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S C Miller

Publications and source records attributed to S C Miller.

At least 235 records · Page 13Linked to original sources
PubMed1982

Inhibition by glucocorticoids of endocytosis in a macrophage-like cell line.

A macrophage-like cell line (P388D1) has been used to demonstrate that glucocorticoids inhibit the fluid-phase endocytosis of fluorescein-labeled dextran (FITC-dextran). Initial experiments demonstrated that the interaction of FITC-dextran with cells had all the features of fluid-phase uptake, ie, the amount taken up was proportional to the concentration in the medium, the uptake proceeded continuously with time and was blocked at 4 degrees C. Dexamethasone (10(-7) M) had no effect on endocytosis until 11 hours after addition of the steroid, when it inhibited the uptake of FITC-dextran by 35%. The amount of inhibition increased with longer exposure times to the hormone up to 50% after 22 hours. Although this effect on endocytosis was observed prior to any effect on growth of the cells, endocytosis as well as cell proliferation were inhibited in a dose dependent fashion. A preliminary survey of selected steroids has established that the inhibition of endocytosis was restricted to steroids of the glucocorticoid class. The key experiments were also performed using horseradish peroxidase instead of FITC-dextran with, essentially, identical results.

Animals↗
PubMed1982

Role of vitamin D in maternal skeletal changes during pregnancy and lactation: a histomorphometric study.

The effect of vitamin D on bone changes during the reproductive cycle in female rats has been investigated. One group of female rats was maintained on a vitamin D-deficient diet and another group of a vitamin D-replete diet from weaning. Both groups were mated with normal males and changes in their bones were determined histomorphometrically during pregnancy, lactation, and after weaning. All vitamin D-deficient rats had bone changes typical of rickets. Pregnancy caused significant reductions in mineralized tissue of trabecular and cortical bone in the vitamin D-deficient rats. Lactation caused further significant reductions in mineralized tissues of cortical and trabecular bone in both the vitamin D-deficient and vitamin D-replete animals, with the greatest changes seen at weaning. Some restoration of mineralized tissues occurred following weaning. There was an increase in tetracycline-labeled bone surface in the vitamin D-replete animals during lactation, likely due to an increase in bone formation rates. In the vitamin D-deficient animals during lactation, there was a decrease in tetracycline-labeled bone surface, likely due to severely depressed bone mineralization. These results indicate that the mobilization of calcium from bone to maintain pregnancy and lactation occurs by a mechanism independent of vitamin D.

Animals↗
PubMed1982

Osteoclast kinetics in osteopetrotic (ia) rats cured by spleen cell transfers from normal littermates.

Excessive skeletal mass and reduced bone resorption characteristic of osteopetrosis in young ia rats can be corrected by irradiation and transfer of spleen cells from normal littermates. Cell population analyses and 3H-thymidine (3H-TdR) autoradiographic methods were used to determine osteoclast population dynamics and kinetics of incorporation of nuclei following whole-body irradiation and spleen cell transfer in ia/ia rats and in untreated ia rats and their (ia/+) normal littermates. The numbers of osteoclasts per metaphyseal area were greater in ia rats than in (ia/+) normal littermates. Untreated ia rats had greater rates of incorporation of 3H-TdR-labeled nuclei into osteoclasts but were reduced to near normal values following irradiation and spleen cell transfer. Labeled osteoclast nuclei were first seen in the primary spongiosa of the femoral metaphysis and with increasing time appeared at greater distances from the epiphyseal growth plate as the bones grew In length. These sites of osteoclast neogenesis correspond to sites where restoration of bone resorption is initially seen following bone marrow and splenic transplants in the treatment of osteopetrosis.

Animals↗
PubMed1982

Localization of plutonium-241 in the testis. An interspecies comparison using light and electron microscope autoradiography.

The distribution and localization of 241Pu in the testes of rats, guinea-pigs and a dog were determined using light and electron microscope autoradiography. These species were used because of the variation in the morphology and ultrastructure exhibited in their testicular tissues. In all animals the 241Pu was localized in testicular interstitial tissue and little was evident in the seminiferous tubules. There were marked species differences in the percentage of interstitial tissue cells labelled with 241Pu; 18 per cent of the cells labelled in rats, 9 per cent in guinea-pigs and 6 per cent in the dog. Electron microscope autoradiography demonstrates that 241Pu is localized in macrophages of the interstitial tissue in all species and appears to be concentrated in the lysosomal system of the cell. Based on differences in the histology and microstructure of testicular interstitial tissues and the patterns of 241Pu incorporation in these species, implications for predicting plutonium localization in human tissue are discussed.

Animals↗
PubMed1982

Further studies on the relationship between allotransplantability and the presence of the cell surface glycoprotein epiglycanin in the TA3-MM mouse mammary carcinoma ascites cell.

The loss of strain specificity in the TA3-St mammary carcinoma ascites cell during passage in ascites form in diseased syngeneic strain A mice was confirmed by the observation that TA3-MM/2 ascites cells were capable of progressive growth in 7 foreign mouse strains. Support for the hypothesis that allotransplantability in the TA3-MM lines may be due to masking of cell surface histocompatibility H-2a antigens by large glycoprotein (epiglycanin) molecules was obtained from the finding that the capacity of the TA3-MM/2 ascites cell to absorb anti-H-2a antibody was several times less than that of the parent TA3-St ascites cell, although it was greater than the capacity of the non-strain-specific TA3-Ha line. Further support for the location of epiglycanin molecules at the cell surface was obtained by transmission electron-microscopic observation of a high concentration of filamentous structures, usually 20-40 nm long, but often extending to 200-300 nm length at the TA3-MM/2 cell surface. Similar structures were also observed at the TA3-Ha cell surface but were not observed at the surface of the TA3-St ascites cell, a cell known to contain no detectable epiglycanin. Epiglycanin molecules, obtained by two different methods from TA3-MM/1, TA3-MM/2, and TA3-Ha ascites cells, were shown to be similar with respect to their capacities to inhibit the binding of 125I-labeled epiglycanin to its antibody, induced in the rabbit by TA3-Ha ascites cells in a radioimmunoassay.

Animals↗
PubMed1981

Osteoclast cell-surface specializations and nuclear kinetics during egg-laying in Japanese quail.

Medullary bone deposits serve as a reservoir of labile calcium for egg-shell calcification in birds. Quantitative transmission-electron-microscope methods and light-microscope autoradiographic cell-population-kinetic analyses were used to determine changes in cell-surface specializations and population dynamics of medullary bone osteoclasts during egg-laying in Japanese quail. Prior to egg-shell formation, from 0 to about 8 hours after the previous oviposition, very few osteoclast profiles had ruffled borders. The appearance of ruffled borders coincided with the beginning of egg-shell calcification, about 9-10 hours after the previous oviposition. During egg-shell calcification, about 10-21 hours after the previous oviposition, most osteoclast profiles had ruffled borders. Ruffled borders disappeared at the completion of egg-shell calcification and commencement of egg-shell pigmentation. Thus, functional activities of medullary bone osteoclasts appear to be closely synchronized with egg-shell calcification during egg-laying. From 1 to 48 hours after a single injection of 3H-thymidine (3H-TdR), very few labeled osteoclast nuclei were seen during egg-laying. Following multiple injections of 3H-TdR, the percentage of labeled nuclei reached a peak at about 170 hours after the first injection. At this peak-labeling time, relatively few of the osteoclast profiles that had labeled nuclei had two or more; although the average number of nuclei per osteoclast profile was about 3.6. These kinetic data suggest that the medullary bone osteoclast population has a prolonged rate of turnover compared to rapid changes in cell activities associated with each 24-hour egg-laying cycle; and collectively they would suggest that rapid changes in osteoclast functions occur independently of changes in cell-population dynamics.

Animals↗
PubMed1981

A physiologically based pharmacokinetic model for the intraocular distribution of pilocarpine in rabbits.

This report presents a mathematical model which has been developed to describe the intraocular disposition of pilocarpine following topical dosing in rabbits. The model uses experimentally determined parameters such as rates of tissue uptake of drug and equilibrium distribution coefficients. Differential mass balance equations for pilocarpine in the cornea, aqueous humor, iris-ciliary body, and lens were written and solved numerically. Measured tear concentrations, following topical dosing wih pilocarpine, were fit by a monoexponential curve and used as the forcing function of the model. By using a combination of known physiological and experimentally determined parameters, predictions of intraocular tissue levels of pilocarpine were made. These predictions were then compared to experimentally determined concentration-time profiles.

Animals↗
PubMed1981

Failure to demonstrate morphologically the presence of colostral or milk cells in the wall of the gastrointestinal tract of the suckling neonatal mouse.

The possibility that intact cells may migrate from ingested colostrum and milk into the gut wall of the nursing neonate has been tested directly by means of radioautographic techniques. [3H]Thymidine was continuously infused into female mice throughout the last 6 days of their pregnancy. Upon delivery, their fully [3H]thymidine-labelled litters were removed and given to nurse from unlabelled surrogate mothers whose own litters were borne simultaneously. These unlabelled litters were similarly removed immediately upon birth and given to the [3H]thymidine-infused mothers to nurse. Infants labelled during gestation and mothers labelled during pregnancy continued to receive thrice-daily injections of isotope for 1-14 days and 1-18 h, respectively, after delivery. The stomach and adjacent portion of small intestine were removed from unlabelled infants nursing from labelled surrogate mothers at intervals of 1-18 h after beginning to suckle, subserially sectioned and prepared for radioautography. From days 1 to 14 after beginning to suckle, the same tissues were removed from labelled infants nursing from unlabelled surrogate mothers and similarly prepared for radioautography. The results indicate that transepithelial migration of intact cells of the colostrum and milk does not appear to be the method by which immunological functions are adoptively transferred to the nursing neonatal mouse.

Animals↗
PubMed1981

Development of natural killer cell activity and genetic resistance to bone marrow transplantation with age: effect of neonatal thymectomy.

The effect of neonatal thymectomy on the development of splenic and bone marrow natural cell-mediated cytotoxicity and on genetic resistance to bone marrow transplantation was examined in mice. Natural cytotoxicity was measured by a 51Cr release assay; the ability to engraft foreign bone marrow was assayed by the spleen colony method. The natural cytolytic response of spleen cells increased progressively from youth to early adulthood, whereas that of the bone marrow declined during the same age period. Neonatal thymectomy significantly elevated the natural killer cell response of young mice only (4 weeks, spleen; 6 weeks, bone marrow). In other experiments, neonatally thymectomized and sham-operated mice were lethally irradiated at 4 or 6 weeks of age and injected with 2.5, 5.0 or 10 million rat marrow cells. Six days later spleen colonies were markedly reduced in both 4- and 6-week-old neonatally thymectomized mice with all rat marrow cell doses tested. Neonatal thymectomy did not alter the percentage of erythroid verus other colonies at either 4 or 6 weeks. In both thymectomized and sham-operated mice the number of colonies increased with increases in marrow cell dose. The data are suggestive of a production and dissemination to the spleen of cels involved in the natural cytotoxic response from the bone marrow.

Aging↗
PubMed1981

Genetic resistance to transplantation of xenogeneic bone marrow in mice of various strains: influence of an interferon inducer and age.

Mice of the C57Bl/6 strain and its hybrids develop at 3-4 weeks of age strong resistance to haemopoietic reconstitution by Lewis rat bone marrow cells (RBMC), whereas mice of other strains show moderate (129/J) or (A/J) such resistance. To test whether interferon (IFN) inducers can boost xenogeneic resistance in these strains, 2-week-old C57Bl/6J and 8-week-old 129/J and A/J mice were injected 4 h after 950 R with the IFN inducer poly I:C and later given various doses of Lewis RBMC. Infant C57Bl/6J mice so injected had significantly fewer numbers of colonies (enhanced resistance) per spleen than did control animals 6 days later. Poly-I:C-injected adult 129/J mice also showed fewer colonies than control mice, whereas poly-I:C-injected and control A/J mice showed similar numbers of spleen colonies. Enhanced resistance induced by poly I:C could be overridden by injecting syngeneic thymocytes with RBMC or by large doses of RBMC alone. Aged and young adult C57Bl/6J mice showed very low numbers of spleen colonies with RBMC inocula up to 20 x 10(6) but resistance breaks at both ages with inocula of 40 x 10(6) RBMC. Young adult and aged A/K mice showed colony confluency with RBMC greater than or equal to 10(6). The results demonstrate that (1) the mechanism of xenogeneic resistance not yet competent in infancy can be driven to functional competence by an IFN inducer in C57Bl/6J mice; (2) resistance can be enhanced in a moderately resistant strain (129/J) by an IFN inducer but not created in a non-resistant strain (A/J); (3) ply-I:C-induced enhancement of resistance can be overridden by giving large numbers of RBMC (+/- syngeneic thymocytes); (4) senescence has no influence on the genetically determined response to marrow xenografts in the strains studied.

Aging↗
PubMed1980

Characterization of endosteal bone-lining cells from fatty marrow bone sites in adult beagles.

Bone-lining cells cover the majority of trabecular bone surfaces in adult long-lived mammals. The morphology, ultrastructure, and population density of bone-lining cells was investigated in several fatty marrow trabecular bone sites in adult beagles of different ages. Although there is a low population density of bone-lining cells on bone surfaces, their total numbers greatly exceed the numbers of osteoblasts and osteoclasts found on these bone surfaces. In one of the bone sites studied, there are significantly fewer bone-lining cells in very old beagles (12-16 years old) when compared to young adult beagles (1.5-3 years old), otherwise there are no differences in the cell population that could be attributed to aging. Bone-lining cells are flattened against bone surfaces and have flat or sometimes ovoid-shaped nuclei which are often located adjacent to areas in the fatty marrow where capillaries are found. When viewed in the electron microscope, bone-lining cells contain few organelles, and the attenuated cytoplasm of these cells is well extended over bone surfaces. The bone-lining cell cytoplasm does not appear to form a continuous layer over the bone surface, as numerous gaps and spaces are seen. Bone-lining cell processes are frequently joined by junctions morphologically similar to gap junctions. Between the lamina limitans of the bone matrix and the bone-lining cell, as well as between the bone-lining cell and the adjacent fat cells, there are layers of connective tissue containing collagenous fibers and other amorphous material. These findings are discussed in relation to the possible role of bone-lining cells in the regulation of mineral homeostasis.

Aging↗
PubMed1980

Augmentation of erythroid burst formation by the addition of thymocytes and other myelo-lymphoid cells.

Bone marrow from barrier-sustained specific pathogen-free (SPF) CBA and C57BL/6 mice gave relatively low numbers of BFU-E colonies in methylcellulose culture, as compared to conventional mice. Addition of thymocytes to the marrow cultures increased the yield of BFU-E colonies more than fourfold in SPF mice but only 1.5-fold in conventional mice. Colony size was also increased. Increased yield of BFU-E colonies was also obtained by co-culture of bone marrow with lymph node cells or with bone marrow or spleen cells from 900R whole-body irradiated mice. The effect appeared to be cellular rather than humoral. It was not reproduced by conditioned medium from thymus or pokeweed mitogen stimulated spleen cells. The helper effect of thymus cells was eliminated or reduced by freezing and thawing, or by 48 hours of incubation after irradiation. Treatment of bone marrow cells in vitro with anti-theta serum and complement did not decrease the number of BFU-E colonies. The putative helper cells appear not to be T cells, were non-adherent to the plastic culture dish, and were cortisone resistant and radioresistant. The low BFU-E colony yield from SPF mouse marrow is presumed to be largely the result of deficiency of these non-T helper cells in SPF bone marrow, rather than of BFU-E progenitor cells.

Animals↗
PubMed1979

The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat.

Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to inorganic pyrophosphate but is resistant to enzymatic and chemical degradation and is known to be a potent inhibitor of bone resorption. The administration of 20 mg/kg/day of Cl2MDP for ten days to growing rats results in marked increases in metaphyseal mineralized tissue mass due to slowed bone resorption. There was an increase in resorption areas covering anorganic bone viewed by scanning electron microscopy (SEM), however, the resorption pits, or Howship's lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is likely due to an inhibition of bone resorption coupled with slow bone formation. Administration of Cl2MDP to growing rats also results in an increase in the numbers and size of osteoclasts. Because this would appear to be a histological paradox, in view of the ability of Cl2MDP to slow bone resorption, the osteoclasts were examined by transmission electron microscopy (TEM). The ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, even though clear zones were frequently seen. Examination of undecalcified light microscope sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in the Cl2MDP-treated animals than in controls. Thus the collaborating TEM observations of smaller ruffled borders, with the SEM observations of smaller, less-defined resorption pits, with the light microscope observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration.

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