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Biomedical subjects

R R Watson

Publications and source records attributed to R R Watson.

At least 19 recordsLinked to original sources
PubMed2003

Immune control of coxsackievirus-induced cardiopathology.

Retrovirally induced acquired immunodeficiency in humans and mice induces immune dysregulation as well as increased oxidative stress as the disease progresses. Both immunodeficiency and oxidative stress make the host susceptible to the development of heat disease either by physiological changes or by the direct influence of cardiovirulance. Antioxidant supplementation has been shown to influence the onset as well as the degree of cardiopathology due to primary infections or co-infections. An alternative treatment is the use of peptide immunomodulatory therapy to enhance cytokine production, immune cell function and resistance to opportunistic infections. This review compiles our in vivo and in vitro studies on the effects of antioxidant supplementation and peptide therapy on the immune control of coxsackievirus induced cardiopathology in AIDS.

Animals↗
PubMed2002

Changes in mesenteric lymph node T cell phenotype and B and T cell homing properties after murine AIDS infection.

We studied MLN (mesenteric lymph nodes) T cell phenotype and MLN T and B cells homing properties after murine AIDS (acquired immunodeficiency syndrome) infection. Our results showed an increase in the percentage of CD4+ cells expressing CD44, CD54 and LPAM-1. There was also a decrease in the proportion of CD8+ cells but an increase in the percentage of CD8+ CD54+ cells. An increased proportion of CD11b+ (Mac1) cells suggested the recruitment of macrophages. Murine AIDS MLN cells labeled with 125I-UDR migrated back to the MLN but did not preferentially migrate to the ILP (intestinal lamina propria). Simultaneous staining for BRDU and IgA confirmed the inability of murine AIDS MLN cells to home to the ILP. These data indicate that murine AIDS infection altered the mucosal immune system while modifying MLN T cell phenotype and MLN T and B cells migratory properties.

Animals↗
PubMed2001

Solar ultraviolet-induced erythema in human skin and nuclear factor-kappa-B-dependent gene expression in keratinocytes are modulated by a French maritime pine bark extract.

The procyanidin-rich French maritime pine bark extract Pycnogenol (PBE) has been investigated for its effect in protecting human skin against solar UV-simulated light-induced erythema. Twenty-one volunteers were given an oral supplementation of Pycnogenol: 1.10 mg/kg body weight (b. wt.)/d for the first 4 weeks and 1.66 mg/kg b. wt./d for the next 4 weeks. The minimal erythema dose (MED) was measured twice before supplementation (baseline MED), once after the first 4 weeks of supplementation, and a last time at the end of the study. The UVR dose necessary to achieve 1 MED was significantly increased during PBE supplementation. Since the activation of the pro-inflammatory and redox-regulated transcription factor NF-kappaB is thought to play a major role in UVR-induced erythema, the effect of PBE was also investigated in the human keratinocyte cell line HaCaT. PBE, added to the cell culture medium, inhibited UVR-induced NF-kappaB-dependent gene expression in a concentration-dependent manner. However, NF-kappaB-DNA-binding activity was not prevented, suggesting that PBE affects the transactivation capacity of NF-kappaB. These data indicate that oral supplementation of PBE reduces erythema in the skin. Inhibition of NF-kappaB-dependent gene expression by PBE possibly contributes to the observed increase in MED.

Administration, Oral↗
PubMed2001

Differential effects of acute ethanol treatment on cardiac contractile function in young adult and senescent mice.

It is understood that marked biochemical, molecular, and performance alterations occur in cardiovascular tissues related to aging. It is logical, therefore, that differences in the cardiovascular response to ethanol consumption, when comparing younger with older individuals, may exist. We compared the left ventricular function of 6- and 15-month-old (senescent) mice and 16-month-old (senescent) inducible nitric oxide synthase knockout mice (n=7 each) before and subsequent to acute treatment with 60% ethanol (2 g/kg, i.p.). A Millar 1.4 Fr conductance/micromanometer catheter was placed into the left ventricle of the mice for acquisition of pressure-volume loops. Heart contractile functions were significantly decreased in the senescent group, compared with findings in the younger mice. Subsequent to ethanol treatment, the younger mice showed a significant reduction in cardiac function, with a 28% decrease in cardiac index, a 29% decrease in end-systolic elastance, and a 16% decrease in preload recruitable stroke work (P<.01). Conversely, the senescent mice showed significantly increased contractile function, with a 40% increase in end-systolic elastance (P<.01) and a 19% increase in preload recruitable stroke work (P<.05). The myocardial cyclic guanosine monophosphate levels were significantly higher in the older group (P<.002), and subsequent to ethanol treatment, they were decreased by 68.5% (P<.001). Northern blot analysis demonstrated inducible nitric oxide synthase message only in senescent myocardial tissues. Moreover, the cardiac function of senescent inducible nitric oxide synthase knockout mice was comparable with that of young mice, and after ethanol treatment, cardiac function decreased significantly, just as that for young mice did, with a 26% decrease in cardiac index (P<.05) and a 23% decrease in preload recruitable stroke work (P<.01). It was concluded that the differential cardiovascular function and response to acute ethanol

Aging↗
PubMed2001

Anti-inflammatory effects of theophylline: modulation of immune functions during murine leukemia virus infection.

LP-BM5 murine leukemia virus induces immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dsyregulation. Theophylline induces apoptosis of leukemia cells in humans. Therefore the effects of theophylline on immune dysfunction in a murine model of leukemia were investigated. C57BL/6 mice consumed drinking water containing 0.3% theophylline beginning 2 weeks after murine retrovirus infection for 4 months. Theophylline largely prevented the retrovirus induced splenomagaly, lymphodenopathy, reduction in B and T cell proliferation, and suppression of Thl cytokines (IL-2) secretion. It also suppressed Th2 cytokine (IL-4, TNF-alpha, and IL-10) production, which was otherwise stimulated by retrovirus infection. These data suggest that immune dysfunction, induced by murine retrovirus infection, was largely prevented by theophylline treatment.

Animals↗
PubMed2001

In vitro response of v-Ha-ras transgenic mouse lymphocytes after in vivo treatment with alcohol.

Oncomouse is a transgenic mouse carrying an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus promoter. The objective of this paper was to learn if the in vitro secretion of IL-2 and IFN-gamma and the release of sIL-2R by Oncomice splenocytes and thymocytes depended on the presence of the oncogene product, on the in vivo pretreatment with alcohol, or on the in vitro treatment with cocaine or morphine. Oncomice thymocytes released less sIL-2R than FVB thymocytes. Alcohol did not increase sIL-2R release in Oncomice as it did in FVB mice thymocytes. Oncomice thymocytes secreted more IFN-gamma than FVB thymocytes, their secretion was downregulated by in vivo treatment with alcohol, while it was upregulated in FVB thymocytes. IFN-gamma secretion was lower in Oncomice splenocytes from animals receiving alcohol. Oncomice thymocytes and splenocytes responded in a nearly opposite fashion to their FVB counterparts. Therefore, the in vivo treatment with alcohol modified the in vitro response to cocaine or morphine in an oncogene-dependent and -independent manner. Hence, our results further emphasize the role of v-Ha-ras oncogene in defining the host immune response, and of alcohol in modulating such response.

Animals↗
PubMed2001

In vitro response of v-Ha-ras transgenic mouse lymphocytes after in vivo treatment with cocaine.

Oncomouse is a transgenic mouse carrying an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus promoter. The objective of this paper was to learn if the in vitro secretion of IL-2 and IFN-gamma and the release of sIL-2R by Oncomice spleen and thymus cells depended on the presence of the oncogene product, on the in vivo pretreatment with cocaine, or on the in vitro treatment with cocaine or morphine. Oncomice thymocytes from different experimental groups released less sIL-2R than FVB thymocytes. Oncomice thymocytes secreted more IFN-gamma than FVB thymocytes. Oncomice thymocytes cultured in the presence of Con A and cocaine showed a diminished release of sIL-2R and a lower secretion of IFN-gamma, a phenomenon not observed in FVB thymocytes. IFN-gamma secretion was lower in Oncomice splenocytes. In general, Oncomice thymocytes and splenocytes responded in a nearly opposite fashion to their FVB counterparts. In this study, the in vitro response to mitogens, cocaine or morphine depended on genetic background and not on the in vivo pretreatment with cocaine. Our results emphasize the role of the v-Ha-ras oncogene in defining the host immune response.

Animals↗
PubMed2001

Antioxidant supplementation prevents oxidation and inflammatory responses induced by sidestream cigarette smoke in old mice.

Sidestream cigarette smoke (SSCS) makes up about 85% of significantly toxic environmental tobacco smoke (ETS). Reactive oxygen species (ROS) in SSCS play an important role in the pathogenesis of a wide range of diseases. Interleukin-6 is a pro-inflammatory cytokine and is closely linked with pathology in cardiovascular disease and conditions that have an inflammatory base. Exposure to SSCS through a burning cigarette for 30 min/day, 5 days a week, for 4 months increased interleukin-6 production in spleen and lipid peroxide level in mouse liver. Our findings suggest that ROS induced by SSCS will promote hepatic lipid peroxidation and may also contribute to an increase in interleukin-6 cytokine production. Multiple antioxidants given as a dietary supplement significantly normalized interleukin-6 cytokine production and prevented hepatic lipid peroxidation. We conclude that the SSCS in moderate intake levels increased oxidation and promoted inflammatory cytokine interleukin-6 production, whereas antioxidants prevented these changes.

Aging↗
PubMed2001

T-cell receptor-derived peptides in immunoregulation and therapy of retrovirally induced immunosuppression.

Retrovirally infected humans and mice showed progressive acquired immunodeficiency accompanied by the production of elevated levels of autoantibodies directed against T-cell receptor variable-domain epitopes. Epitope mapping analyses indicated that a major determinant recognized was defined by a 16-mer peptide containing the entire CDR1 segment and part of the FR2 region of human Vbeta8, and that both species showed reactivity to the same sequence. Either prophylactic or therapeutic administration of this peptide to retrovirus-infected C57/BL/6 mice normalized the balance of T(H)1- and T(H)2-type helper activity and restored the resistance to infection by the opportunistic parasite Cryptosporidium. Administration of the peptide did not generate significantly increased levels of autoantibody, but had a profound effect on T-cell activity as well as other aspects of inflammation, including NK-cell activity. A 16-mer derived from the Jbeta sequence showed similar functional effects on T cells from retrovirus-infected mice. Direct binding of the VbetaCDR1 peptide to recombinant TCR Valpha/Vbeta constructs, as well as to IgM natural autoantibodies, suggests that the cell surface receptor for the peptide is the alpha/beta TCR on T cells and surface IgM in B cells. The Vbeta CDR1 peptide stimulated division of murine splenocytes in vitro, stimulated the production of the T(H)1 cytokine IL-2, and synergized with the T-cell mitogen concanavalin A in proliferation and IL-2 production. These studies indicate that administration of peptides derived from T-cell receptor variable domains to animals immunosuppressed as a result of retroviral infection has a profound immunomodulatory effect enhancing overall T-cell functional capacity, particularly with respect to the cytokine production characteristic of T(H)1-type cells. Our studies are interpreted in the context of other recent investigations of immunomodulatory peptides.

Amino Acid Sequence↗
PubMed2000

Cocaine injection and coxsackievirus B3 infection increase heart disease during murine AIDS.

Coxsackievirus initiates myocarditis especially in the immunologically deficient or immature. To test whether Coxsackievirus B3 (CVB3) induced pronounced cardiomyopathy during severe immune dysfunction of murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3. Some were also injected daily with cocaine hydrochloride in 0.9% saline solution (30 mg/kg) intraperitoneally, because cocaine also suppresses cellular immune response. Heart tissue was analyzed histopathologically. Mice experiencing concurrent retrovirus and Coxsackievirus infection had a high degree of cardiac lesions consistent with myopathy compared with findings in uninfected animals (p <.05). Cocaine injection during murine retrovirus infection greatly exacerbated the pathogenesis of Coxsackievirus infection. C57BL/6 mice, essentially resistant to Coxsackievirus-induced cardiomyopathy, became susceptible during the immune dysfunction in murine AIDS. This suggests that retrovirus infection causes conditions favoring Coxsackie-induced cardiac lesions. Interleukin (IL)-2 and IL-4 expression by splenocytes from the dually infected retrovirus and Coxsackievirus group showed no significant differences when the animals were also cocaine treated. However tumor necrosis factor TNF-alpha production was significantly decreased in dually infected retrovirus + Coxsackievirus mice treated with cocaine, compared with findings in various controls (p <.05).

Animals↗
PubMed2000

Carotenoid supplementation reduces erythema in human skin after simulated solar radiation exposure.

Excessive exposure to solar radiation, especially ultraviolet A (UVA: 320-400 nm) and ultraviolet B (UVB: 290-320 nm) radiation, may induce UV-carcinogenesis and erythema in the skin. Although the protective effects of carotenoids against skin lesions are still unclear, beta-carotene has been proposed as an oral sun protectant. The purpose of this study was to determine the magnitude of the protective effects of oral alpha- and beta-carotene supplementation for 24 weeks on UVA- and UVB-induced erythema in humans. While being exposed to UVA and UVB radiation, 22 subjects (11 men and 11 women) were supplemented with natural carotenoids for 24 weeks. Each day for the first 8 weeks, subjects were given 30 mg of natural carotenoids containing 29.4 mg of beta-carotene, 0.36 mg of alpha-carotene, and traces of other carotenoids in vegetable oil. The natural carotenoid dose was progressively raised by 30-mg increments, at every 8 weeks, from 30 mg to 90 mg. Small areas (1 cm2) of the skin were exposed to increasing doses of UV light (16-42 mJ/cm2) to determine the minimal erythema dose (MED). MED was defined as a uniform pink color with well-defined borders. MED readings were obtained by visual inspection 24 hr postirradiation. Blood samples taken during supplementation were used to determine alpha- and beta-carotene serum levels and for a lipid peroxidation analysis. During natural carotenoid supplementation, the MED of solar simulator radiation increased significantly (P<0.05). After 24 weeks of supplementation, serum beta-carotene levels were increased from 0.22 microg/ml (95% CI; 0.16-0.27) to 1.72 microg/ml (95% CI;1.61-1.83). Similarly, alpha-carotene serum levels increased from 0.07 microg/ml (95% CI;0.048-0.092) to 0.36 microg/ml (95% CI; 0.32-0.40). Serum lipid peroxidation was significantly (P<0.05) inhibited in a dose-dependent manner during natural carotenoid supplementation. The present data suggest that supplementation with natural carotenoids may partially protect human skin from UVA- and UVB-induced erythema, although the magnitude of the protective effect is modest.

Adolescent↗
PubMed2000

Behavioral and immune changes in v-Ha-ras transgenic mice.

Transgenic mice (Oncomice) with an activated v-Ha-ras oncogene under the control of the mouse mammary tumor virus promoter develop mammary tumors. We wondered if the expression of the v-Ha-ras oncogene product would induce changes in mice behavioral activity, that could be associated with alterations in their immune system. Behavior was evaluated in an open field study considering line crossings and rears. Oncomice consistently showed less activity than FVB mice. Lieber-DeCarli diet decreased both types of activity in both strains. Cocaine treatment increased line crossings in both strains. Oncomice spleen and thymus cell supernatants contained higher levels of IL-2. Oncomice serum had higher levels of IL-1alpha. Our results suggest a direct association between higher levels of IL-1alpha and lower open field activity. Therefore, we can infer that the increased level of IL-1alpha found in Oncomice, could have a key role in oncogene induced immune and behavioral changes, and could be a requirement to facilitate its transforming activity.

Animals↗
PubMed2000

Senescent ventricular dysfunction: issues related to cardiopulmonary bypass.

The mean age of the open-heart surgical patient is increasing every year. Therefore, it is logical to define the aging-related changes in cardiovascular function. This study set forth to define the major molecular and performance alterations that occur in the left ventricle related to advanced aging or senescence. In the human, vascular pathologies usually accompany left ventricular dysfunction. The aim of this study was to associate the altered left ventricular mechanics with molecular pathways in mice who lacked these associated vascular pathologies. This study compared the left ventricular function of two groups of mice (N = 20 each), 6 months old and 16 months old (senescent). The mice were anesthetized with urethane and alpha-chloralose, and a Millar 1.4 Fr. conductance micromanometer catheter was placed into the left ventricle for acquisition of pressure-volume loops. Heart tissues were collected immediately for analysis of cGMP concentrations. The cardiac index, preload recruitable stroke work, and the slope (Ees) of the end-systolic pressure volume relationship were significantly less in the senescent group compared to the young mice. It was concluded that the aged heart has significantly reduced systolic and diastolic dysfunction compared to the young heart function and that this dysfunction may be related to pathways leading to increased myocardial cGMP concentrations.

Age Factors↗
PubMed1999

Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol.

The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet function in humans. Cigarette smoking increased heart rate and blood pressure. These increases were not influenced by oral consumption of Pycnogenol or Aspirin just before smoking. However, increased platelet reactivity yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American smokers, blood pressure increased after smoking. It was unchanged after intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19 American smokers, increased platelet aggregation was more significantly reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation. This study showed that a single, high dose, 200 mg Pycnogenol, remained effective for over 6 days against smoking-induced platelet aggregation. Smoking increased platelet aggregation that was prevented after administration of 500 mg Aspirin and 125 mg Pycnogenol. Thus, smoking-induced enhanced platelet aggregation was inhibited by 500 mg Aspirin as well as by a lower range of 100-125 mg Pycnogenol. Aspirin significantly (p<0.001) increased bleeding time from 167 to 236 seconds while Pycnogenol did not. These observations suggest an advantageous risk-benefit ratio for Pycnogenol.

Adult↗
PubMed1999

Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection.

Female C57BL/6 mice infected with the LP-BM5 leukaemia retrovirus developed murine acquired immune-deficiency syndrome (AIDS). Dehydroepiandrosterone (DHEA) and melatonin (MLT) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 (Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B- and T-cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus-induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.

Animals↗
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↗