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Biomedical subjects

S C Miller

Publications and source records attributed to S C Miller.

270 records · Page 15Linked to original sources
PubMedDate not supplied

Alveolar bone augmentation following the local administration of prostaglandin E1 by controlled-release pellets.

E-Series prostaglandins (PGE) are powerful osteogenic substances when given in vivo. The purpose of this work was to determine the ability of locally administered PGE1 to promote alveolar bone formation. Controlled-release pellets containing PGE1 were implanted on the lateral mandibular surface of Beagle dogs and tissues collected 4 weeks later. There was a dose-related increase in alveolar bone thickness and bone formation rates following PGE1 administration. In many cases, there was substantial new bone formation on the alveolar crest. Some increase in alveolar bone remodeling occurred with higher doses of PGE1. These results demonstrate that locally administered PGE1 may be useful for the augmentation of alveolar bone.

Alprostadil↗
PubMedDate not supplied

Local stimulation of new bone formation by prostaglandin E1: quantitative histomorphometry and comparison of delivery by minipumps and controlled-release pellets.

E-series prostaglandins (PGE) given systematically or locally in vivo can have powerful anabolic effects on bone. The comparative dose-response relationships from PGE1 given by osmotic minipump or controlled-release pellet on periosteal and intracortical bone envelopes were determined. Graded doses of PGE1 were delivered by osmotic minipump (0.0 to 16.7 mg PGE1/week) or controlled-release pellet (0.0 to 16.7 mg PGE1/week) to the lateral mandibular surface of adult dogs (2-5 years old). PGE1 was given for three weeks and tissues were collected for histology and histomorphometry one week later. At sites of maximal response, there were dose-related increases in the periosteal surface with new bone formation, average new bone thickness, maximum thickness, and new bone area. Subperiosteal bone formation was greater for comparable doses when PGE1 was delivered by minipumps. The proliferation of new bone at those sites treated with the pellets was greatest with the 8.3 mg PGE1/week/three week treatment. Periosteal bone formation did not appear to be preceded by a resorption phase, indicating that PGE1 treatment stimulated bone modeling in the formation mode. The new bone consisted of woven bone, particularly at sites with high accretion rates, and primary lamellar bone. There were some dose-related changes in intracortical remodeling indices including increases in cortical porosity, single and double-labeled surface, numbers of formation, reversal and resorption osteons, radial closure rate, and surface- and volume-referent bone formation rates. Increases in the bone formation rates indicate that PGE1 increased the recruitment of osteoblasts. Increases in the mineral appositional rate, observed at a higher dose, indicates that PGE1 stimulated bone production at the cellular level.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMedDate not supplied

Comparative morphometric changes in rat cortical bone following ovariectomy and/or immobilization.

Gonadal hormone deficiency following ovariectomy and skeletal unloading by limb immobilization are useful models of osteopenia. The purpose of this study was to compare changes in cortical bone after ovariectomy (OVX) or immobilization (IMM) for 6 and 12 weeks. Comparisons were also made when rats were ovariectomized or immobilized for 6 weeks and then immobilized (OVX/IMM) and ovariectomized (IMM/OVX), respectively, for 6 more weeks. Tibias and femurs were collected and static and dynamic cortical bone indices were determined by morphometric methods. Femurs from animals OVX or IMM for 12 weeks were tested for bone stiffness by torsional testing. Six and 12 weeks after OVX, there were increases in the periosteal perimeter, cortical area, and periosteal bone formation indices, indicating that ovariectomy increased modeling-dependent bone gain on the periosteal envelope, relative to controls. Contrarily, 6 and 12 weeks after IMM, there were decreases, compared with controls, in periosteal perimeter, cortical bone area, and periosteal bone formation indices. This indicates that immobilization decreased modeling-dependent bone gain on the periosteal envelope. These differences in modeling between the animals that were OVX and IMM resulted in a smaller cortical width and minimum cortical width in the IMM compared with the OVX animals. There were significant decreases in cortical bone stiffness and minimum cortical width at the fracture site following mechanical testing in the animals IMM for 12 weeks. Both ovariectomy and immobilization increased endocortical resorption surface, endocortical perimeter and expansion of the marrow cavity. Because of suppressed periosteal bone formation with increased endocortical resorption, immobilization had a greater effect on bone loss and decreased bone stiffness than did ovariectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Systemic administration of recombinant transforming growth factor beta 2 (rTGF-beta 2) stimulates parameters of cancellous bone formation in juvenile and adult rats.

Transforming growth factor beta is a multifunctional protein with known actions on bone and bone cells. The ability of TGF-beta to stimulate osteogenic parameters in vitro and osteogenesis adjacent to injection sites in vivo is well established. The purpose of this study was to determine if systemic administration of recombinant TGF-beta 2 (rTGF-beta 2) could stimulate bone formation in rats of different ages. Juvenile (25-day-old) and adult (160-day-old) rats were treated daily for 5 days and 14 days, respectively, with rTGF-beta 2 given by subcutaneous injection. Bone formation was measured in cancellous bone of the lumbar vertebrae in juvenile rats and the femoral epiphysis in adult rats. Endochondral bone growth rates were measured in the distal femurs from both juvenile and adult rats using histomorphometric methods. Systemic administration of rTGF-beta 2 resulted in substantial increases in bone formation rates (both surface and volume referent) in both juvenile and adult rats. In the juvenile rats, rTGF-beta 2 increased the percent double labeled surface and the mineral appositional rate. In the adult rats, TGF-beta 2 treatment increased the double labeled surface and also endochondral (longitudinal) growth parameters without changing the number of osteoclasts or the number of osteoclast nuclei per cell. These results demonstrate that short-term systemic administration of rTGF-beta 2 substantially increases cancellous bone formation rate in rats.

Aging↗
PubMedDate not supplied

Wall remodeling after wall shear rate normalization in rat mesenteric arterial collaterals.

Previous studies have demonstrated endothelial and smooth muscle hyperplasia occur during arterial luminal expansion associated with elevation of arterial wall shear rates. The current study investigated whether remodeling induced by elevated wall shear would ultimately result in a vessel with intimal and medial cell densities and other wall characteristics similar to control arteries. A rat mesenteric model was used in which collateral wall shear is restored to normal 4 weeks after arterial occlusion. Twelve weeks after shear elevation, paired in vivo measurements indicated that the maximum collateral inner diameter was increased 27-75%. Morphometric evaluation of collateral cross sections indicated that, relative to control arteries, luminal and medial areas were increased 79 +/- 22 and 56 +/- 15%. Collateral medial cell density was decreased (1.12 +/- 0.044 vs. 1.35 +/- 0.005 nuclei/1,000 micrometer(2) but intimal cell density was similar (2.86 +/- 0.166 vs. 2.49 +/- 0.102 nuclei/100 micrometer luminal perimeter). Medial thickness to radius ratio was also similar between control and collateral arteries. Thus, for the wall characteristics evaluated, there are many similarities between enlarged collaterals and control arteries. Comparison of nuclear numbers in arterial cross sections of the current and previous studies suggest that intimal and medial cellular regression is correlated with a decrease in wall shear force toward normal levels.

Animals↗
PubMedDate not supplied

Effects of psychological stress on joint inflammation and adrenal function during induction of arthritis in the Lewis rat.

Glucocorticoids are effective immunosuppressive and anti-inflammatory agents, but some aspects of stress appear to be proinflammatory. This study investigates this apparent paradox as it applies to stress exposure and the development of arthritis in a rat strain that has subnormal hypothalamic-pituitary-adrenal (HPA) responsiveness. Female Lewis rats were subjected to 1 week of rotating, psychological stressors for 5 h daily, beginning 7 days following inoculation with type II collagen. The collagen-induced arthritis (CIA) group exposed to stress showed reduced ankle width increase (p < 0.001) and decreased hindlimb severity scores (p < 0.001). At sacrifice, 2 days following stress termination, no differences in either measure remained and there was no difference in hind paw volume. However, the area of the tibia invaded by stroma, as quantitated by image analysis, was reduced in the stressed rats (p < 0.05). In animals exposed to stress, adrenal weights were increased (p < 0.005) and plasma corticosterone levels were elevated at sacrifice (p < 0.02). Both injected groups had significantly larger adrenal (p < 0.005) and lower thymus weights (p < 0.05) than did uninjected controls. Likewise, both CIA groups had reduced glucocorticoid receptor immunoreactivity in synovial membranes compared to controls (p < 0.001), suggesting that the Lewis rat's HPA deficiency may be intensified by glucocorticoid receptor downregulation during the induction of CIA. These data indicate that the responsiveness of the HPA axis to psychological stress in this strain is sufficient to alter disease progression.

Adrenal Glands↗
PubMedDate not supplied

Effect on leukemia cell numbers of in vivo administration of immunotherapeutic agents is age-dependent.

On the basis of our previous findings that erythroleukemia-bearing mice of different ages responded positively to immunotherapy [indomethacin +/- recombinant interleukin (rIL-2)] in vivo [stimulated natural killer (NK) cells and increased life span], we aimed, in the present study, to determine if changes in these parameters could be correlated to change in erythroleukemia cell numbers. Infant (< 3 weeks old), young adult (5-8 weeks) and aged (> 10 months) DBA/2 mice were injected with erythroleukemia cells. Some mice remained untreated for the 10-day duration of the tumor-bearing period, while others were treated with either indomethacin alone for the 10 days from tumor inoculation, rIL-2 alone for the last 4 days of the 10-day tumor-bearing period, or with both indomethacin and rIL-2 as above. In all cases, both treated and untreated mice were killed at 10 days after tumor inoculation. Cytospot preparations from single cell suspensions of spleen and bone marrow, in all cases, were stained with MacNeal's tetrachrome hematologic stain and the relative and absolute number of erythroleukemia cells in these organs were determined using light microscopy. The results show that indomethacin- and/or rIL-2 treated leukemic infant and young adult mice have significantly lower numbers of erythroleukemia cells in both the spleen and bone marrow relative to untreated, leukemic mice of corresponding age. Leukemic aged mice, however, show no change in erythroleukemia cell numbers in either organ, regardless of treatment, paralleling our observations of a lack of immunotherapeutic value of these agents on NK cell production/function in aged mice.

Adjuvants, Immunologic↗
PubMedDate not supplied

Facility effects on racial differences in nursing home quality of care.

This paper reviews the literature on racial/ethnic differences in nursing home quality, segregated access to nursing home care, and organizational and community factors that may influence access and quality of care. We present illustrative data on county demographics and the racial mix of African American residents in nursing homes in these counties for a sample of four states. We also briefly describe plans for multilevel modeling to test variation in racial/ethnic disparities in care as a function of nursing home structures and processes and community context.

Black or African American↗
PubMedDate not supplied

Population dynamics of natural killer cells and T lymphocytes in murine spleen and bone marrow during the development of erythroleukemia: the effect of indomethacin.

Quantitative and functional methods were used to assess changes in NK (ASGM-1+, nonblast, lymphoid) cells and cytotoxic/suppressor T (Lyt-2+) cells in the spleen and bone marrow (BM) of normal DBA/2 mice and/or mice bearing early (7 days)- and late (14 days)-stage erythroleukemia +/- concomitant oral administration of indomethacin. In normal mice, indomethacin increased ASGM-1+ cells in the spleen and BM by 7 days of continuous drug administration relative to control, while the numbers of Lyt-2+ cells in both organs remained unaltered. The presence of a tumor in untreated mice resulted, by 14 days development, in elevated numbers of ASGM-1+ cells in the spleen and BM. Lyt-2+ cells in the spleen increased transiently (7 days) in tumor-bearing (TB) mice and returned to normal levels by 14 days TB. No difference in either early- or late-stage TB was observed in the numbers of Lyt-2+ cells in the BM. In spleen and BM of TB mice, indomethacin increased ASGM-1+ cells by 7 days TB. ASGM-1+ cells returned to untreated levels by 14 days TB in both organs in spite of continued drug treatment. The numbers of Lyt-2+ cells in both the spleen and BM of 7 days indomethacin-treated TB mice were reduced relative to those of untreated TB mice. By 14 days TB, drug treatment had no effect on Lyt-2+ cell numbers in the spleen or BM. Spontaneous cytolytic activity of the spleen and BM did not always parallel changes in the numbers of ASGM-1+ cells, indicating the presence of late, immature, prelytic NK cells among the ASGM-1+ cell numbers. The results demonstrate that the numbers of NK and cytotoxic/suppressor T cells are markedly but differentially affected during tumor growth and/or time of exposure to indomethacin in an organ-specific manner.

Animals↗
PubMedDate not supplied

Search for a genetic link for mammary cancer in a beagle colony.

BACKGROUND: A possible genetic link for malignant mammary tumor (MMT) was investigated. MATERIALS AND METHODS: Records of an internally-irradiated beagle colony followed from the early 1950's until about 1995 were searched and analyzed by standard statistical procedures. RESULTS: Only a single ancestor yielded a "p" value (Fisher's Exact Test) for an overrepresentation among descendants with MMT at < 0.025 (one-sided test), and the number of comparisons for the 169 ancestors where the relative fraction of animals with MMT was greater than that for non MMT dogs (61) suggests that this could have occurred by chance alone. Results of other statistical tests were not remarkable. CONCLUSION: No genetic link for MMT in this colony could be established with the available data. These findings may or may not be relevant to humans.

Animals↗
PubMedDate not supplied

Inulin disposition following intramuscular administration of an inulin/poloxamer gel matrix.

The disposition of inulin in rats was characterized following the administration of an i.v. solution, an i.m. solution, and an i.m. injectable gel (25% w/w poloxamer 407). Blood activity levels of tritiated inulin were followed over a 6-hour time period for all intravenous (i.v.) and intramuscular (i.m.) formulations. Following i.v. solution administration, a biexponential equation was required to characterize the disposition of inulin from the blood. The total blood clearance was approximately 1.5 mL/min/100 gm body weight. This value, when converted to plasma clearance, Clp/F, (0.807 +/- 0.100 mL/min/100 gm, n = 13), was within the range of values reported for the glomerular filtration rate (GFR) in rats (range 0.55 to 1.2 mL/min/100 gm body weight). The plasma clearance of inulin following administration of an i.m. solution (0.928 +/- 0.173 mL/min/100 gm, n = 9) was in close agreement to the value observed following administration of an i.v. solution. The plasma clearance of inulin following i.m. administration of the inulin/poloxamer gel formulation containing 25% w/w poloxamer 407, however, was markedly reduced (0.316 +/- 0.222 mL/min/100 gm, n = 8). A similar reduction in the value of the plasma clearance (0.309 +/- 0.017 mL/min/100 gm, n = 5) was observed following administration of an inulin solution to rats which had previously (1 hour) been injected i.m. with poloxamer 407 vehicle only (25% w/w). Thus, based on this preliminary study, it appears that simultaneous administration of inulin with poloxamer 407 as a gel formulation results in an alteration of the rat kidney to efficiently clear inulin by means of glomerular filtration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The in vivo effects of steel factor on natural killer lineage cells in murine spleen and bone marrow.

Steel factor (S1F), also known as stem cell factor, is a potent growth stimulator of hemopoietic progenitor cells. In the context of transplantation of hemopoietic cells to irradiated allogeneic hosts, natural killer (NK) cells exert restrictive control on hemopoietic cell proliferation, and are regularly found in elevated concentration in areas of intense hemopoiesis. The present study was designed to examine the effects with time of S1F in vivo on the numbers of NK cells, identified by the presence of the NK 1.1 surface molecule, in the spleen and bone marrow. Throughout the first 3 days of S1F exposure, NK cell numbers, in spite of rapid (1 day) and significant increases in the other hemopoietic cell lineages, did not change in either the spleen or the bone marrow. However, NK cells were increased 2-fold in both organs by 7 days of S1F exposure. At this time, immature granuloid and erythroid cells and the large lymphoid cells in the spleen had more than doubled their respective control numbers and in the bone marrow, immature granuloid cells increased by 47% of control levels. The presence of a late, but not early, influence of S1F on NK cells of the spleen and bone marrow suggests an indirect effect of S1F on this lineage, occurring only when S1F-stimulated hemopoiesis becomes sufficiently intense, providing, thus, an abundance of NK cell targets.

Animals↗
PubMedDate not supplied

Suppression of natural killer cell activity in infant mice occurs after target cell binding.

Natural killer (NK) cell functional activity is absent in mice < 3 weeks of age. However, the mechanism(s) responsible for such inactivity is (are) still unknown. Some evidence suggests basic immaturity of the infant-source NK cells while others suggest suppression of NK cell-mediated activity by other endogenous cells/factors. In the present study, infant-source, spleen-derived, NK cells were highly enriched using anti-NK 1.1 monoclonal antibody coupled to immunomagnetic DYNAbeads. The NK cell characteristics of the isolated cells were tested using three assays: (i) target-binding capacity, (ii) lytic potency as measured in a single cell assay using propidium iodide to label NK cell-lysed dead targets and (iii) proliferative capacity (3H-thymidine incorporation). The results demonstrated that enriched populations of infant NK cells have a greater capacity to bind target cells than unseparated infant or young adult spleen cells. Nevertheless, both unseparated spleen cells and isolated NK cells had a similar 3H-thymidine uptake. The NK cell-mediated lytic capacity of unseparated infant spleen cells was negligible, with 0.5% of YAC-1 targets being killed. However, the lytic capacity of isolated infant-source NK cells was 12% and could be further augmented to 21% after exposure to recombinant interleukin-2. These results suggest that (a) NK cells are present and functional in infant mice, but are suppressed by some endogenous cells/factors, (b) such suppression acts at a postbinding event of NK lysis and (c) such suppression is released when NK cells in infant spleen are removed from that environment.

Aging↗
PubMedDate not supplied

Stimulation of natural killer cell numbers but not function in leukemic infant mice: a system primed in infancy allows survival in adulthood.

Infant mice (< 3-4 weeks) demonstrate no detectable natural killer (NK)-cell-mediated immunity. The aim of the present work was to assess, quantitatively and functionally, the possibility that prostaglandin E2, (PGE2), an NK cell inhibitor, may be responsible for the absence of NK-cell-mediated activity in normal and/or erythroleukemia-bearing infant DBA/2 mice prior to the normal age-related onset of NK-cell-mediated lytic capacity. Infants (7 days after birth) were exposed daily to indomethacin via intraperitoneal injection for 10 days and/or recombinant interleukin-2 (rIL-2) daily for 4 days. Significant increases in the number of NK cells in both the spleen and bone marrow were found after 10 days of indomethacin or 4 days of rIL-2 in normal mice. The spleens but not the bone marrow of infants treated with indomethacin from tumor onset (7 days after birth) contained significantly more NK cells 10 days later than did control (tumor+vehicle) infants. Infants treated with rIL-2 during the last 4 days of tumor bearing, i.e., days 13-16 after birth, contained significantly more NK cells in both their spleen and bone marrow, while combined administration of rIL-2 and indomethacin to tumor-bearing, but not normal, infants resulted in a more than additive increase in the NK cell numbers in both organs relative to control (tumor+vehicle or vehicle alone). However, in neither normal nor tumor-bearing infants, could indomethacin, rIL-2, or a combination of both, induce the development of NK-cell-mediated functional (lytic) activity in spite of the generation, in nearly all instances, of high levels of NK cells in the presence of these agents. The observations collectively suggest that the lack of functional (lytic) reactivity of infant-source NK cells, in the presence of agents which potently enhance adult-source NK cells, reflects (1) the innate immaturity of infant NK lineage cells, or (2) the presence in infant NK-cell-containing organs of a function-suppressive mechanism which is indomethacin insensitive, i.e., not PGE2-mediated. The significantly prolonged survival, and even cure, of infant leukemic mice treated with indomethacin and/or rIL-2 may result from the agent-mediated elevated levels of precursor NK cells coming under the influence of some age-related, as yet unidentified, endogenous factor imbuing them with functional capacity.

Animals↗