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Biomedical subjects

R R Watson

Publications and source records attributed to R R Watson.

At least 163 records · Page 9Linked to original sources
PubMed1989

Beta-carotene stimulates human leukocytes to secrete a novel cytokine.

The effect of beta-carotene on cytokine production by human peripheral blood leukocytes was tested. Beta-carotene stimulated the secretion of a novel cytotoxic cytokine when peripheral blood cells were exposed to carotenoid concentrations between 10(-6) and 10(-10) M. Beta-carotene-treated supernatants caused the cytolysis of four out of the six human tumor cell lines tested. Low level toxicity was also observed when normal diploid fibroblast lines were exposed to beta-carotene-treated leukocyte supernatants. The cytotoxic activity elicited by beta-carotene was found to be distinct from characterized cytokines based on both antisera neutralization and target cell specificity studies. This study demonstrates that beta-carotene can induce human leukocytes to secrete one or more cytokines that can manifest cytotoxic activity against human tumor cells in vitro.

Adjuvants, Immunologic↗
PubMed1989

Osteotoxicity after chronic dietary administration of 13-cis-retinoic acid, retinyl palmitate or selenium in mice exposed to tumor initiation and promotion.

In view of the clinical trials of retinoids as therapeutic agents for premalignant skin lesions, a radiographic study was undertaken to measure skeletal toxicities after chronic dietary administration of retinoids in mice exposed to tumor initiation and promotion. CD-1 mice were initiated with 0.15 moles of 7,12-dimethylbenz[a]anthracene and promoted twice daily with 8 nmoles of 12-0-tetradecanoylphorbol-13-acetate for 23 weeks. Diets were supplemented with 60 IU, 200 IU, or 700 IU of retinyl palmitate (RP) per g diet. After 5 weeks, the 700 IU of RP /g diet was lowered to 350 IU/g diet. Administration of these diets to mice during the 23 weeks of tumor promotion resulted in a 0-fold, 2-fold, or 10-fold increase in bone fractures, respectively. Osteoporotic bone lesions identified on radiographs rose 0-fold, 0-fold, and 10-fold at the respective doses, whereas metaphyseal flares increased 0-fold, 1.4-fold, and 3.6-fold. Bone deformities were augmented 0-fold, 1.8-fold and 2.9-fold at the respective doses. Addition of selenium (2 ppm in the drinking water) did not alter the bone toxicity of RP. 13-cis-retinoic acid (CRA) was less toxic at 700 IU/g diet than was RP at that dose, as evidenced by the death of 12 of 70 mice by the 6th week of dietary RP and no deaths in the 35 mice fed 700 IU CRA/g diet for 23 weeks. CRA at 700 IU/g diet resulted in 3/4 as many osteoporotic bones, 1/3 as many bone fractures, 4/5 as many metaphyseal flares, and a similar number of bone deformities as mice fed 700/350 IU/g diet. At the dose of 200 IU/g food, osteotoxicities were similar in the mice fed diets supplemented with RP and CRA. Thus, the light dose of CRA (700 IU/g diet) was less toxic than the high dose of, RP but at a lower dose (200 IU/g), CRA was as osteotoxic as was RP. Bone fractures in mice exposed to prolonged dietary administration of retinoids was a more sensitive index of retinoid toxicity than was body weight. We have detected osteotoxicity in mice at a total dose of CRA which was about twice the total dose used clinically.

Administration, Oral↗
PubMed1989

The effects on complement component 3 of dietary variation of protein, fat and vitamin E during growth of young mice.

Some studies have shown that nutrition lowers overall immunity to disease. To further elucidate the role of nutrition on immunity, we have investigated the effect on serum Complement C3 by three nutrients, protein, lipid and vitamin E, in BALB/c mice for up to 24 weeks. The group with high dietary vitamin E had slightly higher C3 for the first four months but by the 22nd week was lower than control. The groups receiving high or low protein had, respectively, high or low C3. Injection of thymosin fraction 5 increased the C3, suppressed by the low protein diet. The group on the high lipid diet had high C3 until the 14th week whereupon it declined to control level by the 22nd week. The low lipid diet resulted in low C3 during the early weeks but increased to control level by the 22nd week. We conclude that diet is important to complement mediated immunity of young mice.

Aging↗
PubMed1989

Effect of retinyl palmitate and 13-cis retinoic acid on immune functions in immunodeficient, nude mice.

Nude mice are deficient in thymus gland development and hence lacking functional, mature T-lymphocytes. Weanling nude mice were given various deficient and high retinyl palmitate (RP) or 13-cis retinoic acid (CRA) diets. The high RP (vitamin A) diets stimulated phagocytosis in the absence of mature T-helper cells. However, T-cell dependent mitogens did not cause significant mitogenesis in any group, while LPS, a B-cell mitogen, did. RP had no effect on mitogenesis. NK cell activity was increased only at a very high level of RP, as has been reported with conventional mice. Macrophage production of cytotoxic factors was unaffected by high levels of RP or CRA. Direct cytotoxicity in vitro of tumor cells was increased only at very high RP levels. Thus, mature T cells may be needed for RP to produce normal activation of macrophage, except at very high RP levels.

Animals↗
PubMed1989

Murine models for acquired immune deficiency syndrome.

The mouse has been suggested as a host for comparative studies of several aspects of Human Acquired Immune Deficiency Syndrome (AIDS). Models include studies where part or all of the genome of Human Immunodeficiency Virus (HIV) has been incorporated into murine DNA in living mice. However, the most promising opportunities for study of immunological changes, vaccine development, cofactor involvement in disease, and anti-retroviral and immunostimulatory drug testing involve infection with murine retroviruses which cause many functional changes similar to AIDS. The viruses' effects on immune systems are reviewed with special emphasis. LP-BM5 murine leukemia virus which infects T and B cells, and macrophages. LP-BM5 infection suppresses cell functions while causing polyclonal lymphocyte activation. Murine immunological characterization, availability of inbred mouse strains, economy of using mice versus primates or humans models, and similarity of immune change caused by murine retroviruses compared to those seen in AIDS caused by HIV encourage rapid development of the LP-BM5 murine leukemia model.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Alcohol, cancer, and immunomodulation.

There is a great deal of epidemiological evidence indicating that chronic, excessive alcohol consumption is a major risk factor for cancers in humans. However, the experimental basis for the increased cancer risk associated with alcohol intake is not clear. Since it appears that ethanol alone is not carcinogenic, ethanol effects must be explained in terms of its modifying the actions of other causal agents. Current studies indicate that ethanol and its congeners may act as tumor promoters, thereby enhancing the effect of initiating carcinogens from the environment. Available evidence also shows that ethanol is immunosuppressive. Clearly, cirrhosis due to high, prolonged alcohol intake is an indicator of the immunosuppressive effects of ethanol. It is less clear that more moderate intakes of alcohol could have as profound an effect on immune systems. However, changes do occur yielding alterations in lymphocyte sensitivity to alcohol in vitro and in cell development, as shown by increased NK cell function at low concentrations. Since other conditions, such as cytotoxic drugs which suppress cellular immune functions, are clearly associated with increased cancer risk. It is intriguing to think that prolonged exposure to ethanol-induced immunosuppression may be a cofactor in the promotion of cancer. The tumor promotion may take place via a variety of mechanisms as discussed in this paper, including reduced host defenses by direct effects of ethanol, its metabolites, and/or malnutrition. It may be beneficial to test methods for immunostimulation in prolonged alcohol abusers, where cessation of use is unsuccessful or residual immunosuppression remains, to reduce the risk of development or growth of initiated tumors.

Alcoholism↗
PubMed1989

Comparison of plasma, mononuclear and polymorphonuclear leucocyte vitamin C levels in young and elderly women during depletion and supplementation.

The levels of vitamin C in plasma, mononuclear (MN) and polymorphonuclear (PMN) leucocytes were measured in healthy, free-living, young and elderly women on three occasions over an 8-10-week period: (a) at entry into the study, (b) following 5 weeks of dietary depletion of vitamin C, and (c) following 3 weeks of supplementation with 500 mg of vitamin C per day. The combined mean vitamin C levels (expressed as microgram/10(8) cells) in MN cells were higher than those found in PMN cells at all three times, although the difference was only statistically significant in the depleted state. There were no age-related differences in the levels of vitamin C in plasma, MN or PMN cells at any of the three times. Significant overall differences in vitamin C levels between the entry and depleted and the depleted and supplemented states were observed for plasma and PMN cells but not for MN cells, possibly indicating that plasma and PMN cells are more sensitive indicators of vitamin C status than MN cells. The mean levels of vitamin C found in plasma clearly do 'track' those found in MN and PMN cells. However, attempted correlations between plasma and MN, plasma and PMN, and MN and PMN vitamin C levels at each time proved to be non-significant. In addition, the changes in vitamin C levels from entry to depleted and from depleted to supplemented times were non-significant when comparing plasma to MN and plasma to PMN, whereas the MN vs PMN comparison indicated a significant change in vitamin C levels between the depleted and supplemented states.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Interaction of hemoglobin derivatives with liposomes. Membrane cholesterol protects against the changes of hemoglobin.

Hemoglobin (Hb) was incubated with small unilamellar vesicles of different lipid compositions in physiological or low pH-low ionic strength media, and the alterations in the protein and bilayer structure were analyzed by measuring (i) the sedimentation properties and elution pattern of the vesicles upon gel filtration, (ii) the quenching effect of Hb on the fluorescence of membrane-embedded probes, (iii) the intrinsic fluorescence of Hb, and (iv) the Soret spectra of Hb. The results indicate complex formation between Hb and the membrane, followed by intercalation of the protein into the bilayer. These processes can lead to secondary alterations, including aggregation, peroxidative decomposition of unsaturated fatty acids, unfolding of Hb, oxidation of the heme iron, displacement of the heme relative to globin, and oxidative or nonoxidative deconjugation of the porphyrin ring. Complex formation and intercalation of Hb into the bilayer are primarily due to hydrophobic interaction between the protein and the membrane, whereas displacement of the heme and its nonoxidative deconjugation are elicited by ionic interaction between the heme and negative membrane surface charges. These charges, on the other hand, inhibit the oxidative processes in unsaturated lipid vesicles. The rate and extent of alterations both in the protein and in the membrane show inverse correlation with the stability of the heme-globin linkage. The liquid-crystalline phase state promotes the penetration of Hb into the bilayer, whereas displacement of the heme is most expressed in the case of saturated bilayers in the gel state. Cholesterol inhibits both the hydrophobic and ionic interactions between the protein and bilayer, most remarkably the partition of the heme into negatively charged saturated bilayers. It is suggested that the effects of cholesterol are mediated through changes in membrane fluidity.

Animals↗
PubMed1988

Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS.

Infection by LP-BM5 murine leukemia virus (MuLV) suppressed significantly the percentage of peripheral blood cells showing surface markers for macrophages, lymphocytes and activated lymphoid cells. Chronic administration of a 7% (36% calories) ethanol diet or injection of 1.9 mg/mouse/day of morphine for a 7 day period were followed by 3 week periods of abstinence and then 1 week periods of consumption of 5% ethanol diets or morphine injection to female C57BL/6 mice resulted in changes in the numbers of macrophages and lymphocyte subsets. The number of lymphocytes of various subsets were not significantly changed by the ethanol exposure except those showing activation markers which were reduced. The percentage of peripheral blood cells showing markers for macrophage functions and their activation were significantly reduced after "binge" use of ethanol. Ethanol retarded suppression of cells by retroviral infection. However by 25 weeks of infection there was a 8.6% survival in the ethanol fed mice infected with retrovirus which was much less than virally infected controls (45.0%). Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice. The second and third morphine injection series suppressed lymphocyte T-helper and T-suppressor cells, but not total T cells. However, suppression by morphine was significantly less during retroviral disease than suppression caused by the virus only. At 25 weeks of infection 44.8% of morphine treated, infected mice survived. Morphine treatment also caused deaths such that the survival in morphine treated, retrovirally infected was higher than would have been expected if the death rate in virally infected, and morphine injected animals were combined during combined treatment. Thus these drugs of abuse can modulate peripheral blood lymphoid subsets, suppression caused by retroviral infection, and survival.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Enhanced survival by vitamin A supplementation during a retrovirus infection causing murine AIDS.

Infection by LP-BM5 murine leukemia virus (MuLV) produces an AIDS-like condition in mice. The viral infection suppressed the percentage of peripheral blood cells showing surface markers for macrophages, activated macrophages, T lymphocytes and activated lymphoid cells. High dietary vitamin A (retinyl palmitate) caused increased numbers of activated macrophages. It also increased the percentage of cells with markers for Ia+ cells and macrophages in the retrovirally infected mice compared to infected controls. In uninfected mice retinyl palmitate stimulated the percentage of cells with activated lymphocytes bearing IL-2R, and T cytotoxic cells. These were associated with a retarded death rate during infection with LP-BM5 murine leukemia in C57BL/6 mice. By 25 weeks of infection and 20 weeks of retinyl palmitate supplementation 71.3% survived, while 45.0% virally infected controls survived. The mice also had elevated numbers of B cells measured in the blood after 4 and 8 weeks of dietary treatment. Vitamin A stimulation may play a role in the slower death rate for retrovirally infected mice.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Changes in lymphocyte subsets and macrophage functions from high, short-term dietary ethanol in C57/BL6 mice.

Chronic administration of a diet containing 7% ethanol (36% of total calories) for 8 days to male C57/BL6 mice resulted in significant changes in functioning of macrophages. Peritoneal exudate macrophages from the ethanol-fed mice released more tumor cell cytotoxic materials upon culturing in vitro than cells from controls. However, peritoneal exudate cells continued to respond to exogenous beta carotene in vitro to produce additional cytotoxic materials. Phagocytosis of sheep red blood cells in vitro was suppressed in cells from ethanol treated mice. The number of splenic lymphocytes of various subsets was significantly changed by the ethanol exposure. Total T cells and T suppressor cells were lower, with a significant decrease in B cells containing IgM on their surface. The percentage of spleen cells showing markers for macrophage functions and their activation were significantly reduced. It is concluded that short-term chronic consumption of dietary ethanol, which was sufficient to produce physical dependence, results in significant alterations in lymphocyte subtypes and suppression of some macrophage functions.

Animals↗
PubMed1988

Ethanol, immunomodulation and cancer.

Several major physiological changes or disease states occur more frequently in alcohol abusers or prolonged high users. These include: cancer, immunosuppression, and nutritional deficiencies. They interact with potential enhancement of cancer growth or survival. Clearly alcohol abuse yielding cirrhosis is associated with immunosuppression of cellular immune functions. Severe, prolonged ethanol consumption frequently is associated with one or more nutrient deficiency. Such deficiencies are more common when there are other major problems such as liver or pancreas damage and in prolonged alcohol abusers should influence the host defenses against pathogens and tumors. The amount and frequency of nutritional and immunological deficiencies with "binge" or less severe alcohol abuse is less clear, but animal studies suggest they are frequently present. Clearly, nutrient deficiencies are common in alcohol abusers and could play significant roles in ethanol associated problems including immunosuppression. Data summarized suggest that immunosuppression caused by nutritional deficiencies and/or direct effects of ethanol and its' metabolites on lymphoid cells is a potential component of cancer in alcohol abusers. However the frequent occurrence of nutritional deficiencies, immunosuppression, and certain cancers in severe, prolonged ethanol abusers is an association, not proven cause and effect.

Alcoholism↗
PubMed1987

Immunomodulation by morphine and marijuana.

The immunomodulatory effects of morphine and the active components of marijuana, particularly tetrahydrocannabinol, on various aspects of the host immune parameters include alterations in humoral, cell-mediated and innate immunity. Most studies have shown immunosuppressive effects due to use of these abused substances, although there are reports that they may not produce any deleterious effect and may even enhance some aspects of host immunity. They reduce resistance to cancer growth and microbial pathogens in animals.

Animals↗
PubMed1987

Effects of dietary retinyl palmitate or 13-cis-retinoic acid on the promotion of tumors in mouse skin.

The present study was designed to determine the effects of dietary 13-cis-retinoic acid and retinyl palmitate on mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). Female CD-1 mice were initiated with 150 nmol of 7,12-dimethylbenz(a)anthracene and promoted twice weekly with 8 nmol of TPA. Diets supplemented with retinyl palmitate to yield 60,000 or 200,000 IU or 700,000 for 5 wk followed by 350,000 IU per kg of diet (700,000/350,000) fed to mice during tumor promotion resulted in 9%, 37%, and 65% inhibition of the papilloma yield, respectively, at 21 wk of promotion. Although topical applications of 13-cis-retinoic acid have been almost as effective as retinoic acid in preventing the appearance of mouse skin tumors, dietary 13-cis-retinoic acid at 200,000 or 700,000 IU per kg of diet resulted in no reduction in papilloma yield but did result in a dose-dependent decrease in the tumor burden (weight of tumors per mouse). Therefore, dietary retinyl palmitate yielded a dose-dependent inhibition of the number and weight of tumors promoted by TPA, whereas dietary 13-cis-retinoic acid resulted in a decrease in weight but not in number of tumors promoted by TPA.

Administration, Cutaneous↗