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Biomedical subjects

S C Miller

Publications and source records attributed to S C Miller.

At least 181 records · Page 10Linked to original sources
PubMed1988

The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene.

Ferritin is a ubiquitous and highly conserved protein which plays a major role in iron homeostasis. We have identified and sequenced a full-length cDNA for murine ferritin heavy chain. The isolated cDNA is 819 nucleotides in length. It includes 546 nucleotides which encode a protein of 182 amino acids, a 5' noncoding sequence of 120 nucleotides, and a 3'-noncoding region of 153 nucleotides. The sequence displays a high degree of homology to human ferritin H, and includes a portion of the iron-responsive element conserved in chick, frog, and human ferritin. Tumor necrosis factor (TNF), a cytokine which mediates elements of the stress response, induces expression of ferritin H mRNA. Both mouse TA1 adipocytes and human muscle cells increase expression of ferritin H mRNA 4-6-fold after 48 h exposure to TNF. This increase occurs both prior and subsequent to differentiation of adipocytes and muscle cells, and is accompanied by an increase in the synthesis of the ferritin H subunit. These findings suggest a novel role for TNF in iron metabolism.

Adipose Tissue↗
PubMed1988

Effects of N,N,N',N'-ethylenediaminetetramethylene phosphonic acid on cortical bone remodeling in the adult dog.

Phosphonic acids are of interest because of their potential usefulness in the treatment of disorders of bone and mineral metabolism, as a treatment for dental calculus, and as skeletal imaging agents. The effects of oral doses of N,N,N',N'-ethylenediaminetetramethylene phosphonic acid (EDITEMPA) on cortical bone remodeling and histology of adult dogs were determined. After treatment for 3 and 6 months, there were dose-related changes observed in cortical bone as measured using histomorphometric methods. With higher doses, EDITEMPA treatment resulted in the accumulation of osteoid due to impaired or delayed mineralization of bone. There was an increased mineralized and osseous tissue porosity suggesting an early increase in bone resorption perhaps due to an increased activation of bone remodeling.

Animals↗
PubMed1988

The effects of chronic vitamin D deficiency on the skeleton in the adult rabbit.

Albino rabbits were fed a 1.0% Ca, 0.5% P, vitamin D-deficient diet for 11.7 to 31.3 mo. Control rabbits were fed either this diet with the addition of 2.2 units/gm of vitamin D3 or a standard laboratory rabbit ration. Serum levels of 25-OH-D and 1,25-(OH)2D were both undetectable in all vitamin D-deficient rabbits but were present at levels typically found in other species in the control rabbits. Vitamin D deficiency resulted in elevated serum PTH values but did not produce significant changes in serum Ca levels, femur length, femur ash weight to body weight ratio, or tibial breaking strength. The vitamin D-deficient rabbits could be readily separated into two distinct subgroups. Four of these rabbits were normophosphatemic (P = 3.7 +/- 0.4 mg/dl) whereas the other five were severely hypophosphatemic (P = 0.8 +/- 0.2 mg/dl). During the last 10 days of the study the control and normophosphatemic vitamin D-deficient rabbits were in positive Ca and zero P balance. The hypophosphatemic vitamin D-deficient rabbits were in zero Ca and negative P balance. This negative P balance resulted from a net intestinal secretion, as urinary P excretion was negligible. Femur ash weight as a percentage of dry weight was decreased in hypophosphatemic but not the normophosphatemic vitamin D-deficient rabbits. Histomorphometric analyses indicated the bones from the normophosphatemic vitamin D-deficient rabbits were normal. In contrast, vertebral trabecular bone from the hypophosphatemic rabbits contained large amounts of osteoid that was not mineralizing, as indicated by a failure to take up the fluorescent label calcein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Characteristics of cell mediating spontaneous resistance to bone marrow allografts.

Mice of most strains show a genetically determined ability to reject foreign bone marrow grafts even after lethal irradiation. The effector cells mediating this resistance are spleen localised, lymphoid in morphology, and rapidly renewing. Two additional aspects of these cells were characterized in the present study, i.e., their sensitivity to: 1) anti-T cell and -B cell antibodies, and 2) the immunoregulator PGE2. T and B cell depleted splenocytes, or splenocytes from PGE2 pre-treated, highly resistant mice (C57Bl/6J) were transferred into irradiated, non-resistant secondary host mice (129/J) to establish whether or not they would retain their normally strong ability to spontaneously reject a third party (DBA/2) bone marrow allograft. In all cases, bone marrow seeding was assayed by enumerating the spleen colonies present in the secondary host 7 days after bone marrow grafting. Irradiated 129/J mice injected with low numbers (20 x 10(6) of untreated C57Bl/6J spleen cells prior to DBA/2 bone marrow contained 27.8 +/- 1.9 colonies/spleen, while mice injected with the same number of T and B depleted C57Bl/6J spleen cells contained significantly fewer (16.3 +/- 1.7) colonies/spleen. On the other hand, when C57Bl/6J spleen cells were incubated overnight with PGE2 prior to injection (20 x 10(6) into the 129/J hosts, they were unable to prevent the development of numerous colonies upon challenge with the DBA/2 bone marrow allograft (31.5 +/- 1.5 colonies/spleen: PGE2 pre-treated vs 16.9 +/- 2.1 colonies/spleen: non-pre-treated, control). The results demonstrate firstly, that spleen cells depleted of both Thy-1- and Ig-bearing cells appear to have concentrated for the effector cells responsible for bone marrow allograft rejection, and secondly, such effector cells could be suppressed by short-term exposure to PGE2, resulting in successful "take" of the bone marrow allograft.

Animals↗
PubMed1988

Inhibition of natural killer cell-mediated lysis of tumor cells by normal and regenerating bone marrow.

The natural killer (NK) cells which can lyse certain tumor cells during brief incubation in vitro have also been postulated to be the cells responsible for natural resistance to transplanted hemopoietic cells in vivo. To test this hypothesis, we have now measured: 1) the ability of bone marrow cells to compete with tumor cells as targets for spleen NK cells and 2) the effect of a brief incubation with spleen cells on the hemopoietic grafting potential of bone marrow cells. Firstly, when CBA/J mouse spleen cells were incubated with 51Cr-labelled YAC tumor cells together with DBA/2 mouse bone marrow cells, tumor cell lysis was reduced compared with incubation of spleen cells with tumor cells alone. Tumor cell lysis was even less when post-irradiation regenerating bone marrow was used. Secondly, C57B1/6 mouse bone marrow cells incubated with an excess of DBA/2 mouse spleen cells showed a reduced ability to produce hemopoietic spleen colonies in irradiated 129/J mice, whereas incubation with either thymus cells or fewer spleen cells produced no such effect. The results show that, when incubated with spleen cells under the conditions of a standard NK cell assay, regenerating bone marrow cells competitively inhibit the killing of YAC tumor cells and bone marrow progenitor cells are rendered ineffective in their hemopoietic colony-forming potential (CFU-s). These findings suggest that certain hemopoietic progenitor cells and YAC tumor cells can both serve as targets for NK cells, consistent with the view that the spontaneous cytolysis of tumor cells in vitro and natural resistance to bone marrow transplantation in vivo are mediated by cells of a common lineage.

Animals↗
PubMed1988

Dietary lactose improves endochondral growth and bone development and mineralization in rats fed a vitamin D-deficient diet.

Lactose promotes the intestinal absorption of calcium independent of the vitamin D endocrine system. The purpose of this study was to determine the effect of lactose supplementation on endochondral bone growth, bone development and mineralization in weanling rats fed a vitamin D-deficient diet. Rat pups were weaned from vitamin D-deficient dams and fed a vitamin D-deficient diet containing sucrose as the primary carbohydrate source or a similar diet but containing 20% lactose. After 4 wk, body weights, serum calcium levels and endochondral bone elongation rates in the lactose-fed animals were higher than in rats fed the sucrose diet. In addition, bone weights, bone calcium content, percent bone ash of bone dry weight, percent metaphyseal osseous tissues and bone osteoid content in the lactose-fed rats were different from those in the rats fed the sucrose diet. In all cases the changes in osseous tissues that were observed in the animals fed the lactose-supplemented diet were toward normal values as observed in age-matched animals fed a vitamin D-replete diet. The improvements in bone growth and development due to lactose supplementation occurred independent of the vitamin D endocrine system and are likely the result of improved calcium absorption in the intestine.

Animals↗
PubMed1988

Muscle cell components dictate hepatocyte gene expression and the distribution of the Golgi apparatus in heterokaryons.

Major changes in cytoarchitecture and gene expression were induced in short-term heterokaryons. When human hepatocytes were fused with mouse muscle cells, the hepatocyte Golgi apparatus changed from its usual polar location to a uniformly circumnuclear location typical of striated muscle. Human liver albumin ceased to be expressed, and expression of the human muscle cell-surface antigen 5.1H11 was induced without DNA replication or cell division. Coexpression of liver and muscle proteins was rarely observed. These novel findings provide insight into the regulation of gene expression and the targeting and localization of organelles with a central role in cell polarity, intracellular transport, and secretion.

Animals↗
PubMed1988

The effect of bearing tumours on the ability of mice to reject bone marrow transplants.

To examine the possible relationship between the cells mediating resistance to tumour cells and those mediating rejection of foreign bone marrow transplants (BMT), the effect of tumour-bearing on BMT rejection has been measured by means of the spleen colony assay. Moderate doses (less than 5.0 X 10(6] of bone marrow cells from DBA/2 strain mice, which normally produce few haemopoietic spleen colonies in gamma-irradiated (950R) CBA/J strain mice, gave numerous (confluent) colonies when given soon after injection of Ehrlich ascites tumour (EAT) cells. Transfusion of [3H]UdR-labelled DBA/2 bone marrow cells demonstrated that the increased spleen colony formation in tumour-bearing mice was not due simply to changes in the total number of injected cells homing to the spleen. Injection of EAT ascites fluid alone, given to CBA/J mice before 950R + BMT, transiently reduced spleen colony development, the effect being more marked when fluid from older tumors was used. Supernatant fluid from EAT cells grown in vitro also depressed growth of BMT in vivo. The results reveal two processes in progress in mice bearing an ascites tumour: (1) an early reduction in the natural resistance to BMT allowing successful grafting and spleen colony formation, and (2) a progressive production by the tumour cells of short-acting soluble factors tending to suppress the proliferation of colony forming bone marrow cells in the transplant. The effect of the tumour-bearing state in weakening the natural resistance to foreign BMT strongly suggests that both tumour and foreign marrow graft resistance are mediated by the same or closely related effector cells.

Animals↗
PubMed1988

Tumor necrosis factor inhibits human myogenesis in vitro.

We examined the effects of human recombinant tumor necrosis factor-alpha (TNF) on human primary myoblasts. When added to proliferating myoblasts, TNF inhibited the expression of alpha-cardiac actin, a muscle-specific gene whose expression is observed at low levels in human myoblasts. TNF also inhibited muscle differentiation as measured by several parameters, including cell fusion and the expression of other muscle-specific genes, such as alpha-skeletal actin and myosin heavy chain. Muscle cells were sensitive to TNF in a narrow temporal window of differentiation. Northern (RNA) blot and immunofluorescence analyses revealed that human muscle gene expression became unresponsive to TNF coincident with myoblast differentiation. When TNF was added to differentiated myotubes, there was no effect on muscle gene expression. In contrast, TNF-inducible mRNAs such as interferon beta-2 still responded, suggesting that the signal mediated by TNF binding to its receptor had no effect on muscle-specific genes after differentiation.

Actins↗
PubMed1987

The bone lining cell: a distinct phenotype?

It is argued that the flat cells that line nonremodeling endosteal bone surfaces are a distinct phenotype. These cells have a distinct morphology and they most likely have important functional roles in skeletal physiology, metabolism, and remodeling. For these reasons this cell seems deserving of a proper name. The name bone lining cell seems to have gained some acceptance but there will be continued confusion as long as skeletologists use this same term to generically describe cells that line bone surfaces, regardless of their actual identity.

Animals↗
PubMed1987

Carboxylesterases in the respiratory tracts of rabbits, rats and Syrian hamsters.

Esters are a widespread class of organic compounds found both in industry and the environment. Because esters are often volatile and, therefore, readily inhaled, the capacity of respiratory tract tissues as well as liver S-9 homogenates from rats, rabbits, and Syrian hamsters to hydrolyze a variety of esters was investigated. A new technique to determine hydrolysis rates by measuring carboxylic acid residues using ion chromatography was proven effective. The results indicated that esters, including potentially carcinogenic beta-lactones, are readily hydrolyzed by respiratory tract enzymes. Species and tissue differences were apparent. The nasal ethmoturbinates had especially high levels of esterase activity with tissue weight-normalized activities from rabbits and hamsters for most substrates exceeding all other tissues tested, including liver. Phenyl acetate was the most rapidly hydrolyzed by ethmoturbinate tissue of the esters tested. Among straight chain aliphatic alcohol acetates, hydrolysis rates increased with carbon number up to pentyl alcohol and then decreased. Branched 4-carbon alcohol acetates were less rapidly hydrolyzed than n-butyl acetate. Correlation of hydrophobicity constants with hydrolysis rates indicated that, for the straight chain aliphatic acetates, a bilinear model best fit the data.

Animals↗
PubMed1987

Renewal of natural killer cells in mice having elevated natural killer cell activity.

The present study was designed to examined the dynamics of splenic natural killer (NK) cells under two conditions of enhanced NK cell activity: (1) CBA/J mice given polyinosinic-polycytidylic acid (poly-I:C), an NK-cell-enhancing agent, and 62) untreated athymic nude (nu/nu) mice. The 'total NK cell activity' of the spleen (percentage specific lysis corrected for changes in organ cellularity) increased 5-fold and 2.7-fold after poly-I:C treatment for 1 day and 4 days, respectively. An injection of hydroxyurea (HU), a cell-cycle-toxic drug, given together with either poly-I:C or saline to CBA/J mice resulted in both cases in a 25% reduction in total NK cell activity 1 day later. This suggests that the renewal rate of nondividing NK cells is similar in poly-I:C-treated and saline-injected mice, and that the NK-enhancing effect of poly-I:C is not due to a stimulation of proliferation among NK cell precursors. HU administered simultaneously with poly-I:C or saline for 4 days eliminated NK cell activity in both cases, indicating that spleen NK cell activity is mediated almost entirely by newly formed (less than or equal to 4 days) cells. In nude mice, NK cell activity was assayed at various intervals after an HU depletion period of 2 days. NK depletion was initially more rapid in nu/nu mice than in control (nu/+) mice, although equally profound, and the subsequent recovery of NK cell activity after cessation of HU was also more rapid than in control (nu/+) mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Changes in bone mineral and bone formation rates during pregnancy and lactation in rats.

Changes in bone chemistry, cortical bone morphometry, and periosteal and trabecular bone formation rates were determined during pregnancy and lactation in rats. Data were obtained using chemical, static morphometric, and fluorochrome-based histomorphometric methods in pregnant or lactating animals and compared with age-matched, unmated controls. There were significant increases in bone weight, ash weight, calcium content, and femoral cross-sectional area by late pregnancy and decreases in these same parameters during lactation. There were also decreases in bone mass and increases in surface:volume ratios of trabecular bone during lactation. There were increases in femoral periosteal and endosteal perimeters associated with the reproductive cycle. Bone formation and appositional rates at the periosteal and endosteal surfaces were elevated during pregnancy, particularly evident at midpregnancy. Periosteal bone formation rates declined during lactation, but trabecular bone formation rates increased. These results indicate that during pregnancy there are increases in bone formation rates contributing to the increases in skeletal mass. During lactation in rats, reductions in skeletal mass are accompanied by increases in bone turnover, particularly evident in trabecular bone.

Animals↗
PubMed1986

The proliferation and differentiation of the bone-lining cell in estrogen-induced osteogenesis.

The purpose of this study was to determine the capacity of the bone-lining cell, which covers most nonremodeling bone surfaces in the adult skeleton, to proliferate and contribute to the rapid endosteal osteogenic response following estrogen treatment in male Japanese quail. In control, untreated birds bone-lining cells cover most of the femoral endosteal surface. Bone-lining cells are thinly extended along bone surfaces, have flat nuclei, and account for about 77% of the cells adjacent to the bone surface. The lineal density of bone surface cells in the controls was about 21 cells/mm of bone surface. By 16-20 h after estrogen administration cells with larger, round nuclei were seen on the bone surface and some of these cells contained a 3H-thymidine (3H-TdR) label. Within the first 24 h after estrogen administration the lineal bone surface cell density had increased to about 38 cells/mm. At 20-30 h after estrogen administration, most of the cells adjacent to the bone surface were round. The peak 3H-TdR labeling of cells immediately adjacent to the bone surface occurred about 36 h after estrogen administration. By 48 h the bone surface was covered with osteogenic cells and developing medullary bone. These results suggest that the bone-lining cell in the adult appears to retain some proliferative capability and osteogenic potential. However, because a rapid increase in cell density began prior to the rapid increases in 3H-TdR labeling, as well as the appearance of mitotic figures on the bone surface, another source of cells may have also contributed to the osteogenic response induced by estrogen.

Animals↗
PubMed1986

Pathogenesis of hypercalcemia in nude mice bearing a human renal carcinoma.

When grown as sc tumors in the nude (nu/nu) mouse, cells of the established human renal carcinoma cell line 786-0 produce hypercalcemia; this has an apparent humoral basis because it is reversed by resection of the primary tumor. We have investigated the pathogenesis of hypercalcemia in this model. Tumor-bearing mice were hypercalcemic (13.4 +/- 0.9 vs. 9.52 +/- 0.13 mg/dl in control mice) and hypophosphatemic (10.0 +/- 0.8 vs. 13.8 +/- 1.5 mg/dl in control mice; all values are mean +/- SEM). The serum concentration of 1,25-dihydroxyvitamin D was increased in tumor-bearing animals (70.0 +/- 9.3 vs. 43.8 +/- 4.8 pg/ml in control animals). Urinary excretion of cAMP was similar in control (33.7 +/- 1.4 nmol/mg creatinine) and tumor-bearing mice (38.2 +/- 4.7 nmol/mg creatinine). However, in the latter, the acute response of urinary cAMP to PTH was blunted. Although intestinal calcium transport in everted duodenal sacs in vitro was increased in tumor-bearing mice, hypercalcemia was unaffected by feeding the animals for 8 days a diet containing less than 0.02% calcium. Hence, absorption of dietary calcium did not play a significant role in maintenance of hypercalcemia. In hypercalcemic animals, the calcium content of the humerus was decreased (2.95 +/- 0.08 vs. 3.29 +/- 0.13 mg in controls; P less than 0.05). Quantitative histomorphometric analysis of the distal femoral metaphysis disclosed a significant reduction in trabecular bone volume in tumor-bearing mice (12.0 +/- 1.1% vs. 16.1 +/- 1.1% in controls; P less than 0.02). A strong trend for increased osteoclast surface and number was observed, suggesting that bone resorption was increased. Osteoblast surface and number were also somewhat increased, as was the rate of mineral apposition (2.55 +/- 0.14 vs. 1.91 +/- 0.04 micron/day in controls; P less than 0.01). Thus, the decrease in trabecular bone volume was associated with high turnover of bone, with an apparent net increase in bone resorption. We conclude that hypercalcemia in the nude mouse bearing human renal carcinoma cells is associated with increased bone resorption, high bone turnover, hypophosphatemia, and increased serum levels of 1,25-dihydroxyvitamin D.

Adenocarcinoma↗