Biomedical subjects

A Brouwer

Publications and source records attributed to A Brouwer.

At least 145 records · Page 8Linked to original sources

PubMed1988

Distributions of retinoids, retinoid-binding proteins and related parameters in different types of liver cells isolated from young and old rats.

The levels of retinoids, retinol-binding protein, cellular retinol-binding protein, cellular retinoic-acid-binding protein, transthyretin and the activities of retinyl palmitate hydrolase and cholesteryl oleate hydrolase were determined in purified parenchymal, fat-storing, endothelial and Kupffer cell preparations, and in liver homogenates from young adult (6-month-old) and old (36-month-old) rats. Retinoid levels were also determined in the plasma from young and old rats. Retinoid contents were determined by HPLC. The binding proteins and transthyretin were measured by specific radioimmunoassays; retinyl palmitate and cholesterol oleate hydrolases were measured by sensitive microassays. The retinoid content of both the liver homogenates and of the fat-storing, and parenchymal cell preparations increased between 6 months and 36 months of age. The cellular distribution of retinoids was similar for the two age groups analyzed with the fat-storing cells being the main retinoid storage sites in the rat liver. Concentrations of retinol-binding protein and transthyretin were high in parenchymal cell preparations. Cellular retinol-binding protein was enriched both in parenchymal and in fat-storing cell preparations; the highest concentrations of cellular retinoic-acid-binding protein were present in fat-storing cell preparations. No major differences were observed between the two age groups in the cellular concentrations and distributions of any of these binding proteins. High activity of cholesterol oleate hydrolase was measured in parenchymal and in Kupffer cell preparations; endothelial cell preparations also contained considerable activities. The distribution of this activity over the various cell types reflects their role in lipoprotein metabolism. Retinyl palmitate hydrolase activity was specifically enriched in parenchymal and in fat-storing cell preparations, consistent with the roles of these cells in retinoid metabolism. No major differences were observed between the two age groups in the cellular distributions of the two hydrolase activities. This study indicates that no major changes occur in the retinoid-related parameters analyzed with age, suggesting that rat liver retinoid metabolism does not change dramatically with age and that retinoid homeostasis is maintained.

Aging↗

PubMed1988

Synergism between ethanol and carbon tetrachloride in the generation of liver fibrosis.

In this study, alcohol-induced histological lesions in a short-term experimental rat model were compared with those characteristic of human alcoholic liver disease. In the rat model used, pretreatment with carbon tetrachloride (CCl4) for 6 weeks was employed possibly to sensitize the liver for the effects of alcohol and shorten the time of induction of alcoholic liver disease. After 6 weeks of CCl4 treatment, subsequent maintenance on drinking water containing up to 10 per cent alcohol for 7 weeks potentiated liver fibroplasia as compared with non-alcohol-treated rats. However, steatosis and alcoholic hepatitis, as histological evidence for alcoholic liver disease as seen in humans, were not observed. In non-CCl4-pretreated control animals, alcohol administration had no effect on liver histology. It can be concluded that in the model used, CCl4 pretreatment sensitizes the liver to increase collagen deposition following alcohol administration, but not to steatosis or alcoholic hepatitis as seen in human alcoholic liver disease. In this experimental set-up, direct metabolic interaction of CCl4 with alcohol as a cause of the increased fibroplasia can be excluded.

Animals↗

PubMed1988

Study on the mechanism of interference of 3,4,3',4'-tetrachlorobiphenyl with the plasma retinol-binding proteins in rodents.

The mechanism of plasma retinol reduction in rodents by 3,4,3',4'-tetrachlorobiphenyl (TCB) was investigated by radioimmunochemical analysis of the amounts of circulating and hepatic retinol-binding protein (RBP) and transthyretin (TTR) in exposed and control animals. Plasma RBP concentrations were markedly reduced in C57BL/Rij mice (50%) at 4 days, in DBA/2 mice (37-41%) at 4 and 8 days, and in Sprague-Dawley rats (58%) at 2 days after exposure to TCB. These reductions paralleled the time course of reduction of plasma retinol after exposure to TCB. Hepatic RBP concentrations were somewhat increased in TCB-treated animals, especially in the C57BL/Rij mouse and Sprague-Dawley rat. However, the release of hepatic RBP into the circulation was not blocked by TCB treatment, as analysed in vitamin A deficient rats. In addition, the amount of plasma TTR was in the normal range in TCB-treated rats. The dissociation constants of the RBP-TTR complex as analysed by polarization of fluorescence appeared to be significantly increased (from 0.5 x 10(-7) M-1 to 2.4 x 10(-7) M-1) in the presence of a TCB metabolite, isolated from plasma of TCB-treated rats. In addition, the estimated number of binding sites for RBP on the TTR molecule was reduced (from 2.8 to 1.7 sites) upon treatment of TTR with the TCB metabolite. These data support the hypothesis that plasma retinol reduction by TCB might result from a weakening of the RBP-TTR complex, in the presence of the TCB metabolite bound to the TTR.

Animals↗

PubMed1988

Age-dependent accumulation of alkali-labile sites in DNA of post-mitotic but not in that of mitotic rat liver cells.

The amount of spontaneous damage in the DNA of rat liver cells was measured by using the alkaline elution assay. An age-related increase of approximately 700 detectable alkali-labile sites (80%) was found for rat parenchymal liver cells; cells from 6-month-old rats contained approximately 900 alkali-labile sites per cell while cells from 36-month-old rats contained approximately 1600 alkali-labile sites. In contrast to the situation with the postmitotic parenchymal liver cells, no age-related increase in the number of alkali-labile sites was found for the non-parenchymal liver cell fraction, which has a higher mitotic activity. These results support the hypothesis that aging takes place predominantly in postmitotic cells.

Aging↗

PubMed1988

Comparison of the production of eicosanoids by human and rat peritoneal macrophages and rat Kupffer cells.

Human and rat peritoneal macrophages and rat Kupffer cells were labelled with [1-14C] arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by high pressure liquid chromatography (HPLC). Human peritoneal macrophages formed especially leukotriene B4, 5-hydroxy-6,8,11,14 eicosatetraenoic acid and small amounts of leukotriene C4 and thromboxane B2, 12-hydroxy-5,8,10 heptadecatrienoic acid and 6-keto-prostaglandin F1 alpha, whereas rat peritoneal macrophages mainly produced cyclooxygenase products and in particular thromboxane B2 and 12-hydroxy-5,8,10 heptadecatrienoic acid. Rat Kupffer cells synthesized mainly cyclooxygenase products such as prostaglandin F2 alpha, prostaglandin D2 and prostaglandin E2. These results indicate that the profile of eicosanoids production by macrophages is dependent both on the species and on the tissue from which the macrophage is derived.

Animals↗

PubMed1988

Alterations in retinoid concentrations in several extrahepatic organs of rats by 3,4,3',4'-tetrachlorobiphenyl.

In this study, the effect of polychlorinated biphenyls on retinoid homeostasis was investigated in Sprague-Dawley rats, by analysing [3H]retinoid concentrations in peripheral organs, following exposure to 3,4,3',4'-tetrachlorobiphenyl (TCB). The rats were rendered retinoid-deficient through dietary restriction, followed by dietary supplementation with [3H]retinol for 14 days, in order to facilitate determination of retinoid concentrations in various tissues. At day 7 of [3H]retinol supplementation the rats were exposed to a single i.p. dose of 15 mg TCB dissolved in corn oil/kg body weight. In corn oil-treated control rats, the highest concentrations of [3H]retinoid radioactivity, consisting mainly of retinol and several retinylesters, were obtained in the liver (greater than 10(6) cpm/g,), followed by the kidney and the lung, while only minor concentrations were found in skin and heart. Exposure to TCB resulted in a significant reduction of both retinol and retinylester concentrations in the liver (to 25% of controls) and the lung (to 44% of controls), while in the heart a reduction of retinol to 35% of controls was observed. No significant alterations in retinoid concentrations were observed in the skin and kidney. It is suggested that the reductions in retinoid concentrations might contribute to the toxicological alterations reported in these organs upon exposure to TCB.

Animals↗

PubMed1988

Chronic toxicity of 3,4,3',4'-tetrachlorobiphenyl in the marmoset monkey (Callithrix jacchus).

Cotton top marmoset monkeys (Callithrix jacchus) were orally dosed with 3, 1, 0.1 or 0 mg 3,4,3',4'-tetrachlorobiphenyl (TCB)/kg body weight twice per week for 18-23 weeks. Severe toxicity occurred in the highest dose group. Clinical signs of toxicity were a rapid decrease in body weight, alopecia, abnormal nail growth, nodular enlargement of the nipple area and scaly skin. Haematological analysis of peripheral blood revealed mild leukocytosis and anemia. Biochemical alterations observed were elevated triglyceride levels and cholesterol levels. Histopathology revealed dose dependent changes in a variety of tissues. Squamous metaplasia was found in skin and adnexa as well as in salivary glands. In the stomach, parietal cells were decreased and mucus producing cells were increased. The duodenal mucosa was hyperplastic. Ovaries showed an absence of corpora lutea. In the thyroid follicular cell hyperplasia and hypertrophy were noted. Toxicity was less severe in marmoset monkeys dosed with 1 mg TCB/kg, while minor toxic effects were observed in the animals dosed with 0.1 mg TCB/kg. The marmoset monkey appears to be less sensitive to the toxic action of TCB than the rhesus monkey. The pattern of histological and biochemical changes induced by TCB in marmoset monkeys is comparable to that described in humans and in other primate species exposed to PCBs. The marmoset monkey model may be valuable for investigations on human-related toxicity of PCBs.

Animals↗

PubMed1988

Effects of 3,4,3',4'-tetrachlorobiphenyl on thyroid function and histology in marmoset monkeys.

Marmoset monkeys were treated with oral doses of 0.1, 1 or 3 mg 3,4,3',4'-tetrachlorobiphenyl (TCB) per kg body weight 2 times a week for 18-23 weeks. Histological examination of the thyroid gland revealed a dose-dependent follicular cell hyperplasia. The morphological changes were associated with various disturbances of thyroid function. The average serum thyroxine (T4) levels during the treatment period were reduced by more than 99% in monkeys receiving 3 mg TCB/kg, by 81% in marmosets on a dose of 1 mg TCB/kg, and by 35% with 0.1 mg TCB/kg. The reduction in serum T4 levels was established from the earliest time point (2 weeks) throughout the whole dosing period (18-23 weeks). The reduction in serum T4 levels was reflected in decreased free thyroxine (FT4) index in the 1 and 3 mg TCB/kg dose groups. Serum triiodothyronine (T3) levels were lowered in the 3 mg/kg dose group already after 2 weeks. Evidence for decreased binding to carrier proteins is suggested by increased T3 resin uptake in the highest dose group. Levels of thyrotropin (TSH) were increased in the highest dose group as a feedback response to the dramatically reduced serum T4 levels.

Animals↗

PubMed1988

Isolation and culture of Kupffer cells from human liver. Ultrastructure, endocytosis and prostaglandin synthesis.

Kupffer cells and other sinusoidal cells were isolated after perfusion and incubation with pronase and collagenase of pieces of liver tissue obtained from organ donors. The resulting cell preparations contained endothelial cells, Kupffer cells and fat-storing cells as well as considerable numbers of leucocytes. Attempts to purify the different sinusoidal cell types by density centrifugation and centrifugal elutriation were successful only for Kupffer cells. Kupffer cells, in contrast to endothelial cells and fat-storing cells, could be kept in maintenance culture for at least 5 days. Cultured Kupffer cells were active in the endocytosis of foreign substances, such as colloidal carbon, latex beads, horseradish peroxidase and bacterial endotoxin. The cultured Kupffer cells synthesized and secreted considerable amounts of prostaglandins PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. The production of prostaglandins was influenced by the presence of Escherichia coli endotoxin.

Cells, Cultured↗

PubMed1987

Effects of acute graft-vs-host disease on the liver of the brown Norway rat.

In this study we examined the effects of acute graft-vs-host disease (aGVHD) on the Brown Norway (BN) rat liver. When clinical signs of the disease appeared, rats were inoculated with fluorescent latex beads and 30 min later nonparenchymal cells were isolated from the liver. The cells were then analyzed via flow cytometry, histochemistry, and electron microscopy. Flow cytometry demonstrated that 58% of the cells from the 80 ml/min elutriation fraction (normally rich in Kupffer cells) of the non-GVHD liver had high fluorescence intensity compared to 8% in rats with aGVHD. Determination of the cellular composition of the various fractions with electron microscopy confirmed flow cytometry observations in that only 9% of the 80 ml/min elutriation fraction of GVHD livers had peroxidase-positive rough ER and the morphological appearance of macrophages as compared to 60% in the non-GVHD liver. The low percentage of fluorescent-positive Kupffer cells in the 80 ml/min elutriation fraction of the GVHD liver is attributed to a massive lymphocytic invasion of the liver and not necessarily to a defect in the mononuclear phagocyte system.

Acute Disease↗

PubMed1987

Liver parenchymal cells differ from the fat-storing cells in their lipid composition.

The neutral lipid and phospholipid compositions of purified sinusoidal (fat-storing, endothelial and Kupffer) cells, parenchymal cells and liver homogenates were determined by thin layer chromatography. In addition, the retinoid content of the same purified cell populations was determined by high performance liquid chromatography. From each cell type, both a lipid droplet fraction and a pellet fraction (containing the majority of the remaining cell organelles) were prepared by differential centrifugation. Electron microscopic analysis showed that lipid droplets isolated from fat-storing cells were larger (up to 8 microns) than those isolated from parenchymal cells (up to 2.5 microns). Moreover, the parenchymal lipid droplets seemed to be surrounded by a membranous structure, while the fat-storing lipid droplets seemed not to be. Both fat-storing and parenchymal cells contained high concentrations of neutral lipids, 57.9 micrograms and 71.0 micrograms/10(6) cells, respectively, while endothelial and Kupffer cells contained only 8.6 micrograms and 13.8 micrograms/10(6) cells of neutral lipids, respectively. Sixty-five percent of fat-storing cell lipid droplet fractions comprised esters of retinol and cholesterol. This combined ester fraction contained mainly retinyl esters. In addition, considerable quantities (20%) of triglycerides were present. Parenchymal cell lipid droplet fractions comprised triglycerides (62%) and cholesteryl esters (up to 30%). The pellet fractions prepared from all four cell types consisted mainly of cholesterol (41-67%) and free fatty acids (20-28%). The phospholipid content was much higher in parenchymal cells than in the sinusoidal liver cell types. The relative proportions of the four major phospholipid classes were comparable in all liver cell types analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Endotoxin-induced liver injury in aged and subacutely hypervitaminotic A rats.

The plasma disappearance of endotoxin and endotoxin-induced hepatic injury were studied in two rat models: the aging rat and the subacutely hypervitaminotic A rat. The choice of these models was based on their respective association with a decreased or increased Kupffer cell endocytic activity. The half-life of endotoxin (E. coli O26: B6, phenol extracted) in plasma was significantly prolonged in aged rats as measured by both the Limulus assay (t1/2 = 2.1 +/- 0.1 h in 3-6-month-old, and 3.3 +/- 0.3 h in 24-36-month-old rats) and 51Cr-labeled endotoxin radioactivity assay (t1/2 = 5.3 +/- 0.3 h in 3-6-month old and 7.7 +/- 0.6 h in 24 36-month-old rats). In subacute hypervitaminosis A, the half-life of endotoxin was significantly decreased in the Limulus assay (t1/2 = 2.1 +/- 0.1 h in 3-6-month old and 1.4 +/- 0.2 h in subacutely hypervitaminotic A rats), but not in the radioactivity assay (t1/2 = 5.3 +/- 0.3 h in 3-6-month-old and 5.0 +/- 0.4 h in subacutely hypervitaminotic A rats). Hundred percent mortality was observed at a dose of 2 mg endotoxin/100 g body wt. in old rats, but not in young rats. Only 1 of 7 young subacutely hypervitaminotic A rats died following injection of this dose of endotoxin. The dose of endotoxin which caused only minimal parenchymal liver cell injury in young rats induced substantial parenchymal cell injury in old rats and subacutely hypervitaminotic A rats as determined by both histological and biochemical parameters. It is concluded that some basic characteristics of experimental animals, such as age and nutritional status, can dramatically influence the sensitivity to endotoxin and this is not necessarily correlated with the rate of endotoxin clearance.

Aging↗

PubMed1986

Binding of a metabolite of 3,4,3',4'-tetrachlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin.

The mechanism of serum vitamin A reduction by polychlorinated biphenyls was studied at the level of the plasma transport protein system for vitamin A. Analysis of [3H]retinol-labeled serum proteins by polyacrylamide gel electrophoresis (PAGE) showed association of retinol with two proteins that were identified as retinol binding protein (RBP) and the RBP complex with transthyretin (TTR). The amount of [3H]retinol radioactivity in the serum as well as the label associated with the binding proteins was strongly reduced by 3,4,3',4'-tetrachlorobiphenyl (TCB). A possible interaction of TCB with the retinol binding proteins was investigated, using radiolabeled TCB. Analysis of the plasma proteins by PAGE revealed the presence of four peaks of 3H-TCB label, the major ones being associated with lipoproteins and TTR. No 3H-TCB radioactivity was found in the region of the gel where RBP or the RBP-TTR complex was located. HPLC analysis of the radioactive compound associated with TTR showed the presence of a metabolite of TCB, rather than the parent compound. These data indicate a direct interaction of a metabolite of TCB with TTR leading to an inhibition of formation of the serum transport protein complex carrying both retinol and thyroxin. A model is proposed, which may explain certain characteristic toxicopathological lesions observed in species exposed to polychlorinated biphenyls and related compounds (TCDD, PBBs, etc.).

Animals↗

PubMed1986

Cellular aging of the reticuloendothelial system.

The reticuloendothelial system (RES) consists of macrophages and other endocytic cells which contribute to natural resistance to disease agents. The RES has been implicated as being partly responsible for the observed age-related decrease in resistance to pathogenic microorganisms in man and experimental animals. It is largely unknown to what extent age-related deficiencies in specific functions of reticuloendothelial cells contribute to the decrease of RES functions. This study describes experiments focussed on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of potentially harmful substances from the circulation. The age-related changes in the clearance of a RES test colloid (heat-aggregated colloidal albumin (CA)) and of E. coli endotoxin were investigated using female BN/BiRij rats of various age groups. With CA, studies were performed on the plasma clearance and on the endocytic capacity of whole liver and of Kupffer and endothelial cells in vivo, as well as on the kinetics of endocytosis by Kupffer cells in culture. The results showed that the plasma disappearance of endotoxin was significantly prolonged in rats of 24 and 36 months resulting in an increase in half-life of about 50% as compared to young rats. The plasma clearance of CA, the uptake by the liver and the endocytosis by endothelial cells were unchanged with age. In contrast, an age-related decrease in endocytic capacity was observed in Kupffer cells in vivo and in Kupffer cells which were isolated from rats of various ages and maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1985

Electron microscopic studies on the interaction of rat Kupffer cells and Plasmodium berghei sporozoites.

The interactions between Plasmodium berghei sporozoites and Kupffer cells in rat liver were studied by transmission electron microscopy. Between 10 and 45 min after inoculation, sporozoites were found in the process of entering Kupffer cells and inside phagolysosomes. The sporozoites entered the Kupffer cells by phagocytosis as determined by the presence of pseudopods and local accumulations of aggregated microfilaments and the resulting exclusion of other organelles in the phagocyte cytoplasm beneath the attached parasite. Sporozoites were taken up either with their anterior end first, or backwards. Scanning electron microscopy of in vitro sporozoite Kupffer cell interaction confirmed these observations. It was concluded that sporozoites are taken up in a normal phagocytic way by the Kupffer cells, regardless of their initial place of contact or position. Thirty min after inoculation sporozoites found in phagolysosomes were still morphologically intact but after 45 min we could encounter completely digested sporozoites.

Animals↗

PubMed1985

Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver.

Highly purified sinusoidal (fat-storing, Kupffer and endothelial cells) and parenchymal cells were isolated to assess the cellular distribution of vitamin A in liver of adult vitamin A-sufficient rats. A modified simple procedure was developed for the purification of fat-storing cells from rat liver. This was achieved by a single centrifugation step in a two-layer density Nycodenz gradient. Endothelial and Kupffer cells were obtained from the same gradient and further purified by centrifugal elutriation. Reverse-phase HPLC analysis showed that fat-storing cells contained about 300-fold the amount of retinyl esters present in parenchymal cells on a mg cell protein basis. In fat-storing cells, the same retinyl esters, viz. retinyl palmitate, retinyl stearate and retinyl oleate, were present as in whole liver. It was also observed that, within 12 h after intravenous injection of chylomicron [3H]retinyl ester, most of the radioactivity had accumulated in the fat-storing cells. It is concluded that fat-storing cells are the main storage sites for vitamin A in rat liver.

Aging↗

PubMed1985

Time and dose responses of the reduction in retinoid concentrations in C57BL/Rij and DBA/2 mice induced by 3,4,3',4'-tetrachlorobiphenyl.

A single ip dose of 15 mg 3,4,3',4'-tetrachlorobiphenyl (TCB)/kg induced a 30 to 40% reduction of retinol and retinyl palmitate concentrations in hepatic tissue of C57BL/Rij mice within 2 to 4 days. This level of reduction was maintained for about 14 days. The ED50 was 32 mg TCB/kg for hepatic retinol and 17 mg TCB/kg for hepatic retinyl palmitate. In DBA/2 mice, however, no reduction in hepatic retinoids was observed even at doses up to 729 mg TCB/kg. The duration of the reduction in hepatic retinoids did not correlate with the induced aryl hydrocarbon hydroxylase (AHH) activity in C57BL/Rij mice. These data suggest that AHH and related enzymes are not directly involved in the TCB-induced reduction in retinoids in these mouse strains. No significant differences in the accumulation of TCB in hepatic tissues of C57BL/Rij and DBA/2 mice were observed; however, the estimated elimination rate in C57BL/Rij was two times faster than that in DBA/2 mice. In serum of DBA/2 mice, a rapid 50% decline in the concentration of retinol was observed after only 2 to 6 hr, remaining at the reduced value for about 14 days. The ED50 for serum retinol was 1 to 2 mg TCB/kg. Only a transient reduction in serum retinol, disappearing within 48 hr, was observed in the C57BL/Rij mouse. TCB accumulated to an almost 15-fold higher extent in serum of DBA/2 mice as compared with C57BL/Rij mice. The effect of TCB on retinoids in a few other strains of mice and in the Sprague-Dawley rat showed a reduction in serum retinol rather than in hepatic retinoids.

Animals↗

PubMed1985

Retinoids, retinoid-binding proteins, and retinyl palmitate hydrolase distributions in different types of rat liver cells.

A study was conducted to determine the levels and distributions of retinoids, retinol-binding protein (RBP), retinyl palmitate hydrolase (RPH), cellular retinol-binding protein (CRBP), and cellular retinoic acid-binding protein (CRABP) in different types of isolated liver cells. Highly purified fractions of parenchymal, fat-storing (stellate), endothelial, and Kupffer cells were isolated in high yield from rat livers. The retinoid content of each fraction was measured by HPLC analysis. RBP, CRBP, and CRABP were measured by sensitive and specific radioimmunoassays, and RPH activity was measured by a sensitive microassay. The concentrations of each parameter expressed per 10(6) parenchymal or fat-storing cells were, respectively: retinoids, 1.5 and 83.9 micrograms of retinol equivalents; RBP, 138 and 7.4 ng; RPH, 826 and 1152 pmol FFA formed hr-1; CRBP, 470 and 236 ng; and CRABP, 5.6 and 8.7 ng. When these data were expressed on the basis of per unit mass of cellular protein, the concentrations of RPH, CRBP, and CRABP in the fat-storing cells, which contain 10-fold less protein than the large parenchymal cells, were seen to be greatly enriched over parenchymal cells. The parenchymal cells contained approximately 9% of the total retinoids, 98% of the total RBP, 90% of the total RPH activity, 91% of the total CRBP, and 71% of the total CRABP found in the liver. The fat-storing cells accounted for approximately 88% of the total retinoids, 0.7% of the total RBP, 10% of the RPH activity, 8% of the total CRBP, and 21% of the CRABP in the liver. The endothelial and Kupffer cell fractions contained very low levels of all of these parameters. Thus, the large and abundant parenchymal cells account for greater than 70% of the liver's RBP, RPH, CRBP, and CRABP; but the much smaller and less abundant fat-storing cells contain the majority of hepatic retinoids and greatly enriched concentrations of RPH, CRBP, and CRABP.

Animals↗