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Biomedical subjects

A C Ross

Publications and source records attributed to A C Ross.

At least 73 records · Page 4Linked to original sources
PubMed1992

Effects of timing and dose of vitamin A on tissue retinol concentrations and antibody production in the previously vitamin A-depleted rats.

The effect of retinol repletion in previously vitamin A-depleted Lewis rats on antibody production to pneumococcal polysaccharide (SSS-III) was studied. When vitamin A-depleted rats were given either 0.35 mumol (0.1 mg) or 5.2 mumol (1.5 mg) retinol, plasma retinol became normal within 8 h. Liver and lymphoid-organ retinol concentrations were normalized by 1 d after repletion with 5.2 mumol but not 0.35 mumol retinol. Antibody production to SSS-III was compared after administering 5.2 mumol retinol either as a divided dose (half given 4 d before and half given on the day of immunization) or as a single dose concurrent with immunization. Vitamin A-depleted rats produced very little SSS-III-specific antibody. The divided dose of retinol consistently restored anti-SSS-III production whereas the single concurrent dose was less effective despite equal effects on tissue retinol concentrations. Interestingly, normalization of plasma retinol was not always a good predictor of the immune response to pneumococcal polysaccharide.

Animals↗
PubMed1991

Vitamin A status regulates hepatic lecithin: retinol acyltransferase activity in rats.

The activity of lecithin:retinol acyltransferase (LRAT) was determined in microsomes from the liver and small intestine of rats with differing vitamin A status. In animals depleted of retinol, as judged by undetectable liver vitamin A stores and low plasma retinol concentrations, hepatic LRAT activity was almost undetectable, whether assayed with retinol bound to cellular retinol-binding protein or solvent-dispersed retinol. In contrast, neither the activity of intestinal LRAT nor that of acyl-CoA:retinol acyltransferase in either liver or intestine differed from that of vitamin A-adequate rats. During the course of vitamin A depletion, liver LRAT activity fell progressively, nearly in parallel to the decrease in plasma retinol concentration. Oral repletion of vitamin A-depleted rats with 0.8 mg of retinol resulted in a very rapid restoration of plasma retinol concentration and full recovery of hepatic LRAT activity within 24 h, together with deposition of retinyl ester in the liver. These data strongly implicate LRAT activity in liver as responsible for the storage of hepatic retinyl esters. Retention of the intestine's capacity to esterify retinol during vitamin A deficiency provides a mechanism for capture of dietary vitamin A, while reduced hepatic LRAT activity may function to redirect retinol in liver from storage to other metabolic pathways.

Acyltransferases↗
PubMed1991

Fatty acyl CoA-dependent and -independent retinol esterification by rat liver and lactating mammary gland microsomes.

Retinol esterification was examined in microsomes from rat liver and lactating mammary gland as a function of the form of retinol substrate, dependence on fatty acyl CoA, and sensitivity to phenylmethylsulfonyl fluoride (PMSF). Retinol bound to cellular retinol-binding protein (CRBP) or dispersed in solvent was esterified in a fatty acyl CoA-independent, PMSF-sensitive reaction, consistent with lecithin:retinol acyltransferase (LRAT) activity. LRAT activity exhibited the same Km (2 microM retinol) between tissues but a higher Vmax in liver as compared to that in mammary gland (47 vs 8 pmol/min/mg microsome protein, respectively). Solvent-dispersed retinol was also esterified in a fatty acyl CoA-dependent, PMSF-resistant reaction, consistent with acyl CoA:retinol acyltransferase (ARAT) activity. Retinol bound to CRBP was not a good substrate for this reaction. ARAT activity displayed a similar Vmax (300 pmol/min/mg microsome protein) between tissues but Km values of 15 and 5 microM for retinol and fatty acyl CoA in mammary gland as compared to 30 and 25 microM, respectively, in the liver. Thus, when substrate was near or below Km, retinol esterification occurred predominantly by LRAT in the liver and ARAT in the mammary gland, respectively. The concentration of CRBP in the cytosol, determined by Western blotting, was approximately 2 microM in the liver but was almost nondetectable in the mammary gland. These data suggest that retinol esterification is regulated via different mechanisms in liver and mammary gland and support a specific role for CRBP in the liver.

Acyl Coenzyme A↗
PubMed1991

Vitamin A status and the immune response to pneumococcal polysaccharide: effects of age and early stages of retinol deficiency in rats.

Production of antibodies to pneumococcal polysaccharide from Streptococcus pneumoniae, type III was determined in young rats at different ages and stages of vitamin A deficiency. At 30, 35 and 45 d of age, serum retinol concentrations of vitamin A-depleted rats were 46, 35 and 9%, respectively, of the serum retinol concentrations of pair-fed controls. Specific antibody production was low at 30 d of age for both vitamin A-depleted rats and control rats. Between 30 and 45 d of age, antibody production increased considerably in normal rats; however, the response of vitamin A-depleted rats was only 22% (P less than or equal to 0.001) that of controls at 35 d of age and 8% that of controls (P less than or equal to 0.001) for 45-d-old rats. Lymphocyte populations were examined by flow cytometry. The numbers of immunoglobulin M- and immunoglobulin D-positive cells changed with age, but not as a result of dietary treatment. The numbers of total T cells or helper and suppressor T cell subsets did not differ with age or with vitamin A status. These studies showed that the normal antibody response to pneumococcal polysaccharide develops rapidly after 30 d of age in the rat, that this antibody response is impaired even during the early stages of vitamin A deficiency, and that impaired antibody production does not seem to be accompanied by quantitative differences in splenic lymphocyte populations.

Aging↗
PubMed1991

Immunological memory to tetanus toxoid is established and maintained in the vitamin A-depleted rat.

We have previously shown that vitamin A deficiency severely impairs the young rat's ability to produce specific antibodies after primary immunization with tetanus toxoid (TT). In the present studies, we asked whether immunologic memory to TT is established even in the vitamin A-depleted animal, and if so, whether such memory can be elicited after subsequent repletion with retinol. Vitamin A-depleted rats produced very low concentrations of TT-specific IgM and IgG antibodies in both the primary and secondary responses; however, the ratios of secondary to primary IgM anti-TT and of IgG anti-TT were normal. When rats were repleted with retinol 1 day after immunization, IgM and IgG anti-TT concentrations in both the primary and secondary responses were at least as great as those of control rats. For rats repleted with retinol 2 days before the booster immunization, secondary IgM and IgG anti-TT concentrations were equal in magnitude to those of vitamin A-sufficient controls. For all groups, the kinetics of the antibody response were similar. We conclude that immunological memory is intact in the vitamin A-depleted animal, as shown by 1) the normal ratio of its secondary to primary antibody responses, 2) the restoration of a quantitatively normal secondary antibody response in previously vitamin A-depleted animals repleted with retinol just before boosting with TT, and 3) a normal class switch from IgM to IgG. Retinol deficiency is also characterized by an abnormal elevation of total plasma IgG, despite the inability of the vitamin A-depleted animal to produce normal quantities of specific antibodies after challenge with antigen.

Animals↗
PubMed1991

Infected arthroplasties.

Infection is potentially the most serious complication of total joint arthroplasty. Over the last 10 years, considerable advances have been made in the diagnosis and management of the infected implant. Modern methods of treatment are successful in up to 90% of cases in the lower limb, and results appear to be improving in the upper limb. This review places recent advances in the context of previous published work in the field.

Elbow Joint↗
PubMed1991

Regulation of retinol uptake and esterification in MCF-7 and HepG2 cells by exogenous fatty acids.

The influence of extracellular fatty acids on the uptake and esterification of [3H]retinol bound to human retinol-binding protein (RBP), to RBP-transthyretin (TTR), or in dispersed form by the human hepatoma, HepG2, and human mammary epithelial carcinoma, MCF-7, cell lines was studied. The esterification of [3H]retinol was significantly increased in cells incubated with myristic, palmitic, stearic oleic, or linoleic acid-albumin complexes and was observed for all forms of [3H]retinol. Enhancement of [3H]retinol uptake was also observed in cells incubated with these fatty acids, but this increase was relatively small for the dispersed form as compared to that observed for [3H]retinol bound to RBP or RBP-TTR. Comparing equal concentrations of the [3H]retinol donors, cell uptake and esterification was greatest from the dispersed form and least from that bound to RBP-TTR. After preincubation of cells with oleate, uptake and esterification of [3H]retinol was increased but not to the extent observed when oleate and [3H]retinol donor were co-incubated. Incubation of cells with oleate resulted in rapid and correlated increases in the rates of [3H]retinol uptake and esterification which persisted until the steady state for [3H]retinol uptake was achieved. Beyond this time, net esterification of [3H]retinol continued in the presence of oleate. This kinetic pattern was observed for all [3H]retinol donors. These effects on [3H]retinol uptake and esterification were dose-dependent as the oleate to albumin ratio was varied from 0.5 to 3.0 and were observed across a physiological concentration range of RBP-3H-retinol. The data indicate that: 1) the fatty acid status of cells is a determinant of retinol uptake and esterification; and 2) the form of retinol presentation to cells is not qualitatively important for these processes.

Animals↗
PubMed1990

Effects of food or nutrient restriction on milk vitamin A transfer and neonatal vitamin A stores in the rat.

We have investigated the effects of maternal diets low in fat or protein, or restricted in total food intake on vitamin A transfer from the dam to her pups. When animals were fed on diets moderately restricted in fat or protein, minimal differences in milk, serum, and liver vitamin A concentrations were observed compared with animals fed on a control diet. In a second study, dams were fed on diets more severely restricted in protein, or fat, or both, or were fed on a control diet equal to 50% of the intake of control rats but containing an equal amount of vitamin A. The quantity of milk obtained from these more severely restricted dams' nipples or the pups' stomachs was greatly reduced; however, there were no differences in milk vitamin A concentration. Body-weight, liver weight, and total liver vitamin A stores of undernourished pups were just half those measured for control pups, although serum vitamin A and serum retinol-binding protein were nearly normal in concentration. We conclude that (a) moderate restrictions in fat or protein in the maternal diet are insufficient to affect transfer of vitamin A to the suckling pup; (b) further dietary restrictions could cause decreased milk production with little change in milk vitamin A concentration and, hence, (c) the neonates' hepatic retinol accumulation during the suckling period is markedly reduced when maternal diets are severely deficient in fat or protein or of normal composition but restricted in amount.

Animals↗
PubMed1990

Vitamin A deficiency decreases natural killer cell activity and interferon production in rats.

We examined the effect of vitamin A deficiency on natural killer (NK) cell activity and interferon (IFN) production. Rats were weaned at 16 or 21 d of age onto semisynthetic diets containing either 0 or 4 micrograms retinol/g diet. At the time of study, retinol-depleted rats had serum vitamin A concentrations less than 7% of those of pair-fed controls. In two studies, rats exhibited no external signs of retinol deficiency, but with further depletion some symptoms were observed. Splenic NK cell activity against chromium-51-labeled YAC-1 cells was significantly decreased in vitamin A-depleted rats (22-80% of values for control rats, depending on the degree of retinol deficiency), regardless of the ratio of effector to target cells used. When vitamin A-depleted rats were repleted orally with retinol, NK cell activity was consistently normalized. To understand the possible mechanisms involved in decreasing NK cell activity, we investigated IFN production by concanavalin A-stimulated spleen cells from vitamin A-depleted, from repleted and from control animals. IFN titers were significantly decreased (22-33% of values for control rats) in supernatants of spleen cell cultures of the vitamin A-depleted rats. Repletion with vitamin A resulted in IFN activities ranging from 80 to 130% of controls. Adding alpha/beta IFN in vitro to the spleen cells of vitamin A-depleted animals increased their NK cell activity. The number of spleen cells reacting with a monoclonal antibody specific for rat NK cells was slightly lower in retinol-depleted rats, but not enough to account for the differences in NK cell and IFN activities. These data suggest that vitamin A deficiency affect the nonspecific arm of the immune system, possibly by altering the functional capacity of cells to produce lymphokines needed for the generation of an appropriate cytolytic response.

Animals↗
PubMed1990

Antibody production in vitamin A-depleted rats is impaired after immunization with bacterial polysaccharide or protein antigens.

Vitamin A nutritional status has been implicated as important in maintaining the integrity of immune functions. We have determined the effect of vitamin A (retinol) depletion on the ability of young animals to produce antibodies after challenge with various bacterial antigens. Male Lewis rats raised on vitamin A-free or adequate diets were immunized either near 40 days of age, before signs of vitamin A deficiency were apparent, or near 47 days of age when symptoms of deficiency were beginning to be manifest. For rats immunized with polysaccharide antigens from Streptococcus pneumoniae or Neisseria meningitidis, antibody production did not exceed 0-19% of the response of control rats. Vitamin A depletion also severely compromised the response to two T cell-dependent antigens, tetanus toxoid and sheep red blood cells. In striking contrast, retinol-depleted rats immunized with lipopolysaccharides from Pseudomonas aeruginosa and Serratia marcesens produced an antibody response indistinguishable from retinol-sufficient animals. These lipopolysaccharides could elicit antibodies in rat pups, whereas the capsular polysaccharide antigens could not. This is consistent with the characteristics of type 1 and type 2 antigens, respectively. These studies indicate that retinol status is an important determinant of the humoral immune response to certain types of antigen and suggest that antibody production to capsular polysaccharides and T cell-dependent antigens is particularly dependent on adequate retinol status.

Aging↗
PubMed1989

Expression in Xenopus oocytes of rat liver mRNA coding for a bile salt-dependent cholesteryl ester hydrolase.

A catalytically active bile salt-dependent cholesteryl ester hydrolase (CEH) was expressed when Xenopus oocytes were injected with rat liver mRNA. The expressed CEH activity was highly dependent on the presence of trihydroxy bile salts (cholate or one of its conjugates); maximum hydrolytic activity was observed in the presence of 10 mM sodium cholate. The expressed CEH was not activated by dihydroxy bile salts (deoxycholate and its conjugates). In the presence of 10 mM sodium cholate, the CEH activity was maximal near pH 7 but was significant between pH 6 and 8. Monospecific immune IgG raised against rat pancreatic CEH completely inhibited the CEH expressed in Xenopus oocytes. Phenylmethylsulfonyl fluoride, a serine enzyme inhibitor, was inhibitory to the expressed CEH activity, whereas p-chloromercuribenzoate (up to 5 mM), a potent thiol-blocking agent, did not significantly inhibit the expressed activity. These experiments clearly demonstrate that the liver contains an mRNA encoding a bile salt-dependent CEH activity and suggest that the uptake of pancreatic enzyme is not necessarily the source of liver CEH as has been speculated.

Animals↗
PubMed1989

Vitamin A depletion and repletion: effects on antibody response to the capsular polysaccharide of Streptococcus pneumoniae, type III (SSS-III).

To determine the ability of young rats to produce antibody against pneumococcal polysaccharide (SSS-III), weaning rats were fed a semipurified diet containing no retinol (A-) or 4 micrograms retinol/g diet (A+). Splenic antibody response specific to SSS-III was 17% (p less than or equal to 0.05) of control for A- Sprague-Dawley rats; similarly, the response of retinol-depleted Lewis rats was 22% (p less than or equal to 0.05) of pair-fed controls. No kinetic differences were observed in the antibody response between A- and control Lewis rats. Retinol depletion more markedly reduced the antibody response of male rats than female rats despite equally low tissue retinol concentrations. For both strains, retinol repletion near the time of immunization normalized antibody production. When male Lewis rats were fed the A- diet longer, the antibody response of A- rats was only 3% of pair-fed controls; repletion again normalized antibody production. Thus, retinol supplementation near the time of immunization can restore the immune response in previously compromised A- rats.

Animals↗