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Biomedical subjects

J E Russell

Publications and source records attributed to J E Russell.

At least 55 records · Page 3Linked to original sources
PubMed1986

Bone deficit in ovariectomized rats. Functional contribution of the marrow stromal cell population and the effect of oral dihydrotachysterol treatment.

This study investigates the proliferative and osteogenic role of marrow stromal/osteoprogenitor cells in the development of the cortical bone deficit in ovariectomized (OVX) female rats. In vitro, clonal growth of marrow stromal cells from OVX rats was significantly impaired (vs. sham-operated controls). Yet in vivo, cells from sham-operated and OVX rats had equal osteogenic potential in several in vivo experimental situations, such as in intraperitoneally implanted millipore diffusion chambers and in intramuscular implants of marrow plus osteoinductive bone matrix (composite grafts). Long-term (6 mo) dihydrotachysterol (DHT) treatment of OVX rats enhanced their in vitro proliferative potential and clonal growth, as well as their osteogenic expression in composite grafts. The observation that the in vivo osteogenic performance of OVX rat marrow stromal cells was normal at extraosseous sites suggests that the mechanisms leading to osteopenia may involve an abnormality in cell-matrix interactions.

Animals↗
PubMed1986

Bone maturation and quality of bone material in rats flown on the space shuttle 'Spacelab-3 Mission'.

The maturation profiles of calcium, phosphorus, magnesium and hydroxyproline in the femoral trabecular and cortical bone and in the thoracic vertebrae from male rats flown on the 7-day 'Spacelab-3 Mission' were measured by density gradient analysis. In rats exposed to a spaceflight environment, profiles of the matrix and mineral moieties were shifted toward both the lower (vertebrae) and higher density fractions (femurs and vertebrae), patterns indicating a decrease in bone growth/turnover. X-Ray diffraction of vertebrae indicated that spaceflight is associated with a decrease in apatite crystal size/perfection.

Animals↗
PubMed1985

Effect of an adrenocorticotropin analogue, ACTH 1-17, on DNA synthesis in murine metaphyseal bone.

The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six different timepoints, 4 hr apart, during a single 24-hr span with either a low (0.02 I.U./kg) or a high (20 I.U./kg) dose of ACTH 1-17. Control groups received injections of a placebo at corresponding timepoints. Subgroups of mice were injected with [3H]thymidine ([3H]Tdr) to follow the changes in DNA labeling in the proximal tibial metaphysis at 15 min and 2, 4, 8, 12 and 24 hr after ACTH 1-17 or placebo treatment. All mice were injected with the isotope 30 min before killing, except for those killed 15 min after Rx administration where the isotope had been injected 14 min before killing. The data were analyzed both by analysis of variance and by the cosinor method, the latter of which tests the fit of a 24-hr cosine curve to the data. The effect of ACTH 1-17 on the target cell population was dependent not only upon the dose but upon the time of administration. Both doses exerted time-dependent action, ranging from stimulation to inhibition of DNA labeling. Inhibition was noted when the ACTH 1-17 was administered at 2 hr after the beginning of the daily dark span when nocturnal animals become active. When administered at this circadian stage, the larger dose in particular was associated with an inhibition of DNA labeling lasting for 24 hr. The inhibitory effect was much shorter when the same dose was injected 4 hr earlier. Moreover, the large ACTH 1-17 dose had a stimulatory effect lasting for 24 hr when it was administered 2 hr after the onset of the daily light span, with a much shorter stimulation following administration of the large dose at 6 hr after the beginning of the daily dark span. A circadian stage-dependent stimulation or inhibition of DNA labeling at 2 or 14 hr after light onset, respectively, was thus complemented by an initial inhibition followed by stimulation and vice versa at 10 and 18 hr after light onset respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1985

Effects of deflazacort and the L-6485 metabolite on epiphyseal cartilage carbohydrate metabolism: comparison with prednisone.

Male Sprague-Dawley rats were injected with 1 mg/100 g bw/day of prednisone, 1.25 mg/1--g bw/day of deflazacort, or its metabolite, for a period of 20 days. Epiphyseal cartilage slices were incubated in a modified Krebs Ringer bicarbonate buffer, at 37 degrees C for 60 min, with either 14C-1- or 14C-6-glucose to quantitate both the absolute and relative rates of pentose shunt versus aerobic and anaerobic glycolytic activity, respectively. Measurements of both total and radioactive glucose uptake, lactate production and 14CO2 generation were expressed as either mumoles or DPM/mg cellular DNA/hr, respectively. This study demonstrated: (1) chronic prednisone administration decreased anaerobic glycolysis (glucose uptake and lactate production) 3-fold (P less than 0.01); (2) prednisone on a chronic basis produced no measured alteration in either the pentose shunt or Kreb's cycle activity; (3) both deflazacort and the deflazacort metabolite significantly stimulated (P less than 0.02) anaerobic glycolytic activity in epiphyseal cartilage tissue. In contrast to prednisone, the administration of either deflazacort or its L-6485 metabolite did not inhibit the glycolytic pathway of metabolism so necessary for epiphyseal cartilage growth and mineralization.

Aerobiosis↗
PubMed1985

In vitro evaluation of circadian patterns of bone collagen formation.

The circadian patterns of bone collagen formation were studied in vitro to ascertain whether the biorhythmic profiles previously measured in vivo reflect true differences in collagen synthesis. Alteration of amino acid pool sizes did not negate the circadian-stage differences in bone collagen production. Evaluations of proline uptake and transport, as well as collagenous protein turnover, demonstrated that the intracellular assembly and secretion of bone collagenous protein during the dark span is truly decreased relative to that during the light period. It was further affirmed that PTH is essential for maintenance of the normal circadian collagen synthesis rhythms.

Animals↗
PubMed1984

Adrenal/parathyroid regulation of DNA, collagen and protein synthesis in rat epiphysial cartilage and bone.

Young, growing rats which had been chronically (2 weeks) adrenalectomized or parathyroidectomized were used to define the roles of the adrenal and parathyroid glands on the maintenance of normal circadian rhythms of DNA, collagen and non-collagen protein synthesis in the skeleton. The animals were conditioned to food being available ad libitum and to 12 h light: 12 h darkness (lights on from 08.00 to 20.00 h). The pace of DNA, collagen and non-collagen protein synthesis in different regions of the tibia (tibial growth cartilage, metaphysial bone and diaphysial bone) was measured by the in-vivo incorporation of tritiated thymidine (1 h) and radioactive proline (48 h). In intact rats there were no regional differences in the phasing of the circadian profiles; peak DNA and non-collagen protein synthesis occurred at the onset of the dark period while peak collagen synthesis occurred during the middle of the period of light. Adrenalectomy selectively abolished the regional DNA synthesis rhythms without altering the phases of the serum Ca and phosphorus (P) rhythms, which peak at mid-day and at the onset of darkness respectively. Parathyroidectomy abolished the regional rhythms for collagen and non-collagen protein synthesis and serum Ca rhythms, without altering the phase of the serum P and corticosterone rhythms. Dietary Ca-lactate supplements, which raised serum Ca levels towards normal in parathyroidectomized rats, were able to correct serum corticosterone values but did not normalize bone collagen and non-collagen protein synthesis values. These data indicate that the adrenal rhythm governs the proliferative activities of bone and cartilage cells, and that parathyroid hormone is essential to maintain normal collagen and non-collagen protein synthesis rhythms.

Adrenal Glands↗
PubMed1984

Mineralization in rat metaphyseal bone exhibits a circadian stage dependency.

Density gradient fractionation analysis of rat metaphyseal bone was used to delineate the biorhythmic changes in bone matrix mineralization. Seventy-two 4-week-old rats were entrained to 12-hr light, 12-hr dark cycles (light, 0800-2000 hr; darkness, 2000-0800 hr) for 4 weeks. All animals were fed ad lib. on Purina laboratory rat chow and tap water. Groups of 10-12 rats were killed by cervical dislocation at 4-hr intervals during a 24-hr period, and the tibias were then biopsied and frozen in liquid N2. Metaphyseal bone was fractionated via bromoformtoluene density gradients into specific gravity fractions ranging from 1.7 to 2.8. Density gradient fractions were analyzed for concentrations of calcium and inorganic phosphorus. Chronograms indicated that the accumulation of both calcium and inorganic phosphorus into the newly forming/least-dense mineral moieties of bone (1.3-1.7 sp grav) showed a single peak in the biorhythm of the rat. A statistically significant circadian rhythm of mineralization was detected for calcium (P less than 0.001) and inorganic phosphorus (P less than 0.039), with peaks during the environmental dark span. These results suggest that the physiological phasing of bone mineralization in the light-dark synchronized rat, is similar to that previously noted for cartilage mineralization and is antiphasal to the midday peak in bone collagen synthesis.

Animals↗
PubMed1983

Effect of spaceflight on the non-weight-bearing bones of rat skeleton.

Male Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellite. They were injected with tetracycline for a second and third time on the 6th and 27th days, respectively, after recovery of the Biosatellite. Spaceflight did not alter the rate of periosteal bone formation in the non-weight-bearing ribs and regions of the mandibles, which were covered by masticatory muscles. Bone formation-calcification rates were impaired at those sites in the jaw that had no contiguous muscle (molar region). The remodeling activity on the alveolar bone around the buccal roots of the molar teeth was significantly reduced but without creating a negative balance between formative and resorptive activities. Total Ca, P, and hydroxyproline concentrations in the jaws, incisors, and ribs were normal after spaceflight, but gravity density fractionation studies indicated that in the jaws alone, O-G conditions caused a delay in the maturation of bone mineral and matrix. A 29-day postflight recovery period at earth's gravity was sufficient to fully correct these anomalies. Relative to tooth formation, relatively normal circadian and infradian biorhythmic periodicities of Ca and P in dentin and enamel were maintained during spaceflight. We conclude that most of the non-weight-bearing bones of the rat skeleton are at risk to the effects of hypogravity.

Animals↗
PubMed1983

Meal timing as a Zeitgeber for skeletal deoxyribonucleic acid and collagen synthesis rhythms.

Meal timing protocols were used to probe the circadian regulation of DNA and protein synthesis in the rat tibia. Two groups of 4-week-old rats were entrained to 12-h light, 12-h dark cycles (light, 0800-2000 h; darkness, 2000-0800 h) for 4 weeks. One group was fed for 4 h at the onset of the light span (EL). The other group was fed for 4 h at the onset of the dark span (ED). Forty-eight hours before death, the rats were injected ip with 0.015 microCi/g BW [14C]proline [collagen and noncollagen protein (NCP) synthesis], and they received 0.25 microCi/g BW [3H] thymidine (DNA synthesis) 1 h before death. Groups of 10-12 rats were bled from the abdominal aorta at 4-h intervals under light ether anesthesia (1-2 min/rat) during 2 consecutive 24-h periods, and the tibias were then biopsied and frozen in liquid N2. Serum samples were analyzed for calcium, inorganic phosphorus, and immunoassayable levels of corticosterone (CS), PTH, and calcitonin. Epiphyseal cartilage and metaphyseal and diaphyseal bone were analyzed for DNA and acidic pepsin-digestible collagen. Chronograms indicated that DNA synthesis in cartilage and bone, along with serum CS, showed two approximately equal and positively correlated peaks, with the cycles for rats fed EL vs. ED being in approximate antiphase. The fit of a 12-h cosine curve was statistically significant in all cases (P less than 0.01). The acrophase peaks were: EL, 0800 and 2000 h; and ED, 1600 and 0400 h. These patterns were unrelated to those for NCP and collagen synthesis. EL and ED relationships for NCP synthesis were also antiphasal. A statistically significant circadian rhythm of collagen synthesis was detected in cartilage and bone of ED-fed rats (peak, 0800 h; nadir, 2400 h). In EL-fed rats, the 0800 h peak alone was muted. No consistent correlations were observed between serum calcium and phosphorus chronograms and those of cartilage and bone collagen and DNA synthesis. The results suggest that physiological alterations of CS in vivo serve to modulate cartilage and bone cell proliferation, but they do not seem to regulate the phasing of the net collagen synthetic rhythm.

Animals↗
PubMed1983

The effect of protracted tetracycline treatment on bone growth and maturation.

Mature female rhesus monkeys were used to evaluate the effects of a one-year course of tetracycline (50 mg/kg/day, intramuscularly) on the formation, maturation, and mineralization of mandibular bone. The bones from the treated group contained normal concentrations of calcium (Ca), inorganic phosphorus (Pi), and hydroxyproline (HO-Pr), and the treatment schedule did not alter the distribution (percentage) of total osteons into slightly, moderately, and highly mineralization classes. Tetracycline impairs bone mineralization and the subsequent maturation of the mineral and matrix moieties. The percentage of highly mineralized osteons labeled with tetracycline is subnormal. Density gradient fractionation studies indicate the presence of abnormally high Ca/Pi ratios in the temporally young newly formed bone mineral and somewhat higher ratios in the most mature bone fraction. Protracted tetracycline treatment at high dosages impairs bone growth and maturation in adult rhesus monkeys.

Animals↗
PubMed1983

Simulating certain aspects of hypogravity: effects on bone maturation in the non-weight bearing skeleton.

This study reports the effects of simulation of certain aspects of hypogravity (via partial skeletal unloading) on the growth and maturation of the non-weight bearing mandibles of 41-d and 1-yr-old rats. Partial skeletal unloading was effected by elevating the hindquarters (PULEH), and this simulation was controlled with normally loaded animals fed either ad libitum or the average amount of food consumed by the the experimental group (group-mean fed). The chemical status of the mandibles after 10 d or 14 d PULEH closely resembled that of control rats. The younger PULEH rats and their group-mean fed controls demonstrated a trend toward impaired maturation of mineral and matrix moieties; yet the concentrations of calcium (Ca) and phosphorus (P) expressed as a ratio to collagen hydroxyproline content were normally distributed within a density gradient profile which separates the mineral and matrix moieties into various age-dependent fractions. These data demonstrate that 10 d or 14 d PULEH in young or old rats, respectively, is not sufficient to elicit the maturation deficit observed in the mandibles of rats flown for 18.5 d in the Soviet Biosatellite Cosmos-1129. Unless the duration of PULEH is critical, the cephalad fluid shift which is common to PULEH and spaceflight animals cannot be solely responsible for the flight-induced maturation deficit. Because the mandibles of the PULEH rats remain antigravity-postured, the results emphasize the importance of gravity unloading to the impairment of mandibular bone matrix/mineral maturation during spaceflight. Decreased gravity and, hence, gravity unloading cannot be mimicked in ground-based models of hypokinesia.

Age Factors↗
PubMed1982

Bactericidal activity of human lactoferrin: differentiation from the stasis of iron deprivation.

Previous studies have demonstrated a direct iron-irreversible inhibition of a variety of microorganisms by human apolactoferrin. The present study compared the bactericidal effects of lactoferrin on Streptococcus mutans with the bacteriostatic effects of iron deprivation. Growth (as determined by change in optical density) and macromolecular synthesis, as determined by incorporation of (14)C-labeled uracil, thymidine, and lysine, were inhibited by incubation of washed exponential-phase S. mutans NCTC 10449 with purified human apolactoferrin. Similarly, apolactoferrin inhibited glucose uptake and metabolism. Iron-saturated lactoferrin had no effect on bacterial growth or metabolism and was capable of serving as a source of iron in iron-depleted medium. S. mutans failed to grow, and there was no indication of macromolecular synthesis in iron-depleted partially defined medium; however, glucose metabolism continued, though at a reduced rate, and viability was retained for 72 h. There was no detectable metabolism of glucose by cells maintained for 18 h in iron-free medium. Metabolism was restored by transfer of iron-depleted S. mutans to iron-complete medium. This was in contrast to the irreversible inhibition by lactoferrin after 1 h of incubation. Inhibition could not be reversed by removal of cell surface-associated lactoferrin as detected by rhodamine isothiocyanate-labeled antilactoferrin. This inhibition of metabolism and rapid loss in viability observed with lactoferrin treatment suggest that lactoferrin has a direct bactericidal effect on S. mutans that cannot be attributed to simple iron deprivation.

Glucose↗
PubMed1982

Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat.

Calcium homeostasis was studied in freely fed control, streptozotocin diabetic, long-term and short-term insulin-treated diabetic rats 7 wk after the induction of diabetes. In contrast to the short-term (5-12 day) diabetic rat model, intestinal absorption of calcium was markedly enhanced in chronically insulin-deficient animals. Moreover, conventional balance studies showed that these animals were in positive calcium balance despite severe hypercalciuria. Intestinal hyperabsorption of calcium in long-standing diabetic rats occurred despite low levels of circulating 1,25-dihydroxyvitamin D and hypercorticosteronism and was attended by hypercalcemia and suppression of both plasma parathyroid hormone (PTH) and urinary cyclic 3',5'-AMP (cAMP). Long-term insulin replacement completely normalized the intestinal hyperabsorption of calcium, corrected the plasma calcium, and significantly increased circulating PTH and urinary cAMP excretion. Insulin therapy also corrected the decreased plasma 1,25-dihydroxyvitamin D observed in untreated diabetic animals. Intestinal hyperabsorption of calcium appeared to be only partially corrected by short-term insulin therapy. The accumulated results reveal decided differences in calcium homeostasis and hormonal response between the rats with long-standing diabetes and those with diabetes of short duration.

Animals↗
PubMed1981

Bactericidal activity of human lactoferrin: influence of physical conditions and metabolic state of the target microorganism.

Lactoferrin is an iron-binding protein that is bactericidal against Streptococcus mutans and several other microorganisms. In this study, the influence of several physical conditions as well as the metabolic state of S. mutans on lactoferrin susceptibility were investigated. After exposure to lactoferrin, a 15-min lag period occurred before the initiation of killing, indicating that a two-step process is involved in lactoferrin killing. Cultures harvested during the early exponential phase were very sensitive to lactoferrin, whereas cultures harvested in the early stationary phase were markedly more resistant. The rate of killing was dependent on temperature; there was no loss of viability at 2 degrees C. Killing occurred at pH 5.0 to 6.0 in water and 20 mM glycine, but did not occur at any pH in 50 mM sodium phosphate or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer. Addition of exogenous ferrous or ferric ions did not reverse or prevent lactoferrin killing, nor did addition of 1 mM magnesium chloride.

Humans↗