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Biomedical subjects

R R Watson

Publications and source records attributed to R R Watson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Modification of physical movement in old C57BL/6 mice by DHEA and melatonin supplementation.

As old age results in reduced physical activity as well as less dehydroepiandrosterone (DHEA) and melatonin (MLT) production, low hormone levels may be a component of inactivity. Therefore, we studied the effects of DHEA and/or MLT supplementation on movement and resting in young and old female C57 black mice. Our results showed for the first time that old female C56BL/6 mice have significantly decreased physical activity. Their average speed and resting time were significantly higher than in young mice, whereas ambulatory time, distance traveled, and body movements when stationary (stereo time) were lower. DHEA supplementation significantly increased stereo time in old mice, while decreasing ambulatory time and distance traveled. MLT supplementation of old mice decreased average speed, resting time, and stereo time compared to untreated, old mice. Supplementation with MLT or DHEA, whose production is reduced in aging, restored physical activity levels in old mice. MLT also increased ambulatory time and distance traveled while reducing body movements of young mice.

Age Factors↗
PubMed1999

Effect of short-term cocaine administration on the immune system of young and old C57BL/6 female mice.

It has been shown that either cocaine or aging alone can alter the immune system. Our objective was to study if the immune system of aging mice was more susceptible to the effect of cocaine than the immune system of young mice. We used a short term (20 days) cocaine daily administration protocol. Cocaine only decreased the absolute number of Thy 1+, CD4+, CD8+, IL-2R+, Mac 1+ and B cells, in the spleen of old mice. Old untreated mice had a lower number of Thy 1+ cells in the thymus, and a higher number of cells expressing IL-2R. Cocaine decreased the number of Thy 1+ cells in the thymus of both age groups. Old mice showed a lower number of IgA+ plasma cells in the intestinal lamina propria (ILP) than young mice. Short term cocaine administration provoked a decrease in the number of CD4+ cells in young mice ILP and of CD8+ cells in old mice ILP. Our data suggest that cocaine can potentiate the effect of aging on the thymus and on the mucosal immune system. Taken together, our findings indicate that aging and cocaine can potentiate each other to impairing the host immune system.

Adjuvants, Immunologic↗
PubMed1999

Immune dysfunction during alcohol consumption and murine AIDS: the protective role of dehydroepiandrosterone sulfate.

Acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by the human immunodeficiency virus (HIV) after development of severe immunosuppressive changes. Chronic ethanol (EtOH) consumption accentuates the severity of murine AIDS (MAIDS). Because hormone production is often suppressed by chronic EtOH intake, as well as retrovirus infection, we investigated whether hormone supplementation during chronic EtOH consumption contributes to slowing immune dysfunction caused by LP-BM5 infection and/or EtOH use. Because dehydroepiandrosterone sulfate (DHEAS) was previously shown to have immune-enhancing properties during MAIDS, we determined whether DHEAS reduced cytokine dysregulation otherwise exacerbated by chronic EtOH intake during MAIDS. Adult female C57BL/6 mice were infected with LP-BM5 murine retrovirus. Some were fed 40% EtOH in drinking water and agar gel for 16 weeks postinfection. EtOH consumption further inhibited T- and B-cell proliferation beyond suppression due to retrovirus infection. Interleukin (IL)-2 release produced by concanavalin A-stimulated splenocytes was reduced by EtOH use by infected and uninfected mice. DHEAS overcame much of the effects induced by retrovirus infection and/or EtOH use. IL-4 secretion and IL-6 secretion were enhanced. Hepatic vitamin E levels were decreased by murine retrovirus infection, as well as by EtOH use in both uninfected and infected mice. In addition, DHEAS (0.01%) supplementation during MAIDS prevented the further dysregulation of cytokines and hepatic lipid peroxidation due to EtOH intake, partially restored T- and B-cell proliferation, and maintained hepatic vitamin E levels to near normal levels.

Adult↗
PubMed1998

Detection of ethanol consumption by ELISA assay measurement of acetaldehyde adducts in murine hair.

Acetaldehyde (AA), a principal metabolite of ethanol, reacts with proteins to form protein-AA adducts in vivo and in vitro. We studied three different protein-AA adducts produced in vitro, as well as hair keratin-AA adducts from ethanol-fed and/or cocaine-injected mice. An enzyme linked immunosorbent assay (ELISA) was developed that detected the stable protein-AA adducts in protein isolated from hair. Cocaine injection had little effect on hair AA adduct formation. The indirect ELISA assay showed significantly increased levels of keratin-AA adducts in hair from mice fed ethanol for 8 weeks. Hair collection was noninvasive and the AA-protein adducts were stable. Therefore, this indirect ELISA assay could be further developed as a biochemical parameter for alcoholism in the clinical setting.

Acetaldehyde↗
PubMed1998

Injection of T-cell receptor peptide reduces immunosenescence in aged C57BL/6 mice.

Previous studies established that retrovirally infected young mice produced large amounts of autoantibodies to certain T-cell receptor (TCR) peptides whose administration diminished retrovirus-induced immune abnormalities. C57BL/6 young (4 weeks) and old (16 months) female mice were injected with these same synthetic human TCR V beta 8.1 or 5.2 peptides. Administration of these autoantigenic peptides to old mice prevent immunosenescence, such as age-related reduction in splenocyte proliferation and interleukin-2 (IL-2) secretion. TCR V beta peptide injection into young mice had no effect on T- or B-cell mitogenesis and IL-4 production while modifying tumour necrosis factor-alpha (TNF-alpha), IL-6, and interferon-gamma (IFN-gamma) secreted by mitogen-stimulated spleen cells. TCR V beta injection also retarded the excessive production of IL-4, IL-6 and TNF-alpha induced by ageing. These data suggest that immune dysfunction and abnormal cytokine production, induced by the ageing process, were largely prevented by injection of selected TCR V beta CDR1 peptides.

Aging↗
PubMed1998

Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice.

Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Animals↗
PubMed1998

Dehydroepiandrosterone (DHEA) sulfate prevents reduction in tissue vitamin E and increased lipid peroxidation due to murine retrovirus infection of aged mice.

Dietary effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on tissue antioxidants and lipids were investigated in retrovirus infected mice. DHEA is a powerful antioxidant and immunomodulator whose production declines with age. For this study, twenty-four female, 15-month-old C57BL/6 mice were left uninfected while twenty-four were infected with LP-BM5 murine leukemia virus, causing murine AIDS. The retroviral infection caused immune dysfunction and loss of hepatic and cardiac vitamins E and A, resulting in increased lipid peroxides. Treatment with DHEAS at 0.01 or 0.005% in drinking water for 10 weeks post-infection significantly (P < 0.05) lowered lipid peroxidation in both heart and liver tissues. Treatment with DHEAS also largely prevented loss of the antioxidants, such as vitamin E and A, and prevented loss of phospholipid in the hearts and livers of the old uninfected as well as infected mice. This study suggests that DHEAS supplementation reduces damage associated with elevated oxidation due to aging and retrovirus infection.

Aging↗
PubMed1998

Physical inactivity of murine retrovirus infected C57BL/6 mice is prevented by melatonin and dehydroepiandrosterone.

LP-BM5 retrovirus infection and hormone synthesis modulate many physiological systems that could affect physical activity. Infection induced oxidative damage and immunodeficiency of female mice which hormone supplement prevented. Therefore, the effects of retrovirus infection and hormone supplementation were assessed on physical activity using a computerized video system. Retroviral infection increased activity when stationary while lowering average speed and resting time. Hormone supplementation partially modified changes due to murine AIDS. Dehydroepiandrosterone (DHEA) or melatonin (MLT) supplementation restored the average speed; ambulatory time and distance traveled of retrovirus infected mice. MLT as well as the combination of DHEA + MLT increased body movement, but decreased average speed and distance traveled. Thus, retrovirus infection had significant effects on physical activity. Further studies into the relationship between the DHEA and/or MLT and physical activity will assert the contribution of these hormones to the treatment of murine AIDS.

Animals↗
PubMed1997

Modulation of immune dysfunction during murine leukaemia retrovirus infection of old mice by dehydroepiandrosterone sulphate (DHEAS).

Ageing, leukaemia and acquired immune deficiency syndrome (AIDS) are conditions with dysregulated cytokine production. As dehydroepiandrosterone sulphate (DHEAS) restored normal cytokine production in old mice its effects on retrovirally infected old mice were investigated. Retrovirus infection and ageing-induced immune dysfunction. Murine retrovirus-infected old C57BL/6 female mice consumed 0.22 or 0.44 microgram of DHEAS/mouse/day beginning 2 weeks postinfection for 10 weeks. DHEAS largely prevented the retrovirus-induced reduction in T-cell and B-cell mitogenesis. DHEAS supplement prevented loss of cytokines [interleukin-2 (IL-2) and interferon-gamma] secretion by mitogen-stimulated splenocytes representing T helper 1 (Th1) cell phenotypes. It also suppressed the retrovirus-induced, excessive production of cytokines (IL-6 and IL-10) by Th2 cells. The highest dose of DHEAS reduced IL-6 production by splenocytes from uninfected old mice by 75% while increasing their IL-2 secretion by nearly 50%. Thus immune dysfunction induced by ageing, even when exacerbated by murine retrovirus infection, was largely prevented by DHEAS.

Aging↗
PubMed1997

Melatonin, immune modulation and aging.

Melatonin is a hormone secreted by the pineal gland in response to photoperiods and influences many important biological processes. For one, Melatonin has been shown to produce resistance to cancer and infectious diseases in aged animals. Studies in animals have demonstrated melatonin-related mechanisms of action on immunoregulation. Additionally, melatonin has been successfully used in humans, along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro studies show melatonin enhances both natural and acquired immunity in animals. Despite all of this intriguing evidence, melatonin's mechanism of action on the immune system is only partially defined. It does, however, appear to act through lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate immune cells. In order to understand immunomodulation and anti-cancer effects, information on melatonin and it's interactions with other endocrine hormones are summarized.

Aging↗
PubMed1997

Prevention of retrovirus-induced aberrant cytokine secretion, excessive lipid peroxidation, and tissue vitamin E deficiency by T cell receptor peptide treatments in C57BL/6 mice.

To test whether T cell receptor (TCR) peptide treatment can prevent immune dysfunction, excessive lipid peroxidation, and malnutrition caused by retrovirus infection, female C57BL/6 mice were infected with LP-BM5 retrovirus. Infection with retrovirus inhibited lymphocyte proliferation, cytokine release T helper 1 cells, stimulated cytokine secretion by T helper 2 cells, induced abnormal hepatic and cardiac lipid profiles, and produced excessive tissue lipid peroxidation with hepatic and cardiac vitamin E deficiency. Two weeks after infection, TCR peptides Vbeta5.2, Vbeta8.1, Vbeta8.1 + Vbeta5.2, Vbeta8.1(N), and Vbeta8.1 were injected to the mice at dose of 200 microg/mouse. Vbeta8.1 and Vbeta5.2 treatments largely maintained lymphocyte proliferation and IL-2 and IFN-gamma release, and prevented excessive IL-6, IL-10, and TNF-alpha secretion. Concomitantly, these treatments normalized hepatic and cardiac lipid profiles, reduced tissue lipid peroxidation, and thereby significantly maintained vitamin E in the liver and heart. Vbeta8.1 segments treatment did not prevent the immune dysfunction, abnormal lipid profile and lipid peroxidation, and vitamin E deficiency caused by the retrovirus infection. In conclusion, injection of intact TCR peptides during murine retrovirus infection largely prevented immune dysfunction by blocking the excessive stimulation of a T cell subset caused by retroviral superantigens. It also ameliorated malnutrition status by normalizing lipid profile, lipid peroxidation, and vitamin E deficiency. T cell immune dysfunction and its prevention by TCR peptide treatment is important in the therapy of vitamin E deficiency induced by retrovirus infection.

Amino Acid Sequence↗
PubMed1997

Cytokine dysregulation and increased oxidation is prevented by dehydroepiandrosterone in mice infected with murine leukemia retrovirus.

The effects of murine leukemia retrovirus infection on production of cytokines was investigated in mice fed different doses of dehydroepiandrosterone (DHEA). Young C57BL/6 female mice were injected with LP-BM5 murine retrovirus or were kept as uninfected controls. Two weeks later, each group was divided into subgroups: fed unsupplemented AIN 93 diet as the control, or diets supplemented with 0.02% DHEA (0.9 mg/mouse/day) or 0.06% DHEA (2.7 mg/mouse/day). The uninfected mice supplemented with 0.06% DHEA showed a significant (P < 0.05) increase in interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) production, and hepatic vitamin E levels. Retroviral infection induced severe oxidative stress that was reduced by DHEAS supplementation in retrovirally infected mice. DHEA supplementation prevented the retrovirus-induced loss of cytokines (IL-2 and IFN-gamma) secretion by mitogen stimulated spleen cells. DHEA also suppressed the production of cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by T helper 2 (Th2) cells which were otherwise stimulated by retrovirus infection. Thus, immune dysfunction and increased oxidation induced by murine retrovirus infection were largely prevented by DHEA.

Adjuvants, Immunologic↗
PubMed1996

Alterations of the mucosal immune system due to Cryptosporidium parvum infection in normal mice.

The mechanism with which the immune system of an immunocompetent host responds to Cryptosporidium parvum infection is still poorly understood. We have therefore investigated the immune response of adult immunocompetent C57BL/6 mice at Days 6 and 10 to postinfection during a self-limiting C. parvum infection. We evaluated the immune changes at the levels of intestinal intraepithelium and lamina propria as well as mesenteric lymph nodes. At Day 6 postinfection, there was a decrease in the production of IFN-gamma, IL-5, IL-6, and IL-10 by in vitro mitogen-stimulated intraepithelial lymphocytes. Moreover, an increase in the number of gammadelta-TCR+, CD8+, and cytoplasmic IgE+ cells in intestinal lamina propria was found. Concomitantly, a significant decrease in the number of cytoplasmic IgA+ and IgG+ cells was observed. These phenotypic changes may be associated with the cytokine-producing profile (decreased IL-4, IFN-gamma, and IL-10) by lamina propria lymphocytes. At Days 6 and 10 postinfection cytoplasmic IgA+ and IgG+ cell numbers remained. Nevertheless, the production of IL-5 and IL-10 by intraepithelial lymphocytes was higher than the noninfected control values; these changes may be associated with the decreased CD4+ cell numbers. In mesenteric lymphocytes IgG and IgA production in vitro was elevated while no changes were observed in cytokine production except for a significant decrease in IL-5. In conclusion, our results demonstrate that an immunocompetent defense mechanism leading to a successful recovery from C. parvum infection involved changes of T(H1)- or T(H2)-type cytokine production as well as alterations of the lymphocyte subpopulation at mucosal-associated lymphoid tissues.

Animals↗
PubMed1996

Effects of vaccination against different T cell receptors on maintenance of immune function during murine retrovirus infection.

Murine retrovirus infection causes an aberrant stimulation of several subsets of T helper 2 cells identified by their T cell receptors (TCR). C57BL/6 mice were treated with synthetic peptides based upon different human TCR V beta CDR1 sequences following experimental infection with the murine retrovirus. Previous studies established that retrovirally infected mice produced autoantibodies to certain of these peptides, and their administration after infection diminished many of the cytokine abnormalities induced by the virus. This study determined whether the complete 16-mer synthetic peptides modeling the V beta CDR1/FR3 were required, and whether admixture of autoantigenic peptides synergized immune preservation. Treatment with complete TCR pep beta 3 and pep V beta 5.2 peptide alone and combined largely prevented the retrovirus-induced reduction in B and T cell proliferation and Th1 cytokine secretion while suppressing excessive production of Th2 cytokines, which are stimulated by retrovirus infection. Treatment with overlapping short peptides corresponding to the N-terminal 11-mer and C-terminal 12-mer did not significantly prevent the immune dysfunction in retrovirus-infected mice. These data suggest that immune dysfunction and abnormal cytokine production, induced by murine retrovirus infection, were largely prevented by TCR V beta CDR1 peptides, and the complete CDR1 in association with the five residues from FR2 was required.

Amino Acid Sequence↗