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Biomedical subjects

D L Knook

Publications and source records attributed to D L Knook.

At least 109 records · Page 6Linked to original sources
PubMed1975

Changes in lysosomes during ageing of parenchymal and nonparenchymal liver cells.

Intact and viable parenchymal and non-parenchymal liver cell preparations were isolated by enzyme perfusion techniques from young and old rats. The distribution of the lysosomal enzymes acid phosphatase, beta-galactosidase, cathepsin D, acid DNAse, and arylsulphatase B over parenchymal and non-parenchymal cells was determined. In addition, morphological and morphometric changes which occur in parenchymal cells with age were investigated. All lysosomal enzymes studied are present in both cell classes, but non-parenchymal cells possess much ligher activities per mg protein than do parenchymal cells. This phenomenon is most pronounced for cathepsin D with a 13-times higher specific activity in non-parenchymal cells. Electron microscopic observations demonstrated that the lysosomal activities in non-parenchymal cells can be attributed mainly to the large and numerous lysosomal structures in Kupffer cells. Parenchymal cells from old rats have higher lysosomal enzyme activities per mg protein than do hepatocytes from young rats. This observation is in agreement with the general increase with age in the cytoplasmic volume fraction occupied by lysosomal structures in parenchymal cells. In general, non-parenchymal cells show no increase in specific enzyme activities with age. The results obtained suggest an increase in the heterogeneity--in both appearance and enzyme content--of the lysosomal structures in parenchymal cells with age.

Acid Phosphatase↗
PubMed1971

Function of ubiquinone in electron transport from reduced nicotinamide adenine dinucleotide to nitrate and oxygen in Aerobacter aerogenes.

The possible role of quinones in the electron transport system of Aerobacter aerogenes was investigated. The only quinone found in measurable amounts in bacteria grown in minimal media under both aerobic and anaerobic conditions was ubiquinone-8. Membrane-bound ubiquinone-8 could be removed by extraction with pentane, or destroyed by ultraviolet irradiation, with a concomitant loss of both reduced nicotinamide adenine dinucleotide (NADH) oxidase and NADH-linked respiratory nitrate reductase activity. In the extracted membrane preparations, these enzymatic activities could be restored, both to the same degree, by incorporation of ubiquinone-6, -8, or -10, but not by incorporation of menaquinones. The NADH oxidation and the nitrate reduction were sensitive to the respiratory inhibitors dicoumarol, lapachol, and cyanide. The results obtained indicate that ubiquinone-8 mediates the electron transport between NADH and oxygen as well as between NADH and nitrate. Branching of the electron transport chain to oxygen and nitrate occurs after an initial common pathway.

Alkanes↗
PubMedDate not supplied

Successful aging in the oldest old: Who can be characterized as successfully aged?

BACKGROUND: Successful aging is a worldwide aim, but it is less clear which indicators characterize elderly persons as successfully aged. We explored the meaning of successful aging from 2 perspectives. METHODS: Analysis of data from the first cross-sectional part of the longitudinal Leiden 85-plus Study, conducted in Leiden, the Netherlands. All inhabitants of Leiden aged 85 years were eligible. Data were obtained from 599 participants (response rate, 87%). Successful aging from a public health perspective was defined as a state of being. All participants were classified as successful or not successful based on optimal scores for physical, social, and psychocognitive functioning and on feelings of well-being, using validated quantitative instruments. Qualitative indepth interviews on the perspectives of elderly persons were held with a representative group of 27 participants. RESULTS: Although 45% (267/599) of the participants had optimal scores for well-being, only 13% (79/599) had optimal scores for overall functioning. In total, 10% (58/599) of the participants satisfied all the criteria and could be classified as successfully aged. The qualitative interviews showed that most elderly persons viewed success as a process of adaptation rather than a state of being. They recognized the various domains of successful aging, but valued well-being and social functioning more than physical and psychocognitive functioning. CONCLUSIONS: If successful aging is defined as an optimal state of overall functioning and well-being, only a happy few meet the criteria. However, elderly persons view successful aging as a process of adaptation. Using this perspective, many more persons could be considered to be successfully aged.

Activities of Daily Living↗
PubMedDate not supplied

Maintenance cultures of Kupffer cells isolated from rats of various ages: ultrastructure, enzyme cytochemistry, and endocytosis.

Sinusoidal liver cells were isolated from the livers of 3-, 12-, 30-, and 36-month-old female BN/BiRij rats by enzymatic digestion. The Kupffer cells in the sinusoidal cel suspensions were purified by centrifugal elutriation and kept in maintenance culture for periods of up to about 3 weeks. The viability and yield of Kupffer cells per gram of body weight did not change with the age of the donor rat. The ultrastructural, cytochemical, and functional characteristics of Kupffer cells as observed in perfusion-fixed liver were retained during several days of maintenance culture. The consistent observation of worm-like structures in cultured Kupffer cells indicated the reformation of the specific fuzzy coat of the cells during culture. Endogenous peroxidatic and acid phosphatase activities were evident in cultured Kupffer cells and showed the same localization as observed in perfusion-fixed liver. Kupffer cells in culture were able to endocytose colloidal carbon, latex particles (0.8 micron), horseradish peroxidase, and endotoxin, indicating the reappearance of different types of specific membrane receptors. The ultrastructural appearance of Kupffer cells was not markedly influenced by the age of the donor rat. However, with increasing age, the lysosomes showed increasing amounts of electron dense lipid-like material and iron in the form of ferritin. No qualitative age-related changes in the enzymes tested or in the endocytic capacity of the Kupffer cells were observed. On the basis of these observations, maintenance cultures of purified Kupffer cells can be considered as a valuable model for studying Kupffer cell functions, also in relation to aging phenomena.

Aging↗
PubMedDate not supplied

Purified rat liver fat-storing cells in culture divide and contain collagen.

Primary cultures and cell lines were established from suspensions of purified fat-storing cells isolated from the rat liver. When seeded at a suitable density, fat-storing cells in primary culture reached confluency in 3 to 4 days and could be transferred and established as cell lines for at least two passages. The typical morphological characteristics of fat-storing cells in vivo were retained in the cells during primary culture. Vitamin A fluorescence was still associated with lipid droplets of cells in culture up to and including the second passage. Investigation of the cytoskeletal structure by indirect immunofluorescence showed the presence of vimentin, actin and tubulin in the cells; no alpha-prekeratin was present. The presence of vimentin suggested a fibroblastic or possible myogenic origin for fat-storing cells. The presence of connective tissue components in fat-storing cells in culture was demonstrated by indirect immunofluorescence. Collagen Types I and IV and laminin were present intracellularly in small granules in fat-storing cells in primary culture and in the first passage. Cells in the fourth passage contained only collagen Type 1. Fibronectin was only aligned extracellularly along the cell membrane, which did not exclude an extracellular source. Rat liver fat-storing cells in culture show a high proliferating capacity. Cell multiplication during prolonged culture was associated with phenotypic transition to a more fibroblastic appearance and gradual disappearance of vitamin A. These results indicate that fat-storing cells may be among the cell types involved in pathological changes observed during development of liver fibrosis.

Actins↗
PubMedDate not supplied

Age-related changes in the endocytic capacity of rat liver Kupffer and endothelial cells.

There are many indications that the functional capacity of the reticuloendothelial system (RES) declines with age. The aim of this study was to investigate the cellular basis of age-related changes in the clearance function of the RES. The experiments were focused mainly on Kupffer and endothelial cells of the liver which represent a major part of the RES and are primarily responsible for clearance of colloidal material from the circulation. The clearance capacity of the RES was tested clinically and experimentally by intravenous injection of colloids, such as radiolabeled heat-aggregated colloidal albumin. Age-related changes in the endocytosis of 125I-labeled colloidal albumin (CA) in rats were determined by clearance and organ distribution of different doses of intravenously injected CA, uptake of CA by Kupffer and endothelial liver cells in vivo as determined after isolation of the cells from injected rats and kinetic studies on CA uptake by Kupffer cells in culture. The results show that, at a low dose, the clearance of CA is primarily determined by liver blood flow. At a higher saturating dose, plasma clearance and uptake by the liver are not significantly decreased with age. Endocytosis by endothelial cells, which accounts for about 60% of that of the whole liver, is also unchanged with age. In contrast, a significant decrease in endocytic capacity was observed for Kupffer cells in vivo. This age-related functional decline was also observed in Kupffer cells which were isolated from rats of different ages and maintained in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Rat liver endothelial cells have a greater capacity than Kupffer cells to endocytose N-acetylglucosamine- and mannose-terminated glycoproteins.

The capacity of rat liver Kupffer and endothelial cells to endocytose glycoproteins with N-acetylglucosamine- or mannose-terminated oligosaccharide chains was studied. For this purpose, agalactoorosomucoid, ahexosaminoorosomucoid and horseradish peroxidase were used as ligands. A reliable determination of the amount of ligand endocytosed in vivo or in vitro was made possible by using the recently developed cold pronase method for the isolation and purification of Kupffer and endothelial cells. Both cell types participated in the uptake of the ligands in vivo as well as in vitro, but their endocytic capacity was several times greater in vivo than in vitro. Under both conditions, endothelial cells possessed a greater capacity to endocytose the ligands than did Kupffer cells. Since the total number of endothelial cells in the liver is at least twice the number of Kupffer cells, the contribution of endothelial cells to the liver uptake of N-acetylglucosamine-terminated glycoproteins in vivo was estimated to be 3 to 7 times higher than that of the Kupffer cells. In vitro experiments showed that the uptake of the glycoproteins followed saturation kinetics and was strongly inhibited at 4 degrees C and in the presence of mannan. Ultrastructural investigations revealed that horseradish peroxidase was taken up by all Kupffer and endothelial cells. These results emphasize the important role liver endothelial cells play in the clearance of specific glycoproteins from the circulation.

Animals↗
PubMedDate not supplied

Uptake and processing of [3H]retinoids in rat liver studied by electron microscopic autoradiography.

The role of rat liver cell organelles in retinoid uptake and processing was studied by electron microscopic autoradiography. [3H]Retinoids were administered either orally, to make an inventory of the cell organelles involved, or intravenously as chylomicron remnant constituents to study retinoid processing by the liver with time. No qualitative differences were observed between the two routes of administration. Time-related changes in the distribution of grains were studied using chylomicron remnant [3H]retinoids. The percentages of grains observed over cells and the space of Disse at 5 and 30 min after administration were, respectively: parenchymal cells, 72.6 and 70.4%; fat-storing cells, 5.0 and 18.1%, and the space of Disse, 14.4 and 8.9%. Low numbers of grains were observed over endothelial and Kupffer cells. The percentages of grains observed over parenchymal cell organelles were, respectively: sinusoidal area, 59.6 and 34.4%; smooth endoplasmic reticulum associated with glycogen, 13.8 and 13.4%; mitochondria, 5.4 and 13.6%; rough endoplasmic reticulum, 4.2 and 7.3%, and rough endoplasmic reticulum associated with mitochondria, 3.7 and 6.5%. It is concluded that chylomicron remnant [3H]retinoids in combination with electron microscopic autoradiography provide a good system to study the liver processing of retinoids in vivo. These results, obtained in the intact liver under physiological conditions, further substantiate that retinoids are processed through parenchymal cells before storage occurs in fat-storing cell lipid droplets, that retinoid uptake is not mediated through lysosomes and that the endoplasmic reticulum is a major organelle in retinoid processing.

Administration, Oral↗