations in chromosome number and form accompany an early stage of leukaemia induction (Ilbery et al., 1963; Joneja and Stich, 1965). This report is concerned with the cytogenetic results of mice involved in radiation experiments during the last 5 years and who subsequently exhibited macroscopically leukaemia of the thymic type. Thymomas were passaged so that, where for technical reasons examination ofthe primary neoplasm failed, subsequent sampling of the malignant cells could be made in the passage mice. Cytogenetic results of a total of 43 radiation induced leukaemias are recorded of which 26 were sampled from the propositi. A related paper will give the cytogenetic results of mice exposed to the leukaemogenic effects of radiation and in which attempts were made, by the administration of cell supplements, to modify or prevent the onset of leukaemia. MATERIALS AND METHODS Mice of both sexes between 30 and 40 days of age at the time of irradiation were used in the leukaemia induction experiments. The inbred strains employed were C57BL, CBA, DBA and T6T6 all maintained in this laboratory by selective inbreeding during the last 10 years. CBA/H and CBA.T6T6 have been inbred a further 12 and 9 generations respectively in this laboratory since the importation in 1963 of these syngeneic mice from Dr. Mary Lyon of the M.R.C. Radiobiologica

Anticancer Activity of New Copper (II) Complexes with 6-Thiguanine Drug

Abstract: A new complex has been synthesized of Cu (II) complex with 6-thioguanine and phyico-chemical characterized by amperometry, polarography elemental analysis and FTIR spectroscopy. After Synthesis of metal complex, it was evaluated it for antibacterial and antifungal activities against various pathogenic microorganisms such as; Streptococcus aureus, Proteus. M., klebsiella pneumonia and Asperginus niger, Nigrosporan S.P. B16-F10 melanoma cell and C-57BL/6 mice has been used for anticancer screening of metal complex for in vitro and in vivo study. The result of pharmacological studies with M: L revealed that the complex is more potent as compared to the pure drug as regards to its anticancer activity

Standardization of ethanol addiction model in Swiss albino Mice

Background: Addiction is compulsive need for use of a habit-forming substance. World Health Organization (WHO) reported that worldwide 3.3 million people died due to alcohol addiction in 2012-13 and 11% of the population in India indulged in heavy drinking in 2014. Addiction is a prime socio-economical problem of society. Studying alcohol dependence in humans involved many ethical issues and experimental difficulties. Hence nonhuman animal experimental model has been used for a research on the topic of alcohol intoxication and dependence. Ethanol dependence has been preferred to develop in genetically modified strain of mice, C-57 which has a natural inclination to consume and develop addiction. But studying addiction in this special strain requires top end experimental facilities and financial aids. Authors reported the animal model to study ethanol dependence in Swiss albino mice. Aim of the study was to develop ‘Ethanol Dependence in Swiss albino mice animal model’ by intermitted access of 20% ethanol.Methods: Dependence was developed in Swiss albino mice by intermitted access of 20% ethanol in two groups having six animals in each group. Dependence was confirmed by presence of the withdrawal symptoms like anxiety, muscular incoordination and behavioral changes of animals on abstinence of ethanol.Results: Significant difference was noted on withdrawal symptoms, i.e. anxiety, muscular coordination, muscle spasm and other behavior related to withdrawal.Conclusions: Ethanol dependence can be successfully developed in Swiss albino mice in 14 days

Increased expression of IL-16 in the brain of experimental autoimmune encephalomyelitis

Multiple Sclerosis (MS) is a demyelinating disease of the CNS, whose pathophysiology involves both inflammatory and neurodegenerative components. CD4+ T cells are one of the key mediators of disease initiation and progression; however CD4 i s also the receptor for the pro-inflammatory cytokine, interleukin - 16 (IL - 16). IL - 16 has been proposed to play a role in several autoimmune diseases, but the exact role of IL - 16 in the CNS during MS initiation and progression remains unclear. Therefore, the aim of this study was to examine the expression and distribution of IL - 16 in CNS tissue and investigate whether expression levels correlate with neuro-inflammation in experimental autoimmune encephalomyelitis (EAE), a murine model of MS. EAE was induced in 6 week old C 57BL/6J female mice by immunisation with MOG35 - 55 peptide and adjuvants. Tissue was harvested at onset (day 11), peak (day 16) and resolution (day 26), and immunofluorescence staining carried out to determine CD45, CD4 and IL - 16 expression and localisation in the brain of both control and EAE mice. In addition, co-localisation of IL - 16 with CNS and immune cell subtypes was performed using a Mesolens microscope (McConnell et al., 2016), which allows subcellular detail to be obtained from wide - field epifluorescence images. Expression of IL - 16 and CD4 was observed primarily within the lesions of cerebellum and hippocampus of the EAE brain, whereas little expression was observed in control brains. IL - 16 expression was highest at onset with 76 ±2.8% of cells ( n=3) within these lesions expressing IL - 16. This was reduced to 48±2.4% (n=3) at peak and 16 ±1.3% at resolution (n=3). Co-localization studies revealed that IL - 16 was expressed primarily by infiltrating immune cells but not by neurons or astrocytes. Co-localization of IL - 16 with immune cells in brain lesions of EAE mice suggests that infiltrating immune cells are the primary source of IL - 16. Further investigation is required if IL - 16 is pro-inflammatory or anti-inflammatory in the CNS during EAE

The effects of second-hand smoke on biological processes important in atherogenesis

BACKGROUND: Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis. METHODS: To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB(100 )was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation. RESULTS: "Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein–1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke) to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice. CONCLUSION: Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that leads to lipid accumulation in the liver and in the blood vessels of the heart and aorta. The former potentially can lead to non-alcoholic fatty liver disease and the latter to heart attacks

Phosducin regulates the expression of transducin betagamma subunits in rod photoreceptors and does not contribute to phototransduction adaptation.

For over a decade, phosducin's interaction with the betagamma subunits of the G protein, transducin, has been thought to contribute to light adaptation by dynamically controlling the amount of transducin heterotrimer available for activation by photoexcited rhodopsin. In this study we directly tested this hypothesis by characterizing the dark- and light-adapted response properties of phosducin knockout (Pd- / -) rods. Pd- / - rods were notably less sensitive to light than wild-type (WT) rods. The gain of transduction, as measured by the amplification constant using the Lamb-Pugh model of activation, was 32% lower in Pd- / - rods than in WT rods. This reduced amplification correlated with a 36% reduction in the level of transducin betagamma-subunit expression, and thus available heterotrimer in Pd- / - rods. However, commonly studied forms of light adaptation were normal in the absence of phosducin. Thus, phosducin does not appear to contribute to adaptation mechanisms of the outer segment by dynamically controlling heterotrimer availability, but rather is necessary for maintaining normal transducin expression and therefore normal flash sensitivity in rods

Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence.

The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning

Influence of thyroid secretion on the in­duction of leukemia in Dba mice by methylcholanthrene

1) The influence of thyroid secretion upon the induction of leukemia in Dba/2 male mice by methylcholanthrene was investigated. Radiothyroidectomy significantly reduced the incidence of leukemia in these mice. This reduction in incidence did not occur if radiothyroidectomy was performed after the administration of the carcinogen. 2) Data indicated that hypothyroidism following radiothyroidectomy interfered with the initiation rather than the promotion of methylcholanthrene- induced-Ieukemogenesis. 3) No correlation between incidence of leukemia and body weights in the mice was noted.</p